The effect of right ventricle pacemaker lead position on diastolic function in patients with preserved left ventricle ejection fraction.

PubMed

Mitov, Vladimir; Perisić, Zoran; Jolić, Aleksandar; Adamović, Dragana; Zastranović, Lale; Aleksić, Aleksandar; Kostić, Tomislav; Božinović, Nenad; Aleksić, Zeljka; Soldatović, Ivan

2013-01-01

Our aim was to analyze any changes during diastole in patients with normal left ventricular ejection fraction (LVEF), after pacemaker stimulation from the right ventricular outflow tract (RVOT) and right ventricular apex (RVA) lead position. This was a prospective, randomized, follow up study, which lasted for 12 months. Our research included 132 consecutive patients who were implanted with a permanent antibradycardiac pacemaker. Regarding the right ventricle lead position the patients were divided into two groups: The RVOT group--71 patients, with right ventricle outflow tract lead position and the RVA group--61 patients, with right ventricle apex lead position. We measured LVEF and diastolic parameters: peak filling ratio and time to peak filling ratio obtained by radionuclide ventriculography (RNV). The LVEF and various diastolic parameters and left atrial diameter were obtained by echocardiography. Based on the values of deceleration time of early diastolic filling (DTE), and other diastolic parameters like left atrial diameter, all the patients were classified into three degrees of diastolic dysfunction. Our results showed that there was no group difference in distribution of gender, age, body mass index (BMI), VVI to DDD pacemakers implantation ratio, RNV parameters (LVEF, peak filling rate (PFR), time to PFR (TPFR)) and echocardiography parameters: LVEF and parameters of diastolic dysfunction. After 12 months of pacemaker stimulation, LVEF by RNV remained the same in the RVOT group 51.31±15.80% (P=0.75), and also in the RVA group 53.83±6.57%, (P=0.19). In the RVOT group the PFR was highly lower and this finding was significant (P=0.01), while TPFR was also significantly lower (P=0.03). By dividing the patients according to the degree of diastolic dysfunction we found that most patients in both groups at enrollment had a second degree diastolic dysfunction. In both groups diastolic dysfunction increased, the number of patients with third degree diastolic dysfunction increased, and the number of patients with second degree diastolic dysfunction decreased, however, the worsening of diastolic function was significant only in the RVOT group. In conclusion, pacemaker stimulation from RVOT, but not in RVA, leads to progression of diastolic dysfunction in patients with preserved LVEF. This negative effect of pacemaker stimulation from RVOT on diastolic parameters was confirmed by two independent methods, RNV and echocardiography.

Early and simple detection of diastolic dysfunction during weaning from mechanical ventilation

PubMed Central

2012-01-01

Weaning from mechanical ventilation imposes additional work on the cardiovascular system and can provoke or unmask left ventricular diastolic dysfunction with consecutive pulmonary edema or systolic dysfunction with inadequate increase of cardiac output and unsuccessful weaning. Echocardiography, which is increasingly used for hemodynamic assessment of critically ill patients, allows differentiation between systolic and diastolic failure. For various reasons, transthoracic echocardiographic assessment was limited to patients with good echo visibility and to those with sinus rhythm without excessive tachycardia. In these patients, often selected after unsuccessful weaning, echocardiographic findings were predictive for weaning failure of cardiac origin. In some studies, patients with various degrees of systolic dysfunction were included, making evaluation of the diastolic dysfunction to the weaning failure even more difficult. The recent study by Moschietto and coworkers included unselected patients and used very simple diastolic variables for assessment of diastolic function. They also included patients with atrial fibrillation and repeated echocardiographic examination only 10 minutes after starting a spontaneous breathing trial. The main finding was that weaning failure was not associated with systolic dysfunction but with diastolic dysfunction. By measuring simple and robust parameters for detection of diastolic dysfunction, the study was able to predict weaning failure in patients with sinus rhythm and atrial fibrillation as early as 10 minutes after beginning a spontaneous breathing trial. Further studies are necessary to determine whether appropriate treatment tailored according to the echocardiographic findings will result in successful weaning. PMID:22770365

Early and simple detection of diastolic dysfunction during weaning from mechanical ventilation.

PubMed

Voga, Gorazd

2012-07-06

Weaning from mechanical ventilation imposes additional work on the cardiovascular system and can provoke or unmask left ventricular diastolic dysfunction with consecutive pulmonary edema or systolic dysfunction with inadequate increase of cardiac output and unsuccessful weaning. Echocardiography, which is increasingly used for hemodynamic assessment of critically ill patients, allows differentiation between systolic and diastolic failure. For various reasons, transthoracic echocardiographic assessment was limited to patients with good echo visibility and to those with sinus rhythm without excessive tachycardia. In these patients, often selected after unsuccessful weaning, echocardiographic findings were predictive for weaning failure of cardiac origin. In some studies, patients with various degrees of systolic dysfunction were included, making evaluation of the diastolic dysfunction to the weaning failure even more difficult. The recent study by Moschietto and coworkers included unselected patients and used very simple diastolic variables for assessment of diastolic function. They also included patients with atrial fibrillation and repeated echocardiographic examination only 10 minutes after starting a spontaneous breathing trial. The main finding was that weaning failure was not associated with systolic dysfunction but with diastolic dysfunction. By measuring simple and robust parameters for detection of diastolic dysfunction, the study was able to predict weaning failure in patients with sinus rhythm and atrial fibrillation as early as 10 minutes after beginning a spontaneous breathing trial. Further studies are necessary to determine whether appropriate treatment tailored according to the echocardiographic findings will result in successful weaning.

Impaired left ventricular diastolic function is related to the formation of left ventricular apical thrombus in patients with acute anterior myocardial infarction.

PubMed

Choi, Ung Lim; Park, Jae-Hyeong; Sun, Byung Joo; Oh, Jin Kyung; Seong, Seok Woo; Lee, Jae-Hwan; Choi, Si Wan; Jeong, Jin-Ok; Kwon, In Sun; Seong, In-Whan

2018-05-01

Left ventricular (LV) apical thrombus is a clinically important complication which can cause systemic embolization in patients with anterior acute myocardial infarction (AMI). Systolic dysfunction has been a risk factor for developing LV apical thrombus in AMI patients. However, the role of diastolic dysfunction in the development of LV apical thrombus in these patients is still unknown. We performed this study to evaluate whether diastolic dysfunction can influence the development of LV apical thrombus in anterior AMI patients. We retrospectively analyzed all consecutive anterior AMI patients with available echocardiographic images within 1 month from January 2005 to April 2016. After gathering clinical characteristics from their medical records, systolic and diastolic functions were analyzed from digitally stored echocardiographic images. We included a total of 1045 patients (748 males, mean age 64 ± 12 years) with anterior AMI, and 494 (47%) were diagnosed as STEMI. The incidence of LV apical thrombus was 3.3% (34/1045). The LV apical thrombus group had larger LV diastolic dimension, larger LV diastolic and systolic volumes, and lower LVEF than the no LV thrombus group. The LV apical thrombus group showed higher mitral E velocity over mitral annular E' velocity ratio, an indicator of LV end-diastolic pressure (P < 0.001). In the LV apical thrombus group, the incidence of grade 2 diastolic dysfunction (32 vs 12%, P = 0.001) and grade 3 diastolic dysfunction (26 vs 2%, P < 0.001) were significantly higher than in the no LV apical thrombus group. The presence of more than grade 2 diastolic dysfunction, LVEF and presence of LV apical aneurysm were statistically significant factors associated with LV apical thrombus after the multivariate analysis. In conclusion, along with LV systolic dysfunction and LV apical aneurysm, LV diastolic dysfunction was also related with the presence of LV apical thrombus in patients with anterior AMI.

Diagnosis of Nonischemic Stage B Heart Failure in Type 2 Diabetes Mellitus: Optimal Parameters for Prediction of Heart Failure.

PubMed

Wang, Ying; Yang, Hong; Huynh, Quan; Nolan, Mark; Negishi, Kazuaki; Marwick, Thomas H

2018-05-11

This study sought to identify whether impaired global longitudinal strain (GLS), diastolic dysfunction (DD), or left atrial enlargement (LAE) should be added to stage B heart failure (SBHF) criteria in asymptomatic patients with type 2 diabetes mellitus. SBHF is a precursor to clinical heart failure (HF), and its recognition justifies initiation of cardioprotective therapy. However, original definitions of SBHF were based on LV hypertrophy and impaired ejection fraction. Patients with asymptomatic type 2 diabetes mellitus ≥65 years-of-age (age 71 ± 4 years; 55% men) with preserved ejection fraction and no ischemic heart disease were recruited from a community-based population. All underwent a standard clinical evaluation, and a comprehensive echocardiogram, including assessment of left ventricular hypertrophy (LVH), LAE, DD (abnormal E/e'), and GLS (<16%). Over a median follow-up of 1.5 years (range 0.5 to 3), 20 patients were lost to follow-up, and 290 individuals were entered into the final analyses. In this asymptomatic group, LV dysfunction was identified in 30 (10%) by DD, 68 (23%) by LVH, 102 (35%) by LAE, and 68 (23%) by impaired GLS. New-onset HF developed in 45 patients and 4 died, giving an event rate of 112/1,000 person-years. Survival free of the composite endpoint (HF and death) was about 1.5-fold higher in patients without a normal, compared with an abnormal echocardiogram. LVH, LAE, and GLS <16% were associated with increased risk of the composite endpoint, independent of ARIC risk score and glycosylated hemoglobin, but abnormal E/e' was not. The addition of left atrial volume and GLS provided incremental value to the current standard of clinical risk (ARIC score) and LVH. In a competing-risks regression analysis, LVH (hazard ratio: 2.90; p < 0.001) and GLS <16% (hazard ratio: 2.26; p = 0.008), but not DD and LAE were associated with incident HF. Subclinical left ventricular systolic dysfunction is prevalent in asymptomatic elderly patients with type 2 diabetes mellitus, and impaired GLS is independent and incremental to LVH in the prediction of incident HF. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Is preeclampsia an independent predictor of diastolic dysfunction? A retrospective cohort study.

PubMed

Guirguis, George F; Aziz, Michael M; Boccia Liang, Claire; Williams, Shauna F; Apuzzio, Joseph J; Bilinski, Robyn; Mornan, Adenieki J D; Shah, Leena P

2015-10-01

To determine if preeclampsia is an independent predictor of diastolic dysfunction and what factors among patients with preeclampsia are associated with diastolic dysfunction. This is a retrospective cohort study of patients who delivered between 2008 and 2013 at a single institution who had a maternal echocardiogram during their pregnancy or within 5months of delivery. Patients with structural heart disease, ejection fraction less than 45%, pulmonary embolus, or age over 45years were excluded. Medical records were reviewed for medical and obstetric complications and echocardiogram findings. Demographic characteristics and rate of diastolic dysfunction were compared between patients with preeclampsia and without preeclampsia. Multivariate logistic regression was performed controlling for age, ethnicity, gestational age at delivery, diabetes, preeclampsia, intrauterine growth restriction (IUGR), antihypertensive use and magnesium sulfate administration. Sixty-six patients were identified, of which 39 (59%) had preeclampsia. Past history of preeclampsia, IUGR in the current pregnancy, antihypertensive use and magnesium sulfate use were higher in the preeclampsia group. Fifteen patients (39%) in the preeclampsia group were African-American compared to 2 (3%) in the control group (p<0.01). Seventeen (44%) of the patients with preeclampsia were found to have diastolic dysfunction compared to 3 (11%) controls (OR=6.18, 95% CI 1.59,24.02; p=0.006). Logistic regression analysis did not reveal other independent predictors of diastolic dysfunction. In the patients with preeclampsia, history of preeclampsia with severe features and IUGR were not associated with diastolic dysfunction. Our study supports previous findings that preeclampsia is associated with diastolic dysfunction. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

The influence of type 2 diabetes and gender on ventricular repolarization dispersion in patients with sub-clinic left ventricular diastolic dysfunction

PubMed Central

Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila

2015-01-01

Objective: To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. Background: QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. Material and methods: We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X2 test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. Results: QTc max. interval, QTc dispersion and Tpeak-Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24±14.7 ms vs. 433.55±14.4 ms, P<0.000; 44.98±18.78 ms vs. 32.05±17.9 ms, P<0.000; 32.60±1.6 ms vs. 17.46±2.0 ms, P<0.02. Prolonged QTc max. interval was found in 33% of patients, indiabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function, (Chi-square: 16.77, P<0.0001). A prolonged QTc dispersion, was found in 40.6% of patients, in diabetic group with subclinical left ventricular diastolic dysfunction vs. 20% of patients in diabetic group with normal left ventricular diastolic function Chi-square: 14.11, P<0.0002). A prolonged dispersion of Tpeak-Tend interval was found in 24% of patients in diabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function (Chi-square: 12.00, P<0.005). Females in diabetic group with subclinical left ventricular diastolic dysfunction in comparison with males in diabetic group with subclinical left ventricular diastolic dysfunction, have a significantly prolonged: mean QTc max. interval (23.3% vs. 10%, Chisquare: 12.0, P<0.005), mean QTc dispersion (27.3% vs. 13.3%, Chi-square: 10.24, P<0.001), mean Tpeak-Tend interval (10% vs. 3.3%, Chi-square: 5.77, P<0.01), mean Tpek-Tend dispersion (16.6% vs. 6.6%, Chi-square: 8.39, P<0.003). Conclusion: The present study has shown that influences of type 2 diabetes and gender in diabetics with sub-clinical left-ventricular diastolic dysfunction are reflected in a set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization than in diabetic patients with normal diastolic function. In addition, it demonstrates that there exist differences between diabetic females with sub-clinic LV dysfunction and those with diabetes and normal LV function in the prevalence of increased set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization. PMID:26550530

The influence of type 2 diabetes and gender on ventricular repolarization dispersion in patients with sub-clinic left ventricular diastolic dysfunction.

PubMed

Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila

2015-01-01

To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X(2) test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. QTc max. interval, QTc dispersion and Tpeak-Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24±14.7 ms vs. 433.55±14.4 ms, P<0.000; 44.98±18.78 ms vs. 32.05±17.9 ms, P<0.000; 32.60±1.6 ms vs. 17.46±2.0 ms, P<0.02. Prolonged QTc max. interval was found in 33% of patients, indiabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function, (Chi-square: 16.77, P<0.0001). A prolonged QTc dispersion, was found in 40.6% of patients, in diabetic group with subclinical left ventricular diastolic dysfunction vs. 20% of patients in diabetic group with normal left ventricular diastolic function Chi-square: 14.11, P<0.0002). A prolonged dispersion of Tpeak-Tend interval was found in 24% of patients in diabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function (Chi-square: 12.00, P<0.005). Females in diabetic group with subclinical left ventricular diastolic dysfunction in comparison with males in diabetic group with subclinical left ventricular diastolic dysfunction, have a significantly prolonged: mean QTc max. interval (23.3% vs. 10%, Chisquare: 12.0, P<0.005), mean QTc dispersion (27.3% vs. 13.3%, Chi-square: 10.24, P<0.001), mean Tpeak-Tend interval (10% vs. 3.3%, Chi-square: 5.77, P<0.01), mean Tpek-Tend dispersion (16.6% vs. 6.6%, Chi-square: 8.39, P<0.003). The present study has shown that influences of type 2 diabetes and gender in diabetics with sub-clinical left-ventricular diastolic dysfunction are reflected in a set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization than in diabetic patients with normal diastolic function. In addition, it demonstrates that there exist differences between diabetic females with sub-clinic LV dysfunction and those with diabetes and normal LV function in the prevalence of increased set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization.

Relationship of biomarkers of extracellular matrix with myocardial function in Type 2 diabetes mellitus.

PubMed

Liu, Ju-Hua; Chen, Yan; Zhen, Zhe; Ho, Lai-Ming; Tsang, Anita; Yuen, Michele; Lam, Karen; Tse, Hung-Fat; Yiu, Kai-Hang

2017-07-01

The study evaluated the relationship of extracellular matrix and renin angiotensin system with myocardial dysfunction in Type 2 diabetes mellitus. All patients underwent resting and exercise echocardiography, including conventional parameters, E/E' ratio, global longitudinal strain and diastolic function reserve index. Plasma matrix metalloproteinase-1, TIMP-1, amino-terminal propeptide of type I and type III procollagen and renin angiotensin system activity were measured. As patients with diastolic dysfunction had a higher plasma level of TIMP-1 and propeptide of type III procollagen than those with no diastolic dysfunction. After multivariate adjustment, TIMP-1 associated with E/E' (both at rest and stress) and diastolic function reserve index. TIMP-1 is independently associated with myocardial diastolic dysfunction in patients with Type 2 diabetes mellitus.

Subclinical left ventricular diastolic dysfunction and incident type 2 diabetes risk: the Korean Genome and Epidemiology Study.

PubMed

Park, Juri; Kim, Jin-Seok; Kim, Seong Hwan; Kim, Sunwon; Lim, Sang Yup; Lim, Hong-Euy; Cho, Goo-Yeong; Sung, Ki-Chul; Kim, Jang-Young; Baik, Inkyung; Koh, Kwang Kon; Lee, Jung Bok; Lee, Seung Ku; Shin, Chol

2017-03-14

Subclinical left ventricular (LV) diastolic dysfunction in type 2 diabetes (T2D) is a common finding and represents an early sign of diabetic cardiomyopathy. However, the relationship between LV diastolic dysfunction and the incident T2D has not been previously studied. A total of 1817 non-diabetic participants (mean age, 54 years; 48% men) from the Korean Genome and Epidemiology Study who were free of cardiovascular disease were studied. LV structure and function were assessed by conventional echocardiography and tissue Doppler imaging. Subclinical LV diastolic dysfunction was defined using age-specific cutoff limits for early diastolic (Em) velocity, mitral E/Em ratio, and left atrial volume index. During the 6-year follow-up period, 273 participants (15%) developed T2D. Participants with incident T2D had greater LV mass index (86.7 ± 16.4 vs. 91.2 ± 17.0 g/m 2 ), worse diastolic function, reflected by lower Em velocity (7.67 ± 1.80 vs. 7.47 ± 1.70) and higher E/Em ratio (9.19 ± 2.55 vs. 10.23 ± 3.00), and higher prevalence of LV diastolic dysfunction (34.6 vs. 54.2%), compared with those who did not develop T2D (all P < 0.001). In a multivariate logistic regression model, lower Em velocity (odd ratio [OR], 0.867; 95% confidence interval [CI] 0.786-0.957) and the presence of LV diastolic dysfunction (OR, 1.617; 95% CI 1.191-2.196) were associated with the development of T2D, after adjusting for potential confounding factors. In a community-based cohort, the presence of subclinical LV diastolic dysfunction was a predictor of the progression to T2D. These data suggest that the echocardiographic assessment of LV diastolic function may be helpful in identifying non-diabetic subjects at risk of incident T2D.

Galectin-3 Reflects the Echocardiographic Grades of Left Ventricular Diastolic Dysfunction.

PubMed

Ansari, Uzair; Behnes, Michael; Hoffmann, Julia; Natale, Michele; Fastner, Christian; El-Battrawy, Ibrahim; Rusnak, Jonas; Kim, Seung Hyun; Lang, Siegfried; Hoffmann, Ursula; Bertsch, Thomas; Borggrefe, Martin; Akin, Ibrahim

2018-07-01

The level of Galectin-3 (Gal-3) protein purportedly reflects an ongoing cardiac fibrotic process and has been associated with ventricular remodeling, which is instrumental in the development of heart failure with preserved ejection fraction (HFpEF) syndrome. The aim of this study was to investigate the potential use of Gal-3 in improved characterization of the grades of diastolic dysfunction as defined by echocardiography. Seventy HFpEF patients undergoing routine echocardiography were prospectively enrolled in the present monocentric study. Blood samples for measurements of Gal-3 and amino-terminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 hours pre- or post-echocardiographic examination. The classification of patients into subgroups based on diastolic dysfunction grade permitted detailed statistical analyses of the derived data. The Gal-3 serum levels of all patients corresponded to echocardiographic indices, suggesting HFpEF (E/A, P=0.03 and E/E', P=0.02). Gal-3 was also associated with progressive diastolic dysfunction, and increased levels corresponded to the course of disease (P=0.012). Detailed analyses of ROC curves suggested that Gal-3 levels could discriminate patients with grade III diastolic dysfunction (area under the curve [AUC]=0.770, P=0.005). Gal-3 demonstrates remarkable effectiveness in the diagnosis of patients suffering from severe grade diastolic dysfunction. Increasing levels of Gal-3 possibly reflect the progressive course of HFpEF, as classified by the echocardiographic grades of diastolic dysfunction. © The Korean Society for Laboratory Medicine.

Assessment of diastolic function by tissue Doppler echocardiography: comparison with standard transmitral and pulmonary venous flow

NASA Technical Reports Server (NTRS)

Farias, C. A.; Rodriguez, L.; Garcia, M. J.; Sun, J. P.; Klein, A. L.; Thomas, J. D.

1999-01-01

The objective of this study was to determine the utility of Doppler tissue echocardiography in the evaluation of diastolic filling and in discriminating between normal subjects and those with various stages of diastolic dysfunction. We measured myocardial velocities in 51 patients with various stages of diastolic dysfunction and in 27 normal volunteers. The discriminating power of each of the standard Doppler indexes of left ventricular filling, pulmonary venous flow, and myocardial velocities was determined with the use of Spearman rank correlation and analysis of variance F statistics. Early diastolic myocardial velocity (E(m)) was higher in normal subjects (16.0 +/- 3.8 cm/s) than in patients with either delayed relaxation (n = 15, 7.5 +/- 2.2 cm/s), pseudonormal filling (n = 26, 7.6 +/- 2.3 cm/s), or restrictive filling (n = 10, 7.4 +/- 2.4 cm/s, P <.0001). E(m ) was the best single discriminator between control subjects and patients with diastolic dysfunction (P =.7, F = 64.5). Myocardial velocities assessed by Doppler tissue echocardiography are useful in differentiating patients with normal from those with abnormal diastolic function. Myocardial velocity remains reduced even in those stages of diastolic dysfunction characterized by increased preload compensation.

Percutaneous closure of patent ductus arteriosus in children: Immediate and short-term changes in left ventricular systolic and diastolic function.

PubMed

Gupta, Saurabh Kumar; Krishnamoorthy, Km; Tharakan, Jaganmohan A; Sivasankaran, S; Sanjay, G; Bijulal, S; Anees, T

2011-07-01

To evaluate the effect of percutaneous closure of patent ductus arteriosus (PDA) on left ventricular (LV) systolic and diastolic function in children. Limited studies are available on alteration in LV hemodynamics, especially diastolic function, after PDA closure. Thirty-two consecutive children with isolated PDA treated by trans-catheter closure were studied. The LV systolic and diastolic function were assessed by two-dimensional (2D) echocardiography and tissue Doppler imaging 1 day before the PDA closure, on day 1, and on follow-up. At baseline, none of the patients had LV systolic dysfunction. On day 1 post-PDA closure, 8 (25%) children developed LV systolic dysfunction. The baseline LV ejection fraction (LVEF), LV end-systolic dimension (LVESD), and PDA diastolic gradient predicted the post-closure LVEF. Patients who developed post-closure LV systolic dysfunction had poorer LV diastolic function than those who did not. LV diastolic properties improved after PDA closure; however, the improvement in LV diastolic properties lagged behind the improvement in the LV systolic function. All children were asymptomatic and had normal LVEF on follow up of >3 months. Percutaneous closure of PDA is associated with the reversible LV systolic dysfunction. Improvement in the LV diastolic function lags behind that in the LV systolic function.

Exercise during cardiac catheterization distinguishes between pulmonary and left ventricular causes of dyspnea in systemic sclerosis patients.

PubMed

Hager, W David; Collins, Irina; Tate, Janet P; Azrin, Michael; Foley, Raymond; Lakshminarayanan, Santha; Rothfield, Naomi F

2013-07-01

The cause for shortness of breath among systemic sclerosis (SSc) patients is often lacking. We sought to characterize the hemodynamics of these patients by using simple isotonic arm exercise during cardiac catheterization. Catheterization was performed in 173 SSc patients when resting echocardiographic pulmonary systolic pressures were <40 but >40 mmHg post stress. Patients with resting mean pulmonary arterial pressures (mPAP) ≤ 25 and pulmonary arterial wedge pressures (PAWP) ≤ 15 mmHg exercised with 1-pound hand weights. Normal exercise was defined as a change in mPAP divided by the change in cardiac output (CO) (ΔmPAP/ΔCO) ratio ≤ 2 for patients <50 years (≤3 for >50). An abnormal ΔmPAP/ΔCO ratio, an exercise transpulmonary gradient (TPG) ≥ 15, a PAWP < 20, a ΔTPG > ΔPAWP and a pulmonary vascular resistance (PVR) which increased defined exercise-induced pulmonary arterial hypertension (EIPAH). An abnormal ΔmPAP/ΔCO ratio, an exercise TPG < 15, a PAWP ≥ 20, a ΔTPG < ΔPAWP and a drop in PVR defined left ventricular diastolic dysfunction (DD). Twelve patients without SSc served as controls. Pulmonary pressures increased with exercise in 53 patients. Six had EIPAH and 47 had DD. With exercise, mPAP and PAWP were 20 ± 4 and 13 ± 2 in controls, 36 ± 3 and 12 ± 4 in EIPAH and 34 ± 6 and 26 ± 4 in DD. Control ΔmPAP/ΔCO was 0.8 ± 0.7, 7.5 ± 3.9 in EIPAH and 9.1 ± 7.2 in DD. Rest and exercise TPG was normal for control and DD patients but increased (12 ± 4 to 23 ± 4) in EIPAH (P < 0.0001). PVR decreased in DD but increased in EIPAH with exercise. Exercise during catheterization elucidates the pathophysiology of dyspnea and distinguishes EIPAH from the more common DD in SSc patients. © 2012 John Wiley & Sons Ltd.

Increased night duty loading of physicians caused elevated blood pressure and sympathetic tones in a dose-dependent manner.

PubMed

Lee, Hsiu-Hao; Lo, Shih-Hsiang; Chen, Bing-Yu; Lin, Yen-Hung; Chu, Dachen; Cheng, Tsun-Jen; Chen, Pau-Chung; Guo, Yue-Liang

2016-04-01

Night duty has been recognized as a significantly harmful stressor for physicians. However, the relationship between various levels of duty loading and stress response is unknown. This study examined whether duty load increases cardiovascular stress indicators in a dose-dependent manner. An unallocated prospective observational study was conducted among physicians performing various levels of duties in a secondary referral medical center between 2011 and 2012. Heart rate variability (HRV), blood pressure (BP), and other stress markers of 12 attending physicians were compared during different duty loads: non-duty day (NDD), duty day with one duty area and three wards (1DD), and duty day with two duty areas and six wards (2DD). During the regular sleep time (i.e., 11 p.m. to 5 a.m.), the relative sympathetic modulations measured using the HRV were 59.0 ± 9.3, 61.6 ± 10.4, and 64.4 ± 8.9 for NDD, 1DD, and 2DD, respectively (p = 0.0012); those for relative parasympathetic modulations were 37.4 ± 9.4, 34.8 ± 9.8, and 32.0 ± 8.8 for NDD, 1DD, and 2DD, respectively (p = 0.0015). The percentages of abnormal systolic BPs were 9.7 ± 13.2 %, 25.3 ± 21.8 %, and 31.5 ± 21.0 % for NDD, 1DD, and 2DD, respectively (p = 0.003), and the percentages of abnormal diastolic BP were 6.7 ± 11.0 %, 18.3 ± 11.1 %, and 27.1 ± 30.9 % for NDD, 1DD, and 2DD, respectively (p = 0.002). Total sleep time was negatively associated with sympathetic/parasympathetic balance and the percentage of abnormal diastolic BP. Admitting new patients was positively associated with the percentages of abnormal systolic BP. This observational analysis suggests that the dose-dependent stress responses of the cardiovascular system in physicians were caused by the duty load.

Intravenous Milrinone Infusion Improves Congestive Heart Failure Caused by Diastolic Dysfunction

PubMed Central

Albrecht, Carlos A.; Giesler, Gregory M.; Kar, Biswajit; Hariharan, Ramesh; Delgado, Reynolds M.

2005-01-01

Although there have been significant advances in the medical treatment of heart failure patients with impaired systolic function, very little is known about the diagnosis and treatment of diastolic dysfunction. We report the cases of 3 patients in New York Heart Association functional class IV who had echocardiographically documented diastolic dysfunction as the main cause of heart failure. All 3 patients received medical therapy with long-term milrinone infusion. PMID:16107121

Myocardial tissue deformation is reduced in subjects with coronary microvascular dysfunction but not rescued by treatment with Ranolazine

PubMed Central

Nelson, Michael D.; Sharif, Behzad; Shaw, Jaime L.; Cook-Wiens, Galen; Wei, Janet; Shufelt, Chrisandra; Mehta, Puja K.; Thomson, Louise EJ; Berman, Daniel S.; Thompson, Richard B.; Handberg, Eileen M.; Pepine, Carl J.; Li, Debiao; Bairey Merz, C. Noel

2016-01-01

Background Patients with coronary microvascular dysfunction (CMD) often have diastolic dysfunction, representing an important therapeutic target. Ranolazine—a late-sodium current inhibitor—improves diastolic function in animal models, and subjects with obstructive CAD. We hypothesized that ranolazine would beneficially alter diastolic function in CMD. Methods To test this hypothesis, we performed retrospective tissue tracking analysis to evaluate systolic/diastolic strain, using cardiac magnetic resonance imaging cine images: a) acquired in a recently completed, randomized, double-blind, placebo-controlled, crossover trial of short-term ranolazine in subjects with CMD, and b) from 43 healthy reference controls. Results Diastolic strain rate was impaired in CMD vs. controls (circumferential diastolic strain rate: 99.9 ± 2.5%/s vs. 120.1 ± 4.0%/s, p=0.0003; radial diastolic strain rate: −199.5 ± 5.5%/s vs. −243.1 ± 9.6%/s, p=0.0008, case vs. control). Moreover, peak systolic circumferential (CS) and radial (RS) strain were also impaired in cases vs. controls (CS: −18.8 ± 0.3% vs. −20.7 ± 0.3%; RS: 35.8 ± 0.7% vs. 41.4 ± 0.9%; respectively; both p < 0.0001), despite similar and preserved ejection fraction. In contrast to our hypothesis however, we observed no significant changes in left ventricular diastolic function in CMD cases after two weeks of ranolazine vs. placebo. Conclusions The case-control comparison both confirms and extends our prior observations of diastolic dysfunction in CMD. That CMD cases were also found to have sub-clinical systolic dysfunction is a novel finding, highlighting the utility of this retrospective approach. In contrast to previous studies in obstructive CAD, ranolazine did not improve diastolic function in CMD. PMID:28004395

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles

PubMed Central

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2017-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8–9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits. PMID:28101068

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles.

PubMed

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2016-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8-9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits.

Evaluation of Left Ventricular Diastolic Dysfunction with Early Systolic Dysfunction Using Two-Dimensional Speckle Tracking Echocardiography in Canine Heart Failure Model.

PubMed

Wu, Wei-Chun; Ma, Hong; Xie, Rong-Ai; Gao, Li-Jian; Tang, Yue; Wang, Hao

2016-04-01

This study evaluated the role of two-dimensional speckle tracking echocardiography (2DSTE) for predicting left ventricular (LV) diastolic dysfunction in pacing-induced canine heart failure. Pacing systems were implanted in 8 adult mongrel dogs, and continuous rapid right ventricular pacing (RVP, 240 beats/min) was maintained for 2 weeks. The obtained measurements from 2DSTE included global strain rate during early diastole (SRe) and during late diastole (SRa) in the longitudinal (L-SRe, L-SRa), circumferential (C-SRe, C-SRa), and radial directions (R-SRe, R-SRa). Changes in heart morphology were observed by light microscopy and transmission electron microscopy at 2 weeks. The onset of LV diastolic dysfunction with early systolic dysfunction occurred 3 days after RVP initiation. Most of the strain rate imaging indices were altered at 1 or 3 days after RVP onset and continued to worsen until heart failure developed. Light and transmission electron microscopy showed myocardial vacuolar degeneration and mitochondrial swelling in the left ventricular at 2 weeks after RVP onset. Pearson's correlation analysis revealed that parameters of conventional echocardiography and 2DSTE showed moderate correlation with LV pressure parameters, including E/Esep' (r = 0.58, P < 0.01), L-SRe (r = -0.58, P < 0.01), E/L-SRe (r = 0.65, P < 0.01), and R-SRe (r = 0.53, P < 0.01). ROC curves analysis showed that these indices of conventional echocardiography and strain rate imaging could effectively predict LV diastolic dysfunction (area under the curve: E/Esep' 0.78; L-SRe 0.84; E/L-SRe 0.80; R-SRe 0.80). 2DSTE was a sensitive and accurate technique that could be used for predicting LV diastolic dysfunction in canine heart failure model. © 2015, Wiley Periodicals, Inc.

Subject-specific left ventricular dysfunction modeling using composite material mechanics approach

NASA Astrophysics Data System (ADS)

Haddad, Seyed Mohammad Hassan; Karami, Elham; Samani, Abbas

2017-03-01

Diverse cardiac conditions such as myocardial infarction and hypertension can lead to diastolic dysfunction as a prevalent cardiac condition. Diastolic dysfunctions can be diagnosed through different adverse mechanisms such as abnormal left ventricle (LV) relaxation, filling, and diastolic stiffness. This paper is geared towards evaluating diastolic stiffness and measuring the LV blood pressure non-invasively. Diastolic stiffness is an important parameter which can be exploited for more accurate diagnosis of diastolic dysfunction. For this purpose, a finite element (FE) LV mechanical model, which works based on a novel composite material model of the cardiac tissue, was utilized. Here, this model was tested for inversion-based applications where it was applied for estimating the cardiac tissue passive stiffness mechanical properties as well as diastolic LV blood pressure. To this end, the model was applied to simulate diastolic inflation of the human LV. The start-diastolic LV geometry was obtained from MR image data segmentation of a healthy human volunteer. The obtained LV geometry was discretized into a FE mesh before FE simulation was conducted. The LV tissue stiffness and diastolic LV blood pressure were adjusted through optimization to achieve the best match between the calculated LV geometry and the one obtained from imaging data. The performance of the LV mechanical simulations using the optimal values of tissue stiffness and blood pressure was validated by comparing the geometrical parameters of the dilated LV model as well as the stress and strain distributions through the LV model with available measurements reported on the LV dilation.

Effects of ranolazine in a model of doxorubicin-induced left ventricle diastolic dysfunction.

PubMed

Cappetta, Donato; Esposito, Grazia; Coppini, Raffaele; Piegari, Elena; Russo, Rosa; Ciuffreda, Loreta Pia; Rivellino, Alessia; Santini, Lorenzo; Rafaniello, Concetta; Scavone, Cristina; Rossi, Francesco; Berrino, Liberato; Urbanek, Konrad; De Angelis, Antonella

2017-11-01

Doxorubicin is a highly effective anticancer drug, but its clinical application is hampered by cardiotoxicity. Asymptomatic diastolic dysfunction can be the earliest manifestation of doxorubicin cardiotoxicity. Therefore, a search for therapeutic intervention that can interfere with early manifestations and possibly prevent later development of cardiotoxicity is warranted. Increased doxorubicin-dependent ROS may explain, in part, Ca 2+ and Na + overload that contributes to diastolic dysfunction and development of heart failure. Therefore, we tested whether the administration of ranolazine, a selective blocker of late Na + current, immediately after completing doxorubicin therapy, could affect diastolic dysfunction and interfere with the progression of functional decline. Fischer 344 rats received a cumulative dose of doxorubicin of 15 mg·kg -1 over a period of 2 weeks. After the assessment of diastolic dysfunction, the animals were treated with ranolazine (80 mg·kg -1 , daily) for the following 4 weeks. While diastolic and systolic function progressively deteriorated in doxorubicin-treated animals, treatment with ranolazine relieved diastolic dysfunction and prevented worsening of systolic function, decreasing mortality. Ranolazine lowered myocardial NADPH oxidase 2 expression and oxidative/nitrative stress. Expression of the Na + /Ca 2+ exchanger 1 and Na v 1.5 channels was reduced and of the sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase 2 protein was increased. In addition, ranolazine lowered doxorubicin-induced hyper-phosphorylation and oxidation of Ca 2+ /calmodulin-dependent protein kinase II, and decreased myocardial fibrosis. Ranolazine, by the increased Na + influx, induced by doxorubicin, altered cardiac Ca 2+ and Na + handling and attenuated diastolic dysfunction induced by doxorubicin, thus preventing the progression of cardiomyopathy. This article is part of a themed section on New Insights into Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.21/issuetoc. © 2017 The British Pharmacological Society.

Diastolic dysfunction in hypertension.

PubMed

Nazário Leão, R; Marques da Silva, P

Hypertension and coronary heart disease, often coexisting, are the most common risk factors for heart failure. The progression of hypertensive heart disease involves myocardial fibrosis and alterations in the left ventricular geometry that precede the functional change, initially asymptomatic. The left ventricular diastolic dysfunction is part of this continuum being defined by the presence of left ventricular diastolic dysfunction without signs or symptoms of heart failure or poor left ventricular systolic function. It is highly prevalent in hypertensive patients and is associated with increased cardiovascular morbidity and mortality. Despite its growing importance in clinical practice it remains poorly understood. This review aims to present the epidemiological fundamentals and the latest developments in the pathophysiology, diagnosis and treatment of left ventricular diastolic dysfunction. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

New diagnostic and therapeutic possibilities for diastolic heart failure.

PubMed

Jeong, Euy-Myoung; Dudley, Samuel C

2014-02-03

Despite the fact that up to half of all heart failure occurs in patients without evidence of systolic cardiac dysfunction, there are no universally accepted diagnostic markers and no approved therapies for heart failure with preserved ejection fraction (HFpEF). HFpEF, otherwise known as diastolic heart failure, has nearly the same grim prognosis as systolic heart failure, and diastolic heart failure is increasing in incidence and prevalence. Major trials have shown that many of the treatments that are salutary in systolic heart failure have no beneficial effects in diastolic heart failure, suggesting different underlying mechanisms for these two disorders. Even criteria for diagnosis of HFpEF are still debated, and there is still no gold standard marker to detect diastolic dysfunction. Here, we will review some promising new insights into the pathogenesis of diastolic dysfunction that may lead to new diagnostic and therapeutic tools.

Effects of auto-servo ventilation on patients with sleep-disordered breathing, stable systolic heart failure and concomitant diastolic dysfunction: subanalysis of a randomized controlled trial.

PubMed

Birner, Christoph; Series, Frederic; Lewis, Keir; Benjamin, Amit; Wunderlich, Silke; Escourrou, Pierre; Zeman, Florian; Luigart, Ruth; Pfeifer, Michael; Arzt, Michael

2014-01-01

Systolic heart failure (HF) is frequently accompanied by diastolic dysfunction and sleep-disordered breathing (SDB). The objective of this subset analysis was to determine effect sizes of auto-servo ventilation (ASV and biphasic positive airway pressure ASV) on echocardiographic measures of diastolic function in patients with systolic HF and SDB. Thirty-two patients with stable systolic HF, concomitant diastolic dysfunction [age 66 ± 9 years old, left ventricular (LV) ejection fraction: 30 ± 7% and New York Heart Association class II: 72%] and SDB (apnea-hypopnea index, AHI: 48 ± 19/h; 53% had predominantly obstructive sleep apnea) receiving either ASV (n = 19) or optimal medical treatment (control, n = 13) were analyzed in a randomized controlled clinical trial. Polysomnographic and echocardiographic measurements were obtained at baseline and after 12 weeks. AHI significantly improved in the ASV group compared to the control group (-39 ± 18 vs. -0.2 ± 13.2/h, p < 0.001). At baseline, 24 (75%) patients had impaired LV relaxation, and 8 (25%) had a pseudo-normalized filling pattern. At the 12-week control visit, diastolic function assessed by the isovolumetric relaxation time (-10.3 ± 26.1 vs. 9.3 ± 49.1, p = 0.48) and deceleration time (-43.9 ± 88.8 vs. 12.4 ± 68.8, p = 0.40) tended to improve after ASV treatment, but did not reach statistical significance. Likewise, the proportion of patients whose diastolic dysfunction improved was nonsignificantly higher in the ASV than in the control group, respectively (37 vs. 15%, p = 0.25). ASV treatment efficiently abolishes SDB in patients with stable systolic HF and concomitant diastolic dysfunction, and was associated with a statistically nonsignificant improvement in measures of diastolic dysfunction. Thus, these data provide estimates of effect size and justify the evaluation of the effects of ASV on diastolic function in larger randomized controlled trials. Copyright © 2013 S. Karger AG, Basel.

Protein Changes Contributing to Right Ventricular Cardiomyocyte Diastolic Dysfunction in Pulmonary Arterial Hypertension

PubMed Central

Rain, Silvia; Bos, Denielli da Silva Goncalves; Handoko, M. Louis; Westerhof, Nico; Stienen, Ger; Ottenheijm, Coen; Goebel, Max; Dorfmüller, Peter; Guignabert, Christophe; Humbert, Marc; Bogaard, Harm‐Jan; dos Remedios, Cris; Saripalli, Chandra; Hidalgo, Carlos G.; Granzier, Henk L.; Vonk‐Noordegraaf, Anton; van der Velden, Jolanda; de Man, Frances S.

2014-01-01

Background Right ventricular (RV) diastolic function is impaired in patients with pulmonary arterial hypertension (PAH). Our previous study showed that elevated cardiomyocyte stiffness and myofilament Ca2+ sensitivity underlie diastolic dysfunction in PAH. This study investigates protein modifications contributing to cellular diastolic dysfunction in PAH. Methods and Results RV samples from PAH patients undergoing heart‐lung transplantation were compared to non‐failing donors (Don). Titin stiffness contribution to RV diastolic dysfunction was determined by Western‐blot analyses using antibodies to protein‐kinase‐A (PKA), Cα (PKCα) and Ca2+/calmoduling‐dependent‐kinase (CamKIIδ) titin and phospholamban (PLN) phosphorylation sites: N2B (Ser469), PEVK (Ser170 and Ser26), and PLN (Thr17), respectively. PKA and PKCα sites were significantly less phosphorylated in PAH compared with donors (P<0.0001). To test the functional relevance of PKA‐, PKCα‐, and CamKIIδ‐mediated titin phosphorylation, we measured the stiffness of single RV cardiomyocytes before and after kinase incubation. PKA significantly decreased PAH RV cardiomyocyte diastolic stiffness, PKCα further increased stiffness while CamKIIδ had no major effect. CamKIIδ activation was determined indirectly by measuring PLN Thr17phosphorylation level. No significant changes were found between the groups. Myofilament Ca2+ sensitivity is mediated by sarcomeric troponin I (cTnI) phosphorylation. We observed increased unphosphorylated cTnI in PAH compared with donors (P<0.05) and reduced PKA‐mediated cTnI phosphorylation (Ser22/23) (P<0.001). Finally, alterations in Ca2+‐handling proteins contribute to RV diastolic dysfunction due to insufficient diastolic Ca2+ clearance. PAH SERCA2a levels and PLN phosphorylation were significantly reduced compared with donors (P<0.05). Conclusions Increased titin stiffness, reduced cTnI phosphorylation, and altered levels of phosphorylation of Ca2+ handling proteins contribute to RV diastolic dysfunction in PAH. PMID:24895160

Synergistic role of ADP and Ca2+ in diastolic myocardial stiffness

PubMed Central

Sequeira, Vasco; Najafi, Aref; McConnell, Mark; Fowler, Ewan D; Bollen, Ilse A E; Wüst, Rob C I; dos Remedios, Cris; Helmes, Michiel; White, Ed; Stienen, Ger J M; Tardiff, Jil; Kuster, Diederik W D; van der Velden, Jolanda

2015-01-01

Abstract Heart failure (HF) with diastolic dysfunction has been attributed to increased myocardial stiffness that limits proper filling of the ventricle. Altered cross-bridge interaction may significantly contribute to high diastolic stiffness, but this has not been shown thus far. Cross-bridge interactions are dependent on cytosolic [Ca2+] and the regeneration of ATP from ADP. Depletion of myocardial energy reserve is a hallmark of HF leading to ADP accumulation and disturbed Ca2+ handling. Here, we investigated if ADP elevation in concert with increased diastolic [Ca2+] promotes diastolic cross-bridge formation and force generation and thereby increases diastolic stiffness. ADP dose-dependently increased force production in the absence of Ca2+ in membrane-permeabilized cardiomyocytes from human hearts. Moreover, physiological levels of ADP increased actomyosin force generation in the presence of Ca2+ both in human and rat membrane-permeabilized cardiomyocytes. Diastolic stress measured at physiological lattice spacing and 37°C in the presence of pathological levels of ADP and diastolic [Ca2+] revealed a 76 ± 1% contribution of cross-bridge interaction to total diastolic stress in rat membrane-permeabilized cardiomyocytes. Inhibition of creatine kinase (CK), which increases cytosolic ADP, in enzyme-isolated intact rat cardiomyocytes impaired diastolic re-lengthening associated with diastolic Ca2+ overload. In isolated Langendorff-perfused rat hearts, CK inhibition increased ventricular stiffness only in the presence of diastolic [Ca2+]. We propose that elevations of intracellular ADP in specific types of cardiac disease, including those where myocardial energy reserve is limited, contribute to diastolic dysfunction by recruiting cross-bridges, even at low Ca2+, and thereby increase myocardial stiffness. Key points Diastolic dysfunction in heart failure patients is evident from stiffening of the passive properties of the ventricular wall. Increased actomyosin interactions may significantly limit diastolic capacity, however, direct evidence is absent. From experiments at the cellular and whole organ level, in humans and rats, we show that actomyosin-related force development contributes significantly to high diastolic stiffness in environments where high ADP and increased diastolic [Ca2+] are present, such as the failing myocardium. Our basal study provides a mechanical mechanism which may partly underlie diastolic dysfunction. PMID:26096258

Cats with diabetes mellitus have diastolic dysfunction in the absence of structural heart disease.

PubMed

Pereira, N J; Novo Matos, J; Baron Toaldo, M; Bartoszuk, U; Summerfield, N; Riederer, A; Reusch, C; Glaus, T M

2017-07-01

Diabetes mellitus (DM) can result in cardiovascular dysfunction and heart failure characterized by diastolic dysfunction with or without the presence of systolic dysfunction in people and laboratory animals. The objective of this prospective study was to determine if cats with newly diagnosed DM had myocardial dysfunction and, if present, whether it would progress if appropriate antidiabetic therapy was commenced. Thirty-two diabetic cats were enrolled and received baseline echocardiographic examination; of these, 15 cats were re-examined after 6 months. Ten healthy age- and weight-matched cats served as controls. Diabetic cats at diagnosis showed decreased diastolic, but not systolic function, when compared to healthy controls, with lower mitral inflow E wave (E) and E/E' than controls. After 6 months, E and E/IVRT' decreased further in diabetic cats compared to the baseline evaluation. After excluding cats whose DM was in remission at 6 months, insulin-dependent diabetic cats had lower E, E/A and E' than controls. When classifying diastolic function according to E/A and E'/A', there was shift towards impaired relaxation patterns at 6 months. All insulin-dependent diabetic cats at 6 months had abnormal diastolic function. These results indicate that DM has similar effects on diastolic function in feline and human diabetics. The dysfunction seemed to progress rather than to normalize after 6 months, despite antidiabetic therapy. In cats with pre-existing heart disease, the development of DM could represent an important additional health risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association Between Sedentary Lifestyle and Diastolic Dysfunction Among Outpatients With Normal Left Ventricular Systolic Function Presenting to a Tertiary Referral Center in the Middle East.

PubMed

Matta, Stephanie; Chammas, Elie; Alraies, Chadi; Abchee, Antoine; AlJaroudi, Wael

2016-05-01

Sedentary lifestyle has become prevalent in our community. Recent data showed controversy on the effect of regular exercise on left ventricular compliance and myocardial relaxation. We sought to assess whether physical inactivity is an independent predictor of diastolic dysfunction in or community, after adjustment for several covariates. Consecutive outpatients presenting to the echocardiography laboratory between July 2013 and June 2014 were prospectively enrolled. Clinical variables were collected prospectively at enrollment. Patients were considered physically active if they exercised regularly ≥3× a week, ≥30 minutes each time. The primary endpoint was presence of diastolic dysfunction. The final cohort included 1356 patients (mean age [SD] 52.9 [17.4] years, 51.3% female). Compared with physically active patients, the 1009 (74.4%) physically inactive patients were older, more often female, and had more comorbidities and worse diastolic function (51.3% vs 38.3%; P < 0.001). On univariate analysis, physical inactivity was associated with 70% increased odds of having diastolic dysfunction (odds ratio: 1.70, 95% confidence interval: 1.32-2.18, P < 0.001). There was significant interaction between physical activity and left ventricular mass index (LVMI; P = 0.026). On multivariate analysis, patients who were physically inactive and had LVMI ≥ median had significantly higher odds of having diastolic dysfunction (odds ratio: 2.82, 95% confidence interval: 1.58-5.05, P < 0.001). In a large, prospectively enrolled cohort from a single tertiary center in the Middle East, physically inactive patients with increased LVMI had 2- to 3-fold increased odds of having diastolic dysfunction after multivariate adjustment. © 2016 Wiley Periodicals, Inc.

Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity

PubMed Central

Lovelock, Joshua D.; Monasky, Michelle M.; Jeong, Euy-Myoung; Lardin, Harvey A.; Liu, Hong; Patel, Bindiya G.; Taglieri, Domenico M.; Gu, Lianzhi; Kumar, Praveen; Pokhrel, Narayan; Zeng, Dewan; Belardinelli, Luiz; Sorescu, Dan; Solaro, R. John; Dudley, Samuel C.

2012-01-01

Rationale Previously, we demonstrated that a deoxycorticosterone acetate (DOCA)-salt hypertensive mouse model produces cardiac oxidative stress and diastolic dysfunction with preserved systolic function. Oxidative stress has been shown to increase late inward sodium current (INa), reducing the net cytosolic Ca2+ efflux. Objective Oxidative stress in the DOCA-salt model may increase late INa resulting in diastolic dysfunction amenable to treatment with ranolazine. Methods and Results Echocardiography detected evidence of diastolic dysfunction in hypertensive mice that improved after treatment with ranolazine (E/E′, sham 31.9 ± 2.8, sham+ranolazine 30.2 ± 1.9, DOCA-salt 41.8 ± 2.6, and DOCA-salt+ranolazine 31.9 ± 2.6, p = 0.018). The end diastolic pressure volume relationship slope was elevated in DOCA-salt mice, improving to sham levels with treatment (sham 0.16 ± 0.01 vs. sham+ranolazine 0.18 ± 0.01 vs. DOCA-salt 0.23 ± 0.2 vs. DOCA-salt+ranolazine 0.17 ± 0.01 mm Hg/L, p < 0.005). DOCA-salt myocytes demonstrated impaired relaxation, τ, improving with ranolazine (DOCA-salt 0.18 ± 0.02, DOCA-salt + ranolazine 0.13 ± 0.01, Sham 0.11 ± 0.01, Sham + ranolazine 0.09 ± 0.02 s, p = 0.0004). Neither late INa nor the Ca2+ transients were different from sham myocytes. Detergent extracted fiber bundles from DOCA-salt hearts demonstrated increased myofilament response to Ca2+ with glutathionylation of myosin binding protein C. Treatment with ranolazine ameliorated the Ca2+ response and cross-bridge kinetics. Conclusions Therefore, diastolic dysfunction could be reversed by ranolazine, likely resulting from a direct effect on myofilaments, indicating that cardiac oxidative stress may mediate diastolic dysfunction through altering the contractile apparatus. PMID:22343711

Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity.

PubMed

Lovelock, Joshua D; Monasky, Michelle M; Jeong, Euy-Myoung; Lardin, Harvey A; Liu, Hong; Patel, Bindiya G; Taglieri, Domenico M; Gu, Lianzhi; Kumar, Praveen; Pokhrel, Narayan; Zeng, Dewan; Belardinelli, Luiz; Sorescu, Dan; Solaro, R John; Dudley, Samuel C

2012-03-16

Previously, we demonstrated that a deoxycorticosterone acetate (DOCA)-salt hypertensive mouse model produces cardiac oxidative stress and diastolic dysfunction with preserved systolic function. Oxidative stress has been shown to increase late inward sodium current (I(Na)), reducing the net cytosolic Ca(2+) efflux. Oxidative stress in the DOCA-salt model may increase late I(Na), resulting in diastolic dysfunction amenable to treatment with ranolazine. Echocardiography detected evidence of diastolic dysfunction in hypertensive mice that improved after treatment with ranolazine (E/E':sham, 31.9 ± 2.8, sham+ranolazine, 30.2 ± 1.9, DOCA-salt, 41.8 ± 2.6, and DOCA-salt+ranolazine, 31.9 ± 2.6; P=0.018). The end-diastolic pressure-volume relationship slope was elevated in DOCA-salt mice, improving to sham levels with treatment (sham, 0.16 ± 0.01 versus sham+ranolazine, 0.18 ± 0.01 versus DOCA-salt, 0.23 ± 0.2 versus DOCA-salt+ranolazine, 0.17 ± 0.0 1 mm Hg/L; P<0.005). DOCA-salt myocytes demonstrated impaired relaxation, τ, improving with ranolazine (DOCA-salt, 0.18 ± 0.02, DOCA-salt+ranolazine, 0.13 ± 0.01, sham, 0.11 ± 0.01, sham+ranolazine, 0.09 ± 0.02 seconds; P=0.0004). Neither late I(Na) nor the Ca(2+) transients were different from sham myocytes. Detergent extracted fiber bundles from DOCA-salt hearts demonstrated increased myofilament response to Ca(2+) with glutathionylation of myosin binding protein C. Treatment with ranolazine ameliorated the Ca(2+) response and cross-bridge kinetics. Diastolic dysfunction could be reversed by ranolazine, probably resulting from a direct effect on myofilaments, indicating that cardiac oxidative stress may mediate diastolic dysfunction through altering the contractile apparatus.

Automated calculation of the Tei index from signal averaged left ventricular acoustic quantification wave forms.

PubMed

Spencer, Kirk T; Weinert, Lynn; Avi, Victor Mor; Decara, Jeanne; Lang, Roberto M

2002-12-01

The Tei index is a combined measurement of systolic and diastolic left ventricular (LV) performance and may be more useful for the diagnosis of global cardiac dysfunction than either systolic or diastolic measures alone. We sought to determine whether the Tei index could be accurately calculated from LV area waveforms generated with automated border detection. Twenty-four patients were studied in 3 groups: systolic dysfunction, diastolic dysfunction, and normal. The Tei index was calculated both from Doppler tracings and from analysis of LV area waveforms. Excellent agreement was found between Doppler-derived timing intervals and the Tei index with those obtained from averaged LV area waveforms. A significant difference was seen in the Tei index, computed with both Doppler and automated border detection techniques, between the normal group and those with LV systolic dysfunction and subjects with isolated diastolic dysfunction. This study validates the use of LV area waveforms for the automated calculation of the Tei index.

Skin-autofluorescence, a measure of tissue advanced glycation end-products (AGEs), is related to diastolic function in dialysis patients.

PubMed

Hartog, Jasper W L; Hummel, Yoran M; Voors, Adriaan A; Schalkwijk, Casper G; Miyata, Toshio; Huisman, Roel M; Smit, Andries J; Van Veldhuisen, Dirk J

2008-09-01

Diastolic dysfunction is a frequent cause of heart failure, particularly in dialysis patients. Advanced glycation end-products (AGEs) are increased in dialysis patients and are suggested to play a role in the development of diastolic dysfunction. The aim of our study was to assess whether AGE accumulation in dialysis patients is related to the presence of diastolic dysfunction. Data were analyzed from 43 dialysis patients, age 58 +/- 15 years, of whom 65% were male. Diastolic function was assessed using tissue velocity imaging (TVI) on echocardiography. Tissue AGE accumulation was measured using a validated skin-autofluorescence (skin-AF) reader. Plasma N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL) were measured by stable-isotope-dilution tandem mass spectrometry. Plasma pentosidine was measured by high-performance liquid chromatography. Skin-AF correlated with mean E' (r = -0.51, P < .001), E/A ratio (r = -0.39, P = .014), and E/E' (r = 0.38, P = .019). Plasma AGEs were not significantly associated with diastolic function. Multivariable linear regression analysis revealed that 54% of the variance of average E' was explained by age (P = .007), dialysis type (P = 0.016), and skin-AF (P = .013). Tissue AGEs measured as skin-AF, but not plasma AGE levels, were related to diastolic function in dialysis patients. Although this may support the concept that tissue AGEs explain part of the increased prevalence of diastolic dysfunction in these patients, the ambiguous relation between plasma and tissue AGEs needs further exploring.

Cardiac structure and function in relation to cardiovascular risk factors in Chinese

PubMed Central

2012-01-01

Background Cardiac structure and function are well-studied in Western countries. However, epidemiological data is still scarce in China. Methods Our study was conducted in the framework of cardiovascular health examinations for the current and retired employees of a factory and their family members. According to the American Society of Echocardiography recommendations, we performed echocardiography to evaluate cardiac structure and function, including left atrial volume, left ventricular hypertrophy and diastolic dysfunction. Results The 843 participants (43.0 years) included 288 (34.2%) women, and 191 (22.7%) hypertensive patients, of whom 82 (42.9%) took antihypertensive drugs. The prevalence of left atrial enlargement, left ventricular hypertrophy and concentric remodeling was 2.4%, 5.0% and 12.7%, respectively. The prevalence of mild and moderate-to-severe left ventricular diastolic dysfunction was 14.2% and 3.3%, respectively. The prevalence of these cardiac abnormalities significantly (P ≤ 0.002) increased with age, except for the moderate-to-severe left ventricular diastolic dysfunction. After adjustment for age, gender, body height and body weight, left atrial enlargement was associated with plasma glucose (P = 0.009), and left ventricular hypertrophy and diastolic dysfunction were significantly associated with systolic and diastolic blood pressure (P ≤ 0.03), respectively. Conclusions The prevalence of cardiac structural and functional abnormalities increased with age in this Chinese population. Current drinking and plasma glucose had an impact on left atrial enlargement, whereas systolic and diastolic blood pressures were major correlates for left ventricular hypertrophy and diastolic dysfunction, respectively. PMID:23035836

New insights into the mechanisms of diastolic dysfunction in patients with type 2 diabetes.

PubMed

Bayraktar, Al; Canpolat, Uğur; Demiri, Edis; Kunak, Ayşegül Ulgen; Ozer, Necla; Aksoyek, Serdar; Ovunc, Kenan; Ozkan, Adem; Yildiz, Okan Bülent; Atalar, Enver

2015-06-01

Little is known about the role of advanced glycation end products (AGEs) and their receptor (RAGE) in diabetic cardiovascular complications. Therefore, we aimed to evaluate the association of serum soluble RAGE (sRAGE) levels and left ventricular (LV) diastolic dysfunction in patients with type 2 diabetes. Our study consisted of 40 patients with type 2 diabetes and 40 age- and sex-matched healthy control group. Subjects with age ≥ 50 years old and any cardiovascular risk factors or conditions were excluded from the study. Serum sRAGE levels determined by enzyme-linked immunosorbent assay and LV diastolic dysfunction were evaluated according to current American Society of Echocardiography guidelines. Baseline characteristics were similar between groups except body mass index, waist-hip ratio, and fasting glucose levels. Serum sRAGE level was significantly lower in diabetic group compared with control group (676 ± 128 vs. 1044 ± 344, p < 0.05). Diastolic dysfunction was observed in 50% of diabetic patients (40% grade I and 10% grade II). Correlation analysis showed that serum sRAGE was negatively correlated with duration of diabetes, septal E'/A', lateral E'/A', and average E/E'. In multivariate regression analysis, serum sRAGE level was strongly associated with diastolic dysfunction in patients with type 2 diabetes. Our study showed that serum sRAGE level was significantly lower in type 2 diabetic patients aged < 50 years old. Also, sRAGE has negative correlation with the duration of diabetes and it was significantly associated with the presence of diastolic dysfunction in type 2 diabetes.

Association of angiotensin-converting enzyme DD genotype with 24-h blood pressure abnormalities in normoalbuminuric children and adolescents with Type 1 diabetes.

PubMed

Barkai, L; Soós, A; Vámosi, I

2005-08-01

To assess the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in children and adolescents with Type 1 diabetes and to evaluate the association between ACE genotype and blood pressure (BP). ACE genotypes were assessed in 124 normoalbuminuric, clinically normotensive Type 1 diabetic children and adolescents and 120 non-diabetic controls using polymerase chain reaction. Twenty-four-hour ambulatory BP monitoring was undertaken in all patients. ACE genotypes distributed in patients as follows: 34 (27%) DD, 57 (46%) ID, 33 (27%) II. The distribution was similar in the control group: DD in 28% (33), ID in 45% (54), and II in 27% (33). Patients with DD genotype had higher mean 24-h diastolic BP (73.8 +/- 6.2 vs. 70.2 +/- 5.0 and 69.7 +/- 6.3 mmHg; P = 0.005) and lower diurnal variation in BP (11.8 +/- 4.6 vs. 14.2 +/- 4.2 and 14.8 +/- 4.3%; P = 0.011) compared with ID and II groups. Four patients in the DD group proved to be non-dipper compared with one in the ID and none in the II group (P = 0.026). Twenty-four-hour diastolic blood pressure was independently predictive for AER as dependent variable in the DD genotype patient group (r(2) = 0.12, P = 0.03). Children and adolescents with Type 1 diabetes do not differ from the non-diabetic population regarding the I/D polymorphism of the ACE gene. ACE gene polymorphism is associated with BP abnormalities in normotensive and normoalbuminuric children and adolescents with Type 1 diabetes.

Influence of Angiotensin-Converting-Enzyme Gene Polymorphism on Echocardiographic Data of Patients with Ischemic Heart Failure

PubMed Central

Duque, Gustavo Salgado; da Silva, Dayse Aparecida; de Albuquerque, Felipe Neves; Schneider, Roberta Siuffo; Gimenez, Alinne; Pozzan, Roberto; Rocha, Ricardo Mourilhe; de Albuquerque, Denilson Campos

2016-01-01

Background Association between angiotensin-converting-enzyme (ACE) gene polymorphisms and different clinical and echocardiographic outcomes has been described in patients with heart failure (HF) and coronary artery disease. Studying the genetic profile of the local population with both diseases is necessary to assess the occurrence of that association. Objectives To assess the frequency of ACE gene polymorphisms in patients with ischemic HF in a Rio de Janeiro population, as well as its association with echocardiographic findings. Methods Genetic assessment of I/D ACE polymorphism in association with clinical, laboratory and echocardiographic analysis of 99 patients. Results The allele frequency was: 53 I alleles, and 145 D alleles. Genotype frequencies were: 49.5% DD; 47.48% DI; 3.02% II. Drug treatment was optimized: 98% on beta-blockers, and 84.8% on ACE inhibitors or angiotensin-receptor blocker. Echocardiographic findings: difference between left ventricular diastolic diameters (ΔLVDD) during follow-up: 2.98±8.94 (DD) vs. 0.68±8.12 (DI) vs. -11.0±7.00 (II), p=0.018; worsening during follow-up of the LV systolic diameter (LVSD): 65.3% DD vs. 19.0% DI vs. 0.0% II, p=0.01; of the LV diastolic diameter (LVDD): 65.3% DD vs. 46.8% DI vs. 0.0% II, p=0.03; and of the LV ejection fraction (LVEF): 67.3% DD vs. 40.4% DI vs. 33.3% II, p=0.024. Correlated with D allele: ΔLVEF, ΔLVSD, ΔLVDD. Conclusions More DD genotype patients had worsening of the LVEF, LVSD and LVDD, followed by DI genotype patients, while II genotype patients had the best outcome. The same pattern was observed for ΔLVDD. PMID:27812677

Increased passive stiffness promotes diastolic dysfunction despite improved Ca2+ handling during left ventricular concentric hypertrophy

PubMed Central

Røe, Åsmund T.; Aronsen, Jan Magnus; Skårdal, Kristine; Hamdani, Nazha; Linke, Wolfgang A.; Danielsen, Håvard E.; Sejersted, Ole M.; Sjaastad, Ivar; Louch, William E.

2017-01-01

Abstract Aims Concentric hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the concentrically hypertrophied heart following pressure-overload. Methods and results Rats were subjected to aortic banding (AB), and experiments were performed 6 weeks after surgery using sham-operated rats as controls. In vivo ejection fraction and fractional shortening were normal, confirming preservation of systolic function. Left ventricular concentric hypertrophy and diastolic dysfunction following AB were indicated by thickening of the ventricular wall, reduced peak early diastolic tissue velocity, and higher E/e’ values. Slowed relaxation was also observed in left ventricular muscle strips isolated from AB hearts, during both isometric and isotonic stimulation, and accompanied by increases in passive tension, viscosity, and extracellular collagen. An altered titin phosphorylation profile was observed with hypophosphorylation of the phosphosites S4080 and S3991 sites within the N2Bus, and S12884 within the PEVK region. Increased titin-based stiffness was confirmed by salt-extraction experiments. In contrast, isolated, unloaded cardiomyocytes exhibited accelerated relaxation in AB compared to sham, and less contracture at high pacing frequencies. Parallel enhancement of diastolic Ca2+ handling was observed, with augmented NCX and SERCA2 activity and lowered resting cytosolic [Ca2+]. Conclusion In the hypertrophied heart with preserved systolic function, in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis. PMID:28472418

Evaluating the effectiveness of rosuvastatin in preventing the progression of diastolic dysfunction in aortic stenosis: A substudy of the aortic stenosis progression observation measuring effects of rosuvastatin (ASTRONOMER) study

PubMed Central

2011-01-01

Background Tissue Doppler imaging (TDI) is a noninvasive echocardiographic method for the diagnosis of diastolic dysfunction in patients with varying degrees of aortic stenosis (AS). Little is known however, on the utility of TDI in the serial assessment of diastolic abnormalities in AS. Objective The aim of the current proposal was to examine whether treatment with rosuvastatin was successful in improving diastolic abnormalities in patients enrolled in the Aortic Stenosis Progression Observation Measuring Effects of Rosuvastatin (ASTRONOMER) study. Methods Conventional Doppler indices including peak early (E) and late (A) transmitral velocities, and E/A ratio were measured from spectral Doppler. Tissue Doppler measurements including early (E') and late (A') velocities of the lateral annulus were determined, and E/E' was calculated. Results The study population included 168 patients (56 ± 13 years), whose AS severity was categorized based on peak velocity at baseline (Group I: 2.5-3.0 m/s; Group II: 3.1-3.5 m/s; Group III: 3.6-4.0 m/s). Baseline and follow-up hemodynamics, LV dimensions and diastolic functional parameters were evaluated in all three groups. There was increased diastolic dysfunction from baseline to follow-up in each of the placebo and rosuvastatin groups. In patients with increasing severity of AS in Groups I and II, the lateral E' was lower and the E/E' (as an estimate of increased left ventricular end-diastolic pressure) was higher at baseline (p < 0.05). However, treatment with rosuvastatin did not affect the progression of diastolic dysfunction from baseline to 3.5 year follow-up between patients in any of the three predefined groups. Conclusion In patients with mild to moderate asymptomatic AS, rosuvastatin did not attenuate the progression of diastolic dysfunction. PMID:21299902

The role of N-terminal PRO-brain natriuretic peptide and echocardiography for screening asymptomatic left ventricular dysfunction in a population at high risk for heart failure. The PROBE-HF study.

PubMed

Betti, Irene; Castelli, Gabriele; Barchielli, Alessandro; Beligni, Cinzia; Boscherini, Vittorio; De Luca, Leonardo; Messeri, Gianni; Gheorghiade, Mihai; Maisel, Alan; Zuppiroli, Alfredo

2009-06-01

Screening for asymptomatic left ventricular dysfunction (ALVD) in subjects at risk for heart failure (HF) can affect clinical management. The aim of the present study is to examine the role of NT-pro BNP in the diagnosis of ALVD in subjects with hypertension and diabetes from primary care. A total of 1012 subjects with hypertension and/or diabetes and no symptoms or signs of HF were assessed by B-type natriuretic peptide (NT-proBNP) assay and echocardiography. Diastolic dysfunction was present in 368/1012 subjects (36.4%): 327 (32.4%) with mild diastolic dysfunction and 41 (4%) with a moderate-to-severe diastolic dysfunction. Systolic dysfunction was present in 11/1012 (1.1%). NT-proBNP levels were 170 +/- 206 and 859 +/- 661 pg/mL, respectively, in diastolic and systolic dysfunction and 92 +/- 169 in normal subjects (P < .0001). Pooling moderate-to-severe diastolic with systolic dysfunction, a total of 52 subjects (5.1 %) were obtained: best cutoff value of NT-proBNP was 125 pg/mL (males <67 years: sensitivity [Sens] 87.5%, specificity [Spec] 92.7%, negative predictive value [NPV] 99.5%, positive predictive value [PPV] 33.3%; females <67 years: Sens 100%, Spec 84.1%, NPV 100%, PPV 33.3%; males >or=67 years: Sens 100%, Spec 77.1%, NPV 100%, PPV 32.5%; females >or=67 years: Sens 100%, Spec 59.9%, NPV 100%, PPV 23%). The prevalence of ALVD in subjects at risk for HF is 5.1%. Because of its excellent NPV, NT-proBNP can be used by general practitioners to rule out ALVD in hypertensive or diabetic patients.

Biventricular and atrial diastolic function assessment using conventional echocardiography and tissue-Doppler imaging in adults with Marfan syndrome.

PubMed

Kiotsekoglou, Anatoli; Moggridge, James C; Bijnens, Bart H; Kapetanakis, Venediktos; Alpendurada, Francisco; Mullen, Michael J; Saha, Samir; Nassiri, Dariush K; Camm, John; Sutherland, George R; Child, Anne H

2009-12-01

Previous studies provided evidence about left ventricular systolic and diastolic dysfunction in adults with Marfan syndrome (MFS). However, in the literature, data on right ventricular and bi-atrial diastolic function are limited. We aimed to investigate whether, in the absence of significant valvular disease, diastolic dysfunction is present not only in both ventricles but also in the atrial cavities. Seventy-two adult unoperated MFS patients and 73 controls without significant differences in age, sex, and body surface area from the patient group were studied using two-dimensional, pulsed, and colour-Doppler and tissue-Doppler imaging (TDI). Biventricular early filling measurements were significantly decreased in MFS patients when compared with controls (P < 0.001). Pulsed TDI early filling measurements obtained from five mitral annular regions and over the lateral tricuspid valve corner were significantly reduced in the patient group (P < 0.001). Indices reflecting atrial function at the reservoir, conduit and contractile phases were also significantly decreased in MFS patients (P < 0.001). This study demonstrated significant biventricular diastolic and biatrial systolic and diastolic dysfunction in MFS patients. Our findings suggest that MFS affects diastolic function independently. Diastolic abnormalities could be attributed to fibrillin-1 deficiency and dysregulation of transforming growth factor-beta activity in the cardiac extracellular matrix.

Cardiac-Specific IGF-1 Receptor Transgenic Expression Protects Against Cardiac Fibrosis and Diastolic Dysfunction in a Mouse Model of Diabetic Cardiomyopathy

PubMed Central

Huynh, Karina; McMullen, Julie R.; Julius, Tracey L.; Tan, Joon Win; Love, Jane E.; Cemerlang, Nelly; Kiriazis, Helen; Du, Xiao-Jun; Ritchie, Rebecca H.

2010-01-01

OBJECTIVE Compelling epidemiological and clinical evidence has identified a specific cardiomyopathy in diabetes, characterized by early diastolic dysfunction and adverse structural remodeling. Activation of the insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) promotes physiological cardiac growth and enhances contractile function. The aim of the present study was to examine whether cardiac-specific overexpression of IGF-1R prevents diabetes-induced myocardial remodeling and dysfunction associated with a murine model of diabetes. RESEARCH DESIGN AND METHODS Type 1 diabetes was induced in 7-week-old male IGF-1R transgenic mice using streptozotocin and followed for 8 weeks. Diastolic and systolic function was assessed using Doppler and M-mode echocardiography, respectively, in addition to cardiac catheterization. Cardiac fibrosis and cardiomyocyte width, heart weight index, gene expression, Akt activity, and IGF-1R protein content were also assessed. RESULTS Nontransgenic (Ntg) diabetic mice had reduced initial (E)-to-second (A) blood flow velocity ratio (E:A ratio) and prolonged deceleration times on Doppler echocardiography compared with nondiabetic counterparts, indicative markers of diastolic dysfunction. Diabetes also increased cardiomyocyte width, collagen deposition, and prohypertrophic and profibrotic gene expression compared with Ntg nondiabetic littermates. Overexpression of the IGF-1R transgene markedly reduced collagen deposition, accompanied by a reduction in the incidence of diastolic dysfunction. Akt phosphorylation was elevated ∼15-fold in IGF-1R nondiabetic mice compared with Ntg, and this was maintained in a setting of diabetes. CONCLUSIONS The current study suggests that cardiac overexpression of IGF-1R prevented diabetes-induced cardiac fibrosis and diastolic dysfunction. Targeting IGF-1R–Akt signaling may represent a therapeutic target for the treatment of diabetic cardiac disease. PMID:20215428

Role of Left Ventricular Diastolic Dysfunction in Predicting Atrial Fibrillation Recurrence after Successful Electrical Cardioversion

PubMed Central

Melduni, Rowlens M.; Cullen, Michael W.

2013-01-01

The role of left ventricular (LV) diastolic dysfunction in predicting atrial fibrillation (AF) recurrence after successful electrical cardioversion is largely unknown. Studies suggest that there may be a link between abnormal LV compliance and the initial development, and recurrence of AF after electrical cardioversion. Although direct-current cardioversion (DCCV) is a well-established and highly effective method to convert AF to sinus rhythm, it offers little else beyond immediate rate control because it does not address the underlying cause of AF. Preservation of sinus rhythm after successful cardioversion still remains a challenge for clinicians. Despite the use of antiarrhythmic drugs and serial cardioversions, the rate of AF recurrence remains high in the first year. Current evidence suggests that diastolic dysfunction, which is associated with atrial volume and pressure overload, may be a mechanism underlying the perpetuating cycle of AF recurrence following successful electrical cardioversion. Diastolic dysfunction is considered to be a defect in the ability of the myofibrils, which have shortened against a load in systole to eject blood into the high-pressure aorta, to rapidly or completely return to their resting length. Consequently, LV filling is impaired and the non-compliant left ventricle is unable to fill at low pressures. As a result, left atrial and pulmonary vein pressure rises, and electrical and structural remodeling of the atrial myocardium ensues, creating a vulnerable substrate for AF. In this article, we review the current evidence highlighting the association of LV diastolic dysfunction with AF recurrence after successful electrical cardioversion and provide an approach to the management of LV diastolic dysfunction to prevent AF recurrence. PMID:23525127

Effect of left ventricular diastolic dysfunction on left atrial appendage function and thrombotic potential in nonvalvular atrial fibrillation.

PubMed

Demirçelik, Muhammed Bora; Çetin, Mustafa; Çiçekcioğlu, Hülya; Uçar, Özgül; Duran, Mustafa

2014-05-01

We aimed to investigate effects of left ventricular diastolic dysfunction on left atrial appendage functions, spontaneous echo contrast and thrombus formation in patients with nonvalvular atrial fibrillation. In 58 patients with chronic nonvalvular atrial fibrilation and preserved left ventricular systolic function, left atrial appendage functions, left atrial spontaneous echo contrast grading and left ventricular diastolic functions were evaluated using transthoracic and transoesophageal echocardiogram. Patients divided in two groups: Group D (n=30): Patients with diastolic dysfunction, Group N (n=28): Patients without diastolic dysfunction. Categorical variables in two groups were evaluated with Pearson's chi-square or Fisher's exact test. The significance of the lineer correlation between the degree of spontaneous echo contrast (SEC) and clinical measurements was evaluated with Spearman's correlation analysis. Peak pulmonary vein D velocity of the Group D was significantly higher than the Group N (p=0.006). However, left atrial appendage emptying velocity, left atrial appendage lateral wall velocity, peak pulmonary vein S, pulmonary vein S/D ratio were found to be significantly lower in Group D (p=0.028, p<0.001, p<0.001; p<0.001). Statistically significant negative correlation was found between SEC in left atrium and left atrial appendage emptying, filling, pulmonary vein S/D levels and lateral wall velocities respectively (r=-0.438, r=-0.328, r=-0.233, r=-0.447). Left atrial appendage emptying, filling, pulmonary vein S/D levels and lateral wall velocities were significantly lower in SEC 2-3-4 than SEC 1 (p=0.003, p=0.029, p<0.001, p=0.002). In patients with nonvalvular atrial fibrillation and preserved left ventricular ejection fraction, left atrial appendage functions are decreased in patients with left ventricular diastolic dysfunction. Left ventricular diastolic dysfunction may constitute a potential risk for formation of thrombus and stroke.

Association between urine aldosterone and diastolic function in patients with primary aldosteronism and essential hypertension.

PubMed

Chang, Yi-Yao; Lee, Hsiu-Hao; Hung, Chi-Sheng; Wu, Xue-Ming; Lee, Jen-Kuang; Wang, Shuo-Meng; Liao, Min-Tsun; Chen, Ying-Hsien; Wu, Vin-Cent; Wu, Kwan-Dun; Lin, Yen-Hung

2014-09-01

To investigate the association between aldosterone and cardiac diastolic dysfunction. We prospectively enrolled 20 patients with primary aldosteronism (PA) and 22 patients with essential hypertension (EH). Plasma aldosterone concentration, plasma renin activity, and 24-h urine aldosterone level were measured. Echocardiography, including tissue Doppler image recordings, was performed. PA patients had a significantly higher left ventricular (LV) mass index and worse LV diastolic function than those in EH patients. Among various measures of aldosterone, log-transformed 24-h urine aldosterone level had the most consistent correlation with diastolic function. Aldosterone is strongly associated with LV diastolic dysfunction. Twenty-four hour urine aldosterone is a good indicator to evaluate the impact of aldosterone on LV diastolic function. Copyright © 2014. Published by Elsevier Inc.

Myocardial Hypertrophy and Its Role in Heart Failure with Preserved Ejection Fraction

PubMed Central

Heinzel, Frank R.; Hohendanner, Felix; Jin, Ge; Sedej, Simon; Edelmann, Frank

2015-01-01

Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load and cytokines associated with arterial hypertension, chronic kidney disease, diabetes and other co-morbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood but may include extracellular matrix changes, vascular dysfunction as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca2+ turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound co-morbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training on the other hand, in clinical trials improved exercise tolerance and diastolic function but did not reduce LVH. Thus, current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF. PMID:26183480

[Left ventricular dysfunction measured in diabetic patients with chronic renal failure on continuous ambulatory peritoneal dialysis].

PubMed

Díaz-Arrieta, Gustavo; Mendoza-Hernández, María Elsa; Pacheco-Aranda, Erika; Rivas-Duro, Miguel; Robles-Parra, Héctor Manuel; Espinosa-Vázquez, Raúl Arturo; Hernández-Cabrera, Jorge

2010-01-01

In diabetic patients with chronic renal failure (CRF) treated with dialysis, the diastolic and systolic left ventricular dysfunction is frequent. The aim was to assess by echocardiography the prevalence of diastolic and systolic ventricular dysfunction in diabetic patients with CRF treated with continuous ambulatory peritoneal dialysis (CAPD). Sixty diabetic patients with CRF in CAPD were studied. The mean age was 54.5 +/- 12 years (27-78 years). The left ventricular filling pattern (LVFP) as a diastolic function parameter and left ventricular ejection fraction (LVEF) as a systolic function parameter were measured by transthoracic echocardiography. Descriptive statistical analysis was used. 27 (45 %) patients were women and 33 (55 %) were men. In 55 (91.7 %) left ventricular concentric hypertrophy was observed. Fifty-two patients (86.7 %) showed LVFP type I; three (5 %) had the type II; two (3.3 %) showed pseudonormal pattern and three (5 %) had a normal LVFP. The LVEF was 0.63 +/- 0.09 (CI = 0.41-0.82). Forty nine (81.7 %) patients had LVEF equal or greater than 0.55. The prevalence of diastolic left ventricular dysfunction was 95 % and the prevalence of systolic left ventricular dysfunction was 18.3%.

Echocardiographic evaluation of diastolic parameters in dogs with dilated cardiomyopathy.

PubMed

Garncarz, M A

2007-01-01

Echocardiography is a valuable tool for the evaluation of systolic and diastolic cardiac function. A high correlation between measurements of diastolic mitral inflow parameters analyzed with Doppler echocardiography and invasive methods makes the former valuable. The aim of this study was to ascertain if significant differences occur in diastolic myocardial parameters between dogs with no heart disease and dogs with subclinical or clinical dilated cardiomyopathy. Furthermore the aim of the study was to determine whether heart failure in dilated cardiomypathy is a result of systolic dysfunction alone or both systolic and diastolic dysfunction. Eleven parameters were analyzed: E wave, E-AT, E-DT, E time, A wave, A-AT, A-DT, A time, E+A time, E/A ratio, and IVRT. The study confirmed the value of noninvasive echocardiographic assessment of diastolic function in dogs with dilated cardiomyopathy. Significant differences were found in E wave, E-AT, E time, E/A ratio and IVRT between healthy dogs and dogs with dilated cardiomyopathy. All are characterized by a significant decrease compared to healthy dogs after taking into account age and body weight except for the E/A ratio, which significantly increased in value. There were no significant changes in any of the Doppler parameters for diastolic evaluation in subclinical cases of DCM. Advanced heart failure in dilated cardiomyopathy entails systolic and diastolic dysfunction.

Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy.

PubMed

Hinze, Florian; Dieterich, Christoph; Radke, Michael H; Granzier, Henk; Gotthardt, Michael

2016-12-01

Impaired diastolic filling is a main contributor to heart failure with preserved ejection fraction (HFpEF), a syndrome with increasing prevalence and no treatment. Both collagen and the giant sarcomeric protein titin determine diastolic function. Since titin's elastic properties can be adjusted physiologically, we evaluated titin-based stiffness as a therapeutic target. We adjusted RBM20-dependent cardiac isoform expression in the titin N2B knockout mouse with increased ventricular stiffness. A ~50 % reduction of RBM20 activity does not only maintain cardiac filling in diastole but also ameliorates cardiac atrophy and thus improves cardiac function in the N2B-deficient heart. Reduced RBM20 activity partially normalized gene expression related to muscle development and fatty acid metabolism. The adaptation of cardiac growth was related to hypertrophy signaling via four-and-a-half lim-domain proteins (FHLs) that translate mechanical input into hypertrophy signals. We provide a novel link between cardiac isoform expression and trophic signaling via FHLs and suggest cardiac splicing as a therapeutic target in diastolic dysfunction. Increasing the length of titin isoforms improves ventricular filling in heart disease. FHL proteins are regulated via RBM20 and adapt cardiac growth. RBM20 is a therapeutic target in diastolic dysfunction.

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis

PubMed Central

Yeh, Huei-Ming; Lin, Ting-Tse; Yeh, Chih-Fan; Huang, Ho-Shiang; Chang, Sheng-Nan; Lin, Jou-Wei; Tsai, Chia-Ti; Lai, Ling-Ping; Huang, Yi-You

2017-01-01

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson’s correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis. PMID:29161313

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis.

PubMed

Yeh, Huei-Ming; Lin, Ting-Tse; Yeh, Chih-Fan; Huang, Ho-Shiang; Chang, Sheng-Nan; Lin, Jou-Wei; Tsai, Chia-Ti; Lai, Ling-Ping; Huang, Yi-You; Chu, Chun-Lin

2017-01-01

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

Association of N-Terminal Pro-B-Type Natriuretic Peptide with Left Ventricular Structure and Function in Chronic Kidney Disease (From the Chronic Renal Insufficiency Cohort [CRIC])

PubMed Central

Mishra, Rakesh K.; Li, Yongmei; Ricardo, Ana C.; Yang, Wei; Keane, Martin; Cuevas, Magdalena; Christenson, Robert; DeFilippi, Christopher; Chen, Jing; He, Jiang; Kallem, Radhakrishna R.; Raj, Dominic S.; Schelling, Jeffrey R.; Wright, Jackson; Go, Alan S.; Shlipak, Michael G.

2017-01-01

We evaluated the cross-sectional associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with cardiac structural and functional abnormalities in a cohort of chronic kidney disease (CKD) patients without clinical heart failure (HF), the Chronic Renal Insufficiency Cohort (n=3,232). Associations of NT-proBNP with echocardiographically determined left ventricular (LV) mass and LV systolic and diastolic function were evaluated by multivariable logistic and linear regression models. Reclassification of participants’ predicted risk of LV hypertrophy (LVH), systolic and diastolic dysfunction was performed using a category-free net reclassification improvement (NRI) index that compared a clinical model with and without NT-proBNP. The median (interquartile range) NT-proBNP was 126.6 pg/ml (55.5–303.7). The highest quartile of NT-proBNP was associated with nearly three-fold odds of LVH (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.8–4.0) and LV systolic dysfunction (2.7, 1.7–4.5) and two-fold odds of diastolic dysfunction (2.0, 1.3–2.9) in the fully adjusted models. When evaluated alone as a screening test, NT-proBNP functioned modestly for the detection of LVH (area under the curve, AUC 0.66) and LV systolic dysfunction (AUC 0.62), and poorly for the detection of diastolic dysfunction (AUC 0.51). However, when added to the clinical model, NT-proBNP significantly reclassified participants’ likelihood of having LVH (NRI 0.14, 95% CI 0.13–0.15; p<0.001) and LV systolic dysfunction (0.28, 0.27–0.30; p<0.001), but not diastolic dysfunction (0.10, 0.10–0.11; p=0.07). In conclusion, in this large CKD cohort without HF, NT-proBNP had strong associations with prevalent LVH and LV systolic dysfunction. PMID:23178053

Relationship between occupational exposure to lead and local arterial stiffness and left ventricular diastolic function in individuals with arterial hypertension

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poreba, Rafal, E-mail: sogood@poczta.onet.pl; Gac, Pawel; Poreba, Malgorzata

Relationship between occupational exposure to lead and frequency of complications in persons with arterial hypertension has been poorly investigated. This study aimed at evaluation of the relationship between occupational exposure to lead and manifestation of an increased local arterial stiffness and left ventricular diastolic dysfunction. The studies included 105 men (mean age: 44.47 {+-} 9.12 years) with arterial hypertension, treated with hypotensive drugs: group I - men occupationally exposed to lead (n = 53), and group II - men not exposed to lead (n = 52). In echocardiographic examination, the left ventricular diastolic dysfunction was diagnosed significantly more frequently inmore » group I than in group II. In eTracking examination mean values of stiffness parameter ({beta}), augmentation index (AI) and one-point pulse wave velocity (PWV-{beta}) were significantly higher and mean values of arterial compliance (AC) were significantly lower in group I than in group II. The logistic regression showed that in the group of persons with arterial hypertension occupationally exposed to lead a more advanced age, higher blood lead concentration and higher mean values of augmentation index represent independent risk factors of left ventricular diastolic dysfunction. The multifactorial regression showed that amongst persons with arterial hypertension occupationally exposed to lead higher blood zinc protoporphyrin concentration, a more advanced age and higher value of body mass index (BMI) represent independent risk factors of an increased local arterial stiffness. In summary, we should note that in the group of persons with arterial hypertension occupationally exposed to lead the study has demonstrated a significantly more frequent manifestation of left ventricular diastolic dysfunction and an increase in local arterial stiffness. - Highlights: > Amongst persons with AH exposed to Pb higher ZnPP represent independent risk factor of increased local arterial stiffness. > Higher Pb-B represent independent risk factor of left ventricular diastolic dysfunction. > The study has demonstrated a more frequent manifestation of left ventricular diastolic dysfunction in group exposed to Pb. > Also, in this group the study has demonstrated a more frequent manifestation of increase in local arterial stiffness.« less

Association of left ventricular longitudinal and circumferential systolic dysfunction with diastolic function in hypertension: a nonlinear analysis focused on the interplay with left ventricular geometry.

PubMed

Ballo, Piercarlo; Nistri, Stefano; Cameli, Matteo; Papesso, Barbara; Dini, Frank Lloyd; Galderisi, Maurizio; Zuppiroli, Alfredo; Mondillo, Sergio

2014-02-01

The relationships of left ventricular (LV) longitudinal and circumferential systolic dysfunction with diastolic performance in hypertensive patients have never been compared. In 532 asymptomatic hypertensive patients, circumferential function was assessed with the use of midwall fractional shortening (mFS) and stress-corrected mFS (SCmFS), whereas longitudinal function was assessed with the use of left atrioventricular plane displacement (AVPD) and systolic mitral annulus velocity (s'). Early diastolic annular velocity (e') and the E/e' ratio were measured. Global longitudinal and circumferential strain were determined in a subset of 210 patients. e' was linearly related to all systolic indexes (AVPD: R = 0.40; s': R = 0.39; mFS: R = 0.16; SCmFS: R = 0.17; all P < .0001), but the correlations were stronger with longitudinal indexes than with circumferential ones (P < .0001). E/e' was nonlinearly related to AVPD (R = -0.49; P < .0001) and s' (R = -0.34; P < .0001) and showed no relationship with mFS and SCmFS. Longitudinal indexes were superior to circumferential ones in predicting e' <8 cm/s, E/e' <8, and E/e' ≥13. The effect of LV geometry on LV diastolic function was evident among patients with preserved systolic longitudinal function, but was blunted among patients with impaired longitudinal function. In multivariable analyses, only longitudinal indexes remained associated with e' and E/e'. Analyses using strains provided similar results. In asymptomatic hypertensive subjects, LV diastolic performance is independently associated with longitudinal systolic dysfunction, but not with circumferential systolic dysfunction. Subtle longitudinal systolic impairment plays a role in mediating the effect of LV geometry on diastolic performance. These findings may support the need of critically revising the concept of isolated diastolic dysfunction in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Parental Attributions of Control for Child Behaviour and Their Relation to Discipline Practices in Parents of Children with and Without Developmental Delays.

PubMed

Jacobs, Myrthe; Marks Woolfson, Lisa; Hunter, Simon C

2017-01-01

Children with developmental delays (DD) are at risk for developing behavior problems. Research suggests that parents' causal attributions for child behavior are related to parenting. This study investigated this association in parents of children with DD compared to parents of typically developing (TD) children. It specifically focused on attributions of child control by separating these from attributions of responsibility, blame and intent, and from attributions of parent control and responsibility. Fifty-one parents of children with DD and 69 parents of TD children completed two questionnaires. The Written Analogue Questionnaire measured causal attributions. The Parenting Scale measured dysfunctional discipline practices. Parents of children with DD viewed the child's role in problematic behavior more positively while also viewing misbehavior as more fixed than parents of TD children. Parents of TD children who viewed their child as more in control over misbehavior used less dysfunctional discipline, but this association was not found for parents of children with DD. The results advance understanding of how parents perceive behavior problems in children with DD and the important role these perceptions play in parental behavior management strategies. More importantly, these perceptions relate to discipline practices differently for parents of children with DD compared to parents of TD children, highlighting that parent interventions should be adapted to the specific needs of parents of children with DD.

Experimental study of the intraventricular filling vortex in diastolic dysfunction

NASA Astrophysics Data System (ADS)

Santhanakrishnan, Arvind; Samaee, Milad; Nelsen, Nicholas

2016-11-01

Heart failure with normal ejection fraction (HFNEF) is a clinical syndrome that is prevalent in over half of heart failure patients. HFNEF patients typically show diastolic dysfunction, caused by a decrease in relaxation capability of the left ventricular (LV) muscle tissue and/or an increase in LV chamber stiffness. Numerous studies using non-invasive medical imaging have shown that an intraventricular filling vortex is formed in the LV during diastole. We conducted 2D particle image velocimetry and hemodynamics measurements on a left heart simulator to investigate diastolic flow under increasing LV wall stiffness, LV wall thickness and heart rate (HR) conditions. Flexible-walled, optically clear LV physical models cast from silicone were fitted within a fluid-filled acrylic chamber. Pulsatile flow within the LV model was generated using a piston pump and 2-component Windkessel elements were used to tune the least stiff (baseline) LV model to physiological conditions. The results show that peak circulation of the intraventricular filling vortex is diminished in conditions of diastolic dysfunction as compared to the baseline case. Increasing HR exacerbated the circulation of the filling vortex across all cases.

Prevalence of arterial stiffness and the risk of myocardial diastolic dysfunction in women.

PubMed

Seeland, Ute; Brecht, Anna; Nauman, Ahmad T; Oertelt-Prigione, Sabine; Ruecke, Mirjam; Knebel, Fabian; Stangl, Verena; Regitz-Zagrosek, Vera

2016-10-01

The present study determines the prevalence of vascular dysfunction and arterial stiffness (ASt) in a female urban population by measuring the brachial augmentation index (AIx) and aortic pulse wave velocity (PWV). The study tests the hypothesis that the measurement of AIx and PWV is useful in addition to that of traditional cardiovascular risk factors when assessing the risk for left ventricular diastolic dysfunction (LVDD). This cross-sectional study recruited 965 women aged 25-75 years from 12 districts of Berlin. The ASt indices, brachial AIx, aortic PWV and the central blood pressure were measured by an oscillometric method. A randomly selected subgroup (n=343) was examined by echocardiography. Trans-mitral inflow E/A ratio and diastolic mitral annulus velocity (é) were assessed. Questionnaires, medical history and blood sampling were used for the evaluation of individual risk factors. Normal vascular function was found in 55% of the women included. The prevalence of women with pathological AIx only (AIx ⩾ -10%, PWV normal) was 21.5%, whereas 17.9% were affected by increased AIx and PWV (AIx ⩾ -10%, PWV ⩾9.7 m/s), and 6% with only pathological PWV values. The prevalence of LVDD was 31.7%. LVDD was significantly associated with pathological PWV ⩾ 9.7 m/s [OR: 1.27, 95%CI: 1.02-1.57], age [OR: 4.17, 95%CI: 2.87-6.07] and a waist circumference >80 cm [OR: 3.61, 95%CI: 1.85-7.04] in multiple regression analysis. The high prevalence of markers for vascular dysfunction and ASt in a general female population and their importance as a mediator of diastolic dysfunction should encourage implementation of aortic PWV measurement to improve cardiovascular-risk assessment in particular to identify subclinical myocardial diastolic dysfunction. © 2016 The Author(s).

Knockout of TRPV1 Exacerbates Left Ventricular Diastolic Dysfunction Induced by A High-fat Diet in Mice.

PubMed

Zhong, Beihua; Rubinstein, Jack; Ma, Shuangtao; Wang, Donna H

2018-05-03

Transient receptor potential vanilloid 1 (TRPV1) channels in sensory nerves have anti-oxidative properties and counteract obesity and diabetes that are associated with diastolic dysfunction with preserved ejection fraction. We tested the hypothesis that TRPV1 knockout exacerbates high-fat diet (HFD)-induced glucose intolerance and diastolic dysfunction. Trpv1-/- and wild-type (WT) mice were fed chow diet or HFD for 20 weeks. Then, we performed the intraperitoneal glucose tolerance test, measured the heart function through transthoracic echocardiography and Langendorff heart perfusion system, analyzed cardiac histology, and measured the myocardial superoxide production and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. HFD increased body weight, heart weight, and levels of fasting glucose, insulin, and leptin in both strains, with no differences between two strains. HFD impaired glucose tolerance in both strains with a more profound effect in Trpv1-/- than WT mice. HFD increased left ventricular (LV) internal diameter in diastole in both strains, while increased LV posterior wall thickness in diastole in Trpv1-/- but not in WT mice. HFD increased LV end-diastolic pressure in both strains with a further increase in Trpv1-/- mice, while decreased -dP/dt in Trpv1-/- but not in WT mice. HFD-induced cardiac collagen deposition and superoxide production were enhanced in Trpv1-/- mice. HFD upregulated cardiac p22phox in both strains, while increased p47phox in Trpv1-/- but not in WT mice. In summary, TRPV1 knockout exacerbates HFD-induced glucose intolerance, cardiac oxidative stress and collagen deposition, leading to aggravated LV diastolic dysfunction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Age-related changes in intraventricular kinetic energy: a physiological or pathological adaptation?

PubMed

Wong, James; Chabiniok, Radomir; deVecchi, Adelaide; Dedieu, Nathalie; Sammut, Eva; Schaeffter, Tobias; Razavi, Reza

2016-03-15

Aging has important deleterious effects on the cardiovascular system. We sought to compare intraventricular kinetic energy (KE) in healthy subjects of varying ages with subjects with ventricular dysfunction to understand if changes in energetic momentum may predispose individuals to heart failure. Four-dimensional flow MRI was acquired in 35 healthy subjects (age: 1-67 yr) and 10 patients with left ventricular (LV) dysfunction (age: 28-79 yr). Healthy subjects were divided into age quartiles (1st quartile: <16 yr, 2nd quartile: 17-32 yr, 3rd quartile: 33-48 yr, and 4th quartile: 49-64 yr). KE was measured in the LV throughout the cardiac cycle and indexed to ventricular volume. In healthy subjects, two large peaks corresponding to systole and early diastole occurred during the cardiac cycle. A third smaller peak was seen during late diastole in eight adults. Systolic KE (P = 0.182) and ejection fraction (P = 0.921) were preserved through all age groups. Older adults showed a lower early peak diastolic KE compared with children (P < 0.0001) and young adults (P = 0.025). Subjects with LV dysfunction had reduced ejection fraction (P < 0.001) and compared with older healthy adults exhibited a similar early peak diastolic KE (P = 0.142) but with the addition of an elevated KE in diastasis (P = 0.029). In healthy individuals, peak diastolic KE progressively decreases with age, whereas systolic peaks remain constant. Peak diastolic KE in the oldest subjects is comparable to those with LV dysfunction. Unique age-related changes in ventricular diastolic energetics might be physiological or herald subclinical pathology. Copyright © 2016 the American Physiological Society.

Age-related changes in intraventricular kinetic energy: a physiological or pathological adaptation?

PubMed Central

Wong, James; Chabiniok, Radomir; deVecchi, Adelaide; Dedieu, Nathalie; Sammut, Eva; Schaeffter, Tobias

2016-01-01

Aging has important deleterious effects on the cardiovascular system. We sought to compare intraventricular kinetic energy (KE) in healthy subjects of varying ages with subjects with ventricular dysfunction to understand if changes in energetic momentum may predispose individuals to heart failure. Four-dimensional flow MRI was acquired in 35 healthy subjects (age: 1–67 yr) and 10 patients with left ventricular (LV) dysfunction (age: 28–79 yr). Healthy subjects were divided into age quartiles (1st quartile: <16 yr, 2nd quartile: 17–32 yr, 3rd quartile: 33–48 yr, and 4th quartile: 49–64 yr). KE was measured in the LV throughout the cardiac cycle and indexed to ventricular volume. In healthy subjects, two large peaks corresponding to systole and early diastole occurred during the cardiac cycle. A third smaller peak was seen during late diastole in eight adults. Systolic KE (P = 0.182) and ejection fraction (P = 0.921) were preserved through all age groups. Older adults showed a lower early peak diastolic KE compared with children (P < 0.0001) and young adults (P = 0.025). Subjects with LV dysfunction had reduced ejection fraction (P < 0.001) and compared with older healthy adults exhibited a similar early peak diastolic KE (P = 0.142) but with the addition of an elevated KE in diastasis (P = 0.029). In healthy individuals, peak diastolic KE progressively decreases with age, whereas systolic peaks remain constant. Peak diastolic KE in the oldest subjects is comparable to those with LV dysfunction. Unique age-related changes in ventricular diastolic energetics might be physiological or herald subclinical pathology. PMID:26747496

Detection of Early Right Ventricular Dysfunction in Young Patients With Thalassemia Major Using Tissue Doppler Imaging

PubMed Central

Bornaun, Helen; Dedeoglu, Reyhan; Oztarhan, Kazim; Dedeoglu, Savas; Erfidan, Erkan; Gundogdu, Muge; Aydogan, Gonul; Cengiz, Dicle

2016-01-01

Background Myocardial iron overload is the most common cause of mortality in patients with thalassemia major (TM), also known as beta-thalassemia. T2* cardiovascular magnetic resonance imaging (MRI) is the best way of monitoring cardiac iron, and new echocardiographic techniques can be used to assess cardiac function. Objectives The aim of this study was to assess the systolic and diastolic right ventricular (RV) function of patients with TM using tissue Doppler imaging (TDI) and to determine whether this echocardiographic technique is an adequate diagnostic tool for the screening and detection of subclinical cardiac dysfunction. Patients and Methods Eighty-four patients with TM were evaluated by conventional echocardiography and pulse-wave TDI. The data of the TM group (Group 1) were compared with that of 85 age- and sex-matched healthy controls (Group 2). Cardiovascular T2* MRI examinations were performed in 49 of the 85 patients. Results The patients with TM had significantly lower values for weight, height, body mass index, systolic arterial pressure, deceleration time, E’/A’, and ejection time (ET) than the controls. Group 1 also had significantly higher values for peak early diastolic velocity (E) over peak late diastolic velocity (A), peak early diastolic velocity of TDI (E’), peak late diastolic velocity of TDI (A’), E/E’, isovolumetric relaxation time, isovolumetric contraction time, and RV magnetic perfusion imaging (MPI) than Group 2. Conclusions RV diastolic dysfunction occurs before systolic deterioration in patients with TM and cannot be screened with conventional echocardiographic techniques. In routine practice, TDI measurements, MPI (for global function) and the E/E’ parameter (for diastolic function) can be used to screen and detect early RV dysfunction. PMID:27617076

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

NASA Technical Reports Server (NTRS)

Levine, Benjamin D.; Bungo, Michael W.; Platts, Steven H.; Hamilton, Douglas R.; Johnston, Smith L.

