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

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.

5-Fluorouracil cardiotoxicity: reversible left ventricular systolic dysfunction with early detection.

PubMed

Iskandar, Muhammad Zaid; Quasem, Wahid; El-Omar, Magdi

2015-05-02

A 33-year-old man presented to hospital with acute shortness of breath and evolving ST segment changes on ECG 3 days following a cycle of 5-fluorouracil (5-FU) for colon cancer. Despite no cardiac history, subsequent echocardiogram showed severe left ventricular systolic dysfunction. The patient was initially treated with heart failure medications and his coronary angiogram was normal. Chemotherapy was stopped and he was started on nitrates and calcium channel blockers. A repeat echocardiogram and cardiac MRI a week later showed complete resolution of his left ventricular dysfunction and he was discharged home. This case report summarises 5-FU cardiotoxicity, and emphasises the importance of early recognition and correct treatment, as left ventricular systolic dysfunction in this context is potentially reversible. 2015 BMJ Publishing Group Ltd.

5-Fluorouracil cardiotoxicity: reversible left ventricular systolic dysfunction with early detection

PubMed Central

Iskandar, Muhammad Zaid; Quasem, Wahid; El-Omar, Magdi

2015-01-01

A 33-year-old man presented to hospital with acute shortness of breath and evolving ST segment changes on ECG 3 days following a cycle of 5-fluorouracil (5-FU) for colon cancer. Despite no cardiac history, subsequent echocardiogram showed severe left ventricular systolic dysfunction. The patient was initially treated with heart failure medications and his coronary angiogram was normal. Chemotherapy was stopped and he was started on nitrates and calcium channel blockers. A repeat echocardiogram and cardiac MRI a week later showed complete resolution of his left ventricular dysfunction and he was discharged home. This case report summarises 5-FU cardiotoxicity, and emphasises the importance of early recognition and correct treatment, as left ventricular systolic dysfunction in this context is potentially reversible. PMID:25935919

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.

Dobutamine stress echocardiography for assessment of systolic function in dogs with experimentally induced mitral regurgitation.

PubMed

Suzuki, R; Matsumoto, H; Teshima, T; Mochizuki, Y; Koyama, H

2014-01-01

Systolic dysfunction is associated with poor outcomes in dogs with myxomatous mitral valve disease. However, assessment of systolic variables by conventional echocardiographic methods is difficult in these dogs because of mitral regurgitation (MR). We hypothesized that assessment of systolic function by dobutamine stress may identify systolic dysfunction in dogs with MR, and that 2-dimensional speckle-tracking echocardiography (2D-STE) could quantitatively evaluate myocardial function. Anesthetized dogs with experimentally induced MR. Dogs were examined for systolic myocardial deformations using 2D-STE during dobutamine infusion before and 3 and 6 months after MR induction. We evaluated peak systolic rotation and rotation rate in each basal and apical view; peak systolic torsion and torsion rate were also calculated. Invasive peak positive first derivatives of left ventricular pressure (dp/dt) were significantly decreased in dogs 6 months after induction of MR compared with pre-MR results. After 3 and 6 months of MR, dogs had diminished peak systolic torsion values and torsion rates in response to dobutamine infusion compared with pre-MR results (3 months, P < .001 and P = .006; 6 months, P = .003 and P = .021). These results were significantly correlated with overall invasive dp/dt (r = 0.644, P < .001; r = 0.696, P < .001). Decreased torsion during dobutamine infusion in dogs with MR may reflect latent systolic dysfunction. Dobutamine infusion, therefore, may be useful for the assessment of systolic function in dogs with MR. Copyright © 2014 by the American College of Veterinary Internal Medicine.

[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%.

[Clinical characteristics and medium-term prognosis of patients with heart failure and preserved systolic function. Do they differ in systolic dysfunction?].

PubMed

Ojeda, Soledad; Anguita, Manuel; Muñoz, Juan F; Rodríguez, Marcos T; Mesa, Dolores; Franco, Manuel; Ureña, Isabel; Vallés, Federico

2003-11-01

To assess the prevalence, clinical profile and medium-term prognosis in patients with heart failure and preserved systolic ventricular function compared to those with systolic dysfunction. 153 patients were included, 62 with preserved systolic ventricular function (left ventricular ejection fraction > or = 45%) and 91 with impaired systolic ventricular function (left ventricular ejection fraction < 45%). The mean follow-up period was 25 10 months. Mean age was similar (66 10 vs. 65 10; p = 0.54). There was a higher proportion of women among patients with preserved systolic function (53% vs. 28%; p < 0.01). Ischemic and idiopathic cardiomyopathy were the most common causes of heart failure in patients with systolic dysfunction, whereas valvular disease and hypertensive cardiopathy were the most common in patients with preserved systolic function. Angiotensin-converting enzyme inhibitors and beta-blockers were more often prescribed in patients with impaired systolic ventricular function (86% vs. 52%; p < 0.01 and 33% vs. 11%; p < 0.01, respectively). There were no differences between the groups in terms of mortality rate (37% vs. 29%), readmission rate for other causes (29% vs. 23%), readmission rate for heart failure (45% vs. 45%), cumulative survival (51% vs. 62%) and the likelihood of not being readmitted for heart failure (50% vs. 52%). In the multivariate analysis, left ventricular ejection fraction was not a predictor of death or readmission because of heart failure. In a large proportion of patients with heart failure, systolic ventricular function is preserved. Despite the clinical differences between patients with preserved and impaired systolic ventricular function, the medium-term prognosis was similar in both groups.

MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2.

PubMed

Zhou, Yu; Song, Yan; Shaikh, Zahir; Li, Hui; Zhang, Haiju; Caudle, Yi; Zheng, Shouhua; Yan, Hui; Hu, Dan; Stuart, Charles; Yin, Deling

2017-07-18

Cardiac dysfunction is correlated with detrimental prognosis of sepsis and contributes to a high risk of mortality. After an initial hyperinflammatory reaction, most patients enter a protracted state of immunosuppression (late sepsis) that alters both innate and adaptive immunity. The changes of cardiac function in late sepsis are not yet known. MicroRNA-155 (miR-155) is previously found to play important roles in both regulations of immune activation and cardiac function. In this study, C57BL/6 mice were operated to develop into early and late sepsis phases, and miR-155 mimic was injected through the tail vein 48 h after cecal ligation and puncture (CLP). The effect of miR-155 on CLP-induced cardiac dysfunction was explored in late sepsis. We found that increased expression of miR-155 in the myocardium protected against cardiac dysfunction in late sepsis evidenced by attenuating sepsis-reduced cardiac output and enhancing left ventricular systolic function. We also observed that miR-155 markedly reduced the infiltration of macrophages and neutrophils into the myocardium and attenuated the inflammatory response via suppression of JNK signaling pathway. Moreover, overexpression of β-arrestin 2 (Arrb2) exacerbated the mice mortality and immunosuppression in late sepsis. Furthermore, transfection of miR-155 mimic reduced Arrb2 expression, and then restored immunocompetence and improved survival in late septic mice. We conclude that increased miR-155 expression through systemic administration of miR-155 mimic attenuates cardiac dysfunction and improves late sepsis survival by targeting JNK associated inflammatory signaling and Arrb2 mediated immunosuppression.

Assessment of tenascin-C levels in ventricular noncompaction/hypertrabeculation patients: a cross-sectional study.

PubMed

Erer, Hatice Betul; Guvenc, Tolga Sinan; Kemik, Ahu Sarbay; Yilmaz, Hale; Kul, Seref; Altay, Servet; Oz, Dilaver; Zeren, Gonul; Ekmekci, Ahmet; Zencirci, Aycan Esen; Sayar, Nurten; Eren, Mehmet

2014-02-01

Ventricular noncompaction/hypertrabeculation (NC/HT) is a rare form of congenital cardiomyopathy. We aimed to investigate the presence of serum tenascin-C (TN-C) in adult patients with NC/HT and evaluate its value. Serum TN-C levels were measured by ELISA in 50 NC/HT patients both with/without systolic dysfunction and in 23 normal controls. Systolic dysfunction was defined as ejection fraction (EF) ≤ 40. Mann-Whitney U-test and ROC curve analysis were done. Of 49 NC/HT patients, 24 (49%) patients had systolic dysfunction (mean age 36 ± 15) and 25 patients (51%) had normal systolic function (mean age 36 ± 17). The ages between groups were not different. The mean levels of serum TN-C in patients with or without systolic dysfunction were 26 ± 10 ng/mL and 26 ± 8 ng/mL respectively, compared to normal controls, 7 ± 2 ng/mL (P < 0.001). No significance was observed between 2 groups of NC/HT patients regarding TN-C levels (P = 0.8). The ROC curve analysis revealed that a TN-C value of 11.7 ng/mL identified patients with NC/HT with 100% sensitivity and specifity. High serum TN-C levels are present in adult NC/HT cardiomyopathy even when left ventricular systolic function remains normal. Also, serum TN-C levels could be regarded as a candidate biomarker in the diagnosis of NC/HT which needs to be tested in larger prospective studies. © 2013, Wiley Periodicals, Inc.

Intermittent, noncyclic dysfunction of a mechanical aortic prosthesis by pannus formation.

PubMed

Giroux, Sylvie K; Labinaz, Marino X; Grisoli, Dominique; Klug, Andrew P; Veinot, John P; Burwash, Ian G

2010-01-01

Mechanical aortic prosthesis dysfunction can result from thrombosis or pannus formation. Pannus formation usually restricts systolic excursion of the occluding disk, resulting in progressive stenosis of the aortic prosthesis. Intermittent dysfunction of a mechanical aortic prosthesis is usually ascribed to thrombus formation. We describe an unusual case of intermittent, noncyclic dysfunction of a mechanical aortic prosthesis due to pannus formation in the absence of systolic restriction of disk excursion that presented with intermittent massive aortic regurgitation, severe ischemia, and shock. Pannus formation should be considered as a potential cause of acute intermittent severe aortic regurgitation in a patient with a mechanical aortic prosthesis.

Adrenal, metabolic and cardio-renal dysfunction develops after pregnancy in rats born small or stressed by physiological measurements during pregnancy.

PubMed

Cheong, Jean N; Cuffe, James S M; Jefferies, Andrew J; Moritz, Karen M; Wlodek, Mary E

2016-10-15

Women born small are at an increased risk of developing pregnancy complications. Stress may further increase a woman's likelihood for an adverse pregnancy. Adverse pregnancy adaptations can lead to long-term diseases even after her pregnancy. The current study investigated the effects of stress during pregnancy on the long-term adrenal, metabolic and cardio-renal health of female rats that were born small. Stress programmed increased adrenal Mc2r gene expression, a higher insulin secretory response to glucose during intraperitoneal glucose tolerance test (+36%) and elevated renal creatinine clearance after pregnancy. Females that were born small had increased homeostatic model assessment-insulin resistance and elevated systolic blood pressure after pregnancy, regardless of stress exposure. These findings suggest that being born small or being stressed during pregnancy programs long-term adverse health outcomes after pregnancy. However, stress in pregnancy does not exacerbate the long-term adverse health outcomes for females that were born small. Females born small are more likely to experience complications during their pregnancy, including pregnancy-induced hypertension, pre-eclampsia and gestational diabetes. The risk of developing complications is increased by stress exposure during pregnancy. In addition, pregnancy complications may predispose the mother to diseases after pregnancy. We determined whether stress during pregnancy would exacerbate the adrenal, metabolic and cardio-renal dysfunction of growth-restricted females in later life. Late gestation bilateral uterine vessel ligation was performed in Wistar Kyoto rats to induce growth restriction. At 4 months, growth-restricted and control female offspring were mated with normal males. Those allocated to the stressed group had physiological measurements [metabolic cage, tail cuff blood pressure, intraperitoneal glucose tolerance test (IPGTT)] conducted during pregnancy whilst the unstressed groups were unhandled. After the completion of pregnancy, dams were aged to 12 months and blood pressure, and metabolic and renal function were assessed. At 13 months, adrenal glands, pancreases and plasma were collected at post-mortem. Females stressed during pregnancy had increased adrenal Mc2r gene expression (+22%), higher insulin secretory response to glucose during IPGTT (+36%) and higher creatinine clearance (+29%, indicating increased estimated glomerular filtration rate). In contrast, females that were born small had increased homeostatic model assessment-insulin resistance (+54%), increased water intake (+23%), urine output (+44%) and elevated systolic blood pressure (+7%) regardless of exposure to stress. Our findings suggest that low maternal birth weight and maternal stress exposure during pregnancy are both independently detrimental for long-term adrenal, metabolic and cardio-renal health of the mother, although their effects were not exacerbated. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Adrenal, metabolic and cardio‐renal dysfunction develops after pregnancy in rats born small or stressed by physiological measurements during pregnancy

PubMed Central

Cheong, Jean N.; Cuffe, James S. M.; Jefferies, Andrew J.; Moritz, Karen M.

2016-01-01

Key points Women born small are at an increased risk of developing pregnancy complications. Stress may further increase a woman's likelihood for an adverse pregnancy.Adverse pregnancy adaptations can lead to long‐term diseases even after her pregnancy.The current study investigated the effects of stress during pregnancy on the long‐term adrenal, metabolic and cardio‐renal health of female rats that were born small.Stress programmed increased adrenal Mc2r gene expression, a higher insulin secretory response to glucose during intraperitoneal glucose tolerance test (+36%) and elevated renal creatinine clearance after pregnancy.Females that were born small had increased homeostatic model assessment‐insulin resistance and elevated systolic blood pressure after pregnancy, regardless of stress exposure.These findings suggest that being born small or being stressed during pregnancy programs long‐term adverse health outcomes after pregnancy. However, stress in pregnancy does not exacerbate the long‐term adverse health outcomes for females that were born small. Abstract Females born small are more likely to experience complications during their pregnancy, including pregnancy‐induced hypertension, pre‐eclampsia and gestational diabetes. The risk of developing complications is increased by stress exposure during pregnancy. In addition, pregnancy complications may predispose the mother to diseases after pregnancy. We determined whether stress during pregnancy would exacerbate the adrenal, metabolic and cardio‐renal dysfunction of growth‐restricted females in later life. Late gestation bilateral uterine vessel ligation was performed in Wistar Kyoto rats to induce growth restriction. At 4 months, growth‐restricted and control female offspring were mated with normal males. Those allocated to the stressed group had physiological measurements [metabolic cage, tail cuff blood pressure, intraperitoneal glucose tolerance test (IPGTT)] conducted during pregnancy whilst the unstressed groups were unhandled. After the completion of pregnancy, dams were aged to 12 months and blood pressure, and metabolic and renal function were assessed. At 13 months, adrenal glands, pancreases and plasma were collected at post‐mortem. Females stressed during pregnancy had increased adrenal Mc2r gene expression (+22%), higher insulin secretory response to glucose during IPGTT (+36%) and higher creatinine clearance (+29%, indicating increased estimated glomerular filtration rate). In contrast, females that were born small had increased homeostatic model assessment‐insulin resistance (+54%), increased water intake (+23%), urine output (+44%) and elevated systolic blood pressure (+7%) regardless of exposure to stress. Our findings suggest that low maternal birth weight and maternal stress exposure during pregnancy are both independently detrimental for long‐term adrenal, metabolic and cardio‐renal health of the mother, although their effects were not exacerbated. PMID:27291586

Contribution of serum FGF21 level to the identification of left ventricular systolic dysfunction and cardiac death.

PubMed

Shen, Yun; Zhang, Xueli; Pan, Xiaoping; Xu, Yiting; Xiong, Qin; Lu, Zhigang; Ma, Xiaojing; Bao, Yuqian; Jia, Weiping

2017-08-18

The relationship between fibroblast growth factor 21 (FGF21) and cardiovascular disease has been well established in recent studies. This study aimed to investigate the relationship between FGF21 and left ventricular systolic dysfunction and cardiac death. Two-dimensional echocardiography was used to measure the left ventricular ejection fraction (LVEF) to estimate left ventricular systolic function. The optimal cutoff of FGF21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF21 and their association with cardiac death was analyzed via Kaplan-Meier survival curves. Serum FGF21 level was measured by an enzyme-linked immunosorbent assay kit, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level was determined by a chemiluminescent immunoassay. A total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32 ± 10.10 years. The optimal cutoff values of FGF21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/mL and 131.3 ng/L, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF21, NT-pro-BNP and FGF21 + NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037-9.500], P = 0.043, OR 9.207 [2.036-41.643], P = 0.004, separately). Further Kaplan-Meier survival analysis indicated an association between both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years [RR 5.000 (1.326-18.861), P = 0.026; RR 9.643 (2.596-35.825), P = 0.009, respectively]. Serum FGF21 level was significantly correlated with left ventricular systolic dysfunction at baseline. Patients with higher serum levels of FGF21 tended to suffer greater risks of cardiac death than patients with lower serum levels of FGF21. The identification of FGF21 and its relationship with left ventricular systolic function and cardiac death were non-inferior to NT-pro-BNP.

Changes in plasma levels of B-type natriuretic peptide with acute exacerbations of chronic obstructive pulmonary disease.

PubMed

Nishimura, Koichi; Nishimura, Takashi; Onishi, Katsuya; Oga, Toru; Hasegawa, Yoshinori; Jones, Paul W

2014-01-01

Elevated plasma B-type natriuretic peptide (BNP) levels and their association with heart failure have been reported in subjects with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). To examine and compare plasma BNP levels and diastolic and systolic dysfunction in subjects with AECOPD and stable chronic obstructive pulmonary disease (COPD). In all, 87 unselected consecutive hospitalizations due to AECOPD in 61 subjects and a total of 190 consecutive subjects with stable COPD were recruited. Plasma BNP levels were compared cross-sectionally and longitudinally. Transthoracic echocardiographic examinations were also performed in the hospitalized subjects. In the hospitalized subjects, the median plasma BNP level (interquartile range) was 55.4 (26.9-129.3) pg/mL and was higher than that of patients with stable COPD: 18.3 (10.0-45.3) for Global Initiative for Chronic Obstructive Lung Disease grade I; 25.8 (11.0-53.7) for grade II; 22.1 (9.1-52.6) for grade III; and 17.2 (9.6-22.9) pg/mL for grade I V, all P<0.001. In 15 subjects studied prospectively, the median plasma BNP level was 19.4 (9.8-32.2) pg/mL before AECOPD, 72.7 (27.7-146.3) pg/mL during AECOPD, and 14.6 (12.9-39.0) pg/mL after AECOPD (P<0.0033 and P<0.0013, respectively). Median plasma BNP levels during AECOPD were significantly higher in ten unsuccessfully discharged subjects 260.5 (59.4-555.0) than in 48 successfully discharged subjects 48.5 (24.2-104.0) pg/mL (P=0.0066). Only 5.6% of AECOPD subjects were associated with systolic dysfunction defined as a left ventricular ejection fraction (LVEF) <50%; a further 7.4% were considered to have impaired relaxation defined as an E/A wave velocity ratio <0.8 and a deceleration time of E >240 ms. BNP levels were weakly correlated with the E/peak early diastolic velocity of the mitral annulus (Ea) ratio (Spearman's rank correlation coefficient =0.353, P=0.018), but they were not correlated with the LVEF (Spearman's rank correlation coefficient =-0.221, P=0.108). A modest elevation of plasma BNP is observed during AECOPD. It appears that AECOPD may have an impact on plasma BNP levels that is not attributable to heart failure.

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.

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

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.

Comparison of five-year outcomes of coronary artery bypass grafting versus percutaneous coronary intervention in patients with left ventricular ejection fractions≤50% versus >50% (from the CREDO-Kyoto PCI/CABG Registry Cohort-2).

PubMed

Marui, Akira; Kimura, Takeshi; Nishiwaki, Noboru; Mitsudo, Kazuaki; Komiya, Tatsuhiko; Hanyu, Michiya; Shiomi, Hiroki; Tanaka, Shiro; Sakata, Ryuzo

2014-10-01

Coronary heart disease is a major risk factor for left ventricular (LV) systolic dysfunction. However, limited data are available regarding long-term benefits of percutaneous coronary intervention (PCI) in the era of drug-eluting stent or coronary artery bypass grafting (CABG) in patients with LV systolic dysfunction with severe coronary artery disease. We identified 3,584 patients with 3-vessel and/or left main disease of 15,939 patients undergoing first myocardial revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2. Of them, 2,676 patients had preserved LV systolic function, defined as an LV ejection fraction (LVEF) of >50% and 908 had impaired LV systolic function (LVEF≤50%). In patients with preserved LV function, 5-year outcomes were not different between PCI and CABG regarding propensity score-adjusted risk of all-cause and cardiac deaths. In contrast, in patients with impaired LV systolic function, the risks of all-cause and cardiac deaths after PCI were significantly greater than those after CABG (hazard ratio 1.49, 95% confidence interval 1.04 to 2.14, p=0.03 and hazard ratio 2.39, 95% confidence interval 1.43 to 3.98, p<0.01). In both patients with moderate (35%

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.

Abdominal adiposity, general obesity, and subclinical systolic dysfunction in the elderly: A population-based cohort study.

PubMed

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

2016-05-01

General obesity, measured by body mass index (BMI), and abdominal adiposity, measured as waist circumference (WC) and waist-to-hip ratio (WHR), are associated with heart failure and cardiovascular events. However, the relationship of general and abdominal obesity with subclinical left ventricular (LV) dysfunction is unknown. We assessed the association of general and abdominal obesity with subclinical LV systolic dysfunction in a population-based elderly cohort. Participants from the Cardiovascular Abnormalities and Brain Lesions study underwent measurement of BMI, WC, and WHR. Left ventricular systolic function was assessed by two-dimensional echocardiographic LV ejection fraction (LVEF) and speckle-tracking global longitudinal strain (GLS). The study population included 729 participants (mean age 71 ± 9 years, 60% women). In multivariate analysis, higher BMI (but not WC and WHR) was associated with higher LVEF (β = 0.11, P = 0.003). Higher WC (β = 0.08, P = 0.038) and higher WHR (β = 0.15, P < 0.001) were associated with lower GLS, whereas BMI was not (P = 0.720). Compared with normal WHR, high WHR was associated with lower GLS in all BMI categories (normal, overweight, and obese), and was associated with subclinical LV dysfunction by GLS both in participants without [adjusted odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.6, P = 0.020] and with general obesity (adjusted OR 5.4, 95% CI 1.1-25.9, P = 0.034). WHR was incremental to BMI and risk factors in predicting LV dysfunction. Abdominal adiposity was independently associated with subclinical LV systolic dysfunction by GLS in all BMI categories. BMI was not associated with LV dysfunction. Increased abdominal adiposity may be a risk factor for LV dysfunction regardless of the presence of general obesity. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Interobserver and Intraobserver Agreement on Qualitative Assessments of Right Ventricular Dysfunction With Echocardiography in Patients With Pulmonary Embolism.

PubMed

Weekes, Anthony J; Oh, Laura; Thacker, Gregory; Johnson, Angela K; Runyon, Michael; Rose, Geoffrey; Johnson, Thomas; Templin, Megan; Norton, H James

2016-10-01

To evaluate observer agreement using qualitative goal-directed echocardiographic criteria for right ventricular (RV) dysfunction prognostication in submassive pulmonary embolism (PE). Two emergency physicians and 2 cardiologists independently reviewed 31 packets of goal-directed echocardiographic video clips consisting of at least 3 windows obtained by emergency physicians from normotensive patients with PE. Nine packets were repeated to assess for intraobserver agreement. Right ventricular dysfunction criteria on goal-directed echocardiography were as follows: RV enlargement was present, with a right-to-left ventricular basal diameter ratio of 1.0 or higher and blunting of the apex of the RV in 2 or more different windows; RV systolic dysfunction was present if the tricuspid annulus moved toward the apex 10 mm or less and there was RV free wall hypokinesis; and septal deviation was present with any flattening or deviation of the ventricular septum toward the left ventricle. Among the 4 participants, there was 83.9% agreement on the presence or absence of RV enlargement (κ = 0.84), 74.2% agreement on the presence or absence of RV systolic dysfunction (κ = 0.69), and 71.0% agreement on the presence or absence of septal deviation (κ = 0.59). Intraobserver agreement was 100% for each RV dysfunction variable for each observer (κ = 1.0). Agreement was substantial for both severe RV enlargement and RV systolic dysfunction and moderate for septal deviation. Right ventricular dysfunction assessment with qualitative goal-directed echocardiographic criteria is reproducible for PE risk stratification.

Beta-Blockers (Carvedilol) in Children with Systemic Ventricle Systolic Dysfunction - Systematic Review and Meta-Analysis.

PubMed

Prijic, Sergej; Buchhorn, Reiner; Kosutic, Jovan; Vukomanovic, Vladislav; Prijic, Andreja; Bjelakovic, Bojko; Zdravkovic, Marija

2014-01-01

Numerous prospective randomized clinical trials demonstrated favorable effect of beta-blockers in adults with chronic heart failure. However, effectiveness of beta blockers in pediatric patients with systemic ventricle systolic dysfunction was not recognized sufficiently. Limited number of pediatric patients might be the course of unrecognized carvediolol treatment benefit. Currently, no meta-analysis has examined the impact of carvedilol and conventional therapy on the clinical outcome in children with chronic heart failure due to impaired systemic ventricle systolic function. We have systematically searched the Medline/PubMed and Cochrane Library for the controlled clinical trials that examine carvedilol and standard treatment efficacy in pediatric patients with systemic ventricle systolic dysfunction. Mean differences for continuous variables, odds ratios for dichotomous outcomes, heterogeneity between studies and publication bias were calculated using Cochrane Review Manager (Rev Man 5.2). Total of 8 prospective/observational studies met established criteria. Odds ratio for chronic heart failure related mortality/heart transplantation secondary to carvedilol was 0.52 (95% CI: 0.28-0.97, I(2) = 0%). Our analysis showed that carvedilol could prevent 1 death/ heart transplantation by treating 14 pediatric patients with impaired systemic ventricle systolic function. Meta-analysis demonstrated clinical outcome benefit of carvedilol in children with chronic heart failure.

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.

Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

PubMed

Marriott, James J; Miyasaki, Janis M; Gronseth, Gary; O'Connor, Paul W

2010-05-04

The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a "black box" warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in approximately 12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in approximately 0.4%, and leukemia occurs in approximately 0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking.

Exercise Training for Heart Failure Patients with and without Systolic Dysfunction: An Evidence-Based Analysis of How Patients Benefit

PubMed Central

Smart, Neil

2011-01-01

Significant benefits can be derived by heart failure patients from exercise training. This paper provides an evidence-based assessment of expected clinical benefits of exercise training for heart failure patients. Meta-analyses and randomized, controlled trials of exercise training in heart failure patients were reviewed from a search of PubMed, Cochrane Controlled Trial Registry (CCTR), CINAHL, and EMBASE. Exercise training improves functional capacity, quality of life, hospitalization, and systolic and diastolic function in heart failure patients. Heart failure patients with preserved systolic function (HFnEF) participating in exercise training studies are more likely to be women and are 5–7 years older than their systolic heart failure (CHF) counterparts. All patients exhibit low functional capacities, although in HFnEF patients this may be age related, therefore subtle differences in exercise prescriptions are required. Published works report that exercise training is beneficial for heart failure patients with and without systolic dysfunction. PMID:20953365

Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic.

PubMed

Corona, G; Mannucci, E; Petrone, L; Ricca, V; Balercia, G; Mansani, R; Chiarini, V; Giommi, R; Forti, G; Maggi, M

2006-01-01

Patients with diabetes mellitus (DM) were more often hypogonadal than normal fasting glucose subjects. The aim of this investigation is the assessment of characteristics and psychobiological correlates of DM associated with hypogonadism (DMAH). The Structured Interview SIEDY was used along with several biochemical, psychological and instrumental investigations in a series of more than 1200 patients with erectile dysfunction (ED); 16% of whom with type II DM. Hypogonadism was defined as circulating total testosterone (T) below 10.4 nmol/l. The prevalence of hypogonadism was 24.5% in DM versus 12.6% in the rest of the sample (P < 0.0001); differences in the prevalence of hypogonadism retained significance after adjustment for age and BMI. DMAH was associated with typical hypogonadism-related symptoms, such as reduction in sexual desire, leading to a decreased number of sexual attempts, and with higher depressive symptomatology. In DMAH, testis size and LH concentrations were significantly reduced, suggesting a central origin of the disease. At penile Duplex ultrasound examination, diabetic patients and in particular hypogonadal type II diabetic patients showed lower levels of basal and dynamic (after PGE1 injection) peak systolic velocity and acceleration, when compared to the rest of the sample, even after adjustment for age and BMI. Our results show that hypogonadism is frequently associated with type II DM, at least in the 6th decade. DMAH might exacerbate sexual dysfunction by reducing libido and mood and further compromising penile vascular reactivity.

[Oligomeric procyanidins from hawthorn extract as supplementary therapy in patients with left ventricle systolic dysfunction].

PubMed

Rechciński, Tomasz; Kurpesa, Małgorzata

2005-01-01

The results of recent studies provide the evidence that extract of hawthorn (Crataegus sp.) may provide benefits in left ventricular systolic dysfunction. The authors present a number of in vitro and in vivo studies in which the influence of this herbal drug on contractility of impaired myocardium has been proved. This kind of supplementary therapy was well tolerated and no interactions with the other compounds for heart failure were reported.

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.

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.

Left atrial function in heart failure with impaired and preserved ejection fraction.

PubMed

Fang, Fang; Lee, Alex Pui-Wai; Yu, Cheuk-Man

2014-09-01

Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

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.

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.

Diet-induced obesity promotes altered remodeling and exacerbated cardiac hypertrophy following pressure overload

PubMed Central

Holzem, Katherine M; Marmerstein, Joseph T; Madden, Eli J; Efimov, Igor R

2015-01-01

Heart failure (HF) is the end stage of cardiovascular disease, in which hypertrophic remodeling no longer meets cardiac output demand. Established animal models of HF have provided insights into disease pathogenesis. However, these models are developed on dissimilar metabolic backgrounds from humans – patients with HF are frequently overweight or obese, whereas animal models of HF are typically lean. Thus, we aimed to develop and investigate model for cardiac hypertrophy and failure that also recapitulates the cardiometabolic state of HF in humans. We subjected mice with established diet-induced obesity (DIO) to cardiac pressure overload provoked by transverse aortic constriction (TAC). Briefly, we fed WT male mice a normal chow or high-fat diet for 10 weeks prior to sham/TAC procedures and until surgical follow-up. We then analyzed cardiac hypertrophy, mechanical function, and electrophysiology at 5–6 weeks after surgery. In DIO mice with TAC, hypertrophy and systolic dysfunction were exacerbated relative to chow TAC animals, which showed minimal remodeling with our moderate constriction intensity. Normalized heart weight was 55.8% greater and fractional shortening was 30.9% less in DIO TAC compared with chow TAC hearts. However, electrophysiologic properties were surprisingly similar between DIO sham and TAC animals. To examine molecular pathways activated by DIO and TAC, we screened prohypertrophic signaling cascades, and the exacerbated remodeling was associated with early activation of the c-Jun-N-terminal kinase (JNK1/2) signaling pathway. Thus, DIO aggravates the progression of hypertrophy and HF caused by pressure overload, which is associated with JNK1/2 signaling, and cardiometabolic state can significantly modify HF pathogenesis. PMID:26290533

Noncardiogenic Pulmonary Edema as a Result of Urosepsis

DTIC Science & Technology

2010-03-01

cause could be aortic stenosis , which may require surgery to correct, or it could be coronary artery disease, which can be treated through a variety...systolic dysfunction. Left ventricular dysfunction can occur due to many processes such as aortic or mitral valve dysfunction, coronary artery disease

Jet Fuel Exacerbated Noise-Induced Hearing Loss: Focus on Prediction of Central Auditory Processing Dysfunction

DTIC Science & Technology

2017-09-01

to develop a multi-scale model, together with relevant supporting experimental data, to describe jet fuel exacerbated noise induced hearing loss. In...scale model, together with relevant supporting experimental data, to describe jet fuel exacerbated noise-induced hearing loss. Such hearing loss...project was to develop a multi-scale model, together with relevant supporting experimental data, to describe jet fuel exacerbated NIHL. Herein we

Correlation of left ventricular systolic dysfunction determined by low ejection fraction and 30-day mortality in patients with severe sepsis and septic shock: a systematic review and meta-analysis.

PubMed

Sevilla Berrios, Ronaldo A; O'Horo, John C; Velagapudi, Venu; Pulido, Juan N

2014-08-01

The prognostic implications of myocardial dysfunction in patients with sepsis and its association with mortality are controversial. Several tools have been proposed to evaluate cardiac function in these patients, but their usefulness beyond guiding therapy is unclear. We review the value of echocardiographic estimate of left ventricular ejection fraction (LVEF) in the setting of severe sepsis and/or septic shock and its correlation with 30-day mortality. We conducted a systematic review and meta-analysis to evaluate the prognostic functionality of newly diagnosed LV systolic dysfunction by transthoracic echocardiography on critical ill patients admitted to the intensive care unit with severe sepsis or septic shock. A search of EMBASE and PubMed, Ovide MEDLINE, and Cochrane CENTRAL medical databases yielded 7 studies meeting inclusion criteria reporting on a total of 585 patients. The pooled sensitivity of depressed LVEF for mortality was 52% (95% confidence interval [CI], 29%-73%), and pooled specificity was 63% (95% CI, 53%-71%). Summary receiver operating characteristic curve showed an area under the curve of 0.62 (95% CI, 0.58-0.67). The overall mortality diagnostic odd ratio for septic patients with LV systolic dysfunction was 1.92 (95% CI, 1.27-2.899). Statistical heterogeneity of studies was moderate. The presence of new LV systolic dysfunction associated with sepsis and defined as low LVEF is neither a sensitive nor a specific predictor of mortality. These findings are limited because of the heterogeneity and underpower of the studies. Further research into this method is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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.

Right ventricular dysfunction affects survival after surgical left ventricular restoration.

PubMed

Couperus, Lotte E; Delgado, Victoria; Palmen, Meindert; van Vessem, Marieke E; Braun, Jerry; Fiocco, Marta; Tops, Laurens F; Verwey, Harriëtte F; Klautz, Robert J M; Schalij, Martin J; Beeres, Saskia L M A

2017-04-01

Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function. A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all-cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed. Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was -24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88-0.98; P < .01), tricuspid annular plane systolic excursion (hazard ratio, 0.80; 95% confidence interval, 0.66-0.96; P = .02), and right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26; P < .01) were independently associated with 30-day mortality, after adjusting for left ventricular ejection fraction and aortic crossclamping time. Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was independently associated with increased 30-day mortality (hazard ratio, 2.83; 95% confidence interval, 1.64-4.87, P < .01 per additional impaired parameter). Baseline right ventricular systolic dysfunction is independently associated with increased mortality in patients with ischemic heart failure undergoing surgical left ventricular restoration. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Does load-induced ventricular hypertrophy progress to systolic heart failure?

PubMed

Berenji, Kambeez; Drazner, Mark H; Rothermel, Beverly A; Hill, Joseph A

2005-07-01

Ventricular hypertrophy develops in response to numerous forms of cardiac stress, including pressure or volume overload, loss of contractile mass from prior infarction, neuroendocrine activation, and mutations in genes encoding sarcomeric proteins. Hypertrophic growth is believed to have a compensatory role that diminishes wall stress and oxygen consumption, but Framingham and other studies established ventricular hypertrophy as a marker for increased risk of developing chronic heart failure, suggesting that hypertrophy may have maladaptive features. However, the relative contribution of comorbid disease to hypertrophy-associated systolic failure is unknown. For instance, coronary artery disease is induced by many of the same risk factors that cause hypertrophy and can itself lead to systolic dysfunction. It is uncertain, therefore, whether ventricular hypertrophy commonly progresses to systolic dysfunction without the contribution of intervening ischemia or infarction. In this review, we summarize findings from epidemiologic studies, preclinical experiments in animals, and clinical trials to lay out what is known-and not known-about this important question.

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.

Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction

PubMed Central

ASAHINA, Makoto; SHIMIZU, Fumi; OHTA, Masayuki; TAKEYAMA, Michiyasu; TOZAWA, Ryuichi

2015-01-01

Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome. PMID:25912321

Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction.

PubMed

Asahina, Makoto; Shimizu, Fumi; Ohta, Masayuki; Takeyama, Michiyasu; Tozawa, Ryuichi

2015-01-01

Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome.

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.

Comparison of the clinical utility of atrial and B type natriuretic peptide measurement for the diagnosis of systolic dysfunction in a low‐risk population

PubMed Central

Galasko, Gavin; Collinson, Paul O; Barnes, Sophie C; Gaze, David; Lahiri, Arjivit; Senior, Roxy

2007-01-01

Background Measurement of B type natriuretic peptide and its N terminal prohormone (NTproBNP) can now be performed routinely by automated high‐throughput immunoassays. The study compared measurement of NTproBNP with measurement of N terminal pro‐atrial natriuretic peptide (NTproANP) for detection of ventricular systolic dysfunction in primary care. Methods 734 subjects aged >45 years (349 men and 385 women, median age 58 years, range 45–89, interquartile range 51–67 years) from seven representative general practices attended for echocardiography with determination of ejection fraction and completed a questionnaire. Blood samples were collected into gel serum separation tubes (Becton–Dickinson, Franklin Lakes, New Jersey, USA), the serum separated and aliquots stored frozen at −70°C until analyses. Samples were analysed for NTproBNP (Roche Diagnostics, Lewes, UK; coefficient of variation (CV) 3.2–2.4%) and for NTproANP (Biomedica, Vienna, Austria; CV 5.6–10.1%). Echocardiography was used as the diagnostic “gold standard”, with ventricular systolic dysfunction defined as abnormal when there was an ejection fraction of ⩽40%. Patients were dichotomised by ejection fraction from 50% to 30%, and receiver operating characteristic curves constructed and the area under the curve (AUC) compared. Results At 40% ejection fraction, NTproANP and NTproBNP showed AUCs of, respectively, 0.738 (0.601–0.875) and 0.973 (0.958–0.989), p<0.004. Conclusion NTproBNP is superior to NTproANP for detection of systolic dysfunction. PMID:17513518

Can the Pediatric Logistic Organ Dysfunction-2 Score on Day 1 Be Used in Clinical Criteria for Sepsis in Children?

PubMed

Leclerc, Francis; Duhamel, Alain; Deken, Valérie; Grandbastien, Bruno; Leteurtre, Stéphane

2017-08-01

A recent task force has proposed the use of Sequential Organ Failure Assessment in clinical criteria for sepsis in adults. We sought to evaluate the predictive validity for PICU mortality of the Pediatric Logistic Organ Dysfunction-2 and of the "quick" Pediatric Logistic Organ Dysfunction-2 scores on day 1 in children with suspected infection. Secondary analysis of the database used for the development and validation of the Pediatric Logistic Organ Dysfunction-2. Nine university-affiliated PICUs in Europe. Only children with hypotension-low systolic blood pressure or low mean blood pressure using age-adapted cutoffs-and lactatemia greater than 2 mmol/L were considered in shock. We developed the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 including tachycardia, hypotension, and altered mentation (Glasgow < 11): one point for each variable (range, 0-3). Outcome was mortality at PICU discharge. Discrimination (Area under receiver operating characteristic curve-95% CI) and calibration (goodness of fit test) of the scores were studied. This study included 862 children with suspected infection (median age: 12.3 mo; mortality: n = 60 [7.0%]). Area under the curve of the Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.91 (0.86-0.96) in children with suspected infection, 0.88 (0.79-0.96) in those with low systolic blood pressure and hyperlactatemia, and 0.91 (0.85-0.97) in those with low mean blood pressure and hyperlactatemia; calibration p value was 0.03, 0.36, and 0.49, respectively. A Pediatric Logistic Organ Dysfunction-2 score on day 1 greater than or equal to 8 reflected an overall risk of mortality greater than or equal to 9.3% in children with suspected infection. Area under the curve of the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 was 0.82 (0.76-0.87) with systolic blood pressure or mean blood pressure; calibration p value was 0.89 and 0.72, respectively. A score greater than or equal to 2 reflected a mortality risk greater than or equal to 19.8% with systolic blood pressure and greater than or equal to 15.9% with mean blood pressure. Among children admitted to PICU with suspected infection, Pediatric Logistic Organ Dysfunction-2 score on day 1 was highly predictive of PICU mortality suggesting its use to standardize definitions and diagnostic criteria of pediatric sepsis. Further studies are needed to determine the usefulness of the quick Pediatric Logistic Organ Dysfunction-2 score on day 1 outside of the PICU.

EFFECTS OF A HIGH SATURATED FAT DIET ON CARDIAC HYPERTROPHY AND DYSFUNCTION IN RESPONSE TO PRESSURE OVERLOAD

PubMed Central

Chess, David; Lei, Biao; Hoit, Brian; Azimzadeh, Agnes M.; Stanley, William

2009-01-01

Background Dietary lipid content effects activation of peroxisome proliferator-activated receptor-α (PPARα) and may accelerate cardiac hypertrophy and dysfunction in response to pressure overload. This study investigated the effects of a high fat diet on the development of cardiac hypertrophy. Methods and Results C57BL/6J mice (n=14–16/group) underwent transverse aortic constriction (TAC) or sham surgery and were fed either standard low fat diet (STD; 10% fat) or a high fat diet (HFD; 60% fat) for 16 weeks. Sham mice showed no differences between STD and HFD for heart mass or echocardiographic parameters despite greater plasma free fatty acid and leptin concentrations with HFD. TAC increased heart mass and decreased ejection fraction similarly in both groups. Left ventricular end systolic and diastolic diameters with TAC were increased compared to shams on the HFD (p < 0.05) but were not different from STD TAC mice. High fat feeding increased expression of PPARα-regulated genes. The activity of medium chain acyl-coenzyme A dehydrogenase (MCAD), a marker of fatty acid oxidation capacity, was increased in HFD TAC mice compared to STD, consistent with PPARα activation. Conclusion Increased fat intake prevented the fall in MCAD activity and did not exacerbate the hypertrophic response to TAC compared to a low-fat diet. PMID:18226777

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.

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

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.

Global muscle dysfunction as a risk factor of readmission to hospital due to COPD exacerbations.

PubMed

Vilaró, Jordi; Ramirez-Sarmiento, Alba; Martínez-Llorens, Juana M A; Mendoza, Teresa; Alvarez, Miguel; Sánchez-Cayado, Natalia; Vega, Angeles; Gimeno, Elena; Coronell, Carlos; Gea, Joaquim; Roca, Josep; Orozco-Levi, Mauricio

2010-12-01

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with several modifiable (sedentary life-style, smoking, malnutrition, hypoxemia) and non-modifiable (age, co-morbidities, severity of pulmonary function, respiratory infections) risk factors. We hypothesise that most of these risk factors may have a converging and deleterious effects on both respiratory and peripheral muscle function in COPD patients. A multicentre study was carried out in 121 COPD patients (92% males, 63 ± 11 yr, FEV(1), 49 ± 17%pred). Assessments included anthropometrics, lung function, body composition using bioelectrical impedance analysis (BIA), and global muscle function (peripheral muscle (dominant and non-dominant hand grip strength, HGS), inspiratory (PI(max)), and expiratory (PE(max)) muscle strength). GOLD stage, clinical status (stable vs. non-stable) and both current and past hospital admissions due to COPD exacerbations were included as covariates in the analyses. Respiratory and peripheral muscle weakness were observed in all subsets of patients. Muscle weakness, was significantly associated with both current and past hospitalisations. Patients with history of multiple admissions showed increased global muscle weakness after adjusting by FEV(1) (PE(max), OR = 6.8, p < 0.01; PI(max), OR = 2.9, p < 0.05; HGSd, OR = 2.4, and HGSnd, OR = 2.6, p = 0.05). Moreover, a significant increase in both respiratory and peripheral muscle weakness, after adjusting by FEV(1), was associated with current acute exacerbations. Muscle dysfunction, adjusted by GOLD stage, is associated with an increased risk of hospital admissions due to acute episodes of exacerbation of the disease. Current exacerbations further deteriorate muscle dysfunction. Copyright © 2010 Elsevier Ltd. All rights reserved.

Excessive variability in systolic blood pressure that is self-measured at home exacerbates the progression of brain white matter lesions and cognitive impairment in the oldest old.

PubMed

Liu, Zhendong; Zhao, Yingxin; Zhang, Hua; Chai, Qiang; Cui, Yi; Diao, Yutao; Xiu, Jianchao; Sun, Xiaolin; Jiang, Guosheng

2016-04-01

To investigate the effects of variability in self-measured systolic blood pressure at home on the progression of cognitive impairment and white matter lesions in the oldest old. Between April 2009 and October 2009, 248 oldest old aged 80 years or older were eligibly enrolled from geriatric practices and community-dwelling areas of Shandong, China. Self-measured blood pressure at home (HBP) was measured for 7 consecutive days at the baseline, and the Mini-Mental State Examination (MMSE) score and brain white matter hyperintensities (WMH) were assessed at the baseline and during the final follow-up visit. Variability in systolic HBP was evaluated using coefficient of variation (CV) in serial daily systolic HBP measurements of the last 6 consecutive days. After an average of 2.3 years of follow-up visits, 232 oldest old were included in and 16 were excluded from the analysis. The MMSE score declined -4.76 (interquartile ranges: -10.71, -0.83) %, the periventricular WMH, deep WMH, total WMH and WMH fraction increased 16.46 (s.d.: 6.72)%, 10.05 (s.d.: 6.40)%, 14.69 (s.d.: 6.07)% and 15.95 (s.d.: 6.32)%, respectively, in the total oldest old. A declined percentage of the MMSE score and increased percentages of the periventricular WMH, deep WMH, total WMH and WMH fraction in the high group divided by tertile of the CV of the systolic HBP at baseline were greater than those in the low group (P<0.05). The significant differences were retained after adjusting for covariates, including the MMSE score, periventricular WMH, deep WMH and WMH fraction at the baseline (P<0.05). Excessive variability in self-measured systolic HBP exacerbates the progression of cognitive impairment and brain white matter lesions in the oldest old.

Application of updated guidelines on diastolic dysfunction in patients with severe sepsis and septic shock.

PubMed

Clancy, David J; Scully, Timothy; Slama, Michel; Huang, Stephen; McLean, Anthony S; Orde, Sam R

2017-12-19

Left ventricular diastolic dysfunction is suggested to be associated with higher mortality in severe sepsis and septic shock, yet the methods of diagnosis described in the literature are often inconsistent. The recently published 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) guidelines offer the opportunity to apply a simple pragmatic diagnostic algorithm for the detection of diastolic dysfunction; however, it has not been tested in this cohort. We sought to assess the applicability in septic patients of recently published 2016 ASE/EACVI guidelines on diastolic dysfunction compared with the 2009 ASE guidelines. Our hypothesis was that there would be poor agreement in classifying patients. Prospective observational study includes patients identified as having severe sepsis and septic shock. Patients underwent transthoracic echocardiography on day 1 and day 3 of their ICU admission. Patients with normal and abnormal (ejection fraction < 52%) systolic function had their diastolic function stratified according to both the 2009 ASE and 2016 ASE/EACVI guidelines. On day 1 echocardiography, of the 62 patients analysed, 37 (60%) had diastolic dysfunction according to the 2016 ASE/EACVI guideline with a further 23% having indeterminate diastolic function, compared to the 2009 ASE guidelines where only 13 (21%) had confirmed diastolic dysfunction with 46 (74%) having indeterminate diastolic dysfunction. On day 3, of the 55 patients studied, 22 patients (40%) were defined as having diastolic dysfunction, with 6 (11%) having indeterminate diastolic dysfunction according to the 2016 ASE/EACVI guidelines, compared to the 2009 guidelines where 11 (20%) were confirmed to have diastolic dysfunction and 41 (75%) had indeterminate diastolic function. Systolic dysfunction was identified in 18 of 62 patients (29%) on day 1 and 18 of 55 (33%) on day 3. These patients were classified as having abnormal diastolic function in 94 and 89% with the 2016 guidelines on day 1 and day 3, respectively, compared with 50 and 28% using the 2009 guidelines. The 2016 guidelines had less patients with indeterminate diastolic function on days 1 and 3 (11 and 6%) compared to the 2009 guidelines (50 and 72%). Normal systolic function was identified in 44 patients on day 1 and 37 on day 3. In this group, abnormal diastolic function was present in 45 and 54% on days 1 and 3 according to the 2016 ASE/EACVI guidelines, compared with 9 and 16% using the 2009 guidelines, respectively. In those with normal systolic function, the 2016 guidelines had less indeterminate patients with 30 and 16% on days 1 and 3, respectively, compared to 84 and 76% in the 2009 guidelines. The 2016 ASE/EACVI diastolic function guidelines identify a significantly higher incidence of dysfunction in patients with severe sepsis and septic shock compared to the previous 2009 guidelines. Although the new guidelines seem to be an improvement, issues remain with the application of guidelines using traditional measures of diastolic dysfunction in this cohort.

Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats

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

Chi, Liyi; Departments of Cardiology, The 451st Hospital of People's Liberation Army; Hu, Xiaojing

Angiotensin II (AngII) is the most important component of angiotensin, which has been regarded as a major contributor to the incidence of hypertension and vascular endothelial dysfunction. The adipocytokine C1q/TNF-related protein 6 (CTRP6) was recently reported to have multiple protective effects on cardiac and cardiovascular function. However, the exact role of CTRP6 in the progression of AngII induced hypertension and vascular endothelial function remains unclear. Here, we showed that serum CTRP6 content was significantly downregulated in SHRs, accompanied by a marked increase in arterial systolic pressure and serum AngII, CRP and ET-1 content. Then, pcDNA3.1-mediated CTRP6 delivery or CTRP6 siRNAmore » was injected into SHRs. CTRP6 overexpression caused a significant decrease in AngII expression and AngII-mediated hypertension and vascular endothelial inflammation. In contrast, CTRP6 knockdown had the opposite effect to CTRP6 overexpression. Moreover, we found that CTRP6 positively regulated the activation of the ERK1/2 signaling pathway and the expression of peroxisome proliferator-activated receptor γ (PPARγ), a recently proven negative regulator of AngII, in the brain and vascular endothelium of SHRs. Finally, CTRP6 was overexpressed in endothelial cells, and caused a significant increase in PPARγ activation and suppression in AngII-mediated vascular endothelial dysfunction and apoptosis. The effect of that could be rescued by the ERK inhibitor PD98059. In contrast, silencing CTRP6 suppressed PPARγ activation and exacerbated AngII-mediated vascular endothelial dysfunction and apoptosis. In conclusion, CTRP6 improves PPARγ activation and alleviates AngII-induced hypertension and vascular endothelial dysfunction. - Highlights: • Serum CTRP6 was significantly decreased in spontaneously hypertensive rats (SHRs). • CTRP6 positively regulated the activation of the ERK1/2 signaling pathway. • CTRP6 negatively regulates PPARγ mediated Angiotensin II (AngII) expression. • CTRP6 alleviates AngII-induced hypertension and vascular endothelial dysfunction.« less

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.

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.

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.

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.

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

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.

[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)

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.

Right ventricular presystolic peak velocity represents right ventricular function in stable patients.

PubMed

Giovanardi, Paolo; Tincani, Enrico; Stefanelli, Guglielmo; Turrini, Fabrizio; Magnavacchi, Paolo; Sansoni, Stefania; Zennaro, Mauro; Pinelli, Giovanni; Tondi, Stefano

2017-04-01

Right ventricular (RV) function is difficult to be measured but plays a role in morbility and mortality of patients with cardiopulmonary diseases, so many echocardiographic parameters have been developed from M-mode, B-mode and Doppler tissue imaging (DTI) evaluation. Right ventricular presystolic peak velocity (RVPrP) measured with DTI of the tricuspidal annulus and its changes in RV dysfunction have never been assessed in a patient's cohort of stable patients with cardiovascular risk factors. RVPrP velocity could have a role in RV function evaluation; this study addresses such issue. Four hundred thirty-six consecutive patients were submitted to a complete echocardiographic examination with the contemporary evaluation of the following RV function indexes: Tricuspid Annulus Plane Systolic Excurtion (TAPSE), RV Systolic Peak (RVSyP) and RVPrP. Pulmonary artery systolic pressure (PASP), left ventricular and RV diastolic function were also evaluated. According to TAPSE and RVSyP taken alone or in combination, 113 patients had RV dysfunction, while 323 patients had normal RV function. RVPrP was reduced in patient's group with RV dysfunction with respect to patient's group with preserved RV function (16.48±7.3 cm/s vs. 23.98±8.4 cm/s, respectively, P<0.001). RVPrP was related with RVSyP (P<0.001) and with TAPSE (P=0.002). TAPSE and RVSyP revealed a poor concordance to define RV dysfunction. PASP was higher in patient's group with reduced RV function (P=0.033). The study showed RVPrP able to detect stable patients with RV dysfunction.

Premorbid determinants of left ventricular dysfunction in a novel model of gradually induced pressure overload in the adult canine

NASA Technical Reports Server (NTRS)

Koide, M.; Nagatsu, M.; Zile, M. R.; Hamawaki, M.; Swindle, M. M.; Keech, G.; DeFreyte, G.; Tagawa, H.; Cooper, G. 4th; Carabello, B. A.

1997-01-01

BACKGROUND: When a pressure overload is placed on the left ventricle, some patients develop relatively modest hypertrophy whereas others develop extensive hypertrophy. Likewise, the occurrence of contractile dysfunction also is variable. The cause of this heterogeneity is not well understood. METHODS AND RESULTS: We recently developed a model of gradual proximal aortic constriction in the adult canine that mimicked the heterogeneity of the hypertrophic response seen in humans. We hypothesized that differences in outcome were related to differences present before banding. Fifteen animals were studied initially. Ten developed left ventricular dysfunction (dys group). Five dogs maintained normal function (nl group). At baseline, the nl group had a lower mean systolic wall stress (96 +/- 9 kdyne/cm2; dys group, 156 +/- 7 kdyne/cm2; P < .0002) and greater relative left ventricular mass (left ventricular weight [g]/body wt [kg], 5.1 +/- 0.36; dys group, 3.9 +/- 0.26; P < .02). On the basis of differences in mean systolic wall stress at baseline, we predicted outcome in the next 28 dogs by using a cutoff of 115 kdyne/cm2. Eighteen of 20 dogs with baseline mean systolic stress > 115 kdyne/cm2 developed dysfunction whereas 6 of 8 dogs with resting stress < or = 115 kdyne/cm2 maintained normal function. CONCLUSIONS: We conclude that this canine model mimicked the heterogeneous hypertrophic response seen in humans. In the group that eventually developed dysfunction there was less cardiac mass despite 60% higher wall stress at baseline, suggesting a different set point for regulating myocardial growth in the two groups.

Cytoskeletal Role in the Contractile Dysfunction of Hypertrophied Myocardium

NASA Astrophysics Data System (ADS)

Tsutsui, Hiroyuki; Ishihara, Kazuaki; Cooper, George

1993-04-01

Cardiac hypertrophy in response to systolic pressure loading frequently results in contractile dysfunction of unknown cause. In the present study, pressure loading increased the microtubule component of the cardiac muscle cell cytoskeleton, which was responsible for the cellular contractile dysfunction observed. The linked microtubule and contractile abnormalities were persistent and thus may have significance for the deterioration of initially compensatory cardiac hypertrophy into congestive heart failure.

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.

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.

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.

Intermittent, Non Cyclic Severe Mechanical Aortic Valve Regurgitation

PubMed Central

Choi, Jong Hyun; Song, Seunghwan; Lee, Myung-Yong

2013-01-01

Mechanical aortic prosthesis dysfunction can result from thrombosis or pannus formation. We describe an unusual case of intermittent, non cyclic mechanical aortic prosthesis dysfunction due to pannus formation with thrombus in the absence of systolic restriction of disk excursion, that presented with intermittent severe aortic regurgitation. PMID:24459568

Comparative effects of inhaled diesel exhaust and ambient fine particles on inflammation, atherosclerosis, and vascular dysfunction

PubMed Central

Quan, Chunli; Sun, Qinghua; Lippmann, Morton; Chen, Lung-Chi

2011-01-01

Ambient air PM2.5 (particulate matter less than 2.5 μm in diameter) has been associated with cardiovascular diseases (CVDs), but the underlying mechanisms affecting CVDs are unknown. The authors investigated whether subchronic inhalation of concentrated ambient PM2.5 (CAPs), whole diesel exhaust (WDE), or diesel exhaust gases (DEGs) led to exacerbation of atherosclerosis, pulmonary and systemic inflammation, and vascular dysfunction; and whether DEG interactions with CAPs alter cardiovascular effects. ApoE−/− mice were simultaneously exposed via inhalation for 5 hours/day, 4 days/week, for up to 5 months to one of five different exposure atmospheres: (1) filtered air (FA); (2) CAPs (105 μg/m3); (3) WDE (DEP = 436 μg/m3); (4) DEG (equivalent to gas levels in WDE group); and (5) CAPs+DEG (PM2.5: 113 μg/m3; with DEG equivalent to WDE group). After 3 and 5 months, lung lavage fluid and blood sera were analyzed, and atherosclerotic plaques were quantified by ultrasound imaging, hematoxylin and eosin (H&E stain), and en face Sudan IV stain. Vascular functions were assessed after 5 months of exposure. The authors showed that (1) subchronic CAPs, WDE, and DEG inhalations increased serum vascular cell adhesion molecule (VCAM)-1 levels and enhanced phenylephrine (PE)-induced vasoconstriction; (2) for plaque exacerbation, CAPs > WDE > DEG = FA, thus PM components (not present in WDE) were responsible for plaque development; (3) atherosclerosis can exacerbated through mechanistic pathways other than inflammation and vascular dysfunction; and (4) although there were no significant interactions between CAPs and DEG on plaque exacerbation, it is less clear whether the effects of CAPs on vasomotor dysfunction and pulmonary/systemic inflammation were enhanced by the DEG coexposure. PMID:20462391

Cardiac Dysfunction in HIV-1 Transgenic Mouse: Role of Stress and BAG3.

PubMed

Cheung, Joseph Y; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Tilley, Douglas G; Gao, Erhe; Koch, Walter J; Rabinowitz, Joseph; Klotman, Paul E; Khalili, Kamel; Feldman, Arthur M

2015-08-01

Since highly active antiretroviral therapy improved long-term survival of acquired immunodeficiency syndrome (AIDS) patients, AIDS cardiomyopathy has become an increasingly relevant clinical problem. We used human immunodeficiency virus (HIV)-1 transgenic (Tg26) mouse to explore molecular mechanisms of AIDS cardiomyopathy. Tg26 mice had significantly lower left ventricular (LV) mass and smaller end-diastolic and end-systolic LV volumes. Under basal conditions, cardiac contractility and relaxation and single myocyte contraction dynamics were not different between wild-type (WT) and Tg26 mice. Ten days after open heart surgery, contractility and relaxation remained significantly depressed in Tg26 hearts, suggesting that Tg26 mice did not tolerate surgical stress well. To simulate heart failure in which expression of Bcl2-associated athanogene 3 (BAG3) is reduced, we down-regulated BAG3 by small hairpin ribonucleic acid in WT and Tg26 hearts. BAG3 down-regulation significantly reduced contractility in Tg26 hearts. BAG3 overexpression rescued contractile abnormalities in myocytes expressing the HIV-1 protein Tat. We conclude: (i) Tg26 mice exhibit normal contractile function at baseline; (ii) Tg26 mice do not tolerate surgical stress well; (iii) BAG3 down-regulation exacerbated cardiac dysfunction in Tg26 mice; (iv) BAG3 overexpression rescued contractile abnormalities in myocytes expressing HIV-1 protein Tat; and (v) BAG3 may occupy a role in pathogenesis of AIDS cardiomyopathy. © 2015 Wiley Periodicals, Inc.

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.

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.

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

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

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure.

PubMed

Freestone, Bethan; Gustafsson, Finn; Chong, Aun Yeong; Corell, Pernille; Kistorp, Caroline; Hildebrandt, Per; Lip, Gregory Y H

2008-05-01

Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

Environmental enteric dysfunction and the fecal microbiota in Malawian children

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED) is often measured with a dual sugar absorption test and implicated as a causative factor in childhood stunting. Disturbances in the gut microbiota are hypothesized to be a mechanism by which EED is exacerbated, although this supposition lacks support. We perfo...

Impact of Residual Mitral Regurgitation on Right Ventricular Systolic Function After Left Ventricular Assist Device Implantation.

PubMed

Ertugay, Serkan; Kemal, Hatice S; Kahraman, Umit; Engin, Catagay; Nalbantgil, Sanem; Yagdi, Tahir; Ozbaran, Mustafa

2017-07-01

Significant mitral regurgitation (MR) is thought to decrease after left ventricular assist device (LVAD) implantation, and therefore repair of mitral valve is not indicated in current practice. However, residual moderate and severe MR leads to pulmonary artery pressure increase, thereby resulting in right ventricular (RV) dysfunction during follow-up. We examined the impact of residual MR on systolic function of the right ventricle by echocardiography after LVAD implantation. This study included 90 patients (mean age: 51.7 ± 10.9 years, 14.4% female) who underwent LVAD implantation (HeartMate II = 21, HeartWare = 69) in a single center between December 2010 and June 2014. Echocardiograms obtained at 3-6 months and over after implantation were analyzed retrospectively. RV systolic function was graded as normal, mild, moderate, and severely depressed. MR (≥moderate) was observed in 43 and 44% of patients at early and late period, respectively. Systolic function of the RV was severely depressed in 16 and 9% of all patients. Initial analysis (mean duration of support 174.3 ± 42.5 days) showed a statistically significant correlation between less MR and improved systolic function of RV (P = 0.01). Secondary echocardiographic analysis (following a mean duration of support of 435.1 ± 203 days) was also statistically significant for MR degree and RV systolic dysfunction (P = 0.008). Residual MR after LVAD implantation may cause deterioration of RV systolic function and cause right-sided heart failure symptoms. Repair of severe MR, in selected patients such as those with severe pulmonary hypertension and depressed RV, may be considered to improve the patient's clinical course during pump support. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

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.

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

Echocardiographic evaluation after pediatric heart transplant in Chile: initial application of a functional protocol with global longitudinal strain.

PubMed

Trincado, Claudia; Molina, Víctor; Urcelay, Gonzalo; Dellepiane, Paulina

2018-02-01

The echocardiographic evaluation of patients after heart transplantation is a useful tool. However, it is still necessary to define an optimal follow-up protocol. To describe the results of the application of a functional echocardiographic protocol in patients being followed after pediatric heart transplantation. Alls patients being followed at our institution after pediatric heart transplantation underwent an echocardiographic examination with a functional protocol that included global longitudinal strain. Contemporaneous endomyocardial biopsy results and hemodynamic data were recorded. 9 patients were evaluated with our echocardiographic functional protocol. Of these patients, only 1 showed systolic left ventricular dysfunction according to classic parameters. However, almost all patients had an abnormal global longitudinal strain. Right ventricular systolic dysfunction was observed in all patients. No epidodes of moderate to severe rejectiom were recorded. No correlation was observed between these parameters and pulmonary artery pressure. Subclinical biventricular systolic dysfunction was observed in the majority of the patients in this study. No association with rejection episodes or pulmonary hypertension was observed, which may be related to the absence of moderate or severe rejection episodes during the study period, and to the small sample size. Long term follow-up of these patients may better define the clinical relevance of our findings.

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

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

Importance of angina in patients with coronary disease, heart failure, and left ventricular systolic dysfunction: insights from STICH.

PubMed

Jolicœur, E Marc; Dunning, Allison; Castelvecchio, Serenella; Dabrowski, Rafal; Waclawiw, Myron A; Petrie, Mark C; Stewart, Ralph; Jhund, Pardeep S; Desvigne-Nickens, Patrice; Panza, Julio A; Bonow, Robert O; Sun, Benjamin; San, Tan Ru; Al-Khalidi, Hussein R; Rouleau, Jean L; Velazquez, Eric J; Cleland, John G F

2015-11-10

Patients with left ventricular (LV) systolic dysfunction, coronary artery disease (CAD), and angina are often thought to have a worse prognosis and a greater prognostic benefit from coronary artery bypass graft (CABG) surgery than those without angina. This study investigated: 1) whether angina was associated with a worse prognosis; 2) whether angina identified patients who had a greater survival benefit from CABG; and 3) whether CABG improved angina in patients with LV systolic dysfunction and CAD. We performed an analysis of the STICH (Surgical Treatment for Ischemic Heart Failure) trial, in which 1,212 patients with an ejection fraction ≤35% and CAD were randomized to CABG or medical therapy. Multivariable Cox and logistic models were used to assess long-term clinical outcomes. At baseline, 770 patients (64%) reported angina. Among patients assigned to medical therapy, all-cause mortality was similar in patients with and without angina (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 0.79 to 1.38). The effect of CABG was similar whether the patient had angina (HR: 0.89; 95% CI: 0.71 to 1.13) or not (HR: 0.68; 95% CI: 0.50 to 0.94; p interaction = 0.14). Patients assigned to CABG were more likely to report improvement in angina than those assigned to medical therapy alone (odds ratio: 0.70; 95% CI: 0.55 to 0.90; p < 0.01). Angina does not predict all-cause mortality in medically treated patients with LV systolic dysfunction and CAD, nor does it identify patients who have a greater survival benefit from CABG. However, CABG does improve angina to a greater extent than medical therapy alone. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Tissue angiotensin-converting enzyme inhibitors for the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure: a pooled meta-analysis of randomized placebo-controlled clinical trials.