2009-01-01

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers.

[The prognostic value of cardio-pulmonary exercise test parameters in patients with asymptomatic ischemic heart dysfunction during 2-years observation].

PubMed

Skrzypek, Agnieszka; Nessler, Jadwiga

2015-01-01

Measurement of oxygen uptake at the maximal exercise (VO2max) in the cardio-pulmonary exercise test provides the most reliable information about exertion tolerance. Establishment of VO2peak, VE/CO2 and AT value in the early diagnosis of asymptomatic heart dysfunction in patients with coronary disease (CAD) and prognosis during 2-years observation. The study population: 57 patients (35 M) with CAD, without any signs or symptoms of heart dysfunction, without any features of myocardial infarction, in the age 51.08 +/- 4.01. The analysis was performed twice: in the beginning and after 2-years observation. Physical examinations, echocardiographic parameters [(assessment of systolic and diastolic dysfunction of the left ventricle (LV)] and spiroergometric parameters (VO2peak, VE/CO2 at AT). On the basis of echocardiographic examination, there were created groups of patients: Group A--the patients with normal LV function (n=32; 56.2%; 23 M); Group B--the patients with diastolic heart dysfunction (n=22; 38.6%; 10 M); Group A--32 patients in the age of 50.9 +/- 4, 23 men. Values of VO2pe ak :28.8 +/- 6 ml/kg/min, VE/CO2 28.8 +/- 4.9 and AT 18 +/- 2.5. Group B--the patients with diastolic heart dysfunction: 22 (39%) patients; 10 men, in the age of 51.2 +/- 4.3. Values of VO2peak: 26 +/- 3.4 mi/ kg/min, VE/CO2 31.2 +/- 5.1 and AT 16 +/- 2.5. In the beginning of the study was established significantly differences between anaerobic threshold and degree of heart dysfunction (p=0.039). (1) There was observed that VO2 A and VE/CO2 depended on filling LV profile LV and also of systolic LV function. Anaerobic threshold significantly depended on LV filling pattern. (2) In asymptomatic patients with LV diastolic dysfunction and VO2peak < or = 18.4 ml/kg/min was observed progression of LV diastolic dysfunction during two years.

Systemic inflammation is associated with myocardial fibrosis, diastolic dysfunction, and cardiac hypertrophy in patients with hypertrophic cardiomyopathy

PubMed Central

Fang, Lu; Ellims, Andris H; Beale, Anna L; Taylor, Andrew J; Murphy, Andrew; Dart, Anthony M

2017-01-01

Background: Regional or diffuse fibrosis is an early feature of hypertrophic cardiomyopathy (HCM) and is related to poor prognosis. Previous studies have documented low-grade inflammation in HCM. The aim of this study was to examine the relationships between circulating inflammatory markers and myocardial fibrosis, systolic and diastolic dysfunction, and the degree of cardiac hypertrophy in HCM patients. Methods and results: Fifty HCM patients were recruited while 20 healthy subjects served as the control group. Seventeen inflammatory cytokines/chemokines were measured in plasma. Cardiac magnetic resonance imaging and echocardiography were used to assess cardiac phenotypes. Tumour necrosis factor (TNF)-α, interleukin (IL)-6 and serum amyloid P (SAP) were significantly increased in HCM patients compared to controls. IL-6, IL-4, and monocyte chemotactic protein (MCP)-1 were correlated with regional fibrosis while stromal cell-derived factor-1 and MCP-1 were correlated with diffuse fibrosis. Fractalkine and interferon-γ were associated with left ventricular wall thickness. The above associations remained significant in a linear regression model including age, gender, body mass index and family history. TNF-α, IL-6, SAP, MCP-1 and IL-10 were associated with parameters of diastolic dysfunction. White blood cells were also increased in HCM patients and correlated with diffuse fibrosis and diastolic dysfunction. However the associations between parameters of systemic inflammation and diastolic dysfunction were weakened in the linear regression analysis. Conclusions: Systemic inflammation is associated with parameters of the disease severity of HCM patients, particularly regional and diffuse fibrosis. Modifying inflammation may reduce myocardial fibrosis in HCM patients. PMID:29218105

Multiple Causal Links Between Magnocellular-Dorsal Pathway Deficit and Developmental Dyslexia.

PubMed

Gori, Simone; Seitz, Aaron R; Ronconi, Luca; Franceschini, Sandro; Facoetti, Andrea

2016-10-17

Although impaired auditory-phonological processing is the most popular explanation of developmental dyslexia (DD), the literature shows that the combination of several causes rather than a single factor contributes to DD. Functioning of the visual magnocellular-dorsal (MD) pathway, which plays a key role in motion perception, is a much debated, but heavily suspected factor contributing to DD. Here, we employ a comprehensive approach that incorporates all the accepted methods required to test the relationship between the MD pathway dysfunction and DD. The results of 4 experiments show that (1) Motion perception is impaired in children with dyslexia in comparison both with age-match and with reading-level controls; (2) pre-reading visual motion perception-independently from auditory-phonological skill-predicts future reading development, and (3) targeted MD trainings-not involving any auditory-phonological stimulation-leads to improved reading skill in children and adults with DD. Our findings demonstrate, for the first time, a causal relationship between MD deficits and DD, virtually closing a 30-year long debate. Since MD dysfunction can be diagnosed much earlier than reading and language disorders, our findings pave the way for low resource-intensive, early prevention programs that could drastically reduce the incidence of DD. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Alterations in left ventricular diastolic function in conscious dogs with pacing-induced heart failure

NASA Technical Reports Server (NTRS)

Komamura, K.; Shannon, R. P.; Pasipoularides, A.; Ihara, T.; Lader, A. S.; Patrick, T. A.; Bishop, S. P.; Vatner, S. F.

1992-01-01

We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327 +/- 105 mmHg/s and ejection fraction by -22 +/- 2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., tau increased by +14.0 +/- 2.8 ms and the myocardial stiffness constant by +6.5 +/- 1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV end-systolic (+28.6 +/- 5.7 g/cm2) and LV end-diastolic stresses (+40.4 +/- 5.3 g/cm2). When stresses and heart rate were matched at the same levels in the control and failure states, the increases in tau and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition.

Left ventricular diastolic dysfunction in type 2 diabetes patients: a novel 2D strain analysis based on cardiac magnetic resonance imaging.

PubMed

Chen, Qiang; Gan, Yan; Li, Zhi-Yong

2016-09-01

This study was to develop a strain analysis method to evaluate the left ventricular (LV) functions in type 2 diabetic patients with an asymptomatic LV diastolic dysfunction. Two groups (10 asymptomatic type 2 diabetic subjects and 10 control ones) were considered. All of the subjects had normal ejection fraction values but impaired diastolic functions assessed by the transmitral blood flow velocity. For each subject, based on cardiac MRI, global indexes including LV volume, LV myocardial mass, cardiac index (CI), and transmitral peak velocity, were measured, and regional indexes (i.e., LV deformation, strain and strain rate) were calculated through an image-registration technology. Most of the global indexes did not differentiate between the two groups, except for the CI, LV myocardial mass and transmitral peak velocity. While for the regional indexes, the global LV diastolic dysfunction of the diabetic indicated an increased strain (0.08 ± 0.044 vs. -0.031 ± 0.077, p = 0.001) and a reduced strain rate (1.834 ± 0.909 vs. 3.791 ± 2.394, p = 0.033) compared to the controls, moreover, the local LV diastolic dysfunction reflected by the strain and strain rate varied, and the degree of dysfunction gradually decreased from the basal level to the apical level. The results showed that the strain and strain rates are effective to capture the subtle alterations of the LV functions, and the proposed method can be used to estimate the LV myocardial function based on cardiac MRI.

Tei index correlates with tissue Doppler parameters and reflects neurohormonal activation in patients with an abnormal transmitral flow pattern.

PubMed

Greco, Stefania; Troisi, Federica; Brunetti, Natale Daniele; Di Biase, Matteo

2009-10-01

Tei index (TI) is a Doppler parameter which reflects combined systolic and diastolic function. We aimed to study the relationship between TI, both traditional and tissue Doppler imaging (TDI) echocardiographic parameters and neurohormonal profile in outpatients with diastolic dysfunction expressed by an abnormal transmitral flow pattern. A total of 67 consecutive outpatients with diastolic dysfunction (abnormal transmitral flow pattern) were studied; all patients underwent clinical evaluation, blood sampling for B-type natriuretic peptide (BNP) plasma assaying, echocardiography for the determination of left ventricular ejection fraction (LVEF), dP/dt, left atrium (LA) dimensions, longitudinal systolic (S) and diastolic wall velocities (E'and A'), TI measured with Doppler echocardiography, and mitral regurgitation (MR) quantified on a semicontinuous scale. TI values were significantly correlated with BNP levels (r = 0.33; P < 0.01), LVEF (r =-0.56; P < 0.001), dP/dt (r =-0.52; P < 0.01), S (r =-0.45; P < 0.001), E'(r =-0.36; P < 0.01), A'(r =-0.27; P < 0.05), LA volume (r = 0.35; P < 0.01), and MR (P for trend < 0.05). In a multivariate regression analysis, TI was an independent predictor of increased BNP levels (beta= 0.32; P < 0.05), even after correction for potential confounders. ROC analysis showed as values of TI >0.59 identified subjects with combined systolic and diastolic dysfunction with a sensitivity of 73.8% and a specificity of 71.4%. In outpatients with diastolic dysfunction, TI, an easy to perform parameter for global ventricular performance assessment, might be useful in identifying subjects with concomitant systolic impairment and neurohormonal activation.

N-acetylcysteine reverses diastolic dysfunction and hypertrophy in familial hypertrophic cardiomyopathy

PubMed Central

Wilder, Tanganyika; Ryba, David M.; Wieczorek, David F.; Wolska, Beata M.

2015-01-01

S-glutathionylation of cardiac myosin-binding protein C (cMyBP-C) induces Ca2+ sensitization and a slowing of cross-bridge kinetics as a result of increased oxidative signaling. Although there is evidence for a role of oxidative stress in disorders associated with hypertrophic cardiomyopathy (HCM), this mechanism is not well understood. We investigated whether oxidative myofilament modifications may be in part responsible for diastolic dysfunction in HCM. We administered N-acetylcysteine (NAC) for 30 days to 1-mo-old wild-type mice and to transgenic mice expressing a mutant tropomyosin (Tm-E180G) and nontransgenic littermates. Tm-E180G hearts demonstrate a phenotype similar to human HCM. After NAC administration, the morphology and diastolic function of Tm-E180G mice was not significantly different from controls, indicating that NAC had reversed baseline diastolic dysfunction and hypertrophy in our model. NAC administration also increased sarco(endo)plasmic reticulum Ca2+ ATPase protein expression, reduced extracellular signal-related kinase 1/2 phosphorylation, and normalized phosphorylation of phospholamban, as assessed by Western blot. Detergent-extracted fiber bundles from NAC-administered Tm-E180G mice showed nearly nontransgenic (NTG) myofilament Ca2+ sensitivity. Additionally, we found that NAC increased tension cost and rate of cross-bridge reattachment. Tm-E180G myofilaments were found to have a significant increase in S-glutathionylation of cMyBP-C, which was returned to NTG levels upon NAC administration. Taken together, our results indicate that oxidative myofilament modifications are an important mediator in diastolic function, and by relieving this modification we were able to reverse established diastolic dysfunction and hypertrophy in HCM. PMID:26432840

Maternal left ventricular hypertrophy and diastolic dysfunction and brain natriuretic peptide concentration in early- and late-onset pre-eclampsia.

PubMed

Borges, V T M; Zanati, S G; Peraçoli, M T S; Poiati, J R; Romão-Veiga, M; Peraçoli, J C; Thilaganathan, B

2018-04-01

Pre-eclampsia (PE) is associated with maternal cardiac remodeling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and levels of brain natriuretic peptide (BNP) in women with early-onset (< 34 weeks' gestation) vs those with late-onset (≥ 34 weeks' gestation) PE. This was a prospective, cross-sectional, observational study of 30 women with early-onset PE, 32 with late-onset PE and 23 normotensive controls. Maternal cardiac structure and diastolic function were assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay. Early- and late-onset PE were associated with increased left ventricular mass index and relative wall thickness compared with normotensive controls. In women with early-onset PE, the prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher (both P < 0.05) compared with women with late-onset PE (16% for both). Maternal serum BNP levels were significantly higher (P < 0.05) in women with early-onset PE and correlated with relative wall thickness and left ventricular mass index. Early-onset PE is associated with more severe cardiac impairment than is late-onset PE, as evidenced by an increased prevalence of concentric hypertrophy, diastolic dysfunction and higher levels of BNP. These findings suggest that early-onset PE causes greater myocardial damage, increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Two-dimensional color tissue Doppler imaging detects myocardial dysfunction before occurrence of hypertrophy in a young Maine Coon cat.

PubMed

Chetboul, Valerie; Sampedrano, Carolina Carlos; Gouni, Vassiliki; Nicolle, Audrey P; Pouchelon, Jean-Louis

2006-01-01

A 20-month-old healthy male Maine Coon cat was referred for a cardiovascular evaluation. Physical examination and electrocardiogram were normal. The end-diastolic subaortic interventricular septal thickness (6 mm; reference range: < or = 6mm) and the mitral flow late diastolic velocity (0.89 m/s; reference range: 0.2-0.8m/s) were within the upper ranges. However, M-mode echocardiography did not reveal any sign of hypertrophic cardiomyopathy (HCM). Tissue Doppler imaging (TDI) identified a marked left ventricular free wall dysfunction characterized by decreased myocardial velocities in early diastole, increased myocardial velocities in late diastole and the presence of postsystolic contractions both at the base and the apex for the longitudinal motion. One year later, the diagnosis of HCM was confirmed by conventional echocardiography and the cat died suddenly 2 months later. This report demonstrates for the first time in spontaneous HCM the sensitivity of TDI for early diagnosis of myocardial dysfunction and suggests that TDI should form part of the screening techniques for early diagnosis of feline HCM.

Diastolic dysfunction and heart failure with a preserved ejection fraction: Relevance in critical illness and anaesthesia

PubMed Central

Maharaj, R.

2012-01-01

Epidemiological and clinical studies suggest that HF with a preserved ejection fraction will become the more common form of HF which clinicians will encounter. The spectrum of diastolic disease extends from the asymptomatic phase to fulminant cardiac failure. These patients are commonly encountered in operating rooms and critical care units. A clearer understanding of the underlying pathophysiology and clinical implications of HF with a preserved ejection fraction is fundamental to directing further research and to evaluate interventions. This review highlights the impact of diastolic dysfunction and HF with a preserved ejection fraction during the perioperative period and during critical illness. PMID:23960679

Acceleration rate of mitral inflow E wave: a novel transmitral doppler index for assessing diastolic function.

PubMed

Badkoubeh, Roya Sattarzadeh; Tavoosi, Anahita; Jabbari, Mostafa; Parsa, Amir Farhang Zand; Geraeli, Babak; Saadat, Mohammad; Larti, Farnoosh; Meysamie, Ali Pasha; Salehi, Mehrdad

2016-06-10

We performed comprehensive transmitral and pulmonary venous Doppler echocardiographic studies to devise a novel index of diastolic function. This is the first study to assess the utility of the acceleration rate (AR) of the E wave of mitral inflow as a primary diagnostic modality for assessing diastolic function. Study group consisted of 84 patients (53 + 11 years) with left ventricle (LV) diastolic dysfunction and 34 healthy people (35 ± 9 years) as control group, who were referred for clinically indicated two-dimensional transthoracic echocardiogram (TTE) during 2012 and 2013 to Imam Hospital. Normal controls were defined as patients without clinical evidence of cardiac disease and had normal TTE. LV diastolic function was determined according to standardized protocol of American Society of Echocardiography (ASE). As our new parameter, AR of E wave of mitral inflow was also measured in all patients. It was represented by the slope of the line between onset of E wave and peak of it. Correlation between AR of E wave and LV diastolic function grade was measured using the Spearman correlation coefficient. Receiver operating characteristic (ROC) curve was used to determine the sensitivity and specificity of AR of E wave in diagnosing LV diastolic dysfunction in randomly selected two-thirds of population then its derived cutoff was evaluated in rest of the population. The institutional review board of the hospital approved the study protocol. All participants gave written informed consent. This investigation was in accordance with the Declaration of Helsinki. The mean value of AR was 1010 ± 420 cm/s(2) in patients whereas the mean value for the normal controls was 701 ± 210 cm/s(2). There was a strong and graded relation between AR of E wave of mitral inflow and LV diastolic function grade (Spearman P ≤0.0001, rs =0.69). ROC curve analysis revealed that AR of E wave of mitral inflow =750 cm/s(2) predicted moderate or severe LV diastolic dysfunction with 89 % sensitivity and 89 % specificity (area under curve [AUC] = 0.903, P <0.0001). Application of this cutoff on test group showed 96 % sensitivity and 77 % specificity with AUC = 0.932 and P <0.0001. AR of E wave of mitral inflow could be used for assessment of diastolic function, especially moderate or severe diastolic dysfunction. However, before its clinical application, external validation should be considered.

Right ventricular diastolic performance in children with pulmonary arterial hypertension associated with congenital heart disease: correlation of echocardiographic parameters with invasive reference standards by high-fidelity micromanometer catheter.

PubMed

Okumura, Kenichi; Slorach, Cameron; Mroczek, Dariusz; Dragulescu, Andreea; Mertens, Luc; Redington, Andrew N; Friedberg, Mark K

2014-05-01

Right ventricular diastolic dysfunction influences outcomes in pulmonary arterial hypertension (PAH), but echocardiographic parameters have not been investigated in relation to invasive reference standards in pediatric PAH. We investigated echocardiographic parameters of right ventricular diastolic function in children with PAH in relation to simultaneously measured invasive reference measures. We prospectively recruited children undergoing a clinically indicated cardiac catheterization for evaluation of PAH and pulmonary vasoreactivity testing. Echocardiography was performed simultaneously with invasive reference measurements by high-fidelity micromanometer catheter. For analysis, patients were divided into shunt and nonshunt groups. Sixteen children were studied. In the group as a whole, significant correlations were found among τ and tricuspid deceleration time, E', E/E', TimeE-E', A wave velocity, and global early and late diastolic strain rate. dp/dt minimum correlated significantly with late diastolic tricuspid annular velocity (A'), tissue Doppler imaging-derived systolic:diastolic duration ratio, and global late diastolic strain rate. End-diastolic pressure correlated significantly with tissue Doppler imaging-derived systolic:diastolic duration ratio. On multivariate analysis, tricuspid deceleration time, TimeE-E', and global early diastolic strain rate were independent predictors of τ, whereas tissue Doppler imaging-derived systolic:diastolic duration ratio was an independent predictor of dp/dt minimum. In general, correlations between echocardiographic and invasive parameters were better in the shunt group than in the nonshunt group. Echocardiography correlates with invasive reference measures of right ventricular diastolic function in children with PAH, although it does not differentiate between early versus late diastolic abnormalities. Newer echocardiographic techniques may have added value to assess right ventricular diastolic dysfunction in this population. © 2014 American Heart Association, Inc.

Obesity and heart failure.

PubMed

De Pergola, Giovanni; Nardecchia, Adele; Giagulli, Vito Angelo; Triggiani, Vincenzo; Guastamacchia, Edoardo; Minischetti, Manuela Castiglione; Silvestris, Franco

2013-03-01

Epidemiological studies have recently shown that obesity, and abdominal obesity in particular, is an independent risk factor for the development of heart failure (HF). Higher cardiac oxidative stress is the early stage of heart dysfunction due to obesity, and it is the result of insulin resistance, altered fatty acid and glucose metabolism, and impaired mitochondrial biogenesis. Extense myocyte hypertrophy and myocardial fibrosis are early microscopic changes in patients with HF, whereas circumferential strain during the left ventricular (LV) systole, LV increase in both chamber size and wall thickness (LV hypertrophy), and LV dilatation are the early macroscopic and functional alterations in obese developing heart failure. LV hypertrophy leads to diastolic dysfunction and subendocardial ischemia in obesity, and pericardial fat has been shown to be significantly associated with LV diastolic dysfunction. Evolving abnormalities of diastolic dysfunction may include progressive hypertrophy and systolic dysfunction, and various degrees of eccentric and/or concentric LV hypertrophy may be present with time. Once HF is established, overweight and obese have a better prognosis than do their lean counterparts with the same level of cardiovascular disease, and this phenomenon is called "obesity paradox". It is mainly due to lower muscle protein degradation, brain natriuretic peptide circulating levels and cardio-respiratory fitness than normal weight patients with HF.

Coronary flow reserve/diastolic function relationship in angina-suffering patients with normal coronary angiography.

PubMed

Anchisi, Chiara; Marti, Giuliano; Bellacosa, Ilaria; Mary, David; Vacca, Giovanni; Marino, Paolo; Grossini, Elena

2017-05-01

Coronary blood flow and diastolic function are well known to interfere with each other through mechanical and metabolic mechanisms. We aimed to assess the relationship between coronary flow reserve (CFR) and diastolic dysfunction in patients suffering from angina but with normal coronary angiography. In 16 patients with chest pain and angiographically normal coronary arteries, CFR was measured using transthoracic echo-Doppler by inducing hyperemia through dipyridamole infusion. Diastolic function (E/A, deceleration time, isovolumetric relaxation time [IVRT], propagation velocity [Vp]) and left ventricular mass were evaluated by means of two-dimensional transthoracic echocardiography. The patients were initially divided into two groups on the grounds of CFR only (ACFR: altered CFR, n = 9; NACFR: unaltered CFR, n = 7). Thereafter they were divided into four groups on the grounds of CFR and diastolic function (NN: normal; AA: altered CFR/diastole; AN: altered CFR/normal diastole; NA: normal CFR/altered diastole). Most of the subjects were scheduled in AA (n = 8) or NA (n = 5) groups, which were taken into consideration for further analysis. Patients were not different regarding various risk factors. ACFR and AA patients were older with normal body weight in comparison with NACFR and NA patients (P < 0.05). In the AA group, CFR and diastolic variables were found to be related to each other. Diastolic dysfunction and reduced CFR were correlated in patients with concomitant alterations of those variables only. Because most risk factors were shared with patients with altered diastolic properties only, our findings could represent a direct relationship between altered CFR and diastole.

Endothelial function is associated with myocardial diastolic function in women with systemic lupus erythematosus.

PubMed

Chin, Calvin W L; Chin, Chee-Yang; Ng, Marie X R; Le, Thu-Thao; Huang, Fei-Qiong; Fong, Kok-Yong; Thumboo, Julian; Tan, Ru-San

2014-09-01

Endothelial dysfunction is associated with traditional and systemic lupus erythematosus (SLE)-specific risk factors, and early data suggest reversibility of endothelial dysfunction with therapy. The clinical relevance of endothelial function assessment has been limited by the lack of studies, demonstrating its prognostic significance and impact on early myocardial function. Therefore, we aimed to determine the association between endothelial and myocardial diastolic function in SLE women. Women with SLE and no coronary artery disease were prospectively recruited and underwent radionuclide myocardial perfusion imaging (MPI) (Jetstream, Philips, the Netherlands) to exclude subclinical myocardial ischemia. Cardiac and vascular functions were assessed in all patients (Alpha 10, Aloka, Tokyo). Diastolic function was assessed using pulse wave early (E) and late mitral blood inflow and myocardial tissue Doppler (mean of medial and lateral annulus e') velocities. Endothelial function was measured using brachial artery flow-mediated vasodilatation (FMD%). Univariate and multivariate linear regressions were used to assess the association between FMD% and myocardial diastolic function, adjusting for potential confounders. Thirty-eight patients without detectable myocardial ischemia on MPI were studied (mean age 44 ± 10 years; mean disease duration 14 ± 6 years). About 61 % of patients had normal diastolic function (E/e' ≤ 8), and 5 % of patients had definite diastolic dysfunction with E/e' > 13 (mean 7.1 ± 2.9). FMD% was associated with E/e' (regression coefficient β = -0.35; 95 % CI -0.62 to -0.08; p = 0.01) independent of systolic blood pressure, age, and SLICC/ACR Damage Index.

Daily exercise prevents diastolic dysfunction and oxidative stress in a female mouse model of western diet induced obesity by maintaining cardiac heme oxygenase-1 levels.

PubMed

Bostick, Brian; Aroor, Annayya R; Habibi, Javad; Durante, William; Ma, Lixin; DeMarco, Vincent G; Garro, Mona; Hayden, Melvin R; Booth, Frank W; Sowers, James R

2017-01-01

Obesity is a global epidemic with profound cardiovascular disease (CVD) complications. Obese women are particularly vulnerable to CVD, suffering higher rates of CVD compared to non-obese females. Diastolic dysfunction is the earliest manifestation of CVD in obese women but remains poorly understood with no evidence-based therapies. We have shown early diastolic dysfunction in obesity is associated with oxidative stress and myocardial fibrosis. Recent evidence suggests exercise may increase levels of the antioxidant heme oxygenase-1 (HO-1). Accordingly, we hypothesized that diastolic dysfunction in female mice consuming a western diet (WD) could be prevented by daily volitional exercise with reductions in oxidative stress, myocardial fibrosis and maintenance of myocardial HO-1 levels. Four-week-old female C57BL/6J mice were fed a high-fat/high-fructose WD for 16weeks (N=8) alongside control diet fed mice (N=8). A separate cohort of WD fed females was allowed a running wheel for the entire study (N=7). Cardiac function was assessed at 20weeks by high-resolution cardiac magnetic resonance imaging (MRI). Functional assessment was followed by immunohistochemistry, transmission electron microscopy (TEM) and Western blotting to identify pathologic mechanisms and assess HO-1 protein levels. There was no significant body weight decrease in exercising mice, normalized body weight 14.3g/mm, compared to sedentary mice, normalized body weight 13.6g/mm (p=0.38). Total body fat was also unchanged in exercising, fat mass of 6.6g, compared to sedentary mice, fat mass 7.4g (p=0.55). Exercise prevented diastolic dysfunction with a significant reduction in left ventricular relaxation time to 23.8ms for exercising group compared to 33.0ms in sedentary group (p<0.01). Exercise markedly reduced oxidative stress and myocardial fibrosis with improved mitochondrial architecture. HO-1 protein levels were increased in the hearts of exercising mice compared to sedentary WD fed females. This study provides seminal evidence that exercise can prevent diastolic dysfunction in WD-induced obesity in females even without changes in body weight. Furthermore, the reduction in myocardial oxidative stress and fibrosis and improved HO-1 levels in exercising mice suggests a novel mechanism for the antioxidant effect of exercise. Copyright © 2016 Elsevier Inc. All rights reserved.

Dysfunctional Neural Network of Spatial Working Memory Contributes to Developmental Dyscalculia

ERIC Educational Resources Information Center

Rotzer, S.; Loenneker, T.; Kucian, K.; Martin, E.; Klaver, P.; von Aster, M.

2009-01-01

The underlying neural mechanisms of developmental dyscalculia (DD) are still far from being clearly understood. Even the behavioral processes that generate or influence this heterogeneous disorder are a matter of controversy. To date, the few studies examining functional brain activation in children with DD mainly focus on number and counting…

Application of a simplified definition of diastolic function in severe sepsis and septic shock.

PubMed

Lanspa, Michael J; Gutsche, Andrea R; Wilson, Emily L; Olsen, Troy D; Hirshberg, Eliotte L; Knox, Daniel B; Brown, Samuel M; Grissom, Colin K

2016-08-04

Left ventricular diastolic dysfunction is common in patients with severe sepsis or septic shock, but the best approach to categorization is unknown. We assessed the association of common measures of diastolic function with clinical outcomes and tested the utility of a simplified definition of diastolic dysfunction against the American Society of Echocardiography (ASE) 2009 definition. In this prospective observational study, patients with severe sepsis or septic shock underwent transthoracic echocardiography within 24 h of onset of sepsis (median 4.3 h). We measured echocardiographic parameters of diastolic function and used random forest analysis to assess their association with clinical outcomes (28-day mortality and ICU-free days to day 28) and thereby suggest a simplified definition. We then compared patients categorized by the ASE 2009 definition and our simplified definition. We studied 167 patients. The ASE 2009 definition categorized only 35 % of patients. Random forest analysis demonstrated that the left atrial volume index and deceleration time, central to the ASE 2009 definition, were not associated with clinical outcomes. Our simplified definition used only e' and E/e', omitting the other measurements. The simplified definition categorized 87 % of patients. Patients categorized by either ASE 2009 or our novel definition had similar clinical outcomes. In both definitions, worsened diastolic function was associated with increased prevalence of ischemic heart disease, diabetes, and hypertension. A novel, simplified definition of diastolic dysfunction categorized more patients with sepsis than ASE 2009 definition. Patients categorized according to the simplified definition did not differ from patients categorized according to the ASE 2009 definition in respect to clinical outcome or comorbidities.

The association of visuospatial working memory with dysthymic disorder in pre-pubertal children.

PubMed

Franklin, T; Lee, A; Hall, N; Hetrick, S; Ong, J; Haslam, N; Karsz, F; Vance, A

2010-02-01

Visuospatial working memory (VSWM) deficits have not been investigated specifically in children with dysthymic disorder (DD), although they are associated with impairments in attention that commonly occur in DD. This study investigates VSWM impairment in children with DD. A cross-sectional study of VSWM in 6- to 12-year-old children with medication-naive DD (n=26) compared to an age-, gender- and 'performance IQ' (PIQ)-matched healthy control group (n=28) was completed. The DD group demonstrated impairment in VSWM, including impairment in the spatial span and strategy components of VSWM. Furthermore, the VSWM impairment remained after controlling for spatial span. Inattentive symptoms were significantly associated with the VSWM impairment. This study of children with DD found deficits in performance on VSWM tasks, suggesting that fronto-striatal-parietal neural networks that underlie processes of attention and the executive component of VSWM are dysfunctional in children with DD. These findings further our understanding of DD and suggest more specific interventions that might improve functioning.

Vascular extracellular vesicles in comorbidities of heart failure with preserved ejection fraction in men and women: The hidden players. A mini review.

PubMed

Gohar, Aisha; de Kleijn, Dominique P V; Hoes, Arno W; Rutten, Frans H; Hilfiker-Kleiner, Denise; Ferdinandy, Péter; Sluijter, Joost P G; den Ruijter, Hester M

2018-05-25

Left ventricular diastolic dysfunction, the main feature of heart failure with preserved ejection fraction (HFpEF), is thought to be primarily caused by comorbidities affecting the endothelial function of the coronary microvasculature. Circulating extracellular vesicles, released by the endothelium have been postulated to reflect endothelial damage. Therefore, we reviewed the role of extracellular vesicles, in particularly endothelium microparticles, in these comorbidities, including obesity and hypertension, to identify if they may be potential markers of the endothelial dysfunction underlying left ventricular diastolic dysfunction and HFpEF. Copyright © 2017. Published by Elsevier Inc.

Evaluation of left ventricular function in obese children without hypertension by a tissue Doppler imaging study.

PubMed

Ghandi, Yazdan; Sharifi, Mehrzad; Habibi, Danial; Dorreh, Fatemeh; Hashemi, Mojtaba

2018-01-01

The prevalence of obesity is increasing worldwide. Obese children without hypertension are becoming an important health challenge. Complications of obesity in adults are well established, but in obese children, cardiac dysfunction has not been reported clinically. The present crosssectional study investigates subclinical systolic and diastolic dysfunction using echocardiographic modalities. Twentyfive youngsters with body mass index (BMI) >30 and 25 healthy children with BMI <25 were assigned into case and control group, respectively. In all participants, complete cardiovascular examination, electrocardiography, and echocardiography were fulfilled. Echocardiography surveys included standard, pulsed wave Doppler (PWD), and tissue Doppler imaging (TDI). SPSS software, version 24. The two groups were matched for age and sex. The resting heart rate and blood pressure were markedly higher in the obese group ( P = 0.0001) though they were within the normal range in either category. Ejection fraction in the two groups was similar. Left ventricular (LV) mass ( P = 0.0001), LV mass index ( P = 0.029), left atrialtoaortic diameter ratio ( P = 0.0001), and LV enddiastolic diameter ( P = 0.008) were significantly greater in the case group, indicating cardiomegaly and subclinical systolic and diastolic dysfunction. Except for the aortic velocity, all PWD variables were considerably lower in the case group, suggesting subclinical diastolic dysfunction. All TDI parameters varied significantly between the two categories. There was a direct correlation between isovolumetric relaxation time and BMI. Obesity in children without hypertension is associated with subclinical systolic and diastolic cardiac dysfunction. We propose the evaluation of blood pressure as well as myocardial performance using PWD and TDI in all obese children without hypertension, regularly.

Copeptin in patients with heart failure and preserved ejection fraction: a report from the prospective KaRen-study

PubMed Central

Hage, Camilla; Lund, Lars H; Donal, Erwan; Daubert, Jean-Claude; Linde, Cecilia; Mellbin, Linda

2015-01-01

Introduction Underlying mechanisms of heart failure (HF) with preserved ejection fraction (HFPEF) remain unknown. We explored copeptin, a biomarker of the arginine vasopressin system, hypothesising that copeptin in HFPEF is elevated, associated with diastolic dysfunction and N-terminal pro-brain natriuretic peptide (NT-proBNP) and predictive of HF hospitalisation and mortality. Methods and analysis In a prospective observational substudy of the The Karolinska Rennes (KaRen) 86 patients with symptoms of acute HF and ejection fraction (EF) ≥45% were enrolled. After 4–8 weeks, blood sampling and echocardiography was performed. Plasma-copeptin was analysed in 86 patients and 62 healthy controls. Patients were followed in median 579 days (quartile 1; quartile 3 (Q1;Q3) 276;1178) regarding the composite end point all-cause mortality or HF hospitalisation. Ethics and dissemination The patients with HFPEF had higher copeptin levels, median 13.56 pmol/L (Q1;Q3 8.56;20.55) than controls 5.98 pmol/L (4.15;9.42; p<0.001). Diastolic dysfunction, assessable in 75/86 patients, was present in 45 and absent in 30 patients. Copeptin did not differ regarding diastolic dysfunction and did not correlate with cardiac function but with NT-proBNP (r=0.223; p value=0.040). In univariate Cox regression analysis log copeptin predicted the composite end point (HR 1.56 (95% CI 1.03 to 2.38; p value=0.037)) but not after adjusting for NT-proBNP (HR 1.39 (95% CI 0.91 to 2.12; p value=0.125)). Conclusions In the present patients with HFPEF, copeptin is elevated, correlates with NT-proBNP but not markers of diastolic dysfunction, and has prognostic implications, however blunted after adjustment for NT-proBNP. The HFPEF pathophysiology may be better reflected by markers of neurohormonal activation than by diastolic dysfunction. Trial registration number ClinicalTrials.gov NCT00774709. PMID:26568833

Blood pressure normalization post-jugular venous balloon angioplasty.

PubMed

Sternberg, Zohara; Grewal, Prabhjot; Cen, Steven; DeBarge-Igoe, Frances; Yu, Jinhee; Arata, Michael

2015-05-01

This study is the first in a series investigating the relationship between autonomic nervous system dysfunction and chronic cerebrospinal venous insufficiency in multiple sclerosis patients. We screened patients for the combined presence of the narrowing of the internal jugular veins and symptoms of autonomic nervous system dysfunction (fatigue, cognitive dysfunction, sleeping disorders, headache, thermal intolerance, bowel/bladder dysfunction) and determined systolic and diastolic blood pressure responses to balloon angioplasty. The criteria for eligibility for balloon angioplasty intervention included ≥ 50% narrowing in one or both internal jugular veins, as determined by the magnetic resonance venography, and ≥ 3 clinical symptoms of autonomic nervous system dysfunction. Blood pressure was measured at baseline and post-balloon angioplasty. Among patients who were screened, 91% were identified as having internal jugular veins narrowing (with obstructing lesions) combined with the presence of three or more symptoms of autonomic nervous system dysfunction. Balloon angioplasty reduced the average systolic and diastolic blood pressure. However, blood pressure categorization showed a biphasic response to balloon angioplasty. The procedure increased blood pressure in multiple sclerosis patients who presented with baseline blood pressure within lower limits of normal ranges (systolic ≤ 105 mmHg, diastolic ≤ 70 mmHg) but decreased blood pressure in patients with baseline blood pressure above normal ranges (systolic ≥ 130 mmHg, diastolic ≥ 80 mmHg). In addition, gender differences in baseline blood pressure subcategories were observed. The coexistence of internal jugular veins narrowing and symptoms of autonomic nervous system dysfunction suggests that the two phenomena may be related. Balloon angioplasty corrects blood pressure deviation in multiple sclerosis patients undergoing internal jugular vein dilation. Further studies should investigate the association between blood pressure deviation and internal jugular veins narrowing, and whether blood pressure normalization affects Patient's clinical outcomes. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies.

PubMed

Axell, Richard G; Giblett, Joel P; White, Paul A; Klein, Andrew; Hampton-Til, James; O'Sullivan, Michael; Braganza, Denise; Davies, William R; West, Nick E J; Densem, Cameron G; Hoole, Stephen P

2017-06-06

We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. Ten subjects with single-vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low-pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia-induced diastolic dysfunction was seen 1 minute after RP (end-diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P <0.001) and BO (end-diastolic pressure [mm Hg]: 8.1 ± 4.0 versus 8.7±4.0, P =0.03). Impairment of systolic and diastolic function after BO remained at 15-minutes recovery (ejection fraction [%]: 55.7±9.0 versus 47.8±6.3, P <0.01; end-diastolic pressure [mm Hg]: 8.1±4.0 versus 9.2±3.9, P <0.01). Persistent diastolic dysfunction was also evident in the RP group at 15-minutes recovery (end-diastolic pressure [mm Hg]: 8.1±4.1 versus 9.9±4.4, P =0.03) and there was also sustained impairment of load-independent indices of systolic function at 15 minutes after RP (end-systolic elastance and ventriculo-arterial coupling [mm Hg/mL]: 1.25±0.31 versus 0.85±0.43, P <0.01). RP and right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Genome-Wide Analysis Identifies IL-18 and FUCA2 as Novel Genes Associated with Diastolic Function in African Americans with Sickle Cell Disease

PubMed Central

Sysol, Justin R.; Abbasi, Taimur; Patel, Amit R.; Lang, Roberto M.; Gupta, Akash; Garcia, Joe G. N.; Gordeuk, Victor R.; Machado, Roberto F.

2016-01-01

Background Diastolic dysfunction is common in sickle cell disease (SCD), and is associated with an increased risk of mortality. However, the molecular pathogenesis underlying this development is poorly understood. The aim of this study was to identify a gene expression profile that is associated with diastolic function in SCD, potentially elucidating molecular mechanisms behind diastolic dysfunction development. Methods Diastolic function was measured via echocardiography in 65 patients with SCD from two independent study populations. Gene expression microarray data was compared with diastolic function in both study cohorts. Candidate genes that associated in both analyses were tested for validation in a murine SCD model. Lastly, genotyping array data from the replication cohort was used to derive cis-expression quantitative trait loci (cis-eQTLs) and genetic associations within the candidate gene regions. Results Transcriptome data from both patient cohorts implicated 7 genes associated with diastolic function, and mouse SCD myocardial expression validated 3 of these genes. Genetic associations and eQTLs were detected in 2 of the 3 genes, FUCA2 and IL18. Conclusions FUCA2 and IL18 are associated with diastolic function in SCD patients, and may be involved in the pathogenesis of the disease. Genetic polymorphisms within the FUCA2 and IL18 gene regions are also associated with diastolic function in SCD, likely by affecting expression levels of the genes. PMID:27636371

Cardiac diastolic function after recovery from pre-eclampsia.

PubMed

Soma-Pillay, P; Louw, M C; Adeyemo, A O; Makin, J; Pattinson, R C

Pre-eclampsia is associated with significant changes to the cardiovascular system during pregnancy. Eccentric and concentric remodelling of the left ventricle occurs, resulting in impaired contractility and diastolic dysfunction. It is unclear whether these structural and functional changes resolve completely after delivery. The objective of the study was to determine cardiac diastolic function at delivery and one year post-partum in women with severe pre-eclampsia, and to determine possible future cardiovascular risk. This was a descriptive study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria, South Africa. Ninety-six women with severe preeclampsia and 45 normotensive women with uncomplicated pregnancies were recruited during the delivery admission. Seventy-four (77.1%) women in the pre-eclamptic group were classified as a maternal near miss. Transthoracic Doppler echocardiography was performed at delivery and one year post-partum. At one year post-partum, women with pre-eclampsia had a higher diastolic blood pressure (p = 0.001) and body mass index (p = 0.02) than women in the normotensive control group. Women with early onset pre-eclampsia requiring delivery prior to 34 weeks' gestation had an increased risk of diastolic dysfunction at one year post-partum (RR 3.41, 95% CI: 1.11-10.5, p = 0.04) and this was irrespective of whether the patient had chronic hypertension or not. Women who develop early-onset pre-eclampsia requiring delivery before 34 weeks are at a significant risk of developing cardiac diastolic dysfunction one year after delivery compared to normotensive women with a history of a low-risk pregnancy.

Increased left ventricular mass and diastolic dysfunction are associated with endothelial dysfunction in normotensive offspring of subjects with essential hypertension.

PubMed

Zizek, Bogomir; Poredos, Pavel

2007-01-01

We aimed to investigate left ventricular (LV) morphology and function in normotensive offspring of subjects with essential hypertension (familial trait - FT), and to determine the association between LV mass and determinants of LV diastolic function and endothelium-dependent (NO-mediated) dilation of the brachial artery (BA). The study encompassed 76 volunteers of whom 44 were normotonics with FT aged 28-39 (mean 33) years and 32 age-matched controls without FT. LV mass and LV diastolic function was measured using conventional echocardiography and tissue Doppler imaging (TDI). LV diastolic filling properties were assessed and reported as the peak E/A wave ratio, and peak septal annular velocities (E(m) and E(m)/A(m) ratio) on TDI. Using high-resolution ultrasound, BA diameters at rest and during reactive hyperaemia (flow-mediated dilation--FMD) were measured. In subjects with FT, the LV mass index was higher than in controls (92.14+/-24.02 vs 70.08+/-20.58); p<0.001). Offspring of hypertensive families had worse LV diastolic function than control subjects (lower E/A ratio, lower E(m) and E(m)/A(m) ratio; p<0.001). In subjects with FT, FMD was decreased compared with the controls (6.11+/-3.28% vs 10.20+/-2.07%; p<0.001). LV mass index and E(m)/A(m) ratio were associated with FMD (p<0.001). In normotensive individuals with FT, LV morphological and functional changes were found. We demonstrated that an increase in LV mass and alterations in LV diastolic function are related to endothelial dysfunction.

Impact of HIV Infection on Diastolic Function and Left Ventricular Mass

PubMed Central

Hsue, Priscilla Y.; Hunt, Peter W.; Ho, Jennifer E.; Farah, Husam H.; Schnell, Amanda; Hoh, Rebecca; Martin, Jeffrey N.; Deeks, Steven G.; Bolger, Ann F.

2010-01-01

Background HIV patients have increased risk for cardiovascular disease, but the underlying mechanisms remain unknown. The purpose of this study was to determine the prevalence of echocardiographic abnormalities among asymptomatic HIV-infected individuals compared to HIV-uninfected individuals. Methods/Results We performed echocardiography in 196 HIV-infected adults and 52 controls. Left ventricular ejection fraction (LVEF), left ventricular mass indexed to the body surface area (LVMI), and diastolic function were assessed according to American Society of Echocardiography standards. LVMI was higher in HIV-infected patients (77.2g/m2 in HIV patients vs. 66.5g/m2 in controls, p<0.0001). LVEF was similar in both groups. Eight(4%) of the HIV patients had evidence of LV systolic dysfunction (defined as an EF<50%) versus none of the controls; 97(50%) had mild diastolic dysfunction compared to 29% of the HIV-uninfected subjects (p=0.008). After adjustment for hypertension and race, HIV-infected participants had a mean 8g/m2 larger LVMI compared to controls (p=0.001). Higher LVMI was independently associated with lower nadir CD4 T cell count, suggesting that immunodeficiency may play a role in this process. After adjustment for age and traditional risk factors, HIV patients had a 2.4 greater odds of having diastolic dysfunction as compared to controls (p=0.019). Conclusions HIV-infected patients had a higher prevalence of diastolic dysfunction and higher LVMI compared to controls. These differences were not readily explained by differences in traditional risk factors and were independently associated with HIV infection. These results suggest that contemporary asymptomatic HIV patients manifest mild functional and morphological cardiac abnormalities which are independently associated with HIV infection. PMID:19933410

Overweight female rats selectively breed for low aerobic capacity exhibit increased myocardial fibrosis and diastolic dysfunction

PubMed Central

Johnson, Megan S.; Ma, Lixin; Pulakat, Lakshmi; Mugerfeld, Irina; Hayden, Melvin R.; Garro, Mona; Knight, William; Britton, Steven L.; Koch, Lauren G.; Sowers, James R.

2012-01-01

The statistical association between endurance exercise capacity and cardiovascular disease suggests that impaired aerobic metabolism underlies the cardiovascular disease risk in men and women. To explore this connection, we applied divergent artificial selection in rats to develop low-capacity runner (LCR) and high-capacity runner (HCR) rats and found that disease risks segregated strongly with low running capacity. Here, we tested if inborn low aerobic capacity promotes differential sex-related cardiovascular effects. Compared with HCR males (HCR-M), LCR males (LCR-M) were overweight by 34% and had heavier retroperitoneal, epididymal, and omental fat pads; LCR females (LCR-F) were 20% heavier than HCR females (HCR-F), and their retroperitoneal, but not perireproductive or omental, fat pads were heavier as well. Unlike HCR-M, blood pressure was elevated in LCR-M, and this was accompanied by left ventricular (LV) hypertrophy. Like HCR-F, LCR-F exhibited normal blood pressure and LV weight as well as increased spontaneous cage activity compared with males. Despite normal blood pressures, LCR-F exhibited increased myocardial interstitial fibrosis and diastolic dysfunction, as indicated by increased LV stiffness, a decrease in the initial filling rate, and an increase in diastolic relaxation time. Although females exhibited increased arterial stiffness, ejection fraction was normal. Increased interstitial fibrosis and diastolic dysfunction in LCR-F was accompanied by the lowest protein levels of phosphorylated AMP-actived protein kinase [phospho-AMPK (Thr172)] and silent information regulator 1. Thus, the combination of risk factors, including female sex, intrinsic low aerobic capacity, and overweightness, promote myocardial stiffness/fibrosis sufficient to induce diastolic dysfunction in the absence of hypertension and LV hypertrophy. PMID:22345570

Effect of exercise on diastolic function in heart failure patients: a systematic review and meta-analysis.

PubMed

Pearson, M J; Mungovan, S F; Smart, N A

2017-03-01

Diastolic dysfunction contributes to the development and progression of heart failure. Conventional echocardiography and tissue Doppler imaging are widely utilised in clinical research providing a number of indices of diastolic function valuable in the diagnosis and prognosis of heart failure patients. The aim of this meta-analysis was to quantify the effect of exercise training on diastolic function in patients with heart failure. Exercise training studies that investigate different indices of diastolic function in patients with heart failure have reported that exercise training improves diastolic function in these patients. We sought to add to the current literature by quantifying, where possible, the effect of exercise training on diastolic function. We conducted database searches (PubMed, EBSCO, EMBASE, and Cochrane Trials Register to 31 July 2016) for exercise based rehabilitation trials in heart failure, using the search terms 'exercise training, diastolic function and diastolic dysfunction'. Data from six studies, with a total of 266 heart failure with reduced ejection fraction (HFrEF) participants, 144 in intervention groups and 122 in control groups, indicated a significant reduction in the ratio of early diastolic transmitral velocity (E) to early diastolic tissue velocity (E') (E/E' ratio) with exercise training, exercise vs. control mean difference (MD) of -2.85 (95% CI -3.66 to -2.04, p < 0.00001). Data from five studies in heart failure with preserved ejection fraction (HFpEF) patients, with a total of 204 participants, 115 in intervention groups and 89 in control groups, also demonstrated a significant improvement in E/E' in exercise vs. control MD of -2.38 (95% CI -3.47 to -1.28, p < 0.0001).

Burden of Systolic and Diastolic Left Ventricular Dysfunction among Hispanics in the United States: Insights from the Echocardiographic Study of Latinos (ECHO-SOL)

PubMed Central

Mehta, Hardik; Armstrong, Anderson; Swett, Katrina; Shah, Sanjiv J.; Allison, Matthew A.; Hurwitz, Barry; Bangdiwala, Shrikant; Dadhania, Rupal; Kitzman, Dalane W.; Arguelles, William; Lima, Joao; Youngblood, Marston; Schneiderman, Neil; Daviglus, Martha L.; Spevack, Daniel; Talavera, Greg A.; Raisinghani, Ajit; Kaplan, Robert; Rodriguez, Carlos J.

2016-01-01

Background Population-based estimates of cardiac dysfunction and clinical heart failure (HF) remain undefined among Hispanics/Latino adults. Methods and Results Participants of Hispanic/Latino origin across the US, aged 45–74 years were enrolled into the Echocardiographic Study of Latinos (ECHO-SOL) and underwent a comprehensive echocardiography exam to define left ventricular systolic dysfunction (LVSD) and left ventricular diastolic dysfunction (LVDD). Clinical HF was defined according to self-report; and those with cardiac dysfunction but without clinical HF were characterized as having subclinical or unrecognized cardiac dysfunction. Of 1,818 ECHO-SOL participants (mean age 56.4 years; 42.6% male) , 49.7% had LVSD and/or LVDD. LVSD prevalence was 3.6%, while LVDD was detected in 50.3%. Participants with LVSD were more likely to be males and current smokers (all p<0.05). Female sex, hypertension, diabetes, higher body-mass index and renal dysfunction were more common among those with LVDD (all p<0.05). In age-sex adjusted models, individuals of Central American and Cuban backgrounds were almost two-fold more likely to have LVDD compared to those of Mexican backgrounds. Prevalence of clinical HF with LVSD (HF with reduced EF) was 7.3%; prevalence of clinical HF with LVDD (HF with preserved EF) was 3.6%. 96.1% of the cardiac dysfunction seen was subclinical or unrecognized. Compared to those with clinical cardiac dysfunction, prevalent coronary heart disease was the only factor independently associated with subclinical or unrecognized cardiac dysfunction (odds ratio: 0.1; 95% confidence interval: 0.1–0.4). Conclusions Among Hispanics/Latinos, most cardiac dysfunction is subclinical or unrecognized, with a high prevalence of diastolic dysfunction. This identifies a high-risk population for the development of clinical HF. PMID:27048764

Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Corrigan, Neva M.; Shaw, Dennis. W. W.; Richards, Todd L.; Estes, Annette M.; Friedman, Seth D.; Petropoulos, Helen; Artru, Alan A.; Dager, Stephen R.

2012-01-01

Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ([superscript 1]HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally…

Cardiac DPP-4 inhibition by saxagliptin ameliorates isoproterenol-induced myocardial remodeling and cardiac diastolic dysfunction in rats.

PubMed

Ikeda, Junichi; Kimoto, Naoya; Kitayama, Tetsuya; Kunori, Shunji

2016-09-01

Saxagliptin, a potent and selective DPP-4 inhibitor, is characterized by its slow dissociation from DPP-4 and its long half-life and is expected to have a potent tissue membrane-bound DPP-4-inhibitory effect in various tissues. In the present study, we examined the effects of saxagliptin on in situ cardiac DPP-4 activity. We also examined the effects of saxagliptin on isoproterenol-induced the changes in the early stage such as, myocardial remodeling and cardiac diastolic dysfunction. Male SD rats treated with isoproterenol (1 mg/kg/day via osmotic pump) received vehicle or saxagliptin (17.5 mg/kg via drinking water) for 2 weeks. In situ cardiac DPP-4 activity was measured by a colorimetric assay. Cardiac gene expressions were examined and an echocardiographic analysis was performed. Saxagliptin treatment significantly inhibited in situ cardiac DPP-4 activity and suppressed isoproterenol-induced myocardial remodeling and the expression of related genes without altering the blood glucose levels. Saxagliptin also significantly ameliorated cardiac diastolic dysfunction in isoproterenol-treated rats. In conclusion, the inhibition of DPP-4 activity in cardiac tissue by saxagliptin was associated with suppression of myocardial remodeling and cardiac diastolic dysfunction independently of its glucose-lowering action in isoproterenol-treated rats. Cardiac DPP-4 activity may contribute to myocardial remodeling in the development of heart failure. Copyright © 2016 Kyowa Hakko Kirin Co.,Ltd. Production and hosting by Elsevier B.V. All rights reserved.

[Effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension].

PubMed

Ye, Ping-xian; Ye, Ping-zhen; Zhu, Jian-hua; Chen, Wei; Gao, Dan-chen

2014-05-01

To investigate the effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension. A randomized, double-blind, placebo-controlled prospective study was performed. Sixty patients with diastolic dysfunction (mitral flow velocity E/A <1) and exercise-induced hypertension (SBP>200 mm Hg) treated with atorvastatin (20 mg q.d) or placebo for 1 year. Cardiopulmonary exercise test and exercise blood pressure measurement were performed. Plasma B-natriuretic peptide (BNP) concentration at rest and at peak exercise, plasma high sensitive-C reaction protein (hs-CRP) and endothelin (ET) concentration were determined at baseline and after treatment. After treatment by atorvastatin, the resting SBP, pulse pressure, the peak exercise SBP and BNP were significantly decreased; and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were increased. All of these parameters had significant differences with baseline levels (P<0.05) and the rest pulse pressure, the peak exercise SBP and BNP, and the exercise time had significant differences compared with placebo treatment (P<0.05). Plasma concentrations of hs-CRP and ET were markedly reduced by atorvastatin treatment compared with baseline and placebo (P<0.05). No difference in above parameters was found before and after placebo treatment (P>0.05). In patients with diastolic dysfunction at rest and exercise-induced hypertension, atorvastatin can effectively reduce plasma hs-CRP and ET level, lower blood pressure and peak exercise SBP, decrease peak exercise plasma BNP concentration, and ultimately improve exercise tolerance.

Evaluation of left ventricular function in obese children without hypertension by a tissue Doppler imaging study

PubMed Central

Ghandi, Yazdan; Sharifi, Mehrzad; Habibi, Danial; Dorreh, Fatemeh; Hashemi, Mojtaba

2018-01-01

Background: The prevalence of obesity is increasing worldwide. Obese children without hypertension are becoming an important health challenge. Aims: Complications of obesity in adults are well established, but in obese children, cardiac dysfunction has not been reported clinically. Settings and Design: The present crosssectional study investigates subclinical systolic and diastolic dysfunction using echocardiographic modalities. Materials and Methods: Twentyfive youngsters with body mass index (BMI) >30 and 25 healthy children with BMI <25 were assigned into case and control group, respectively. In all participants, complete cardiovascular examination, electrocardiography, and echocardiography were fulfilled. Echocardiography surveys included standard, pulsed wave Doppler (PWD), and tissue Doppler imaging (TDI). Statistical Analysis Used: SPSS software, version 24. Results: The two groups were matched for age and sex. The resting heart rate and blood pressure were markedly higher in the obese group (P = 0.0001) though they were within the normal range in either category. Ejection fraction in the two groups was similar. Left ventricular (LV) mass (P = 0.0001), LV mass index (P = 0.029), left atrialtoaortic diameter ratio (P = 0.0001), and LV enddiastolic diameter (P = 0.008) were significantly greater in the case group, indicating cardiomegaly and subclinical systolic and diastolic dysfunction. Except for the aortic velocity, all PWD variables were considerably lower in the case group, suggesting subclinical diastolic dysfunction. All TDI parameters varied significantly between the two categories. There was a direct correlation between isovolumetric relaxation time and BMI. Conclusions: Obesity in children without hypertension is associated with subclinical systolic and diastolic cardiac dysfunction. We propose the evaluation of blood pressure as well as myocardial performance using PWD and TDI in all obese children without hypertension, regularly. PMID:29440827

Customized laboratory TLR4 and TLR2 detection method from peripheral human blood for early detection of doxorubicin-induced cardiotoxicity.

PubMed

Pop-Moldovan, A L; Trofenciuc, N-M; Dărăbanţiu, D A; Precup, C; Branea, H; Christodorescu, R; Puşchiţă, M

2017-05-01

Cancer treatments can have significant cardiovascular adverse effects that can cause cardiomyopathy and heart failure with reduced survival benefit and considerable decrease in the use of antineoplastic therapy. The purpose of this study is to assess the role of TLR2 and TLR4 gene expression as an early marker for the risk of doxorubicin-induced cardiomyopathy in correlation with early diastolic dysfunction in patients treated with doxorubicin. Our study included 25 consecutive patients who received treatment with doxorubicin for hematological malignancies (leukemia, lymphomas or multiple myeloma), aged 18-65 years, with a survival probability>6 months and with left ventricular ejection fraction>50%. Exclusion criteria consisted of the following: previous anthracycline therapy, previous radiotherapy, history of heart failure or chronic renal failure, atrial fibrillation, and pregnancy. In all patients, in fasting state, a blood sample was drawn for the assessment of TLR2 and TLR4 gene expression. Gene expression was assessed by quantitative reverse transcription PCR (qRT-PCR) using blood collection, RNA isolation, cDNA reverse transcription, qRT-PCR and quantification of the relative expression. At enrollment, all patients were evaluated clinically; an ECG and an echocardiography were performed. The average amount of gene expression units was 0.113 for TLR4 (range 0.059-0.753) and 0.218 for TLR2 (range 0.046-0.269). The mean mRNA extracted quantity was 113 571 ng/μl. As for the diastolic function parameters, criteria for diastolic dysfunction were present after 6 months in 16 patients (64%). In these patients, the mean values for TLR4 were 0.1198625 and for TLR2 were 0.16454 gene expression units. As for the diastolic function parameters, criteria for diastolic dysfunction were present after 6 months in 16 patients (64%). In these patients, the mean value for TLR2 was 0.30±0.19 and for TLR4 was 0.15±0.04. The corresponding values for the patients who did not develop diastolic dysfunction were 0.16±0.07 for TLR2 (P=0.01) and 0.11±0.10 for TLR4 (P=0.2). Our study suggests that TLR4 and TLR2 expression is higher in patients under doxorubicin therapy who develop diastolic dysfunction. This may suggest a predisposition to myocardial involvement, a higher sensitivity to doxorubicin cardiac effects.

The enemy in the mirror: self-perception-induced stress results in dissociation of psychological and physiological responses in patients with dissociative disorder

PubMed Central

Sattel, Heribert; Schmidt, Ulrike; Sack, Martin

2018-01-01

ABSTRACT Background: Patients suffering from dissociative disorders (DD) are characterized by an avoidance of aversive stimuli. Clinical experience has shown that DD patients typically avoid the confrontation with their own faces in a mirror (CFM). Objective: To investigate potential CFM-associated self-reported and psychophysiological stress reactions of DD patients, which most likely inform on the still unknown pathophysiology of dysfunctional self-perception in DD. Method: Eighteen DD patients and 18 healthy controls (HCs) underwent CFM. They were assessed for CFM-induced subjective self-reported stress, acute dissociative symptoms and sympathetic and parasympathetic drive using impedance cardiography. Results: DD patients experienced more subjective stress and acute dissociation than HCs upon CFM. Their psychological stress response did not activate the sympathetic and parasympathetic nervous system. Conclusions: In DD patients, CFM constitutes serious self-reported stress and is associated with a blunted autonomic reactivity. Therapeutic approaches promoting self-perception and self-compassion, in particular by using CFM, might serve as goal-oriented diagnostic and therapeutic tools in DD.

The enemy in the mirror: self-perception-induced stress results in dissociation of psychological and physiological responses in patients with dissociative disorder.

PubMed

Schäflein, Eva; Sattel, Heribert; Schmidt, Ulrike; Sack, Martin

2018-01-01

Background : Patients suffering from dissociative disorders (DD) are characterized by an avoidance of aversive stimuli. Clinical experience has shown that DD patients typically avoid the confrontation with their own faces in a mirror (CFM). Objective : To investigate potential CFM-associated self-reported and psychophysiological stress reactions of DD patients, which most likely inform on the still unknown pathophysiology of dysfunctional self-perception in DD. Method : Eighteen DD patients and 18 healthy controls (HCs) underwent CFM. They were assessed for CFM-induced subjective self-reported stress, acute dissociative symptoms and sympathetic and parasympathetic drive using impedance cardiography. Results : DD patients experienced more subjective stress and acute dissociation than HCs upon CFM. Their psychological stress response did not activate the sympathetic and parasympathetic nervous system. Conclusions : In DD patients, CFM constitutes serious self-reported stress and is associated with a blunted autonomic reactivity. Therapeutic approaches promoting self-perception and self-compassion, in particular by using CFM, might serve as goal-oriented diagnostic and therapeutic tools in DD.

The ACE/DD genotype is associated with the extent of exercise-induced left ventricular growth in endurance athletes.

PubMed

Hernández, Domingo; de la Rosa, Alejandro; Barragán, Antonio; Barrios, Ysamar; Salido, Eduardo; Torres, Armando; Martín, Basilio; Laynez, Ignacio; Duque, Amelia; De Vera, Antonia; Lorenzo, Victor; González, Antonio

2003-08-06

We studied the impact of the angiotensin-converting enzyme (ACE)/DD genotype on morphologic and functional cardiac changes in adult endurance athletes. Trained athletes usually develop adaptive left ventricular hypertrophy (LVH), and ACE gene polymorphisms may regulate myocardial growth. However, little is known about the impact of the ACE/DD genotype and D allele dose on the cardiac changes in adult endurance athletes. METHODS; Echocardiographic studies (including tissue Doppler) were performed in 61 male endurance athletes ranging in age from 25 to 40 years, with a similar period of training (15.6 +/- 4 h/week for 12.6 +/- 5.7 years). The ACE genotype (insertion [I] or deletion [D] alleles) was ascertained by polymerase chain reaction (DD = 27, ID = 31, and II = 3). Athletes with the DD genotype were compared with their ID counterparts. The DD genotype was associated with a higher left ventricular mass index (LVMI) than the ID genotype (162.6 +/- 36.5 g/m(2) vs. 141.6 +/- 34 g/m(2), p = 0.031), regardless of other confounder variables. As a result, 70.4% of DD athletes and only 42% of ID athletes met the criteria for LVH (p = 0.037). Although systolic and early diastolic myocardial velocities were similar in DD and ID subjects, a more prolonged E-wave deceleration time (DT) was observed in DD as compared with ID athletes, after adjusting for other biologic variables (210 +/- 48 ms vs. 174 +/- 36 ms, respectively; p = 0.008). Finally, a positive association between DT and myocardial systolic peak velocity (medial and lateral peak S(m)) was only observed in DD athletes (p = 0.013, r = 0.481). The ACE/DD genotype is associated with the extent of exercise-induced LVH in endurance athletes, regardless of other known biologic factors.

Evaluation of Daily Blood Pressure Alteration in Subclinical Hypothyroidism.

PubMed

Polat Canbolat, Ismail; Belen, Erdal; Bayyigit, Akif; Helvaci, Aysen; Kilickesmez, Kadriye

2017-09-01

Subclinical hypothyroidism is the most common thyroid dysfunction in the general population. The relationship between overt thyroid dysfunction and hypertension is generally understood. Besides high blood pressure, non-dipper hypertension is known to increase cardiovascular risk. Our aim is to investigate daily blood pressure changes and the frequency of non-dipping patterns in patients with subclinical hypothyroidism. Forty-nine patients without hypertension with subclinical hypothyroidism were compared with 50 healthy sex- and age-matched controls using ambulatory blood pressure monitoring. Thyroid-stimulating hormone (TSH) levels were significantly higher in the subclinic hypothyroidism group, and there was no difference between free triiodothyronine (FT3) and free thyroxine (FT4) levels which could be predicted as a result of the study design. Levels of mean diastolic, daytime diastolic, nighttime diastolic and nighttime systolic blood pressure were significantly higher in the subclinic hypothyroidism group (p = 0.001 for mean, daytime and nighttime diastolic and p = 0.01 for nighttime systolic). Diastolic non-dipping occurred more frequently in the subclinic hypothyroidism group [subclinical hypothyroidism group 24 patients (49%), control group 13 patients (26%), p = 0.01]. On multivariate analysis, subclinical hypothyroidism was independently associated with diastolic non-dipping (95% confidence interval 1.162-8.053, odds ratio 1.182, p = 0.024). Our study found that both the frequency of diastolic non-dipping pattern and diastolic blood pressure increase with subclinical hypothyroidism. Therfore, it would appear that searching for non-dipping pattern can add valuable information for patients with subclinical hypothyroidism.

Computational modelling of left-ventricular diastolic mechanics: effect of fibre orientation and right-ventricle topology.

PubMed

Palit, Arnab; Bhudia, Sunil K; Arvanitis, Theodoros N; Turley, Glen A; Williams, Mark A

2015-02-26

Majority of heart failure patients who suffer from diastolic dysfunction retain normal systolic pump action. The dysfunction remodels the myocardial fibre structure of left-ventricle (LV), changing its regular diastolic behaviour. Existing LV diastolic models ignored the effects of right-ventricular (RV) deformation, resulting in inaccurate strain analysis of LV wall during diastole. This paper, for the first time, proposes a numerical approach to investigate the effect of fibre-angle distribution and RV deformation on LV diastolic mechanics. A finite element modelling of LV passive inflation was carried out, using structure-based orthotropic constitutive law. Rule-based fibre architecture was assigned on a bi-ventricular (BV) geometry constructed from non-invasive imaging of human heart. The effect of RV deformation on LV diastolic mechanics was investigated by comparing the results predicted by BV and single LV model constructed from the same image data. Results indicated an important influence of RV deformation which led to additional LV passive inflation and increase of average fibre and sheet stress-strain in LV wall during diastole. Sensitivity of LV passive mechanics to the changes in the fibre distribution was also examined. The study revealed that LV diastolic volume increased when fibres were aligned more towards LV longitudinal axis. Changes in fibre angle distribution significantly altered fibre stress-strain distribution of LV wall. The simulation results strongly suggest that patient-specific fibre structure and RV deformation play very important roles in LV diastolic mechanics and should be accounted for in computational modelling for improved understanding of the LV mechanics under normal and pathological conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Understanding heart failure].

PubMed

Boo, José Fernando Guadalajara

2006-01-01

Heart failure is a disease with several definitions. The term "heart failure" is used by has brougth about confusion in the terminology. For this reason, the value of the ejection fraction (< 0.40 or < 0.35) is used in most meganalyses on the treatment of heart failure, avoiding the term "heart failure" that is a confounding concept. In this paper we carefully analyze the meaning of contractility, ventricular function or performance, preload, afterload, heart failure, compensation mechanisms in heart failure, myocardial oxygen consumption, inadequate, adequate and inappropriate hypertrophy, systole, diastole, compliance, problems of relaxation, and diastolic dysfunction. Their definitions are supported by the original scientific descriptions in an attempt to clarify the concepts about ventricular function and heart failure and, in this way, use the same scientific language about the meaning of ventricular function, heart failure, and diastolic dysfunction.

Churg-Strauss syndrome associated with rapid deterioration of left ventricular diastolic dysfunction and conduction disturbance.

PubMed

Chin, Jung Yeon; Yi, Jeong Eun; Youn, Ho-Joong

2013-10-01

Cardiac involvement in Churg-Strauss syndrome (CSS) is a major cause of mortality. Here we report a case of a 75-year-old woman with eosinophilic endomyocarditis due to CSS. An electrocardiogram showed intraventricular conduction delay, and echocardiography showed an impaired relaxation pattern and biventricular apical thickening. Magnetic resonance imaging revealed subendocardial delayed enhancement with biventricular apical thrombi. Endomyocardial biopsy showed perivascular eosinophilic infiltration. Despite resolution of the hypereosinophilia after steroid therapy, her left ventricular (LV) diastolic function worsened into a restrictive pattern and she died with a ventricular escape rhythm on her 14th day in the hospital. This case is unusual in that there was rapid progression of the LV diastolic dysfunction and conduction disturbance due to CSS. © 2013, Wiley Periodicals, Inc.

Calorie restriction attenuates cardiac remodeling and diastolic dysfunction in a rat model of metabolic syndrome.

PubMed

Takatsu, Miwa; Nakashima, Chieko; Takahashi, Keiji; Murase, Tamayo; Hattori, Takuya; Ito, Hiromi; Murohara, Toyoaki; Nagata, Kohzo

2013-11-01

Calorie restriction (CR) can modulate the features of obesity-related metabolic and cardiovascular diseases. We have recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome. DS/obese rats develop hypertension and manifest left ventricular remodeling and diastolic dysfunction, as well as increased cardiac oxidative stress and inflammation. We have now investigated the effects of CR on cardiac pathophysiology in DS/obese rats. DS/obese rats were fed either normal laboratory chow ad libitum or a calorie-restricted diet (65% of the average food intake for ad libitum) from 9 to 13 weeks. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+) or DS/lean) littermates served as controls. CR reduced body weight in both DS/obese and DS/lean rats, as well as attenuated the development of hypertension in DS/obese rats without affecting blood pressure in DS/lean rats. CR also reduced body fat content, ameliorated left ventricular hypertrophy, fibrosis, and diastolic dysfunction, and attenuated cardiac oxidative stress and inflammation in DS/obese rats. In addition, it increased serum adiponectin concentration, as well as downregulated the expression of angiotensin-converting enzyme and angiotensin II type 1A receptor genes in the heart of DS/obese rats. Our results thus show that CR attenuated obesity and hypertension, as well as left ventricular remodeling and diastolic dysfunction in DS/obese rats, with these latter effects being associated with reduced cardiac oxidative stress and inflammation.

Common presentation of rare diseases: Left ventricular hypertrophy and diastolic dysfunction.

PubMed

Linhart, Ales; Cecchi, Franco

2018-04-15

Left ventricular hypertrophy may be a consequence of a hemodynamic overload or a manifestation of several diseases affecting different structural and functional proteins of cardiomyocytes. Among these, sarcomeric hypertrophic cardiomyopathy (HCM) represents the most frequent cause. In addition, several metabolic diseases lead to myocardial thickening, either due to intracellular storage (glycogen storage and lysosomal diseases), extracellular deposition (TTR and AL amyloidosis) or due to abnormal energy metabolism (mitochondrial diseases). The recognition of these rare causes of myocardial hypertrophy is important for family screening strategies, risk assessment, and treatment. Moreover, as there are specific therapies for some forms of HCM including enzyme substitution and chaperone therapies and specific treatments for TTR amyloidosis, a differential diagnosis should be sought in all patients with unexplained left ventricular hypertrophy. Diastolic dysfunction is a key feature of HCM and its phenocopies. Its assessment is complex and requires evaluation of several functional parameters and structural changes. Severe diastolic dysfunction carries a negative prognostic implication and its value in differential diagnosis is limited. Copyright © 2018 Elsevier B.V. All rights reserved.

Physical health correlates of pathological and healthy dependency in urban women.

PubMed

Porcerelli, John H; Bornstein, Robert F; Markova, Tsveti; Huprich, Steven K

2009-10-01

This study assessed the relationship between dependency and indicators of health/illness, healthcare costs, and utilization. Dependency ratings were obtained using the Relationship Profile Test (Bornstein and Languirand, 2003), a questionnaire that assesses healthy and pathological dependency: destructive overdependence (DO), dysfunctional detachment (DD), and healthy dependency (HD). The sample consisted of primarily low-income, African-American, and female primary care patients (N = 110). DO and DD were significantly associated with indices of increased illness, with DO evidencing slightly larger effect sizes than DD. HD was significantly (negatively) associated with 1 health/illness variable. DD and DO were associated with higher total outpatient costs with DD also being associated with average costs per visit. DO and HD were associated with utilization (increased hospital days and fewer emergency room visits, respectively). Further research is recommended to inform researchers and clinicians about the dependency-illness relationship and to develop interventions that maximize HD and minimize pathological dependency.

Effect of well-controlled gestational diabetes on left ventricular diastolic dysfunction in neonates.

PubMed

Ghandi, Yazdan; Habibi, Danial; Nasri, Khadijeh; Alinejad, Saeed; Taherahmad, Hassan; Arjmand Shabestari, Ali; Nematinejad, Ali

2018-06-17

There are some evidences supporting the relation between gestational diabetes mellitus (GDM) and diastolic dysfunction. The aim of our study was to investigate the effect of well-controlled GDM on morphological and functional myocardium. We designed a prospective cross-sectional study to evaluate left ventricular (LV) diastolic function of 60 neonates born from mothers with well-controlled GDM (case group) on days of 3-5 after birth. The infants of diabetic mothers (IDM) group were divided into two groups: diabetic mothers treated only with diet (class A) and group of mothers on medical therapy by insulin or metformin (class B). Traditional echocardiography and pulsed-wave Doppler (PWD), tissue Doppler imaging (TDI) were performed for all the neonates. The study group consisted of 60 neonates as males (M) = 32, (0.53%) and females (F) = 28, (0.46%). Using M-mode echocardiography, interventricular septum thickness (IVS), and LV mass were significantly higher in IDM than control group (p = .0001). The PWD showed both a significantly more peak mitral flow at early diastolic wave (E) and an early filling deceleration time (E-DT) (p = .0001). Tissue Doppler echocardiography parameters A' (cm/s) (p = .0001), E' (cm/s) (p = .002), and E'/A' ratio (p = .0001), left ventricular myocardial performance index (LVMPI), and isovolumetric relaxation time (IVRT) were outstandingly different between the two groups (p = .0001, respectively). Evaluating the GDM group mothers of class A and class B, no significant difference was noted in PWD or TDI parameters compared with the healthy ones. It seems that neonates of mothers with well-controlled GDM are still at increased risk of cardiac hypertrophy, subclinical diastolic dysfunction, and impaired left ventricular relaxation. This can be interpreted that focusing only on glycemic control is not enough to prevent cardiac dysfunction.

Fenestrated Transcatheter ASD Closure in Adults with Diastolic Dysfunction and/or Pulmonary Hypertension: Case Series and Review of the Literature.

PubMed

Abdelkarim, Ayman; Levi, Daniel S; Tran, Bao; Ghobrial, Joanna; Aboulhosn, Jamil

2016-12-01

This study aims to evaluate the safety and efficacy of transcatheter fenestrated ASD closure and to summarize the literature regarding the published techniques and outcomes of transcatheter partial ASD closure. Patients with left ventricular diastolic dysfunction (LVDD) or right ventricular (RV) dysfunction and/or pulmonary hypertension (PHT) may suffer untoward consequences of complete closure of an ostium secundum atrial septal defect (ASD). Therefore, for patients that fall under these categories we suggest partial occlusion of the defect, which may be better tolerated than complete defect closure. After obtaining IRB approval, a search for patients that have undergone percutaneous ASD closure was performed in the Ahmanson/UCLA Adult Congenital Heart Disease Center database to identify which patients received a fenestrated ASD closure device. Eight consecutive patients ranging between 22 and 83 years of age (mean 48 years) with PHT and/or LVDD or RV dysfunction who underwent fenestrated transcatheter ASD closure at UCLA were identified. None of the subjects experienced complications related to the procedure. Postprocedure clinical evaluation showed improvement in symptoms and exercise capacity. Available follow-up transthoracic echocardiography data (mean 4 months, range 0-20 months) demonstrated patent fenestrations in four of eight patients. None of the patients had thromboembolic or infectious complications and there were no device migrations, erosions or embolizations. Partial ASD occlusion in patients with diastolic dysfunction or RV dysfunction and/or PHT is safe and may be better tolerated than complete ASD closure in selected patients. © 2016 Wiley Periodicals, Inc.

Right Heart Vorticity and Right Ventricular Diastolic Dysfunction

NASA Astrophysics Data System (ADS)

Browning, James; Hertzberg, Jean; Fenster, Brett; Schroeder, Joyce

2015-11-01

Recent advances in cardiac magnetic resonance imaging (CMR) have allowed for the 3-dimensional characterization of blood flow in the right ventricle (RV) and right atrium (RA). In this study, we investigate and quantify differences in the characteristics of coherent rotating flow structures (vortices) in the RA and RV between subjects with right ventricular diastolic dysfunction (RVDD) and normal controls. Fifteen RVDD subjects and 10 age-matched controls underwent same day 3D time resolved CMR and echocardiography. Echocardiography was used to determine RVDD stage as well as pulmonary artery systolic pressure (PASP). CMR data was used for RA and RV vortex quantification and visualization during early ventricular diastole and the results are compared between healthy subjects and those with RVDD. The resulting trends are discussed and hypotheses are presented regarding differences in vortex characteristics between healthy and RVDD subjects cohorts.

Effects of cardiac energy efficiency in diastolic heart failure: assessment with positron emission tomography with 11C-acetate.

PubMed

Hasegawa, Shinji; Yamamoto, Kazuhiro; Sakata, Yasushi; Takeda, Yasuharu; Kajimoto, Katsufumi; Kanai, Yasukazu; Hori, Masatsugu; Hatazawa, Jun

2008-06-01

Diastolic heart failure (DHF) has become a high social burden, and its major underlying cardiovascular disease is hypertensive heart disease. However, the pathogenesis of DHF remains to be clarified. This study aimed to assess the effects of cardiac energy efficiency in DHF patients. (11)C-Acetate positron emission tomography and echocardiography were conducted in 11 DHF Japanese patients and 10 normal volunteers. The myocardial clearance rate of radiolabeled (11)C-acetate was measured to calculate the work metabolic index (WMI), an index of cardiac efficiency. The ratio of peak mitral E wave velocity to peak early diastolic septal myocardial velocity (E/e') was calculated to assess left ventricular (LV) filling pressure. The LV mass index was greater and the mean age was higher in the DHF patients than in the normal volunteers. There was no difference in WMI between the two groups. However, WMI varied widely among the DHF patients and was inversely correlated with E/e' (r=-0.699, p=0.017). In contrast, there was no correlation in the normal volunteers. In conclusion, the inefficiency of energy utilization is not a primary cause of diastolic dysfunction or DHF, and cardiac efficiency may not affect diastolic function in normal hearts. However, the energy-wasting state may induce the elevation of LV filling pressure in DHF patients, which was considered to principally result from the progressive diastolic dysfunction.

A functional genetic variant (N521D) in natriuretic peptide receptor 3 is associated with diastolic dysfunction: the prevalence of asymptomatic ventricular dysfunction study.

PubMed

Pereira, Naveen L; Redfield, Margaret M; Scott, Christopher; Tosakulwong, Nirubol; Olson, Timothy M; Bailey, Kent R; Rodeheffer, Richard J; Burnett, John C

2014-01-01

To evaluate the impact of a functional genetic variant in the natriuretic peptide clearance receptor, NPR3, on circulating natriuretic peptides (NPs) and myocardial structure and function in the general community. NPR3 plays an important role in the clearance of NPs and through direct signaling mechanisms modulates smooth muscle cell function and cardiac fibroblast proliferation. A NPR3 nonsynonymous single nucleotide polymorphism (SNP) rs2270915, resulting in a N521D substitution in the intracellular catalytic domain that interacts with Gi could affect receptor function. Whether this SNP is associated with alterations in NPs levels and altered cardiac structure and function is unknown. DNA samples of 1931 randomly selected residents of Olmsted County, Minnesota were genotyped. Plasma NT-proANP1-98, ANP1-28, proBNP1-108, NT-proBNP1-76, BNP1-32 and BNP3-32 levels were measured. All subjects underwent comprehensive echocardiography. Genotype frequencies for rs2270915 were as follows: (A/A 60%, A/G 36%, G/G 4%). All analyses performed were for homozygotes G/G versus wild type A/A plus the heterozygotes A/G. Diastolic dysfunction was significantly more common (p = 0.007) in the homozygotes G/G (43%) than the A/A+A/G (28%) group. Multivariate regression adjusted for age, sex, body mass index and hypertension demonstrated rs2270915 to be independently associated with diastolic dysfunction (odds ratio 1.94, p = 0.03). There was no significant difference in NPs levels between the 2 groups suggesting that the clearance function of the receptor was not affected. A nonsynonymous NPR3 SNP is independently associated with diastolic dysfunction and this association does not appear to be related to alterations in circulating levels of natriuretic peptides.

Urinary type IV collagen is related to left ventricular diastolic function and brain natriuretic peptide in hypertensive patients with prediabetes.

PubMed

Iida, Masato; Yamamoto, Mitsuru; Ishiguro, Yuko S; Yamazaki, Masatoshi; Ueda, Norihiro; Honjo, Haruo; Kamiya, Kaichirou

2014-01-01

Urinary type IV collagen is an early biomarker of diabetic nephropathy. Concomitant prediabetes (the early stage of diabetes) was associated with left ventricular (LV) diastolic dysfunction and increased brain natriuretic peptide (BNP) in hypertensive patients. We hypothesized that urinary type IV collagen may be related to these cardiac dysfunctions. We studied hypertensive patients with early prediabetes (HbA1c <5.7% and fasting glucose >110, n=18), those with prediabetes (HbA1c 5.7-6.4, n=98), and those with diabetes (HbA1c>6.5 or on diabetes medications, n=92). The participants underwent echocardiography to assess left atrial volume/body surface area (BSA) and the ratio of early mitral flow velocity to mitral annular velocity (E/e'). Left ventricular diastolic dysfunction (LVDD) was defined if patients had E/e'≥15, or E/e'=9-14 accompanied by left atrial volume/BSA≥32ml/mm(2). Urinary samples were collected for type IV collagen and albumin, and blood samples were taken for BNP and HbA1c. Urinary type IV collagen and albumin increased in parallel with the deterioration of glycemic status. In hypertensive patients with prediabetes, subjects with LVDD had higher levels of BNP and urinary type IV collagen than those without LVDD. In contrast, in hypertensive patients with diabetes, subjects with LVDD had higher urinary albumin and BNP than those without LVDD. Urinary type IV collagen correlated positively with BNP in hypertensive patients with prediabetes, whereas it correlated with HbA1c in those with diabetes. In hypertensive patients with prediabetes, urinary type IV collagen was associated with LV diastolic dysfunction and BNP. Copyright © 2014 Elsevier Inc. All rights reserved.

Pharmacologic inhibition of the enzymatic effects of tissue transglutaminase reduces cardiac fibrosis and attenuates cardiomyocyte hypertrophy following pressure overload.

PubMed

Shinde, Arti V; Su, Ya; Palanski, Brad A; Fujikura, Kana; Garcia, Mario J; Frangogiannis, Nikolaos G

2018-04-01

Tissue transglutaminase (tTG) is a multifunctional protein with a wide range of enzymatic and non-enzymatic functions. We have recently demonstrated that tTG expression is upregulated in the pressure-overloaded myocardium and exerts fibrogenic actions promoting diastolic dysfunction, while preventing chamber dilation. Our current investigation dissects the in vivo and in vitro roles of the enzymatic effects of tTG on fibrotic remodeling in pressure-overloaded myocardium. Using a mouse model of transverse aortic constriction, we demonstrated perivascular and interstitial tTG activation in the remodeling pressure-overloaded heart. tTG inhibition through administration of the selective small molecule tTG inhibitor ERW1041E attenuated left ventricular diastolic dysfunction and reduced cardiomyocyte hypertrophy and interstitial fibrosis in the pressure-overloaded heart, without affecting chamber dimensions and ejection fraction. In vivo, tTG inhibition markedly reduced myocardial collagen mRNA and protein levels and attenuated transcription of fibrosis-associated genes. In contrast, addition of exogenous recombinant tTG to fibroblast-populated collagen pads had no significant effects on collagen transcription, and instead increased synthesis of matrix metalloproteinase (MMP)3 and tissue inhibitor of metalloproteinases (TIMP)1 through transamidase-independent actions. However, enzymatic effects of matrix-bound tTG increased the thickness of pericellular collagen in fibroblast-populated pads. tTG exerts distinct enzymatic and non-enzymatic functions in the remodeling pressure-overloaded heart. The enzymatic effects of tTG are fibrogenic and promote diastolic dysfunction, but do not directly modulate the pro-fibrotic transcriptional program of fibroblasts. Targeting transamidase-dependent actions of tTG may be a promising therapeutic strategy in patients with heart failure and fibrosis-associated diastolic dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Diagnostic Value of Pulsed Wave Tissue Doppler Imaging in Asymptomatic Beta- Thalassemia Major Children and Young Adults; Relation to Chemical Biomarkers of Left Ventricular Function and Iron Overload

PubMed Central

Ragab, Seham M; Fathy, Waleed M; El-Aziz, Walaa FAbd; Helal, Rasha T

2015-01-01

Background Cardiac iron toxicity is the leading cause of death among β-halassaemia major (TM) patients. Once heart failure becomes overt, it is difficult to reverse. Objectives To investigate non-overt cardiac dysfunctions in TM patients using pulsed wave Tissue Doppler Imaging (TD I) and its relation to iron overload and brain natriuretic peptide (BNP). Methods Thorough clinical, conventional echo and pulsed wave TDI parameters were compared between asymptomatic 25 β-TM patients and 20 age and gender matched individuals. Serum ferritin and plasma BNP levels were assayed by ELISA. Results TM patients had significant higher mitral inflow early diastolic (E) wave and non significant other conventional echo parameters. In the patient group, pulsed wave TDI revealed systolic dysfunctions, in the form of significant higher isovolumetric contraction time (ICT), and lower ejection time (E T), with diastolic dysfunction in the form of higher isovolumetric relaxation time (IRT), and lower mitral annulus early diastolic velocity E′ (12.07 ±2.06 vs 15.04±2.65, P= 0.003) compared to the controls. Plasma BNP was higher in patients compared to the controls. Plasma BNP and serum ferritin had a significant correlation with each other and with pulsed wave conventional and TDI indices of systolic and diastolic functions. Patients with E/E′ ≥ 8 had significant higher serum ferritin and plasma BNP levels compared to those with ratio < 8 without a difference in Hb levels. Conclusion Pulsed wave TDI is an important diagnostic tool for latent cardiac dysfunction in iron-loaded TM patients and is related to iron overload and BNP. PMID:26401240

Carbonylation Contributes to SERCA2a Activity Loss and Diastolic Dysfunction in a Rat Model of Type 1 Diabetes

PubMed Central

Shao, Chun Hong; Capek, Haley L.; Patel, Kaushik P.; Wang, Mu; Tang, Kang; DeSouza, Cyrus; Nagai, Ryoji; Mayhan, William; Periasamy, Muthu; Bidasee, Keshore R.

2011-01-01

OBJECTIVE Approximately 25% of children and adolescents with type 1 diabetes will develop diastolic dysfunction. This defect, which is characterized by an increase in time to cardiac relaxation, results in part from a reduction in the activity of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a), the ATP-driven pump that translocates Ca2+ from the cytoplasm to the lumen of the sarcoplasmic reticulum. To date, mechanisms responsible for SERCA2a activity loss remain incompletely characterized. RESEARCH DESIGN AND METHODS The streptozotocin (STZ)-induced murine model of type 1 diabetes, in combination with echocardiography, high-speed video detection, confocal microscopy, ATPase and Ca2+ uptake assays, Western blots, mass spectrometry, and site-directed mutagenesis, were used to assess whether modification by reactive carbonyl species (RCS) contributes to SERCA2a activity loss. RESULTS After 6–7 weeks of diabetes, cardiac and myocyte relaxation times were prolonged. Total ventricular SERCA2a protein remained unchanged, but its ability to hydrolyze ATP and transport Ca2+ was significantly reduced. Western blots and mass spectroscopic analyses revealed carbonyl adducts on select basic residues of SERCA2a. Mutating affected residues to mimic physio-chemical changes induced on them by RCS reduced SERCA2a activity. Preincubating with the RCS, methylglyoxal (MGO) likewise reduced SERCA2a activity. Mutating an impacted residue to chemically inert glutamine did not alter SERCA2a activity, but it blunted MGO's effect. Treating STZ-induced diabetic animals with the RCS scavenger, pyridoxamine, blunted SERCA2a activity loss and minimized diastolic dysfunction. CONCLUSIONS These data identify carbonylation as a novel mechanism that contributes to SERCA2a activity loss and diastolic dysfunction during type 1 diabetes. PMID:21300842

Uric acid predicts mortality and ischaemic stroke in subjects with diastolic dysfunction: the Tromsø Study 1994-2013.

PubMed

Norvik, Jon V; Schirmer, Henrik; Ytrehus, Kirsti; Storhaug, Hilde M; Jenssen, Trond G; Eriksen, Bjørn O; Mathiesen, Ellisiv B; Løchen, Maja-Lisa; Wilsgaard, Tom; Solbu, Marit D

2017-05-01

To investigate whether serum uric acid predicts adverse outcomes in persons with indices of diastolic dysfunction in a general population. We performed a prospective cohort study among 1460 women and 1480 men from 1994 to 2013. Endpoints were all-cause mortality, incident myocardial infarction, and incident ischaemic stroke. We stratified the analyses by echocardiographic markers of diastolic dysfunction, and uric acid was the independent variable of interest. Hazard ratios (HR) were estimated per 59 μmol/L increase in baseline uric acid. Multivariable adjusted Cox proportional hazards models showed that uric acid predicted all-cause mortality in subjects with E/A ratio <0.75 (HR 1.12, 95% confidence interval [CI] 1.00-1.25) or E/A ratio >1.5 (HR 1.51, 95% CI 1.09-2.09, P for interaction between E/A ratio category and uric acid = 0.02). Elevated uric acid increased mortality risk in persons with E-wave deceleration time <140 ms or >220 ms (HR 1.46, 95% CI 1.01-2.12 and HR 1.13, 95% CI 1.02-1.26, respectively; P for interaction = 0.04). Furthermore, in participants with isovolumetric relaxation time ≤60 ms, mortality risk was higher with increasing uric acid (HR 4.98, 95% CI 2.02-12.26, P for interaction = 0.004). Finally, elevated uric acid predicted ischaemic stroke in subjects with severely enlarged left atria (HR 1.62, 95% CI 1.03-2.53, P for interaction = 0.047). Increased uric acid was associated with higher all-cause mortality risk in subjects with echocardiographic indices of diastolic dysfunction, and with higher ischaemic stroke risk in persons with severely enlarged left atria.

The Diagnostic Value of Pulsed Wave Tissue Doppler Imaging in Asymptomatic Beta- Thalassemia Major Children and Young Adults; Relation to Chemical Biomarkers of Left Ventricular Function and Iron Overload.

PubMed

Ragab, Seham M; Fathy, Waleed M; El-Aziz, Walaa FAbd; Helal, Rasha T

2015-01-01

Cardiac iron toxicity is the leading cause of death among β-halassaemia major (TM) patients. Once heart failure becomes overt, it is difficult to reverse. To investigate non-overt cardiac dysfunctions in TM patients using pulsed wave Tissue Doppler Imaging (TD I) and its relation to iron overload and brain natriuretic peptide (BNP). Thorough clinical, conventional echo and pulsed wave TDI parameters were compared between asymptomatic 25 β-TM patients and 20 age and gender matched individuals. Serum ferritin and plasma BNP levels were assayed by ELISA. TM patients had significant higher mitral inflow early diastolic (E) wave and non significant other conventional echo parameters. In the patient group, pulsed wave TDI revealed systolic dysfunctions, in the form of significant higher isovolumetric contraction time (ICT), and lower ejection time (E T), with diastolic dysfunction in the form of higher isovolumetric relaxation time (IRT), and lower mitral annulus early diastolic velocity E' (12.07 ±2.06 vs 15.04±2.65, P= 0.003) compared to the controls. Plasma BNP was higher in patients compared to the controls. Plasma BNP and serum ferritin had a significant correlation with each other and with pulsed wave conventional and TDI indices of systolic and diastolic functions. Patients with E/E' ≥ 8 had significant higher serum ferritin and plasma BNP levels compared to those with ratio < 8 without a difference in Hb levels. Pulsed wave TDI is an important diagnostic tool for latent cardiac dysfunction in iron-loaded TM patients and is related to iron overload and BNP.

Significance of left ventricular diastolic function on outcomes after surgical ventricular restoration.

PubMed

Marui, Akira; Nishina, Takeshi; Saji, Yoshiaki; Yamazaki, Kazuhiro; Shimamoto, Takeshi; Ikeda, Tadashi; Sakata, Ryuzo

2010-05-01

Surgical ventricular restoration (SVR) has been introduced to restore the dilated left ventricular (LV) chamber and improve LV systolic function; however, SVR has also been reported to detrimentally affect LV diastolic properties. We sought to investigate the impact of preoperative LV diastolic function on outcomes after SVR in patients with heart failure. Sixty-seven patients (60 +/- 14 years) with LV systolic dysfunction (LV ejection fraction, 0.27 +/- 0.10) underwent SVR. They were evaluated by echocardiography preoperatively, and early (

Arterial stiffness and wave reflection: sex differences and relationship with left ventricular diastolic function.

PubMed

Russo, Cesare; Jin, Zhezhen; Palmieri, Vittorio; Homma, Shunichi; Rundek, Tatjana; Elkind, Mitchell S V; Sacco, Ralph L; Di Tullio, Marco R

2012-08-01

Increased arterial stiffness and wave reflection have been reported in heart failure with normal ejection fraction (HFNEF) and in asymptomatic left ventricular (LV) diastolic dysfunction, a precursor of HFNEF. It is unclear whether women, who have higher frequency of HFNEF, are more vulnerable than men to the deleterious effects of arterial stiffness on LV diastolic function. We investigated, in a large community-based cohort, whether sex differences exist in the relationship among arterial stiffness, wave reflection, and LV diastolic function. Arterial stiffness and wave reflection were assessed in 983 participants from the Cardiovascular Abnormalities and Brain Lesions study using applanation tonometry. The central pulse pressure/stroke volume index, total arterial compliance, pulse pressure amplification, and augmentation index were used as parameters of arterial stiffness and wave reflection. LV diastolic function was evaluated by 2-dimensional echocardiography and tissue-Doppler imaging. Arterial stiffness and wave reflection were greater in women compared with men, independent of body size and heart rate (all P<0.01), and showed inverse relationships with parameters of diastolic function in both sexes. Further adjustment for cardiovascular risk factors attenuated these relationships; however, a higher central pulse pressure/stroke volume index predicted LV diastolic dysfunction in women (odds ratio, 1.54; 95% confidence intervals, 1.03 to 2.30) and men (odds ratio, 2.09; 95% confidence interval, 1.30 to 3.39), independent of other risk factors. In conclusion, in our community-based cohort study, higher arterial stiffness was associated with worse LV diastolic function in men and women. Women's higher arterial stiffness, independent of body size, may contribute to their greater susceptibility to develop HFNEF.

Long-term outcome of patients with triphasic mitral flow with a mid-diastolic L wave: prognostic role of left atrial volume and N-terminal pro-brain natriuretic peptide.

PubMed

Kim, Sung-Ai; Son, Jungwoo; Shim, Chi-Young; Choi, Eui-Young; Ha, Jong-Won

2017-09-01

A mid-diastolic L wave has been recognized as a marker of advanced left ventricular (LV) diastolic dysfunction. However, its prognostic implication is unclear. This study assessed long-term prognosis and independent predictors of adverse outcomes in patients with a mid-diastolic L wave. A total of 144 consecutive patients (mean age 63 ± 12 years, 88 female) with a mid-diastolic L wave of ≥0.2 m/s and in sinus rhythm were identified. Patients with significant valvular heart disease, low LV ejection fraction and arrhythmias were excluded. Subjects were followed up for cardiovascular (CV) mortality and hospitalization for heart failure (HF). During follow-up for a median of 44 months (1-76), CV deaths and hospitalization for HF occurred in 41 (28%) patients. In multivariate Cox analysis, age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.11; p = 0.001), log N-terminal pro-brain natriuretic peptide (NT-proBNP)(HR 3.81; 95% CI 1.78-8.15; p = 0.001), and left atrial volume index (HR 1.02; 95% CI 1.01-1.04; p = 0.019) were independent predictors of adverse outcomes in patients with a mid-diastolic L wave. In a stepwise model, NT-proBNP showed an incremental prognostic value for prediction of adverse outcomes when added to the clinical and echocardiographic parameters (Chi square from 30.1 to 41.1, p < 0.001). Patients with a mid-diastolic L wave and clinical, biochemical, and echocardiographic evidence of advanced diastolic dysfunction showed poor long-term clinical outcome.

Interplay between arterial stiffness and diastolic function: a marker of ventricular-vascular coupling.

PubMed

Zito, Concetta; Mohammed, Moemen; Todaro, Maria Chiara; Khandheria, Bijoy K; Cusmà-Piccione, Maurizio; Oreto, Giuseppe; Pugliatti, Pietro; Abusalima, Mohamed; Antonini-Canterin, Francesco; Vriz, Olga; Carerj, Scipione

2014-11-01

We evaluated the interplay between left ventricular diastolic function and large-artery stiffness in asymptomatic patients at increased risk of heart failure and no structural heart disease (Stage A). We divided 127 consecutive patients (mean age 49 ± 17 years) with risk factors for heart failure who were referred to our laboratory to rule out structural heart disease into two groups according to presence (Group 1, n = 35) or absence (Group 2, n = 92) of grade I left ventricular diastolic dysfunction. Doppler imaging with high-resolution echo-tracking software was used to measure intima-media thickness (IMT) and stiffness of carotid arteries. Group 1 had significantly higher mean age, blood pressure, left ventricular mass index, carotid IMT and arterial stiffness than Group 2 (P < 0.05). Overall, carotid stiffness indices (β-stiffness index, augmentation index and elastic modulus) and 'one-point' pulse wave velocity each showed inverse correlation with E-wave velocity, E' velocity and E/A ratio, and direct correlation with A-wave velocity, E-wave deceleration time and E/E' ratio (P < 0.05). Arterial compliance showed negative correlations with the echocardiographic indices of left ventricular diastolic function (P < 0.05). On logistic regression analysis, age, hypertension, SBP, pulse pressure, left ventricular mass index, carotid IMT and stiffness parameters were associated with grade I left ventricular diastolic dysfunction (P < 0.05 for each). However, on multivariate logistic analysis, only 'one-point' pulse wave velocity and age were independent predictors (P = 0.038 and P = 0.016, respectively). An independent association between grade I left ventricular diastolic dysfunction and increased arterial stiffness is demonstrated at the earliest stage of heart failure. Hence, assessment of vascular function, beyond cardiac function, should be included in a comprehensive clinical evaluation of these patients.

I(f) inhibition in cardiovascular diseases.

PubMed

Thollon, Catherine; Vilaine, Jean-Paul

2010-01-01

Heart rate (HR) is determined by the pacemaker activity of cells from the sinoatrial node (SAN), located in the right atria. Spontaneous electrical activity of SAN cells results from a diastolic depolarization (DD). Despite controversy in the exact contribution of funny current (I(f)) in pacemaking, it is a major contributor of DD. I(f) is an inward Na(+)/K(+) current, activated upon hyperpolarization and directly modulated by cyclic adenosine monophosphate. The f-proteins are hyperpolarization-activated cyclic nucleotide-gated channels, HCN4 being the main isoform of SAN. Ivabradine (IVA) decreases DD and inhibits I(f) in a use-dependent manner. Under normal conditions IVA selectively reduces HR and limits exercise-induced tachycardia, in animals and young volunteers. Reduction in HR with IVA both decreases myocardial oxygen consumption and increases its supply due to prolongation of diastolic perfusion time. In animal models and in human with coronary artery disease (CAD), IVA has anti-anginal and anti-ischemic efficacy, equipotent to classical treatments, β-blockers, or calcium channel blockers. As expected from its selectivity for I(f), the drug is safe and well tolerated with minor visual side effects. As a consequence, IVA is the first inhibitor of I(f) approved for the treatment of stable angina. Available clinical data indicate that IVA could improve the management of stable angina in all patients including those treated with β-blockers. As chronic elevation of resting HR is an independent predictor of mortality, pure HR reduction by inhibition of I(f) could, beyond the control of anti-anginal symptoms, improve the prognosis of CAD and heart failure; this therapeutic potential is currently under evaluation with IVA. Copyright © 2010 Elsevier Inc. All rights reserved.

Prognostic value of depressed midwall systolic function in cardiac light-chain amyloidosis.

PubMed

Perlini, Stefano; Salinaro, Francesco; Musca, Francesco; Mussinelli, Roberta; Boldrini, Michele; Raimondi, Ambra; Milani, Paolo; Foli, Andrea; Cappelli, Francesco; Perfetto, Federico; Palladini, Giovanni; Rapezzi, Claudio; Merlini, Giampaolo

2014-05-01

Cardiac amyloidosis represents an archetypal form of restrictive heart disease, characterized by profound diastolic dysfunction. As ejection fraction is preserved until the late stage of the disease, the majority of patients do fulfill the definition of diastolic heart failure, that is, heart failure with preserved ejection fraction (HFpEF). In another clinical model of HFpEF, that is, pressure-overload hypertrophy, depressed midwall fractional shortening (mFS) has been shown to be a powerful prognostic factor. To assess the potential prognostic role of mFS in cardiac light-chain amyloidosis with preserved ejection fraction, we enrolled 221 consecutive untreated patients, in whom a first diagnosis of cardiac light-chain amyloidosis was concluded between 2008 and 2010. HFpEF was present in 181 patients. Patients in whom cardiac involvement was excluded served as controls (n = 121). Prognosis was assessed after a median follow-up of 561 days. When compared with light-chain amyloidosis patients without myocardial involvement, cardiac light-chain amyloidosis was characterized by increased wall thickness (P <0.001), reduced end-diastolic left ventricular volumes (P <0.001), and diastolic dysfunction (P <0.001). In patients with preserved ejection fraction, mFS was markedly depressed [10.6% (8.7-13.5) vs. 17.8% (15.9-19.5) P <0.001]. At multivariable analysis, mFS, troponin I, and NT-pro-brain natriuretic peptide were the only significant prognostic determinants (P <0.001), whereas other indices of diastolic (E/E' ratio, transmitral and pulmonary vein flow velocities) and systolic function (tissue Doppler systolic indices, ejection fraction), or the presence/absence of congestive heart failure did not enter the model. In cardiac light-chain amyloidosis with normal ejection fraction, depressed circumferential mFS, a marker of myocardial contractile dysfunction, is a powerful predictor of survival.

Vorticity is a marker of diastolic ventricular interdependency in pulmonary hypertension

PubMed Central

Browning, James; Schroeder, Joyce D.; Shandas, Robin; Kheyfets, Vitaly O.; Buckner, J. Kern; Hunter, Kendall S.; Hertzberg, Jean R.; Fenster, Brett E.

2016-01-01

Abstract Our objective was to determine whether left ventricular (LV) vorticity (ω), the local spinning motion of a fluid element, correlated with markers of ventricular interdependency in pulmonary hypertension (PH). Maladaptive ventricular interdependency is associated with interventricular septal shift, impaired LV performance, and poor outcomes in PH patients, yet the pathophysiologic mechanisms underlying fluid-structure interactions in ventricular interdependency are incompletely understood. Because conformational changes in chamber geometry affect blood flow formations and dynamics, LV ω may be a marker of LV-RV (right ventricular) interactions in PH. Echocardiography was performed for 13 PH patients and 10 controls for assessment of interdependency markers, including eccentricity index (EI), and biventricular diastolic dysfunction, including mitral valve (MV) and tricuspid valve (TV) early and late velocities (E and A, respectively) as well as MV septal and lateral early tissue Doppler velocities (e′). Same-day 4-dimensional cardiac magnetic resonance was performed for LV E (early)-wave ω measurement. LV E-wave ω was significantly decreased in PH patients (P = 0.008) and correlated with diastolic EI (Rho = −0.53, P = 0.009) as well as with markers of LV diastolic dysfunction, including MV E(Rho = 0.53, P = 0.011), E/A (Rho = 0.56, P = 0.007), septal e′ (Rho = 0.63, P = 0.001), and lateral e′ (Rho = 0.57, P = 0.007). Furthermore, LV E-wave ω was associated with indices of RV diastolic dysfunction, including TV e′ (Rho = 0.52, P = 0.012) and TV E/A (Rho = 0.53, P = 0.009). LV E-wave ω is decreased in PH and correlated with multiple echocardiographic markers of ventricular interdependency. LV ω may be a novel marker for fluid-tissue biomechanical interactions in LV-RV interdependency. PMID:27162613

Impact of chronic obstructive pulmonary diseases on left ventricular diastolic function in hospitalized elderly patients.

PubMed

Huang, Ying-Shuo; Feng, Ying-Chao; Zhang, Jian; Bai, Li; Huang, Wei; Li, Min; Sun, Ying

2015-01-01

To evaluate the impact of chronic obstructive pulmonary disease (COPD) on left ventricular (LV) diastolic function in hospitalized elderly patients. This was a case-control observational study of 148 consecutive hospitalized elderly patients (≥65 years old): 73 subjects without COPD as controls and 75 patients with COPD. Mild-to-moderate COPD was defined as stages 1 and 2, while severe and very severe COPD was defined as stages 3 and 4, according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. Clinical characteristics and echocardiographic parameters were analyzed and compared. Compared with the control group, patients with COPD had a higher frequency of LV diastolic dysfunction and heart failure with preserved ejection fraction. Smoking frequency, frequency of cerebrovascular diseases and diabetes, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were higher in the COPD group (all P<0.05). COPD patients showed more abnormalities in diastolic function (E/e': 11.51±2.50 vs 10.42±3.25, P=0.047), but no differences in systolic function and right ventricular function (all P>0.05). Patients with severe/very severe COPD showed no differences in LV diastolic function compared to patients with mild/moderate COPD (P>0.05), but serum NT-proBNP levels were higher in severe/very severe COPD (P<0.05). Results suggest that early-stage COPD may have an impact on the LV diastolic function. Severe COPD mainly affected right ventricular function. In hospitalized elderly patients with COPD, LV diastolic dysfunction should be taken into account together with right ventricular function.

Long-term effects of L- and N-type calcium channel blocker on uric acid levels and left atrial volume in hypertensive patients.

PubMed

Masaki, Mitsuru; Mano, Toshiaki; Eguchi, Akiyo; Fujiwara, Shohei; Sugahara, Masataka; Hirotani, Shinichi; Tsujino, Takeshi; Komamura, Kazuo; Koshiba, Masahiro; Masuyama, Tohru

2016-11-01

Left ventricular (LV) diastolic dysfunction is associated with hypertension and hyperuricemia. However, it is not clear whether the L- and N-type calcium channel blocker will improve LV diastolic dysfunction through the reduction of uric acid. The aim of this study was to investigate the effects of anti-hypertensive therapy, the L- and N-type calcium channel blocker, cilnidipine or the L-type calcium channel blocker, amlodipine, on left atrial reverse remodeling and uric acid in hypertensive patients. We studied 62 patients with untreated hypertension, randomly assigned to cilnidipine or amlodipine for 48 weeks. LV diastolic function was assessed with the left atrial volume index (LAVI), mitral early diastolic wave (E), tissue Doppler early diastolic velocity (E') and the ratio (E/E'). Serum uric acid levels were measured before and after treatment. After treatment, systolic and diastolic blood pressures equally dropped in both groups. LAVI, E/E', heart rate and uric acid levels decreased at 48 weeks in the cilnidipine group but not in the amlodipine group. The % change from baseline to 48 weeks in LAVI, E wave, E/E' and uric acid levels were significantly lower in the cilnidipine group than in the amlodipine group. Larger %-drop in uric acid levels were associated with larger %-reduction of LAVI (p < 0.01). L- and N-type calcium channel blocker but not L-type calcium channel blocker may improve LV diastolic function in hypertensive patients, at least partially through the decrease in uric acid levels.

Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction - an experimental study.

PubMed

Fu, Mingqiang; Zhou, Jingmin; Qian, Juying; Jin, Xuejuan; Zhu, Hongmin; Zhong, Chunlin; Fu, Michael; Zou, Yunzeng; Ge, Junbo

2012-08-30

Adiponectin is reported to relate with cardiovascular diseases, we sought to examine whether adiponectin is associated with disease progression of heart failure from hypertension in rats in comparison with other known biomarkers and echocardiographic parameters. Spontaneously hypertensive rats (SHR, n = 35), aged 1 month, were used and followed up to 18 months. High frequency echocardiography was performed both at baseline and every 3 months thereafter. Moreover, serum levels of N-terminal pro-natriuretic peptide (NT-proBNP) and interleukin-6 (IL-6) as well as serum level and tissue expression of adiponectin were determined at the same time as echocardiography. The results clearly demonstrated time-dependent progression of hypertension and heart dysfunction as evidenced by gradually increased left ventricular mass index, NT-proBNP, IL-6 as well as gradually decreased cardiac function as assessed by echocardiography. Meanwhile, tissue and serum adiponectin decreased from 3 months and reached plateau until 12 months in parallel with decreasing of cardiac diastolic function. Thereafter, adiponectin levels increased prior to occurrence of systolic dysfunction. Adiponectin concentration is inversely related with NT-proBNP, IL-6 and E/E' (correlation coefficient (r) = -0.756 for NT-proBNP, p < 0.001, -0.635 for IL-6, p = 0.002, and -0.626 for E/E', p = 0.002, respectively) while positively correlated with E/A and E'/A' (r = 0.683 for E/A, p = 0.001, 0.671 for E'/A', p = 0.001, respectively). No difference for adiponectin distribution among visceral adipose tissues was found. Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction.

Cirrhotic cardiomyopathy

PubMed Central

Ruiz-del-Árbol, Luis; Serradilla, Regina

2015-01-01

During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to a failure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the follow-up progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function. PMID:26556983

miR-21 is associated with fibrosis and right ventricular failure

PubMed Central

Hu, Dong-Qing; Zhao, Mingming; Blay, Eddie; Sandeep, Nefthi; Ong, Sang-Ging; Jung, Gwanghyun; Kooiker, Kristina B.; Coronado, Michael; Fajardo, Giovanni; Bernstein, Daniel

2017-01-01

Combined pulmonary insufficiency (PI) and stenosis (PS) is a common long-term sequela after repair of many forms of congenital heart disease, causing progressive right ventricular (RV) dilation and failure. Little is known of the mechanisms underlying this combination of preload and afterload stressors. We developed a murine model of PI and PS (PI+PS) to identify clinically relevant pathways and biomarkers of disease progression. Diastolic dysfunction was induced (restrictive RV filling, elevated RV end-diastolic pressures) at 1 month after generation of PI+PS and progressed to systolic dysfunction (decreased RV shortening) by 3 months. RV fibrosis progressed from 1 month (4.4% ± 0.4%) to 3 months (9.2% ± 1%), along with TGF-β signaling and tissue expression of profibrotic miR-21. Although plasma miR-21 was upregulated with diastolic dysfunction, it was downregulated with the onset of systolic dysfunction), correlating with RV fibrosis. Plasma miR-21 in children with PI+PS followed a similar pattern. A model of combined RV volume and pressure overload recapitulates the evolution of RV failure unique to patients with prior RV outflow tract surgery. This progression was characterized by enhanced TGF-β and miR-21 signaling. miR-21 may serve as a plasma biomarker of RV failure, with decreased expression heralding the need for valve replacement. PMID:28469078

Cardiac valve evaluation and adipokine levels in obese women treated with sibutramine.

PubMed

Saraç, Sefa; Saraç, Fulden

2010-06-01

The aims of present study were 1) to evaluate cardiac valve characteristics, 2) to determine the plasma concentrations of fibrinogen, high sensitivity C-reactive protein (hsCRP), adiponectin, and tumor necrosis factor-alpha (TNF-alpha) in the obese women before and after 19 months sibutramine treatment in the obese women. Sixty obese women were enrolled in this prospective, randomized study. Thirty women received 10 mg once daily dose of sibutramine for 19 months. The rest of the obese women received 15 mg once daily dose of sibutramine for 19 months. All patients were evaluated with echocardiography. Plasma levels of adiponectin and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA) and hsCRP by immunoturbimetric assay. Student paired and unpaired t tests were used to compare the 10 mg or 15 mg dose sibutramine effects either in groups or between the groups. There were no signs of significant regurgitation or thickening of the mitral and aortic valves on echocardiographic evaluation performed after 19 months of treatment. Parameters of systolic function after 10 or 15 mg treatment were not different from pretreatment characteristics. Minimal tricuspid regurgitation was found in one (1/27) patient treated with 10 mg sibutramine after 19 months. Among obese patients treated with 15 mg sibutramine one patient (1/28) had minimal mitral valve regurgitation and 2 patients (2/28) had minimal aortic insufficiency. Stage II diastolic dysfunction in the 15 obese treated with 15 mg regressed to stage I diastolic dysfunction (50%). Stage II diastolic dysfunction in the 10 obese treated with 10 mg regressed to stage I diastolic dysfunction (33.3%). Mean levels of TNF-alpha(p=0.04), fibrinogen (p=0.03) and hsCRP (p=0.04)i decreased and adiponectin (p=0.03) levels increased in the obese treated with 10 mg sibutramine. Likewise, in the patients treated with 15 mg sibutramine, mean levels of TNF- alpha(p=0.01), fibrinogen (p= 0.02), and hsCRP (p= 0.04) decreased and adiponectin (p= 0.02) levels increased. Nineteen months of sibutramine treatment does not affect heart valve and systolic functions, however, diastolic dysfunction severity reduced with sibutramine treatment. Also In addition, mean levels of adiponectin, TNF- alpha, fibrinogen and hs- CRP change with 19 months sibutramine treatment.

A high-sugar and high-fat diet impairs cardiac systolic and diastolic function in mice.

PubMed

Carbone, Salvatore; Mauro, Adolfo G; Mezzaroma, Eleonora; Kraskauskas, Donatas; Marchetti, Carlo; Buzzetti, Raffaella; Van Tassell, Benjamin W; Abbate, Antonio; Toldo, Stefano

2015-11-01

Heart failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, exercise intolerance and cardiac dysfunction. Unhealthy diet has been associated with increased risk of obesity and heart disease, but whether it directly affects cardiac function, and promotes the development and progression of HF is unknown. We fed 8-week old male or female CD-1 mice with a standard diet (SD) or a diet rich in saturated fat and sugar, resembling a "Western" diet (WD). Cardiac systolic and diastolic function was measured at baseline and 4 and 8 weeks by Doppler echocardiography, and left ventricular (LV) end-diastolic pressure (EDP) by cardiac catheterization prior to sacrifice. An additional group of mice received WD for 4 weeks followed by SD (wash-out) for 8 weeks. WD-fed mice experienced a significant decreased in LV ejection fraction (LVEF), reflecting impaired systolic function, and a significant increase in isovolumetric relaxation time (IRT), myocardial performance index (MPI), and LVEDP, showing impaired diastolic function, without any sex-related differences. Switching to a SD after 4 weeks of WD partially reversed the cardiac systolic and diastolic dysfunction. A diet rich in saturated fat and sugars (WD) impairs cardiac systolic and diastolic function in the mouse. Further studies are required to define the mechanism through which diet affects cardiac function, and whether dietary interventions can be used in patients with, or at risk for, HF. Published by Elsevier Ireland Ltd.

Heart Failure with Preserved Ejection Fraction - Concept, Pathophysiology, Diagnosis and Challenges for Treatment.

PubMed

Miljkovik, Lidija Veterovska; Spiroska, Vera

2015-09-15

Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) occurs in 40 to 60% of the patients with HF, with a prognosis which is similar to HF with reduced ejection fraction (HFrEF). HFpEF pathophysiology is different from that of HFrEF, and has been characterized with diastolic dysfunction. Diastolic dysfunction has been defined with elevated left ventricular stiffness, prolonged iso-volumetric LV relaxation, slow LV filing and elevated LV end-diastolic pressure. Arterial hypertension occurs in majority cases with HFpEF worldwide. Patients are mostly older and obese. Diabetes mellitus and atrial fibrillation appear proportionally in a high frequency of patients with HFpEF. The HFpEF diagnosis is based on existence of symptoms and signs of heart failure, normal or approximately normal ejection and diagnosing of LV diastolic dysfunction by means of heart catheterization or Doppler echocardiography and/or elevated concentration of plasma natriuretic peptide. The present recommendations for HFpEF treatment include blood pressure control, heart chamber frequency control when atrial fibrillation exists, in some situations even coronary revascularization and an attempt for sinus rhythm reestablishment. Up to now, it is considered that no medication or a group of medications improve the survival of HFpEF patients. Due to these causes and the bad prognosis of the disorder, rigorous control is recommended of the previously mentioned precipitating factors for this disorder. This paper presents a universal review of the most important parameters which determine this disorder.

Pathological hypertrophy and cardiac dysfunction are linked to aberrant endogenous unsaturated fatty acid metabolism

PubMed Central

Salomé Campos, Dijon Henrique; Grippa Sant’Ana, Paula; Okoshi, Katashi; Padovani, Carlos Roberto; Masahiro Murata, Gilson; Nguyen, Son; Kolwicz, Stephen C.; Cicogna, Antonio Carlos

2018-01-01

Pathological cardiac hypertrophy leads to derangements in lipid metabolism that may contribute to the development of cardiac dysfunction. Since previous studies, using high saturated fat diets, have yielded inconclusive results, we investigated whether provision of a high-unsaturated fatty acid (HUFA) diet was sufficient to restore impaired lipid metabolism and normalize diastolic dysfunction in the pathologically hypertrophied heart. Male, Wistar rats were subjected to supra-valvar aortic stenosis (SVAS) or sham surgery. After 6 weeks, diastolic dysfunction and pathological hypertrophy was confirmed and both sham and SVAS rats were treated with either normolipidic or HUFA diet. At 18 weeks post-surgery, the HUFA diet failed to normalize decreased E/A ratios or attenuate measures of cardiac hypertrophy in SVAS animals. Enzymatic activity assays and gene expression analysis showed that both normolipidic and HUFA-fed hypertrophied hearts had similar increases in glycolytic enzyme activity and down-regulation of fatty acid oxidation genes. Mass spectrometry analysis revealed depletion of unsaturated fatty acids, primarily linoleate and oleate, within the endogenous lipid pools of normolipidic SVAS hearts. The HUFA diet did not restore linoleate or oleate in the cardiac lipid pools, but did maintain body weight and adipose mass in SVAS animals. Overall, these results suggest that, in addition to decreased fatty acid oxidation, aberrant unsaturated fatty acid metabolism may be a maladaptive signature of the pathologically hypertrophied heart. The HUFA diet is insufficient to reverse metabolic remodeling, diastolic dysfunction, or pathologically hypertrophy, possibly do to preferentially partitioning of unsaturated fatty acids to adipose tissue. PMID:29494668

Working Memory for Serial Order Is Dysfunctional in Adults With a History of Developmental Dyscalculia: Evidence From Behavioral and Neuroimaging Data.

PubMed

Attout, Lucie; Salmon, Eric; Majerus, Steve

2015-01-01

Recent studies suggest that order working memory (WM) may be specifically associated with numerical abilities. This study explored behavioral performance and neural networks associated with verbal WM in adults with a history of developmental dyscalculia (DD). The DD group performed significantly poorer but with the same precision than the control group in order WM tasks and showed a lower activation of the right middle frontal gyrus during the order WM and the alphabetical order judgment tasks. This study suggests a persistent impairment in order WM in adults with DD, characterized by more general difficulties in controlled activation of order information.

New-Onset Heart Failure and Mortality in Hospital Survivors of Sepsis-Related Left Ventricular Dysfunction.

PubMed

Vallabhajosyula, Saraschandra; Jentzer, Jacob C; Geske, Jeffrey B; Kumar, Mukesh; Sakhuja, Ankit; Singhal, Akhil; Poterucha, Joseph T; Kashani, Kianoush; Murphy, Joseph G; Gajic, Ognjen; Kashyap, Rahul

2018-02-01

The association between new-onset left ventricular (LV) dysfunction during sepsis with long-term heart failure outcomes is lesser understood. Retrospective cohort study of all adult patients with severe sepsis and septic shock between 2007 and 2014 who underwent echocardiography within 72 h of admission to the intensive care unit. Patients with prior heart failure, LV dysfunction, and structural heart disease were excluded. LV systolic dysfunction was defined as LV ejection fraction <50% and LV diastolic dysfunction as ≥grade II. Primary composite outcome included new hospitalization for acute decompensated heart failure and all-cause mortality at 2-year follow-up. Secondary outcomes included persistent LV dysfunction, and hospital mortality and length of stay. During this 8-year period, 434 patients with 206 (48%) patients having LV dysfunction were included. The two groups had similar baseline characteristics, but those with LV dysfunction had worse function as demonstrated by worse LV ejection fraction, cardiac index, and LV diastolic dysfunction. In the 331 hospital survivors, new-onset acute decompensated heart failure hospitalization did not differ between the two cohorts (15% vs. 11%). The primary composite outcome was comparable at 2-year follow-up between the groups with and without LV dysfunction (P = 0.24). Persistent LV dysfunction was noted in 28% hospital survivors on follow-up echocardiography. Other secondary outcomes were similar between the two groups. In patients with severe sepsis and septic shock, the presence of new-onset LV dysfunction did not increase the risk of long-term adverse heart failure outcomes.

Nitric Oxide Bioavailability and Adiponectin Production in Chronic Systolic Heart Failure: Relation to Severity of Cardiac Dysfunction

PubMed Central

Tang, W.H. Wilson; Shrestha, Kevin; Tong, Wilson; Wang, Zeneng; Troughton, Richard W.; Borowski, Allen G.; Klein, Allan L.; Hazen, Stanley L.

2013-01-01

Adiponectin is an anti-inflammatory, anti-atherogenic adipokine elevated in heart failure (HF) that may protect against endothelial dysfunction by influencing underlying nitric oxide bioavailablity. In this study, we examine the relationship between plasma adiponectin levels and measures of nitric oxide bioavailability and myocardial performance in patients with chronic systolic HF. In 139 ambulatory patients with stable, chronic systolic HF (left ventricular [LV] ejection fraction ≤40%, New York Heart Association [NYHA] class I to IV), we measured plasma levels of adiponectin, asymmetric dimethylarginine (ADMA) and global arginine bioavailability (GABR), and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse events (all-cause mortality or cardiac transplantation) were prospectively tracked for a median of 39 months. Plasma adiponectin levels directly correlated with plasma ADMA levels (Spearman’s r=0.41, p<0.001) and NT-proBNP levels (r=0.55, p<0.001), inversely correlated with GABR (r= −0.39, p<0.001), and were not associated with hsCRP (p=0.81) or MPO (p=0.07). Interestingly, increased plasma adiponectin levels remained positively correlated with plasma ADMA levels only in patients with elevated NT-proBNP levels (r= 0.33, p=0.009). Higher plasma adiponectin levels were associated with worse LV diastolic dysfunction (rank sums p=0.002), RV systolic dysfunction (rank sums p=0.002), and RV diastolic dysfunction (rank sums p=0.011), but not after adjustment for plasma ADMA and NT-proBNP levels. Plasma adiponectin levels predicted increased risk of adverse clinical events (HR [95% CI]: 1.45 [1.02–2.07], p=0.038) but not after adjustment for plasma ADMA and NT-proBNP levels, or echocardiographic indices of diastolic or RV systolic dysfunction. In patients with chronic systolic HF, adiponectin production is more closely linked with nitric oxide bioavailability than inflammation, and appears to be more robust in the setting of cardiac dysfunction or elevated natriuretic peptide levels. PMID:23499315

Assessing the Risk of Progression From Asymptomatic Left Ventricular Dysfunction to Overt Heart Failure: A Systematic Overview and Meta-Analysis.

PubMed

Echouffo-Tcheugui, Justin B; Erqou, Sebhat; Butler, Javed; Yancy, Clyde W; Fonarow, Gregg C

2016-04-01

This study sought to provide estimates of the risk of progression to overt heart failure (HF) from systolic or diastolic asymptomatic left ventricular dysfunction through a systematic review and meta-analysis. Precise population-based estimates on the progression from asymptomatic left ventricular dysfunction (or stage B HF) to clinical HF (stage C HF) remain limited, despite its prognostic and clinical implications. Pre-emptive intervention with neurohormonal modulation may attenuate disease progression. MEDLINE and EMBASE were systematically searched (until March 2015). Cohort studies reporting on the progression from asymptomatic left ventricular systolic dysfunction (ALVSD) or asymptomatic left ventricular diastolic dysfunction (ALVDD) to overt HF were included. Effect estimates (prevalence, incidence, and relative risk) were pooled using a random-effects model meta-analysis, separately for systolic and diastolic dysfunction, with heterogeneity assessed with the I(2) statistic. Thirteen reports based on 11 distinct studies of progression of ALVSD were included in the meta-analysis assessing a total of 25,369 participants followed for 7.9 years on average. The absolute risks of progression to HF were 8.4 per 100 person-years (95% confidence interval [CI]: 4.0 to 12.8 per 100 person-years) for those with ALVSD, 2.8 per 100 person-years (95% CI: 1.9 to 3.7 per 100 person-years) for those with ALVDD, and 1.04 per 100 person-years (95% CI: 0.0 to 2.2 per 100 person-years) without any ventricular dysfunction evident. The combined maximally adjusted relative risk of HF for ALVSD was 4.6 (95% CI: 2.2 to 9.8), and that of ALVDD was 1.7 (95% CI: 1.3 to 2.2). ALVSD and ALVDD are each associated with a substantial risk for incident HF indicating an imperative to develop effective intervention at these stages. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Implications of persistent prehypertension for ageing-related changes in left ventricular geometry and function: the MONICA/KORA Augsburg study.

PubMed

Markus, Marcello Ricardo Paulista; Stritzke, Jan; Lieb, Wolfgang; Mayer, Björn; Luchner, Andreas; Döring, Angela; Keil, Ulrich; Hense, Hans-Werner; Schunkert, Heribert

2008-10-01

It is unclear whether persistent prehypertension causes structural or functional alterations of the heart. We examined echocardiographic data of 1005 adults from a population-based survey at baseline in 1994/1995 and at follow-up in 2004/2005. We compared individuals who had either persistently normal (<120 mmHg systolic and <80 mmHg diastolic, n = 142) or prehypertensive blood pressure (120-139 mmHg or 80-89 mmHg, n = 119) at both examinations using multivariate regression modeling. Over 10 years, left ventricular end-diastolic diameters were stable and did not differ between the two groups. However, the prehypertensive blood pressure group displayed more pronounced ageing-related increases of left ventricular wall thickness (+4.7 versus +11.9%, P < 0.001) and left ventricular mass (+8.6 versus +15.7%, P = 0.006). Prehypertension was associated with a raised incidence of left ventricular concentric remodeling (adjusted odds ratio 10.7, 95% confidence interval 2.82-40.4) and left ventricular hypertrophy (adjusted odds ratio 5.33, 1.58-17.9). The ratio of early and late diastolic peak transmitral flow velocities (E/A) decreased by 7.7% in the normal blood pressure versus 15.7% in the prehypertensive blood pressure group (P = 0.003) and at follow-up the ratio of early diastolic peak transmitral flow and early diastolic peak myocardial relaxation velocities (E/EM) was higher (9.1 versus 8.5, P = 0.031) and left atrial size was larger (36.5 versus 35.3 mm, P = 0.024) in the prehypertensive blood pressure group. Finally, the adjusted odds ratio for incident diastolic dysfunction was 2.52 (1.01-6.31) for the prehypertensive blood pressure group. Persistent prehypertension accelerates the development of hypertrophy and diastolic dysfunction of the heart.

Impact of chronic obstructive pulmonary diseases on left ventricular diastolic function in hospitalized elderly patients

PubMed Central

Huang, Ying-Shuo; Feng, Ying-Chao; Zhang, Jian; Bai, Li; Huang, Wei; Li, Min; Sun, Ying

2015-01-01

Objective To evaluate the impact of chronic obstructive pulmonary disease (COPD) on left ventricular (LV) diastolic function in hospitalized elderly patients. Methods This was a case–control observational study of 148 consecutive hospitalized elderly patients (≥65 years old): 73 subjects without COPD as controls and 75 patients with COPD. Mild-to-moderate COPD was defined as stages 1 and 2, while severe and very severe COPD was defined as stages 3 and 4, according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. Clinical characteristics and echocardiographic parameters were analyzed and compared. Results Compared with the control group, patients with COPD had a higher frequency of LV diastolic dysfunction and heart failure with preserved ejection fraction. Smoking frequency, frequency of cerebrovascular diseases and diabetes, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were higher in the COPD group (all P<0.05). COPD patients showed more abnormalities in diastolic function (E/e′: 11.51±2.50 vs 10.42±3.25, P=0.047), but no differences in systolic function and right ventricular function (all P>0.05). Patients with severe/very severe COPD showed no differences in LV diastolic function compared to patients with mild/moderate COPD (P>0.05), but serum NT-proBNP levels were higher in severe/very severe COPD (P<0.05). Conclusion Results suggest that early-stage COPD may have an impact on the LV diastolic function. Severe COPD mainly affected right ventricular function. In hospitalized elderly patients with COPD, LV diastolic dysfunction should be taken into account together with right ventricular function. PMID:25565790

Use of milrinone to treat cardiac dysfunction in infants with pulmonary hypertension secondary to congenital diaphragmatic hernia: a review of six patients.

PubMed

Patel, Neil

2012-01-01

Pulmonary hypertension and secondary cardiac dysfunction are important contributors of morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). Milrinone, a phosphodiesterase-3 inhibitor, may be useful in this setting for its combined actions as a pulmonary vasodilator and to improve systolic and diastolic function. This study aimed to assess the effects of milrinone on cardiac function and pulmonary artery pressure in infants with CDH. A retrospective review of echocardiograms performed on infants with CDH who received milrinone was performed. Tissue Doppler imaging velocities were used to assess systolic and diastolic function. Pulmonary artery pressure was assessed from the pattern and velocity of ductal shunting. Six infants with CDH and severe pulmonary hypertension were identified. Systolic and diastolic myocardial velocities were reduced in the right ventricle (RV) and interventricular septum (IVS) at baseline. In the 72 h after commencement of milrinone, there was a significant increase in early diastolic myocardial velocities in the RV, accompanied by increasing systolic velocities in the RV and IVS. Oxygenation index was significantly reduced, blood pressure unchanged, and ductal shunt velocity minimally altered over the same time period. Milrinone use was associated with an improvement in systolic and diastolic function in the RV, corresponding to an improvement in clinical status. Copyright © 2012 S. Karger AG, Basel.

Left ventricular early diastolic inflow velocity and atrial ventricular plane downward velocity: useful parameters to test diastolic function in clinical practice? Diastolic parameters tested in a clinical setting.

PubMed

Winter, R; Gudmundsson, P; Ericsson, G; Willenheimer, R

2001-06-01

To study the clinical value of the colour-M-mode slope of the early diastolic left ventricular filling phase (Vp) and the early diastolic downward M-mode slope of the left atrioventricular plane displacement (EDS), compared with diastolic function assessed by traditional Doppler evaluation. In 65 consecutive patients EDS and Vp were compared with a four-degree traditional diastolic function classification, based on pulsed Doppler assessment of the early to atrial transmitral flow ratio (E/A), the E-wave deceleration time (Edt), and the systolic to diastolic (S/D) pulmonary venous inflow ratio. Vp (P=0.006) and EDS (P=0.045) were related to traditional diastolic function (Kruskal--Wallis analysis). EDS showed a trend brake between the moderate and severe diastolic dysfunction groups by traditional Doppler evaluation. Vp and EDS correlated weakly in simple linear regression analysis (r=0.33). Vp and EDS discriminated poorly between normal and highly abnormal diastolic function. Vp and EDS were significantly related to diastolic function by traditional Doppler evaluation. They were, however, not useful as single parameters of left ventricular diastolic function due to a small difference between normal and highly abnormal values, allowing for little between-measurement variability. Consequently, these methods for the evaluation of left ventricular diastolic function do not add significantly to traditional Doppler evaluation.

Patients with a hypertensive response to exercise have impaired systolic function without diastolic dysfunction or left ventricular hypertrophy.

PubMed

Mottram, Philip M; Haluska, Brian; Yuda, Satoshi; Leano, Rodel; Marwick, Thomas H

2004-03-03

We sought to determine if a hypertensive response to exercise (HRE) is associated with myocardial changes consistent with early hypertensive heart disease. An HRE predicts the development of chronic hypertension (HT) and may reflect a preclinical stage of HT. Patients with a normal left ventricular (LV) ejection fraction and a negative stress test were recruited into three matched groups: 41 patients (age 56 +/- 10 years) with HRE (>210/105 mm Hg in men; >190/105 in women), comprising 22 patients with (HT+) and 19 without resting hypertension (HT-); and 17 matched control subjects without HRE. Long-axis function was determined by measurement of the strain rate (SR), peak systolic strain, and cyclic variation (CV) of integrated backscatter in three apical views. An HRE was not associated with significant differences in LV mass index. Exercise performance and diastolic function were reduced in HRE(HT+) patients, but similar in HRE(HT-) patients and controls. Systolic dysfunction (peak systolic strain, SR, and CV) was significantly reduced in HRE patients (p < 0.001 for all). These reductions were equally apparent in patients with and without a history of resting HT (p = NS) and were independent of LV mass index and blood pressure (p < 0.01). An HRE is associated with subtle systolic dysfunction, even in the absence of resting HT. These changes occur before the development of LV hypertrophy or detectable diastolic dysfunction and likely represent early hypertensive heart disease.

The relationship between arterial wall stiffness and left ventricular dysfunction.

PubMed

Hu, Y; Li, L; Shen, L; Gao, H

2013-05-01

The purpose of this study was to explore the relationship between left ventricular (LV) dysfunction and arterial wall stiffening. A total of 218 patients over the age of 45 diagnosed with hypertension in Jinan City and hospitalised between 2010 and 2011 were included in this study. LV function was evaluated using echocardiography (ECHO). Blood pressure was monitored with an automated tonometric device, and the parameters of arterial wall stiffness were measured. In addition, the metabolic parameters of blood samples, such as glucose and lipids, were also determined using the Cobas E601 analyser. Stiffness parameter beta positively correlated with LV diastolic function (E/Em ratio) (r = 0.255, p < 0.001). LV end-diastolic diameter not only related to the E/Em ratio (r = 0.196, p = 0.009) but also with beta (r = 0.220, p = 0.002). The stiffness parameter beta was an early indicator of E/Em ratio as determined by multiple regression analysis (R (2) = 0.381, p < 0.01). Age, blood pressure and fasting blood glucose contributed to stiffness parameter beta (p < 0.05), as well as the E/Em ratio (p < 0.01). Our findings suggested that LV dysfunction may have a direct relationship to arterial stiffening, independently of having similar risk factors. In addition, arterial stiffness can be an independent predictor of LV diastolic function, suggesting that the severity of arterial stiffness directly correlates with the severity of LV dysfunction.

Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure

PubMed Central

Wilson Tang, Wai Hong; Tong, Wilson; Shrestha, Kevin; Wang, Zeneng; Levison, Bruce S.; Delfraino, Brian; Hu, Bo; Troughton, Richard W.; Klein, Allan L.; Hazen, Stanley L.

2008-01-01

Aims To investigate the association of arginine methylation with myocardial function and prognosis in chronic systolic heart failure patients. Methods and results Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), as well as N-mono-methylarginine (MMA) and methyl-lysine, were simultaneously measured by tandem mass spectrometry in 132 patients with chronic systolic heart failure with echocardiographic evaluation and follow-up. Increasing ADMA and SDMA levels were associated with elevated natriuretic peptide levels (both P < 0.001), and increasing SDMA levels were associated with worsening renal function (P < 0.001). Higher plasma levels of methylated arginine metabolites (but not methyl-lysine) were associated with the presence of left ventricular (LV) diastolic dysfunction (E/septal E′, Spearman's r = 0.31–0.36, P < 0.001). Patients taking beta-blockers had lower ADMA levels than those not taking beta-blockers [0.42 (0.33, 0.50) vs. 0.51 (0.40, 0.58), P < 0.001]. Only increasing ADMA levels were associated with advanced right ventricular (RV) systolic dysfunction. Elevated ADMA levels remained a consistent independent predictor of adverse clinical events (hazard ratio = 1.64, 95% CI: 1.20–2.22, P = 0.002). Conclusion In chronic systolic heart failure, accumulation of methylated arginine metabolites is associated with the presence of LV diastolic dysfunction. Among the methylated derivatives of arginine, ADMA provides the strongest independent prediction of disease progression and adverse long-term outcomes. PMID:18687662

Right Heart Vortex Entrainment Volume and Right Ventricular Diastolic Dysfunction

NASA Astrophysics Data System (ADS)

Browning, James; Hertzberg, Jean; Fenster, Brett; Schroeder, Joyce

2014-11-01

Recent advances in cardiac magnetic resonance imaging (CMR) have allowed for the 3-dimensional characterization of blood flow in the right ventricle (RV) and right atrium (RA). In this study, we investigate and quantify differences in the characteristics of coherent rotating flow structures (vortices) in the RA and RV between subjects with right ventricular diastolic dysfunction (RVDD) and normal controls. Fifteen RVDD subjects and 10 age-matched controls underwent same day 3D time resolved CMR and echocardiography. Echocardiography was used to determine RVDD stage as well as pulmonary artery systolic pressure (PASP). CMR data was used for RA and RV vortex quantification and visualization during early and late ventricular diastole. RA and RV vortex entrainment volume is quantified and visualized using the Lambda-2 criterion, and the results are compared between healthy subjects and those with RVDD. The resulting trends are discussed and hypotheses are presented regarding differences in vortex characteristics between healthy and RVDD subjects cohorts.

Non-alcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in essential hypertension.

PubMed

Fallo, F; Dalla Pozza, A; Sonino, N; Lupia, M; Tona, F; Federspil, G; Ermani, M; Catena, C; Soardo, G; Di Piazza, L; Bernardi, S; Bertolotto, M; Pinamonti, B; Fabris, B; Sechi, L A

2009-11-01

Insulin resistance is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). A relation between insulin sensitivity and left ventricular morphology and function has been reported in essential hypertension, where a high prevalence of NAFLD has been recently found. We investigated the inter-relationship between left ventricular morphology/function, metabolic parameters and NAFLD in 86 never-treated essential hypertensive patients subdivided in two subgroups according to the presence (n = 48) or absence (n = 38) of NAFLD at ultrasonography. The two groups were similar as to sex, age and blood pressure levels. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for liver disease. Body mass index, waist circumference, triglycerides, glucose, insulin, homeostasis model of assessment index for insulin resistance (HOMA-IR), aspartate aminotransferase and alanine aminotransferase were higher and adiponectin levels were lower in patients with NAFLD than in patients without NAFLD, and were associated with NAFLD at univariate analysis. Patients with NAFLD had similar prevalence of left ventricular hypertrophy compared to patients without NAFLD, but a higher prevalence of diastolic dysfunction (62.5 vs 21.1%, P < 0.001), as defined by E/A ratio <1 and E-wave deceleration time >220 ms. Diastolic dysfunction (P = 0.040) and HOMA-IR (P = 0.012) remained independently associated with NAFLD at backward multivariate analysis. Non-alcoholic fatty liver disease was associated with insulin resistance and abnormalities of left ventricular diastolic function in a cohort of patients with essential hypertension, suggesting a concomitant increase of metabolic and cardiac risk in this condition.

Cardiac Impairment Evaluated by Transesophageal Echocardiography and Invasive Measurements in Rats Undergoing Sinoaortic Denervation

PubMed Central

Sirvente, Raquel A.; Irigoyen, Maria C.; Souza, Leandro E.; Mostarda, Cristiano; La Fuente, Raquel N.; Candido, Georgia O.; Souza, Pamella R. M.; Medeiros, Alessandra; Mady, Charles; Salemi, Vera M. C.

2014-01-01

Background Sympathetic hyperactivity may be related to left ventricular (LV) dysfunction and baro- and chemoreflex impairment in hypertension. However, cardiac function, regarding the association of hypertension and baroreflex dysfunction, has not been previously evaluated by transesophageal echocardiography (TEE) using intracardiac echocardiographic catheter. Methods and Results We evaluated exercise tests, baroreflex sensitivity and cardiovascular autonomic control, cardiac function, and biventricular invasive pressures in rats 10 weeks after sinoaortic denervation (SAD). The rats (n = 32) were divided into 4 groups: 16 Wistar (W) with (n = 8) or without SAD (n = 8) and 16 spontaneously hypertensive rats (SHR) with (n = 8) or without SAD (SHRSAD) (n = 8). Blood pressure (BP) and heart rate (HR) did not change between the groups with or without SAD; however, compared to W, SHR groups had higher BP levels and BP variability was increased. Exercise testing showed that SHR had better functional capacity compared to SAD and SHRSAD. Echocardiography showed left ventricular (LV) concentric hypertrophy; segmental systolic and diastolic biventricular dysfunction; indirect signals of pulmonary arterial hypertension, mostly evident in SHRSAD. The end-diastolic right ventricular (RV) pressure increased in all groups compared to W, and the end-diastolic LV pressure increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD. Conclusions Our results suggest that baroreflex dysfunction impairs cardiac function, and increases pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of hypertensive cardiac disease. Moreover, TEE is a useful and feasible noninvasive technique that allows the assessment of cardiac function, particularly RV indices in this model of cardiac disease. PMID:24828834

N-Terminal pro-brain natriuretic peptide levels in dichorionic diamniotic twins with selective intrauterine growth restriction.

PubMed

Fujioka, Kazumichi; Mizobuchi, Masami; Sakai, Hitomi; Iwatani, Sota; Wada, Keiko; Yoshimoto, Seiji; Nakao, Hideto

2014-03-04

Monochorionic diamniotic (MD) twins with selective intrauterine growth restriction (sIUGR) have known associations with cardiac complications. However, the cardiac load of dichorionic diamniotic (DD) twins with sIUGR (DD-sIUGR) remains unclear. N-terminal pro-brain natriuretic peptide (NT-pro BNP) is a convenient marker of cardiac dysfunction in neonates, and is elevated in MD twins with sIUGR (MD-sIUGR). However, there are no reports assessing serum NT-pro BNP levels in DD-sIUGR. Here, we aimed to clarify serum NT-pro BNP levels at birth in DD-sIUGR, and to compare them with those of MD-sIUGR. Forty-one DD twin pairs admitted to our center between October 2007 and January 2013 were enrolled in this study and separated into two groups: nine twins with sIUGR (DD-sIUGR group) and 32 twins without sIUGR (DD without sIUGR group). Sixteen MD twins with sIUGR (MD-sIUGR group) served as positive controls. Serum NT-pro BNP levels at birth in DD-sIUGR [median 2,115 pg/ml (range, 443-6,590 pg/ml)] were significantly higher than in DD without sIUGR [1,080 pg/ml (range, 313-3,470 pg/ml); p=0.001], and significantly lower than in MD twins with sIUGR [4,520 pg/ml (range, 529-62,400 pg/ml); p=0.04]. Serum NT-pro BNP levels between larger and smaller DD co-twins were significantly correlated (r = 0.582; p<0.0001). In conclusion, serum NT-pro BNP levels at birth in DD twins with sIUGR were higher than those without, and lower than in MD twins with sIUGR.

High Prevalence of Cardiovascular Disease in End-Stage Kidney Disease Patients Ongoing Hemodialysis in Peru: Why Should We Care About It?

PubMed

Bravo-Jaimes, Katia; Whittembury, Alvaro; Santivañez, Vilma

2015-01-01

Purpose. To determine clinical, biochemical, and pharmacological characteristics as well as cardiovascular disease prevalence and its associated factors among end-stage kidney disease patients receiving hemodialysis in the main hemodialysis center in Lima, Peru. Methods. This cross-sectional study included 103 patients. Clinical charts were reviewed and an echocardiogram was performed to determine prevalence of cardiovascular disease, defined as the presence of systolic/diastolic dysfunction, coronary heart disease, ventricular dysrhythmias, cerebrovascular disease, and/or peripheral vascular disease. Associations between cardiovascular disease and clinical, biochemical, and dialysis factors were sought using prevalence ratio. A robust Poisson regression model was used to quantify possible associations. Results. Cardiovascular disease prevalence was 81.6%, mainly due to diastolic dysfunction. It was significantly associated with age older than 50 years, metabolic syndrome, C-reactive protein levels, effective blood flow ≤ 300 mL/min, severe anemia, and absence of mild anemia. However, in the regression analysis only age older than 50 years, effective blood flow ≤ 300 mL/min, and absence of mild anemia were associated. Conclusions. Cardiovascular disease prevalence is high in patients receiving hemodialysis in the main center in Lima. Diastolic dysfunction, age, specific hemoglobin levels, and effective blood flow may play an important role.

A Feline HFpEF Model with Pulmonary Hypertension and Compromised Pulmonary Function.

PubMed

Wallner, Markus; Eaton, Deborah M; Berretta, Remus M; Borghetti, Giulia; Wu, Jichuan; Baker, Sandy T; Feldsott, Eric A; Sharp, Thomas E; Mohsin, Sadia; Oyama, Mark A; von Lewinski, Dirk; Post, Heiner; Wolfson, Marla R; Houser, Steven R

2017-11-29

Heart Failure with preserved Ejection Fraction (HFpEF) represents a major public health problem. The causative mechanisms are multifactorial and there are no effective treatments for HFpEF, partially attributable to the lack of well-established HFpEF animal models. We established a feline HFpEF model induced by slow-progressive pressure overload. Male domestic short hair cats (n = 20), underwent either sham procedures (n = 8) or aortic constriction (n = 12) with a customized pre-shaped band. Pulmonary function, gas exchange, and invasive hemodynamics were measured at 4-months post-banding. In banded cats, echocardiography at 4-months revealed concentric left ventricular (LV) hypertrophy, left atrial (LA) enlargement and dysfunction, and LV diastolic dysfunction with preserved systolic function, which subsequently led to elevated LV end-diastolic pressures and pulmonary hypertension. Furthermore, LV diastolic dysfunction was associated with increased LV fibrosis, cardiomyocyte hypertrophy, elevated NT-proBNP plasma levels, fluid and protein loss in pulmonary interstitium, impaired lung expansion, and alveolar-capillary membrane thickening. We report for the first time in HFpEF perivascular fluid cuff formation around extra-alveolar vessels with decreased respiratory compliance. Ultimately, these cardiopulmonary abnormalities resulted in impaired oxygenation. Our findings support the idea that this model can be used for testing novel therapeutic strategies to treat the ever growing HFpEF population.

"Pulmonary valve replacement diminishes the presence of restrictive physiology and reduces atrial volumes": a prospective study in Tetralogy of Fallot patients.

PubMed

Pijuan-Domenech, Antonia; Pineda, Victor; Castro, Miguel Angel; Sureda-Barbosa, Carlos; Ribera, Aida; Cruz, Luz M; Ferreira-Gonzalez, Ignacio; Dos-Subirà, Laura; Subirana-Domènech, Teresa; Garcia-Dorado, David; Casaldàliga-Ferrer, Jaume

2014-11-15

Pulmonary valve replacement (PVR) reduces right ventricular (RV) volumes in the setting of long-term pulmonary regurgitation after Tetralogy of Fallot (ToF) repair; however, little is known of its effect on RV diastolic function. Right atrial volumes may reflect the burden of RV diastolic dysfunction. The objective of this paper is to evaluate the clinical, echocardiographic, biochemical and cardiac magnetic resonance (CMR) variables, focusing particularly on right atrial response and right ventricular diastolic function prior to and after elective PVR in adult patients with ToF. This prospective study was conducted from January 2009 to April 2013 in consecutive patients > 18 years of age who had undergone ToF repair in childhood and were accepted for elective PVR. Twenty patients (mean age: 35 years; 70% men) agreed to enter the study. PVR was performed with a bioporcine prosthesis. Concomitant RV reduction was performed in all cases when technically possible. Pulmonary end-diastolic forward flow (EDFF) decreased significantly from 5.4 ml/m(2) to 0.3 ml/m(2) (p < 0.00001), and right atrial four-chamber echocardiographic measurements and volumes by 25% (p = 0.0024): mean indexed diastolic/systolic atrial volumes prior to surgery were 43 ml/m(2) (SD+/-4.6)/63 ml/m(2) (SD+/-5.5), and dropped to 33 ml/m(2) (SD+/-3)/46 ml/m(2) (SD+/-2.55) post-surgery. All patients presented right ventricular diastolic and systolic volume reductions, with a mean volume reduction of 35% (p < 0.00001). Right ventricular diastolic dysfunction was common in a population of severely dilated RV patients long term after ToF repair. Right ventricular diastolic parameters improved as did right atrial volumes in keeping with the known reduction in RV volumes, after PVR. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pulmonary Hypertension with Left Heart Disease: Prevalence, Temporal Shifts in Etiologies and Outcome.

PubMed

Weitsman, Tatyana; Weisz, Giora; Farkash, Rivka; Klutstein, Marc; Butnaru, Adi; Rosenmann, David; Hasin, Tal

2017-11-01

Pulmonary hypertension has many causes. While it is conventionally thought that the most prevalent is left heart disease, little information about its proportion, causes, and implications on outcome is available. Between 1993 and 2015, 12,115 of 66,949 (18%) first adult transthoracic echocardiograms were found to have tricuspid incompetence gradient ≥40 mm Hg, a pulmonary hypertension surrogate. Left heart disease was identified in 8306 (69%) and included valve malfunction in 4115 (49%), left ventricular systolic dysfunction in 2557 (31%), and diastolic dysfunction in 1776 (21%). Patients with left heart disease, as compared with those without left heart disease, were of similar age, fewer were females (50% vs 63% P <.0001), and they had higher tricuspid incompetence gradient (median 48 mm Hg [interquartile range 43, 55] vs 46 mm Hg [42, 54] P <.0001). In reviewing trends over 20 years, the relative proportions of systolic dysfunction decreased and diastolic dysfunction increased (P for trend <.001), while valve malfunction remained the most prevalent cause of pulmonary hypertension with left heart disease. Independent predictors of mortality were age (hazard ratio [HR] 1.05; 95% CI, 1.04-1.05; P <.0001), tricuspid incompetence gradient (HR 1.02; 95% CI, 1.01-1.02, P <.0001 per mm Hg increase), and female sex (HR 0.87; 95% CI, 0.83-0.91, P <.0001). Overall, left heart disease was not an independent risk factor for mortality (HR 1.04; 95% CI, 0.99-1.09; P = .110), but patients with left ventricular systolic dysfunction and with combined systolic dysfunction and valve malfunction had increased mortality compared with patients with pulmonary hypertension but without left heart disease (HR 1.30; 95% CI, 1.20-1.42 and HR 1.44; 95% CI, 1.33-1.55, respectively; P <.0001 for both). Pulmonary hypertension was found to be associated with left heart disease in 69% of patients. Among these patients, valve malfunction and diastolic dysfunction emerged as prominent causes. Left ventricular dysfunction carries additional risk to patients with pulmonary hypertension. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute changes in pulmonary artery pressures due to exercise and exposure to high altitude do not cause left ventricular diastolic dysfunction.

PubMed

Bernheim, Alain M; Kiencke, Stephanie; Fischler, Manuel; Dorschner, Lorenz; Debrunner, Johann; Mairbäurl, Heimo; Maggiorini, Marco; Brunner-La Rocca, Hans Peter

2007-08-01

Altitude-induced pulmonary hypertension has been suggested to cause left ventricular (LV) diastolic dysfunction due to ventricular interaction. In this study, we evaluate the effects of exercise- and altitude-induced increase in pulmonary artery pressures on LV diastolic function in an interventional setting investigating high-altitude pulmonary edema (HAPE) prophylaxis. Among 39 subjects, 29 were HAPE susceptible (HAPE-S) and 10 served as control subjects. HAPE-S subjects were randomly assigned to prophylactic tadalafil (10 mg), dexamethasone (8 mg), or placebo bid, starting 1 day before ascent. Doppler echocardiography at rest and during submaximal exercise was performed at low altitude (490 m) and high altitude (4,559 m). The ratio of early transmitral inflow peak velocity (E) to atrial transmitral inflow peak velocity (A), pulmonary venous flow parameters, and tissue velocity within the septal mitral annulus during early diastole (E') were used to assess LV diastolic properties. LV filling pressures were estimated by E/E'. Systolic right ventricular to atrial pressure gradients (RVPGs) were measured in order to estimate pulmonary artery pressures. At 490 m, E/A decreased similarly with exercise in HAPE-S and control subjects (HAPE-S, 1.5 +/- 0.3 to 1.3 +/- 0.3; control, 1.7 +/- 0.4 to 1.3 +/- 0.3; p = 0.12 between groups) [mean +/- SD], whereas RVPG increased significantly more in HAPE-S subjects (20 +/- 5 to 43 +/- 9 mm Hg vs 18 +/- 3 to 28 +/- 3 mm Hg, p < 0.001). Changes in RVPG levels during exercise did not correlate with changes in E/A (p > 0.1). From 490 to 4,559 m, no correlations between changes in RVPG and changes in E/A or atrial reversal (both p > 0.1) were observed. Neither of the groups showed an increase in E/E' from 490 to 4,559 m. Increased pulmonary artery pressure associated with exercise and acute exposure to 4,559 m appears not to cause LV diastolic dysfunction in healthy subjects. Therefore, ventricular interaction seems not to be of hemodynamic relevance in this setting.

Left ventricular diastolic dysfunction and increased left ventricular mass index related to pulmonary hypertension in patients with systemic autoimmune disease without pericardial effusion.

PubMed

Sugiura, Atsushi; Funabashi, Nobusada; Ozawa, Koya; Kobayashi, Yoshio

2016-10-01

We investigated the relationship of left ventricular (LV) diastolic dysfunction and LV mass index (LVMI) against pulmonary hypertension (PH) in systemic autoimmune disease (SAD). A total of 84 SAD patients (68 females; 53±17years; systemic lupus erythematosus, 27%; scleroderma, 17%; vasculitis, 16%; mixed connective tissue disease, 13% and polymyositis/dermatomyositis complex, 10%) without significant pericardial effusion (PE) on TTE (Vivid E9, GE) were analyzed. On TTE, PH was defined as peak tricuspid regurgitation velocity (TRV) of ≥2.9m/s based upon 2015 ESC guideline. Left atrial volume index (LAVI) and E/E' were measured as indicators of LV diastolic dysfunction. LVMI was also measured. Seven patients (8%) had PH. PH patients had greater LAVI (p<0.001), E/E' (p=0.004), LVMI (p=0.009) than non-PH patients. LAVI (R=0.458), E/E' (R=0.337), and LVMI (R=0.313) significantly and positively correlated with TRV (all p<0.05). Multiple regression analysis was performed to explore determinants of TRV. Age, female sex, and brain natriuretic peptide (BNP) were included in all the models. Three multiple regression models were generated using 1) LAVI, 2) E/E', and 3) LVMI and included LAVI, E/E', LVMI, and BNP as significant variables influencing TRV. Multi logistic regression analysis for predicting TRV of ≥2.9m/s showed that LAVI, and E/E' were significant predictors (Odds ratio, 1.296, and 1.370, respectively). In SAD patients without PE, LV diastolic dysfunction and increment of LVMI was closely associated with PH based upon TRV. LAVI and E/E' were independent predictors for PH. Measuring LAVI and E/E' may be a key to determine the mechanism of PH in these patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Biomechanics of Cardiac Function

PubMed Central

Voorhees, Andrew P.; Han, Hai-Chao

2015-01-01

The heart pumps blood to maintain circulation and ensure the delivery of oxygenated blood to all the organs of the body. Mechanics play a critical role in governing and regulating heart function under both normal and pathological conditions. Biological processes and mechanical stress are coupled together in regulating myocyte function and extracellular matrix structure thus controlling heart function. Here we offer a brief introduction to the biomechanics of left ventricular function and then summarize recent progress in the study of the effects of mechanical stress on ventricular wall remodeling and cardiac function as well as the effects of wall mechanical properties on cardiac function in normal and dysfunctional hearts. Various mechanical models to determine wall stress and cardiac function in normal and diseased hearts with both systolic and diastolic dysfunction are discussed. The results of these studies have enhanced our understanding of the biomechanical mechanism in the development and remodeling of normal and dysfunctional hearts. Biomechanics provide a tool to understand the mechanism of left ventricular remodeling in diastolic and systolic dysfunction and guidance in designing and developing new treatments. PMID:26426462

Role of myocardial collagen degradation and fibrosis in right ventricle dysfunction in transposition of the great arteries after atrial switch.

PubMed

Ladouceur, Magalie; Baron, Stephanie; Nivet-Antoine, Valérie; Maruani, Gérard; Soulat, Gilles; Pereira, Helena; Blanchard, Anne; Boutouyrie, Pierre; Paul, Jean Louis; Mousseaux, Elie

2018-05-01

Heart failure is a serious event in patients with transposition of the great arteries (D-TGA) after atrial redirection surgery. We aimed to determine the association between myocardial fibrosis and systolic and diastolic systemic right ventricle (sRV) dysfunction. Diastolic and systolic function of sRV was prospectively assessed using echocardiography and cardiac magnetic resonance imaging (CMR) in 48 patients with atrially switched D-TGA and 26 healthy subjects. Diastolic function of the subaortic ventricle was assessed by echocardiography Doppler and DTI. In CMR, ejection fraction of sRV and wall stress defined as the product of the systolic blood pressure and volume/mass ratio were assessed. Fibrosis extent within sRV myocardium was evaluated using gadolinium-enhanced magnetic resonance and serum collagen turnover biomarkers. Late gadolinium enhancement (LGE) was found in 35% of D-TGA patients, and the collagen degradation biomarker pro-MMP1:TIMP1 ratio was significantly increased in D-TGA patients compared to healthy subjects (1.0 × 10 -2 vs. 2.5 × 10 -2 , p = 0.04). Increase in sRV wall stress was significantly associated with LGE (p = 0.01) and pro-MMP1:TIMP1 ratio (r = 0.77, p < 0.01). After adjustment for age, sex, BMI, blood pressure and cardiac treatment, pro-MMP1:TIMP1 ratio was the strongest determinant of sRVEF (R 2  = 0.85, p < 0.01). Pro-MMP1:TIMP1 ratio was also significantly correlated with the early diastolic filling parameter E/E' (r = 0.53, p = 0.02), but this was not anymore the case after adjustment. Diastolic and systolic sRV dysfunction is related to myocardial collagen degradation and fibrosis. Research in medical therapies that reduce systemic sRV afterload and limit collagen degradation is warranted in this setting. Copyright © 2018 Elsevier B.V. All rights reserved.

Increasing Pyruvate Dehydrogenase Flux as a Treatment for Diabetic Cardiomyopathy: A Combined 13C Hyperpolarized Magnetic Resonance and Echocardiography Study.

PubMed

Le Page, Lydia M; Rider, Oliver J; Lewis, Andrew J; Ball, Vicky; Clarke, Kieran; Johansson, Edvin; Carr, Carolyn A; Heather, Lisa C; Tyler, Damian J

2015-08-01

Although diabetic cardiomyopathy is widely recognized, there are no specific treatments available. Altered myocardial substrate selection has emerged as a candidate mechanism behind the development of cardiac dysfunction in diabetes. As pyruvate dehydrogenase (PDH) activity appears central to the balance of substrate use, we aimed to investigate the relationship between PDH flux and myocardial function in a rodent model of type 2 diabetes and to explore whether or not increasing PDH flux, with dichloroacetate, would restore the balance of substrate use and improve cardiac function. All animals underwent in vivo hyperpolarized [1-(13)C]pyruvate magnetic resonance spectroscopy and echocardiography to assess cardiac PDH flux and function, respectively. Diabetic animals showed significantly higher blood glucose levels (10.8 ± 0.7 vs. 8.4 ± 0.5 mmol/L), lower PDH flux (0.005 ± 0.001 vs. 0.017 ± 0.002 s(-1)), and significantly impaired diastolic function (transmitral early diastolic peak velocity/early diastolic myocardial velocity ratio [E/E'] 12.2 ± 0.8 vs. 20 ± 2), which are in keeping with early diabetic cardiomyopathy. Twenty-eight days of treatment with dichloroacetate restored PDH flux to normal levels (0.018 ± 0.002 s(-1)), reversed diastolic dysfunction (E/E' 14 ± 1), and normalized blood glucose levels (7.5 ± 0.7 mmol/L). The treatment of diabetes with dichloroacetate therefore restored the balance of myocardial substrate selection, reversed diastolic dysfunction, and normalized blood glucose levels. This suggests that PDH modulation could be a novel therapy for the treatment and/or prevention of diabetic cardiomyopathy. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Cardiovascular dysfunction in symptomatic primary hyperparathyroidism and its reversal after curative parathyroidectomy: results of a prospective case control study.

PubMed

Agarwal, Gaurav; Nanda, Gitika; Kapoor, Aditya; Singh, Kul Ranjan; Chand, Gyan; Mishra, Anjali; Agarwal, Amit; Verma, Ashok K; Mishra, Saroj K; Syal, Sanjeev K

2013-12-01

Cardiovascular mortality in primary hyperparathyroidism (PHPT) is attributed to myocardial and endothelial dysfunction. In this prospective, case-control study we assessed cardiovascular dysfunction in patients with symptomatic PHPT and its reversal after successful parathyroidectomy. Fifty-six patients with symptomatic PHPT underwent two-dimensional echocardiography, tissue Doppler (diastolic function assessment), serum N-terminal pro-brain natriuretic peptide (s-NTproBNP, a myocardial damage marker), and endothelial- and smooth muscle-dependent vasodilatory response (vascular dysfunction) studies before, 3, and 6 months after parathyroidectomy; 25 age-matched controls were studied similarly. Patients had greater left ventricular mass (192 ± 70 vs. 149 ± 44 g; P = .006), interventricular septal thickness (10.8 ± 2.5 vs. 9.0 ± 1.6 mm; P = .001), posterior wall thickness (9.9 ± 2.0 vs. 8.6 ± 2.2 mm; P = .004), and diastolic dysfunction (lower E/A trans-mitral flow velocity ratio [1.0 ± 0.4 vs. 1.3 ± 0.4; P = .01). Patients had greater s-NTproBNP (4,625 ± 1,130 vs. 58 ± 49 pg/mL; P = .002) and lower endothelial-mediated vasodilation (9.3 ± 8.6 vs. 11.7 ± 6.3%; P = .03) and smooth muscle-mediated vasodilation (20.1 ± 17.9 vs. 23.8 ± 11.2%; P = .01). Improvements in left ventricular mass, systolic and diastolic function, and smooth muscle-mediated vasodilation were noted from 3 to 6 months after parathyroidectomy. Endothelial-mediated vasodilation did not improve significantly. S-NTproBNP levels mirrored echocardiographic changes with a substantial, sustained decrease. Results were similar in hypertensive and normotensive patients. Symptomatic PHPT patients have substantial cardiac and vascular dysfunction, which improve by 6 months after parathyroidectomy. Objective cardiovascular evaluation may improve outcomes in symptomatic PHPT patients. Copyright © 2013 Mosby, Inc. All rights reserved.

Spatial correlation of action potential duration and diastolic dysfunction in transgenic and drug-induced LQT2 rabbits.

PubMed

Odening, Katja E; Jung, Bernd A; Lang, Corinna N; Cabrera Lozoya, Rocio; Ziupa, David; Menza, Marius; Relan, Jatin; Franke, Gerlind; Perez Feliz, Stefanie; Koren, Gideon; Zehender, Manfred; Bode, Christoph; Brunner, Michael; Sermesant, Maxime; Föll, Daniela

2013-10-01

Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias. To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS. Female transgenic LQTS type 2 (LQT2; n = 11) and wild-type littermate control (LMC) rabbits (n = 9 without E4031 and n = 10 with E4031) were subjected to phase contrast magnetic resonance imaging to assess regional myocardial velocities. In the same rabbits' hearts, monophasic APDs were assessed in corresponding segments. In LQT2 and E4031-treated rabbits, APD was longer in all left ventricular segments (P < .01) and APD dispersion was greater than that in LMC rabbits (P < .01). In diastole, peak radial velocities (Vr) were reduced in LQT2 and E4031-treated compared to LMC rabbits in LV base and mid (LQT2: -3.36 ± 0.4 cm/s, P < .01; E4031-treated: -3.24 ± 0.6 cm/s, P < .0001; LMC: -4.42 ± 0.5 cm/s), indicating an impaired diastolic function. Regionally heterogeneous diastolic Vr correlated with APD (LQT2: correlation coefficient [CC] 0.38, P = .01; E4031-treated: CC 0.42, P < .05). Time-to-diastolic peak Vr were prolonged in LQT2 rabbits (LQT2: 196.8 ± 2.9 ms, P < .001; E4031-treated: 199.5 ± 2.2 ms, P < .0001, LMC 183.1 ± 1.5), indicating a prolonged contraction duration. Moreover, in transgenic LQT2 rabbits, diastolic time-to-diastolic peak Vr correlated with APD (CC 0.47, P = .001). In systole, peak Vr were reduced in LQT2 and E4031-treated rabbits (P < .01) but longitudinal velocities or ejection fraction did not differ. Finally, random forest machine learning algorithms enabled a differentiation between LQT2, E4031-treated, and LMC rabbits solely based on "mechanical" magnetic resonance imaging data. The prolongation of APD led to impaired diastolic and systolic function in transgenic and drug-induced LQT2 rabbits. APD correlated with regional diastolic dysfunction, indicating that LQTS is not purely an electrical but an electromechanical disorder. © 2013 Heart Rhythm Society. All rights reserved.

Elevated arterial stiffness and diastolic dysfunction in subclinical hypothyroidism.

PubMed

Masaki, Mitsuru; Komamura, Kazuo; Goda, Akiko; Hirotani, Shinichi; Otsuka, Misato; Nakabo, Ayumi; Fukui, Miho; Fujiwara, Shohei; Sugahara, Masataka; Lee-Kawabata, Masaaki; Tsujino, Takeshi; Koshiba, Masahiro; Masuyama, Tohru

2014-01-01

Thyroid hormone is associated with arterial stiffness and left ventricular diastolic function in hypothyroid disease. The relationship of thyroid hormone level to cardio-ankle vascular index (CAVI) and left ventricular diastolic function, however, remains unclear in subjects with subclinical hypothyroidism. We conducted a cross-sectional study of 83 patients with untreated subclinical hypothyroidism and compared them with 83 randomly selected controls from health check-ups. Log N-terminal prohormone of brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP), and arterial stiffness were measured. In addition, we measured early diastolic mitral annular velocity (E') in 43 participants with subclinical hypothyroidism and in 40 controls. When compared with the control group, patients with subclinical hypothyroidism had higher logNT-proBNP (1.9±0.5 vs. 1.7±0.3pg/ml, P<0.05), CRP (0.22±0.04 vs. 0.09±0.06mg/dl, P<0.05), and CAVI (8.8±1.7 vs. 7.8±1.4, P<0.001) and lower E' (5.8±1.7 vs. 7.5±2.1cm/s, P<0.001). CAVI was significantly associated with logNT-proBNP, CRP and E' in the subclinical hypothyroidism group. High logNT-proBNP was associated with a raised CAVI in patients with subclinical hypothyroidism. Subclinical hypothyroidism may be a risk factor for cardiovascular events related to arterial stiffening and left ventricular diastolic dysfunction.

Tissue Doppler-derived E/e' ratio as a parameter for assessing diastolic heart failure and as a predictor of mortality in patients with chronic kidney disease.

PubMed

Kim, Min Keun; Kim, Biro; Lee, Jun Young; Kim, Jae Seok; Han, Byoung-Geun; Choi, Seung Ok; Yang, Jae Won

2013-01-01

Diastolic dysfunction occurs frequently in patients with chronic kidney disease (CKD) and is associated with heart failure (HF) or mortality. We investigated whether the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e' ratio), estimated using tissue Doppler imaging, has prognostic value for cardiovascular morbidity and all-cause mortality in patients with CKD. For 186 patients with CKD of stages III to V, we obtained echocardiograms with tissue Doppler imaging. A 5-year follow-up of 136 patients was performed based on hospital records and telephone interviews. The enrolled patients (79 males and 57 females) were categorized into the following CKD subgroups: stage III (n = 25); stage IV (n = 22); and stage V (n = 89). The average follow-up period was 30.45 months and the mean age of the patients was 61.13 years. The mortality rate after 5 years was 60.0%. The causes of death were: sepsis, 21.9%; HF, 16.2%; and sudden death, 15.2%. Age (p = 0.000), increased C-reactive protein level (p = 0.018), and increased E/e' ratio (p = 0.048) were found to correlate with mortality. Age (p = 0.000), decreased ejection fraction (p = 0.003), and increased E/e' ratio (p = 0.045) correlated with cardiovascular event. The E/e' ratio can predict mortality and cardiovascular events in patients with CKD who have diastolic dysfunction.

Soy Protein Alleviates Hypertension and Fish Oil Improves Diastolic Heart Function in the Han:SPRD-Cy Rat Model of Cystic Kidney Disease.

PubMed

Ibrahim, Naser H M; Thandapilly, Sijo J; Jia, Yong; Netticadan, Thomas; Aukema, Harold

2016-05-01

Abnormalities in cardiac structure and function are very common among people with chronic kidney disease, in whom cardiovascular disease is the major cause of death. Dietary soy protein and fish oil reduce kidney disease progression in the Han:SPRD-Cy model of cystic renal disease. However, the effects of these dietary interventions in preventing alterations in cardiac structure and function due to kidney disease (reno-cardiac syndrome) in a cystic kidney disease model are not known. Therefore, weanling Han:SPRD-Cy diseased (Cy/+) and normal (+/+) rats were given diets containing either casein or soy protein, and either soy or fish oil in a three-way design for 8 weeks. Diseased rats had larger hearts, augmented left ventricular mass, and higher systolic and mean arterial blood pressure compared to the normal rats. Assessment of cardiac function using two-dimensional guided M-mode and pulse-wave Doppler echocardiography revealed that isovolumic relaxation time was prolonged in the diseased compared to normal rats, reflecting a diastolic heart dysfunction, and fish oil prevented this elevation. Soy protein resulted in a small improvement in systolic and mean arterial pressure but did not improve diastolic heart function, while fish oil prevented diastolic heart dysfunction in this model of cystic kidney disease.

Chagas cardiomyopathy: The potential effect of benznidazole treatment on diastolic dysfunction and cardiac damage in dogs chronically infected with Trypanosoma cruzi.

PubMed

Santos, Fabiane M; Mazzeti, Ana L; Caldas, Sérgio; Gonçalves, Karolina R; Lima, Wanderson G; Torres, Rosália M; Bahia, Maria Terezinha

2016-09-01

Cardiac involvement represents the main cause of mortality among patients with Chagas disease, and the relevance of trypanocidal treatment to improving diastolic dysfunction is still doubtful. In the present study, we used a canine model infected with the benznidazole-sensitive Berenice-78 Trypanosoma cruzi strain to verify the efficacy of an etiologic treatment in reducing the parasite load and ameliorating cardiac muscle tissue damage and left ventricular diastolic dysfunction in the chronic phase of the infection. The effect of the treatment on reducing the parasite load was monitored by blood PCR and blood culture assays, and the effect of the treatment on the outcome of heart tissue damage and on diastolic function was evaluated by histopathology and echo Doppler cardiogram. The benefit of the benznidazole-treatment in reducing the parasite burden was demonstrated by a marked decrease in positive blood culture and PCR assay results until 30days post-treatment. At this time, the PCR and blood culture assays yielded negative results for 82% of the treated animals, compared with only 36% of the untreated dogs. However, a progressive increase in the parasite load could be detected in the peripheral blood for one year post-treatment, as evidenced by a progressive increase in positive results for both the PCR and the blood culture assays at follow-up. The parasite load reduction induced by treatment was compatible with the lower degree of tissue damage among animals euthanized in the first month after treatment and with the increased cardiac damage after this period, reaching levels similar to those in untreated animals at the one-year follow-up. The two infected groups also presented similar, significantly smaller values for early tissue septal velocity (E' SIV) than the non-infected dogs did at this later time. Moreover, in the treated animals, an increase in the E/E' septal tissue filling pressure ratio was observed when compared with basal values as well as with values in non-infected dogs. These findings strongly suggest that the temporary reduction in the parasite load that was induced by benznidazole treatment was not able to prevent myocardial lesions and diastolic dysfunction for long after treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Early Impairment of Cardiac Function and Asynchronization of Systemic Amyloidosis with Preserved Ejection Fraction Using Two-Dimensional Speckle Tracking Echocardiography.

PubMed

Huang, He; Jing, Xian-chao; Hu, Zhang-xue; Chen, Xi; Liu, Xiao-qin

2015-12-01

To observe the ventricular global and regional function of the patients with systemic amyloidosis using two-dimensional speckle tracking echocardiography. The study enrolled 31 consecutive biopsy-proved patients with systemic amyloidosis who underwent echocardiographic examination and EF ≥ 55% and 37 age- and gender-matched healthy controls. We compared systolic strain and strain rate, diastolic strain rate, time to peak strain, peak delay time in longitudinal, radial, circumferential directions in 16 left ventricular segments. The global peak systolic longitudinal and radial strain of left ventricle, peak systolic longitudinal strain and strain rate, diastolic strain rate of right ventricular free wall were also compared. (1) Global peak systolic longitudinal strain (GPSLS), peak systolic longitudinal strain (PSLS) and strain rate (PSLSR), peak early diastolic longitudinal strain rate (PELSR) in 16 segments were decreased in case (P < 0.05). (2) Peak systolic radial strain and strain rate of inferoseptum and inferolateral at the level of papillary muscle were lower (P < 0.05), and peak early diastolic radial strain rate (PERSR) was reduced (P < 0.05). (3) Peak early diastolic circumferential strain rate was lower (P < 0.05). (4) Time to peak systolic longitudinal, radial, circumferential strain was longer, and peak delay time at the same level retarded (P < 0.05). (5) Into right ventricular wall, PSLS and PSLSR at mid-segment, and PSLSR, PELSR, peak atrial systolic longitudinal strain rate (PALSR) at basal were reduced (P < 0.05). (6) Inverse correlation between interventricular septum (IVS) thickness and GPSLS and GPSRS was found (P < 0.05). Systolic and diastolic dysfunction existed in systemic amyloidosis with preserved EF. Mechanical contraction disorder may be one reason for systolic dysfunction. GPLSR and GPRSR were negatively related to IVS thickness. © 2015, Wiley Periodicals, Inc.

Effects of exercise training on systo-diastolic ventricular dysfunction in patients with hypertension: an echocardiographic study with tissue velocity and strain imaging evaluation.

PubMed

Leggio, Massimo; Mazza, Andrea; Cruciani, Giancarlo; Sgorbini, Luca; Pugliese, Marco; Bendini, Maria Grazia; Severi, Paolo; Jesi, Anna Patrizia

2014-07-01

There is a lack of detailed data regarding the effect of exercise training in pharmacologically treated hypertensive patients. Therefore, the aim of this study was to evaluate the effects of exercise training on left and right ventricular morphologic and functional parameters by means of conventional echocardiography and sensitive new echocardiographic techniques including tissue Doppler velocity and strain imaging, that were performed in pharmacologically treated hypertensive patients at baseline and at the end of a specific exercise training protocol for primary prevention of cardiovascular disease. We selected 116 pharmacologically treated hypertensive patients who completed the exercise training protocol. All patients underwent a clinical history and examination; transthoracic echocardiography and exercise testing were performed at baseline and at the end of the exercise training protocol. Conventional echocardiography revealed a mild degree of diastolic dysfunction without significant differences or variations from baseline to the end of the exercise training protocol. In contrast, tissue Doppler velocity and strain imaging measurements demonstrated and highlighted the positive influence of exercise training: for both left and right ventricle myocardial early peak diastolic velocities (Em), the ratio of myocardial early-late peak diastolic velocity (Em/Am), myocardial peak systolic velocities (Sm) and peak strain and strain rate values significantly increased at the end of the exercise training protocol, suggesting a relationship between exercise capacity and both left and right ventricular systo-diastolic function. Our study, by means of newer more sensitive echocardiographic techniques, clearly demonstrated the positive impact of exercise training on both left and right ventricular systo-diastolic function, in terms of adjunctive subclinical improvement, in pharmacologically treated hypertensive patients.

INCREASED MYOCARDIAL STIFFNESS DUE TO CARDIAC TITIN ISOFORM SWITCHING IN A MOUSE MODEL OF VOLUME OVERLOAD LIMITS ECCENTRIC REMODELING

PubMed Central

Hutchinson, Kirk R; Saripalli, Chandra; Chung, Charles S.; Granzier, Henk

2014-01-01

We investigated the cellular and molecular mechanisms of diastolic dysfunction in pure volume overload induced by aortocaval fistula (ACF) surgery in the mouse. Four weeks of volume overload resulted in significant biventricular hypertrophy; protein expression analysis in left ventricular (LV) tissue showed a marked decrease in titin's N2BA/N2B ratio with no change in phosphorylation of titin's spring region. Titin-based passive tensions were significantly increased; a result of the decreased N2BA/N2B ratio. Conscious echocardiography in ACF mice revealed eccentric remodeling and pressure volume analysis revealed systolic dysfunction: reductions in ejection fraction (EF), +dP/dt, and the slope of the endsystolic pressure volume relationships (ESPVR). ACF mice also had diastolic dysfunction: increased LV end-diastolic pressure and reduced relaxation rates. Additionally, a decrease in the slope of the end diastolic pressure volume relationship (EDPVR) was found. However, correcting for altered geometry of the LV normalized the change in EDPVR and revealed, in line with our skinned muscle data, increased myocardial stiffness in vivo. ACF mice also had increased expression of the signaling proteins FHL-1, FHL-2, and CARP that bind to titin's spring region suggesting that titin stiffening is important to the volume overload phenotype. To test this we investigated the effect of volume overload in the RBM20 heterozygous (HET) mouse model, which exhibits reduced titin stiffness. It was found that LV hypertrophy was attenuated and that LV eccentricity was exacerbated. We propose that pure volume overload induces an increase in titin stiffness that is beneficial and limits eccentric remodeling. PMID:25450617

Ia diastolic dysfunction: an echocardiographic grade.

PubMed

Pandit, Anil; Mookadam, Farouk; Hakim, Fayaz A; Mulroy, Eoin; Saadiq, Rayya; Doherty, Mairead; Cha, Stephen; Seward, James; Wilansky, Susan

2015-01-01

To demonstrate that a distinct group of patients with Grade Ia diastolic dysfunction who do not conform to present ASE/ESE diastolic grading exists. Echocardiographic and demographic data of the Grade Ia diastolic dysfunction were extracted and compared with that of Grades I and II in 515 patients. The mean of age of the cohort was 75 ± 9 years and body mass index did not differ significantly between the 3 groups (P = 0.45). Measurements of left atrial volume index (28.58 ± 7 mL/m(2) in I, 33 ± 10 mL/m(2) in Ia, and 39 ± 12 mL/m(2) in II P < 0.001), isovolumic relaxation time (IVRT) (100 ± 17 msec in I, 103 ± 21 msec in Ia, and 79 ± 15 msec in II P < 0.001), deceleration time (248 ± 52 msec in I, 263 ± 58 msec in Ia, and 217 ± 57 msec in II P < 0.001), medial E/e' (10 ± 3 in I, 18 ± 5.00 in Ia, and 22 ± 8 in II), and lateral E/e' (8 ± 3 in I, 15 ± 6 in Ia, and 18 ± 9 in II P < 0.001) were significantly different in grade Ia compared with I and II. These findings remained significant even after adjusting for age, gender, diabetes, and smoking. Patients with echocardiographic characteristics of relaxation abnormality (E/A ratio of <0.8) and elevated filling pressures (septal E/e' ≥15, lateral E/e' ≥12, average E/e' ≥13) should be graded as a separate Grade Ia group. © 2014, Wiley Periodicals, Inc.

Aerobic exercise training promotes additional cardiac benefits better than resistance exercise training in postmenopausal rats with diabetes.

PubMed

Quinteiro, Hugo; Buzin, Morgana; Conti, Filipe Fernandes; Dias, Danielle da Silva; Figueroa, Diego; Llesuy, Susana; Irigoyen, Maria-Cláudia; Sanches, Iris Callado; De Angelis, Kátia

2015-05-01

The aim of this study was to evaluate the effects of aerobic exercise training or resistance exercise training on cardiac morphometric, functional, and oxidative stress parameters in rats with ovarian hormone deprivation and diabetes. Female Wistar rats (200-220 g) were divided into a sham-operated group (euglycemic sham-operated sedentary [ES]; n = 8) and three ovariectomized (bilateral removal of ovaries) and diabetic (streptozotocin 50 mg/kg IV) groups as follows: diabetic ovariectomized sedentary (DOS; n = 8), diabetic ovariectomized undergoing aerobic exercise training (DOTA; n = 8), and diabetic ovariectomized undergoing resistance exercise training (DOTR; n = 8). After 8 weeks of resistance (ladder) or aerobic (treadmill) exercise training, left ventricle function and morphometry were evaluated by echocardiography, whereas oxidative stress was evaluated at the left ventricle. The DOS group presented with increased left ventricle cavity in diastole and relative wall thickness (RWT), and these changes were attenuated in both DOTA and DOTR groups. Systolic and diastolic function was impaired in the DOS group compared with the ES group, and only the DOTA group was able to reverse this dysfunction. Lipoperoxidation and glutathione redox balance were improved in both trained groups compared with the DOS group. Glutathione peroxidase and superoxide dismutase were higher in the DOTA group than in the other studied groups. Correlations were observed between lipoperoxidation and left ventricle cavity in diastole (r = 0.55), between redox balance and RWT (r = 0.62), and between lipoperoxidation and RWT (r = -0.60). Aerobic exercise training and resistance exercise training promote attenuation of cardiac morphometric dysfunction associated with a reduction in oxidative stress in an experimental model of diabetes and menopause. However, only dynamic aerobic exercise training is able to attenuate systolic and diastolic dysfunction under this condition.

Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.

PubMed

Catino, Anna B; Hubbard, Rebecca A; Chirinos, Julio A; Townsend, Ray; Keefe, Stephen; Haas, Naomi B; Puzanov, Igor; Fang, James C; Agarwal, Neeraj; Hyman, David; Smith, Amanda M; Gordon, Mary; Plappert, Theodore; Englefield, Virginia; Narayan, Vivek; Ewer, Steven; ElAmm, Chantal; Lenihan, Daniel; Ky, Bonnie

2018-03-01

Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e'), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0-17.1; P =0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3-10.0; P <0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P <0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function. © 2018 American Heart Association, Inc.

SIRT1 activation attenuates diastolic dysfunction by reducing cardiac fibrosis in a model of anthracycline cardiomyopathy.

PubMed

Cappetta, Donato; Esposito, Grazia; Piegari, Elena; Russo, Rosa; Ciuffreda, Loreta Pia; Rivellino, Alessia; Berrino, Liberato; Rossi, Francesco; De Angelis, Antonella; Urbanek, Konrad

2016-02-15

Doxorubicin (DOXO) is an effective anti-neoplastic drug but its clinical benefits are hampered by cardiotoxicity. Oxidative stress, apoptosis and myocardial fibrosis mediate the anthracycline cardiomyopathy. ROS trigger TGF-β pathway that activates cardiac fibroblasts promoting fibrosis. Myocardial stiffness contributes to diastolic dysfunction, less studied aspect of anthracycline cardiomyopathy. Considering the role of SIRT1 in the inhibition of the TGF-β/SMAD3 pathway, resveratrol (RES), a SIRT1 activator, might improve cardiac function by interfering with the development of cardiac fibrosis in a model of DOXO-induced cardiomyopathy. F344 rats received a cumulative dose of 15 mg/kg of DOXO in 2 weeks or DOXO+RES (DOXO and RES, 2.5mg/kg/day, concomitantly for 2 weeks and then RES alone for 1 more week). The effects of RES on cardiac fibroblasts were also tested in vitro. Along with systolic dysfunction, DOXO was also responsible of diastolic abnormalities. Myocardial stiffness correlated with fibroblast activation and collagen deposition. DOXO+RES co-treatment significantly improved ± dP/dt and, more interestingly, ameliorated end-diastolic pressure/volume relationship. Treatment with RES resulted in reduced fibrosis and fibroblast activation and, most importantly, the mortality rate was significantly reduced in DOXO+RES group. Fibroblasts isolated from DOXO+RES-treated rats, in which SIRT1 was upregulated, showed decreased levels of TGF-β and pSMAD3/SMAD3 when compared to cells isolated from DOXO-exposed hearts. Our findings reveal a key role of SIRT1 in supporting animal survival and functional parameters of the heart. SIRT1 activation by interfering with fibrogenesis can improve relaxation properties of myocardium and attenuate myocardial remodeling related to chemotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Influence of Angiotensin-Converting-Enzyme Gene Polymorphism on Echocardiographic Data of Patients with Ischemic Heart Failure.

PubMed

Duque, Gustavo Salgado; Silva, Dayse Aparecida da; Albuquerque, Felipe Neves de; Schneider, Roberta Siuffo; Gimenez, Alinne; Pozzan, Roberto; Rocha, Ricardo Mourilhe; Albuquerque, Denilson Campos de

2016-11-01

Association between angiotensin-converting-enzyme (ACE) gene polymorphisms and different clinical and echocardiographic outcomes has been described in patients with heart failure (HF) and coronary artery disease. Studying the genetic profile of the local population with both diseases is necessary to assess the occurrence of that association. To assess the frequency of ACE gene polymorphisms in patients with ischemic HF in a Rio de Janeiro population, as well as its association with echocardiographic findings. Genetic assessment of I/D ACE polymorphism in association with clinical, laboratory and echocardiographic analysis of 99 patients. The allele frequency was: 53 I alleles, and 145 D alleles. Genotype frequencies were: 49.5% DD; 47.48% DI; 3.02% II. Drug treatment was optimized: 98% on beta-blockers, and 84.8% on ACE inhibitors or angiotensin-receptor blocker. Echocardiographic findings: difference between left ventricular diastolic diameters (ΔLVDD) during follow-up: 2.98±8.94 (DD) vs. 0.68±8.12 (DI) vs. -11.0±7.00 (II), p=0.018; worsening during follow-up of the LV systolic diameter (LVSD): 65.3% DD vs. 19.0% DI vs. 0.0% II, p=0.01; of the LV diastolic diameter (LVDD): 65.3% DD vs. 46.8% DI vs. 0.0% II, p=0.03; and of the LV ejection fraction (LVEF): 67.3% DD vs. 40.4% DI vs. 33.3% II, p=0.024. Correlated with D allele: ΔLVEF, ΔLVSD, ΔLVDD. More DD genotype patients had worsening of the LVEF, LVSD and LVDD, followed by DI genotype patients, while II genotype patients had the best outcome. The same pattern was observed for ΔLVDD. Associação entre polimorfismos genéticos da enzima conversora da angiotensina (ECA) e diferentes evoluções clínicas e ecocardiográficas foi descrita em pacientes com insuficiência cardíaca (IC) e coronariopatia. O estudo do perfil genético da população local com as duas doenças torna-se necessário para verificar a ocorrência dessa associação. Avaliar a frequência dos polimorfismos genéticos da ECA em pacientes com IC de etiologia isquêmica de uma população do Rio de Janeiro e sua associação com achados ecocardiográficos. Avaliação genética do polimorfismo I/D da ECA associada a análise de dados clínicos, laboratoriais e ecocardiográficos de 99 pacientes. Foram encontrados 53 alelos I, 145 alelos D, quanto aos genótipos da ECA: 49,5% DD, 47,48% DI, 3,02% II. O tratamento medicamentoso foi otimizado com 98% usando betabloqueadores e 84,8%, IECA ou bloqueador do receptor de angiotensina. Achados ecocardiográficos: diferença entre os diâmetros diastólicos do ventrículo esquerdo (ΔVED): 2,98±8,94 (DD) vs. 0,68±8,12 (DI) vs. -11,0±7,00 (II), p=0,018; piora evolutiva do diâmetro sistólico do VE (VES): 65,3 % DD vs. 19,0 % DI vs. 0,0 % II, p=0,01; do diâmetro diastólico do VE (VED): 65,3 % DD vs. 46,8 % DI vs. 0,0 % II, p=0,03; e da fração de ejeção do VE (FEVE): 67,3 % DD vs. 40,4 % DI vs. 33,3 % II, p=0,024. Correlação com alelo D: ΔFEVE, ΔVES, ΔVED. Foram identificados mais pacientes com piora evolutiva da FEVE e dos diâmetros cavitários do VE no genótipo DD, seguido do DI, sendo o II o de melhor evolução. O mesmo padrão foi observado na ΔVED.

Predictive factor of secondary tricuspid regurgitation after aortic valve replacement for aortic stenosis: the importance of myocardial hypertrophy and diastolic dysfunction.

PubMed

Igarashi, Takashi; Tanji, Masahiro; Takahashi, Koki; Ishida, Keiichi; Sasaki, Satomi; Yokoyama, Hitoshi

2017-05-01

The aim of this study is to determine the predictors of secondary tricuspid regurgitation after aortic valve replacement for aortic stenosis. Seventy-one patients, who underwent aortic valve replacement for aortic stenosis at our institute from January 2006 to July 2011, were divided into two groups: an STR group, which included 15 patients with moderate or greater than moderate secondary tricuspid regurgitation at a follow-up visit and a control group. Echocardiography was performed before surgery, at discharge, and at a late follow-up visit (mean follow-up 36 ± 19 months, range 0-77). Preoperatively, the number of women (p < .01), body surface area (p < .001), and relative wall thickness (0.60 ± 0.15 vs 0.71 ± 0.13, p = .022) showed significant differences between the two groups. At a follow-up visit, moderate or severe mitral regurgitation (p = .0001) and severe diastolic dysfunction (p = .003) showed significant differences between the two groups. In the Cox regression analysis, moderate or severe mitral regurgitation at follow-up (p = .038, hazard ratio 4.394, 95% CI 1.085-17.791) was the only independent predictor of secondary tricuspid regurgitation. This study suggested that preoperative concentric myocardial hypertrophy and diastolic dysfunction were associated with development of the secondary tricuspid regurgitation at late follow-up.

Impact of a systolic parameter, defined as the ratio of right brachial pre-ejection period to ejection time, on the relationship between brachial-ankle pulse wave velocity and left ventricular diastolic function.

PubMed

Hsu, Po-Chao; Lin, Tsung-Hsien; Lee, Chee-Siong; Chu, Chun-Yuan; Su, Ho-Ming; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung

2011-04-01

Arterial stiffness is correlated with left ventricular (LV) diastolic function as well as susceptibility to LV systolic function. Therefore, if LV systolic function is not known, the relationship between arterial stiffness and LV diastolic function is difficult to determine. A total of 260 patients were included in the study. The brachial-ankle pulse wave velocity (baPWV) and the ratio of right brachial pre-ejection period to ejection time (rbPEP/rbET) were measured using an ABI-form device. Patients were classified into four groups. Groups 1, 2, 3 and 4 were patients with rbPEP/rbET and baPWV below the median, rbPEP/rbET above but baPWV below the median, rbPET/rbET below but baPWV above the median, and rbPET/rbET and baPWV above the median, respectively. The LV ejection fractions in groups 1 and 3 were higher than those in groups 2 and 4 (P<0.001 for all). Patients in group 1 had a lower left atrial volume index (LAVI) and higher early diastolic mitral annular velocity (Ea) than patients in the other groups (P≤0.002). Patients in group 2 had a LAVI and ratio of transmitral E wave velocity to Ea that were comparable to those in groups 3 and 4. In conclusion, rbPEP/rbET had an impact on the relationship between baPWV and LV diastolic function. In patients with high rbPEP/rbET but low baPWV, low baPWV may not indicate good LV diastolic function but implies that cardiac dysfunction may precede vascular dysfunction in such patients. When interpreting the relationship between baPWV and LV diastolic function, the rbPEP/rbET value obtained from the same examination should be considered.

ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension.

PubMed

Makris, T K; Stavroulakis, G A; Dafni, U G; Gialeraki, A E; Krespi, P G; Hatzizacharias, A N; Tsoukala, C G; Vythoulkas, J S; Kyriakidis, M K

2000-11-01

Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with an increased incidence of myocardial infarction. Recent studies have investigated a potential influence of ACE gene polymorphism on fibrinolysis or endothelial function. It has been previously established that essential hypertension is accompanied by endothelial dysfunction and fibrinolytic balance disorders. The aim of our study was to study the relation between ACE gene polymorphism and fibrinolytic/hemostatic factors as well as endothelial cell damage markers in patients with hypertension. The following parameters were evaluated in 104 patients with previously untreated hypertension: plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) antigen, fibrinogen, D-dimer, and von Willebrand factor (vWF). The genotype of the ACE gene was also determined (by the polymerase chain reaction method), and patients were characterized according to the observed alleles as deletion/deletion (DD), insertion/insertion (II), or insertion/deletion (ID). Those with DD genotype (n = 42) had significantly higher plasma levels of PAI-1 antigen (P =. 012), tPA antigen (P =.0001), fibrinogen (P =.0002), D-dimer (P =. 0001) and vWF (P =.0004) compared with ID (n = 30) or II (n = 32) genotypes. The ACE gene genotypes appeared to be significant predictors for plasma PAI-1 antigen, tPA antigen, fibrinogen, D -dimer, and vWF even after adjustment for age, sex, body mass index, triglyceride and cholesterol levels, and blood pressure. Our findings suggest that the ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial damage in patients with untreated hypertension.

Speckle tracking evaluation of right ventricular functions in children with sickle cell disease.

PubMed

Tolba, Osama Abd Rab Elrasol; El-Shanshory, Mohamed Ramadan; El-Gamasy, Mohamed Abd Elaziz; El-Shehaby, Walid Ahmed

2017-01-01

Cardiac dysfunction is a risk factor for death in patients with sickle cell disease (SCD). Aim of the work is to evaluate the right ventricular systolic and diastolic functions by tissue Doppler and speckling tracking imaging in children with SCD. Thirty children with SCD and thirty controls were subjected to clinical, laboratory evaluations, and echocardiographic study using GE Vivid 7 (GE Medical System, Horten, Norway with a 3.5-MHz multifrequency transducer) including; Two-dimensional and tissue Doppler echocardiographic study (lateral tricuspid valve annulus peak E' velocity, lateral tricuspid valve annulus peak A' velocity, E'/A' ratio, isovolumetric relaxation time, lateral tricuspid valve annulus S' and septal S' waves and peak longitudinal systolic strain [PLSS] and time to PLSS) were done in six right ventricular segments. There was a significant decrease in right ventricular systolic and diastolic function in patients group when compared to controls. Children with SCD have impaired right ventricular systolic and diastolic functions when compared to healthy children with early evaluation of the systolic dysfunction by speckle tracking imaging technique.

Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*.

PubMed

Landesberg, Giora; Jaffe, Allan S; Gilon, Dan; Levin, Phillip D; Goodman, Sergey; Abu-Baih, Abed; Beeri, Ronen; Weissman, Charles; Sprung, Charles L; Landesberg, Amir

2014-04-01

Serum troponin concentrations predict mortality in almost every clinical setting they have been examined, including sepsis. However, the causes for troponin elevations in sepsis are poorly understood. We hypothesized that detailed investigation of myocardial dysfunction by echocardiography can provide insight into the possible causes of troponin elevation and its association with mortality in sepsis. Prospective, analytic cohort study. Tertiary academic institute. A cohort of ICU patients with severe sepsis or septic shock. Advanced echocardiography using global strain, strain-rate imaging and 3D left and right ventricular volume analyses in addition to the standard echocardiography, and concomitant high-sensitivity troponin-T measurement in patients with severe sepsis or septic shock. Two hundred twenty-five echocardiograms and concomitant high-sensitivity troponin-T measurements were performed in a cohort of 106 patients within the first days of severe sepsis or septic shock (2.1 ± 1.4 measurements/patient). Combining echocardiographic and clinical variables, left ventricular diastolic dysfunction defined as increased mitral E-to-strain-rate e'-wave ratio, right ventricular dilatation (increased right ventricular end-systolic volume index), high Acute Physiology and Chronic Health Evaluation-II score, and low glomerular filtration rate best correlated with elevated log-transformed concomitant high-sensitivity troponin-T concentrations (mixed linear model: t = 3.8, 3.3, 2.8, and -2.1 and p = 0.001, 0.0002, 0.006, and 0.007, respectively). Left ventricular systolic dysfunction determined by reduced strain-rate s'-wave or low ejection fraction did not significantly correlate with log(concomitant high-sensitivity troponin-T). Forty-one patients (39%) died in-hospital. Right ventricular end-systolic volume index and left ventricular strain-rate e'-wave predicted in-hospital mortality, independent of Acute Physiology and Chronic Health Evaluation-II score (logistic regression: Wald = 8.4, 6.6, and 9.8 and p = 0.004, 0.010, and 0.001, respectively). Concomitant high-sensitivity troponin-T predicted mortality in univariate analysis (Wald = 8.4; p = 0.004), but not when combined with right ventricular end-systolic volume index and strain-rate e'-wave in the multivariate analysis (Wald = 2.3, 4.6, and 6.2 and p = 0.13, 0.032, and 0.012, respectively). Left ventricular diastolic dysfunction and right ventricular dilatation are the echocardiographic variables correlating best with concomitant high-sensitivity troponin-T concentrations. Left ventricular diastolic and right ventricular systolic dysfunction seem to explain the association of troponin with mortality in severe sepsis and septic shock.

Diastolic Dysfunction

MedlinePlus

... the sinoatrial or SA node) sends out an electrical signal that causes the atria to contract. This ... when the ventricles are full of blood. The electrical signals cause the ventricles to contract and push ...

Left ventricular diastolic dysfunction in women with nonobstructive ischemic heart disease: insights from magnetic resonance imaging and spectroscopy.

PubMed

Nelson, Michael D

2017-10-01

Ischemic heart disease, in the absence of obstructive coronary artery disease, is prevalent in women and constitutes a major risk factor for developing major adverse cardiovascular events, including myocardial infarction, stroke, and heart failure. For decades, diagnosis was considered benign and often minimized; however, it is now known that this etiology carries much risk and is a significant burden to the health care system. This review summarizes the current state of knowledge on nonobstructive ischemic heart disease (NOIHD), the association between NOIHD and left ventricular diastolic dysfunction, potential links between NOIHD and the development of heart failure with preserved ejection fraction (HFpEF), and therapeutic options and knowledge gaps for patients living with NOIHD. Copyright © 2017 the American Physiological Society.

The contribution of discrete-trial naming and visual recognition to rapid automatized naming deficits of dyslexic children with and without a history of language delay

PubMed Central

Gasperini, Filippo; Brizzolara, Daniela; Cristofani, Paola; Casalini, Claudia; Chilosi, Anna Maria

2014-01-01

Children with Developmental Dyslexia (DD) are impaired in Rapid Automatized Naming (RAN) tasks, where subjects are asked to name arrays of high frequency items as quickly as possible. However the reasons why RAN speed discriminates DD from typical readers are not yet fully understood. Our study was aimed to identify some of the cognitive mechanisms underlying RAN-reading relationship by comparing one group of 32 children with DD with an age-matched control group of typical readers on a naming and a visual recognition task both using a discrete-trial methodology, in addition to a serial RAN task, all using the same stimuli (digits and colors). Results showed a significant slowness of DD children in both serial and discrete-trial naming (DN) tasks regardless of type of stimulus, but no difference between the two groups on the discrete-trial recognition task. Significant differences between DD and control participants in the RAN task disappeared when performance in the DN task was partialled out by covariance analysis for colors, but not for digits. The same pattern held in a subgroup of DD subjects with a history of early language delay (LD). By contrast, in a subsample of DD children without LD the RAN deficit was specific for digits and disappeared after slowness in DN was partialled out. Slowness in DN was more evident for LD than for noLD DD children. Overall, our results confirm previous evidence indicating a name-retrieval deficit as a cognitive impairment underlying RAN slowness in DD children. This deficit seems to be more marked in DD children with previous LD. Moreover, additional cognitive deficits specifically associated with serial RAN tasks have to be taken into account when explaining deficient RAN speed of these latter children. We suggest that partially different cognitive dysfunctions underpin superficially similar RAN impairments in different subgroups of DD subjects. PMID:25237301

Brain hyper-connectivity and operation-specific deficits during arithmetic problem solving in children with developmental dyscalculia

PubMed Central

Rosenberg-Lee, Miriam; Ashkenazi, Sarit; Chen, Tianwen; Young, Christina B.; Geary, David C.; Menon, Vinod

2014-01-01

Developmental dyscalculia (DD) is marked by specific deficits in processing numerical and mathematical information despite normal intelligence (IQ) and reading ability. We examined how brain circuits used by young children with DD to solve simple addition and subtraction problems differ from those used by typically developing (TD) children who were matched on age, IQ, reading ability, and working memory. Children with DD were slower and less accurate during problem solving than TD children, and were especially impaired on their ability to solve subtraction problems. Children with DD showed significantly greater activity in multiple parietal, occipito-temporal and prefrontal cortex regions while solving addition and subtraction problems. Despite poorer performance during subtraction, children with DD showed greater activity in multiple intra-parietal sulcus (IPS) and superior parietal lobule subdivisions in the dorsal posterior parietal cortex as well as fusiform gyrus in the ventral occipito-temporal cortex. Critically, effective connectivity analyses revealed hyper-connectivity, rather than reduced connectivity, between the IPS and multiple brain systems including the lateral fronto-parietal and default mode networks in children with DD during both addition and subtraction. These findings suggest the IPS and its functional circuits are a major locus of dysfunction during both addition and subtraction problem solving in DD, and that inappropriate task modulation and hyper-connectivity, rather than under-engagement and under-connectivity, are the neural mechanisms underlying problem solving difficulties in children with DD. We discuss our findings in the broader context of multiple levels of analysis and performance issues inherent in neuroimaging studies of typical and atypical development. PMID:25098903

Brain hyper-connectivity and operation-specific deficits during arithmetic problem solving in children with developmental dyscalculia.