PubMed

Saha, S A; Molnar, J; Arora, R R

2008-01-01

The aim of this study was to determine the role of tissue angiotensin-converting enzyme (ACE) inhibitors in the prevention of cardiovascular disease in patients with diabetes mellitus without left ventricular systolic dysfunction or clinical evidence of heart failure in randomized placebo-controlled clinical trials using pooled meta-analysis techniques. Randomized placebo-controlled clinical trials of at least 12 months duration in patients with diabetes mellitus without left ventricular systolic dysfunction or heart failure who had experienced a prior cardiovascular event or were at high cardiovascular risk were selected. A total of 10 328 patients (43 517 patient-years) from four selected trials were used for meta-analysis. Relative risk estimations were made using data pooled from the selected trials and statistical significance was determined using the Chi-squared test (two-sided alpha error <0.05). The number of patients needed to treat was also calculated. Tissue ACE inhibitors significantly reduced the risk of cardiovascular mortality by 14.9% (p = 0.022), myocardial infarction by 20.8% (p = 0.002) and the need for invasive coronary revascularization by 14% (p = 0.015) when compared to placebo. The risk of all-cause mortality also tended to be lower among patients randomized to tissue ACE inhibitors, whereas the risks of stroke and hospitalization for heart failure were not significantly affected. Treating about 65 patients with tissue ACE inhibitors for about 4.2 years would prevent one myocardial infarction, whereas treating about 85 patients would prevent one cardiovascular death. Pooled meta-analysis of randomized placebo-controlled trials suggests that tissue ACE inhibitors modestly reduce the risk of myocardial infarction and cardiovascular death and tend to reduce overall mortality in diabetic patients without left ventricular systolic dysfunction or heart failure.

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

"Reversibility of Cardiovascular Injury With CPAP Use: Mechanisms Involved"

ClinicalTrials.gov

2015-09-29

Sleep Apnea, Obstructive; Hypoxia; Hypercapnia; Sleep Disorders; Obesity; Hypertension; Coronary Artery Vasospasm; Right Ventricular Overload; Left Ventricular Function Systolic Dysfunction; Ventricular Hypertrophy

Left ventricular systolic dysfunction after transcatheter closure of a large patent ductus arteriosus.

PubMed

Galal, Mohammed Omar; Arfi, Muhammed Amin; Nicole, Sekarski; Payot, Maurice; Hussain, Arif; Qureshi, Shakeel

2005-11-01

A 12-year-old boy reported in outpatient department with history of shortness of breath and dyspnoea on moderate exertion. Physical examination was significant for bounding pulses and for a continuous murmur III/VI, best heard at the left upper sternal border. Echocardiography confirmed a large patent arterial duct with shortening fraction of 33%. He underwent successful transcatheter closure of the patent arterial, using Amplatzer duct occluder 12/10. Few hours later echocardiography revealed an unexpected, yet important depression of left ventricular systolic function with shortening fraction decreasing to 24% and then two weeks later decreasing further to 20%. At a follow-up after four months, he had improved clinically but left ventricular dysfunction still persisted with shortening fraction of 24%.

Right ventricular systolic dysfunction and vena cava dilatation precede alteration of renal function in adult patients undergoing cardiac surgery: An observational study.

PubMed

Guinot, Pierre Grégoire; Abou-Arab, Osama; Longrois, Dan; Dupont, Herve

2015-08-01

Several authors have suggested that right ventricular dysfunction (RVd) may contribute to renal dysfunction in nonsurgical patients. We tested the hypothesis that RVd diagnosed immediately after cardiac surgery may be associated with subsequent development of renal dysfunction and tried to identify the possible mechanisms. A single-centre, prospective observational study. Amiens University Hospital, France. All adult patients undergoing cardiac surgery were considered eligible for participation. Patients who had undergone pulmonary or tricuspid valve surgery, repeat surgery or who underwent immediate postoperative renal replacement therapy were excluded. Data from 74 patients were analysed. Left ventricular and right ventricular function were assessed before surgery and on admission to ICU by transthoracic echocardiography (TTE): left ventricular and right ventricular ejection fractions (LVEF/RVEF), tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (Sr(t)) and right ventricular dilatation. RVd was defined as values in the lowest quartile of at least two echocardiographic variables. Renal dysfunction was defined as an increase in serum creatinine concentration (sCr) on postoperative day 1. All right ventricular TTE variables decreased (P < 0.05) after surgery: RVEF from 50% (49 to 60) to 40% (35 to 50); TAPSE from 22.3 mm (19.4 to 25.3) to 12.2 mm (8.8 to 14.8); and Sr(t) from 15.0 cm s(-1) (12.0 to 18.0) to 8.1 cm s(-1) (6.3 to 9.2). Fourteen (19%) patients had right ventricular dilatation and RVd was present in 23 (31%) patients. Forty patients had a positive variation in sCr. In multivariate analysis, patients with RVd had an odds ratio (OR) of 12.7 [95% confidence interval (95% CI) 2.6 to 63.4, P = 0.02] for development of renal dysfunction. Renal dysfunction was associated with increased central venous pressure but was not associated with cardiac index (CI). These results suggest that early postoperative RVd is associated with a subsequent increase of sCr and that the mechanism involved is congestion (vena cava dilatation/elevated CVP) rather than decreased CI.

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

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.

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.

Uteroplacental insufficiency temporally exacerbates salt-induced hypertension associated with a reduced natriuretic response in male rat offspring.

PubMed

Gallo, Linda A; Walton, Sarah L; Mazzuca, Marc Q; Tare, Marianne; Parkington, Helena C; Wlodek, Mary E; Moritz, Karen M

2018-03-31

Low weight at birth increases the risk of developing chronic diseases in adulthood A diet that is high in salt is known to elevate blood pressure, which is a major risk factor for cardiovascular and kidney diseases The present study demonstrates that growth restricted male rats have a heightened sensitivity to high dietary salt, in the context of raised systolic blood pressure, reduced urinary sodium excretion and stiffer mesenteric resistance vessels Other salt-induced effects, such as kidney hyperfiltration, albuminuria and glomerular damage, were not exacerbated by being born small The present study demonstrates that male offspring born small have an increased cardiovascular susceptibility to high dietary salt, such that that minimizing salt intake is probably of particular benefit to this at-risk population ABSTRACT: Intrauterine growth restriction increases the risk of developing chronic diseases in adulthood. Lifestyle factors, such as poor dietary choices, may elevate this risk. We determined whether being born small increases the sensitivity to a dietary salt challenge, in the context of hypertension, kidney disease and arterial stiffness. Bilateral uterine vessel ligation or sham surgery (offspring termed Restricted and Control, respectively) was performed on 18-day pregnant Wistar Kyoto rats. Male offspring were allocated to receive a diet high in salt (8% sodium chloride) or remain on standard rat chow (0.52% sodium chloride) from 20 to 26 weeks of age for 6 weeks. Systolic blood pressure (tail-cuff), renal function (24 h urine excretions) and vascular stiffness (pressure myography) were assessed. Restricted males were born 15% lighter than Controls and remained smaller throughout the study. Salt-induced hypertension was exacerbated in Restricted offspring, reaching a peak systolic pressure of ∼175 mmHg earlier than normal weight counterparts. The natriuretic response to high dietary salt in Restricted animals was less than in Controls and may explain the early rise in arterial pressure. Growth restricted males allocated to a high salt diet also had increased passive arterial stiffness of mesenteric resistance arteries. Other aspects of renal function, including salt-induced hyperfiltration, albuminuria and glomerular damage, were not exacerbated by uteroplacental insufficiency. The present study demonstrates that male offspring exposed to uteroplacental insufficiency and born small have an increased sensitivity to salt-induced hypertension and arterial remodelling. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

The Effects of Antigen-Specific IgG1 Antibody for the Pulmonary-Hypertension-Phenotype and B Cells for Inflammation in Mice Exposed to Antigen and Fine Particles from Air Pollution

PubMed Central

Park, Sung-Hyun; Chen, Wen-Chi; Durmus, Nedim; Bleck, Bertram; Reibman, Joan; Riemekasten, Gabriela; Grunig, Gabriele

2015-01-01

Air pollution is known to exacerbate chronic inflammatory conditions of the lungs including pulmonary hypertension, cardiovascular diseases and autoimmune diseases. Directly pathogenic antibodies bind pro-inflammatory cell receptors and cause or exacerbate inflammation. In contrast, anti-inflammatory antibody isotypes (e.g. mouse immunoglobulin G1, IgG1) bind inhibitory cell receptors and can inhibit inflammation. Our previous studies showed that co-exposure to antigen and urban ambient particulate matter (PM2.5) induced severe pulmonary arterial thickening and increased right ventricular systolic pressures in mice via T-cell produced cytokines, Interleukin (IL)-13 and IL-17A. The aim of the current study was to understand how B cell and antibody responses integrate into this T cell cytokine network for the pulmonary hypertension phenotype. Special focus was on antigen-specific IgG1 that is the predominant antibody in the experimental response to antigen and urban ambient PM2.5. Wild type and B cell-deficient mice were primed with antigen and then challenged with antigen and urban particulate matter and injected with antibodies as appropriate. Our data surprisingly showed that B cells were necessary for the development of increased right ventricular pressures and molecular changes in the right heart in response to sensitization and intranasal challenge with antigen and PM2.5. Further, our studies showed that both, the increase in right ventricular systolic pressure and right ventricular molecular changes were restored by reconstituting the B cell KO mice with antigen specific IgG1. In addition, our studies identified a critical, non-redundant role of B cells for the IL-17A-directed inflammation in response to exposure with antigen and PM2.5, which was not corrected with antigen-specific IgG1. In contrast, IL-13-directed inflammatory markers, as well as severe pulmonary arterial remodeling induced by challenge with antigen and PM2.5 were similar in B cell-deficient and wild type mice. Our studies have identified B cells and antigen specific IgG1 as potential therapeutic targets for pulmonary hypertension associated with immune dysfunction and environmental exposures. PMID:26079807

Diagnostic and prognostic value of right ventricular strain in patients with pulmonary arterial hypertension and relatively preserved functional capacity studied with echocardiography and magnetic resonance.

PubMed

da Costa Junior, Augusto Alberto; Ota-Arakaki, Jaquelina Sonoe; Ramos, Roberta Pulcheri; Uellendahl, Marly; Mancuso, Frederico José Neves; Gil, Manuel Adan; Fischer, Cláudio Henrique; Moises, Valdir Ambrosio; de Camargo Carvalho, Antonio Carlos; Campos, Orlando

2017-01-01

Right ventricular (RV) dysfunction harbingers adverse prognosis in pulmonary arterial hypertension (PAH). Although conventional two-dimensional echocardiography (2DE) is limited for RV systolic function quantitation, RV strain can be a useful tool. The diagnostic and prognostic impact of 2DE speckle-tracking RV longitudinal strain was evaluated, including other 2DE systolic indexes, in a group of PAH patients without severe impairment of functional capacity, chronic pulmonary thromboembolism or left ventricular dysfunction. Sixty-six group I PAH patients, 67 % NYHA functional class I or II (none in IV) were studied by 2DE to obtain: RV fractional area change, tricuspid annular plane systolic excursion, RV myocardial performance index, tissue Doppler tricuspid annulus systolic velocity. Global, free wall (RVFreeWSt) and septal RV longitudinal systolic strain were obtained. RV ejection fraction by cardiac magnetic resonance (CMR-RVEF) was also assessed. All patients were followed up to 3.9 years (mean 3.3 years). Combined endpoints were hospitalization for worsening PAH or cardiovascular death. Among all the 2DE indexes of RV systolic function, RVFreeWSt exhibited the best correlation with CMR-RVEF (r = 0.83; p < 0.005). Combined endpoints occurred in 15 (22.7 %) patients (6 hospitalizations and 9 deaths). Multivariate analysis identified RVFreeWSt ≤-14 % as the only 2DE independent variable associated with combined endpoints [HR 4.66 (1.25-17.37); p < 0.05]. We conclude that RVFreeWSt may be a suitable non-geometric 2DE surrogate of CMR-RVEF in PAH patients, constituting a powerful independent predictor of long-term outcome in this cohort with relatively preserved functional capacity.

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

Aldosterone-Induced Vascular Remodeling and Endothelial Dysfunction Require Functional Angiotensin Type 1a Receptors.

PubMed

Briet, Marie; Barhoumi, Tlili; Mian, Muhammad Oneeb Rehman; Coelho, Suellen C; Ouerd, Sofiane; Rautureau, Yohann; Coffman, Thomas M; Paradis, Pierre; Schiffrin, Ernesto L

2016-05-01

We investigated the role of angiotensin type 1a receptors (AGTR1a) in vascular injury induced by aldosterone activation of mineralocorticoid receptors in Agtr1a(-/-) and wild-type (WT) mice infused with aldosterone for 14 days while receiving 1% NaCl in drinking water. Aldosterone increased systolic blood pressure (BP) by ≈30 mm Hg in WT mice and ≈50 mm Hg in Agtr1a(-/-) mice. Aldosterone induced aortic and small artery remodeling, impaired endothelium-dependent relaxation in WT mice, and enhanced fibronectin and collagen deposition and vascular inflammation. None of these vascular effects were observed in Agtr1a(-/-) mice. Aldosterone effects were prevented by the AGTR1 antagonist losartan in WT mice. In contrast to aldosterone, norepinephrine caused similar BP increase and mesenteric artery remodeling in WT and Agtr1a(-/-) mice. Agtr1a(-/-) mice infused with aldosterone did not increase sodium excretion in response to a sodium chloride challenge, suggesting that sodium retention could contribute to the exaggerated BP rise induced by aldosterone. Agtr1a(-/-) mice had decreased mesenteric artery expression of the calcium-activated potassium channel Kcnmb1, which may enhance myogenic tone and together with sodium retention, exacerbate BP responses to aldosterone/salt in Agtr1a(-/-) mice. We conclude that although aldosterone activation of mineralocorticoid receptors raises BP more in Agtr1a(-/-) mice, AGTR1a is required for mineralocorticoid receptor stimulation to induce vascular remodeling and inflammation and endothelial dysfunction. © 2016 American Heart Association, Inc.

ALDOSTERONE-INDUCED VASCULAR REMODELING AND ENDOTHELIAL DYSFUNCTION REQUIRE FUNCTIONAL ANGIOTENSIN TYPE 1a RECEPTORS

PubMed Central

Coelho, Suellen C.; Ouerd, Sofiane; Rautureau, Yohann; Coffman, Thomas M.; Paradis, Pierre; Schiffrin, Ernesto L.

2016-01-01

We investigated the role of angiotensin type 1a receptors (AGTR1a) in vascular injury induced by aldosterone activation of mineralocorticoid receptors (MR) in Agtr1a−/− and wild-type mice infused with aldosterone for 14 days while receiving 1% NaCl in drinking water. Aldosterone increased systolic blood pressure by ~30 mmHg in wild-type mice, and ~50 mmHg in Agtr1a−/− mice. Aldosterone induced aortic and small artery remodeling and impaired endothelium-dependent relaxation in wild-type mice, and enhanced fibronectin and collagen deposition, and vascular inflammation. None of these vascular effects were observed in Agtr1a−/− mice. Aldosterone effects were prevented by the AGTR1 antagonist losartan in wild-type mice. In contrast to aldosterone, norepinephrine caused similar BP increase and mesenteric artery remodeling in wild-type and Agtr1a−/− mice. Agtr1a−/− mice infused with aldosterone did not increase sodium excretion in response to a sodium chloride challenge, suggesting sodium retention that could contribute to the exaggerated blood pressure rise induced by aldosterone. Agtr1a−/− mice had decreased mesenteric artery expression of the calcium-activated potassium channel Kcnmb1, which may enhance myogenic tone and together with sodium retention exacerbate BP responses to aldosterone/salt in Agtr1a−/− mice. We conclude that although aldosterone activation of MR raises BP more in Agtr1a−/− mice, AGTR1a is required for MR stimulation to induce vascular remodeling and inflammation, and endothelial dysfunction. PMID:27045029

Interdependence of right ventricular systolic function and left ventricular filling and its association with outcome for patients with pulmonary hypertension.

PubMed

Motoji, Yoshiki; Tanaka, Hidekazu; Fukuda, Yuko; Sano, Hiroyuki; Ryo, Keiko; Imanishi, Junichi; Miyoshi, Tatsuya; Sawa, Takuma; Mochizuki, Yasuhide; Matsumoto, Kensuke; Emoto, Noriaki; Hirata, Ken-ichi

2015-04-01

Although impaired right ventricular (RV) performance has been associated with adverse outcomes for pulmonary hypertension (PH) patients, the relationship between bi-ventricular interdependence and outcomes is not yet fully understood. We studied 96 PH patients. RV systolic function was assessed by means of RV free-wall longitudinal speckle-tracking strain (RV-free), and left ventricular (LV) filling as early diastolic transmitral flow velocity (TMF-E). RV-free ≤19 % and TMF-E <60 cm/s were adopted as pre-defined cut-offs for RV systolic dysfunction and LV under-filling, respectively, associated with worse outcomes. Long-term outcome was tracked over 2.2 years. RV-free correlated significantly with TMF-E (r = 0.57, p < 0.001).TMF-E and RV-free were significantly lower in patients with than in those without cardiac events. RV systolic dysfunction and LV under-filling was observed in 35 patients. These features were associated with worse long-term survival compared to other sub-groups (log-rank p = 0.012). A sequential Cox model based on clinical variables including world health organization functional class IV and brain natriuretic peptide >150 pg/dl (χ(2) = 1.2) was improved by the addition of RV-free (χ(2) = 5.5, p = 0.04) as well as of TMF-E (χ(2) = 11.5, p = 0.01). In conclusions, RV systolic function was shown to correlate significantly with LV filling in PH patients. In addition, not only assessment of RV systolic function, but also of a combined bi-ventricular parameter comprising RV systolic function and LV filling may well have clinical implications for more successful management of PH patients.

What is the association between left ventricular diastolic dysfunction and 6-minute walk test in hypertensive patients?

PubMed

Farag, El-Sayed M; Al-Daydamony, Mohammad M; Gad, Marwa M

2017-03-01

Heart failure (HF) is a major health problem. Hypertension is an important cause of HF. Most hypertensive patients have some degree of left ventricular (LV) diastolic dysfunction. The 6-minute walk test (6MWT) provides objective data about the exercise tolerance. We aimed to find the association between the degree of LV diastolic dysfunction and the functional capacity assessed by 6MWT in hypertensive patients. The study included 200 asymptomatic hypertensive patients. All patients had undergone full history taking, complete clinical examination, electrocardiography, echocardiography for assessment of LV dimensions, systolic and diastolic dysfunction, and 6MWT. Patients were classified into two groups according to the presence or absence of LV diastolic dysfunction. Clinical and echocardiographic data were comparable between the two groups. Regarding 6MWT, at the end of the test, patients with diastolic dysfunction had significantly higher systolic (P = .0088) and diastolic (P = .019) blood pressure and higher Borg score for dyspnea (P < .00001). The distant walked and percentage of the distance to predicted value were significantly lower in patients with diastolic dysfunction (P = .0322 and .0002, respectively). Incidence of abnormal 6MWT was significantly higher in patients with diastolic dysfunction (P = .00041). Compared to patients with grades I and II, patients with grade III diastolic dysfunction had significantly higher Borg score (P = .013), lower distance walked (P = .039), and lower percentage of distance to predicted vale (P = .009). Independent predictors for abnormal 6MWT were as follows: E/E' ≥15 (P = .0022), E'/A' <1 (P = .0081), and deceleration time of E-wave <160 (P = .013). The presence of LV diastolic dysfunction in hypertensive patients has a bad effect on 6MWT. The degree of LV diastolic dysfunction was correlated with 6MWT results. It may be important to investigate LV diastolic function in asymptomatic hypertensive patients. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

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

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.

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.

Echocardiography Criteria for Structural Heart Disease in Patients With End-Stage Renal Disease Initiating Hemodialysis.

PubMed

Hickson, LaTonya J; Negrotto, Sara M; Onuigbo, Macaulay; Scott, Christopher G; Rule, Andrew D; Norby, Suzanne M; Albright, Robert C; Casey, Edward T; Dillon, John J; Pellikka, Patricia A; Pislaru, Sorin V; Best, Patricia J M; Villarraga, Hector R; Lin, Grace; Williams, Amy W; Nkomo, Vuyisile T

2016-03-15

Cardiovascular disease among hemodialysis (HD) patients is linked to poor outcomes. The Acute Dialysis Quality Initiative Workgroup proposed echocardiographic (ECHO) criteria for structural heart disease (SHD) in dialysis patients. The association of SHD with important patient outcomes is not well defined. This study sought to determine prevalence of ECHO-determined SHD and its association with survival among incident HD patients. We analyzed patients who began chronic HD from 2001 to 2013 who underwent ECHO ≤1 month prior to or ≤3 months following initiation of HD (n = 654). Mean patient age was 66 ± 16 years, and 60% of patients were male. ECHO findings that met 1 or more and ≥3 of the new criteria were discovered in 87% and 54% of patients, respectively. Over a median of 2.4 years, 415 patients died: 108 (26%) died within 6 months. Five-year mortality was 62%. Age- and sex-adjusted structural heart disease variables associated with death were left ventricular ejection fraction (LVEF) ≤45% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.20 to 1.83) and right ventricular (RV) systolic dysfunction (HR: 1.68; CI: 1.35 to 2.07). An additive of higher death risk included LVEF ≤45% and RV systolic dysfunction rather than neither (HR: 2.04; CI: 1.57 to 2.67; p = 0.53 for test for interaction). Following adjustment for age, sex, race, diabetic kidney disease, and dialysis access, RV dysfunction was independently associated with death (HR: 1.66; CI 1.34 to 2.06; p < 0.001). SHD was common in our HD study population, and RV systolic dysfunction independently predicted mortality. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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

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.

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.

Right ventricular dysfunction in the R6/2 transgenic mouse model of Huntington's disease is unmasked by dobutamine.

PubMed

Buonincontri, Guido; Wood, Nigel I; Puttick, Simon G; Ward, Alex O; Carpenter, T Adrian; Sawiak, Stephen J; Morton, A Jennifer

2014-01-01

Increasingly, evidence from studies in both animal models and patients suggests that cardiovascular dysfunction is important in HD. Previous studies measuring function of the left ventricle (LV) in the R6/2 model have found a clear cardiac abnormality, albeit with preserved LV systolic function. It was hypothesized that an impairment of RV function might play a role in this condition via mechanisms of ventricular interdependence. To investigate RV function in the R6/2 mouse model of Huntington's disease (HD). Cardiac cine-magnetic resonance imaging (MRI) was used to determine functional parameters in R6/2 mice. In a first experiment, these parameters were derived longitudinally to determine deterioration of cardiac function with disease progression. A second experiment compared the response to a stress test (using dobutamine) of wildtype and early-symptomatic R6/2 mice. There was progressive deterioration of RV systolic function with age in R6/2 mice. Furthermore, beta-adrenergic stimulation with dobutamine revealed RV dysfunction in R6/2 mice before any overt symptoms of the disease were apparent. This work adds to accumulating evidence of cardiovascular dysfunction in R6/2 mice, describing for the first time the involvement of the right ventricle. Cardiovascular dysfunction should be considered, both when treatment strategies are being designed, and when searching for biomarkers for HD.

Gastrointestinal Dysfunctions as a Risk Factor for Sleep Disorders in Children with Idiopathic Autism Spectrum Disorder: A Retrospective Cohort Study

ERIC Educational Resources Information Center

McCue, Lena M.; Flick, Louise H.; Twyman, Kimberly A.; Xian, Hong

2017-01-01

Sleep disorders often co-occur with autism spectrum disorder. They further exacerbate autism spectrum disorder symptoms and interfere with children's and parental quality of life. This study examines whether gastrointestinal dysfunctions increase the odds of having sleep disorders in 610 children with idiopathic autism spectrum disorder, aged 2-18…

Left ventricular mechanics in isolated mild mitral stenosis: a three dimensional speckle tracking study.

PubMed

Poyraz, Esra; Öz, Tuğba Kemaloğlu; Zeren, Gönül; Güvenç, Tolga Sinan; Dönmez, Cevdet; Can, Fatma; Güvenç, Rengin Çetin; Dayı, Şennur Ünal

2017-09-01

In a fraction of patients with mild mitral stenosis, left ventricular systolic function deteriorates despite the lack of hemodynamic load imposed by the dysfunctioning valve. Neither the predisposing factors nor the earlier changes in left ventricular contractility were understood adequately. In the present study we aimed to evaluate left ventricular mechanics using three-dimensional (3D) speckle tracking echocardiography. A total of 31 patients with mild rheumatic mitral stenosis and 27 healthy controls were enrolled to the study. All subjects included to the study underwent echocardiographic examination to collect data for two- and three-dimensional speckle-tracking based stain, twist angle and torsion measurements. Data was analyzed offline with a echocardiographic data analysis software. Patients with rheumatic mild MS had lower global longitudinal (p < 0.001) circumferential (p = 0.02) and radial (p < 0.01) strain compared to controls, despite ejection fraction was similar for both groups [(p = 0.45) for three dimensional and (p = 0.37) for two dimensional measurement]. While the twist angle was not significantly different between groups (p = 0.11), left ventricular torsion was significantly higher in mitral stenosis group (p = 0.03). All strain values had a weak but significant positive correlation with mitral valve area measured with planimetry. Subclinical left ventricular systolic dysfunction develops at an early stage in rheumatic mitral stenosis. Further work is needed to elucidate patients at risk for developing overt systolic dysfunction.

The management of patients with aortic regurgitation and severe left ventricular dysfunction: a systematic review.

PubMed

Badar, Athar A; Brunton, Alan P T; Mahmood, Ammad H; Dobbin, Stephen; Pozzi, Andrea; McMinn, Jenna F; Sinclair, Andrew J E; Gardner, Roy S; Petrie, Mark C; Curry, Phil A; Al-Attar, Nawwar H K; Pettit, Stephen J

2015-01-01

A systematic search of Medline, EMBASE and CINAHL electronic databases was performed. Original research articles reporting all-cause mortality following surgery in patients with aortic regurgitation and severe left ventricular systolic dysfunction (LVSD) were identified. Nine of the 10 eligible studies were observational, single-center, retrospective analyses. Survival ranged from 86 to 100% at 30 days; 81 to 100% at 1 year and 68 to 84% at 5 years. Three studies described an improvement in mean left ventricular ejection fraction (LVEF) following aortic valve replacement (AVR) of 5-14%; a fourth study reported an increase in mean left ventricular ejection fraction (LVEF) of 9% in patients undergoing isolated AVR but not when AVR was combined with coronary artery bypass graft and/or mitral valve surgery. Three studies demonstrated improvements in functional New York Heart Association (NYHA) class following AVR. Additional studies are needed to clarify the benefits of AVR in patients with more extreme degrees of left ventricular systolic dysfunction (LVSD) and the potential roles of cardiac transplantation and transaortic valve implantation.

Catheter-based intervention for symptomatic patient with severe mitral regurgitation and very poor left ventricular systolic function - Safe but no room for complacency.

PubMed

Loh, Poay Huan; Bourantas, Christos V; Chan, Pak Hei; Ihlemann, Nikolaj; Gustafsson, Fin; Clark, Andrew L; Price, Susanna; Mario, Carlo Di; Moat, Neil; Alamgir, Farqad; Estevez-Loureiro, Rodrigo; Søndergaard, Lars; Franzen, Olaf

2015-11-26

Many patients with left ventricular systolic dysfunction have concomitant mitral regurgitation (MR). Their symptoms and prognosis worsen with increasing severity of MR. Percutaneous MitraClip(®) can be used safely to reduce the severity of MR even in patients with advanced heart failure and is associated with improved symptoms, quality of life and exercise tolerance. However, a few patients with very poor left ventricular systolic function may experience significant haemodynamic disturbance in the peri-procedural period. We present three such patients, highlighting some of the potential problems encountered and discuss their possible pathophysiological mechanisms and safety measures.

Catheter-based intervention for symptomatic patient with severe mitral regurgitation and very poor left ventricular systolic function - Safe but no room for complacency

PubMed Central

Loh, Poay Huan; Bourantas, Christos V; Chan, Pak Hei; Ihlemann, Nikolaj; Gustafsson, Fin; Clark, Andrew L; Price, Susanna; Mario, Carlo Di; Moat, Neil; Alamgir, Farqad; Estevez-Loureiro, Rodrigo; Søndergaard, Lars; Franzen, Olaf

2015-01-01

Many patients with left ventricular systolic dysfunction have concomitant mitral regurgitation (MR). Their symptoms and prognosis worsen with increasing severity of MR. Percutaneous MitraClip® can be used safely to reduce the severity of MR even in patients with advanced heart failure and is associated with improved symptoms, quality of life and exercise tolerance. However, a few patients with very poor left ventricular systolic function may experience significant haemodynamic disturbance in the peri-procedural period. We present three such patients, highlighting some of the potential problems encountered and discuss their possible pathophysiological mechanisms and safety measures. PMID:26635930

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.

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.

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.

UCP3 Ablation Exacerbates High-Salt Induced Cardiac Hypertrophy and Cardiac Dysfunction.

PubMed

Lang, Hongmei; Xiang, Yang; Ai, Zhihua; You, Zhiqing; Jin, Xiaolan; Wan, Yong; Yang, Yongjian

2018-04-20

Excessive salt intake and left ventricular hypertrophy (LVH) are both critical for the development of hypertension and heart failure. The uncoupling protein 3 (UCP3) plays a cardio-protective role in early heart failure development. However, the potential role for UCP3 in salt intake and LVH is unclear. UCP3-/- and C57BL/6 mice were placed on either a normal-salt (NS, 0.5%) or a high-salt (HS, 8%) diet for 24 weeks. The cardiac function, endurance capacity, energy expenditure, and mitochondrial functional capacity were measured in each group. Elevated blood pressure was only observed in HS-fed UCP3-/- mice. High salt induced cardiac hypertrophy and dysfunction were observed in both C57BL/6 and UCP3-/- mice. However, the cardiac lesions were more profound in HS-fed UCP3-/- mice. Furthermore, HS-fed UCP3-/-mice experienced more severe mitochondrial respiratory dysfunction compared with HS-fed C57BL/6 mice, represented by the decreased volume of oxygen consumption and heat production at the whole-body level. UCP3 protein was involved in the incidence of high-salt induced hypertension and the progression of cardiac dysfunction in the early stages of heart failure. UCP3 ablation exacerbated high-salt-induced cardiac hypertrophy and cardiac dysfunction. © 2018 The Author(s). Published by S. Karger AG, Basel.

Impedance cardiography: a comparison of cardiac output vs waveform analysis for assessing left ventricular systolic dysfunction.

PubMed

DeMarzo, Arthur P; Kelly, Russell F; Calvin, James E

2007-01-01

Early detection of asymptomatic left ventricular systolic dysfunction (LVSD) is beneficial in managing heart failure. Recent studies have cast doubt on the usefulness of cardiac output as an indicator of LVSD. In impedance cardiography (ICG), the dZ/dt waveform has a systolic wave called the E wave. This study looked at measurements of the amplitude and area of the E wave compared with ICG-derived cardiac output, stroke volume, cardiac index, and stroke index as methods of assessing LVSD. ICG data were obtained from patients (n=26) admitted to a coronary care unit. Clinical LVSD severity was stratified into 4 groups (none, mild, moderate, and severe) based on echocardiography data and standard clinical assessment by a cardiologist blinded to ICG data. Statistical analysis showed that the E wave amplitude and area were better indicators of the level of LVSD than cardiac output, stroke volume, cardiac index, or stroke index. ICG waveform analysis has potential as a simple point-of-care test for detecting LVSD in asymptomatic patients at high risk for developing heart failure and for monitoring LVSD in patients being treated for heart failure.

Unexpected and rapid recovery of left ventricular function in patients with peripartum cardiomyopathy: impact of cardiac resynchronization therapy.

PubMed

Mouquet, Frederic; Mostefa Kara, Meriem; Lamblin, Nicolas; Coulon, Capucine; Langlois, Stephane; Marquie, Christelle; de Groote, Pascal

2012-05-01

Aim Peripartum cardiomyopathy (PPCM) is a rare cause of dilated cardiomyopathy responsible for heart failure toward the end of pregnancy, which can lead to chronic heart failure in 50% of cases. In this short report, we assessed the benefit of cardiac resynchronization in patients with PPCM and chronic systolic dysfunction despite optimal medical treatment. For the last 10 years, we managed eight patients diagnosed with PPCM. Two of them presented severe systolic dysfunction, and medical treatment resulted in limited improvement from 10% to 25% and from 25% to 28% despite optimal treatment for 9 and 6 years, respectively. These two patients were porposed to receive an implantatable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT). Six months after ICD-CRT treatment, we observed a significant improvement in systolic function from 25% to 45% and 28% to 50%, respectively, and positive remodelling with reduction of left ventricular end-diastolic volume from 216 to 144 mL and from 354 to 105 mL, which represent a 34% and a 70% reduction, respectively. Physicians in charge of patients with PPCM should offer the opportunity of CRT for patients whose cardiac function has not significantly improved under standard medical treatment.

Combination treatment with a calcium channel blocker and an angiotensin blocker in a rat systolic heart failure model with hypertension.

PubMed

Namba, Masashi; Kim, Shokei; Zhan, Yumei; Nakao, Takafumi; Iwao, Hiroshi

2002-05-01

The mechanism and treatment of hypertensive systolic heart failure are not well defined. We compared the effect of an angiotensin-converting enzyme inhibitor (cilazapril, 10 mg/kg), an angiotensin receptor blocker (candesartan, 3 mg/kg), a calcium channel blocker (benidipine, 1, 3 or 6 mg/kg), and the same calcium channel blocker combined with renin-angiotensin blockers on systolic heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed an 8% Na diet from 6 weeks of age and then subjected to the above drug treatments. Benidipine (1 mg/kg), cilazapril, and candesartan had compatible hypotensive effects and similar beneficial effects on cardiac hypertrophy, gene expression, and survival rate. The combination of benidipine with cilazapril or candesartan was found to have no additional beneficial effects on the above parameters, with the exception of a reduction in atrial natriuretic polypeptide gene expression. On the other hand, candesartan normalized serum creatinine, but serum creatinine was unaffected by either benidipine at 1 or 3 mg/kg or cilazapril. Further, the combined use of benidipine and either candesartan or cilazapril resulted in an additional reduction of urinary albumin excretion in DS rats. Thus systolic heart failure in DS rats is mainly mediated by hypertension, while renal dysfunction of DS rats is due to both hypertension and the AT1 receptor itself. These findings suggest that the combination of a calcium channel blocker with an AT1 receptor blocker or ACE inhibitor may be more effective in treating the renal dysfunction associated with systolic heart failure than monotherapy with either agent alone. However, further studies will be needed before reaching any definitive conclusion on the efficacy of this combination therapy in patients with heart failure.

Optimal right heart filling pressure in acute respiratory distress syndrome determined by strain echocardiography.

PubMed

Garcia-Montilla, Romel; Imam, Faryal; Miao, Mi; Stinson, Kathryn; Khan, Akram; Heitner, Stephen

2017-06-01

Right ventricular (RV) systolic dysfunction is common in acute respiratory distress syndrome (ARDS). While preload optimization is crucial in its management, dynamic fluid responsiveness indices lack reliability, and there is no consensus on target central venous pressure (CVP). We analyzed the utility of RV free wall longitudinal strain (RVFWS) in the estimation of optimal RV filling pressure in ARDS. A retrospective cross-sectional analysis of clinical data and echocardiograms of patients with ARDS was performed. Tricuspid annular plane systolic excursion (TAPSE), tricuspid peak systolic velocity (S'), RV fractional area change (RVFAC), RVFWS, CVP, systolic pulmonary artery pressure (SPAP), and left ventricular ejection fraction (LVEF) were measured. Fifty-one patients with moderate-severe ARDS were included. There were inverse correlations between CVP and TAPSE, S', RVFAC, RVFWS, and LVEF. The most significant was with RVFWS (r:.74, R 2 :.55, P:.00001). Direct correlations with creatinine and lactate were noted. Receiver operating characteristic analysis showed that RVFWS -21% (normal reference value) was associated with CVP: 13 mm Hg (AUC: 0.92, 95% CI: 0.83-1.00). Regression model analysis of CVP, and RVFWS interactions established an RVFWS range from -18% to -24%. RVFWS -24% corresponded to CVP: 11 mm Hg and RVFWS -18% to CVP: 15 mm Hg. Beyond a CVP of 15 mm Hg, biventricular systolic dysfunction rapidly ensues. Our data are the first to show that an RV filling pressure of 13±2 mm Hg-as by CVP-correlates with optimal RV mechanics as evaluated by strain echocardiography in patients with moderate-severe ARDS. © 2017, Wiley Periodicals, Inc.

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.

Acute Right Ventricular Dysfunction in Intensive Care Unit

PubMed Central

Domingo, Enric

2017-01-01

The role of the left ventricle in ICU patients with circulatory shock has long been considered. However, acute right ventricle (RV) dysfunction causes and aggravates many common critical diseases (acute respiratory distress syndrome, pulmonary embolism, acute myocardial infarction, and postoperative cardiac surgery). Several supportive therapies, including mechanical ventilation and fluid management, can make RV dysfunction worse, potentially exacerbating shock. We briefly review the epidemiology, pathophysiology, diagnosis, and recommendations to guide management of acute RV dysfunction in ICU patients. Our aim is to clarify the complex effects of mechanical ventilation, fluid therapy, vasoactive drug infusions, and other therapies to resuscitate the critical patient optimally. PMID:29201914

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.

Right ventricular function in heart failure with preserved ejection fraction: a community-based study.

PubMed

Mohammed, Selma F; Hussain, Imad; AbouEzzeddine, Omar F; Abou Ezzeddine, Omar F; Takahama, Hiroyuki; Kwon, Susan H; Forfia, Paul; Roger, Véronique L; Redfield, Margaret M

2014-12-23

The prevalence and clinical significance of right ventricular (RV) systolic dysfunction (RVD) in patients with heart failure and preserved ejection fraction (HFpEF) are not well characterized. Consecutive, prospectively identified HFpEF (Framingham HF criteria, ejection fraction ≥50%) patients (n=562) from Olmsted County, Minnesota, underwent echocardiography at HF diagnosis and follow-up for cause-specific mortality and HF hospitalization. RV function was categorized by tertiles of tricuspid annular plane systolic excursion and by semiquantitative (normal, mild RVD, or moderate to severe RVD) 2-dimensional assessment. Whether RVD was defined by semiquantitative assessment or tricuspid annular plane systolic excursion ≤15 mm, HFpEF patients with RVD were more likely to have atrial fibrillation, pacemakers, and chronic diuretic therapy. At echocardiography, patients with RVD had slightly lower left ventricular ejection fraction, worse diastolic dysfunction, lower blood pressure and cardiac output, higher pulmonary artery systolic pressure, and more severe RV enlargement and tricuspid valve regurgitation. After adjustment for age, sex, pulmonary artery systolic pressure, and comorbidities, the presence of any RVD by semiquantitative assessment was associated with higher all-cause (hazard ratio=1.35; 95% confidence interval, 1.03-1.77; P=0.03) and cardiovascular (hazard ratio=1.85; 95% confidence interval, 1.20-2.80; P=0.006) mortality and higher first (hazard ratio=1.99; 95% confidence interval, 1.35-2.90; P=0.0006) and multiple (hazard ratio=1.81; 95% confidence interval, 1.18-2.78; P=0.007) HF hospitalization rates. RVD defined by tricuspid annular plane systolic excursion values showed similar but weaker associations with mortality and HF hospitalizations. In the community, RVD is common in HFpEF patients, is associated with clinical and echocardiographic evidence of more advanced HF, and is predictive of poorer outcomes. © 2014 American Heart Association, Inc.

Effects of exercise training on pulmonary vessel muscularization and right ventricular function in an animal model of COPD.

PubMed

Hassel, Erlend; Berre, Anne Marie; Skjulsvik, Anne Jarstein; Steinshamn, Sigurd

2014-09-28

Right ventricular dysfunction in COPD is common, even in the absence of pulmonary hypertension. The aim of the present study was to examine the effects of high intensity interval training (HIIT) on right ventricular (RV) function, as well as pulmonary blood vessel remodeling in a mouse model of COPD. 42 female A/JOlaHsd mice were randomized to exposure to either cigarette smoke or air for 6 hours/day, 5 days/week for 14 weeks. Mice from both groups were further randomized to sedentariness or HIIT for 4 weeks. Cardiac function was evaluated by echocardiography and muscularization of pulmonary vessel walls by immunohistochemistry. Smoke exposure induced RV systolic dysfunction demonstrated by reduced tricuspid annular plane systolic excursion. HIIT in smoke-exposed mice reversed RV dysfunction. There were no significant effects on the left ventricle of neither smoke exposure nor HIIT. Muscularization of the pulmonary vessels was reduced after exercise intervention, but no significant effects on muscularization were observed from smoke exposure. RV function was reduced in mice exposed to cigarette smoke. No Increase in pulmonary vessel muscularization was observed in these mice, implying that other mechanisms caused the RV dysfunction. HIIT attenuated the RV dysfunction in the smoke exposed mice. Reduced muscularization of the pulmonary vessels due to HIIT suggests that exercise training not only affects the heart muscle, but also has important effects on the pulmonary vasculature.

Early detection of right ventricular dysfunction using transthoracic echocardiography in ARDS: a more objective approach.

PubMed

Wadia, Subeer Kanwar; Shah, Trushil G; Hedstrom, Grady; Kovach, Julie A; Tandon, Rajive

2016-12-01

Right ventricular (RV) dysfunction is an independent predictor of morbidity and mortality in acute respiratory distress syndrome (ARDS). Our goal was to describe morphologic changes in the RV using objective measures on transthoracic echocardiography (TTE) that occur following ARDS. We retrospectively measured changes in the following RV parameters from a pre-ARDS TTE to an ARDS TTE: tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI), fractional area change (FAC), systolic pulmonary artery pressure (SPAP), peak tricuspid regurgitant (TR) velocity, and septal shift. Over 24 months, 14 patients met inclusion/exclusion criteria. Mean TAPSE decreased from 22.4 mm pre-ARDS to 16.3 mm during ARDS, P<.001. Mean MPI increased from 0.19 to 0.38, P=.001. Mean FAC decreased from 60.8% to 41.2%, P=.003. Peak TR velocity increased from 2.67 m/s pre-ARDS to 3.31 m/s during ARDS, P=.02. SPAP and septal shift demonstrated trends but not statistically different between pre-ARDS and ARDS states. TAPSE correlated with ARDS severity (PaO 2 /FiO 2 ratios), P=.004, and was lower among 30-day nonsurvivors compared with survivors, P=.002. Mild RV dysfunction is common after ARDS onset. RV morphologic changes coupled with dysfunction can be detected noninvasively through TTE changes with TAPSE, MPI, and FAC. Mild RV dysfunction by TAPSE is associated with ARDS severity and mortality. © 2016, Wiley Periodicals, Inc.

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.

Hypercholesterolaemia exacerbates ventricular remodelling after myocardial infarction in the rat: role of angiotensin II type 1 receptors

PubMed Central

Mączewski, M; Mączewska, J; Duda, M

2008-01-01

Background and purpose: Diet-induced hypercholesterolaemia exacerbates post-myocardial infarction (MI) ventricular remodelling and heart failure, but the mechanism of this phenomenon remains unknown. This study examined whether worsening of post-MI ventricular remodelling induced by dietary hypercholesterolaemia was related to upregulation of angiotensin II type 1 (AT1) receptor in the rat heart. Experimental approach: MI was induced surgically in rats fed normal or high cholesterol diet. Both groups of rats were then assigned to control, atorvastatin, losartan or atorvastatin+losartan-treated subgroups and followed for 8 weeks. Left ventricular (LV) function was assessed with echocardiography. In isolated hearts, LV pressures were measured with a latex balloon and a tip catheter. AT1-receptor density was assessed in LV membranes with radioligand-binding assays. Key results: High cholesterol diet exacerbated LV dilation and dysfunction in post-MI hearts. Atorvastatin or losartan prevented these hypercholesterolaemia-induced effects, whereas their combination was not more effective than each drug alone. AT1 receptors were upregulated 8 weeks after MI, this was further increased by hypercholesterolaemia and restored to baseline levels by atorvastatin. Conclusions and implications: Hypercholesterolaemia exacerbated LV remodelling and dysfunction in post-MI rat hearts and upregulated cardiac AT1 receptors. All these effects were effectively prevented by atorvastatin. Thus, the pleiotropic statin effects may include interference with the renin-angiotensin system through downregulation of AT1 receptors. PMID:18536757

New and emerging biomarkers in left ventricular systolic dysfunction--insight into dilated cardiomyopathy.

PubMed

Gopal, Deepa M; Sam, Flora

2013-08-01

Dilated cardiomyopathy (DCM) is characterized by deteriorating cardiac performance, impaired contraction and dilation of the left ventricle (or both ventricles). Blood markers--known as "biomarkers"--allow insight into underlying pathophysiologic mechanisms and biologic pathways while predicting outcomes and guiding heart failure management and/or therapies. In this review, we provide an alternative approach to conceptualize heart failure biomarkers: the cardiomyocyte, its surrounding microenvironment, and the macroenvironment, integrating these entities which may impact cellular processes involved in the pathogenesis and/or propagation of DCM. Newer biomarkers of left ventricular systolic dysfunction can be categorized under: (a) myocyte stress and stretch, (b) myocyte apoptosis, (c) cardiac interstitium, (d) inflammation, (e) oxidative stress, (f) cardiac energetics, (g) neurohormones, and (h) renal biomarkers. Biomarkers provide insight into the pathogenesis of DCM while predicting and potentially providing prognostic information in these patients with heart failure.

New and Emerging Biomarkers in Left Ventricular Systolic Dysfunction - Insight into Dilated Cardiomyopathy

PubMed Central

Gopal, Deepa M.; Sam, Flora

2013-01-01

Background Dilated cardiomyopathy (DCM) is characterized by deteriorating cardiac performance and impaired contraction and dilation of the left (or both) ventricles. Blood markers – known as “biomarkers” allow insight into underlying pathophysiologic mechanisms and biologic pathways, while predicting outcomes and guiding heart failure management and/or therapies. Content In this review, we provide an alternative approach to conceptualize heart failure biomarkers: the cardiomyocyte, its surrounding microenvironment, and the macroenvironment with clear interaction between these entities which may impact cellular processes involved in the pathogenesis and/or propagation of DCM. Newer biomarkers of left ventricular systolic dysfunction can be categorized under: (a) myocyte stress and stretch, (b) myocyte apoptosis, (c) cardiac interstitium, (d) inflammation, (e) oxidative stress, (f) cardiac energetics, (g) neurohormones and (h) renal biomarkers. Summary Biomarkers provide insight into the pathogenesis of DCM while predicting and potentially providing prognostic information in these patients with heart failure. PMID:23609585

Meibomian Gland Dysfunction and Treatment (Posterior Blepharitis)

MedlinePlus

... if left untreated, MGD can cause or exacerbate dry eye symptoms and eyelid inflammation. The oil glands become ... in permanent changes in the tear film and dry eyes. Symptoms include: ... Stickiness/ Crustiness Watering ...

Mitochondrial redox system, dynamics, and dysfunction in lung inflammaging and COPD.

PubMed

Lerner, Chad A; Sundar, Isaac K; Rahman, Irfan

2016-12-01

Myriad forms of endogenous and environmental stress disrupt mitochondrial function by impacting critical processes in mitochondrial homeostasis, such as mitochondrial redox system, oxidative phosphorylation, biogenesis, and mitophagy. External stressors that interfere with the steady state activity of mitochondrial functions are generally associated with an increase in reactive oxygen species, inflammatory response, and induction of cellular senescence (inflammaging) potentially via mitochondrial damage associated molecular patterns (DAMPS). Many of these are the key events in the pathogenesis of chronic obstructive pulmonary disease (COPD) and its exacerbations. In this review, we highlight the primary mitochondrial quality control mechanisms that are influenced by oxidative stress/redox system, including role of mitochondria during inflammation and cellular senescence, and how mitochondrial dysfunction contributes to the pathogenesis of COPD and its exacerbations via pathogenic stimuli. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sod2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice

PubMed Central

Guachalla, Luis Miguel; Ju, Zhenyu; Koziel, Rafal; von Figura, Guido; Song, Zhangfa; Fusser, Markus; Epe, Bernd; Jansen-Dűrr, Pidder; Rudolph, K. Lenhard

2009-01-01

Telomere shortening represents a causal factor of cellular senescence. At the same time, several lines of evidence indicate a pivotal role of oxidative DNA damage for the aging process in vivo. A causal connection between the two observations was suggested by experiments showing accelerated telomere shorting under conditions of oxidative stress in cultured cells, but has never been studied in vivo. We therefore have analysed whether an increase in mitochondrial derived oxidative stress in response to heterozygous deletion of superoxide dismutase (Sod2+/-) would exacerbate aging phenotypes in telomere dysfunctional (mTerc-/-) mice. Heterozygous deletion of Sod2 resulted in reduced SOD2 protein levels and increased oxidative stress in aging telomere dysfunctional mice, but this did not lead to an increase in basal levels of oxidative nuclear DNA damage, an accumulation of nuclear DNA breaks, or an increased rate of telomere shortening in the mice. Moreover, heterozygous deletion of Sod2 did not accelerate the depletion of stem cells and the impairment in organ maintenance in aging mTerc-/- mice. In agreement with these observations, Sod2 haploinsufficiency did not lead to a further reduction in lifespan of mTerc-/- mice. Together, these results indicate that a decrease in SOD2-dependent antioxidant defence does not exacerbate aging in the context of telomere dysfunction. PMID:20195488

Prevalence and Correlates of Early Right Ventricular Dysfunction in Sarcoidosis and Its Association with Outcome.

PubMed

Joyce, Emer; Kamperidis, Vasileios; Ninaber, Maarten K; Katsanos, Spyridon; Debonnaire, Philippe; Schalij, Martin J; Taube, Christian; Bax, Jeroen J; Delgado, Victoria; Ajmone Marsan, Nina

2016-09-01

Right ventricular (RV) function has not been systematically assessed in sarcoidosis. The aim of this study was to assess the prevalence and associates of RV dysfunction in sarcoidosis using global longitudinal peak systolic strain (GLS). Furthermore, whether RV dysfunction was associated with clinical outcomes was investigated. A total of 88 patients with sarcoidosis (mean age, 54 ± 13 years; 51% men) without known sarcoid-related or other structural heart disease or alternative etiologies of pulmonary hypertension were retrospectively included. RV GLS was measured using two-dimensional speckle-tracking echocardiography, and patients were stratified (using a previously defined cutoff value) as having preserved (RV GLS < -19%) or impaired (RV GLS ≥ -19%) RV function. An age- and gender-matched control group (n = 50) was included. The main outcome was all-cause mortality or clinical heart failure (hospitalization or New York Heart Association functional class ≥ III and/or deterioration by one or more classes). RV GLS was significantly reduced (-20.1 ± 4.6 vs -24.6 ± 1.8%, P = .001) in patients compared with control subjects. Patients with impaired RV function (n = 41) were older and had worse pulmonary function, worse left ventricular diastolic function, and lower tricuspid annular plane systolic excursion compared with patients with preserved RV function (n = 47). Lower tricuspid annular plane systolic excursion and diabetes were independent correlates of RV GLS. Over a median follow-up period of 37 months, 19 clinical end points occurred. Patients with impaired RV function were more likely to experience the clinical end point (log-rank P = .003). RV contractile dysfunction, identified using RV GLS, is common in patients with sarcoidosis without manifest cardiac involvement or pulmonary hypertension and is associated with adverse outcome. RV GLS may therefore be useful to detect sarcoidosis-related RV dysfunction at an earlier and potentially modifiable stage. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials.

PubMed

Danchin, Nicolas; Cucherat, Michel; Thuillez, Christian; Durand, Eric; Kadri, Zena; Steg, Philippe G

2006-04-10

Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction. We searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years. Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced. Angiotensin-converting enzyme inhibitors reduce total mortality and major cardiovascular end points in patients who have CAD and no left ventricular systolic dysfunction or heart failure.

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

Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial.

PubMed

Dai, Yuk-Ling; Luk, Ting-Hin; Yiu, Kai-Hang; Wang, Mei; Yip, Pandora M C; Lee, Stephen W L; Li, Sheung-Wai; Tam, Sidney; Fong, Bonnie; Lau, Chu-Pak; Siu, Chung-Wah; Tse, Hung-Fat

2011-06-01

Coronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD). We performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300 mg/day, n=28) vs. placebo (controls, n=28) for 8 weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8 weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20 μg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect -2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=-0.29, P=0.047). In patients with ischaemic LVSD, 8 weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

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.

Subclinical right ventricle systolic dysfunction in childhood-onset systemic lupus erythematosus: insights from two-dimensional speckle-tracking echocardiography.

PubMed

Leal, G N; Silva, K F; França, C M P; Lianza, A C; Andrade, J L; Campos, L M A; Bonfá, E; Silva, C A

2015-05-01

The objective of this article is to evaluate right ventricle strain imaging by two-dimensional speckle-tracking (2DST) in childhood-onset systemic lupus erythematosus (c-SLE). Thirty-five c-SLE patients with no signs or symptoms of heart failure and 33 healthy volunteers were evaluated by standard echocardiogram and 2DST. Conventional parameters included tricuspid annular plane systolic excursion (TAPSE), RV tissue-Doppler-derived Tei index and systolic pulmonary artery pressure. Global peak longitudinal systolic strain (PLSS) and strain rate (PLSSR) of RV were obtained by 2DST. Demographic/clinical features, SLEDAI-2K/SLICC/ACR-DI and treatment were also assessed. The median current age was similar in patients and controls (14.75 vs. 14.88 years, p = 0.62). RV PLSS was significantly reduced in c-SLE (-24.5 ± 5.09 vs. -27.62 ± 3.02%, p = 0.003). Similar findings were observed after excluding patients with pulmonary hypertension (-24.62 ± 4.87% vs. -27.62 ± 3.02%, p = 0.0041). RV PLSS was positively correlated with TAPSE (r = +0.49, p = 0.0027) and negatively correlated with Tei index (r = -0.34, p = 0.04) in c-SLE. RV PLSSR was not different comparing patients and controls (-0.65 s(-1 )± 0.47 vs. -1.87 ± 0.49 s(-1), p = 0.07). Further analysis of c-SLE patients revealed higher frequencies of neuropsychiatric manifestations (39% vs. 0%, p = 0.007) and antiphospholipid antibodies (55% vs. 18%, p = 0.035) in those with RV PLSS ≤ -23.7% vs >-23.7%. No differences were evidenced in demographic data, disease activity/damage or treatments (p > 0.05). The present study, using a new and more sensitive technique, revealed subclinical RV systolic dysfunction in c-SLE patients that may have future prognostic implications. The novel association of asymptomatic RV dysfunction with neuropsychiatric manifestations and antiphospholipid antibodies may suggest common physiopathological pathways. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Left ventricular systolic function assessed by echocardiography in children and adolescents with osteosarcoma treated with doxorubicin alone or in combination with dexrazoxane.

PubMed

de Matos Neto, Ranulfo Pinheiro; Petrilli, Antônio Sérgio; Silva, Célia Maria Campos; Campos Filho, Orlando; Oporto, Victor Manuel; Gomes, Lourdes de Fátima Gonçalves; Paiva, Marcelo Goulart; Carvalho, Antônio Carlos Camargo; Moisés, Valdir Ambrósio

2006-12-01

To evaluate left ventricular (LV) systolic function by means of echocardiography in patients with osteosarcoma treated with doxorubicin alone or in combination with dexrazoxane. The study analyzed 55 patients with osteosarcoma, with or without metastasis, undergoing a six-cycle chemotherapy regimen of doxorubicin, who were divided into two groups according to dexrazoxane use. Group I: Thirty-seven patients who did not receive dexrazoxane (28 males, average age 15.4 years). Group II: Eighteen patients who did receive dexrazoxane (15 males, average age 15.1 years). Four echocardiographic evaluations were performed: 1) before the beginning of the chemotherapy (initial evaluation); 2) up to two weeks after the third cycle; 3) up to two weeks after the fifth cycle; and 4) up to four weeks after the sixth cycle of chemotherapy (final evaluation). The left ventricular systolic function was assessed by the fractional percentage of systolic shortening (FS%) on echocardiography. Alterations in the contractile function or cardiac toxicity were defined as FS% values equal to or lower than 29%, and/or by a drop in FS% by an absolute value equal to or greater than 10 units of the baseline value of each patient. No significant difference as to age, gender, and race was observed between the groups. The cumulative dose of doxorubicin was significantly higher in group II throughout all phases of the treatment: 174 x 203 mg/m(2); 292 x 338 mg/m(2) and 345 x 405 mg/(2) (p < 0.0001). According to previously established criteria, the incidence of LV systolic dysfunction was not significantly different (p=0.248) between patients in group I (18.92%) and patients in group II (11.1%). The variance analysis with repeated measurements did not show significant differences in the means of fractional percentage of systolic percentage (FS%) throughout the study (p=0.967). However, a significant difference (p=0.029) was observed between the FS% means in groups I and II at evaluations 2 (35.67 x 37.21%), 3 (34.95 x 38.47%) and 4 (35.26 x 38.22%). Data in this study show that in patients with osteosarcoma treated with doxorubicin alone or combined with dexrazoxane, the LV systolic function, as assessed by the fractional percentage of systolic shortening mean, showed a better performance in the group that received dexrazoxane. On the other hand, the occurrence of systolic dysfunction was similar in both groups.

Chronic chagasic cardiopathy in Amazon region: an etiology to remember.

PubMed

Ferreira, João Marcos Bemfica Barbosa; Guerra, Jorge Augusto de Oliveira; Magalhães, Belisa Maria Lopes; Coelho, Leíla I A R C; Maciel, Marcel Gonçalves; Barbosa, Maria das Graças Vale

2009-12-01

This study assessed the frequency of chronic chagasic cardiopathy (CCC) in 37 autochthonus patients from Amazon region with left ventricular systolic dysfunction of undefined etiology. Three cases were diagnosed in the studied sample, with an 8.1% frequency.

Orthostatic blood pressure regulation predicts classroom effort in children.

PubMed

Carapetian, Stephanie; Siedlarz, Monika; Jackson, Sandra; Perlmuter, Lawrence C

2008-04-01

The increase in orthostatic systolic blood pressure associated with the shift in posture from lying to standing requires several compensatory mechanisms to ensure adequate cerebral perfusion. Decreased efficiency in the various mechanisms controlling orthostatic blood pressure regulation can result in dizziness, lightheadedness, and syncope. The degree of effectiveness of orthostatic systolic blood pressure regulation (OBPR) serves as a marker for a variety of problems including fatigue, depression, anxiety, reduced attention, impulsive behavior and reduced volition. In normal children, an insufficient increase in systolic blood pressure in response to upright posture is predictive of mild cognitive and affective problems. The present study examined orthostatic systolic blood pressure regulation in relation to yearlong teachers' evaluations of academic grades and effort in 7-11 year old children. Poorer systolic blood pressure regulation in response to orthostasis was associated with reduced levels of classroom effort, while academic grades were spared. Converging evidence from clinical as well as experimental studies suggests that the linkage between (OBPR) and effort may be partially mediated by sympathetic dysfunction, altered release of neurotransmitters, or reduced cerebral blood flow.

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

Microorganism-induced exacerbations in atopic dermatitis: a possible preventive role for vitamin D?

PubMed

Benetti, Cecilia; Piacentini, Giorgio L; Capristo, Carlo; Boner, Attilio L; Peroni, Diego G

2015-01-01

Atopic dermatitis (AD) is a common skin disease characterized by a complex pathogenesis not completely understood despite numerous studies to date. The clinical patterns result from interactions between genetic disorders determining abnormalities in the epidermis differentiation complex, modification of the cutaneous barrier, and dysfunction of immune responses. Several studies have shown that an alteration of the skin barrier combined with immune dysfunction is important for the onset, maintenance, and risk of exacerbations of the disease. In recent years, new aspects regarding the pathogenesis of the disease, such as the effects of vitamin D (VD) on immunity at the skin level and the role of certain microorganisms (particularly Staphylococcus and Malassezia species) on eczema exacerbations, have been evaluated. This article provides an overview of the evidences supporting the link between VD (deficiency) and microorganisms (skin colonization/sensitization) in AD pathogenesis, based on comprehensive review of the literature. By considering different aspects of disease, it might be possible to improve our understanding, particularly in those patients refractory to conventional treatments. An electronic research strategy was used to search in Medline Pub-Med Library using as research words AD, exacerbation, VD, Staphylococcus aureus (SA), and Malassezia. The results were downloaded and analyzed for systematic review. Few studies actually consider the relationship between VD deficiency (VDD), AD, and SA and Malassezia, but many suggest a correlation between these factors. VDs play a major role against microorganisms in the development of AD and should be considered when treating patients.

[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.

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.

Right Ventricular Ejection Fraction Is Incremental to Left Ventricular Ejection Fraction for the Prediction of Future Arrhythmic Events in Patients With Systolic Dysfunction.

PubMed

Mikami, Yoko; Jolly, Umjeet; Heydari, Bobak; Peng, Mingkai; Almehmadi, Fahad; Zahrani, Mohammed; Bokhari, Mahmoud; Stirrat, John; Lydell, Carmen P; Howarth, Andrew G; Yee, Raymond; White, James A

2017-01-01

Left ventricular ejection fraction remains the primary risk stratification tool used in the selection of patients for implantable cardioverter defibrillator therapy. However, this solitary marker fails to identify a substantial portion of patients experiencing sudden cardiac arrest. In this study, we examined the incremental value of considering right ventricular ejection fraction for the prediction of future arrhythmic events in patients with systolic dysfunction using the gold standard of cardiovascular magnetic resonance. Three hundred fourteen consecutive patients with ischemic cardiomyopathy or nonischemic dilated cardiomyopathy undergoing cardiovascular magnetic resonance were followed for the primary outcome of sudden cardiac arrest or appropriate implantable cardioverter defibrillator therapy. Blinded quantification of left ventricular and right ventricular (RV) volumes was performed from standard cine imaging. Quantification of fibrosis from late gadolinium enhancement imaging was incrementally performed. RV dysfunction was defined as right ventricular ejection fraction ≤45%. Among all patients (164 ischemic cardiomyopathy, 150 nonischemic dilated cardiomyopathy), the mean left ventricular ejection fraction was 32±12% (range, 6-54%) with mean right ventricular ejection fraction of 48±15% (range, 7-78%). At a median of 773 days, 49 patients (15.6%) experienced the primary outcome (9 sudden cardiac arrest, 40 appropriate implantable cardioverter defibrillator therapies). RV dysfunction was independently predictive of the primary outcome (hazard ratio=2.98; P=0.002). Among those with a left ventricular ejection fraction >35% (N=121; mean left ventricular ejection fraction, 45±6%), RV dysfunction provided an adjusted hazard ratio of 4.2 (P=0.02). RV dysfunction is a strong, independent predictor of arrhythmic events. Among patients with mild to moderate LV dysfunction, a cohort greatly contributing to global sudden cardiac arrest burden, this marker provides robust discrimination of high- versus low-risk subjects. © 2017 American Heart Association, Inc.

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.

Visit-to-visit blood pressure variation is associated with outcomes in a U-shaped fashion in patients with myocardial infarction complicated with systolic dysfunction and/or heart failure: findings from the EPHESUS and OPTIMAAL trials.

PubMed

Ferreira, João Pedro; Duarte, Kévin; Pitt, Bertram; Dickstein, Kenneth; McMurray, John J V; Zannad, Faiez; Rossignol, Patrick

2018-04-21

Visit-to-visit office blood pressure variation (BPV) has prognostic implications independent from mean BP across several populations in the cardiovascular field. The association of BPV with outcomes in patients with myocardial infarction (MI) with systolic dysfunction and/or heart failure is yet to be determined. Two independent cohorts were assessed: the EPHESUS and the OPTIMAAL trials with a total of more than 12 000 patients. The primary outcome was all-cause death. BPV was calculated as a coefficient of variation, that is, the ratio of the SD to the mean BP along the postbaseline follow-up. Cox regression models were used to determine the associations between BPV and events. Compared with the middle and lower BPV tertiles, patients in the upper BPV tertile were older, more often women, hypertensive, diabetic, with peripheral artery disease, and had more frequent use of loop diuretics and ACEi/ARBs. They also had lower LVEF, hemoglobin, and eGFR (all P < 0.001). BPV was independently associated with worse prognosis in a U-shaped manner. In the EPHESUS trial, both low and high BPV were associated with higher rates of death (and also cardiovascular death and the composite of cardiovascular death/ cardiovascular hospitalization): adjusted hazard ratio (95% CI) for the outcome of death is 1.99 (1.68-2.36) for high BPV and is 1.60 (1.35-1.90) for low BPV. Similar results were observed in the OPTIMAAL trial population. In two independent cohorts of MI patients with systolic dysfunction and/or heart failure, BPV was associated with worse prognosis in a U-shaped manner independently of the mean BP.

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.

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.