PubMed

Rosenberg-Lee, Miriam; Ashkenazi, Sarit; Chen, Tianwen; Young, Christina B; Geary, David C; Menon, Vinod

2015-05-01

Developmental dyscalculia (DD) is marked by specific deficits in processing numerical and mathematical information despite normal intelligence (IQ) and reading ability. We examined how brain circuits used by young children with DD to solve simple addition and subtraction problems differ from those used by typically developing (TD) children who were matched on age, IQ, reading ability, and working memory. Children with DD were slower and less accurate during problem solving than TD children, and were especially impaired on their ability to solve subtraction problems. Children with DD showed significantly greater activity in multiple parietal, occipito-temporal and prefrontal cortex regions while solving addition and subtraction problems. Despite poorer performance during subtraction, children with DD showed greater activity in multiple intra-parietal sulcus (IPS) and superior parietal lobule subdivisions in the dorsal posterior parietal cortex as well as fusiform gyrus in the ventral occipito-temporal cortex. Critically, effective connectivity analyses revealed hyper-connectivity, rather than reduced connectivity, between the IPS and multiple brain systems including the lateral fronto-parietal and default mode networks in children with DD during both addition and subtraction. These findings suggest the IPS and its functional circuits are a major locus of dysfunction during both addition and subtraction problem solving in DD, and that inappropriate task modulation and hyper-connectivity, rather than under-engagement and under-connectivity, are the neural mechanisms underlying problem solving difficulties in children with DD. We discuss our findings in the broader context of multiple levels of analysis and performance issues inherent in neuroimaging studies of typical and atypical development. © 2014 John Wiley & Sons Ltd.

The effect of different atrioventricular delays on left atrium and left atrial appendage function in patients with DDD pacemaker.

PubMed

Kanadaşı, Mehmet; Caylı, Murat; Sahin, Durmuş Yıldıray; Sen, Ömer; Koç, Mevlüt; Usal, Ayhan; Batur, Mustafa Kemal; Demirtaş, Mustafa

2011-07-01

Although it has been known that optimization of atrioventricular delay (AVD) has favorable effect on the left ventricular functions in patients with DDD pacemaker, the effect of different AVDs on left atrium (LA) and left atrial appendage (LAA) functions has not been exactly evaluated. The aim of the present study was to assess the effect of different AVDs on LA and LAA functions in DDD pacemaker implanted patients with atrioventricular block. Forty-eight patients with DDD pacemaker were enrolled into the study. Patients were divided into two groups according to the echocardiographic diastolic function: Group I (normal diastolic function) and Group II (diastolic dysfunction). LAA emptying velocity on pulsed wave Doppler and LAA late systolic wave velocity by using tissue Doppler were recorded. Patients were paced for five successive continuous pacing periods of 10 minutes duration using five selective AVDs (80-250 ms). Significant effect on LA and LAA functions has not been observed by the setting of AVD in Group I. However, when the AVD was gradually shortened form 150 ms to 80 ms, LA and LAA functions gradually decreased in Group II patients. When AVD increased to 200 ms, LA and LAA functions were improved. Further increase in AVD resulted in decreased LA and LAA functions. Setting of AVD has not significant effect on the LA and LAA functions in patients with normal diastolic function, but moderate prolongation of AVD in physiological limits improved LA and LAA functions in DDD pacemaker implanted patients with diastolic dysfunction. © 2011, Wiley Periodicals, Inc.

Routine Chest X-ray: Still Valuable for the Assessment of Left Ventricular Size and Function in the Era of Super Machines?

PubMed Central

Morales, Maria-Aurora; Prediletto, Renato; Rossi, Giuseppe; Catapano, Giosuè; Lombardi, Massimo; Rovai, Daniele

2012-01-01

Objectives: The development of technologically advanced, expensive techniques has progressively reduced the value of chest X-ray in clinical practice for the assessment of left ventricular (LV) dilatation and dysfunction. Although controversial data are reported on the role of this widely available technique in cardiac assessment, it is known that the cardio-thoracic ratio is predictive of risk of progression in the NYHA Class, hospitalization, and outcome in patients with LV dysfunction. This study aimed to evaluate the reliability of the transverse diameter of heart shadow [TDH] by chest X-ray for detecting LV dilatation and dysfunction as compared to Magnetic Resonance Imaging (MRI) performed for different clinical reasons. Materials and Methods: In 101 patients, TDH was measured in digital chest X-ray and LV volumes and ejection fraction (EF) by MRI, both exams performed within 2 days. Results: A direct correlation between TDH and end-diastolic volumes (r = .75, P<0.0001) was reported. TDH cut-off values of 14.5 mm in females identified LV end-diastolic volumes >150 mL (sensitivity: 82%, specificity: 69%); in males a cut-off value of 15.5 mm identified LV end-diastolic volumes >210 mL (sensitivity: 84%; specificity: 72%). A negative relation was found between TDH and LVEF (r = -.54, P<0.0001). The above cut-off values of TDH discriminated patients with LV systolic dysfunction – LVEF <35% (sensitivity and specificity: 67% and 57% in females; 76% and 59% in males, respectively). Conclusions: Chest X-ray may still be considered a reliable technique in predicting LV dilatation by the accurate measurement of TDH as compared to cardiac MRI. Technologically advanced, expensive, and less available imaging techniques should be performed on the basis of sound clinical requests. PMID:22754739

Routine Chest X-ray: Still Valuable for the Assessment of Left Ventricular Size and Function in the Era of Super Machines?

PubMed

Morales, Maria-Aurora; Prediletto, Renato; Rossi, Giuseppe; Catapano, Giosuè; Lombardi, Massimo; Rovai, Daniele

2012-01-01

The development of technologically advanced, expensive techniques has progressively reduced the value of chest X-ray in clinical practice for the assessment of left ventricular (LV) dilatation and dysfunction. Although controversial data are reported on the role of this widely available technique in cardiac assessment, it is known that the cardio-thoracic ratio is predictive of risk of progression in the NYHA Class, hospitalization, and outcome in patients with LV dysfunction. This study aimed to evaluate the reliability of the transverse diameter of heart shadow [TDH] by chest X-ray for detecting LV dilatation and dysfunction as compared to Magnetic Resonance Imaging (MRI) performed for different clinical reasons. In 101 patients, TDH was measured in digital chest X-ray and LV volumes and ejection fraction (EF) by MRI, both exams performed within 2 days. A direct correlation between TDH and end-diastolic volumes (r = .75, P<0.0001) was reported. TDH cut-off values of 14.5 mm in females identified LV end-diastolic volumes >150 mL (sensitivity: 82%, specificity: 69%); in males a cut-off value of 15.5 mm identified LV end-diastolic volumes >210 mL (sensitivity: 84%; specificity: 72%). A negative relation was found between TDH and LVEF (r = -.54, P<0.0001). The above cut-off values of TDH discriminated patients with LV systolic dysfunction - LVEF <35% (sensitivity and specificity: 67% and 57% in females; 76% and 59% in males, respectively). Chest X-ray may still be considered a reliable technique in predicting LV dilatation by the accurate measurement of TDH as compared to cardiac MRI. Technologically advanced, expensive, and less available imaging techniques should be performed on the basis of sound clinical requests.

Cardiac-Specific Deletion of Pyruvate Dehydrogenase Impairs Glucose Oxidation Rates and Induces Diastolic Dysfunction.

PubMed

Gopal, Keshav; Almutairi, Malak; Al Batran, Rami; Eaton, Farah; Gandhi, Manoj; Ussher, John Reyes

2018-01-01

Obesity and type 2 diabetes (T2D) increase the risk for cardiomyopathy, which is the presence of ventricular dysfunction in the absence of underlying coronary artery disease and/or hypertension. As myocardial energy metabolism is altered during obesity/T2D (increased fatty acid oxidation and decreased glucose oxidation), we hypothesized that restricting myocardial glucose oxidation in lean mice devoid of the perturbed metabolic milieu observed in obesity/T2D would produce a cardiomyopathy phenotype, characterized via diastolic dysfunction. We tested our hypothesis via producing mice with a cardiac-specific gene knockout for pyruvate dehydrogenase (PDH, gene name Pdha1 ), the rate-limiting enzyme for glucose oxidation. Cardiac-specific Pdha1 deficient ( Pdha1 Cardiac-/- ) mice were generated via crossing a tamoxifen-inducible Cre expressing mouse under the control of the alpha-myosin heavy chain (αMHC-MerCreMer) promoter with a floxed Pdha1 mouse. Energy metabolism and cardiac function were assessed via isolated working heart perfusions and ultrasound echocardiography, respectively. Tamoxifen administration produced an ~85% reduction in PDH protein expression in Pdha1 Cardiac-/- mice versus their control littermates, which resulted in a marked reduction in myocardial glucose oxidation and a corresponding increase in palmitate oxidation. This myocardial metabolism profile did not impair systolic function in Pdha1 Cardiac-/- mice, which had comparable left ventricular ejection fractions and fractional shortenings as their αMHC-MerCreMer control littermates, but did produce diastolic dysfunction as seen via the reduced mitral E/A ratio. Therefore, it does appear that forced restriction of glucose oxidation in the hearts of Pdha1 Cardiac-/- mice is sufficient to produce a cardiomyopathy-like phenotype, independent of the perturbed metabolic milieu observed in obesity and/or T2D.

Flow in the left anterior descending coronary artery in patients with migraine headache.

PubMed

Aslan, Gamze; Sade, Leyla Elif; Yetis, Begum; Bozbas, Huseyin; Eroglu, Serpil; Pirat, Bahar; Can, Ufuk; Muderrisoglu, Haldun

2013-11-15

Migraine is a common neurovascular disorder characterized by attacks of severe headache, autonomic and neurologic symptoms. Migraine can affect many systems in the body, yet its effects on cardiovascular system are unclear. We hypothesized that migraine and coronary microvascular angina may be manifestations of a common systemic microvascular dysfunction and clinically associated. Forty patients with migraine and 35 healthy volunteers were included into the study. Using transthoracic Doppler echocardiography, coronary flow was visualized in the middle or distal part of the left anterior descending artery. Coronary diastolic peak flow velocities were measured with pulse wave Doppler at baseline and after dipyridamole infusion (0.56 mg/kg/4 min). Coronary flow reserve of <2 was considered normal. In addition, thorough 2-dimensional and Doppler echocardiographic examinations were also performed. Fifty-two women and 23 men were included. Coronary flow reserve was significantly lesser in the migraine group than in the control group (1.99 ± 0.3 vs 2.90 ± 0.5, p <0.05). In addition, mitral annular velocities were lower and the ratio of early mitral inflow velocity to early mitral annular velocity (E/E' lateral and E/E' septal) was higher in migraineurs than in the control group (p <0.05 for all), indicating diastolic function abnormalities in the migraine group. In conclusion, these findings suggest that there is an association between coronary microvascular dysfunction and migraine independently of the metabolic state of the patients. A common pathophysiologic pathway of impaired endothelial vasodilatation, vasomotor dysfunction, and increased systemic inflammatory factors may play a role in these 2 clinical conditions and could be the underlying cause of subclinical systolic and diastolic left ventricular dysfunction in migraineurs. Copyright © 2013 Elsevier Inc. All rights reserved.

Mechanistic insights and characterization of sickle cell disease-associated cardiomyopathy.

PubMed

Desai, Ankit A; Patel, Amit R; Ahmad, Homaa; Groth, John V; Thiruvoipati, Thejasvi; Turner, Kristen; Yodwut, Chattanong; Czobor, Peter; Artz, Nicole; Machado, Roberto F; Garcia, Joe G N; Lang, Roberto M

2014-05-01

Cardiovascular disease is an important cause of morbidity and mortality in sickle cell disease (SCD). We sought to characterize sickle cell cardiomyopathy using multimodality noninvasive cardiovascular testing and identify potential causative mechanisms. Stable adults with SCD (n=38) and healthy controls (n=13) prospectively underwent same day multiparametric cardiovascular magnetic resonance (cine, T2* iron, vasodilator first pass myocardial perfusion, and late gadolinium enhancement imaging), transthoracic echocardiography, and applanation tonometry. Compared with controls, patients with SCD had severe dilation of the left ventricle (124±27 vs 79±12 mL/m(2)), right ventricle (127±28 vs 83±14 mL/m(2)), left atrium (65±16 vs 41±9 mL/m(2)), and right atrium (78±17 vs 56±17 mL/m(2); P<0.01 for all). Patients with SCD also had a 21% lower myocardial perfusion reserve index than control subjects (1.47±0.34 vs 1.87±0.37; P=0.034). A significant subset of patients with SCD (25%) had evidence of late gadolinium enhancement, whereas only 1 patient had evidence of myocardial iron overload. Diastolic dysfunction was present in 26% of patients with SCD compared with 8% in controls. Estimated filling pressures (E/e', 9.3±2.7 vs 7.3±2.0; P=0.0288) were higher in patients with SCD. Left ventricular dilation and the presence of late gadolinium enhancement were inversely correlated to hepatic T2* times (ie, hepatic iron overload because of frequent blood transfusions; P<0.05 for both), whereas diastolic dysfunction and increased filling pressures were correlated to aortic stiffness (augmentation pressure and index, P<0.05 for all). Sickle cell cardiomyopathy is characterized by 4-chamber dilation and in some patients myocardial fibrosis, abnormal perfusion reserve, diastolic dysfunction, and only rarely myocardial iron overload. Left ventricular dilation and myocardial fibrosis are associated with increased blood transfusion requirements, whereas left ventricular diastolic dysfunction is predominantly correlated with increased aortic stiffness. http://www.clinicaltrials.gov. Unique identifier: NCT01044901. © 2014 American Heart Association, Inc.

High-intensity interval training vs. moderate-intensity continuous exercise training in heart failure with preserved ejection fraction: a pilot study.

PubMed

Angadi, Siddhartha S; Mookadam, Farouk; Lee, Chong D; Tucker, Wesley J; Haykowsky, Mark J; Gaesser, Glenn A

2015-09-15

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality. Exercise training is an established adjuvant therapy in heart failure; however, the effects of high-intensity interval training (HIIT) in HFpEF are unknown. We compared the effects of HIIT vs. moderate-intensity aerobic continuous training (MI-ACT) on peak oxygen uptake (V̇o₂peak), left ventricular diastolic dysfunction, and endothelial function in patients with HFpEF. Nineteen patients with HFpEF (age 70 ± 8.3 yr) were randomized to either HIIT (4 × 4 min at 85-90% peak heart rate, with 3 min active recovery) or MI-ACT (30 min at 70% peak heart rate). Fifteen patients completed exercise training (HIIT: n = 9; MI-ACT: n = 6). Patients trained 3 days/wk for 4 wk. Before and after training patients underwent a treadmill test for V̇o₂peak determination, 2D-echocardiography for assessment of left ventricular diastolic dysfunction, and brachial artery flow-mediated dilation (FMD) for assessment of endothelial function. HIIT improved V̇o₂peak (pre = 19.2 ± 5.2 ml·kg(-1)·min(-1); post = 21.0 ± 5.2 ml·kg(-1)·min(-1); P = 0.04) and left ventricular diastolic dysfunction grade (pre = 2.1 ± 0.3; post = 1.3 ± 0.7; P = 0.02), but FMD was unchanged (pre = 6.9 ± 3.7%; post = 7.0 ± 4.2%). No changes were observed following MI-ACT. A trend for reduced left atrial volume index was observed following HIIT compared with MI-ACT (-3.3 ± 6.6 vs. +5.8 ± 10.7 ml/m(2); P = 0.06). In HFpEF patients 4 wk of HIIT significantly improved V̇o₂peak and left ventricular diastolic dysfunction. HIIT may provide a more robust stimulus than MI-ACT for early exercise training adaptations in HFpEF. Copyright © 2015 the American Physiological Society.

Dipeptidyl peptidase 4 inhibitor attenuates obesity-induced myocardial fibrosis by inhibiting transforming growth factor-βl and Smad2/3 pathways in high-fat diet-induced obesity rat model.

PubMed

Hong, Seul-Ki; Choo, Eun-Ho; Ihm, Sang-Hyun; Chang, Kiyuk; Seung, Ki-Bae

2017-11-01

Obesity-induced myocardial fibrosis may lead to diastolic dysfunction and ultimately heart failure. Activation of the transforming growth factor (TGF)-βl and its downstream Smad2/3 pathways may play a pivotal role in the pathogenesis of obesity-induced myocardial fibrosis, and the antidiabetic dipeptidyl peptidase 4 inhibitors (DPP4i) might affect these pathways. We investigated whether DPP4i reduces myocardial fibrosis by inhibiting the TGF-β1 and Smad2/3 pathways in the myocardium of a diet-induced obesity (DIO) rat model. Eight-week-old male spontaneously hypertensive rats (SHRs) were fed either a normal fat diet (chow) or a high-fat diet (HFD) and then the HFD-fed SHRs were randomized to either the DPP4i (MK-0626) or control (distilled water) groups for 12weeks. At 20weeks old, all the rats underwent hemodynamic and metabolic studies and Doppler echocardiography. Compared with the normal fat diet (chow)-fed SHRs, the HFD-fed SHRs developed a more intense degree of hyperglycemia and dyslipidemia and showed a constellation of left ventricular (LV) diastolic dysfunction, and exacerbated myocardial fibrosis, as well as activation of the TGF-β1 and Smad2/3 pathways. DPP4i significantly improved the metabolic and hemodynamic parameters. The echocardiogram showed that DPP4i improved the LV diastolic dysfunction (early to late ventricular filling velocity [E/A] ratio, 1.49±0.21 vs. 1.77±0.09, p<0.05). Furthermore, DPP4i significantly reduced myocardial fibrosis and collagen production by the myocardium and suppressed TGF-β1 and phosphorylation of Smad2/3 in the heart. In addition, DPP4i decreased TGF-β1-induced collagen production and TGF-β1-mediated phosphorylation and nuclear translocation of Smad2/3 in rat cardiac fibroblasts. In conclusion, DPP4 inhibition attenuated myocardial fibrosis and improved LV diastolic dysfunction in a DIO rat model by modulating the TGF-β1 and Smad2/3 pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

The usefulness of left atrial volume index and left ventricular mass index in determining subclinical cardiac involvement in patients with early-stage sarcoidosis.

PubMed

Kasapkara, H A; Şentürk, A; Bilen, E; Duran Karaduman, B; Ayhan, H; Özen, M B; Durmaz, T; Keleş, T; Bozkurt, E

2016-08-01

Sarcoidosis is a multi-systemic granulomatous disease of unknown etiology. The present study has been designed to evaluate the importance of diastolic dysfunction with left atrial volume index (LAVi) and left ventricular mass index (LVMi) in determining subclinical cardiac involvement in subjects with stage I-II pulmonary sarcoidosis. A total of 54 patients under follow-up for sarcoidosis without cardiac involvement and 56 healthy subjects were included in the study. The echocardiographic assessment of the patients revealed no significant difference between the two groups regarding left ventricular end-systolic and end-diastolic diameters, ejection fraction (LVEF) and annular velocity determined by tissue Doppler evaluation. The LVEF calculated was 61.8 ± 7.8 % in the sarcoidosis group versus 64.1 ± 2.7 % in the control group (p = 0.04). Left ventricular interventricular septum thickness, posterior wall thickness, and relative wall thickness were significantly higher in the sarcoidosis group compared to the control group (p < 0.001). The sarcoidosis group had higher LVM and LVMi values compared to the control group (145 ± 18.1 and 79 ± 14 g/m(2), 135 ± 27.7 and 74 ± 14.2 g/m(2); p = 0.020 and p = 0.021, respectively). Left atrial end-systolic volume and LAVi were higher in the sarcoidosis group (28.7 ± 18.5; 15.6 ± 10.2) compared to the control group (16.6 ± 10.9; 8.9 ± 5.5) with a statistically significant difference (p < 0.001). The present study indicates diastolic dysfunction and increased LVMi despite normal systolic function in patients with early-stage sarcoidosis without cardiac involvement. Also, the diastolic parameters were normal without showing any significant difference compared to the control group while there was a statistically significant increase in LAVi. This finding suggests that LAVi may be the earliest marker of diastolic dysfunction in patients with early-stage sarcoidosis without cardiac involvement.

Cardiovascular Disease in Acromegaly.

PubMed

Sharma, Morali D; Nguyen, Anh V; Brown, Spandana; Robbins, Richard J

2017-01-01

In patients with acromegaly, chronic excess of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) leads to the development of acromegalic cardiomyopathy. Its main features are biventricular hypertrophy, diastolic dysfunction, and in later stages, systolic dysfunction and congestive heart failure. Surgical and/or pharmacological treatment of acromegaly and control of cardiovascular risk factors help reverse some of these pathophysiologic changes and decrease the high risk of cardiovascular complications.

Basic and advanced echocardiographic evaluation of myocardial dysfunction in sepsis and septic shock.

PubMed

Vallabhajosyula, S; Pruthi, S; Shah, S; Wiley, B M; Mankad, S V; Jentzer, J C

2018-01-01

Sepsis continues to be a leading cause of mortality and morbidity in the intensive care unit. Cardiovascular dysfunction in sepsis is associated with worse short- and long-term outcomes. Sepsis-related myocardial dysfunction is noted in 20%-65% of these patients and manifests as isolated or combined left or right ventricular systolic or diastolic dysfunction. Echocardiography is the most commonly used modality for the diagnosis of sepsis-related myocardial dysfunction. With the increasing use of ultrasonography in the intensive care unit, there is a renewed interest in sepsis-related myocardial dysfunction. This review summarises the current scope of literature focused on sepsis-related myocardial dysfunction and highlights the use of basic and advanced echocardiographic techniques for the diagnosis of sepsis-related myocardial dysfunction and the management of sepsis and septic shock.

Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology

PubMed Central

Bakeer, Nihal; James, Jeanne; Roy, Swarnava; Wansapura, Janaka; Shanmukhappa, Shiva Kumar; Lorenz, John N.; Osinska, Hanna; Backer, Kurt; Huby, Anne-Cecile; Shrestha, Archana; Niss, Omar; Fleck, Robert; Quinn, Charles T.; Taylor, Michael D.; Purevjav, Enkhsaikhan; Aronow, Bruce J.; Towbin, Jeffrey A.; Malik, Punam

2016-01-01

Cardiopulmonary complications are the leading cause of mortality in sickle cell anemia (SCA). Elevated tricuspid regurgitant jet velocity, pulmonary hypertension, diastolic, and autonomic dysfunction have all been described, but a unifying pathophysiology and mechanism explaining the poor prognosis and propensity to sudden death has been elusive. Herein, SCA mice underwent a longitudinal comprehensive cardiac analysis, combining state-of-the-art cardiac imaging with electrocardiography, histopathology, and molecular analysis to determine the basis of cardiac dysfunction. We show that in SCA mice, anemia-induced hyperdynamic physiology was gradually superimposed with restrictive physiology, characterized by progressive left atrial enlargement and diastolic dysfunction with preserved systolic function. This phenomenon was absent in WT mice with experimentally induced chronic anemia of similar degree and duration. Restrictive physiology was associated with microscopic cardiomyocyte loss and secondary fibrosis detectable as increased extracellular volume by cardiac-MRI. Ultrastructural mitochondrial changes were consistent with severe chronic hypoxia/ischemia and sarcomere diastolic-length was shortened. Transcriptome analysis revealed up-regulation of genes involving angiogenesis, extracellular-matrix, circadian-rhythm, oxidative stress, and hypoxia, whereas ion-channel transport and cardiac conduction were down-regulated. Indeed, progressive corrected QT prolongation, arrhythmias, and ischemic changes were noted in SCA mice before sudden death. Sudden cardiac death is common in humans with restrictive cardiomyopathies and long QT syndromes. Our findings may thus provide a unifying cardiac pathophysiology that explains the reported cardiac abnormalities and sudden death seen in humans with SCA. PMID:27503873

Diorcinol D Exerts Fungicidal Action against Candida albicans through Cytoplasm Membrane Destruction and ROS Accumulation

PubMed Central

Li, Ying; Chang, Wenqiang; Zhang, Ming; Li, Xiaobin; Jiao, Yang; Lou, Hongxiang

2015-01-01

Candida albicans, which is the most common human fungal pathogen, causes high mortality among immunocompromised patients. Antifungal drug resistance becomes a major challenge for the management of Candida infection. Diorcinol D (DD), a diphenyl ether derivative isolated from an endolichenic fungus, exerted fungicidal action against Candida species. In this study, we investigated the possible mechanism of its antifungal activity. The change of membrane dynamics and permeability suggested that the cell membrane was disrupted by the treatment of DD. This was further supported by the evidences of intracellular glycerol accumulation, alteration of cell ultrastructure, and down-regulation of genes involved in cell membrane synthesis. In addition, the treatment of C. albicans with DD resulted in the elevation of reactive oxygen species (ROS), which caused the dysfunction of mitochondria. These altogether suggested that DD exerted its antifungal activity through cytoplasmic membrane destruction and ROS accumulation. This finding is helpful to uncover the underlying mechanisms for the diphenyl ether derivatives and provides a potential application in fighting clinical fungal infections. PMID:26047493

The ACE-DD genotype is associated with endothelial dysfunction in postmenopausal women.

PubMed

Méthot, Julie; Hamelin, Bettina A; Arsenault, Marie; Bogaty, Peter; Plante, Sylvain; Poirier, Paul

2006-01-01

To evaluate the effects of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), the angiotensinogen M235T and the angiotensin II type 1 receptor A1166C polymorphisms, and hormone therapy used on endothelial function in postmenopausal women without manifestation of coronary artery disease. Sixty-four postmenopausal women (42 hormone therapy users and 22 hormone therapy nonusers) without clinical manifestation of coronary artery disease were evaluated using external vascular ultrasonography to measure endothelium-dependent (hyperemic response, flow-mediated dilatation) and -independent (nitroglycerin) dilatation. Genotypes were determined by polymerase chain reaction amplification. Women with the ACE-DD genotype displayed a lower flow-mediated dilatation compared to those with the ACE-II genotype (8.4% +/- 3.9% vs 12.6% +/- 5.4%, P = 0.04). Endothelial function was not associated with the angiotensinogen M235T and anglotensin II type 1 receptor A1166C polymorphisms. ACE polymorphism seems to modulate endothelial function among postmenopausal women without hormone therapy (8.2% +/- 5.1% vs 18.4% +/- 5.9% for the DD and the II genotype, respectively, P = 0.02). However, in hormone therapy users, flow-mediated dilatation was similar according to the ACE genotypes. Our findings suggest that ACE-I/D polymorphism is related to endothelial dysfunction in postmenopausal women. Furthermore, a potential interaction between estrogen users and ACE polymorphism on endothelial function may be present.

Subclinical hypothyroidism in combination with vitamin D deficiency increases the risk of impaired left ventricular diastolic function.

PubMed

Yilmaz, H; Cakmak, M; Darcin, T; Inan, O; Gurel, O M; Bilgic, M A; Bavbek, N; Akcay, A

2015-04-01

Subclinical hypothyroidism and vitamin D deficiency are common. The diastolic function of patients with both subclinical hypothyroidism and vitamin D deficiency remains unknown. This study aimed to investigate diastolic dysfunction in patients with both subclinical hypothyroidism and vitamin D deficiency. This study included 254 patients. All patients underwent standard Doppler echocardiography. Patients who had risk factors for diastolic dysfunction or had used L-thyroxine and vitamin D within the previous 3 months were excluded. Vitamin D deficiency was defined as a 25-OH-vitamin D level lower than 20 ng/ml, and vitamin D sufficiency was defined as a 25-OH-vitamin D level ≥ 30 ng/ml. Subclinical hypothyroidism was defined as a TSH level of 4.5-10 mU/l when the free T4 concentration was normal. The patients were divided into 4 groups. Group 1 (n=71) included patients with subclinical hypothyroidism and vitamin D deficiency; Group 2 (n=66) included patients with subclinical hypothyroidism and vitamin D sufficiency; Group 3 (n=65) included euthyroid patients with vitamin D deficiency; and Group 4 (n=52) included euthyroid patients with vitamin D sufficiency. LAVI (31.3 ± 3.2, 28.7 ± 3.0, 28.4 ± 3.4, and 27.9 ± 3.9; p<0.001) and E/E' values (11.2 ± 2.7, 8.9 ± 2.7, 9.1 ± 2.9, 8.8 ± 2.5; p<0.001) were significantly higher in Group 1 than in Groups 2, 3 and 4. E' values were significantly lower in Group 1 than in Groups 2, 3 and 4. The coexistence of subclinical hypothyroidism with vitamin D deficiency can lead to further deterioration in the LV diastolic function via the regulation of intracellular calcium and induction of inflammatory activity. Therefore, close follow-up of the diastolic functions of these patients could be beneficial.

Hyperinsulinemia and sulfonylurea use are independently associated with left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus with suboptimal blood glucose control

PubMed Central

Inoue, Tomoaki; Maeda, Yasutaka; Sonoda, Noriyuki; Sasaki, Shuji; Kabemura, Teppei; Kobayashi, Kunihisa; Inoguchi, Toyoshi

2016-01-01

Objective Although diabetes mellitus is associated with an increased risk of heart failure with preserved ejection fraction, the underlying mechanisms leading to left ventricular diastolic dysfunction (LVDD) remain poorly understood. The study was designed to assess the risk factors for LVDD in patients with type 2 diabetes mellitus. Research design and methods The study cohort included 101 asymptomatic patients with type 2 diabetes mellitus without overt heart disease. Left ventricular diastolic function was estimated as the ratio of early diastolic velocity (E) from transmitral inflow to early diastolic velocity (e’) of tissue Doppler at mitral annulus (E/e’). Parameters of glycemic control, plasma insulin concentration, treatment with antidiabetic drugs, lipid profile, and other clinical characteristics were evaluated, and their association with E/e’ determined. Patients with New York Heart Association class >1, ejection fraction <50%, history of coronary artery disease, severe valvulopathy, chronic atrial fibrillation, or creatinine clearance <30 mL/min, as well as those receiving insulin treatment, were excluded. Results Univariate analysis showed that E/e’ was significantly correlated with age (p<0.001), sex (p<0.001), duration of diabetes (p=0.002), systolic blood pressure (p=0.017), pulse pressure (p=0.010), fasting insulin concentration (p=0.025), and sulfonylurea use (p<0.001). Multivariate linear regression analysis showed that log E/e’ was significantly and positively correlated with log age (p=0.034), female sex (p=0.019), log fasting insulin concentration (p=0.010), and sulfonylurea use (p=0.027). Conclusions Hyperinsulinemia and sulfonylurea use may be important in the development of LVDD in patients with type 2 diabetes mellitus. PMID:27648285

Evaluation of P-Wave Dispersion, Diastolic Function, and Atrial Electromechanical Conduction in Pediatric Patients with Subclinical Hypothyroidism.

PubMed

Irdem, Ahmet; Aydın Sahin, Derya; Kervancioglu, Mehmet; Baspinar, Osman; Sucu, Murat; Keskin, Mehmet; Kilinc, Metin

2016-09-01

This study aimed to evaluate ventricular diastolic dysfunction, inter- and intraatrial conduction delay, and P-wave dispersion in pediatric patients with subclinical hypothyroidism. The study comprised a total of 30 pediatric patients with subclinical hypothyroidism (SH) (mean age 7.8 ± 3.2 years) and 30 healthy children (mean age 8.4 ± 3.6 years) as the control group. A SH diagnosis was made in the event of increased serum thyroid-stimulating hormone (TSH) and decreased serum free triiodothyronine (T3 ) and free thyroxine (T4 ) concentrations. Conventional Doppler imaging (TDI) showed low mitral early diastolic E-wave velocity and E/A ratio (P < 0.001) and significantly higher mitral late diastolic A-wave velocity (P = 0.001) in hypothyroidism patients. Moreover, patients with hypothyroidism had significantly lower left ventricular (LV) septal Em velocity and Em /Am ratios compared with the control group (P < 0.001), whereas Am velocity was higher in hypothyroidism patients (P = 0.018). LV lateral Em velocity and Em /Am ratio were significantly lower in patients with hypothyroidism compared with the control group (P < 0.001). With regard to atrial electromechanical conduction, atrial electromechanical delay (PA) lateral, PA septum, PA tricuspid, and each of interatrial and intraatrial conduction delay were significantly prolonged in hypothyroidism patients as compared with the control group (P < 0.001, P < 0.001, P = 0.023, P = 0.002, and P = 0.003, respectively). P-wave dispersion was significantly different in the pediatric patients with hypothyroidism (P < 0.001). This study demonstrated atrial electromechanical conduction delay, abnormal P-wave dispersion, and ventricle diastolic dysfunction in pediatric patients with hypothyroidism. © 2016, Wiley Periodicals, Inc.

[Course of ejection fraction, regurgitation fraction and ventricular volumes during exertion in chronic aortic insufficiency. Study using technetium 99m gamma-cineangiography].

PubMed

Bassand, J P; Faivre, R; Berthout, P; Cardot, J C; Verdenet, J; Bidet, R; Maurat, J P

1985-06-01

Previous studies have shown that variations of the ejection fraction (EF) during exercise were representative of the contractile state of the left ventricle: an increased EF on effort is considered to be physiological, whilst a decrease would indicate latent LV dysfunction unmasked during exercise. This hypothesis was tested by performing Technetium 99 gamma cineangiography at equilibrium under basal conditions and at maximal effort in 8 healthy subjects and 44 patients with pure, severe aortic regurgitation to measure the ejection and regurgitant fractions and the variations in end systolic and end diastolic LV volume. In the control group the EF increased and end systolic volume decreased significantly on effort whilst the regurgitant fraction and end diastolic volume were unchanged. In the 44 patients with aortic regurgitation no significant variations in EF, end systolic and end diastolic volumes were observed because the individual values were very dispersed. Variations of the EF and end systolic volume were inversely correlated. The regurgitant fraction decreased significantly on effort. Based on the variations of the EF and end systolic volume three different types of response to effort could be identified: in 7 patients, the EF increased on effort and end systolic volume decreased without any significant variation in the end diastolic volume, as in the group of normal control subjects; in 22 patients, a reduction in EF was observed on effort, associated with an increased end systolic volume. These changes indicated latent IV dysfunction inapparent at rest and unmasked by exercise; in a third group of 15 patients, the EF decreased on effort despite a physiological decrease in end systolic volume due to a greater decrease in end diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of manual thrombus aspiration on left ventricular diastolic function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

PubMed

Ilić, Ivan; Stanković, Ivan; Vidaković, Radosav; Janićijević, Aleksandra; Cerović, Milivoje; Jovanović, Vladimir; Aleksić, Aleksandar; Obradović, Gojko; Nikolajević, Ivica; Kafedzić, Srdjan; Milicević, Dusan; Kusić, Jovana; Putniković, Biljana; Nesković, Aleksandar N

2016-01-01

Data on effects of thrombus aspiration on left ventricular diastolic function in ST-elevation myocardial infarction (STEMI) population are scarce. We sought to compare echocardiographic indices of the diastolic function and outcomes in STEMI patients treated with and without manual thrombus aspiration, in an academic, high-volume percutaneous coronary intervention (PCI) center. A total of 433 consecutive patients who underwent primary PCI in 2011-2012 were enrolled in the study. Patients were not eligible for the study if they already suffered a myocardial infarction, had been previously revascularized, received thrombolytics, presented with cardiogenic shock, had significant valvular disease, atrial fibrillation or had previously implanted pacemaker. Comprehensive echocardiogram was performed within 48 hours. During follow-up patients'status was assessed by an office visit or telephone interview. Patients treated with thrombus aspiration (TA+, n=216) had similar baseline characteristics as those without thrombus aspiration (TA-, n = 217). Groups had similar total ischemic time (319 ± 276 vs. 333 ± 372 min; p = 0.665), but TA+ group had higher maximum values of troponin I (39.5 ± 30.5 vs. 27.6 ± 26.9 ng/ml; p < 0.001). The echocardiography revealed similar left ventricular volumes and systolic function, but TA+ group had significantly higher incidence of E/e' > 15, as a marker of severe diastolic dysfunction' (TA+ 23.1% vs. TA- 15.2%; p = 0.050). During average follow-up of 14 ± 5 months, major adverse cardiac/cerebral events occurred at the similar rate (log rank p = 0.867). Thrombus aspiration is associated with a greater incidence of severe diastolic dysfunction in unselected STEMI patients treated with primary PCI, but it doesn't influence the incidence of major adverse cardiovascular events.

High Serum Phosphorus Level Is Associated with Left Ventricular Diastolic Dysfunction in Peritoneal Dialysis Patients.

PubMed

Ye, Min; Tian, Na; Liu, Yanqiu; Li, Wei; Lin, Hong; Fan, Rui; Li, Cuiling; Liu, Donghong; Yao, Fengjuan

We initiated this study to explore the relationships of serum phosphorus level with left ventricular ultrasound features and diastolic function in peritoneal dialysis (PD) patients. 174 patients with end-stage renal disease (ESRD) receiving PD were enrolled in this retrospective observational study. Conventional echocardiography examination and tissue Doppler imaging (TDI) were performed in each patient. Clinical information and laboratory data were also collected. Analyses of echocardiographic features were performed according to phosphorus quartiles groups. And multivariate regression models were used to determine the association between serum phosphorus and Left ventricular diastolic dysfunction (LVDD). With the increase of serum phosphorus levels, patients on PD showed an increased tissue Doppler-derived E/e' ratio of lateral wall (P < 0.001), indicating a deterioration of left ventricular diastolic function. Steady growths of left atrium and left ventricular diameters as well as increase of left ventricular muscle mass were also observed across the increasing quartiles of phosphorus, while left ventricular ejection fraction remained normal. In a multivariate analysis, the regression coefficient for E/e' ratio in the highest phosphorus quartile was almost threefold higher relative to those in the lowest quartile group. And compared with patients in the lowest phosphorus quartile (<1.34 mmol/L) those in the highest phosphorus quartile (>1.95 mmol/L) had a more than fivefold increased odds of E/e' ratio >15. Our study showed an early impairment of left ventricular diastolic function in peritoneal dialysis patients. High serum phosphorus level was independently associated with greater risk of LVDD in these patients. Whether serum phosphorus will be a useful target for prevention or improvement of LVDD remains to be proved by further studies.

Influence of deceased donor hemodynamic factors in transplant recipients renal function.

PubMed

Baptista, Ana Paula Maia; Silva, Hélio Tedesco; Pestana, José Osmar Medina

2013-01-01

The incidence of delayed graft function (DGF) and unsatisfactory creatinine clearance (UCC) after renal transplantation is significantly higher in Brazil, when compared with that observed in United States or Europe. Deceased donor (DD) characteristics should directly influence the occurrence of these two outcomes. This study aim to evaluate the influence of DD characteristics on DGF and UCC incidence in Brazil. DD clinical and laboratory variables were correlated with outcome's incidence. We evaluated 787 DD whose organs were transplanted in 1298 patients. We noted a high prevalence of vasoactive drugs use (90.2%), hypernatremia (66.6%) and renal dysfunction (34.8%). The incidence of DGF and UCC was 60.6% and 55.2%, respectively. We observed a progressive increase in DGF risk for age groups over 30 years and for cold ischemia time (CIT) greater than 24 hours. DGF risk was two times higher in recipients of donor kidney final serum creatinine (Cr) over than 1.5 mg/dl. Hypertension and CIT over 36 hours was associated with an increasing of 82% and 99% in UCC risk, respectively. Donor age above 40 years was associated with a progressive increase in UCC risk. DD age, renal function, hypertension and prolonged CIT were associated with increased risk DGF and UCC.

Attention Dysfunction Subtypes of Developmental Dyslexia

PubMed Central

Lewandowska, Monika; Milner, Rafał; Ganc, Małgorzata; Włodarczyk, Elżbieta; Skarżyński, Henryk

2014-01-01

Background Previous studies indicate that many different aspects of attention are impaired in children diagnosed with developmental dyslexia (DD). The objective of the present study was to identify cognitive profiles of DD on the basis of attentional test performance. Material/Methods 78 children with DD (30 girls, 48 boys, mean age of 12 years ±8 months) and 32 age- and sex-matched non-dyslexic children (14 girls, 18 boys) were examined using a battery of standardized tests of reading, phonological and attentional processes (alertness, covert shift of attention, divided attention, inhibition, flexibility, vigilance, and visual search). Cluster analysis was used to identify subtypes of DD. Results Dyslexic children showed deficits in alertness, covert shift of attention, divided attention, flexibility, and visual search. Three different subtypes of DD were identified, each characterized by poorer performance on the reading, phonological awareness, and visual search tasks. Additionally, children in cluster no. 1 displayed deficits in flexibility and divided attention. In contrast to non-dyslexic children, cluster no. 2 performed poorer in tasks involving alertness, covert shift of attention, divided attention, and vigilance. Cluster no. 3 showed impaired covert shift of attention. Conclusions These results indicate different patterns of attentional impairments in dyslexic children. Remediation programs should address the individual child’s deficit profile. PMID:25387479

Obese subjects show sex-specific differences in right ventricular hypertrophy.

PubMed

Rider, Oliver J; Lewis, Andrew J M; Lewandowski, Adam J; Ntusi, Ntobeko; Nethononda, Richard; Petersen, Steffen E; Francis, Jane M; Pitcher, Alex; Banerjee, Rajarshi; Leeson, Paul; Neubauer, Stefan

2015-01-01

As right ventricular (RV) remodeling in obesity remains underinvestigated, and the impact of left ventricular (LV) diastolic dysfunction on RV hypertrophy is unknown, we aimed to investigate whether (1) sex-specific patterns of RV remodeling exist in obesity and (2) LV diastolic dysfunction in obesity is related to RV hypertrophy. Seven hundred thirty-nine subjects (women, n=345; men, n=394) without identifiable cardiovascular risk factors (body mass index [BMI], 15.3-59.2 kg/m2) underwent cardiovascular magnetic resonance (1.5 T) to measure RV mass (g), RV end-diastolic volume (mL), RV mass/volume ratio, and LV diastolic peak filling rate (mL/s). All subjects were normotensive (average, 119±11/73±8 mm Hg), normoglycaemic (4.8±0.5 mmol/L), and normocholesterolaemic (4.8±0.9 mmol/L) at the time of scanning. Across both sexes, there was a moderately strong positive correlation between BMI and RV mass (men, +0.8 g per BMI point increase; women, +1.0 g per BMI point increase; both P<0.001). Whereas women exhibited RV cavity dilatation (RV end-diastolic volume, +1.0 mL per BMI point increase; P<0.001), BMI was not correlated with RV end-diastolic volume in men (R=0.04; P=0.51). Concentric RV remodeling was present in both sexes, with RV mass/volume ratio being positively correlated to BMI (men, R=0.41; women, R=0.51; both P<0.001). Irrespective of sex, the LV peak filling rate was negatively correlated with both RV mass (men, R=-0.43; women, R=-0.44; both P<0.001) and RV mass/volume ratio (men, R=-0.37; women, R=-0.35; both P<0.001). A sex difference in RV remodeling exists in obesity. Whereas men exhibit concentric RV remodeling, women exhibit a mixed pattern of eccentric and concentric remodeling. Regardless of sex, reduced LV diastolic function is associated with concentric RV remodeling. © 2014 American Heart Association, Inc.

Comparison of speckle-tracking echocardiography with invasive hemodynamics for the detection of characteristic cardiac dysfunction in type-1 and type-2 diabetic rat models.

PubMed

Mátyás, Csaba; Kovács, Attila; Németh, Balázs Tamás; Oláh, Attila; Braun, Szilveszter; Tokodi, Márton; Barta, Bálint András; Benke, Kálmán; Ruppert, Mihály; Lakatos, Bálint Károly; Merkely, Béla; Radovits, Tamás

2018-01-16

Measurement of systolic and diastolic function in animal models is challenging by conventional non-invasive methods. Therefore, we aimed at comparing speckle-tracking echocardiography (STE)-derived parameters to the indices of left ventricular (LV) pressure-volume (PV) analysis to detect cardiac dysfunction in rat models of type-1 (T1DM) and type-2 (T2DM) diabetes mellitus. Rat models of T1DM (induced by 60 mg/kg streptozotocin, n = 8) and T2DM (32-week-old Zucker Diabetic Fatty rats, n = 7) and corresponding control animals (n = 5 and n = 8, respectively) were compared. Echocardiography and LV PV analysis were performed. LV short-axis recordings were used for STE analysis. Global circumferential strain, peak strain rate values in systole (SrS), isovolumic relaxation (SrIVR) and early diastole (SrE) were measured. LV contractility, active relaxation and stiffness were measured by PV analysis. In T1DM, contractility and active relaxation were deteriorated to a greater extent compared to T2DM. In contrast, diastolic stiffness was impaired in T2DM. Correspondingly, STE described more severe systolic dysfunction in T1DM. Among diastolic STE parameters, SrIVR was more decreased in T1DM, however, SrE was more reduced in T2DM. In T1DM, SrS correlated with contractility, SrIVR with active relaxation, while in T2DM SrE was related to cardiac stiffness, cardiomyocyte diameter and fibrosis. Strain and strain rate parameters can be valuable and feasible measures to describe the dynamic changes in contractility, active relaxation and LV stiffness in animal models of T1DM and T2DM. STE corresponds to PV analysis and also correlates with markers of histological myocardial remodeling.

ASSESSMENT OF DIASTOLIC DYSFUNCTION, ARTERIAL STIFFNESS, AND CAROTID INTIMA-MEDIA THICKNESS IN PATIENTS WITH ACROMEGALY.

PubMed

Cansu, Güven Barış; Yılmaz, Nusret; Yanıkoğlu, Atakan; Özdem, Sebahat; Yıldırım, Aytül Belgi; Süleymanlar, Gültekin; Altunbaş, Hasan Ali

2017-05-01

Early diagnosis and treatment of cardiovascular diseases, the most frequent cause of morbidity and mortality in acromegaly, may be an efficient approach to extending the lifespan of affected patients. Therefore, it is crucial to determine any cardiovascular diseases in the subclinical period. The study objectives were to determine markers of subclinical atherosclerosis and asses heart structure and function. This was a cross-sectional, single-center study of 53 patients with acromegaly and 22 age- and sex-matched healthy individuals. Carotid intima-media thickness (CIMT), pulse-wave velocity (PWV), and echocardiographic data were compared between these groups. CIMT and PWV were higher in the acromegaly group than in the healthy group (P = .008 and P = .002, respectively). Echocardiography showed that left ventricular diastolic dysfunction was present in 11.3% of patients. Left ventricular mass index and left atrial volume index were higher in the patients (P = .016 and P<.001, respectively). No differences in the CIMT, PWV, or echocardiographic measurements were identified between the patients with biochemically controlled and uncontrolled acromegaly and the control group. Our results showed that subclinical atherosclerosis (i.e., CIMT and PWV markers) and heart structure and function were worse in patients with acromegaly than in healthy individuals. Because there were no differences in these parameters between patients with controlled and uncontrolled acromegaly, our results suggest that the structural and functional changes do not reverse with biochemical control. AA = active acromegaly BSA = body surface area CA = biochemically controlled acromegaly CH = concentric hypertrophy CIMT = carotid intima-media thickness DBP = diastolic blood pressure DM = diabetes mellitus ECHO = echocardiography EDV = enddiastolic volume EF = ejection fraction ESV = endsystolic volume GH = growth hormone HC = healthy control HL = hyperlipidemia HT = hypertension IGF-1 = insulin-like growth factor 1 LA = left atrial LAV = left atrial volume LAVI = left atrial volume index LV = left ventricular LVDD = left ventricular diastolic dysfunction LVEF = left ventricular ejection fraction LVH = left ventricular hypertrophy LVMI = left ventricular mass index PWV = pulse-wave velocity RWT = relative wall thickness.

The influence of genetic polymorphisms on performance and cardiac and hemodynamic parameters among Brazilian soccer players.

PubMed

Dionísio, Thiago José; Thiengo, Carlos Rogério; Brozoski, Daniel Thomas; Dionísio, Evandro José; Talamoni, Guilherme Augusto; Silva, Roberto Braga; Garlet, Gustavo Pompermaier; Santos, Carlos Ferreira; Amaral, Sandra Lia

2017-06-01

This study investigated whether ACTN3 R577X, AMPD1 C34T, I/D ACE, and M235T AGT polymorphisms can affect performance tests such as jumping, sprinting, and endurance in 220 young male athletes from professional minor league soccer team from São Paulo Futebol Clube, Brazil. I/D ACE and M235T AGT polymorphisms were also analyzed according to cardiac and hemodynamic parameters. Athletes were grouped or not by age. DNA from saliva and Taqman assays were used for genotyping 220 athletes and the results were associated with performance tests. Ventricle mass, ventricle end-diastolic diameter, end-diastolic volume, and ejection fraction were assessed by echocardiogram. Arterial pressure, heart rate, and oximetry were assessed by a cardioscope. The main results of this study were that athletes who carried RR/RX (ACTN3) and DD (ACE) genotypes presented better performance during jump and sprint tests. On the other hand, athletes with ID/II genotype presented better results during endurance test, while AGT genotypes did not seem to favor the athletes during the evaluated physical tests. CC genotype (AMPD1) only favored the athletes during 10-m sprint test. Although there are environmental interactions influencing performance, the present results suggest that RR/RX ACTN3 and ACE DD genotypes may benefit athletes in activities that require strength and speed, while II ACE genotype may benefit athletes in endurance activities. This information could help coaches to plan the training session to improve the athletes' performance.

Hydraulic forces contribute to left ventricular diastolic filling

PubMed Central

Maksuti, Elira; Carlsson, Marcus; Arheden, Håkan; Kovács, Sándor J.; Broomé, Michael; Ugander, Martin

2017-01-01

Myocardial active relaxation and restoring forces are known determinants of left ventricular (LV) diastolic function. We hypothesize the existence of an additional mechanism involved in LV filling, namely, a hydraulic force contributing to the longitudinal motion of the atrioventricular (AV) plane. A prerequisite for the presence of a net hydraulic force during diastole is that the atrial short-axis area (ASA) is smaller than the ventricular short-axis area (VSA). We aimed (a) to illustrate this mechanism in an analogous physical model, (b) to measure the ASA and VSA throughout the cardiac cycle in healthy volunteers using cardiovascular magnetic resonance imaging, and (c) to calculate the magnitude of the hydraulic force. The physical model illustrated that the anatomical difference between ASA and VSA provides the basis for generating a hydraulic force during diastole. In volunteers, VSA was greater than ASA during 75–100% of diastole. The hydraulic force was estimated to be 10–60% of the peak driving force of LV filling (1–3 N vs 5–10 N). Hydraulic forces are a consequence of left heart anatomy and aid LV diastolic filling. These findings suggest that the relationship between ASA and VSA, and the associated hydraulic force, should be considered when characterizing diastolic function and dysfunction. PMID:28256604

Co-Occurrence of Developmental Disorders: The Case of Developmental Dyscalculia

ERIC Educational Resources Information Center

Rubinsten, Orly

2009-01-01

Five to seven percent of children experience severe difficulties in learning mathematics and/or reading. Current trials that are focused on identifying biological markers suggest that these learning disabilities, known as Developmental Dyscalculia (DD) and Dyslexia (for reading), are due to underlying brain dysfunctions. One ongoing controversy…

Presence and Implication of Temporal Nonuniformity of Early Diastolic Left Ventricular Wall Expansion in Patients With Heart Failure.

PubMed

Iwano, Hiroyuki; Kamimura, Daisuke; Fox, Ervin R; Hall, Michael E; Vlachos, Pavlos; Little, William C

2016-12-01

Early-diastolic left ventricular (LV) longitudinal expansion is delayed with diastolic dysfunction. We hypothesized that, in patients with heart failure (HF), regardless of LV ejection fraction (EF), there is diastolic temporal nonuniformity with a delay of longitudinal relative to circumferential expansion. Echocardiography was performed in 143 HF patients-50 with preserved EF (HFpEF) and 93 with reduced EF (HFrEF)-as well as 31 normal control subjects. The delay of early-diastolic mitral annular velocity from the mitral Doppler E (T E-e' ) was measured as a parameter of the longitudinal expansion delay. The delay of the longitudinal early-diastolic global strain rate (SR E ) relative to circumferential SR E (Delay C-L ) was calculated as a parameter of temporal nonuniformity. Intra-LV pressure difference (IVPD) was estimated with the use of color M-mode Doppler data as a parameter of LV diastolic suction. Although normal control subjects had symmetric LV expansion in early diastole, T E-e' and Delay C-L were significantly prolonged in HF regardless of EF (P < .01 vs control for all). Multivariate analysis revealed that Delay C-L was the independent determinant of IVPD among the parameters of LV geometry and contraction (β = -0.21; P < .05). An abnormal temporal nonuniformity of early-diastolic expansion is present in HF regardless of EF, which was associated with reduced LV suction. Copyright © 2016 Elsevier Inc. All rights reserved.

[Relationship between magnocellular function and reading skills in children: a study using visual evoked potentials].

PubMed

Kobayashi, Tomoka; Inagaki, Masumi; Yamazaki, Hiroko; Kita, Yosuke; Kaga, Makiko; Oka, Akira

2014-11-01

Developmental dyslexia (DD) is a neurodevelopmental disorder that is characterized by difficulties with accurate and/or fluent word recognition and by poor spelling and decoding abilities. The magnocellular deficit theory is one of several hypotheses that have been proposed to explain the pathophysiology of DD. In this study, we investigated magnocellular system dysfunction in Japanese dyslexic children. Subjects were 19 dyslexic children (DD group) and 19 aged-matched healthy children (TD group). They were aged between 7 and 16 years. Reversed patterns of black and white sinusoidal gratings generated at a low spatial frequency, high reversal frequency of 7.5 Hz, and low contrasts were used specifically to stimulate the magnocellular system. We recorded visual evoked potentials (VEP) from the occipital area and examined their relationship with reading and naming tasks, such as the time to read hiragana characters, rapid automatized naming of pictured objects, and phonological manipulation. Compared to the TD group, the DD group showed a significantly lower peak amplitude of VEPs through the complex demodulation method. Structural equation modeling showed that VEP peak amplitudes were related to the rapid automatized naming of pictured objects, and better rapid automatized naming resulted in higher reading skills. There was no correlation between VEP findings and the capacity for phonological manipulation. VEPs in response to the magnocellular system are useful for understanding the pathophysiology of DD. Single phonological deficit may not be sufficient to cause DD.

Effects of Obesity on Cardiovascular Hemodynamics, Cardiac Morphology, and Ventricular Function.

PubMed

Alpert, Martin A; Omran, Jad; Bostick, Brian P

2016-12-01

Obesity produces a variety of hemodynamic alterations that may cause changes in cardiac morphology which predispose to left and right ventricular dysfunction. Various neurohormonal and metabolic alterations commonly associated with obesity may contribute to these abnormalities of cardiac structure and function. These changes in cardiovascular hemodynamics, cardiac morphology, and ventricular function may, in severely obese patients, predispose to heart failure, even in the absence of other forms of heart disease (obesity cardiomyopathy). In normotensive obese patients, cardiac involvement is commonly characterized by elevated cardiac output, low peripheral vascular resistance, and increased left ventricular (LV) end-diastolic pressure. Sleep-disordered breathing may lead to pulmonary arterial hypertension and, in association with left heart failure, may contribute to elevation of right heart pressures. These alterations, in association with various neurohormonal and metabolic abnormalities, may produce LV hypertrophy; impaired LV diastolic function; and less commonly, LV systolic dysfunction. Many of these alterations are reversible with substantial voluntary weight loss.

Comparison of effects of sitagliptin and voglibose on left ventricular diastolic dysfunction in patients with type 2 diabetes: results of the 3D trial.

PubMed

Oe, Hiroki; Nakamura, Kazufumi; Kihara, Hajime; Shimada, Kenei; Fukuda, Shota; Takagi, Tsutomu; Miyoshi, Toru; Hirata, Kumiko; Yoshikawa, Junichi; Ito, Hiroshi

2015-06-19

Left ventricular (LV) diastolic dysfunction is frequently observed in patients with type 2 diabetes. Dipeptidyl peptidase-4 inhibitor (DPP-4i) attenuates postprandial hyperglycemia (PPH) and may have cardio-protective effects. It remains unclear whether DPP-4i improves LV diastolic function in patients with type 2 diabetes, and, if so, it is attributable to the attenuation of PPH or to a direct cardiac effect of DPP-4i. We compared the effects of the DPP-4i, sitagliptin, and the alpha-glucosidase inhibitor, voglibose, on LV diastolic function in patients with type 2 diabetes. We conducted a prospective, randomized, open-label, multicenter study of 100 diabetic patients with LV diastolic dysfunction. Patients received sitagliptin (50 mg/day) or voglibose (0.6 mg/day). The primary endpoints were changes in the e' velocity and E/e' ratio from baseline to 24 weeks later. The secondary efficacy measures included HbA1c, GLP-1, lipid profiles, oxidative stress markers and inflammatory markers. The study was completed with 40 patients in the sitagliptin group and 40 patients in the voglibose group. There were no significant changes in the e' velocity and E/e' ratio from baseline to 24 weeks later in both groups. However, analysis of covariance demonstrated that pioglitazone use is an independent factor associated with changes in the e' and E/e' ratio. Among patients not using pioglitazone, e' increased and the E/e' ratio decreased in both the sitagliptin and voglibose groups. GLP-1 level increased from baseline to 24 weeks later only in the sitagliptin group (4.8 ± 4.7 vs. 7.3 ± 5.5 pmol/L, p < 0.05). The reductions in HbA1c and body weight were significantly greater in the sitagliptin group than in the voglibose group (-0.7 ± 0.6 % vs. -0.3 ± 0.4, p < 0.005; -1.3 ± 3.2 kg vs. 0.4 ± 2.8 kg, p < 0.05, respectively). There were no changes in lipid profiles and inflammatory markers in both groups. Our trial showed that sitagliptin reduces HbA1c levels more greatly than voglibose does, but that neither was associated with improvement in the echocardiographic parameters of LV diastolic function in patients with diabetes. Registered at http://www.umin.ac.jp under UMIN000003784.

Oxidative stress contributes to methamphetamine-induced left ventricular dysfunction.

PubMed

Lord, Kevin C; Shenouda, Sylvia K; McIlwain, Elizabeth; Charalampidis, Dimitrios; Lucchesi, Pamela A; Varner, Kurt J

2010-07-01

Our aim was to test the hypothesis that the repeated, binge administration of methamphetamine would produce oxidative stress in the myocardium leading to structural remodeling and impaired left ventricular function. Echocardiography and Millar pressure-volume catheters were used to monitor left ventricular structure and function in rats subjected to four methamphetamine binges (3 mg/kg, iv for 4 days, separated by a 10-day drug-free period). Hearts from treated and control rats were used for histological or proteomic analysis. When compared with saline treatment, four methamphetamine binges produced eccentric left ventricular hypertrophy. The drug also significantly impaired systolic function (decreased fractional shortening, ejection fraction, and adjusted maximal power) and produced significant diastolic dysfunction (increased -dP/dt and tau). Dihydroethedium staining showed that methamphetamine significantly increased (285%) the levels of reactive oxygen species in the left ventricle. Treatment with methamphetamine also resulted in the tyrosine nitration of myofilament (desmin, myosin light chain) and mitochondrial (ATP synthase, NADH dehydrogenase, cytochrome c oxidase, prohibitin) proteins. Treatment with the superoxide dismutase mimetic, tempol in the drinking water prevented methamphetamine-induced left ventricular dilation and systolic dysfunction; however, tempol (2.5 mM) did not prevent the diastolic dysfunction. Tempol significantly reduced, but did not eliminate dihydroethedium staining in the left ventricle, nor did it prevent the tyrosine nitration of mitochondrial and contractile proteins. This study shows that oxidative stress plays a significant role in mediating methamphetamine-induced eccentric left ventricular dilation and systolic dysfunction.

Oxidative stress contributes to methamphetamine-induced left ventricular dysfunction

PubMed Central

Lord, Kevin C.; Shenouda, Sylvia K.; McIlwain, Elizabeth; Charalampidis, Dimitrios; Lucchesi, Pamela A.; Varner, Kurt J.

2010-01-01

Aims Our aim was to test the hypothesis that the repeated, binge administration of methamphetamine would produce oxidative stress in the myocardium leading to structural remodeling and impaired left ventricular function. Methods and results Echocardiography and Millar pressure–volume catheters were used to monitor left ventricular structure and function in rats subjected to four methamphetamine binges (3 mg/kg, iv for 4 days, separated by a 10-day drug-free period). Hearts from treated and control rats were used for histological or proteomic analysis. When compared with saline treatment, four methamphetamine binges produced eccentric left ventricular hypertrophy. The drug also significantly impaired systolic function (decreased fractional shortening, ejection fraction, and adjusted maximal power) and produced significant diastolic dysfunction (increased −dP/dt and tau). Dihydroethedium staining showed that methamphetamine significantly increased (285%) the levels of reactive oxygen species in the left ventricle. Treatment with methamphetamine also resulted in the tyrosine nitration of myofilament (desmin, myosin light chain) and mitochondrial (ATP synthase, NADH dehydrogenase, cytochrome c oxidase, prohibitin) proteins. Treatment with the superoxide dismutase mimetic, tempol in the drinking water prevented methamphetamine-induced left ventricular dilation and systolic dysfunction; however, tempol (2.5 mM) did not prevent the diastolic dysfunction. Tempol significantly reduced, but did not eliminate dihydroethedium staining in the left ventricle, nor did it prevent the tyrosine nitration of mitochondrial and contractile proteins. Conclusion This study shows that oxidative stress plays a significant role in mediating methamphetamine-induced eccentric left ventricular dilation and systolic dysfunction. PMID:20139112

Development of an Echocardiographic Risk-Stratification Index to Predict Heart Failure in Patients With Stable Coronary Artery Disease

PubMed Central

Stevens, Steven M.; Farzaneh-Far, Ramin; Na, Beeya; Whooley, Mary A.; Schiller, Nelson B.

2009-01-01

OBJECTIVES We sought to determine which transthoracic echocardiographic (TTE) measurements most strongly predict heart failure (HF) and to develop an index for risk stratification in outpatients with coronary artery disease (CAD). BACKGROUND Many TTE measurements have been shown to be predictive of HF, and they might be useful if aggregated into a risk-prediction index. METHODS We performed TTE in 1,024 outpatients with stable CAD enrolled in the Heart and Soul study and followed them for 4.4 years. With Cox proportional hazard models, we evaluated the association of 15 TTE measurements with subsequent HF hospital stay. Those measurements that independently predicted HF were combined into an index. Variables were defined as normal or abnormal on the basis of dichotomous cutoffs determined from the American Society of Echocardiography. Abnormal variables in each measurement were assigned points on the basis of strength of association with HF. RESULTS Of the 15 variables, 5 measurements were independent predictors of HF: left ventricular mass index (LVMI), left atrial volume index (LAVI), mitral regurgitation (MR), left ventricular outflow tract velocity-time integral (VTILVOT), and diastolic dysfunction (DD). In multivariate analysis, each of the 5 measurements independently predicted HF: LVMI >90 g/m2 (hazard ratio [HR]: 4.1; 95% confidence interval [CI]: 2.3 to 7.2, p < 0.0001); pseudo-normal or restrictive DD (HR: 2.9; 95% CI: 1.8 to 4.5, p < 0.0001); VTILVOT <22 mm (HR: 2.2; 95% CI: 1.4 to 3.5, p = 0.0004); mild, moderate, or severe MR (HR: 1.8; 95% CI: 1.2 to 2.8, p = 0.009); and LAVI >29 ml/m2 (HR: 1.6; 95% CI: 1.0 to 2.5, p = 0.06). Combining these measurements, the Heart Failure Index ranged from 0 to 8, representing risk as follows: 3 points for LVMI, 2 points for DD, and 1 point for VTILVOT, MR, and LAVI. Among participants with 0 to 2 points: 4% had HF hospital stays (reference); 3 to 4 points: 10% (HR: 2.4; 95% CI: 1.3 to 4.4, p = 0.003); 5 to 6 points: 24% (HR: 6.2; 95% CI: 3.6 to 10.6, p < 0.0001); 7 to 8 points: 48% (HR: 13.7; 95% CI: 7.2 to 25.9, p < 0.0001). CONCLUSIONS We identified 5 TTE measurements that independently predict HF in patients with stable CAD and combined them as an index that might be useful for risk stratification and serial observations. PMID:19356527

Truncation of titin's elastic PEVK region leads to cardiomyopathy with diastolic dysfunction.

PubMed

Granzier, Henk L; Radke, Michael H; Peng, Jun; Westermann, Dirk; Nelson, O Lynne; Rost, Katharina; King, Nicholas M P; Yu, Qianli; Tschöpe, Carsten; McNabb, Mark; Larson, Douglas F; Labeit, Siegfried; Gotthardt, Michael

2009-09-11

The giant protein titin plays key roles in myofilament assembly and determines the passive mechanical properties of the sarcomere. The cardiac titin molecule has 2 mayor elastic elements, the N2B and the PEVK region. Both have been suggested to determine the elastic properties of the heart with loss of function data only available for the N2B region. The purpose of this study was to investigate the contribution of titin's proline-glutamate-valine-lysine (PEVK) region to biomechanics and growth of the heart. We removed a portion of the PEVK segment (exons 219 to 225; 282 aa) that corresponds to the PEVK element of N2B titin, the main cardiac titin isoform. Adult homozygous PEVK knockout (KO) mice developed diastolic dysfunction, as determined by pressure-volume loops, echocardiography, isolated heart experiments, and muscle mechanics. Immunoelectron microscopy revealed increased strain of the N2B element, a spring region retained in the PEVK-KO. Interestingly, the PEVK-KO mice had hypertrophied hearts with an induction of the hypertrophy and fetal gene response that includes upregulation of FHL proteins. This contrasts the cardiac atrophy phenotype with decreased FHL2 levels that result from the deletion of the N2B element. Titin's PEVK region contributes to the elastic properties of the cardiac ventricle. Our findings are consistent with a model in which strain of the N2B spring element and expression of FHL proteins trigger cardiac hypertrophy. These novel findings provide a molecular basis for the future differential therapy of isolated diastolic dysfunction versus more complex cardiomyopathies.

Diastolic dysfunction in prediabetic male rats: Role of mitochondrial oxidative stress

PubMed Central

Koncsos, Gábor; Varga, Zoltán V.; Boengler, Kerstin; Rohrbach, Susanne; Li, Ling; Schlüter, Klaus-Dieter; Schreckenberg, Rolf; Radovits, Tamás; Oláh, Attila; Mátyás, Csaba; Lux, Árpád; Al-Khrasani, Mahmoud; Komlódi, Tímea; Bukosza, Nóra; Máthé, Domokos; Deres, László; Barteková, Monika; Rajtík, Tomáš; Adameová, Adriana; Szigeti, Krisztián; Helyes, Zsuzsanna; Tretter, László; Pacher, Pál; Merkely, Béla; Schulz, Rainer; Ferdinandy, Péter

2016-01-01

Although incidence and prevalence of prediabetes are increasing, little is known about its cardiac effects. Therefore, our aim was to investigate the effect of prediabetes on cardiac function and to characterize parameters and pathways associated with deteriorated cardiac performance. Long-Evans rats were fed with either control or high-fat chow for 21 wk and treated with a single low dose (20 mg/kg) of streptozotocin at week 4. High-fat and streptozotocin treatment induced prediabetes as characterized by slightly elevated fasting blood glucose, impaired glucose and insulin tolerance, increased visceral adipose tissue and plasma leptin levels, as well as sensory neuropathy. In prediabetic animals, a mild diastolic dysfunction was observed, the number of myocardial lipid droplets increased, and left ventricular mass and wall thickness were elevated; however, no molecular sign of fibrosis or cardiac hypertrophy was shown. In prediabetes, production of reactive oxygen species was elevated in subsarcolemmal mitochondria. Expression of mitofusin-2 was increased, while the phosphorylation of phospholamban and expression of Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3, a marker of mitophagy) decreased. However, expression of other markers of cardiac auto- and mitophagy, mitochondrial dynamics, inflammation, heat shock proteins, Ca2+/calmodulin-dependent protein kinase II, mammalian target of rapamycin, or apoptotic pathways were unchanged in prediabetes. This is the first comprehensive analysis of cardiac effects of prediabetes indicating that mild diastolic dysfunction and cardiac hypertrophy are multifactorial phenomena that are associated with early changes in mitophagy, cardiac lipid accumulation, and elevated oxidative stress and that prediabetes-induced oxidative stress originates from the subsarcolemmal mitochondria. PMID:27521417

From the liver to the heart: Cardiac dysfunction in obese children with non-alcoholic fatty liver disease

PubMed Central

Di Sessa, Anna; Umano, Giuseppina Rosaria; Miraglia del Giudice, Emanuele; Santoro, Nicola

2017-01-01

In the last decades the prevalence of non-alcoholic fatty liver disease (NAFLD) has increased as a consequence of the childhood obesity world epidemic. The liver damage occurring in NAFLD ranges from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Recent findings reported that fatty liver disease is related to early atherosclerosis and cardiac dysfunction even in the pediatric population. Moreover, some authors have shown an association between liver steatosis and cardiac abnormalities, including rise in left ventricular mass, systolic and diastolic dysfunction and epicardial adipose tissue thickness. In this editorial, we provide a brief overview of the current knowledge concerning the association between NAFLD and cardiac dysfunction. PMID:28144387

From the liver to the heart: Cardiac dysfunction in obese children with non-alcoholic fatty liver disease.

PubMed

Di Sessa, Anna; Umano, Giuseppina Rosaria; Miraglia Del Giudice, Emanuele; Santoro, Nicola

2017-01-18

In the last decades the prevalence of non-alcoholic fatty liver disease (NAFLD) has increased as a consequence of the childhood obesity world epidemic. The liver damage occurring in NAFLD ranges from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Recent findings reported that fatty liver disease is related to early atherosclerosis and cardiac dysfunction even in the pediatric population. Moreover, some authors have shown an association between liver steatosis and cardiac abnormalities, including rise in left ventricular mass, systolic and diastolic dysfunction and epicardial adipose tissue thickness. In this editorial, we provide a brief overview of the current knowledge concerning the association between NAFLD and cardiac dysfunction.

Validation of the Omron MIT Elite blood pressure device in a pregnant population with large arm circumference.

PubMed

James, Lauren; Nzelu, Diane; Hay, Anna; Shennan, Andrew; Kametas, Nikos A

2017-04-01

The aim of this study was to evaluate the accuracy of the Omron MIT Elite automated device in pregnant women with an arm circumference of or above 32 cm, using the British Hypertension Society validation protocol. Blood pressure was measured sequentially in 46 women of any gestation requiring the use of a large cuff (arm circumference ≥32 cm) alternating between the mercury sphygmomanometer and the Omron MIT Elite device. The Omron MIT Elite achieved an overall D/D grade with a mean of the device-observer difference being 7.17±6.67 and 9.31±6.59 for systolic and diastolic blood pressure respectively. Interobserver accuracy was 94.6% for systolic and 95% for diastolic readings within 5 mmHg. The Omron MIT Elite overestimates blood pressure and has failed the British Hypertension Society protocol requirements. Therefore, it cannot be recommended for use in pregnant women with an arm circumference of or above 32 cm.

Intestinal Microbiota-Dependent Phosphatidylcholine Metabolites, Diastolic Dysfunction and Adverse Clinical Outcomes in Chronic Systolic Heart Failure

PubMed Central

Wilson Tang, W. H.; Wang, Zeneng; Shrestha, Kevin; Borowski, Allen G; Wu, Yuping; Troughton, Richard W; Klein, Allan L; Hazen, Stanley L

2014-01-01

Background Trimethylamine-N-oxide (TMAO) has been linked to increased cardiovascular risk. We aim to determine the prognostic value of TMAO and its dietary precursors, choline and betaine, in heart failure (HF). Methods and Results In 112 patients with chronic systolic HF with comprehensive echocardiographic evaluation, we measured plasma TMAO, choline, and betaine by mass spectrometry. Median TMAO levels, choline, and betaine levels were 5.8 [3.6, 12.1] μM, 10.9 [8.4, 14.0] μM, 43.8 [37.1, 53.0] μM, respectively, and were correlated with each other (all p<0.0001 for both). TMAO levels were significantly higher in patients with diabetes mellitus (9.4 [4.9, 13.2] vs 4.8 [3.4, 9.8] μM, p=0.005) and in subjects with New York Heart Association (NYHA) class III or greater (7.0 [4.7, 14.8] vs 4.7 [3.4, 11.3] μM, p=0.02). Elevated TMAO, choline, and betaine levels were each associated with higher plasma NT-proBNP levels and more advanced left ventricular diastolic dysfunction, but not systolic dysfunction or inflammatory and endothelial biomarkers. Higher choline (Hazard ratio (HR) 1.64 [95% CI: 1.22 2.20], p=0.001), betaine (HR 1.51 [1.10–2.08], p=0.01), and TMAO (HR 1.48 [1.10–1.96], p=0.01) predicted increased risk for 5-year adverse clinical events (death/transplant). Only higher TMAO levels predicted incident adverse clinical events independent of age, eGFR, mitral E/septal Ea, and NT-proBNP levels (HR 1.46 [1.03 2.14], p=0.03). Conclusion Elevated plasma TMAO, choline and betaine levels are each associated with more advanced left ventricular diastolic dysfunction and portend poorer long-term adverse clinical outcomes in chronic systolic HF. However, only higher plasma TMAO levels was associated with poor prognosis after adjustment for cardio-renal indices. PMID:25459686

Premorbid Anomalies and Risk of Schizophrenia and Depressive Disorders in a Birth Cohort Exposed to Prenatal Rubella

ERIC Educational Resources Information Center

Penner, Justin D.; Brown, Alan S.

2007-01-01

In a birth cohort prenatally exposed to rubella, we assessed whether prospectively documented premorbid neuromotor dysfunction, mannerisms, deviant behaviors, and temperament during childhood and adolescence were impaired in cases who developed depressive disorder (DD) relative to rubella-exposed controls and cases who developed schizophrenia…

Authoritative parenting and parental stress in parents of pre-school and older children with developmental disabilities.

PubMed

Woolfson, L; Grant, E

2006-03-01

Rearing a child with a developmental disability is associated with increased parental stress. Theories of stress and adjustment and bi-directional theories of child development suggest that parenting could influence these negative outcomes. Relationships between parenting approaches and stress in parents of children with developmental disabilities (DD) (N = 53) were examined across two age groups, 3-5 years and 9-11 years and compared with a contrast group of typically developing children (TD) (N = 60). Measures used were the Parenting Stress Index-Short Form and Rickel and Biasatti's modification of Block's Child Rearing Practices Report, classified into Baumrind's parenting styles using Reitman and Gross's method. Parents in the older DD group used Authoritative parenting less than parents in the younger DD group, while the opposite developmental pattern was seen in the TD group. Multivariate analysis of variance showed a significant group x parenting style interaction for Parental Distress, Parent-Child Dysfunctional Interaction and Difficult Child. Stress measures were higher for the DD group and seemed to be associated with Authoritative parenting approaches, an effect that was not observed in the TD group. Findings suggest that the well-established effect of group on stress may be moderated by parenting style. Authoritative parenting may be highly stressful for parents of children with DD to implement, resulting in a decrease in its use across the two age groups.

Conditional deletion of Tsc1 in the female reproductive tract impedes normal oviductal and uterine function by enhancing mTORC1 signaling in mice

PubMed Central

Daikoku, Takiko; Yoshie, Mikihiro; Xie, Huirong; Sun, Xiaofei; Cha, Jeeyeon; Ellenson, Lora Hedrick; Dey, Sudhansu K.

2013-01-01

Heightened mammalian target of rapamycin complex 1 (mTORC1) activity by genetic deletion of its direct inhibitor, Tsc1, is associated with aberrant development and dysfunction of the female reproductive tract in mice. Here, we compared the phenotypes of mice with conditional deletion of Tsc1 in the female reproductive tract by either progesterone receptor (PR)-Cre (Tsc1PR(d/d)), which inactivates Tsc1 in all major cell types in the uterus (epithelium, stroma and myometrium), or anti-Mullerian hormone type 2 receptor (Amhr2)-Cre (Tsc1Amhr2(d/d)), which inactivates stromal and myometrial Tsc1. Tsc1PR(d/d) and Tsc1Amhr2(d/d) females are infertile resulting from oviductal hyperplasia, retention of embryos in the oviduct and implantation failure. In contrast to the appropriate embryonic development after fertilization seen in Tsc1Amhr2(d/d) females, embryo development was disrupted in Tsc1PR(d/d) females. In addition, uteri in Tsc1PR(d/d) and Tsc1Amhr2(d/d) females showed epithelial hyperplasia but not endometrial cancer. In conclusion, Tsc1PR(d/d) and Tsc1Amhr2(d/d) have overlapping yet distinct phenotypes in the context of compartment-specific deletion of Tsc1. PMID:23475984

B-type natriuretic peptide testing for detection of heart failure.

PubMed

Saul, Lauren; Shatzer, Melanie

2003-01-01

The incidence of heart failure (HF) is on the increase with the aging population. Heart failure can manifest as either systolic or diastolic dysfunction. Systolic dysfunction causes impaired ventricular contractility with an ejection fraction of less than 45%. In contrast, diastolic dysfunction is evidenced by impaired ventricular relaxation and an ejection fraction greater than 45%. The diagnosis of HF is challenging with patients who present with acute dyspnea and a history of chronic obstructive pulmonary disease or pneumonia. The pathophysiology of HF and the resulting compensatory mechanisms involve a complex neuroendocrine response that includes a release of natriuretic peptides including B-type natriuretic peptides (BNPs). Elevation of BNP is in response to ventricular wall stress and volume overload from HF. BNP promotes natriuresis, diuresis, and vasodilitation and therefore counteracts some of the deleterious effects of the neuroendocrine response in HF Recently, a new laboratory test for BNP has been developed to assist in rapid identification of patients with HF. Research studies have shown that BNP testing assists in differentiating between cardiac and pulmonary causes of acute dyspnea and could be used to evaluate effectiveness of therapy and as a predictor for length of stay and readmission.

Cardiovascular adaptation to extrauterine life after intrauterine growth restriction.

PubMed

Rodriguez-Guerineau, Luciana; Perez-Cruz, Miriam; Gomez Roig, María D; Cambra, Francisco J; Carretero, Juan; Prada, Fredy; Gómez, Olga; Crispi, Fátima; Bartrons, Joaquim

2018-02-01

Introduction The adaptive changes of the foetal heart in intrauterine growth restriction can persist postnatally. Data regarding its consequences for early circulatory adaptation to extrauterine life are scarce. The aim of this study was to assess cardiac morphometry and function in newborns with late-onset intrauterine growth restriction to test the hypothesis that intrauterine growth restriction causes cardiac shape and functional changes at birth. A comprehensive echocardiographic study was performed in 25 neonates with intrauterine growth restriction and 25 adequate-for-gestational-age neonates. Compared with controls, neonates with intrauterine growth restriction had more globular ventricles, lower longitudinal tricuspid annular motion, and higher left stroke volume without differences in the heart rate. Neonates with intrauterine growth restriction also showed subclinical signs of diastolic dysfunction in the tissue Doppler imaging with lower values of early (e') diastolic annular peak velocities in the septal annulus. Finally, the Tei index in the tricuspid annulus was higher in the intrauterine growth restriction group. Neonates with history of intrauterine growth restriction showed cardiac remodelling and signs of systolic and diastolic dysfunction. Overall, there was a significant tendency to worse cardiac function results in the right heart. The adaptation to extrauterine life occurred with more globular hearts, higher stroke volumes but a similar heart rate compared to adequate-for-gestational-age neonates.

L wave in echo Doppler.

PubMed

Kumar, Vipin; Jose, John; Jose, V Jacob

2014-01-01

62-year-old female presented with progressive dyspnea NYHA class III for six months. Echocardiography showed normal left ventricular (LV) systolic function, mild biatrial enlargement, an L wave in pulse wave Doppler at mitral inflow and in M mode echocardiography across mitral valve. Tissue Doppler imaging at medial mitral annulus showed an L' wave in mid diastole in addition to E' and A' wave. An L wave in pulse wave Doppler and M mode echocardiography represents continued pulmonary vein mid diastolic flow through the left atrium in to LV across mitral valve after early rapid filling. Presence of an L' wave in these patients associated with higher E/E' is indicative of advance diastolic dysfunction with elevated filling pressures. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice

DOE PAGES

Yuan, Chen-Ching; Muthu, Priya; Kazmierczak, Katarzyna; ...

2015-06-29

Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory light chain (RLC) of cardiac myosin is known to play a beneficial role in heart disease, but the idea of a phosphorylation-mediated reversal of a hypertrophic cardiomyopathy (HCM) phenotype is novel. Our previous studies on transgenic (Tg) HCM-RLC mice revealed that the D166V (Aspartate166 →Valine) mutation-induced changes in heart morphology and function coincided with largely reduced RLC phosphorylation in situ. In this paper, we hypothesized that the introduction of a constitutively phosphorylated Serine15 (S15D) into the hearts of D166V mice would prevent the development of a deleterious HCM phenotype. In supportmore » of this notion, MLCK-induced phosphorylation of D166V-mutated hearts was found to rescue some of their abnormal contractile properties. Tg-S15D-D166V mice were generated with the human cardiac RLC-S15D-D166V construct substituted for mouse cardiac RLC and were subjected to functional, structural, and morphological assessments. The results were compared with Tg-WT and Tg-D166V mice expressing the human ventricular RLC-WT or its D166V mutant, respectively. Echocardiography and invasive hemodynamic studies demonstrated significant improvements of intact heart function in S15D-D166V mice compared with D166V, with the systolic and diastolic indices reaching those monitored in WT mice. A largely reduced maximal tension and abnormally high myofilament Ca 2+ sensitivity observed in D166V-mutated hearts were reversed in S15D-D166V mice. Low-angle X-ray diffraction study revealed that altered myofilament structures present in HCM-D166V mice were mitigated in S15D-D166V rescue mice. Finally, our collective results suggest that expression of pseudophosphorylated RLC in the hearts of HCM mice is sufficient to prevent the development of the pathological HCM phenotype.« less

Maternal Stress and Coping Strategies in Developmental Dyslexia: An Italian Multicenter Study.

PubMed

Carotenuto, Marco; Messina, Antonietta; Monda, Vincenzo; Precenzano, Francesco; Iacono, Diego; Verrotti, Alberto; Piccorossi, Alessandra; Gallai, Beatrice; Roccella, Michele; Parisi, Lucia; Maltese, Agata; Lavano, Francesco; Marotta, Rosa; Lavano, Serena Marianna; Lanzara, Valentina; Ferrentino, Roberta Ida; Pisano, Simone; Salerno, Margherita; Valenzano, Anna; Triggiani, Antonio Ivano; Polito, Anna N; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni; Ruberto, Maria; Esposito, Maria

2017-01-01

Studies about the impact of developmental dyslexia (DD) on parenting are scarce. Our investigation aimed to assess maternal stress levels and mothers' copying styles in a population of dyslexic children. A total of 874 children (500 boys, 374 girls; mean age 8.32 ± 2.33 years) affected by DD was included in the study. A total of 1,421 typically developing children (789 boys, 632 girls; mean age 8.25 ± 3.19 years) were recruited from local schools of participating Italian Regions (Abruzzo, Calabria, Campania, Puglia, Umbria, Sicily) and used as control-children group. All mothers (of both DD and typically developing children) filled out an evaluation for parental stress (Parenting Stress Index-Short Form) and coping strategies [Coping Inventory for Stressful Situations (CISS)]. No statistical differences for mean age ( p  = 0.456) and gender ( p  = 0.577) were found between DD and control children. Mothers of children affected by DD showed an higher rate of all parental stress indexes (Parental Distress domain p  < 0.001, Difficult Child p  < 0.001, Parent-Child Dysfunctional Interaction p  < 0.001, and Total Stress subscale score p  < 0.001) than controls mothers. According to the CISS evaluation, mothers of DD children reported a significantly higher rate of emotion-oriented ( p  < 0.001) and avoidance-oriented ( p  < 0.001) coping styles than mothers of typical developing children. On the other hand, a lower representation of task-oriented coping style was found in mothers of DD children ( p  < 0.001) in comparison to mothers of control-children. Our study shows the clinical relevance of the burden carried by the mothers of children affected by DD and suggests the importance to assess parents, particularly mothers, to improve family compliance and clinical management of this disorder.

Evaluation of the Causes of Erectile Dysfunction in Patients Undergoing Penile Doppler Ultrasonography in Pakistan

PubMed Central

Khanzada, Usman; Khan, Sohail Ahmed; Hussain, Munawar; Adel, Hatem; Masood, Kamran; Manohar, Murli

2017-01-01

Purpose In patients with erectile dysfunction, it is important to differentiate psychogenic from organic causes. Penile Doppler ultrasonography is a relatively inexpensive and minimally invasive tool for this purpose. This study was conducted to evaluate the causes of erectile dysfunction in an adult male population, using penile Doppler ultrasonography. Materials and Methods A retrospective study was conducted in a single center. All patients who presented with complaints of erectile dysfunction and underwent penile Doppler ultrasonography between July 2014 and June 2016 were included in this study. All examinations were performed using GE Voluson S6 and GE Logiq P5 devices. Following baseline scans, an intracavernosal injection of 20 µg of prostaglandin E1 was given. Peak systolic and end diastolic velocities were measured in each cavernosal artery. Patients with a peak systolic velocity of <25 cm/s were considered to have arterial insufficiency, while an end diastolic velocity of >5 cm/s was considered to indicate venous incompetence. Results Out of 97 patients (mean age, 37.09±11.59 years; range, 19~69 years), 50 patients (51.5%) had normal findings, 24 patients (24.7%) had arterial insufficiency, 15 patients (15.5%) had a venous leak, and 8 patients (8.2%) patients had arterial insufficiency with a venous leak. Psychogenic erectile dysfunction was significantly higher among patients aged ≤40 years, while arterial insufficiency with or without a venous leak was significantly higher among patients aged >40 years (p=0.022). Conclusions A majority of the studied individuals demonstrated no organic cause of erectile dysfunction, thus confirming a high prevalence of the psychogenic etiology, particularly in relatively young individuals. PMID:28459144

Interstudy heterogeneity of definitions of diastolic dysfunction severely affects reported prevalence

PubMed Central

Selmeryd, Jonas; Henriksen, Egil; Leppert, Jerzy; Hedberg, Pär

2016-01-01

Aims The aim of this article is to examine how the European Association of Cardiovascular Imaging (EACVI) and the American Society of Echocardiography (ASE) recommendations on the classification of diastolic dysfunction (DDF) are interpreted in the scientific community and to explore how variations in the DDF definition affect the reported prevalence. Methods and results A systematic review of studies citing the EACVI/ASE consensus document ‘Recommendations for the evaluation of left ventricular diastolic function by echocardiography’ was performed. The definition of DDF used in each study was recorded. Subsequently, several possible interpretations of the EACVI/ASE classification scheme were used to obtain DDF prevalence in a community-based sample (n = 714). In the systematic review, 60 studies were included. In 13 studies, no specification of DDF definition was presented, a one-level classification tree was used in 13, a two-level classification tree in 18, and in the remaining 16 studies, a DDF definition was presented but no grading of DDF was performed. In 17 studies, the DDF definition relied solely on early diastolic tissue velocity and/or left atrial size. In eight of these studies, a single parameter was used, in two studies the logical operator AND was used to combine two or more parameters, and the remaining seven studies used the logical operator OR. The resulting prevalence of DDF in the community-based sample varied from 12 to 84%, depending on the DDF definition used. Conclusion A substantial heterogeneity of definitions of DDF was evident among the studies reviewed, and the different definitions had a substantial impact on the reported prevalence of DDF. PMID:26374880

The impact of depressed mood, working memory capacity, and priming on delay discounting.

PubMed

Szuhany, Kristin L; MacKenzie, Danny; Otto, Michael W

2018-09-01

The impaired ability to delay rewards, delay discounting (DD), is associated with several problematic conditions in which impulsive decision-making derails long-term goals. Working memory (WM), the ability to actively store and manipulate information, is associated with DD. The purpose of this study was to examine the effect of cognitive priming on DD and to identify moderation of this effect dependent on degree of WM capacity (WMC) and depressed mood. A WM task (n-back) was used as a cognitive prime before assessment of DD (Monetary Choice Questionnaire) and was compared to a similar prime from an inhibition task in a factorial design in 183 community participants. All participants completed a DD task and assessment of depressive symptoms (Beck Depression Inventory-II). Priming effects were evaluated relative to WMC of participants. Higher WMC and lower depression scores were associated with greater relative preference for larger, delayed rewards. The effects of a WM prime were moderated by WMC; benefits of the prime were only evident for individuals with lower WMC. No effects were found for an alternative inhibition task. Limitations included depression scores mainly in subclinical range, use of hypothetical instead of real rewards in the DD task, and no examination of the time course of effects. This study provides support for the effectiveness of a brief WM prime in enhancing ability to delay rewards. Priming may be a useful adjunctive intervention for individuals with WM dysfunction or conditions in which impulsive decision-making may derail long-term goals. Copyright © 2018. Published by Elsevier Ltd.

Assessment of structural cardiac abnormalities and diastolic function in women with gestational diabetes mellitus.

PubMed

Oliveira, Alexandra P; Calderon, Iracema M P; Costa, Roberto A A; Roscani, Meliza G; Magalhães, Claudia G; Borges, Vera T M

2015-05-01

The main manifestation of hyperglycaemia during pregnancy is gestational diabetes mellitus. It can herald diabetes mellitus type 2 and its deleterious long-term effects, such as hypertension and cardiovascular disease. The aim of this study was to assess diastolic function in women with gestational diabetes mellitus, one of the first signs of future cardiovascular disease. A total of 21 women with gestational diabetes mellitus and 23 healthy pregnant women (control group) between 34 and 37 weeks of gestation underwent echocardiographic assessment. The diagnosis of gestational diabetes mellitus was made in agreement with the American Diabetes Association criteria. Echocardiographic images obtained were analysed according to the criteria of the American Society of Echocardiography. Data were analysed using Pearson correlation coefficient, analysis of variance and Student's t-test. Women with gestational diabetes mellitus had higher posterior wall and interventricular septum thickness, increased left ventricular mass and left ventricular mass index, lower early diastolic annular velocity and early diastolic annular velocity/late diastolic annular velocity ratio. There was a positive correlation between left ventricular mass index and fasting glucose and pregnancy body mass index. Patients with gestational diabetes mellitus seem to have a different diastolic profile as well as a mildly dysfunctional pattern on echocardiogram, which may show a need for greater glycaemic control. © The Author(s) 2015.

DD angiotensin-converting enzyme gene polymorphism is associated with endothelial dysfunction in normal humans.

PubMed

Butler, R; Morris, A D; Burchell, B; Struthers, A D

1999-05-01

A polymorphism within the angiotensin-converting enzyme (ACE) gene may increase the risk of myocardial infarction in individuals previously thought to be at low cardiovascular risk. The mechanism through which it exerts this effect is unknown but may be due to increased angiotensin II-induced nitric oxide (NO) breakdown and/or reduced bradykinin-mediated NO release. We investigated whether endothelial function was different between different ACE genotypes. We performed a cross-sectional study comparing the endothelial function of the 3 genotypes (II: n=25; ID: n=31; DD: n=12). Mean+/-SD ages of the subjects were 24+/-4 (II), 25+/-6 (ID), and 25+/-6 (DD) years. We assessed the impact of the genotypes on endothelial function and found that the DD genotype was associated with a significant blunting in endothelial-dependent vasodilatation (forearm blood flow data are presented as mean+/-SD ratio of blood flow in response to 3 incrementally increasing doses of each vasoactive agent in the test arm to blood flow in the control arm; the comparison is between DD versus ID versus II; the P value is an expression of an overall difference by ANOVA, and the 95% CIs are of a pairwise comparison between genotypes): acetylcholine, 2.88+/-1.45 versus 3.81+/-1.93 versus 4.23+/-2.37 (P=0.002; 95% CI [II versus ID], -0.19 to 0.91; 95% CI [II versus DD], 0.36 to 1.80; 95% CI [ID versus DD], 0.02 to 1.42). There was also a significant difference with the endothelial-independent vasodilator sodium nitroprusside, with values of 2.11+/-1.00 versus 2.55+/-1.36 versus 2.75+/-1.18 (P<0.05; 95% CI [II versus ID], -0.15 to 0.51; 95% CI [II versus DD], 0.03 to 0.89; 95% CI [ID versus DD], -0.13 to 0.71), but not with verapamil. There was no effect of the ACE genotype on endothelial-dependent or -independent vasoconstrictors NG-monomethyl-L-arginine or norepinephrine. Investigating the effects of cigarette smoking on each genotype demonstrated that for II and DD genotypes, acetylcholine responses were further blunted if subjects smoked. These data demonstrate that the DD ACE genotype in a young population is associated with a blunting of stimulated endothelial NO and donated NO responses but not to non-NO vasodilators or vasoconstrictors.

No association between ACE I/D polymorphism and cardiovascular hemodynamics during exercise in young women.

PubMed

Roltsch, M H; Brown, M D; Hand, B D; Kostek, M C; Phares, D A; Huberty, A; Douglass, L W; Ferrell, R E; Hagberg, J M

2005-10-01

The ACE I/D polymorphism has been shown to interact with habitual physical activity levels in postmenopausal women to associate with submaximal and with maximal exercise hemodynamics. This investigation was designed to assess the potential relationships between ACE genotype and oxygen consumption (VO2), cardiac output (Q), stroke volume (SV), heart rate (HR), blood pressure (BP), total peripheral resistance (TPR), and arteriovenous oxygen difference ([a-v]O2 diff) during submaximal and maximal exercise in young sedentary and endurance-trained women. Seventy-seven 18-35-yr-old women underwent a maximal exercise test and a number of cardiac output tests on a treadmill using the acetylene rebreathing technique. ACE genotype was not significantly associated with VO2max (II 41.4+/-1.2, ID 39.8+/-0.9, DD 39.8+/-1.1 ml/kg/min, p=ns) or maximal HR (II 191+/-2, ID 191+/-1, DD 193+/-2 bpm, p=ns). In addition, systolic and diastolic BP, (a-v)O2 diff, TPR, SV, and Q during maximal exercise were not significantly associated with ACE genotype. During submaximal exercise, SBP, Q, SV, HR, TPR, and (a-v)O2 diff were not significantly associated with ACE genotype. However, the association between diastolic BP during submaximal exercise and ACE genotype approached significance (p=0.08). In addition, there were no statistically significant interactions between ACE genotype and habitual physical activity (PA) levels for any of the submaximal or the maximal exercise hemodynamic variables. We conclude that the ACE I/D polymorphism was not associated, independently or interacting with habitual PA levels, submaximal, or maximal cardiovascular hemodynamics in young women.

Diastolic dysfunction in prediabetic male rats: Role of mitochondrial oxidative stress.

PubMed

Koncsos, Gábor; Varga, Zoltán V; Baranyai, Tamás; Boengler, Kerstin; Rohrbach, Susanne; Li, Ling; Schlüter, Klaus-Dieter; Schreckenberg, Rolf; Radovits, Tamás; Oláh, Attila; Mátyás, Csaba; Lux, Árpád; Al-Khrasani, Mahmoud; Komlódi, Tímea; Bukosza, Nóra; Máthé, Domokos; Deres, László; Barteková, Monika; Rajtík, Tomáš; Adameová, Adriana; Szigeti, Krisztián; Hamar, Péter; Helyes, Zsuzsanna; Tretter, László; Pacher, Pál; Merkely, Béla; Giricz, Zoltán; Schulz, Rainer; Ferdinandy, Péter

2016-10-01

Although incidence and prevalence of prediabetes are increasing, little is known about its cardiac effects. Therefore, our aim was to investigate the effect of prediabetes on cardiac function and to characterize parameters and pathways associated with deteriorated cardiac performance. Long-Evans rats were fed with either control or high-fat chow for 21 wk and treated with a single low dose (20 mg/kg) of streptozotocin at week 4 High-fat and streptozotocin treatment induced prediabetes as characterized by slightly elevated fasting blood glucose, impaired glucose and insulin tolerance, increased visceral adipose tissue and plasma leptin levels, as well as sensory neuropathy. In prediabetic animals, a mild diastolic dysfunction was observed, the number of myocardial lipid droplets increased, and left ventricular mass and wall thickness were elevated; however, no molecular sign of fibrosis or cardiac hypertrophy was shown. In prediabetes, production of reactive oxygen species was elevated in subsarcolemmal mitochondria. Expression of mitofusin-2 was increased, while the phosphorylation of phospholamban and expression of Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3, a marker of mitophagy) decreased. However, expression of other markers of cardiac auto- and mitophagy, mitochondrial dynamics, inflammation, heat shock proteins, Ca 2+ /calmodulin-dependent protein kinase II, mammalian target of rapamycin, or apoptotic pathways were unchanged in prediabetes. This is the first comprehensive analysis of cardiac effects of prediabetes indicating that mild diastolic dysfunction and cardiac hypertrophy are multifactorial phenomena that are associated with early changes in mitophagy, cardiac lipid accumulation, and elevated oxidative stress and that prediabetes-induced oxidative stress originates from the subsarcolemmal mitochondria. Copyright © 2016 the American Physiological Society.

An evaluation of the use of new Doppler methods for detecting longitudinal function abnormalities in a pacing-induced heart failure model

NASA Technical Reports Server (NTRS)

Tabata, Tomotsugu; Cardon, Lisa A.; Armstrong, Guy P.; Fukamach, Kiyotaka; Takagaki, Masami; Ochiai, Yoshie; McCarthy, Patrick M.; Thomas, James D.

2003-01-01

BACKGROUND: Doppler tissue echocardiography and color M-mode Doppler flow propagation velocity have proven useful in evaluating cross-sections of patients with left ventricular (LV) dysfunction, but experience with serial changes is limited. Purpose and methods: We tested their use by evaluating the temporal changes of LV function in a pacing-induced congestive heart failure model. Rapid ventricular pacing was initiated and maintained in 20 dogs for 4 weeks. Echocardiography was performed at baseline and weekly during brief pacing cessation. RESULTS: With rapid pacing, LV volume significantly increased and ejection fraction (57%-28%), stroke volume (37-18 mL), and mitral annulus systolic velocity (16.1-6.6 cm/s) by Doppler tissue echocardiography significantly decreased, with ejection fraction and mitral annulus systolic velocity closely correlated (r = 0.706, P <.0001). In contrast to the mitral inflow velocities, mitral annulus early diastolic velocity decreased steadily (12.3-7.3 cm/s) resulting in a dramatic decrease in mitral annulus early/late (1.22-0.57) diastolic velocity with no tendency toward pseudonormalization. The color M-mode Doppler flow propagation velocity also showed significant steady decrease (57-24 cm/s) throughout the pacing period. Multiple regression analysis chose mitral annulus systolic velocity (r = 0.895, P <.0001) and propagation velocity (r = 0.782, P <.0001) for the most important factor predicting LV systolic and diastolic function, respectively. CONCLUSIONS: Doppler tissue echocardiography and color M-mode Doppler flow could evaluate the serial deterioration in LV dysfunction throughout the pacing period. These were more useful in quantifying progressive LV dysfunction than conventional ehocardiographic techniques, and were probably relatively independent of preload. These techniques could be suitable for longitudinal evaluation in addition to the cross-sectional study.

Comparative effects of valsartan in combination with cilnidipine or amlodipine on cardiac remodeling and diastolic dysfunction in Dahl salt-sensitive rats.

PubMed

Nagasawa, Kai; Takahashi, Keiji; Matsuura, Natsumi; Takatsu, Miwa; Hattori, Takuya; Watanabe, Shogo; Harada, Eri; Niinuma, Kazumi; Murohara, Toyoaki; Nagata, Kohzo

2015-01-01

Angiotensin receptor blockers (ARBs) are often supplemented with calcium channel blockers (CCBs) for treatment of hypertension. We recently showed that the L/N-type CCB cilnidipine has superior cardioprotective effects compared with the L-type CCB amlodipine in Dahl salt-sensitive (DS) rats. We have now compared the effects of the ARB valsartan combined with cilnidipine or amlodipine on cardiac pathophysiology in DS rats. DS rats fed a high-salt diet from 6 weeks of age were treated with vehicle, valsartan alone (10 mg kg(-1) per day), or valsartan combined with either cilnidipine (1 mg kg(-1) per day) or amlodipine (1 mg kg(-1) per day) from 7 to 11 weeks. The salt-induced increase in systolic blood pressure apparent in the vehicle group was attenuated similarly in the three drug treatment groups. Valsartan-cilnidipine attenuated left ventricular (LV) fibrosis and diastolic dysfunction as well as cardiac oxidative stress and inflammation to a greater extent than did valsartan alone or valsartan-amlodipine. In addition, the increases in urinary excretion of dopamine and epinephrine as well as in cardiac renin-angiotensin-aldosterone-system (RAAS) gene expression apparent in vehicle-treated rats were attenuated to a greater extent by valsartan-cilnidipine than by the other two treatments. Valsartan-cilnidipine thus attenuated LV remodeling and diastolic dysfunction more effectively than did valsartan or valsartan-amlodipine in rats with salt-sensitive hypertension, and this superior cardioprotective action of valsartan-cilnidipine compared with valsartan-amlodipine is likely attributable, at least in part, to the greater antioxidant and antiinflammatory effects associated with both greater inhibition of cardiac RAAS gene expression and N-type calcium channel blockade.

Utility of Cardiovascular Magnetic Resonance-Derived Wave Intensity Analysis As a Marker of Ventricular Function in Children with Heart Failure and Normal Ejection Fraction.

PubMed

Ntsinjana, Hopewell N; Chung, Robin; Ciliberti, Paolo; Muthurangu, Vivek; Schievano, Silvia; Marek, Jan; Parker, Kim H; Taylor, Andrew M; Biglino, Giovanni

2017-01-01

This study sought to explore the diagnostic insight of cardiovascular magnetic resonance (CMR)-derived wave intensity analysis to better study systolic dysfunction in young patients with chronic diastolic dysfunction and preserved ejection fraction (EF), comparing it against other echocardiographic and CMR parameters. Evaluating systolic and diastolic dysfunctions in children is challenging, and a gold standard method is currently lacking. Patients with presumed diastolic dysfunction [ n  = 18; nine aortic stenosis (AS), five hypertrophic, and four restrictive cardiomyopathies] were compared with age-matched control subjects ( n  = 18). All patients had no mitral or aortic incompetence, significant AS, or reduced systolic EF. E / A ratio, E / E ' ratio, deceleration time, and isovolumetric contraction time were assessed on echocardiography, and indexed left atrial volume (LAVi), acceleration time (AT), ejection time (ET), and wave intensity analyses were calculated from CMR. The latter was performed on CMR phase-contrast flow sequences, defining a ratio of the peaks of the early systolic forward compression wave (FCW) and the end-systolic forward expansion wave (FEW). Significant differences between patients and controls were seen in the E / E ' ratio (8.7 ± 4.0 vs. 5.1 ± 1.3, p  = 0.001) and FCW/FEW ratio (2.5 ± 1.6 vs. 7.2 ± 4.2 × 10 -5 m/s, p  < 0.001), as well as-as expected-LAVi (80.7 ± 22.5 vs. 51.0 ± 10.9 mL/m 2 , p  < 0.001). In particular, patients exhibited a lower FCW (2.5 ± 1.6 vs. 7.2 ± 4.2 × 10 -5 m/s, p  < 0.001) in the face of preserved EF (67 ± 11 vs. 69 ± 5%, p  = 0.392), as well as longer isovolumetric contraction time (49 ± 7 vs. 34 ± 7 ms, p  < 0.001) and ET/AT (0.35 ± 0.04 vs. 0.27 ± 0.04, p  < 0.001). This study shows that the wave intensity-derived ratio summarizing systolic and diastolic function could provide insight into ventricular function in children, on top of CMR and echocardiography, and it was here able to identify an element of ventricular dysfunction with preserved EF in a small group of young patients.

Left atrial volume is not an index of left ventricular diastolic dysfunction in patients with sickle cell anaemia.

PubMed

Hammoudi, Nadjib; Charbonnier, Magali; Levy, Pierre; Djebbar, Morad; Stankovic Stojanovic, Katia; Ederhy, Stéphane; Girot, Robert; Cohen, Ariel; Isnard, Richard; Lionnet, François

2015-03-01

Left ventricular diastolic dysfunction (LVDD) is common in sickle cell anaemia (SCA). Left atrial (LA) size is widely used as an index of LVDD; however, LA enlargement in SCA might also be due to chronic volume overload. To investigate whether LA size can be used to diagnose LVDD in SCA. One hundred and twenty-seven adults with stable SCA underwent echocardiographic assessment. LA volume was measured by the area-length method and indexed to body surface area (LAVi). Left ventricular (LV) filling pressures were assessed using the ratio of early peak diastolic velocities of mitral inflow and septal annular mitral plane (E/e'). Using mitral inflow profile and E/e', LV diastolic function was classified as normal or abnormal. LAVi>28mL/m(2) was used as the threshold to define LA enlargement. The mean age was 28.6±8.5years; there were 83 women. Mean LAVi was 48.3±11.1mL/m(2) and 124 (98%) patients had LA dilatation. In multivariable analysis, age, haemoglobin concentration and LV end-diastolic volume index were independent determinants of LAVi (R(2)=0.51; P<0.0001). E/e' was not linked to LAVi (P=0.43). Twenty patients had LVDD; when compared with patients without LVDD, they had a similar LAVi (52.2±14.7 and 47.5±10.2mL/m(2), respectively; P=0.29). Receiver operating characteristics curve analysis showed that LAVi could not be used to diagnose LVDD (area under curve=0.58; P=0.36). LA enlargement is common in SCA but appears not to be linked to LVDD. LAVi in this population is related to age, haemoglobin concentration and LV morphology. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Left ventricular functions in children with newly diagnosed Graves' disease. A single-center study from Upper Egypt.

PubMed

Metwalley, Kotb Abbass; Farghaly, Hekma Saad; Abdelhamid, Abdelrahman

2018-01-01

This study aimed to evaluate the left ventricular (LV) functions in a cohort of children with Graves' disease (GD). This is a cross-sectional case-control study. It included 36 children with GD and 36 healthy children matched for age and gender. Thyroid hormones (TSH, FT4, and FT3) and anti-thyroid autoantibodies [anti-thyroid peroxidase (anti-TPO), thyrotropin receptor (TRAbs), and thyroglobulin antibodies] were measured. Conventional and tissue Doppler imaging (TDI) echocardiographies were used to assess left ventricular systolic and diastolic functions. LV mass index (LVMI) and myocardial performance index (MPI) were also measured. Compared to healthy children, conventional echocardiography of patients with GD revealed higher LVMI (P = 0.001) indicating LV hypertrophy but normal LV functions while TDI revealed lower Em/Am ratio indicating LV diastolic dysfunction (P = 0.001). Significant correlations were reported between FT4 with LVMI (P = 0.05), Em/Am (P = 0.01), and MPI (P = 0.01). In multivariate analysis, a positive correlation was identified between FT4 with MPI (OR = 1.17; 95% CI = 1.09-1.15; P = 0.001). Children with newly diagnosed GD may have significant subclinical changes in LV structure and function (diastolic and global). TDI is more sensitive than conventional Doppler in detecting LV dysfunction. These findings highlight the importance of early monitoring of children with GD for left ventricular mass index and diastolic function. What is Known: • There is an increased risk for cardiac abnormalities in children with Graves' disease (GD). • Limited studies assessed left ventricular function in patients with GD. What is New: • Children with newly diagnosed GD may have significant subclinical changes in left ventricular structure and functions. • Children with newly diagnosed GD should be monitored for left ventricular mass index and diastolic function.

Ventricular Diastolic Function in Normal Fetuses and Fetuses with Hb Bart's Disease Assessed by Color M-Mode Propagation Velocity using Cardio-STIC-M (Spatio-Temporal Image Correlation M-Mode).

PubMed

Tongsong, T; Tongprasert, F; Srisupundit, K; Luewan, S; Traisrisilp, K

2016-10-01

Purpose: To determine whether ventricular diastolic dysfunction contributes to the pathogenesis of fetal cardiac failure due to fetal anemia using fetal Hb Bart's disease as a live model and cardio-STIC-M as a diagnostic tool. Materials and Methods: Color cardio-STIC volume datasets were acquired from fetuses at risk for Hb Bart's disease during 18 - 22 weeks of gestation and normal pregnancies and pregnancies with hydrops fetalis caused by Hb Bart's disease at 28 - 32 weeks. The volumes were analyzed off-line for velocity propagation (Vp) of the right and left ventricles to assess ventricular diastolic function using color cardio-STIC-M. Results: The Vp for the right and left ventricles was studied in fetuses at 18 - 22 weeks, including 64 normal fetuses (group 1) and 22 fetuses with Hb Bart's disease (group 2), and in fetuses at 28 - 32 weeks, including 22 normal fetuses (group 3) and 16 fetuses with Hb Bart's hydrops fetalis (group 4). The Vp of the fetuses in group 1 and group 2 was not significantly different. However, the Vp for the right and left ventricles in group 4 was significantly lower than in group 3 (19.02 vs. 9.78, p < 0.001; and 20.24 vs. 13.40, p < 0.001, respectively). The inter-observer variability had fair agreement with the intra-class correlation coefficient of 0.531 (95 % CI 0.393 - 0.646, p < 0.001). Conclusion: Hydrops fetalis secondary to fetal anemia is initially caused by hypervolemia rather than ventricular diastolic dysfunction while ventricular diastolic compromise is a late occurring consequence of persistent hypervolemia, different from the mechanism of hydropic changes caused by cardiac causes. © Georg Thieme Verlag KG Stuttgart · New York.

Early-onset growth hormone deficiency results in diastolic dysfunction in adult-life and is prevented by growth hormone supplementation.

PubMed

Groban, L; Lin, M; Kassik, K A; Ingram, R L; Sonntag, W E

2011-04-01

The primary goal of growth hormone (GH) replacement is to promote linear growth in children with growth hormone deficiency (GHD). GH and insulin-like growth factor-1 (IGF-1) are also known to have roles in cardiac development and as modulators of myocardial structure and function in the adult heart. However, little is known about cardiac diastolic function in young adults with childhood onset GH deficiency in which GH treatment was discontinued following puberty. The aim of the study was to evaluate the effects of long standing GHD and peri-pubertal or continuous GH replacement therapy on diastolic function in the adult dwarf rat. The dwarf rat, which possesses a mutation in a transcription factor necessary for development of the somatotroph, does not exhibit the normal peri-pubertal rise in GH around day 28 and was used to model childhood or early-onset GHD (EOGHD). In another group of male dwarfs, GH replacement therapy was initiated at 4 weeks of age when GH pulsatility normally begins. Ten weeks after initiation of injections, GH-treated dwarf rats were divided into 2 groups; continued treatment with GH for 12 weeks (GH-replete) or treatment with saline for 12 weeks. This latter group models GH supplementation during adolescence with GHD beginning in adulthood (adult-onset GHD; AOGHD). Saline-treated heterozygous (HZ) rats were used as age-matched controls. At 26 weeks of age, cardiac function was assessed using invasive or noninvasive (conventional and tissue Doppler) indices of myocardial contractility and lusitropy. Systolic function, as determined by echocardiography, was similar among groups. Compared with HZ rats and GH-replete dwarfs, the EOGHD group exhibited significant reductions in myocardial relaxation and increases in left ventricular filling pressure, indicative of moderate diastolic dysfunction. This was further associated with a decrease in the cardiac content of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), one of the important cardiac calcium regulatory proteins. Dwarfs supplemented with GH during the peri-adolescence stage, but not beyond (AOGHD), exhibited a subtle prolongation in the deceleration time to early filling. In contrast, continual GH replacement preserved diastolic function such that the cardiac phenotype of the GH-replete dwarfs resembled that of their age-matched HZ counterpart. Our data indicate that GHD during adolescence leads to overt diastolic dysfunction in early adulthood and this is prevented by continual GH replacement therapy. Since discontinuation of GH replacement following adolescence only mitigated the lusitropic deficits that were observed in untreated dwarfs, GH treatment into adulthood could be beneficial. Copyright © 2011 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.

A rash with a heavy heart

PubMed Central

Barros-Gomes, Sergio; Naksuk, Niyada; Jevremovic, Dragan

2017-01-01

Cardiac amyloidosis (CA) is relatively rare and frequently misdiagnosed. Other disorders presenting with increased left ventricular (LV) mass can mimic its diagnosis. This case illustrates unique findings of primary light chain (AL) amyloidosis in a patient with remarkable signs of CA. Here, we report a 49-year-old male with prior diagnosis of hypertrophic cardiomyopathy (HCM) based on an echocardiogram performed 1 year earlier, which presented with 8 weeks of periorbital rash. The patient had numbness in the past 3 years. More recently, the patient presented with shortness of breath. Physical examination was remarkable for periorbital purpura, macroglossia and orthostatic hypotension. Cardiac auscultation showed S3 and S4. Electrocardiography showed diffuse low-voltage QRS complexes. Echocardiography revealed severe diastolic impairment; granular ‘sparkling’ pattern of the myocardium with thickened walls, interatrial septum and valves; and pericardial effusion. Diastolic dysfunction and thick walls with low ECG voltage are compelling diagnostic findings. Laboratory workup showed increased free light chain-differential (FLC-diff), N-terminal fragment of brain natriuretic peptide (NT-BNP) and cardiac Troponin T (cTnT). Bone marrow biopsy confirmed AL amyloidosis. A diagnosis of AL amyloidosis with cardiac involvement mimicking HCM was made. The patient died during hospitalization due to sudden cardiac death. This case illustrates the importance of the combination of clinical, serological, and electro- and echocardiographic findings to establish the diagnosis of CA. Learning points: Several disorders presenting with increased LV mass can mimic CA. Echocardiography is one of the most important methods to diagnose CA and HCM. Signs of CA include LV wall thickness; thickening of interatrial septum, valves and right ventricular free wall; and pericardial effusion. Diastolic dysfunction and thick walls on echocardiography with low ECG voltage are the hallmark of disease. CA is a major prognostic factor in AL amyloidosis. Signs of HCM on echocardiography include several patterns of LV hypertrophy, such as sigmoidal, reverse curve, neutral and apical morphologies; LV outflow tract or mid-cavity obstruction; systolic anterior motion of mitral leaflets; mitral regurgitation and diastolic dysfunction. The combination of clinical and serological features, along morphological and functional structures, has an important role for establishing diagnosis and predicting prognosis. PMID:28687586

Effect of CPAP on diastolic function in coronary artery disease patients with nonsleepy obstructive sleep apnea: A randomized controlled trial.

PubMed

Glantz, Helena; Johansson, Magnus C; Thunström, Erik; Guron, Cecilia Wallentin; Uzel, Harun; Saygin, Mustafa; Herlitz, Johan; Peker, Yüksel

2017-08-15

Obstructive sleep apnea (OSA) has been associated with worse diastolic function in patients with coronary artery disease (CAD). This analysis determined whether continuous positive airway pressure (CPAP) treatment would improve diastolic function in CAD patients with nonsleepy OSA. Between December 2005 and November 2010, 244 revascularized CAD patients with nonsleepy OSA (apnea-hypopnea index (AHI) ≥15/h, Epworth Sleepiness Scale [ESS] score<10) were randomly assigned to CPAP or no-CPAP. Echocardiographic measurements were obtained at baseline, and after 3 and 12months. A total of 171 patients with preserved left ventricular ejection fraction (≥50%), no atrial fibrillation or severe valve abnormalities, and technically adequate echocardiograms at baseline and follow-up visits were included (CPAP, n=87; no-CPAP, n=84). In the intention-to-treat analysis, CPAP had no significant effect on echocardiographic parameters of mild (enlarged left atrium or decreased diastolic relaxation velocity) or worse (increased E/é filling index [presumed elevated left ventricular filling pressure]) diastolic function. Post-hoc analysis revealed a significant association between CPAP usage for ≥4h/night and an increase in diastolic relaxation velocity at 12months' follow-up (odds ratio 2.3, 95% confidence interval 1.0-4.9; p=0.039) after adjustment for age, sex, body mass index, and left atrium diameter at baseline. CPAP did not improve diastolic dysfunction in CAD patients with nonsleepy OSA. However, good CPAP adherence was significantly associated with an increase in diastolic relaxation velocity after one year. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Left ventricular morphology and diastolic function in uraemia: echocardiographic evidence of a specific cardiomyopathy.

PubMed Central

Facchin, L.; Vescovo, G.; Levedianos, G.; Zannini, L.; Nordio, M.; Lorenzi, S.; Caturelli, G.; Ambrosio, G. B.

1995-01-01

OBJECTIVE--To see whether cardiac morphological and functional abnormalities in uraemic patients are determined by high blood pressure or if they are an expression of a specific cardiomyopathy. DESIGN--Cross sectional study. SETTING--City general hospital in Italy. SUBJECTS--35 uraemic patients receiving haemodialysis (17 men, 18 women; mean age 60.3 (11.2); mean duration of dialysis 52 months) were selected from the 64 patients in Venice who were receiving dialysis; subjects with diabetes, haemochromatosis, valvar dysfunction, regional dyskinesias, and pericarditis were excluded. 19 control normotensive subjects (6 men and 13 women), matched for age. MAIN OUTCOME MEASURES--Echocardiographic measurements of left atrium, left ventricular end diastolic and end systolic volume, aortic root diameter, posterior wall and interventricular septum thickness, left ventricle mass index, and ejection fraction in controls and in patients according to whether they were normotensive (five men, eight women) or hypertensive (12 men, 10 women) on 48 hour ambulatory monitoring; left ventricular diastolic function by Doppler ultrasonography. RESULTS--Mean systolic and diastolic pressures, daytime systolic and diastolic pressures, and night time systolic and diastolic pressures were significantly higher in the hypertensive patients than in the normotensive patients. The normotensive patients had similar blood pressures to the controls. Left ventricular mass correlated significantly with the mean diastolic pressure and mean night time systolic and diastolic pressures. Parathyroid hormone concentrations were similar in the two groups of patients. Diastolic relaxation was impaired to the same degree in the two groups of patients. Parameters of diastolic function showed no relation to left ventricular mass, which was significantly higher in the hypertensive than in the normotensive patients. CONCLUSIONS--Uraemia is likely to induce specific changes in the relaxation properties of the myocardium. These changes are responsible for the impaired diastolic function independently of blood pressure, degree of hypertrophy, and metabolic changes, which suggests the existence of a specific cardiomyopathy. Hypertension remains a determinant of left ventricular mass. PMID:7546998

Impairment in delay discounting in schizophrenia and schizoaffective disorder but not primary mood disorders.

PubMed

Brown, Hannah E; Hart, Kamber L; Snapper, Leslie A; Roffman, Joshua L; Perlis, Roy H

2018-05-28

A measure of planning and impulse control, the delay-discounting (DD) task estimates the extent to which an individual decreases the perceived value of a reward as the reward is delayed. We examined cross-disorder performance between healthy controls (n = 88), individuals with bipolar disorder (n = 23), major depressive disorder (n = 43), and primary psychotic disorders (schizophrenia and schizoaffective disorder; n = 51) on the DD task (using a $10 delayed larger reward), as well as the interaction of DD scores with other symptom domains (cognition, psychosis, and affect). We found that individuals with schizophrenia and schizoaffective disorder display significantly greater rates of discounting compared to healthy controls, while individuals with a primary mood disorder do not differ from healthy controls after adjustment for IQ. Further, impairment in working memory is associated with higher discounting rates among individuals with schizophrenia and schizoaffective disorder, but cognitive dysfunction alone does not account for the extent of impairment in DD. Taken together, these results suggest an impaired ability to plan for the future and make adaptive decisions that are specific to individuals with psychotic disorders, and likely related to adverse functional outcomes. More generally, this work demonstrates the presence of variation in impulsivity across major psychiatric illnesses, supporting the use of a trans-diagnostic perspective.

Role of Myocardial Collagen in Severe Aortic Stenosis With Preserved Ejection Fraction and Symptoms of Heart Failure.

PubMed

Echegaray, Kattalin; Andreu, Ion; Lazkano, Ane; Villanueva, Iñaki; Sáenz, Alberto; Elizalde, María Reyes; Echeverría, Tomás; López, Begoña; Garro, Asier; González, Arantxa; Zubillaga, Elena; Solla, Itziar; Sanz, Iñaki; González, Jesús; Elósegui-Artola, Alberto; Roca-Cusachs, Pere; Díez, Javier; Ravassa, Susana; Querejeta, Ramón

2017-10-01

We investigated the anatomical localization, biomechanical properties, and molecular phenotype of myocardial collagen tissue in 40 patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure. Two transmural biopsies were taken from the left ventricular free wall. Mysial and nonmysial regions of the collagen network were analyzed. Myocardial collagen volume fraction (CVF) was measured by picrosirius red staining. Young's elastic modulus (YEM) was measured by atomic force microscopy in decellularized slices to assess stiffness. Collagen types I and III were measured as C I VF and C III VF, respectively, by confocal microscopy in areas with YEM evaluation. Compared with controls, patients exhibited increased mysial and nonmysial CVF and nonmysial:mysial CVF ratio (P < .05). In patients, nonmysial CVF (r = 0.330; P = .046) and the nonmysial:mysial CVF ratio (r = 0.419; P = .012) were directly correlated with the ratio of maximal early transmitral flow velocity in diastole to early mitral annulus velocity in diastole. Both the C I VF:C III VF ratio and YEM were increased (P ≤ .001) in nonmysial regions compared with mysial regions in patients, with a direct correlation (r = 0.895; P < .001) between them. These findings suggest that, in patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure, diastolic dysfunction is associated with increased nonmysial deposition of collagen, predominantly type I, resulting in increased extracellular matrix stiffness. Therefore, the characteristics of collagen tissue may contribute to diastolic dysfunction in these patients. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Acute and chronic hypothyroidism are associated with similar left ventricular diastolic dysfunction relative to the euthyroid state: results of doppler echocardiographic comparisons.

PubMed

Gauna, A; Messuti, H; Papadopulos, G; Benchuga, G; Viale, F; Marlowe, R J; Silva Croome, M C

2011-10-01

How the duration of hypothyroidism affects left ventricular diastolic function is not well-characterized. We sought to compare left ventricular diastolic function in acutely vs chronically hypothyroid patients vs euthyroid controls, and within individuals while on vs off T4. We prospectively performed such comparisons measuring pulsed-wave and color M-mode Doppler echocardiographic variables: early or late mitral peak velocities (E wave or A wave, respectively), E wave/A wave ratio, E wave deceleration time, isovolumic relaxation time (IVRT), mitral flow propagation velocity (Vp), E wave/Vp ratio. Subjects comprised the acute HYPO group, 10 patients undergoing T4 withdrawal ≥ 6 months post-primary treatment for differentiated thyroid cancer (DTC); the chronic HYPO group, 23 treatment-naïve Hashimoto thyroiditis patients; and 21 healthy euthyroid controls. Subjects were adults aged ≤ 60 yr, predominantly female, with sinus rhythm; exclusion criteria were cardiovascular or thyroid disorder besides DTC (Hashimoto thyroiditis) in acute (chronic) HYPO patients or medication (besides thyroid hormone) affecting cardiac or thyroid function. Mean IVRT was significantly delayed and mean Vp, significantly slowed in both HYPO groups vs controls (p<0.0005), but did not differ between HYPO groups. These variables also were significantly impaired (p<0.05) within individuals when off vs on T4 (no.=8 acute, 10 chronic HYPO patients). Both HYPO groups had elevated mean E wave/Vp ratios vs controls, but the elevation reached significance (p<0.05) only in the larger chronic HYPO group. Left ventricular diastolic dysfunction is largely similar in acutely or chronically hypothyroid patients off T4 vs healthy controls or the same patients on T4.

The importance of integrated left atrial evaluation: From hypertension to heart failure with preserved ejection fraction.

PubMed

Beltrami, Matteo; Palazzuoli, Alberto; Padeletti, Luigi; Cerbai, Elisabetta; Coiro, Stefano; Emdin, Michele; Marcucci, Rossella; Morrone, Doralisa; Cameli, Matteo; Savino, Ketty; Pedrinelli, Roberto; Ambrosio, Giuseppe

2018-02-01

Functional analysis and measurement of left atrium are an integral part of cardiac evaluation, and they represent a key element during non-invasive analysis of diastolic function in patients with hypertension (HT) and/or heart failure with preserved ejection fraction (HFpEF). However, diastolic dysfunction remains quite elusive regarding classification, and atrial size and function are two key factors for left ventricular (LV) filling evaluation. Chronic left atrial (LA) remodelling is the final step of chronic intra-cavitary pressure overload, and it accompanies increased neurohormonal, proarrhythmic and prothrombotic activities. In this systematic review, we aim to purpose a multi-modality approach for LA geometry and function analysis, which integrates diastolic flow with LA characteristics and remodelling through application of both traditional and new diagnostic tools. The most important studies published in the literature on LA size, function and diastolic dysfunction in patients with HFpEF, HT and/or atrial fibrillation (AF) are considered and discussed. In HFpEF and HT, pulsed and tissue Doppler assessments are useful tools to estimate LV filling pressure, atrio-ventricular coupling and LV relaxation but they need to be enriched with LA evaluation in terms of morphology and function. An integrated evaluation should be also applied to patients with a high arrhythmic risk, in whom eccentric LA remodelling and higher LA stiffness are associated with a greater AF risk. Evaluation of LA size, volume, function and structure are mandatory in the management of patients with HT, HFpEF and AF. A multi-modality approach could provide additional information, identifying subjects with more severe LA remodelling. Left atrium assessment deserves an accurate study inside the cardiac imaging approach and optimised measurement with established cut-offs need to be better recognised through multicenter studies. © 2017 John Wiley & Sons Ltd.

Right ventricular end-systolic area as a simple first-line marker predicting right ventricular enlargement and decreased systolic function in children referred for cardiac magnetic resonance imaging.

PubMed

Barczuk-Falęcka, M; Małek, Ł A; Roik, D; Werys, K; Werner, B; Brzewski, M

2018-06-01

To assess the accuracy of simple cardiovascular magnetic resonance imaging (CMR) parameters for first-line analysis of right ventricle (RV) dysfunction in children to identify those who require in-depth analysis and those in whom simple assessment is sufficient. Sixty paediatric CMR studies were analysed. The following CMR parameters were measured: RV end-diastolic and end-systolic area (4CH EDA and 4CH ESA), fractional area change (FAC), RV diameter in end-diastole (RVD1), tricuspid annular plane systolic excursion (TAPSE), and RV outflow tract diameter in end-diastole (RVOT prox). They were correlated with RV end-diastolic volume (RVEDVI) and RV ejection fraction (RVEF). RVEDVI correlated best with 4CH ESA (r=0.85, <0.001) and EDA (r=0.82, <0.001). For RVEF only a moderate reverse correlation was found for 4CH ESA (-0.56, <0.001), 4CH EDA (-0.49, 0.001) and positive correlation for FAC (0.49, <0.001). There was no correlation between TAPSE and RVEF and only weak between RVD1 and RVEDVI. A 4CH ESA cut-off value of 8.5 cm 2 /m 2 had a very high diagnostic accuracy for predicting an enlarged RV (AUC=0.912, p<0.001, sensitivity 92.3%, specificity 79%) and a cut-off value of 10.5 cm 2 /m 2 was also a good predictor of depressed RV systolic function (AUC=0.873, p<0.001, sensitivity 83%, specificity 89%). For routine screening in clinical practice, 4CH ESA seems a reliable and easy method to identify patients with RV dysfunction. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Chronic sustained inflammation links to left ventricular hypertrophy and aortic valve sclerosis: a new link between S100/RAGE and FGF23.

PubMed

Yan, Ling; Bowman, Marion A Hofmann

Cardiovascular disease including left ventricular hypertrophy, diastolic dysfunction and ectopic valvular calcification are common in patients with chronic kidney disease (CKD). Both S100A12 and fibroblast growth factor 23 (FGF23) have been identified as biomarkers of cardiovascular morbidity and mortality in patients with CKD. We tested the hypothesis that human S100/calgranulin would accelerate cardiovascular disease in mice subjected to CKD. This review paper focuses on S100 proteins and their receptor for advanced glycation end products (RAGE) and summarizes recent findings obtained in novel developed transgenic hBAC-S100 mice that express S100A12 and S100A8/9 proteins. A bacterial artificial chromosome of the human S100/calgranulin gene cluster containing the genes and regulatory elements for S100A8, S100A9 and S100A12 was expressed in C57BL/6J mice (hBAC-S100). CKD was induced by ureteral ligation, and hBAC-S100 mice and WT mice were studied after 10 weeks of chronic uremia. hBAC-S100 mice with CKD showed increased FGF23 in the heart, left ventricular hypertrophy (LVH), diastolic dysfunction, focal cartilaginous metaplasia and calcification of the mitral and aortic valve annulus together with aortic valve sclerosis. This phenotype was not observed in WT mice with CKD or in hBAC-S100 mice lacking RAGE with CKD, suggesting that the inflammatory milieu mediated by S100/RAGE promotes pathological cardiac hypertrophy in CKD. In vitro, inflammatory stimuli including IL-6, TNFα, LPS, or serum from hBAC-S100 mice up regulated FGF23 mRNA and protein in primary murine neonatal and adult cardiac fibroblasts. Taken together, our study shows that myeloid-derived human S100/calgranulin is associated with the development of cardiac hypertrophy and ectopic cardiac calcification in a RAGE dependent manner in a mouse model of CKD. We speculate that FGF23 produced by cardiac fibroblasts in response to cytokines may act in a paracrine manner to accelerate LVH and diastolic dysfunction in hBAC-S100 mice with CKD. We suggest that S100/RAGE-mediated chronic sustained systemic inflammation is linked to pathological cardiac remodeling via direct up regulation of FGF23 in cardiac fibroblasts, thereby providing a new mechanistic understanding for the common association between CKD, diabetes, metabolic syndrome, or hypertension with left ventricular hypertrophy with diastolic dysfunction.

High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts

PubMed Central

Kang, Bong Jin; Park, Jinhyoung; Kim, Jieun; Kim, Hyung Ham; Lee, Changyang; Hwang, Jae Youn; Lien, Ching-Ling; Shung, K. Kirk

2015-01-01

Adult zebrafish is a well-known small animal model for studying heart regeneration. Although the regeneration of scars made by resecting the ventricular apex has been visualized with histological methods, there is no adequate imaging tool for tracking the functional recovery of the damaged heart. For this reason, high-frequency Doppler echocardiography using dual mode pulsed wave Doppler, which provides both tissue Doppler (TD) and Doppler flow in a same cardiac cycle, is developed with a 30 MHz high-frequency array ultrasound imaging system. Phantom studies show that the Doppler flow mode of the dual mode is capable of measuring the flow velocity from 0.1 to 15 cm s−1 with high accuracy (p-value = 0.974 > 0.05). In the in vivo study of zebrafish, both TD and Doppler flow signals were simultaneously obtained from the zebrafish heart for the first time, and the synchronized valve motions with the blood flow signals were identified. In the longitudinal study on the zebrafish heart regeneration, the parameters for diagnosing the diastolic dysfunction, for example, E/Em < 10, E/A < 0.14 for wild-type zebrafish, were measured, and the type of diastolic dysfunction caused by the amputation was found to be similar to the restrictive filling. The diastolic function was fully recovered within four weeks post-amputation. PMID:25505135

Diastolic dysfunction is associated with insulin resistance, but not with aldosterone level in normotensive offspring of hypertensive families.

PubMed

Zizek, Bogomir; Poredos, Pavel; Trojar, Andrej; Zeljko, Tadej

2008-01-01

We investigated left ventricular (LV) morphology and function in association with insulin level/insulin resistance (IR) and aldosterone level in normotensive offspring of subjects with essential hypertension (familial trait, FT). The study encompassed 76 volunteers of whom 44 were normotensive with FT (aged 28-39 years) and 32 age-matched controls without FT. LV mass and function were measured using conventional echocardiography and tissue Doppler imaging. LV diastolic function was reported as peak septal annular velocities (E(m) and E(m)/A(m) ratio) in tissue Doppler imaging. Fasting insulin and aldosterone were determined. In subjects with FT, the LV mass was higher than in controls (92.14 +/- 24.02 vs. 70.08 +/- 20.58 g; p < 0.001). The study group had a worse LV diastolic function than control subjects (lower E(m) and E(m)/A(m) ratio; p < 0.001). In subjects with FT, the E(m)/A(m) ratio was independently associated with IR (partial p = 0.029 in multivariate model, R(2) = 0.51), but not with LV mass. The aldosterone level was comparable in both groups. In normotensive individuals with FT, LV morphological and functional abnormalities were found. LV dysfunction but not an increase in LV mass is associated with IR. The aldosterone level is probably not responsible for the development of early hypertensive heart disease. (c) 2008 S. Karger AG, Basel.

A Shld1-controlled POT1a provides support for repression of ATR signaling at telomeres through RPA exclusion.

PubMed

Gong, Yi; de Lange, Titia

2010-11-12

We previously proposed that POT1 prevents ATR signaling at telomeres by excluding RPA from the single-stranded TTAGGG repeats. Here, we use a Shld1-stabilized degron-POT1a fusion (DD-POT1a) to study the telomeric ATR kinase response. In the absence of Shld1, DD-POT1a degradation resulted in rapid and reversible activation of the ATR pathway in G1 and S/G2. ATR signaling was abrogated by shRNAs to ATR and TopBP1, but shRNAs to the ATM kinase or DNA-PKcs did not affect the telomere damage response. Importantly, ATR signaling in G1 and S/G2 was reduced by shRNAs to RPA. In S/G2, RPA was readily detectable at dysfunctional telomeres, and both POT1a and POT1b were required to exclude RPA and prevent ATR activation. In G1, the accumulation of RPA at dysfunctional telomeres was strikingly less, and POT1a was sufficient to repress ATR signaling. These results support an RPA exclusion model for the repression of ATR signaling at telomeres. Copyright © 2010 Elsevier Inc. All rights reserved.

Myocardial Dysfunction and Shock after Cardiac Arrest

PubMed Central

Jentzer, Jacob C.; Chonde, Meshe D.; Dezfulian, Cameron

2015-01-01

Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies. PMID:26421284

Myocardial Dysfunction and Shock after Cardiac Arrest.

PubMed

Jentzer, Jacob C; Chonde, Meshe D; Dezfulian, Cameron

2015-01-01

Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies.

Cardiac left ventricular thrombus in protein C deficiency.

PubMed

Sabzi, Feridoun; Faraji, Reza

2014-07-01

We report an exceptional case of, 33-year-old woman presenting with, dyspnoea and chest pain, Cardio respiratory sign and symptom related to diastolic dysfunction caused by mass effect of thrombosis on diastolic filling of left ventricule (LV). The common aetiologies of these devastating complication results in thrombophillia diagnosis, and echocardioghraphy showed a large mass in left ventricular cavity. In laboratory exam, protein C-S deficiency was confirmed however, others related test of thrombophillia were negative. The patient underwent cardiopulmonary bypass with thrombosis extraction and her sign and symptom, recovered uneventfully. This case report illustrates an exceedingly rare case of thrombophilia-induced left ventricular clot formation.

Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure.

PubMed

Tang, W H Wilson; Wang, Zeneng; Shrestha, Kevin; Borowski, Allen G; Wu, Yuping; Troughton, Richard W; Klein, Allan L; Hazen, Stanley L

2015-02-01

Trimethylamine-N-oxide (TMAO) has been linked to increased cardiovascular risk. We aimed to determine the prognostic value of TMAO and its dietary precursors, choline and betaine, in heart failure (HF). In 112 patients with chronic systolic HF with comprehensive echocardiographic evaluation, we measured plasma TMAO, choline, and betaine by mass spectrometry. Median (interquartile range) TMAO levels, choline, and betaine levels were 5.8 (3.6-12.1) μmol/L, 10.9 (8.4-14.0) μmol/L, and 43.8 (37.1-53.0) μmol/L, respectively, and were correlated with each other (all P < .0001 for both). TMAO levels were significantly higher in patients with diabetes mellitus (9.4 [4.9-13.2] vs 4.8 [3.4-9.8] μmol/L; P = .005) and in subjects with New York Heart Association functional class III or greater (7.0 [4.7-14.8] vs 4.7 [3.4-11.3] μmol/L; P = .02). Elevated TMAO, choline, and betaine levels were each associated with higher plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and more advanced left ventricular diastolic dysfunction, but not systolic dysfunction or inflammatory and endothelial biomarkers. Higher choline (hazard ratio [HR] 1.64, 95% CI 1.22-2.20; P = .001), betaine (HR 1.51, 95% CI 1.10-2.08; P = .01), and TMAO (HR 1.48, 95% CI 1.10-1.96; P = .01) predicted increased risk for 5-year adverse clinical events (death/transplantation). Only higher TMAO levels predicted incident adverse clinical events independently from age, estimated glomerular filtration rate, mitral E/septal Ea, and NT-proBNP levels (HR 1.46, 95% CI 1.03-2.14; P = .03). Elevated plasma TMAO, choline, and betaine levels are each associated with more advanced left ventricular diastolic dysfunction and portend poorer long-term adverse clinical outcomes in chronic systolic HF. However, only higher plasma TMAO was associated with poor prognosis after adjustment for cardiorenal indices. Copyright © 2015 Elsevier Inc. All rights reserved.

Coronary microvascular dysfunction and diastolic load correlate with cardiac troponin T release measured by a highly sensitive assay in patients with nonischemic heart failure.

PubMed

Takashio, Seiji; Yamamuro, Megumi; Izumiya, Yasuhiro; Sugiyama, Seigo; Kojima, Sunao; Yamamoto, Eiichiro; Tsujita, Kenichi; Tanaka, Tomoko; Tayama, Shinji; Kaikita, Koichi; Hokimoto, Seiji; Ogawa, Hisao

2013-08-13

This study investigated factors associated with cardiac troponin T (cTnT) release from failing myocardium. Persistent and modest elevation of serum cTnT is frequently observed in heart failure (HF) patients free of coronary artery disease, although the mechanisms underlying this finding remain unclear. We evaluated serum cTnT levels in the aortic root (Ao) and coronary sinus (CS) using a highly sensitive assay in 90 nonischemic HF patients and 47 non-HF patients. Transcardiac cTnT and plasma B-type natriuretic peptide (BNP) release were described as the differences between CS and Ao cTnT levels [ΔcTnT (CS-Ao)] and BNP levels [ΔBNP (CS-Ao)], respectively. Coronary flow reserve (CFR) was measured in 68 HF patients using an intracoronary Doppler guidewire. ΔcTnT (CS-Ao) levels were available in 76 HF patients and 28 non-HF patients (84% vs. 60%; p = 0.001), and higher in HF patients than non-HF patients (p < 0.001). Among HF patients, log[ΔcTnT (CS-Ao)] correlated with log[ΔBNP (CS-Ao)] (r = 0.368, p = 0.001), pulmonary capillary wedge pressure (r = 0.253, p = 0.03) and left ventricular end-diastolic pressure (LVEDP) (r = 0.321, p = 0.005). Multivariate regression analysis identified LVEDP as an independent parameter that correlated with ΔcTnT (CS-Ao). ΔcTnT (CS-Ao) levels were available in 58 HF patients who were evaluated for CFR. Coronary microvascular dysfunction, diagnosed by CFR <2.0, was observed in 18 HF patients. ΔcTnT (CS-Ao) was higher in patients with coronary microvascular dysfunction (4.8 [2.0 to 8.1] ng/l) than those without (2.0 [1.2 to 4.6] ng/l; p = 0.04). cTnT release from failing myocardium correlated with diastolic load and coronary microvascular dysfunction in nonischemic HF patients. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Comorbid depressive disorders in anxiety-disordered youth: demographic, clinical, and family characteristics.

PubMed

O'Neil, Kelly A; Podell, Jennifer L; Benjamin, Courtney L; Kendall, Philip C

2010-06-01

Research indicates that depression and anxiety are highly comorbid in youth. Little is known, however, about the clinical and family characteristics of youth with principal anxiety disorders and comorbid depressive diagnoses. The present study examined the demographic, clinical, and family characteristics of 200 anxiety-disordered children and adolescents (aged 7-17) with and without comorbid depressive disorders (major depressive disorder or dysthymic disorder), seeking treatment at a university-based anxiety clinic. All participants met DSM-IV diagnostic criteria for a principal anxiety disorder (generalized anxiety disorder, separation anxiety disorder, or social phobia). Of these, twelve percent (n = 24) also met criteria for a comorbid depressive disorder. Results suggest that anxiety-disordered youth with comorbid depressive disorders (AD-DD) were older at intake, had more severe anxious and depressive symptomatology, and were more impaired than anxiety-disordered youth without comorbid depressive disorders (AD-NDD). AD-DD youth also reported significantly more family dysfunction than AD-NDD youth. Future research should examine how this diagnostic and family profile may impact treatment for AD-DD youth.

[Evaluation of left ventricular diastolic function using gated SPECT with 99mTc-MIBI].

PubMed

Toba, M; Kumita, S I; Mizumura, S; Cho, K; Kijima, T; Takahama, K; Kumazaki, T

1996-04-01

Development of 3 head SPECT system and 99mTc-labeled radiopharmaceuticals enable us to evaluate left ventricular systolic function on the basis of once gated SPECT routine. This study was focused on assessment of left ventricular diastolic function using 99mTc-MIBI gated SPECT data. Twenty nine patients with ischemic heart diseases underwent 99mTc-MIBI gated SPECT and 99mTc-HSAD ventriculographic assessment of left ventricular diastolic function within 1 month. Region of interests (ROI), simultaneously calculating counts per pixel within ROI, were placed over whole myocardium of 16 serial phasic images reconstructed from gated SPECT data, following selection of the central slice within short axial images. Then, 29 patients were classified into 3 patterns of phase count curve (normal, mixed, and delayed relaxation = diastolic dysfunction). Moreover, 1/3 Count Decreasing Fraction (1/3 CDF) was calculated on the same concept as 1/3 FF. The curve pattern showed significant differences between normal and abnormal group divided on the basis of established indices such as 1/3 FF and PFR, and 1/3 CDF has correlations with 1/3 FF (r = 0.61) and PFR (r = 0.58). We concluded that the new parameters drawn from 99mTc-MIBI gated SPECT data might be feasible for evaluation of diastolic function.

Impact of Major Pulmonary Resections on Right Ventricular Function: Early Postoperative Changes.

PubMed

Elrakhawy, Hany M; Alassal, Mohamed A; Shaalan, Ayman M; Awad, Ahmed A; Sayed, Sameh; Saffan, Mohammad M

2018-01-15

Right ventricular (RV) dysfunction after pulmonary resection in the early postoperative period is documented by reduced RV ejection fraction and increased RV end-diastolic volume index. Supraventricular arrhythmia, particularly atrial fibrillation, is common after pulmonary resection. RV assessment can be done by non-invasive methods and/or invasive approaches such as right cardiac catheterization. Incorporation of a rapid response thermistor to pulmonary artery catheter permits continuous measurements of cardiac output, right ventricular ejection fraction, and right ventricular end-diastolic volume. It can also be used for right atrial and right ventricular pacing, and for measuring right-sided pressures, including pulmonary capillary wedge pressure. This study included 178 patients who underwent major pulmonary resections, 36 who underwent pneumonectomy assigned as group (I) and 142 who underwent lobectomy assigned as group (II). The study was conducted at the cardiothoracic surgery department of Benha University hospital in Egypt; patients enrolled were operated on from February 2012 to February 2016. A rapid response thermistor pulmonary artery catheter was inserted via the right internal jugular vein. Preoperatively the following was recorded: central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, right ventricular ejection fraction and volumes. The same parameters were collected in fixed time intervals after 3 hours, 6 hours, 12 hours, 24 hours, and 48 hours postoperatively. For group (I): There were no statistically significant changes between the preoperative and postoperative records in the central venous pressure and mean arterial pressure; there were no statistically significant changes in the preoperative and 12, 24, and 48 hour postoperative records for cardiac index; 3 and 6 hours postoperative showed significant changes. There were statistically significant changes between the preoperative and postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index, in all postoperative records. For group (II): There were no statistically significant changes between the preoperative and all postoperative records for the central venous pressure, mean arterial pressure and cardiac index. There were statistically significant changes between the preoperative and postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index in all postoperative records. There were statistically significant changes between the two groups in all postoperative records for heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction and right ventricular end diastolic volume index. There is right ventricular dysfunction early after major pulmonary resection caused by increased right ventricular afterload. This dysfunction is more present in pneumonectomy than in lobectomy. Heart rate, mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, right ventricular ejection fraction, and right ventricular end diastolic volume index are significantly affected by pulmonary resection.

Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM.

PubMed

Penno, G; Chaturvedi, N; Talmud, P J; Cotroneo, P; Manto, A; Nannipieri, M; Luong, L A; Fuller, J H

1998-09-01

We examined whether the ACE gene insertion/deletion (I/D) polymorphism modulates renal disease progression in IDDM and how ACE inhibitors influence this relationship. The EURODIAB Controlled Trial of Lisinopril in IDDM is a multicenter randomized placebo-controlled trial in 530 nonhypertensive, mainly normoalbuminuric IDDM patients aged 20-59 years. Albumin excretion rate (AER) was measured every 6 months for 2 years. Genotype distribution was 15% II, 58% ID, and 27% DD. Between genotypes, there were no differences in baseline characteristics or in changes in blood pressure and glycemic control throughout the trial. There was a significant interaction between the II and DD genotype groups and treatment on change in AER (P = 0.05). Patients with the II genotype showed the fastest rate of AER progression on placebo but had an enhanced response to lisinopril. AER at 2 years (adjusted for baseline AER) was 51.3% lower on lisinopril than placebo in the II genotype patients (95% CI, 15.7 to 71.8; P = 0.01), 14.8% in the ID group (-7.8 to 32.7; P = 0.2), and 7.7% in the DD group (-36.6 to 37.6; P = 0.7). Absolute differences in AER between placebo and lisinopril at 2 years were 8.1, 1.7, and 0.8 microg/min in the II, ID, and DD groups, respectively. The significant beneficial effect of lisinopril on AER in the II group persisted when adjusted for center, blood pressure, and glycemic control, and also for diastolic blood pressure at 1 month into the study. Progression from normoalbuminuria to microalbuminuria (lisinopril versus placebo) was 0.27 (0.03-2.26; P = 0.2) in the II group, and 1.30 (0.33-5.17; P = 0.7) in the DD group (P = 0.6 for interaction). Knowledge of ACE genotype may be of value in determining the likely impact of ACE inhibitor treatment.

Altered expression pattern of molecular factors involved in colonic smooth muscle functions: an immunohistochemical study in patients with diverticular disease.

PubMed

Mattii, Letizia; Ippolito, Chiara; Segnani, Cristina; Battolla, Barbara; Colucci, Rocchina; Dolfi, Amelio; Bassotti, Gabrio; Blandizzi, Corrado; Bernardini, Nunzia

2013-01-01

The pathogenesis of diverticular disease (DD) is thought to result from complex interactions among dietary habits, genetic factors and coexistence of other bowel abnormalities. These conditions lead to alterations in colonic pressure and motility, facilitating the formation of diverticula. Although electrophysiological studies on smooth muscle cells (SMCs) have investigated colonic motor dysfunctions, scarce attention has been paid to their molecular abnormalities, and data on SMCs in DD are lacking. Accordingly, the main purpose of this study was to evaluate the expression patterns of molecular factors involved in the contractile functions of SMCs in the tunica muscularis of colonic specimens from patients with DD. By means of immunohistochemistry and image analysis, we examined the expression of Cx26 and Cx43, which are prominent components of gap junctions in human colonic SMCs, as well as pS368-Cx43, PKCps, RhoA and αSMA, all known to regulate the functions of gap junctions and the contractile activity of SMCs. The immunohistochemical analysis revealed significant abnormalities in DD samples, concerning both the expression and distribution patterns of most of the investigated molecular factors. This study demonstrates, for the first time, that an altered pattern of factors involved in SMC contractility is present at level of the tunica muscularis of DD patients. Moreover, considering that our analysis was conducted on colonic tissues not directly affected by diverticular lesions or inflammatory reactions, it is conceivable that these molecular alterations may precede and predispose to the formation of diverticula, rather than being mere consequences of the disease.

A Feasibility Study of Bevacizumab Plus Dose-Dense Doxorubicin–Cyclophosphamide (AC) Followed by Nanoparticle Albumin–Bound Paclitaxel in Early-Stage Breast Cancer

PubMed Central

McArthur, Heather L.; Rugo, Hope; Nulsen, Benjamin; Hawks, Laura; Grothusen, Jill; Melisko, Michelle; Moasser, Mark; Paulson, Matthew; Traina, Tiffany; Patil, Sujata; Zhou, Qin; Steingart, Richard; Dang, Chau; Morrow, Monica; Cordeiro, Peter; Fornier, Monica; Park, John; Seidman, Andrew; Lake, Diana; Gilewski, Theresa; Theodoulou, Maria; Modi, Shanu; D’Andrea, Gabriella; Sklarin, Nancy; Robson, Mark; Moynahan, Mary Ellen; Sugarman, Steven; Sealey, Jane E.; Laragh, John H.; Merali, Carmen; Norton, Larry; Hudis, Clifford A.; Dickler, Maura N.

2016-01-01

Purpose Bevacizumab confers benefits in metastatic breast cancer but may be more effective as adjuvant therapy. We evaluated the cardiac safety of bevacizumab plus dose-dense doxorubicin–cyclophosphamide (ddAC)→nanoparticle albumin−bound (nab)-paclitaxel in human epidermal growth factor receptor 2 normal early-stage breast cancer. Experimental Design Eighty patients with normal left ventricular ejection fraction (LVEF) were enrolled. Bevacizumab was administered for 1 year, concurrently with ddAC→nab-paclitaxel then as a single agent. LVEF was evaluated at months 0, 2, 6, 9, and 18. This regimen was considered safe if fewer than three cardiac events or fewer than two deaths from left ventricular dysfunction occurred. Correlative studies of cardiac troponin (cTn) and plasma renin activity (PRA) were conducted. Results The median age was 48 years (range, 27−75 years), and baseline LVEF was 68% (53%−82%). After 39 months’ median follow-up (5−45 months): median LVEF was 68% (53%−80%) at 2 months (n=78), 64% (51%−77%) at 6 months (n=66), 63% (48%−77%) at 9 months (n=61), and 66% (42%−76%) at 18 months (n=54). One patient developed symptomatic LV dysfunction at month 15. Common toxicities necessitating treatment discontinuation were hypertension (HTN, 4%), wound-healing complications (4%), and asymptomatic LVEF declines (4%). Neither cTn nor PRA predicted CHF or HTN, respectively. Conclusions Bevacizumab with ddAC→nab-paclitaxel had a low rate of cardiac events; cTn and PRA levels are not predictive of CHF or HTN, respectively. The efficacy of bevacizumab as adjuvant treatment will be established in several ongoing phase III trials. PMID:21350003

Mitochondrial reactive oxygen species production and respiratory complex activity in rats with pressure overload-induced heart failure

PubMed Central

Schwarzer, Michael; Osterholt, Moritz; Lunkenbein, Anne; Schrepper, Andrea; Amorim, Paulo; Doenst, Torsten

2014-01-01

We investigated the impact of cardiac reactive oxygen species (ROS) during the development of pressure overload-induced heart failure. We used our previously described rat model where transverse aortic constriction (TAC) induces compensated hypertrophy after 2 weeks, heart failure with preserved ejection fraction at 6 and 10 weeks, and heart failure with systolic dysfunction after 20 weeks. We measured mitochondrial ROS production rates, ROS damage and assessed the therapeutic potential of in vivo antioxidant therapies. In compensated hypertrophy (2 weeks of TAC) ROS production rates were normal at both mitochondrial ROS production sites (complexes I and III). Complex I ROS production rates increased with the appearance of diastolic dysfunction (6 weeks of TAC) and remained high thereafter. Surprisingly, maximal ROS production at complex III peaked at 6 weeks of pressure overload. Mitochondrial respiratory capacity (state 3 respiration) was elevated 2 and 6 weeks after TAC, decreased after this point and was significantly impaired at 20 weeks, when contractile function was also impaired and ROS damage was found with increased hydroxynonenal. Treatment with the ROS scavenger α-phenyl-N-tert-butyl nitrone or the uncoupling agent dinitrophenol significantly reduced ROS production rates at 6 weeks. Despite the decline in ROS production capacity, no differences in contractile function between treated and untreated animals were observed. Increased ROS production occurs early in the development of heart failure with a peak at the onset of diastolic dysfunction. However, ROS production may not be related to the onset of contractile dysfunction. PMID:24951621

Relationship of left ventricular hypertrophy and diastolic function with cardiovascular and renal outcomes in African Americans with hypertensive chronic kidney disease.

PubMed

Peterson, Gail E; de Backer, Tine; Contreras, Gabriel; Wang, Xuelei; Kendrick, Cynthia; Greene, Tom; Appel, Lawrence J; Randall, Otelio S; Lea, Janice; Smogorzewski, Miroslaw; Vagaonescu, Tudor; Phillips, Robert A

2013-09-01

African Americans with hypertension are at high risk for adverse outcomes from cardiovascular and renal disease. Patients with stage 3 or greater chronic kidney disease have a high prevalence of left ventricular (LV) hypertrophy and diastolic dysfunction. Our goal was to study prospectively the relationships of LV mass and diastolic function with subsequent cardiovascular and renal outcomes in the African American Study of Kidney Disease and Hypertension cohort study. Of 691 patients enrolled in the cohort, 578 had interpretable echocardiograms and complete relevant clinical data. Exposures were LV hypertrophy and diastolic parameters. Outcomes were cardiovascular events requiring hospitalization or causing death; a renal composite outcome of doubling of serum creatinine or end-stage renal disease (censoring death); and heart failure. We found strong independent relationships between LV hypertrophy and subsequent cardiovascular (hazard ratio, 1.16; 95% confidence interval, 1.05-1.27) events, but not renal outcomes. After adjustment for LV mass and clinical variables, lower systolic tissue Doppler velocities and diastolic parameters reflecting a less compliant LV (shorter deceleration time and abnormal E/A ratio) were significantly (P<0.05) associated with future heart failure events. This is the first study to show a strong relationship among LV hypertrophy, diastolic parameters, and adverse cardiac outcomes in African Americans with hypertension and chronic kidney disease. These echocardiographic risk factors may help identify high-risk patients with chronic kidney disease for aggressive therapeutic intervention.

[Structural and functional changes of myocardium in Chernobyl disaster clean-up workers with atrial fibrillation].

PubMed

Khomaziuk, I M; Habulavichene, Zh M; Khomaziuk, V A

2011-01-01

Particularities and clinical importance of the structural and functional changes of myocardium were estimated in Chernobyl disaster clean-up workers with atrial fibrillation (AF). We examined 122 men with AF, which was associated with ischemic heart disease and arterial hypertension. Paroxysmal AF was diagnosed in 42 patients, 80 patients had permanent AE Control group comprised 80 men without AF. Echocardiography and Doppler studies were performed using ultrasound scanner Aloka SSD-630 (Japan). Significant structural and functional changes of the heart were revealed already in paroxysmal AF and became more pronounced in permanent AF. Increased left atrial size, its ratio to left ventricular end diastolic diameter, diastolic dysfunction were important echocardiographic predictors of AF. Heart walls thickening was accompanied by disorders of myocardial relaxation, increase in myocardial mass led to ischemia, and together they promoted overload, dysfunction of atrium and development of AF. Obligatory echocardiographic examination of the Chernobyl disaster clean-up workers with ischemic heart disease and arterial hypertension is necessary for predicting AF early, ordering adequate therapy in proper time and improving prognosis.

Insulin resistance-associated decreases in left ventricular diastolic function are strongly modified by the extent of concentric remodeling in a community sample.

PubMed

Peterson, Vernice; Norton, Gavin R; Raymond, Andrew; Libhaber, Carlos D; Millen, Aletta M E; Majane, Olebogeng H I; Maseko, Muzi J; Woodiwiss, Angela J

2016-10-01

Whether excess adiposity, associated metabolic abnormalities or alternative risk factors for left ventricular (LV) diastolic function are modified rather than mediated by geometric LV remodeling, is uncertain. Echocardiographic LV mass index (LVMI), relative wall thickness (RWT) and diastolic function (lateral and septal wall myocardial tissue lengthening at the level of the mitral annulus [e'] [n=430], ratio of early-to-late transmitral blood flow velocity (E/A), and E/e' [n=430]) were determined in 737 randomly recruited participants of a community-based study (43% obese). Independent of LVMI and confounders, indexes of adiposity and the homeostasis model of insulin resistance (HOMA-IR) were independently associated with LV diastolic function (p<0.05). In addition, RWT was independently associated with LV diastolic function (p<0.002). Importantly, an independent interaction between HOMA-IR and RWT, but not between blood pressure or age and RWT, was related to LV diastolic function (p<0.05). This translated into an independent relationship between HOMA-IR and lateral e' (partial r=-0.17, p<0.02), septal e' (partial r=-0.14, p=0.05), E/A (partial r=-0.17, p<0.005) and E/e' (partial r=0.19, p<0.01) in those with RWT above, but a lack of relationship between HOMA-IR and LV diastolic function (p>0.59) in those with RWT below the median for the sample. Similarly, HOMA-IR was independently associated with LV diastolic dysfunction in those with RWT above (p<0.05) but not below (p>0.19) the median for the sample. The relationship between insulin resistance, but not alternative risk factors and LV diastolic function is markedly modified by the presence of a more concentrically remodeled LV. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Static cardiomyoplasty with synthetic elastic net suppresses ventricular dilatation and dysfunction after myocardial infarction in the rat: a chronic study.

PubMed

Kato, Nobusuke; Kawaguchi, Akira T; Kishida, Akio; Yamaoka, Tetsuji

2013-07-01

Although static cardiomyoplasty prevents the left ventricle (LV) from dilatation, it may interfere with diastolic relaxation, or cause restriction. We developed a synthetic net with dual elasticity and tested its effect late after myocardial infarction in the rat. LV pressure-volume relationships (PVR) were successively analyzed before, after intravenous volume load, and 10 minutes after occlusion of the left anterior descending artery. Rats were then randomized into groups receiving synthetic net wrapping around the heart (NET+, n = 8) and only partially behind LV (NET-, n = 9), and they underwent the same PVR studies 6 weeks later. End-diastolic and end-systolic PVR were defined, and LV size and function were compared under standardized loading conditions. Although there was no difference in Day 0, increase in LV end-diastolic and end-systolic volumes were significantly attenuated in NET+ rats 6 weeks later when there was a significant correlation between LV volumes by PVR estimation and actual measurements, with significant differences in both measures between the groups: NET+ < NET-. The presence or absence of net did not show restrictive hemodynamics under acute volume load. Static cardiomyoplasty using a synthetic elastic net significantly attenuated LV dilatation and dysfunction without restriction late after myocardial infarction in the rat. © 2013, Copyright the Authors. Artificial Organs © 2013, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Characterization of Cardiopulmonary Exercise Testing Variables in Patients with Endomyocardial Fibrosis after Endocardial Resection

PubMed Central

Sayegh, Ana Luiza C.; dos Santos, Marcelo R.; de Oliveira, Patricia; Fernandes, Fábio; Rondon, Eduardo; de Souza, Francis R.; Salemi, Vera M. C.; Alves, Maria Janieire de N. N.; Mady, Charles

2017-01-01

Background Endomyocardial fibrosis (EMF) is a rare disease, characterized by diastolic dysfunction which leads to reduced peak oxygen consumption (VO2). Cardiopulmonary exercise testing (CPET) has been proved to be a fundamental tool to identify central and peripheral alterations. However, most studies prioritize peak VO2 as the main variable, leaving aside other important CPET variables that can specify the severity of the disease and guide the clinical treatment. Objective The aim of this study was to evaluate central and peripheral limitations in symptomatic patients with EMF by different CPET variables. Methods Twenty-six EMF patients (functional class III, NYHA) were compared with 15 healthy subjects (HS). Functional capacity was evaluated using CPET and diastolic and systolic functions were evaluated by echocardiography. Results Age and gender were similar between EMF patients and HS. Left ventricular ejection fraction was normal in EMF patients, but decreased compared to HS. Peak heart rate, peak workload, peak VO2, peak oxygen (O2) pulse and peak pulmonary ventilation (VE) were decreased in EMF compared to HS. Also, EMF patients showed increased Δ heart rate /Δ oxygen uptake and Δ oxygen uptake /Δ work rate compared to HS. Conclusion Determination of the aerobic capacity by noninvasive respiratory gas exchange during incremental exercise provides additional information about the exercise tolerance in patients with EMF. The analysis of different CPET variables is necessary to help us understand more about the central and peripheral alterations cause by both diastolic dysfunction and restrictive pattern. PMID:29364349

Relationship between diastolic ventricular dysfunction and subclinical sleep-disordered breathing in atrial fibrillation ablation candidates.

PubMed

Kaitani, Kazuaki; Kondo, Hirokazu; Hanazawa, Koji; Onishi, Naoaki; Hayama, Yukiko; Tsujimura, Akira; Kuroda, Maiko; Nishimura, Shunsuke; Yoshikawa, Yusuke; Takahashi, Yusuke; Amano, Masashi; Imamura, Sari; Tamaki, Yodo; Enomoto, Soichiro; Miyake, Makoto; Tamura, Toshihiro; Motooka, Makoto; Izumi, Chisato; Nakagawa, Yoshihisa

2016-07-01

Sleep-disordered breathing (SDB) is recognized as a primary factor or mediator of atrial fibrillation (AF). We hypothesized that the severity of SDB among AF ablation candidates would be associated with left ventricular diastolic dysfunction (LVDD) even for subclinical SDB. A total of 246 patients hospitalized for initial pulmonary vein isolation (PVI) were analyzed. Known SDB cases were excluded. We measured the oxygen desaturation index (ODI) by pulse oximetry overnight as an indicator of SDB, and classified SDB severity by 3 % ODI as normal (ODI < 5 events/h), mild (ODI ≤ 5 to <15 events/h), or moderate-to-severe (ODI ≥15 events/h). The LVDD was assessed by echocardiography using combined categories with tissue Doppler imaging and left atrial (LA) volume measurement. Among the participants, 42 patients (17.1 %) had LVDD. The prevalence of LVDD increased with the SDB severity from 8.6 % (normal) to 12.7 % (mild) to 40.0 % (moderate-to-severe SDB) (p < 0.0001). In the multivariate logistic regression analysis, the odds ratio of having LVDD in the moderate-to-severe SDB group (ODI ≥ 15) vs. normal group (ODI < 5) was 5.96 (95 % CI, 2.10-19.00, P = 0.006). The presence of moderate-to-severe SDB in AF ablation candidates adversely affected LV diastolic function even during a subclinical state of SDB.

Heart disease and left ventricular rotation - a systematic review and quantitative summary.

PubMed

Phillips, Aaron A; Cote, Anita T; Bredin, Shannon S D; Warburton, Darren E R

2012-06-24

Left ventricular (LV) rotation is increasingly examined in those with heart disease. The available evidence measuring LV rotation in those with heart diseases has not been systematically reviewed. To review systematically the evidence measuring LV rotational changes in various heart diseases compared to healthy controls, literature searches were conducted for appropriate articles using several electronic databases (e.g., MEDLINE, EMBASE). All randomized-controlled trials, prospective cohort and case-controlled studies that assessed LV rotation in relation to various heart conditions were included. Three independent reviewers evaluated each investigation's quality using validated scales. Results were tabulated and levels of evidence assigned. A total of 1,782 studies were found through the systematic literature search. Upon review of the articles, 47 were included. The articles were separated into those investigating changes in LV rotation in participants with: aortic stenosis, myocardial infarction, hypertrophic cardiomyopathy, dilated cardiomyopathy, non-compaction, restrictive cardiomyopathy/ constrictive pericarditis, heart failure, diastolic dysfunction, heart transplant, implanted pacemaker, coronary artery disease and cardiovascular disease risk factors. Evidence showing changes in LV rotation due to various types of heart disease was supported by evidence with limited to moderate methodological quality. Despite a relatively low quality and volume of evidence, the literature consistently shows that heart disease leads to marked changes in LV rotation, while rotational systolic-diastolic coupling is preserved. No prognostic information exists on the potential value of rotational measures of LV function. The literature suggests that measures of LV rotation may aid in diagnosing subclinical aortic stenosis and diastolic dysfunction.

Interrelationship between diabetes mellitus and heart failure: the role of peroxisome proliferator-activated receptors in left ventricle performance.

PubMed

Oikonomou, Evangelos; Mourouzis, Konstantinos; Fountoulakis, Petros; Papamikroulis, Georgios Angelos; Siasos, Gerasimos; Antonopoulos, Alexis; Vogiatzi, Georgia; Tsalamadris, Sotiris; Vavuranakis, Manolis; Tousoulis, Dimitris

2018-05-01

Heart failure (HF) is a common cardiac syndrome, whose pathophysiology involves complex mechanisms, some of which remain unknown. Diabetes mellitus (DM) constitutes not only a glucose metabolic disorder accompanied by insulin resistance but also a risk factor for cardiovascular disease and HF. During the last years though emerging data set up, a bidirectional interrelationship between these two entities. In the case of DM impaired calcium homeostasis, free fatty acid metabolism, redox state, and advance glycation end products may accelerate cardiac dysfunction. On the other hand, when HF exists, hypoperfusion of the liver and pancreas, b-blocker and diuretic treatment, and autonomic nervous system dysfunction may cause impairment of glucose metabolism. These molecular pathways may be used as therapeutic targets for novel antidiabetic agents. Peroxisome proliferator-activated receptors (PPARs) not only improve insulin resistance and glucose and lipid metabolism but also manifest a diversity of actions directly or indirectly associated with systolic or diastolic performance of left ventricle and symptoms of HF. Interestingly, they may beneficially affect remodeling of the left ventricle, fibrosis, and diastolic performance but they may cause impaired water handing, sodium retention, and decompensation of HF which should be taken into consideration in the management of patients with DM. In this review article, we present the pathophysiological data linking HF with DM and we focus on the molecular mechanisms of PPARs agonists in left ventricle systolic and diastolic performance providing useful insights in the molecular mechanism of this class of metabolically active regiments.

Constitutive properties of adult mammalian cardiac muscle cells

NASA Technical Reports Server (NTRS)

Zile, M. R.; Richardson, K.; Cowles, M. K.; Buckley, J. M.; Koide, M.; Cowles, B. A.; Gharpuray, V.; Cooper, G. 4th

1998-01-01

BACKGROUND: The purpose of this study was to determine whether changes in the constitutive properties of the cardiac muscle cell play a causative role in the development of diastolic dysfunction. METHODS AND RESULTS: Cardiocytes from normal and pressure-hypertrophied cats were embedded in an agarose gel, placed on a stretching device, and subjected to a change in stress (sigma), and resultant changes in cell strain (epsilon) were measured. These measurements were used to examine the passive elastic spring, viscous damping, and myofilament activation. The passive elastic spring was assessed in protocol A by increasing the sigma on the agarose gel at a constant rate to define the cardiocyte sigma-versus-epsilon relationship. Viscous damping was assessed in protocol B from the loop area between the cardiocyte sigma-versus-epsilon relationship during an increase and then a decrease in sigma. In both protocols, myofilament activation was minimized by a reduction in [Ca2+]i. Myofilament activation effects were assessed in protocol C by defining cardiocyte sigma versus epsilon during an increase in sigma with physiological [Ca2+]i. In protocol A, the cardiocyte sigma-versus-epsilon relationship was similar in normal and hypertrophied cells. In protocol B, the loop area was greater in hypertrophied than normal cardiocytes. In protocol C, the sigma-versus-epsilon relation in hypertrophied cardiocytes was shifted to the left compared with normal cells. CONCLUSIONS: Changes in viscous damping and myofilament activation in combination may cause pressure-hypertrophied cardiocytes to resist changes in shape during diastole and contribute to diastolic dysfunction.

Preoperative left ventricular internal dimension in end-diastole as earlier identification of early patent ductus arteriosus operation and postoperative intensive care in very low birth weight infants.

PubMed

Saida, Ken; Nakamura, Tomohiko; Hiroma, Takehiko; Takigiku, Kiyohiro; Yasukochi, Satoshi

2013-10-01

Patent ductus arteriosus (PDA) is common in premature infants. In very low birth weight infants (VLBWI), PDA requires surgical therapy in many cases. It is unclear to know at-risk infants showing cardio-dysfunction after PDA surgery. The purpose of this study was to identify at-risk infants showing cardio-dysfunction after surgery for patent ductus arteriosus (PDA). We examined the relationship between left ventricular (LV) performance before and after PDA ligation in a retrospective observational cohort study. We studied 64 preterm neonates with symptomatic PDA before and after surgical ligation. Echocardiographic examinations were performed pre- and postoperatively. M-mode measurements included left ventricular internal dimension in end-diastole (LVIDd) and LV fractional shortening (FS). All cases showed decreased LVFS after PDA closure. Most cases (49/64, 77%) showed postoperative FS decreased to below normal (<28%). Preoperative relative LVIDd was significantly larger in abnormal FS infants (137 ± 18%) than in normal FS infants (118 ± 11%; p<0.01). A cut-off value of preoperative relative LVIDd (absolute LVIDd/normal value) for predicting postoperative cardio-dysfunction was 127.4% (sensitivity, 0.735; specificity, 0.933; area under curve, 0.817). Determination of preoperative LVIDd might facilitate earlier identification of infants needing early PDA surgery and postoperative intensive care. © 2013 Elsevier Ireland Ltd. All rights reserved.

The value of assessing pulmonary venous flow velocity for predicting severity of mitral regurgitation: A quantitative assessment integrating left ventricular function

NASA Technical Reports Server (NTRS)

Pu, M.; Griffin, B. P.; Vandervoort, P. M.; Stewart, W. J.; Fan, X.; Cosgrove, D. M.; Thomas, J. D.

1999-01-01

Although alteration in pulmonary venous flow has been reported to relate to mitral regurgitant severity, it is also known to vary with left ventricular (LV) systolic and diastolic dysfunction. There are few data relating pulmonary venous flow to quantitative indexes of mitral regurgitation (MR). The object of this study was to assess quantitatively the accuracy of pulmonary venous flow for predicting MR severity by using transesophageal echocardiographic measurement in patients with variable LV dysfunction. This study consisted of 73 patients undergoing heart surgery with mild to severe MR. Regurgitant orifice area (ROA), regurgitant stroke volume (RSV), and regurgitant fraction (RF) were obtained by quantitative transesophageal echocardiography and proximal isovelocity surface area. Both left and right upper pulmonary venous flow velocities were recorded and their patterns classified by the ratio of systolic to diastolic velocity: normal (>/=1), blunted (<1), and systolic reversal (<0). Twenty-three percent of patients had discordant patterns between the left and right veins. When the most abnormal patterns either in the left or right vein were used for analysis, the ratio of peak systolic to diastolic flow velocity was negatively correlated with ROA (r = -0.74, P <.001), RSV (r = -0.70, P <.001), and RF (r = -0.66, P <.001) calculated by the Doppler thermodilution method; values were r = -0.70, r = -0.67, and r = -0.57, respectively (all P <.001), for indexes calculated by the proximal isovelocity surface area method. The sensitivity, specificity, and predictive values of the reversed pulmonary venous flow pattern for detecting a large ROA (>0.3 cm(2)) were 69%, 98%, and 97%, respectively. The sensitivity, specificity, and predictive values of the normal pulmonary venous flow pattern for detecting a small ROA (<0.3 cm(2)) were 60%, 96%, and 94%, respectively. However, the blunted pattern had low sensitivity (22%), specificity (61%), and predictive values (30%) for detecting ROA of greater than 0.3 cm(2) with significant overlap with the reversed and normal patterns. Among patients with the blunted pattern, the correlation between the systolic to diastolic velocity ratio was worse in those with LV dysfunction (ejection fraction <50%, r = 0.23, P >.05) than in those with normal LV function (r = -0.57, P <.05). Stepwise linear regression analysis showed that the peak systolic to diastolic velocity ratio was independently correlated with RF (P <.001) and effective stroke volume (P <.01), with a multiple correlation coefficient of 0.71 (P <.001). In conclusion, reversed pulmonary venous flow in systole is a highly specific and reliable marker of moderately severe or severe MR with an ROA greater than 0.3 cm(2), whereas the normal pattern accurately predicts mild to moderate MR. Blunted pulmonary venous flow can be seen in all grades of MR with low predictive value for severity of MR, especially in the presence of LV dysfunction. The blunted pulmonary venous flow pattern must therefore be interpreted cautiously in clinical practice as a marker for severity of MR.

Matrix Metalloproteinases and their Tissue Inhibitors in Cardiac Amyloidosis: Relationship to Structural, Functional Myocardial Changes and to Light Chain Amyloid Deposition

PubMed Central

Biolo, Andreia; Ramamurthy, Sujata; Connors, Lawreen H.; O'Hara, Carl J.; Meier-Ewert, Hans K.; Hoo, Pamela T. Soo; Sawyer, Douglas B.; Seldin, David S.; Sam, Flora

2009-01-01

Background Cardiac amyloidosis is characterized by amyloid infiltration resulting in extracellular matrix (ECM) disruption. Amyloid cardiomyopathy due to immunoglobulin light chain protein (AL-CMP) deposition, has an accelerated clinical course and a worse prognosis compared to non-light chain cardiac amyloidoses i.e., forms associated with wild-type or mutated transthyretin (TTR). We therefore tested the hypothesis that determinants of proteolytic activity of the ECM, the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), would have distinct patterns and contribute to the pathogenesis of AL-CMP vs. TTR. Methods / Results We studied 40 patients with systemic amyloidosis: 10 AL-CMP patients, 20 patients with TTR-associated forms of cardiac amyloidosis, i.e. senile systemic amyloidois (SSA, involving wild-type TTR) or mutant TTR (ATTR), and 10 patients with AL amyloidosis without cardiac involvement. Serum MMP-2 and −9, TIMP-1, −2 and −4, brain natriuretic peptide (BNP) values and echocardiography were determined. AL-CMP and SSA-ATTR groups had similar degrees of increased left ventricular wall thickness (LVWT). However, BNP, MMP-9 and TIMP-1 levels were distinctly elevated accompanied by marked diastolic dysfunction in the AL-CMP group vs. no or minimal increases in the SSA-ATTR group. BNP, MMPs and TIMPs were not correlated with the degree of LVWT but were correlated to each other and to measures of diastolic dysfunction. Immunostaining of human endomyocardial biopsies showed diffuse expression of MMP-9 and TIMP-1 in AL-CMP and limited expression in SSA or ATTR hearts. Conclusions Despite comparable LVWT with TTR-related cardiac amyloidosis, AL-CMP patients have higher BNP, MMPs and TIMPs, which correlated with diastolic dysfunction. These findings suggest a relationship between light chains and ECM proteolytic activation that may play an important role in the functional and clinical manifestations of AL-CMP, distinct from the other non-light chain cardiac amyloidoses. PMID:19808299

Autonomic components of Complex Regional Pain Syndrome (CRPS) are favourably affected by Electrical Twitch-Obtaining Intramuscular Stimulation (ETOIMS): effects on blood pressure and heart rate.

PubMed

Chu, Jennifer; Bruyninckx, Frans; Neuhauser, Duncan V

2017-07-01

Favourable pain relief results on evoking autonomous twitches at myofascial trigger points with Electrical Twitch Obtaining Intramuscular Stimulation (ETOIMS). To document autonomic nervous system (ANS) dysfunction in Complex Regional Pain Syndrome (CRPS) from blood pressure (BP) and pulse/heart rate changes with ETOIMS. A patient with persistent pain regularly received serial ETOIMS sessions of 60, 90, 120 or ≥150 min over 24 months. Outcome measures include BP: systolic, diastolic, pulse pressure and pulse/heart rate, pre-session/immediate-post-session summed differences (SDPPP index), and pain reduction. His results were compared with that of two other patients and one normal control. Each individual represented the following maximal elicitable twitch forces (TWF) graded 1-5: maximum TWF2: control subject; maximum TWF3: CRPS patient with suspected ANS dysfunction; and maximum TWF4 and TWF5: two patients with respective slow-fatigue and fast-fatigue twitches who during ETOIMS had autonomous twitching at local and remote myotomes simultaneously from denervation supersensitivity. ETOIMS results between TWFs were compared using one-way analysis of variance test. The patients showed immediate significant pain reduction, BP and pulse/heart rate changes/reduction(s) except for diastolic BP in the TWF5 patient. TWF2 control subject had diastolic BP reduction with ETOIMS but not with rest. Linear regression showed TWF grade to be the most significant variable in pain reduction, more so than the number of treatments, session duration and treatment interval. TWF grade was the most important variable in significantly reducing outcome measures, especially pulse/heart rate. Unlike others, the TWF3 patient had distinctive reductions in SDPPP index. Measuring BP and pulse/heart rate is clinically practical for alerting ANS dysfunction maintained CRPS. SDPPP index (≥26) and pulse/heart rate (≥8) reductions with almost every ETOIMS treatment, plus inability to evoke autonomous twitches due to pain-induced muscle hypertonicity, are pathognomonic of this problem.

Impaired Right Ventricular-Pulmonary Arterial Coupling and Effect of Sildenafil in Heart Failure With Preserved Ejection Fraction: An Ancillary Analysis From the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) Trial.

PubMed

Hussain, Imad; Mohammed, Selma F; Forfia, Paul R; Lewis, Gregory D; Borlaug, Barry A; Gallup, Dianne S; Redfield, Margaret M

2016-04-01

Right ventricular (RV) dysfunction (RVD) is a poor prognostic factor in heart failure with preserved ejection fraction (HFpEF). The physiological perturbations associated with RVD or RV function indexed to load (RV-pulmonary arterial [PA] coupling) in HFpEF have not been defined. HFpEF patients with marked impairment in RV-PA coupling may be uniquely sensitive to sildenafil. In a subset of HFpEF patients enrolled in the Phosphodiesteas-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial, physiological variables and therapeutic effect of sildenafil were examined relative to the severity of RVD (tricuspid annular plane systolic excursion [TAPSE]) and according to impairment in RV-PA coupling (TAPSE/pulmonary artery systolic pressure) ratio. The prevalence of atrial fibrillation and diuretic use, n-terminal probrain natriuretic peptide levels, renal dysfunction, neurohumoral activation, myocardial necrosis and fibrosis biomarkers, and the severity of diastolic dysfunction all increased with severity of RVD. Peak oxygen consumption decreased and ventilatory inefficiency (VE/VCO2 slope) increased with increasing severity of RVD. Many but not all physiological derangements were more closely associated with the TAPSE/pulmonary artery systolic pressure ratio. Compared with placebo, at 24 weeks, TAPSE decreased, and peak oxygen consumption and VE/CO2 slope were unchanged with sildenafil. There was no interaction between RV-PA coupling and treatment effect, and sildenafil did not improve TAPSE, peak oxygen consumption, or VE/VCO2 in patients with pulmonary hypertension and RVD. HFpEF patients with RVD and impaired RV-PA coupling have more advanced heart failure. In RELAX patients with RVD and impaired RV-PA coupling, sildenafil did not improve RV function, exercise capacity, or ventilatory efficiency. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867. © 2016 American Heart Association, Inc.

Association of Blood Pressure Control Level With Left Ventricular Morphology and Function and With Subclinical Cerebrovascular Disease.

PubMed

Nakanishi, Koki; Jin, Zhezhen; Homma, Shunichi; Elkind, Mitchell S V; Rundek, Tatjana; Tugcu, Aylin; Sacco, Ralph L; Di Tullio, Marco R

2017-07-30

Left ventricular (LV) hypertrophy and subclinical cerebrovascular disease are early manifestations of cardiac and brain target organ damage caused by hypertension. This study aimed to investigate whether intensive office systolic blood pressure (SBP) control has beneficial effects on LV morphology and function and subclinical cerebrovascular disease in elderly patients with hypertension. We examined 420 patients treated for hypertension without history of heart failure and stroke from the CABL (Cardiovascular Abnormalities and Brain Lesions) study. All patients underwent 2-dimensional echocardiographic examination and brain magnetic resonance imaging. Subclinical cerebrovascular disease was defined as silent brain infarcts and white matter hyperintensity volume. Patients were divided into 3 groups: SBP <120 mm Hg (intensive control); SBP 120 to 139 mm Hg (less intensive control); and SBP ≥140 mm Hg (uncontrolled). Prevalence of LV hypertrophy and diastolic dysfunction were lowest in the intensive control, intermediate in the less intensive control, and highest in the uncontrolled groups (12.8%, 31.8%, and 44.7%, respectively [ P <0.001], for LV hypertrophy; 46.8%, 61.7%, and 72.6%, respectively [ P =0.003], for diastolic dysfunction). Patients with less intensive SBP control had greater risk of LV hypertrophy than those with intensive control (adjusted odds ratio, 3.26; P =0.013). A similar trend was observed for LV diastolic dysfunction but did not reach statistical significance (adjusted odds ratio, 1.65; P =0.144). Conversely, intensive SBP control was not significantly associated with reduced risk of silent brain infarcts and white matter hyperintensity volume compared with less intensive control. Compared with less intensive control, intensive SBP control may have a stronger beneficial effect on cardiac than cerebral subclinical disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Determinants of left ventricular diastolic dysfunction in hypertensive patients.

PubMed

Nazário Leão, R; Marques da Silva, P; Marques Pocinho, R; Alves, M; Virella, D; Palma Dos Reis, R

2018-02-02

The progression of hypertensive heart disease leads to the left ventricular diastolic dysfunction (LVDD), which is associated with increased cardiovascular morbidity and mortality. The purpose of this analysis is to explore the determinants for LVDD in patients with hypertension. This is a secondary analysis of data of Impedance Cardiography in the Evaluation of Left Ventricular Diastolic Dysfunction in Patients with Arterial Hypertension (IMPEDDANS) Study. Mann-Whitney and Chi-square tests were used for univariable analysis. Multiple logistic regression was used to model for LVDD occurrence and discriminative capacity of the model assessed by the value of the area under the curve given by the receiver-operating characteristic curve. Older age (65 vs. 58 years, p<0.001), longer duration of hypertension (160 vs. 48 months, p<0.001), uncontrolled hypertension (59.8 vs. 15.9%, p<0.001), tobacco smoking (17.8 vs. 3.8%, p=0.016), higher systolic blood pressure (133 vs. 124mmHg, p=0.001) and slower heart rate (62 vs. 66bpm, p=0.023) were associated with LVDD. Multivariate model identified uncontrolled hypertension (AdjOR 36.90; 95% CI 7.94-171.58; p<0.001), smoking (AdjOR 6.66; 95% CI 1.63-27.26; p=0.008), eccentric hypertrophy (AdjOR 3.59; 95% CI 0.89-14.39; p=0.072), duration of hypertension (AdjOR 1.03; 95% CI 1.02-1.05; p<0.001) and concentric remodeling (AdjOR 0.19; 95% CI 0.04-0.93; p=0.041) as the more determinant for occurrence of LVDD. The discriminative capacity of the model was AUC=0.95 (95% CI 0.91-0.98). The occurrence of LVDD in hypertensive patients was strongly associated to long-lasting, uncontrolled hypertension, tobacco smoking, concentric remodeling and eccentric hypertrophy. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

The less familiar side of heart failure: symptomatic diastolic dysfunction.

PubMed

Morris, Spencer A; Van Swol, Mark; Udani, Bela

2005-06-01

Arrange for echocardiography or radionuclide angiography within 72 hours of a heart failure exacerbation. An ejection fraction >50% in the presence of signs and symptoms of heart failure makes the diagnosis of diastolic heart failure probable. To treat associated hypertension, use angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, calcium channel blockers, or diuretics to achieve a blood pressure goal of <130/80 mm Hg. When using beta-blockers to control heart rate, titrate doses more aggressively than would be done for systolic failure, to reach a goal of 60 to 70 bpm. Use ACE inhibitors/ARBs to decrease hospitalizations, decrease symptoms, and prevent left ventricular remodeling.

Rare adipose disorders (RADs) masquerading as obesity

PubMed Central

Herbst, Karen L

2012-01-01

Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum's disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidence-based data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations. PMID:22301856

Abnormal left ventricular longitudinal functional reserve in patients with diabetes mellitus: implication for detecting subclinical myocardial dysfunction using exercise tissue Doppler echocardiography

PubMed Central

Ha, Jong‐Won; Lee, Hyun‐Chul; Kang, Eun‐Seok; Ahn, Chul‐Min; Kim, Jin‐Mi; Ahn, Jeong‐Ah; Lee, Se‐Wha; Choi, Eui‐Young; Rim, Se‐Joong; Oh, Jae K; Chung, Namsik

2007-01-01

Background Sublinical myocardial dysfunction occurs in a significant number of patients with type 2 diabetes. Assessment of ventricular long‐axis function by measuring mitral annular velocities using tissue Doppler echocardiography (TDE) is thought to provide a more sensitive index of systolic and diastolic function. We hypothesised that augmentation of left ventricular (LV) longitudinal contraction and relaxation during exercise would be blunted in patients with type 2 diabetes. Methods Mitral annular systolic (S′) and early diastolic (E′) velocities were measured at rest and during supine bicycle exercise (25 W, 3 min increments) in 53 patients (27 male, mean age 53±14 years) with type 2 diabetes and 53 subjects with age and gender‐matched control. None had echocardiographic evidence of resting or inducible myocardial ischaemia. Results There were no significant differences in mitral inflow velocities at rest between the two groups. E′ and S′ at rest were also similar between the groups. However, S′ (7.1±1.3 vs 8.3±1.8 cm/s at 25 W, p = 0.0021; 8.1±1.5 vs 9.1±2.0 cm/s at 50 W, p = 0.026) and E′ (8.5±2.3 vs 9.9±3.1 cm/s at 25 W, p = 0.054; 9.1±2.1 vs 10.9±2.5 cm/s at 50 W, p = 0.0093) during exercise were significantly lower in patients with diabetes compared with controls. Longitudinal systolic and diastolic function reserve indices were significantly lower in patients with diabetes compared with that of controls (systolic index, 0.6±0.70 vs 1.2±1.5 cm/s at 25 W, p = 0.029; 1.2±1.2 vs 2.1±1.6 cm/s at 50 W, p = 0.009; diastolic index, 1.9±1.2 vs 2.5±2.2 cm/s at 25 W, p = 0.07; 2.3±1.3 vs 3.2±2.2 cm/s at 50 W, p = 0.031). Conclusion In conclusion, unlike resting mitral inflow and annular velocities, changes of systolic and diastolic velocities of the mitral annulus during exercise were significantly reduced in patients with type 2 diabetes compared with the control group. The assessment of LV longitudinal functional reserve with exercise using TDE appears to be helpful in identifying early myocardial dysfunction in patients with type 2 diabetes. PMID:17449503

[RyR-bound FKBP12.6 and the modulation].

PubMed

Yano, M; Matsuzaki, M

2001-06-01

In the pathogenesis of cardiac dysfunction in heart failure, a decrease in the activity of the sarcoplasmic reticulum (SR) Ca(2+) -ATPase is believed to be a major determinant. Recently, a novel mechanism of cardiac dysfunction in heart failure has been reported on the basis of the following findings:1) PKA hyperphosphorylation of RyR causes a dissociation of FKBP12.6 from RyR, resulting in the abnormal single-channel properties (increased Ca(2+) sensitivity for activation and elevated channel activity associated with destabilization of RyR (Marx et al, Cell 101:365, 2000), 2) a prominent abnormal Ca(2+) leak occurs through RyR, following a partial loss of RyR-bound FKBP12.6 and the resultant conformational change in RyR (Yano M et al, Circulation 102:2131, 2000). This abnormal Ca(2+) leak might possibly cause Ca(2+) overload and consequent diastolic dysfunction, as well as systolic dysfunction.

Mutant DD genotype of NFKB1 gene is associated with the susceptibility and severity of coronary artery disease.

PubMed

Luo, Jun-Yi; Li, Xiao-Mei; Zhou, Yun; Zhao, Qiang; Chen, Bang-Dang; Liu, Fen; Chen, Xiao-Cui; Zheng, Hong; Ma, Yi-Tong; Gao, Xiao-Ming; Yang, Yi-Ning

2017-02-01

Nuclear factor κappa B (NF-κB) is an important transcription factor in the development and progression of coronary artery disease (CAD). Recent evidence suggests that -94 ATTG ins/del mutant in the promoter of NFKB1 gene is an essential functional mutant. The present study demonstrated the frequencies of the del/del (DD) genotype and del (D) allele were significantly higher in CAD patients than in controls. CAD patients carrying mutant DD genotype had worse stenosis of diseased coronary arteries compared to those carrying ins/ins (II) or ins/del (ID) genotype. Plasma levels of endothelial nitric oxide synthase (eNOS) were lower, while inflammatory cytokine incnterlukin-6 (IL-6) was higher in CAD patients with DD genotype than those with II or ID genotype (both P<0.05). In vitro study showed that mutant human umbilical vein endothelial cells (DD genotype HUVECs) were more susceptible to H 2 O 2 -induced apoptosis, which was accompanied with a decreased Bcl-2 expression. Further, mutant HUVECs had lower eNOS but higher IL-6 mRNA levels and decreased phosphorylation of eNOS under H 2 O 2 -stimulation (both P<0.05). Compared to wild type cells (II genotype), significantly downregulated protein expression of total NF-κB p50 subunit were observed in mutant HUVECs with or without oxidative stress, and a lower expression of unclear p50 was associated with a decreased p50 nuclear translocation in mutant HUVECs versus wild type cells under H 2 O 2 -stimulation (both P<0.05). In conclusion, mutant DD genotype of NFKB1 gene is associated with the risk and severity of CAD. Dwonregulation of NF-κB p50 subunit leads to exacerbated endothelial dysfunction and apoptosis and enhanced inflammatory response that is the potential underlying mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

E-wave generated intraventricular diastolic vortex to L-wave relation: model-based prediction with in vivo validation.

PubMed

Ghosh, Erina; Caruthers, Shelton D; Kovács, Sándor J

2014-08-01

The Doppler echocardiographic E-wave is generated when the left ventricle's suction pump attribute initiates transmitral flow. In some subjects E-waves are accompanied by L-waves, the occurrence of which has been correlated with diastolic dysfunction. The mechanisms for L-wave generation have not been fully elucidated. We propose that the recirculating diastolic intraventricular vortex ring generates L-waves and based on this mechanism, we predict the presence of L-waves in the right ventricle (RV). We imaged intraventricular flow using Doppler echocardiography and phase-contrast magnetic resonance imaging (PC-MRI) in 10 healthy volunteers. L-waves were recorded in all subjects, with highest velocities measured typically 2 cm below the annulus. Fifty-five percent of cardiac cycles (189 of 345) had L-waves. Color M-mode images eliminated mid-diastolic transmitral flow as the cause of the observed L-waves. Three-dimensional intraventricular flow patterns were imaged via PC-MRI and independently validated our hypothesis. Additionally as predicted, L-waves were observed in the RV, by both echocardiography and PC-MRI. The re-entry of the E-wave-generated vortex ring flow through a suitably located echo sample volume can be imaged as the L-wave. These waves are a general feature and a direct consequence of LV and RV diastolic fluid mechanics. Copyright © 2014 the American Physiological Society.

The role of a structured exercise training program on cardiac structure and function after acute myocardial infarction: study protocol for a randomized controlled trial.

PubMed

Fontes-Carvalho, Ricardo; Sampaio, Francisco; Teixeira, Madalena; Gama, Vasco; Leite-Moreira, Adelino F

2015-03-12

Exercise training is effective in improving functional capacity and quality of life in patients with coronary artery disease, but its effects on left ventricular systolic and diastolic function are controversial. Diastolic dysfunction is a major determinant of adverse outcome after myocardial infarction and, contrary to systolic function, no therapy or intervention has proved to significantly improve diastolic function. Data from animal studies and from patients with diastolic heart failure has suggested that exercise training can have a positive effect on diastolic function parameters. This trial aims to evaluate if a structured exercise training program can improve resting left ventricular diastolic and systolic function in patients who have had an acute myocardial infarction. This is a phase II, prospective, randomized, open-label, blinded-endpoint trial that will include at least 96 consecutive patients who have had an acute myocardial infarction one month previously. Patients will be randomized (1:1) to an exercise training program or a control group, receiving standard of care. At enrolment, and at the end of the follow-up period, patients will be submitted to an echocardiography (with detailed assessment of diastolic and systolic function using recent consensus guidelines), cardiopulmonary exercise testing, an anthropometric assessment, blood testing, and clinical evaluation. Patients randomized to the intervention group will be submitted to an eight-week outpatient exercise program, combining endurance and resistance training, for three sessions per week. The primary endpoint will be the change in lateral E' velocity immediately after the eight-week exercise training program. Secondary endpoints will include other echocardiographic parameters of left ventricular diastolic and systolic function, cardiac structure, metabolic and inflammation biomarkers (high-sensitivity C-reactive protein and pro-BNP), functional capacity (peak oxygen consumption and anaerobic threshold) and anthropometric measurements. New strategies that can improve left ventricular diastolic function are clinically needed. This will be the first trial to evaluate, in patients who have had an acute myocardial infarction, the effects of a structured program of exercise training on diastolic and systolic function, assessed by novel echocardiographic parameters. Registered with ClinicalTrials.gov (reference: NCT02224495 ) on 21 August 2014.

Left ventricular assist device implantation in a patient who had previously undergone apical myectomy for hypertrophic cardiomyopathy.

PubMed

Cho, Yang Hyun; Deo, Salil V; Topilsky, Yan; Grogan, Martha A; Park, Soon J

2012-03-01

Apical hypertrophy is a rare variant of hypertropic cardiomyopathy. These patients may present with end-stage congestive heart failure subsequent to long standing diastolic dysfunction. We report the technique for left ventricular assist device insertion in a patient with previous apical myectomy for hypertrophic cardiomyopathy. © 2012 Wiley Periodicals, Inc.

Systolic and diastolic assessment by 3D-ASM segmentation of gated-SPECT Studies: a comparison with MRI

NASA Astrophysics Data System (ADS)

Tobon-Gomez, C.; Bijnens, B. H.; Huguet, M.; Sukno, F.; Moragas, G.; Frangi, A. F.

2009-02-01

Gated single photon emission tomography (gSPECT) is a well-established technique used routinely in clinical practice. It can be employed to evaluate global left ventricular (LV) function of a patient. The purpose of this study is to assess LV systolic and diastolic function from gSPECT datasets in comparison with cardiac magnetic resonance imaging (CMR) measurements. This is achieved by applying our recently implemented 3D active shape model (3D-ASM) segmentation approach for gSPECT studies. This methodology allows for generation of 3D LV meshes for all cardiac phases, providing volume time curves and filling rate curves. Both systolic and diastolic functional parameters can be derived from these curves for an assessment of patient condition even at early stages of LV dysfunction. Agreement of functional parameters, with respect to CMR measurements, were analyzed by means of Bland-Altman plots. The analysis included subjects presenting either LV hypertrophy, dilation or myocardial infarction.

Late Na+ current and protracted electrical recovery are critical determinants of the aging myopathy

PubMed Central

Signore, Sergio; Sorrentino, Andrea; Borghetti, Giulia; Cannata, Antonio; Meo, Marianna; Zhou, Yu; Kannappan, Ramaswamy; Pasqualini, Francesco; O'Malley, Heather; Sundman, Mark; Tsigkas, Nikolaos; Zhang, Eric; Arranto, Christian; Mangiaracina, Chiara; Isobe, Kazuya; Sena, Brena F.; Kim, Junghyun; Goichberg, Polina; Nahrendorf, Matthias; Isom, Lori L.; Leri, Annarosa; Anversa, Piero; Rota, Marcello

2015-01-01

The aging myopathy manifests itself with diastolic dysfunction and preserved ejection fraction. We raised the possibility that, in a mouse model of physiological aging, defects in electromechanical properties of cardiomyocytes are important determinants of the diastolic characteristics of the myocardium, independently from changes in structural composition of the muscle and collagen framework. Here we show that an increase in the late Na+ current (INaL) in aging cardiomyocytes prolongs the action potential (AP) and influences temporal kinetics of Ca2+ cycling and contractility. These alterations increase force development and passive tension. Inhibition of INaL shortens the AP and corrects dynamics of Ca2+ transient, cell contraction and relaxation. Similarly, repolarization and diastolic tension of the senescent myocardium are partly restored. Thus, INaL offers inotropic support, but negatively interferes with cellular and ventricular compliance, providing a new perspective of the biology of myocardial aging and the aetiology of the defective cardiac performance in the elderly. PMID:26541940

A Global Assessment of Circulating Prolysyl Oxidase in Nonischemic Patients With Garden-variety Heart Failure With Preserved Ejection Fraction.

PubMed

Muñoz Calvo, Benjamín; Villa Martínez, Ana; López Orgil, Susana; López Andrés, Natalia; Román García, Feliciano; Víctor Palomares, Virginia; de la Calle de la Villa, Esther; Nadador Patiño, Verónica; Arribas-Gómez, Ignacio

2018-05-25

Lysyl oxidase is overexpressed in the myocardium of patients with hypertensive cardiomyopathy. We aimed to explore whether patients with hypertensive-metabolic heart failure with preserved ejection fraction (HM-HFpEF) also have increased concentrations of circulating prolysyl oxidase (cpLOX) and its possible consequences. We quantified cpLOX concentrations in 85 nonischemic patients with stage C, HM-HFpEF, and compared them with those of 51 healthy controls. We also assessed the correlations of cpLOX with myocardial stiffness parameters, collagen turnover products and fibrogenic cytokines, as well as the predictive value of plasma proenzyme levels at 1-year of follow-up. We detected raised cpLOX values and found that they correlated with calculated E/E' ratios and stiffness constants. The subgroup of patients with type I diastolic dysfunction showed a single negative correlation between cpLOX and B-type natriuretic peptide whereas patients with a restrictive diastolic pattern showed a strong correlation between cpLOX and galectin-3. Kaplan-Meier analysis revealed that cpLOX > 52.20 ng/mL slightly increased the risk of a fatal outcome (log-rank = 4.45; P = .034). When Cox regression was used, cpLOX was found to be a significant independent predictor of cardiovascular death or hospitalization due to the decompensation of HM-HFpEF (HR, 1.360; 95%CI, 1.126-1.638; P = .046). Patients with symptomatic HM-HFpEF show high cpLOX serum levels associated with restrictive diastolic filling indices. These levels represent a moderate risk factor for poor clinical outcome. Throughout the natural history of HM-HFpEF, we observed that cpLOX concentrations were initially negatively correlated with B-type natriuretic peptide but positively correlated with galectin-3 as advanced diastolic dysfunction developed. Copyright © 2018. Published by Elsevier España, S.L.U.

Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case-control study.