Angiotensin-Converting Enzyme ID Polymorphism in Patients with Heart Failure Secondary to Chagas Disease

PubMed Central

da Silva, Silene Jacinto; Rassi, Salvador; Pereira, Alexandre da Costa

2017-01-01

Background Changes in the angiotensin-converting enzyme (ACE) gene may contribute to the increase in blood pressure and consequently to the onset of heart failure (HF). The role of polymorphism is very controversial, and its identification in patients with HF secondary to Chagas disease in the Brazilian population is required. Objective To determine ACE polymorphism in patients with HF secondary to Chagas disease and patients with Chagas disease without systolic dysfunction, and to evaluate the relationship of the ACE polymorphism with different clinical variables. Methods This was a comparative clinical study with 193 participants, 103 of them with HF secondary to Chagas disease and 90 with Chagas disease without systolic dysfunction. All patients attended the outpatient department of the General Hospital of the Federal University of Goias general hospital. Alleles I and D of ACE polymorphism were identified by polymerase chain reaction of the respective intron 16 fragments in the ACE gene and visualized by electrophoresis. Results In the group of HF patients, 63% were male, whereas 53.6% of patients with Chagas disease without systolic dysfunction were female (p = 0,001). The time from diagnosis varied from 1 to 50 years. Distribution of DD, ID and II genotypes was similar between the two groups, without statistical significance (p = 0,692). There was no difference in clinical characteristics or I/D genotypes between the groups. Age was significantly different between the groups (p = 0,001), and mean age of patients with HF was 62.5 years. Conclusion No differences were observed in the distribution of (Insertion/Deletion) genotype frequencies of ACE polymorphism between the studied groups. The use of this genetic biomarker was not useful in detecting a possible relationship between ACE polymorphism and clinical manifestations in HF secondary to Chagas disease. PMID:28977050

Risk of Incident Heart Failure in Patients With Diabetes and Asymptomatic Left Ventricular Systolic Dysfunction.

PubMed

Rørth, Rasmus; Jhund, Pardeep S; Mogensen, Ulrik M; Kristensen, Søren L; Petrie, Mark C; Køber, Lars; McMurray, John J V

2018-06-01

Although diabetes is well known to be common in prevalent heart failure (HF) and portends a poor prognosis, the role of diabetes in the development of incident HF is less well understood. We studied the role of diabetes in the transition from asymptomatic left ventricular systolic dysfunction (ALVSD) to overt HF in the prevention arm of the Studies of Left Ventricular Dysfunction (SOLVD-P). We examined the development of symptomatic HF, HF hospitalization, and cardiovascular death according to diabetes status at baseline in patients in SOLVD-P. These outcomes were analyzed by using cumulative incidence curves and Cox regression models adjusted for age, sex, and other prognostic factors, including randomized treatment, HF severity, and comorbidity. Of the 4,223 eligible participants, 647 (15%) had diabetes at baseline. Patients with diabetes were older and had a higher average weight, systolic blood pressure, and heart rate. During the median follow-up of 36 months, 861 of the 3,576 patients without diabetes (24%) developed HF compared with 214 of the 647 patients with diabetes (33%). In unadjusted analyses, patients with diabetes had a higher risk of development of HF (hazard ratio 1.53 [95% CI 1.32-1.78]; P < 0.001), HF hospitalization (2.04 [1.65-2.52]; P < 0.0001), and the composite outcome of development of HF or cardiovascular death (1.48 [1.30-1.69]; P < 0.001). The effect of enalapril on outcomes was not modified by diabetes status. In patients with ALVSD, diabetes is associated with an increased risk of developing HF. Development of HF is associated with an increased risk of death irrespective of diabetes status. © 2018 by the American Diabetes Association.

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.

Angiotensin-Converting Enzyme ID Polymorphism in Patients with Heart Failure Secondary to Chagas Disease.

PubMed

Silva, Silene Jacinto da; Rassi, Salvador; Pereira, Alexandre da Costa

2017-10-01

Changes in the angiotensin-converting enzyme (ACE) gene may contribute to the increase in blood pressure and consequently to the onset of heart failure (HF). The role of polymorphism is very controversial, and its identification in patients with HF secondary to Chagas disease in the Brazilian population is required. To determine ACE polymorphism in patients with HF secondary to Chagas disease and patients with Chagas disease without systolic dysfunction, and to evaluate the relationship of the ACE polymorphism with different clinical variables. This was a comparative clinical study with 193 participants, 103 of them with HF secondary to Chagas disease and 90 with Chagas disease without systolic dysfunction. All patients attended the outpatient department of the General Hospital of the Federal University of Goias general hospital. Alleles I and D of ACE polymorphism were identified by polymerase chain reaction of the respective intron 16 fragments in the ACE gene and visualized by electrophoresis. In the group of HF patients, 63% were male, whereas 53.6% of patients with Chagas disease without systolic dysfunction were female (p = 0,001). The time from diagnosis varied from 1 to 50 years. Distribution of DD, ID and II genotypes was similar between the two groups, without statistical significance (p = 0,692). There was no difference in clinical characteristics or I/D genotypes between the groups. Age was significantly different between the groups (p = 0,001), and mean age of patients with HF was 62.5 years. No differences were observed in the distribution of (Insertion/Deletion) genotype frequencies of ACE polymorphism between the studied groups. The use of this genetic biomarker was not useful in detecting a possible relationship between ACE polymorphism and clinical manifestations in HF secondary to Chagas disease.

Sexual dysfunction, depression, and the impact of antidepressants.

PubMed

Kennedy, Sidney H; Rizvi, Sakina

2009-04-01

Sexual dysfunction is a common symptom of depression. Although decreased libido is most often reported, difficulties with arousal, resulting in vaginal dryness in women and erectile dysfunction in men, and absent or delayed orgasm are also prevalent. Sexual dysfunction is also a frequent adverse effect of treatment with most antidepressants and is one of the predominant reasons for premature drug discontinuation. Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants and have significant effects on arousal and orgasm compared with antidepressants that target norepinephrine, dopamine, and melatonin systems. The availability of an antidepressant that does not cause or exacerbate sexual dysfunction represents an advance in pharmacotherapy for mood disorders and should reduce treatment noncompliance and decrease the need for switching antidepressants or adding antidotes. The purpose of this review was to provide an update on the prevalence, psychobiology, and relative adverse effect burden of sexual dysfunction associated with different antidepressants.

Left ventricular systolic function in sickle cell anaemia: an echocardiographic evaluation in adult Nigerian patients.

PubMed

Ejim, Emmanuel; Oguanobi, Nelson

2016-09-01

Reliable diagnostic measures for the evaluation of left ventricular systolic performance in the setting of altered myocardial loading characteristics in sickle cell anaemia remains unresolved. The study was designed to assess left ventricular systolic function in adult sickle cell patients using non-invasive endsystolic stress - end-systolic volume index ratio. A descriptive cross sectional comparative study was done using 52 patients recruited at the adult sickle cell anaemia clinic of the University of Nigeria Teaching Hospital Enugu. An equal number of age and sex-matched healthy volunteers served as controls. All the participants had haematocrit estimation, haemoglobin electrophoresis, as well as echocardiographic evaluation. The mean age of the patients and controls were 23.93 ± 5.28 (range 18-42) and 24.17 ± 4.39 (range 19 -42) years respectively, (t = 0.262; p= .794). No significant difference was seen in estimate of fractional shortening, and ejection fraction. The cardiac out-put, cardiac index and velocity of circumferential shortening were all significantly increased in the cases compared with the controls. The end systolic stress - end systolic volume index ratio (ESS/ESVI) was significantly lower in cases than controls. There were strong positive correlation between the ejection phase indices (ejection fraction and fractional shortening) and end systolic stress and ESS/ESVI. The study findings suggest the presence of left ventricular systolic dysfunction in adult sickle cell anaemia. This is best detected using the loading-pressures independent force-length relationship expressed in ESS/ESVI ratio.

Arterial wave reflection and subclinical left ventricular systolic dysfunction.

PubMed

Russo, Cesare; Jin, Zhezhen; Takei, Yasuyoshi; Hasegawa, Takuya; Koshaka, Shun; Palmieri, Vittorio; Elkind, Mitchell Sv; Homma, Shunichi; Sacco, Ralph L; Di Tullio, Marco R

2011-03-01

Increased arterial wave reflection is a predictor of cardiovascular events and has been hypothesized to be a cofactor in the pathophysiology of heart failure. Whether increased wave reflection is inversely associated with left-ventricular (LV) systolic function in individuals without heart failure is not clear. Arterial wave reflection and LV systolic function were assessed in 301 participants from the Cardiovascular Abnormalities and Brain Lesions (CABL) study using two-dimensional echocardiography and applanation tonometry of the radial artery to derive central arterial waveform by a validated transfer function. Aortic augmentation index (AIx) and wasted energy index (WEi) were used as indices of wave reflection. LV systolic function was measured by LV ejection fraction (LVEF) and tissue Doppler imaging (TDI). Mitral annulus peak systolic velocity (Sm), peak longitudinal strain and strain rate were measured. Participants with history of coronary artery disease, atrial fibrillation, LVEF less than 50% or wall motion abnormalities were excluded. Mean age of the study population was 68.3 ± 10.2 years (64.1% women, 65% hypertensive). LV systolic function by TDI was lower with increasing wave reflection, whereas LVEF was not. In multivariate analysis, TDI parameters of LV longitudinal systolic function were significantly and inversely correlated to AIx and WEi (P values from 0.05 to 0.002). In a community cohort without heart failure and with normal LVEF, an increased arterial wave reflection was associated with subclinical reduction in LV systolic function assessed by novel TDI techniques. Further studies are needed to investigate the prognostic implications of this relationship.

Significance of NT-pro-BNP in acute exacerbation of COPD patients without underlying left ventricular dysfunction.

PubMed

Adrish, Muhammad; Nannaka, Varalaxmi Bhavani; Cano, Edison J; Bajantri, Bharat; Diaz-Fuentes, Gilda

2017-01-01

B-type natriuretic peptide (BNP) and the N-terminal fragment of pro-BNP (NT-pro-BNP) are established biomarkers of heart failure. Increased levels of natriuretic peptide (NP) have been associated with poor outcomes in acute exacerbation of COPD (AECOPD); however, most studies did not address the conditions that can also increase NT-pro-BNP levels. We aimed to determine if NT-pro-BNP levels correlate with outcomes of AECOPD in patients without heart failure and other conditions that can affect NT-pro-BNP levels. We conducted a retrospective study in patients hospitalized for AECOPD with available NT-pro-BNP levels and normal left ventricular ejection fraction. We compared patients with normal and elevated NT-pro-BNP levels and analyzed the clinical and outcome data. A total of 167 of 1,420 (11.7%) patients met the study criteria. A total of 77% of male patients and 53% of female patients had elevated NT-pro-BNP levels ( P =0.0031). NT-pro-BNP levels were not associated with COPD severity and comorbid illnesses. Log-transformed NT-pro-BNP levels were positively associated with echocardiographically estimated right ventricular systolic pressure ( r =0.3658; 95% confidence interval [CI]: 0.2060-0.5067; P <0.0001). Patients with elevated NT-pro-BNP levels were more likely to require intensive care (63% vs 43%; P =0.0207) and had a longer hospital length of stay ( P =0.0052). There were no differences in the need for noninvasive positive pressure ventilation ( P =0.1245) or mechanical ventilation ( P =0.9824) or in regard to in-hospital mortality ( P =0.5273). Patients with AECOPD and elevated NT-pro-BNP levels had increased hospital length of stay and need for intensive care. Based on our study, serum NT-pro-BNP levels cannot be used as a biomarker for increased mortality or requirement for invasive or noninvasive ventilation in this group of patients.

Improvement of cardiac function persists long term with medical therapy for left ventricular systolic dysfunction.

PubMed

Chen, David; Chang, Richard; Umakanthan, Branavan; Stoletniy, Liset N; Heywood, J Thomas

2007-09-01

In certain patients with left ventricular (LV) systolic dysfunction, improvements in cardiac function are seen after initiation of medical therapy; however, the long-term stability of ventricular function in such patients is not well described. We retrospectively analyzed 171 patients who had a baseline ejection fraction of 45% or less, a follow-up echocardiogram at 2 to 12 months after initiation of medical therapy, and a final echocardiogram. We found that 48.5% of the patients demonstrated initial improvements in LV function after initiation of medical therapy, and the improvements appear to be sustained (88% of patients) at 44 +/- 21 months follow-up. A nonischemic etiology and younger age were the only independent predictors of change of LV ejection fraction of 10 or more at a mean 8.4 +/- 3.4 months after optimal medical therapy. Our study revealed a trend toward improved long-term survival in individuals with an early improvement in LV ejection fraction with medical therapy, especially in those with sustained improvement.

Do plasma concentrations of apelin predict prognosis in patients with advanced heart failure?

PubMed

Dalzell, Jonathan R; Jackson, Colette E; Chong, Kwok S; McDonagh, Theresa A; Gardner, Roy S

2014-01-01

Apelin is an endogenous vasodilator and inotrope, plasma concentrations of which are reduced in advanced heart failure (HF). We determined the prognostic significance of plasma concentrations of apelin in advanced HF. Plasma concentrations of apelin were measured in 182 patients with advanced HF secondary to left ventricular systolic dysfunction. The predictive value of apelin for the primary end point of all-cause mortality was assessed over a median follow-up period of 544 (IQR: 196-923) days. In total, 30 patients (17%) reached the primary end point. Of those patients with a plasma apelin concentration above the median, 14 (16%) reached the primary end point compared with 16 (17%) of those with plasma apelin levels below the median (p = NS). NT-proBNP was the most powerful prognostic marker in this population (log rank statistic: 10.37; p = 0.001). Plasma apelin concentrations do not predict medium to long-term prognosis in patients with advanced HF secondary to left ventricular systolic dysfunction.

Pacemaker syndrome with sub-acute left ventricular systolic dysfunction in a patient with a dual-chamber pacemaker: consequence of lead switch at the header.

PubMed

Khurwolah, Mohammad Reeaze; Vezi, Brian Zwelethini

In the daily practice of pacemaker insertion, the occurrence of atrial and ventricular lead switch at the pacemaker box header is a rare and unintentional phenomenon, with less than five cases reported in the literature. The lead switch may have dire consequences, depending on the indication for the pacemaker. One of these consequences is pacemaker syndrome, in which the normal sequence of atrial and ventricular activation is impaired, leading to sub-optimal ventricular filling and cardiac output. It is important for the attending physician to recognise any worsening of symptoms in a patient who has recently had a permanent pacemaker inserted. In the case of a dual-chamber pacemaker, switching of the atrial and ventricular leads at the pacemaker box header should be strongly suspected. We present an unusual case of pacemaker syndrome and right ventricular-only pacinginduced left ventricular systolic dysfunction in a patient with a dual-chamber pacemaker.

Concomitant Wolff-Parkinson-White and Atrioventricular Nodal Reentrant Tachycardia: Which Pathway to Ablate?

PubMed

Sarsam, Sinan; Sidiqi, Ibrahim; Shah, Dipak; Zughaib, Marcel

2015-12-11

Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common form of supraventricular tachycardia. In contrast, Wolff-Parkinson-White (WPW) pattern consists of an accessory pathway, which may result in the development of ventricular arrhythmias. Frequent tachycardia caused by AVNRT and accessory pathways may play a role in left ventricular systolic dysfunction. A 54-year-old man presented with palpitations and acute decompensated congestive heart failure. His baseline EKG showed Wolff-Parkinson-White (WPW) pattern. While hospitalized, he had an episode of atrioventricular nodal reentrant tachycardia (AVNRT). He underwent radiofrequency catheter ablation for AVNRT, and his accessory pathway was also ablated even though its conduction was found to be weak. He was clinically doing well on follow-up visit, with resolution of his heart failure symptoms and normalization of left ventricular function on echocardiography. This case raises the question whether the accessory pathway plays a role in the development of systolic dysfunction, and if there is any role for ablation in patients with asymptomatic WPW pattern.

Has the Time Come to Be More Aggressive With Bariatric Surgery in Obese Patients With Chronic Systolic Heart Failure?

PubMed

Vest, Amanda R

2018-06-01

Obesity is a strong risk factor for the development of heart failure (HF). Diet, exercise, and weight-loss pharmacotherapies have limited potential to achieve significant and sustainable weight loss, especially in patients with symptomatic systolic HF. This review seeks to determine the role of bariatric surgery for patients with systolic HF and obesity. Bariatric surgeries such as the laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) represent the most successful long-term strategy for achieving weight loss and diabetes and hypertension remission in the general obese population. These benefits translate to reductions in cardiovascular events and mortality, as well as improvements in myocardial structure and function. There is also now data supporting the safety of LSG or RYGB in patients with systolic dysfunction and a reduction in HF admissions post-operatively. Current literature and clinical experience suggest that the most appropriate bariatric surgery candidates with HF are patients aged < 50-60 years, with severely depressed systolic function and NYHA II-III symptoms, who have failed non-surgical strategies and have a high likelihood of future cardiac transplantation candidacy after weight loss. This review seeks to determine the role of bariatric surgery for patients with systolic HF and obesity.

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.

Resting electrocardiogram and stress myocardial perfusion imaging in the determination of left ventricular systolic function: an assessment enhancing the performance of gated SPET.

PubMed

Moralidis, Efstratios; Spyridonidis, Tryfon; Arsos, Georgios; Skeberis, Vassilios; Anagnostopoulos, Constantinos; Gavrielidis, Stavros

2010-01-01

This study aimed to determine systolic dysfunction and estimate resting left ventricular ejection fraction (LVEF) from information collected during routine evaluation of patients with suspected or known coronary heart disease. This approach was then compared to gated single photon emission tomography (SPET). Patients having undergone stress (201)Tl myocardial perfusion imaging followed by equilibrium radionuclide angiography (ERNA) were separated into derivation (n=954) and validation (n=309) groups. Logistic regression analysis was used to develop scoring systems, containing clinical, electrocardiographic (ECG) and scintigraphic data, for the discrimination of an ERNA-LVEF<0.50. Linear regression analysis provided equations predicting ERNA-LVEF from those scores. In 373 patients LVEF was also assessed with (201)Tl gated SPET. Our results showed that an ECG-Scintigraphic scoring system was the best simple predictor of an ERNA-LVEF<0.50 in comparison to other models including ECG, clinical and scintigraphic variables in both the derivation and validation subpopulations. A simple linear equation was derived also for the assessment of resting LVEF from the ECG-Scintigraphic model. Equilibrium radionuclide angiography-LVEF had a good correlation with the ECG-Scintigraphic model LVEF (r=0.716, P=0.000), (201)Tl gated SPET LVEF (r=0.711, P=0.000) and the average LVEF from those assessments (r=0.796, P=0.000). The Bland-Altman statistic (mean+/-2SD) provided values of 0.001+/-0.176, 0.071+/-0.196 and 0.040+/-0.152, respectively. The average LVEF was a better discriminator of systolic dysfunction than gated SPET-LVEF in receiver operating characteristic (ROC) analysis and identified more patients (89%) with a

Point mutations in the tri-helix bundle of the M-domain of cardiac myosin binding protein-C influence systolic duration and delay cardiac relaxation.

PubMed

van Dijk, Sabine J; Kooiker, Kristina B; Napierski, Nathaniel C; Touma, Katia D; Mazzalupo, Stacy; Harris, Samantha P

2018-06-01

Cardiac myosin binding protein-C (cMyBP-C) is an essential regulatory protein required for proper systolic contraction and diastolic relaxation. We previously showed that N'-terminal domains of cMyBP-C stimulate contraction by binding to actin and activating the thin filament in vitro. In principle, thin filament activating effects of cMyBP-C could influence contraction and relaxation rates, or augment force amplitude in vivo. cMyBP-C binding to actin could also contribute to an internal load that slows muscle shortening velocity as previously hypothesized. However, the functional significance of cMyBP-C binding to actin has not yet been established in vivo. We previously identified an actin binding site in the regulatory M-domain of cMyBP-C and described two missense mutations that either increased (L348P) or decreased (E330K) binding affinity of recombinant cMyBP-C N'-terminal domains for actin in vitro. Here we created transgenic mice with either the L348P or E330K mutations to determine the functional significance of cMyBP-C binding to actin in vivo. Results showed that enhanced binding of cMyBP-C to actin in L348P-Tg mice prolonged the time to end-systole and slowed relaxation rates. Reduced interactions between cMyBP-C and actin in E330K-Tg mice had the opposite effect and significantly shortened the duration of ejection. Neither mouse model displayed overt systolic dysfunction, but L348P-Tg mice showed diastolic dysfunction presumably resulting from delayed relaxation. We conclude that cMyBP-C binding to actin contributes to sustained thin filament activation at the end of systole and during isovolumetric relaxation. These results provide the first functional evidence that cMyBP-C interactions with actin influence cardiac function in vivo. Copyright © 2018 Elsevier Ltd. All rights reserved.

Alcohol dehydrogenase accentuates ethanol-induced myocardial dysfunction and mitochondrial damage in mice: role of mitochondrial death pathway.

PubMed

Guo, Rui; Ren, Jun

2010-01-18

Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH). ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways) were examined. Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O(2) (*-). Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-alpha, Fas receptor, Fas L and cytosolic AIF. Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis.

Phagocyte dysfunction, tissue aging and degeneration

PubMed Central

2013-01-01

Immunologically-silent phagocytosis of apoptotic cells is critical to maintaining tissue homeostasis and innate immune balance. Aged phagocytes reduce their functional activity, leading to accumulation of unphagocytosed debris, chronic sterile inflammation and exacerbation of tissue aging and damage. Macrophage dysfunction plays an important role in immunosenescence. Microglial dysfunction has been linked to age-dependent neurodegenerations. Retinal pigment epithelial (RPE) cell dysfunction has been implicated in the pathogenesis of age-related macular degeneration (AMD). Despite several reports on the characterization of aged phagocytes, the role of phagocyte dysfunction in tissue aging and degeneration is yet to be fully appreciated. Lack of knowledge of molecular mechanisms by which aging reduces phagocyte function has hindered our capability to exploit the therapeutic potentials of phagocytosis for prevention or delay of tissue degeneration. This review summarizes our current knowledge of phagocyte dysfunction in aged tissues and discusses possible links to age-related diseases. We highlight the challenges to decipher the molecular mechanisms, present new research approaches and envisage future strategies to prevent phagocyte dysfunction, tissue aging and degeneration. PMID:23748186

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.

The BEAUTIFUL study: randomized trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction - baseline characteristics of the study population.

PubMed

Ferrari, R; Ford, I; Fox, K; Steg, P G; Tendera, M

2008-01-01

Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline. BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%). A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%). Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients. (c) 2007 S. Karger AG, Basel

Hemodynamic effect and safety of intermittent sequential pneumatic compression leg sleeves in patients with congestive heart failure.

PubMed

Bickel, Amitai; Shturman, Alexander; Sergeiev, Michael; Ivry, Shimon; Eitan, Arieh; Atar, Shaul

2014-10-01

Pneumatic leg sleeves are widely used after prolonged operations for prevention of venous stasis. In healthy volunteers they increase cardiac function. We evaluated the hemodynamic effects and safety of intermittent sequential pneumatic compression (ISPC) leg sleeves in patients with chronic congestive heart failure (CHF). We studied 19 patients with systolic left ventricular dysfunction and CHF. ISPC leg sleeves, each with 10 air cells, were operated by a computerized compressor, exerting 2 cycles/min. Hemodynamic and echocardiographic parameters were measured before, during, and after ISPC activation. The baseline mean left ventricular ejection fraction was 29 ± 9.2%, median 32%, range 10%-40%. Cardiac output (from 4.26 to 4.83 L/min; P = .008) and stroke volume (from 56.1 to 63.5 mL; P = .029) increased significantly after ISPC activation, without a reciprocal increase in heart rate, and declined after sleeve deactivation. Systemic vascular resistance (SVR) decreased significantly (from 1,520 to 1,216 dyne-s/cm5; P = .0005), and remained lower than the baseline level throughout the study. There was no detrimental effect on diastolic function and no adverse clinical events, despite increased pulmonary venous return. ISPC leg sleeves in patients with chronic CHF do not exacerbate symptoms and transiently improve cardiac output through an increase in stroke volume and a reduction in SVR. Copyright © 2014 Elsevier Inc. All rights reserved.

Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat.

PubMed

Choi, Seul Min; Kim, Jee Eun; Kang, Kyung Koo

2006-02-09

This study examined the effects of chronic treatment of a new phosphodiesterase type 5 inhibitor, DA-8159, on endothelial dysfunction in stroke-prone spontaneously hypertensive rats (SHR-SP). Six-week-old male SHR-SP were divided into 4 groups; vehicle control, DA-8159 1, 3, and 10 mg/kg/day. During a 32-week experimental period, the animals were administered DA-8159 orally and fed a 4% NaCl-loaded diet. The systolic blood pressure was measured every two weeks throughout the experimental period using the tail-cuff method. At the end of experiments, the vascular function (acetylcholine-induced vasodilation) in the endothelium-intact aortic rings was investigated. In addition, the mortality, the left ventricular hypertrophy index, the plasma parameters and the incidence of a cerebral infarction were assessed. In the DA-8159 treated-rats, the vascular reactivity improved significantly in a dose-dependent manner. Although DA-8159 did not alter the elevation of the systolic blood pressure directly, the 3 and 10 mg/kg/day DA-8159 treatment delayed the early death caused by stroke. DA-8159 significantly reduced the left ventricular heart weight/body weight ratio compared with the vehicle control group. Furthermore, the DA-8159 treatment significantly increased the plasma nitric oxide, cGMP, and the total antioxidative status. The DA-8159 treatment also reduced the occurrence of stroke-associated cerebral damage. These results indicate that DA-8159 can ameliorate an endothelial dysfunction-related vascular injury. Therefore, pharmacological intervention aimed at attenuating an endothelial dysfunction is important and might be useful in both preventing and treating endothelial dysfunction-related complications.

Mineralocorticoid receptor antagonists modulate galectin-3 and interleukin-33/ST2 signaling in left ventricular systolic dysfunction after acute myocardial infarction.

PubMed

Lax, Antonio; Sanchez-Mas, Jesus; Asensio-Lopez, Maria C; Fernandez-Del Palacio, Maria J; Caballero, Luis; Garrido, Iris P; Pastor-Perez, Francisco J; Januzzi, James L; Pascual-Figal, Domingo A

2015-01-01

This study aimed to evaluate the specific role of the 2 available mineralocorticoid receptor antagonists (MRAs), eplerenone and spironolactone, on the modulation of galectin-3 (Gal-3) and interleukin (IL)-33/ST2 signaling in an experimental model of left ventricular systolic dysfunction after acute myocardial infarction (MI). The molecular mechanisms of benefits of MRAs in patients with left ventricular systolic dysfunction after MI not well understood. MI and left ventricular systolic dysfunction were induced by permanent ligation of the anterior coronary artery in 45 male Wistar rats, randomly assigned to no therapy (MI group, n = 15) or to receive MRAs (100 mg/kg/day) for 4 weeks; either eplerenone (n = 15) or spironolactone (n = 15) was used. A sham group was used as a control (n = 8). Elements of the pathway for Gal-3 including transforming growth factor (TGF)-β and SMAD3, as well as that for IL-33/ST2 (including IL-33 and soluble ST2 [sST2]) were analyzed in the infarcted and noninfarcted myocardium by quantitative real-time reverse transcription polymerase chain reaction. Expression of markers of fibrosis (collagen types I and III, tissue inhibitor of metalloproteinase-1) and inflammation (IL-6, tumor necrosis factor-α, monocyte chemotactic protein-1) was also examined. In the infarcted myocardium, compared with sham animals, the MI group had higher concentrations of Gal-3, TGF-β, SMAD3, IL-33, and sST2, as well as higher concentrations of markers of fibrosis and inflammation. Treatment with MRAs down-regulated Gal-3, TGF-β, and SMAD3 and enhanced IL-33/ST2 signaling with lower expression of sST2; protective IL-33 up-regulation was unaffected by MRAs. Modulation of Gal-3 and IL-33/ST2 signaling induced by MRAs correlated with lower expression levels of fibrosis and inflammatory markers. No differences were found between eplerenone and spironolactone. In the noninfarcted myocardium, compared with sham animals, the MI group exhibited a higher expression of Gal-3 and IL-33, but no signs of inflammation or fibrosis were observed; in the presence of MRAs, IL-33 expression was significantly up-regulated, but Gal-3 was unaffected. MRAs play a pivotal role in the Gal-3 and IL-33/ST2 modulation in post-MI cardiac remodeling. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

[Interest of tricuspid annular displacement (TAD) in evaluation of right ventricular ejection fraction].

PubMed

Hugues, T; Ducreux, D; Bertora, D; Berthier, F; Lemoigne, F; Padovani, B; Gibelin, P

2010-04-01

The ultrasound assessment of RV structure and function is often sub-optimal. The range of excursions of the mitral or tricuspid annulus measured in millimetre by 2D or TM-mode in centimetre per second by DTI-mode echocardiography has been shown to reflect the systolic function of both ventricles. We studied a new technique based on a tissue tracking algorithm that is ultrasound beam angle independent for automated detection of tricuspid annular displacement (TAD) (QLAB, Philips Medical Imaging). Twenty-six patients (pts) referred for magnetic resonance imaging (MRI) and 44 control subjects underwent a complete transthoracic echocardiography. MRI of the right ventricular ejection fraction (RVEF) was correlated by linear regression with TAD. Sixteen pts (61.5%) exhibited right ventricular systolic dysfunction (MRI RVEF<40%). The MRI RVEF was positively correlated with TAD (R(2)=0,65; p<0,0001). A value of TAD <14mm predicted right ventricular dysfunction with a sensitivity of 87.5% and a specificity of 90%. Most of (90%) healthy subjects exhibited TAD values exceeding this cut-off point (mean: 16.9+/-1.64mm; range: 13.3 to 24.8mm). Negative correlation was found between TAD and age (R(2)=0,36; p<0,0001). Our study is the first to correlate TAD with MRI RVEF. TAD is a simple, rapid, and non-invasive tool for right ventricular systolic function assessment.

Echocardiographic Parameters and Survival in Chagas Heart Disease with Severe Systolic Dysfunction

PubMed Central

Rassi, Daniela do Carmo; Vieira, Marcelo Luiz Campos; Arruda, Ana Lúcia Martins; Hotta, Viviane Tiemi; Furtado, Rogério Gomes; Rassi, Danilo Teixeira; Rassi, Salvador

2014-01-01

Background Echocardiography provides important information on the cardiac evaluation of patients with heart failure. The identification of echocardiographic parameters in severe Chagas heart disease would help implement treatment and assess prognosis. Objective To correlate echocardiographic parameters with the endpoint cardiovascular mortality in patients with ejection fraction < 35%. Methods Study with retrospective analysis of pre-specified echocardiographic parameters prospectively collected from 60 patients included in the Multicenter Randomized Trial of Cell Therapy in Patients with Heart Diseases (Estudo Multicêntrico Randomizado de Terapia Celular em Cardiopatias) - Chagas heart disease arm. The following parameters were collected: left ventricular systolic and diastolic diameters and volumes; ejection fraction; left atrial diameter; left atrial volume; indexed left atrial volume; systolic pulmonary artery pressure; integral of the aortic flow velocity; myocardial performance index; rate of increase of left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave velocities; E wave deceleration time; E/A and E/Em ratios; and mitral regurgitation. Results In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction was 26.6 ± 5.34%. In the multivariate analysis, the parameters ejection fraction (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p < 0.0001) and E/Em ratio (HR = 0.95; p = 0.1261) were excluded. The indexed left atrial volume was an independent predictor in relation to the endpoint, and values > 70.71 mL/m2 were associated with a significant increase in mortality (log rank p < 0.0001). Conclusion The indexed left atrial volume was the only independent predictor of mortality in this population of Chagasic patients with severe systolic dysfunction. PMID:24553982

Echocardiographic parameters and survival in Chagas heart disease with severe systolic dysfunction.

PubMed

Rassi, Daniela do Carmo; Vieira, Marcelo Luiz Campos; Arruda, Ana Lúcia Martins; Hotta, Viviane Tiemi; Furtado, Rogério Gomes; Rassi, Danilo Teixeira; Rassi, Salvador

2014-03-01

Echocardiography provides important information on the cardiac evaluation of patients with heart failure. The identification of echocardiographic parameters in severe Chagas heart disease would help implement treatment and assess prognosis. To correlate echocardiographic parameters with the endpoint cardiovascular mortality in patients with ejection fraction < 35%. Study with retrospective analysis of pre-specified echocardiographic parameters prospectively collected from 60 patients included in the Multicenter Randomized Trial of Cell Therapy in Patients with Heart Diseases (Estudo Multicêntrico Randomizado de Terapia Celular em Cardiopatias) - Chagas heart disease arm. The following parameters were collected: left ventricular systolic and diastolic diameters and volumes; ejection fraction; left atrial diameter; left atrial volume; indexed left atrial volume; systolic pulmonary artery pressure; integral of the aortic flow velocity; myocardial performance index; rate of increase of left ventricular pressure; isovolumic relaxation time; E, A, Em, Am and Sm wave velocities; E wave deceleration time; E/A and E/Em ratios; and mitral regurgitation. In the mean 24.18-month follow-up, 27 patients died. The mean ejection fraction was 26.6 ± 5.34%. In the multivariate analysis, the parameters ejection fraction (HR = 1.114; p = 0.3704), indexed left atrial volume (HR = 1.033; p < 0.0001) and E/Em ratio (HR = 0.95; p = 0.1261) were excluded. The indexed left atrial volume was an independent predictor in relation to the endpoint, and values > 70.71 mL/m2 were associated with a significant increase in mortality (log rank p < 0.0001). The indexed left atrial volume was the only independent predictor of mortality in this population of Chagasic patients with severe systolic dysfunction.

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.

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 (

Doppler echocardiographic myocardial stunning index predicts recovery of left ventricular systolic function after primary percutaneous coronary intervention.

PubMed

Sharif, Dawod; Matanis, Wisam; Sharif-Rasslan, Amal; Rosenschein, Uri

2016-10-01

Myocardial stunning is responsible for partially reversible left ventricular (LV) systolic dysfunction after successful primary percutaneous coronary intervention (PPCI) in patients with acute ST-elevation myocardial infarction (STEMI). To test the hypothesis that early coronary blood flow (CBF) to LV systolic function ratios, as an equivalent to LV stunning index (SI), predict recovery of LV systolic function after PPCI in patients with acute STEMI. Twenty-four patients with acute anterior STEMI who had successful PPCI were evaluated and compared to 96 control subjects. Transthoracic echocardiography with measurement of LV ejection fraction (EF), LV, and left anterior descending (LAD) coronary artery area wall-motion score index (WMSI) as well as Doppler sampling of LAD blood velocities, early after PPCI and 5 days later, were performed. SI was evaluated as the early ratio of CBF parameters in the LAD to LV systolic function parameters. Early SI-LVEF well predicted late LVEF (r=.51, P<.01) and the change in LVEF (r=.48, P<.017). Early SI-LVMSI predicted well late LVEF (r=.56, P<.006) and the change in LVEF (r=.46, P<.028). Early SI-LADWMSI predicted late LVEF (r=.44, P<.028). Other SI indices measured as other LAD-CBF to LV systolic function parameters were not predictive of late LV systolic function. LV stunning indices measured as early LAD flow to LVEF, LVWMSI, and LADWMSI ratios well predicted late LVEF and the change in LVEF. Thus, greater early coronary artery flow to LV systolic function parameter ratios predict a better improvement in late LV systolic function after PPCI. © 2016, Wiley Periodicals, Inc.

Exercise for Those with Chronic Heart Failure: Matching Programs to Patients.

ERIC Educational Resources Information Center

Braith, Randy W.

2002-01-01

Exercise training increases functional capacity and improves symptoms in selected patients with chronic heart failure and moderate-to-severe left ventricular systolic dysfunction. Aerobic training forms the basis of such a program. This paper describes contributors to exercise intolerance, responses to exercise training, favorable outcomes with…

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.

Taxonomy of segmental myocardial systolic dysfunction

PubMed Central

McDiarmid, Adam K.; Pellicori, Pierpaolo; Cleland, John G.; Plein, Sven

2017-01-01

The terms used to describe different states of myocardial health and disease are poorly defined. Imprecision and inconsistency in nomenclature can lead to difficulty in interpreting and applying trial outcomes to clinical practice. In particular, the terms ‘viable’ and ‘hibernating’ are commonly applied interchangeably and incorrectly to myocardium that exhibits chronic contractile dysfunction in patients with ischaemic heart disease. The range of inherent differences amongst imaging modalities used to define myocardial health and disease add further challenges to consistent definitions. The results of several large trials have led to renewed discussion about the classification of dysfunctional myocardial segments. This article aims to describe the diverse myocardial pathologies that may affect the myocardium in ischaemic heart disease and cardiomyopathy, and how they may be assessed with non-invasive imaging techniques in order to provide a taxonomy of myocardial dysfunction. PMID:27147609

Coronary artery disease detection - limitations of stress testing in left ventricular dysfunction

PubMed Central

Bomb, Ritin; Kumar, Senthil; Chockalingam, Anand

2017-01-01

Incidental diagnosis of left ventricular systolic dysfunction (LVD) is common in clinical practice. The prevalence of asymptomatic LVD (Ejection Fraction, EF < 50%) is 6.0% in men and 0.8% in women and is twice as common as symptomatic LVD. The timely and definitive exclusion of an ischemic etiology is central to optimizing care and reducing mortality in LVD. Advances in cardiovascular imaging provide many options for imaging of patients with left ventricular dysfunction. Clinician experience, patient endurance, imaging modality characteristics, cost and safety determine the choice of testing. In this review, we have compared the diagnostic utility of established tests - nuclear and echocardiographic stress testing with newer techniques like coronary computerized tomography and cardiac magnetic resonance imaging and highlight their inherent limitations in patients with underlying left ventricular dysfunction. PMID:28515848

Assessment of Aerobic Exercise Adverse Effects during COPD Exacerbation Hospitalization

PubMed Central

Mesquita, Carolina Bonfanti; Caram, Laura M. O.; Dourado, Victor Zuniga; de Godoy, Irma; Tanni, Suzana Erico

2017-01-01

Introduction. Aerobic exercise performed after hospital discharge for exacerbated COPD patients is already recommended to improve respiratory and skeletal muscle strength, increase tolerance to activity, and reduce the sensation of dyspnea. Previous studies have shown that anaerobic activity can clinically benefit patients hospitalized with exacerbated COPD. However, there is little information on the feasibility and safety of aerobic physical activity performed by patients with exacerbated COPD during hospitalization. Objective. To evaluate the effects of aerobic exercise on vital signs in hospitalized patients with exacerbated COPD. Patients and Methods. Eleven COPD patients (63% female, FEV1: 34.2 ± 13.9% and age: 65 ± 11 years) agreed to participate. Aerobic exercise was initiated 72 hours after admission on a treadmill; speed was obtained from the distance covered in a 6-minute walk test (6MWT). Vital signs were assessed before and after exercise. Results. During the activity systolic blood pressure increased from 125.2 ± 13.6 to 135.8 ± 15.0 mmHg (p = 0.004) and respiratory rate from 20.9 ± 4.4 to 24.2 ± 4.5 rpm (p = 0.008) and pulse oximetry (SpO2) decreased from 93.8 ± 2.3 to 88.5 ± 5.7% (p < 0.001). Aerobic activity was considered intense, heart rate ranged from 99.2 ± 11.5 to 119.1 ± 11.1 bpm at the end of exercise (p = 0.092), and patients reached on average 76% of maximum heart rate. Conclusion. Aerobic exercise conducted after 72 hours of hospitalization in patients with exacerbated COPD appears to be safe. PMID:28265180

Targeted Expression of Catalase to Mitochondria Protects Against Ischemic Myopathy in High-Fat Diet–Fed Mice

PubMed Central

Ryan, Terence E.; Schmidt, Cameron A.; Green, Thomas D.; Spangenburg, Espen E.; Neufer, P. Darrell

2016-01-01

Patients with type 2 diabetes respond poorly to treatments for peripheral arterial disease (PAD) and are more likely to present with the most severe manifestation of the disease, critical limb ischemia. The underlying mechanisms linking type 2 diabetes and the severity of PAD manifestation are not well understood. We sought to test whether diet-induced mitochondrial dysfunction and oxidative stress would increase the susceptibility of the peripheral limb to hindlimb ischemia (HLI). Six weeks of high-fat diet (HFD) in C57BL/6 mice was insufficient to alter skeletal muscle mitochondrial content and respiratory function or the size of ischemic lesion after HLI, despite reducing blood flow. However, 16 weeks of HFD similarly decreased ischemic limb blood flow, but also exacerbated limb tissue necrosis, increased the myopathic lesion size, reduced muscle regeneration, attenuated muscle function, and exacerbated ischemic mitochondrial dysfunction. Mechanistically, mitochondrial-targeted overexpression of catalase prevented the HFD-induced ischemic limb necrosis, myopathy, and mitochondrial dysfunction, despite no improvement in limb blood flow. These findings demonstrate that skeletal muscle mitochondria are a critical pathological link between type 2 diabetes and PAD. Furthermore, therapeutically targeting mitochondria and oxidant burden is an effective strategy to alleviate tissue loss and ischemic myopathy during PAD. PMID:27284110

Evaluation of Trastuzumab-induced early cardiac dysfunction using two-dimensional Strain Echocardiography.

PubMed

Emren, Sadik Volkan; Tuluce, Selcen Yakar; Levent, Fatih; Tuluce, Kamil; Kalkan, Toygar; Yildiz, Yasar; Alacacioğlu, Ahmet; Kucukzeybek, Yüksel; Akyol, Murat; Salman, Tarık

2015-12-01

Trastuzumab, a chemotherapeutic agent used in the treatment of breast cancer. has been shown to induce subclinical left ventricular (LV) dysfunction during a three to six month period as evidenced by strain echocardiographic examination without any change occurring in the ejection fraction of LV. The present study evaluated the presence of subclinical LV dysfunction using strain echocardiography 1 day and 7 days after the initiation of trastuzumab therapy. The patients with breast cancer receiving adjuvant trastuzumab therapy underwent 2-dimensional, tissue Doppler, and strain echocardiographic examination at baseline and 1 day and 7 days after therapy. LV global longitudinal strain (GLS), global circumferential strain (GCS) values, and other echocardiographic parameters were calculated. A total of 40 females, mean age 50+/-10 years, were evaluated. Of these patients, 97% received anthracycline and 73% received radiotherapy before the initiation of trastuzumab therapy. No change was observed in any of the echocardiographic parameters 1 day after the initiation of trastuzumab therapy (p>0.05). The LV ejection fraction, tissue Doppler parameters, and GCS values did not show any changes 7 days after the initiation of therapy, whereas significant decreases were observed in GLS value (19.2+/-4.0% vs. 17.2+/-3.4, p=0.001) and systolic annular velocity of the lateral LV wall (S' velocity) (10.5+/-3.2 vs. 8.6+/-2.2, p=0.002). Trastuzumab therapy is associated with subclinical LV dysfunction as early as 7 days after initiation of the therapy as evidenced by the decreases in GLS value of LV and systolic annular velocity of the lateral LV wall.

Blood Pressure, Sexual Activity, and Dysfunction in Women With Hypertension: Baseline Findings From the Systolic Blood Pressure Intervention Trial (SPRINT).

PubMed

Foy, Capri G; Newman, Jill C; Berlowitz, Dan R; Russell, Laurie P; Kimmel, Paul L; Wadley, Virginia G; Thomas, Holly N; Lerner, Alan J; Riley, William T

2016-09-01

Sexual function, an important component of quality of life, is gaining increased research and clinical attention in older women with hypertension. To assess the association between systolic blood pressure (SBP) and other variables, and sexual activity and sexual dysfunction in hypertensive women. Baseline analysis of 635 women participants of a larger randomized clinical trial of 9361 men and women. Self-reported sexual activity (yes/no), and sexual function using the Female Sexual Function Inventory (FSFI). 452 participants (71.2%) reported having no sexual activity during the previous 4 weeks. The mean (SD) FSFI score for sexually active participants was 25.3 (6.0), and 52.6% of the sample reported a FSFI score ≤26.55 designating sexual dysfunction. In logistic regression models, SBP was not significantly associated with sexual activity (AOR = 1.002; P > .05). Older age (AOR = 0.95, P < .05), and lower education (AOR for < high school vs college degree = 0.29, P < .05) were associated with lower odds of being sexually active, as was living alone versus living with others (AOR = 0.56, P < .05). Higher weekly alcohol consumption was associated with increased odds of being sexually active (AOR = 1.39; P < .05). In logistic regression models among sexually active participants, SBP was not associated with sexual dysfunction (AOR = 1.01; P > .05). Higher depressive symptoms from the Patient Health Questionnaire-9 (PHQ-9) was associated with higher odds of sexual dysfunction (AOR = 1.24, P < .05), as was increased number of physical comorbidities (AOR = 1.25, P < .05). Diuretic use was associated with lower odds of being sexually active in participants with chronic kidney disease (AOR = 0.33, P < .05). Younger age, higher education, living with others, and higher weekly alcohol consumption were significantly associated with higher odds of being sexually active in a sample of middle-aged and older women with hypertension. Increased depressive symptoms and increased physical comorbidities were significantly associated with increased odds of sexual dysfunction. SBP was not significantly associated with sexual activity or sexual dysfunction. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Phagocyte dysfunction, tissue aging and degeneration.

PubMed

Li, Wei

2013-09-01

Immunologically-silent phagocytosis of apoptotic cells is critical to maintaining tissue homeostasis and innate immune balance. Aged phagocytes reduce their functional activity, leading to accumulation of unphagocytosed debris, chronic sterile inflammation and exacerbation of tissue aging and damage. Macrophage dysfunction plays an important role in immunosenescence. Microglial dysfunction has been linked to age-dependent neurodegenerations. Retinal pigment epithelial (RPE) cell dysfunction has been implicated in the pathogenesis of age-related macular degeneration (AMD). Despite several reports on the characterization of aged phagocytes, the role of phagocyte dysfunction in tissue aging and degeneration is yet to be fully appreciated. Lack of knowledge of molecular mechanisms by which aging reduces phagocyte function has hindered our capability to exploit the therapeutic potentials of phagocytosis for prevention or delay of tissue degeneration. This review summarizes our current knowledge of phagocyte dysfunction in aged tissues and discusses possible links to age-related diseases. We highlight the challenges to decipher the molecular mechanisms, present new research approaches and envisage future strategies to prevent phagocyte dysfunction, tissue aging and degeneration. Copyright © 2013 Elsevier B.V. All rights reserved.

Paradoxical Sleep Deprivation Causes Cardiac Dysfunction and the Impairment Is Attenuated by Resistance Training.

PubMed

Giampá, Sara Quaglia de Campos; Mônico-Neto, Marcos; de Mello, Marco Tulio; Souza, Helton de Sá; Tufik, Sergio; Lee, Kil Sun; Koike, Marcia Kiyomi; Dos Santos, Alexandra Alberta; Antonio, Ednei Luiz; Serra, Andrey Jorge; Tucci, Paulo José Ferreira; Antunes, Hanna Karen Moreira

2016-01-01

Paradoxical sleep deprivation activates the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, subsequently interfering with the cardiovascular system. The beneficial effects of resistance training are related to hemodynamic, metabolic and hormonal homeostasis. We hypothesized that resistance training can prevent the cardiac remodeling and dysfunction caused by paradoxical sleep deprivation. Male Wistar rats were distributed into four groups: control (C), resistance training (RT), paradoxical sleep deprivation for 96 hours (PSD96) and both resistance training and sleep deprivation (RT/PSD96). Doppler echocardiograms, hemodynamics measurements, cardiac histomorphometry, hormonal profile and molecular analysis were evaluated. Compared to the C group, PSD96 group had a higher left ventricular systolic pressure, heart rate and left atrium index. In contrast, the left ventricle systolic area and the left ventricle cavity diameter were reduced in the PSD96 group. Hypertrophy and fibrosis were also observed. Along with these alterations, reduced levels of serum testosterone and insulin-like growth factor-1 (IGF-1), as well as increased corticosterone and angiotensin II, were observed in the PSD96 group. Prophylactic resistance training attenuated most of these changes, except angiotensin II, fibrosis, heart rate and concentric remodeling of left ventricle, confirmed by the increased of NFATc3 and GATA-4, proteins involved in the pathologic cardiac hypertrophy pathway. Resistance training effectively attenuates cardiac dysfunction and hormonal imbalance induced by paradoxical sleep deprivation.

Growth hormone and IGF-1 deficiency exacerbate high-fat diet-induced endothelial impairment in obese Lewis dwarf rats: implications for vascular aging.

PubMed

Bailey-Downs, Lora C; Sosnowska, Danuta; Toth, Peter; Mitschelen, Matthew; Gautam, Tripti; Henthorn, Jim C; Ballabh, Praveen; Koller, Akos; Farley, Julie A; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2012-06-01

Previous studies suggest that the age-related decline in circulating growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels significantly contribute to vascular dysfunction in aging by impairing cellular oxidative stress resistance pathways. Obesity in elderly individuals is increasing at alarming rates, and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging, GH/IGF-1 deficiency, and obesity interact to promote the development of cardiovascular disease remain unclear. To test the hypothesis that low circulating GH/IGF-1 levels exacerbate the pro-oxidant and proinflammatory vascular effects of obesity, GH/IGF-1-deficient Lewis dwarf rats and heterozygous control rats were fed either a standard diet or a high-fat diet (HFD) for 7 months. Feeding an HFD resulted in similar relative weight gains and increases in body fat content in Lewis dwarf rats and control rats. HFD-fed Lewis dwarf rats exhibited a relative increase in blood glucose levels, lower insulin, and impaired glucose tolerance as compared with HFD-fed control rats. Analysis of serum cytokine expression signatures indicated that chronic GH/IGF-1 deficiency exacerbates HFD-induced inflammation. GH/IGF-1 deficiency also exacerbated HFD-induced endothelial dysfunction, oxidative stress, and expression of inflammatory markers (tumor necrosis factor-α, ICAM-1) in aortas of Lewis dwarf rats. Overall, our results are consistent with the available clinical and experimental evidence suggesting that GH/IGF-1 deficiency renders the cardiovascular system more vulnerable to the deleterious effects of obesity.

Growth Hormone and IGF-1 Deficiency Exacerbate High-Fat Diet–Induced Endothelial Impairment in Obese Lewis Dwarf Rats: Implications for Vascular Aging

PubMed Central

Bailey-Downs, Lora C.; Sosnowska, Danuta; Toth, Peter; Mitschelen, Matthew; Gautam, Tripti; Henthorn, Jim C.; Ballabh, Praveen; Koller, Akos; Farley, Julie A.; Sonntag, William E.; Csiszar, Anna

2012-01-01

Previous studies suggest that the age-related decline in circulating growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels significantly contribute to vascular dysfunction in aging by impairing cellular oxidative stress resistance pathways. Obesity in elderly individuals is increasing at alarming rates, and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging, GH/IGF-1 deficiency, and obesity interact to promote the development of cardiovascular disease remain unclear. To test the hypothesis that low circulating GH/IGF-1 levels exacerbate the pro-oxidant and proinflammatory vascular effects of obesity, GH/IGF-1–deficient Lewis dwarf rats and heterozygous control rats were fed either a standard diet or a high-fat diet (HFD) for 7 months. Feeding an HFD resulted in similar relative weight gains and increases in body fat content in Lewis dwarf rats and control rats. HFD-fed Lewis dwarf rats exhibited a relative increase in blood glucose levels, lower insulin, and impaired glucose tolerance as compared with HFD-fed control rats. Analysis of serum cytokine expression signatures indicated that chronic GH/IGF-1 deficiency exacerbates HFD-induced inflammation. GH/IGF-1 deficiency also exacerbated HFD-induced endothelial dysfunction, oxidative stress, and expression of inflammatory markers (tumor necrosis factor-α, ICAM-1) in aortas of Lewis dwarf rats. Overall, our results are consistent with the available clinical and experimental evidence suggesting that GH/IGF-1 deficiency renders the cardiovascular system more vulnerable to the deleterious effects of obesity. PMID:22080499

Cognitive Dysfunction and Malnutrition Are Independent Predictor of Dysphagia in Patients with Acute Exacerbation of Congestive Heart Failure

PubMed Central

Yamanaka, Shinsuke; Takahashi, Yoshimi; Fujita, Hiroshi; Yamaguchi, Nobuhiro; Onoue, Noriko; Ishizuka, Takeshi; Shinozaki, Tsuyoshi; Kohzuki, Masahiro

2016-01-01

Early detection and intervention for dysphagia is important in patients with congestive heart failure (CHF). However, previous studies have focused on how many patients with dysphagia develop CHF. Studies focusing on the comorbidity of dysphagia in patients with CHF are rare. Additionally, risk factors for dysphagia in patients with CHF are unclear. Thus, the aim of this study was to clarify risk factors for dysphagia in patients with acute exacerbation of CHF. A total of 105 patients, who were admitted with acute exacerbation of CHF, were enrolled. Clinical interviews, blood chemistry analysis, electrocardiography, echocardiography, Mini-Mental State Examination (MMSE), exercise tolerance tests, phonatory function tests, and evaluation of activities of daily living (ADL) and nutrition were conducted on admission. After attending physicians permitted the drinking of water, swallowing screening tests were performed. Patients were divided into a dysphagia group (DG) or a non-dysphagia group (non-DG) based on Functional Oral Intake Scale level. Among the 105 patients, 38 had dysphagia. A greater number of patients had history of aspiration pneumonia and dementia, and there was a higher age, N-terminal pro-B-type natriuretic peptide level in the DG compared with the non-DG. MMSE scores, exercise tolerance, phonatory function, status of ADL, nutrition, albumin, and transthyretin were lower in the DG compared with the non-DG. In multivariate analysis, after adjusting for age and sex, MMSE, BI score, and transthyretin was independently associated with dysphagia. Comorbidity of dysphagia was 36.1% in patients with acute exacerbation of CHF, and cognitive dysfunction and malnutrition may be an independent predictor of dysphagia. PMID:27898735

Cognitive Dysfunction and Malnutrition Are Independent Predictor of Dysphagia in Patients with Acute Exacerbation of Congestive Heart Failure.

PubMed

Yokota, Junichi; Ogawa, Yoshiko; Yamanaka, Shinsuke; Takahashi, Yoshimi; Fujita, Hiroshi; Yamaguchi, Nobuhiro; Onoue, Noriko; Ishizuka, Takeshi; Shinozaki, Tsuyoshi; Kohzuki, Masahiro

2016-01-01

Early detection and intervention for dysphagia is important in patients with congestive heart failure (CHF). However, previous studies have focused on how many patients with dysphagia develop CHF. Studies focusing on the comorbidity of dysphagia in patients with CHF are rare. Additionally, risk factors for dysphagia in patients with CHF are unclear. Thus, the aim of this study was to clarify risk factors for dysphagia in patients with acute exacerbation of CHF. A total of 105 patients, who were admitted with acute exacerbation of CHF, were enrolled. Clinical interviews, blood chemistry analysis, electrocardiography, echocardiography, Mini-Mental State Examination (MMSE), exercise tolerance tests, phonatory function tests, and evaluation of activities of daily living (ADL) and nutrition were conducted on admission. After attending physicians permitted the drinking of water, swallowing screening tests were performed. Patients were divided into a dysphagia group (DG) or a non-dysphagia group (non-DG) based on Functional Oral Intake Scale level. Among the 105 patients, 38 had dysphagia. A greater number of patients had history of aspiration pneumonia and dementia, and there was a higher age, N-terminal pro-B-type natriuretic peptide level in the DG compared with the non-DG. MMSE scores, exercise tolerance, phonatory function, status of ADL, nutrition, albumin, and transthyretin were lower in the DG compared with the non-DG. In multivariate analysis, after adjusting for age and sex, MMSE, BI score, and transthyretin was independently associated with dysphagia. Comorbidity of dysphagia was 36.1% in patients with acute exacerbation of CHF, and cognitive dysfunction and malnutrition may be an independent predictor of dysphagia.

The role of heme oxygenase-1 in drug metabolizing dysfunction in the alcoholic fatty liver exposed to ischemic injury

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

Park, Sang Won; Kang, Jung-Woo; Lee, Sun-Mee, E-mail: sunmee@skku.edu

This study was designed to investigate the role of heme oxygenase-1 (HO-1) in hepatic drug metabolizing dysfunction after ischemia/reperfusion (IR) in alcoholic fatty liver (AFL). Rats were fed a Lieber–DeCarli diet for five weeks to allow for development of AFL and were then subjected to 90 min of hepatic ischemia and 5 h of reperfusion. Rats were pretreated with hemin (HO-1 inducer) or ZnPP (HO-1 inhibitor) for 16 h and 3 h before hepatic ischemia. After hepatic IR, ethanol diet (ED)-fed rats had higher serum aminotransferase activities and more severe hepatic necrosis compared to the control diet (CD)-fed rats. Thesemore » changes were attenuated by hemin and exacerbated by ZnPP. The activity and gene expression of HO-1 and its transcription factor (Nrf2) level increased significantly after 5 h of reperfusion in CD-fed rats but not in ED-fed rats. After reperfusion, cytochrome P450 (CYP) 1A1, 1A2, and 2B1 activities were reduced to levels lower than those observed in sham group, whereas CYP2E1 activity increased. The decrease in CYP2B1 activity and the increase in CYP2E1 activity were augmented after hepatic IR in ED-fed animals. These changes were significantly attenuated by hemin but aggravated by ZnPP. Finally, CHOP expression and PERK phosphorylation, microsomal lipid peroxidation, and levels of proinflammatory mediators increased in ED-fed rats compared to CD-fed rats after reperfusion. These increases were attenuated by hemin. Our results suggest that AFL exacerbates hepatic drug metabolizing dysfunction during hepatic IR via endoplasmic reticulum stress and lipid peroxidation and this is associated with impaired HO-1 induction. - Highlights: • Endogenous HO-1 is generated in insufficient quantities in steatotic ischemic injury. • Impaired HO-1 induction leads to excessive ER stress response and lipid peroxidation. • Alcoholic steatosis exacerbates IR-induced hepatic drug-metabolizing dysfunction. • HO-1 induction is required for appropriate medication in patients with steatosis.« less

[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.

Taxonomy of segmental myocardial systolic dysfunction.

PubMed

McDiarmid, Adam K; Pellicori, Pierpaolo; Cleland, John G; Plein, Sven

2017-04-01

The terms used to describe different states of myocardial health and disease are poorly defined. Imprecision and inconsistency in nomenclature can lead to difficulty in interpreting and applying trial outcomes to clinical practice. In particular, the terms 'viable' and 'hibernating' are commonly applied interchangeably and incorrectly to myocardium that exhibits chronic contractile dysfunction in patients with ischaemic heart disease. The range of inherent differences amongst imaging modalities used to define myocardial health and disease add further challenges to consistent definitions. The results of several large trials have led to renewed discussion about the classification of dysfunctional myocardial segments. This article aims to describe the diverse myocardial pathologies that may affect the myocardium in ischaemic heart disease and cardiomyopathy, and how they may be assessed with non-invasive imaging techniques in order to provide a taxonomy of myocardial dysfunction. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Left atrial ejection force predicts the outcome after catheter ablation for paroxysmal atrial fibrillation.

PubMed

Kishima, Hideyuki; Mine, Takanao; Takahashi, Satoshi; Ashida, Kenki; Ishihara, Masaharu; Masuyama, Tohru

2018-02-01

Left atrium (LA) systolic dysfunction is observed in the early stages of atrial fibrillation (AF) prior to LA anatomical change. We investigated whether LA systolic dysfunction predicts recurrent AF after catheter ablation (CA) in patients with paroxysmal AF. We studied 106 patients who underwent CA for paroxysmal AF. LA systolic function was assessed with the LA emptying volume = Maximum LA volume (LAV max ) - Minimum LA volume (LAV min ), LA emptying fraction = [(LAV max - LAV min )/LAV max ] × 100, and LA ejection force calculated with Manning's method [LA ejection force = (0.5 × ρ × mitral valve area × A 2 )], where ρ is the blood density and A is the late-diastolic mitral inflow velocity. Recurrent AF was detected in 35/106 (33%) during 14.6 ± 9.1 months. Univariate analysis revealed reduced LA ejection force, decreased LA emptying fraction, larger LA diameter, and elevated brain natriuretic peptide as significant variables. On multivariate analysis, reduced LA ejection force and larger LA diameter were independently associated with recurrent AF. Moreover, patients with reduced LA ejection force and larger LA diameter had a higher risk of recurrent AF than preserved LA ejection force (log-rank P = 0.0004). Reduced LA ejection force and larger LA diameter were associated with poor outcome after CA for paroxysmal AF, and could be a new index to predict recurrent AF. © 2017 Wiley Periodicals, Inc.

Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy.

PubMed

Mahmoudabady, Maryam; Mathieu, Myrielle; Touihri, Karim; Hadad, Ielham; Da Costa, Agnes Mendes; Naeije, Robert; Mc Entee, Kathleen

2009-10-09

Insulin-like growth factor-1 (IGF-1), transforming growth factor beta (TGFbeta) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy. Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFbeta and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs. Ischemic cardiomyopathy was characterized by moderate left ventricular systolic dysfunction and eccentric hypertrophy, with increased expressions of IGF-1, IGF-1R and cyclins B, D1, D3 and E. Tachycardiomyopathy was characterized by severe left ventricular systolic dysfunction and dilation with no identifiable hypertrophic response. In the latter model, only IGF-1 was overexpressed while IGF-1R, cyclins B, D1, D3 and E stayed unchanged as compared to controls. The expressions of TGFbeta, cyclins A and D2 were comparable in the 3 groups. The expression of IGF-1R was correlated with the thickness of the interventricular septum, in systole and diastole, and to cyclins B, D1, D3 and E expression. These results agree with the notion that IGF-1/IGF-1R and cyclins are involved in the hypertrophic response observed in cardiomyopathies.

Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy

PubMed Central

Mahmoudabady, Maryam; Mathieu, Myrielle; Touihri, Karim; Hadad, Ielham; Da Costa, Agnes Mendes; Naeije, Robert; Mc Entee, Kathleen

2009-01-01

Background Insulin-like growth factor-1 (IGF-1), transforming growth factor β (TGFβ) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy. Methods Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFβ and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs. Results Ischemic cardiomyopathy was characterized by moderate left ventricular systolic dysfunction and eccentric hypertrophy, with increased expressions of IGF-1, IGF-1R and cyclins B, D1, D3 and E. Tachycardiomyopathy was characterized by severe left ventricular systolic dysfunction and dilation with no identifiable hypertrophic response. In the latter model, only IGF-1 was overexpressed while IGF-1R, cyclins B, D1, D3 and E stayed unchanged as compared to controls. The expressions of TGFβ, cyclins A and D2 were comparable in the 3 groups. The expression of IGF-1R was correlated with the thickness of the interventricular septum, in systole and diastole, and to cyclins B, D1, D3 and E expression. Conclusion These results agree with the notion that IGF-1/IGF-1R and cyclins are involved in the hypertrophic response observed in cardiomyopathies. PMID:19818143

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.

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.

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.

Relationship between hematologic parameters and left ventricular systolic dysfunction in stable patients with multi-vessel coronary artery disease.

PubMed

Doğdu, Orhan; Akpek, Mahmut; Yarlıoğlueş, Mikail; Kalay, Nihat; Ardıç, Idris; Elçik, Deniz; Senarslan, Omer; Kaya, Mehmet Güngör

2012-12-01

Multi-vessel coronary artery disease (MVCAD) has long been recognized as an important predictor of adverse outcomes in patients with chronic stable angina. The aim of this study is to investigate the relationship between hematologic parameters and impairment of left ventricular systolic functions in patients with stable MVCAD. Patients (n=202) with stable angina and MVCAD were included in this study. According to the left ventricle ejection fraction (LVEF) determined by echocardiography, patients were divided into two groups as the preserved group (LVEF >50%) and the impaired group (LVEF <50%). The preserved group consisted of 106 patients and the impaired group consisted of 96 patients. The frequency of diabetes mellitus was significantly higher in the impaired group compared to the preserved group (respectively, 50% vs. 33%, p=0.01). High sensitivity C-reactive protein (hs-CRP) levels and, neutrophil/lymphocyte ratio (N/L ratio) were significantly higher in the impaired group than in the preserved group (3.9±2.4 vs. 7.9±3.8, p<0.001; 2.7±0.7 vs. 3.9±1.2, p<0.001, respectively). There was a significant correlation between LVEF, N/L ratio and hs-CRP; hs-CRP and N/L ratio were positively correlated (r=0.584; p<0.001), and LVEF was negatively correlated with both hs-CRP and N/L ratio (r=-0.48, p<0.001 and r=-0.43, p<0.001, respectively). A N/L ratio >3.0 had 77% sensitivity and 68% specificity in predicting left ventricular dysfunction in patients with stable MVCAD. In multivariate analysis, N/L ratio (OR: 2.456, <95% Cl 2.056-4.166; p<0.001) was an independent predictor of left ventricular dysfunction in stable patients with MVCAD. N/L ratio and hs-CRP, which is inexpensive and easily measurable in the laboratory, is independently associated with impaired LV systolic functions in patients with stable MVCAD.

Short-term Effects of High-Dose Caffeine on Cardiac Arrhythmias in Patients With Heart Failure: A Randomized Clinical Trial.

PubMed

Zuchinali, Priccila; Souza, Gabriela C; Pimentel, Maurício; Chemello, Diego; Zimerman, André; Giaretta, Vanessa; Salamoni, Joyce; Fracasso, Bianca; Zimerman, Leandro I; Rohde, Luis E

2016-12-01

The presumed proarrhythmic action of caffeine is controversial. Few studies have assessed the effect of high doses of caffeine in patients with heart failure due to left ventricular systolic dysfunction at high risk for ventricular arrhythmias. To compare the effect of high-dose caffeine or placebo on the frequency of supraventricular and ventricular arrhythmias, both at rest and during a symptom-limited exercise test. Double-blinded randomized clinical trial with a crossover design conducted at the heart failure and cardiac transplant clinic of a tertiary-care university hospital. The trial included patients with chronic heart failure with moderate-to-severe systolic dysfunction (left ventricular ejection fraction <45%) and New York Heart Association functional class I to III between March 5, 2013, and October 2, 2015. Caffeine (100 mg) or lactose capsules, in addition to 5 doses of 100 mL decaffeinated coffee at 1-hour intervals, for a total of 500 mg of caffeine or placebo during a 5-hour protocol. After a 1-week washout period, the protocol was repeated. Number and percentage of ventricular and supraventricular premature beats assessed by continuous electrocardiographic monitoring. We enrolled 51 patients (37 [74%] male; mean [SD] age, 60.6 [10.9] years) with predominantly moderate-to-severe left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 29% [7%]); 31 [61%] had an implantable cardioverter-defibrillator device. No significant differences between the caffeine and placebo groups were observed in the number of ventricular (185 vs 239 beats, respectively; P = .47) and supraventricular premature beats (6 vs 6 beats, respectively; P = .44), as well as in couplets, bigeminal cycles, or nonsustained tachycardia during continuous electrocardiographic monitoring. Exercise test-derived variables, such as ventricular and supraventricular premature beats, duration of exercise, estimated peak oxygen consumption, and heart rate, were not influenced by caffeine ingestion. We observed no increases in ventricular premature beats (91 vs 223 vs 207 beats, respectively) in patients with higher levels of plasma caffeine concentration compared with lower plasma levels (P = .91) or with the placebo group (P = .74). Acute ingestion of high doses of caffeine did not induce arrhythmias in patients with systolic heart failure and at high risk for ventricular arrhythmias. clinicaltrials.gov Identifier: NCT02045992.

Mild Cognitive Dysfunction Does Not Affect Diabetes Mellitus Control in Minority Elderly Adults

PubMed Central

Palta, Priya; Golden, Sherita H.; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S.; Shea, Steven; Manly, Jennifer J.; Luchsinger, Jose A.

2015-01-01

OBJECTIVES To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. DESIGN Prospective cohort study. SETTING A minority cohort in New York City previously recruited for a trial of telemedicine. PARTICIPANTS Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). MEASUREMENTS Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. RESULTS Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. CONCLUSION Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. PMID:25439094

Mild cognitive dysfunction does not affect diabetes mellitus control in minority elderly adults.

PubMed

Palta, Priya; Golden, Sherita H; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S; Shea, Steven; Manly, Jennifer J; Luchsinger, Jose A

2014-12-01

To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. Prospective cohort study. A minority cohort in New York City previously recruited for a trial of telemedicine. Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Endothelial dysfunction in the regulation of portal hypertension

PubMed Central

Iwakiri, Yasuko

2013-01-01

Portal hypertension is caused by an increased intrahepatic resistance, a major consequence of cirrhosis. Endothelial dysfunction in liver sinusoidal endothelial cells (LSECs) decreases the production of vasodilators, such as nitric oxide (NO) and favors vasoconstriction. This contributes to an increased vascular resistance in the intrahepatic/sinusoidal microcirculation. Portal hypertension, once developed, causes endothelial cell (EC) dysfunction in the extrahepatic, i.e. splanchnic and systemic, circulation. Unlike LSEC dysfunction, EC dysfunction in the splanchnic and systemic circulation overproduces vasodilator molecules, leading to arterial vasodilatation. In addition, portal hypertension leads to the formation of portosystemic collateral vessels. Both arterial vasodilatation and portosystemic collateral vessel formation exacerbate portal hypertension by increasing the blood flow through the portal vein. Pathologic consequences, such as esophageal varices and ascites, result. While the sequence of pathological vascular events in cirrhosis and portal hypertension have been elucidated, the underlying cellular and molecular mechanisms causing EC dysfunctions are not yet fully understood. This review article summarizes the current cellular and molecular studies on EC dysfunctions found during the development of cirrhosis and portal hypertension with a focus on intra- and extrahepatic circulation. The article ends by discussing future directions of study for EC dysfunctions. PMID:21745318

Right Ventricular Dysfunction in Chronic Lung Disease

PubMed Central

Kolb, Todd M.; Hassoun, Paul M.

2012-01-01

Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, except during acute exacerbations of chronic lung disease or when multiple co-morbidities are present. Treatment is targeted at correcting hypoxia and improving pulmonary gas exchange and mechanics. There are presently no convincing data to support the use of pulmonary hypertension-specific therapies in patients with right ventricular dysfunction secondary to chronic lung disease. PMID:22548815

The Outward Spiral: A vicious cycle model of obesity and cognitive dysfunction.

PubMed

Hargrave, Sara L; Jones, Sabrina; Davidson, Terry L

2016-06-01

Chronic failure to suppress intake during states of positive energy balance leads to weight gain and obesity. The ability to use context - including interoceptive satiety states - to inhibit responding to previously rewarded cues appears to depend on the functional integrity of the hippocampus. Recent evidence implicates energy dense Western diets in several types of hippocampal dysfunction, including reduced expression of neurotrophins and nutrient transporters, increased inflammation, microglial activation, and blood brain barrier permeability. The functional consequences of such insults include impairments in an animal's ability to modulate responding to a previously reinforced cues. We propose that such deficits promote overeating, which can further exacerbate hippocampal dysfunction and thus initiate a vicious cycle of both obesity and progressive cognitive decline.

Five-year follow-up two-dimensional speckle tracking echocardiography in a juvenile with a double-chambered left ventricle.

PubMed

Harada, Kenji; Mori, Kazuhiro; Ichimiya, Chiyo; Terada, Naho; Iima, Tsutomu; Harada, Takafumi; Fujisawa, Kazutoshi; Kawata, Atsushi; Okada, Ayumi; Yamamoto, Hirofumi; Fujinaga, Hiroyuki

2017-05-01

Double-chambered left ventricle (DCLV) is a particularly rare congenital entity characterized by the presence of two ventricular cavities separated by an abnormal muscle band. An asymptomatic 15-year-old boy was referred to our hospital because of electrocardiographic (ECG) abnormalities. His initial transthoracic echocardiography (TTE) demonstrated a DCLV with mild left ventricular systolic dysfunction. During a 5-year follow-up period, he remained symptom free with no changes in ECG and conventional TTE findings. However, two-dimensional speckle tracking echocardiography revealed a subtle progressive deterioration of left ventricular systolic function during the 5-year follow-up. © 2017, Wiley Periodicals, Inc.

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

A pilot study to explore the effectiveness of "early" rehabilitation after a hospital admission for chronic heart failure.

PubMed

Houchen, Linzy; Watt, Amye; Boyce, Sally; Singh, Sally

2012-07-01

People with chronic heart failure (CHF) experience acute exacerbations of their symptoms. These episodes are costly to patients and the health service. The study was a single group, pretest and posttest design. Seventeen patients with left ventricular systolic dysfunction (LVSD) started rehabilitation within 4 weeks of hospital discharge. The 6 week rehabilitation programme included exercise and self-management education. The hospital anxiety and depression scale (HADS), the incremental and endurance shuttle walking tests (ISWT/ESWT) were assessed at baseline and after rehabilitation. The number and duration of any CHF admissions in the year before and the year after rehabilitation were also recorded. Improvements in the ISWT, ESWT, and depression were, mean (95% confidence interval [CI]) 60.6 (36.0-85.2) metres, 356.0 (173.0-539.0) seconds (both p≤0.001) and (-)1.0 ((-)1.8-(-)0.2) points (p<0.05), respectively. HADS anxiety improvements failed to reach significance. At 1 year, there was a significant decrease in CHF-related hospitalisations, mean change (95% CI) (-)0.8 ((-)1.1-(-)0.4), p≤0.001 and CHF bed days (-)13.0 ((-)24.4-(-)1.6), p<0.05. Early rehabilitation significantly improved exercise capacity and depression and reduced CHF-associated health care utilisation in patients who had recently been hospitalised. The intervention was safe. However, the sample size was small and results were not compared to a control group. Therefore, the effects of natural recovery are unknown.

Independent roles of the priming and the triggering of the NLRP3 inflammasome in the heart

PubMed Central

Toldo, Stefano; Mezzaroma, Eleonora; McGeough, Matthew D.; Peña, Carla A.; Marchetti, Carlo; Sonnino, Chiara; Van Tassell, Benjamin W.; Salloum, Fadi N.; Voelkel, Norbert F.; Hoffman, Hal M.; Abbate, Antonio

2015-01-01

Aims The NLRP3 inflammasome is activated in the ischaemic heart promoting caspase-1 activation, inflammation, and cell death. Ischaemic injury establishes both a priming signal (transcription of inflammasome components) and a trigger (NLRP3 activation). Whether NLRP3 activation, without priming, induces cardiac dysfunction and/or failure is unknown. The aim of this study was to assess the independent and complementary roles of the priming and the triggering signals in the heart, in the absence of ischaemia or myocardial injury. Methods and results We used mice with mutant NLRP3 (constitutively active), NLRP3-A350V, under the control of tamoxifen-driven expression of the Cre recombinase (Nlrp3-A350V/CreT mice). The mice were treated for 10 days with tamoxifen before measuring the activity of caspase-1, the effector enzyme in the inflammasome. Tamoxifen treatment induced the inflammasome in the spleen but not in the heart, despite expression of the mutant NLRP3-A350V. The components of the inflammasome were significantly less expressed in the heart compared with the spleen. Subclinical low-dose lipopolysaccharide (LPS; 2 mg/kg) in Nlrp3-A350V/CreT mice induced the expression of the components of the inflammasome (priming), measured using real-time PCR and western blot, leading to the formation of an active inflammasome (caspase-1 activation) in the heart and LV systolic dysfunction while low-dose LPS was insufficient to induce LV systolic dysfunction in wild-type mice (all P < 0.01 for mutant vs. wild-type mice). Conclusion The signalling pathway governing the inflammasome formation in the heart requires a priming signal in order for an active NLRP3 to induce caspase-1 activation and LV dysfunction. PMID:25524927

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

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.

Dietary sodium restriction reverses vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure

PubMed Central

Jablonski, Kristen L.; Racine, Matthew L.; Geolfos, Candace J.; Gates, Phillip E.; Chonchol, Michel; McQueen, Matthew B.; Seals, Douglas R.

2013-01-01

Objectives We determined the efficacy of dietary sodium restriction (DSR) for improving vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure (SBP; 130–159 mmHg) and the associated physiological mechanisms. Background Vascular endothelial dysfunction develops with advancing age and elevated SBP, contributing to increased cardiovascular risk. DSR lowers BP, but its effect on vascular endothelial function and mechanisms involved are unknown. Methods Seventeen subjects (11M/6F; 62±7 yrs, mean±S.D.) completed a randomized, crossover study of 4 weeks of both low and normal sodium intake. Vascular endothelial function (endothelium-dependent dilation; EDD), nitric oxide (NO)/tetrahydrobiopterin (BH4) bioavailability and oxidative stress-associated mechanisms were assessed following each condition. Results Urinary sodium excretion was reduced by ~50% (to 70±30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMDBA]) and resistance (forearm blood flow responses to acetylcholine [FBFACh]) artery EDD were 68% and 42% (peak FBFACh) higher following the low sodium diet (p<0.005). Low sodium markedly enhanced NO- mediated EDD (greater ΔFBFACh with endothelial NO synthase [eNOS] inhibition) without changing eNOS expression/activation (Ser1177 phosphorylation), restored BH4 bioactivity (less ΔFMDBA with acute BH4), abolished tonic superoxide suppression of EDD (less ΔFMDBA and ΔFBFACh with ascorbic acid infusion), and increased circulating superoxide dismutase activity (p<0.05). These effects were independent of ΔSBP. Other subject characteristics/dietary factors and endothelium-independent dilation were unchanged. Conclusions DSR largely reverses both macro- and microvascular endothelial dysfunction by enhancing NO and BH4 bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces “vascular protection” beyond that attributable to its BP-lowering effects. PMID:23141486

The Impact of Exercising During Haemodialysis on Blood Pressure, Markers of Cardiac Injury and Systemic Inflammation--Preliminary Results of a Pilot Study.

PubMed

Dungey, Maurice; Bishop, Nicolette C; Young, Hannah M L; Burton, James O; Smith, Alice C

2015-01-01

Patients requiring haemodialysis have cardiovascular and immune dysfunction. Little is known about the acute effects of exercise during haemodialysis. Exercise has numerous health benefits but in other populations has a profound impact upon blood pressure, inflammation and immune function; therefore having the potential to exacerbate cardiovascular and immune dysfunction in this vulnerable population. Fifteen patients took part in a randomised-crossover study investigating the effect of a 30-min bout of exercise during haemodialysis compared to resting haemodialysis. We assessed blood pressure, plasma markers of cardiac injury and systemic inflammation and neutrophil degranulation. Exercise increased blood pressure immediately post-exercise; however, 1 hour after exercise blood pressure was lower than resting levels (106±22 vs. 117±25 mm Hg). No differences in h-FABP, cTnI, myoglobin or CKMB were observed between trial arms. Exercise did not alter circulating concentrations of IL-6, TNF-α or IL-1ra nor clearly suppress neutrophil function. This study demonstrates fluctuations in blood pressure during haemodialysis in response to exercise. However, since the fall in blood pressure occurred without evidence of cardiac injury, we regard it as a normal response to exercise superimposed onto the haemodynamic response to haemodialysis. Importantly, exercise did not exacerbate systemic inflammation or immune dysfunction; intradialytic exercise was well tolerated. © 2015 The Author(s) Published by S. Karger AG, Basel.

Thyroid Hormone-Dependent Formation of a Subcortical Band Heterotopia (SBH) in the Neonatal Brain is not Exacerbated Under Conditions of Low Dietary Iron (FeD)

EPA Science Inventory

Although the critical role of thyroid hormone (TH) in brain development is well established - severe deficiency producing significant neurological dysfunction - there is a paucity of data on neurological impairments that accompany modest degrees of TH disruption. Quantitative m...

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.

Standard and Strain Measurements by Echocardiography Detect Early Overloaded Right Ventricular Dysfunction: Validation against Hemodynamic and Myocyte Contractility Changes in a Large Animal Model.

PubMed

Hodzic, Amir; Bobin, Pierre; Mika, Delphine; Ly, Mohamed; Lefebvre, Florence; Lechêne, Patrick; Le Bret, Emmanuel; Gouadon, Elodie; Coblence, Mathieu; Vandecasteele, Grégoire; Capderou, André; Leroy, Jérôme; Rucker-Martin, Catherine; Lambert, Virginie

2017-11-01

Early detection of right ventricular (RV) failure is required to improve the management of patients with congenital heart diseases. The aim of this study was to validate echocardiography for the early detection of overloaded RV dysfunction, compared with hemodynamic and myocyte contractility assessment. Using a porcine model reproducing repaired tetralogy of Fallot, RV function was evaluated over 4 months using standard echocardiography and speckle-tracking compared with hemodynamic parameters (conductance catheter). Sarcomere shortening and calcium transients were recorded in RV isolated myocytes. Contractile reserve (ΔE max ) was assessed by β-adrenergic stimulation in vivo (dobutamine 5 μg/kg) and ex vivo (isoproterenol 100 nM). Six operated animals were compared with four age- and sex-matched controls. In the operated group, hemodynamic RV efficient ejection fraction was significantly decreased (29.7% [26.2%-34%] vs 42.9% [40.7%-48.6%], P < .01), and inotropic responses to dobutamine were attenuated (ΔE max was 51% vs 193%, P < .05). Echocardiographic measurements of fraction of area change, tricuspid annular plane systolic excursion, tricuspid annular peak systolic velocity (S') and RV free wall longitudinal systolic strain and strain rate were significantly decreased. Strain rate, S', and tricuspid annular plane systolic excursion were correlated with ΔE max (r = 0.75, r = 0.78, and r = 0.65, respectively, P < .05). These alterations were associated in RV isolated myocytes with the decrease of sarcomere shortening in response to isoproterenol and perturbations of calcium homeostasis assessed by the increase of spontaneous calcium waves. In this porcine model, both standard and strain echocardiographic parameters detected early impairments of RV function and cardiac reserve, which were associated with cardiomyocyte excitation-contraction coupling alterations. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial.

PubMed

McMurray, John J V; Ezekowitz, Justin A; Lewis, Basil S; Gersh, Bernard J; van Diepen, Sean; Amerena, John; Bartunek, Jozef; Commerford, Patrick; Oh, Byung-Hee; Harjola, Veli-Pekka; Al-Khatib, Sana M; Hanna, Michael; Alexander, John H; Lopes, Renato D; Wojdyla, Daniel M; Wallentin, Lars; Granger, Christopher B

2013-05-01

We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin. The risk of a number of outcomes, including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding, or death (net clinical benefit) were calculated in 3 patient groups: (1) no HF/no LVSD (n=8728), (2) HF/no LVSD (n=3207), and (3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding, or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24), and lowest in patients without HF or LVSD (1.54; 5.27); each comparison P<0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death was 0.89 (95% confidence interval, 0.81-0.98; P=0.02); for SSE, major bleed, or death it was 0.85 (0.78-0.92; P<0.001). There was no heterogeneity of treatment effect across the 3 groups. Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Spectrum and clinical significance of systolic function and myocardial fibrosis assessed by cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

PubMed

Olivotto, Iacopo; Maron, Barry J; Appelbaum, Evan; Harrigan, Caitlin J; Salton, Carol; Gibson, C Michael; Udelson, James E; O'Donnell, Christopher; Lesser, John R; Manning, Warren J; Maron, Martin S

2010-07-15

In hypertrophic cardiomyopathy (HCM), the clinical significance attributable to the broad range of left ventricular (LV) systolic function, assessed as the ejection fraction (EF), is incompletely resolved. We evaluated the EF using cardiovascular magnetic resonance (CMR) imaging in a large cohort of patients with HCM with respect to the clinical status and evidence of left ventricular remodeling with late gadolinium enhancement (LGE). CMR imaging was performed in 310 consecutive patients, aged 42 +/- 17 years. The EF in patients with HCM was 71 +/- 10% (range 28% to 89%), exceeding that of 606 healthy controls without cardiovascular disease (66 +/- 5%, p <0.001). LGE reflecting LV remodeling showed an independent, inverse relation to the EF (B-0.69, 95% confidence interval -0.86 to -0.52; p <0.001) and was greatest in patients with an EF <50%, in whom it constituted a median value of 29% of the LV volume (interquartile range 16% to 40%). However, the substantial subgroup with low-normal EF values of 50% to 65% (n = 45; 15% of the whole cohort), who were mostly asymptomatic or mildly symptomatic (37 or 82% with New York Heart Association functional class I to II), showed substantial LGE (median 5% of LV volume, interquartile range 2% to 10%). This overlapped with the subgroup with systolic dysfunction and significantly exceeded that of patients with an EF of 66% to 75% and >75% (median 2% of the LV volume, interquartile range 1.5% to 4%; p <0.01). In conclusion, in a large cohort of patients with HCM, a subset of patients with low-normal EF values (50% to 65%) was identified by contrast-enhanced CMR imaging as having substantial degrees of LGE, suggesting a transition phase, potentially heralding advanced LV remodeling and systolic dysfunction, with implications for clinical surveillance and management. Copyright (c) 2010. Published by Elsevier Inc.

Improved recovery of regional left ventricular function after PCI of chronic total occlusion in STEMI patients: a cardiovascular magnetic resonance study of the randomized controlled EXPLORE trial.

PubMed

Elias, Joëlle; van Dongen, Ivo M; Hoebers, Loes P; Ouweneel, Dagmar M; Claessen, Bimmer E P M; Råmunddal, Truls; Laanmets, Peep; Eriksen, Erlend; van der Schaaf, René J; Ioanes, Dan; Nijveldt, Robin; Tijssen, Jan G; Hirsch, Alexander; Henriques, José P S

2017-07-19

The Evaluating Xience and left ventricular function in PCI on occlusiOns afteR STEMI (EXPLORE) trial did not show a significant benefit of percutaneous coronary intervention (PCI) of the concurrent chronic total occlusion (CTO) in ST-segment elevation myocardial infarction (STEMI) patients on global left ventricular (LV) systolic function. However a possible treatment effect will be most pronounced in the CTO territory. Therefore, we aimed to study the effect of CTO PCI compared to no-CTO PCI on the recovery of regional LV function, particularly in the CTO territory. Using cardiovascular magnetic resonance (CMR) we studied 180 of the 302 EXPLORE patients with serial CMR (baseline and 4 months follow-up). Segmental wall thickening (SWT) was quantified on cine images by an independent core laboratory. Dysfunctional segments were defined as SWT < 45%. Dysfunctional segments were further analyzed by viability (transmural extent of infarction (TEI) ≤50%.). All outcomes were stratified for randomization treatment. In the dysfunctional segments in the CTO territory recovery of SWT was better after CTO PCI compared to no-CTO PCI (ΔSWT 17 ± 27% vs 11 ± 23%, p = 0.03). This recovery was most pronounced in the dysfunctional but viable segments(TEI < 50%) (ΔSWT 17 ± 27% vs 11 ± 22%, p = 0.02). Furthermore in the CTO territory, recovery of SWT was significantly better in the dysfunctional segments in patients with Rentrop grade 2-3 collaterals compared to grade 0-1 collaterals to the CTO (16 ± 26% versus 11 ± 24%, p = 0.04). CTO PCI compared with no-CTO PCI is associated with a greater recovery of regional systolic function in the CTO territory, especially in the dysfunctional but viable segments. Further research is needed to evaluate the use of CMR in selecting post-STEMI patients for CTO PCI and the effect of regional LV function recovery on clinical outcome. Trialregister.nl NTR1108 , Date registered NTR: 30-okt-2007.

Speckle tracking echocardiography to assess regional ventricular function in patients with apical hypertrophic cardiomyopathy.

PubMed

Saccheri, María Cristina; Cianciulli, Tomás Francisco; Morita, Luis Alberto; Méndez, Ricardo José; Beck, Martín Alejandro; Guerra, Juan Enrique; Cozzarin, Alberto; Puente, Luciana Jimena; Balletti, Lorena Romina; Lax, Jorge Alberto

2017-04-26

To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy (HCM). We prospectively assessed 20 patients (mean age 53 ± 16 years, range: 18-81 years, 10 were male), with apical HCM. We measured global longitudinal peak systolic strain (GLPSS) in the midwall and endocardium of the left ventricle. The diastolic thickness of the 4 apical segments was 16.25 ± 2.75 mm. All patients had a normal global systolic function with a fractional shortening of 50% ± 8%. In spite of supernormal left ventricular (LV) systolic function, midwall GLPSS was decreased in all patients, more in the apical (-7.3% ± -8.8%) than in basal segments (-15.5% ± -6.93%), while endocardial GLPPS was significantly greater and reached normal values (apical: -22.8% ± -7.8%, basal: -17.9% ± -7.5%). This study shows that two-dimensional strain was decreased mainly confined to the mesocardium, while endocardium myocardial deformation was preserved in HCM and allowed to identify subclinical LV dysfunction. This transmural heterogeneity in systolic strain had not been previously described in HCM and could be explained by the distribution of myofibrillar disarray in deep myocardial areas. The clinical application of this novel finding may help further understanding of the pathophysiology of HCM.

Exercise reveals impairments in left ventricular systolic function in patients with metabolic syndrome

PubMed Central

Fournier, Sara B.; Reger, Brian L.; Donley, David A.; Bonner, Daniel E.; Warden, Bradford E.; Gharib, Wissam; Failinger, Conard F.; Olfert, Melissa D.; Frisbee, Jefferson C.; Olfert, I. Mark; Chantler, Paul D.

2013-01-01

MetS is the manifestation of a cluster of cardiovascular (CV) risk factors and is associated with a three-fold increase risk of CV morbidity and mortality, which is suggested to be mediated, in part, by resting left ventricular (LV) systolic dysfunction. However, to what extent resting LV systolic function is impaired in MetS is controversial, and there are no data indicating whether LV systolic function is impaired during exercise. Accordingly, the objective of this study was to comprehensively examine LV and arterial responses to exercise in MetS individuals without diabetes and/or overt CVD compared to a healthy control population. CV function was characterized using Doppler echocardiography and gas exchange in MetS (n=27) vs. healthy controls (n=20) at rest and during peak exercise. At rest, MetS individuals displayed normal LV systolic function but reduced LV diastolic function vs. healthy controls. During peak exercise, individuals with MetS had impaired contractility; pump performance, and vasodilator reserve capacity vs. controls. A blunted contractile reserve response resulted in diminished arterial-ventricular coupling reserve and limited aerobic capacity in MetS vs. controls. These findings possess clinical importance as they provide insight to the pathophysiological changes in MetS that may predispose this population of individuals to an increased risk of CV morbidity and mortality. PMID:24036595

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.

Methamphetamine-associated cardiomyopathy: patterns and predictors of recovery.

PubMed

Voskoboinik, A; Ihle, J F; Bloom, J E; Kaye, D M

2016-06-01

Methamphetamine abuse is a growing public health problem, and increasing numbers of patients are admitted with methamphetamine-associated cardiomyopathy (MAC). We sought to characterise the patterns of this disease and identify predictors of recovery. We retrospectively studied consecutive patients diagnosed with MAC between January 2006 and July 2015. We identified 20 patients (14 males, 6 females) with mean age 35 ± 9 years. Most had very severe systolic dysfunction (mean left ventricular ejection fraction (LVEF) 19.7 ± 11.4%) at presentation with 14 requiring inotropes and 5 requiring mechanical support. The pattern of systolic dysfunction was global in 14 patients, while 6 patients had a 'reverse Takotsubo' (RT) pattern with severely hypokinetic basal-mid segments and apical preservation. RT patients were predominantly female, had a short history of methamphetamine abuse and had higher cardiac enzyme levels. Patients with global dysfunction tended to have mid-wall fibrosis on cardiac magnetic resonance imaging. On follow-up transthoracic echocardiography, 6 out of 19 (32%) had normalisation of LVEF (LVEF ≥ 50%) within 6 weeks. Smaller left ventricular and left atrial size, shorter duration of methamphetamine use and RT pattern appeared to predict early recovery. A subset of MAC patients, particularly those with a RT pattern and lesser ventricular dilatation have the potential for early recovery of ventricular function. By contrast, those with evidence of myocardial fibrosis and ventricular enlargement have limited scope for recovery. © 2016 Royal Australasian College of Physicians.

Diastolic dysfunction characterizes cirrhotic cardiomyopathy

PubMed Central

Somani, Piyush O.; contractor, Qais; Chaurasia, Ajay S.; Rathi, Pravin M.

2014-01-01

Aim Present study aims to study the occurrence of cirrhotic cardiomyopathy and its correlation to hepatorenal syndrome by assessing the cardiac status in patients with cirrhosis of liver and healthy controls. Methods Thirty alcoholic cirrhotic, thirty non-alcoholic cirrhotic and thirty controls were enrolled for the study. Cardiac parameters were assessed by color doppler echocardiography. Patients were followed up for twelve months period for development of hepatorenal syndrome. Results Mild diastolic dysfunction was present in 18 cirrhotic patients (30%): grade I in fifteen patients and grade II in three. Diastolic dysfunction was unrelated to age; sex and etiology of cirrhosis. Among all the echocardiographic parameters, only deceleration time was found to be statistically significant. Echocardiographic parameters in systolic and diastolic function were not different in compensated vs decompensated patients in different Child-Pugh classes or cirrhosis aetiologies. At one year follow-up, no significant differences were found in survival between patients with or without diastolic dysfunction. Hepatorenal syndrome developed in only two patients and its correlation with diastolic dysfunction was not statistically significant. Conclusions Present study shows that although diastolic dysfunction is a frequent event in cirrhosis, it is usually of mild degree and does not correlate with severity of liver dysfunction. There are no significant differences in echocardiographic parameters between alcoholic and non-alcoholic cirrhosis. HRS is not correlated to diastolic dysfunction in cirrhotic patients. There is no difference in survival at one year between patients with or without diastolic dysfunction. Diastolic dysfunction in cirrhosis is unrelated to circulatory dysfunction, ascites and HRS. PMID:25634400

[Establishment of a nurse-led heart failure clinic. Design and baseline data from the first two years].

PubMed

Galatius, Søren; Gustafsson, Finn; Kistorp, Caroline M N; Nielsen, Per H; Atar, Dan; Hildebrandt, Per Rossen

2003-02-10

Previous studies on the effect of heart failure clinics have shown a reduction in hospitalizations, reduced cost and improved quality of life. We report on the establishment of a heart failure clinic and its impact on heart failure hospitalizations. Since September 1, 1999, a heart failure clinic has been operated at the Frederiksberg University Hospital. The clinic was designed with both a diagnostic and a therapeutic unit. The diagnostic unit offers open access to all patients with suspected heart failure, either through referral from general practitioners or from the medical departments of the hospital. In case of confirmed systolic heart failure, the patient is referred to the therapeutic unit. During the two years of operation, a total of 510 patients were registered in a newly established database (HJERTER+). Of these, 352 (69%) were found to have clinical evidence of heart failure, and 304 (86% of the heart failure patients) had left ventricular (LV) systolic dysfunction (ejection fraction < or = 0.45). Before referral, most patients with LV dysfunction had been treated with no or insufficient dose of ACE inhibitor (55%), and one third received beta-blockers (32%). During the two years of operation of the clinic, there was a 23% decline in heart failure related hospital admissions to the department of cardiology. Patients with systolic heart failure are not always optimally treated. The establishment of a heart failure clinic offering the combination of diagnosing and managing congestive heart failure appears to be effective both in terms of therapy optimization and with respect to a concomitant decline in hospitalization for heart failure.

Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance

PubMed Central

van Geuns, Robert‐Jan; Ainslie, Gillian; Ector, Joris; Heidbuchel, Hein; Crijns, Harry J.G.M.

2017-01-01

Abstract Aims Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast‐enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. Methods and results We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast‐enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non‐invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P < 0.001). Right ventricular enhancement correlated with systolic ventricular dysfunction (P < 0.001), hypertrophy (P = 0.001), and dilation (P < 0.001). Conclusions Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation. PMID:29154434

Clinical significance of hyperglycaemia in acute coronary syndrome patients.

PubMed

Cherneva, Zheyna Vlaeva; Denchev, Stefan Veselinov; Gospodinova, Mariana Vasileva; Milcheva, Nora Petrova; Petrova, Mariana Genova; Cherneva, Radostina Vlaeva

2011-12-01

The clinical significance of moment measurements (admission and fasting glycaemia), persistent (hyperglycaemic index, HGI; time average glucose, TAG; mean glucose; maximum glucose) or chronic hyperglycaemia (HbA1c), estimated average glucose, eAG) is still elusive in clinical practice. To identify the clinical significance of hyperglycaemia in ACS. The study included 226 consecutive patients with ACS. Indicators for hyperglycaemia were defined, calculated and a correlation analysis with standard parameters-EF, maximum CPK, maximum CPK-MB and troponin was performed. Patients were followed up for 12 months. Indicators for persistent and chronic hyperglycaemia correlated neither to ejection fraction, nor to the enzymes for myocardial necrosis (P > 0.05). In contrast, acute hyperglycaemia correlated negatively with ventricular systolic dysfunction (P = 0.001/0.007) and positively with maximum CPK, MB and troponin (P = 0.0001/0.008). TAG was an independent predictor for 6-month re-hospitalization (P = 0.027) because of cardiac complications. Glycaemia at admission and fasting glucose could be used as metabolic surrogate markers for ventricular systolic dysfunction and TAG as an independent surrogate marker for six-month re-hospitalization. None of the indicators for hyperglycaemia could be used as independent prognostic factors for survival. Hyperglycaemia rather reflects an underlying impairment in glucose metabolism.

Causes and prevention of sudden cardiac death in the elderly.

PubMed

Tung, Patricia; Albert, Christine M

2013-03-01

Sudden cardiac death (SCD) is a major cause of mortality in elderly individuals owing to a high prevalence of coronary heart disease, systolic dysfunction, and congestive heart failure (CHF). Although the incidence of SCD increases with age, the proportion of cardiac deaths that are sudden decreases owing to high numbers of other cardiac causes of death in elderly individuals. Implantable cardioverter-defibrillator (ICD) therapy has been demonstrated to improve survival and prevent SCD in selected patients with systolic dysfunction and CHF. However, ICD therapy in elderly patients might not be effective because of a greater rate of pulseless electrical activity underlying SCD and other competing nonarrhythmic causes of death in this population. Although under-represented in randomized trials of ICD use, elderly patients comprise a substantial proportion of the population that qualifies for and receives an ICD for primary prevention under current guidelines. Cardiac resynchronization therapy (CRT), which has been demonstrated to reduce mortality in selected populations with heart failure, is also more commonly used in this group of patients than in younger individuals. In this Review, we examine the causes of SCD in elderly individuals, and discuss the existing evidence for effectiveness of ICD therapy and CRT in this growing population.

Characterizing cardiac dysfunction in fetuses with left congenital diaphragmatic hernia.

PubMed

Cruz-Lemini, Mónica; Valenzuela-Alcaraz, Brenda; Granados-Montiel, Julio; Martínez, Josep M; Crispi, Fátima; Gratacós, Eduard; Cruz-Martínez, Rogelio

2018-03-23

To evaluate cardiac function by conventional echocardiography and tissue Doppler imaging in fetuses with left congenital diaphragmatic hernia (CDH). Conventional echocardiography (myocardial performance index, ventricular filling velocities, and E/A ratios) and tissue Doppler imaging (annular myocardial peak velocities, E/E' and E'/A' ratios) in mitral, septal, and tricuspid annulus were evaluated in a cohort of 31 left-sided CDH fetuses and compared with 75 controls matched for gestational age 2:1. In comparison to controls, CDH fetuses had prolonged isovolumetric time periods (isovolumetric contraction time 35 ms vs 28 ms, P < .001), with higher myocardial performance index (0.49 vs 0.42, P < .001) and tricuspid E/A ratios (0.77 vs 0.72, P = .033). Longitudinal function assessed by tissue Doppler showed signs of impaired relaxation (mitral lateral A' 8.0 vs 10.1 cm/s, P < .001 and an increased mitral lateral E'/A' ratio 0.93 vs 0.78, P < .001) in the CDH fetuses as compared with controls, with preserved systolic function. Left CDH fetuses show echocardiographic signs of diastolic dysfunction, probably secondary to fetal heart compression, maintaining a preserved systolic function. © 2018 John Wiley & Sons, Ltd.

Comparative RNA-Seq transcriptome analyses reveal distinct metabolic pathways in diabetic nerve and kidney disease.

PubMed

Hinder, Lucy M; Park, Meeyoung; Rumora, Amy E; Hur, Junguk; Eichinger, Felix; Pennathur, Subramaniam; Kretzler, Matthias; Brosius, Frank C; Feldman, Eva L

2017-09-01

Treating insulin resistance with pioglitazone normalizes renal function and improves small nerve fibre function and architecture; however, it does not affect large myelinated nerve fibre function in mouse models of type 2 diabetes (T2DM), indicating that pioglitazone affects the body in a tissue-specific manner. To identify distinct molecular pathways regulating diabetic peripheral neuropathy (DPN) and nephropathy (DN), as well those affected by pioglitazone, we assessed DPN and DN gene transcript expression in control and diabetic mice with or without pioglitazone treatment. Differential expression analysis and self-organizing maps were then used in parallel to analyse transcriptome data. Differential expression analysis showed that gene expression promoting cell death and the inflammatory response was reversed in the kidney glomeruli but unchanged or exacerbated in sciatic nerve by pioglitazone. Self-organizing map analysis revealed that mitochondrial dysfunction was normalized in kidney and nerve by treatment; however, conserved pathways were opposite in their directionality of regulation. Collectively, our data suggest inflammation may drive large fibre dysfunction, while mitochondrial dysfunction may drive small fibre dysfunction in T2DM. Moreover, targeting both of these pathways is likely to improve DN. This study supports growing evidence that systemic metabolic changes in T2DM are associated with distinct tissue-specific metabolic reprogramming in kidney and nerve and that these changes play a critical role in DN and small fibre DPN pathogenesis. These data also highlight the potential dangers of a 'one size fits all' approach to T2DM therapeutics, as the same drug may simultaneously alleviate one complication while exacerbating another. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Does Attention-Deficit-Hyperactivity Disorder Exacerbate Executive Dysfunction in Children with Neurofibromatosis Type 1?

ERIC Educational Resources Information Center

Payne, Jonathan M.; Arnold, Shelley S.; Pride, Natalie A.; North, Kathryn N.

2012-01-01

Aim: Although approximately 40% of children with neurofibromatosis type 1 (NF1) meet diagnostic criteria for attention-deficit-hyperactivity disorder (ADHD), the impact of ADHD on the executive functioning of children with NF1 is not understood. We investigated whether spatial working memory and response inhibition are impaired in children with…

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.

An integrated approach to diagnosis and therapeutic management of patients with systolic heart failure in the Copenhagen metropolitan area.

PubMed

Galatius, Søren; Gustafsson, Finn; Nielsen, Per H; Atar, Dan; Hildebrandt, Per R

2002-08-01

Studies on the effect of heart failure clinics have been encouraging and convincing with respect to reduced hospitalizations, improved quality of life, and reduced cost. However, previous results have been derived from patient populations either recently discharged and with specific exclusion criteria or from heart transplant lists. We here report the establishment of a heart failure clinic that offers an integrated approach to both diagnosing and managing heart failure patients, the baseline characteristics of the first 283 patients treated, and the impact on heart failure hospitalizations during establishment. Since September l, 1999, a heart failure clinic has been in operation at Frederiksberg University Hospital. The clinic was designed with both a diagnostic and a therapeutic unit. The diagnostic unit offers open access to all patients with suspected heart failure, either through referral from general practitioners or from the medical departments of the hospital. In the case of confirmed systolic heart failure, the patient is referred to the therapeutic unit for (1) uptitration and optimization of medical therapy and thorough information and education. In addition, the unit offers a rapid access track and the possibility of intravenous diuretic treatment. During the 21 months of operation, a total of 460 patients were referred to the clinic. Of these, 320 (70%) were found to have clinical evidence of heart failure, and 283 (88% of the patients with heart failure) had left ventricular systolic dysfunction (defined by an ejection fraction of < or =45%). These patients were seen in the clinic for education, control of fluid retention, and uptitration of medications. These patients with left ventricular dysfunction were predominantly elderly (aged 72.7 +/- 10.7 y) and most often male (73%). Ischemic heart disease was the most common etiology (55%). Before referral, most patients with left ventricular dysfunction had been treated with none or only low-dose angiotensin-converting enzyme inhibitor (55%), and fewer than one third received beta-blockers (29%). During the first year of operation of the clinic, there was a 23% decline of heart failure-related hospital admissions to the department of cardiology (from 396 to 306). Patients with systolic heart failure are not always optimally treated. The establishment of a heart failure clinic, which offers the combination of diagnosing and managing congestive heart failure, appears to be efficient both in terms of therapy optimization and with respect to a concomitant decline in hospitalization for heart failure.

Diastolic Dysfunction Following Anthracycline-Based Chemotherapy in Breast Cancer Patients: Incidence and Predictors

PubMed Central

González, Iria; Del Castillo, Silvia; Muñiz, Javier; Morales, Luis J.; Moreno, Fernando; Jiménez, Rosa; Cristóbal, Carmen; Graupner, Catherine; Talavera, Pedro; Curcio, Alejandro; Martínez, Paula; Guerra, Juan A.; Alonso, Joaquín J.

2015-01-01

Introduction. Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data from longitudinal studies of diastolic dysfunction (DD) in this group of patients are scarce. The objective of the present study was to assess the incidence, evolution, and predictors of DD in patients with breast cancer treated with anthracyclines. Methods. This analytical, observational cohort study comprised 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) for breast cancer. All patients underwent clinical evaluation, echocardiogram, and measurement of cardiac biomarkers at baseline, end of anthracycline-based CHT, and at 3 months and 9 months after anthracycline-based CHT was completed. Fifteen patients receiving trastuzumab were followed with two additional visits at 6 and 12 months after the last dose of anthracycline-based CHT. A multivariate analysis was performed to find variables related to the development of DD. Fifteen of the 100 patients had baseline DD and were excluded from this analysis. Results. At the end of follow-up (median: 12 months, interquartile range: 11.1–12.8), 49 patients (57.6%) developed DD. DD was persistent in 36 (73%) but reversible in the remaining 13 patients (27%). Four patients developed cardiotoxicity (three patients had left ventricular systolic dysfunction and one suffered a sudden cardiac death). None of the patients with normal diastolic function developed systolic dysfunction during follow-up. In the logistic regression model, body mass index (BMI) and age were independently related to the development of DD, with the following odds ratio values: BMI: 1.19 (95% confidence interval [CI]: 1.04–1.36), and age: 1.12 (95% CI: 1.03–1.19). Neither cardiac biomarkers nor remaining clinical variables were predictors of DD. Conclusion. Development of diastolic dysfunction after treatment with anthracycline or anthracycline- plus trastuzumab chemotherapy is common. BMI and age were independently associated with DD following anthracycline chemotherapy. Implications for Practice: This study characterizes the incidence of diastolic dysfunction in a cohort of patients undergoing anthracycline treatment. The incidence of diastolic dysfunction during follow-up was 57% and persisted at the last follow-up visit in 73% of patients. Age and body mass index were found to be independent predictors of anthracycline-related diastolic dysfunction. These findings may help identify patients at higher risk for developing a clinically relevant anthracycline cardiotoxicity from those at lower risk and to differentiate monitoring programs for breast cancer patients according to their risk. PMID:26185196

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

Sekine, Shuichi; Ito, Konomi; Watanabe, Haruna

Patients with long-lasting hepatitis C virus (HCV) infection are at major risk of hepatocellular carcinoma (HCC). Iron accumulation in the livers of these patients is thought to exacerbate conditions of oxidative stress. Transgenic mice that express the HCV core protein develop HCC after the steatosis stage and produce an excess of hepatic reactive oxygen species (ROS). The overproduction of ROS in the liver is the net result of HCV core protein-induced dysfunction of the mitochondrial respiratory chain. This study examined the impact of ferric nitrilacetic acid (Fe-NTA)-mediated iron overload on mitochondrial damage and ROS production in HCV core protein-expressing HepG2more » (human HCC) cells (Hep39b cells). A decrease in mitochondrial membrane potential and ROS production were observed following Fe-NTA treatment. After continuous exposure to Fe-NTA for six days, cell toxicity was observed in Hep39b cells, but not in mock (vector-transfected) HepG2 cells. Moreover, mitochondrial iron ({sup 59}Fe) uptake was increased in the livers of HCV core protein-expressing transgenic mice. This increase in mitochondrial iron uptake was inhibited by Ru360, a mitochondrial Ca{sup 2+} uniporter inhibitor. Furthermore, the Fe-NTA-induced augmentation of mitochondrial dysfunction, ROS production, and cell toxicity were also inhibited by Ru360 in Hep39b cells. Taken together, these results indicate that Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates hepatocyte toxicity caused by the HCV core protein. - Highlights: • Iron accumulation in the livers of patients with hepatitis C virus (HCV) infection is thought to exacerbate oxidative stress. • The impact of iron overload on mitochondrial damage and ROS production in HCV core protein-expressing cells were examined. • Mitochondrial iron uptake was increased in the livers of HCV core protein-expressing transgenic mice. • Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates hepatocyte toxicity caused by the HCV core protein.« less

Chronic methamphetamine self-administration disrupts cortical control of cognition.

PubMed

Bernheim, Aurelien; See, Ronald E; Reichel, Carmela M

2016-10-01

Methamphetamine (meth) is one of the most abused substances worldwide. Chronic use has been associated with repeated relapse episodes that may be exacerbated by cognitive impairments during drug abstinence. Growing evidence demonstrates that meth compromises prefrontal cortex activity, resulting in persisting attentional and memory impairments. After summarizing recent studies of meth-induced cognitive dysfunction using a translationally relevant model of self-administered meth, this review emphasizes the cortical brain changes contributing to cognitive dysregulation during abstinence. Finally, we propose the use of cognitive enhancers during abstinence that may promote a drug-free state by reversing cortical dysfunction linked with prolonged meth abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Obsessive-compulsive disorders in forensic-psychiatric opinions].

PubMed

Kocur, Józef; Trendak, Wiesława

2009-01-01

Obsessive-compulsive disorders and disorders within their spectrum pose a serious diagnostic and therapeutic problem, as the symptoms that appear along with the disorders result from dysfunction of the emotional, motivational and cognitive sphere. The dysfunction is determined by complex genetic, neurochemical and neurophysiological factors. Exacerbation of the symptoms may weaken the control over the disturbed impulses and compulsions, which in turn may lead to violation of law. Therefore, a forensic-psychiatric evaluation in cases related to patients suffering from obsessive-compulsive disorders has to include very complex relations between the type and the circumstances of the committed act or the undertaken actions and the type and intensity of these disorders.

Asthma mimic: Case report and literature review of vocal cord nodule associated with wheezing.

PubMed

Kashif, Muhammad; Singh, Tushi; Aslam, Ahsan; Khaja, Misbahuddin

2017-01-01

Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. Various clinical conditions can mimic asthma, such as foreign body aspiration, subglottic stenosis, congestive heart failure, diffuse panbronchiolitis, aortic arch anomalies, reactive airway dysfunction syndrome, chronic obstructive pulmonary disease, retrosternal goiter, vocal cord tumors, other airway tumors, and vocal cord dysfunction. Upper airway obstruction can be a life-threatening emergency. Here, we present the case of a 58-year-old female with recurrent hospital visits for wheezing and exacerbations of asthma, who was later found to have a vocal cord nodule confirmed to be squamous cell carcinoma, which was mimicking like asthma.

Sexuality in the Older Adult.

PubMed

Morton, Laura

2017-09-01

Sexuality is an important part of a person's life continuing into older age. Physiologic changes that occur with aging can affect sexual function and may be exacerbated by comorbid disease. To diagnose sexual dysfunction, providers must obtain a thorough history and physical examination, including psychosocial factors. The causes of sexual dysfunction along with patient preferences within the patient's social system serve as the foundation for developing person-centered strategies to address these concerns. To improve care of older adults with sexual concerns, providers should initiate discussions with, listen to, and work with patients to create a comprehensive management plan. Copyright © 2017 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

Portal vein thrombosis in paroxysmal nocturnal haemoglobinuria.

PubMed

Tomizuka, H; Hatake, K; Kitagawa, S; Yamashita, K; Arai, H; Miura, Y

1999-01-01

A 28-year-old man was hospitalized with nausea, vomiting, abdominal pain and low-grade fever. He had a 6-month history of paroxysmal nocturnal haemoglobinuria (PNH), and laboratory data showed anaemia and liver dysfunction. An abdominal ultrasonography showed ascites and portal vein thrombosis. After receiving antithrombotic treatment, the portal vein thrombosis did not extend. Portal vein thrombosis is very rare but should be considered when we encounter liver dysfunction associated with PNH as well as hepatic vein thrombosis. Ultrasonography is very useful in detecting portal vein thrombosis and facilitating early diagnosis. Warfarin is very effective in preventing exacerbation of portal vein thrombosis in PNH.

Effect of normative masculinity on males' dysfunctional sexual beliefs, sexual attitudes, and perceptions of sexual functioning.

PubMed

Clarke, Michael J; Marks, Anthony D G; Lykins, Amy D

2015-01-01

Male sexual dysfunction is a prevalent and distressing condition, which may be exacerbated by the sufferer's perceptions of masculinity and normative sexual behavior. This study sought to investigate the effect of social context on males' beliefs regarding sexual behavior. The research examined the effect of male role modeling and masculine cues on males' dysfunctional sexual beliefs, sexual attitudes, and self-perceptions of sexual functioning. A sample of 140 male participants, with a mean age of 29 years, was exposed to pictorial and verbal cues that presented different versions of male behavior across three conditions. Results indicated that males exposed to models and cues of traditional masculinity showed significantly increased levels of dysfunctional sexual beliefs and traditional sexual attitudes relative to males exposed to models of modern masculinity. Results also indicated that males exposed to traditional masculine stimuli reported lower levels of sexual inhibition due to fear of performance failure than males exposed to models of modern masculinity. The potential role of social context is discussed in the development and maintenance of male sexual dysfunction and its implications for treatment.

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.

Associations Between Left Ventricular Dysfunction and Brain Structure and Function: Findings From the SABRE (Southall and Brent Revisited) Study.

PubMed

Park, Chloe M; Williams, Emily D; Chaturvedi, Nish; Tillin, Therese; Stewart, Robert J; Richards, Marcus; Shibata, Dean; Mayet, Jamil; Hughes, Alun D

2017-04-18

Subclinical left ventricular (LV) dysfunction has been inconsistently associated with early cognitive impairment, and mechanistic pathways have been poorly considered. We investigated the cross-sectional relationship between LV dysfunction and structural/functional measures of the brain and explored the role of potential mechanisms. A total of 1338 individuals (69±6 years) from the Southall and Brent Revisited study underwent echocardiography for systolic (tissue Doppler imaging peak systolic wave) and diastolic (left atrial diameter) assessment. Cognitive function was assessed and total and hippocampal brain volumes were measured by magnetic resonance imaging. Global LV function was assessed by circulating N-terminal pro-brain natriuretic peptide. The role of potential mechanistic pathways of arterial stiffness, atherosclerosis, microvascular disease, and inflammation were explored. After adjusting for age, sex, and ethnicity, lower systolic function was associated with lower total brain (beta±standard error, 14.9±3.2 cm 3 ; P <0.0001) and hippocampal volumes (0.05±0.02 cm 3 , P =0.01). Reduced diastolic function was associated with poorer working memory (-0.21±0.07, P =0.004) and fluency scores (-0.18±0.08, P =0.02). Reduced global LV function was associated with smaller hippocampal volume (-0.10±0.03 cm 3 , P =0.004) and adverse visual memory (-0.076±0.03, P =0.02) and processing speed (0.063±0.02, P =0.006) scores. Separate adjustment for concomitant cardiovascular risk factors attenuated associations with hippocampal volume and fluency only. Further adjustment for the alternative pathways of microvascular disease or arterial stiffness attenuated the relationship between global LV function and visual memory. In a community-based sample of older people, measures of LV function were associated with structural/functional measures of the brain. These associations were not wholly explained by concomitant risk factors or potential mechanistic pathways. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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.

Hypogonadism as a possible link between metabolic diseases and erectile dysfunction in aging men.

PubMed

Corona, Giovanni; Bianchini, Silvia; Sforza, Alessandra; Vignozzi, Linda; Maggi, Mario

2015-01-01

There is evidence demonstrating that sexual complaints represent the most specific symptoms associated with late onset hypogonadism, while central obesity is the most specific sign. In obese men, hypogonadism can further worsen the metabolic profile and increase abdominal fat. In addition, although hypogonadism can exacerbate obesity-associated erectile dysfunction (ED), recent data suggest that a direct contribution of fat-derived factors could be hypothesized. In particular, an animal model recently documented that fat accumulation induces several hepatic pro-inflammatory genes closely linked to corpora cavernosa endothelial dysfunction. Lifestyle modifications and weight loss are the first steps in the treatment of ED patients with obesity or metabolic diseases. In symptomatic hypogonadal men with metabolic impairment and obesity, combining the effect of testosterone substitution with lifestyle modifications could result in better outcomes.

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.

Exercise reveals impairments in left ventricular systolic function in patients with metabolic syndrome.

PubMed

Fournier, Sara B; Reger, Brian L; Donley, David A; Bonner, Daniel E; Warden, Bradford E; Gharib, Wissam; Failinger, Conard F; Olfert, Melissa D; Frisbee, Jefferson C; Olfert, I Mark; Chantler, Paul D

2014-01-01

Metabolic syndrome (MetS) is the manifestation of a cluster of cardiovascular risk factors and is associated with a threefold increase in the risk of cardiovascular morbidity and mortality, which is suggested to be mediated, in part, by resting left ventricular (LV) systolic dysfunction. However, to what extent resting LV systolic function is impaired in MetS is controversial, and there are no data indicating whether LV systolic function is impaired during exercise. Accordingly, the objective of this study was to examine comprehensively the LV and arterial responses to exercise in individuals with MetS without diabetes and/or overt cardiovascular disease in comparison to a healthy control population. Cardiovascular function was characterized using Doppler echocardiography and gas exchange in individuals with MetS (n = 27) versus healthy control subjects (n = 20) at rest and during peak exercise. At rest, individuals with MetS displayed normal LV systolic function but reduced LV diastolic function compared with healthy control subjects. During peak exercise, individuals with MetS had impaired contractility, pump performance and vasodilator reserve capacity versus control subjects. A blunted contractile reserve response resulted in diminished arterial-ventricular coupling reserve and limited aerobic capacity in individuals with MetS versus control subjects. These findings are of clinical importance, because they provide insight into the pathophysiological changes in MetS that may predispose this population of individuals to an increased risk of cardiovascular morbidity and mortality.

Effects of maternal high-fat diet and sedentary lifestyle on susceptibility of adult offspring to ozone exposure in rats.

PubMed

Gordon, C J; Phillips, P M; Johnstone, A F M; Schmid, J; Schladweiler, M C; Ledbetter, A; Snow, S J; Kodavanti, U P

2017-05-01

Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O 3 ). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O 3 susceptibility of offspring could thus be manifested by maternal obesity. Thirty-day-old female Long-Evans rats were fed a control (CD) or high-fat (HF) (60% calories) diet for 6 wks and then bred. GD1 rats were then housed with a running wheel (RW) or without a wheel (SED) until parturition, creating four groups of offspring: CD-SED, CD-RW, HF-SED and HF-RW. HF diet was terminated at PND 35 and all offspring were placed on CD. Body weight and %fat of dams were greatest in order; HF-SED > HF-RW > CD-SED > CD-RW. Adult offspring were exposed to O 3 for two consecutive days (0.8 ppm, 4 h/day). Glucose tolerance tests (GTT), ventilatory parameters (plethysmography), and bronchoalveolar fluid (BALF) cell counts and protein biomarkers were performed to assess response to O 3 . Exercise and diet altered body weight and %fat of young offspring. GTT, ventilation and BALF cell counts were exacerbated by O 3 with responses markedly exacerbated in males. HF diet and O 3 led to significant exacerbation of several BALF parameters: total cell count, neutrophils and lymphocytes were increased in male HF-SED versus CD-SED. Males were hyperglycemic after O 3 exposure and exhibited exacerbated GTT responses. Ventilatory dysfunction was also exacerbated in males. Maternal exercise had minimal effects on O 3 response. The results of this exploratory study suggest a link between maternal obesity and susceptibility to O 3 in their adult offspring in a sex-specific manner.

Crafting in context: Exploring when job crafting is dysfunctional for performance effectiveness.

PubMed

Dierdorff, Erich C; Jensen, Jaclyn M

2018-05-01

Job crafting theory purports that the consequences of revising one's work role can be simultaneously beneficial and detrimental. Previous research, however, has almost exclusively emphasized the beneficial outcomes of job crafting. In the current study, we proposed dysfunctional consequences of crafting for performance-related outcomes in the form of a U-shaped relationship between job crafting and performance effectiveness (managerial ratings of job proficiency and peer ratings of citizenship behavior). We further predicted that elements of the task context (autonomy and ambiguity) and the social context (interdependence and social support) moderate these curvilinear relationships. Consistent with previous research, job crafting displayed positive and linear effects on work-related attitudes (job satisfaction and affective commitment). Consistent with our predictions, moderate levels of crafting were associated with dysfunctional performance-related outcomes and features of work context either exacerbated or dissipated these dysfunctional consequences of job crafting for individuals. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Dysfunctional HDL containing L159R apoA-I leads to exacerbation of atherosclerosis in hyperlipidemic mice

USDA-ARS?s Scientific Manuscript database

In this study, the effect of the mutation L159R apoA-I or apoA-IL159R (FIN) was assessed. apoA-IL159R (FIN) is associated with a dominant negative phenotype, displaying hypoalphaproteinemia and an increased risk for atherosclerosis in humans. Transgenic mice lines were created through strategic mati...

Advanced mitral-tricuspid disease with severe right ventricular dysfunction: the double-staged approach.

PubMed

Jouan, Jérôme; Achouh, Paul; Besson, Laila; Carpentier, Alain; Fabiani, Jean-Noël

2012-09-01

Tricuspid valve surgery in the presence of severe right ventricular dysfunction and pulmonary hypertension secondary to mitral valve stenosis is associated with poor early outcomes. We report the case of a young patient, presenting with severe chronic mitral-tricuspid disease responsible for long-lasting pulmonary hypertension and altered right ventricular function, who initially underwent mitral valve replacement and 7 days later the correction of her tricuspid insufficiency. This 2-staged approach permitted progressive reduction of pulmonary pressure and partial right ventricular remodeling before closing the systolic release valve of the right ventricle represented by tricuspid regurgitation. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Increased Blood Pressure Variability Prior to Chronic Kidney Disease Exacerbates Renal Dysfunction in Rats

PubMed Central

Freitas, Frederico F. C. T.; Araujo, Gilberto; Porto, Marcella L.; Freitas, Flavia P. S.; Graceli, Jones B.; Balarini, Camille M.; Vasquez, Elisardo C.; Meyrelles, Silvana S.; Gava, Agata L.

2016-01-01

Increased blood pressure variability (BPV), which can be experimentally induced by sinoaortic denervation (SAD), has emerged as a new marker of the prognosis of cardiovascular and renal outcomes. Considering that increased BPV can lead to organ-damage, the goal of the present study was to evaluate the effects of SAD on renal function in an experimental model of chronic kidney disease (CKD). SAD was performed in male Wistar rats 2 weeks before 5/6 nephrectomy and the animals were evaluated 4 weeks after the induction of CKD. Our data demonstrated that BPV was increased in SAD and CKD animals and that the combination of both conditions (SAD+CKD) exacerbated BPV. The baroreflex sensitivity index was diminished in the SAD and CKD groups; this reduction was more pronounced when SAD and CKD were performed together. 5/6 nephrectomy led to hypertension, which was higher in SAD+CKD animals. Regarding renal function, the combination of SAD and CKD resulted in reduced renal plasma and blood flow, increased renal vascular resistance and augmented uraemia when compared to CKD animals. Glomerular filtration rate and BPV were negatively correlated in SAD, CKD, and SAD+CKD animals. Moreover, SAD+CKD animals presented a higher level of glomerulosclerosis when compared to all other groups. Cardiac and renal hypertrophy, as well as oxidative stress, was also further increased when SAD and CKD were combined. These results show that SAD prior to 5/6 nephrectomy exacerbates renal dysfunction, suggesting that previous augmented BPV should be considered as an important factor to the progression of renal diseases. PMID:27721797

A H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice

PubMed Central

Liu, Mi; Sun, Ying; Zhang, Aihua; Yang, Tianxin

2016-01-01

Accumulating evidence demonstrated that hydrogen sulfide (H2S) is highly involved in inflammation, oxidative stress, and apoptosis and contributes to the pathogenesis of kidney diseases. However, the role of H2S in cisplatin nephrotoxicity is still debatable. Here we investigated the effect of GYY4137, a novel slow-releasing H2S donor, on cisplatin nephrotoxicity in mice. Male C57BL/6 mice were pretreated with GYY4137 for 72 h prior to cisplatin injection. After cisplatin treatment for 72 h, mice developed obvious renal dysfunction and kidney injury as evidenced by elevated blood urea nitrogen (BUN) and histological damage. Consistently, these mice also showed increased proinflammatory cytokines such as TNF-α, IL-6, and IL-1β in circulation and/or kidney tissues. Meanwhile, circulating thiobarbituric aid-reactive substances (TBARS) and renal apoptotic indices including caspase-3, Bak, and Bax were all elevated. However, application of GYY4137 further aggravated renal dysfunction and kidney structural injury in line with promoted inflammation, oxidative stress, and apoptotic response following cisplatin treatment. Taken together, our results suggested that GYY4137 exacerbated cisplatin-induced nephrotoxicity in mice possibly through promoting inflammation, oxidative stress, and apoptotic response. PMID:27340345

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.

Broken heart as work-related accident: Occupational stress as a cause of takotsubo cardiomyopathy in 55-year-old female teacher - Role of automated function imaging in diagnostic workflow.

PubMed

Mielczarek, Agnieszka; Kasprzak, Jarosław Damian; Marcinkiewicz, Andrzej; Kurpesa, Małgorzata; Uznańska-Loch, Barbara; Wierzbowska-Drabik, Karina

2015-01-01

Takotsubo cardiomiopathy (TTC) (known also as "ampulla cardiomyopathy," "apical ballooning" or "broken heart syndrome") is connected with a temporary systolic left ventricular dysfunction without the culprit coronary lesion. Takotsubo cardiomyopathy was first described in 1990 in Japan after octopus trapping pot with a round bottom and narrow neck similar in shape to left ventriculogram in TTC patients. The occurrence of TTC is usually precipitated by a stressful event with a clinical presentation mimicking myocardial infarction: chest pain, ST-T segment elevation or T-wave inversion, a rise in cardiac troponin, and contractility abnormalities in echocardiography. A left ventricular dysfunction is transient and improves within a few weeks. Takotsubo cardiomyopathy typically occurs in postmenopausal women and the postulated mechanism is catecholamine overstimulation. Moreover, the distribution of contractility impairments usually does not correspond with typical region supplied by a single coronary artery. Therefore, the assessment of regional pattern of systolic dysfunction with speckle-tracking echocardiography and automated function imaging (AFI) technique may be important in diagnosis of TTC and may improve our insight into its patophysiology. We described a 55-year-old female teacher with TTC diagnosed after acute psychological stress in workplace. The provoking factor related with occupational stress and pattern of contraction abnormalities documented with AFI technique including basal segments of left ventricle make this case atypical. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Contribution of autonomic dysfunction to abnormal exercise blood pressure in type 2 diabetes mellitus.

PubMed

Weston, Kassia S; Sacre, Julian W; Jellis, Christine L; Coombes, Jeff S

2013-01-01

The purpose of this study was to compare the presence and severity of autonomic dysfunction in type 2 diabetes mellitus patients, with and without exaggerated blood pressure responses to exercise. We performed a cross-sectional analysis of 98 patients with type 2 diabetes mellitus (aged 59±9). Both time (standard deviation of RR intervals, root-mean-square of successive RR interval differences) and frequency (total spectral power, high frequency, low frequency, very low frequency) domains of heart rate variability were analysed in a 5 min recording at rest and 20 min after a maximal treadmill test. An exaggerated blood pressure response to exercise was identified by peak blood pressure ≥190/105 mmHg (women) or ≥210/105 mmHg (men). Each group of either exaggerated exercise blood pressure response or normal blood pressure response consisted of 49 patients. At rest there were no significant differences between groups for all time and frequency domain parameters of heart rate variability. Post-exercise, there was a significant (p<0.05) reduction in the SDNN, RMSSD and TP in the exaggerated exercise blood pressure group. Independent correlates (p<0.01) of exercise systolic blood pressure included post-exercise TP, resting systolic blood pressure, cardiac autonomic neuropathy and beta-blockers (beta=-0.28, adj. R² = 0.32, p<0.001). Reduced post-exercise heart rate variability in patients with type 2 diabetes mellitus, with an exaggerated exercise blood pressure response suggests preclinical autonomic dysfunction characterized by impaired vagal modulation. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

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.

Interobserver agreement on the echocardiographic parameters that estimate right ventricular systolic function in the early postoperative period of cardiac surgery.

PubMed

Olmos-Temois, S G; Santos-Martínez, L E; Álvarez-Álvarez, R; Gutiérrez-Delgado, L G; Baranda-Tovar, F M

2016-11-01

To know the variability of transthoracic echocardiographic parameters that assess right ventricular systolic function by analyzing interobserver agreement in the early postoperative period of cardiovascular surgery. To assess the feasibility of these echocardiographic measurements. A cross-sectional study, double-blind pilot study was carried out from May 2011 to February 2013. Cardiovascular postoperative critical care at the National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico. Consecutive, non-probabilistic sampling. Fifty-six patients were studied in the postoperative period of cardiac surgery. The first echocardiographic parameters were obtained between 6-8hours after cardiac surgery, followed by blinded second measurements. Tricuspid annular plane systolic excursion (TAPSE), tricuspid annular peak systolic velocity on tissue Doppler imaging (VSPAT), diameters and right ventricular outflow area, tract fractional shortening. The agreement was analyzed by the Bland-Altman method, and its magnitude was assessed by the intraclass correlation coefficient (95% confidence interval). Both observers evaluated TAPSE and VSPAT in 48 patients (92%). The average TAPSE was 11.68±4.53mm (range 4-27mm). Right ventricular systolic dysfunction was observed in 41 cases (85%) and normal TAPSE in 7 patients (15%). The average difference and its limits according to TAPSE were -0.917±2.95 (-6.821, 4.988), with a magnitude of 0.725 (0.552, 0.837); the tricuspid annular peak systolic velocity on tissue Doppler imaging was -0.001±0.015 (-0.031, 0.030), and its magnitude 0.825 (0.708, 0.898), respectively. VSPAT and TAPSE were estimated by both observers in 92% of the patients, these parameters exhibiting the lowest interobserver variability. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Beta-erythropoietin effects on ventricular remodeling, left and right systolic function, pulmonary pressure, and hospitalizations in patients affected with heart failure and anemia.