PubMed

Bahramali, Ehsan; Rajabi, Mona; Jamshidi, Javad; Mousavi, Seyyed Mohammad; Zarghami, Mehrdad; Manafi, Alireza; Firouzabadi, Negar

2016-02-09

To explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors. Case control study. An Iranian referral university hospital. 176 patients with hypertension and a diagnosis of HFpEF on presence of symptoms of heart failure plus Doppler echocardiographic documentation of left ventricular (LV) diastolic dysfunction and/or elevated NT-proBNP levels. Those with significant coronary, valvular, pericardial and structural heart diseases were excluded as well as patients with atrial fibrillation, renal failure and pulmonary causes of dyspnoea. They were divided into two cohorts of 88 cases with and 88 controls without LVH, after determination of LV mass index, using two-dimensional and M-mode echocardiography. The I/D polymorphism of the ACE gene was determined using the PCR method. The D allele was significantly more prevalent among cases with compared with controls without LVH (p=0.0007). Genotype distributions also differed significantly under additive (p=0.005, OR=0.53, 95% CI 0.34 to 0.84) and recessive (p=0.001, OR=0.29, 95% CI 0.13 to 0.66) models. In patients with hypertension who develop HFpEF, the D allele of the ACE gene is probably associated with the development of LVH. With the detrimental effects of LVH on the heart's diastolic properties, this can signify the role of genetic contributors to the development of HFpEF in patients with hypertension and may serve as a future risk predictor for the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

TDP1 repairs nuclear and mitochondrial DNA damage induced by chain-terminating anticancer and antiviral nucleoside analogs

PubMed Central

Huang, Shar-yin N.; Murai, Junko; Dalla Rosa, Ilaria; Dexheimer, Thomas S.; Naumova, Alena; Gmeiner, William H.; Pommier, Yves

2013-01-01

Chain-terminating nucleoside analogs (CTNAs) that cause stalling or premature termination of DNA replication forks are widely used as anticancer and antiviral drugs. However, it is not well understood how cells repair the DNA damage induced by these drugs. Here, we reveal the importance of tyrosyl–DNA phosphodiesterase 1 (TDP1) in the repair of nuclear and mitochondrial DNA damage induced by CTNAs. On investigating the effects of four CTNAs—acyclovir (ACV), cytarabine (Ara-C), zidovudine (AZT) and zalcitabine (ddC)—we show that TDP1 is capable of removing the covalently linked corresponding CTNAs from DNA 3′-ends. We also show that Tdp1−/− cells are hypersensitive and accumulate more DNA damage when treated with ACV and Ara-C, implicating TDP1 in repairing CTNA-induced DNA damage. As AZT and ddC are known to cause mitochondrial dysfunction, we examined whether TDP1 repairs the mitochondrial DNA damage they induced. We find that AZT and ddC treatment leads to greater depletion of mitochondrial DNA in Tdp1−/− cells. Thus, TDP1 seems to be critical for repairing nuclear and mitochondrial DNA damage caused by CTNAs. PMID:23775789

Cardiac diastolic and autonomic dysfunction are aggravated by central chemoreflex activation in heart failure with preserved ejection fraction rats

PubMed Central

Toledo, Camilo; Andrade, David C.; Lucero, Claudia; Arce‐Alvarez, Alexis; Díaz, Hugo S.; Aliaga, Valentín; Schultz, Harold D.; Marcus, Noah J.; Manríquez, Mónica; Faúndez, Marcelo

2017-01-01

Key points Heart failure with preserved ejection fraction (HFpEF) is associated with disordered breathing patterns, and sympatho‐vagal imbalance.Although it is well accepted that altered peripheral chemoreflex control plays a role in the progression of heart failure with reduced ejection fraction (HFrEF), the pathophysiological mechanisms underlying deterioration of cardiac function in HFpEF are poorly understood.We found that central chemoreflex is enhanced in HFpEF and neuronal activation is increased in pre‐sympathetic regions of the brainstem.Our data showed that activation of the central chemoreflex pathway in HFpEF exacerbates diastolic dysfunction, worsens sympatho‐vagal imbalance and markedly increases the incidence of cardiac arrhythmias in rats with HFpEF. Abstract Heart failure (HF) patients with preserved ejection fraction (HFpEF) display irregular breathing, sympatho‐vagal imbalance, arrhythmias and diastolic dysfunction. It has been shown that tonic activation of the central and peripheral chemoreflex pathway plays a pivotal role in the pathophysiology of HF with reduced ejection fraction. In contrast, no studies to date have addressed chemoreflex function or its effect on cardiac function in HFpEF. Therefore, we tested whether peripheral and central chemoreflexes are hyperactive in HFpEF and if chemoreflex activation exacerbates cardiac dysfunction and autonomic imbalance. Sprague‐Dawley rats (n = 32) were subjected to sham or volume overload to induce HFpEF. Resting breathing variability, chemoreflex gain, cardiac function and sympatho‐vagal balance, and arrhythmia incidence were studied. HFpEF rats displayed [mean ± SD; chronic heart failure (CHF) vs. Sham, respectively] a marked increase in the incidence of apnoeas/hypopnoeas (20.2 ± 4.0 vs. 9.7 ± 2.6 events h−1), autonomic imbalance [0.6 ± 0.2 vs. 0.2 ± 0.1 low/high frequency heart rate variability (LF/HFHRV)] and cardiac arrhythmias (196.0 ± 239.9 vs. 19.8 ± 21.7 events h−1). Furthermore, HFpEF rats showed increase central chemoreflex sensitivity but not peripheral chemosensitivity. Accordingly, hypercapnic stimulation in HFpEF rats exacerbated increases in sympathetic outflow to the heart (229.6 ± 43.2% vs. 296.0 ± 43.9% LF/HFHRV, normoxia vs. hypercapnia, respectively), incidence of cardiac arrhythmias (196.0 ± 239.9 vs. 576.7 ± 472.9 events h−1) and diastolic dysfunction (0.008 ± 0.004 vs. 0.027 ± 0.027 mmHg μl−1). Importantly, the cardiovascular consequences of central chemoreflex activation were related to sympathoexcitation since these effects were abolished by propranolol. The present results show that the central chemoreflex is enhanced in HFpEF and that acute activation of central chemoreceptors leads to increases of cardiac sympathetic outflow, cardiac arrhythmogenesis and impairment in cardiac function in rats with HFpEF. PMID:28181258

Association of Cardiac Troponin T With Left Ventricular Structure and Function in CKD

PubMed Central

Mishra, Rakesh K.; Li, Yongmei; DeFilippi, Christopher; Fischer, Michael J.; Yang, Wei; Keane, Martin; Chen, Jing; He, Jiang; Kallem, Radhakrishna; Horwitz, Ed; Rafey, Mohammad; Raj, Dominic S.; Go, Alan S.; Shlipak, Michael G.

2013-01-01

Background Serum cardiac troponin T (cTnT) is associated with increased risk of heart failure and cardiovascular death in several population settings. We evaluated associations of cTnT with cardiac structural and functional abnormalities in a cohort of chronic kidney disease (CKD) patients without heart failure. Study Design Cross-sectional. Setting & Participants Chronic Renal Insufficiency Cohort (CRIC; N= 3,243) Predictor The primary predictor was cTnT. Secondary predictors included demographic and clinical characteristics, hemoglobin level, high-sensitivity C-reactive protein, and estimated glomerular filtration rate using cystatin C. Outcomes Echocardiography was used to determine left ventricular (LV) mass and LV systolic and diastolic function. Measurements Circulating cTnT was measured in stored sera using the highly sensitive assay. Logistic and linear regression models were used to examine associations of cTnT with each echocardiographic outcome. Results cTnT was detectable in 2,735 (84%) persons; the median was 13.3 (IQR, 7.7–23.8) pg/mL. Compared with undetectable cTnT (<3.0 pg/mL), the highest quartile (23.9 – 738.7 pg/mL) was associated with approximately two times as likely to experience LV hypertrophy (OR, 2.43; 95% CI, 1.44–4.09) in the fully adjusted model. cTnT had a more modest association with LV systolic dysfunction; as a log-linear variable, a significant association was present in the fully adjusted model (OR of 1.4 [95% CI, 1.1–1.7] per 1-log unit; p<0.01). There was no significant independent association between cTnT and LV diastolic dysfunction. When evaluated as a screening test, cTnT functioned only modestly for LV hypertrophy and concentric hypertrophy detection (area under the curve, 0.64 for both) with weaker areas under the curve for the other outcomes. Limitations The presence of coronary artery disease was not formally assessed using either noninvasive or angiographic techniques in this study. Conclusions In this large CKD cohort without heart failure, detectable cTnT had a strong association with LV hypertrophy, a more modest association with LV systolic dysfunction, and no association with diastolic dysfunction. These findings indicate that circulating cTnT levels in CKD are predominantly an indicator of pathological LV hypertrophy. PMID:23291148

Association of cardiac troponin T with left ventricular structure and function in CKD.

PubMed

Mishra, Rakesh K; Li, Yongmei; DeFilippi, Christopher; Fischer, Michael J; Yang, Wei; Keane, Martin; Chen, Jing; He, Jiang; Kallem, Radhakrishna; Horwitz, Edward J; Rafey, Mohammad; Raj, Dominic S; Go, Alan S; Shlipak, Michael G

2013-05-01

Serum cardiac troponin T (cTnT) is associated with increased risk of heart failure and cardiovascular death in several population settings. We evaluated associations of cTnT levels with cardiac structural and functional abnormalities in a cohort of patients with chronic kidney disease (CKD) without heart failure. Cross-sectional. Chronic Renal Insufficiency Cohort (CRIC; N=3,243). The primary predictor was cTnT level. Secondary predictors included demographic and clinical characteristics, hemoglobin level, high-sensitivity C-reactive protein level, and estimated glomerular filtration rate using cystatin C. Echocardiography was used to determine left ventricular (LV) mass and LV systolic and diastolic function. Circulating cTnT was measured in stored sera using the highly sensitive assay. Logistic and linear regression models were used to examine associations of cTnT level with each echocardiographic outcome. cTnT was detectable in 2,735 (84%) persons; median level was 13.3 (IQR, 7.7-23.8) pg/mL. Compared with undetectable cTnT (<3.0 pg/mL), the highest quartile (23.9-738.7 pg/mL) was approximately 2 times as likely to have LV hypertrophy (OR, 2.43; 95% CI, 1.44-4.09) in the fully adjusted model. cTnT level had a more modest association with LV systolic dysfunction; as a log-linear variable, a significant association was present in the fully adjusted model (OR of 1.4 [95% CI, 1.2-1.7] per 1-log unit; P < 0.001). There was no significant independent association between cTnT level and LV diastolic dysfunction. When evaluated as a screening test, cTnT level functioned only modestly for LV hypertrophy and concentric hypertrophy detection (area under the curve, 0.64 for both), with weaker areas under the curve for the other outcomes. The presence of coronary artery disease was not formally assessed using either noninvasive or angiographic techniques in this study. In this large CKD cohort without heart failure, detectable cTnT had a strong association with LV hypertrophy, a more modest association with LV systolic dysfunction, and no association with diastolic dysfunction. These findings indicate that circulating cTnT levels in patients with CKD are predominantly an indicator of pathologic LV hypertrophy. Published by Elsevier Inc.

Galectin-3 in heart failure with preserved ejection fraction. A RELAX trial substudy (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure).

PubMed

AbouEzzeddine, Omar F; Haines, Phillip; Stevens, Susanna; Nativi-Nicolau, Jose; Felker, G Michael; Borlaug, Barry A; Chen, Horng H; Tracy, Russell P; Braunwald, Eugene; Redfield, Margaret M

2015-03-01

This study hypothesized that elevated galectin-3 (Gal-3) levels would identify patients with more advanced heart failure (HF) with preserved ejection fraction (HFpEF) as assessed by key pathophysiological domains. Gal-3 is implicated in the pathogenesis of cardiac fibrosis but is also increased with normal aging and renal dysfunction. Cardiac fibrosis may contribute to cardiac dysfunction, exercise intolerance, and congestion in HFpEF. Two hundred eight patients from the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial of sildenafil in HFpEF had Gal-3 measured at enrollment. Pathophysiological domains assessed included biomarkers of neurohumoral activation, fibrosis, inflammation and myocardial necrosis, congestion severity and quality of life, cardiac structure and function, and exercise performance. Analysis adjusted for age, sex, and/or cystatin-C levels. Potential interaction between baseline Gal-3 and treatment (sildenafil) effect on the RELAX study primary endpoint (change in peak oxygen consumption) was tested. Gal-3 levels were associated with age and severity of renal dysfunction. Adjusting for age, sex, and/or cystatin-C, Gal-3 was not associated with biomarkers of neurohumoral activation, fibrosis, inflammation or myocardial necrosis, congestion or quality-of-life impairment, cardiac remodeling or dysfunction, or exercise intolerance. Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p = 0.53). In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. These findings underscore the need to adjust for renal function when interpreting Gal-3 levels, and call into question the value of Gal-3 to quantify disease severity in overt HFpEF. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Estrogen modulation of the ethanol-evoked myocardial oxidative stress and dysfunction via DAPK3/Akt/ERK activation in male rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com; Abdel-Rahman, Abdel A., E-mail: abdelrahmana@ecu.edu

Evidence suggests that male rats are protected against the hypotensive and myocardial depressant effects of ethanol compared with females. We investigated whether E{sub 2} modifies the myocardial and oxidative effects of ethanol in male rats. Conscious male rats received ethanol (0.5, 1 or 1.5 g/kg i.v.) 30-min after E{sub 2} (1 μg/kg i.v.) or its vehicle (saline), and hearts were collected at the conclusion of hemodynamic measurements for ex vivo molecular studies. Ethanol had no effect in vehicle-treated rats, but it caused dose-related reductions in LV developed pressure (LVDP), end-diastolic pressure (LVEDP), rate of rise in LV pressure (dP/dt{sub max})more » and systolic (SBP) and diastolic (DBP) blood pressures in E{sub 2}-pretreated rats. These effects were associated with elevated (i) indices of reactive oxygen species (ROS), (ii) malondialdehyde (MDA) protein adducts, and (iii) phosphorylated death-associated protein kinase-3 (DAPK3), Akt, and extracellular signal-regulated kinases (ERK1/2). Enhanced myocardial anti-oxidant enzymes (heme oxygenase-1, catalase and aldehyde dehydrogenase 2) activities were also demonstrated. In conclusion, E{sub 2} promotes ethanol-evoked myocardial oxidative stress and dysfunction in male rats. The present findings highlight the risk of developing myocardial dysfunction in men who consume alcohol while receiving E{sub 2} for specific medical conditions. - Highlights: • Ethanol lowers blood pressure and causes LV dysfunction in E{sub 2}-treated rats. • E{sub 2}/ethanol aggravates cardiac oxidative state via of DAPK3/Akt/ERK activation. • E{sub 2}/ethanol causes a feedback increase in cardiac HO-1, catalase and ALDH2. • Alcohol might increase risk of myocardial dysfunction in men treated with E{sub 2}.« less

Heart Disease and Left Ventricular Rotation – A Systematic Review and Quantitative Summary

PubMed Central

2012-01-01

Background Left ventricular (LV) rotation is increasingly examined in those with heart disease. The available evidence measuring LV rotation in those with heart diseases has not been systematically reviewed. Methods To review systematically the evidence measuring LV rotational changes in various heart diseases compared to healthy controls, literature searches were conducted for appropriate articles using several electronic databases (e.g., MEDLINE, EMBASE). All randomized-controlled trials, prospective cohort and case–controlled studies that assessed LV rotation in relation to various heart conditions were included. Three independent reviewers evaluated each investigation’s quality using validated scales. Results were tabulated and levels of evidence assigned. Results A total of 1,782 studies were found through the systematic literature search. Upon review of the articles, 47 were included. The articles were separated into those investigating changes in LV rotation in participants with: aortic stenosis, myocardial infarction, hypertrophic cardiomyopathy, dilated cardiomyopathy, non-compaction, restrictive cardiomyopathy/ constrictive pericarditis, heart failure, diastolic dysfunction, heart transplant, implanted pacemaker, coronary artery disease and cardiovascular disease risk factors. Evidence showing changes in LV rotation due to various types of heart disease was supported by evidence with limited to moderate methodological quality. Conclusions Despite a relatively low quality and volume of evidence, the literature consistently shows that heart disease leads to marked changes in LV rotation, while rotational systolic-diastolic coupling is preserved. No prognostic information exists on the potential value of rotational measures of LV function. The literature suggests that measures of LV rotation may aid in diagnosing subclinical aortic stenosis and diastolic dysfunction. PMID:22726250

Coronary flow reserve is impaired in patients with aortic valve calcification.

PubMed

Bozbas, Huseyin; Pirat, Bahar; Yildirir, Aylin; Simşek, Vahide; Sade, Elif; Eroglu, Serpil; Atar, Ilyas; Altin, Cihan; Demirtas, Saadet; Ozin, Bulent; Muderrisoglu, Haldun

2008-04-01

Calcific aortic valve disease is an active and progressive condition. Data indicate that aortic valve calcification (AVC) is associated with endothelial dysfunction and accepted as a manifestation of atherosclerosis. Coronary flow reserve (CFR) determined by transthoracic echocardiography has been introduced as a reliable indicator for coronary microvascular function. In this study we aimed to evaluate CFR in patients with AVC. Eighty patients, aged more than 60 years, without coronary heart disease or diabetes mellitus were included: 40 had AVC without significant stenosis (peak gradient across the valve <25 mm Hg) and 40 had normal aortic valves (controls). Using transthoracic Doppler echocardiography, we measured coronary diastolic peak flow velocities (PFV) at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic PFV and was compared between groups. Mean ages for patients with AVC and controls were 68.9+/-6.2 and 67.6+/-5.9 years (P=.3). There were no significant differences regarding clinical characteristics, laboratory findings, ejection fraction, or peak aortic valve gradients. Mean diastolic PFV at baseline and during hyperemia were 28.4+/-4.2 and 59.2+/-7.8 cm/s for AVC and 27.7+/-3.9 and 68.5+/-10.5 cm/s for controls. Compared with controls, patients with AVC had significantly lower CFR values (2.12+/-0.41 versus 2.51+/-0.51; P<.0001). CFR is impaired in patients with AVC before valve stenosis develops, suggesting that microvascular-endothelial dysfunction is present during the early stages of the calcific aortic valve disease.

New approaches to the Doppler echocardiographic assessment of diastolic function: from research laboratory to clinical practice

NASA Technical Reports Server (NTRS)

Pasquet, A.; Garcia, M. J.; Thomas, J. D.

1999-01-01

Over the past decade, Doppler echocardiography has become a well-established tool for the diagnosis of left ventricular diastolic dysfunction. Unfortunately, in many clinical situations traditional Doppler indices of transmittal and pulmonary venous flow are inconclusive, primarily due to their dependence on left atrial pressure. Recently, new Doppler indices that are much less dependent on preload have been developed, based on intraventricular flow propagation and intrinsic myocardial velocity. These methodologies provide direct assessment of ventricular relaxation and the small intraventricular pressure gradients essential to efficient filling of the ventricle. We review in this article the theoretical and experiment background of these new echo techniques as well as how they can be implemented in routine clinical practice.

Hemodynamic changes during weaning: can we assess and predict cardiac-related weaning failure by transthoracic echocardiography?

PubMed Central

2010-01-01

Cardiac-related failure of weaning from mechanical ventilation is an important reason for prolonged mechanical ventilation, intensive care unit treatment, and increased morbidity and mortality. When transthoracic echocardiography (TTE) is routinely performed before a weaning trial, patients at high risk of cardiac-related failure can be detected by low left ventricular (LV) ejection fraction, diastolic dysfunction, and elevated LV filling pressure. During the weaning trial, a further increase of LV filling pressure and progression of diastolic failure can be observed by repeated TTE. Owing to certain limitations concerning patients and methodology, TTE cannot be employed in every patient and invasive hemodynamic monitoring is still mandatory in selected patients with repetitive weaning failure. PMID:20619005

Hemodynamic changes during weaning: can we assess and predict cardiac-related weaning failure by transthoracic echocardiography?

PubMed

Voga, Gorazd

2010-01-01

Cardiac-related failure of weaning from mechanical ventilation is an important reason for prolonged mechanical ventilation, intensive care unit treatment, and increased morbidity and mortality. When transthoracic echocardiography (TTE) is routinely performed before a weaning trial, patients at high risk of cardiac-related failure can be detected by low left ventricular (LV) ejection fraction, diastolic dysfunction, and elevated LV filling pressure. During the weaning trial, a further increase of LV filling pressure and progression of diastolic failure can be observed by repeated TTE. Owing to certain limitations concerning patients and methodology, TTE cannot be employed in every patient and invasive hemodynamic monitoring is still mandatory in selected patients with repetitive weaning failure.

Inadequate RAAS suppression is associated with excessive left ventricular mass and systo-diastolic dysfunction.

PubMed

Gregori, Mario; Tocci, Giuliano; Marra, Andrea; Pignatelli, Giulia; Santolamazza, Caterina; Befani, Alberto; Ciavarella, Giuseppino Massimo; Ferrucci, Andrea; Paneni, Francesco

2013-10-01

Inadequate suppression of renin-angiotensin-aldosterone system (RAAS) following postural maneuvers may have detrimental effects on cardiac structure and function. In this study, we aimed to appraise the clinical significance of this phenomenon by assessing its relation with inappropriate ventricular mass (ILVM), an adverse phenotype of LV remodeling and dysfunction. Both supine and upright plasma renin activity (PRA) and aldosterone concentrations (PAC) were measured in 115 young newly diagnosed hypertensive subjects. 24-h ambulatory blood pressure monitoring and echocardiographic evaluation including tissue Doppler imaging (TDI) were also performed. Patients were divided as follows: (1) normal PRA and PAC (N) (n = 63); (2) suppressible RAAS (SR) in supine position (n = 27); (3) not suppressible RAAS (NSR) (n = 25). ILVM was expressed as the observed/predicted LV mass ratio ×100 (%PLVM), while LV dysfunction (LVD) was identified by TDI-derived myocardial performance index (MPI). NSR showed a higher prevalence of ILVM than SR and N. As compared with N and SR, NSR patients had reduced indices of systolic and diastolic function. MPI of the LV as well as prevalence of LVD was also significantly higher in the NSR group. Regression models showed that lack of RAAS suppression was independently associated with ILVM and LVD. Prevalence of ILVM and LVD is higher in patients without clinostatic RAAS suppression. Our findings encourage the assessment of RAAS deregulation to better estimate individual cardiovascular risk in patients with arterial hypertension.

Current Perspectives on Systemic Hypertension in Heart Failure with Preserved Ejection Fraction.

PubMed

Tam, Marty C; Lee, Ran; Cascino, Thomas M; Konerman, Matthew C; Hummel, Scott L

2017-02-01

Heart failure with preserved ejection fraction (HFpEF) is a prevalent but incompletely understood syndrome. Traditional models of HFpEF pathophysiology revolve around systemic HTN and other causes of increased left ventricular afterload leading to left ventricular hypertrophy (LVH) and diastolic dysfunction. However, emerging models attribute the development of HFpEF to systemic proinflammatory changes secondary to common comorbidities which include HTN. Alterations in passive ventricular stiffness, ventricular-arterial coupling, peripheral microvascular function, systolic reserve, and chronotropic response occur. As a result, HFpEF is heterogeneous in nature, making it difficult to prescribe uniform therapies to all patients. Nonetheless, treating systemic HTN remains a cornerstone of HFpEF management. Antihypertensive therapies have been linked to LVH regression and improvement in diastolic dysfunction. However, to date, no therapies have definitive mortality benefit in HFpEF. Non-pharmacologic management for HTN, including dietary modification, exercise, and treating sleep disordered breathing, may provide some morbidity benefit in the HFpEF population. Future research is need to identify effective treatments, perhaps in more specific subgroups, and focus may need to shift from reducing mortality to improving exercise capacity and symptoms. Tailoring antihypertensive therapies to specific phenotypes of HFpEF may be an important component of this strategy.

Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes.

PubMed

Matsutani, Daisuke; Sakamoto, Masaya; Kayama, Yosuke; Takeda, Norihiko; Horiuchi, Ryuzo; Utsunomiya, Kazunori

2018-05-22

Type 2 diabetes mellitus (T2DM) greatly increases the risks of cardiovascular disease and heart failure. In particular, left ventricular diastolic dysfunction that develops from the early stages of T2DM is an important factor in the onset and exacerbation of heart failure. The effect of sodium-glucose cotransporter 2 inhibitors on left ventricular diastolic function has not been elucidated. We have performed the first prospective study on the effects of canagliflozin on left ventricular diastolic function in T2DM. This study was performed to evaluate the effects of additional treatment with canagliflozin for 3 months on left ventricular diastolic function in patients with T2DM. A total of 38 patients with T2DM were consecutively recruited for this study. Left ventricular diastolic function was assessed by echocardiography. The primary study outcome was a change in the septal E/e' as a parameter of left ventricular diastolic function. A total of 37 patients (25 males and 12 females) were included in the analysis. Mean age of participants was 64.2 ± 8.1 years (mean ± SD), mean duration of diabetes was 13.5 ± 8.1 years, and mean HbA1c was 7.9 ± 0.7%. Of the participants, 86.5% had hypertension, 100% had dyslipidemia, and 32.4% had cardiovascular disease. Canagliflozin significantly improved left ventricular diastolic function (septal E/e' ratio 13.7 ± 3.5-12.1 ± 2.8, p = 0.001). Furthermore, among the various parameters that changed through the administration of canagliflozin, only changes in hemoglobin significantly correlated with changes in the septal E/e' ratio (p = 0.002). In multiple regression analysis, changes in hemoglobin were also revealed to be an independent predictive factor for changes in the septal E/e' ratio. This study showed for the first time that canagliflozin could improve left ventricular diastolic function within 3 months in patients with T2DM. The benefit was especially apparent in patients with substantially improved hemoglobin values. Trial registration UMIN Clinical Trials Registry UMIN000028141.

Cardiac Amyloidosis Shows Decreased Diastolic Function as Assessed by Echocardiographic Parameterized Diastolic Filling.

PubMed

Salman, Katrin; Cain, Peter A; Fitzgerald, Benjamin T; Sundqvist, Martin G; Ugander, Martin

2017-07-01

Cardiac amyloidosis is a rare but serious condition with poor survival. One of the early findings by echocardiography is impaired diastolic function, even before the development of cardiac symptoms. Early diagnosis is important, permitting initiation of treatment aimed at improving survival. The parameterized diastolic filling (PDF) formalism entails describing the left ventricular filling pattern during early diastole using the mathematical equation for the motion of a damped harmonic oscillator. We hypothesized that echocardiographic PDF analysis could detect differences in diastolic function between patients with amyloidosis and controls. Pulsed-wave Doppler echocardiography of transmitral flow was measured in 13 patients with amyloid heart disease and 13 age- and gender matched controls. E- waves (2 to 3 per subject) were analyzed using in-house developed software. Nine PDF-derived parameters were obtained in addition to conventional echocardiographic parameters of diastolic function. Compared to controls, cardiac amyloidosis patients had a larger left atrial area (23.7 ± 7.5 cm 2 vs. 18.5 ± 4.8 cm 2 , p = 0.04), greater interventricular septum wall thickness (14.4 ± 2.6 mm vs. 9.3 ± 1.3 mm, p < 0.001), lower e' (0.06 ± 0.02 m/s vs. 0.09 ± 0.02 m/s, p < 0.001) and higher E/e' (18.0 ± 12.9 vs. 7.7 ± 1.3, p = 0.001). The PDF parameter peak resistive force was greater in cardiac amyloidosis patients compared to controls (17.9 ± 5.7 mN vs. 13.1 ± 3.1 mN, p = 0.03), and other PDF parameters did not differ. PDF analysis revealed that patients with cardiac amyloidosis had a greater peak resistive force compared to controls, consistent with a greater degree of diastolic dysfunction. PDF analysis may be useful in characterizing diastolic function in amyloid heart disease. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Endocannabinoids as mediators in the heart: a potential target for therapy of remodelling after myocardial infarction?

PubMed Central

Hiley, C Robin; Ford, William R

2003-01-01

Endocannabinoid production by platelets and macrophages is increased in circulatory shock. This may be protective of the cardiovascular system as blockade of CB1 cannabinoid receptors exacerbates endothelial dysfunction in haemorrhagic and endotoxin shock and reduces survival. Now evidence suggests that blockade of CB1 receptors starting 24 h after myocardial infarction in rats has a deleterious effect on cardiac performance, while use of a nonselective cannabinoid receptor agonist prevents hypotension and reduces endothelial dysfunction, although left ventricular end diastolic pressure is elevated. Cannabinoids and endocannabinoid systems may therefore present useful targets for therapy following myocardial infarction. PMID:12711614

Correlation between increased urinary sodium excretion and decreased left ventricular diastolic function in patients with type 2 diabetes mellitus.

PubMed

Kagiyama, Shuntaro; Koga, Tokushi; Kaseda, Shigeru; Ishihara, Shiro; Kawazoe, Nobuyuki; Sadoshima, Seizo; Matsumura, Kiyoshi; Takata, Yutaka; Tsuchihashi, Takuya; Iida, Mitsuo

2009-10-01

Increased salt intake may induce hypertension, lead to cardiac hypertrophy, and exacerbate heart failure. When elderly patients develop heart failure, diastolic dysfunction is often observed, although the ejection fraction has decreased. Diabetes mellitus (DM) is an established risk factor for heart failure. However, little is known about the relationship between cardiac function and urinary sodium excretion (U-Na) in patients with DM. We measured 24-hour U-Na; cardiac function was evaluated directly during coronary catheterization in type 2 DM (n = 46) or non-DM (n = 55) patients with preserved cardiac systolic function (ejection fraction > or = 60%). Cardiac diastolic and systolic function was evaluated as - dp/dt and + dp/dt, respectively. The average of U-Na was 166.6 +/- 61.2 mEq/24 hour (mean +/- SD). In all patients, stepwise multivariate regression analysis revealed that - dp/dt had a negative correlation with serum B-type natriuretic peptide (BNP; beta = - 0.23, P = .021) and U-Na (beta = - 0.24, P = .013). On the other hand, + dp/dt negatively correlated with BNP (beta = - 0.30, P < .001), but did not relate to U-Na. In the DM-patients, stepwise multivariate regression analysis showed that - dp/dt still had a negative correlation with U-Na (beta = - 0.33, P = .025). The results indicated that increased urinary sodium excretion is associated with an impairment of cardiac diastolic function, especially in patients with DM, suggesting that a reduction of salt intake may improve cardiac diastolic function.

Left ventricular stiffness estimated by diastolic wall strain is associated with paroxysmal atrial fibrillation in structurally normal hearts.

PubMed

Uetake, Shunsuke; Maruyama, Mitsunori; Yamamoto, Teppei; Kato, Katsuhito; Miyauchi, Yasushi; Seino, Yoshihiko; Shimizu, Wataru

2016-12-01

Left ventricular (LV) diastolic dysfunction depends on an impaired relaxation and stiffness. Abnormal LV relaxation contributes to the development of atrial fibrillation (AF), but the role of LV stiffness in AF remains unclear. Diastolic wall strain (DWS), a load-independent, noninvasive direct measure of LV stiffness, correlates with prevalent AF. This study included 328 consecutive subjects with structurally normal hearts: 164 paroxysmal AF patients and 164 age- and sex-matched (1:1) controls. We calculated the DWS from the M-mode echocardiographic measurements of the LV posterior wall thickness at end-systole and end-diastole during sinus rhythm. The DWS was lower in the AF patients (0.35 ± 0.07) than in the controls (0.41 ± 0.06; P < 0.001). After adjusting for the risk factors of AF using a conditional logistic regression analysis, a history of hypertension, plasma brain-type natriuretic peptide level, and DWS were independently associated with AF prevalence, whereas body mass index, LV mass index, left atrial volume, and any conventional indices of the diastolic function were not. A low DWS (<0.380) was the strongest indicator of AF (odds ratio: 6.22, 95% confidence interval: 3.08-14.2, P < 0.001). Increased LV stiffness estimated by DWS was a strong determinant of the prevalence of AF. LV stiffness may play a role in the pathogenesis of paroxysmal AF in structurally normal hearts. © 2016 Wiley Periodicals, Inc.

Wall Thickness, Pulmonary Hypertension, and Diastolic Filling Abnormalities Predict Response to Postoperative Biventricular Pacing

PubMed Central

Brusen, Robin M.; Hahn, Rebecca; Cabreriza, Santos E.; Cheng, Bin; Wang, Daniel Y.; Truong, Wanda; Spotnitz, Henry M.

2017-01-01

Objective Post-cardiopulmonary bypass biventricular pacing improves hemodynamics but without clearly defined predictors of response. Based on preclinical studies and prior observations, it was suspected that diastolic dysfunction or pulmonary hypertension is predictive of hemodynamic benefit. Design Randomized controlled study of temporary biventricular pacing after cardiopulmonary bypass. Setting Single-center study at university-affiliated tertiary care hospital. Interventions Patients who underwent bypass with pre-operative ejection fraction ≤40% and QRS duration ≥100 ms or double-valve surgery were enrolled. At 3 time points between separation from bypass and postoperative day 1, pacing delays were varied to optimize hemodynamics. Participants Data from 43 patients were analyzed. Measurements and Main Results Cardiac output and arterial pressure were measured under no pacing, atrial pacing, and biventricular pacing. Preoperative echocardiograms and pulmonary artery catheterizations were reviewed, and measures of both systolic and diastolic function were compared to hemodynamic response. Early after separation, improvement in cardiac output was positively correlated with pulmonary vascular resistance (R2 = 0.97, p < 0.001), ventricle wall thickness (R2 = 0.72, p = 0.002)), and E/e′, a measure of abnormal diastolic ventricular filling velocity (R2 = 0.56, p = 0.04). Similar trends were seen with mean arterial pressure. QRS duration and ejection fraction did not correlate significantly with improvements in hemodynamics. Conclusions There may be an effect of biventricular pacing related to amelioration of abnormal diastolic filling patterns rather than electrical resynchronization in the postoperative state. PMID:25998068

Does oxidative stress modulate left ventricular diastolic function in asymptomatic subjects with hereditary hemochromatosis?

PubMed

Shizukuda, Yukitaka; Bolan, Charles D; Tripodi, Dorothy J; Sachdev, Vandana; Nguyen, Tammy T; Botello, Gilberto; Yau, Yu-Ying; Sidenko, Stanislav; Inez, Ernst; Ali, Mir I; Waclawiw, Myron A; Leitman, Susan F; Rosing, Douglas R

2009-11-01

Little is known about the early mechanisms mediating left ventricular (LV) diastolic dysfunction in patients with hereditary hemochromatosis (HH). However, the increased oxidative stress related to iron overload may be involved in this process, and strain rate (SR), a sensitive echocardiography-derived measure of diastolic function, may detect such changes. we evaluated the relationship between left ventricular diastolic function measured with tissue Doppler SR and oxidative stress in asymptomatic HH subjects and control normal subjects. Ninety-four consecutive visits of 43 HH subjects, age 30-74 (50 +/- 10, mean +/- SD), and 37 consecutive visits of 21 normal volunteers, age 30-63 (48 +/- 8), were evaluated over a 3-year period. SR was obtained from the basal septum in apical four-chamber views. All patients had confirmed C282Y homozygosity, a documented history of iron overload, and were New York Heart Association functional class I. Normal volunteers lacked HFE gene mutations causing HH. In the HH subjects, the SR demonstrated moderate but significant correlations with biomarkers of oxidative stress; however, no correlations were noted in normal subjects. The biomarkers of iron overload per se did not show significant correlations with the SR. Although our study was limited by the relatively small subject number, these results suggest that a possible role of oxidative stress to affect LV diastolic function in asymptomatic HH subjects and SR imaging may be a sensitive measure to detect that effect.

Exposure to chronic alcohol accelerates development of wall stress and eccentric remodeling in rats with volume overload.

PubMed

Mouton, Alan J; Ninh, Van K; El Hajj, Elia C; El Hajj, Milad C; Gilpin, Nicholas W; Gardner, Jason D

2016-08-01

Chronic alcohol abuse is one of the leading causes of dilated cardiomyopathy (DCM) in the United States. Volume overload (VO) also produces DCM characterized by left ventricular (LV) dilatation and reduced systolic and diastolic function, eventually progressing to congestive heart failure. For this study, we hypothesized that chronic alcohol exposure would exacerbate cardiac dysfunction and remodeling due to VO. Aortocaval fistula surgery was used to induce VO, and compensatory cardiac remodeling was allowed to progress for either 3days (acute) or 8weeks (chronic). Alcohol was administered via chronic intermittent ethanol vapor (EtOH) for 2weeks before the acute study and for the duration of the 8week chronic study. Temporal alterations in LV function were assessed by echocardiography. At the 8week end point, pressure-volume loop analysis was performed by LV catheterization and cardiac tissue collected. EtOH did not exacerbate LV dilatation (end-systolic and diastolic diameter) or systolic dysfunction (fractional shortening, ejection fraction) due to VO. The combined stress of EtOH and VO decreased the eccentric index (posterior wall thickness to end-diastolic diameter ratio), increased end-diastolic pressure (EDP), and elevated diastolic wall stress. VO also led to increases in posterior wall thickness, which was not observed in the VO+EtOH group, and wall thickness significantly correlated with LV BNP expression. VO alone led to increases in interstitial collagen staining (picrosirius red), which while not statistically significant, tended to be decreased by EtOH. VO increased LV collagen I protein expression, whereas in rats with VO+EtOH, LV collagen I was not elevated relative to Sham. The combination of VO and EtOH also led to increases in LV collagen III expression relative to Sham. Rats with VO+EtOH had significantly lower collagen I/III ratio than rats with VO alone. During the acute remodeling phase of VO (3days), VO significantly increased collagen III expression, whereas this effect was not observed in rats with VO+EtOH. In conclusion, chronic EtOH accelerates the development of elevated wall stress and promotes early eccentric remodeling in rats with VO. Our data indicate that these effects may be due to disruptions in compensatory hypertrophy and extracellular matrix remodeling in response to volume overload. Copyright © 2016 Elsevier Ltd. All rights reserved.

Noninvasive Doppler Tissue Measurement of Pulmonary Artery Compliance in Children with Pulmonary Hypertension

PubMed Central

Dyer, Karrie; Lanning, Craig; Das, Bibhuti; Lee, Po-Feng; Ivy, D. Dunbar; Valdes-Cruz, Lilliam; Shandas, Robin

2007-01-01

Background We have shown previously that input impedance of the pulmonary vasculature provides a comprehensive characterization of right ventricular afterload by including compliance. However, impedance-based compliance assessment requires invasive measurements. Here, we develop and validate a noninvasive method to measure pulmonary artery (PA) compliance using ultrasound color M-mode (CMM) Doppler tissue imaging (DTI). Methods Dynamic compliance (Cdyn) of the PA was obtained from CMM DTI and continuous wave Doppler measurement of the tricuspid regurgitant velocity. Cdyn was calculated as: [(Ds − Dd)/(Dd × Ps)] × 104; where Ds = systolic diameter, Dd = diastolic diameter, and Ps = systolic pressure. The method was validated both in vitro and in 13 patients in the catheterization laboratory, and then tested on 27 pediatric patients with pulmonary hypertension, with comparison with 10 age-matched control subjects. Cdyn was also measured in an additional 13 patients undergoing reactivity studies. Results Instantaneous diameter measured using CMM DTI agreed well with intravascular ultrasound measurements in the in vitro models. Clinically, Cdyn calculated by CMM DTI agreed with Cdyn calculated using invasive techniques (23.4 ± 16.8 vs 29.1 ± 20.6%/100 mm Hg; P = not significant). Patients with pulmonary hypertension had significantly lower peak wall velocity values and lower Cdyn values than control subjects (P < .01). Cdyn values followed an exponentially decaying relationship with PA pressure, indicating the nonlinear stress–strain behavior of these arteries. Reactivity in Cdyn agreed with reactivity measured using impedance techniques. Conclusion The Cdyn method provides a noninvasive means of assessing PA compliance and should be useful as an additional measure of vascular reactivity subsequent to pulmonary vascular resistance in patients with pulmonary hypertension. PMID:16581479

The effects of obesity and type 2 diabetes mellitus on cardiac structure and function in adolescents and young adults.

PubMed

Shah, A S; Khoury, P R; Dolan, L M; Ippisch, H M; Urbina, E M; Daniels, S R; Kimball, T R

2011-04-01

We sought to evaluate the effects of obesity and obesity-related type 2 diabetes mellitus on cardiac geometry (remodelling) and systolic and diastolic function in adolescents and young adults. Cardiac structure and function were compared by echocardiography in participants who were lean, obese or obese with type 2 diabetes (obese diabetic), in a cross sectional study. Group differences were assessed using ANOVA. Independent determinants of cardiac outcome measures were evaluated with general linear models. Adolescents with obesity and obesity-related type 2 diabetes were found to have abnormal cardiac geometry compared with lean controls (16% and 20% vs <1%, p < 0.05). These two groups also had increased systolic function. Diastolic function decreased from the lean to obese to obese diabetic groups with the lowest diastolic function observed in the obese diabetic group (p < 0.05). Regression analysis showed that group, BMI z score (BMIz), group × BMIz interaction and systolic BP z score (BPz) were significant determinants of cardiac structure, while group, BMIz, systolic BPz, age and fasting glucose were significant determinants of the diastolic function (all p < 0.05). Adolescents with obesity and obesity-related type 2 diabetes demonstrate changes in cardiac geometry consistent with cardiac remodelling. These two groups also demonstrate decreased diastolic function compared with lean controls, with the greatest decrease observed in those with type 2 diabetes. Adults with diastolic dysfunction are known to be at increased risk of progressing to heart failure. Therefore, our findings suggest that adolescents with obesity-related type 2 diabetes may be at increased risk of progressing to early heart failure compared with their obese and lean counterparts.

Patients with a hypertensive response to exercise have impaired left ventricular diastolic function.

PubMed

Takamura, Takeshi; Onishi, Katsuya; Sugimoto, Tadafumi; Kurita, Tairo; Fujimoto, Naoki; Dohi, Kaoru; Tanigawa, Takashi; Isaka, Naoki; Nobori, Tsutomu; Ito, Masaaki

2008-02-01

An exaggerated increase in systolic blood pressure prolongs myocardial relaxation and increases left ventricular (LV) chamber stiffness, resulting in an increase in LV filling pressure. We hypothesize that patients with a marked hypertensive response to exercise (HRE) have LV diastolic dysfunction leading to exercise intolerance, even in the absence of resting hypertension. We recruited 129 subjects (age 63+/-9 years, 64% male) with a preserved ejection fraction and a negative stress test. HRE was evaluated at the end of a 6-min exercise test using the modified Bruce protocol. Patients were categorized into three groups: a group without HRE and without resting hypertension (control group; n=30), a group with HRE but without resting hypertension (HRE group; n=25), and a group with both HRE and resting hypertension (HTN group; n=74). Conventional Doppler and tissue Doppler imaging were performed at rest. After 6-min exercise tests, systolic blood pressure increased in the HRE and HTN groups, compared with the control group (226+/-17 mmHg, 226+/-17 mmHg, and 180+/-15 mmHg, respectively, p<0.001). There were no significant differences in LV ejection fraction, LV end-diastolic diameter, and early mitral inflow velocity among the three groups. However, early diastolic mitral annular velocity (E') was significantly lower and the ratio of early diastolic mitral inflow velocity (E) to E' (E/E') was significantly higher in patients of the HRE and HTN groups compared to controls (E': 5.9+/-1.6 cm/s, 5.9+/-1.7 cm/s, 8.0+/-1.9 cm/s, respectively, p<0.05). In conclusion, irrespective of the presence of resting hypertension, patients with hypertensive response to exercise had impaired LV longitudinal diastolic function and exercise intolerance.

Doppler ultrasound study of penis in men with systemic sclerosis: a correlation with Doppler indices of renal and digital arteries.

PubMed

Rosato, E; Barbano, B; Gigante, A; Cianci, R; Molinaro, I; Quarta, S; Digiulio, M A; Messineo, D; Pisarri, S; Salsano, F

2013-01-01

Erectile dysfunction (ED) prevalence in male systemic sclerosis (SSc) is high and its pathogenesis is unclear. The aim of the study is to assess correlation between Doppler ultrasound indices of penis and kidneys or digital arteries in male systemic sclerosis. Fourteen men with systemic sclerosis were enrolled in this study. Erectile function was investigated by the International Index of Erectile Function-5. Peak systolic velocity, end diastolic velocity, resistive index, pulsative index, and systolic/diastolic ratio were measured on the cavernous arteries at the peno-scrotal junction in the flaccid state, on the interlobar artery of both kidneys and all ten proper palmar digital arteries. Ten (71 percent) patients have an International Index of Erectile Function-5 less than 21. Reduction of penis peak systolic velocity was observed in all SSc subjects. Doppler indices of cavernous arteries correlate with the International Index of Erectile Function-5. The renal and digital arteries resistive index demonstrated a good correlation (p less than 0.0001) with International Index of Erectile Function-5. A positive correlation exists between penis and kidney arteries Doppler indices: end diastolic velocity (p less than 0.05, r=0.54), resistive index (p less than 0.0001, r=0.90), systolic/diastolic ratio (p less than 0.01, r=0.69). A positive correlation was observed between penis and digital arteries Doppler indices: peak systolic velocity (p less than 0.01, r=0.68), end diastolic velocity (p less than 0.01, r=0.75), resistive index (p less than 0.001, r=0.79), systolic/diastolic ratio (p less than 0.05, r=0.59). A correlation exists between arterial impairment of penis and renal or digital arteries.

Relationship of carotid arterial functional and structural changes to left atrial volume in untreated hypertension.

PubMed

Jaroch, Joanna; Rzyczkowska, Barbara; Bociąga, Zbigniew; Vriz, Olga; Driussi, Caterina; Loboz-Rudnicka, Maria; Dudek, Krzysztof; Łoboz-Grudzień, Krystyna

2016-04-01

The contribution of arterial functional and structural changes to left ventricular (LV) diastolic dysfunction has been the area of recent research. There are some studies on the relationship between arterial stiffness (a.s.) and left atrial (LA) remodelling as a marker of diastolic burden. Little is known about the association of arterial structural changes and LA remodelling in hypertension (H). The aim of this study was to examine the relationship between carotid a.s. and intima-media thickness (IMT) and LA volume in subjects with H. The study included 245 previously untreated hypertensives (166 women and 79 men, mean age 53.7 ± 11.8 years). Each patient was subjected to echocardiography with measurement of LA volume, evaluation of left ventricular hypertrophy (LVH) and LV systolic/diastolic function indices, integrated assessment of carotid IMT and echo-tracking of a.s. and wave reflection parameters. Univariate regression analysis revealed significant correlations between indexed LA volume and selected clinical characteristics, echocardiographic indices of LVH and LV diastolic/systolic function and a.s./wave reflection parameters. The following parameters were identified as independent determinants of indexed LA volume on multivariate regression analysis: diastolic blood pressure (beta = -0.229, P < 0.001), left ventricular mass index (LVMI; beta = 0.258, P < 0.001), E/e’ index (ratio of early mitral flow wave velocity – E to early diastolic mitral annular velocity – e’; beta = 0.266, P = 0.001), augmentation index (AI; beta = 0.143, P = 0.008) and body mass index (BMI; beta = 0.132, P = 0.017). No correlations between indexed LA volume and IMT were found. There is a significant relationship between carotid arterial stiffness but not intima-media thickness and LA volume in patients with untreated hypertension.

The Role of Oxidative Stress and Inflammation in Cardiovascular Aging

PubMed Central

Wu, Junzhen; Xia, Shijin; Kalionis, Bill; Sun, Tao

2014-01-01

Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66Shc, and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol. PMID:25143940

Mitochondrial impairment contributes to cocaine-induced cardiac dysfunction: Prevention by the targeted antioxidant MitoQ.

PubMed

Vergeade, Aurélia; Mulder, Paul; Vendeville-Dehaudt, Cathy; Estour, François; Fortin, Dominique; Ventura-Clapier, Renée; Thuillez, Christian; Monteil, Christelle

2010-09-01

The goal of this study was to assess mitochondrial function and ROS production in an experimental model of cocaine-induced cardiac dysfunction. We hypothesized that cocaine abuse may lead to altered mitochondrial function that in turn may cause left ventricular dysfunction. Seven days of cocaine administration to rats led to an increased oxygen consumption detected in cardiac fibers, specifically through complex I and complex III. ROS levels were increased, specifically in interfibrillar mitochondria. In parallel there was a decrease in ATP synthesis, whereas no difference was observed in subsarcolemmal mitochondria. This uncoupling effect on oxidative phosphorylation was not detectable after short-term exposure to cocaine, suggesting that these mitochondrial abnormalities were a late rather than a primary event in the pathological response to cocaine. MitoQ, a mitochondrial-targeted antioxidant, was shown to completely prevent these mitochondrial abnormalities as well as cardiac dysfunction characterized here by a diastolic dysfunction studied with a conductance catheter to obtain pressure-volume data. Taken together, these results extend previous studies and demonstrate that cocaine-induced cardiac dysfunction may be due to a mitochondrial defect. Copyright 2010 Elsevier Inc. All rights reserved.

Impaired atrioventricular transport in patients with transposition of the great arteries palliated by atrial switch and preserved systolic right ventricular function: A magnetic resonance imaging study.

PubMed

Ladouceur, Magalie; Kachenoura, Nadjia; Soulat, Gilles; Bollache, Emilie; Redheuil, Alban; Azizi, Michel; Delclaux, Christophe; Chatellier, Gilles; Boutouyrie, Pierre; Iserin, Laurence; Bonnet, Damien; Mousseaux, Elie

2017-07-01

We aimed (1) determine if systemic right ventricle filling parameters influence systemic right ventricle stroke volume in adult patients with D-transposition of the great arteries (D-TGA) palliated by atrial switch, using cardiac magnetic resonance imaging and echocardiography, and (2) to study relationship of these diastolic parameters with exercise performance and BNP, in patients with preserved systolic systemic right ventricle function. Single-center, cross-sectional, prospective study. In patients with D-TGA palliated by atrial switch, diastolic dysfunction of the systemic right ventricle may precede systolic dysfunction. Forty-five patients with D-TGA and atrial switch and 45 age and sex-matched healthy subjects underwent cardiac magnetic resonance imaging and echocardiography. Filling flow-rates measured by phase-contrast cardiac magnetic resonance imaging were analyzed using customized software to estimate diastolic parameters and compared with exercise performance. In D-TGA, early filling of systemic right ventricle was impaired with a lower peak filling rate normalized by filling volume (Ef/FV measured by cardiac magnetic resonance imaging) and a higher early filling peak velocity normalized by early peak myocardial velocity (E US /Ea measured by echocardiography) compared with controls (P ≤ .04). Stroke volume of systemic right ventricle showed a direct and significant association with pulmonary venous pathway size (respectively r = 0.50, P < .01). Systemic right atrial area and systemic right ventricle mass/volume index measured by cardiac magnetic resonance imaging, as well as Ef/FV were significantly correlated with exercise performances and BNP (P < .01). All correlations were independent of age, gender, body mass index and blood pressure. Systemic right ventricle pre-load and stroke volume depend mainly on intraatrial pathway function. Moreover, systemic right ventricle remodeling and right atrial dysfunction impair systemic right ventricle filling, leading to BNP increase and exercise limitation. Cardiac magnetic resonance imaging should assess systemic right ventricle filling abnormalities in D-TGA patients. © 2017 Wiley Periodicals, Inc.

Prevalence of Pulmonary Hypertension in Patients with Thalassemia Intermedia in 2009: a single center's experience.

PubMed

Moghaddam, Hassan Mottaghi; Badiei, Zahra; Eftekhari, Kambiz; Shakeri, Reza; Farhangi, Hamid

2015-07-01

There are various clinical symptoms of thalassemia intermedia, and they lie roughly between those of major and minor forms of the disease. Patients with thalassemia intermedia occasionally require blood transfusions. This renders them susceptible to pulmonary arterial hypertension (PAH) syndrome, which is one of the most significant complications in patients with thalassemia intermedia. PAH is more common in in thalassemia intermedia than in thalassemia major, and it may cause cardiac complications in patients who are older than 30. The objective of this study was to estimate the prevalence of PAH in thalassemia intermedia patients so that they can be referred expeditiously for treatment, thereby preventing the complications that occur later. This cross sectional study was conducted under the supervision of hematology department of Mashhad Medical University. Forty-one patients with thalassemia intermedia were examined at the Sarvar Thalassemia and Hemophilia Clinic of Mashhad. Electrocardiography, chest radiography, and echocardiography tests were performed for all of the patients by the same pediatric cardiologist. The data were processed by SPSS software, version 11.5, and the results were analyzed using chi-squared, Student's t, and Mann-Whitney tests. The mean age of the patients was 21.93±8.34. They had been under pediatric heart specialists' constant examination and treatment since their childhood when they were diagnosed with TI, and continue to receive regular follow-up care. The prevalence of pulmonary hypertension was 24% in our study population. In patients with thalassemia intermedia, the left ventricular (LV) mass indices were about 3-5 times higher than would be expected in a normal population. Patients with higher LV mass indices have a greater risk of developing pulmonary hypertension, and those with serum ferritin levels below 1000 ng/ml are less susceptible to diastolic dysfunction. Pulmonary hypertension is common in patients with thalassemia intermedia. Irregular chelation therapy or absence of this treatment might lead to diastolic dysfunction, and serum ferritin levels below 1000 ng/ml could be an important factor in preventing the development of diastolic dysfunction or slowing down its progression.

Exercise haemodynamics may unmask the diagnosis of diastolic dysfunction among patients with pulmonary hypertension.

PubMed

Maor, Elad; Grossman, Yoni; Balmor, Ronen Gingy; Segel, Michael; Fefer, Paul; Ben-Zekry, Sagit; Buber, Jonathan; DiSegni, Elio; Guetta, Victor; Ben-Dov, Issahar; Segev, Amit

2015-02-01

Heart failure with preserved ejection fraction can lead to pulmonary hypertension. The aim of the present study was to evaluate the role of exercise during right heart catheterization in the unmasking of diastolic dysfunction. Between 2004 and 2012, 200 symptomatic patients with exertional dyspnoea, preserved left ventricular systolic function and suspected pulmonary hypertension, underwent right heart catheterization. Included in the study were 63 patients with resting pulmonary arterial wedge pressure (PAWP) ≤15 mmHg. Patients were divided to three tertiles based on their peak exercise PAWP. Mean age was 60 ± 20 years and 29% were males. Mean pulmonary arterial pressure was 31 ± 14 mmHg at rest and 42 ± 18 mmHg upon exercise. Mean change in PAWP between rest and exercise was 0.0 ± 4.3, 4.6 ± 2.4, and 16.6 ± 7.1 mmHg in the lower, middle, and upper tertiles, respectively (P < 0.001). Higher exercise PAWP tertiles were associated with reduced pulmonary vascular resistance (8.3 ± 6.7, 2.9 ± 2.7, and 5.8 ± 4.6 Woods units, respectively; P = 0.004). A multivariate linear regression model demonstrated that each 5 kg/m(2) increase in body mass index was associated with 2.5 ± 1.0 mmHg increase in exercise PAWP (P = 0.017). A multivariate binary logistic model showed that subjects with borderline PAWP at rest (12-15 mmHg) were 4.5 times more likely to be in the upper tertile of exercise PAWP (P = 0.011). In symptomatic patients with pulmonary hypertension, preserved left ventricular ejection fraction and PAWP ≤15 mmHg, exercise during right heart catheterization may unmask diastolic dysfunction. This is especially true for obese patients and patients with borderline resting PAWP. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

Geographic origin as a determinant of left ventricular mass and diastolic function - the Cardiovascular Risk in Young Finns Study.

PubMed

Vähämurto, L; Juonala, M; Ruohonen, S; Hutri-Kähönen, N; Kähönen, M; Laitinen, T; Tossavainen, P; Jokinen, E; Viikari, J; Raitakari, O T; Pahkala, K

2018-03-01

Eastern Finns have higher risk of coronary heart disease (CHD) and carotid intima-media thickness than western Finns although current differences in CHD risk factors are minimal. Left ventricular (LV) mass and diastolic function predict future cardiovascular events but their east-west differences are unknown. We examined the association of eastern/western baseline origin with LV mass and diastolic function. The study population included 2045 subjects of the Cardiovascular Risk in Young Finns Study with data from the baseline survey (1980) and the latest follow-up (2011) when echocardiography was performed at the age of 34-49 years. Subjects with eastern baseline origin had in 2011 higher LV mass (139±1.0 vs. 135±1.0 g, p=0.006) and E/e'-ratio indicating weaker LV diastolic function (4.86±0.03 vs. 4.74±0.03, p=0.02) than western subjects. Results were independent of age, sex, area of examination and CHD risk factors such as blood pressure and BMI (LV mass indexed with height: p<0.0001; E/e'-ratio: p=0.01). LV end-diastolic volume was higher among subjects with eastern baseline origin (135±0.9 vs. 131±0.9 ml, p=0.0011) but left atrial end-systolic volume, also indicating LV diastolic function, was not different between eastern and western subjects (43.4±0.5 vs. 44.0±0.5 ml, p=0.45). Most of the subjects were well within the normal limits of these echocardiographic measurements. In our healthy middle-aged population, geographic origin in eastern Finland associated with higher LV mass compared to western Finland. Higher E/e'-ratio suggests that subjects with eastern baseline origin might have higher prevalence of diastolic dysfunction in the future than western subjects.

The structure function of the death domain of human IRAK-M.

PubMed

Du, Jiangfeng; Nicolaes, Gerry Af; Kruijswijk, Danielle; Versloot, Miranda; van der Poll, Tom; van 't Veer, Cornelis

2014-12-07

IRAK-M is an inhibitor of Toll-like receptor signaling that acts by re-directing IRAK-4 activity to TAK1 independent NF-κB activation and by inhibition of IRAK-1/IRAK-2 activity. IRAK-M is expressed in monocytes/macrophages and lung epithelial cells. Lack of IRAK-M in mice greatly improves the resistance to nosocomial pneumonia and lung tumors, which entices IRAK-M as a potential therapeutic target. IRAK-M consists of an N-terminal death domain (DD), a dysfunctional kinase domain and unstructured C-terminal domain. Little is known however on IRAK-M's structure-function relationships. Since death domains provide the important interactions of IRAK-1, IRAK-2 and IRAK-4 molecules, we generated a 3D structure model of the human IRAK-M-DD (residues C5-G119) to guide mutagenesis studies and predict protein-protein interaction points. First we identified the DD residues involved in the endogenous capacity of IRAK-M to activate NF-κB that is displayed upon overexpression in 293T cells. W74 and R97, at distinct interfaces of the IRAK-M-DD, were crucial for this endogenous NF-κB activating capacity, as well as the C-terminal domain (S445-E596) of IRAK-M. Resulting anti-inflammatory A20 and pro-inflammatory IL-8 transcription in 293T cells was W74 dependent, while IL-8 protein expression was dependent on R97 and the TRAF6 binding motif at P478. The IRAK-M-DD W74 and R97 binding interfaces are predicted to interact with opposite sides of IRAK-4-DD's. Secondly we identified DD residues important for the inhibitory action of IRAK-M by stable overexpression of mutants in THP-1 macrophages and H292 lung epithelial cells. IRAK-M inhibited TLR2/4-mediated cytokine production in macrophages in a manner that is largely dependent on W74. R97 was not involved in inhibition of TNF production but was engaged in IL-6 down-regulation by IRAK-M. Protein-interactive residues D19-A23, located in between W74 and R97, were also observed to be crucial for inhibition of TLR2/4 mediated cytokine induction in macrophages. Remarkably, IRAK-M inhibited TLR5 mediated IL-8 production by lung epithelial cells independent of W74 and R97, but dependent on D19-A23 and R70, two surface-exposed regions that harbor predicted IRAK-2-DD interaction points of IRAK-M. IRAK-M employs alternate residues of its DD to inhibit the different inflammatory mediators induced by varying TLRs and cells.

Central arterial stiffness and diastolic dysfunction are associated with insulin resistance and abdominal obesity in young women but polycystic ovary syndrome does not confer additional risk.

PubMed

Rees, E; Coulson, R; Dunstan, F; Evans, W D; Blundell, H L; Luzio, S D; Dunseath, G; Halcox, J P; Fraser, A G; Rees, D A

2014-09-01

Are arterial stiffness, carotid intima-media thickness and diastolic dysfunction increased in young women with polycystic ovary syndrome (PCOS) independently of the effects of obesity? Insulin resistance and central obesity are associated with subclinical cardiovascular dysfunction in young women, but a diagnosis of PCOS does not appear to confer additional risk at this age. Some studies have shown that young women with PCOS may have increased measures of cardiovascular risk, including arterial stiffness, carotid intima-media thickness and myocardial dysfunction. However, it is difficult to establish how much of this risk is due to PCOS per se and how much is due to obesity and insulin resistance, which are common in PCOS and themselves associated with greater vascular risk. This cross-sectional study comprised 84 women with PCOS and 95 healthy volunteers, aged 16-45 years. The study was conducted in a university hospital. Subjects underwent a comprehensive assessment of body composition (including computed tomography (CT) assessment of visceral fat; VF), measurements of arterial stiffness (aortic pulse wave velocity; aPWV), common carotid intima-media thickness (ccIMT), diastolic function (longitudinal tissue velocity; e':a') and endocrinological measures. A sample size of 80 in each group gave 80% power for detecting a difference of 0.45 m/s in aPWV or a difference of 0.25 in e':a'. After adjustment for age and body mass index (BMI), PCOS subjects had a greater insulin response (insulin area under the curve-IAUC) following glucose challenge (adjusted difference [AD] 35 900 pmol min/l, P < 0.001) and higher testosterone (AD 0.57 nmol/l, P < 0.001) and high molecular weight adiponectin than controls (AD 3.01 µg/ml, P = 0.02), but no significant differences in aPWV (AD -0.13 m/s, P = 0.33), ccIMT (AD -0.01 mm, P = 0.13), or e':a' (AD -0.01, P = 0.86) were observed. After adjustment for age, height and central pulse pressure, e':a' and aPWV were associated with logVF and IAUC. ccIMT was not related to logVF. The relationships between e':a' or aPWV and insulin resistance were only partly attenuated by adjusting for logVF. There was no significant relationship between aPWV or e':a' and either testosterone or adiponectin. The study recruited young women meeting the Rotterdam criteria for PCOS diagnosis; hence our findings may not be generalizable to older patients or those meeting other definitions of the syndrome. Biochemical hyperandrogenism was based solely on measurement of total testosterone. Cases and controls were not matched in advance for age and BMI, although the influence of these variables on the cardiovascular outcome measures was adjusted for. This study shows that central arterial stiffness and diastolic dysfunction are not increased in young women with PCOS, whereas they are associated with both insulin resistance and central obesity. Obesity thus represents the greatest modifiable risk factor for cardiovascular disease in young women with PCOS and lifestyle measures which target weight reduction are critical. This study received no specific grant support from any funding body. The authors have no conflicts of interest to declare. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Defective chromatic and achromatic visual pathways in developmental dyslexia: Cues for an integrated intervention programme.

PubMed

Bonfiglio, Luca; Bocci, Tommaso; Minichilli, Fabrizio; Crecchi, Alessandra; Barloscio, Davide; Spina, Donata Maria; Rossi, Bruno; Sartucci, Ferdinando

2017-01-01

As well as obtaining confirmation of the magnocellular system involvement in developmental dyslexia (DD); the aim was primarily to search for a possible involvement of the parvocellular system; and, furthermore, to complete the assessment of the visual chromatic axis by also analysing the koniocellular system. Visual evoked potentials (VEPs) in response to achromatic stimuli with low luminance contrast and low spatial frequency, and isoluminant red/green and blue/yellow stimuli with high spatial frequency were recorded in 10 dyslexic children and 10 age- and sex-matched, healthy subjects. Dyslexic children showed delayed VEPs to both achromatic stimuli (magnocellular-dorsal stream) and isoluminant red/green and blue/yellow stimuli (parvocellular-ventral and koniocellular streams). To our knowledge, this is the first time that a dysfunction of colour vision has been brought to light in an objective way (i.e., by means of electrophysiological methods) in children with DD. These results give rise to speculation concerning the need for a putative approach for promoting both learning how to read and/or improving existing reading skills of children with or at risk of DD. The working hypothesis would be to combine two integrated interventions in a single programme aimed at fostering the function of both the magnocellular and the parvocellular streams.

Intravenous Xenogeneic Transplantation of Human Adipose-Derived Stem Cells Improves Left Ventricular Function and Microvascular Integrity in Swine Myocardial Infarction Model

PubMed Central

Jun Hong, Soon; Rogers, Pamela I.; Kihlken, John; Warfel, Jessica; Bull, Chris; Deuter-Reinhard, Maja; Feng, Dongni; Xie, Jie; Kyle, Aaron; Merfeld-Clauss, Stephanie; Johnstone, Brian H.; Traktuev, Dmitry O.; Chen, Peng-Sheng; Lindner, Jonathan R.; March, Keith L.

2018-01-01

Objectives The potential for beneficial effects of adipose-derived stem cells(ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia(MI) has not been tested following intravenous delivery. Methods Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n=7), the single bolus group (SB)(n=7, 15×107 ASCs), or the divided dose group (DD)(n=7, 5×107 ASCs/day for three consecutive days). Myocardial perfusion defect area and coronary flow reserve (CFR) were compared during the 28-day follow-up. Also, serial changes in the absolute number of circulating CD4+T and CD8+T cells were measured. Results The increases in ejection fraction were significantly greater in both the SB and the DD groups compared to the placebo group (5.4±0.9%, 3.7±0.7%, and -0.4±0.6%, respectively), and the decrease in the perfusion defect area was significantly greater in the SB group than the placebo group (-36.3±1.8 and -11.5±2.8). CFR increased to a greater degree in the SB and the DD groups than in the placebo group (0.9±0.2, 0.8±0.1, and 0.2±0.2, respectively). The circulating number of CD8+T cells was significantly greater in the SB and DD groups than the placebo group at day 7(3,687±317/μL, 3,454±787/μL, and 1,928±457/μL, respectively). The numbers of small vessels were significantly greater in the SB and the DD groups than the placebo group in the peri-infarct area. Conclusions Both intravenous SB and DD delivery of ASCs are effective modalities for the treatment of MI in swine. Intravenous delivery of ASCs, with its immunomodulatory and angiogenic effects, is an attractive noninvasive approach for myocardial rescue. PMID:24905889

Interactive effects of the ACE DD polymorphism with the NOS III homozygous G849T (Glu298-->Asp) variant in determining endothelial function in coronary artery disease.

PubMed

Schmidt, Michael A; Chakrabarti, Anjan K; Kehrer, Chris; Pfeninnger, Dana; Brook, Robert D; Kaciroti, Niko; Duvernoy, Claire; Killeen, Anthony A; Rajagopalan, Sanjay

2003-01-01

The products of nitric oxide synthase (NOS) and angiotensin-converting enzyme (ACE) play a critical role in determining vessel wall structure and function. Polymorphisms in both genes have been independently demonstrated to influence propensity to cardiovascular events. The purpose of this study was to determine the influence of the homozygous G849T (Glu298-->Asp) polymorphism in NOS III on peripheral conduit artery endothelial function and to elucidate the modifier role, if any, of a common ACE polymorphism. Three hundred and ninety-seven consecutive subjects presenting to the cardiac catheterization laboratory of the University of Michigan over a period of 18 months were recruited. DNA was extracted and polymerase chain reaction (PCR) analysis for ACE and NOS polymorphisms performed. Patients with homozygosity for G849T at both loci (TT) who belong to DD and II ACE genotype (groups 1 and 2) and those who are negative for this polymorphism (GG) and belong to either DD or II genotype (groups 3 and 4) were identified. The four groups then underwent determination of conduit endothelial function. Heterozygosity of Glu298-Asp or the ID variant of the ACE were not studied. Median FMD value in the TT-DD group was 0.20 (-3.17, 2.01) compared with 2.23% (-0.29, 4.17) in the GG-II group. Median values in the TT-II and the GG-DD groups were 3.04 (-1.16, 6.61) and 2.46% (-1.83, 6.52) respectively. These values were not statistically significant (p > 0.05 by one-way ANOVA). Median nitroglycerin-mediated dilation in the four groups did not differ between the four groups (p = NS by ANOVA). Atherosclerosis burdens as assessed by angiography were not different across the groups. In conclusion, the homozygous NOS III variant (GG) status does not seem to interact additively with the ACE homozygous DD genotype in determining flow-mediated vasodilation in individuals with established atherosclerosis and pre-existent endothelial dysfunction.

Cardiac structure and function, and ventricular-arterial interaction 11 years following a pregnancy with preeclampsia.

PubMed

Al-Nashi, Maha; Eriksson, Maria J; Östlund, Eva; Bremme, Katarina; Kahan, Thomas

2016-04-01

Preeclampsia (PE) is associated with acute left ventricular dysfunction. Whether these changes eventually resolve remains unclear. This study assessed left and right ventricular structure and function, and ventricular-arterial interaction in 15 women 11 years after a pregnancy with PE and 16 matched control subjects with a normal pregnancy. We found normal left and right ventricular dimensions, systolic function, and global left ventricular strain, with no differences between the groups. In addition, indices of diastolic function, left and right atrial size, and amino-terminal pro-brain natriuretic peptide were normal and did not differ between the groups. Women with a previous PE had impaired night/day ratios for systolic and diastolic ambulatory blood pressure. However, indices of aortic stiffness or ventricular-arterial coupling did not differ between the groups. In conclusion, we could not demonstrate remaining alterations in systolic or diastolic left or right ventricular function, or in ventricular-arterial interaction in women 11 years after PE. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

A new twist on an old idea part 2: cyclosporine preserves normal mitochondrial but not cardiomyocyte function in mini‐swine with compensated heart failure

PubMed Central

Hiemstra, Jessica A.; Gutiérrez‐Aguilar, Manuel; Marshall, Kurt D.; McCommis, Kyle S.; Zgoda, Pamela J.; Cruz‐Rivera, Noelany; Jenkins, Nathan T.; Krenz, Maike; Domeier, Timothy L.; Baines, Christopher P.; Emter, Craig A.

2014-01-01

Abstract We recently developed a clinically relevant mini‐swine model of heart failure with preserved ejection fraction (HFpEF), in which diastolic dysfunction was associated with increased mitochondrial permeability transition (MPT). Early diastolic function is ATP and Ca2+‐dependent, thus, we hypothesized chronic low doses of cyclosporine (CsA) would preserve mitochondrial function via inhibition of MPT and subsequently maintain normal cardiomyocyte Ca2+ handling and contractile characteristics. Left ventricular cardiomyocytes were isolated from aortic‐banded Yucatan mini‐swine divided into three groups; control nonbanded (CON), HFpEF nontreated (HF), and HFpEF treated with CsA (HF‐CsA). CsA mitigated the deterioration of mitochondrial function observed in HF animals, including functional uncoupling of Complex I‐dependent mitochondrial respiration and increased susceptibility to MPT. Attenuation of mitochondrial dysfunction in the HF‐CsA group was not associated with commensurate improvement in cardiomyocyte Ca2+ handling or contractility. Ca2+ transient amplitude was reduced and transient time to peak and recovery (tau) prolonged in HF and HF‐CsA groups compared to CON. Alterations in Ca2+ transient parameters observed in the HF and HF‐CsA groups were associated with decreased cardiomyocyte shortening and shortening rate. Cellular function was consistent with impaired in vivo systolic and diastolic whole heart function. A significant systemic hypertensive response to CsA was observed in HF‐CsA animals, and may have played a role in the accelerated the development of heart failure at both the whole heart and cellular levels. Given the significant detriment to cardiac function observed in response to CsA, our findings suggest chronic CsA treatment is not a viable therapeutic option for HFpEF. PMID:24963034

Shared biomarkers between female diastolic heart failure and pre‐eclampsia: a systematic review and meta‐analysis

PubMed Central

Bokslag, Anouk; Maas, Angela H.E.M.; Franx, Arie; Paulus, Walter J.; de Groot, Christianne J.M.

2017-01-01

Abstract Evidence accumulates for associations between hypertensive pregnancy disorders and increased cardiovascular risk later. The main goal of this study was to explore shared biomarkers representing common pathogenic pathways between heart failure with preserved ejection fraction (HFpEF) and pre‐eclampsia where these biomarkers might be potentially eligible for cardiovascular risk stratification in women after hypertensive pregnancy disorders. We sought for blood markers in women with diastolic dysfunction in a first literature search, and through a second search, we investigated whether these same biochemical markers were present in pre‐eclampsia.This systematic review and meta‐analysis presents two subsequent systematic searches in PubMed and EMBASE. Search I yielded 3014 studies on biomarkers discriminating women with HFpEF from female controls, of which 13 studies on 11 biochemical markers were included. Cases had HFpEF, and controls had no heart failure. The second search was for studies discriminating women with pre‐eclampsia from women with non‐hypertensive pregnancies with at least one of the biomarkers found in Search I. Search II yielded 1869 studies, of which 51 studies on seven biomarkers were included in meta‐analyses and 79 studies on 12 biomarkers in systematic review.Eleven biological markers differentiated women with diastolic dysfunction from controls, of which the following 10 markers differentiated women with pre‐eclampsia from controls as well: C‐reactive protein, HDL, insulin, fatty acid‐binding protein 4, brain natriuretic peptide, N terminal pro brain natriuretic peptide, adrenomedullin, mid‐region pro adrenomedullin, cardiac troponin I, and cancer antigen 125.Our study supports the hypothesis that HFpEF in women shares a common pathogenic background with pre‐eclampsia. The biomarkers representing inflammatory state, disturbances in myocardial function/structure, and unfavourable lipid metabolism may possibly be eligible for future prognostic tools. PMID:28451444

Implication of left ventricular diastolic dysfunction in cryptogenic ischemic stroke.

PubMed

Seo, Jae-Young; Lee, Kyung Bok; Lee, Jung-Gon; Kim, Ji-Sun; Roh, Hakjae; Ahn, Moo-Young; Park, Byoung Won; Hyon, Min Su

2014-09-01

Left ventricular diastolic dysfunction (LVDD) is a predictor for atrial fibrillation (AF). This study was aimed to investigate whether LVDD in cryptogenic ischemic stroke (CS) could be a clue to stroke mechanism. The clinical and echocardiographic findings of 1589 consecutive patients with acute ischemic stroke or transient ischemic attack between 2004 and 2013 were reviewed. LVDDs among stroke subtypes were graded by transthoracic echocardiography into 4 groups by severity: normal, abnormal relaxation (grade I), pseudonormal (grade II), and restrictive diastolic filling (grade III), whereas severe LVDD was defined as grade III. We classified the lesion pattern of CS into cardioembolism-mimic or non-cardioembolism-mimic and determined whether cardioembolism-mimic lesions were associated with severe LVDD. The fraction of severe LVDD in CS was not different from that of stroke with AF (27.3% versus 37.1%; P=0.173) but was significantly higher than that of stroke without AF (27.3% versus 13.4%; P=0.008). Cardioembolism-mimic CS had more severe LVDD than non-cardioembolism-mimic CS (41.4% versus 11.5%; P=0.013). LVDD of grade II (odds ratio, 4.37; 95% confidence interval, 2.99-6.41) and grade III (odds ratio, 5.60; 95% confidence interval, 3.42-9.17) were independently related to stroke with AF after adjusting covariates. The severe LVDD could be a predictor of stroke with AF, and its frequency was similar between CS and stroke with AF. Cardioembolism-mimic CS had significantly more severe LVDD than non-cardioembolism-mimic CS. LVDD could be helpful to discriminate the stroke mechanism in the patients with acute CS. © 2014 American Heart Association, Inc.

Accumulation of epicardial fat rather than visceral fat is an independent risk factor for left ventricular diastolic dysfunction in patients undergoing peritoneal dialysis.

PubMed

Lin, Heng-Hsu; Lee, Jen-Kuang; Yang, Chung-Yi; Lien, Yu-Chung; Huang, Jenq-Wen; Wu, Cho-Kai

2013-08-30

Symptoms of heart failure with preserved left ventricular systolic function are common among patients undergoing peritoneal dialysis (PD). Epicardial fat (EpF) is an ectopic fat depot with possible paracrine or mechanical effects on myocardial function. The aim of our current study is to assess the association between EpF and Left ventricular diastolic dysfunction (LVDD) in patients undergoing PD and to clarify the relationships among EpF, inflammation, and LVDD in this population. This was a cross-sectional study of 149 patients with preserved left ventricular systolic function who were undergoing PD. LVDD was diagnosed (according to the European Society of Cardiology guidelines) and EpF thickness measured by echocardiography. The patients without LVDD were used as controls. The serum inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) was measured. The location and amount of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra. Subjects with LVDD had higher levels of hsCRP, more visceral and peritoneal fat, and thicker EpF (all p < 0.001) than controls. Visceral adipose tissue, hsCRP, and EpF all correlated significantly (p < 0.05) with LVDD. Multivariate regression analysis rendered the relationship between visceral adipose tissue and LVDD insignificant, whereas EpF was the most powerful determinant of LVDD (odds ratio = 2.41, 95% confidence interval = 1.43-4.08, p < 0.01). EpF thickness also correlated significantly with the ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e'; r = 0.27, p < 0.01). EpF thickness is significantly independently associated with LVDD in patients undergoing PD and may be involved in its pathogenesis.

Accumulation of epicardial fat rather than visceral fat is an independent risk factor for left ventricular diastolic dysfunction in patients undergoing peritoneal dialysis

PubMed Central

2013-01-01

Background Symptoms of heart failure with preserved left ventricular systolic function are common among patients undergoing peritoneal dialysis (PD). Epicardial fat (EpF) is an ectopic fat depot with possible paracrine or mechanical effects on myocardial function. The aim of our current study is to assess the association between EpF and Left ventricular diastolic dysfunction (LVDD) in patients undergoing PD and to clarify the relationships among EpF, inflammation, and LVDD in this population. Methods This was a cross-sectional study of 149 patients with preserved left ventricular systolic function who were undergoing PD. LVDD was diagnosed (according to the European Society of Cardiology guidelines) and EpF thickness measured by echocardiography. The patients without LVDD were used as controls. The serum inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) was measured. The location and amount of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra. Results Subjects with LVDD had higher levels of hsCRP, more visceral and peritoneal fat, and thicker EpF (all p < 0.001) than controls. Visceral adipose tissue, hsCRP, and EpF all correlated significantly (p < 0.05) with LVDD. Multivariate regression analysis rendered the relationship between visceral adipose tissue and LVDD insignificant, whereas EpF was the most powerful determinant of LVDD (odds ratio = 2.41, 95% confidence interval = 1.43–4.08, p < 0.01). EpF thickness also correlated significantly with the ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e’; r = 0.27, p < 0.01). Conclusion EpF thickness is significantly independently associated with LVDD in patients undergoing PD and may be involved in its pathogenesis. PMID:24001037

Abdominal obesity and structure and function of the heart in healthy male Koreans: The ARIRANG study.

PubMed

Son, Jung-Woo; Sung, Joong Kyung; Lee, Jun-Won; Youn, Young Jin; Ahn, Min-Soo; Ahn, Sung Gyun; Yoo, Byung-Su; Lee, Seung-Hwan; Yoon, Junghan; Koh, Sang Baek; Kim, Jang-Young

2016-09-01

Although central obesity is a more powerful predictor of cardiovascular disease (CVD) than general obesity, there is limited information on structural and functional changes of the heart in central obesity. Therefore, we evaluated the association between abdominal obesity and geometric and functional changes of the heart in healthy males. A total of 1460 healthy males aged 40 to 70 years without known CVD from the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population were included. All individuals underwent conventional 2-dimensional echocardiography and tissue Doppler imaging to measure left atrial (LA) and left ventricle (LV) geometry and function. Increasing tertiles of waist circumference (WC) were associated with stepwise increases in LA volume, LV end-diastolic dimension, LV mass to height, deceleration time of E wave, and lower E/A ratio (all P trends <0.001). In multivariable logistic regression models, the odds ratios for LA enlargement, LV hypertrophy, LV enlargement, and diastolic dysfunction comparing the upper tertile of WC (>89 cm) to the lowest tertile (<82 cm) were 2.81 (95% confidence interval [CI] 2.24-3.54), 3.65 (95% CI 2.54-5.26), 4.23 (95% CI 2.61-6.87), and 1.75 (95% CI 1.37-2.22), respectively. LV ejection fraction and relative wall thickness were not increased with increasing WC. The association between WC and LA enlargement, LV enlargement, and diastolic dysfunction persisted after stratification by body mass index tertiles. Central obesity may be a stronger predictor than general obesity of geometric and functional changes in the LV and LA.

Vortex-ring mixing as a measure of diastolic function of the human heart: Phantom validation and initial observations in healthy volunteers and patients with heart failure.

PubMed

Töger, Johannes; Kanski, Mikael; Arvidsson, Per M; Carlsson, Marcus; Kovács, Sándor J; Borgquist, Rasmus; Revstedt, Johan; Söderlind, Gustaf; Arheden, Håkan; Heiberg, Einar

2016-06-01

To present and validate a new method for 4D flow quantification of vortex-ring mixing during early, rapid filling of the left ventricle (LV) as a potential index of diastolic dysfunction and heart failure. 4D flow mixing measurements were validated using planar laser-induced fluorescence (PLIF) in a phantom setup. Controls (n = 23) and heart failure patients (n = 23) were studied using 4D flow at 1.5T (26 subjects) or 3T (20 subjects) to determine vortex volume (VV) and inflowing volume (VVinflow ). The volume mixed into the vortex-ring was quantified as VVmix-in = VV-VVinflow . The mixing ratio was defined as MXR = VVmix-in /VV. Furthermore, we quantified the fraction of the end-systolic volume (ESV) mixed into the vortex-ring (VVmix-in /ESV) and the fraction of the LV volume at diastasis (DV) occupied by the vortex-ring (VV/DV). PLIF validation of MXR showed fair agreement (R(2) = 0.45, mean ± SD 1 ± 6%). MXR was higher in patients compared to controls (28 ± 11% vs. 16 ± 10%, P < 0.001), while VVmix-in /ESV and VV/DV were lower in patients (10 ± 6% vs. 18 ± 12%, P < 0.01 and 25 ± 8% vs. 50 ± 6%, P < 0.0001). Vortex-ring mixing can be quantified using 4D flow. The differences in mixing parameters observed between controls and patients motivate further investigation as indices of diastolic dysfunction. J. Magn. Reson. Imaging 2016;43:1386-1397. © 2015 Wiley Periodicals, Inc.

IGF-1 Prevents Diastolic and Systolic Dysfunction Associated with Cardiomyopathy and Preserves Adrenergic Sensitivity

PubMed Central

Roof, Steve R.; Boslett, James; Russell, Duncan; del Rio, Carlos; Alecusan, Joe; Zweier, Jay L.; Ziolo, Mark T.; Hamlin, Robert; Mohler, Peter J.; Curran, Jerry

2015-01-01

Aims Insulin-like growth factor 1 (IGF-1)-dependent signaling promotes exercise-induced physiological cardiac hypertrophy. However, the in vivo therapeutic potential of IGF-1 for heart disease is not well established. Here we test the potential therapeutic benefits of IGF-1 on cardiac function using an in vivo model of chronic catecholamine-induced cardiomyopathy. Methods Rats were perfused with isoproterenol via osmotic pump (1 mg/kg/day) and treated with 2 mg/kg IGF-1 (2 mg/kg/day, 6 days a week) for 2 or 4 weeks. Echocardiography, ECG, and blood pressure were assessed. In vivo pressure-volume loop studies were conducted at 4 weeks. Heart sections were analyzed for fibrosis and apoptosis, and relevant biochemical signaling cascades were assessed. Results After 4 weeks, diastolic function (EDPVR, EDP, tau, E/A ratio), systolic function (PRSW, ESPVR, dP/dtmax), and structural remodeling (LV chamber diameter, wall thickness) were all adversely affected in isoproterenol-treated rats. All these detrimental effects were attenuated in rats treated with Iso+IGF-1. Isoproterenol-dependent effects on BP were attenuated by IGF-1 treatment. Adrenergic sensitivity was blunted in isoproterenol-treated rats but was preserved by IGF-1 treatment. Immunoblots indicate that cardioprotective p110α signaling and activated Akt are selectively upregulated in Iso+IGF-1 treated hearts. Expression of iNOS was significantly increased in both the Iso and Iso+IGF-1 groups, however tetrahydrobiopterin (BH4) levels were decreased in the Iso group and maintained by IGF-1 treatment. Conclusion IGF-1 treatment attenuates diastolic and systolic dysfunction associated with chronic catecholamine-induced cardiomyopathy while preserving adrenergic sensitivity and promoting BH4 production. These data support the potential use of IGF-1 therapy for clinical applications for cardiomyopathies. PMID:26399932

Left ventricular function quantified by myocardial strain imaging in small-breed dogs with chronic mitral regurgitation.

PubMed

Smith, Danielle N; Bonagura, John D; Culwell, Nicole M; Schober, Karsten E

2012-03-01

The presence of left ventricular (LV) systolic dysfunction may influence prognosis or therapy in dogs with chronic mitral regurgitation (MR). Assessment of LV function in MR by conventional echocardiography is confounded by altered ventricular loading. Myocardial deformation (strain) imaging might offer more sensitive estimates of LV function in this disease. Prospectively measure myocardial strain in dogs with asymptomatic MR compared to a control group. Forty healthy dogs (3.5-11.5 kg): 20 Controls; 20 dogs with MR and LV remodeling (Stage B2), were evaluated in this study. LV size and function were assessed in a short-axis plane. Segmental radial strain and strain rate and global circumferential strain were measured using a 2D echocardiographic speckle-tracking algorithm (GE EchoPAC). Groups were compared using Bonferroni t-tests. Influences of heart rate and body weight were explored with linear regression. The MR group had significantly greater mean values for heart rate, LV size, and LV systolic function. Specifically, LV diastolic diameter, diastole area, shortening fraction, averaged peak systolic and early diastolic radial strain, global circumferential strain, and averaged radial strain rate were significantly greater in the MR group (p < 0.015 to p < 0.001). Strain was unrelated to weight, but weakly correlated with heart rate. Similar to conventional indices, Stage B2 dogs with MR demonstrate hyperdynamic deformation in the short-axis plane. Short-axis strain variables measured by 2D speckle tracking are greater than for controls of similar age and weight. These results imply either preserved LV systolic function or that LV dysfunction is masked by altered ventricular loading. Copyright © 2012 Elsevier B.V. All rights reserved.

Pulmonary artery stiffness in chronic obstructive pulmonary disease (COPD) and emphysema: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study.

PubMed

Liu, Chia-Ying; Parikh, Megha; Bluemke, David A; Balte, Pallavi; Carr, James; Dashnaw, Stephen; Poor, Hooman D; Gomes, Antoinette S; Hoffman, Eric A; Kawut, Steven M; Lima, Joao A C; McAllister, David A; Prince, Martin A; Vogel-Claussen, Jens; Barr, R Graham

2018-01-01

Chronic obstructive pulmonary disease (COPD) and particularly emphysema are characterized by stiffness of the aorta, due in part to accelerated elastin degradation in the lungs and aorta. Stiffness of the pulmonary arteries (PAs) may also be increased in COPD and emphysema, but data are lacking. We assessed PA stiffness using MRI in patients with COPD and related these measurements to COPD severity and percent emphysema. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited 290 participants, age 50-79 years with 10 or more packyears and free of clinical cardiovascular disease. COPD severity were defined on postbronchodilator spirometry by ATS/ERS criteria. Percent emphysema was defined as the percentage of regions of the lung < -950 Hounsfield units on full-lung computed tomography (CT). PA stain was defined by the percent change in cross-sectional PA area between systole and diastole on MRI. Blood flow across the tricuspid and mitral valves was assessed by phase-contrast MRI for determination of the ventricular diastolic dysfunction (E/A ratio). PA strain was reduced in COPD compared with controls (P = 0.002) and was inversely correlated with COPD severity (P = 0.004). PA strain was inversely associated to percent emphysema (P = 0.01). PA strain was also markedly correlated with right ventricular diastolic dysfunction measured by E/A ratios in the fully adjusted mix models (P = 0.02). PA strain is reduced in COPD, related in part to percent emphysema on CT scan, which may have implications for pulmonary small vessel flow and right ventricular function. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:262-271. © 2017 International Society for Magnetic Resonance in Medicine.

Left Ventricular Mass Progression Despite Stable Blood Pressure and Kidney Function in Stage 3 CKD

PubMed Central

Seifert, Michael E.; Fuentes, Lisa de las; Ginsberg, Charles; Rothstein, Marcos; Dietzen, Dennis J.; Cheng, Steven C.; Ross, Will; Windus, David; Dávila-Román, Victor G.; Hruska, Keith A.

2014-01-01

Background/Aims Progressive chronic kidney disease (CKD) is associated with worsening cardiovascular risk not explained by traditional risk factors. Left ventricular hypertrophy (LVH) is an important cardiovascular risk factor, but its progression has not been documented in early CKD. We explored whether progression of LVH in early CKD would occur despite stable kidney function. Methods We conducted a post hoc analysis of a 12-m nth study of lanthanum carbonate in stage 3 CKD, which included longitudinal assessments of cardiovascular biomarkers. Primary outcome for the analysis was the change in LV mass indexed to height in meters2.7 (LVM/Ht2.7). Secondary outcomes were changes in blood pressure (BP), pulse-wave velocity, LV systolic/diastolic function, fibroblast growth factor-23 (FGF23), klotho, and eGFR. Results 31 of 38 original subjects had sufficient data for analysis. LVM/Ht2.7 increased (47 ± 13 vs. 53 ± 13 g/m2.7, P=0.006) over 12 months despite stable BP, stable eGFR and normal LV systolic function. Vascular stiffness and LV diastolic dysfunction persisted throughout the study. Klotho levels decreased (748 ± 289 to 536 ± 410 pg/ml, P=0.03) but were unrelated to changes in LVM/Ht2.7. The change in FGF23/klotho ratio was strongly correlated with changes in LVM/Ht2.7 (r2 0.582, P=0.03). Conclusion Subjects with stage 3 CKD exhibited increasing LV mass, persistent LV diastolic dysfunction and vascular stiffness despite stable kidney function, BP and LV systolic function. Abnormal FGF23 signaling due to reduced klotho expression may be associated with increasing LV mass. These findings deserve further evaluation in a larger population, given the adverse prognostic value of these cardiovascular biomarkers. PMID:24818573

Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling

PubMed Central

de Albuquerque, Felipe Neves; Brandão, Andréa Araujo; da Silva, Dayse Aparecida; Mourilhe-Rocha, Ricardo; Duque, Gustavo Salgado; Gondar, Alyne Freitas Pereira; Neves, Luiza Maceira de Almeida; Bittencourt, Marcelo Imbroinise; Pozzan, Roberto; de Albuquerque, Denilson Campos

2014-01-01

Background The role of angiotensin-converting enzyme genetic polymorphisms as a predictor of echocardiographic outcomes on heart failure is yet to be established. The local profile should be identified so that the impact of those genotypes on the Brazilian population could be identified. This is the first study on exclusively non-ischemic heart failure over a follow-up longer than 5 years. Objective To determine the distribution of angiotensin-converting enzyme genetic polymorphism variants and their relation with echocardiographic outcome of patients with non-ischemic heart failure. Methods Secondary analysis of the medical records of 111 patients and identification of the angiotensin-converting enzyme genetic polymorphism variants, classified as DD (Deletion/Deletion), DI (Deletion/Insertion) or II (Insertion/Insertion). Results The cohort means were as follows: follow-up, 64.9 months; age, 59.5 years; male sex, 60.4%; white skin color, 51.4%; use of beta-blockers, 98.2%; and use of angiotensin-converting-enzyme inhibitors or angiotensin receptor blocker, 89.2%. The angiotensin-converting enzyme genetic polymorphism distribution was as follows: DD, 51.4%; DI, 44.1%; and II, 4.5%. No difference regarding the clinical characteristics or treatment was observed between the groups. The final left ventricular systolic diameter was the only isolated echocardiographic variable that significantly differed between the angiotensin-converting enzyme genetic polymorphisms: 59.2 ± 1.8 for DD versus 52.3 ± 1.9 for DI versus 59.2 ± 5.2 for II (p = 0.029). Considering the evolutionary behavior, all echocardiographic variables (difference between the left ventricular ejection fraction at the last and first consultation; difference between the left ventricular systolic diameter at the last and first consultation; and difference between the left ventricular diastolic diameter at the last and first consultation) differed between the genotypes (p = 0.024; p = 0.002; and p = 0.021, respectively). Conclusion The distribution of the angiotensin-converting enzyme genetic polymorphisms differed from that of other studies with a very small number of II. The DD genotype was independently associated with worse echocardiographic outcome, while the DI genotype, with the best echocardiographic profile (increased left ventricular ejection fraction and decreased left ventricular diameters). PMID:24270863

Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling.

PubMed

Albuquerque, Felipe Neves de; Brandão, Andréa Araujo; Silva, Dayse Aparecida da; Mourilhe-Rocha, Ricardo; Duque, Gustavo Salgado; Gondar, Alyne Freitas Pereira; Neves, Luiza Maceira de Almeida; Bittencourt, Marcelo Imbroinise; Pozzan, Roberto; Albuquerque, Denilson Campos de

2014-01-01

The role of angiotensin-converting enzyme genetic polymorphisms as a predictor of echocardiographic outcomes on heart failure is yet to be established. The local profile should be identified so that the impact of those genotypes on the Brazilian population could be identified. This is the first study on exclusively non-ischemic heart failure over a follow-up longer than 5 years. To determine the distribution of angiotensin-converting enzyme genetic polymorphism variants and their relation with echocardiographic outcome of patients with non-ischemic heart failure. Secondary analysis of the medical records of 111 patients and identification of the angiotensin-converting enzyme genetic polymorphism variants, classified as DD (Deletion/Deletion), DI (Deletion/Insertion) or II (Insertion/Insertion). The cohort means were as follows: follow-up, 64.9 months; age, 59.5 years; male sex, 60.4%; white skin color, 51.4%; use of beta-blockers, 98.2%; and use of angiotensin-converting-enzyme inhibitors or angiotensin receptor blocker, 89.2%. The angiotensin-converting enzyme genetic polymorphism distribution was as follows: DD, 51.4%; DI, 44.1%; and II, 4.5%. No difference regarding the clinical characteristics or treatment was observed between the groups. The final left ventricular systolic diameter was the only isolated echocardiographic variable that significantly differed between the angiotensin-converting enzyme genetic polymorphisms: 59.2 ± 1.8 for DD versus 52.3 ± 1.9 for DI versus 59.2 ± 5.2 for II (p = 0.029). Considering the evolutionary behavior, all echocardiographic variables (difference between the left ventricular ejection fraction at the last and first consultation; difference between the left ventricular systolic diameter at the last and first consultation; and difference between the left ventricular diastolic diameter at the last and first consultation) differed between the genotypes (p = 0.024; p = 0.002; and p = 0.021, respectively). The distribution of the angiotensin-converting enzyme genetic polymorphisms differed from that of other studies with a very small number of II. The DD genotype was independently associated with worse echocardiographic outcome, while the DI genotype, with the best echocardiographic profile (increased left ventricular ejection fraction and decreased left ventricular diameters).

Intermittent, moderate-intensity aerobic exercise for only eight weeks reduces arterial stiffness: evaluation by measurement of stiffness parameter and pressure-strain elastic modulus by use of ultrasonic echo tracking.

PubMed

Tanaka, Midori; Sugawara, Motoaki; Ogasawara, Yasuo; Izumi, Tadafumi; Niki, Kiyomi; Kajiya, Fumihiko

2013-04-01

Aerobic exercise has been reported to be associated with reduced arterial stiffness. However, the intensity, duration, and frequency of aerobic exercise required to improve arterial stiffness have not been established. In addition, most reports base their conclusions on changes in pulse wave velocity, which is an indirect index of arterial stiffness. We studied the effects of short-term, intermittent, moderate-intensity exercise training on arterial stiffness based on measurements of the stiffness parameter (β) and pressure-strain elastic modulus (E p), which are direct indices of regional arterial stiffness. A total of 25 young healthy volunteers (18 men) were recruited. By use of ultrasonic diagnostic equipment we measured β and E p of the carotid artery before and after 8 weeks of exercise training. After exercise training, systolic pressure (P s), diastolic pressure (P d), pulse pressure, systolic arterial diameter (D s), and diastolic arterial diameter (D d) did not change significantly. However, the pulsatile change in diameter ((D s - D d)/D d) increased significantly, and β and E p decreased significantly. For healthy young subjects, β and E p were reduced by intermittent, moderate-intensity exercise training for only 8 weeks.

Exercise training prevents the development of cardiac dysfunction in the low-dose streptozotocin diabetic rats fed a high-fat diet.

PubMed

Epp, Riley A; Susser, Shanel E; Morissette, Marc P; Kehler, D Scott; Jassal, Davinder S; Duhamel, Todd A

2013-01-01

This study tested the hypothesis that exercise training would prevent the development of diabetes-induced cardiac dysfunction and altered expression of sarcoplasmic reticulum Ca(2 +)-transport proteins in the low-dose streptozotocin-induced diabetic rats fed a high-fat diet (HFD+STZ). Male Sprague-Dawley rats (4 weeks old; 125-150 g) were made diabetic using a high-fat diet (40% fat, w/w) and a low-dose of streptozotocin (35 mg·(kg body mass)(-1)) by intravenous injection. Diabetic animals were divided among a sedentary group (Sed+HFD+STZ) or an exercise-trained group (Ex+HFD+STZ) that accumulated 3554 ± 338 m·day(-1) of voluntary wheel running (mean ± SE). Sedentary animals fed a low-fat diet served as the control (Sed+LFD). Oral glucose tolerance was impaired in the sedentary diabetic group (1179 ± 29; area under the curve (a.u.c.)) compared with that in the sedentary control animals (1447 ± 42 a.u.c.). Although left ventricular systolic function was unchanged by diabetes, impaired E/A ratios (i.e., diastolic function) and rates of pressure decay (-dP/dt) indicated the presence of diastolic dysfunction. Diabetes also reduced SERCA2a protein content and maximal SERCA2a activity (V(max)) by 21% and 32%, respectively. In contrast, the change in each parameter was attenuated by exercise training. Based on these data, it appears that exercise training prevented the development of diabetic cardiomyopathy and the dysregulation of sarcoplasmic reticulum protein content in an inducible animal model of type 2 diabetes.

Hyaluronidase 2 Deficiency Causes Increased Mesenchymal Cells, Congenital Heart Defects, and Heart Failure.

PubMed

Chowdhury, Biswajit; Xiang, Bo; Liu, Michelle; Hemming, Richard; Dolinsky, Vernon W; Triggs-Raine, Barbara

2017-01-01

Hyaluronan (HA) is required for endothelial-to-mesenchymal transition and normal heart development in the mouse. Heart abnormalities in hyaluronidase 2 (HYAL2)-deficient ( Hyal2 - /- ) mice and humans suggested removal of HA is also important for normal heart development. We have performed longitudinal studies of heart structure and function in Hyal2 -/- mice to determine when, and how, HYAL2 deficiency leads to these abnormalities. Echocardiography revealed atrial enlargement, atrial tissue masses, and valvular thickening at 4 weeks of age, as well as diastolic dysfunction that progressed with age, in Hyal2 -/- mice. These abnormalities were associated with increased HA, vimentin-positive cells, and fibrosis in Hyal2 -/- compared with control mice. Based on the severity of heart dysfunction, acute and chronic groups of Hyal2 -/- mice that died at an average of 12 and 25 weeks respectively, were defined. Increased HA levels and mesenchymal cells, but not vascular endothelial growth factor in Hyal2 -/- embryonic hearts, suggest that HYAL2 is important to inhibit endothelial-to-mesenchymal transition. Consistent with this, in wild-type embryos, HYAL2 and HA were readily detected, and HA levels decreased with age. These data demonstrate that disruption of normal HA catabolism in Hyal2 -/- mice causes increased HA, which may promote endothelial-to-mesenchymal transition and proliferation of mesenchymal cells. Excess endothelial-to-mesenchymal transition, resulting in increased mesenchymal cells, is the likely cause of morphological heart abnormalities in both humans and mice. In mice, these abnormalities result in progressive and severe diastolic dysfunction, culminating in heart failure. © 2016 The Authors.

Relationship of Office and Ambulatory Blood Pressure With Left Ventricular Global Longitudinal Strain.

PubMed

Sera, Fusako; Jin, Zhezhen; Russo, Cesare; Lee, Edward S; Schwartz, Joseph E; Rundek, Tatjana; Elkind, Mitchell S V; Homma, Shunichi; Sacco, Ralph L; Di Tullio, Marco R

2016-11-01

Left ventricular (LV) global longitudinal strain (GLS) is an early indicator of subclinical cardiac dysfunction, even when LV ejection fraction (LVEF) is normal, and is an independent predictor of cardiovascular events. Ambulatory blood pressure (BP) is a better predictor of cardiovascular events, including heart failure, than office BP. We investigated the association of office and ambulatory BP measurements with subclinical LV systolic dysfunction in a community-based cohort with normal LVEF. Two-dimensional speckle-tracking echocardiography and 24-hour ambulatory BP monitoring were performed in 577 participants (mean age 70±9 years; 60% women) with LVEF ≥50% from the Cardiovascular Abnormalities and Brain Lesions (CABL) study. Univariable and multivariable linear regression analyses were used to assess the associations of BP measures with GLS. Higher ambulatory and office BP values were consistently associated with impaired GLS. After adjustment for pertinent covariates (age, sex, race/ethnicity, body mass index, diabetes mellitus, coronary artery disease, LV mass index, and antihypertensive medication), office diastolic BP and ambulatory systolic and diastolic BPs (24-hour, daytime and nighttime) were independently associated with GLS (P = 0.003 for office DBP, P ≤ 0.001 for all ambulatory BPs). When ambulatory and office BP values were included in the same model, all ambulatory BP measures remained significantly associated with GLS (all P < 0.01), whereas office BP values were not. Ambulatory BP values are significantly associated with impaired GLS and the association is stronger than for office BP. Ambulatory BP monitoring might have a role in the risk stratification of hypertensive patients for early LV dysfunction.

[CARDIOREABILITATION PECULIARITIES AND CORRECTION OF VIOLATIONS OF SISTOLIC, DIASOLIC FUNCTION AND HEART RATE VARIABILITY IN PATIENTS WITH ACUTE CORONARY SYNDROME AND CORONARY ARTERY REVASCULARIZATION].