PubMed

Palazzuoli, Alberto; Silverberg, Donald S; Calabrò, Anna; Spinelli, Tommaso; Quatrini, Ilaria; Campagna, Maria S; Franci, Beatrice; Nuti, Ranuccio

2009-06-01

Anemia in heart failure is related to advanced New York Heart Association classes, severe systolic dysfunction, and reduced exercise tolerance. Although anemia is frequently found in congestive heart failure (CHF), little is known about the effect of its' correction with erythropoietin (EPO) on cardiac structure and function. The present study examines, in patients with advanced CHF and anemia, the effects of beta-EPO on left ventricular volumes, left ventricular ejection fraction (LVEF), left and right longitudinal function mitral anular plane systolic excursion (MAPSE), tricuspid anular plane excursion (TAPSE), and pulmonary artery pressures in 58 patients during 1-year follow-up in a double-blind controlled study of correction of anemia with subcutaneous beta-EPO. Echocardiographic evaluation, B-Type natriuretic peptide (BNP) levels, and hematological parameters are reported at 4 and 12 months. The patients in group A after 4 months of follow-up period demonstrated an increase in LVEF and MAPSE (P < 0.05 and P < 0.01, respectively) with left ventricular systolic volume reduction (P < 0.02) with respect to baseline and controls. After 12 months, results regarding left ventricular systolic volume LVEF and MAPSE persisted (P < 0.001). In addition, TAPSE increased and pulmonary artery pressures fell significantly in group A (P < 0.01). All these changes occurred together with a significant BNP reduction and significant hemoglobin increase in the treated group. Therefore, we revealed a reduced hospitalization rate in treated patients with respect to the controls (25% in treated vs. 54% in controls). In patients with anemia and CHF, correction of anemia with beta-EPO and oral iron over 1 year leads to an improvement in left and right ventricular systolic function by reducing cardiac remodeling, BNP levels, and hospitalization rate.

The relationship between heart rate recovery and brain natruretic Peptide in patients with chest discomfort: a study for relationship between heart rate recovery and pre-exercise, post-exercise levels of brain natruretic Peptide in patients with normal systolic function and chest discomfort.

PubMed

Lee, Jae Eun; Kim, Bum Soo; Park, Wan; Huh, Jung Kwon; Kim, Byung Jin; Sung, Ki Chul; Kang, Jin Ho; Lee, Man Ho; Park, Jung Ro

2010-04-01

The correlation between brain natruretic peptide (BNP) level and cardiac autonomic function has been studied in type 2 diabetic patients. However, there is limited data from patients with normal systolic function. We evaluated the association between heart rate recovery (HRR) representing autonomic dysfunction and three plasma BNP levels: pre-exercise, post-exercise, and change during exercise in patients with normal systolic function. Subjects included 105 patients with chest pain and normal systolic function. HRR was defined as the difference between the peak heart rate and the rate measured two minutes after completion of a treadmill exercise test. We measured plasma BNP levels before exercise, 5 minutes after completion of exercise, and during exercise (absolute value of difference between pre- and post-exercise BNP levels). Patients with abnormal HRR values (

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.

Non-volumetric echocardiographic indices and qualitative assessment of right ventricular systolic function in Ebstein's anomaly: comparison with CMR-derived ejection fraction in 49 patients.

PubMed

Kühn, Andreas; Meierhofer, Christian; Rutz, Tobias; Rondak, Ina-Christine; Röhlig, Christoph; Schreiber, Christian; Fratz, Sohrab; Ewert, Peter; Vogt, Manfred

2016-08-01

Ebstein's anomaly (EA) is often associated with right ventricular (RV) dysfunction. Data on echocardiographic quantification of RV function are, however, rare. The aim of this study was to determine how non-volumetric echocardiographic indices and qualitative assessment of global systolic RV function correlate with cardiovascular magnetic resonance (CMR)-derived RV ejection fraction (EF). We compared six echocardiographic indices and qualitative assessment of RV function with the gold standard CMR. A total of 49 unoperated patients with EA and a mean age of 32 ± 18 years were examined. Tricuspid annular plane systolic excursion, tissue Doppler myocardial velocities (peak S and IVA) and 2D strain and strain rate measures for the RV were compared with CMR-derived EF. Only 2D global longitudinal strain (2D-GLS), out of the six parameters investigated, showed a weak, although statistically significant correlation with CMR-derived RVEF (R = -0.4, P = 0.01). Using a cut-off value of -20.15, 2D-GLS sensitivity (77%) and specificity (46%) in detecting patients with a CMR-derived EF of <50% were comparable with qualitative assessment (sensitivity 77%, specificity 45%). Overall echocardiographic parameters of RV function correlate poorly with CMR-derived EF in patients with EA. Only 2D global longitudinal RV strain correlated weakly with CMR-derived RVEF. However, the sensitivity and specificity for detecting RV dysfunction using 2D strain imaging were comparable with qualitative RV functional assessment. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Practice patterns, outcomes, and end-organ dysfunction for patients with acute severe hypertension: the Studying the Treatment of Acute hyperTension (STAT) registry.

PubMed

Katz, Jason N; Gore, Joel M; Amin, Alpesh; Anderson, Frederick A; Dasta, Joseph F; Ferguson, James J; Kleinschmidt, Kurt; Mayer, Stephan A; Multz, Alan S; Peacock, W Frank; Peterson, Eric; Pollack, Charles; Sung, Gene Yong; Shorr, Andrew; Varon, Joseph; Wyman, Allison; Emery, Leigh A; Granger, Christopher B

2009-10-01

Limited data are available on the care of patients with acute severe hypertension requiring hospitalization. We characterized contemporary practice patterns and outcomes for this population. STAT is a 25-institution, US registry of consecutive patients with acute severe hypertension (>180 mm Hg systolic and/or >110 mm Hg diastolic; >140 and/or >90 for subarachnoid hemorrhage) treated with intravenous therapy in a critical care setting. One thousand five hundred eighty-eight patients were enrolled (January 2007 to April 2008). Median age was 58 years (interquartile range 49-70 years), 779 (49%) were women, and 892 (56%) were African American; 27% (n = 425) had a prior admission for acute hypertension and 486 (31%) had chronic kidney disease. Median qualifying blood pressure (BP) was 200 (186, 220) systolic and 110 (93, 123) mm Hg diastolic. Initial intravenous antihypertensive therapies used to control BP varied, with 1,009 (64%) patients requiring multiple drugs. Median time to achieve a systolic BP <160 mm Hg (<140 mm Hg for subarachnoid hemorrhage) was 4.0 (0.8, 12) hours; 893 (60%) had reelevation to >180 (>140 for subarachnoid hemorrhage) after initial control; and 63 (4.0%) developed iatrogenic hypotension. Hospital mortality was 6.9% (n = 109) with an aggregate 90-day mortality rate of 11% (174/1,588); 59% (n = 943) had acute/worsening end-organ dysfunction during hospitalization. The 90-day readmission rate was 37% (523/1,415), of which one quarter (132/523) was due to recurrent acute severe hypertension. This study highlights heterogeneity in care, BP control, and outcomes of patients hospitalized with acute severe hypertension.

Role of echocardiography in the evaluation of syncope: a prospective study

PubMed Central

Sarasin, F P; Junod, A-F; Carballo, D; Slama, S; Unger, P-F; Louis-Simonet, M

2002-01-01

Objective: To study the role of echocardiography in the stepwise evaluation of syncope. Design: A prospective observational study with an 18 month follow up. Setting: University teaching hospital providing primary and tertiary care. Subjects: 650 consecutive patients with syncope and clinical suspicion of an obstructive valvar lesion, or with syncope not explained by history, physical examination, or a 12 lead ECG, who underwent bidimensional Doppler transthoracic echocardiography. Main outcome measures: The causes of syncope were assigned using published diagnostic criteria. Echocardiography was considered diagnostic when confirming a suspected diagnosis, or when revealing occult cardiac disease explaining the syncope. Results: A systolic murmur was identified in 61 of the 650 patients (9%). Severe aortic stenosis was suspected in 20 of these and was confirmed by echocardiography in eight. Follow up excluded further cases of aortic stenosis. In patients with unexplained syncope (n = 155), routine echocardiography showed no abnormalities that established the cause of the syncope. Echocardiography was normal or non-relevant in all patients with a negative cardiac history and a normal ECG (n = 67). In patients with a positive cardiac history or an abnormal ECG (n = 88), echocardiography showed systolic dysfunction (left ventricular ejection fraction ≤ 40%) in 24 (27%) and minor non-relevant findings in the remaining 64. Arrhythmias were diagnosed in 12 of the 24 patients with systolic dysfunction (50%), and in 12 of the 64 remaining patients (19%) (p < 0.01). Conclusions: Echocardiography was most useful for assessing the severity of the underlying cardiac disease and for risk stratification in patients with unexplained syncope but with a positive cardiac history or an abnormal ECG. PMID:12231593

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.

Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance.

PubMed

Smedema, Jan-Peter; van Geuns, Robert-Jan; Ainslie, Gillian; Ector, Joris; Heidbuchel, Hein; Crijns, Harry J G M

2017-11-01

Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast-enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast-enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non-invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P < 0.001). Right ventricular enhancement correlated with systolic ventricular dysfunction (P < 0.001), hypertrophy (P = 0.001), and dilation (P < 0.001). Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Prediction of subtle left ventricular systolic dysfunction in homozygous and heterozygous familial hypercholesterolemia: Genetic analyses and speckle tracking echocardiography study.

PubMed

Saracoglu, Erhan; Kılıç, Salih; Vuruşkan, Ertan; Düzen, Irfan; Çekici, Yusuf; Kuzu, Zülfiye; Yıldırım, Arafat; Küçükosmanoğlu, Mehmet; Çetin, Mustafa

2018-06-05

Few studies have shown the direct effect of familial hypercholesterolemia (FH) on myocardial systolic function. Studies focused on heterozygote FH patients but not homozygote ones, and they did not perform genetic analyses. We aimed to evaluate all types of patients with FH using the potentially more sensitive speckle tracking echocardiography (STE) technique to identify early left ventricular (LV) dysfunction. Genetic analyses of patients with FH were conducted for LDL-receptor, PCSK9, and ApoB100. Nine homozygote, two compound heterozygote, and 82 heterozygote FH patients and 85 healthy subjects were prospectively studied. Longitudinal and circumferential strain measurements and conventional echocardiography findings were obtained. LV ejection fractions were similar for all (homozygote, heterozygote, and control) groups. The LV average longitudinal strain (aLS) and average circumferential strain (aCS) levels were significantly reduced in the homozygote and heterozygote groups when compared with the controls (for aLS, P = .008 (<.001); for aCS, P =< .001). A significant inverse correlation was found between LDL-C levels and LS (P < .001, r = .728) and CS (P < .001, r = .642) for all FH patients. This study demonstrates the potential of using systolic strain values obtained using 2D STE for determining lipotoxicity in the myocardium owing to hypercholesterolemia. Our study found that cardiac functions of homozygote patients who had the highest cholesterol levels were disrupted at very early ages. Therefore, starting lipid reduction treatment and early reverse LV remodelling therapy at early ages may be beneficial for high-risk patients. © 2018 Wiley Periodicals, Inc.

Two-dimensional speckle tracking echocardiography demonstrates no effect of active acromegaly on left ventricular strain.

PubMed

Volschan, I C M; Kasuki, L; Silva, C M S; Alcantara, M L; Saraiva, R M; Xavier, S S; Gadelha, M R

2017-06-01

Speckle tracking echocardiography (STE) allows for the study of myocardial strain (ε), a marker of early and subclinical ventricular systolic dysfunction. Cardiac disease may be present in patients with acromegaly; however, STE has never been used to evaluate these patients. To evaluate left ventricular (LV) global longitudinal strain in patients with active acromegaly with normal LV systolic function. Cross-sectional clinical study. Patients with active acromegaly with no detectable heart disease and a control group were matched for age, gender, arterial hypertension and diabetes mellitus underwent STE. Global LV longitudinal ε (GLS), left ventricular mass index (LVMi), left ventricular ejection fraction (LVEF) and relative wall thickness (RWT) were obtained via two-dimensional (2D) echocardiography using STE. Thirty-seven patients with active acromegaly (mean age 45.6 ± 13.8; 48.6% were males) and 48 controls were included. The mean GLS was not significantly different between the acromegaly group and the control group (in %, -20.1 ± 3.1 vs. -19.4 ± 2.2, p = 0.256). Mean LVMi was increased in the acromegaly group (in g/m 2 , 101.6 ± 27.1 vs. 73.2 ± 18.6, p < 0.01). There was a negative correlation between LVMi and GLS (r = -0.39, p = 0.01). Acromegaly patients, despite presenting with a higher LVMi when analyzed by 2D echocardiography, did not present with impairment in the strain when compared to a control group; this finding indicates a low chance of evolution to systolic dysfunction and agrees with recent studies that show a lower frequency of cardiac disease in these patients.

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

Long-Term Preservation of Left Ventricular Systolic Function in Patients With Refractory Angina Pectoris and Inducible Myocardial Ischemia on Optimal Medical Therapy.

PubMed

Slavich, Massimo; Maranta, Francesco; Fumero, Andrea; Godino, Cosmo; Giannini, Francesco; Oppizzi, Michele; Colombo, Antonio; Fragasso, Gabriele; Margonato, Alberto

2016-05-15

Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p <0.0001). The duration time and the number of angina attacks did not correlate with EF in the whole population and in patients without previous myocardial infarction. In patients with previous myocardial infarction, the number of anginal attacks did not correlate with EF, but EF appeared higher in patients with angina duration >5 years (<5 years EF 37% ± 1 [n = 26]; >5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Value of Combined Circumferential and Longitudinal Left Ventricular Systolic Dysfunction to Predict Adverse Outcome 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

2016-01-01

BACKGROUND AND AIM OF THE STUDY: Patients with asymptomatic aortic stenosis (AS) may have left ventricular systolic dysfunction (LVSD) defined as an impairment of the circumferential and/or longitudinal (C&L) myocardial fibers, despite a preserved left ventricular ejection fraction (LVEF). An assessment was made as to whether the combined LVSD of C&L fibers has a prognostic impact in asymptomatic AS. METHODS: A total of 200 asymptomatic AS patients was analyzed. Midwall shortening and mitral annular peak systolic velocity were considered as indices of C&L function and classified as low if <16.5% and <8.5 cm/s, respectively. The primary outcome was a composite of major cardiovascular events (MACE), including aortic valve-related and ischemic cardiovascular-related events. RESULTS: During a 25-month follow up period, MACE occurred in 69 patients (35%),while 46 of 72 patients (64%) had C&L LVSD and 23 of 128 patients (18%) had not (p <0.001). Cox analysis identified C&L LVSD as an independent MACE predictor, together with aortic transvalvular peak gradient, E/E′ ratio and excessive left ventricular mass. C&L-LVSD also predicted the occurrence of aortic valve-related events and ischemic cardiovascular-related events analyzed separately. A receiver operating characteristic curve analysis showed that the area under the curve (AUC) for C&L LVSD in predicting MACE was 0.77, significantly higher (p = 0.002, z-statistic) than the AUCs of C&L fibers considered individually (0.64 and 0.63, respectively). CONCLUSION: C&L-LVSD provides additional prognostic information into traditional risk factors for patients with asymptomatic AS.

RIP1-mediated mitochondrial dysfunction and ROS production contributed to tumor necrosis factor alpha-induced L929 cell necroptosis and autophagy.

PubMed

Ye, Yuan-Chao; Wang, Hong-Ju; Yu, Lu; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2012-12-01

Tumor necrosis factor alpha (TNFα) induces necroptosis and autophagy; however, the detailed molecular mechanism is not fully understood. In this study, we found that TNFα administration caused mitochondrial dysfunction and reactive oxygen species (ROS) production, which led to necroptosis and autophagy in murine fibrosarcoma L929 cells. Notably, the RIP1 (serine-threonine kinase receptor-interacting protein 1, a main adaptor protein of necroptosis) specific inhibitor necrostatin-1 (Nec-1) recovered mitochondrial dysfunction and ROS production due to TNFα administration. Moreover, pan-caspase inhibitor z-VAD-fmk (zVAD) increased RIP1 expression and exacerbated TNFα-induced mitochondrial dysfunction and ROS production, indicating that RIP1 led to mitochondrial dysfunction and ROS production. In addition, cytochrome c release from mitochondria was accompanied with TNFα administration, and Nec-1 blocked the release of cytochrome c upon TNFα administration, while zVAD enhanced the release. These further suggested that RIP1 induced mitochondrial dysfunction accompanied with cytochrome c release. Furthermore, autophagy inhibitor 3-methyladenine (3MA) did not affect RIP1 expression as well as mitochondrial dysfunction and ROS production. Together with our previous publication that autophagy was a downstream consequence of necroptosis, we concluded that TNFα induced mitochondrial dysfunction accompanied with ROS production and cytochrome c release via RIP1, leading to necroptosis and resulting autophagic cell death. Copyright © 2012 Elsevier B.V. All rights reserved.

Associations between N-terminal pro-B-type natriuretic peptide and cardiac function in adults with corrected tetralogy of Fallot.

PubMed

Eindhoven, Jannet A; Menting, Myrthe E; van den Bosch, Annemien E; Cuypers, Judith A A E; Ruys, Titia P E; Witsenburg, Maarten; McGhie, Jackie S; Boersma, Eric; Roos-Hesselink, Jolien W

2014-07-01

Amino-terminal B-type natriuretic peptide (NT-proBNP) may detect early cardiac dysfunction in adults with tetralogy of Fallot (ToF) late after corrective surgery. We aimed to determine the value of NT-proBNP in adults with ToF and establish its relationship with echocardiography and exercise capacity. NT-proBNP measurement, electrocardiography and detailed 2D-echocardiography were performed on the same day in 177 consecutive adults with ToF (mean age 34.6 ± 11.8 years, 58% male, 89% NYHA I, 29.3 ± 8.5 years after surgical correction). Thirty-eight percent of the patients also underwent a cardiopulmonary-exercise test. Median NT-proBNP was 16 [IQR 6.7-33.6] pmol/L, and was elevated in 55%. NT-proBNP correlated with right ventricular (RV) dilatation (r = 0.271, p < 0.001) and RV systolic dysfunction (r = -0.195, p = 0.022), but more strongly with LV systolic dysfunction (r=-0.367, p<0.001), which was present in 69 patients (39%). Moderate or severe pulmonary regurgitation was not associated with higher NT-proBNP. Tricuspid and pulmonary regurgitation peak velocities correlated with NT-proBNP (r = 0.305, p < 0.001 and r = 0.186, p = 0.045, respectively). LV twist was measured with speckle-tracking echocardiography in 71 patients. An abnormal LV twist (20 patients, 28%) was associated with elevated NT-proBNP (p = 0.030). No relationship between NT-proBNP and exercise capacity was found. NT-proBNP levels are elevated in more than 50% of adults with corrected ToF, while they are in stable clinical condition. Higher NT-proBNP is most strongly associated with elevated pulmonary pressures, and with LV dysfunction rather than RV dysfunction. NT-proBNP has the potential to become routine examination in patients with ToF to monitor ventricular function and may be used for timely detection of clinical deterioration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Echocardiographic evaluation of right ventricular systolic function: The traditional and innovative approach.

PubMed

Smolarek, Dorota; Gruchała, Marcin; Sobiczewski, Wojciech

2017-01-01

Estimation of right ventricular (RV) performance still remains technically challenging due to its anatomical and functional distinctiveness. The current guidelines for the echocardiographic quantification of RV function recommend using multiple indices to describe the RV in a thorough and comprehensive manner, such as RV index of myocardial performance, tricuspid annular plane systolic excursion, fractional area change, Doppler tissue imaging-derived tricuspid lateral annular systolic velocity (S'-wave), three-dimensional RV ejection fraction (3D RVEF), RV longitudinal strain (RVLS)/strain rate by speckle- tracking echocardiography (STE). Among these, the last one mentioned here is an innovative and a particularly promising tool that yields more precise information about complex regional and global RV mechanics. STE was initially designed to evaluate left ventricular function, but recently it has been introduced to assess RV performance, which is difficult due to its unique structure and physiology. Many studies have shown that both free wall and 6-segment RVLS present a stronger correlation with the RVEF assessed by cardiac magnetic resonance than conventional parameters and seem to be more sensitive in detecting myocardial dysfunction at an earlier, subclinical stage.

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.

Drinking Water Sodium and Elevated Blood Pressure of Healthy Pregnant Women in Salinity-Affected Coastal Areas.

PubMed

Scheelbeek, Pauline F D; Khan, Aneire E; Mojumder, Sontosh; Elliott, Paul; Vineis, Paolo

2016-08-01

Coastal areas in Southeast Asia are experiencing high sodium concentrations in drinking water sources that are commonly consumed by local populations. Salinity problems caused by episodic cyclones and subsequent seawater inundations are likely (partly) related to climate change and further exacerbated by changes in upstream river flow and local land-use activities. Dietary (food) sodium plays an important role in the global burden of hypertensive disease. It remains unknown, however, if sodium in drinking water-rather than food-has similar effects on blood pressure and disease risk. In this study, we examined the effect of drinking water sodium on blood pressure of pregnant women: increases in blood pressure in this group could severely affect maternal and fetal health. Data on blood pressure, drinking water source, and personal, lifestyle, and environmental confounders was obtained from 701 normotensive pregnant women residing in coastal Bangladesh. Generalized linear mixed regression models were used to investigate association of systolic and diastolic blood pressure of these-otherwise healthy-women with their water source. After adjustment for confounders, drinkers of tube well and pond water (high saline sources) were found to have significantly higher average systolic (+4.85 and +3.62 mm Hg) and diastolic (+2.30 and +1.72 mm Hg) blood pressures than rainwater drinkers. Drinking water salinity problems are expected to exacerbate in the future, putting millions of coastal people-including pregnant women-at increased risk of hypertension and associated diseases. There is an urgent need to further explore the health risks associated to this understudied environmental health problem and feasibility of possible adaptation strategies. © 2016 American Heart Association, Inc.

Ongoing right ventricular hemodynamics in heart failure: clinical value of measurements derived from an implantable monitoring system.

PubMed

Adamson, Philip B; Magalski, Anthony; Braunschweig, Frieder; Böhm, Michael; Reynolds, Dwight; Steinhaus, David; Luby, Allyson; Linde, Cecilia; Ryden, Lars; Cremers, Bodo; Takle, Teri; Bennett, Tom

2003-02-19

This study examined the characteristics of continuously measured right ventricular (RV) hemodynamic information derived from an implantable hemodynamic monitor (IHM) in heart failure patients. Hemodynamic monitoring might improve the day-to-day management of patients with chronic heart failure (CHF). Little is known about the characteristics of long-term hemodynamic information in patients with CHF or how such information relates to meaningful clinical events. Thirty-two patients with CHF received a permanent RV IHM system similar to a single-lead pacemaker. Right ventricular systolic and diastolic pressures, heart rate, and pressure derivatives were continuously measured for nine months without using the data for clinical decision-making or management of patients. Data were then made available to clinical providers, and the patients were followed up for 17 months. Pressure characteristics during optimal volume, clinically determined volume-overload exacerbations, and volume depletion events were examined. The effect of IHM on hospitalizations was examined using the patients' historical controls. Long-term RV pressure measurements had either marked variability or minimal time-related changes. During 36 volume-overload events, RV systolic pressures increased by 25 +/- 4% (p < 0.05) and heart rate increased by 11 +/- 2% (p < 0.05). Pressure increases occurred in 9 of 12 events 4 +/- 2 days before the exacerbations requiring hospitalization. Hospitalizations before using IHM data for clinical management averaged 1.08 per patient year and decreased to 0.47 per patient-year (57% reduction, p < 0.01) after hemodynamic data were used. Long-term ambulatory pressure measurements from an IHM may be helpful in guiding day-to-day clinical management, with a potentially favorable impact on CHF hospitalizations.

Minocycline attenuates cardiac dysfunction in tumor-burdened mice.

PubMed

Devine, Raymond D; Eichenseer, Clayton M; Wold, Loren E

2016-11-01

Cardiovascular dysfunction as a result of tumor burden is becoming a recognized complication; however, the mechanisms remain unknown. A murine model of cancer cachexia has shown marked increases of matrix metalloproteinases (MMPs), known mediators of cardiac remodeling, in the left ventricle. The extent to which MMPs are involved in remodeling remains obscured. To this end a common antibiotic, minocycline, with MMP inhibitory properties was used to elucidate MMP involvement in tumor induced cardiovascular dysfunction. Tumor-bearing mice showed decreased cardiac function with reduced posterior wall thickness (PWTs) during systole, increased MMP and collagen expression consistent with fibrotic remodeling. Administration of minocycline preserved cardiac function in tumor bearing mice and decreased collagen RNA expression in the left ventricle. MMP protein levels were unaffected by minocycline administration, with the exception of MMP-9, indicating minocycline inhibition mechanisms are directly affecting MMP activity. Cancer induced cardiovascular dysfunction is an increasing concern; novel therapeutics are needed to prevent cardiac complications. Minocycline is a well-known antibiotic and recently has been shown to possess MMP inhibitory properties. Our findings presented here show that minocycline could represent a novel use for a long established drug in the prevention and treatment of cancer induced cardiovascular dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Correlation between cardiac remodelling, function, and myocardial contractility in rat hearts 5 weeks after myocardial infarction.

PubMed

Gosselin, H; Qi, X; Rouleau, J L

1998-01-01

Early after infarction, ventricular dysfunction occurs as a result of loss of myocardial tissue. Although papillary muscle studies suggest that reduced myocardial contractility contributes to this ventricular dysfunction, in vivo studies indicate that at rest, cardiac output is normal or near normal, suggesting that contractility of the remaining viable myocardium of the ventricular wall is preserved. However, this has never been verified. To explore this further, 100 rats with various-sized myocardial infarctions had ventricular function assessed by Langendorff preparation or by isolated papillary muscle studies 5 weeks after infarction. Morphologic studies were also done. Rats with large infarctions (54%) had marked ventricular dilatation (dilatation index from 0.23 to 0.75, p < 0.01) and papillary muscle dysfunction (total tension from 6.7 to 3.2 g/mm2, p < 0.01) but only moderate left ventricular dysfunction (maximum developed tension from 206 to 151 mmHg (1 mmHg = 133.3 Pa), p < 0.01), a decrease less than one would expect with an infarct size of 54%. The contractility of the remaining viable myocardium of the ventricle was also moderately depressed (peak systolic midwall stress 91 to 60 mmHg, p < 0.01). Rats with moderate infarctions (32%) had less marked but still moderate ventricular dilatation (dilatation index 0.37, p < 0.001) and moderate papillary muscle dysfunction (total tension 4.2 g/mm2, p < 0.01). However, their decrease in ventricular function was only mild (maximum developed pressure 178 mmHg, p < 0.01) and less than one would expect with an infarct size of 32%. The remaining viable myocardium of the ventricular wall appeared to have normal contractility (peak systolic midwall stress = 86 mmHg, ns). We conclude that in this postinfarction model, in large myocardial infarctions, a loss of contractility of the remaining viable myocardium of the ventricular wall occurs as early as 5 weeks after infarction and that papillary muscle studies slightly overestimate the degree of ventricular dysfunction. In moderate infarctions, the remaining viable myocardium of the ventricular wall has preserved contractility while papillary muscle function is depressed. In this relatively early postinfarction phase, ventricular remodelling appears to help maintain left ventricular function in both moderate and large infarctions.

Endothelial dysfunction correlates with exaggerated exercise pressor response during whole body maximal exercise in chronic kidney disease.

PubMed

Downey, Ryan M; Liao, Peizhou; Millson, Erin C; Quyyumi, Arshed A; Sher, Salman; Park, Jeanie

2017-05-01

Chronic kidney disease (CKD) patients have exercise intolerance associated with increased cardiovascular mortality. Previous studies demonstrate that blood pressure (BP) and sympathetic nerve responses to handgrip exercise are exaggerated in CKD. These patients also have decreased nitric oxide (NO) bioavailability and endothelial dysfunction, which could potentially lead to an impaired ability to vasodilate during exercise. We hypothesized that CKD patients have exaggerated BP responses during maximal whole body exercise and that endothelial dysfunction correlates with greater exercise pressor responses in these patients. Brachial artery flow-mediated dilation (FMD) was assessed before maximal treadmill exercise in 56 participants: 38 CKD (56.7 ± 1.2 yr old, 38 men) and 21 controls (52.8 ± 1.8 yr old, 20 men). During maximal treadmill exercise, the slope-of-rise in systolic BP (+10.32 vs. +7.75 mmHg/stage, P < 0.001), mean arterial pressure (+3.50 vs. +2.63 mmHg/stage, P = 0.004), and heart rate (+11.87 vs. +10.69 beats·min -1 ·stage -1 , P = 0.031) was significantly greater in CKD compared with controls. Baseline FMD was significantly lower in CKD (2.76 ± 0.42% vs. 5.84 ± 0.97%, P = 0.008). Lower FMD values were significantly associated with a higher slope-of-rise in systolic BP (+11.05 vs. 8.71 mmHg/stage, P = 0.003) during exercise in CKD, as well as poorer exercise capacity measured as peak oxygen uptake (V̇o 2peak ; 19.47 ± 1.47 vs. 24.57 ± 1.51 ml·min -1 ·kg -1 , P < 0.001). These findings demonstrate that low FMD in CKD correlates with augmented BP responses during exercise and lower V̇o 2peak , suggesting that endothelial dysfunction may contribute to exaggerated exercise pressor responses and poor exercise capacity in CKD patients.

Independent roles of the priming and the triggering of the NLRP3 inflammasome in the heart.

PubMed

Toldo, Stefano; Mezzaroma, Eleonora; McGeough, Matthew D; Peña, Carla A; Marchetti, Carlo; Sonnino, Chiara; Van Tassell, Benjamin W; Salloum, Fadi N; Voelkel, Norbert F; Hoffman, Hal M; Abbate, Antonio

2015-02-01

The NLRP3 inflammasome is activated in the ischaemic heart promoting caspase-1 activation, inflammation, and cell death. Ischaemic injury establishes both a priming signal (transcription of inflammasome components) and a trigger (NLRP3 activation). Whether NLRP3 activation, without priming, induces cardiac dysfunction and/or failure is unknown. The aim of this study was to assess the independent and complementary roles of the priming and the triggering signals in the heart, in the absence of ischaemia or myocardial injury. We used mice with mutant NLRP3 (constitutively active), NLRP3-A350V, under the control of tamoxifen-driven expression of the Cre recombinase (Nlrp3-A350V/CreT mice). The mice were treated for 10 days with tamoxifen before measuring the activity of caspase-1, the effector enzyme in the inflammasome. Tamoxifen treatment induced the inflammasome in the spleen but not in the heart, despite expression of the mutant NLRP3-A350V. The components of the inflammasome were significantly less expressed in the heart compared with the spleen. Subclinical low-dose lipopolysaccharide (LPS; 2 mg/kg) in Nlrp3-A350V/CreT mice induced the expression of the components of the inflammasome (priming), measured using real-time PCR and western blot, leading to the formation of an active inflammasome (caspase-1 activation) in the heart and LV systolic dysfunction while low-dose LPS was insufficient to induce LV systolic dysfunction in wild-type mice (all P < 0.01 for mutant vs. wild-type mice). The signalling pathway governing the inflammasome formation in the heart requires a priming signal in order for an active NLRP3 to induce caspase-1 activation and LV dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Echocardiographic parameters of right ventricular function predict mortality in acute respiratory distress syndrome: a pilot study

PubMed Central

Wadia, Subeer K.; Kovach, Julie; Fogg, Louis; Tandon, Rajive

2016-01-01

Abstract Right ventricular (RV) dysfunction in acute respiratory distress syndrome (ARDS) contributes to increased mortality. Our aim is to identify reproducible transthoracic echocardiography (TTE) parameters of RV dysfunction that can be used to predict outcomes in ARDS. We performed a retrospective single-center cohort pilot study measuring tricuspid annular plane systolic excursion (TAPSE), Tei index, RV-fractional area change (RV-FAC), pulmonary artery systolic pressure (PASP), and septal shift, reevaluated by an independent blinded cardiologist (JK). Thirty-eight patients were included. Patients were divided on the basis of 30-day survival. Thirty-day mortality was 47%. Survivors were younger than nonsurvivors. Survivors had a higher pH, PaO2∶FiO2 ratio, and TAPSE. Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) scores were lower in survivors. TAPSE has the strongest association with increased 30-day mortality from date of TTE. Accordingly, TAPSE has a strong positive correlation with PaO2∶FiO2 ratios, and Tei index has a strong negative correlation with PaO2∶FiO2 ratios. Septal shift was associated with lower PaO2∶FiO2 ratios. Decrease in TAPSE, increase in Tei index, and septal shift were seen in the severe ARDS group. In multivariate logistic regression models, TAPSE maintained a significant association with mortality independent of age, pH, PaO2∶FiO2 ratios, positive end expiratory pressure, PCO2, serum bicarbonate, plateau pressures, driving pressures, APACHE II, SAPS II, and SOFA scores. In conclusion, TAPSE and other TTE parameters should be used as novel predictive indicators for RV dysfunction in ARDS. These parameters can be used as surrogate noninvasive RV hemodynamic measurements to be manipulated to improve mortality in patients with ARDS and contributory RV dysfunction. PMID:27252840

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.

Right ventricular dyssynchrony in idiopathic pulmonary arterial hypertension: determinants and impact on pump function.

PubMed

Badagliacca, Roberto; Poscia, Roberto; Pezzuto, Beatrice; Papa, Silvia; Gambardella, Cristina; Francone, Marco; Mezzapesa, Mario; Nocioni, Martina; Nona, Alfred; Rosati, Riccardo; Sciomer, Susanna; Fedele, Francesco; Dario Vizza, Carmine

2015-03-01

Right ventricular (RV) dyssynchrony has been described in pulmonary arterial hypertension (PAH), but no evidence is available on its morphologic determinants and its effect on systolic function. The aim of this study was to evaluate the morphologic determinants of RV dyssynchrony by echocardiographic and cardiac magnetic resonance imaging and its effect on systolic function. In 60 consecutive idiopathic PAH (IPAH) patients with narrow QRS, RV dyssynchrony was evaluated by 2D speckle-tracking echocardiography, calculating the standard deviation of the times to peak systolic strain for the four mid-basal RV segments (RV-SD4). Patients were grouped by the median value of RV-SD4 (19 milliseconds) and compared for RV remodeling and systolic function parameters, WHO class, pulmonary hemodynamics and 6-minute walk test (6MWT). Despite similar pulmonary vascular resistance and mean pulmonary arterial pressure, patients with RV-SD4 at >19 milliseconds had advanced WHO class and worse 6MWT, RV hemodynamics, RV remodeling and systolic function parameters compared with patients at ≤19 milliseconds. The morphologic determinants of RV dyssynchrony resulted RV end-diastolic area, LV diastolic eccentricity index and RV mass volume ratio (r = 0.69, r(2) = 0.47, p < 0.0001). Finally, we found a significant inverse correlation between RV mid-basal segments post-systolic shortening time and cardiac index (r = -0.64, r(2) = 0.41, p = 0.001), accounting for the significant correlation between RV-SD4 and cardiac index (r = 0.57, r(2) = 0.32, p = 0.003). In IPAH with narrow QRS, RV dyssynchrony is associated with RV dilation and eccentric hypertrophy pattern, suggesting a role of segmental wall stress heterogeneity as the major determinant of mechanical delay. Post-systolic shortening, as inefficient contraction, contributes to pump dysfunction. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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.

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.

Correlation of Space Shuttle Landing Performance with Post-Flight Cardiovascular Dysfunction

NASA Technical Reports Server (NTRS)

McCluskey, R.

2004-01-01

Introduction: Microgravity induces cardiovascular adaptations resulting in orthostatic intolerance on re-exposure to normal gravity. Orthostasis could interfere with performance of complex tasks during the re-entry phase of Shuttle landings. This study correlated measures of Shuttle landing performance with post-flight indicators of orthostatic intolerance. Methods: Relevant Shuttle landing performance parameters routinely recorded at touchdown by NASA included downrange and crossrange distances, airspeed, and vertical speed. Measures of cardiovascular changes were calculated from operational stand tests performed in the immediate post-flight period on mission commanders from STS-41 to STS-66. Stand test data analyzed included maximum standing heart rate, mean increase in maximum heart rate, minimum standing systolic blood pressure, and mean decrease in standing systolic blood pressure. Pearson correlation coefficients were calculated with the null hypothesis that there was no statistically significant linear correlation between stand test results and Shuttle landing performance. A correlation coefficient? 0.5 with a p<0.05 was considered significant. Results: There were no significant linear correlations between landing performance and measures of post-flight cardiovascular dysfunction. Discussion: There was no evidence that post-flight cardiovascular stand test data correlated with Shuttle landing performance. This implies that variations in landing performance were not due to space flight-induced orthostatic intolerance.

Right Ventricular Longitudinal Strain Is Depressed in a Bovine Model of Pulmonary Hypertension.

PubMed

Bartels, Karsten; Brown, R Dale; Fox, Daniel L; Bull, Todd M; Neary, Joseph M; Dorosz, Jennifer L; Fonseca, Brian M; Stenmark, Kurt R

2016-05-01

Pulmonary hypertension and resulting right ventricular (RV) dysfunction are associated with significant perioperative morbidity and mortality. Although echocardiography permits real-time, noninvasive assessment of RV function, objective and comparative measures are underdeveloped, and appropriate animal models to study their utility are lacking. Longitudinal strain analysis is a novel echocardiographic method to quantify RV performance. Herein, we hypothesized that peak RV longitudinal strain would worsen in a bovine model of pulmonary hypertension compared with control animals. Newborn Holstein calves were randomly chosen for induction of pulmonary hypertension versus control conditions. Pulmonary hypertension was induced by exposing animals to 14 days of hypoxia (equivalent to 4570 m above sea level or 430 mm Hg barometric pressure). Control animals were kept at ambient pressure/normoxia. At the end of the intervention, transthoracic echocardiography was performed in awake calves. Longitudinal wall strain was analyzed from modified apical 4-chamber views focused on the RV. Comparisons between measurements in hypoxic versus nonhypoxic conditions were performed using Student t test for independent samples and unequal variances. After 14 days at normoxic versus hypoxic conditions, 15 calves were examined with echocardiography. Pulmonary hypertension was confirmed by right heart catheterization and associated with reduced RV systolic function. Mean systolic strain measurements were compared in normoxia-exposed animals (n = 8) and hypoxia-exposed animals (n = 7). Peak global systolic longitudinal RV strain after hypoxia worsened compared to normoxia (-10.5% vs -16.1%, P = 0.0031). Peak RV free wall strain also worsened after hypoxia compared to normoxia (-9.6% vs -17.3%, P = 0.0031). Findings from strain analysis were confirmed by measurement of tricuspid annular peak systolic excursion. Peak longitudinal RV strain detected worsened RV function in animals with hypoxia-induced pulmonary hypertension compared with control animals. This relationship was demonstrated in the transthoracic echocardiographic 4-chamber view independently for the RV free wall and for the combination of the free and septal walls. This innovative model of bovine pulmonary hypertension may prove useful to compare different monitoring technologies for the assessment of early events of RV dysfunction. Further studies linking novel RV imaging applications with mechanistic and therapeutic approaches are needed.

[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.

[Usefulness of tricuspid annular displacement (TAD) to identify right ventricular dysfunction in normotensive patients with acute pulmonary embolism].

PubMed

Hugues, T; Yaici, K; Latcu, D-G; Rinaldi, J-P; Zarqane, N; Saoudi, N; Gibelin, P

2011-02-01

Echocardiographic criteria of right ventricular dysfunction (RVD) in acute pulmonary embolism (PE) differ among published studies. Assessment of RV systolic function remains difficult because of the RV's complex shape. We aimed to evaluate RV systolic function with TAD in patients (pts) with acute PE. TAD (QLAB, Philips Medical Imaging) was based on a tissue-tracking algorithm that is ultrasound beam angle independent for automated detection of tricuspid annular displacement. Prospective and observational study. All adults' pts who were diagnosed with PE from December 2008 to December 2009 at Princess Grace Hospital, Monaco were eligible for this study after exclusion of history of heart failure. We evaluated 36 consecutive pts with PE (18 male, mean age 62.7 years), which underwent echocardiography, plasma BNP titration during the first day after admission, and a second echocardiography obtained within 48 hours before discharge. TAD value were significantly lower in pts with abnormal RV function by echocardiogram (15.9 ± 0.3 vs. 12.7 ± 0.2 ; P = 0.026). Pts with a normal BNP (<80 pg/ml) had an elevated TAD (16.4 ± 0.2 vs. 11.2 ± 0.3 mm ; P < 0.0001). At discharge, echocardiographic data were obtained from 33 pts (mean: 8.3 ± 3.5 days). RV end diastolic diameter, RV to LV diameter, pulmonary arterial systolic pressure, mean pulmonic valve acceleration time, RV FAC, Sa and TAD were significantly improved. There was no difference between TAD among pts with echocardiographic RVD at baseline vs. pts without RVD (14.9 ± 3.7 vs. 16.1 ± 2.9 mm ; P = 0.3). Four pts who deteriorated during short-term observation had substantially lower TAD values than those with uncomplicated courses (7.7 ± 0.4mm vs. 14.6 ± 0.2 mm ; P = 0.001). In conclusion, impaired TAD was associated with decreased RV systolic function in pts with acute PE. To identify the clinical meaning of decreased TAD, larger trials with longer follow-up periods are needed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Prevalence of scarred and dysfunctional myocardium in patients with heart failure of ischaemic origin: A cardiovascular magnetic resonance study

PubMed Central

2011-01-01

Background Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) can provide unique data on the transmural extent of scar/viability. We assessed the prevalence of dysfunctional myocardium, including partial thickness scar, which could contribute to left ventricular contractile dysfunction in patients with heart failure and ischaemic heart disease who denied angina symptoms. Methods We invited patients with ischaemic heart disease and a left ventricular ejection fraction < 50% by echocardiography to have LGE CMR. Myocardial contractility and transmural extent of scar were assessed using a 17-segment model. Results The median age of the 193 patients enrolled was 70 (interquartile range: 63-76) years and 167 (87%) were men. Of 3281 myocardial segments assessed, 1759 (54%) were dysfunctional, of which 581 (33%) showed no scar, 623 (35%) had scar affecting ≤50% of wall thickness and 555 (32%) had scar affecting > 50% of wall thickness. Of 1522 segments with normal contractile function, only 98 (6%) had evidence of scar on CMR. Overall, 182 (94%) patients had ≥1 and 107 (55%) patients had ≥5 segments with contractile dysfunction that had no scar or ≤50% transmural scar suggesting viability. Conclusions In this cohort of patients with left ventricular systolic dysfunction and ischaemic heart disease, about half of all segments had contractile dysfunction but only one third of these had > 50% of the wall thickness affected by scar, suggesting that most dysfunctional segments could improve in response to an appropriate intervention. PMID:21936915

Adverse ventricular-ventricular interactions in right ventricular pressure load: Insights from pediatric pulmonary hypertension versus pulmonary stenosis.

PubMed

Driessen, Mieke M P; Hui, Wei; Bijnens, Bart H; Dragulescu, Andreea; Mertens, Luc; Meijboom, Folkert J; Friedberg, Mark K

2016-06-01

Right ventricular (RV) pressure overload has a vastly different clinical course in children with idiopathic pulmonary arterial hypertension (iPAH) than in children with pulmonary stenosis (PS). While RV function is well recognized as a key prognostic factor in iPAH, adverse ventricular-ventricular interactions and LV dysfunction are less well characterized and the pathophysiology is incompletely understood. We compared ventricular-ventricular interactions as hypothesized drivers of biventricular dysfunction in pediatric iPAH versus PS Eighteen iPAH, 16 PS patients and 18 age- and size-matched controls were retrospectively studied. Cardiac cycle events were measured by M-mode and Doppler echocardiography. Measurements were compared between groups using ANOVA with post hoc Dunnet's or ANCOVA including RV systolic pressure (RVSP; iPAH 96.8 ± 25.4 mmHg vs. PS 75.4 ± 18.9 mmHg; P = 0.011) as a covariate. RV-free wall thickening was prolonged in iPAH versus PS, extending beyond pulmonary valve closure (638 ± 76 msec vs. 562 ± 76 msec vs. 473 ± 59 msec controls). LV and RV isovolumetric relaxation were prolonged in iPAH (P < 0.001; LV 102.8 ± 24.1 msec vs. 63.1 ± 13.7 msec; RV 95 [61-165] vs. 28 [0-43]), associated with adverse septal kinetics; characterized by rightward displacement in early systole and leftward displacement in late RV systole (i.e., early LV diastole). Early LV diastolic filling was decreased in iPAH (73 ± 15.9 vs. PS 87.4 ± 14.4 vs. controls 95.8 ± 12.5 cm/sec; P = 0.004). Prolonged RVFW thickening, prolonged RVFW isovolumetric times, and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in pediatric iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency in iPAH and may form the basis for worse clinical outcomes. We used clinically derived data to study the pathophysiology of ventricular-ventricular interactions in right ventricular pressure overload, demonstrating distinct differences between pediatric pulmonary arterial hypertension (iPAH) and pulmonary stenosis (PS). Altered timing of right ventricular free wall contraction and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency, independent of right ventricular systolic pressure. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

[Thyroid dysfunction and amiodarone].

PubMed

Lima, Jandira; Carvalho, Patrícia; Molina, M Auxiliadora; Rebelo, Marta; Dias, Patrícia; Vieira, José Diniz; Costa, José M Nascimento

2013-02-01

Although most patients remain clinically euthyroid, some develop amiodarone-induced hyperthyroidism (HPEAI) or hypothyroidism (HPOAI). The authors present a retrospective analysis of ten patients with amiodarone-induced thyroid dysfunction. Six patients were female and mean amiodarone intake was 17.7 months. HPOIA was more common (six patients). From all the patients with HPEAI, two had type 2, one had type 1, and one had type 3 hyperthyroidism. Symptoms suggestive of thyroid dysfunction occurred in five patients, most of them with HPOAI. In HPEAI, the most frequent symptom was exacerbation of arrhythmia (three patients). Discontinuation of amiodarone and treatment with levothyroxine was chosen in 83.3% of the HPOAI cases, while thyonamide treatment with corticosteroids and without amiodarone was the option in 75% of the HPEAI cases. There were three deaths, all in patients with HPEAI. HPEAI is potentially fatal. The clinical picture may be vague, so the thyroid monitoring is mandatory.

Thyroid hormone-induced oxidative stress.

PubMed

Venditti, P; Di Meo, S

2006-02-01

Hypermetabolic state in hyperthyroidism is associated with tissue oxidative injury. Available data indicate that hyperthyroid tissues exhibit an increased ROS and RNS production. The increased mitochondrial ROS generation is a side effect of the enhanced level of electron carriers, by which hyperthyroid tissues increase their metabolic capacity. Investigations of antioxidant defence system have returned controversial results. Moreover, other thyroid hormone-linked biochemical changes increase tissue susceptibility to oxidative challenge, which exacerbates the injury and dysfunction they suffer under stressful conditions. Mitochondria, as a primary target for oxidative stress, might account for hyperthyroidism linked tissue dysfunction. This is consistent with the inverse relationship found between functional recovery of ischemic hyperthyroid hearts and mitochondrial oxidative damage and respiration impairment. However, thyroid hormone-activated mitochondrial mechanisms provide protection against excessive tissue dysfunction, including increased expression of uncoupling proteins, proteolytic enzymes and transcriptional coactivator PGC-1, and stimulate opening of permeability transition pores.

An overview of lymphatic vessels and their emerging role in cardiovascular disease

PubMed Central

Jones, Dennis; Min, Wang

2011-01-01

Over the past decade, molecular details of lymphatic vessels (lymphatics) have been rapidly acquired due to the identification of lymphatic endothelial-specific markers. Separate from the cardiovascular system, the lymphatic system is also an elaborate network of vessels that are important in normal physiology. Lymphatic vessels have the unique task to regulate fluid homeostasis, assist in immune surveillance, and transport dietary lipids. However, dysfunctional lymphatic vessels can cause pathology, while normal lymphatics can exacerbate pathology. This review summarizes the development and growth of lymphatic vessels in addition to highlighting their critical roles in physiology and pathology. Also, we discuss recent work that suggests a connection between lymphatic dysfunction and cardiovascular disease. PMID:22022141

Benefits of Heart Rate Slowing With Ivabradine in Patients With Systolic Heart Failure and Coronary Artery Disease.

PubMed

Borer, Jeffrey S; Deedwania, Prakash C; Kim, Jae B; Böhm, Michael

2016-12-15

Heart rate (HR) is a risk factor in patients with chronic systolic heart failure (HF) that, when reduced, provides outcome benefits. It is also a target for angina pectoris prevention and a risk marker in chronic coronary artery disease without HF. HR can be reduced by drugs; however, among those used clinically, only ivabradine reduces HR directly in the sinoatrial nodal cells without other known effects on the cardiovascular system. This review provides current information regarding the safety and efficacy of HR reduction with ivabradine in clinical studies involving >36,000 patients with chronic stable coronary artery disease and >6,500 patients with systolic HF. The largest trials, Morbidity-Mortality Evaluation of the I f Inhibitor Ivabradine in Patients With Coronary Disease and Left Ventricular Dysfunction and Study Assessing the Morbidity-Mortality Benefits of the I f Inhibitor Ivabradine in Patients With Coronary Artery Disease, showed no effect on outcomes. The Systolic Heart Failure Treatment With the I f Inhibitor Ivabradine Trial, a randomized controlled trial in >6,500 patients with HF, revealed marked and significant HR-mediated reduction in cardiovascular mortality or HF hospitalizations while improving quality of life and left ventricular mechanical function after treatment with ivabradine. The adverse effects of ivabradine predominantly included bradycardia and atrial fibrillation (both uncommon) and ocular flashing scotomata (phosphenes) but otherwise were similar to placebo. In conclusion, ivabradine improves outcomes in patients with systolic HF; rates of overall adverse events are similar to placebo. Copyright © 2016 Elsevier Inc. All rights reserved.

Upregulation of adenosine A1 receptors facilitates sinoatrial node dysfunction in chronic canine heart failure by exacerbating nodal conduction abnormalities revealed by novel dual-sided intramural optical mapping.

PubMed

Lou, Qing; Hansen, Brian J; Fedorenko, Olga; Csepe, Thomas A; Kalyanasundaram, Anuradha; Li, Ning; Hage, Lori T; Glukhov, Alexey V; Billman, George E; Weiss, Raul; Mohler, Peter J; Györke, Sándor; Biesiadecki, Brandon J; Carnes, Cynthia A; Fedorov, Vadim V

2014-07-22

Although sinoatrial node (SAN) dysfunction is a hallmark of human heart failure (HF), the underlying mechanisms remain poorly understood. We aimed to examine the role of adenosine in SAN dysfunction and tachy-brady arrhythmias in chronic HF. We applied multiple approaches to characterize SAN structure, SAN function, and adenosine A1 receptor expression in control (n=17) and 4-month tachypacing-induced chronic HF (n=18) dogs. Novel intramural optical mapping of coronary-perfused right atrial preparations revealed that adenosine (10 μmol/L) markedly prolonged postpacing SAN conduction time in HF by 206 ± 99 milliseconds (versus 66 ± 21 milliseconds in controls; P=0.02). Adenosine induced SAN intranodal conduction block or microreentry in 6 of 8 dogs with HF versus 0 of 7 controls (P=0.007). Adenosine-induced SAN conduction abnormalities and automaticity depression caused postpacing atrial pauses in HF versus control dogs (17.1 ± 28.9 versus 1.5 ± 1.3 seconds; P<0.001). Furthermore, 10 μmol/L adenosine shortened atrial repolarization and led to pacing-induced atrial fibrillation in 6 of 7 HF versus 0 of 7 control dogs (P=0.002). Adenosine-induced SAN dysfunction and atrial fibrillation were abolished or prevented by adenosine A1 receptor antagonists (50 μmol/L theophylline/1 μmol/L 8-cyclopentyl-1,3-dipropylxanthine). Adenosine A1 receptor protein expression was significantly upregulated during HF in the SAN (by 47 ± 19%) and surrounding atrial myocardium (by 90 ± 40%). Interstitial fibrosis was significantly increased within the SAN in HF versus control dogs (38 ± 4% versus 23 ± 4%; P<0.001). In chronic HF, adenosine A1 receptor upregulation in SAN pacemaker and atrial cardiomyocytes may increase cardiac sensitivity to adenosine. This effect may exacerbate conduction abnormalities in the structurally impaired SAN, leading to SAN dysfunction, and potentiate atrial repolarization shortening, thereby facilitating atrial fibrillation. Atrial fibrillation may further depress SAN function and lead to tachy-brady arrhythmias in HF. © 2014 American Heart Association, Inc.

High-sugar intake does not exacerbate metabolic abnormalities or cardiac dysfunction in genetic cardiomyopathy.

PubMed

Hecker, Peter A; Galvao, Tatiana F; O'Shea, Karen M; Brown, Bethany H; Henderson, Reney; Riggle, Heather; Gupte, Sachin A; Stanley, William C

2012-05-01

A high-sugar intake increases heart disease risk in humans. In animals, sugar intake accelerates heart failure development by increased reactive oxygen species (ROS). Glucose-6-phosphate dehydrogenase (G6PD) can fuel ROS production by providing reduced nicotinamide adenine dinucleotide phosphate (NADPH) for superoxide generation by NADPH oxidase. Conversely, G6PD also facilitates ROS scavenging using the glutathione pathway. We hypothesized that a high-sugar intake would increase flux through G6PD to increase myocardial NADPH and ROS and accelerate cardiac dysfunction and death. Six-week-old TO-2 hamsters, a non-hypertensive model of genetic cardiomyopathy caused by a δ-sarcoglycan mutation, were fed a long-term diet of high starch or high sugar (57% of energy from sucrose plus fructose). After 24 wk, the δ-sarcoglycan-deficient animals displayed expected decreases in survival and cardiac function associated with cardiomyopathy (ejection fraction: control 68.7 ± 4.5%, TO-2 starch 46.1 ± 3.7%, P < 0.05 for TO-2 starch versus control; TO-2 sugar 58.0 ± 4.2%, NS, versus TO-2 starch or control; median survival: TO-2 starch 278 d, TO-2 sugar 318 d, P = 0.133). Although the high-sugar intake was expected to exacerbate cardiomyopathy, surprisingly, there was no further decrease in ejection fraction or survival with high sugar compared with starch in cardiomyopathic animals. Cardiomyopathic animals had systemic and cardiac metabolic abnormalities (increased serum lipids and glucose and decreased myocardial oxidative enzymes) that were unaffected by diet. The high-sugar intake increased myocardial superoxide, but NADPH and lipid peroxidation were unaffected. A sugar-enriched diet did not exacerbate ventricular function, metabolic abnormalities, or survival in heart failure despite an increase in superoxide production. Copyright © 2012 Elsevier Inc. All rights reserved.

Respiratory exacerbation in a young adult with cystic fibrosis and tricuspid atresia.

PubMed

Wood, Jamie; Sawyer, Abbey; Mulrennan, Siobhain; Bullock, Andrew

2018-07-01

Tricuspid atresia (TAt) is a complex congenital heart defect (CHD) characterized by the absence of the tricuspid valve and right ventricular hypoplasia requiring surgery in childhood, the Fontan procedure. We present a case of a 21-year-old male with TAt and cystic fibrosis (CF), who underwent a Fontan procedure in childhood, presenting to an adult CF clinic with severe deterioration in his respiratory status and multi-organ dysfunction associated with CF. This report describes problems associated with the management of a CF respiratory exacerbation and extrapulmonary manifestations of CF in the unique situation of a Fontan circulation, a circulation with absence of a subpulmonary ventricle and pulsatile pulmonary arterial blood flow where maintenance of systemic cardiac output is totally dependent on good respiratory function and low pulmonary artery pressures.

[A unique case of secondary takotsubo syndrome].

PubMed

Arcari, Luca; Limite, Luca Rosario; Autore, Camillo; Volpe, Massimo; Musumeci, Maria Beatrice

2018-04-01

Takotsubo syndrome (TTS) is an acute cardiac syndrome characterized by transient systolic left ventricular dysfunction frequently preceded by stressful events. It typically affects postmenopausal women without angiographic evidence of obstructive coronary artery disease. We report here an uncommon occurrence of secondary TTS in a male with coronary artery disease after exogenous catecholamine administration and pacemaker implantation. This unexpected case suggests that, in such clinical scenario, a TTS diagnosis might be considered even in unsuspected individuals.

Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension

PubMed Central

Hussain, I; Brady, C; Swinn, M; Mathias, C; Fowler, C

2001-01-01

OBJECTIVES—To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy.
METHODS—Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital.
RESULTS—Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with multiple system atrophy reported a good erectile response and were reluctant to discontinue the medication.
CONCLUSIONS—Sidenafil citrate (50 mg) is efficacious in the treatment of erectile dysfunction in parkinsonism due to Parkinson's disease or multiple system atrophy; however, it may unmask or exacerbate hypotension in multiple system atrophy. As Parkinson's disease may be diagnostically difficult to distinguish from multiple system atrophy, especially in the early stages, we recommend measurement of lying and standing blood pressure before prescribing sildenafil to men with parkinsonism. Furthermore, such patients should be made aware of seeking medical advice if they develop symptoms on treatment suggestive of orthostatic hypotension.

 PMID:11511713

The cardiovascular system in growth hormone excess and growth hormone deficiency.

PubMed

Lombardi, G; Di Somma, C; Grasso, L F S; Savanelli, M C; Colao, A; Pivonello, R

2012-12-01

The clinical conditions associated with GH excess and GH deficiency (GHD) are known to be associated with an increased risk for the cardiovascular morbidity and mortality, suggesting that either an excess or a deficiency in GH and/or IGF-I is deleterious for cardiovascular system. In patients with acromegaly, chronic GH and IGF-I excess commonly causes a specific cardiomyopathy characterized by a concentric cardiac hypertrophy associated with diastolic dysfunction and, in later stages, with systolic dysfunction ending in heart failure if GH/IGF-I excess is not controlled. Abnormalities of cardiac rhythm and anomalies of cardiac valves can also occur. Moreover, the increased prevalence of cardiovascular risk factors, such as hypertension, diabetes mellitus, and insulin resistance, as well as dyslipidemia, confer an increased risk for vascular atherosclerosis. Successful control of the disease is accompanied by a decrease of the cardiac mass and improvement of cardiac function and an improvement in cardiovascular risk factors. In patients with hypopituitarism, GHD has been considered the under- lying factor of the increased mortality when appropriate standard replacement of the pituitary hormones deficiencies is given. Either childhood-onset or adulthood-onset GHD are characterized by a cluster of abnormalities associated with an increased cardiovascular risk, including altered body composition, unfavorable lipid profile, insulin resistance, endothelial dysfunction and vascular atherosclerosis, a decrease in cardiac mass together with an impairment of systolic function mainly after exercise. Treatment with recombinant GH in patients with GHD is followed by an improvement of the cardiovascular risk factors and an increase in cardiac mass together with an improvement in cardiac performance. In conclusion, acromegaly and GHD are associated with an increased risk for cardiovascular morbidity and mortality, but the control of GH/IGF-I secretion reverses cardiovascular abnormalities and restores the normal life expectancy.

A mathematical model for active contraction in healthy and failing myocytes and left ventricles.

PubMed

Cai, Li; Wang, Yongheng; Gao, Hao; Li, Yiqiang; Luo, Xiaoyu

2017-01-01

Cardiovascular disease is one of the leading causes of death worldwide, in particular myocardial dysfunction, which may lead to heart failure eventually. Understanding the electro-mechanics of the heart will help in developing more effective clinical treatments. In this paper, we present a multi-scale electro-mechanics model of the left ventricle (LV). The Holzapfel-Ogden constitutive law was used to describe the passive myocardial response in tissue level, a modified Grandi-Pasqualini-Bers model was adopted to model calcium dynamics in individual myocytes, and the active tension was described using the Niederer-Hunter-Smith myofilament model. We first studied the electro-mechanics coupling in a single myocyte in the healthy and diseased left ventricle, and then the single cell model was embedded in a dynamic LV model to investigate the compensation mechanism of LV pump function due to myocardial dysfunction caused by abnormality in cellular calcium dynamics. The multi-scale LV model was solved using an in-house developed hybrid immersed boundary method with finite element extension. The predictions of the healthy LV model agreed well with the clinical measurements and other studies, and likewise, the results in the failing states were also consistent with clinical observations. In particular, we found that a low level of intracellular Ca2+ transient in myocytes can result in LV pump function failure even with increased myocardial contractility, decreased systolic blood pressure, and increased diastolic filling pressure, even though they will increase LV stroke volume. Our work suggested that treatments targeted at increased contractility and lowering the systolic blood pressure alone are not sufficient in preventing LV pump dysfunction, restoring a balanced physiological Ca2+ handling mechanism is necessary.

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.

Assessment of subclinical right ventricular systolic dysfunction in coal miners using myocardial isovolumic acceleration.

PubMed

Ozcan Abacıoglu, Ozge; Kaplan, Mehmet; Abacıoglu, Serkan; Quisi, Ala

2017-09-01

Several studies have been conducted regarding the effects of coal mining on the respiratory system. However, there is a lack of data concerning potential effects of coal mining on the cardiovascular system. In this study, we aimed to evaluate the potential subclinical right and left ventricular dysfunction in coal miners. This single-center, prospective study included a total of 102 patients. Patient and control groups consisted of 54 coal miners and 48 healthy men, respectively. All patients underwent 12-lead electrocardiography, transthoracic echocardiography, and pulmonary function test. As compared to control group, coal miners had significantly higher right ventricular myocardial performance index (RVMPI) (0.41 ± 0.03 vs 0.37 ± 0.02, P < .001), lower right ventricular fractional area change (RVFAC) (33.55% ± 6.70% vs 37.04 ± 9.26 P < .05), lower tricuspid annular plane systolic excursion (TAPSE) (1.54 ± 0.17 vs 1.73 ± 0.25, P < .001), lower myocardial isovolumic acceleration (IVA) (2.13 ± 0.16 vs 2.56 ± 0.36 P < .001) and decreased aortic distensibility (AD) (4.14 ± 2.18 vs 6.63 ± 3.91 P < .001). All of the echocardiographic parameters were positively correlated with exposure time to coal mine dust, except IVA. Echocardiographic parameters of both right and left ventricular dysfunction, including RVMPI, RVFAC, TAPSE, IVA, and AD, are impaired in coal miners. © 2017 The Authors Echocardiography Published by 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.

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

Impaired cardiac contractile function in arginine:glycine amidinotransferase knockout mice devoid of creatine is rescued by homoarginine but not creatine

PubMed Central

Faller, Kiterie M E; Atzler, Dorothee; McAndrew, Debra J; Zervou, Sevasti; Whittington, Hannah J; Simon, Jillian N; Aksentijevic, Dunja; ten Hove, Michiel; Choe, Chi-un; Isbrandt, Dirk; Casadei, Barbara; Schneider, Jurgen E; Neubauer, Stefan; Lygate, Craig A

2018-01-01

Abstract Aims Creatine buffers cellular adenosine triphosphate (ATP) via the creatine kinase reaction. Creatine levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) in the kidney catalyses both the first step in creatine biosynthesis as well as homoarginine (HA) synthesis. AGAT-/- mice fed a creatine-free diet have a whole body creatine-deficiency. We hypothesized that AGAT-/- mice would develop cardiac dysfunction and rescue by dietary creatine would imply causality. Methods and results Withdrawal of dietary creatine in AGAT-/- mice provided an estimate of myocardial creatine efflux of ∼2.7%/day; however, in vivo cardiac function was maintained despite low levels of myocardial creatine. Using AGAT-/- mice naïve to dietary creatine we confirmed absence of phosphocreatine in the heart, but crucially, ATP levels were unchanged. Potential compensatory adaptations were absent, AMPK was not activated and respiration in isolated mitochondria was normal. AGAT-/- mice had rescuable changes in body water and organ weights suggesting a role for creatine as a compatible osmolyte. Creatine-naïve AGAT-/- mice had haemodynamic impairment with low LV systolic pressure and reduced inotropy, lusitropy, and contractile reserve. Creatine supplementation only corrected systolic pressure despite normalization of myocardial creatine. AGAT-/- mice had low plasma HA and supplementation completely rescued all other haemodynamic parameters. Contractile dysfunction in AGAT-/- was confirmed in Langendorff perfused hearts and in creatine-replete isolated cardiomyocytes, indicating that HA is necessary for normal cardiac function. Conclusions Our findings argue against low myocardial creatine per se as a major contributor to cardiac dysfunction. Conversely, we show that HA deficiency can impair cardiac function, which may explain why low HA is an independent risk factor for multiple cardiovascular diseases. PMID:29236952

Carotid atherosclerosis and right ventricular diastolic dysfunction in a sample of hypertensive Nigerian patients

PubMed Central

Akintunde, Adeseye A.; Adebayo, Philip B.; Aremu, Ademola A.; Opadijo, Oladimeji G.

2013-01-01

Aim To determine the association of carotid atherosclerosis and right ventricular diastolic dysfunction (DD) among treated hypertensive Nigerian patients. Methods This was a single center cross-sectional study performed at the Cardiology Clinic of LAUTECH Teaching Hospital, Ogbomoso, Nigeria between January and December 2012. The study included 122 hypertensive Nigerians (mean age, 57.3 ± 14.7 years, 36.9% women). Patients’ clinical, demographic, and echocardiographic parameters were obtained. Diastolic dysfunction was assessed with the trans-tricuspid Doppler flow. Results Patients with DD were significantly older than those with normal diastolic function. Mean and maximum carotid intima media thickness measurements were significantly higher among patients with right ventricular DD than in those with normal diastolic function. Mean systolic blood pressure (148.3 ± 31.9 vs 128.0 ± 2.8 mm Hg, P = 0.049) and interventricular septal thickness in diastole (12.8 ± 2.3 vs 11.6 ± 2.8mm, P = 0.048) were significantly higher and tricuspid annular pulmonary systolic excursion (33.6 ± 4.9 vs 23.0 ± 4.2 mm, P = 0.035) was significantly lower in patients with right ventricular DD than in those with normal diastolic function. Carotid intima media thickness measurements were correlated with early trans-tricuspid Doppler flow and early transtricuspid diastolic flow/late right atrial transtricupsid diastolic flow ratio. Conclusion Right ventricular DD in hypertensive patients was significantly correlated with increased carotid atherosclerosis. Carotid intima media thickness measurements may therefore be a surrogate marker for DD in hypertensive subjects. PMID:24382850

Effect of Statins on Skeletal Muscle: Exercise, Myopathy, and Muscle Outcomes

PubMed Central

Parker, Beth A.; Thompson, Paul D.

2012-01-01

Statins are effective for reducing low-density lipoprotein cholesterol and cardiac events, but can produce muscle side effects. We have hypothesized that statin-related muscle complaints are exacerbated by exercise and influenced by factors including mitochondrial dysfunction, membrane disruption and/or calcium handling. The interaction between statins, exercise and muscle symptoms may be more effectively diagnosed and treated as rigorous scientific studies accumulate. PMID:23000957

Work-related asthma: diagnosis and prognosis of immunological occupational asthma and work-exacerbated asthma.

PubMed

Muñoz, X; Cruz, M J; Bustamante, V; Lopez-Campos, J L; Barreiro, E

2014-01-01

The incidence and prevalence of asthma are increasing. One reason for this trend is the rise in adult-onset asthma, especially occupational asthma, which is 1 of the 2 forms of work-related asthma. Occupational asthma is defined as asthma caused by agents that are present exclusively in the workplace. The presence of pre-existing asthma does not rule out the possibility of developing occupational asthma. A distinction has traditionally been made between immunological occupational asthma (whether IgE-mediated or not) and nonimmunological occupational asthma caused by irritants, the most characteristic example of which is reactive airway dysfunction syndrome. The other form of work-related asthma is known as work-exacerbated asthma, which affects persons with pre-existing or concurrent asthma that is worsened by work-related factors. It is important to differentiate between the 2 entities because their treatment, prognosis, and medical and social repercussions can differ widely. In this review, we discuss diagnostic methods, treatment, and avoidance/nonavoidance of the antigen in immunological occupational asthma and work-exacerbated asthma. Key words: Specific inhalation challenge. Peak expiratory flow. Workplace. Irritants.

Ca(2+) mishandling and cardiac dysfunction in obesity and insulin resistance: role of oxidative stress.

PubMed

Carvajal, Karla; Balderas-Villalobos, Jaime; Bello-Sanchez, Ma Dolores; Phillips-Farfán, Bryan; Molina-Muñoz, Tzindilu; Aldana-Quintero, Hugo; Gómez-Viquez, Norma L

2014-11-01

Obesity and insulin resistance (IR) are strongly connected to the development of subclinical cardiac dysfunction and eventually can lead to heart failure, which is the main cause of morbidity and death in patients having these metabolic diseases. It has been considered that excessive fat tissue may play a critical role in producing systemic IR and enhancing reactive oxygen species (ROS) generation. This oxidative stress (OS) may elicit or exacerbate IR. On the other hand, evidence suggests that some of the cellular mechanisms involved in the pathophysiology of obesity and IR-related cardiomyopathy are excessive myocardial ROS production and abnormal Ca(2+) homeostasis. In addition, emerging evidence suggests that augmented ROS production may contribute to Ca(2+) mishandling by affecting the redox state of key proteins implicated in this process. In this review, we focus on the role of Ca(2+) mishandling in the development of cardiac dysfunction in obesity and IR and address the evidence suggesting that OS might also contribute to cardiac dysfunction by affecting Ca(2+) handling. Copyright © 2014 Elsevier Ltd. All rights reserved.

Targeting the Endoplasmic Reticulum Unfolded Protein Response to Counteract the Oxidative Stress-Induced Endothelial Dysfunction

PubMed Central

Moltedo, Ornella; Faraonio, Raffaella

2018-01-01

In endothelial cells, the tight control of the redox environment is essential for the maintenance of vascular homeostasis. The imbalance between ROS production and antioxidant response can induce endothelial dysfunction, the initial event of many cardiovascular diseases. Recent studies have revealed that the endoplasmic reticulum could be a new player in the promotion of the pro- or antioxidative pathways and that in such a modulation, the unfolded protein response (UPR) pathways play an essential role. The UPR consists of a set of conserved signalling pathways evolved to restore the proteostasis during protein misfolding within the endoplasmic reticulum. Although the first outcome of the UPR pathways is the promotion of an adaptive response, the persistent activation of UPR leads to increased oxidative stress and cell death. This molecular switch has been correlated to the onset or to the exacerbation of the endothelial dysfunction in cardiovascular diseases. In this review, we highlight the multiple chances of the UPR to induce or ameliorate oxidative disturbances and propose the UPR pathways as a new therapeutic target for the clinical management of endothelial dysfunction. PMID:29725497

Advances in our understanding of immunization and vaccines for patients with systemic lupus erythematosus.

PubMed

Bragazzi, Nicola Luigi; Watad, Abdulla; Sharif, Kassem; Adawi, Mohammad; Aljadeff, Gali; Amital, Howard; Shoenfeld, Yehuda

2017-10-01

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. In SLE, immune system dysfunction is postulated to result by virtue of the disease itself as well as by the impact of treatment modalities employed. A myriad of immune dysregulations occur including complement system dysfunction among others. Infectious agents are known to complicate the disease course in close to 25-45% of SLE patients. Areas covered: In this review a discussion of the immunogenicity and safety of viral and bacterial vaccinations in SLE was performed. The search included ISI Web of Science (WoS), Scopus, MEDLINE/PubMed, Google-Scholar, DOAJ, EbscoHOST, Scirus, Science Direct, Cochrane Library and ProQuest. Proper string made up of a key-words including 'SLE', 'vaccination', 'safety' and 'efficacy' was used. Expert commentary: Vaccination of SLE patients is proven to be immunogenic. Concerns regarding vaccine safety are postulated, yet no direct relationship between vaccination and disease exacerbation were established. While live virus vaccines are generally contraindicated in immunosuppressive states, generally live attenuated vaccinations are recommended in SLE patients on a case-to-case basis. In SLE patients, clinical parameters such as vaccination during disease exacerbations have not been intensively studied and therefore while apparently safe, vaccination is generally recommended while disease is quiescent.

Puberty is an important developmental period for the establishment of adipose tissue mass and metabolic homeostasis.

PubMed

Holtrup, Brandon; Church, Christopher D; Berry, Ryan; Colman, Laura; Jeffery, Elise; Bober, Jeremy; Rodeheffer, Matthew S

2017-07-03

Over the past 2 decades, the incidence of childhood obesity has risen dramatically. This recent rise in childhood obesity is particularly concerning as adults who were obese during childhood develop type II diabetes that is intractable to current forms of treatment compared with individuals who develop obesity in adulthood. While the mechanisms responsible for the exacerbated diabetic phenotype associated with childhood obesity is not clear, it is well known that childhood is an important time period for the establishment of normal white adipose tissue in humans. This association suggests that exposure to obesogenic stimuli during adipose development may have detrimental effects on adipose function and metabolic homeostasis. In this study, we identify the period of development associated with puberty, postnatal days 18-34, as critical for the establishment of normal adipose mass in mice. Exposure of mice to high fat diet only during this time period results in metabolic dysfunction, increased leptin expression, and increased adipocyte size in adulthood in the absence of sustained increased fat mass or body weight. These findings indicate that exposure to obesogenic stimuli during critical developmental periods have prolonged effects on adipose tissue function that may contribute to the exacerbated metabolic dysfunctions associated with childhood obesity.

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

Pseudo-acute myocardial infarction due to transient apical ventricular dysfunction syndrome (Takotsubo syndrome).

PubMed

Maciel, Bruno Araújo; Cidrão, Alan Alves de Lima; Sousa, Italo Bruno Dos Santos; Ferreira, José Adailson da Silva; Messias Neto, Valdevino Pedro

2013-03-01

Takotsubo syndrome is characterized by predominantly medial-apical transient left ventricular dysfunction, which is typically triggered by physical or emotional stress. The present article reports the case of a 61-year-old female patient presenting with dizziness, excessive sweating, and sudden state of ill feeling following an episode involving intense emotional stress. The physical examination and electrocardiogram were normal upon admission, but the troponin I and creatine kinase-MB concentrations were increased. Acute myocardial infarction without ST segment elevation was suspected, and coronary angiography was immediately performed, which showed severe diffuse left ventricular hypokinesia, medial-apical systolic ballooning, and a lack of significant coronary injury. The patient was referred to the intensive care unit and was successfully treated with supportive therapy. As this case shows, Takotsubo syndrome might simulate the clinical manifestations of acute myocardial infarction, and coronary angiography is necessary to distinguish between both myocardial infarction and myocardial infarction in the acute stage. The present patient progressed with spontaneous resolution of the ventricular dysfunction without any sequelae.

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.

Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis

PubMed Central

Yamaguchi, Osamu; Watanabe, Tetsuya; Nishida, Kazuhiko; Kashiwase, Kazunori; Higuchi, Yoshiharu; Takeda, Toshihiro; Hikoso, Shungo; Hirotani, Shinichi; Asahi, Michio; Taniike, Masayuki; Nakai, Atsuko; Tsujimoto, Ikuko; Matsumura, Yasushi; Miyazaki, Jun-ichi; Chien, Kenneth R.; Matsuzawa, Atsushi; Sadamitsu, Chiharu; Ichijo, Hidenori; Baccarini, Manuela; Hori, Masatsugu; Otsu, Kinya

2004-01-01

The Raf/MEK/extracellular signal–regulated kinase (ERK) signaling pathway regulates diverse cellular processes such as proliferation, differentiation, and apoptosis and is implicated as an important contributor to the pathogenesis of cardiac hypertrophy and heart failure. To examine the in vivo role of Raf-1 in the heart, we generated cardiac muscle–specific Raf-1–knockout (Raf CKO) mice with Cre-loxP–mediated recombination. The mice demonstrated left ventricular systolic dysfunction and heart dilatation without cardiac hypertrophy or lethality. The Raf CKO mice showed a significant increase in the number of apoptotic cardiomyocytes. The expression level and activation of MEK1/2 or ERK showed no difference, but the kinase activity of apoptosis signal–regulating kinase 1 (ASK1), JNK, or p38 increased significantly compared with that in controls. The ablation of ASK1 rescued heart dysfunction and dilatation as well as cardiac fibrosis. These results indicate that Raf-1 promotes cardiomyocyte survival through a MEK/ERK–independent mechanism. PMID:15467832

Pseudo-acute myocardial infarction due to transient apical ventricular dysfunction syndrome (Takotsubo syndrome)

PubMed Central

Maciel, Bruno Araújo; Cidrão, Alan Alves de Lima; Sousa, Ítalo Bruno dos Santos; Ferreira, José Adailson da Silva; Messias Neto, Valdevino Pedro

2013-01-01

Takotsubo syndrome is characterized by predominantly medial-apical transient left ventricular dysfunction, which is typically triggered by physical or emotional stress. The present article reports the case of a 61-year-old female patient presenting with dizziness, excessive sweating, and sudden state of ill feeling following an episode involving intense emotional stress. The physical examination and electrocardiogram were normal upon admission, but the troponin I and creatine kinase-MB concentrations were increased. Acute myocardial infarction without ST segment elevation was suspected, and coronary angiography was immediately performed, which showed severe diffuse left ventricular hypokinesia, medial-apical systolic ballooning, and a lack of significant coronary injury. The patient was referred to the intensive care unit and was successfully treated with supportive therapy. As this case shows, Takotsubo syndrome might simulate the clinical manifestations of acute myocardial infarction, and coronary angiography is necessary to distinguish between both myocardial infarction and myocardial infarction in the acute stage. The present patient progressed with spontaneous resolution of the ventricular dysfunction without any sequelae. PMID:23887762

Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study.

PubMed

Prabhu, Sandeep; Taylor, Andrew J; Costello, Ben T; Kaye, David M; McLellan, Alex J A; Voskoboinik, Aleksandr; Sugumar, Hariharan; Lockwood, Siobhan M; Stokes, Michael B; Pathik, Bhupesh; Nalliah, Chrishan J; Wong, Geoff R; Azzopardi, Sonia M; Gutman, Sarah J; Lee, Geoffrey; Layland, Jamie; Mariani, Justin A; Ling, Liang-Han; Kalman, Jonathan M; Kistler, Peter M

2017-10-17

Atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) frequently co-exist despite adequate rate control. Existing randomized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy. The goal of this study was to determine whether catheter ablation (CA) for AF could improve LVSD compared with medical rate control (MRC) where the etiology of the LVSD was unexplained, apart from the presence of AF. This multicenter, randomized clinical trial enrolled patients with persistent AF and idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%). After optimization of rate control, patients underwent cardiac magnetic resonance (CMR) to assess LVEF and late gadolinium enhancement, indicative of ventricular fibrosis, before randomization to either CA or ongoing MRC. CA included pulmonary vein isolation and posterior wall isolation. AF burden post-CA was assessed by using an implanted loop recorder, and adequacy of MRC was assessed by using serial Holter monitoring. The primary endpoint was change in LVEF on repeat CMR at 6 months. A total of 301 patients were screened; 68 patients were enrolled between November 2013 and October 2016 and randomized with 33 in each arm (accounting for 2 dropouts). The average AF burden post-CA was 1.6 ± 5.0% at 6 months. In the intention-to-treat analysis, absolute LVEF improved by 18 ± 13% in the CA group compared with 4.4 ± 13% in the MRC group (p < 0.0001) and normalized (LVEF ≥50%) in 58% versus 9% (p = 0.0002). In those undergoing CA, the absence of late gadolinium enhancement predicted greater improvements in absolute LVEF (10.7%; p = 0.0069) and normalization at 6 months (73% vs. 29%; p = 0.0093). AF is an underappreciated reversible cause of LVSD in this population despite adequate rate control. The restoration of sinus rhythm with CA results in significant improvements in ventricular function, particularly in the absence of ventricular fibrosis on CMR. This outcome challenges the current treatment paradigm that rate control is the appropriate strategy in patients with AF and LVSD. (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction [CAMERA-MRI]; ACTRN12613000880741). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The preserved autonomic functions may provide the asymptomatic clinical status in heart failure despite advanced left ventricular systolic dysfunction.

PubMed

Kocaman, Sinan Altan; Taçoy, Gülten; Ozdemir, Murat; Açıkgöz, Sadık Kadri; Cengel, Atiye

2010-12-01

Autonomic dysfunction is an important marker of prognosis in congestive heart failure (CHF) and may determine the symptoms and progression of CHF. The aim of our study was to investigate whether preserved autonomic function assessed by heart rate variability (HRV) analyses is related to absence of CHF symptoms despite prominently reduced systolic function. The study had a cross-sectional observational design. Fifty patients with left ventricular ejection fraction (EF) below 40% were enrolled. The patients were divided into two groups according to their CHF symptomatic status as Group 1 (NYHA functional class I, asymptomatic group) and Group 2 (NYHA functional class ≥ II, symptomatic group). Plasma C-reactive protein (CRP), N-terminal proB-type natriuretic peptide (NT-proBNP) levels, echocardiographic parameters and HRV indices were measured while the patients were clinically stable in each group. Possible factors associated with the development of CHF symptoms were assessed by using multiple regression analysis. Baseline clinical characteristics and left ventricular EF were similar in the two groups. Serum CRP (15 ± 21 vs 7 ± 18 mg/L, p=0.011) and NT-proBNP levels (1935 ± 1088 vs 1249 ± 1083 pg/mL, p=0.020) were significantly higher in symptomatic group. The HRV parameters (SDNN: 78 ± 57 vs 122 ± 42 ms, p=0.001; SDANN: 65 ± 55 vs 84 ± 38 ms, p=0.024; SDNNi: 36 ± 41 vs 70 ± 46 ms, p<0.001; triangular index [Ti]: 17 ± 12 vs 32 ± 14, p<0.001) were also significantly depressed in symptomatic group. When multiple regression analysis was performed, only HRV indices of autonomic function were significantly associated with the asymptomatic status (SDNN, OR: 1.016, 95%CI: 1.002-1.031, p=0.028; SDNNi, OR: 1.030, 95%CI: 1.008-1.052, p=0.006; TI, OR: 1.088, 95%CI: 1.019-1.161, p=0.011). Preserved autonomic functions were shown to be associated with absence of CHF symptoms independently of angiotensin converting enzyme inhibitor/angiotensin receptor blocker's treatment and BNP levels and may be protective against the development of CHF symptoms despite advanced left ventricular systolic dysfunction.

Transient left ventricular systolic dysfunction following surgical closure of large patent ductus arteriosus among children and adolescents operated at the cardiac centre, Ethiopia.

PubMed

Tilahun, Birkneh; Tefera, Endale

2013-05-31

Patent ductus arteriosus (PDA) is one of the commonest congenital heart diseases that require closure within the first few months after birth. The residential area of patients affects the size of the PDA: living in highlands, like most places in Ethiopia, is a risk for having larger sized PDA. Closure of these congenital heart defects is usually performed at an early age in places where capable centers are available. In Ethiopia, closure of these defects is done on mission basis often at an older age. Recently, limited reports came about the occurrence of postoperative left ventricular systolic dysfunction (POLVD) following closure of PDA though full explanation is still lacking. To determine the rate of and time to improvement of POLVD and the factors associated with it in children and adolescents who underwent surgical closure of PDA. All children and adolescents who underwent surgical closure of PDA at the Cardiac Center, Ethiopia (CCE) had postoperative follow up with echocardiography. Serial left ventricular ejection fraction (LVEF) and fiber shortening (FS) values were recorded for all of them. SPSS 20 was used to analyze the data. A total of 36 children and adolescents who underwent surgical closure of PDA from January 2009 to December 2012 and who fulfilled the inclusion criteria were studied. Their mean age at intervention was 8.52 years (SD = 5.23 years), 77.80% were females. The mean duct size as determined by either echocardiography or intra-operative by the surgeon was 10.31 mm (SD = 3.20 mm). They were followed for a mean duration of 24.80 months (SD = 12.36 months) following surgical closure of PDA. The mean LVEF and FS decreased from 65.06% and 35.28% preoperatively to 54.83% and 28.40% post-operatively respectively. Fifteen (42.86%) of the patients had a post-operative LVEF of less than 55%. The mean time to normalization of systolic function was 5.11 weeks (SD = 3.30 weeks). Having an associated cardiac lesion was an independent predictor of POLVD. We conclude that there is a high rate of POLVD following surgical closure of large PDA in highlanders. We recommend a serial and systematic follow up of these children postoperatively. Those with a significant cardiac dysfunction may need cardiac medications like Angiotensin Converting Enzyme Inhibitors (ACEI).

[Endoscopic nasobiliary and nasopancreatic drainage contributing to healing of duodenal ulcer perforation: a case report].

PubMed

Enokida, Kohei; Kikuyama, Masataka; Kurokami, Takafumi; Shirane, Naofumi; Aoyama, Haruna; Aoyama, Hiroyuki; Sato, Tatsunori; Taki, Yusuke

2015-10-01

A 75-year-old man with vomiting and right abdominal pain was admitted to the Department of Surgery in our hospital. With a diagnosis of perforated duodenal ulcer, he was treated conservatively. On the day 8 of hospitalization, his general condition worsened and he underwent surgery. During operation, the perforated duodenal ulcer and paraduodenal fluid collection was observed, and percutaneous drainage was accordingly established. After this procedure, renal dysfunction was exacerbated and he was transferred to our department for endoscopic treatment. On day 28 of hospitalization, nasobiliary and nasopancreatic drainage was administered. Renal dysfunction gradually improved, and healing of the perforated duodenal ulcer was recognized on day 93. On day 112, the patient was discharged.

Long term effects of cocaine on the heart assessed by cardiovascular magnetic resonance at 3T

PubMed Central

2014-01-01

Background Cocaine is an addictive, sympathomimetic drug with potentially lethal effects. The prevalence and features of cocaine cardiotoxicity are not well known. We aimed to assess these effects using a comprehensive cardiovascular magnetic resonance (CMR) protocol in a large group of asymptomatic cocaine users. Methods Consecutive (n = 94, 81 males, 36.6 ±7 years), non-selected, cocaine abusers were recruited and had a medical history, examination, ECG, blood test and CMR. The CMR study included measurement of left and right ventricular (LV, RV) dimensions and ejection fraction (EF), sequences for detection of myocardial oedema and late gadolinium enhancement (LGE). Images were compared to a cohort of healthy controls. Results Years of regular cocaine use were 13.9 ± 9. When compared to the age-matched healthy cohort, the cocaine abusers had increased LV end-systolic volume, LV mass index and RV end-systolic volume, with decreased LVEF and RVEF. No subject had myocardial oedema, but 30% had myocardial LGE indicating myocardial damage. Conclusions CMR detected cardiovascular disease in 71% of this cohort of consecutive asymptomatic cocaine abusers and mean duration of abuse was related to probability of LV systolic dysfunction. PMID:24758161

Use of wave intensity analysis of carotid arteries in identifying and monitoring left ventricular systolic function dynamics in rabbits.

PubMed

Zhang, Hui; Zheng, Rongqin; Qian, Xiaoxian; Zhang, Chengxi; Hao, Baoshun; Huang, Zeping; Wu, Tao

2014-03-01

Wave intensity analysis (WIA) of the carotid artery was conducted to determine the changes that occur in left ventricular systolic function after administration of doxorubicin in rabbits. Each randomly selected rabbit was subject to routine ultrasound, WIA of the carotid artery, cardiac catheterization and pathologic examination every week and was followed for 16 wk. The first positive peak (WI1) of the carotid artery revealed that left ventricular systolic dysfunction occurred earlier than conventional indexes of heart function. WI1 was highly, positively correlated with the maximum rate of rise in left ventricular pressure in cardiac catheterization (r = 0.94, p < 0.01) and moderately negatively correlated with the apoptosis index of myocardial cells, an indicator of myocardial damage (r = -0.69, p < 0.01). Ultrasound WIA of the carotid artery sensitively reflects early myocardial damage and cardiac function, and the result is highly consistent with cardiac catheterization findings and the apoptosis index of myocardial cells. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Aldosterone antagonists in heart failure.

PubMed

Miller, Susan E; Alvarez, René J

2013-01-01

Chronic, systolic heart failure is an increasing and costly health problem, and treatments based on pathophysiology have evolved that include the use of aldosterone antagonists. Advances in the understanding of neurohormonal responses to heart failure have led to better pharmacologic treatments. The steroid hormone aldosterone has been associated with detrimental effects on the cardiovascular system, such as ventricular remodeling and endothelial dysfunction. This article will review the literature and guidelines that support the use of aldosterone antagonists in the treatment of chronic, systolic heart failure. Aldosterone antagonists are life-saving drugs that have been shown to decrease mortality in patients with New York Heart Association class III to IV heart failure and in patients with heart failure after an acute myocardial infarction. Additional studies are being conducted to determine if the role of aldosterone antagonists can be expanded to patients with less severe forms of heart failure. Aldosterone antagonists are an important pharmacologic therapy in the neurohormonal blockade necessary in the treatment of systolic heart failure. These drugs have been shown to decrease mortality and reduce hospital readmission rates. The major complication of aldosterone antagonists is hyperkalemia, which can be avoided with appropriate patient selection and diligent monitoring.

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.

[VIABILITY OF MYOCAROIUM AS RISK FACTOR FOR MORTALITY IN EARLY AND LATE PERIOD AFTER BYPASS SURGERY OF CORONARY ARTERIES IN PATIENTS WITH CORONARY HEART DISEASE AND SEVERE LEFT VENTRICULAR DYSFUNCTION].

PubMed

Todurov, B M; Zelenchuk, V; Kuzmich, I M; Ivanyuk, N B; Nikolaichuk, M V

2015-06-01

In coronary heart disease and low ejection fraction of the left ventricle (LV) in patients after coronary artery bypass surgery tend mortality and complication rate higher than preserved LV systolic function. Significant preoperative predictors of early mortality and remote in these patients, and the incidence of complications in the early postoperative period were reveald.

Mechanisms of Autonomic Dysfunction Associated with Extreme Exertional Heat Stroke and Potential Efficacy of Novel Pharmacological Treatments

DTIC Science & Technology

2014-12-01

cardiovascular diseases. At higher doses, these medications have been prescribed to treat high blood pressure in humans and both may have relevance as...HR, and Tc. § Low frequency (LF) systolic blood pressure variability as an index of sympathetic modulation of vascular tone. § LF and high ... blood pressure variability (LFSYS), LF heart rate variability (LFHR), and high frequency heart rate variability (HFHR) in placebo-, clonidine-, and

Relation of Erectile Dysfunction to Subclinical Myocardial Injury.

PubMed

Omland, Torbjørn; Randby, Anna; Hrubos-Strøm, Harald; Røsjø, Helge; Einvik, Gunnar

2016-12-15

The circulating concentration of cardiac troponin I (cTnI) is an index of subclinical myocardial injury in several patient populations and in the general population. Erectile dysfunction is associated with greater risk for cardiovascular events, but the association with subclinical myocardial injury is not known. We aimed to test the hypothesis that the presence and severity of erectile dysfunction is associated with greater concentrations of cTnI in the general population. The presence and severity of erectile dysfunction was assessed by administering the International Index of Erectile Function 5 (IIEF-5) questionnaire to 260 men aged 30 to 65 years recruited from a population-based study. Concentrations of cTnI were determined by a high-sensitivity (hs) assay. Hs-cTnI levels were significantly higher in subjects with than in those without erectile dysfunction (median 2.9 vs 1.6 ng/l; p <0.001). Men with erectile dysfunction (i.e., IIEF-5 sum score <22) were also significantly older; had a higher systolic blood pressure, lower estimated glomerular filtration rate, higher augmentation index and N-terminal pro-B-type natriuretic peptide; and had a higher prevalence of hypertension, diabetes mellitus, and previous coronary artery disease than subjects without erectile dysfunction. These covariates were adjusted for in a multivariate linear regression model, yet the IIEF-5 sum score remained significantly negatively associated with the hs-cTnI concentration (standardized β -0.206; p <0.001). In conclusion, the presence and severity of erectile dysfunction is associated with circulating concentrations of hs-cTnI, indicating subclinical myocardial injury independently of cardiovascular risk factors, endothelial dysfunction and heart failure biomarkers. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Plasma Serotonin in Heart Failure: Possible Marker and Potential Treatment Target.

PubMed

Selim, Ahmed M; Sarswat, Nitasha; Kelesidis, Iosif; Iqbal, Muhammad; Chandra, Ramesh; Zolty, Ronald

2017-05-01

The relationship between heart failure (HF) and the serotonergic system has been established in animal studies. However, data on human plasma serotonin level in HF and its significance over the course of the disease is lacking. Serotonin levels were measured in 173 patients (108 males, 65 females), 116 were stable HF and 40 were acute decompensated HF patients. The normal control group included 17 healthy volunteers with no known medical or psychiatric conditions. Patients receiving medications affecting serotonin receptors and those with pulmonary hypertension were excluded. All patients, except for those in the decompensated group, were on stable doses of HF medications. Plasma serotonin levels were significantly elevated in decompensated HF patients compared with stable patients (P=0.002). Higher plasma serotonin levels were associated with worse HF symptoms (NYHA class) and the presence of systolic dysfunction, and was borderline associated with low peak oxygen consumption during cardiopulmonary exercise testing (P=0.055). These results were independent of age, gender, race, hypertension, diabetes, renal failure, weight, coronary artery disease (CAD), atrial fibrillation and medication use. Serotonin is a marker for decompensation in patients with chronic heart failure. Higher serotonin levels were associated with worse HF symptoms and systolic dysfunction. 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.

Detection of heart disease by open access echocardiography: a retrospective analysis of general practice referrals

PubMed Central

Chambers, John; Kabir, Saleha; Cajeat, Eric

2014-01-01

Background Heart disease is difficult to detect clinically and it has been suggested that echocardiography should be available to all patients with possible cardiac symptoms or signs. Aim To analyse the results of 2 years of open access echocardiography for the frequency of structural heart disease according to request. Design and setting Retrospective database analysis in a teaching hospital open access echocardiography service. Method Reports of all open access transthoracic echocardiograms between January 2011 and December 2012 were categorised as normal, having minor abnormalities, or significant abnormalities according to the indication. Results There were 2343 open access echocardiograms performed and there were significant abnormalities in 29%, predominantly valve disease (n = 304, 13%), LV systolic dysfunction (n = 179, 8%), aortic dilatation (n = 80, 3%), or pulmonary hypertension (n = 91, 4%). If echocardiography had been targeted at a high-risk group, 267 with valve disease would have been detected (compared to 127 with murmur alone) and 139 with LV systolic dysfunction (compared to 91 with suspected heart failure alone). Most GP practices requested fewer than 10 studies, but 6 practices requested over 70 studies. Conclusion Open access echocardiograms are often abnormal but structural disease may not be suspected from the clinical request. Uptake by individual practices is patchy. A targeted expansion of echocardiography in patients with a high likelihood of disease is therefore likely to increase the detection of clinically important pathology. PMID:24567615

The KEEPS-Cognitive and Affective Study: baseline associations between vascular risk factors and cognition.

PubMed

Wharton, Whitney; Gleason, Carey E; Dowling, N Maritza; Carlsson, Cynthia M; Brinton, Eliot A; Santoro, M Nanette; Neal-Perry, Genevieve; Taylor, Hugh; Naftolin, Frederick; Lobo, Rogerio A; Merriam, George; Manson, Joann E; Cedars, Marcelle I; Miller, Virginia M; Black, Dennis M; Budoff, Matthew; Hodis, Howard N; Harman, S Mitchell; Asthana, Sanjay

2014-01-01

Midlife vascular risk factors influence later cognitive decline and Alzheimer's disease (AD). The decrease in serum estradiol levels during menopause has been associated with cognitive impairment and increased vascular risk, such as high blood pressure (BP), which independently contributes to cognitive dysfunction and AD. We describe the extent to which vascular risk factors relate to cognition in healthy, middle-aged, recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Cognitive and Affective Study (KEEPS-Cog) at baseline. KEEPS-Cog is a double-blind, randomized, placebo-controlled, parallel group, clinical trial, investigating the efficacy of low-dose, transdermal 17β-estradiol and oral conjugated equine estrogen on cognition. All results are cross-sectional and represent baseline data only. Analyses confirm that the KEEPS-Cog cohort (n = 571) was middle aged (mean 52.7 years, range 42-59 years), healthy, and free of cognitive dysfunction. Higher systolic BP was weakly related to poorer performance in auditory working memory and attention (p = 0.004; adjusted for multiple comparisons p = 0.10). This relationship was not associated with endogenous hormone levels, and systolic BP was not related to any other cognitive domain. BP levels may be more sensitive than other vascular risk factors in detecting subtle differences in cognitive task performance in healthy, recently menopausal women. Lower BP early in menopause may affect cognitive domains known to be associated with AD.

Detection of heart disease by open access echocardiography: a retrospective analysis of general practice referrals.

PubMed

Chambers, John; Kabir, Saleha; Cajeat, Eric

2014-02-01

Heart disease is difficult to detect clinically and it has been suggested that echocardiography should be available to all patients with possible cardiac symptoms or signs. To analyse the results of 2 years of open access echocardiography for the frequency of structural heart disease according to request. Retrospective database analysis in a teaching hospital open access echocardiography service. Reports of all open access transthoracic echocardiograms between January 2011 and December 2012 were categorised as normal, having minor abnormalities, or significant abnormalities according to the indication. There were 2343 open access echocardiograms performed and there were significant abnormalities in 29%, predominantly valve disease (n = 304, 13%), LV systolic dysfunction (n = 179, 8%), aortic dilatation (n = 80, 3%), or pulmonary hypertension (n = 91, 4%). If echocardiography had been targeted at a high-risk group, 267 with valve disease would have been detected (compared to 127 with murmur alone) and 139 with LV systolic dysfunction (compared to 91 with suspected heart failure alone). Most GP practices requested fewer than 10 studies, but 6 practices requested over 70 studies. Open access echocardiograms are often abnormal but structural disease may not be suspected from the clinical request. Uptake by individual practices is patchy. A targeted expansion of echocardiography in patients with a high likelihood of disease is therefore likely to increase the detection of clinically important pathology.

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.

[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.

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.

Low dietary sodium intake is associated with enhanced vascular endothelial function in middle-aged and older adults with elevated systolic blood pressure

PubMed Central

Jablonski, Kristen L.; Gates, Phillip E.; Pierce, Gary L.; Seals, Douglas R.

2012-01-01

Background Age and increasing systolic blood pressure (BP) are associated with vascular endothelial dysfunction, but the factors involved are incompletely understood. We tested the hypothesis that vascular endothelial function is related to dietary sodium intake among middle-aged and older adults (MA and O) with elevated systolic BP. Methods Data were analyzed on 25 otherwise healthy adults aged 48–73 years with high normal systolic BP or stage I systolic hypertension (130–159 mmHg). Self-reported sodium intake was <100 mmol/d in 12 (7 M) subjects (low sodium, 73 ± 6 mmol/d) and between 100 and 200 mmol/d in 13 (9 M) subjects (normal sodium, 144 ± 6 mmol/d). Results Groups did not differ in other dietary factors, age, body weight and composition, BP, metabolic risk factors, physical activity and maximal aerobic capacity. Plasma concentrations of norepinephrine, endothelin-1, oxidized low-density lipoproteins (LDL), antioxidant status and inflammatory markers did not differ between groups. Brachial artery flow-mediated dilation (FMD) was 42% (mm Δ) to 52% (% Δ) higher in the low versus normal sodium group (p <0.05). In all subjects, brachial artery FMD was inversely related to dietary sodium intake (FMD mm Δr =−0.40, p <0.05; %Δr =−0.53, p <0.01). Brachial artery FMD was not related to any other variable. In contrast, endothelium-independent dilation did not differ between groups (p ≥ 0.24) and was not related to sodium intake in the overall group (p ≥ 0.29). Conclusions Low sodium intake is associated with enhanced brachial artery FMD in MA and O with elevated systolic BP. These results suggest that dietary sodium restriction may be an effective intervention for improving vascular endothelial function in this high-risk group. PMID:19723834

Right ventricular function in acute pulmonary embolism: a combined assessment by three-dimensional and speckle-tracking echocardiography.

PubMed

Vitarelli, Antonio; Barillà, Francesco; Capotosto, Lidia; D'Angeli, Ilaria; Truscelli, Giovanni; De Maio, Melissa; Ashurov, Rasul

2014-03-01

The aim of this study was to assess changes in right ventricular (RV) parameters determined by three-dimensional (3D) echocardiography and speckle-tracking echocardiography in patients with acute pulmonary embolism and RV dysfunction without systemic hypotension (submassive pulmonary embolism). Sixty-six patients were prospectively studied at the onset of the acute episode and after median follow-up periods of 30 days and 6 months. Sixty-six controls were selected. RV fractional area change, tricuspid annular plane systolic excursion, and myocardial performance index were determined. RV systolic pressure was assessed using continuous-wave Doppler echocardiography. Three-dimensional RV ejection fraction (RVEF) was calculated. Two-dimensional peak systolic RV longitudinal strain (RVLS) was measured in the basal free wall, mid free wall (MFW), and apical free wall and the septum. Tricuspid annular plane systolic excursion and fractional area change were smaller and myocardial performance index was larger compared with controls (P < .05). Global RVLS (P < .05), MFW RVLS (P < .001), and 3D RVEF (P < .001) were lower in patients with pulmonary embolism than in controls. There was earlier reversal of MFW RVLS values on 30-day follow-up and longer reversal of 3D RVEF and RV systolic pressure values at 6-month follow-up. Receiver operating characteristic curve analysis showed that changes in 3D RVEF and MFW RVLS were the most sensitive predictors of adverse events. By multivariate analysis, RV systolic pressure (P = .007), MFW RVLS (P = .002), and 3D RVEF (P = .001) were independently associated with adverse outcomes. Acute submassive pulmonary embolism has a significant impact on RV function as assessed by 3D echocardiography and speckle-tracking echocardiography. Decreases in MFW RVLS and 3D RVEF may persist during short-term and long-term follow-up and correlate with unfavorable outcomes. Copyright © 2014 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

Comparison of Right Ventricle Systolic Function between Long-Term Anabolic-Androgenic Steroid User and Nonuser Bodybuilder Athletes: A Study of Two-Dimensional Speckle Tracking Echocardiography.

PubMed

Alizade, Elnur; Avci, Anil; Tabakcı, Mehmet Mustafa; Toprak, Cuneyt; Zehir, Regayip; Acar, Goksel; Kargin, Ramazan; Emiroğlu, Mehmet Yunas; Akçakoyun, Mustafa; Pala, Selçuk

2016-08-01

Right ventricular (RV) effects of long-term use of anabolic-androgenic steroids (AAS) are not clearly known. The aim of this study was to assess RV systolic functions by two-dimensional speckle tracking echocardiography (2DSTE) in AAS user and nonuser bodybuilders. A total of 33 competitive male bodybuilders (15 AAS users, 18 AAS nonusers) were assessed. To assess RV systolic functions, all participants underwent standard two-dimensional and Doppler echocardiography, and 2DSTE. Interventricular septal thickness, left ventricle posterior wall thickness, relative wall thickness, and left ventricle mass index were significantly higher in AAS users than nonusers. While standard diastolic parameters were not statistically different between the groups, tissue Doppler parameters including RV E' and E'/A' were lower in AAS users than nonusers (10.1 ± 2.0 vs. 12.7 ± 2.1; P = 0.001, 1.1 ± 0.1 vs. 1.5 ± 0.4; P = 0.009, respectively). Tricuspid annular plane systolic excursion, RV fractional area change, and RV S' were in normal ranges. However, RV S' was found to be lower in users than nonusers (12.2 ± 2.2 vs. 14.6 ± 2.8, P = 0.011). RV free wall longitudinal strain and strain rate were decreased in AAS users in comparison with nonusers (-20.2 ± 3.1 vs. -23.3 ± 3.5; P = 0.012, -3.2 ± 0.1 vs. -3.4 ± 0.1; P = 0.022, respectively). In addition, there were good correlations between 2DSTE parameters and RV S', E', and E'/A'. Despite normal standard systolic echo parameters, peak systolic RV free wall strain and strain rate were reduced in AAS user bodybuilders in comparison with nonusers. Strain and strain rate by 2DSTE may be useful for early determination of subclinical RV dysfunction in AAS user bodybuilders. © 2016, Wiley Periodicals, Inc.

Left Ventricular Reverse Remodeling With Biventricular Versus Right Ventricular Pacing in Patients With Atrioventricular Block and Heart Failure in the BLOCK HF Trial.

PubMed

St John Sutton, Martin; Plappert, Ted; Adamson, Philip B; Li, Pei; Christman, Shelly A; Chung, Eugene S; Curtis, Anne B

2015-05-01

Biventricular pacing in heart failure (HF) improves survival, relieves symptoms, and attenuates left ventricular (LV) remodeling. However, little is known about biventricular pacing in HF patients with atrioventricular block because they are typically excluded from biventricular trials. The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) trial randomized patients with atrioventricular block, New York Heart Association symptom classes I to III HF, and LV ejection fraction ≤50% to biventricular or right ventricular pacing. Doppler echocardiograms were obtained at randomization (after 30 to 60 days of right ventricular pacing postimplant) and every 6 months through 24 months. Data analysis comparing changes in 10 prespecified echo parameters over time was conducted using a Bayesian design. LV end systolic volume index was also evaluated as a predictor of mortality/morbidity. Of 691 randomized subjects, 624 had paired Doppler echocardiogram data for ≥1 analyses at 6, 12, 18, or 24 months. Biventricular pacing significantly reduced LV volume indices and intraventricular mechanical delay, and improved LV ejection fraction, consistent with LV reverse remodeling. These parameters showed little change with right ventricular pacing alone, indicating no systematic reverse remodeling with right ventricular pacing. LV end systolic volume index was predictive of mortality/morbidity; the estimated risk increased up to 1% for every 1 mL/m(2) increase in LV end systolic volume index. LV end systolic volume index is a significant predictor of mortality/morbidity in this population. Cardiac structure and function are improved with biventricular pacing for patients with atrioventricular block and LV systolic dysfunction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00267098. © 2015 American Heart Association, Inc.

Left ventricular remodeling and change of systolic function after closure of patent ductus arteriosus in adults: device and surgical closure.

PubMed

Jeong, Young-Hoon; Yun, Tae-Jin; Song, Jong-Min; Park, Jung-Jun; Seo, Dong-Man; Koh, Jae-Kon; Lee, Se-Whan; Kim, Mi-Jeong; Kang, Duk-Hyun; Song, Jae-Kwan

2007-09-01

Left ventricular (LV) remodeling and predictors of LV systolic function late after closure of patent ductus arteriosus (PDA) in adults remain to be clearly demonstrated. In 45 patients with PDA, including 28 patients who received successful occlusion using the Amplatzer device (AD group) (AGA, Golden Valley, MN) and 17 patients who received surgical closure (OP group), echocardiography studies were performed before closure and 1 day (AD group) or within 7 days (OP group) after closure, and then were repeated at > or = 6 months (17 +/- 13 months). In both groups, LV ejection fraction (EF) and end-diastolic volume index were significantly decreased immediately after closure, whereas end-systolic volume index did not change. During the long-term follow-up period, end-systolic as well as end-diastolic volume indices decreased significantly in both groups and LV EF recovered compared to the immediate postclosure state. However, LV EF remained low compared to the preclosure state. Five patients (11.1%) including 3 patients in the AD group and 2 patients in the OP group showed persistent late LV systolic dysfunction (EF <50%). In stepwise, multiple logistic regression analysis, preclosure EF was the only independent predictor of late normal postclosure EF (odds ratio, 1.230; 95% CI, 1.054-1.434; P = .008). Receiver operating characteristic curve analysis showed that preclosure EF > or = 62% had a sensitivity of 72% and a specificity of 83% for predicting late normal LV EF after closure. Left ventricular EF remains low late after PDA closure compared with preclosure state in adults. Preclosure LV EF is the best index to predict late postclosure LV EF.

Acute impairment of regional myocardial glucose uptake in the apical ballooning (takotsubo) syndrome.

PubMed

Bybee, Kevin A; Murphy, Joseph; Prasad, Abhiram; Wright, R Scott; Lerman, Amir; Rihal, Charanjit S; Chareonthaitawee, Panithaya

2006-01-01

Apical ballooning syndrome (ABS) is a poorly understood clinical entity characterized by acute, transient systolic dysfunction of the left ventricular (LV) apex in the absence of epicardial coronary artery disease and commonly associated with acute emotional stress. We report abnormal regional myocardial perfusion and glucose uptake in 4 consecutive ABS patients studied using positron emission tomography with 13N-ammonia and 18F-fluorodeoxyglucose within 72 hours of presentation with ABS. All patients were postmenopausal females, 3 of whom had a major recent life stress event. Coronary angiography revealed no or minimal obstructive epicardial coronary artery disease. All patients exhibited reduced glucose uptake in the mid-LV and apical myocardial segments, which was out of proportion to perfusion abnormalities in half of the cases. In all 4 patients, affected regions subsequently recovered regional LV systolic function within 6 weeks.

[Echocardiographic indices of the right heart in patients with coronary artery disease in different age groups].

PubMed

Gajfulin, R A; Sumin, A N; Arhipov, O G

2016-01-01

The aim of study was to examine echocardiographic indices of right heart chambers in patients with coronary artery disease in different age groups. On 678 patients aged 38-85 years, who underwent echocardiography, are including with the use of spectral tissue Doppler. Obtained 2 age groups: 1st - patients up to 60 years (n=282) and group 2nd - patients 60 years and older (n=396). In the analysis the obtained results in patients with coronary heart disease in older age groups showed an increase in right ventricular wall thickness, systolic and average pressure in the pulmonary artery. These changes were accompanied by deterioration in left ventricular diastolic function, while the systolic function of the left and right ventricle were independent of age. Thus, the results can be recommended for assessment of right ventricular dysfunction in patients of older age groups.

A case of an unexplained eosinophilic myocarditis in a dog.

PubMed

Keeshen, T P; Chalkley, M; Stauthammer, C

2016-09-01

An 8-year-old spayed female Munsterlander was evaluated for a chronic low grade fever and a two month history of exercise intolerance. On physical examination, tachycardia and a grade II/VI right systolic heart murmur were detected. Echocardiography revealed marked thickening of the atrial and ventricular walls with mixed echogenicity and concentric hypertrophy of the left and right ventricles and equivocal systolic dysfunction. Serum cardiac troponin I level was markedly elevated. Endomyocardial biopsy was attempted; however, the patient arrested during the procedure and resuscitation was unsuccessful. Post-mortem examination revealed severe, chronic atrial and ventricular eosinophilic myocarditis associated with marked interstitial fibrosis. Serological testing, histopathology and immunohistochemistry staining did not reveal an underlying infectious agent or neoplasm. To our knowledge, this is the first reported case of primary eosinophilic myocarditis in the absence of a peripheral eosinophilia and multi-organ eosinophilic inflammation in a dog. Published by Elsevier B.V.

Positive inotropes in heart failure: a review article

PubMed Central

Amin, Ahmad; Maleki, Majid

2012-01-01

Increasing myocardial contractility has long been considered a big help for patients with systolic heart failure, conferring an augmented haemodynamic profile in terms of higher cardiac output, lower cardiac filling pressure and better organ perfusion. Though concerns have been raised over the safety issues regarding the clinical trials of different inotropes in hearts with systolic dysfunction, they still stand as a main therapeutic strategy in many centres dealing with such patients. They must be used as short in duration, low in dose and stopped as early as possible. Evidence-based guidelines have provided clinicians with valuable data for better applying inotropes in heart failure patients. In this paper, the authors address clinical trials with different agents used for increasing cardiac contractility in heart failure patients. Furthermore, the authors focus on recent guidelines on making the most out of inotropes in heart failure patients. PMID:27326019

A case of reversible dilated cardiomyopathy after alpha-interferon therapy in a patient with renal cell carcinoma.

PubMed

Kuwata, Akiko; Ohashi, Masuo; Sugiyama, Masaya; Ueda, Ryuzo; Dohi, Yasuaki

2002-12-01

A 47-year-old man with renal cell carcinoma underwent nephrectomy, and postoperative chemotherapy was performed with recombinant alpha-interferon. Five years later, he experienced dyspnea during physical exertion. An echocardiogram revealed dilatation and systolic dysfunction of the left ventricle, and thallium-201 myocardial scintigraphy showed diffuse heterogeneous perfusion. We diagnosed congestive heart failure because of cardiomyopathy induced by alpha-interferon therapy. Withdrawal of interferon therapy and the combination of an angiotensin-converting enzyme inhibitor, diuretics, and digitalis improved left ventricular systolic function. Furthermore, myocardial scintigraphy using [123I] beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) or [123 I]metaiodobenzylguanidine (123I-MIBG) revealed normal perfusion after the improvement of congestive heart failure. This is a rare case of interferon-induced cardiomyopathy that resulted in normal myocardial images in 123I-BMIPP and 123I-MIBG scintigrams after withdrawal of interferon therapy.

Reduced cardiac fructose 2,6 bisphosphate increases hypertrophy and decreases glycolysis following aortic constriction.

PubMed

Wang, Jianxun; Xu, Jianxiang; Wang, Qianwen; Brainard, Robert E; Watson, Lewis J; Jones, Steven P; Epstein, Paul N

2013-01-01

This study was designed to test whether reduced levels of cardiac fructose-2,6-bisphosphate (F-2,6-P(2)) exacerbates cardiac damage in response to pressure overload. F-2,6-P(2) is a positive regulator of the glycolytic enzyme phosphofructokinase. Normal and Mb transgenic mice were subject to transverse aortic constriction (TAC) or sham surgery. Mb transgenic mice have reduced F-2,6-P(2) levels, due to cardiac expression of a transgene for a mutant, kinase deficient form of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) which controls the level of F-2,6-P(2). Thirteen weeks following TAC surgery, glycolysis was elevated in FVB, but not in Mb, hearts. Mb hearts were markedly more sensitive to TAC induced damage. Echocardiography revealed lower fractional shortening in Mb-TAC mice as well as larger left ventricular end diastolic and end systolic diameters. Cardiac hypertrophy and pulmonary congestion were more severe in Mb-TAC mice as indicated by the ratios of heart and lung weight to tibia length. Expression of α-MHC RNA was reduced more in Mb-TAC hearts than in FVB-TAC hearts. TAC produced a much greater increase in fibrosis of Mb hearts and this was accompanied by 5-fold more collagen 1 RNA expression in Mb-TAC versus FVB-TAC hearts. Mb-TAC hearts had the lowest phosphocreatine to ATP ratio and the most oxidative stress as indicated by higher cardiac content of 4-hydroxynonenal protein adducts. These results indicate that the heart's capacity to increase F-2,6-P(2) during pressure overload elevates glycolysis which is beneficial for reducing pressure overload induced cardiac hypertrophy, dysfunction and fibrosis.

Fructose intake exacerbates the contractile response elicited by norepinephrine in mesenteric vascular bed of rats via increased endothelial prostanoids.

PubMed

Sousa, Glauciene J; Oliveira, Phablo Wendell C; Nogueira, Breno V; Melo, Antônio F; Faria, Thaís de Oliveira; Meira, Eduardo Frizera; Mill, José G; Bissoli, Nazaré S; Baldo, Marcelo P

2017-10-01

Chronic fructose intake induces major cardiovascular and metabolic disturbances and is associated with the development of hypertension due to changes in vascular function. We hypothesized that high fructose intake for 6 weeks would cause metabolic syndrome and lead to initial vascular dysfunction. Male Wistar rats were assigned to receive fructose (FRU, 10%) or drinking water (CON) for 6 weeks. Systolic blood pressure was evaluated by tail plethysmography. Fasting glucose, insulin and glucose tolerance were measured at the end of the follow-up. Mesenteric vascular bed reactivity was tested before and after pharmacological blockade. Western blot analysis was performed for iNOS, eNOS, Nox2 and COX-2. DHE staining was used for vascular superoxide anion detection. Vessel structure was evaluated by optical and electronic microscopy. Fructose intake did not alter blood pressure, but did increase visceral fat deposition and fasting glucose as well as impair insulin and glucose tolerance. Fructose increased NE-induced vasoconstriction compared with CON, and this difference was abrogated by indomethacin perfusion as well as endothelium removal. ACh-induced relaxation was preserved, and the NO modulation tested after L-NAME perfusion was similar between groups. SNP-induced relaxation was not altered. Inducible NOS was increased; however, there were no changes in eNOS, Nox2 or COX-2 protein expression. Basal or stimulated superoxide anion production was not changed by fructose intake. In conclusion, high fructose intake increased NE-induced vasoconstriction through the endothelial prostanoids even in the presence of a preserved endothelium-mediated relaxation. No major changes in vessel structure were detected. Copyright © 2017 Elsevier Inc. All rights reserved.

Interactive effects of ethanol on ulcerative colitis and its associated testicular dysfunction in pubertal BALB/c mice.

PubMed

Adedara, Isaac A; Ajayi, Babajide O; Awogbindin, Ifeoluwa O; Farombi, Ebenezer O

2017-11-01

Available epidemiological reports have indicated an increase in the incidence of ulcerative colitis, as well as alcohol consumption, globally. The present study investigated the possible interactive effects of ethanol consumption on ulcerative colitis and its associated testicular dysfunction using six groups of 12 pubertal mice each. Group I (Control) mice received drinking water alone. Group II mice received ethanol alone at 5 g/kg body weight. Group III mice received 2.5% dextran sulphate sodium (DSS) in drinking water followed by normal drinking water. Groups IV, V, and VI mice received DSS followed by ethanol at 1.25, 2.5, and 5 g/kg, respectively. Administration of ethanol to mice with ulcerative colitis intensified the disease-activity index with marked reduction in colon length, colon mass index, body weight gain, and organo-somatic indices of testes and epididymis when compared with the DSS-alone group. Moreover, ethanol exacerbated colitis-mediated decrease in enzymatic and non-enzymatic antioxidants but increased the oxidative stress and inflammatory biomarkers in the testes and epididymis. The diminution in luteinizing hormone, follicle stimulating hormone, and testosterone levels was intensified following administration of ethanol to mice with ulcerative colitis that were administered 5 g/kg ethanol alone. The decrease in sperm functional parameters and testicular spermatogenic indices as well as histopathological damage in colon, testes, and epididymis was aggravated following administration of ethanol to mice with ulcerative colitis. In conclusion, the exacerbating effects of ethanol on ulcerative colitis-induced testicular dysfunction are related to increased oxidative stress and inflammation in the treated mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of Characteristics and Outcomes of Asymptomatic Versus Symptomatic Left Ventricular Dysfunction in Subjects 65 Years Old or Older (from the Cardiovascular Health Study)

PubMed Central

Pandhi, Jay; Gottdiener, John S.; Bartz, Traci M.; Kop, Willem J.; Mehra, Mandeep R.

2014-01-01

Although asymptomatic left ventricular (LV) systolic dysfunction (ALVSD) is common, its phenotype and prognosis for incident heart failure (HF) and mortality are insufficiently understood. Echocardiography was done in 5,649 participants in the Cardiovascular Health Study (age 73.0 ± 5.6 years, 57.6% women). The clinical characteristics and cardiovascular risk factors of the participants with ALVSD were compared to those with normal LV function (ejection fraction ≥55%) and with symptomatic LV systolic dysfunction (SLVSD; ejection fraction <55% and a history of HF). Cox proportional hazards models were used to estimate the risk of incident HF and mortality in those with ALVSD. Also, comparisons were made among the LV ejection fraction subgroups using previously validated cutoff values (<45% and 45% to 55%), adjusting for the demographic and cardiovascular disease risk factors. Those with ALVSD (7.3%) were more likely to have cardiovascular risk factors than those in the reference group (without LV dysfunction or symptomatic HF) but less likely than those with SLVSD. The HF rate was 24 occurrences per 1,000 person-years in the reference group and 57 occurrences per 1,000 person-years in those with ALVSD. The HF rate was 45 occurrences per 1,000 person-years for those with ALVSD and mildly impaired LV dysfunction and 93 occurrences per 1,000 person-years for those with ALVSD and moderate to severe LV dysfunction. The mortality rate was 51 deaths per 1,000 person-years in the reference group, 90 deaths per 1,000 person-years in the ALVSD group, and 156 deaths per 1,000 person-years in the SLVSD group. Adjusting for covariates, compared to the reference group, ALVSD was associated with an increased risk of incident HF (hazard ratio 1.60,95% confidence interval 1.35 to 1.91), cardiovascular mortality (hazard ratio 2.13, 95% confidence interval 1.81 to 2.51), and all-cause mortality (hazard ratio 1.46, 95% confidence interval 1.29 to 1.64). In conclusion, subjects with ALVSD are characterized by a greater prevalence of cardiovascular risk factors and co-morbidities than those with normal LV function and without HF. However, the prevalence is lower than in those with SLVSD. Patients with ALVSD are at an increased risk of HF and mortality, particularly those with greater severity of LV impairment. PMID:21575752

Comparison of characteristics and outcomes of asymptomatic versus symptomatic left ventricular dysfunction in subjects 65 years old or older (from the Cardiovascular Health Study).

PubMed

Pandhi, Jay; Gottdiener, John S; Bartz, Traci M; Kop, Willem J; Mehra, Mandeep R

2011-06-01

Although asymptomatic left ventricular (LV) systolic dysfunction (ALVSD) is common, its phenotype and prognosis for incident heart failure (HF) and mortality are insufficiently understood. Echocardiography was done in 5,649 participants in the Cardiovascular Health Study (age 73.0 ± 5.6 years, 57.6% women). The clinical characteristics and cardiovascular risk factors of the participants with ALVSD were compared to those with normal LV function (ejection fraction ≥55%) and with symptomatic LV systolic dysfunction (SLVSD; ejection fraction <55% and a history of HF). Cox proportional hazards models were used to estimate the risk of incident HF and mortality in those with ALVSD. Also, comparisons were made among the LV ejection fraction subgroups using previously validated cutoff values (<45% and 45% to 55%), adjusting for the demographic and cardiovascular disease risk factors. Those with ALVSD (7.3%) were more likely to have cardiovascular risk factors than those in the reference group (without LV dysfunction or symptomatic HF) but less likely than those with SLVSD. The HF rate was 24 occurrences per 1,000 person-years in the reference group and 57 occurrences per 1,000 person-years in those with ALVSD. The HF rate was 45 occurrences per 1,000 person-years for those with ALVSD and mildly impaired LV dysfunction and 93 occurrences per 1,000 person-years for those with ALVSD and moderate to severe LV dysfunction. The mortality rate was 51 deaths per 1,000 person-years in the reference group, 90 deaths per 1,000 person-years in the ALVSD group, and 156 deaths per 1,000 person-years in the SLVSD group. Adjusting for covariates, compared to the reference group, ALVSD was associated with an increased risk of incident HF (hazard ratio 1.60, 95% confidence interval 1.35 to 1.91), cardiovascular mortality (hazard ratio 2.13, 95% confidence interval 1.81 to 2.51), and all-cause mortality (hazard ratio 1.46, 95% confidence interval 1.29 to 1.64). In conclusion, subjects with ALVSD are characterized by a greater prevalence of cardiovascular risk factors and co-morbidities than those with normal LV function and without HF. However, the prevalence is lower than in those with SLVSD. Patients with ALVSD are at an increased risk of HF and mortality, particularly those with greater severity of LV impairment. Copyright © 2011 Elsevier Inc. All rights reserved.

Hepatitis C, human immunodeficiency virus and metabolic syndrome: interactions.

PubMed

Kotler, Donald P

2009-03-01

Significant concerns have been raised about the metabolic effects of antiretroviral medication, including the classic triad of dyslipidaemia, insulin resistance (IR) and characteristic alterations in fat distribution (lipoatrophy and lipohypertrophy). Co-infection with hepatitis C appears to exacerbate IR, reduce serum lipids and induce prothrombotic changes in the treated human immunodeficiency virus patient. The effects of co-infection are complex. While combination antiretroviral therapy has been shown to be associated with an increased risk of cardiovascular events through promotion of dyslipidaemia, IR and fat redistribution, co-infection exacerbates IR while reducing serum lipids. Co-infection also promotes a prothrombotic state characterized by endothelial dysfunction and platelet activation, which may enhance risk for cardiovascular disease. Consideration must be given to selection of appropriate treatment regimens and timing of therapy in co-infected patients to minimize metabolic derangements and, ultimately, reduce cardiovascular risk.

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.

Shuttle walking test and 6-minute walking test induce a similar cardiorespiratory performance in patients recovering from an acute exacerbation of chronic obstructive pulmonary disease.

PubMed

Vagaggini, B; Taccola, M; Severino, S; Marcello, M; Antonelli, S; Brogi, S; De Simone, C; Giardina, A; Paggiaro, P L

2003-01-01

The incremental shuttle walking test (SWT) has recently been proposed as a more valid and reproducible alternative to the conventional 6-min walking test (6MWT) in the evaluation of exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). To compare the cardiorespiratory performance obtained during two sessions of SWT with that obtained during two sessions of 6MWT. We examined 18 patients (forced expiratory volume in 1 s: 48 +/- 14%) recovering from an acute exacerbation of COPD that had required hospitalization. In the same afternoon, each patient performed two SWT and two 6MWT, with an interval of at least 30 min between each test; the sequence of the tests was randomized. Mean walking distance was greater in the second SWT test than in the first SWT. The changes from baseline in systolic blood pressure, heart rate, respiratory rate, oxygen saturation and dyspnea Borg index at the end of the test were similar between the two 6MWT and the two SWT. There was a highly significant correlation between walking distances measured during SWT and during 6MWT (rho: 0.85, p < 0.0005). Neither SWT nor 6MWT correlated with functional data of COPD. SWT, though being considered to be closer to a submaximal exercise test than 6MWT, does not induce a greater cardiorespiratory performance than 6MWT in patients recovering from acute exacerbation of COPD. Copyright 2003 S. Karger AG, Basel

Macrophage Migration Inhibitory Factor (MIF) Deficiency Exacerbates Aging-Induced Cardiac Remodeling and Dysfunction Despite Improved Inflammation: Role of Autophagy Regulation.

PubMed

Xu, Xihui; Pang, Jiaojiao; Chen, Yuguo; Bucala, Richard; Zhang, Yingmei; Ren, Jun

2016-03-04

Aging leads to unfavorable geometric and functional sequelae in the heart. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) plays a role in the maintenance of cardiac homeostasis under stress conditions although its impact in cardiac aging remains elusive. This study was designed to evaluate the role of MIF in aging-induced cardiac anomalies and the underlying mechanism involved. Cardiac geometry, contractile and intracellular Ca(2+) properties were examined in young (3-4 mo) or old (24 mo) wild type and MIF knockout (MIF(-/-)) mice. Our data revealed that MIF knockout exacerbated aging-induced unfavorable structural and functional changes in the heart. The detrimental effect of MIF knockout was associated with accentuated loss in cardiac autophagy with aging. Aging promoted cardiac inflammation, the effect was attenuated by MIF knockout. Intriguingly, aging-induced unfavorable responses were reversed by treatment with the autophagy inducer rapamycin, with improved myocardial ATP availability in aged WT and MIF(-/-) mice. Using an in vitro model of senescence, MIF knockdown exacerbated doxorubicin-induced premature senescence in H9C2 myoblasts, the effect was ablated by MIF replenishment. Our data indicated that MIF knockout exacerbates aging-induced cardiac remodeling and functional anomalies despite improved inflammation, probably through attenuating loss of autophagy and ATP availability in the heart.

Dependent, but not Perfectionistic, Dysfunctional Attitudes Predict Worsened Mood and Appraisals after Emotional Support from a Romantic Partner

PubMed Central

Felix, Steven A. M.; Hooker, Christine I.

2016-01-01

Background: Receiving emotional support from a romantic partner often leads to emotional costs via negative appraisals about the self and one's relationship, but it is unclear whether certain individuals are more susceptible to these costs. We evaluate whether the presence of perfectionistic and dependent dysfunctional attitudes leads to more negative effects of receiving emotional support from a romantic partner. Methods: Twenty-nine couples (27 men, 31 women; mean age 24.5) completed the Dysfunctional Attitudes Scale and then a daily online questionnaire by recording their mood, appraisals, and received emotional support. Mixed-effects regressions were used to evaluate whether perfectionistic and dependent dysfunctional attitudes moderated the relationship between emotional support receipt and subsequent mood and appraisals. Results: Perfectionism did not interact with emotional support but exerted a main effect of increasing negative moods and appraisals. Dependency interacted with emotional support such that those with more dependent attitudes reported greater negative next-day moods and appraisals as a function of emotional support. Conclusions: Individuals with dependent, but not perfectionistic, dysfunctional attitudes are more likely to experience emotional and cognitive costs after receiving emotional support. These costs may stem from activation or exacerbation of the attitudes specific to dependency, including need for acceptance, support, and approval of others. PMID:27790161

Executive functions and psychiatric symptoms in drug-refractory juvenile myoclonic epilepsy.

PubMed

Walsh, Jordana; Thomas, Rhys H; Church, Carla; Rees, Mark I; Marson, Anthony G; Baker, Gus A

2014-06-01

The pattern of executive dysfunction reported in juvenile myoclonic epilepsy (JME) resembles that of patients with cluster B personality disorders. This study examined whether executive dysfunction and maladaptive behavior reported in patients with JME are related. Sixty patients with drug-refractory JME were administered tests of intellect, memory, and executive dysfunction. Anxiety, depression, personality traits, impact of epilepsy, and perceived cognitive effects of antiepileptic drugs were measured. Half of the cohort exhibited moderate to severe anxiety symptoms. The patients performed most poorly on naming ability and inhibition switching. Duration of epilepsy exacerbated poor performance on inhibition switching. Females presented with pathological scores for neurotic and introvert traits and males for introvert traits. Abnormal personality traits and psychiatric disorders were associated with worse intellectual and executive functioning. People with extreme Eysenck Personality Scale - Brief Version (EPQ-BV) scores demonstrated the greatest level of executive impairment. Furthermore, the same degree of dysfunction was not seen in any individual with unremarkable EPQ-BV scores. This study indicates that specific patterns of executive dysfunction are related to maladaptive behavior in JME. Distinct behavioral patterns may be used to identify functional and anatomical differences between people with JME and for stratification to enable gene discovery. Copyright © 2014. Published by Elsevier Inc.

Clinical management of chronic obstructive pulmonary disease patients with muscle dysfunction

PubMed Central

Casadevall, Carme; Pascual, Sergi; Orozco-Levi, Mauricio; Barreiro, Esther

2016-01-01

Muscle dysfunction is frequently observed in chronic obstructive pulmonary disease (COPD) patients, contributing to their exercise limitation and a worsening prognosis. The main factor leading to limb muscle dysfunction is deconditioning, whereas respiratory muscle dysfunction is mostly the result of pulmonary hyperinflation. However, both limb and respiratory muscles are also influenced by other negative factors, including smoking, systemic inflammation, nutritional abnormalities, exacerbations and some drugs. Limb muscle weakness is generally diagnosed through voluntary isometric maneuvers such as handgrip or quadriceps muscle contraction (dynamometry); while respiratory muscle loss of strength is usually recognized through a decrease in maximal static pressures measured at the mouth. Both types of measurements have validated reference values. Respiratory muscle strength can also be evaluated determining esophageal, gastric and transdiaphragmatic maximal pressures although there is a lack of widely accepted reference equations. Non-volitional maneuvers, obtained through electrical or magnetic stimulation, can be employed in patients unable to cooperate. Muscle endurance can also be assessed, generally using repeated submaximal maneuvers until exhaustion, but no validated reference values are available yet. The treatment of muscle dysfunction is multidimensional and includes improvement in lifestyle habits (smoking abstinence, healthy diet and a good level of physical activity, preferably outside), nutritional measures (diet supplements and occasionally, anabolic drugs), and different modalities of general and muscle training. PMID:28066619

Echocardiographic evaluation of myocardial changes observed after closure of patent ductus arteriosus in dogs.