PubMed

Shved, M; Tsuglevych, L; Kyrychok, I; Levytska, L; Boiko, T; Kitsak, Ya

2017-04-01

In patients with acute coronary syndrome (ACS) who underwent coronary arteries revascularization, violations of hemodynamics, metabolism and heart rate variability often develop in the postoperative period, therefore, the goal of the study was to establish the features of disturbances and the effectiveness of correction of left ventricular systolic and diastolic dysfunction and heart rate variability in stages of cardiorehabilitation in patients with acute coronary syndrome who underwent coronary arteries revascularization. The experimental group included 40 patients with ACS in the postoperative period who underwent balloon angioplasty and stenting of the coronary arteries (25 patients with ST-segment elevation ACS and 15 patients without ST-segment elevation ACS). The age of examined patients was 37 to 74 years, an average of 52.6±6.7 years. The control group consisted of 20 patients, comparable in age and clinico-laboratory manifestations of ACS, who underwent drug treatment with direct anticoagulants, double antiplatelet therapy, β-blockers, ACE inhibitors and statins. Clinical efficacy of cardiorespiratory process in patients of both groups was assessed by the dynamics of general clinical symptoms and parameters of natriuretic propeptide, systolic and diastolic function of the left ventricle and heart rate variability. In the initial state, clinical and laboratory-instrumental signs of myocardial ischemia disappear in patients with ACS undergoing surgical revascularization of the coronary arteries, but clinical and subclinical manifestations of heart failure were diagnosed. The use of the accelerated program of cardiac rehabilitation already during the first month of studies leads to a decreasement of the signs of systolic and diastolic dysfunction, the level of NT-proBNP and improve in the variability of the heart rhythm wich significantly improves the life quality of patients with ACS. To monitor the effectiveness and safety of cardiac rehabilitation in patients with ACS who underwent coronary arteries revascularization, in addition to the generally accepted methods (determination of heart rate, blood pressure, a 6-minute test), it is advisable to diagnose the subclinical stage of heart failure by determining the level of NT-proBNP, Doppler echocardiogram, parameters of the left ventricular systolic and diastolic function and heart rate variability.

Dragon Boat training exerts a positive effect on myocardial function in breast cancer survivors.

PubMed

Stefani, Laura; Galanti, Giorgio; Di Tante, Valentina; Klika, Riggs J; Maffulli, Nicola

2015-07-01

Dragon Boat training is often suggested to control upper limb edema in breast cancer (BC) survivors, but little information is available regarding the cardiac impact of such activity. The present study evaluates this aspect during a 4-year follow-up of BC survivors. From 2006 to 2010, 55 women diagnosed with BC in 2005, treated with adjuvant therapy without evidence of metastases, were enrolled for competitive Dragon Boat training. They underwent ergometric tests yearly, and 2D echocardiography to evaluate hemodynamic, morphological and functional cardiac parameters. The data were compared with those from a group of 36 healthy women (HW). Both groups maintained normal systolic function throughout the period, with Cardiac Mass index, Body Mass Index and Ejection Fraction values being higher in HW. At the onset of the study, the diastolic function of BC survivors was normal though compatible with initial diastolic dysfunction when compared to the diastolic function of HW. After 4 years of competitive activity, the diastolic parameters improved in both groups and particularly in BC survivors (A peak: from 68.5 ± 15.1 cm/s to 50 ± 14.1 cm/s, p < 0.05; Ea: from 9.3 ± 2 cm/s to 11.89 ± 1.7 cm/s, p < 0.001). BC survivors experienced a significant improvement in diastolic function after 4 years of Dragon Boat training. Dragon Boat training impacts favorably on the myocardial performance in patients previously treated with chemotherapy. These results support the positive role of sport activity in myocardial function of BC survivors.

Effect of beta blockers (carvedilol or metoprolol XL) in patients with transposition of great arteries and dysfunction of the systemic right ventricle.

PubMed

Doughan, Abdul Rahman K; McConnell, Michael E; Book, Wendy M

2007-03-01

This study evaluated the effects of beta blockers (carvedilol and metoprolol XL) on New York Heart Association functional class and systemic right ventricular (RV) function in patients with complete transposition of the great arteries who had systemic RV dysfunction late after atrial inflow correction. A significant improvement in New York Heart Association functional class was found after 4 months of therapy with beta blockers. Functional recovery was significant mostly in those patients with pacemakers who received higher maintenance doses of carvedilol. RV end-diastolic area was significantly greater in untreated patients at the end of the follow-up period, whereas it was unchanged in treated patients. In conclusion, beta blockers prevent RV remodeling, with a concomitant improvement in exercise tolerance in patients with complete transposition of the great arteries and systemic RV dysfunction.

Phaeochromocytoma in a 86-year-old patient presenting with reversible myocardial dysfunction.

PubMed

Szwench, Elżbieta; P Czkowska, Mariola; Marczewski, Krzysztof; Klisiewicz, Anna; Micha Owska, Ilona; Ciuba, Iwona; Januszewicz, Magdalena; Prejbisz, Aleksander; Hoffman, Piotr; Januszewicz, Andrzej

2011-12-01

BACKGROUND. Phaeochromocytomas and paragangliomas are rare, mostly benign catecholamine-producing tumours of chromaffin cells of the adrenal medulla or of extra-adrenal paraganglia. Phaeochromocytoma may occur at any age, the greatest frequency being in the fourth and fifth decades. Only on extremely rare occasions does the tumour develop in the very old patients. METHODS. We are describing an 86-year-old patient with phaeochromocytoma, presenting with reversible myocardial dysfunction. RESULTS. This very old patient with phaeochromocytoma had hypertension characterized by labile blood pressure values and increased daytime blood pressure variability. This patient exhibited reversible myocardial dysfunction suggestive for "catecholaminergic cardiomyopathy", as the complication of phaeochromocytoma. After surgical removal of the tumour, recovery of left ventricular function was documented by echocardiography showing normalization of systolic function and improvement of diastolic function. CONCLUSION. Phaeochromocytomas are rare forms of secondary hypertension, but should be considered in the differential diagnosis, regardless of age, even in very old patients.

Cardiac dysfunction in the diabetic rat: quantitative evaluation using high resolution magnetic resonance imaging.

PubMed

Loganathan, Rajprasad; Bilgen, Mehmet; Al-Hafez, Baraa; Alenezy, Mohammed D; Smirnova, Irina V

2006-04-04

Diabetes is a major risk factor for cardiovascular disease. In particular, type 1 diabetes compromises the cardiac function of individuals at a relatively early age due to the protracted course of abnormal glucose homeostasis. The functional abnormalities of diabetic myocardium have been attributed to the pathological changes of diabetic cardiomyopathy. In this study, we used high field magnetic resonance imaging (MRI) to evaluate the left ventricular functional characteristics of streptozotocin treated diabetic Sprague-Dawley rats (8 weeks disease duration) in comparison with age/sex matched controls. Our analyses of EKG gated cardiac MRI scans of the left ventricle showed a 28% decrease in the end-diastolic volume and 10% increase in the end-systolic volume of diabetic hearts compared to controls. Mean stroke volume and ejection fraction in diabetic rats were decreased (48% and 28%, respectively) compared to controls. Further, dV/dt changes were suggestive of phase sensitive differences in left ventricular kinetics across the cardiac cycle between diabetic and control rats. Thus, the MRI analyses of diabetic left ventricle suggest impairment of diastolic and systolic hemodynamics in this rat model of diabetic cardiomyopathy. Our studies also show that in vivo MRI could be used in the evaluation of cardiac dysfunction in this rat model of type 1 diabetes.

New and Evolving Concepts Regarding the Prognosis and Treatment of Cardiac Amyloidosis.

PubMed

Perlini, Stefano; Mussinelli, Roberta; Salinaro, Francesco

2016-12-01

Systemic amyloidoses are rare and proteiform diseases, caused by extracellular accumulation of insoluble misfolded fibrillar proteins. Prognosis is dictated by cardiac involvement, which is especially frequent in light chain (AL) and in transthyretin variants (ATTR, both mutated, (ATTRm), and wild-type, (ATTRwt)). Recently, ATTRwt has emerged as a potentially relevant cause of a heart failure with preserved ejection fraction (HFpEF). Cardiac amyloidosis is an archetypal example of restrictive cardiomyopathy, with signs and symptoms of global heart failure and diastolic dysfunction. Independent of the aetiology, cardiac amyloidosis is associated with left ventricular concentric "hypertrophy" (i.e. increased wall thickness), preserved (or mildly depressed) ejection fraction, reduced midwall fractional shortening and global longitudinal function, as well as evident diastolic dysfunction, up to an overly restrictive pattern of the left ventricular filling. Cardiac biomarkers such as troponins and natriuretic peptides are very robust and widely accepted diagnostic as well as prognostic tools. Owing to its dismal prognosis, accurate and early diagnosis is mandatory and potentially life-saving. Although pathogenesis is still not completely understood, direct cardiomyocyte toxicity of the amyloidogenic precursor proteins and/or oligomer aggregates adds on tissue architecture disruption caused by amyloid deposition. The clarification of mechanisms of cardiac damage is offering new potential therapeutic targets, and several treatment options with a relevant impact on prognosis are now available.

Association of isolated minor nonspecific ST-T abnormalities with left ventricular hypertrophy and diastolic dysfunction.

PubMed

Kang, Jeong Gyu; Chang, Yoosoo; Sung, Ki-Chul; Kim, Jang-Young; Shin, Hocheol; Ryu, Seungho

2018-06-08

The aim of this study was to examine the associations of isolated minor nonspecific ST-T abnormalities (NSSTTA) on 12-lead electrocardiogram (ECG) with left ventricular (LV) diastolic function and LV geometry on echocardiography. A cross-sectional study comprised of 74,976 Koreans who underwent ECG and echocardiography as part of a comprehensive health examination between March 2011 and December 2014. ECG was coded using Minnesota Code criteria. The frequencies of NSSTTA, impaired LV relaxation, and echocardiographic LVH were 1,139 (1.5%), 21,118 (28.2%), and 1,687 (2.3%) patients, respectively. The presence of NSSTTA was positively associated with the prevalence of impaired LV relaxation and LVH on echocardiography. In a multivariable-adjusted model, the odds ratio (95% CIs) comparing patients with NSSTTA to control patients was 1.55 (1.33-1.80) for impaired LV relaxation and 3.15 (2.51-3.96) for echocardiographic LVH. The association between NSSTTA and impaired LV relaxation was stronger in the intermediate to high cardiovascular disease-risk group than in the low-risk group according to Framingham Risk Score stratification (P for interaction = 0.02). NSSTTA were associated with increased prevalence of impaired LV relaxation and LVH, suggesting NSSTTA as an early indicator of subclinical cardiac dysfunction and geometric abnormalities.

HDL mimetic peptide CER-522 treatment regresses left ventricular diastolic dysfunction in cholesterol-fed rabbits.

PubMed

Merlet, Nolwenn; Busseuil, David; Mihalache-Avram, Teodora; Mecteau, Melanie; Shi, Yanfen; Nachar, Walid; Brand, Genevieve; Brodeur, Mathieu R; Charpentier, Daniel; Rhainds, David; Sy, Gavin; Schwendeman, Anna; Lalwani, Narendra; Dasseux, Jean-Louis; Rhéaume, Eric; Tardif, Jean-Claude

2016-07-15

High-density lipoprotein (HDL) infusions induce rapid improvement of experimental atherosclerosis in rabbits but their effect on ventricular function remains unknown. We aimed to evaluate the effects of the HDL mimetic peptide CER-522 on left ventricular diastolic dysfunction (LVDD). Rabbits were fed with a cholesterol- and vitamin D2-enriched diet until mild aortic valve stenosis and hypercholesterolemia-induced LV hypertrophy and LVDD developed. Animals then received saline or 10 or 30mg/kg CER-522 infusions 6 times over 2weeks. We performed serial echocardiograms and LV histology to evaluate the effects of CER-522 therapy on LVDD. LVDD was reduced by CER-522 as shown by multiple parameters including early filling mitral deceleration time, deceleration rate, Em/Am ratio, E/Em ratio, pulmonary venous velocities, and LVDD score. These findings were associated with reduced macrophages (RAM-11 positive cells) in the pericoronary area and LV, and decreased levels of apoptotic cardiomyocytes in CER-522-treated rabbits. CER-522 treatment also resulted in decreased atheromatous plaques and internal elastic lamina area in coronary arteries. CER-522 improves LVDD in rabbits, with reductions of LV macrophage accumulation, cardiomyocyte apoptosis, coronary atherosclerosis and remodelling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Left ventricular diastolic function in workers occupationally exposed to mercury vapour without clinical presentation of cardiac involvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poręba, Rafał, E-mail: sogood@poczta.onet.pl; Skoczyńska, Anna; Gać, Paweł

2012-09-15

The aim of the study was to evaluate left ventricular diastolic function in workers occupationally exposed to mercury vapour without clinical presentation of cardiac involvement. The studies included 115 workers (92 men and 23 women) occupationally exposed to mercury vapour without clinical presentation of cardiac involvement (mean age: 47.83 ± 8.29). Blood samples were taken to determine blood lipid profile, urine was collected to estimate mercury concentration (Hg-U) and echocardiographic examination was performed to evaluate diastolic function of the left ventricle. In the entire group of workers occupationally exposed to mercury vapour without clinical presentation of cardiac involvement, Spearman correlationsmore » analysis demonstrated the following significant linear relationships: between body mass index (BMI) and ratio of maximal early diastolic mitral flow velocity/early diastolic mitral annular velocity (E/E') (r = 0.32, p < 0.05), between serum HDL concentration and E/E' (r = − 0.22, p < 0.05), between Hg-U and E/E' (r = 0.35, p < 0.05), between Hg-U and isovolumetric relaxation time (IVRT') (r = 0.41, p < 0.05), between Hg-U and ratio of maximal early diastolic mitral flow velocity/maximal late diastolic mitral flow velocity (E/A) (r = − 0.31, p < 0.05) and between serum HDL concentration and E/A (r = 0.43, p < 0,05). In logistic regression analysis it as shown that independent factors of left ventricular diastolic dysfunction risk in the study group included a higher urine mercury concentration, a higher value of BMI and a lower serum HDL concentration (OR{sub Hg}-{sub U} = 1.071, OR{sub BMI} = 1.200, OR{sub HDL} = 0.896, p < 0.05). Summing up, occupational exposure to mercury vapour may be linked to impaired left ventricular diastolic function in workers without clinical presentation of cardiac involvement. -- Highlights: ► Study aimed at evaluation of LVDD in workers occupationally exposed to Hg. ► There was significant linear relationships between Hg-U and E/E'. ► Independent risk factor of LVDD in study group included higher Hg-U. ► Independent risk factor of LVDD in study group included higher BMI and lower HDL. ► Occupational exposure to Hg may be linked to LVDD.« less

Increased response of diastolic blood pressure to exercise in patients with coronary artery disease: an index of latent ventricular dysfunction?

PubMed Central

Paraskevaidis, I A; Kremastinos, D T; Kassimatis, A S; Karavolias, G K; Kordosis, G D; Kyriakides, Z S; Toutouzas, P K

1993-01-01

OBJECTIVE--To determine whether an abnormal response of diastolic blood pressure during treadmill exercise stress testing correlated with the number of obstructed vessels and with left ventricular systolic function in patients with coronary artery disease. DESIGN--Diastolic blood pressure was measured invasively during exercise stress testing and coronary angiograms and left ventriculograms were obtained at rest in patients with coronary artery disease. The abnormal (> or = 15 mm Hg) diastolic blood pressure response was compared with the number of obstructed coronary arteries and with left ventricular systolic function. SETTING--Two tertiary referral centres. PATIENTS--50 consecutive patients (mean age 57 years) with coronary artery disease. MAIN OUTCOME MEASURES--The increase in diastolic blood pressure during exercise and its correlation with the appearance and disappearance of ST segment deviation, resting left ventricular systolic function, and the number of obstructed coronary arteries. RESULTS--Group 1: 10 (20%) patients (three with one, four with two, and three with three vessel coronary artery disease) (mean (SD) age 54.7 (12) years) had an abnormal diastolic blood pressure response that appeared 1.2 (0.3) min before ST segment deviation and became normal 0.9 (0.3) min after the ST segment returned to normal. Group 2: 40 (80%) patients (12 with one, 16 with two, and 12 with three vessel coronary arteries disease) (aged 56.8 (8.2) years) had a normal diastolic blood pressure response to stress testing. The ejection fraction (46.3 (5)%) and cardiac index (2.6 (0.1) 1/min/m2) in group 1 were less than in group 2 (61.6 (4.2)% and 3.8 (0.3) 1/min/m2 respectively, p < or = 0.001). The end systolic volume was greater in group 1 than in group 2: 38.7 (0.7 ml/m2 v 28.2 (2.1) ml/m2, p < or = 0.001. CONCLUSION--In patients with coronary artery disease an abnormal increase in diastolic blood pressure during exercise stress testing correlated well with left ventricular systolic function at rest but not with the number of obstructed coronary arteries. The abnormal response of diastolic blood pressure probably reflects deterioration of myocardial function. Images PMID:8343317

Use of Ventricular Assist Device in Univentricular Physiology: The Role of Lumped Parameter Models.

PubMed

Di Molfetta, Arianna; Ferrari, Gianfranco; Filippelli, Sergio; Fresiello, Libera; Iacobelli, Roberta; Gagliardi, Maria G; Amodeo, Antonio

2016-05-01

Failing single-ventricle (SV) patients might benefit from ventricular assist devices (VADs) as a bridge to heart transplantation. Considering the complex physiopathology of SV patients and the lack of established experience, the aim of this work was to realize and test a lumped parameter model of the cardiovascular system, able to simulate SV hemodynamics and VAD implantation effects. Data of 30 SV patients (10 Norwood, 10 Glenn, and 10 Fontan) were retrospectively collected and used to simulate patients' baseline. Then, the effects of VAD implantation were simulated. Additionally, both the effects of ventricular assistance and cavopulmonary assistance were simulated in different pathologic conditions on Fontan patients, including systolic dysfunction, diastolic dysfunction, and pulmonary vascular resistance increment. The model can reproduce patients' baseline well. Simulation results suggest that the implantation of VAD: (i) increases the cardiac output (CO) in all the three palliation conditions (Norwood 77.2%, Glenn 38.6%, and Fontan 17.2%); (ii) decreases the SV external work (SVEW) (Norwood 55%, Glenn 35.6%, and Fontan 41%); (iii) increases the mean pulmonary arterial pressure (Pap) (Norwood 39.7%, Glenn 12.1%, and Fontan 3%). In Fontan circulation, with systolic dysfunction, the left VAD (LVAD) increases CO (35%), while the right VAD (RVAD) determines a decrement of inferior vena cava pressure (Pvci) (39%) with 34% increment of CO. With diastolic dysfunction, the LVAD increases CO (42%) and the RVAD decreases the Pvci. With pulmonary vascular resistance increment, the RVAD allows the highest CO (50%) increment with the highest decrement of Pvci (53%). The single ventricular external work (SVEW) increases (decreases) increasing the VAD speed in cavopulmonary (ventricular) assistance. Numeric models could be helpful in this challenging and innovative field to support patients and VAD selection to optimize the clinical outcome and personalize the therapy. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet-Induced Metabolic Heart Disease.

PubMed

Sverdlov, Aaron L; Elezaby, Aly; Qin, Fuzhong; Behring, Jessica B; Luptak, Ivan; Calamaras, Timothy D; Siwik, Deborah A; Miller, Edward J; Liesa, Marc; Shirihai, Orian S; Pimentel, David R; Cohen, Richard A; Bachschmid, Markus M; Colucci, Wilson S

2016-01-11

Mitochondrial reactive oxygen species (ROS) are associated with metabolic heart disease (MHD). However, the mechanism by which ROS cause MHD is unknown. We tested the hypothesis that mitochondrial ROS are a key mediator of MHD. Mice fed a high-fat high-sucrose (HFHS) diet develop MHD with cardiac diastolic and mitochondrial dysfunction that is associated with oxidative posttranslational modifications of cardiac mitochondrial proteins. Transgenic mice that express catalase in mitochondria and wild-type mice were fed an HFHS or control diet for 4 months. Cardiac mitochondria from HFHS-fed wild-type mice had a 3-fold greater rate of H2O2 production (P=0.001 versus control diet fed), a 30% decrease in complex II substrate-driven oxygen consumption (P=0.006), 21% to 23% decreases in complex I and II substrate-driven ATP synthesis (P=0.01), and a 62% decrease in complex II activity (P=0.002). In transgenic mice that express catalase in mitochondria, all HFHS diet-induced mitochondrial abnormalities were ameliorated, as were left ventricular hypertrophy and diastolic dysfunction. In HFHS-fed wild-type mice complex II substrate-driven ATP synthesis and activity were restored ex vivo by dithiothreitol (5 mmol/L), suggesting a role for reversible cysteine oxidative posttranslational modifications. In vitro site-directed mutation of complex II subunit B Cys100 or Cys103 to redox-insensitive serines prevented complex II dysfunction induced by ROS or high glucose/high palmitate in the medium. Mitochondrial ROS are pathogenic in MHD and contribute to mitochondrial dysfunction, at least in part, by causing oxidative posttranslational modifications of complex I and II proteins including reversible oxidative posttranslational modifications of complex II subunit B Cys100 and Cys103. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Myocardial recovery from ischemia-reperfusion is compromised in the absence of tissue inhibitor of metalloproteinase 4.

PubMed

Takawale, Abhijit; Fan, Dong; Basu, Ratnadeep; Shen, Mengcheng; Parajuli, Nirmal; Wang, Wang; Wang, Xiuhua; Oudit, Gavin Y; Kassiri, Zamaneh

2014-07-01

Myocardial reperfusion after ischemia (I/R), although an effective approach in rescuing the ischemic myocardium, can itself trigger several adverse effects including aberrant remodeling of the myocardium and its extracellular matrix. Tissue inhibitor of metalloproteinases (TIMPs) protect the extracellular matrix against excess degradation by matrix metalloproteinases (MMPs). TIMP4 levels are reduced in myocardial infarction; however, its causal role in progression of post-I/R injury has not been explored. In vivo I/R (20-minute ischemia, 1-week reperfusion) resulted in more severe systolic and diastolic dysfunction in TIMP4(-/-) mice with enhanced inflammation, oxidative stress (1 day post-I/R), hypertrophy, and interstitial fibrosis (1 week). After an initial increase in TIMP4 (1 day post-I/R), TIMP4 mRNA and protein decreased in the ischemic myocardium from wild-type mice by 1 week post-I/R and in tissue samples from patients with myocardial infarction, which correlated with enhanced activity of membrane-bound MMP, membrane-type 1 MMP. By 4 weeks post-I/R, wild-type mice showed no cardiac dysfunction, elevated TIMP4 levels (to baseline), and normalized membrane-type 1 MMP activity. TIMP4-deficient mice, however, showed exacerbated diastolic dysfunction, sustained elevation of membrane-type 1 MMP activity, and worsened myocardial hypertrophy and fibrosis. Ex vivo I/R (20- or 30-minute ischemia, 45-minute reperfusion) resulted in comparable cardiac dysfunction in wild-type and TIMP4(-/-) mice. TIMP4 is essential for recovery from myocardial I/R in vivo, primarily because of its membrane-type 1 MMP inhibitory function. TIMP4 deficiency does not increase susceptibility to ex vivo I/R injury. Replenishment of myocardial TIMP4 could serve as an effective therapy in post-I/R recovery for patients with reduced TIMP4. © 2014 American Heart Association, Inc.

TIMP3 deficiency exacerbates iron overload-mediated cardiomyopathy and liver disease.

PubMed

Zhabyeyev, Pavel; Das, Subhash K; Basu, Ratnadeep; Shen, Mengcheng; Patel, Vaibhav B; Kassiri, Zamaneh; Oudit, Gavin Y

2018-05-01

Chronic iron overload results in heart and liver diseases and is a common cause of morbidity and mortality in patients with genetic hemochromatosis and secondary iron overload. We investigated the role of tissue inhibitor of metalloproteinase 3 (TIMP3) in iron overload-mediated tissue injury by subjecting male mice lacking Timp3 ( Timp3 -/- ) and wild-type (WT) mice to 12 wk of chronic iron overload. Whereas WT mice with iron overload developed diastolic dysfunction, iron-overloaded Timp3 -/- mice showed worsened cardiac dysfunction coupled with systolic dysfunction. In the heart, loss of Timp3 was associated with increased myocardial fibrosis, greater Timp1, matrix metalloproteinase ( Mmp) 2, and Mmp9 expression, increased active MMP-2 levels, and gelatinase activity. Iron overload in Timp3 -/- mice showed twofold higher iron accumulation in the liver compared with WT mice because of constituently lower levels of ferroportin. Loss of Timp3 enhanced the hepatic inflammatory response to iron overload, leading to greater neutrophil and macrophage infiltration and increased hepatic fibrosis. Expression of inflammation-related MMPs (MMP-12 and MMP-13) and inflammatory cytokines (IL-1β and monocyte chemoattractant protein-1) was elevated to a greater extent in iron-overloaded Timp3 -/- livers. Gelatin zymography demonstrated equivalent increases in MMP-2 and MMP-9 levels in WT and Timp3 -/- iron-overloaded livers. Loss of Timp3 enhanced the susceptibility to iron overload-mediated heart and liver injury, suggesting that Timp3 is a key protective molecule against iron-mediated pathology. NEW & NOTEWORTHY In mice, loss of tissue inhibitor of metalloproteinase 3 ( Timp3) was associated with systolic and diastolic dysfunctions, twofold higher hepatic iron accumulation (attributable to constituently lower levels of ferroportin), and increased hepatic inflammation. Loss of Timp3 enhanced the susceptibility to iron overload-mediated injury, suggesting that Timp3 plays a key protective role against iron-mediated pathology.

Association of morning blood pressure surge with carotid intima-media thickness and cardiac dysfunction in patients with cardiac syndrome-X.

PubMed

Mahfouz, Ragab A; Goda, Mohammad; Galal, Islam; Ghareb, Mohamed S

2018-05-23

Background & hypothesis: We hypothesized that exaggerated morning blood pressure surge, may contribute in cardiac dysfunction and arterial stiffness in patients with cardiac syndrome X. Thus we investigated the impact of morning blood pressure surge on cardiac function and carotid intima-media thickness in subjects with cardiac syndrome X. We studied patients with cardiac syndrome X using ambulatory blood pressure monitoring and investigated the association of morning blood pressure surge with carotid intima thickness, left atrial volume index and left ventricular filling (E/e'). Seventy patients with cardiac syndrome X were enrolled for the study and compared with 70 age and sex matched controls. Patients with cardiac syndrome X were stratified based on the systolic morning blood pressure surge value of control subjects to patients with exaggerated blood pressure surge (n = 42) and those with normal morning blood pressure surge (n = 28). Basal heart rate (p < .05), high sensitive C-reactive protein (p < .01), left atrial volume index (p < .01), E/e' (p < .01); carotid intima-media thickness (p < .001) and percentage of detected plaque (p < .005) were significantly higher in patients with exaggerated morning blood pressure surge group than those with morning blood pressure surge group. Morning blood pressure surge was significantly correlated with carotid intima-media thickness, high sensitive C-reactive protein, left atrial volume index and E/e' ratio in patients with cardiac syndrome X. In multivariate analysis, exaggerated morning blood pressure surge was the only independent predictor of increased carotid intima-media thickness (OR = 2.379; p < .001), and diastolic dysfunction (OR = 2.464; p < .001) in patients with cardiac syndrome X. Our data suggest that excessive morning blood pressure surge is an independent predictor for arterial stiffness and diastolic dysfunction in patients with cardiac syndrome X.

ACE polymorphisms and the acute response of blood pressure to a walk in medicated hypertensive patients.

PubMed

Goessler, Karla F; Cornelissen, Véronique A; de Oliveira, Edilamar M; de F Mota, Glória; Polito, Marcos D

2015-12-01

Polymorphisms of the angiotensin converting enzyme (ACE) gene can interfere with exercise-induced acute blood pressure (BP) reduction. This cross-over study investigated the acute effect of a single walk on BP and tested whether polymorphisms of the ACE gene might explain the variation in BP responses. Thirty-four healthy medicated individuals were randomized to one control and one walking session at 60-75% of heart rate reserve. Subjects left the laboratory wearing an ambulatory BP monitor until waking the next morning. Overall, systolic BP was somewhat lower following the walking session (p=.06), which could be attributed to a consistently lower systolic BP for 5 h after exercise (p-interaction<.04) compared with control rest. Similarly, II/ID individuals had a lower systolic BP (p-interaction=.02) and diastolic BP (p-interaction<.01) for 5 h after walking compared with control rest. Among DD individuals, a single walk did not induce a reduction in BP (p-interaction>.05). Our results showed that postexercise hypotension can occur after a walk at moderate intensity in carriers of the I allele; we were not able to demonstrate this in DD individuals. Our results suggest that genetic variation in the ACE gene might affect the BP response to exercise, although more research is needed to confirm these findings. © The Author(s) 2015.

Association of angiotensin-converting-enzyme gene polymorphism with the depressor response to mild exercise therapy in patients with mild to moderate essential hypertension.

PubMed

Zhang, B; Sakai, T; Miura, S; Kiyonaga, A; Tanaka, H; Shindo, M; Saku, K

2002-10-01

We studied the association of angiotensin I-converting enzyme (ACE) gene polymorphism with the depressor response to exercise therapy in 64 Japanese subjects with mild to moderate essential hypertension. Each subject performed 10 weeks of mild (lactate threshold intensity: approximately 50% maximum oxygen consumption) exercise therapy on a bicycle ergometer. Systolic blood pressure (SPB), diastolic blood pressure (DPB), and mean arterial pressure (MAP) were significantly decreased by exercise therapy in subjects with the ACE-II and ID genotypes but not in DD subjects. The time-by-genotype interaction effects were significant for DBP and MAP. According to a multiple logistic regression analysis, the age- and baseline plasma renin activity-adjusted relative risk (odds ratio) for the lack of a depressor response conferred by the D allele (assuming an additive effect) was 2.72 [95% confidence interval (CI), 1.07-6.91; p = 0.034]; for DD genotypes, as compared with the DI and II genotypes (assuming that the D allele is recessive), it was 11.7 (95% CI, 2.25-60.6; p = 0.003). ACE gene I/D polymorphism is associated with the depressor response of essential hypertensives to mild exercise therapy, which suggests that genetic features may underlie, at least in part, the heterogeneity of the depressor response in essential hypertensives to mild exercise therapy.

Epicatechin as a Therapeutic Strategy to Mitigate the Development of Cardiac Remodeling and Fibrosis

DTIC Science & Technology

2017-09-01

Currently, no drugs target HFpEF and the development of animal models can assist in therapy evaluation. We developed a female rat model of aging...allocated into an aging group, aging + ovariectomy and aging + ovariectomy + 10% fructose in drinking water. At 22 months of age, animals were...epicatechin (Epi) will ameliorate adverse tissue remodeling and cardiac fibrosis in female animal models developing diastolic dysfunction as seen in women

Impaired decision-making and impulse control in Internet gaming addicts: evidence from the comparison with recreational Internet game users.

PubMed

Wang, Yifan; Wu, Lingdan; Wang, Lingxiao; Zhang, Yifen; Du, Xiaoxia; Dong, Guangheng

2017-11-01

Although Internet games have been proven to be addictive, only a few game players develop online gaming addiction. A large number of players play online games recreationally without being addicted to it. These individuals are defined as recreational Internet gaming users (RGU). So far, no research has investigated decision-making and impulse control in RGU. In the current study, we used delay discounting (DD) task and probabilistic discounting (PD) task to examine decision-making and impulse control in 20 healthy controls, 20 subjects with Internet gaming disorder (IGD) and 23 RGU during fMRI scanning. At the behavioral level, RGU showed lower DD rate and higher PD rate than subjects with IGD and there was no significant difference between RGU and healthy controls on the DD and PD rates. At the neural level, RGU showed increased neural response in the parahippocampal gyrus, the anterior cingulate cortex, the medial frontal gyrus and the inferior frontal gyrus as compared with subjects with IGD. These brain regions may play an important role in preventing RGU from developing addiction. The results suggest that the RGU are capable of inhibiting impulse due to additional cognitive endeavor and the subjects with IGD have deficit in decision-making and impulsive control, which are associated with brain dysfunction. © 2016 Society for the Study of Addiction.

Effects of atorvastatin treatment on left ventricular diastolic function in peritoneal dialysis patients-The ALEVENT clinical trial.

PubMed

Wu, Cho-Kai; Yeh, Chih-Fan; Chiang, Jiun-Yang; Lin, Ting-Tse; Wu, Yi-Fan; Chiang, Chih-Kang; Kao, Tze-Wah; Hung, Kuan-Yu; Huang, Jenq-Wen

Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dialysis (PD). Increased levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein, predict the development of LVDD. We hypothesized that PD patients with elevated high-sensitivity C-reactive protein levels might benefit from statin treatment for LVDD and designed a randomized clinical trial to prove the hypothesis. We screened 213 PD patients and randomly assigned 32 men and women with low-density lipoprotein cholesterol levels <130 mg/dL, high-sensitivity C-reactive protein levels of ≥1.5 mg/L, and LVDD, diagnosed by conventional and tissue Doppler imaging (TDI) echocardiography, to treatment with atorvastatin, 40 mg daily, or without. The primary end points were changes in TDI diastolic parameters or global strain imaging diastolic parameters. Atorvastatin reduced low-density lipoprotein cholesterol levels by 43% and high-sensitivity C-reactive protein levels by 45% (both P < .001). Follow-up TDI showed significant improvement of early mitral flow velocities divided by early diastolic peak velocities of the mitral annulus at the medial and lateral site (Nominal change for E/E medial : -5.01 ± 6.36 vs 1.80 ± 6.59 for atorvastatin and control, respectively, P = .02). There was also a significant improvement in global strain imaging after atorvastatin treatment (global strain rate, -17.12 ± 1.42 vs -14.61 ± 1.78 for atorvastatin and control, respectively, P = .002 and E/SR IVR , 462.35 ± 110.54 vs 634.09 ± 116.81, P = .003). In this trial of PD patients without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels and LVDD, atorvastatin significantly improved cardiac diastolic function (ClinicalTrials.gov number, NCT01503671). Copyright © 2017. Published by Elsevier Inc.

Ergotamine-derived dopamine agonists and left ventricular function in Parkinson patients: systolic and diastolic function studied by conventional echocardiography, tissue Doppler imaging, and two-dimensional speckle tracking.

PubMed

Rasmussen, Vibeke Guldbrand; Poulsen, Steen Hvitfeldt; Dupont, Erik; Ostergaard, Karen; Safikhany, Gholamhossein; Egeblad, Henrik

2008-11-01

Ergot-derived dopamine agonists (EDDA) induce fibrotic heart valve disease. We aimed to investigate whether EDDA treatment also affects left ventricular (LV) function. Myocardial function was evaluated in 110 Parkinson patients [mean age (63.4 +/- 9.0 years)] treated for at least 6 months with either EDDA (n = 71) or non-EDDA (n = 39). LV ejection fraction did not differ between EDDA and non-EDDA patients [63 +/- 4% vs. 65 +/- 4% (ns)]. There was no difference in prevalence of diastolic dysfunction between EDDA and non-EDDA patients [7% vs. 8% (ns)]. Finally, averaged LV systolic myocardial strain and longitudinal displacement analysed by means of two-dimensional speckle tracking showed no difference between EDDA and non-EDDA patients [strain: 19 +/- 3% vs. 19 +/- 2% (ns) and longitudinal displacement: 12 +/- 2 mm vs. 12 +/- 2 mm (ns)]. Elevated p-NT-proBNP was found in 38% of EDDA patients and in 59% of non-EDDA patients (ns). In contrast to the well-established association between EDDA treatment and valvular fibrosis, EDDA did not have a detectable adverse impact on myocardial systolic and diastolic function.

Enhanced pulmonary vasodilator reserve and abnormal right ventricular: pulmonary artery coupling in heart failure with preserved ejection fraction.

PubMed

Andersen, Mads J; Hwang, Seok-Jae; Kane, Garvan C; Melenovsky, Vojtech; Olson, Thomas P; Fetterly, Kenneth; Borlaug, Barry A

2015-05-01

Pulmonary hypertension and right ventricular (RV) dysfunction are common in patients with advanced heart failure with preserved ejection fraction (HFpEF), yet their underlying mechanisms remain poorly understood. We sought to examine RV-pulmonary artery (PA) functional reserve responses and RV-PA coupling at rest and during β-adrenergic stimulation in subjects with earlier stage HFpEF. In a prospective trial, subjects with HFpEF (n=39) and controls (n=18) underwent comprehensive invasive and noninvasive hemodynamic assessment using high fidelity micromanometer catheters, echocardiography, and expired gas analysis at rest and during dobutamine infusion. HFpEF subjects displayed similar RV structure but significantly impaired RV systolic (lower RV dP/dtmax/IP and s') and diastolic function (higher RV τ) coupled with more severe pulmonary vascular disease, manifest by higher PA pressures, higher PA resistance, and lower PA compliance compared with controls. Dobutamine infusion caused greater pulmonary vasodilation in HFpEF compared with controls, with enhanced reductions in PA resistance, greater increase in PA compliance, and a more negative slope in the PA pressure-flow relationship when compared with controls (all P<0.001). RV-PA coupling analysis revealed that dobutamine improved RV ejection in HFpEF subjects through afterload reduction alone, rather than through enhanced contractility, indicating RV systolic reserve dysfunction. Pulmonary hypertension in early stage HFpEF is related to partially reversible pulmonary vasoconstriction coupled with RV systolic and diastolic dysfunction, even in the absence of RV structural remodeling. Pulmonary vascular tone is more favorably responsive to β-adrenergic stimulation in HFpEF than controls, suggesting a potential role for β-agonists in the treatment of patients with HFpEF and pulmonary hypertension. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01418248. © 2015 American Heart Association, Inc.

Latent cardiac dysfunction as assessed by echocardiography in bed-bound patients following cerebrovascular accidents: comparison with nutritional status.

PubMed

Masugata, Hisashi; Senda, Shoichi; Goda, Fuminori; Yoshihara, Yumiko; Yoshikawa, Kay; Fujita, Norihiro; Himoto, Takashi; Okuyama, Hiroyuki; Taoka, Teruhisa; Imai, Masanobu; Kohno, Masakazu

2007-07-01

The aim of this study was to elucidate the cardiac function in bed-bound patients following cerebrovascular accidents. In accord with the criteria for activities of daily living (ADL) of the Japanese Ministry of Health, Labour and Welfare, 51 age-matched poststroke patients without heart disease were classified into 3 groups: rank A (house-bound) (n = 16, age, 85 +/- 6 years), rank B (chair-bound) (n = 16, age, 84 +/- 8 years), and rank C (bed-bound) (n = 19, age, 85 +/- 9 years). Using echocardiography, the left ventricular (LV) diastolic function was assessed by the ratio of early filling (E) and atrial contraction (A) transmitral flow velocities (E/A) of LV inflow. LV systolic function was assessed by LV ejection fraction (LVEF), and the Tei index was also measured to assess both LV systolic and diastolic function. No difference was observed in the E/A and LVEF among the 3 groups. The Tei index was higher in rank C (0.56 +/- 0.17) than in rank A (0.39 +/- 0.06) and rank B (0.48 +/- 0.17), and a statistically significant difference was observed between rank A and rank C (P < 0.05). Serum albumin and blood hemoglobin were significantly lower in rank C (3.1 +/- 0.4 and 10.6 +/- 1.8 g/dL) than in rank A (4.1 +/- 0.3 and 12.4 +/- 1.2 g/dL) (P < 0.001 and P < 0.05, respectively). These results indicate that latent cardiac dysfunction and poor nutritional status may exist in bed-bound patients (rank C) following cerebrovascular accidents. The Tei index may be a useful index of cardiac dysfunction in bed-bound patients because it is independent of the cardiac loading condition.

Effects of Combined Milrinone and Levosimendan Treatment on Systolic and Diastolic Function During Postischemic Myocardial Dysfunction in a Porcine Model.

PubMed

Axelsson, Birger; Häggmark, Sören; Svenmarker, Staffan; Johansson, Göran; Gupta, Anil; Tydén, Hans; Wouters, Patrick; Haney, Michael

2016-09-01

It is not known whether there are positive or negative interactions on ventricular function when a calcium-sensitizing inotrope is added to a phosphodiesterase inhibitor in the clinical setting of acute left ventricular (LV) dysfunction. We hypothesized that when levosimendan is added to milrinone treatment, there will be synergetic inotropic and lusitropic effects. This was tested in an anesthetized porcine postischemic global LV injury model, where ventricular pressures and volumes (conductance volumetry) were measured. A global ischemic injury was induced by repetitive left main stem coronary artery occlusions. Load-independent indices of LV function were assessed before and after ventricular injury, after milrinone treatment, and finally after addition of levosimendan to the milrinone treatment. Nonparametric, within-group comparisons were made. The protocol was completed in 12 pigs, 7 of which received the inotrope treatment and 5 of which served as controls. Milrinone led to positive lusitropic effects seen by improvement in tau after myocardial stunning. The addition of levosimendan to milrinone further increased lusitropic state. The latter effect could however not be attributed solely to levosimendan, since lusitropic state also improved spontaneously in time-matched controls at the same rate during the corresponding period. When levosimendan was added to milrinone infusion, there was no increase in systolic function (preload recruitable stroke work) compared to milrinone treatment alone. We conclude that in this model of postischemic LV dysfunction, there appears to be no clear improvement in systolic or diastolic function after addition of levosimendan to established milrinone treatment but also no negative effects of levosimendan in this context. © The Author(s) 2016.

Vascular effects of intravenous intralipid and dextrose infusions in obese subjects

PubMed Central

Gosmanov, Aidar R.; Smiley, Dawn D.; Peng, Limin; Siquiera, Joselita; Robalino, Gonzalo; Newton, Christopher; Umpierrez, Guillermo E.

2013-01-01

Hyperglycemia and elevated free fatty acids (FFA) are implicated in the development of endothelial dysfunction. Infusion of soy-bean oil-based lipid emulsion (Intralipid®) increases FFA levels and results in elevation of blood pressure (BP) and endothelial dysfunction in obese healthy subjects. The effects of combined hyperglycemia and high FFA on BP, endothelial function and carbohydrate metabolism are not known. Twelve obese healthy subjects received four random, 8-h IV infusions of saline, Intralipid 40 mL/h, Dextrose 10% 40 mL/h, or combined Intralipid and dextrose. Plasma levels of FFA increased by 1.03±0.34 mmol/L (p=0.009) after Intralipid, but FFAs remained unchanged during saline, dextrose, and combined Intralipid and dextrose infusion. Plasma glucose and insulin concentrations significantly increased after dextrose and combined Intralipid and dextrose (all, p<0.05) and were not different from baseline during saline and lipid infusion. Intralipid increased systolic BP by 12±9 mmHg (p<0.001) and diastolic BP by 5±6 mmHg (p=0.022), and decreased flow-mediated dilatation (FMD) from baseline by 3.2%±1.4% (p<0.001). Saline and dextrose infusion had neutral effects on BP and FMD. The co-administration of lipid and dextrose decreased FMD by 2.4%±2.1% (p=0.002) from baseline, but did not significantly increase systolic or diastolic BP. Short-term Intralipid infusion significantly increased FFA and BP; in contrast, FFA and BP were unchanged during combined infusion of Intralipid and dextrose. Combined Intralipid and dextrose infusion resulted in endothelial dysfunction similar to Intralipid alone. PMID:22483976

Prevalence and factors related to left ventricular systolic dysfunction in asymptomatic patients with rheumatoid arthritis. A prospective tissue Doppler echocardiography study.

PubMed

Cioffi, Giovanni; Viapiana, Ombretta; Ognibeni, Federica; Dalbeni, Andrea; Gatti, Davide; Adami, Silvano; Mazzone, Carmine; Faganello, Giorgio; Di Lenarda, Andre; Rossini, Maurizio

2015-11-01

Patients with rheumatoid arthritis (RA) have a high risk for cardiovascular disease due to a chronic inflammatory state, accelerated atherosclerosis, and changes in left ventricular (LV) geometry. These conditions predispose patients to LV systolic dysfunction (LVSD). In this study we assessed whether RA is a condition associated with LVSD, and analyzed the prevalence and factors associated with LVSD in patients with RA. Echocardiographic and clinical data from 198 patients with RA without presence or history of symptoms of cardiac disease were compared with 198 non-RA controls matched for cardiovascular risk factors. LVSD was identified with tissue Doppler echocardiography (TDE) when mitral annular peak systolic velocity (S') was < 9.0 cm/s. Patients with RA were 61 ± 12 years old and 71 % were female (disease duration 14 ± 10 years). LVSD was found in 89 patients with RA (45 %). By multiple regression analysis including both RA patients and controls, RA emerged as an independent condition associated with LVSD (exp β 3.89; CI: 1.87-8.08) together with higher E/E' ratio (index of LV diastolic function) and diabetes mellitus. For the 198 patients with RA, the variables associated with LVSD were higher E/E' ratio and systolic blood pressure. Almost half of asymptomatic RA patients without history of cardiac disease have subclinical LVSD easily detectable with TDE. RA is closely related to LVSD. A higher degree of LV diastolic dysfunction and systolic blood pressure are associated with LVSD in these patients, whose risk for cardiovascular events could be better defined using such information in the asymptomatic stage of cardiac disease.

Importance of SERCA2a on early isolated diastolic dysfunction induced by supravalvular aortic stenosis in rats

PubMed Central

Silveira, C.F.S.M.P.; Campos, D.H.S.; Freire, P.P.; Deus, A.F.; Okoshi, K.; Padovani, C.R.; Cicogna, A.C.

2017-01-01

Cardiac remodeling is defined as changes in shape and function of the heart in response to aggression (pressure overload). The sarcoplasmic reticulum calcium ATPase cardiac isoform 2a (SERCA2a) is a known factor that influences function. A wide spectrum of studies report a decrease in SERCA2a in heart failure, but none evaluate it's the role in early isolated diastolic dysfunction in supravalvular aortic stenosis (AoS). Our hypothesis was that SERCA2a participates in such dysfunction. Thirty-day-old male Wistar rats (60-80 g) were divided into AoS and Sham groups, which were submitted to surgery with or without aorta clipping, respectively. After 6 weeks, the animals were submitted to echocardiogram and functional analysis by isolated papillary muscle (IPM) in basal condition, hypoxia, and SERCA2a blockage with cyclopiazonic acid at calcium concentrations of 0.5, 1.5, and 2.5 mM. Western-blot analyses were used for SERCA2a and phospholamban detection. Data analysis was carried out with Student's t-test and ANOVA. AoS enhanced left atrium and E and A wave ratio, with preserved ejection fraction. Basal condition in IPM showed similar increases in developed tension (DT) and resting tension (RT) in AoS, and hypoxia was similar between groups. After cyclopiazonic acid blockage, final DT was equally decreased and RT was similar between groups, but the speed of relaxation was decreased in the AoS group. Western-blot was uniform in all evaluations. The hypothesis was confirmed, since functional parameters regarding SERCA2a were changed in the AoS group. PMID:28423119

Females Are Protected From Iron-Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress.

PubMed

Das, Subhash K; Patel, Vaibhav B; Basu, Ratnadeep; Wang, Wang; DesAulniers, Jessica; Kassiri, Zamaneh; Oudit, Gavin Y

2017-01-23

Sex-related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron-overload cardiomyopathy is poorly understood. Male and female wild-type and hemojuvelin-null mice were injected and fed with a high-iron diet, respectively, to develop secondary iron overload and genetic hemochromatosis. Female mice were completely protected from iron-overload cardiomyopathy, whereas iron overload resulted in marked diastolic dysfunction in male iron-overloaded mice based on echocardiographic and invasive pressure-volume analyses. Female mice demonstrated a marked suppression of iron-mediated oxidative stress and a lack of myocardial fibrosis despite an equivalent degree of myocardial iron deposition. Ovariectomized female mice with iron overload exhibited essential pathophysiological features of iron-overload cardiomyopathy showing distinct diastolic and systolic dysfunction, severe myocardial fibrosis, increased myocardial oxidative stress, and increased expression of cardiac disease markers. Ovariectomy prevented iron-induced upregulation of ferritin, decreased myocardial SERCA2a levels, and increased NCX1 levels. 17β-Estradiol therapy rescued the iron-overload cardiomyopathy in male wild-type mice. The responses in wild-type and hemojuvelin-null female mice were remarkably similar, highlighting a conserved mechanism of sex-dependent protection from iron-overload-mediated cardiac injury. Male and female mice respond differently to iron-overload-mediated effects on heart structure and function, and females are markedly protected from iron-overload cardiomyopathy. Ovariectomy in female mice exacerbated iron-induced myocardial injury and precipitated severe cardiac dysfunction during iron-overload conditions, whereas 17β-estradiol therapy was protective in male iron-overloaded mice. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Kinematic Characterization of Left Ventricular Chamber Stiffness and Relaxation

NASA Astrophysics Data System (ADS)

Mossahebi, Sina

Heart failure is the most common cause of hospitalization today, and diastolic heart failure accounts for 40-50% of cases. Therefore, it is critical to identify diastolic dysfunction at a subclinical stage so that appropriate therapy can be administered before ventricular function is further, and perhaps irreversibly impaired. Basic concepts in physics such as kinematic modeling provide a unique method with which to characterize cardiovascular physiology, specifically diastolic function (DF). The advantage of an approach that is standard in physics, such as the kinematic modeling is its causal formulation that functions in contrast to correlative approaches traditionally utilized in the life sciences. Our research group has pioneered theoretical and experimental quantitative analysis of DF in humans, using both non-invasive (echocardiography, cardiac MRI) and invasive (simultaneous catheterization-echocardiography) methods. Our group developed and validated the Parametrized Diastolic Filling (PDF) formalism which is motivated by basic physiologic principles (LV is a mechanical suction pump at the mitral valve opening) that obey Newton's Laws. PDF formalism is a kinematic model of filling employing an equation of motion, the solution of which accurately predicts all E-wave contours in accordance with the rules of damped harmonic oscillatory motion. The equation's lumped parameters---ventricular stiffness, ventricular viscoelasticity/relaxation and ventricular load---are obtained by solving the 'inverse problem'. The parameters' physiologic significance and clinical utility have been repeatedly demonstrated in multiple clinical settings. In this work we apply our kinematic modeling approach to better understand how the heart works as it fills in order to advance the relationship between physiology and mathematical modeling. Through the use of this modeling, we thereby define and validate novel, causal indexes of diastolic function such as early rapid filling energy, diastatic stiffness, and relaxation and stiffness components of E-wave deceleration time.

Left ventricular diastolic dysfunction without left ventricular hypertrophy in obese children and adolescents: a Tissue Doppler Imaging and Cardiac Troponin I Study.

PubMed

El Saiedi, Sonia A; Mira, Marwa F; Sharaf, Sahar A; Al Musaddar, Maysoun M; El Kaffas, Rania M H; AbdelMassih, Antoine F; Barsoum, Ihab H Y

2018-01-01

Obesity increases the risk for various cardiovascular problems. Increase in body mass index is often an independent risk factor for the development of elevated blood pressure and clustering of various cardiovascular risk factors. To determine early markers of left ventricular affection in obese patients before the appearance of left ventricular hypertrophy. In this cross-sectional study, we evaluated 42 obese patients and 30 healthy controls. Their ages ranged from 6 to 19 years. Studied children were subjected to anthropometric, lipid profile, and serum Troponin I level measurements. Echocardiographic evaluation performed to assess the left ventricle included left ventricular dimension measurement using motion-mode echocardiography, based on which patients with left ventricular hypertrophy (10 patients) were eliminated, as well as conventional and tissue Doppler imaging. Tissue Doppler findings in the study groups showed that the ratio of transmitral early diastolic filling velocity to septal peak early diastolic myocardial velocity (E/e') was significantly higher in cases compared with controls [6.9±1.4 versus 9.0±1.6, p (Pearson's coefficient)=0.001, respectively]. The level of cardiac troponin I was significantly higher in cases compared with controls [0.14±0.39 ng/ml versus 0.01±0.01 ng/ml, p (Pearson's coefficient)=0.047, respectively] and there was a significant correlation between troponin I and transmitral early diastolic filling velocity to septal peak early diastolic myocardial velocity ratio (E/e') [R (correlation coefficient)=0.6]. Tissue Doppler Imaging and Troponin I evaluation proved useful tools to detect early affection of the left ventricle in obese patients even in the absence of left ventricular hypertrophy.

Influence of collaterals on the left ventricular end-diastolic pressure and serum NT-proBNP levels in patients with coronary chronic total occlusion.

PubMed

Samadov, Fuad; Yesildag, Osman; Sari, Ibrahim; Atas, Halil; Akhundova, Aysel; Basaran, Yelda

2017-06-01

Although numerous studies have shown the protective effects of the well-developed coronary collaterals on left ventricular functions, the relationship between collateral grade and left ventricular end diastolic pressure has not been studied in chronic total occlusion patients. Also, there are conflicting data on the effect of collaterals on NT-proBNP levels. The aim of our study was to evaluate the relationship between coronary collateral circulation and left ventricular end diastolic pressure and NT-proBNP levels in chronic total occlusion patients. Study group was retrospectively selected from the patients who had undergone coronary angiography at our hospital between June 2011 and March 2013. Clinical, biochemical, angiographic and hemodynamic data of 199 consecutive patients having at least one totally occluded major epicardial coronary artery were evaluated. Coronary collateral circulation was graded according to Rentrop classification. While Rentrop grade 3 was defined as well-developed, all the remaining collateral grades were regarded as poor collaterals. Overall 87 patients were found to have good collaterals and 112 patients had poor collaterals. There was no significant difference between the patients with well- or poorly developed coronary collaterals with regard to left ventricular end diastolic pressure (16.84 ± 5.40 mmHg vs 16.10 ± 6.09, respectively, p  = 0,632) and log NT-proBNP (2.46 ± 0.58 vs 2.59 ± 0.76, respectively, p  = 0,335). In patients with coronary chronic total occlusion even well-developed coronary collaterals are not capable of protecting the rise of left ventricular end diastolic pressure and NT-proBNP levels which are reliable markers of the left ventricular dysfunction.

The prognostic role of exercise echocardiography in heart failure.

PubMed

Rubiś, Paweł; Drabik, Leszek; Kopeć, Grzegorz; Olszowska, Maria; Płazak, Wojciech; Podolec, Piotr

2011-01-01

Gradual impairment of exercise tolerance is the commonest sign of heart failure (HF). Little is known as to which cardiac contributors of poor exercise capacity carry an independent prognostic information in HF. We investigated the prognostic role of exercise echocardiography (ex-echo) in HF patients. We studied 85 consecutive, symptomatic HF patients (66 males, mean age 62.5 ± 11.8 [range 21-83] years, mean left ventricular ejection fraction [LVEF] 27.2 ± 9.5%). The end-point was all-cause mortality. During the follow-up period (mean 43 ± 21 months) 21 patients died. Resting echocardiography and ex-echo, with the simultaneous measurement of peak oxygen uptake (VO(2peak)), was performed in each patient using a semi-supine ergometer (20 W, 2-min increments). Apart from conventional assessment of systolic and diastolic function (EF, E/A, DT, IVRT) or right ventricular systolic pressure (RVSP), tissue Doppler imaging was used for the assessment of LV and RV peak velocity (IVV) as well as acceleration during isovolumic contraction (IVA), peak velocity during ejection phase (S'), peak early diastolic velocity (E'), peak late diastolic velocity (A'), and ratio of early diastolic mitral/tricuspid velocity to peak early diastolic velocity (E/E'). Patients who died were significantly older, had lower exercise capacity, more advanced HF, greater impairment of baseline systolic function, higher baseline pulmonary artery systolic pressure, and most importantly a lack of improvement in EF, diastolic function, and further increase of RVSP during exercise. Out of all echocardiographic parameters, only peak stress EF (x(2) 6.1; p = 0.01), baseline and peak exercise RVSP (x(2) 12.5 and c(2) 18.7; p 〈 0.001; respectively), and mitral E/E' ratio (x(2) 8.9; p 〈 0.01) were univariate predictors of prognosis and remained independently prognostic when adjusted for age and sex but were eliminated from the model by NT-proBNP. During exercise, more severe systolic and diastolic dysfunction with the elevation of pulmonary arterial pressure is more prevalent in HF patients who have a poorer outcome. The estimation of common parameters such as EF, RVSP and E/E' using ex-echo, provides prognostic information in HF.

Prognostic value of systolic mitral annular velocity measured with Doppler tissue imaging in patients with chronic heart failure caused by left ventricular systolic dysfunction

PubMed Central

Nikitin, N P; Loh, P H; de Silva, R; Ghosh, J; Khaleva, O Y; Goode, K; Rigby, A S; Alamgir, F; Clark, A L; Cleland, J G F

2006-01-01

Objective To assess the prognostic value of various conventional and novel echocardiographic indices in patients with chronic heart failure (CHF) caused by left ventricular (LV) systolic dysfunction. Methods 185 patients with a mean (SD) age of 67 (11) years with CHF and LV ejection fraction < 45% despite optimal pharmacological treatment were prospectively enrolled. The patients underwent two dimensional echocardiography with tissue harmonic imaging to assess global LV systolic function and obtain volumetric data. Transmitral flow was assessed with conventional pulse wave Doppler. Systolic (Sm), early, and late diastolic mitral annular velocities were measured with the use of colour coded Doppler tissue imaging. Results During a median follow up of 32 months (range 24–38 months in survivors), 34 patients died and one underwent heart transplantation. Sm velocity (hazard ratio (HR) 0.648, 95% confidence interval (CI) 0.463 to 0.907, p  =  0.011), diastolic arterial pressure (HR 0.965, 95% CI 0.938 to 0.993, p  =  0.015), serum creatinine (HR 1.006, 95% CI 1.001 to 1.011, p  =  0.023), LV ejection fraction (HR 0.945, 95% CI 0.899 to 0.992, p  =  0.024), age (HR 1.035, 95% CI 1.000 to 1.071, p  =  0.052), LV end systolic volume index (HR 1.009, 95% CI 0.999 to 1.019, p  =  0.067), and restrictive pattern of transmitral flow (HR 0.543, 95% CI 0.278 to 1.061, p  =  0.074) predicted the outcome of death or transplantation on univariate analysis. On multivariate analysis, only Sm velocity (HR 0.648, 95% CI 0.460 to 0.912, p  =  0.013) and diastolic arterial pressure (HR 0.966, 95% CI 0.938 to 0.994, p  =  0.016) emerged as independent predictors of outcome. Conclusions In patients with CHF and LV systolic dysfunction despite optimal pharmacological treatment, the strongest independent echocardiographic predictor of prognosis was Sm velocity measured with quantitative colour coded Doppler tissue imaging. PMID:16251233

Modelling passive diastolic mechanics with quantitative MRI of cardiac structure and function.

PubMed

Wang, Vicky Y; Lam, H I; Ennis, Daniel B; Cowan, Brett R; Young, Alistair A; Nash, Martyn P

2009-10-01

The majority of patients with clinically diagnosed heart failure have normal systolic pump function and are commonly categorized as suffering from diastolic heart failure. The left ventricle (LV) remodels its structure and function to adapt to pathophysiological changes in geometry and loading conditions, which in turn can alter the passive ventricular mechanics. In order to better understand passive ventricular mechanics, a LV finite element (FE) model was customized to geometric data segmented from in vivo tagged magnetic resonance images (MRI) data and myofibre orientation derived from ex vivo diffusion tensor MRI (DTMRI) of a canine heart using nonlinear finite element fitting techniques. MRI tissue tagging enables quantitative evaluation of cardiac mechanical function with high spatial and temporal resolution, whilst the direction of maximum water diffusion in each voxel of a DTMRI directly corresponds to the local myocardial fibre orientation. Due to differences in myocardial geometry between in vivo and ex vivo imaging, myofibre orientations were mapped into the geometric FE model using host mesh fitting (a free form deformation technique). Pressure recordings, temporally synchronized to the tagging data, were used as the loading constraints to simulate the LV deformation during diastole. Simulation of diastolic LV mechanics allowed us to estimate the stiffness of the passive LV myocardium based on kinematic data obtained from tagged MRI. Integrated physiological modelling of this kind will allow more insight into mechanics of the LV on an individualized basis, thereby improving our understanding of the underlying structural basis of mechanical dysfunction under pathological conditions.

Hypothyroidism leads to increased collagen-based stiffness and re-expression of large cardiac titin isoforms with high compliance.

PubMed

Wu, Yiming; Peng, Jun; Campbell, Kenneth B; Labeit, Siegfried; Granzier, Henk

2007-01-01

Because long-term hypothyroidism results in diastolic dysfunction, we investigated myocardial passive stiffness in hypothyroidism and focused on the possible role of titin, an important determinant of diastolic stiffness. A rat model of hypothyroidism was used, obtained by administering propylthiouracil (PTU) for times that varied from 1 month (short-term) to 4 months (long-term). Titin expression was determined by transcript analysis, gel electrophoresis and immunoelectron microscopy. Diastolic function was measured at the isolated heart, skinned muscle, and cardiac myocyte levels. We found that hypothyroidism resulted in expression of a large titin isoform, the abundance of which gradually increased with time to become the most dominant isoform in long-term hypothyroid rats. This isoform co-migrates on high-resolution gels with fetal cardiac titin. Transcript analysis on myocardium of long-term PTU rats, provided evidence for expression of additional PEVK and Ig domain exons, similar to what has been described in fetal myocardium. Consistent with the expression of a large titin isoform, titin-based restoring and passive forces were significantly reduced in single cardiac myocytes and muscle strips of long-term hypothyroid rats. Overall muscle stiffness and LV diastolic wall stiffness were increased, however, due to increased collagen-based stiffness. We conclude that long term hypothyroidism triggers expression of a large cardiac titin isoform and that the ensuing reduction in titin-based passive stiffness functions as a compensatory mechanism to reduce LV wall stiffness.

The endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) predicts LV mass independent of afterload.

PubMed

Sverdlov, A L; Ngo, D T M; Nightingale, A K; Rajendran, S; Mishra, K; Heresztyn, T; Ritchie, R H; Marwick, T H; Frenneaux, M P; Horowitz, J D

2011-06-30

Nitric oxide (NO) is a modulator of left ventricular hypertrophy (LVH) and myocardial relaxation. The impact of NO availability on development of LVH has never been demonstrated in humans. We tested the hypotheses that elevation of asymmetric dimethylarginine (ADMA) concentrations (biochemical marker of decreased NO generation), and impairment of vascular responsiveness to NO donor GTN, would each predict the presence of LVH and associated LV diastolic dysfunction in a normal aging population. In 74 subjects aged 68±6 years, LV volumes and mass indexed to height(2.7) (LVMI) were calculated from cardiac MRI. Despite the absence of clinically-defined LVH, there was a relationship (r=0.29; p=0.01) between systolic BP and LVMI. Both elevation of ADMA levels to the highest quartile or impairment of GTN responsiveness (determined by applanation tonometry) to the lowest quartile were determinants of LVMI independent of systolic BP (p=0.01 and p=0.03, respectively). Filling pressure (E/E' ratio from echocardiography) was increased in patients with impaired vascular NO responsiveness (p<0.05) irrespective of LVMI. ADMA remained a significant determinant of LVMI on multivariate analysis. These data imply that NO bioavailability within the myocardium modulates earliest stages of LVH development and facilitates development of diastolic dysfunction at a given LV mass. Copyright © 2011. Published by Elsevier Inc.

Doppler-derived myocardial performance index in patients with impaired left ventricular relaxation and preserved systolic function.

PubMed

Fernandes, José Maria G; Rivera, Ivan Romero; de Oliveira Romão, Benício; Mendonça, Maria Alayde; Vasconcelos, Miriam Lira Castro; Carvalho, Antônio Carlos; Campos, Orlando; De Paola, Angelo Amato V; Moisés, Valdir A

2009-09-01

The Doppler-derived myocardial performance index (MPI) has been used in the evaluation of left ventricular (LV) function in several diseases. In patients with isolated diastolic dysfunction, the diagnostic utility of this index remains unclear. The aim of this study was to determine the diagnostic utility of MPI in patients with systemic hypertension, impaired LV relaxation, and normal ejection fraction. Thirty hypertensive patients with impaired LV relaxation were compared to 30 control subjects. MPI and its components, isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), and the ejection time (ET), were measured from LV outflow and mitral inflow Doppler velocity profiles. MPI was higher in patients than in control subjects (0.45 +/- 0.13 vs 0.37 +/- 0.07 P < 0.0029). The increase in MPI was due to the prolongation of IRT without significant change of ICT and ET. MPI cutoff value of > or =0.40 identified impaired LV relaxation with a sensitivity of 63% and specificity of 70% while an IRT >94 ms had a sensitivity of 67% and specificity of 80%. Multivariate analysis identified relative wall thickness, mitral early filling wave velocity (E), and systolic myocardial velocity (Sm) as independent predictors of MPI in patients with hypertension. MPI was increase in patients with hypertension, diastolic dysfunction, and normal ejection fraction but was not superior to IRT to detect impaired LV relaxation.

Asymptomatic cardiovascular manifestations in diabetes mellitus: left ventricular diastolic dysfunction and silent myocardial ischemia.

PubMed

Seferović-Mitrović, Jelena P; Lalić, Nebojsa M; Vujisić-Tesić, Bosiljka; Lalić, Katarina; Jotić, Aleksandra; Ristić, Arsen D; Giga, Vojislav; Tesić, Milorad; Milić, Natasa; Lukić, Ljiljana; Milicić, Tanja; Singh, Sandra; Seferović, Petar M

2011-01-01

Several cardiovascular manifestations in patients with diabetes may be asymptomatic. Left ventricular diastolic dysfunction (LVDD) is considered to be the earliest metabolic myocardial lesion in these patients, and can be diagnosed with tissue Doppler echocardiography. Silent myocardial ischemia (SMI) is a characteristic and frequently described form of ischemic heart disease in patients with diabetes. Objective The aim of the study was to assess the prevalence of LVDD and SMI in patients with type 2 diabetes, as well as to compare demographic, clinical, and metabolic data among defined groups (patients with LVDD, patients with SMI and patients with type 2 diabetes, without LVDD and SMI). We investigated 104 type 2 diabetic patients (mean age 55.4 +/- 9.1 years, 64.4% males) with normal blood pressure, prehypertension and arterial hypertension stage I. Study design included basic laboratory assessment and cardiological workup (transthoracic echocardiography and tissue Doppler, as well as the exercise stress echocardiography). LVDD was diagnosed in twelve patients (11.5%), while SMI was revealed in six patients (5.8%). Less patients with LVDD were using metformin, in comparison to other two groups (chi2 =12.152; p=0.002). Values of HDL cholesterol (F=4.515; p=0.013) and apolipoprotein A1 (F=5.128; p= 0.008) were significantly higher in patients with LVDD. The study confirmed asymptomatic cardiovascular complications in 17.3% patients with type 2 diabetes.

Heart involvement in cystic fibrosis: A specific cystic fibrosis-related myocardial changes?

PubMed

Labombarda, Fabien; Saloux, Eric; Brouard, Jacques; Bergot, Emmanuel; Milliez, Paul

2016-09-01

Cystic fibrosis is a complex multi-systemic chronic disease characterized by progressive organ dysfunction with development of fibrosis, possibly affecting the heart. Over the last four decades pathological, experimental, and clinical evidence points towards the existence of a specific myocardial involvement in cystic fibrosis. Multi-modality cardiac imaging, especially recent echocardiographic techniques, evidenced diastolic and/or systolic ventricular dysfunction in cystic fibrosis leading to the concept of a cystic fibrosis-related cardiomyopathy. Hypoxemia and inflammation are among the most important factors for heart involvement in cystic fibrosis. Cystic Fibrosis Transmembrane Regulator was found to be involved in the regulation of cardiomyocyte contraction and may also account for cystic fibrosis-related myocardial dysfunction. This review, mainly focused on echocardiographic studies, seeks to synthesize the existing literature for and against the existence of heart involvement in cystic fibrosis, its mechanisms and prognostic implications. Careful investigation of the heart function may be helpful for risk stratification and therapeutic decisions in patients with cystic fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early detection of myocardial dysfunction using two-dimensional speckle tracking echocardiography in a young cat with hypertrophic cardiomyopathy

PubMed Central

Mochizuki, Yohei; Yoshimatsu, Hiroki; Niina, Ayaka; Teshima, Takahiro; Matsumoto, Hirotaka; Koyama, Hidekazu

2018-01-01

Case summary A 5-month-old intact female Scottish Fold cat was presented for cardiac evaluation. Careful auscultation detected a slight systolic murmur (Levine I/VI). The findings of electrocardiography, thoracic radiography, non-invasive blood pressure measurements and conventional echocardiographic studies were unremarkable. However, two-dimensional speckle tracking echocardiography revealed abnormalities in myocardial deformations, including decreased early-to-late diastolic strain rate ratios in longitudinal, radial and circumferential directions, and deteriorated segmental systolic longitudinal strain. At the follow-up examinations, the cat exhibited echocardiographic left ventricular hypertrophy and was diagnosed with hypertrophic cardiomyopathy using conventional echocardiography. Relevance and novel information This is the first report on the use of two-dimensional speckle tracking echocardiography for the early detection of myocardial dysfunction in a cat with hypertrophic cardiomyopathy; the myocardial dysfunction was detected before the development of hypertrophy. The findings from this case suggest that two-dimensional speckle tracking echocardiography can be useful for myocardial assessment when conventional echocardiographic and Doppler findings are ambiguous. PMID:29449957

Evolution of echocardiography in subclinical detection of cancer therapy-related cardiac dysfunction.

PubMed

Moudgil, Rohit; Hassan, Saamir; Palaskas, Nicolas; Lopez-Mattei, Juan; Banchs, Jose; Yusuf, Syed Wamique

2018-05-11

Cancer therapies have resulted in increased survivorship in oncological patients. However, the benefits have been marred by the development of premature cardiovascular disease. The current definition outlines measurement of ejection fraction as a mean to diagnose cancer therapeutic-related cardiac dysfunction (CTRCD); however, up to 58% of the patients do not regain their cardiac function after the CTRCD diagnosis, despite therapeutic interventions. Therefore, there has been a growing interest in the markers for early myocardial changes (ie, changes with normal left ventricular ejection fraction [LVEF]) that may predict the development of subsequent left ventricular ejection fraction reduction or progression to heart failure. This review will highlight the use of diastolic parameters, tissue Doppler imaging (TDI), and speckle tracking echocardiogram (STE) as emerging technologies which can potentially detect cardiac dysfunction thereby stratifying patients for cardioprotective therapies. The goal of this manuscript was to highlight the concepts and discuss the current controversies surrounding these echocardiographic imaging modalities. © 2018 Wiley Periodicals, Inc.

Disturbed left and right ventricular kinetic energy in patients with repaired tetralogy of Fallot: pathophysiological insights using 4D-flow MRI.

PubMed

Sjöberg, Pia; Bidhult, Sebastian; Bock, Jelena; Heiberg, Einar; Arheden, Håkan; Gustafsson, Ronny; Nozohoor, Shahab; Carlsson, Marcus

2018-04-17

Indications for pulmonary valve replacement (PVR) in patients with pulmonary regurgitation (PR) after repaired tetralogy of Fallot (rToF) are debated. We aimed to compare right (RV) and left ventricular (LV) kinetic energy (KE) measured by 4D-flow magnetic resonance imaging (MRI) in patients to controls, to further understand the pathophysiological effects of PR. Fifteen patients with rToF with PR > 20% and 14 controls underwent MRI. Ventricular volumes and KE were quantified from cine MRI and 4D-flow, respectively. Lagrangian coherent structures were used to discriminate KE in the PR. Restrictive RV physiology was defined as end-diastolic forward flow. LV systolic peak KE was lower in rToF, 2.8 ± 1.1 mJ, compared to healthy volunteers, 4.8 ± 1.1 mJ, p < 0.0001. RV diastolic peak KE was higher in rToF (7.7 ± 4.3 mJ vs 3.1 ± 1.3 mJ, p = 0.0001) and the difference most pronounced in patients with non-restrictive RV physiology. KE was primarily located in the PR volume at the time of diastolic peak KE, 64 ± 17%. This is the first study showing disturbed KE in patients with rToF and PR, in both the RV and LV. The role of KE as a potential early marker of ventricular dysfunction to guide intervention needs to be addressed in future studies. • Kinetic energy (KE) reflects ventricular performance • KE is a potential marker of ventricular dysfunction in Fallot patients • KE is disturbed in both ventricles in patients with tetralogy of Fallot • KE contributes to the understanding of the pathophysiology of pulmonary regurgitation • Lagrangian coherent structures enable differentiation of ventricular inflows.

Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic-Banded Mini-Swine.

PubMed

Hiemstra, Jessica A; Lee, Dong I; Chakir, Khalid; Gutiérrez-Aguilar, Manuel; Marshall, Kurt D; Zgoda, Pamela J; Cruz Rivera, Noelany; Dozier, Daniel G; Ferguson, Brian S; Heublein, Denise M; Burnett, John C; Scherf, Carolin; Ivey, Jan R; Minervini, Gianmaria; McDonald, Kerry S; Baines, Christopher P; Krenz, Maike; Domeier, Timothy L; Emter, Craig A

2016-04-20

Cyclic guanosine monophosphate-protein kinase G-phosphodiesterase 5 signaling may be disturbed in heart failure (HF) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was to manipulate cyclic guanosine monophosphate signaling using the dipeptidyl-peptidase 4 inhibitor saxagliptin and phosphodiesterase 5 inhibitor tadalafil. We hypothesized that preservation of cyclic guanosine monophosphate cGMP signaling would attenuate pathological cardiac remodeling and improve left ventricular (LV) function. We assessed LV hypertrophy and function at the organ and cellular level in aortic-banded pigs. Concentric hypertrophy was equal in all groups, but LV collagen deposition was increased in only HF animals. Prevention of fibrotic remodeling by saxagliptin and tadalafil was correlated with neuropeptide Y plasma levels. Saxagliptin better preserved integrated LV systolic and diastolic function by maintaining normal LV chamber volumes and contractility (end-systolic pressure-volume relationship, preload recruitable SW) while preventing changes to early/late diastolic longitudinal strain rate. Function was similar to the HF group in tadalafil-treated animals including increased LV contractility, reduced chamber volume, and decreased longitudinal, circumferential, and radial mechanics. Saxagliptin and tadalafil prevented a negative cardiomyocyte shortening-frequency relationship observed in HF animals. Saxagliptin increased phosphodiesterase 5 activity while tadalafil increased cyclic guanosine monophosphate levels; however, neither drug increased downstream PKG activity. Early mitochondrial dysfunction, evident as decreased calcium-retention capacity and Complex II-dependent respiratory control, was present in both HF and tadalafil-treated animals. Both saxagliptin and tadalafil prevented increased LV collagen deposition in a manner related to the attenuation of increased plasma neuropeptide Y levels. Saxagliptin appears superior for treating heart failure with preserved ejection fraction, considering its comprehensive effects on integrated LV systolic and diastolic function. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Evaluation of Cardiovascular Risk Factors in the Wistar Audiogenic Rat (WAR) Strain

PubMed Central

Fazan, Rubens; Silva, Carlos Alberto A.; Oliveira, José Antônio Cortes; Salgado, Helio Cesar; Montano, Nicola; Garcia-Cairasco, Norberto

2015-01-01

Introduction Risk factors for life-threatening cardiovascular events were evaluated in an experimental model of epilepsy, the Wistar Audiogenic Rat (WAR) strain. Methods We used long-term ECG recordings in conscious, one year old, WAR and Wistar control counterparts to evaluate spontaneous arrhythmias and heart rate variability, a tool to assess autonomic cardiac control. Ventricular function was also evaluated using the pressure-volume conductance system in anesthetized rats. Results Basal RR interval (RRi) was similar between WAR and Wistar rats (188±5 vs 199±6 ms). RRi variability strongly suggests that WAR present an autonomic imbalance with sympathetic overactivity, which is an isolated risk factor for cardiovascular events. Anesthetized WAR showed lower arterial pressure (92±3 vs 115±5 mmHg) and exhibited indices of systolic dysfunction, such as higher ventricle end-diastolic pressure (9.2±0.6 vs 5.6±1 mmHg) and volume (137±9 vs 68±9 μL) as well as lower rate of increase in ventricular pressure (5266±602 vs 7320±538 mmHg.s-1). Indices of diastolic cardiac function, such as lower rate of decrease in ventricular pressure (-5014±780 vs -7766±998 mmHg.s-1) and a higher slope of the linear relationship between end-diastolic pressure and volume (0.078±0.011 vs 0.036±0.011 mmHg.μL), were also found in WAR as compared to Wistar control rats. Moreover, Wistar rats had 3 to 6 ventricular ectopic beats, whereas WAR showed 15 to 30 ectopic beats out of the 20,000 beats analyzed in each rat. Conclusions The autonomic imbalance observed previously at younger age is also present in aged WAR and, additionally, a cardiac dysfunction was also observed in the rats. These findings make this experimental model of epilepsy a valuable tool to study risk factors for cardiovascular events in epilepsy. PMID:26029918

N-terminal pro-brain natriuretic peptide is related with coronary flow velocity reserve and diastolic dysfunction in patients with asymmetric hypertrophic cardiomyopathy.

PubMed

Tesic, Milorad; Seferovic, Jelena; Trifunovic, Danijela; Djordjevic-Dikic, Ana; Giga, Vojislav; Jovanovic, Ivana; Petrovic, Olga; Marinkovic, Jelena; Stankovic, Sanja; Stepanovic, Jelena; Ristic, Arsen; Petrovic, Milan; Mujovic, Nebojsa; Vujisic-Tesic, Bosiljka; Beleslin, Branko; Vukcevic, Vladan; Stankovic, Goran; Seferovic, Petar

2017-10-01

The relations of elevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac ischemia in hypertrophic cardiomyopathy (HCM) patients is uncertain. Therefore we designed the study with the following aims: (1) to analyze plasma concentrations of NT-pro-BNP in various subsets of HCM patients; (2) to reveal the correlations of NT-pro-BNP, myocardial ischemia, and diastolic dysfunction; (3) to assess predictors of the elevated plasma levels of NT-pro-BNP. In 61 patients (mean age 48.9±16.3 years; 26 male) with asymmetric HCM plasma levels of NT-pro-BNP were obtained. Standard transthoracic examination, tissue Doppler echocardiography with measurement of transthoracic coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD) was done. Mean natural logarithm value of NT-pro-BNP was 7.11±0.95pg/ml [median value 1133 (interquartile range 561-2442)pg/ml]. NT-pro-BNP was significantly higher in patients with higher NYHA class, in obstructive HCM, more severe mitral regurgitation, increased left atrial volume index (LAVI), presence of calcified mitral annulus, elevated left ventricular (LV) filling pressure and in decreased CFVR. Levels of NT-pro-BNP significantly correlated with the ratio of E/e' (r=0.534, p<0.001), LV outflow tract gradient (r=0.503, p=0.024), LAVI (r=0.443, p<0.001), while inversely correlated with CFVR LAD (r=-0.569, p<0.001). When multivariate analysis was done only CFVR LAD and E/e' emerged as independent predictors of NT-pro-BNP. Plasma levels of NT-pro-BNP were significantly higher in HCM patients with more advanced disease. Elevated NT-pro-BNP not only reflects the diastolic impairment of the LV, but it might also be the result of cardiac ischemia in patients with HCM. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Naringin Improves Diet-Induced Cardiovascular Dysfunction and Obesity in High Carbohydrate, High Fat Diet-Fed Rats

PubMed Central

Alam, Md. Ashraful; Kauter, Kathleen; Brown, Lindsay

2013-01-01

Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day) improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats. PMID:23446977

The left heart can only be as good as the right heart: determinants of function and dysfunction of the right ventricle.

PubMed

Magder, Sheldon

2007-12-01

Discussions of cardiac physiology and pathophysiology most often emphasise the function of the left heart. However, right heart dysfunction plays an important role in critically ill patients and is often not recognised. This is probably because the role of the right ventricle is for generating flow more than pressure, and flow is not easy to evaluate. Of importance, when right ventricular function limits cardiac output, assessing left ventricular function gives little indication of overall cardiac performance. It has recently become evident that the right ventricle also has different genetic origins and characteristics from the left ventricle. The right and left ventricles interact through series effects, diastolic interactions and systolic interactions. The mechanisms of these, and their physiological and pathological significance are discussed.

[The state of carotid arteries in young men with arterial hypertension].

PubMed

Safarova, A F; Iurtaeva, V R; Kotovskaia, Iu V; Kobalava, Zh D

2012-01-01

To study elastic properties of carotid arteries in young men with arterial hypertension (AH). We examined men aged 18-25 years (mean 21.1+/-0.14 years): 36 with normal blood pressure (BP), 123 with stable and 51 with unstable AH. Parameters studied comprised intima-media thickness (IMT) of carotid arteries, their M-mode measured maximal systolic and minimal diastolic diameters (Ds and Dd), stiffness of common carotid artery (CCA) wall determined on the basis of analysis of elasticity and distensibility coefficients (CC and DC), Peterson's and Young's modules of elasticity (Ep and E), and index of flow deformation (CS). Compared with young men with normal BP and unstable AH patients with stable AH had abnormal elastic properties of CCA and increased IMT. Stable AH in young men is associated with signs of remodeling of CCA walls and increase of their rigidity.

Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

PubMed Central

El Massioui, Nicole; Lamirault, Charlotte; Yagüe, Sara; Adjeroud, Najia; Garces, Daniel; Maillard, Alexis; Tallot, Lucille; Yu-Taeger, Libo; Riess, Olaf; Allain, Philippe; Nguyen, Huu Phuc; von Hörsten, Stephan; Doyère, Valérie

2016-01-01

Cognitive deficits associated with Huntington disease (HD) are generally dominated by executive function disorders often associated with disinhibition and impulsivity/compulsivity. Few studies have directly examined symptoms and consequences of behavioral disinhibition in HD and its relation with decision-making. To assess the different forms of impulsivity in a transgenic model of HD (tgHD rats), two tasks assessing cognitive/choice impulsivity were used: risky decision-making with a rat gambling task (RGT) and intertemporal choices with a delay discounting task (DD). To assess waiting or action impulsivity the differential reinforcement of low rate of responding task (DRL) was used. In parallel, the volume as well as cellular activity of the amygdala was analyzed. In contrast to WT rats, 15 months old tgHD rats exhibited a poor efficiency in the RGT task with difficulties to choose advantageous options, a steep DD curve as delays increased in the DD task and a high rate of premature and bursts responses in the DRL task. tgHD rats also demonstrated a concomitant and correlated presence of both action and cognitive/choice impulsivity in contrast to wild type (WT) animals. Moreover, a reduced volume associated with an increased basal cellular activity of the central nucleus of amygdala indicated a dysfunctional amygdala in tgHD rats, which could underlie inhibitory dyscontrol. In conclusion, tgHD rats are a good model for impulsivity disorder that could be used more widely to identify potential pharmacotherapies to treat these invasive symptoms in HD. PMID:27833538

Hypertension as a risk factor for heart failure.

PubMed

Kannan, Arun; Janardhanan, Rajesh

2014-07-01

Hypertension remains a significant risk factor for development of congestive heart failure CHF), with various mechanisms contributing to both systolic and diastolic dysfunction. The pathogenesis of myocardial changes includes structural remodeling, left ventricular hypertrophy, and fibrosis. Activation of the sympathetic nervous system and renin-angiotensin system is a key contributing factor of hypertension, and thus interventions that antagonize these systems promote regression of hypertrophy and heart failure. Control of blood pressure is of paramount importance in improving the prognosis of patients with heart failure.

Effects of Calorie Restriction on Cardioprotection and Cardiovascular Health

PubMed Central

Ahmet, Ismayil; Tae, Hyun-Jin; de Cabo, Rafael; Lakatta, Edward G.; Talan, Mark I.

2011-01-01

Multiple health benefits of calorie restriction (CR) and alternate day fasting (ADF) regimens are widely recognized. Experimental data concerning the effects of calorie restriction on cardiac health are more controversial, ranging from evidence that ADF protects heart from ischemic damage but results in developing of diastolic dysfunction, to reports that CR ameliorates the age-associated diastolic dysfunction. Here we investigated the effects of chronic CR on morphology and function of the cardiovascular system of aged rats and cardioprotective effect of CR against ischemic damage in the experimental rat model of MI. Cardiovascular fitness of 24-mo old Fisher 344 rats maintained through life on ad libitum (AL) or CR diets was extensively evaluated via echocardiography, dobutamine stress test, pressure-volume loop analyses, pulse wave velocity measurements, and histology. Groups of 2-mo old AL and 29-mo old CR rats were studied for comparison. Myocardial infarction (MI) was induced by a permanent ligation of the anterior descending coronary artery in 5-mo old rats maintained for 3 months on CR or AL. MI size was evaluated histologically 24 hrs following coronary ligation. Cardiac remodeling was followed-up via echocardiography. Age-associated changes in 24-mo old rats consisted of 33% increase of fibrosis in the myocardium and more than 2 fold increase of the collagen in the tunica media of the aorta. There was a significant decrease in the density and total number of cardiomyocytes, while their size was increased. These morphological changes were manifested in a decline of systolic and diastolic cardiac function, increase of left ventricular and aortic stiffness, and arterio-ventricular uncoupling. Tachycardic response to dobutamine challenge was absent in the old rats. Compared to AL rats, 24-mo old CR rats had reduced levels of cardiac and aortic fibrosis, increased density of cardiomyocytes that were smaller in size, attenuated diastolic dysfunction, normal systolic function and arterio-ventricular coupling. Tachycardic response to dobutamine was also intact in CR 24-mo old rats and aortic stiffness was reduced. Adjustment for body weight differences through ratiometric or allometric scaling did not affect the overall pattern of differences between AL and CR rats. Attenuation of morphological and functional age-associated changes in 24-mo old CR rats either was not observed at all or was smaller in 29-mo old CR rats. Size of MI induced by a permanent coronary ligation as well as post-MI cardiac remodeling and function were similar in CR and AL rats. CR does not increase tolerance of myocardium to ischemic damage, but attenuates the age-associated changes in the heart and major vessels. The attenuation of age-associated changes by CR cannot be explained by the effect of lower body weight but are attributable to more intimate cellular mechanisms of CR itself. Attenuation of age-associated changes by CR waned with advancing age, and is consistent with the idea that CR postponed senescence. PMID:21586294

ASSOCIATIONS OF MACRO- AND MICROVASCULAR ENDOTHELIAL DYSFUNCTION WITH SUBCLINICAL VENTRICULAR DYSFUNCTION IN END-STAGE RENAL DISEASE

PubMed Central

Dubin, Ruth F; Guajardo, Isabella; Ayer, Amrita; Mills, Claire; Donovan, Catherine; Beussink, Lauren; Scherzer, Rebecca; Ganz, Peter; Shah, Sanjiv J

2016-01-01

Patients with end-stage renal disease (ESRD) suffer high rates of heart failure and cardiovascular mortality, and we lack a thorough understanding of what, if any, modifiable factors contribute to cardiac dysfunction in these high-risk patients. In order to evaluate endothelial function as a potentially modifiable cause of cardiac dysfunction in ESRD, we investigated cross-sectional associations of macro- and microvascular dysfunction with left and right ventricular dysfunction in a well-controlled ESRD cohort. We performed comprehensive echocardiography, including tissue Doppler imaging and speckle tracking echocardiography of the left and right ventricle, in 149 ESRD patients enrolled in an ongoing prospective, observational study. Of these participants, 123 also underwent endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (macrovascular function). Microvascular function was measured as the velocity time integral (VTI) of hyperemic blood flow following cuff deflation. Impaired FMD was associated with higher LV mass, independently of age and blood pressure: per two-fold lower FMD, LV mass was 4.1% higher (95%CI [0.49, 7.7], p=0.03). After adjustment for demographics, blood pressure, comorbidities and medications, a two-fold lower VTI was associated with 9.5% higher E/e’ ratio (95% CI [1.0, 16], p=0.03) and 6.7% lower absolute RV longitudinal strain (95% CI [2.0, 12], p=0.003). Endothelial dysfunction is a major correlate of cardiac dysfunction in ESRD, particularly diastolic and right ventricular dysfunction, in patients whose volume status is well-controlled. Future investigations are needed to determine whether therapies targeting the vascular endothelium could improve cardiac outcomes in ESRD. PMID:27550915

ACE insertion/deletion polymorphism and submaximal exercise hemodynamics in postmenopausal women.

PubMed

Hagberg, James M; McCole, Steve D; Brown, Michael D; Ferrell, Robert E; Wilund, Kenneth R; Huberty, Andrea; Douglass, Larry W; Moore, Geoffrey E

2002-03-01

We sought to determine whether the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism is associated with submaximal exercise cardiovascular hemodynamics. Postmenopausal healthy women (20 sedentary, 20 physically active, 22 endurance athletes) had cardiac output (acetylene rebreathing) measured during 40, 60, and 80% VO(2 max) exercise. The interaction of ACE genotype and habitual physical activity (PA) level was significantly associated with submaximal exercise systolic blood pressure, with only sedentary women exhibiting differences among genotypes. No significant effects of ACE genotype or its interaction with PA levels was observed for submaximal exercise diastolic blood pressure. ACE genotype was significantly associated with submaximal exercise heart rate (HR) with ACE II having approximately 10 beats/min higher HR than ACE ID/DD genotype women. ACE genotype did not interact significantly with habitual PA level to associate with submaximal exercise HR. ACE genotype was not independently, but was interactively with habitual PA levels, associated with differences in submaximal exercise cardiac output and stroke volume. For cardiac output, ACE II genotype women athletes had ~25% greater cardiac output than ACE DD genotype women athletes, whereas for stroke volume genotype-dependent differences were observed in both the physically active and athletic women. ACE genotype was not significantly associated, either independently or interactively with habitual PA levels, with submaximal exercise total peripheral resistance or arteriovenous O(2) difference. Thus the common ACE locus polymorphic variation is associated with many submaximal exercise cardiovascular hemodynamic responses.

Validation and use of the Finometer for blood pressure measurement in normal, hypertensive and pre-eclamptic pregnancy.

PubMed

Elvan-Taşpinar, Ayten; Uiterkamp, Leonore A; Sikkema, J Marko; Bots, Michiel L; Koomans, Hein A; Bruinse, Hein W; Franx, Arie

2003-11-01

Although a large variety of automated blood pressure devices are available, only some have been validated for use in clinical practice. The British Hypertension Society (BHS) recommends separate validation of automated devices in special subgroups, e.g. the elderly and pregnant women. The aim of this study was to compare the Finometer (FM) and the earlier validated SpaceLabs 90207 (SL) with standard auscultatory blood pressure measurements in normal, pre-eclamptic and hypertensive pregnancy, following the guidelines of the BHS and the Association for the Advancement of Medical Instrumentation (AAMI). The total study group consisted of 123 pregnant women, of whom were 54 normotensive, 31 pre-eclamptic and 38 hypertensive. Automated readings with the FM and SL were compared with auscultatory blood pressure measurements. Bland-Altman plots, BHS grades, mean pressure differences and 95% limits of agreement were used for analysis. Bland-Altman plots showed a wide scatter of the pressure differences between auscultatory and automated measurements. FM achieved BHS grades C/D, C/B, D/D and D/D in the total, normotensive, pre-eclamptic and hypertensive group, respectively. The AAMI criteria were only met for diastolic blood pressure in the normotensive group. For SL almost identical BHS grades and 95% limits of agreement as compared to our earlier study were found. The accuracy and precision of the Finometer are not sufficient for determination of absolute blood pressure levels in individual pregnant women. Our present findings on the SpaceLabs 90207 reconfirm our earlier results.

Angiotensin-converting enzyme insertion/deletion polymorphism association with obesity and some related disorders in Egyptian females: a case-control observational study.

PubMed

Motawi, Tarek K; Shaker, Olfat G; Shahin, Nancy N; Ahmed, Nancy M

2016-01-01

According to the WHO report in 2015, obesity is the fifth leading cause of death worldwide, and the prevalence of Egyptian female obesity is 37.5 %. Since obesity is highly influenced by genetics, and adipose tissue renin-angiotensin system is over-activated in obesity, the effect of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on obesity and related disorders was studied in several populations, because of its effect on ACE activity. Our objective was to study the association of ACE I/D polymorphism with obesity and certain related disorders, namely hypertension, insulin resistance and metabolic syndrome, in Egyptian females. Eighty female volunteers were recruited, blood pressure and body measurements were recorded and a fasting blood sample was obtained for the quantitation of glucose, lipid profile, insulin, leptin and identification of ACE I/D polymorphs. Subjects were grouped based on hypertension and obesity states. Comparisons of continuous parameters were made with independent sample t -test between two groups. The frequencies of ACE genotypes and alleles, and the association between gene polymorphism and metabolic parameters were assessed using chi-square or Fisher's exact test. Genotype frequencies were in Hardy-Weinberg equilibrium for all groups. Genotype distribution did not differ significantly between controls and cases of all the studied disorders. Although DD carriers had apparently higher parameters of blood pressure, lipid profile and insulin resistance, only diastolic blood pressure was almost significant ( p  = 0.057). I-carriers were significantly less susceptible to hypertension than DD carriers having normal waist/hip ratio ( p  = 0.007, OR = 17.29, CI = 1.81-164.96) and normal conicity index ( p  = 0.024, OR = 7.00, CI = 1.36-35.93). In DD genotype carriers, a significant association was found between insulin resistance and high body mass index ( p  = 0.004, OR = 8.89, CI = 1.94-40.71), waist circumference ( p  = 0.003, OR = 9.63, CI = 2.14-43.36) and waist/height ratio ( p  = 0.034, OR = 6.86, CI = 1.25-37.61), although the variations in percentages between DD and I-carriers were not high enough to conclude an effect of ACE I/D on such an association. In this sample of Egyptian females, ACE I/D polymorphism was not significantly associated with obesity nor with any of its related disorders studied. The I allele seemed protective against hypertension in subjects with normal, not high, waist/hip ratio and conicity index compared to DD genotype carriers.

Simulation of Ventricular, Cavo-Pulmonary, and Biventricular Ventricular Assist Devices in Failing Fontan.

PubMed

Di Molfetta, Arianna; Amodeo, Antonio; Fresiello, Libera; Trivella, Maria Giovanna; Iacobelli, Roberta; Pilati, Mara; Ferrari, Gianfranco

2015-07-01

Considering the lack of donors, ventricular assist devices (VADs) could be an alternative to heart transplantation for failing Fontan patients, in spite of the lack of experience and the complex anatomy and physiopathology of these patients. Considering the high number of variables that play an important role such as type of Fontan failure, type of VAD connection, and setting (right VAD [RVAD], left VAD [LVAD], or biventricular VAD [BIVAD]), a numerical model could be useful to support clinical decisions. The aim of this article is to develop and test a lumped parameter model of the cardiovascular system simulating and comparing the VAD effects on failing Fontan. Hemodynamic and echocardiographic data of 10 Fontan patients were used to simulate the baseline patients' condition using a dedicated lumped parameter model. Starting from the simulated baseline and for each patient, a systolic dysfunction, a diastolic dysfunction, and an increment of the pulmonary vascular resistance were simulated. Then, for each patient and for each pathology, the RVAD, LVAD, and BIVAD implantations were simulated. The model can reproduce patients' baseline well. In the case of systolic dysfunction, the LVAD unloads the single ventricle and increases the cardiac output (CO) (35%) and the arterial systemic pressure (Pas) (25%). With RVAD, a decrement of inferior vena cava pressure (Pvci) (39%) was observed with 34% increment of CO, but an increment of the single ventricle external work (SVEW). With the BIVAD, an increment of Pas (29%) and CO (37%) was observed. In the case of diastolic dysfunction, the LVAD increases CO (42%) and the RVAD decreases the Pvci, while both increase the SVEW. In the case of pulmonary vascular resistance increment, the highest CO (50%) and Pas (28%) increment is obtained with an RVAD with the highest decrement of Pvci (53%) and an increment of the SVEW but with the lowest VAD power consumption. The use of numerical models could be helpful in this innovative field to evaluate the effect of VAD implantation on Fontan patients to support patient and VAD type selection personalizing the assistance. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Left ventricular structural and functional characteristics in Cushing's syndrome.

PubMed

Muiesan, Maria Lorenza; Lupia, Mario; Salvetti, Massimo; Grigoletto, Consuelo; Sonino, Nicoletta; Boscaro, Marco; Rosei, Enrico Agabiti; Mantero, Franco; Fallo, Francesco

2003-06-18

This study was designed to evaluate left ventricular (LV) anatomy and function in patients with Cushing's syndrome. A high prevalence of LV hypertrophy and concentric remodeling has been reported in Cushing's syndrome, although no data have been reported on LV systolic and diastolic function. Forty-two consecutive patients with Cushing's syndrome and 42 control subjects, matched for age, gender, and blood pressure, were studied. Left ventricular mass index (LVMI) and relative wall thickness (RWT) were measured by echocardiography, endocardial and midwall fractional shortening (FS) were assessed, and diastolic filling was measured by Doppler transmitral flow. The RWT was significantly greater in Cushing patients than in controls. Left ventricular hypertrophy and concentric remodeling were observed in 10 and 26 patients with Cushing's syndrome, respectively. In Cushing patients, midwall FS was significantly reduced compared with controls (16.2 +/- 3% vs. 21 +/- 4.5%, p = 0.01). The ratio of transmitral E and A flow velocities was reduced and E deceleration time was prolonged in Cushing patients compared with controls (p = 0.03 and p < 0.001, respectively). In patients with Cushing's syndrome, cardiac structural changes are associated with reduced midwall systolic performance and with diastolic dysfunction that may contribute to the high risk of cardiovascular events observed in these patients.

Coronary microvascular function in patients with isolated systolic and combined systolic/diastolic hypertension.

PubMed

Bozbas, Huseyin; Pirat, Bahar; Yildirir, Aylin; Eroglu, Serpil; Simsek, Vahide; Sade, Elif; Atar, Ilyas; Aydinalp, Alp; Ozin, Bulent; Muderrisoglu, Haldun

2012-12-01

Isolated systolic hypertension (ISH) is a common condition in the elderly that is associated with endothelial dysfunction. Concerning the effect of type of hypertension on coronary microvascular function, coronary flow reserve (CFR) in patients with ISH was evaluated and the results were compared with patients with combined systolic/diastolic hypertension (SDH). Seventy-six elderly patients (older than 60 years) who were free of coronary artery disease and diabetes mellitus were enrolled in the study (38 with ISH and 38 with combined SDH). Using transthoracic Doppler echocardiography, CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities. A CFR value of >2 was accepted as normal. The mean age was 68.6±6.3 years and the groups had similar features with regard to demographic and clinical characteristics. Patients with ISH had significantly lower CFR values compared with those with combined SDH (2.22±0.51 vs 2.49±0.56, respectively; P=.03). On multivariate regression analysis, ISH (β=-0.40, P=.004) and dyslipidemia (β=-0.29, P=.04) were the independent predictors of CFR. These findings indicate that CFR, an indicator of coronary microvascular/endothelial function, is impaired more profoundly in patients with ISH than in patients with combined SDH. © 2012 Wiley Periodicals, Inc.

Passive Ventricular Mechanics Modelling Using MRI of Structure and Function

PubMed Central

Wang, V.Y.; Lam, H.I.; Ennis, D.B.; Young, A.A.; Nash, M.P.

2009-01-01

Patients suffering from dilated cardiomyopathy or myocardial infarction can develop left ventricular (LV) diastolic impairment. The LV remodels its structure and function to adapt to pathophysiological changes in geometry and loading conditions and this remodeling process can alter the passive ventricular mechanics. In order to better understand passive ventricular mechanics, a LV finite element model was developed to incorporate physiological and mechanical information derived from in vivo magnetic resonance imaging (MRI) tissue tagging, in vivo LV cavity pressure recording and ex vivo diffusion tensor MRI (DTMRI) of a canine heart. MRI tissue tagging enables quantitative evaluation of cardiac mechanical function with high spatial and temporal resolution, whilst the direction of maximum water diffusion (the primary eigenvector) in each voxel of a DTMRI directly correlates with the myocardial fibre orientation. This model was customized to the geometry of the canine LV during diastasis by fitting the segmented epicardial and endocardial surface data from tagged MRI using nonlinear finite element fitting techniques. Myofibre orientations, extracted from DTMRI of the same heart, were incorporated into this geometric model using a free form deformation methodology. Pressure recordings, temporally synchronized to the tissue tagging MRI data, were used to simulate the LV deformation during diastole. Simulation of the diastolic LV mechanics allowed us to estimate the stiffness of the passive LV myocardium based on kinematic data obtained from tagged MRI. This integrated physiological model will allow more insight into the regional passive diastolic mechanics of the LV on an individualized basis, thereby improving our understanding of the underlying structural basis of mechanical dysfunction in pathological conditions. PMID:18982680

Predictors of Renal Denervation Efficacy in the Treatment of Resistant Hypertension.

PubMed

Ripp, Tatiana M; Mordovin, Victor F; Pekarskiy, Stanislav E; Ryabova, Tamara R; Zlobina, Marina V; Baev, Andrei E; Anfinogenova, Yana; Popov, Sergey V

2015-12-01

The aims of the study were to evaluate the effects of renal sympathetic denervation (RSD) on the heart and to identify the predictors of RSD efficacy in patients with resistant arterial hypertension. The study comprised 60 RSD patients (54.6 ± 9.5 years) who received full-dose antihypertensive therapy (4.1 drugs) including diuretics. Initially, 58.6% of patients had abnormal left ventricular (LV) diastolic function. All patients received echocardiography before and 24 weeks after RSD. Renal sympathetic denervation was achieved through the endovascular radiofrequency ablation (RFA) of the renal arteries. Drug therapy continued for the entire period of observation. After RSD, all patients were retrospectively assigned to two groups: group 1 comprised patients (n = 22; 36.7%) in whom the myocardial mass (MM) of the left ventricle decreased by more than 10 g after RSD; group 2 comprised patients (n = 38; 63.3%) in whom LV MM increased or decreased by less than 10 g. Anthropometry, arterial blood pressure, heart rate, therapy, and LV end-diastolic dimensions (EDD) were comparable in these groups. After RSD, the values of office blood pressure significantly decreased and MM regressed by more than 10 g in 36.7% of patients; LV diastolic function normalized in 31% of patients, and diastolic dysfunction improved in 14% of patients. The study found the associations between the initial LV wall dimensions and LV MM changes. Unlike LV EDD, arterial blood pressure, or heart rate, the initial values of LV wall thickness predicted LV MM regress. #NCT01499810 https://clinicaltrials.gov/ct2/show/NCT01499810.

Left atrial strain: a new parameter for assessment of left ventricular filling pressure.

PubMed

Cameli, Matteo; Mandoli, Giulia Elena; Loiacono, Ferdinando; Dini, Frank Lloyd; Henein, Michael; Mondillo, Sergio

2016-01-01

In order to obtain accurate diagnosis, treatment and prognostication in many cardiac conditions, there is a need for assessment of left ventricular (LV) filling pressure. While systole depends on ejection function of LV, diastole and its disturbances influence filling function and pressures. The commonest condition that represents the latter is heart failure with preserved ejection fraction in which LV ejection is maintained, but diastole is disturbed and hence filling pressures are raised. Significant diastolic dysfunction results in raised LV end-diastolic pressure, mean left atrial (LA) pressure and pulmonary capillary wedge pressure, all referred to as LV filling pressures. Left and right heart catheterization has traditionally been used as the gold standard investigation for assessing these pressures. More recently, Doppler echocardiography has taken over such application because of its noninvasive nature and for being patient friendly. A number of indices are used to achieve accurate assessment of filling pressures including: LV pulsed-wave filling velocities (E/A ratio, E wave deceleration time), pulmonary venous flow (S wave and D wave), tissue Doppler imaging (E' wave and E/E' ratio) and LA volume index. LA longitudinal strain derived from speckle tracking echocardiography (STE) is also sensitive in estimating intracavitary pressures. It is angle-independent, thus overcomes Doppler limitations and provides highly reproducible measures of LA deformation. This review examines the application of various Doppler echocardiographic techniques in assessing LV filling pressures, in particular the emerging role of STE in assessing LA pressures in various conditions, e.g., HF, arterial hypertension and atrial fibrillation.

Passive ventricular mechanics modelling using MRI of structure and function.

PubMed

Wang, V Y; Lam, H I; Ennis, D B; Young, A A; Nash, M P

2008-01-01

Patients suffering from dilated cardiomyopathy or myocardial infarction can develop left ventricular (LV) diastolic impairment. The LV remodels its structure and function to adapt to pathophysiological changes in geometry and loading conditions and this remodeling process can alter the passive ventricular mechanics. In order to better understand passive ventricular mechanics, a LV finite element model was developed to incorporate physiological and mechanical information derived from in vivo magnetic resonance imaging (MRI) tissue tagging, in vivo LV cavity pressure recording and ex vivo diffusion tensor MRI (DTMRI) of a canine heart. MRI tissue tagging enables quantitative evaluation of cardiac mechanical function with high spatial and temporal resolution, whilst the direction of maximum water diffusion (the primary eigenvector) in each voxel of a DTMRI directly correlates with the myocardial fibre orientation. This model was customized to the geometry of the canine LV during diastasis by fitting the segmented epicardial and endocardial surface data from tagged MRI using nonlinear finite element fitting techniques. Myofibre orientations, extracted from DTMRI of the same heart, were incorporated into this geometric model using a free form deformation methodology. Pressure recordings, temporally synchronized to the tissue tagging MRI data, were used to simulate the LV deformation during diastole. Simulation of the diastolic LV mechanics allowed us to estimate the stiffness of the passive LV myocardium based on kinematic data obtained from tagged MRI. This integrated physiological model will allow more insight into the regional passive diastolic mechanics of the LV on an individualized basis, thereby improving our understanding of the underlying structural basis of mechanical dysfunction in pathological conditions.

Using Simulation to Determine a Strategy for Positively Tracking a Cruise Missile by CMMCA

DTIC Science & Technology

1990-03-01

ANPOS/SS(6),ATC/SS(7),ATAS/ SS(8),ABANGLE/SS(9),CBANGLE/DD(1),CEVEL/ DD(2),CNVEL/DD(3),CTCC/DD(4),AEVEL/ DD(5), ANVEL /DD(6),ATCC RECORD,TNOW,MINUTES,20...ABANGLE),(SS(9),CBANGLE), & (DD(1),CEVEL),(DD(2),CNVEL).(DD(3),CTCC), & (DD(4),AEVEL),(DD(5), ANVEL ),(DD(6).ATCC) GOTO(l,2,3,4,5,6) ,I 1IF (XX(14) *EQ. 1...ABANGLE),(SS(9),CBANGLE), & (DD(l),CEVEL),(DD(2),CNVEL),(DD(3),CTCG), & (DD(4),AEVEL),(DD(5), ANVEL ),CDD(6),ATCC) REAL COSD EXTERNAL COSD REAL SIND

Therapeutic effect of radiofrequency ablation on children with supraventricular tachycardia and the risk factors for postoperative recurrence

PubMed Central

Li, Chunli; Jia, Libo; Wang, Zhenzhou; Niu, Ling; An, Xinjiang

2018-01-01

The present study investigated the therapeutic effect of radiofrequency ablation on children with supraventricular tachycardia (SVT), and explored the risk factors for postoperative recurrence. A total of 312 patients with pediatric SVT were selected in the Affiliated Children's Hospital of Xuzhou Medical University from April, 2011 to March, 2017. All the patients were subjected to radiofrequency ablation, and clinical data were retrospectively analyzed. Tilt table test was performed before and after treatment, and heart rate, systolic and diastolic blood pressure before and after treatment were compared. Plasma levels of D-dimer (D-D), platelet α-granule membrane protein (GMP-140) and thrombin-antithrombin III complex (TAT) were detected by enzyme-linked immunosorbent assay before treatment, immediately after radiofrequency oblation, and at 1, 3 and 7 days after treatment. Treatment outcomes were compared between the atrioventricular reentrant tachycardia (AVRT) and atrioventricular nodal reentrant tachycardia (AVNRT) groups. Risk factors for postoperative recurrence were analyzed. Supine position heart rate after treatment was not significantly different from that before treatment (P>0.05), while the upright position heart rate was significantly increased after treatment (P<0.05). Systolic pressures of the supine and upright positions were significantly reduced after treatment compared with the levels before (P<0.05), but no significant differences were found in diastolic blood pressure of supine and the upright position (P>0.05). No significant difference in radiofrequency ablation rate, recurrence rate and incidence of complications were found between the AVRT and AVNRT groups (P>0.05). After radiofrequency, the levels of D-D, GMP-140 and TAT ablation showed an upward trend, but decreased at day 7 to reach preoperative levels. Logistic regression analysis revealed that residual slow pathway (OR=6.718, P=0.005) and inaccurate targeting (OR=2.815, P=0.007) were independent risk factors for postoperative recurrence (P<0.05). Although radiofrequency ablation can damage the cardiac vagal nerve, resulting in an increase in the heart rate after ablation during the course of the tilt table test and changed hemagglutination state within one week after ablation, those changes returned to normal after one week. The efficacy of radiofrequency ablation in the treatment of pediatric SVT is clear, and recurrence rate is low. Residual slow pathway and inaccurate targeting were independent risk factors for postoperative recurrence. PMID:29725383

Therapeutic effect of radiofrequency ablation on children with supraventricular tachycardia and the risk factors for postoperative recurrence.

PubMed

Li, Chunli; Jia, Libo; Wang, Zhenzhou; Niu, Ling; An, Xinjiang

2018-05-01

The present study investigated the therapeutic effect of radiofrequency ablation on children with supraventricular tachycardia (SVT), and explored the risk factors for postoperative recurrence. A total of 312 patients with pediatric SVT were selected in the Affiliated Children's Hospital of Xuzhou Medical University from April, 2011 to March, 2017. All the patients were subjected to radiofrequency ablation, and clinical data were retrospectively analyzed. Tilt table test was performed before and after treatment, and heart rate, systolic and diastolic blood pressure before and after treatment were compared. Plasma levels of D-dimer (D-D), platelet α-granule membrane protein (GMP-140) and thrombin-antithrombin III complex (TAT) were detected by enzyme-linked immunosorbent assay before treatment, immediately after radiofrequency oblation, and at 1, 3 and 7 days after treatment. Treatment outcomes were compared between the atrioventricular reentrant tachycardia (AVRT) and atrioventricular nodal reentrant tachycardia (AVNRT) groups. Risk factors for postoperative recurrence were analyzed. Supine position heart rate after treatment was not significantly different from that before treatment (P>0.05), while the upright position heart rate was significantly increased after treatment (P<0.05). Systolic pressures of the supine and upright positions were significantly reduced after treatment compared with the levels before (P<0.05), but no significant differences were found in diastolic blood pressure of supine and the upright position (P>0.05). No significant difference in radiofrequency ablation rate, recurrence rate and incidence of complications were found between the AVRT and AVNRT groups (P>0.05). After radiofrequency, the levels of D-D, GMP-140 and TAT ablation showed an upward trend, but decreased at day 7 to reach preoperative levels. Logistic regression analysis revealed that residual slow pathway (OR=6.718, P=0.005) and inaccurate targeting (OR=2.815, P=0.007) were independent risk factors for postoperative recurrence (P<0.05). Although radiofrequency ablation can damage the cardiac vagal nerve, resulting in an increase in the heart rate after ablation during the course of the tilt table test and changed hemagglutination state within one week after ablation, those changes returned to normal after one week. The efficacy of radiofrequency ablation in the treatment of pediatric SVT is clear, and recurrence rate is low. Residual slow pathway and inaccurate targeting were independent risk factors for postoperative recurrence.

An updated computational model of rabbit sinoatrial action potential to investigate the mechanisms of heart rate modulation

PubMed Central

Severi, Stefano; Fantini, Matteo; Charawi, Lara A; DiFrancesco, Dario

2012-01-01

The cellular basis of cardiac pacemaking is still debated. Reliable computational models of the sinoatrial node (SAN) action potential (AP) may help gain a deeper understanding of the phenomenon. Recently, novel models incorporating detailed Ca2+-handling dynamics have been proposed, but they fail to reproduce a number of experimental data, and more specifically effects of ‘funny’ (If) current modifications. We therefore developed a SAN AP model, based on available experimental data, in an attempt to reproduce physiological and pharmacological heart rate modulation. Cell compartmentalization and intracellular Ca2+-handling mechanisms were formulated as in the Maltsev–Lakatta model, focusing on Ca2+-cycling processes. Membrane current equations were revised on the basis of published experimental data. Modifications of the formulation of currents/pumps/exchangers to simulate If blockers, autonomic modulators and Ca2+-dependent mechanisms (ivabradine, caesium, acetylcholine, isoprenaline, BAPTA) were derived from experimental data. The model generates AP waveforms typical of rabbit SAN cells, whose parameters fall within the experimental ranges: 352 ms cycle length, 80 mV AP amplitude, −58 mV maximum diastolic potential (MDP), 108 ms APD50, and 7.1 V s−1 maximum upstroke velocity. Rate modulation by If-blocking drugs agrees with experimental findings: 20% and 22% caesium-induced (5 mm) and ivabradine-induced (3 μm) rate reductions, respectively, due to changes in diastolic depolarization (DD) slope, with no changes in either MDP or take-off potential (TOP). The model consistently reproduces the effects of autonomic modulation: 20% rate decrease with 10 nm acetylcholine and 28% increase with 1 μm isoprenaline, again entirely due to increase in the DD slope, with no changes in either MDP or TOP. Model testing of BAPTA effects showed slowing of rate, −26%, without cessation of beating. Our up-to-date model describes satisfactorily experimental data concerning autonomic stimulation, funny-channel blockade and inhibition of the Ca2+-related system by BAPTA, making it a useful tool for further investigation. Simulation results suggest that a detailed description of the intracellular Ca2+ fluxes is fully compatible with the observation that If is a major component of pacemaking and rate modulation. PMID:22711956

Epigenetic regulation of cardiac fibrosis

PubMed Central

Stratton, Matthew S.; McKinsey, Timothy A.

2016-01-01

Fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In the heart, fibrosis may be reparative, replacing areas of myocyte loss with a structural scar following infarction, or reactive, which is triggered in the absence of cell death and involves interstitial ECM deposition in response to long-lasting stress. Interstitial fibrosis can increase the passive stiffness of the myocardium, resulting in impaired relaxation and diastolic dysfunction. Additionally, fibrosis can lead to disruption of electrical conduction in the heart, causing arrhythmias, and can limit myocyte oxygen availability and thus exacerbate myocardial ischemia. Here, we review recent studies that have illustrated key roles for epigenetic events in the control of pro-fibrotic gene expression, and highlight the potential of small molecules that target epigenetic regulators as a means of treating fibrotic cardiac diseases. PMID:26876451

Differential phenotype profile between main right ventricular chamber and outflow tract in chronic pulmonary hypertension: echocardiographic observation.

PubMed

López-Candales, Angel

2014-07-01

Right ventricular (RV) dilatation and systolic dysfunction are known remodeling changes occurring in chronic pulmonary hypertension and are likely the result of increases in pulmonary vascular resistance (PVR). It remains unclear whether PVR affects primarily the main RV chamber (mRVc) or the RV outflow tract (RVOT). Standard echocardiography data were collected from a heterogeneous population of 85 consecutive patients (mean age of 54 ± 12 years and mean pulmonary artery systolic pressure of 56 ± 28 mm Hg) to determine how PVR affected size and function of both RV chambers. Regarding size, PVR correlated more with mRVc end systolic area (r = 0.77; P < 0.0001) than either mRVc end diastolic area (r = 0.58; P < 0.0001) or RVOT systolic length (r = 0.54; P < 0.0001), although it did not correlate with RVOT end diastolic length. In terms of fractional area change, a stronger negative correlation was seen between PVR and mRVc (r = -0.77; P < 0.0001) than with PVR and RVOT (r = -0.69; P < 0.0001). Systolic velocity of the tricuspid annulus was the best parameter in identifying elevated PVR. Based on the echocardiography results, increasing PVR values appear to result in differential RV remodeling with significant mRVc dilation and systolic dysfunction when compared with RVOT. It is important to determine whether the different RV remodeling processes occur in all patients with chronic pulmonary hypertension, regardless of etiology; alter therapeutic response; or determine clinical outcomes.

Pulmonary Hypertension due to Radiofrequency Catheter Ablation (RFCA) for Atrial Fibrillation: The Lungs, the Atrium or the Ventricle?

PubMed

Verma, Isha; Tripathi, Hemantkumar; Sikachi, Rutuja Rajanikant; Agrawal, Abhinav

2016-12-01

Atrial fibrillation is the most common heart rhythm disorder in United States, characterised by rapid and irregular beating of both the atria resulting in the similar ventricular response. While rate and rhythm control using pharmacological regimens remain the primary management strategies in these patients, radiofrequency catheter ablation (RFCA) is rapidly rising as an alternative modality of treatment. Increase in the incidence of RFCA has shed light on complications associated with this procedure. Pulmonary hypertension (PH) is one of the long-term complications that has been observed postcatheter ablation. There have been multiple mechanisms which have been proposed to explain these elevated pulmonary pressures. These include the involvement of the lungs due to pulmonary vein stenosis, pulmonary vein occlusion and, rarely, pulmonary embolism. Radiofrequency catheter ablation can also lead to scarring of the atrium which can cause left atrial diastolic dysfunction leading to elevated pulmonary pressures. Recently, it was also proposed that elevated pulmonary pressure was related to the unmasking of left ventricular diastolic dysfunction occurring after this procedure. In this article, we review all the mechanisms that are associated with the development of pulmonary hypertension in patients undergoing RCFA for atrial fibrillation and the approach to diagnosis and management of such patients. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Echocardiographic predictors of atrial fibrillation recurrence after catheter ablation: A literature review.

PubMed

Liżewska-Springer, Aleksandra; Dąbrowska-Kugacka, Alicja; Lewicka, Ewa; Drelich, Łukasz; Królak, Tomasz; Raczak, Grzegorz

2018-06-20

Catheter ablation (CA) is a well-known treatment option for patients with symptomatic drug-resistant atrial fibrillation (AF). Multiple factors have been identified to determine AF recurrence after CA, however their predictive value is rather small. Identification of novel predictors of CA outcome is therefore of primary importance to reduce health costs and improve long-term results of this intervention. The recurrence of AF following CA is related to the severity of left ventricular (LV) dysfunction, extend of atrial dilatation and fibrosis. The aim of this paper was to present and discuss the latest studies on utility of echocardiographic parameters in terms of CA effectiveness in patients with paroxysmal and persistent AF. PubMed, Google Scholar, EBSCO databases were searched for studies reporting echocardiographic preprocedural predictors of AF recurrence after CA. LV systolic and diastolic function, as well as atrial size, strain and dyssynchrony were taken into consideration. Twenty one full-text articles were analyzed, including three meta-analyses. Several echocardiographic parameters have been reported to determine a risk of AF recurrence after CA. There are conventional methods that measure left atrial (LA) size and volume, LV ejection fraction, parameters assessing LV diastolic dysfunction, and methods using more innovative technologies based on speckle tracking echocardiography (STE) to determine LA synchrony and strain. Each of these parameters has its own predictive value. Regarding CA effectiveness, every patient has to be evaluated individually to estimate the risk of AF recurrence, optimally using a combination of several echocardiographic parameters.

Evaluation of coronary microvascular function in patients with end-stage renal disease, and renal allograft recipients.

PubMed

Bozbas, Huseyin; Pirat, Bahar; Demirtas, Saadet; Simşek, Vahide; Yildirir, Aylin; Sade, Elif; Sayin, Burak; Sezer, Siren; Karakayali, Hamdi; Muderrisoglu, Haldun

2009-02-01

Approximately half of all deaths in patients with end-stage renal disease (ESRD) are due to cardiovascular diseases. Although renal transplant improves survival and quality of life in these patients, cardiovascular events significantly affect survival. We sought to evaluate coronary flow reserve (CFR), an indicator of coronary microvascular function, in patients with ESRD and in patients with a functioning kidney graft. Eighty-six patients (30 with ESRD, 30 with a functioning renal allograft, and 26 controls) free of coronary artery disease or diabetes mellitus were included. Transthoracic Doppler echocardiography was used to measure coronary peak flow velocities at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities and was compared among the groups. The mean age of the study population was 36.1+/-7.3 years. No between-group differences were found regarding age, sex, or prevalences of traditional coronary risk factors other than hypertension. Compared with the renal transplant and control groups, the ESRD group had significantly lower mean CFR values. On multivariate regression analysis, serum levels of creatinine, age, and diastolic dysfunction were independent predictors of CFR. CFR is impaired in patients with ESRD suggesting that coronary microvascular dysfunction, an early finding of atherosclerosis, is evident in these patients. Although associated with a decreased CFR compared with controls, renal transplant on the other hand seems to have a favorable effect on coronary microvascular function.

Distinct right ventricle remodeling in response to pressure overload in the rat.

PubMed

Mendes-Ferreira, P; Santos-Ribeiro, D; Adão, R; Maia-Rocha, C; Mendes-Ferreira, M; Sousa-Mendes, C; Leite-Moreira, A F; Brás-Silva, C

2016-07-01

Pulmonary arterial hypertension (PAH), the most serious chronic disorder of the pulmonary circulation, is characterized by pulmonary vasoconstriction and remodeling, resulting in increased afterload on the right ventricle (RV). In fact, RV function is the main determinant of prognosis in PAH. The most frequently used experimental models of PAH include monocrotaline- and chronic hypoxia-induced PAH, which primarily affect the pulmonary circulation. Alternatively, pulmonary artery banding (PAB) can be performed to achieve RV overload without affecting the pulmonary vasculature, allowing researchers to determine the RV-specific effects of their drugs/interventions. In this work, using two different degrees of pulmonary artery constriction, we characterize, in full detail, PAB-induced adaptive and maladaptive remodeling of the RV at 3 wk after PAB surgery. Our results show that application of a mild constriction resulted in adaptive hypertrophy of the RV, with preserved systolic and diastolic function, while application of a severe constriction resulted in maladaptive hypertrophy, with chamber dilation and systolic and diastolic dysfunction up to the isolated cardiomyocyte level. By applying two different degrees of constriction, we describe, for the first time, a reliable and short-duration PAB model in which RV adaptation can be distinguished at 3 wk after surgery. We characterize, in full detail, structural and functional changes of the RV in its response to moderate and severe constriction, allowing researchers to better study RV physiology and transition to dysfunction and failure, as well as to determine the effects of new therapies. Copyright © 2016 the American Physiological Society.

[Experts consensus on the management of the right heart function in critically ill patients].

PubMed

Wang, X T; Liu, D W; Zhang, H M; Long, Y; Guan, X D; Qiu, H B; Yu, K J; Yan, J; Zhao, H; Tang, Y Q; Ding, X; Ma, X C; Du, W; Kang, Y; Tang, B; Ai, Y H; He, H W; Chen, D C; Chen, H; Chai, W Z; Zhou, X; Cui, N; Wang, H; Rui, X; Hu, Z J; Li, J G; Xu, Y; Yang, Y; Ouyan, B; Lin, H Y; Li, Y M; Wan, X Y; Yang, R L; Qin, Y Z; Chao, Y G; Xie, Z Y; Sun, R H; He, Z Y; Wang, D F; Huang, Q Q; Jiang, D P; Cao, X Y; Yu, R G; Wang, X; Chen, X K; Wu, J F; Zhang, L N; Yin, M G; Liu, L X; Li, S W; Chen, Z J; Luo, Z

2017-12-01

To establish the experts consensus on the right heart function management in critically ill patients. The panel of consensus was composed of 30 experts in critical care medicine who are all members of Critical Hemodynamic Therapy Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 52 experts to reassess all the statements. (1) Right heart function is prone to be affected in critically illness, which will result in a auto-exaggerated vicious cycle. (2) Right heart function management is a key step of the hemodynamic therapy in critically ill patients. (3) Fluid resuscitation means the process of fluid therapy through rapid adjustment of intravascular volume aiming to improve tissue perfusion. Reversed fluid resuscitation means reducing volume. (4) The right ventricle afterload should be taken into consideration when using stroke volume variation (SVV) or pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload alone could lead to septal displacement and damage the diastolic function of the left ventricle. (6) The Starling curve of the right ventricle is not the same as the one applied to the left ventricle,the judgement of the different states for the right ventricle is the key of volume management. (7) The alteration of right heart function has its own characteristics, volume assessment and adjustment is an important part of the treatment of right ventricular dysfunction (8) Right ventricular enlargement is the prerequisite for increased cardiac output during reversed fluid resuscitation; Nonetheless, right heart enlargement does not mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance induced by a variety of factors could affect right heart function by obstructing the blood flow. (10) When pulmonary hypertension was detected in clinical scenario, the differentiation of critical care-related pulmonary hypertension should be a priority. (11) Attention should be paid to the change of right heart function before and after implementation of mechanical ventilation and adjustment of ventilator parameter. (12) The pulmonary arterial pressure should be monitored timingly when dealing with critical care-related pulmonary hypertension accompanied with circulatory failure.(13) The elevation of pulmonary aterial pressure should be taken into account in critical patients with acute right heart dysfunction. (14) Prone position ventilation is an important measure to reduce pulmonary vascular resistance when treating acute respiratory distress syndrome patients accompanied with acute cor pulmonale. (15) Attention should be paid to right ventricle-pulmonary artery coupling during the management of right heart function. (16) Right ventricular diastolic function is more prone to be affected in critically ill patients, the application of critical ultrasound is more conducive to quantitative assessment of right ventricular diastolic function. (17) As one of the parameters to assess the filling pressure of right heart, central venous pressure can be used to assess right heart diastolic function. (18). The early and prominent manifestation of non-focal cardiac tamponade is right ventricular diastolic involvement, the elevated right atrial pressure should be noticed. (19) The effect of increased intrathoracic pressure on right heart diastolic function should be valued. (20) Ttricuspid annular plane systolic excursion (TAPSE) is an important parameter that reflects right ventricular systolic function, and it is recommended as a general indicator of critically ill patient. (21) Circulation management with right heart protection as the core strategy is the key point of the treatment of acute respiratory distress syndrome. (22) Right heart function involvement after cardiac surgery is very common and should be highly valued. (23) Right ventricular dysfunction should not be considered as a routine excuse for maintaining higher central venous pressure. (24) When left ventricular dilation, attention should be paid to the effect of left ventricle on right ventricular diastolic function. (25) The impact of left ventricular function should be excluded when the contractility of the right ventricle is decreased. (26) When the right heart load increases acutely, the shunt between the left and right heart should be monitored. (27) Attention should be paid to the increase of central venous pressure caused by right ventricular dysfunction and its influence on microcirculation blood flow. (28) When the vasoactive drugs was used to reduce the pressure of pulmonary circulation, different effects on pulmonary and systemic circulation should be evaluated. (29) Right atrial pressure is an important factor affecting venous return. Attention should be paid to the influence of the pressure composition of the right atrium on the venous return. (30) Attention should be paid to the role of the right ventricle in the acute pulmonary edema. (31) Monitoring the difference between the mean systemic filling pressure and the right atrial pressure is helpful to determine whether the infusion increases the venous return. (32) Venous return resistance is often considered to be a insignificant factor that affects venous return, but attention should be paid to the effect of the specific pathophysiological status, such as intrathoracic hypertension, intra-abdominal hypertension and so on. Consensus can promote right heart function management in critically ill patients, optimize hemodynamic therapy, and even affect prognosis.

Assessment of atrial electromechanical delay by tissue Doppler echocardiography in obese subjects.

PubMed

Yagmur, Julide; Cansel, Mehmet; Acikgoz, Nusret; Ermis, Necip; Yagmur, Murat; Atas, Halil; Tasolar, Hakan; Karakus, Yasin; Pekdemir, Hasan; Ozdemir, Ramazan

2011-04-01

Our aim was to evaluate whether atrial electromechanical delay measured by tissue Doppler imaging (TDI), which is an early predictor of atrial fibrillation (AF) development, is prolonged in obese subjects. A total of 40 obese and 40 normal-weight subjects with normal coronary angiograms were included in this study. P-wave dispersion (PWD) was calculated on the 12-lead electrocardiogram (ECG). Systolic and diastolic left ventricular (LV) functions, inter- and intra-atrial electromechanical delay were measured by TDI and conventional echocardiography. Inter- and intra-atrial electromechanical delay were significantly longer in the obese subjects compared with the controls (44.08 ± 10.06 vs. 19.35 ± 5.94 ms and 23.63 ± 6.41 vs. 5.13 ± 2.67 ms, P < 0.0001 for both, respectively). PWD was higher in obese subjects (53.40 ± 5.49 vs. 35.95 ± 5.93 ms, P < 0.0001). Left atrial (LA) diameter, LA volume index and LV diastolic parameters were significantly different between the groups. Interatrial electromechanical delay was correlated with PWD (r = 0.409, P = 0.009), high-sensitivity C-reactive protein (hsCRP) levels (r = 0.588, P < 0.0001). Interatrial electromechanical delay was positively correlated with LA diameter, LA volume index, and LV diastolic function parameters consisting of mitral early wave (E) deceleration time (DT) and isovolumetric relaxation time (IVRT; r = 0.323, P = 0.042; r = 0.387, P = 0.014; r = 0.339, P = 0.033; r = 0.325, P = 0.041; respectively) and, negatively correlated with mitral early (E) to late (A) wave ratio (E/A) (r = -0.380, P = 0.016) and myocardial early-to-late diastolic wave ratio (E(m)/A(m)) (r = -0.326, P = 0.040). This study showed that atrial electromechanical delay is prolonged in obese subjects. Prolonged atrial electromechanical delay is due to provoked low-grade inflammation as well as LA enlargement and early LV diastolic dysfunction in obese subjects.

Prognostication of valvular aortic stenosis using tissue Doppler echocardiography: underappreciated importance of late diastolic mitral annular velocity.

PubMed

Poh, Kian-Keong; Chan, Mark Yan-Yee; Yang, Hong; Yong, Quek-Wei; Chan, Yiong-Huak; Ling, Lieng H

2008-05-01

Intact left atrial booster pump function helps maintain cardiac compensation in patients with aortic valve stenosis (AS). Because late diastolic mitral annular (A') velocity reflects left atrial systolic function, we hypothesized that A' velocity correlates with plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and clinical outcome in AS. We prospectively enrolled 53 consecutive patients (median age 74 years) with variable degrees of AS, in sinus rhythm, and left ventricular ejection fraction greater than 50%. Indices of valvular stenosis, left ventricular diastolic dysfunction, and mitral annular motion were correlated with plasma NT-proBNP and a composite clinical end point comprising cardiac death and symptom-driven aortic valve replacement. Tissue Doppler echocardiographic parameters, including early diastolic (E') velocity and A' velocity and ratio of early diastolic transmitral (E) to E' velocity (E/E') at the annular septum correlated better with NT-proBNP levels than body surface area-indexed aortic valve area. Eighteen patients had the composite end point, which was univariately predicted by body surface area-indexed aortic valve area, NT-proBNP, and all tissue Doppler echocardiographic indices. This outcome was most strongly predicted by the combination of septal A' velocity and E/E' ratio in bivariate Cox modeling. Septal annular A' velocity less than 9.6 cm/s was associated with significantly reduced event-free survival (Kaplan Meier log rank = 27.3, P < .0001) and predicted the end point with a sensitivity, specificity, and accuracy of 94%, 80%, and 85%, respectively. In patients with AS and normal ejection fraction, annular tissue Doppler echocardiographic indices may better reflect the physiologic consequences of afterload burden on the left ventricle than body surface area-indexed aortic valve area. Lower A' velocity is a predictor of cardiac death and need for valve surgery, suggesting an important role for compensatory left atrial booster pump function.

Long Term Ablation of Protein Kinase A (PKA)-mediated Cardiac Troponin I Phosphorylation Leads to Excitation-Contraction Uncoupling and Diastolic Dysfunction in a Knock-in Mouse Model of Hypertrophic Cardiomyopathy*

PubMed Central

Dweck, David; Sanchez-Gonzalez, Marcos A.; Chang, Audrey N.; Dulce, Raul A.; Badger, Crystal-Dawn; Koutnik, Andrew P.; Ruiz, Edda L.; Griffin, Brittany; Liang, Jingsheng; Kabbaj, Mohamed; Fincham, Frank D.; Hare, Joshua M.; Overton, J. Michael; Pinto, Jose R.

2014-01-01

The cardiac troponin I (cTnI) R21C (cTnI-R21C) mutation has been linked to hypertrophic cardiomyopathy and renders cTnI incapable of phosphorylation by PKA in vivo. Echocardiographic imaging of homozygous knock-in mice expressing the cTnI-R21C mutation shows that they develop hypertrophy after 12 months of age and have abnormal diastolic function that is characterized by longer filling times and impaired relaxation. Electrocardiographic analyses show that older R21C mice have elevated heart rates and reduced cardiovagal tone. Cardiac myocytes isolated from older R21C mice demonstrate that in the presence of isoproterenol, significant delays in Ca2+ decay and sarcomere relaxation occur that are not present at 6 months of age. Although isoproterenol and stepwise increases in stimulation frequency accelerate Ca2+-transient and sarcomere shortening kinetics in R21C myocytes from older mice, they are unable to attain the corresponding WT values. When R21C myocytes from older mice are treated with isoproterenol, evidence of excitation-contraction uncoupling is indicated by an elevation in diastolic calcium that is frequency-dissociated and not coupled to shorter diastolic sarcomere lengths. Myocytes from older mice have smaller Ca2+ transient amplitudes (2.3-fold) that are associated with reductions (2.9-fold) in sarcoplasmic reticulum Ca2+ content. This abnormal Ca2+ handling within the cell may be attributed to a reduction (2.4-fold) in calsequestrin expression in conjunction with an up-regulation (1.5-fold) of Na+-Ca2+ exchanger. Incubation of permeabilized cardiac fibers from R21C mice with PKA confirmed that the mutation prevents facilitation of mechanical relaxation. Altogether, these results indicate that the inability to enhance myofilament relaxation through cTnI phosphorylation predisposes the heart to abnormal diastolic function, reduced accessibility of cardiac reserves, dysautonomia, and hypertrophy. PMID:24973218

The Role of Autonomic Function in Exercise-induced Endogenous Analgesia: A Case-control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Healthy People.

PubMed

Oosterwijck, Jessica Van; Marusic, Uros; De Wandele, Inge; Paul, Lorna; Meeus, Mira; Moorkens, Greta; Lambrecht, Luc; Danneels, Lieven; Nijs, Jo

2017-03-01

Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are unable to activate brain-orchestrated endogenous analgesia (or descending inhibition) in response to exercise. This physiological impairment is currently regarded as one factor explaining post-exertional malaise in these patients. Autonomic dysfunction is also a feature of ME/CFS. This study aims to examine the role of the autonomic nervous system in exercise-induced analgesia in healthy people and those with ME/CFS, by studying the recovery of autonomic parameters following aerobic exercise and the relation to changes in self-reported pain intensity. A controlled experimental study. The study was conducted at the Human Physiology lab of a University. Twenty women with ME/CFS- and 20 healthy, sedentary controls performed a submaximal bicycle exercise test known as the Aerobic Power Index with continuous cardiorespiratory monitoring. Before and after the exercise, measures of autonomic function (i.e., heart rate variability, blood pressure, and respiration rate) were performed continuously for 10 minutes and self-reported pain levels were registered. The relation between autonomous parameters and self-reported pain parameters was examined using correlation analysis. Some relationships of moderate strength between autonomic and pain measures were found. The change (post-exercise minus pre-exercise score) in pain severity was correlated (r = .580, P = .007) with the change in diastolic blood pressure in the healthy group. In the ME/CFS group, positive correlations between the changes in pain severity and low frequency (r = .552, P = .014), and between the changes in bodily pain and diastolic blood pressure (r = .472, P = .036), were seen. In addition, in ME/CHFS the change in headache severity was inversely correlated (r = -.480, P = .038) with the change in high frequency heart rate variability. Based on the cross-sectional design of the study, no firm conclusions can be drawn on the causality of the relations. Reduced parasympathetic reactivation during recovery from exercise is associated with the dysfunctional exercise-induced analgesia in ME/CFS. Poor recovery of diastolic blood pressure in response to exercise, with blood pressure remaining elevated, is associated with reductions of pain following exercise in ME/CFS, suggesting a role for the arterial baroreceptors in explaining dysfunctional exercise-induced analgesia in ME/CFS patients.Key words: Aerobic exercise, aerobic power index, autonomic nervous system, exercise-induced analgesia, exercise-induced hypoalgesia, fibromyalgia, heart rate variability, stress-induced analgesia, pain.

Heart Failure with Preserved Ejection Fraction: Molecular Pathways of the Aging Myocardium

PubMed Central

Loffredo, Francesco S.; Nikolova, Andriana P.; Pancoast, James R.; Lee, Richard T.

2014-01-01

Age-related diastolic dysfunction is a major factor in the epidemic of heart failure. In patients hospitalized with heart failure, diastolic heart failure is now as common as systolic heart failure. We now have many successful treatments for HFrEF, while specific treatment options for HFpEF patients remain elusive. The lack of treatments for HFpEF reflects our very incomplete understanding of this constellation of diseases. There are many pathophysiological factors in HFpEF, but aging appears to play an important role. Here we propose that aging of the myocardium is itself a specific pathophysiological process. New insights into the aging heart, including hormonal controls and specific molecular pathways such as microRNAs, are pointing to myocardial aging as a potentially reversible process. While the overall process of aging remains mysterious, understanding the molecular pathways of myocardial aging has never been more important. Unraveling these pathways could lead to new therapies for the enormous and growing problem of HFpEF. PMID:24951760

Quantifying subtle changes in cardiovascular mechanics in acromegaly: a Doppler myocardial imaging study.

PubMed

Jurcut, R; Găloiu, S; Florian, A; Vlădaia, A; Ioniţă, O R; Amzulescu, M S; Baciu, I; Popescu, B A; Coculescu, M; Ginghina, C

2014-11-01

To describe morphological and functional cardiovascular changes in acromegaly (ACM) patients, as well as to investigate the ability of Doppler-based myocardial deformation imaging (DMI) to characterize subtle dysfunction in ACM. 69 patients (pts) with ACM (mean age 47 ± 10 years, 27 men) and 31 controls (mean age 43 ± 16 years, matched for age and gender) were recruited. Standard echocardiography and DMI data were obtained for all patients. Peak systolic longitudinal strain values (S) were determined for the left and right ventricles. Radial S was measured at the level of the mid inferolateral segment. Using a high-resolution echo-tracking system, the main indices of arterial stiffness were measured. Of the ACM subjects, 57 had active disease (group A), and 12 controlled ACM (group B). All pts with ACM presented structural changes: a higher LV indexed mass (112 ± 36, 118 ± 23 vs 74 ± 18 g/m(2), p < 0.001) and a higher relative wall thickness (0.45 ± 0.09, 0.50 ± 0.07 vs 0.40 ± 0.07, p = 0.003) compared to controls. Also, ACM pts had functional changes: reduced LV ejection fraction (57 ± 5, 55 ± 5 vs 64 ± 4%, p < 0.001) and altered diastolic function (E/A 1.0 ± 0.4, 1.1 ± 0.1 vs 1.3 ± 0.3, p = 0.005) compared to controls. Both longitudinal and radial LV S values were lower in ACM compared to controls: -16.5 ± 3.5, -16.8 ± 4.3 vs -21.5 ± 3.8%, p < 0.001 for longitudinal and 38.3 ± 12.3, 35.6 ± 11.8 vs 52.2 ± 11.7%, p = 0.002 for radial strain. ACM pts present LV concentric hypertrophy and LV systolic and diastolic dysfunction, even in controlled disease. Altered global LV systolic function appears to be due both to longitudinal and radial dysfunction.

Tricuspid regurgitation contributes to renal dysfunction in patients with heart failure.

PubMed

Maeder, Micha T; Holst, Diane P; Kaye, David M

2008-12-01

In heart failure (HF), renal dysfunction is associated with an adverse prognosis. Impaired renal perfusion from left ventricular dysfunction is thought to be a principal underlying mechanism. Less is known about the influence of venous congestion, including the potential contribution of tricuspid regurgitation (TR). Echocardiograms and a simultaneous (+/-1 day) blood sample from 196 HF patients were analyzed. Patients with at least moderate TR (n = 78) had larger right-sided cardiac cavities, higher right ventricular systolic pressure, lower estimated glomerular filtration rate (eGFR), higher serum urea nitrogen (SUN), and SUN/creatinine ratio than patients with less than moderate TR (n = 118). In multivariate linear regression analysis, TR severity (P = .003), older age (P < .001), and loop diuretic use (P = .008) were independently associated with lower eGFR, and use of inhibitors of the renin-angiotensin-aldosterone system was associated with higher eGFR (P = .001). TR severity (P < .001) and older age (P < .001) were independently associated with higher SUN. TR severity (P = .004) and smaller left ventricular end-diastolic diameter (P = .048) were independent predictors of a higher SUN/creatinine ratio (P = .004). Although a causal relationship cannot be proven, we suggest that significant TR contributes to renal dysfunction in HF patients, probably by elevation of central and renal venous pressure.

Febuxostat improves endothelial function in hemodialysis patients with hyperuricemia: A randomized controlled study.

PubMed

Tsuruta, Yuki; Kikuchi, Kan; Tsuruta, Yukio; Sasaki, Yuko; Moriyama, Takahito; Itabashi, Mitsuyo; Takei, Takashi; Uchida, Keiko; Akiba, Takashi; Tsuchiya, Ken; Nitta, Kosaku

2015-10-01

Endothelial dysfunction is often found in both hyperuricemia and hemodialysis patients. Recent studies have shown that treating hyperuricemia with allopurinol improves endothelial dysfunction. This study is performed to assess the effect of febuxostat on endothelial dysfunction in hemodialysis patients with hyperuricemia. We randomly assigned 53 hemodialysis patients with hyperuricemia to a febuxostat (10 mg daily) group and a control group and measured flow-mediated dilation, serum uric acid (UA) levels, systolic and diastolic blood pressure, malondialdehyde-modified low-density lipoprotein (MDA-LDL), and highly sensitive C-reactive protein (hsCRP) at baseline and at the end of a 4-week study period. Flow-mediated dilation increased from 5.3% ± 2.4% to 8.9% ± 3.6% in the febuxostat group but did not change significantly in the control group. Treatment with febuxostat resulted in a significant decrease in serum UA level and a significant decrease in MDA-LDL compared with baseline, but no significant difference was observed in hsCRP level or blood pressure. No significant differences were observed in the control group. Febuxostat improved endothelial dysfunction and reduced serum UA levels and oxidative stress in hemodialysis patients with hyperuricemia. © 2015 International Society for Hemodialysis.

Cardiac and Metabolic Variables in Obese Dogs.

PubMed

Tropf, M; Nelson, O L; Lee, P M; Weng, H Y

2017-07-01

The etiology of obesity-related cardiac dysfunction (ORCD) is linked to metabolic syndrome in people. Studies have indicated that obese dogs have components of metabolic syndrome, warranting evaluation for ORCD in obese dogs. To evaluate cardiac structure and function and metabolic variables in obese dogs compared to ideal weight dogs. Forty-six healthy, small-breed (<25 pounds), obese dogs (n = 29) compared to ideal weight dogs (n = 17). A cross-sectional study of cardiac structure and function by standard and strain echocardiographic measurements and quantification of serum metabolic variables (insulin:glucose ratios, lipid analysis, adiponectin, inflammatory markers). Compared to the ideal weight controls, obese dogs had cardiac changes characterized by an increased interventricular septal width in diastole to left ventricular internal dimension in diastole ratio, decreased ratios of peak early to peak late left ventricular inflow velocities, and ratios of peak early to peak late mitral annular tissue velocities, and increased fractional shortening and ejection fraction percentages. The left ventricular posterior wall width in diastole to left ventricular internal dimension in diastole ratios were not significantly different between groups. Systolic blood pressure was not significantly different between groups. Obese dogs had metabolic derangements characterized by increased insulin:glucose ratios, dyslipidemias with increased cholesterol, triglyceride, and high-density lipoprotein concentrations, decreased adiponectin concentrations, and increased concentrations of interleukin 8 and keratinocyte-derived chemokine-like inflammatory cytokines. Compared to ideal weight controls, obese dogs have alterations in cardiac structure and function as well as insulin resistance, dyslipidemia, hypoadiponectinemia, and increased concentrations of inflammatory markers. These findings warrant additional studies to investigate inflammation, dyslipidemia, and possibly systemic hypertension as potential contributing factors for altered cardiac function. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Addition of rituximab to chop does not increase the risk of cardiotoxicity in patients with non-Hodgkin's lymphoma.

PubMed

Kilickap, Saadettin; Yavuz, Bunyamin; Aksoy, Sercan; Sahiner, Levent; Dincer, Murat; Harputluoglu, Hakan; Erman, Mustafa; Aytemir, Kudret; Tokgozoglu, Lale; Barista, Ibrahim

2008-01-01

The addition of rituximab to doxorubicin-containing standard chemotherapy significantly improves response to therapy and reduces the risk of death in B-cell non-Hodgkin's lymphoma (NHL) patients. However, the impact of this approach on doxorubicin-induced cardiotoxicity has not been elucidated. Patients who had been planned to receive CHOP or rituximab plus CHOP (R-CHOP) combination chemotherapy with a diagnosis of NHL were included in the study. In all patients, systolic and diastolic parameters were measured by using conventional and pulsed-wave tissue Doppler echocardiography, which is more sensitive than conventional lead-dependent techniques, both before and in the sixth month of therapy. There were 28 (M/F; 14/14) patients on CHOP and 33 (M/F; 16/17) patients on R-CHOP. Median age in CHOP and R-CHOP was 49 and 50 years (P = 0.44), respectively. Cumulative doxorubicin doses were 280 and 286 mg/m(2) on CHOP and R-CHOP (P = 0.65), respectively. None of the patients developed clinically evident congestive heart failure. Parameters of systolic function such as LVEF and FS did not significantly change in any patients. In both arms, tissue Doppler parameters of diastolic function such as lateral E and septal E velocity of mitral annulus decreased significantly after therapy (P < 0.001). However, the decrease in diastolic function was similar in both arms (P > 0.05). Conventional Doppler echocardiography yielded consistent findings. Both CHOP and R-CHOP cause diastolic dysfunction in the early period following their administration. The addition of rituximab to CHOP chemotherapy does not significantly increase the risk of doxorubicin-induced cardiotoxicity during this period.

Dual ACE-inhibition and AT1 receptor antagonism improves ventricular lusitropy without affecting cardiac fibrosis in the congenic mRen2.Lewis rat.

PubMed

Jessup, Jewell A; Westwood, Brian M; Chappell, Mark C; Groban, Leanne

2009-08-01

Hypertension and left ventricular (LV) hypertrophy often precede diastolic dysfunction and are risk factors for diastolic heart failure. Although pharmacologic inhibition of the renin-angiotensin system (RAS) improves diastolic function and functional capacity in hypertensive patients with LV hypertrophy, the effects of combination therapy with an angiotensin converting enzyme inhibitor (ACEi) and an angiotensin receptor blocker (ARB) are unclear. We assessed the effects of the combined 10-week administration of lisinopril (10 mg/kg/ day, p.o.) and losartan (10 mg/kg/day, p.o.) (LIS/LOS) on diastolic function and LV structure in seven young (5 weeks), prehypertensive congenic mRen2.Lewis male rat, a model of tissue renin overexpression and angiotensin II (Ang II)-dependent hypertension compared to vehicle (VEH) treated (n = 7), age-matched rats. Systolic blood pressures were 64% lower with the combination therapy (p < 0.001), but there were no differences in heart rate or systolic function between groups. RAS inhibition increased myocardial relaxation, defined by tissue Doppler mitral annular descent (e') by 2.2 fold (p < 0.001). The preserved lusitropy in the LIS/LOS-treated rats was accompanied by a reduction in phospholamban-to-SERCA2 ratio (p < 0.001). Despite lower relative wall thicknesses (VEH: 1.56+/-0.17 versus LIS/LOS: 0.78+/-0.05) and filling pressures, defined by the transmitral Doppler-to-mitral annular descent ratio (E/e', VEH: 28.7+/-1.9 versus LIS/LOS: 17.96+/-1.5), no differences in cardiac collagen were observed. We conclude that the lusitropic benefit of early dual RAS blockade may be due to improved vascular hemodynamics and/or cardiac calcium handling rather than effects on extracellular matrix reduction.

Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction.

PubMed

Borlaug, Barry A; Melenovsky, Vojtech; Russell, Stuart D; Kessler, Kristy; Pacak, Karel; Becker, Lewis C; Kass, David A

2006-11-14

Nearly half of patients with heart failure have a preserved ejection fraction (HFpEF). Symptoms of exercise intolerance and dyspnea are most often attributed to diastolic dysfunction; however, impaired systolic and/or arterial vasodilator reserve under stress could also play an important role. Patients with HFpEF (n=17) and control subjects without heart failure (n=19) generally matched for age, gender, hypertension, diabetes mellitus, obesity, and the presence of left ventricular hypertrophy underwent maximal-effort upright cycle ergometry with radionuclide ventriculography to determine rest and exercise cardiovascular function. Resting cardiovascular function was similar between the 2 groups. Both had limited exercise capacity, but this was more profoundly reduced in HFpEF patients (exercise duration 180+/-71 versus 455+/-184 seconds; peak oxygen consumption 9.0+/-3.4 versus 14.4+/-3.4 mL x kg(-1) x min(-1); both P<0.001). At matched low-level workload, HFpEF subjects displayed approximately 40% less of an increase in heart rate and cardiac output and less systemic vasodilation (all P<0.05) despite a similar rise in end-diastolic volume, stroke volume, and contractility. Heart rate recovery after exercise was also significantly delayed in HFpEF patients. Exercise capacity correlated with the change in cardiac output, heart rate, and vascular resistance but not end-diastolic volume or stroke volume. Lung blood volume and plasma norepinephrine levels rose similarly with exercise in both groups. HFpEF patients have reduced chronotropic, vasodilator, and cardiac output reserve during exercise compared with matched subjects with hypertensive cardiac hypertrophy. These limitations cannot be ascribed to diastolic abnormalities per se and may provide novel therapeutic targets for interventions to improve exercise capacity in this disorder.

Role of gender in heart failure with normal left ventricular ejection fraction.

PubMed

Regitz-Zagrosek, Vera; Brokat, Sebastian; Tschope, Carsten

2007-01-01

Heart failure with normal ejection fraction (HF-NEF) is frequently believed to be more common in women than in men. However, the interaction of gender and age has rarely been analyzed in detail, and knowledge of the distinction between pre- and postmenopausal women is lacking. Some of the studies that have described a higher prevalence of HF-NEF in women relied on clinical diagnoses of HF together with normal systolic function and did not measure diastolic function. This applies to the analysis of patients hospitalized for HF and some epidemiological investigations that agree on the greater prevalence of HF-NEF in women. Population-based studies with echocardiographic determination of diastolic function have suggested equal or greater prevalence of diastolic dysfunction in men. Major risk factors for HF-NEF include hypertension, aging, obesity, diabetes, and ischemia. Hypertension is more frequent in women and can contribute to left ventricular and arterial stiffening in a gender-specific way. Aging, obesity, and diabetes affect myocardial and vascular stiffness differently and lead to different forms of myocardial hypertrophy in women and men. In contrast, ischemia may play a greater role in men. Gender differences in ventricular diastolic distensibility, in vascular stiffness and ventricular/vascular coupling, in skeletal muscle adaptation to HF, and in the perception of symptoms may contribute to a greater rate of HF-NEF in women. The underlying molecular mechanisms include gender differences in calcium handling, in the NO system, and in natriuretic peptides. Estrogen affects collagen synthesis and degradation and inhibits the renin-angiotensin system. Effects of estrogen may provide benefit to premenopausal women, and the loss of its protective mechanisms may render the heart of postmenopausal women more vulnerable. Thus, a number of molecular mechanisms can contribute to the gender differences in HF-NEF.

Significant correlation of P-wave parameters with left atrial volume index and left ventricular diastolic function.

PubMed

Tsai, Wei-Chung; Lee, Kun-Tai; Wu, Ming-Tsang; Chu, Chih-Sheng; Lin, Tsung-Hsien; Hsu, Po-Chao; Su, Ho-Ming; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung

2013-07-01

The 12-lead electrocardiogram (ECG) is a commonly used tool to access left atrial enlargement, which is a marker of left ventricular diastolic dysfunction (LVDD). The aim of this study was to evaluate any association of the P-wave measurements in ECG with left atrial volume (LAV) index and LVDD. This study enrolled 270 patients. In this study, 4 ECG P-wave parameters corrected by heart rate, that is, corrected P-wave maximum duration (PWdurMaxC), corrected P-wave dispersion (PWdisperC), corrected P-wave area (PWareaC) and corrected mean P-wave duration (meanPWdurC), were measured. LAV and left ventricular diastolic parameters were measured from echocardiography. LVDD was defined as a pseudonormal or restrictive mitral inflow pattern. The 4 P-wave parameters were significantly correlated with the LAV index after adjusting for age, sex, diabetes, hypertension, coronary artery disease, body mass index and diastolic blood pressure in multivariate analysis. The standardized β coefficients of PWdurMaxC, PWdisperC, meanPWdurC and PWareaC were 0.338, 0.298, 0.215 and 0.296, respectively. The 4 P-wave parameters were also significantly correlated with LVDD after multivariate logistic regression analysis. The odds ratios (95% confidence intervals) of PWdurMaxC, PWdisperC, meanPWdurC and PWareaC were 1.03 (1.01-1.04), 1.02 (1.04-1.04), 1.04 (1.02-1.07) and 1.01 (1.00-1.02), respectively. This study demonstrated that PWdurMaxC, PWdisperC, meanPWdurC and PWareaC were important determinants of the LAV index and LVDD. Therefore, screening patients by means of the 12-lead ECG may be helpful in identifying a high-risk group of increased LAV index and LVDD.

Natural history of severe aortic stenosis: Diastolic wall strain as a novel prognostic marker.

PubMed

Obasare, Edinrin; Bhalla, Vikas; Gajanana, Deepakraj; Rodriguez Ziccardi, Mary; Codolosa, Jose N; Figueredo, Vincent M; Morris, Dennis Lynn; Pressman, Gregg S

2017-04-01

Diastolic wall strain (DWS) has been proposed as a simple noninvasive measure of left ventricular (LV) stiffness. This study investigated DWS as a possible predictor of mortality in severe aortic stenosis (AS). 138 patients with severe AS (indexed aortic valve area [AVA]<0.6 cm 2 /m 2 ) and normal ejection fraction (>55%) were included. 52 patients (38%) had aortic valve interventions or poor image quality (n=5) and were excluded leaving 86 in the study group (84±8 years, 70% female, 69% African American). DWS was defined as (LVPWs-LVPWd)/LVPWs where LVPWs=left ventricular posterior wall thickness in systole and LVPWd=left ventricular wall thickness in diastole. Follow-up extended 2.0±1.9 years (median 1.6 years). Mean DWS for the group was 0.21±0.11 (normal=0.4±0.07). In patients who died, DWS was significantly lower than in survivors (0.18±0.09 vs 0.24±0.11, P=.02). By contrast, traditional measures of diastolic dysfunction did not predict death. Regression analysis showed DWS predicted death even after adjusting for age, sex, race, indexed AVA, symptoms (angina, shortness of breath, dizziness, syncope), and clinical factors (creatinine, smoking, diabetes, hypertension, hyperlipidemia) (HR 2.5 [95% CI 1.02-5.90], P<.05). The best cutoff value for DWS of 0.25 had a sensitivity of 42% and specificity of 83% for predicting death. DWS is an independent predictor of all-cause mortality in patients with severe AS, even after accounting for traditional clinical and echocardiographic parameters. © 2017, Wiley Periodicals, Inc.

Treatment of hypertension with perindopril reduces plasma atrial natriuretic peptide levels, left ventricular mass, and improves echocardiographic parameters of diastolic function

NASA Technical Reports Server (NTRS)

Yalcin, F.; Aksoy, F. G.; Muderrisoglu, H.; Sabah, I.; Garcia, M. J.; Thomas, J. D.

2000-01-01

BACKGROUND: Hypertension is a major independent risk factor for cardiac deaths, and diastolic dysfunction is a usual finding during the course of this disease. HYPOTHESIS: This study was designed to investigate the effects of chronic therapy with perindopril on left ventricular (LV) mass, left atrial size, diastolic function, and plasma level of atrial natriuretic peptide (ANP) in patients with hypertension. METHODS: Twenty four patients who had not been previously taking any antihypertensive medication and without prior history of angina pectoris, myocardial infarction, congestive heart failure, dysrhythmias, valvular heart disease, or systemic illnesses received 4-8 mg/day of perindopril orally. Echocardiographic studies were acquired at baseline and 6 months after the initiation of therapy. RESULTS: Systolic and diastolic blood pressure decreased from 174 +/- 19.7 and 107.5 +/- 7.8 mmHg to 134 +/- 10.6 and 82 +/- 6.7 mmHg, respectively (p < 0.001). Left ventricular mass decreased from 252.4 +/- 8.3 to 205.7 +/- 7.08 g and left atrial volume from 20.4 +/- 5.1 to 17.6 +/- 5.2 ml, respectively (p < 0.001). Transmitral Doppler early and atrial filling velocity ratio (E/A) increased from 0.69 +/- 0.06 to 0.92 +/- 0.05 m/s and plasma ANP level decreased from 71.9 +/- 11.7 to 35.3 +/- 7.8 pg/ml (p < 0.001). Reduction of LV mass correlated positively with a reduction in ANP levels (r = 0.66, p < 0.0005). CONCLUSIONS: Perindopril caused a significant reduction of LV mass, left atrial volume, and plasma ANP levels, as well as improvement in Doppler parameters of LV filling in this group of patients with hypertension.

Drug discovery with an RBM20 dependent titin splice reporter identifies cardenolides as lead structures to improve cardiac filling.

PubMed

Liss, Martin; Radke, Michael H; Eckhard, Jamina; Neuenschwander, Martin; Dauksaite, Vita; von Kries, Jens-Peter; Gotthardt, Michael

2018-01-01

Diastolic dysfunction is increasingly prevalent in our ageing society and an important contributor to heart failure. The giant protein titin could serve as a therapeutic target, as its elastic properties are a main determinant of cardiac filling in diastole. This study aimed to develop a high throughput pharmacological screen to identify small molecules that affect titin isoform expression through differential inclusion of exons encoding the elastic PEVK domains. We used a dual luciferase splice reporter assay that builds on the titin splice factor RBM20 to screen ~34,000 small molecules and identified several compounds that inhibit the exclusion of PEVK exons. These compounds belong to the class of cardenolides and affect RBM20 dependent titin exon exclusion but did not affect RBFOX1 mediated splicing of FMNL3. We provide evidence that cardenolides do not bind to the RNA interacting domain of RBM20, but reduce RBM20 protein levels and alter transcription of select splicing factors that interact with RBM20. Cardenolides affect titin isoform expression. Understanding their mode of action and harnessing the splice effects through chemical modifications that suppress the effects on ion homeostasis and more selectively affect cardiac splicing has the potential to improve cardiac filling and thus help patients with diastolic heart failure, for which currently no targeted therapy exists.

Decreased Left Ventricular Torsion and Untwisting in Children with Dilated Cardiomyopathy

PubMed Central

Jin, Seon Mi; Bae, Eun Jung; Choi, Jung Yun; Yun, Yong Soo

2007-01-01

The purpose of this study was to analyze left ventricular (LV) torsion and untwisting, and to evaluate the correlation between torsion and other components of LV contraction in children with dilated cardiomyopathy (DCM). Segmental and global rotation, rotational rate (Vrot) were measured at three levels of LV using the two-dimensional (2D) speckle tracking imaging (STI) method in 10 DCM patients (range 0.6-15 yr, median 6.5 yr, 3 females) and 17 age- and sex-matched normal controls. Global torsion was decreased in DCM (peak global torsion; 10.9±4.6° vs. 0.3±2.1°, p<0.001). Loss of LV torsion occurred mainly by the diminution of counterclockwise apical rotation and was augmented by somewhat less reduction in clockwise basal rotation. In DCM, the normal counterclockwise apical rotation was not observed, and the apical rotation about the central axis was clockwise or slightly counterclockwise (peak apical rotation; 5.9±4.1° vs. -0.9±3.1°, p<0.001). Systolic counterclockwise Vrot and early diastolic clockwise Vrot at the apical level were decreased or abolished. In DCM, decreased systolic torsion and loss of early diastolic recoil contribute to LV systolic and diastolic dysfunction. The STI method may facilitate the serial evaluation of the LV torsional behavior in clinical settings and give new biomechanical concepts for better management of patients with DCM. PMID:17728501

Intermediate Diastolic Velocity as a Parameter of Cardiac Dysfunction in Growth-Restricted Fetuses.

PubMed

Tang, Xiangna; Hernandez-Andrade, Edgar; Ahn, Hyunyoung; Garcia, Maynor; Saker, Homam; Korzeniewski, Steven J; Tarca, Adi L; Yeo, Lami; Hassan, Sonia S; Romero, Roberto

2016-01-01

To evaluate the intermediate intracardiac diastolic velocities in fetuses with growth restriction. Doppler waveforms of the two atrioventricular valves were obtained. Peak velocities of the E (early) and A (atrial) components, and the lowest intermediate velocity (IDV) between them, were measured in 400 normally grown and in 100 growth-restricted fetuses. The prevalence of abnormal IDV, E/IDV, and A/IDV ratios in fetuses presenting with perinatal death or acidemia at birth (pH ≤7.1) was estimated. IDV was significantly lower and E/IDV ratios significantly higher in the two ventricles of growth-restricted fetuses with reduced diastolic velocities in the umbilical artery (p < 0.05). In 13 fetuses presenting with perinatal death or acidemia at birth, 11 (85%) had either an E/IDV or A/IDV ratio >95th percentile, whereas 5 (38%) showed absent or reversed atrial velocities in the ductus venosus (DV-ARAV; p < 0.04). Fetuses without DV-ARAV but with elevated E/IDV ratios in either ventricle were nearly 7-fold more likely to have perinatal demise or acidemia at birth (OR 6.9, 95% CI 1.4-34) than those with E/IDV ratios <95th percentile. The E/IDV and A/IDV ratios in the two cardiac ventricles might provide information about the risk of perinatal demise or acidemia in growth-restricted fetuses. © 2015 S. Karger AG, Basel.

32 CFR 65.8 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... assigned Report Control Symbols DD-P&R(AR)1221, DD-P&R(Q)2077, DD-RA(M)1147, DD-RA(D)1148, DD-RA(D)2170, DD-RA(M)2171, DD-RA(D)2302, and DD-RA(M)2303 in accordance with the requirements of DoD 8910.1-M...

Mitochondria and Cardiovascular Aging

PubMed Central

Dai, Dao-Fu; Ungvari, Zoltan

2013-01-01

Old age is a major risk factor for cardiovascular diseases. Several lines of evidence in experimental animal models have indicated the central role of mitochondria both in lifespan determination and cardiovascular aging. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and biogenesis as well as the crosstalk between mitochondria and cellular signaling in cardiac and vascular aging. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans (left ventricular hypertrophy, fibrosis and diastolic dysfunction), while the phenotype of vascular aging include endothelial dysfunction, reduced vascular elasticity and chronic vascular inflammation. Both cardiac and vascular aging involve neurohormonal signaling (e.g. renin-angiotensin, adrenergic, insulin-IGF1 signaling) and cell-autonomous mechanisms. The potential therapeutic strategies to improve mitochondrial function in aging and cardiovascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants, calorie restriction, calorie restriction mimetics and exercise training. PMID:22499901

Hyperthyroidism and cardiovascular complications: a narrative review on the basis of pathophysiology

PubMed Central

Cicero, Arrigo F.

2013-01-01

Cardiovascular complications are important in hyperthyroidism because of their high frequency in clinical presentation and increased mortality and morbidity risk. The cause of hyperthyroidism, factors related to the patient, and the genetic basis for complications are associated with risk and the basic underlying mechanisms are important for treatment and management of the disease. Besides cellular effects, hyperthyroidism also causes hemodynamic changes, such as increased preload and contractility and decreased systemic vascular resistance causes increased cardiac output. Besides tachyarrythmias, impaired systolic ventricular dysfunction and diastolic dysfunction may cause thyrotoxic cardiomyopathy in a small percentage of the patients, as another high mortality complication. Although the medical literature has some conflicting data about benefits of treatment of subclinical hyperthyroidism, even high-normal thyroid function may cause cardiovascular problems and it should be treated. This review summarizes the cardiovascular consequences of hyperthyroidism with underlying mechanisms. PMID:24273583

The Total Artificial Heart in End-Stage Congenital Heart Disease.

PubMed

Villa, Chet R; Morales, David L S

2017-01-01

The development of durable ventricular assist devices (VADs) has improved mortality rates and quality of life in patients with end stage heart failure. While the use of VADs has increased dramatically in recent years, there is limited experience with VAD implantation in patients with complex congenital heart disease (CHD), despite the fact that the number of patients with end stage CHD has grown due to improvements in surgical and medical care. VAD use has been limited in patients with CHD and end stage heart failure due to anatomic (systemic right ventricle, single ventricle, surgically altered anatomy, valve dysfunction, etc.) and physiologic constraints (diastolic dysfunction). The total artificial heart (TAH), which has right and left sided pumps that can be arranged in a variety of orientations, can accommodate the anatomic variation present in CHD patients. This review provides an overview of the potential use of the TAH in patients with CHD.

The Total Artificial Heart in End-Stage Congenital Heart Disease

PubMed Central

Villa, Chet R.; Morales, David L. S.

2017-01-01

The development of durable ventricular assist devices (VADs) has improved mortality rates and quality of life in patients with end stage heart failure. While the use of VADs has increased dramatically in recent years, there is limited experience with VAD implantation in patients with complex congenital heart disease (CHD), despite the fact that the number of patients with end stage CHD has grown due to improvements in surgical and medical care. VAD use has been limited in patients with CHD and end stage heart failure due to anatomic (systemic right ventricle, single ventricle, surgically altered anatomy, valve dysfunction, etc.) and physiologic constraints (diastolic dysfunction). The total artificial heart (TAH), which has right and left sided pumps that can be arranged in a variety of orientations, can accommodate the anatomic variation present in CHD patients. This review provides an overview of the potential use of the TAH in patients with CHD. PMID:28536530

[The role of natriuretic peptides in heart failure].

PubMed

Ancona, R; Limongelli, G; Pacileo, G; Miele, T; Rea, A; Roselli, T; Masarone, D; Messina, S; Palmieri, R; Golia, E; Iacomino, M; Gala, S; Calabrò, P; Di Salvo, G; Calabrò, R

2007-10-01

Over the last decades, there has been a significant increase in incidence and prevalence of heart failure, a major cause of cardiac morbidity and mortality. Measurements of neurohormones, in particular B-type natriuretic peptide (BNP), can significantly improve diagnostic accuracy, and also correlate with long-term morbidity and mortality in patients with chronic heart failure presenting to the emergency department. BNP is secreted by cardiac ventricles mainly in response to wall stress and neurohormonal factors like the sympathetic nervous system, endothelins, and the rennin-angiotensin-aldosterone system. BNP increases myocardial relaxation and oppose the vasoconstrictive, sodium retaining, and natriuretic effects caused by vasoconstrictive factors. BNP is the first biomarker to prove its clinical value for the diagnosis of left ventricular systolic and diastolic dysfunction but also for the right ventricular dysfunction, guiding prognosis and therapy management. Emerging clinical data will help further refine biomarker-guided therapeutic and monitoring strategies involving BNP.

[Features of metabolic syndrome in patients with depressive disorder].

PubMed

Zeman, M; Jirák, R; Zák, A; Jáchymová, M; Vecka, M; Tvrzická, E; Vávrová, L; Kodydková, J; Stanková, B

2009-01-01

Depressive disorder is a serious illness with a high incidence, proxime accessit after anxiety disorders among the psychiatric diseases. It is accompanied by an increased risk of development of type 2 diabetes mellitus, cardiovascular disease, and by increased all-cause mortality. Recently published data have suggested that factors connected with the insulin resistance are at the background of this association. In this pilot study we have investigated parameters of lipid metabolism and glucose homeostasis in consecutively admitted patients suffering from depressive disorder (DD) (group of 42 people), in 57 patients with the metabolic syndrome (MetS) and in a control group of 49 apparently healthy persons (CON). Depressive patients did not differ from the control group by age or body mass index (BMI) value, but they had statistically significantly higher concentrations of serum insulin, C-peptide, glucose, triglycerides (TG), conjugated dienes in LDL particles (CD-LDL), higher value of microalbuminuria and of insulin resistance (HOMA-IR) index. They simultaneously had significantly lower value of the insulin sensitivity (QUICKI) index. In comparison with the MetS group the depressive patients were characterized by significantly lower both systolic and diastolic blood pressure, BMI , serum TG, apolipoprotein B, uric acid, C-peptide and by higher concentrations of apolipoprotein A-I and HDL-cholesterol. On the contrary, we have not found statistically significant differences between the DD and MetS groups in the concentrations of serum insulin, glucose, HOMA and QUICKI indices, in CD-LDL and MAU. In this pilot study, we have found in patients with depressive disorder certain features of metabolic syndrome, especially insulin resistance and oxidative stress.

Combined circumferential and longitudinal left ventricular systolic dysfunction in patients with asymptomatic aortic stenosis.

PubMed

Cioffi, Giovanni; Mazzone, Carmine; Barbati, Giulia; Rossi, Andrea; Nistri, Stefano; Ognibeni, Federica; Tarantini, Luigi; Di Lenarda, Andrea; Faggiano, Pompilio; Pulignano, Giovanni; Stefenelli, Carlo; de Simone, Giovanni; Devereux, Richard B

2015-07-01

Early detection of left ventricular (LV) systolic dysfunction is pivotal in the management of patients with aortic stenosis (AS). LV circumferential and/or longitudinal shortening may be impaired in these patients despite LV ejection fraction is preserved. We focused on prevalence and factors associated with combined impairment of circumferential and longitudinal shortening (C&L) in asymptomatic AS patients. Echocardiographic and clinical data from 200 patients with asymptomatic AS of any degree without history of heart failure and normal LV ejection fraction were analyzed. C&L were evaluated by mid-wall shortening (MS) and tissue Doppler mitral annular peak systolic velocity (S'), and classified low if <16.5% and if <8.5 cm/sec, respectively (10th percentiles of controls). Combined C&L dysfunction was detected in 72 patients (36%). The variables associated with this condition were higher LV mass (OR 1.02 [CI 1.01-1.04], P = 0.03), concentric LV geometry (OR 4.30 [CI 1.79-10.34], P = 0.001), increasing pulmonary artery wedge pressure (by E/e' ratio; OR 1.11 [CI 1.04-1.19], P = 0.001). The relation of MS and peak S' was linear and slightly significant in the whole population (r = 0.23; F statistic=0.001), absent in patients with C&L dysfunction (r = 0.04; F = ns), negative (linear model) in the subgroup of patients without C&L dysfunction (r = -0.22; F = 0.02). C&L dysfunction is present in more than one-third of patients with asymptomatic AS and is associated with concentric LV geometry and higher degree of diastolic dysfunction. The relation between MS and peak S' largely varies in the subgroups with different C&L function. © 2014, Wiley Periodicals, Inc.

Relation of N-Terminal Pro-B-Type Natriuretic Peptide and Left Ventricular Diastolic Function to Exercise Tolerance in Patients With Significant Valvular Heart Disease and Normal Left Ventricular Systolic Function.

PubMed

Hwang, Ji-Won; Park, Sung-Ji; Cho, Eun Jeong; Kim, Eun Kyoung; Lee, Ga Yeon; Chang, Sung-A; Choi, Jin-Oh; Lee, Sang-Chol; Park, Seung Woo

2017-06-01

An association between N-terminal prohormone brain natriuretic peptide (NT-proBNP) and exercise tolerance in patients with valvular heart disease (VHD) has been suggested; however, there are few data available regarding this relation. The aim of this study is to evaluate the correlation between exercise tolerance and NT-proBNP in patients with asymptomatic or mildly symptomatic significant VHD and normal left ventricular ejection fraction (LV EF). A total of 96 patients with asymptomatic or mildly symptomatic VHD and normal LV EF (≥50%) underwent cardiopulmonary exercise echocardiography. NT-proBNP levels were determined at baseline and after exercise in 3 hours. Patients were divided in 2 groups based on lower (<26 ml/kg/min, n = 47) or higher (≥26 ml/kg/min, n = 49) peak oxygen consumption (VO 2 ) as a representation of exercise tolerance. In the 2 groups, after adjusting for age and gender, the NT-proBNP level after exercise in 3 hours, left atrial volume index before exercise, right ventricular systolic pressure before exercise, E velocity after exercise, and E/e' ratio after exercise varied significantly. In addition, peak VO 2 was inversely related to NT-proBNP before (r = -0.352, p <0.001) and after exercise (r = -0.351, p <0.001). The NT-proBNP level before exercise was directly related to the left atrial volume index, E/e' ratio, and right ventricular systolic pressure before and after exercise. NT-proBNP after exercise was also directly related to the same parameters. NT-proBNP levels both before and after exercise were higher in the group with lower exercise tolerance. In conclusion, through the correlation among exercise tolerance, NT-proBNP, and parameters of diastolic dysfunction, we demonstrated that diastolic dysfunction and NT-proBNP could predict exercise tolerance in patients with significant VHD and normal LV EF. Copyright © 2017 Elsevier Inc. All rights reserved.

Three-Dimensional Volumetric Assessment of Diastolic Function by Cardiac Magnetic Resonance Imaging: The Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Nacif, Marcelo S; Almeida, Andre L C; Young, Alistair A; Cowan, Brett R; Armstrong, Anderson C; Yang, Eunice; Sibley, Christopher T; Hundley, W Gregory; Liu, Songtao; Lima, Joao Ac; Bluemke, David A

2017-01-01

Cardiac Magnetic Resonance is in need of a simple and robust method for diastolic function assessment that can be done with routine protocol sequences. To develop and validate a three-dimensional (3D) model-based volumetric assessment of diastolic function using cardiac magnetic resonance (CMR) imaging and compare the results obtained with the model with those obtained by echocardiography. The study participants provided written informed consent and were included if having undergone both echocardiography and cine steady-state free precession (SSFP) CMR on the same day. Guide points at the septal and lateral mitral annulus were used to define the early longitudinal relaxation rate (E'), while a time-volume curve from the 3D model was used to assess diastolic filling parameters. We determined the correlation between 3D CMR and echocardiography and the accuracy of CMR in classifying the diastolic function grade. The study included 102 subjects. The E/A ratio by CMR was positively associated with the E/A ratio by echocardiography (r = 0.71, p < 0.0001). The early diastolic relaxation velocity by tissue Doppler and longitudinal relaxation rate for the lateral mitral annulus displacement were positively associated (p = 0.007), as were the ratio between Doppler E/e' and CMR E/E' (p = 0.01). CMR-determined normalized peak E (NE) and deceleration time (DT) were able to predict diastolic dysfunction (areas under the curve [AUCs] = 0.70 and 0.72, respectively). In addition, the lateral E/E' ratio showed good utility in identifying diastolic dysfunction (AUC = 0.80). Overall, echocardiography and CMR interobserver and intraobserver agreements were excellent (intraclass correlation coefficient range 0.72 - 0.97). 3D modeling of standard cine CMR images was able to identify study subjects with reduced diastolic function and showed good reproducibility, suggesting a potential for a routine diastolic function assessment by CMR. A ressonância magnética cardíaca necessita de um método simples e robusto para a avaliação da função diastólica que pode ser feito com sequências protocolares de rotina. Desenvolver e validar a avaliação volumétrica da função diastólica através de um modelo tridimensional (3D) com utilização de imagens de ressonância magnética cardíaca (RMC) e comparar os resultados obtidos com este modelo com os obtidos por ecocardiografia. Os participantes do estudo assinaram um termo de consentimento e foram incluídos se tivessem sido submetidos no mesmo dia tanto à ecocardiografia quanto à cine RMC com precessão livre no estado estacionário (steady-state free precession, SSFP). Pontos-guia foram utilizados no anel mitral septal e lateral para definir a velocidade de estiramento no início da diástole (E'), enquanto curvas de volume-tempo do modelo 3D foram utilizadas para avaliar os parâmetros de enchimento diastólico. Foram determinadas a correlação entre a RMC 3D e a ecocardiografia, além da acurácia da RMC em classificar o grau de função diastólica. Ao todo, 102 sujeitos foram incluídos no estudo. A razão E/A pela RMC esteve positivamente associada com a razão E/A obtida pela ecocardiografia (r = 0,71, p < 0,0001). Estiveram positivamente associadas a velocidade de relaxamento diastólico inicial ao Doppler tecidual e a velocidade de relaxamento longitudinal de deslocamento do anel mitral lateral (p = 0,007), bem como a razão entre E/e' por Doppler e E/E' pela RMC (p = 0,01). A velocidade normalizada de pico de enchimento (EM) determinada pela RMC e o tempo de desaceleração (TD) foram capazes de predizer a disfunção diastólica (áreas sob a curva [AUCs] = 0,70 e 0,72, respectivamente). Além disso, a razão E/E' lateral mostrou boa utilidade para a identificação da disfunção diastólica (AUC = 0,80). No geral, a ecocardiografia e a RMC apresentaram excelente concordância interobservador e intraobservador (coeficiente de correlação intraclasse 0,72 - 0,97). Uma modelagem 3D de imagens padrões de cine RMC foi capaz de identificar os indivíduos do estudo com função diastólica reduzida e mostrou uma boa reprodutibilidade, sugerindo ter potencial na avaliação rotineira da função diastólica por RMC.

Increased myocardial short-range forces in a rodent model of diabetes reflect elevated content of β myosin heavy chain.

PubMed

Chung, Charles S; Mitov, Mihail I; Callahan, Leigh Ann; Campbell, Kenneth S

2014-06-15

Diastolic dysfunction is a clinically significant problem for patients with diabetes and often reflects increased ventricular stiffness. Attached cross-bridges contribute to myocardial stiffness and produce short-range forces, but it is not yet known whether these forces are altered in diabetes. In this study, we tested the hypothesis that cross-bridge-based short-range forces are increased in the streptozotocin (STZ) induced rat model of type 1 diabetes. Chemically permeabilized myocardial preparations were obtained from 12week old rats that had been injected with STZ or vehicle 4weeks earlier, and activated in solutions with pCa (=-log10[Ca(2+)]) values ranging from 9.0 to 4.5. The short-range forces elicited by controlled length changes were ∼67% greater in the samples from the diabetic rats than in the control preparations. This change was mostly due to an increased elastic limit (the length change at the peak short-range force) as opposed to increased passive muscle stiffness. The STZ-induced increase in short-ranges forces is thus unlikely to reflect changes to titin and/or collagen filaments. Gel electrophoresis showed that STZ increased the relative expression of β myosin heavy chain. This molecular mechanism can explain the increased short-ranges forces observed in the diabetic tissue if β myosin molecules remain bound between the filaments for longer durations than α molecules during imposed movements. These results suggest that interventions that decrease myosin attachment times may be useful treatments for diastolic dysfunction associated with diabetes. Copyright © 2013 Elsevier Inc. All rights reserved.

Relationship of epicardial fat thickness with endothelial and cardiac functions in children with family history of type 2 diabetes mellitus.

PubMed

Mahfouz, Ragab A; Alzaiat, Ahmad; Yousry, Ahmad

2015-01-01

We hypothesized that many of the pathophysiological mechanisms that cause atherosclerotic disease may be present in early childhood in children with family history of type 2 diabetes. We aimed to investigate the relation of epicardial fat thickness (EFT) with flow-mediated dilatation (FMD) and diastolic function in children with family history of type 2 diabetes mellitus. We measured EFT, FMD, in 209 children (mean age 8.6 + 3.2 years). Children were classified into 2 groups: 109 children with a family history of type 2 diabetes (group at risk) and 100 healthy children with age and body mass index matched and without parental history of diabetes constituted the control group. Epicardial fat thickness was significantly increased in group at risk compared with control children (P < 0.001), while FMD was significantly lower in group at risk versus controls (P < 0.001). EFT was inversely correlated with FMD (r = -0.46; P < 0.001), while it was positively correlated with E/E' (r = 0.48; P < 0.001) and hsCRP (r = 0.39; P < 0.001). Receiver-operating characteristic curve analysis revealed a cutoff value of 5 mm for EFT can predict endothelial dysfunction in children with family history of DM area under the curve (AUC = 0.852) with a specificity of 92.2% and a sensitivity of 77.4%. Our results suggest that children with family history of type 2 diabetes bear considerably impaired FMD% and diastolic dysfunction associated with increased EFT, that reflecting process that promote the development of cardiovascular disease (CVD). © 2014, Wiley Periodicals, Inc.

Cardiac structure and function in Cushing's syndrome: a cardiac magnetic resonance imaging study.

PubMed

Kamenický, Peter; Redheuil, Alban; Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

2014-11-01

Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2-12 mo) after the treatment of hypercortisolism. Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement. Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism.

The Heart Failure Adherence and Retention Trial (HART): Design and Rationale

PubMed Central

Powell, Lynda H.; Calvin, James E.; Mendes de Leon, Carlos F.; Richardson, Dejuran; Grady, Kathleen L.; Flynn, Kristin J.; Rucker-Whitaker, Cheryl S.; Janssen, Imke; Kravitz, Glenda; Eaton, Claudia

2008-01-01

Background Heart failure (HF) is increasing in prevalence and associated with prolonged morbidity, repeat hospitalizations, and high costs. Drug therapies and lifestyle changes can reduce hospitalizations, but non-adherence is high, ranging from 30–80%. There is an urgent need to identify cost-effective ways to improve adherence and reduce hospitalizations. Trial Design HART evaluated the benefit of patient self-management (SM) skills training in combination with HF education, over HF education alone, on the composite endpoints of death/HF hospitalizations and death/all-cause hospitalizations in patients with mild to moderate systolic or diastolic dysfunction. Secondary endpoints included progression of HF, quality of life, adherence to drug and lifestyle regimens, and psychosocial function. The HART cohort was comprised of 902 patients including 47% women, 40% minorities, and 23% with diastolic dysfunction. After a baseline exam, patients were randomized to SM or education control, received 18 treatment contacts over one year, annual follow-ups, and 3-month phone calls to assess primary endpoints. SM treatment was conducted in small groups and aimed to activate the patient to implement HF education through training in problem-solving and 5 SM skills. The education control received HF education in the mail followed by a phone call to check comprehension. Conclusions The significance of HART lies in its ability to determine the clinical value of activating the patient to collaborate in his/her care. Support for the trial hypotheses would encourage interdisciplinary HF treatment, drawing on an evidence base not only from medicine but also from the behavioral sciences. PMID:18760125

48 CFR 53.303-DD-254 - Department of Defense DD Form 254, Contract Security Classification Specification.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Department of Defense DD Form 254, Contract Security Classification Specification. 53.303-DD-254 Section 53.303-DD-254 Federal... Illustrations of Forms 53.303-DD-254 Department of Defense DD Form 254, Contract Security Classification...

48 CFR 53.303-DD-254 - Department of Defense DD Form 254, Contract Security Classification Specification.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Department of Defense DD Form 254, Contract Security Classification Specification. 53.303-DD-254 Section 53.303-DD-254 Federal... Illustrations of Forms 53.303-DD-254 Department of Defense DD Form 254, Contract Security Classification...

48 CFR 53.303-DD-254 - Department of Defense DD Form 254, Contract Security Classification Specification.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Department of Defense DD Form 254, Contract Security Classification Specification. 53.303-DD-254 Section 53.303-DD-254 Federal... Illustrations of Forms 53.303-DD-254 Department of Defense DD Form 254, Contract Security Classification...

48 CFR 53.303-DD-441 - Department of Defense DD Form 441, Security Agreement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Department of Defense DD Form 441, Security Agreement. 53.303-DD-441 Section 53.303-DD-441 Federal Acquisition Regulations...-DD-441 Department of Defense DD Form 441, Security Agreement. EC01MY91.163 EC01MY91.164 ...

48 CFR 53.303-DD-441 - Department of Defense DD Form 441, Security Agreement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Department of Defense DD Form 441, Security Agreement. 53.303-DD-441 Section 53.303-DD-441 Federal Acquisition Regulations...-DD-441 Department of Defense DD Form 441, Security Agreement. EC01MY91.163 EC01MY91.164 ...

48 CFR 53.303-DD-441 - Department of Defense DD Form 441, Security Agreement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Department of Defense DD Form 441, Security Agreement. 53.303-DD-441 Section 53.303-DD-441 Federal Acquisition Regulations...-DD-441 Department of Defense DD Form 441, Security Agreement. EC01MY91.163 EC01MY91.164 ...

48 CFR 53.303-DD-254 - Department of Defense DD Form 254, Contract Security Classification Specification.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Department of Defense DD Form 254, Contract Security Classification Specification. 53.303-DD-254 Section 53.303-DD-254 Federal... Illustrations of Forms 53.303-DD-254 Department of Defense DD Form 254, Contract Security Classification...

48 CFR 53.303-DD-254 - Department of Defense DD Form 254, Contract Security Classification Specification.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Department of Defense DD Form 254, Contract Security Classification Specification. 53.303-DD-254 Section 53.303-DD-254 Federal... Illustrations of Forms 53.303-DD-254 Department of Defense DD Form 254, Contract Security Classification...

48 CFR 53.303-DD-441 - Department of Defense DD Form 441, Security Agreement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Department of Defense DD Form 441, Security Agreement. 53.303-DD-441 Section 53.303-DD-441 Federal Acquisition Regulations...-DD-441 Department of Defense DD Form 441, Security Agreement. EC01MY91.163 EC01MY91.164 ...

48 CFR 53.303-DD-441 - Department of Defense DD Form 441, Security Agreement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Department of Defense DD Form 441, Security Agreement. 53.303-DD-441 Section 53.303-DD-441 Federal Acquisition Regulations...-DD-441 Department of Defense DD Form 441, Security Agreement. EC01MY91.163 EC01MY91.164 ...

Vitamin D deficiency is associated with orthostatic hypotension in oldest-old women.

PubMed

Annweiler, C; Schott, A-M; Rolland, Y; Beauchet, O

2014-09-01

Orthostatic hypotension, a condition that mostly affects 'oldest-old' (i.e. ≥80 years) adults, is primarily explained by age-related dysfunction of blood pressure control. Vitamin D may contribute to blood pressure control. The aim of this study was to determine whether vitamin D deficiency is associated with orthostatic hypotension in oldest-old adults. Cross-sectional analysis at baseline of the EPIDOS study. Five French areas. A total of 329 community-dwelling oldest-old women (mean age 83.3 ± 0.2 years). Orthostatic hypotension was defined as a systolic blood pressure drop of ≥20 mmHg and/or a diastolic blood pressure drop of ≥10 mmHg within 3 min of standing. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25OHD) concentration ≤10 ng mL(-1) . Covariates included in the models were age, body mass index, diabetes mellitus, supine mean arterial pressure, number of drugs taken per day, use of antihypertensive or psychoactive drugs, cognition, quadriceps strength, current smoking, alcohol consumption, serum concentrations of parathyroid hormone, calcium and creatinine and season of testing. Diastolic orthostatic hypotension was observed more often among women with vitamin D deficiency (19.2%) compared to those without (10.0%; P = 0.03). There was an inverse linear association between 25OHD concentration and change in diastolic blood pressure after 3 min of standing (adjusted β = -0.07, P = 0.046). Similarly, 25OHD deficiency was associated with orthostatic hypotension [adjusted odds ratio (OR) 3.36, P = 0.004], specifically with diastolic orthostatic hypotension (adjusted OR 3.81, P = 0.003). 25OHD deficiency was associated with orthostatic hypotension in oldest-old women, due to a greater drop in diastolic blood pressure on standing. This finding may lead to better understanding of the pathophysiology of falls in oldest-old adults with vitamin D deficiency. © 2014 The Association for the Publication of the Journal of Internal Medicine.

The a´ velocity in the tissue Doppler predicts S/D ratio <1 in patients with a normal ejection fraction.

PubMed

Johansson, Benny; Lundin, Fredrik; Tegeback, Rolf; Bojö, Leif

2018-04-13

To compare the ability of the a´ velocity and the e´ velocity in predicting a dominant diastolic pulmonary vein flow (S/D ratio <1) in patients with normal ejection fraction. We retrospectively evaluated the diastolic function according to the ASE/EACVI guidelines, the S/D ratio and the septal, lateral and average a´ velocity in 293 unselected in-hospital patients, aged 39-86 years, in sinus rhythm and with no or mild valve disease, having a normal systolic function (EF >50%). There was a good linear correlation between the S/D ratio and the a´ velocity, but a tendency towards a negative correlation between the S/D ratio and the e´ velocity. S/D ratio <1 was seen in 43 patients. These patients had a significantly lower a´ velocity compared to those with S/D-ratio ≥1, septal (6,1 ± 2,4 v 8,8 ± 2,1 cm/s; p < .001) and lateral (6,0 ± 2,6 v 9,3 ± 2,5 cm/s; p < .001) No significant difference was seen in the septal e´ velocity (6,8 ± 2,4 v 6,8 ± 2,1 cm/s), lateral e´ velocity (9,4 ± 2,6 v 9,1 ± 2,8 cm/s) or in the ejection fraction (58,6 ± 4,4% v 58,7 ± 4,0%). A diastolic dysfunction was present in 62 patients, normal diastolic function in 231 patients. The a´ velocity was significantly lower in patients with S/D ratio <1 in both groups (p < .01). The a´ velocity is superior to the e´ velocity in predicting S/D ratio <1 in patients with normal ejection fraction regardless the ASE/EACVI diastolic classification. A failing left atrium seems to be the explanation.

[A role of the autonomic nervous system in cerebro-cardiac disorders].

PubMed

Basantsova, N Yu; Tibekina, L M; Shishkin, A N

The authors consider anatomical/physiological characteristics and a role of different autonomic CNS regions, including insula cortex, amygdala complex, anterior cingulate cortex, ventral medial prefrontal cortex, hypothalamus and epiphysis, involved in the regulation of cardiovascular activity. The damage of these structures, e.g., due to the acute disturbance of cerebral blood circulation, led to arrhythmia, including fatal arrhythmia, in previously intact myocardium; systolic and diastolic dysfunction, ischemic changes considered in the frames of cerebro-cardial syndrome. On the cellular level, the disturbance of autonomic regulation resulted in catechol amine excitotoxicity, oxidative stress and free radical myocardium injury.

Dipeptidyl peptidase-4 independent cardiac dysfunction links saxagliptin to heart failure.

PubMed

Koyani, Chintan N; Kolesnik, Ewald; Wölkart, Gerald; Shrestha, Niroj; Scheruebel, Susanne; Trummer, Christopher; Zorn-Pauly, Klaus; Hammer, Astrid; Lang, Petra; Reicher, Helga; Maechler, Heinrich; Groschner, Klaus; Mayer, Bernd; Rainer, Peter P; Sourij, Harald; Sattler, Wolfgang; Malle, Ernst; Pelzmann, Brigitte; von Lewinski, Dirk

2017-12-01

Saxagliptin treatment has been associated with increased rate of hospitalization for heart failure in type 2 diabetic patients, though the underlying mechanism(s) remain elusive. To address this, we assessed the effects of saxagliptin on human atrial trabeculae, guinea pig hearts and cardiomyocytes. We found that the primary target of saxagliptin, dipeptidyl peptidase-4, is absent in cardiomyocytes, yet saxagliptin internalized into cardiomyocytes and impaired cardiac contractility via inhibition of the Ca 2+ /calmodulin-dependent protein kinase II-phospholamban-sarcoplasmic reticulum Ca 2+ -ATPase 2a axis and Na + -Ca 2+ exchanger function in Ca 2+ extrusion. This resulted in reduced sarcoplasmic reticulum Ca 2+ content, diastolic Ca 2+ overload, systolic dysfunction and impaired contractile force. Furthermore, saxagliptin reduced protein kinase C-mediated delayed rectifier K + current that prolonged action potential duration and consequently QTc interval. Importantly, saxagliptin aggravated pre-existing cardiac dysfunction induced by ischemia/reperfusion injury. In conclusion, our novel results provide mechanisms for the off-target deleterious effects of saxagliptin on cardiac function and support the outcome of SAVOR-TIMI 53 trial that linked saxagliptin with the risk of heart failure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cardioprotection Induced by Activation of GPER in Ovariectomized Rats With Pulmonary Hypertension.

PubMed

Alencar, Allan K N; Montes, Guilherme C; Costa, Daniele G; Mendes, Luiza V P; Silva, Ananssa M S; Martinez, Sabrina T; Trachez, Margarete M; Cunha, Valéria do M N; Montagnoli, Tadeu L; Fraga, Aline G M; Wang, Hao; Groban, Leanne; Fraga, Carlos A M; Sudo, Roberto T; Zapata-Sudo, Gisele

2018-05-21

Pulmonary hypertension (PH) is a disease of women (female-to-male ratio 4:1), and is associated with cardiac and skeletal muscle dysfunction. Herein, the activation of a new estrogen receptor (GPER) by the agonist G1 was evaluated in oophorectomized rats with monocrotaline (MCT)-induced PH. Depletion of estrogen was induced by bilateral oophorectomy (OVX) in Wistar rats. Experimental groups included SHAM or OVX rats that received a single intraperitoneal injection of MCT (60 mg/kg) for PH induction. Animals received s.c. injection of either vehicle or G1, a GPER agonist, (400 µg/kg/day) for 14 days after the onset of disease. Rats with PH exhibited exercise intolerance and cardiopulmonary alterations, including reduced pulmonary artery flow, biventricular remodeling, and left ventricular systolic and diastolic dysfunction. The magnitude of these PH-induced changes was significantly greater in OVX versus SHAM rats. G1 treatment reversed both cardiac and skeletal muscle functional aberrations caused by PH in OVX rats. G1 reversed PH-related cardiopulmonary dysfunction and exercise intolerance in female rats, a finding that may have important implications for the ongoing clinical evaluation of new drugs for the treatment of the disease in females after the loss of endogenous estrogens.

Left atrial physiology and pathophysiology: Role of deformation imaging

PubMed Central

Kowallick, Johannes Tammo; Lotz, Joachim; Hasenfuß, Gerd; Schuster, Andreas

2015-01-01

The left atrium (LA) acts as a modulator of left ventricular (LV) filling. Although there is considerable evidence to support the use of LA maximum and minimum volumes for disease prediction, theoretical considerations and a growing body of literature suggest to focus on the quantification of the three basic LA functions: (1) Reservoir function: collection of pulmonary venous return during LV systole; (2) Conduit function: passage of blood to the left ventricle during early LV diastole; and (3) Contractile booster pump function (augmentation of ventricular filling during late LV diastole. Tremendous advances in our ability to non-invasively characterize all three elements of atrial function include speckle tracking echocardiography (STE), and more recently cardiovascular magnetic resonance myocardial feature tracking (CMR-FT). Corresponding imaging biomarkers are increasingly recognized to have incremental roles in determining prognosis and risk stratification in cardiac dysfunction of different origins. The current editorial introduces the role of STE and CMR-FT for the functional assessment of LA deformation as determined by strain and strain rate imaging and provides an outlook of how this exciting field may develop in the future. PMID:26131333

Genetic requirements for sensitivity of bacteriophage t7 to dideoxythymidine.

PubMed

Tran, Ngoc Q; Tabor, Stanley; Richardson, Charles C

2014-08-01

We previously reported that the presence of dideoxythymidine (ddT) in the growth medium selectively inhibits the ability of bacteriophage T7 to infect Escherichia coli by inhibiting phage DNA synthese (N. Q. Tran, L. F. Rezende, U. Qimron, C. C. Richardson, and S. Tabor, Proc. Natl. Acad. Sci. U. S. A. 105:9373-9378, 2008, doi:10.1073/pnas.0804164105). In the presence of T7 gene 1.7 protein, ddT is taken up into the E. coli cell and converted to ddTTP. ddTTP is incorporated into DNA as ddTMP by the T7 DNA polymerase, resulting in chain termination. We have identified the pathway by which exogenous ddT is converted to ddTTP. The pathway consists of ddT transport by host nucleoside permeases and phosphorylation to ddTMP by the host thymidine kinase. T7 gene 1.7 protein phosphorylates ddTMP and ddTDP, resulting in ddTTP. A 74-residue peptide of the gene 1.7 protein confers ddT sensitivity to the same extent as the 196-residue wild-type gene 1.7 protein. We also show that cleavage of thymidine to thymine and deoxyribose-1-phosphate by the host thymidine phosphorylase greatly increases the sensitivity of phage T7 to ddT. Finally, a mutation in T7 DNA polymerase that leads to discrimination against the incorporation of ddTMP eliminates ddT sensitivity. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Genetic Requirements for Sensitivity of Bacteriophage T7 to Dideoxythymidine

PubMed Central

Tran, Ngoc Q.; Tabor, Stanley

2014-01-01

We previously reported that the presence of dideoxythymidine (ddT) in the growth medium selectively inhibits the ability of bacteriophage T7 to infect Escherichia coli by inhibiting phage DNA synthese (N. Q. Tran, L. F. Rezende, U. Qimron, C. C. Richardson, and S. Tabor, Proc. Natl. Acad. Sci. U. S. A. 105:9373–9378, 2008, doi:10.1073/pnas.0804164105). In the presence of T7 gene 1.7 protein, ddT is taken up into the E. coli cell and converted to ddTTP. ddTTP is incorporated into DNA as ddTMP by the T7 DNA polymerase, resulting in chain termination. We have identified the pathway by which exogenous ddT is converted to ddTTP. The pathway consists of ddT transport by host nucleoside permeases and phosphorylation to ddTMP by the host thymidine kinase. T7 gene 1.7 protein phosphorylates ddTMP and ddTDP, resulting in ddTTP. A 74-residue peptide of the gene 1.7 protein confers ddT sensitivity to the same extent as the 196-residue wild-type gene 1.7 protein. We also show that cleavage of thymidine to thymine and deoxyribose-1-phosphate by the host thymidine phosphorylase greatly increases the sensitivity of phage T7 to ddT. Finally, a mutation in T7 DNA polymerase that leads to discrimination against the incorporation of ddTMP eliminates ddT sensitivity. PMID:24858186

Impact of age and sex on normal left heart structure and function.

PubMed

Hagström, Linn; Henein, Michael Y; Karp, Kjell; Waldenström, Anders; Lindqvist, Per

2017-11-01

Accurate age- and sex-related normal reference values of ventricular structure and function are important to determine the level of dysfunction in patients. The aim of this study therefore was to document normal age range sex-related measurements of LV structural and functional measurements to serve such purpose. We evaluated left ventricular structure and function in 293 healthy subjects between 20 and 90 years with equally distributed gender. Doppler echocardiography was used including measure of both systolic and diastolic functions. Due to systolic LV function, only long axis function correlated with age (r = 0·55, P<0·01) and the correlation was stronger in females. Concerning diastolic function, there was a strong age correlation in all parameters used (r = 0·40-0·74, P<0·001). Due to LV structural changes over age, females showed a larger reduction in end-diastolic volumes, but no or trivial difference in wall thickness after the age of 60 years. Age is associated with significant normal changes in left ventricular structure and function, which should be considered when deciding on normality. These changes are related to systemic arterial changes as well as body stature, thus reflecting overall body ageing process. Furthermore, normal cardiac ageing in females might partly explain the higher prevalence of heart failure with preserved ejection in females. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Clinical and ultrasound results after aortic valve replacement: intermediate-term follow-up with the St. Jude Medical prosthesis.

PubMed

Montalescot, G; Thomas, D; Drobinski, G; Evans, J I; Vicaut, E; Chatellier, G; Whyte, R I; Busquet, P; Bejean-Lebuisson, A; Grosgogeat, Y

1989-07-01

Mortality, morbidity, quality of life, and left ventricular (LV) function were evaluated in 49 patients after aortic valve replacement with the St. Jude prosthesis. Total follow-up was 2577 patient-months; survivors were followed-up for 4 to 7 years by clinical examination and echocardiography. The actuarial survival rate at 6 years was 79.6%, and there were no valve-related deaths. The linearized rates for thromboembolism and hemorrhage were 0.93% and 3.26% per patient-year, respectively. In 34% of the survivors the quality of life was poor. In the first three postoperative months, patients with aortic stenosis (n = 12) had a significant decrease in the muscle cross-sectional area (p less than 0.01) and patients with aortic regurgitation (n = 11) had decreases in both LV end-diastolic diameter (p less than 0.05) and cross-sectional area (p less than 0.001). All of these results were maintained at 5 years without modification of LV systolic function. Despite the good overall results, six patients deteriorated and had major LV dilatation. Multivariate logistic regression analysis identified two independent preoperative variables associated with a poor outcome defined as death of LV dysfunction (p less than 0.05): age and end-diastolic diameter. Thus meticulous follow-up showed a high incidence of hemorrhage and a poor quality of life in many of the survivors. It was concluded that in high-risk patients (age and end-diastolic diameter) surgery should probably be considered earlier.

Cardiac structure and function predicts functional decline in the oldest old.

PubMed

Leibowitz, David; Jacobs, Jeremy M; Lande-Stessman, Irit; Gilon, Dan; Stessman, Jochanan

2018-02-01

Background This study examined the association between cardiac structure and function and the deterioration in activities of daily living (ADLs) in an age-homogenous, community-dwelling population of patients born in 1920-1921 over a five-year follow-up period. Design Longitudinal cohort study. Methods Patients were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920-1921. Patients underwent home echocardiography and were followed up for five years. Dependence was defined as needing assistance with one or more basic ADL. Standard echocardiographic assessment of cardiac structure and function, including systolic and diastolic function, was performed. Reassessment of ADLs was performed at the five-year follow-up. Results A total of 459 patients were included in the study. Of these, 362 (79%) showed a deterioration in at least one ADL at follow-up. Patients with functional deterioration had a significantly higher left ventricular mass index and left atrial volume with a lower ejection fraction. There was no significant difference between the diastolic parameters the groups in examined. When the data were examined categorically, a significantly larger percentage of patients with functional decline had an abnormal left ventricular ejection fraction and left ventricular hypertrophy. The association between left ventricular mass index and functional decline remained significant in all multivariate models. Conclusions In this cohort of the oldest old, an elevated left ventricular mass index, higher left atrial volumes and systolic, but not diastolic dysfunction, were predictive of functional disability.