PubMed

Hamabe, L; Kim, S; Yoshiyuki, R; Fukayama, T; Nakata, T M; Fukushima, R; Tanaka, R

2015-01-01

Closure of PDA can be associated with echocardiographic changes including deterioration of LV systolic function. Although PDA is commonly encountered in dogs, few comprehensive reports of echocardiographic changes in dogs with PDA closure are available. To evaluate the short-term echocardiographic changes observed after PDA closure in dogs using strain analysis. Seventeen client-owned dogs with left-to-right PDA. Echocardiographic evaluations, including standard echocardiography and two-dimensional tissue tracking (2DTT), were performed before and within 3 days of PDA closure. Preclosure examination showed LV and left atrial dilatation indicating volume overload as a result of PDA. Closure of PDA resulted in significant reduction of LVIDd (<.0001) and LA/Ao (0.01) without change in LVIDs, suggestive of decreased preload. Postclosure LV systolic dysfunction was observed with significant decreased in FS (<.0001) and strain values (P = .0039 for radial strains, P = .0005 for circumferential strains). Additionally, significant LV dyssynchrony (P = .0162) was observed after closure of PDA. Closure of PDA resulted in decreased preload as a result of alleviation of LV volume overload, which in turn caused transient deterioration of LV systolic function. Additionally, this study demonstrated that strain analysis is load dependent. Therefore, care should be taken when interpreting strain measurements as an indicator of LV systolic function. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

Respiratory muscle dysfunction: a multicausal entity in the critically ill patient undergoing mechanical ventilation.

PubMed

Díaz, Magda C; Ospina-Tascón, Gustavo A; Salazar C, Blanca C

2014-02-01

Respiratory muscle dysfunction, particularly of the diaphragm, may play a key role in the pathophysiological mechanisms that lead to difficulty in weaning patients from mechanical ventilation. The limited mobility of critically ill patients, and of the diaphragm in particular when prolonged mechanical ventilation support is required, promotes the early onset of respiratory muscle dysfunction, but this can also be caused or exacerbated by other factors that are common in these patients, such as sepsis, malnutrition, advanced age, duration and type of ventilation, and use of certain medications, such as steroids and neuromuscular blocking agents. In this review we will study in depth this multicausal origin, in which a common mechanism is altered protein metabolism, according to the findings reported in various models. The understanding of this multicausality produced by the same pathophysiological mechanism could facilitate the management and monitoring of patients undergoing mechanical ventilation. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats.

PubMed

Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R; Cortés-Rojo, Christian

2015-01-01

Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (ΔΨ m ), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

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.

Underlying mechanism of the contractile dysfunction in atrophied ventricular myocytes from a murine model of hypothyroidism.

PubMed

Montalvo, Dolores; Pérez-Treviño, Perla; Madrazo-Aguirre, Katheryne; González-Mondellini, Fabio A; Miranda-Roblero, Hipólito O; Ramonfaur-Gracia, Diego; Jacobo-Antonio, Mariana; Mayorga-Luna, Maritza; Gómez-Víquez, Norma L; García, Noemí; Altamirano, Julio

2018-06-01

Hypothyroidism (Hypo) is a risk factor for cardiovascular diseases, including heart failure. Hypo rapidly induces Ca 2+ mishandling and contractile dysfunction (CD), as well as atrophy and ventricular myocytes (VM) remodeling. Hypo decreases SERCA-to-phospholamban ratio (SERCA/PLB), and thereby contributes to CD. Nevertheless, detailed spatial and temporal Ca 2+ cycling characterization in VM is missing, and contribution of other structural and functional changes to the mechanism underlying Ca 2+ mishandling and CD, as transverse tubules (T-T) remodeling, mitochondrial density (D mit ) and energy availability, is unclear. Therefore, in a rat model of Hypo, we aimed to characterize systolic and diastolic Ca 2+ signaling, T-T remodeling, D mit , citrate synthase (CS) activity and high-energy phosphate metabolites (ATP and phosphocreatine). We confirmed a decrease in SERCA/PLB (59%), which slowed SERCA activity (48%), reduced SR Ca 2+ (19%) and blunted Ca 2+ transient amplitude (41%). Moreover, assessing the rate of SR Ca 2+ release (dRel/dt), we found that early and maximum dRel/dt decreased, and this correlated with staggered Ca 2+ transients. However, dRel/dt persisted during Ca 2+ transient relaxation due to abundant late Ca 2+ sparks. Isoproterenol significantly up-regulated systolic Ca 2+ cycling. T-T were unchanged, hence, cannot explain staggered Ca 2+ transients and altered dRel/dt. Therefore, we suggest that these might be caused by RyR2 clusters desynchronization, due to diminished Ca 2+ -dependent sensitivity of RyR2, which also caused a decrease in diastolic SR Ca 2+ leak. Furthermore, D mit was unchanged and CS activity slightly decreased (14%), however, the ratio phosphocreatine/ATP did not change, therefore, energy deficiency cannot account for Ca 2+ and contractility dysregulation. We conclude that decreased SR Ca 2+ , due to slower SERCA, disrupts systolic RyR2 synchronization, and this underlies CD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Desmin loss and mitochondrial damage precede left ventricular systolic failure in volume overload heart failure.

PubMed

Guichard, Jason L; Rogowski, Michael; Agnetti, Giulio; Fu, Lianwu; Powell, Pamela; Wei, Chih-Chang; Collawn, James; Dell'Italia, Louis J

2017-07-01

Heart failure due to chronic volume overload (VO) in rats and humans is characterized by disorganization of the cardiomyocyte desmin/mitochondrial network. Here, we tested the hypothesis that desmin breakdown is an early and continuous process throughout VO. Male Sprague-Dawley rats had aortocaval fistula (ACF) or sham surgery and were examined 24 h and 4 and 12 wk later. Desmin/mitochondrial ultrastructure was examined by transmission electron microscopy (TEM) and immunohistochemistry (IHC). Protein and kinome analysis were performed in isolated cardiomyocytes, and desmin cleavage was assessed by mass spectrometry in left ventricular (LV) tissue. Echocardiography demonstrated a 40% decrease in the LV mass-to-volume ratio with spherical remodeling at 4 wk with ACF and LV systolic dysfunction at 12 wk. Starting at 24 h and continuing to 4 and 12 wk, with ACF there is TEM evidence of extensive mitochondrial clustering, IHC evidence of disorganization associated with desmin breakdown, and desmin protein cleavage verified by Western blot analysis and mass spectrometry. IHC results revealed that ACF cardiomyocytes at 4 and 12 wk had perinuclear translocation of αB-crystallin from the Z disk with increased α, β-unsaturated aldehyde 4-hydroxynonelal. Use of protein markers with verification by TUNEL staining and kinome analysis revealed an absence of cardiomyocyte apoptosis at 4 and 12 wk of ACF. Significant increases in protein indicators of mitophagy were countered by a sixfold increase in p62/sequestosome-1, which is indicative of an inability to complete autophagy. An early and continuous disruption of the desmin/mitochondrial architecture, accompanied by oxidative stress and inhibition of apoptosis and mitophagy, suggests its causal role in LV dilatation and systolic dysfunction in VO. NEW & NOTEWORTHY This study provides new evidence of early onset (24 h) and continuous (4-12 wk) desmin misarrangement and disruption of the normal sarcomeric and mitochondrial architecture throughout the progression of volume overload heart failure, suggesting a causal link between desmin cleavage and mitochondrial disorganization and damage.

Early Detection of Subclinical Uremic Cardiomyopathy Using Two-Dimensional Speckle Tracking Echocardiography.

PubMed

Hassanin, Noha; Alkemary, Alkhateeb

2016-04-01

Overhydration has a deleterious effect on cardio myocytes. This study was designated to evaluate left ventricular (LV) systolic and diastolic dysfunction in patients with various stages of chronic kidney disease (CKD) using conventional, tissue Doppler and two-dimensional speckle tracking echocardiography (2DSTE). Forty controls and 90 CKD patients, aged 49.3 ± 14 years old, were enrolled in the study. Patients were divided into 3 groups depending on their glomerular filtration rate. Group 1 (≥60 mL/min per 1.73 m(2) ), group 2 (≤60 mL/min per 1.73 m(2) ), and group 3 (≤60 mL/min per 1.73 m(2) and on regular dialysis for at least 12 months). Pulsed-Doppler and tissue Doppler studies were used to estimate LV filling pressure E/E'. Using 2DSTE, circumferential, radial, and longitudinal functions of the LV have been measured. LV longitudinal systolic strain, early, and late diastolic strain rates were significantly reduced in CKD patients (-16.9 ± 3.8%, 1.6 ± 0.5%, and 1.3 ± 0.4% in CKD vs. -22.5 ± 0.6%, 2.3 ± 0.2%, and 1.9 ± 0.1% in controls, P < 0.001 for all), and no difference was observed in terms of the circumferential LV functions (-22.4 ± 1.7 vs. -22.5 ± 1.4, P = 0.567). Severity of the kidney dysfunction appears to parallel with the rise of E/E' significantly (P < 0.001). In CKD, although the longitudinal and radial systolic functions were reduced, LV ejection fraction may remain within normal limits due to the preservation of the circumferential functions. Early detection of uremic cardiomyopathy might provide useful information for the risk stratification and decide the proper dialysis therapy in these patients. © 2015, Wiley Periodicals, Inc.

Paced QT interval as a risk factor for new-onset left ventricular systolic dysfunction and cardiac death after permanent pacemaker implantation.

PubMed

Cho, Eun Jeong; Park, Seung-Jung; Park, Kyoung Min; On, Young Keun; Kim, June Soo

2016-01-15

Prolongation of corrected QT (QTc) interval reflects an increased risk of fatal arrhythmia and cardiac death in various populations. However, it is not clear whether the paced-QTc (p-QTc) interval is associated with new-onset left ventricular systolic dysfunction (new-LVSD) or cardiac death. In 491 consecutive patients (64 ± 14 years) with preserved LV ejection fraction (64 ± 7%), the p-QTc interval was measured within 2 weeks after PPM implantation. We assessed the rates of new-LVSD and cardiac death based on the degree of p-QTc interval. During the follow-up period (78 ± 51 months), new-LVSD and cardiac death were identified in 53 (10.8%) and 26 (5.3%) patients, respectively. Patients with new-LVSD had more frequent atrioventricular block (P=0.041), a higher percentage of ventricular pacing (P=0.005), a longer p-QRS duration (P<0.001), and more prolonged p-QTc interval (P<0.001) compared to those without new-LVSD. There was a graded increase in the rates of new-LVSD (P<0.001) and cardiac death (P=0.001) from the patients in the lowest to those in the highest tertile of the p-QTc interval. Additionally, the incidence of cardiac death was significantly elevated especially in the patients with new-LVSD and wider p-QTc interval. In Cox regression analyses, the p-QTc interval was independently associated with new-LVSD and cardiac death even after adjusted with various relevant confounding factors. Prolonged p-QTc interval was closely associated with new-LVSD and cardiac death after PPM implantation in patients with preserved LV systolic function. The rate of cardiac death significantly increased especially in patients who showed more p-QTc widening along with new-LVSD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ethnic differences in macrovascular and microvascular function in systolic heart failure.

PubMed

Shantsila, Eduard; Wrigley, Benjamin; Shantsila, Alena; Tapp, Luke D; Blann, Andrew D; Gill, Paramjit S; Lip, Gregory Y H

2011-11-01

Endothelial dysfunction is implicated in the pathophysiological features of heart failure (HF), and ethnic differences in the presentation of cardiovascular disease are evident, with an excess seen among South Asians (SAs). However, data on ethnic differences in endothelial function in HF are limited. In a cross-sectional study, we recruited 128 subjects with systolic HF: 50 SAs, 50 whites, and 28 African Caribbeans (ACs). In addition, SAs with systolic HF were compared with 40 SAs with coronary artery disease without HF ("disease controls") and 40 SA healthy controls. Macrovascular endothelial function was assessed by measurement of flow-mediated dilation (FMD) in response to hyperemia, arterial stiffness was assessed by the pulse-wave velocity, and microvascular endothelial function was assessed by forearm laser Doppler flowmetry. CD144-expressing endothelial microparticles were measured by flow cytometry. When compared with disease controls and healthy controls, SAs with HF had an impaired microvascular response to acetylcholine (P=0.001) and reduced FMD (P<0.001). In comparing ethnic groups, SAs with HF had an impaired response to acetylcholine (123±95.5%) compared with whites (258±156%) and ACs (286±173%, P<0.001 for both). Whites had a higher FMD (8.49±4.63%) than SAs (4.76±4.78%, P<0.001) and ACs (4.55±3.56%, P=0.01). No difference in endothelial-independent response was observed between study groups or in pulse-wave velocity. Ethnicity remained associated with microvascular endothelial function even after adjustment for age, presence of hypertension and diabetes mellitus, blood pressure, and glucose levels (P=0.003). There were no differences in numbers of endothelial microparticles. The SAs with HF have impaired microvascular and macrovascular endothelial function but preserved arterial elastic properties. Significant ethnic differences in endothelial function are evident in subjects with HF, with ethnicity being associated with microvascular endothelial dysfunction in this disorder.

Prognostic incremental role of right ventricular function in acute decompensation of advanced chronic heart failure.

PubMed

Frea, Simone; Pidello, Stefano; Bovolo, Virginia; Iacovino, Cristina; Franco, Erica; Pinneri, Francesco; Galluzzo, Alessandro; Volpe, Alessandra; Visconti, Massimiliano; Peirone, Andrea; Morello, Mara; Bergerone, Serena; Gaita, Fiorenzo

2016-05-01

The purpose of this study was to evaluate the additional prognostic value of echocardiography in acute decompensation of advanced chronic heart failure (CHF), focusing on right ventricular (RV) dysfunction and its interaction with loading conditions. Few data are available on the prognostic role of echocardiography in acute HF and on the significance of pulmonary hypertension in patients with severe RV failure. A total of 265 NYHA IV patients admitted for acute decompensation of advanced CHF (EF 22 ± 7%, systolic blood pressure 107 ± 20 mmHg) were prospectively enrolled. Fifty-nine patients met the primary composite endpoint of cardiac death, urgent heart transplantation, and urgent mechanical circulatory support implantation at 90 days. Pulmonary hypertension failed to predict events, while patients with a low transtricuspid systolic gradient (TR gradient <20 mmHg) showed a worse outcome [hazard ratio (HR) 2.37, 95% confidence interval (CI) 1.12-5.00, P = 0.02]. RV dysfunction [tricuspid annular plane systolic excursion (TAPSE) ≤14 mm] in the presence of a low TR gradient identified patients at higher risk of events (HR 2.97, 95% CI 1.19-7.41, P = 0.02). Multivariate analysis showed as best predictors of outcome low RV contraction pressure index (RVCPI), defined as TAPSE × TR gradient, and high estimated right atrial pressure (eRAP). Adding RVCPI (<400 mm*mmHg) and eRAP (≥20 mmHg) to conventional clinical (ADHERE risk tree and NT-proBNP) and echocardiographic risk evaluation resulted in an increase in net reclassification improvement of +19.1% and +20.1%, respectively (P = 0.01) and in c-statistic from 0.59 to 0.73 (P < 0.01). In acute decompensation of advanced CHF, pulmonary hypertension failed to predict events. The in-hospital and short-term prognosis can be better predicted by eRAP and RVCPI. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Guideline adherence for pharmacotherapy of chronic systolic heart failure in general practice: a closer look on evidence-based therapy.

PubMed

Peters-Klimm, F; Müller-Tasch, T; Schellberg, D; Remppis, A; Barth, A; Holzapfel, N; Jünger, J; Herzog, W; Szecsenyi, J

2008-04-01

There is robust evidence for effective pharmacotherapy of chronic (systolic) heart failure (CHF) which has led to the creation of guidelines, but many surveys evaluating CHF treatment show an under-utilisation of relevant drugs, while setting and patient population appear to be crucial for adequate appraisal of treatment patterns. To evaluate the guideline adherence (GA) of general practitioners (GPs) in a well-defined patient population with CHF in primary care (PC). A cross-sectional analysis was performed with the data of 167 patients enrolled in 37 GP practices (Germany) with documented left ventricular systolic dysfunction (LVEF: 33.3 +/- 6.9%). GA was assessed as usual (prescribing "yes" or "no"), through evaluation of target dosing, while adjusting for potential clinical contraindications, and through a modified Guideline Adherence Indicator-3 (mGAI-3), which assesses three relevant groups of substances according to New York Heart Association (NYHA) functional class: ACE-Inhibitors (ACE-I) or angiotensin receptor blockers (ARB), beta-blockers (BB) and aldosterone-antagonists (AA). Prescription rates for ACE-I/ARB, BB or both were 80%, 75% and 62%, respectively. The proportion of target doses reached for ACE-I was 16%, for BB only 8%. When adjusted for potential (mainly relative) contraindications (COPD, heart rate <60/min, hypotension, hyperkalaemia and renal dysfunction), the percentage of target doses reached increased to 49% for ACE-I/ARBs and 46% for BB. Application of the mGAI-3 showed moderate to perfect GA for usual assessment, proportion of target dose reached and adjusted in 83%, 16% and 55% of the patients, respectively. In the context of this patient and doctor setting, life-saving treatment was provided above average when assessed by usual criteria. The application of additional criteria showed further room for improvement. Future interventions aiming at optimisation should be tailored to the needs of doctors and patients likewise.

Predicting Cardiotoxic Effects of Carbon Monoxide Poisoning Using Speckle Tracking Echocardiography.

PubMed

Saraçoğlu, Erhan; Vuruşkan, Ertan; Kılıç, Salih; Çekici, Yusuf; Onur, Bahaeddin; Arslan, Yavuz; Kılıç, Ertuğrul; Aykut, Ömer

2018-04-01

Carbon monoxide (CO) poisoning could cause significant cardiac injury. This study aimed to evaluate patients with CO poisoning by using speckle tracking echocardiography (STE), a potentially more sensitive technique, to identify left systolic ventricular dysfunction for the first time in the literature. Seventy-two patients who were exposed to CO poisoning were studied. Blood collection and echocardiography were performed at admission and after patients' discharge on days 10-15 (mean 12 days). Global longitudinal strain (GLS) and global circumferential strain (GCS) were calculated using STE. In order to find the normal strain levels and to compare it to the patient with CO poisoning, 35 healthy subjects were included in the study. Left ventricular ejection fraction was analyzed according to Simpson's method. Patients were divided into two groups based on their LVEF values. LVEF < 55%, Group 1 (n = 24); LVEF ≥ 55%, Group 2 (n = 48). The reduction in Group 1 strain levels decreased in correlation with LVEF (p < 0.001) while in Group 2, there were no significant changes in LVEF but strain levels were significantly reduced (p = 0.091; p < 0.001). Compared with the control group patients, admission GLS and GLC values of CO-poisoned patients were significantly low both in Group 1 and 2. On the contrary, no significant difference was observed when compared with follow-up GLS value. For prediction of CO cardiotoxicity, the cutoff value of GLS was ≥ - 19.1 with a sensitivity of 70.3% and a specificity of 100% [(AUC) 0.840, 95% (CI) 0.735-0.916; p < 0.001] in the ROC curve analyses. GLS was found as independent predictors of cardiotoxicity. Our study demonstrates the potential of using systolic strain values obtained using 2D-STE in determining cardiotoxicity due to CO poisoning. Speckle tracking echocardiography has the potential of demonstrating subtle LV systolic dysfunction even in CO poisoning patients with preserved EF.

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.

Exposure to low mercury concentration in vivo impairs myocardial contractile function

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

Furieri, Lorena Barros; Fioresi, Mirian; Junior, Rogerio Faustino Ribeiro

2011-09-01

Increased cardiovascular risk after mercury exposure has been described but cardiac effects resulting from controlled chronic treatment are not yet well explored. We analyzed the effects of chronic exposure to low mercury concentrations on hemodynamic and ventricular function of isolated hearts. Wistar rats were treated with HgCl{sub 2} (1st dose 4.6 {mu}g/kg, subsequent dose 0.07 {mu}g/kg/day, im, 30 days) or vehicle. Mercury treatment did not affect blood pressure (BP) nor produced cardiac hypertrophy or changes of myocyte morphometry and collagen content. This treatment: 1) in vivo increased left ventricle end diastolic pressure (LVEDP) without changing left ventricular systolic pressure (LVSP)more » and heart rate; 2) in isolated hearts reduced LV isovolumic systolic pressure and time derivatives, and {beta}-adrenergic response; 3) increased myosin ATPase activity; 4) reduced Na{sup +}-K{sup +} ATPase (NKA) activity; 5) reduced protein expression of SERCA and phosphorylated phospholamban on serine 16 while phospholamban expression increased; as a consequence SERCA/phospholamban ratio reduced; 6) reduced sodium/calcium exchanger (NCX) protein expression and {alpha}-1 isoform of NKA, whereas {alpha}-2 isoform of NKA did not change. Chronic exposure for 30 days to low concentrations of mercury does not change BP, heart rate or LVSP but produces small but significant increase of LVEDP. However, in isolated hearts mercury treatment promoted contractility dysfunction as a result of the decreased NKA activity, reduction of NCX and SERCA and increased PLB protein expression. These findings offer further evidence that mercury chronic exposure, even at small concentrations, is an environmental risk factor affecting heart function. - Highlights: > Unchanges blood pressure, heart rate, systolic pressure. > Increases end diastolic pressure. > Promotes cardiac contractility dysfunction. > Decreases NKA activity, NCX and SERCA, increases PLB protein expression. > Small concentrations constitutes environmental cardiovascular risk factor.« less

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.

Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance.

PubMed

Kim, Jiwon; Medicherla, Chaitanya B; Ma, Claudia L; Feher, Attila; Kukar, Nina; Geevarghese, Alexi; Goyal, Parag; Horn, Evelyn; Devereux, Richard B; Weinsaft, Jonathan W

2016-01-01

Non-ischemic fibrosis (NIF) on cardiac magnetic resonance (CMR) has been linked to poor prognosis, but its association with adverse right ventricular (RV) remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress. The population comprised patients with RV dysfunction (EF<50%) undergoing CMR and transthoracic echo within a 14 day (5 ± 3) interval. Cardiac structure, function, and NIF were assessed on CMR. Pulmonary artery systolic pressure (PASP) was measured on echo. 118 patients with RV dysfunction were studied, among whom 47% had NIF. Patients with NIF had lower RVEF (34 ± 10 vs. 39 ± 9%; p = 0.01) but similar LVEF (40 ± 21 vs. 39 ± 18%; p = 0.7) and LV volumes (p = NS). RV wall stress was higher with NIF (17 ± 7 vs. 12 ± 6 kPa; p < 0.001) corresponding to increased RV end-systolic volume (143 ± 79 vs. 110 ± 36 ml; p = 0.006), myocardial mass (60 ± 21 vs. 53 ± 17 gm; p = 0.04), and PASP (52 ± 18 vs. 41 ± 18 mmHg; p = 0.001). NIF was associated with increased wall stress among subgroups with isolated RV (p = 0.005) and both RV and LV dysfunction (p = 0.003). In multivariable analysis, NIF was independently associated with RV volume (OR = 1.17 per 10 ml, [CI 1.04-1.32]; p = 0.01) and PASP (OR = 1.43 per 10 mmHg, [1.14-1.81]; p = 0.002) but not RV mass (OR = 0.91 per 10 gm, [0.69-1.20]; p = 0.5) [model χ2 = 21; p<0.001]. NIF prevalence was higher in relation to PA pressure and RV dilation and was > 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001). Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling.

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.

Coronary arterial BK channel dysfunction exacerbates ischemia/reperfusion-induced myocardial injury in diabetic mice.

PubMed

Lu, Tong; Jiang, Bin; Wang, Xiao-Li; Lee, Hon-Chi

2016-09-01

The large conductance Ca(2+)-activated K(+) (BK) channels, abundantly expressed in coronary artery smooth muscle cells (SMCs), play a pivotal role in regulating coronary circulation. A large body of evidence indicates that coronary arterial BK channel function is diminished in both type 1 and type 2 diabetes. However, the consequence of coronary BK channel dysfunction in diabetes is not clear. We hypothesized that impaired coronary BK channel function exacerbates myocardial ischemia/reperfusion (I/R) injury in streptozotocin-induced diabetic mice. Combining patch-clamp techniques and cellular biological approaches, we found that diabetes facilitated the colocalization of angiotensin II (Ang II) type 1 receptors and BK channel α-subunits (BK-α), but not BK channel β1-subunits (BK-β1), in the caveolae of coronary SMCs. This caveolar compartmentation in vascular SMCs not only enhanced Ang II-mediated inhibition of BK-α but also produced a physical disassociation between BK-α and BK-β1, leading to increased infarct size in diabetic hearts. Most importantly, genetic ablation of caveolae integrity or pharmacological activation of coronary BK channels protected the cardiac function of diabetic mice from experimental I/R injury in both in vivo and ex vivo preparations. Our results demonstrate a vascular ionic mechanism underlying the poor outcome of myocardial injury in diabetes. Hence, activation of coronary BK channels may serve as a therapeutic target for cardiovascular complications of diabetes.

Obstructive Sleep Apnea is Linked to Depression and Cognitive Impairment: Evidence and Potential Mechanisms

PubMed Central

Kerner, Nancy A.; Roose, Steven P.

2017-01-01

Obstructive sleep apnea (OSA) is highly prevalent but very frequently undiagnosed. OSA is an independent risk factor for depression and cognitive impairment/dementia. Herein the authors review studies in the literature pertinent to the effects of OSA on the cerebral microvascular and neurovascular systems and present a model to describe the key pathophysiologic mechanisms that may underlie the associations, including hypoperfusion, endothelial dysfunction, and neuroinflammation. Intermittent hypoxia plays a critical role in initiating and amplifying these pathologic processes. Hypoperfusion and impaired cerebral vasomotor reactivity lead to the development or progression of cerebral small vessel disease (C-SVD). Hypoxemia exacerbates these processes, resulting in white matter lesions, white matter integrity abnormalities, and gray matter loss. Blood–brain barrier (BBB) hyperpermeability and neuroinflammation lead to altered synaptic plasticity, neuronal damage, and worsening C-SVD. Thus, OSA may initiate or amplify the pathologic processes of C-SVD and BBB dysfunction, resulting in the development or exacerbation of depressive symptoms and cognitive deficits. Given the evidence that adequate treatment of OSA with continuous positive airway pressure improves depression and neurocognitive functions, it is important to identify OSA when assessing patients with depression or cognitive impairment. Whether treatment of OSA changes the deteriorating trajectory of elderly patients with already-diagnosed vascular depression and cognitive impairment/dementia remains to be determined in randomized controlled trials. PMID:27139243

Mitochondrial dysfunction in obesity.

PubMed

de Mello, Aline Haas; Costa, Ana Beatriz; Engel, Jéssica Della Giustina; Rezin, Gislaine Tezza

2018-01-01

Obesity leads to various changes in the body. Among them, the existing inflammatory process may lead to an increase in the production of reactive oxygen species (ROS) and cause oxidative stress. Oxidative stress, in turn, can trigger mitochondrial changes, which is called mitochondrial dysfunction. Moreover, excess nutrients supply (as it commonly is the case with obesity) can overwhelm the Krebs cycle and the mitochondrial respiratory chain, causing a mitochondrial dysfunction, and lead to a higher ROS formation. This increase in ROS production by the respiratory chain may also cause oxidative stress, which may exacerbate the inflammatory process in obesity. All these intracellular changes can lead to cellular apoptosis. These processes have been described in obesity as occurring mainly in peripheral tissues. However, some studies have already shown that obesity is also associated with changes in the central nervous system (CNS), with alterations in the blood-brain barrier (BBB) and in cerebral structures such as hypothalamus and hippocampus. In this sense, this review presents a general view about mitochondrial dysfunction in obesity, including related alterations, such as inflammation, oxidative stress, and apoptosis, and focusing on the whole organism, covering alterations in peripheral tissues, BBB, and CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

Xanthine Oxidase Inhibition with Febuxostat Attenuates Systolic Overload-induced Left Ventricular Hypertrophy and Dysfunction in Mice

PubMed Central

Xu, Xin; Hu, Xinli; Lu, Zhongbing; Zhang, Ping; Zhao, Lin; Wessale, Jerry L.; Bache, Robert J.; Chen, Yingjie

2008-01-01

The purine analog xanthine oxidase (XO) inhibitors (XOIs), allopurinol and oxypurinol, have been reported to protect against heart failure secondary to myocardial infarction or rapid ventricular pacing. Since these agents might influence other aspects of purine metabolism that could influence their effect, this study examined the effect of the non-purine XOI, febuxostat, on pressure overload-induced left ventricular (LV) hypertrophy and dysfunction. Transverse aortic constriction (TAC) in mice caused LV hypertrophy and dysfunction as well as increased myocardial nitrotyrosine at 8 days. TAC also caused increased phosphorylated Akt (p-AktSer473), p42/44 extracellular signal-regulated kinase (p-ErkThr202/Tyr204) and mammalian target of rapamycin (mTOR) (p-mTORSer2488). XO inhibition with febuxostat (5mg/kg/day by gavage for 8 days) beginning ~60 minutes after TAC attenuated the TAC-induced LV hypertrophy and dysfunction. Febuxostat blunted the TAC-induced increases in nitrotyrosine (indicating reduced myocardial oxidative stress), p-ErkThr202/Tyr204 and p-mTORSer2488, with no effect on total Erk or total mTOR. Febuxostat had no effect on myocardial p-AktSer473 or total Akt. The results suggest that XO inhibition with febuxostat reduced oxidative stress in the pressure overloaded LV, thereby diminishing the activation of pathways that result in pathologic hypertrophy and contractile dysfunction. PMID:18995179

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.

[Treatment of multiple sclerosis symptoms and exacerbations].

PubMed

Prieto González, José María

2014-12-01

In the last few years, there has been an explosion of new drugs acting on the clinical course of multiple sclerosis (MS) but less attention has been paid to better knowledge of the symptoms of this disease and their pathogenesis and treatment, which is essential to improve patients' quality of life. Because many patients have numerous concurrent symptoms during their clinical course, their management is complex and consequently it is important to know which symptoms are a direct result of the degenerative lesions of MS. The present article describes all the therapeutic options available for spasticity and its associated pain, paroxystic symptoms, fatigue, genitourinary disorders and sexual dysfunction, tremor, ataxia, gait disorder and cognitive impairment, with special emphasis on novel treatments. The article also defines exacerbations, how to recognize them and the available treatments, mainly oral administration of high-dose methylprednisolone and plasmapheresis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Combined Circumferential and Longitudinal Left Ventricular Systolic Dysfunction in Patients with Rheumatoid Arthritis without Overt Cardiac Disease.

PubMed

Cioffi, Giovanni; Viapiana, Ombretta; Ognibeni, Federica; Dalbeni, Andrea; Gatti, Davide; Mazzone, Carmine; Faganello, Giorgio; Di Lenarda, Andrea; Adami, Silvano; Rossini, Maurizio

2016-07-01

Patients with rheumatoid arthritis have an increased risk for cardiovascular disease. Because of accelerated atherosclerosis and changes in left ventricular (LV) geometry, circumferential and longitudinal (C&L) LV systolic dysfunction (LVSD) may be impaired in these patients despite preserved LV ejection fraction. The aim of this study was to determine the prevalence of and factors associated with combined C&L LVSD in patients with rheumatoid arthritis. One hundred ninety-eight outpatients with rheumatoid arthritis without overt cardiac disease were prospectively analyzed from January through June 2014 and compared with 198 matched control subjects. C&L systolic function was evaluated by stress-corrected midwall shortening (sc-MS) and tissue Doppler mitral annular peak systolic velocity (S'). Combined C&L LVSD was defined if sc-MS was <86.5% and S' was <9.0 cm/sec (the 10th percentiles of sc-MS and S' derived in 132 healthy subjects). Combined C&L LVSD was detected in 56 patients (28%) and was associated with LV mass (odds ratio, 1.03; 95% CI, 1.01-1.06; P = .04) and concentric LV geometry (odds ratio, 2.76; 95% CI, 1.07-7.15; P = .03). By multiple logistic regression analysis, rheumatoid arthritis emerged as an independent predictor of combined C&L LVSD (odds ratio, 2.57; 95% CI, 1.06-6.25). The relationship between sc-MS and S' was statistically significant in the subgroup of 142 patients without combined C&L LVSD (r = 0.40, F < 0.001), having the best fitting by a linear function (sc-MS = 58.1 + 3.34 × peak S'; r(2) = 0.19, P < .0001), absent in patients with combined C&L LVSD. Combined C&L LVSD is detectable in about one fourth of patients with asymptomatic rheumatoid arthritis and is associated with LV concentric remodeling and hypertrophy. Rheumatoid arthritis predicts this worrisome condition, which may explain the increased risk for cardiovascular events in these patients. The aim of this "notice of clarification" is to analyze in brief the similarities and to underline the differences between the current article (defined as "paper J") and a separate article entitled "Prevalence and Factors Associated with Subclinical Left Ventricular Systolic Dysfunction Evaluated by Mid-Wall Mechanics in Rheumatoid Arthritis" (defined as "paper E"), which was written several months before paper J, and recently accepted for publication by the journal "Echocardiography" (Cioffi et al. http://dx.doi.org/10.1111/echo.13186). We wish to explain more clearly how the manuscript described in "paper J" relates to the "paper E" and the context in which it ought to be considered. Data in both papers were derived from the same prospective database, so that it would appear questionable if the number of the enrolled patients and/or their clinical/laboratory/echocardiographic characteristics were different. Accordingly, both papers reported that 198 patients with rheumatoid arthritis (RA) were considered and their characteristics were identical, due to the fact that they were the same subjects (this circumstance is common and mandatory among all studies in which the patients were recruited from the same database). These are the similarities between the papers. In paper E, which was written several months before paper J, we focused on the prevalence and factors associated with impaired circumferential left ventricular (LV) systolic function measured as mid-wall shortening (corrected for circumferential end-systolic stress). We found that 110 patients (56% of the whole population) demonstrated this feature. Thus, these 110 patients were the object of the study described in paper E, in which we specifically analyzed the factors associated with the impairment of stress-corrected mid-wall shortening (sc-MS). The conclusions of that paper were: (i) subclinical LV systolic dysfunction (LVSD) is detectable in more than half RA population without overt cardiac disease as measured by sc-MS, (ii) RA per se is associated with LVSD, and (iii) in RA patients only LV relative wall thickness was associated with impaired sc-MS based upon multivariate logistic regression analysis. Differently, in the paper J, we focused on the prevalence and factors associated with combined impairment of circumferential and longitudinal shortening (C&L) in 198 asymptomatic patients with RA. We found that 56 patients (28% of the whole population) presented this feature. Thus, these 56 patients were analyzed in detail in this study, as well as the factors associated with the combined impairment of C&L shortening. In paper J, we evaluated sc-MS as an indicator of circumferential systolic LV shortening, and we also determined the average of tissue Doppler measures of maximal systolic mitral annular velocity at four different sampling sites ( S') as an indicator of longitudinal LV systolic shortening. This approach clearly demonstrates that in paper J, we analyzed data deriving from the tissue Doppler analysis, which were not taken into any consideration in paper E. The investigation described in paper J made evident several original and clinically relevant findings. In patients with RA: (i) the condition of combined C&L left ventricular systolic dysfunction (LVSD) is frequent; (ii) these patients have comparable clinical and laboratory characteristics with those without combined C&L LVSD, but exhibit remarkable concentric LV geometry and increased LV mass, a phenotype that can be consider a model of compensated asymptomatic chronic heart failure; (iii) RA is an independent factor associated with combined C&L LVSD; (iv) no relationship between indexes of circumferential and longitudinal function exists in patients with combined C&L LVSD, while it is statistically significant and positive when the subgroup of patients without combined C&L LVSD is considered, having the best fitting by a linear function. All these findings are unique to the paper J and are not presented (they could not have been) in paper E. It appears clear that, starting from the same 198 patients included in the database, different sub-groups of patients were selected and analyzed in the two papers (they had different echocardiographic characteristics) and, consequently, different factors emerged by the statistical analyses as covariates associated with the different phenotypes of LVSD considered. Importantly, both papers E and J had a very long gestation because all reviewers for the different journals found several and important issues that merited to be addressed: a lot of changes were proposed and much additional information was required, particularly by the reviewers of paper E. Considering this context, it emerges that although paper E was written well before paper J, the two manuscripts were accepted at the same time (we received the letters of acceptance within a couple of weeks). Thus, the uncertainty about the fate of both manuscripts made it very difficult (if not impossible) to cite either of them in the other one and, afterward, we just did not think about this point anymore. Of note, the idea to combine in the analysis longitudinal function came therefore well after the starting process of revision of the paper E and was, in some way inspired by a reviewer's comment. That is why we did not put both findings in the same paper. We think that our explanations provide the broad audience of your journal a perspective of transparency and our respect for the readers' right to understand how the work described in the paper J relates to other work by our research group. Giovanni Cioffi On behalf of all co-authors Ombretta Viapiana, Federica Ognibeni, Andrea Dalbeni, Davide Gatti, Carmine Mazzone, Giorgio Faganello, Andrea Di Lenarda, Silvano Adami, and Maurizio Rossini. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

PubMed

Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2013-07-01

Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

Bromide supplementation exacerbated the renal dysfunction, injury and fibrosis in a mouse model of Alport syndrome.

PubMed

Yokota, Tsubasa; Omachi, Kohei; Suico, Mary Ann; Kojima, Haruka; Kamura, Misato; Teramoto, Keisuke; Kaseda, Shota; Kuwazuru, Jun; Shuto, Tsuyoshi; Kai, Hirofumi

2017-01-01

A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown. In this study, we administered daily for 16 weeks 75 mg/kg or 250 mg/kg (within clinical dosage) NaBr or NaCl (control) via drinking water to 6-week-old AS mice (mouse model of X-linked AS). Treatment with 75 mg/kg NaBr had no effect on AS progression. Surprisingly, compared with 250 mg/kg NaCl, 250 mg/kg NaBr exacerbated the progressive proteinuria and increased the serum creatinine and blood urea nitrogen in AS mice. Histological analysis revealed that glomerular injury, renal inflammation and fibrosis were exacerbated in mice treated with 250 mg/kg NaBr compared with NaCl. The expressions of renal injury markers (Lcn2, Lysozyme), matrix metalloproteinase (Mmp-12), pro-inflammatory cytokines (Il-6, Il-8, Tnf-α, Il-1β) and pro-fibrotic genes (Tgf-β, Col1a1, α-Sma) were also exacerbated by 250 mg/kg NaBr treatment. Notably, the exacerbating effects of Br- were not observed in wild-type mice. These findings suggest that Br- supplementation needs to be carefully evaluated for real positive health benefits and for the absence of adverse side effects especially in GBM diseases such as AS.

Aging Exacerbates Obesity-Induced Oxidative Stress and Inflammation in Perivascular Adipose Tissue in Mice: A Paracrine Mechanism Contributing to Vascular Redox Dysregulation and Inflammation

PubMed Central

Bailey-Downs, Lora C.; Tucsek, Zsuzsanna; Toth, Peter

2013-01-01

Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet–fed obese C57BL/6 mice. High-fat diet–induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet–induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals. PMID:23213032

Angiotensin II, hypertension and angiotensin II receptor antagonism: Roles in the behavioural and brain pathology of a mouse model of Alzheimer's disease.

PubMed

Wiesmann, Maximilian; Roelofs, Monica; van der Lugt, Robert; Heerschap, Arend; Kiliaan, Amanda J; Claassen, Jurgen Ahr

2017-07-01

Elevated angiotensin II causes hypertension and contributes to Alzheimer's disease by affecting cerebral blood flow. Angiotensin II receptor blockers may provide candidates to reduce (vascular) risk factors for Alzheimer's disease. We studied effects of two months of angiotensin II-induced hypertension on systolic blood pressure, and treatment with the angiotensin II receptor blockers, eprosartan mesylate, after one month of induced hypertension in wild-type C57bl/6j and AβPPswe/PS1ΔE9 (AβPP/PS1/Alzheimer's disease) mice. AβPP/PS1 showed higher systolic blood pressure than wild-type. Subsequent eprosartan mesylate treatment restored this elevated systolic blood pressure in all mice. Functional connectivity was decreased in angiotensin II-infused Alzheimer's disease and wild-type mice, and only 12 months of Alzheimer's disease mice showed impaired cerebral blood flow. Only angiotensin II-infused Alzheimer's disease mice exhibited decreased spatial learning in the Morris water maze. Altogether, angiotensin II-induced hypertension not only exacerbated Alzheimer's disease-like pathological changes such as impairment of cerebral blood flow, functional connectivity, and cognition only in Alzheimer's disease model mice, but it also induced decreased functional connectivity in wild-type mice. However, we could not detect hypertension-induced overexpression of Aβ nor increased neuroinflammation. Our findings suggest a link between midlife hypertension, decreased cerebral hemodynamics and connectivity in an Alzheimer's disease mouse model. Eprosartan mesylate treatment restored and beneficially affected cerebral blood flow and connectivity. This model could be used to investigate prevention/treatment strategies in early Alzheimer's disease.

Randomized trial of perindopril, enalapril, losartan and telmisartan in overweight or obese patients with hypertension.

PubMed

Nedogoda, Sergey V; Ledyaeva, Alla A; Chumachok, Elena V; Tsoma, Vera V; Mazina, Galina; Salasyuk, Alla S; Barykina, Irina N

2013-08-01

Obesity exacerbates hypertension and stimulates the renin-angiotensin-aldosterone system (RAAS). Full-dose RAAS inhibition could be a therapeutic option in overweight or obese patients with hypertension. This study compared four RAAS inhibitors at full therapeutic doses to determine their effect on blood pressure (BP) and cardiovascular risk factors in these patients. We conducted a 24-week, single-blind, randomized, parallel-group study in 120 overweight or obese patients (body mass index ≥27 kg/m(2)) with hypertension, aged 18-60 years. The primary endpoint was the change in mean 24-h systolic BP and diastolic BP from baseline to study end. Central BP, arterial stiffness, and metabolic and cardiac indices were also investigated. Patients were randomly allocated to perindopril 10 mg/day, enalapril 20 mg/day, losartan 100 mg/day or telmisartan 80 mg/day. Nonpharmacological interventions were also recommended. Reductions in mean 24-h systolic BP (and diastolic BP) were all significant (p < 0.05 versus baseline) for perindopril, enalapril, losartan and telmisartan: systolic BP -22, -11, -12 and -15 mmHg, respectively; (and diastolic BP -13, -6, -13 and -12 mmHg, respectively). Aortic elasticity improved with perindopril and telmisartan. Perindopril was associated with the greatest reductions in central aortic BP and leptin levels [30 % versus 2 %, 7 % and 14 % with enalapril, losartan and telmisartan, respectively (all p < 0.05 versus perindopril)]. Reductions in other BP, echocardiographic, metabolic and anthropometric parameters occurred with all treatments. Full-dose RAAS inhibition, particularly with perindopril, effectively reduces BP, improves arterial structure and regulates cardiovascular risk factors in overweight or obese patients with hypertension.

Case report: paradoxical ventricular septal motion in the setting of primary right ventricular myocardial failure.

PubMed

Maslow, Andrew; Schwartz, Carl; Mahmood, Feroze; Singh, Arun; Heerdt, Paul M

2009-07-01

In this report, a case of right ventricular (RV) failure, hemodynamic instability, and systemic organ failure is described to highlight how paradoxical ventricular systolic septal motion (PVSM), or a rightward systolic displacement of the interventricular septum, may contribute to RV ejection. Multiple inotropic medications and vasopressors were administered to treat right heart failure and systemic hypotension in a patient following combined aortic and mitral valve replacement. In the early postoperative period, echocardiographic evaluation revealed adequate left ventricular systolic function, akinesis of the RV myocardial tissues, and PVSM. In the presence of PVSM, RV fractional area of contraction was > or =35% despite akinesis of the primary RV myocardial walls. The PVSM appeared to contribute toward RV ejection. As a result, the need for multiple inotropes was re-evaluated, in considering that end-organ dysfunction was the result of systemic hypotension and prolonged vasopressor administration. After discontinuation of phosphodiesterase inhibitors, native vascular tone returned and the need for vasopressors declined. This was followed by recovery of systemic organ function. Echocardiographic re-evaluation two years later, revealed persistent akinesis of the RV myocardial tissues and PVSM, the latter appearing to contribute toward RV ejection. This case highlights the importance of left to RV interactions, and how PVSM may mediate these hemodynamic interactions.

Sleep-disordered breathing in patients with atrial fibrillation and normal systolic left ventricular function.

PubMed

Bitter, Thomas; Langer, Christoph; Vogt, Jürgen; Lange, Mathias; Horstkotte, Dieter; Oldenburg, Olaf

2009-03-01

Obstructive sleep apnea (OSA) is more common in patients with atrial fibrillation (AFib). Recently, an additional association between central sleep apnea/Cheyne-Stokes respiration (CSA/CSR) and AFib has been described. The aim of this study was to investigate the prevalence and type of sleep-disordered breathing in patients with AFib and normal systolic left ventricular function. 150 patients (110 men and 40 women, aged 66.1 +/- 1.7 years) underwent cardiorespiratory polygraphy, capillary blood gas analysis, measurement of NT-proBNP, and echocardiography to determine the diameter of the left atrium (LAD) and the peak systolic pulmonary artery pressure (PAP). Sleep-disordered breathing was documented in 74% of all patients with AFib (43% had OSA and 31% had CSA/CSR). Patients with CSA/CSR had a higher PAP, a higher apnea-hypopnea index, a greater LAD, and a lower capillary blood pCO(2) than patients with OSA. Patients with AFib were found to have not only a high prevalence of obstructive sleep apnea, as has been described previously, but also a high prevalence of CSA/CSR. It remains unknown whether CSA/CSR is more common in AFib because of diastolic dysfunction or whether phenomena associated with CSA/CSR predispose to AFib. Further research on this question is needed.

Reversion of left ventricular systolic dysfunction and abnormal stress test: by catheter ablation, in a patient with Wolff-Parkinson-White syndrome from Para-Hisian Kent bundle.

PubMed

Tu, Chung-Ming; Chu, Kai-Ming; Cheng, Cheng-Chung; Cheng, Shu-Mung; Lin, Wei-Shiang

2010-01-01

The diagnosis of Wolff-Parkinson-White syndrome is typically reserved for patients who experience ventricular pre-excitation and symptoms that are related to paroxysmal supraventricular tachycardia, such as chest pain, dyspnea, dizziness, palpitations, or syncope. Herein, we report the case of a 38-year-old woman who presented at our outpatient department because of exercise intolerance. Cardiac auscultation revealed a grade 2/6 pansystolic murmur over the left lower sternal border. Twelve-lead electrocardiography showed sinus rhythm at a rate of 76 beats/min, with a significant delta wave. Transthoracic echocardiography revealed abnormal left ventricular systolic function. The results of a thallium stress test were also abnormal. Coronary artery disease was suspected; however, coronary angiography yielded normal results. Electrophysiologic study revealed a para-Hisian Kent bundle and a dual atrioventricular nodal pathway. After radiofrequency catheter ablation was performed, the patient's left ventricular function improved and her symptoms disappeared. In Wolff-Parkinson-White syndrome, left ventricular systolic dyssynchrony can yield abnormal findings on echocardiography and thallium scanning--even in persons who have no cardiovascular risk factors. Physicians who are armed with this knowledge can avoid performing coronary angiography unnecessarily. Catheter ablation can reverse the dyssynchrony of the ventricle and improve the patient's symptoms.

Ameliorating Endothelial Mitochondrial Dysfunction Restores Coronary Function via Transient Receptor Potential Vanilloid 1-Mediated Protein Kinase A/Uncoupling Protein 2 Pathway.

PubMed

Xiong, Shiqiang; Wang, Peijian; Ma, Liqun; Gao, Peng; Gong, Liuping; Li, Li; Li, Qiang; Sun, Fang; Zhou, Xunmei; He, Hongbo; Chen, Jing; Yan, Zhencheng; Liu, Daoyan; Zhu, Zhiming

2016-02-01

Coronary heart disease arising from atherosclerosis is a leading cause of cardiogenic death worldwide. Mitochondria are the principal source of reactive oxygen species (ROS), and defective oxidative phosphorylation by the mitochondrial respiratory chain contributes to ROS generation. Uncoupling protein 2 (UCP2), an adaptive antioxidant defense factor, protects against mitochondrial ROS-induced endothelial dysfunction in atherosclerosis. The activation of transient receptor potential vanilloid 1 (TRPV1) attenuates vascular dysfunction. Therefore, whether TRPV1 activation antagonizes coronary lesions by alleviating endothelial mitochondrial dysfunction and enhancing the activity of the protein kinase A/UCP2 pathway warrants examination. ApoE(-/-), ApoE(-/-)/TRPV1(-/-), and ApoE(-/-)/UCP2(-/-) mice were fed standard chow, a high-fat diet (HFD), or the HFD plus 0.01% capsaicin. HFD intake profoundly impaired coronary vasodilatation and myocardial perfusion and shortened the survival duration of ApoE(-/-) mice. TRPV1 or UCP2 deficiency exacerbated HFD-induced coronary dysfunction and was associated with increased ROS generation and reduced nitric oxide production in the endothelium. The activation of TRPV1 by capsaicin upregulated UCP2 expression via protein kinase A phosphorylation, thereby alleviating endothelial mitochondrial dysfunction and inhibiting mitochondrial ROS generation. In vivo, dietary capsaicin supplementation enhanced coronary relaxation and prolonged the survival duration of HFD-fed ApoE(-/-) mice. These effects were not observed in ApoE(-/-) mice lacking the TRPV1 or UCP2 gene. The upregulation of protein kinase A /UCP2 via TRPV1 activation ameliorates coronary dysfunction and prolongs the lifespan of atherosclerotic mice by ameliorating endothelial mitochondrial dysfunction. Dietary capsaicin supplementation may represent a promising intervention for the primary prevention of coronary heart disease. © 2015 American Heart Association, Inc.

Endothelial Dysfunction Exacerbates Renal Interstitial Fibrosis through Enhancing Fibroblast Smad3 Linker Phosphorylation in the Mouse Obstructed Kidney

PubMed Central

Sun, Yu Bo Yang; Qu, Xinli; Li, Xueling; Nikolic-Paterson, David J.; Li, Jinhua

2013-01-01

Endothelial dysfunction and enhanced transforming growth factor-β (TGF-β)/Smad3 signalling are common features of progressive renal fibrosis. This study investigated a potential link between these mechanisms. In unilateral ureteric obstruction (UUO) we observed an acute (6 hr) down-regulation of nitric oxide synthase 3 (NOS3/eNOS) levels and increased phosphorylation of the linker region of Smad3 at T179 and S208 in Smad3/JNK complexes. These events preceded Smad3 C-terminal domain phosphorylation and the induction of myofibroblast proliferation at 48 hrs. Mice deficient in NOS3 showed enhanced myofibroblast proliferation and collagen accumulation compared to wild type mice in a 7 day UUO model. This was associated with enhanced phosphorylation of Smad3 T179 and S208 by 92% and 88%, respectively, whereas Smad3-C-terminal phosphorylation was not affected. Resolvin D1 (RvD1) can suppress renal fibrosis in the UUO model, and further analysis herein showed that RvD1 protected against endothelial dysfunction and suppressed Smad3/JNK complex formation with a consequent reduction in phosphorylation of Smad3 T179 and S208 by 78% and 65%, respectively, while Smad3 C-terminal phosphorylation was unaltered. In vitro, conditioned media from mouse microvascular endothelial cells (MMEC) treated with a general inhibitor of nitric oxide synthase (L-NAME) augmented the proliferation and collagen production of renal fibroblasts (NRK49F cells) compared to control MMEC media and this was associated with increased phosphorylation of JNK and Smad3 T179 and S208, whereas Smad3-C-terminal domain phosphorylation was unaffected. The addition of RvD1 to L-NAME treated MMEC abrogated these effects of the conditioned media on renal fibroblasts. Finally, Smad3 T179/V and S208/A mutations significantly inhibit TGF-β1 induced up-regulation collagen I promoter. In conclusion, these data suggest that endothelial dysfunction can exacerbate renal interstitial fibrosis through increased fibroblast proliferation and collagen production via enhanced Smad3 linker phosphorylation. PMID:24391884

Endothelial dysfunction exacerbates renal interstitial fibrosis through enhancing fibroblast Smad3 linker phosphorylation in the mouse obstructed kidney.

PubMed

Sun, Yu Bo Yang; Qu, Xinli; Li, Xueling; Nikolic-Paterson, David J; Li, Jinhua

2013-01-01

Endothelial dysfunction and enhanced transforming growth factor-β (TGF-β)/Smad3 signalling are common features of progressive renal fibrosis. This study investigated a potential link between these mechanisms. In unilateral ureteric obstruction (UUO) we observed an acute (6 hr) down-regulation of nitric oxide synthase 3 (NOS3/eNOS) levels and increased phosphorylation of the linker region of Smad3 at T179 and S208 in Smad3/JNK complexes. These events preceded Smad3 C-terminal domain phosphorylation and the induction of myofibroblast proliferation at 48 hrs. Mice deficient in NOS3 showed enhanced myofibroblast proliferation and collagen accumulation compared to wild type mice in a 7 day UUO model. This was associated with enhanced phosphorylation of Smad3 T179 and S208 by 92% and 88%, respectively, whereas Smad3-C-terminal phosphorylation was not affected. Resolvin D1 (RvD1) can suppress renal fibrosis in the UUO model, and further analysis herein showed that RvD1 protected against endothelial dysfunction and suppressed Smad3/JNK complex formation with a consequent reduction in phosphorylation of Smad3 T179 and S208 by 78% and 65%, respectively, while Smad3 C-terminal phosphorylation was unaltered. In vitro, conditioned media from mouse microvascular endothelial cells (MMEC) treated with a general inhibitor of nitric oxide synthase (L-NAME) augmented the proliferation and collagen production of renal fibroblasts (NRK49F cells) compared to control MMEC media and this was associated with increased phosphorylation of JNK and Smad3 T179 and S208, whereas Smad3-C-terminal domain phosphorylation was unaffected. The addition of RvD1 to L-NAME treated MMEC abrogated these effects of the conditioned media on renal fibroblasts. Finally, Smad3 T179/V and S208/A mutations significantly inhibit TGF-β1 induced up-regulation collagen I promoter. In conclusion, these data suggest that endothelial dysfunction can exacerbate renal interstitial fibrosis through increased fibroblast proliferation and collagen production via enhanced Smad3 linker phosphorylation.

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.

Is everything clear about Tako-tsubo syndrome?

PubMed

Petrov, Ivo S; Tokmakova, Mariya P; Marchov, Daniel N; Kichukov, Kostadin N

2011-01-01

Tako-tsubo syndrome is a novel cardio-vascular disease affecting predominantly postmenopausal women exposed to unexpected strong emotional or physical stress, in the absence of significant coronary heart disease. It is characterized by acute onset of severe chest pain and/or acute left ventricular failure, ECG-changes, typical left ventricular angiographic findings, good prognosis and positive resolution of the morphological and clinical manifestations. First described in 1990 in Japan by Sato, Tako-tsubo cardiomyopathy is characterized by transient contractile abnormalities of the left ventricle, causing typical left ventricular apical ballooning at end-systole with concomitant compensatory basal hyperkinesia. There are also atypical forms, presenting with left ventricular systolic dysfunction which affects the mid-portions of the left ventricle. The etiology of the disease still remains unclear. Many theories have been put forward about the potential underlying pathophysiological mechanisms that may trigger this syndrome among which are the theory of catecholamine excess, the theory of multivessel coronary vasospasm, the ischemic theory, and the theory of microvascular dysfunction and dynamic left ventricular gradient induced by elevated circulating catecholamine levels. Adequate management of Tako-tsubo syndrome demands immediate preparation for coronary angiography. Once the diagnosis is made, treatment is primarily symptomatic and includes monitoring for complications. Patients with Tako-tsubo syndrome most frequently develop acute LV failure, pulmonary edema, rhythm and conductive disturbances and apical thrombosis. Treatment is symptomatic and includes administration of diuretics, vasodilators and mechanical support of circulation with intra-aortic balloon counterpulsation.

Surgical technique of double switch procedure: Senning with arterial switch operation for congenitally corrected transposition of the great arteries with ventricular septal defect.

PubMed

Ilin, Alexey S; Teplov, Pavel V; Sakovich, Valeriy A; Ohye, Richard G

2016-01-01

We present a case of 12-month-old boy with congenitally corrected transposition of great arteries with L-looped ventricles and L-transposition of great arteries and ventricular septal defect. When admitted to the hospital, the patient had the appearance of congestive heart failure due to moderate to severe tricuspid valve regurgitation and right ventricle dysfunction. The pulmonary artery (PA) banding was required first because of low systolic pressure in the morphological left ventricle less than 70% confirmed by catheterization. Three months later, the patient appeared to be a good candidate for anatomical repair and a double switch procedure-Senning with arterial switch-was performed. The early postoperative period was relatively smooth and uneventful. Tricuspid valve insufficiency was resolved immediately after surgery. Mild systolic dysfunction of the left ventricle with mild mitral insufficiency was confirmed by the 2D strain method of echocardiography on the second day of the postoperative period and it improved over the next 21 days. Thirty days later after the procedure, the patient underwent catheterization of his superior vena cava tunnel because of the slightly increased blood flow velocity diagnosed by echocardiography. In 3 months after the surgery, the boy was asymptomatic and was doing well. The patient's functional status was I according to the NYHA classification. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Platelet TGF-β1 contributions to plasma TGF-β1, cardiac fibrosis, and systolic dysfunction in a mouse model of pressure overload

PubMed Central

Meyer, Alexander; Wang, Wei; Qu, Jiaxiang; Croft, Lori; Degen, Jay L.; Coller, Barry S.

2012-01-01

Circulating platelets contain high concentrations of TGF-β1 in their α-granules and release it on platelet adhesion/activation. We hypothesized that uncontrolled in vitro release of platelet TGF-β1 may confound measurement of plasma TGF-β1 in mice and that in vivo release and activation may contribute to cardiac pathology in response to constriction of the transverse aorta, which produces both high shear and cardiac pressure overload. Plasma TGF-β1 levels in blood collected from C57Bl/6 mice by the standard retro-bulbar technique were much higher than those obtained when prostaglandin E1 was added to inhibit release or when blood was collected percutaneously from the left ventricle under ultrasound guidance. Even with optimal blood drawing, plasma TGF-β1 was lower in mice rendered profoundly thrombocytopenic or mice with selectively low levels of platelet TGF-β1 because of megakaryocytespecific disruption of their TGF-β1 gene (Tgfb1flox). Tgfb1flox mice were also partially protected from developing cardiac hypertrophy, fibrosis, and systolic dysfunction in response to transverse aortic constriction. These studies demonstrate that plasma TGF-β1 levels can be assessed accurately, but it requires special precautions; that platelet TGF-β1 contributes to plasma levels of TGF-β1; and that platelet TGF-β1 contributes to the pathologic cardiac changes that occur in response to aortic constriction. PMID:22134166

Animal model of neuropathic tachycardia syndrome

NASA Technical Reports Server (NTRS)

Carson, R. P.; Appalsamy, M.; Diedrich, A.; Davis, T. L.; Robertson, D.

2001-01-01

Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.

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.

Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism.

PubMed

de Oliveira, Amanda Priscila; Bernardo, Cássia Rubia; Camargo, Ana Vitória da Silveira; Ronchi, Luiz Sérgio; Borim, Aldenis Albaneze; de Mattos, Cinara Cássia Brandão; de Campos Júnior, Eumildo; Castiglioni, Lílian; Netinho, João Gomes; Cavasini, Carlos Eugênio; Bestetti, Reinaldo Bulgarelli; de Mattos, Luiz Carlos

2015-01-01

The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region--rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.

Asymptomatic left ventricular systolic dysfunction in essential hypertension: prevalence, determinants, and prognostic value.

PubMed

Verdecchia, Paolo; Angeli, Fabio; Gattobigio, Roberto; Sardone, Mariagrazia; Porcellati, Carlo

2005-03-01

Prevalence, determinants, and prognostic value of asymptomatic left ventricular systolic dysfunction (LVSD) in uncomplicated subjects with essential hypertension are still incompletely known. We studied 2384 initially untreated subjects with hypertension, no previous cardiovascular disease, and no symptoms or physical signs of congestive heart failure (CHF). These subjects were studied at entry and followed for up to 17 years (mean 6.0). Asymptomatic LVSD (ALVSD), defined by an echocardiographic ejection fraction <50%, was found in 3.6% of subjects. Cigarette smoking (P=0.013), increased left ventricular (LV) mass (P=0.001), and higher 24-hour heart rate (P=0.014) were independent correlates of ALVSD. During follow-up, a first cardiovascular event occurred in 227 subjects, and 24 of these events were hospitalizations for symptomatic CHF. Incidence of CHF per 100 persons per year was 0.12 in patients without and 1.48 in patients with ALVSD (log-rank test P=0.0001). In a Cox model, after adjustment for age (P=0.0001), LV mass (P=0.0001), and cigarette smoking (P=0.039), LVSD conferred a markedly increased risk for CHF (odds ratio, 9.99; 95% confidence interval, 3.67 to 27.2). Incidence of coronary (0.84 versus 0.62x100 person years) and cerebrovascular (0.80 versus 0.62x100 person years) events did not differ (all P=NS) between subjects with and without ALVSD. ALVSD is a potent and early marker of evolution toward severe CHF requiring hospitalization in subjects with essential hypertension.

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.

Telemedicine Facilitates CHF Home Health Care for Those with Systolic Dysfunction

PubMed Central

Seibert, Pennie S.; Whitmore, Tiffany A.; Patterson, Carin; Parker, Patrick D.; Otto, Caitlin; Basom, Jean; Whitener, Nichole; Zimmerman, Christian G.

2008-01-01

An estimated 5 million Americans have congestive heart failure (CHF) and one in five over the age of 40 will develop CHF. There are numerous examples of CHF patients living beyond the years normally expected for people with the disease, usually attributed to taking an active role in disease management. A relatively new alternative for CHF outpatient care is telemedicine and e-health. We investigated the effects of a 6-week in-home telemedicine education and monitoring program for those with systolic dysfunction on the utilization of health care resources. We also measured the effects of the unit 4.5 months after its removal (a total of 6 months post introduction of the unit into the home). Concurrently, we assessed participants' perceptions of the value of having a telemedicine unit. Participants in the telemedicine group reported weighing more times a week with less variability than did the control group. Telemedicine led to a reduction in physician and emergency department visits and those in the experimental group reported the unit facilitating self-care, though this was not significantly different from the control group (possibly due to small sample size). These findings suggest a possibility for improvement in control of CHF when telemedicine is implemented. Our review of the literature also supports the role of telemedicine in facilitating home health care and self-management for CHF patients. There are many challenges still to be addressed before this potential can be reached and further research is needed to identify opportunities in telemedicine. PMID:18369411

What is the most cost-effective strategy to screen for left ventricular systolic dysfunction: natriuretic peptides, the electrocardiogram, hand-held echocardiography, traditional echocardiography, or their combination?

PubMed

Galasko, Gavin I W; Barnes, Sophie C; Collinson, Paul; Lahiri, Avijit; Senior, Roxy

2006-01-01

To assess the screening characteristics and cost-effectiveness of screening for left ventricular systolic dysfunction (LVSD) in community subjects. A total of 1392 members of the general public and 928 higher risk subjects were randomly selected from seven community practices. Attending subjects underwent an ECG, N-terminal pro-brain natriuretic peptide (NTproBNP) serum levels, and traditional echocardiography (TE). A total of 533 consecutive subjects underwent hand-held echocardiography (HE). The screening characteristics and cost-effectiveness (cost per case of LVSD diagnosed) of eight strategies to predict LVSD (LVSD <45% on TE) were compared. A total of 1205 subjects attended. Ninety six per cent of subjects with LVSD in the general population had identifiable risk factors. All screening strategies gave excellent negative predictive value. Screening high-risk subjects was most cost-effective, screening low-risk subjects least cost-effective. TE screening was the least cost-effective strategy. NTproBNP screening gave similar cost savings to ECG screening; HE screening greater cost-savings, and HE screening following NTproBNP or ECG pre-screening the greatest cost-savings, costing approximately 650 Euros per case of LVSD diagnosed in high-risk subjects (63% cost-savings vs.TE). Thus several different modalities allow cost-effective community-based screening for LVSD, especially in high-risk subjects. Such programmes would be cost-effective and miss few cases of LVSD in the community.

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.

Acute Exacerbation of Sleep Apnea by Hyperoxia Impairs Cognitive Flexibility in Brown-Norway Rats

PubMed Central

Topchiy, Irina; Amodeo, Dionisio A.; Ragozzino, Michael E.; Waxman, Jonathan; Radulovacki, Miodrag; Carley, David W.

2014-01-01

Study Objectives: To determine whether learning deficits occur during acute exacerbation of spontaneous sleep related breathing disorder (SRBD) in rats with high (Brown Norway; BN) and low (Zucker Lean; ZL) apnea propensity. Design: Spatial acquisition (3 days) and reversal learning (3 days) in the Morris water maze (MWM) with polysomnography (12:00–08:00): (1) with acute SRBD exacerbation (by 20-h hyperoxia immediately preceding reversal learning) or (2) without SRBD exacerbation (room air throughout). Setting: Randomized, placebo-controlled, repeated-measures design. Participants: 14 BN rats; 16 ZL rats. Interventions: 20-h hyperoxia. Measurements and Results: Apneas were detected as cessation of respiration ≥ 2 sec. Swim latency in MWM, apnea indices (AI; apneas/hour of sleep) and percentages of recording time for nonrapid eye movement (NREM), rapid eye movement (REM), and total sleep were assessed. Baseline AI in BN rats was more than double that of ZL rats (22.46 ± 2.27 versus 10.7 ± 0.9, P = 0.005). Hyperoxia increased AI in both BN (34.3 ± 7.4 versus 22.46 ± 2.27) and ZL rats (15.4 ± 2.7 versus 10.7 ± 0.9) without changes in sleep stage percentages. Control (room air) BN and ZL rats exhibited equivalent acquisition and reversal learning. Acute exacerbation of AI by hyperoxia produced a reversal learning performance deficit in BN but not ZL rats. In addition, the percentage of REM sleep and REM apnea index in BN rats during hyperoxia negatively correlated with reversal learning performance. Conclusions: Acute exacerbation of sleep related breathing disorder by hyperoxia impairs reversal learning in a rat strain with high apnea propensity, but not a strain with a low apnea propensity. This suggests a non-linear threshold effect may contribute to the relationships between sleep apnea and cognitive dysfunctions, but strain-specific differences also may be important. Citation: Topchiy I, Amodeo DA, Ragozzino ME, Waxman J, Radulovacki M, Carley DW. Acute exacerbation of sleep apnea by hyperoxia impairs cognitive flexibility in brown-norway rats. SLEEP 2014;37(11):1851-1861. PMID:25364080

Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature

PubMed Central

Brunetti, Orazio; Imbrici, Paola; Botti, Fabio Massimo; Pettorossi, Vito Enrico; D'Adamo, Maria Cristina; Valentino, Mario; Zammit, Christian; Mora, Marina; Gibertini, Sara; Di Giovanni, Giuseppe; Muscat, Richard; Pessia, Mauro

2012-01-01

Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K+ channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1V408A/+). Here, we investigated the neuromuscular transmission of Kv1.1V408A/+ ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve–muscle from Kv1.1+/+ and Kv1.1V408A/+ mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca2 + signals that occurred abnormally only in preparations dissected from Kv1.1V408A/+ mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca2 + homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K+ channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during fatigue or ischemic insult. PMID:22609489

Complex inhibition of autophagy by mitochondrial aldehyde dehydrogenase shortens lifespan and exacerbates cardiac aging.

PubMed

Zhang, Yingmei; Wang, Cong; Zhou, Jingmin; Sun, Aijun; Hueckstaedt, Lindsay K; Ge, Junbo; Ren, Jun

2017-08-01

Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a cascade of biological processes including aging. A number of autophagy regulators have been identified. Here we demonstrated that mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme with the most common single point mutation in humans, governs cardiac aging through regulation of autophagy. Myocardial mechanical and autophagy properties were examined in young (4months) and old (26-28months) wild-type (WT) and global ALDH2 transgenic mice. ALDH2 overexpression shortened lifespan by 7.7% without affecting aging-associated changes in plasma metabolic profiles. Myocardial function was compromised with aging associated with cardiac hypertrophy, the effects were accentuated by ALDH2. Aging overtly suppressed autophagy and compromised autophagy flux, the effects were exacerbated by ALDH2. Aging dampened phosphorylation of JNK, Bcl-2, IKKβ, AMPK and TSC2 while promoting phosphorylation of mTOR, the effects of which were exaggerated by ALDH2. Co-immunoprecipitation revealed increased dissociation between Bcl-2 and Beclin-1 (result of decreased Bcl-2 phosphorylation) in aging, the effect of which was exacerbated with ALDH2. Chronic treatment of the autophagy inducer rapamycin alleviated aging-induced cardiac dysfunction in both WT and ALDH2 mice. Moreover, activation of JNK and inhibition of either Bcl-2 or IKKβ overtly attenuated ALDH2 activation-induced accentuation of cardiomyocyte aging. Examination of the otherwise elderly individuals revealed a positive correlation between cardiac function/geometry and ALDH2 gene mutation. Taken together, our data revealed that ALDH2 enzyme may suppress myocardial autophagy possibly through a complex JNK-Bcl-2 and IKKβ-AMPK-dependent mechanism en route to accentuation of myocardial remodeling and contractile dysfunction in aging. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Interferon-γ-Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients

PubMed Central

Zhou, Jing; Qin, Lingfeng; Yi, Tai; Ali, Rahmat; Li, Qingle; Jiao, Yang; Li, Guangxin; Tobiasova, Zuzana; Huang, Yan; Zhang, Jiasheng; Yun, James J.; Sadeghi, Mehran M.; Giordano, Frank J.; Pober, Jordan S.; Tellides, George

2015-01-01

Rationale Transplantation, the most effective therapy for end-stage organ failure, is markedly limited by early-onset cardiovascular disease (CVD) and premature death of the host. The mechanistic basis of this increased CVD is not fully explained by known risk factors. Objective To investigate the role of alloimmune responses in promoting CVD of organ transplant recipients. Methods and Results We established an animal model of graft-exacerbated host CVD by combining murine models of atherosclerosis (apolipoprotein E-deficient recipients on standard diet) and of intra-abdominal graft rejection (heterotopic cardiac transplantation without immunosuppression). CVD was absent in normolipidemic hosts receiving allogeneic grafts and varied in severity among hyperlipidemic grafted hosts according to recipient-donor genetic disparities, most strikingly across an isolated major histocompatibility complex class II antigen barrier. Host disease manifested as increased atherosclerosis of the aorta that also involved the native coronary arteries and new findings of decreased cardiac contractility, ventricular dilatation, and diminished aortic compliance. Exacerbated CVD was accompanied by greater levels of circulating cytokines, especially interferon-γ and other Th1-type cytokines, and showed both systemic and intra-lesional activation of leukocytes, particularly T helper cells. Serologic neutralization of interferon-γ after allotransplantation prevented graft-related atherosclerosis, cardiomyopathy, and aortic stiffening in the host. Conclusions Our study reveals that sustained activation of the immune system due to chronic allorecognition exacerbates the atherogenic diathesis of hyperlipidemia and results in de novo cardiovascular dysfunction in organ transplant recipients. PMID:26399469

The association between metabolic syndrome and its components and heart failure in patients referred to a primary care facility.

PubMed

Coelho, Flávio Augusto Colucci; Moutinho, Marco Aurélio Espósito; Miranda, Verônica Alcooforado de; Tavares, Leandro Reis; Rachid, Maurício; Rosa, Maria Luiza Garcia; Mesquita, Evandro Tinoco

2007-07-01

Metabolic syndrome (MS) is characterized by a collection of risk factors that are associated with elevated rates of cardiovascular events and the risk of developing heart failure (HF). In our field, the association of MS in stable chronic HF patients has not been established. To determine the prevalence of MS in relation to gender and HF type in patients treated at a Primary Care Facility. Between January 2005 and August 2006, 144 patients were included in a cross sectional study. An echocardiogram, using the modified criteria of the EPICA study, was performed to determine whether or not the patient had HF, and of which type. Statistical analysis was conducted using the software SAS System, version 6.04, and statistical significance was established as 5%. MS was observed in 111 patients (77%), of which 73 (66%) were females: odds ratio (OR) 0.195--(confidence interval--CI = 0.08 - 0.46) and p< 0.0001. HF was identified in 102 patients (71%) with a great correlation between females and the presence of MS: 51 patients (65%); OR 0.116 (CI = 0.36- 0.37) and p < 0.0001. Among the HF patients, 61 (42%) presented HF with preserved systolic function and 41 (29%) with systolic dysfunction; p = ns. HF with preserved systolic function was associated with the presence of MS in 53 (87%) of the 61 patients, p = 0.022. In our community, MS is closely related to HF with preserved systolic function and to the female gender.

Transient left ventricular systolic dysfunction following surgical closure of large patent ductus arteriosus among children and adolescents operated at the cardiac centre, Ethiopia

PubMed Central

2013-01-01

Background Patent ductus arteriosus (PDA) is one of the commonest congenital heart diseases that require closure within the first few months after birth. The residential area of patients affects the size of the PDA: living in highlands, like most places in Ethiopia, is a risk for having larger sized PDA. Closure of these congenital heart defects is usually performed at an early age in places where capable centers are available. In Ethiopia, closure of these defects is done on mission basis often at an older age. Recently, limited reports came about the occurrence of postoperative left ventricular systolic dysfunction (POLVD) following closure of PDA though full explanation is still lacking. Objective To determine the rate of and time to improvement of POLVD and the factors associated with it in children and adolescents who underwent surgical closure of PDA. Method All children and adolescents who underwent surgical closure of PDA at the Cardiac Center, Ethiopia (CCE) had postoperative follow up with echocardiography. Serial left ventricular ejection fraction (LVEF) and fiber shortening (FS) values were recorded for all of them. SPSS 20 was used to analyze the data. Results A total of 36 children and adolescents who underwent surgical closure of PDA from January 2009 to December 2012 and who fulfilled the inclusion criteria were studied. Their mean age at intervention was 8.52 years (SD = 5.23 years), 77.80% were females. The mean duct size as determined by either echocardiography or intra-operative by the surgeon was 10.31 mm (SD = 3.20 mm). They were followed for a mean duration of 24.80 months (SD = 12.36 months) following surgical closure of PDA. The mean LVEF and FS decreased from 65.06% and 35.28% preoperatively to 54.83% and 28.40% post-operatively respectively. Fifteen (42.86%) of the patients had a post-operative LVEF of less than 55%. The mean time to normalization of systolic function was 5.11 weeks (SD = 3.30 weeks). Having an associated cardiac lesion was an independent predictor of POLVD. Conclusions We conclude that there is a high rate of POLVD following surgical closure of large PDA in highlanders. We recommend a serial and systematic follow up of these children postoperatively. Those with a significant cardiac dysfunction may need cardiac medications like Angiotensin Converting Enzyme Inhibitors (ACEI). PMID:23721219

Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.

PubMed

Fox, Kim; Ford, Ian; Steg, P Gabriel; Tendera, Michal; Ferrari, Roberto

2008-09-06

Ivabradine specifically inhibits the I(f) current in the sinoatrial node to lower heart rate, without affecting other aspects of cardiac function. We aimed to test whether lowering the heart rate with ivabradine reduces cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction. Between December, 2004, and December, 2006, we screened 12 473 patients at 781 centres in 33 countries. We enrolled 10 917 eligible patients who had coronary artery disease and a left-ventricular ejection fraction of less than 40% in a randomised, double-blind, placebo-controlled, parallel-group trial. 5479 patients received 5 mg ivabradine, with the intention of increasing to the target dose of 7.5 mg twice a day, and 5438 received matched placebo in addition to appropriate cardiovascular medication. The primary endpoint was a composite of cardiovascular death, admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure. We analysed patients by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00143507. Mean heart rate at baseline was 71.6 (SD 9.9) beats per minute (bpm). Median follow-up was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (SE 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. Ivabradine did not affect the primary composite endpoint (hazard ratio 1.00, 95% CI 0.91-1.1, p=0.94). 1233 (22.5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22.8%) controls (p=0.70). In a prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect the primary composite outcome (hazard ratio 0.91, 95% CI 0.81-1.04, p=0.17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0.64, 95% CI 0.49-0.84, p=0.001) and coronary revascularisation (0.70, 95% CI 0.52-0.93, p=0.016). Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have heart rates of 70 bpm or greater.

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.

Pudendal Nerve and Internal Pudendal Artery Damage May Contribute to Radiation-Induced Erectile Dysfunction

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

Nolan, Michael W., E-mail: mwnolan@ncsu.edu; Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado; Marolf, Angela J.

Purpose/Objectives: Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction (RI-ED) remains poorly understood. A novel animal model was developed to study RI-ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose was to describe vascular and neurogenic injuries after the irradiation of only the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB) with varying doses of radiation. Methods and Materials: Dogs were treated with 50, 40, or 30 Gy to themore » prostate, NVB, and PB, or 50 Gy to either the NVB or the PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed before and after SBRT. The results of these bioassays were correlated with histopathologic changes. Results: SBRT caused slowing of the systolic rise time, which corresponded to decreased arterial patency. Alterations in the response of the internal pudendal artery to vasoactive drugs were observed, wherein SBRT caused a paradoxical response to papaverine, slowing the systolic rise time after 40 and 50 Gy; these changes appeared to have some dose dependency. The neurofilament content of penile nerves was also decreased at high doses and was more profound when the PB was irradiated than when the NVB was irradiated. These findings are coincident with slowing of motor nerve conduction velocities in the pudendal nerve after SBRT. Conclusions: This is the first report in which prostatic irradiation was shown to cause morphologic arterial damage that was coincident with altered internal pudendal arterial tone, and in which decreased motor function in the pudendal nerve was attributed to axonal degeneration and loss. Further investigation of the role played by damage to these structures in RI-ED is warranted.« less

Prevalence and Prognostic Significance of Right Ventricular Systolic Dysfunction in Patients Undergoing Transcatheter Aortic Valve Implantation.

PubMed

Lindsay, Alistair C; Harron, Katie; Jabbour, Richard J; Kanyal, Ritesh; Snow, Thomas M; Sawhney, Paramvir; Alpendurada, Francisco; Roughton, Michael; Pennell, Dudley J; Duncan, Alison; Di Mario, Carlo; Davies, Simon W; Mohiaddin, Raad H; Moat, Neil E

2016-07-01

Cardiovascular magnetic resonance (CMR) can provide important structural information in patients undergoing transcatheter aortic valve implantation. Although CMR is considered the standard of reference for measuring ventricular volumes and mass, the relationship between CMR findings of right ventricular (RV) function and outcomes after transcatheter aortic valve implantation has not previously been reported. A total of 190 patients underwent 1.5 Tesla CMR before transcatheter aortic valve implantation. Steady-state free precession sequences were used for aortic valve planimetry and to assess ventricular volumes and mass. Semiautomated image analysis was performed by 2 specialist reviewers blinded to patient treatment. Patient follow-up was obtained from the Office of National Statistics mortality database. The median age was 81.0 (interquartile range, 74.9-85.5) years; 50.0% were women. Impaired RV function (RV ejection fraction ≤50%) was present in 45 (23.7%) patients. Patients with RV dysfunction had poorer left ventricular ejection fractions (42% versus 69%), higher indexed left ventricular end-systolic volumes (96 versus 40 mL), and greater indexed left ventricular mass (101 versus 85 g/m(2); P<0.01 for all) than those with normal RV function. Median follow-up was 850 days; 21 of 45 (46.7%) patients with RV dysfunction died, compared with 43 of 145 (29.7%) patients with normal RV function (P=0.035). After adjustment for significant baseline variables, both RV ejection fraction ≤50% (hazard ratio, 2.12; P=0.017) and indexed aortic valve area (hazard ratio, 4.16; P=0.025) were independently associated with survival. RV function, measured on preprocedural CMR, is an independent predictor of mortality after transcatheter aortic valve implantation. CMR assessment of RV function may be important in the risk stratification of patients undergoing transcatheter aortic valve implantation. © 2016 American Heart Association, Inc.

Sildenafil Preserves Exercise Capacity in Patients With Idiopathic Pulmonary Fibrosis and Right-sided Ventricular Dysfunction

PubMed Central

Bach, David S.; Hagan, Peter G.; Yow, Eric; Flaherty, Kevin R.; Toews, Galen B.; Anstrom, Kevin J.; Martinez, Fernando J.

2013-01-01

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with pulmonary vasculopathy. Objective: The purpose of this study was to determine whether sildenafil improves 6-min walk distance (6MWD) in subjects with IPF and right ventricular dysfunction. Methods: The IPFnet, a network of IPF research centers in the United States, conducted a randomized trial examining the effect of sildenafil on 6MWD in patients with advanced IPF, defined by carbon monoxide diffusing capacity < 35% predicted. A substudy examined 119 of 180 randomized subjects where echocardiograms were available for independent review by two cardiologists. Right ventricular (RV) hypertrophy (RVH), right ventricular systolic dysfunction (RVSD), and right ventricular systolic pressure (RVSP) were assessed. Multivariable linear regression models estimated the relationship between RV abnormality, sildenafil treatment, and changes in 6MWD, St. George’s Respiratory Questionnaire (SGRQ), the EuroQol instrument, and SF-36 Health Survey (SF-36) from enrollment to 12 weeks. Results: The prevalence of RVH and RVSD were 12.8% and 18.6%, respectively. RVSP was measurable in 71 of 119 (60%) subjects; mean RVSP was 42.5 mm Hg. In the subgroup of subjects with RVSD, subjects treated with sildenafil experienced less decrement in 6MWD (99.3 m; P = .01) and greater improvement in SGRQ (13.4 points; P = .005) and EuroQol visual analog scores (17.9 points; P = .04) than subjects receiving placebo. In the subgroup with RVH, sildenafil was not associated with change in 6MWD (P = .13), but was associated with greater relative improvement in SGRQ (14.8 points; P = .02) vs subjects receiving placebo. Sildenafil treatment in those with RVSD and RVH was not associated with change in SF-36. Conclusions: Sildenafil treatment in IPF with RVSD results in better preservation of exercise capacity as compared with placebo. Sildenafil also improves quality of life in subjects with RVH and RVSD. PMID:23732584

Chronic plus binge ethanol feeding induces myocardial oxidative stress, mitochondrial and cardiovascular dysfunction, and steatosis

PubMed Central

Matyas, Csaba; Varga, Zoltan V.; Mukhopadhyay, Partha; Paloczi, Janos; Lajtos, Tamas; Erdelyi, Katalin; Nemeth, Balazs T.; Nan, Mintong; Hasko, Gyorgy; Gao, Bin

2016-01-01

Alcoholic cardiomyopathy in humans develops in response to chronic excessive alcohol consumption; however, good models of alcohol-induced cardiomyopathy in mice are lacking. Herein we describe mouse models of alcoholic cardiomyopathies induced by chronic and binge ethanol (EtOH) feeding and characterize detailed hemodynamic alterations, mitochondrial function, and redox signaling in these models. Mice were fed a liquid diet containing 5% EtOH for 10, 20, and 40 days (d) combined with single or multiple EtOH binges (5 g/kg body wt). Isocalorically pair-fed mice served as controls. Left ventricular (LV) function and morphology were assessed by invasive pressure-volume conductance approach and by echocardiography. Mitochondrial complex (I, II, IV) activities, 3-nitrotyrosine (3-NT) levels, gene expression of markers of oxidative stress (gp91phox, p47phox), mitochondrial biogenesis (PGC1α, peroxisome proliferator-activated receptor α), and fibrosis were examined. Cardiac steatosis and fibrosis were investigated by histological/immunohistochemical methods. Chronic and binge EtOH feeding (already in 10 days EtOH plus single binge group) was characterized by contractile dysfunction (decreased slope of end-systolic pressure-volume relationship and preload recruitable stroke work), impaired relaxation (decreased time constant of LV pressure decay and maximal slope of systolic pressure decrement), and vascular dysfunction (impaired arterial elastance and lower total peripheral resistance). This was accompanied by enhanced myocardial oxidative/nitrative stress (3-NT; gp91phox; p47phox; angiotensin II receptor, type 1a) and deterioration of mitochondrial complex I, II, IV activities and mitochondrial biogenesis, excessive cardiac steatosis, and higher mortality. Collectively, chronic plus binge EtOH feeding in mice leads to alcohol-induced cardiomyopathies (National Institute on Alcohol Abuse and Alcoholism models) characterized by increased myocardial oxidative/nitrative stress, impaired mitochondrial function and biogenesis, and enhanced cardiac steatosis. PMID:27106042

Chronic plus binge ethanol feeding induces myocardial oxidative stress, mitochondrial and cardiovascular dysfunction, and steatosis.

PubMed

Matyas, Csaba; Varga, Zoltan V; Mukhopadhyay, Partha; Paloczi, Janos; Lajtos, Tamas; Erdelyi, Katalin; Nemeth, Balazs T; Nan, Mintong; Hasko, Gyorgy; Gao, Bin; Pacher, Pal

2016-06-01

Alcoholic cardiomyopathy in humans develops in response to chronic excessive alcohol consumption; however, good models of alcohol-induced cardiomyopathy in mice are lacking. Herein we describe mouse models of alcoholic cardiomyopathies induced by chronic and binge ethanol (EtOH) feeding and characterize detailed hemodynamic alterations, mitochondrial function, and redox signaling in these models. Mice were fed a liquid diet containing 5% EtOH for 10, 20, and 40 days (d) combined with single or multiple EtOH binges (5 g/kg body wt). Isocalorically pair-fed mice served as controls. Left ventricular (LV) function and morphology were assessed by invasive pressure-volume conductance approach and by echocardiography. Mitochondrial complex (I, II, IV) activities, 3-nitrotyrosine (3-NT) levels, gene expression of markers of oxidative stress (gp91phox, p47phox), mitochondrial biogenesis (PGC1α, peroxisome proliferator-activated receptor α), and fibrosis were examined. Cardiac steatosis and fibrosis were investigated by histological/immunohistochemical methods. Chronic and binge EtOH feeding (already in 10 days EtOH plus single binge group) was characterized by contractile dysfunction (decreased slope of end-systolic pressure-volume relationship and preload recruitable stroke work), impaired relaxation (decreased time constant of LV pressure decay and maximal slope of systolic pressure decrement), and vascular dysfunction (impaired arterial elastance and lower total peripheral resistance). This was accompanied by enhanced myocardial oxidative/nitrative stress (3-NT; gp91phox; p47phox; angiotensin II receptor, type 1a) and deterioration of mitochondrial complex I, II, IV activities and mitochondrial biogenesis, excessive cardiac steatosis, and higher mortality. Collectively, chronic plus binge EtOH feeding in mice leads to alcohol-induced cardiomyopathies (National Institute on Alcohol Abuse and Alcoholism models) characterized by increased myocardial oxidative/nitrative stress, impaired mitochondrial function and biogenesis, and enhanced cardiac steatosis. Copyright © 2016 the American Physiological Society.

Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trials.

PubMed

Ezekowitz, Justin A; McAlister, Finlay A

2009-02-01

Aldosterone blockade has been used to treat acute myocardial infarction (MI) and chronic heart failure. The aim of this study is to summarize the evidence on the efficacy of spironolactone (SP), eplerenone (EP), or canrenoate (CAN) in patients with left ventricular dysfunction. A search of multiple electronic databases until June 2008 was supplemented by hand searches of reference lists of included studies and review articles, meeting abstracts, FDA reports, and contact with study authors and drug manufacturers. Studies were eligible for inclusion if they included patients with left ventricular systolic or diastolic dysfunction, treatment with SP, EP, or CAN vs. control, and reported clinical outcomes. Nineteen randomized controlled trials (four in acute MI and 15 in heart failure, n = 10 807 patients) were included -- 14 of SP, three of EP, and three of CAN. Analysis was performed using relative risks (RRs) with 95% confidence intervals (CIs) and a random effects model with statistical heterogeneity assessed by I(2). Aldosterone blockade reduced all-cause mortality by 20% (RR 0.80, 95% CI 0.74-0.87). All-cause mortality was reduced in both heart failure (RR = 0.75, 95% CI 0.67-0.84) and post-MI (RR 0.85, 95% CI 0.76-0.95) patients. Only nine trials reported hospitalizations, and the RR reduction was 23% (RR 0.77, 95% CI 0.68-0.87), although 98% of the outcomes came from two trials. Ejection fraction (EF) improved in the seven heart failure trials, which assessed this outcome (weighted mean difference 3.1%, 95% CI 1.6-4.5). We demonstrated a 20% reduction in all-cause mortality with the use of aldosterone blockade in a clinically heterogeneous group of clinical trial participants with heart failure and post-MI. In addition, we found a 3.1% improvement in EF. Further study in those with less severe symptoms or preserved systolic function is warranted.

Alpha-lipoic acid improves subclinical left ventricular dysfunction in asymptomatic patients with type 1 diabetes.

PubMed

Hegazy, Sahar K; Tolba, Osama A; Mostafa, Tarek M; Eid, Manal A; El-Afify, Dalia R

2013-01-01

Oxidative stress plays an important role in the development of diabetic cardiomyopathy. Alpha-lipoic acid (ALA) is a powerful antioxidant that may have a protective role in diabetic cardiac dysfunction. We investigated the possible beneficial effect of alpha-lipoic acid on diabetic left ventricular (LV) dysfunction in children and adolescents with asymptomatic type 1 diabetes (T1D). Thirty T1D patients (aged 10-14) were randomized to receive insulin treatment (n = 15) or insulin plus alpha-lipoic acid 300 mg twice daily (n = 15) for four months. Age and sex matched healthy controls (n = 15) were also included. Patients were evaluated with conventional 2-dimensional echocardiographic examination (2D), pulsed tissue Doppler (PTD), and 2-dimensional longitudinal strain echocardiography (2DS) before and after therapy. Glutathione, malondialdhyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), Fas ligand (Fas-L), matrix metalloproteinase 2 (MMP-2), and troponin-I were determined and correlated to echocardiographic parameters. Diabetic patients had significantly lower levels of glutathione and significantly higher MDA, NO, TNF-alpha, Fas-L, MMP-2, and troponin-I levels than control subjects. The expression of transforming growth factor beta (TGF-beta) mRNA in peripheral blood mononuclear cells was also increased in diabetic patients. Significant correlations of mitral e'/a' ratio and left ventricular global peak systolic strain with glutathione, MDA, NO, TNF-alpha, and Fas-L were observed in diabetic patients. Alpha-lipoic acid significantly increased glutathione level and significantly decreased MDA, NO, TNF-alpha, Fas-L, MMP-2, troponin-I levels, and TGF-beta gene expression. Moreover, alpha-lipoic acid significantly increased mitral e'/a' ratio and left ventricular global peak systolic strain in diabetic patients. These findings suggest that alpha-lipoic acid may have a role in preventing the development of diabetic cardiomyopathy in type 1 diabetes.

Uric acid is a strong independent predictor of renal dysfunction in patients with rheumatoid arthritis.

PubMed

Daoussis, Dimitrios; Panoulas, Vasileios; Toms, Tracey; John, Holly; Antonopoulos, Ioannis; Nightingale, Peter; Douglas, Karen M J; Klocke, Rainer; Kitas, George D

2009-01-01

Recent evidence suggests that uric acid (UA), regardless of crystal deposition, may play a direct pathogenic role in renal disease. We have shown that UA is an independent predictor of hypertension and cardiovascular disease (CVD), and that CVD risk factors associate with renal dysfunction, in patients with rheumatoid arthritis (RA). In this study we investigated whether UA associates with renal dysfunction in patients with RA and whether such an association is independent or mediated through other comorbidities or risk factors for renal impairment. Renal function was assessed in 350 consecutive RA patients by estimated glomerular filtration rate (GFR) using the six-variable Modification of Diet in Renal Disease equation. Risk factors for renal dysfunction were recorded or measured in all participants. Linear regression was used to test the independence of the association between GFR and UA. Univariable analysis revealed significant associations between GFR and age, systolic blood pressure, total cholesterol, triglycerides, RA duration and UA. UA had the most powerful association with renal dysfunction (r = -0.45, P < 0.001). A basic model was created, incorporating all of the above parameters along with body mass index and gender. UA ranked as the first correlate of GFR (P < 0.001) followed by age. Adjustments for the use of medications (diuretics, low-dose aspirin, cyclooxygenase II inhibitors and nonsteroidal anti-inflammatory drugs) and further adjustment for markers of inflammation and insulin resistance did not change the results. UA is a strong correlate of renal dysfunction in RA patients. Further studies are needed to address the exact causes and clinical implications of this new finding. RA patients with elevated UA may require screening for renal dysfunction and appropriate management.

Prediction of left ventricular dysfunction after device closure of patent ductus arteriosus: proposal for a new functional classification.

PubMed

Kiran, Viralam S; Tiwari, Ashish

2018-04-06

The aims of this study were to determine the incidence and correlates of left ventricular (LV) dysfunction amongst percutaneous patent ductus arteriosus (PDA) device closure patients, and to propose an indexed parameter for predicting LV dysfunction. In a retrospective cross-sectional analysis of 30 months duration, 447 patients who underwent PDA device closure were studied. The diameter of the PDA at the pulmonary artery end was measured in the angiograms in all patients and was indexed for their body surface area. The indexed PDA size was categorised into group A (1-2.9 mm/m², 35/447), B (3-5.9 mm/m², 254/447), C (6-8.9 mm/m², 66/447) and D (>9 mm/m², 35/447). Systolic LV function was evaluated using echocardiography at frequent intervals. Overall, 62.63% of the patients were female (280/447). At baseline, all 447 patients had normal LV function. LV dysfunction was seen in 102/447 (22.8%) patients with 2.8% in category A (1/35), 10.6% in category B (27/254), 34.1% in category C (42/123) and 91.4% in category D (32/35) after PDA device closure. Correlation of indexed PDA size and LV dysfunction was statistically significant (p<0.05). Accurate prediction of LV dysfunction is important in risk stratification, ICU management and counselling in PDA device closures. Indexed PDA size correlates well with post-procedural LV dysfunction. The authors propose a new classification of PDA utilising this accurate, reproducible and easy to perform parameter, which does not involve any extra cost, for risk stratification and early management in device closure of PDA.

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

Combined deficiency of Notch1 and Notch3 causes pericyte dysfunction, models CADASIL, and results in arteriovenous malformations

PubMed Central

Kofler, Natalie M.; Cuervo, Henar; Uh, Minji K.; Murtomäki, Aino; Kitajewski, Jan

2015-01-01

Pericytes regulate vessel stability and pericyte dysfunction contributes to retinopathies, stroke, and cancer. Here we define Notch as a key regulator of pericyte function during angiogenesis. In Notch1+/−; Notch3−/− mice, combined deficiency of Notch1 and Notch3 altered pericyte interaction with the endothelium and reduced pericyte coverage of the retinal vasculature. Notch1 and Notch3 were shown to cooperate to promote proper vascular basement membrane formation and contribute to endothelial cell quiescence. Accordingly, loss of pericyte function due to Notch deficiency exacerbates endothelial cell activation caused by Notch1 haploinsufficiency. Mice mutant for Notch1 and Notch3 develop arteriovenous malformations and display hallmarks of the ischemic stroke disease CADASIL. Thus, Notch deficiency compromises pericyte function and contributes to vascular pathologies. PMID:26563570

Quantitative Assessment of Regional Wall Motion Abnormalities Using Dual-Energy Digital Subtraction Intravenous Ventriculography

NASA Astrophysics Data System (ADS)

McCollough, Cynthia H.

Healthy portions of the left ventricle (LV) can often compensate for regional dysfunction, thereby masking regional disease when global indices of LV function are employed. Thus, quantitation of regional function provides a more useful method of assessing LV function, especially in diseases that have regional effects such as coronary artery disease. This dissertation studied the ability of a phase -matched dual-energy digital subtraction angiography (DE -DSA) technique to quantitate changes in regional LV systolic volume. The potential benefits and a theoretical description of the DE imaging technique are detailed. A correlated noise reduction algorithm is also presented which raises the signal-to-noise ratio of DE images by a factor of 2 -4. Ten open-chest dogs were instrumented with transmural ultrasonic crystals to assess regional LV function in terms of systolic normalized-wall-thickening rate (NWTR) and percent-systolic-thickening (PST). A pneumatic occluder was placed on the left-anterior-descending (LAD) coronary artery to temporarily reduce myocardial blood flow, thereby changing regional LV function in the LAD bed. DE-DSA intravenous left ventriculograms were obtained at control and four levels of graded myocardial ischemia, as determined by reductions in PST. Phase-matched images displaying changes in systolic contractile function were created by subtracting an end-systolic (ES) control image from ES images acquired at each level of myocardial ischemia. The resulting wall-motion difference signal (WMD), which represents a change in regional systolic volume between the control and ischemic states, was quantitated by videodensitometry and compared with changes in NWTR and PST. Regression analysis of 56 data points from 10 animals shows a linear relationship between WMD and both NWTR and PST: WMD = -2.46 NWTR + 13.9, r = 0.64, p < 0.001; WMD = -2.11 PST + 18.4, r = 0.54, p < 0.001. Thus, changes in regional ES LV volume between rest and ischemic states, as measured using the described imaging technique, appear linearly related to changes in wall-thickening, as measured using transmural ultrasonic crystals. This type of image analysis may prove useful in a variety of clinical and research applications and further investigation is proposed.

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.

Cardio-oncology/onco-cardiology.

PubMed

Hong, Robert A; Iimura, Takeshi; Sumida, Kenneth N; Eager, Robert M

2010-12-01

An understanding of onco-cardiology or cardio-oncology is critical for the effective care of cancer patients. Virtually all antineoplastic agents are associated with cardiotoxicity, which can be divided into 5 categories: direct cytotoxic effects of chemotherapy and associated cardiac systolic dysfunction, cardiac ischemia, arrhythmias, pericarditis, and chemotherapy-induced repolarization abnormalities. Radiation therapy can also lead to coronary artery disease and fibrotic changes to the valves, pericardium, and myocardium. All patients being considered for chemotherapy, especially those who have prior cardiac history, should undergo detailed cardiovascular evaluation to optimize the treatment. Serial assessment of left ventricular systolic function and cardiac biomarkers might also be considered in selected patient populations. Cardiotoxic effects of chemotherapy might be decreased by the concurrent use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers. Antiplatelet or anticoagulation therapy might be considered in patients with a potential hypercoagulable state associated with chemotherapy or cancer. Open dialogue between both cardiologists and oncologists will be required for optimal patient care. Copyright © 2010 Wiley Periodicals, Inc.

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.

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 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.

The Moderating Role of Dysfunctional Parent-Child Relationships on the Association Between Outward Anger Expression and Physical Health in Youth From Low-Income Families.

PubMed

Guenther, Kassie D; Van Dyk, Tori R; Kidwell, Katherine M; Nelson, Timothy D

2016-01-01

The purpose of this study is to examine the role of outward anger expression on physical health outcomes (number of illnesses in the past year, 2-year medical service utilization, and health-related quality of life) while also expanding on previous research by assessing the moderating effect of parent-child dysfunction. An ethnically diverse sample of 125 children, ages 8 to 11 years, was recruited from a family medicine practice serving a low-income population. High levels of outward anger expression were related to a greater number of illnesses, greater medical service utilization, and lower health-related quality of life. Additionally, worse parent-child dysfunction exacerbated this relationship for a number of illnesses and medical service utilization. Results suggest that health care providers should consider the influence of environmental and familial factors on the physical health of children with anger. Recommendations for identifying at-risk youth and improving anger expression as well as parent-child relationships are provided. Copyright © 2016 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

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.

Tau-Dependent Kv4.2 Depletion and Dendritic Hyperexcitability in a Mouse Model of Alzheimer's Disease

PubMed Central

Hall, Alicia M.; Throesch, Benjamin T.; Buckingham, Susan C.; Markwardt, Sean J.; Peng, Yin; Wang, Qin

2015-01-01

Neuronal hyperexcitability occurs early in the pathogenesis of Alzheimer's disease (AD) and contributes to network dysfunction in AD patients. In other disorders with neuronal hyperexcitability, dysfunction in the dendrites often contributes, but dendritic excitability has not been directly examined in AD models. We used dendritic patch-clamp recordings to measure dendritic excitability in the CA1 region of the hippocampus. We found that dendrites, more so than somata, of hippocampal neurons were hyperexcitable in mice overexpressing Aβ. This dendritic hyperexcitability was associated with depletion of Kv4.2, a dendritic potassium channel important for regulating dendritic excitability and synaptic plasticity. The antiepileptic drug, levetiracetam, blocked Kv4.2 depletion. Tau was required, as crossing with tau knock-out mice also prevented both Kv4.2 depletion and dendritic hyperexcitability. Dendritic hyperexcitability induced by Kv4.2 deficiency exacerbated behavioral deficits and increased epileptiform activity in hAPP mice. We conclude that increased dendritic excitability, associated with changes in dendritic ion channels including Kv4.2, may contribute to neuronal dysfunction in early stages AD. PMID:25878292

A2B Adenosine Receptor–Mediated Induction of IL-6 Promotes CKD

PubMed Central

Dai, Yingbo; Zhang, Weiru; Wen, Jiaming; Zhang, Yujin; Kellems, Rodney E.

2011-01-01

Chronic elevation of adenosine, which occurs in the setting of repeated or prolonged tissue injury, can exacerbate cellular dysfunction, suggesting that it may contribute to the pathogenesis of CKD. Here, mice with chronically elevated levels of adenosine, resulting from a deficiency in adenosine deaminase (ADA), developed renal dysfunction and fibrosis. Both the administration of polyethylene glycol–modified ADA to reduce adenosine levels and the inhibition of the A2B adenosine receptor (A2BR) attenuated renal fibrosis and dysfunction. Furthermore, activation of A2BR promoted renal fibrosis in both mice infused with angiotensin II (Ang II) and mice subjected to unilateral ureteral obstruction (UUO). These three mouse models shared a similar profile of profibrotic gene expression in kidney tissue, suggesting that they share similar signaling pathways that lead to renal fibrosis. Finally, both genetic and pharmacologic approaches showed that the inflammatory cytokine IL-6 mediates adenosine-induced renal fibrosis downstream of A2BR. Taken together, these data suggest that A2BR-mediated induction of IL-6 contributes to renal fibrogenesis and shows potential therapeutic targets for CKD. PMID:21511827

Sall2 knockdown exacerbates palmitic acid induced dysfunction and apoptosis of pancreatic NIT-1 beta cells.

PubMed

Wang, Ye; Liu, Jie; Liu, Zheng; Chen, Jing; Hu, Xuemei; Hu, Yimeng; Yuan, Yin; Wu, Guijun; Dai, Zhe; Xu, Yancheng

2018-05-18

Spalt-like (Sall) proteins are a class of transcription factors. The role of Sall2 in beta cells remain poorly understood. Here, we aimed to explore whether Sall2 involved in lipotoxicity-mediated dysfunction and apoptosis in pancreatic NIT-1 beta cells. Our results showed that high concentrations of palmitic acid (PA) led to impaired cell viability and decreased Sall2 expression in NIT-1 cells. Knocking down of Sall2 in NIT-1 cells resulted in increased sensitivity to lipotoxicity and caused higher rates of cell apoptosis following PA treatment. Additionally, Sall2 Knockdown impaired insulin synthesis and secretion in response to glucose. Further research indicated Sall2 knockdown attenuate antioxidant capacity and decreased expression level of Peroxiredoxin 2 in NIT-1 cells. These finding implicate that Sall2 may play a significant role in NIT-1 cell function and cell apoptosis under lipotoxic conditions. Therefore, the study of Sall2 in NIT-1 cells provided a new perspective for molecular mechanism of lipotoxicity mediating dysfunction and apoptosis of beta cells. Copyright © 2018 Elsevier Masson SAS. 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

Folic acid prevents cardiac dysfunction and reduces myocardial fibrosis in a mouse model of high-fat diet-induced obesity.

PubMed

Li, Wei; Tang, Renqiao; Ouyang, Shengrong; Ma, Feifei; Liu, Zhuo; Wu, Jianxin

2017-01-01

Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity. Six-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam. Phenotypic analysis included measurements of body and heart weight, blood glucose and tissue homocysteine (Hcy) content, and heart oxidative stress status. HFD consumption elevated fasting blood glucose levels and caused obesity and heart enlargement. FA supplementation in HFD-fed mice resulted in reduced fasting blood glucose, heart weight, and heart tissue Hcy content. We also observed a significant cardiac systolic dysfunction when mice were subjected to HFD feeding as indicated by a reduction in the left ventricular ejection fraction and fractional shortening. However, FAD treatment improved cardiac function. FA supplementation protected against cardiac fibrosis induced by HFD. In addition, HFD increased malondialdehyde concentration of the heart tissue and reduced the levels of antioxidant enzyme, glutathione, and catalase. HFD consumption induced myocardial oxidant stress with amelioration by FA treatment. FA supplementation significantly lowers blood glucose levels and heart tissue Hcy content and reverses cardiac dysfunction induced by HFD in mice. These functional improvements of the heart may be mediated by the alleviation of oxidative stress and myocardial fibrosis.

Obesity-Induced Diabetes and Lower Urinary Tract Fibrosis Promote Urinary Voiding Dysfunction in a Mouse Model

PubMed Central

Gharaee-Kermani, Mehrnaz; Rodriguez-Nieves, Jose A.; Mehra, Rohit; Vezina, Chad A.; Sarma, Aruna V.; Macoska, Jill A.

2017-01-01

BACKGROUND Progressive aging- and inflammation-associated fibrosis effectively remodels the extracellular matrix (ECM) to increase prostate tissue stiffness and reduce urethral flexibility, resulting in urinary flow obstruction and lower urinary tract symptoms (LUTS). In the current study, we sought to test whether senescence-accelerated mouse prone (SAMP)6 mice, which were reported to develop prostatic fibrosis, would also develop LUTS, and whether these symptoms would be exacerbated by diet-induced obesity and concurrent Type 2 Diabetes Mellitus (T2DM). METHODS To accomplish this, SAMP6 and AKR/J background strain mice were fed regular mouse chow, low fat diet chow, or high fat diet chow for 8 months, then subjected to glucose tolerance tests, assessed for plasma insulin levels, evaluated for urinary voiding function, and assessed for lower urinary tract fibrosis. RESULTS The results of these studies show that SAMP6 mice and AKR/J background strain mice develop diet-induced obesity and T2DM concurrent with urinary voiding dysfunction. Moreover, urinary voiding dysfunction was more severe in SAMP6 than AKR/J mice and was associated with pronounced prostatic and urethral tissue fibrosis. CONCLUSIONS Taken together, these studies suggest that obesity, T2DM, lower urinary tract fibrosis, and urinary voiding dysfunction are inextricably and biologically linked. Prostate. PMID:23532836

Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging

PubMed Central

Toth, Peter; Tarantini, Stefano; Csiszar, Anna

2017-01-01

Increasing evidence from epidemiological, clinical and experimental studies indicate that age-related cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including Alzheimer’s disease. Understanding and targeting the age-related pathophysiological mechanisms that underlie vascular contributions to cognitive impairment and dementia (VCID) are expected to have a major role in preserving brain health in older individuals. Maintenance of cerebral perfusion, protecting the microcirculation from high pressure-induced damage and moment-to-moment adjustment of regional oxygen and nutrient supply to changes in demand are prerequisites for the prevention of cerebral ischemia and neuronal dysfunction. This overview discusses age-related alterations in three main regulatory paradigms involved in the regulation of cerebral blood flow (CBF): cerebral autoregulation/myogenic constriction, endothelium-dependent vasomotor function, and neurovascular coupling responses responsible for functional hyperemia. The pathophysiological consequences of cerebral microvascular dysregulation in aging are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages, microvascular rarefaction, and ischemic neuronal dysfunction and damage. Due to the widespread attention that VCID has captured in recent years, the evidence for the causal role of cerebral microvascular dysregulation in cognitive decline is critically examined. PMID:27793855

Loss of Angiotensin-Converting Enzyme 2 Exacerbates Diabetic Retinopathy by Promoting Bone Marrow Dysfunction.

PubMed

Duan, Yaqian; Beli, Eleni; Li Calzi, Sergio; Quigley, Judith L; Miller, Rehae C; Moldovan, Leni; Feng, Dongni; Salazar, Tatiana E; Hazra, Sugata; Al-Sabah, Jude; Chalam, Kakarla V; Le Phuong Trinh, Thao; Meroueh, Marya; Markel, Troy A; Murray, Matthew C; Vyas, Ruchi J; Boulton, Michael E; Parsons-Wingerter, Patricia; Oudit, Gavin Y; Obukhov, Alexander G; Grant, Maria B

2018-05-15

Angiotensin-converting enzyme 2 (ACE2) is the primary enzyme of the vasoprotective axis of the renin angiotensin system (RAS). We tested the hypothesis that loss of ACE2 would exacerbate diabetic retinopathy by promoting bone marrow dysfunction. ACE2 -/y were crossed with Akita mice, a model of type 1 diabetes. When comparing the bone marrow of the ACE2 -/y -Akita mice to that of Akita mice, we observed a reduction of both short-term and long-term repopulating hematopoietic stem cells, a shift of hematopoiesis towards myelopoiesis, and an impairment of lineage - c-kit + hematopoietic stem/progenitor cell (HS/PC) migration and proliferation. Migratory and proliferative dysfunction of these cells was corrected by exposure to angiotensin-1-7 (Ang-1-7), the protective peptide generated by ACE2. Over the duration of diabetes examined, ACE2 deficiency led to progressive reduction in electrical responses assessed by electroretinography and to increases in neural infarcts observed by fundus photography. Compared to Akita mice, ACE2 -/y -Akita at 9-months of diabetes showed an increased number of acellular capillaries indicative of more severe diabetic retinopathy. In diabetic and control human subjects, CD34 + cells, a key bone marrow HS/PC population, were assessed for changes in mRNA levels for MAS, the receptor for Ang-1-7. Levels were highest in CD34 + cells from diabetics without retinopathy. Higher serum Ang-1-7 levels predicted protection from development of retinopathy in diabetics. Treatment with Ang-1-7 or alamandine restored the impaired migration function of CD34 + cells from subjects with retinopathy. These data support that activation of the protective RAS within HS/PCs may represent a therapeutic strategy for prevention of diabetic retinopathy. This article is protected by copyright. All rights reserved. © 2018 AlphaMed Press.

Sex differences in depression-like behavior after nerve injury are associated with differential changes in brain-derived neurotrophic factor levels in mice subjected to early life stress.

PubMed

Nishinaka, Takashi; Kinoshita, Megumi; Nakamoto, Kazuo; Tokuyama, Shogo

2015-04-10

We recently demonstrated that exposure to early life stress exacerbates nerve injury-induced thermal and mechanical hypersensitivity in adult male and female mice. Accumulating evidence suggests that chronic pain causes emotional dysfunction, such as anxiety and depression. In the present study, we investigated the impact of early life stress on depression-like behavior after nerve injury in mice. In addition, we examined the expression of brain-derived neurotrophic factor (BDNF), which is known to be involved in the pathogenesis of depression. Early life stress was induced by maternal separation between 2 and 3 weeks of age combined with social isolation after weaning (MSSI). At 9 weeks of age, the sciatic nerve was partially ligated to elicit neuropathic pain. Depression-like behavior was evaluated using the forced swim test at 12 weeks of age. Tissue samples from different regions of the brain were collected at the end of maternal separation (3 weeks of age) or after the forced swim test (12 weeks of age). At 12 weeks of age, immobility time in the forced swim test was increased only in MSSI-stressed female mice with nerve injury. BDNF expression was increased in male, but not female, MSSI-stressed mice at 3 weeks of age. However, MSSI stress did not impact BDNF expression in male or female mice at 12 weeks of age. Our findings suggest that exposure to early life stress exacerbates emotional dysfunction induced by neuropathic pain in a sex-dependent manner. Changes in BDNF expression after early life stress may be associated with neuropathic pain-induced depression-like behavior in adulthood. Furthermore, sex differences in BDNF expression after exposure to early life stress may contribute to sex-specific susceptibility to neuropathic pain-induced emotional dysfunction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Limitations of Stroke Volume Estimation by Non-Invasive Blood Pressure Monitoring in Hypergravity

PubMed Central

2015-01-01

Background Altitude and gravity changes during aeromedical evacuations induce exacerbated cardiovascular responses in unstable patients. Non-invasive cardiac output monitoring is difficult to perform in this environment with limited access to the patient. We evaluated the feasibility and accuracy of stroke volume estimation by finger photoplethysmography (SVp) in hypergravity. Methods Finger arterial blood pressure (ABP) waveforms were recorded continuously in ten healthy subjects before, during and after exposure to +Gz accelerations in a human centrifuge. The protocol consisted of a 2-min and 8-min exposure up to +4 Gz. SVp was computed from ABP using Liljestrand, systolic area, and Windkessel algorithms, and compared with reference values measured by echocardiography (SVe) before and after the centrifuge runs. Results The ABP signal could be used in 83.3% of cases. After calibration with echocardiography, SVp changes did not differ from SVe and values were linearly correlated (p<0.001). The three algorithms gave comparable SVp. Reproducibility between SVp and SVe was the best with the systolic area algorithm (limits of agreement −20.5 and +38.3 ml). Conclusions Non-invasive ABP photoplethysmographic monitoring is an interesting technique to estimate relative stroke volume changes in moderate and sustained hypergravity. This method may aid physicians for aeronautic patient monitoring. PMID:25798613

Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance

PubMed Central

Kim, Jiwon; Medicherla, Chaitanya B.; Ma, Claudia L.; Feher, Attila; Kukar, Nina; Geevarghese, Alexi; Goyal, Parag; Horn, Evelyn; Devereux, Richard B.; Weinsaft, Jonathan W.

2016-01-01

Background Non-ischemic fibrosis (NIF) on cardiac magnetic resonance (CMR) has been linked to poor prognosis, but its association with adverse right ventricular (RV) remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress. Methods and Results The population comprised patients with RV dysfunction (EF<50%) undergoing CMR and transthoracic echo within a 14 day (5±3) interval. Cardiac structure, function, and NIF were assessed on CMR. Pulmonary artery systolic pressure (PASP) was measured on echo. 118 patients with RV dysfunction were studied, among whom 47% had NIF. Patients with NIF had lower RVEF (34±10 vs. 39±9%; p = 0.01) but similar LVEF (40±21 vs. 39±18%; p = 0.7) and LV volumes (p = NS). RV wall stress was higher with NIF (17±7 vs. 12±6 kPa; p<0.001) corresponding to increased RV end-systolic volume (143±79 vs. 110±36 ml; p = 0.006), myocardial mass (60±21 vs. 53±17 gm; p = 0.04), and PASP (52±18 vs. 41±18 mmHg; p = 0.001). NIF was associated with increased wall stress among subgroups with isolated RV (p = 0.005) and both RV and LV dysfunction (p = 0.003). In multivariable analysis, NIF was independently associated with RV volume (OR = 1.17 per 10 ml, [CI 1.04–1.32]; p = 0.01) and PASP (OR = 1.43 per 10 mmHg, [1.14–1.81]; p = 0.002) but not RV mass (OR = 0.91 per 10 gm, [0.69–1.20]; p = 0.5) [model χ2 = 21; p<0.001]. NIF prevalence was higher in relation to PA pressure and RV dilation and was > 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001). Conclusion Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling. PMID:26799498

Hopelessness and cognitive impairment are risk markers for mortality in systolic heart failure patients.

PubMed

Byrne, Claire J; Toukhsati, Samia R; Toia, Deidre; O'Halloran, Paul D; Hare, David L

2018-06-01

Depression exacerbates the burden of heart failure and independently predicts mortality. The aim of this study was to investigate which specific symptoms of depression predict all-cause mortality in systolic heart failure patients. Consecutive outpatients with heart failure and impaired left ventricular ejection fraction (LVEF), attending an Australian metropolitan heart function clinic between 2001 and 2011, were enrolled. The Cardiac Depression Scale (CDS) was completed as a component of usual care. Baseline clinical characteristics were drawn from hospital databases. The primary end-point was all-cause mortality, obtained from the Australian National Death Index. A total of 324 patients (68.5% male) were included (mean age at enrolment = 66.8 ± 14.36 years), with a median follow-up time of 6.7 years (95% CI 5.97-7.39) and a mortality rate of 50% by the census date. Mean LVEF = 31.0 ± 11.31%, with 25% having NYHA functional class of III or IV. Factor analysis of the CDS extracted six symptom dimensions: Hopelessness, Cognitive Impairment, Anhedonia/Mood, Irritability, Worry, and Sleep Disturbance. Cox regression analyses identified Hopelessness (HR 1.024, 95% CI 1.004-1.045, p = .018) and Cognitive Impairment (HR 1.048, 95% CI 1.005-1.093, p = .028) as independent risk markers of all-cause mortality, following adjustment of known prognostic clinical factors. Hopelessness and cognitive impairment are stronger risk markers for all-cause mortality than other symptoms of depression in systolic heart failure. These data will allow more specific risk assessment and potentially new targets for more effective treatment and management of depression in this population. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of water drinking on cardiovascular responses to supine exercise and on orthostatic hypotension after exercise in pure autonomic failure.

PubMed

Humm, A M; Mason, L M; Mathias, C J

2008-10-01

Patients with pure autonomic failure (PAF) have an abnormal fall in blood pressure (BP) with supine exercise and exacerbation of orthostatic hypotension (OH) after exercise. This study assessed the pressor effect of water on the cardiovascular responses to supine exercise and on OH after exercise. 8 patients with PAF underwent a test protocol consisting of standing for 5 min, supine rest for 10 min, supine exercise by pedalling a cycle ergometer at workloads of 25, 50 and 75 W (each for 3 min), supine rest for 10 min and standing for 5 min. The test protocol was performed without water ingestion and on a separate occasion after 480 ml of distilled water immediately after pre-exercise standing. Beat to beat cardiovascular indices were measured with the Portapres II device with subsequent Modelflow analysis. All patients had severe OH pre-exercise (BP fall systolic 65.0 (26.1) mm Hg, diastolic 22.7 (13.5) mm Hg), with prompt recovery of BP in the supine position. 5 min after water drinking, there was a significant rise in BP in the supine position. With exercise, there was a clear fall in BP (systolic 42.1 (24.4) mm Hg, diastolic 25.9 (10.0) mm Hg) with a modest rise in heart rate; this occurred even after water ingestion (BP fall systolic 49.8 (18.9) mm Hg, diastolic 26.0 (9.1) mm Hg). BP remained low after exercise but was significantly higher after water intake, resulting in better tolerance of post-exercise standing. Water drinking did not change the abnormal cardiovascular responses to supine exercise. However, water drinking improved orthostatic tolerance post-exercise.

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.

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

Tricuspid Annular Plane Systolic Excursion and Its Association with Mortality in Critically Ill Patients.

PubMed

Gajanana, Deepakraj; Seetha Rammohan, Harish; Alli, Oluseun; Romero-Corral, Abel; Purushottam, Bhaskar; Ponamgi, Shiva; Figueredo, Vincent M; Pressman, Gregg S

2015-08-01

Transient left ventricular dysfunction can occur under conditions of extreme emotional or physiological stress. There is little data on right ventricular function in such situations. One hundred twenty patients admitted to an ICU with a noncardiac illness were studied. Those with documented coronary disease, ejection fraction <40%, sepsis, or intracranial hemorrhage were excluded. Echocardiograms were performed within 24 hours of admission. Tricuspid annular plane systolic excursion (TAPSE) was measured to assess right ventricular systolic function. Plasma catecholamines (norepinephrine, epinephrine, dopamine) were measured on admission. Clinical and demographic data were collected, along with data on ICU length of stay (LOS), hospital LOS, and in-hospital and long-term mortality. TAPSE was tested for correlation with adverse outcomes and length of stay. Mean TAPSE for the group was 2.05 ± 0.66 cm. Based on area under the ROC curve analysis, TAPSE <2.4 cm was the best cutoff for predicting in-hospital and long-term mortality. There were 13 in-hospital deaths, 12 in the group with TAPSE <2.4 cm and one among those with TAPSE ≥2.4 cm. On multivariate analysis, TAPSE <2.4 cm was a significant predictor of in-hospital mortality (χ(2)  = 4.6, P = 0.03). When tested against hospital LOS, an inverse correlation was found (P = 0.04). No association was found between TAPSE and catecholamine levels. Right ventricular systolic function, as assessed by TAPSE, has important prognostic value in critically ill patients. Mean values were lower in patients who died in-hospital versus those who survived to discharge. In addition, patients with TAPSE <2.4 cm had a longer hospital length of stay. © 2015, Wiley Periodicals, Inc.

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.

The effect of heart failure and left ventricular assist device treatment on right ventricular mechanics: a computational study.

PubMed

Park, Jun I K; Heikhmakhtiar, Aulia Khamas; Kim, Chang Hyun; Kim, Yoo Seok; Choi, Seong Wook; Song, Kwang Soup; Lim, Ki Moo

2018-05-22

Although it is important to analyze the hemodynamic factors related to the right ventricle (RV) after left ventricular assist device (LVAD) implantation, previous studies have focused only on the alteration of the ventricular shape and lack quantitative analysis of the various hemodynamic parameters. Therefore, we quantitatively analyzed various hemodynamic parameters related to the RV under normal, heart failure (HF), and HF incorporated with continuous flow LVAD therapy by using a computational model. In this study, we combined a three-dimensional finite element electromechanical model of ventricles, which is based on human ventricular morphology captured by magnetic resonance imaging (MRI) with a lumped model of the circulatory system and continuous flow LVAD function in order to construct an integrated model of an LVAD implanted-cardiovascular system. To induce systolic dysfunction, the magnitude of the calcium transient function under HF condition was reduced to 70% of the normal value, and the time constant was reduced by 30% of the normal value. Under the HF condition, the left ventricular end systolic pressure decreased, the left ventricular end diastolic pressure increased, and the pressure in the right atrium (RA), RV, and pulmonary artery (PA) increased compared with the normal condition. The LVAD therapy decreased the end-systolic pressure of the LV by 41%, RA by 29%, RV by 53%, and PA by 71%, but increased the right ventricular ejection fraction by 52% and cardiac output by 40%, while the stroke work was reduced by 67% compared with the HF condition without LVAD. The end-systolic ventricular tension and strain decreased with the LVAD treatment. LVAD enhances CO and mechanical unloading of the LV as well as those of the RV and prevents pulmonary hypertension which can be induced by HF.

Sex differences regarding the impact of physical activity on left ventricular systolic function in elderly patients with an acute coronary event.

PubMed

Aggelopoulos, Panagiotis; Chrysohoou, Christina; Pitsavos, Christos; Panagiotakos, Demosthenes B; Vaina, Sophia; Brili, Stella; Lazaros, George; Vavouranakis, Manolis; Stefanadis, Christodoulos

2014-01-01

Regular physical activity has been associated with less severity of an acute coronary syndrome (ACS), lower in-hospital mortality rates, and an improved short term prognosis. This study evaluated the relationship between physical activity status and the development of left ventricular systolic dysfunction (LVSD) according to inflammation and sex in elderly patients who had had an ACS. We analyzed prospectively collected data from 355 male (age 74 ± 6 years) and 137 female (76 ± 6 years) patients who were hospitalized with an ACS. LVSD was evaluated by echocardiography on the 5th day of hospitalization and physical activity status was assessed by a self-reported questionnaire. Inflammatory response was evaluated by measuring C-reactive protein levels. Logistic regression models were applied to evaluate the effect of physical activity status on the development of LVSD and inflammatory response at entry. Physical inactivity had a higher prevalence in women who developed LVSD than in the female patients with preserved systolic function (46% vs. 20%, p=0.02). There was a significant positive association between physical activity levels and ejection fraction in women (p=0.06), but not in men (p=0.30). Multiadjusted logistic regression showed that women who were physically active had 76% lower odds (95%CI: 1-94%) of developing LVSD compared to their sedentary counterparts. Furthermore, physical activity was inversely associated with C-reactive protein levels in both sexes (p=0.08). Long-term involvement in a physically active lifestyle seems to confer further cardio-protection by reducing the inflammatory response and preserving left ventricular systolic function in elderly female, but not male patients with an ACS.

Mitral annular plane systolic excursion/left ventricular length (MAPSE/L) as a simple index for assessing left ventricular longitudinal function in children.

PubMed

Terada, Tomomasa; Mori, Kazuhiro; Inoue, Miki; Yasunobu, Hayabuchi

2016-11-01

Assessment of longitudinal left ventricular (LV) function is important for early detection of cardiac dysfunction. Although mitral annular plane systolic excursion (MAPSE) obtained by M-mode echocardiography offers a simple method for assessing longitudinal LV function, normal values of MAPSE for children change according to body size. To minimize the effects of body size, MAPSE was divided by LV long-axis length (MAPSE/L). MAPSE/L was measured in 210 healthy children from birth to 15 years of age and classified into five subgroups. MAPSE/L was then compared with 10 parameters in 136 children (age, heart rate, mean blood pressure, ejection fraction of the LV (EF), peak atrial flow velocity/peak early diastolic flow velocity of mitral flow, tissue Doppler velocity during systole (s') and early diastole (e'), E/e' ratio, Tei index, and global longitudinal strain (GLS) of the LV by the speckle tracking method). MAPSE/L was significantly lower in the neonate group than in the remaining four groups. MAPSE/L then increased with age to peak at 1-5 years and gradually decreased thereafter. In all cases beyond the neonatal period, MAPSE/L was more than 0.17. Among various parameters, GLS, age, EF, Tei index and s' were significantly associated with MAPSE/L in that order. In univariate analysis, GLS was most significantly associated with MAPSE/L (r=.56). We have established normal reference values for MPSE/L in healthy children. MAPSE/L is expected to offer a simple parameter to evaluate LV longitudinal systolic function during daily routine echocardiography in children. © 2016, Wiley Periodicals, Inc.

Reliability of N-terminal proBNP assay in diagnosis of left ventricular systolic dysfunction within representative and high risk populations.

PubMed

Hobbs, F D R; Davis, R C; Roalfe, A K; Hare, R; Davies, M K

2004-08-01

To determine the performance of a new NT-proBNP assay in comparison with brain natriuretic peptide (BNP) in identifying left ventricular systolic dysfunction (LVSD) in randomly selected community populations. Blood samples were taken prospectively in the community from 591 randomly sampled individuals over the age of 45 years, stratified for age and socioeconomic status and divided into four cohorts (general population; clinically diagnosed heart failure; patients on diuretics; and patients deemed at high risk of heart failure). Definite heart failure (left ventricular ejection fraction (LVEF) < 40%) was identified in 33 people. Samples were handled as though in routine clinical practice. The laboratories undertaking the assays were blinded. Using NT-proBNP to diagnose LVEF < 40% in the general population, a level of > 40 pmol/l had 80% sensitivity, 73% specificity, 5% positive predictive value (PPV), 100% negative predictive value (NPV), and an area under the receiver-operator characteristic curve (AUC) of 76% (95% confidence interval (CI) 46% to 100%). For BNP to diagnose LVSD, a cut off level of > 33 pmol/l had 80% sensitivity, 88% specificity, 10% PPV, 100% NPV, and AUC of 88% (95% CI 75% to 100%). Similar NPVs were found for patients randomly screened from the three other populations. Both NT-proBNP and BNP have value in diagnosing LVSD in a community setting, with similar sensitivities and specificities. Using a high cut off for positivity will confirm the diagnosis of LVSD but will miss cases. At lower cut off values, positive results will require cardiac imaging to confirm LVSD.

Left Ventricular Function Across the Spectrum of Body Mass Index in African Americans: The Jackson Heart Study.

PubMed

Patel, Vivek G; Gupta, Deepak K; Terry, James G; Kabagambe, Edmond K; Wang, Thomas J; Correa, Aldolfo; Griswold, Michael; Taylor, Herman; Carr, John Jeffrey

2017-03-01

This study sought to assess whether body mass index (BMI) was associated with subclinical left ventricular (LV) systolic dysfunction in African-American individuals. Higher BMI is a risk factor for cardiovascular disease, including heart failure. Obesity disproportionately affects African Americans; however, the association between higher BMI and LV function in African Americans is not well understood. Peak systolic circumferential strain (ECC) was measured by tagged cardiac magnetic resonance in 1,652 adult African-American participants of the Jackson Heart Study between 2008 and 2012. We evaluated the association between BMI and ECC in multivariate linear regression and restricted cubic spline analyses adjusted for prevalent cardiovascular disease, conventional cardiovascular risk factors, LV mass, and ejection fraction. In exploratory analyses, we also examined whether inflammation, insulin resistance, or volume of visceral adipose tissue altered the association between BMI and ECC. The proportions of female, nonsmokers, diabetic, and hypertensive participants rose with increase in BMI. In multivariate-adjusted models, higher BMI was associated with worse ECC (β = 0.052; 95% confidence interval: 0.028 to 0.075), even in the setting of preserved LV ejection fraction. Higher BMI was also associated with worse ECC when accounting for markers of inflammation (C-reactive protein, E-selection, and P-selectin), insulin resistance, and volume of visceral adipose tissue. Higher BMI is significantly associated with subclinical LV dysfunction in African Americans, even in the setting of preserved LV ejection fraction. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Plasma L-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction.

PubMed

Sandqvist, Anna; Schneede, Jörn; Kylhammar, David; Henrohn, Dan; Lundgren, Jakob; Hedeland, Mikael; Bondesson, Ulf; Rådegran, Göran; Wikström, Gerhard

2018-03-01

Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from L-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, L-arginine, L-ornithine, and L-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas L-arginine and L-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of L-arginine than patients with LVSD (p < 0.05). L-Arginine correlated to 6 min walking distance (6MWD) (r s  = 0.58, p = 0.006) and L-arginine/ADMA correlated to WHO functional class (r s  = -0.46, p = 0.043) in PAH. In conclusion, L-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, L-arginine correlated with 6MWD in PAH. L-arginine may provide useful information in differentiating PAH from LVSD.

Participation of reactive oxygen species in diabetes-induced endothelial dysfunction.

PubMed

Zúrová-Nedelcevová, Jana; Navarová, Jana; Drábiková, Katarína; Jancinová, Viera; Petríková, Margita; Bernátová, Iveta; Kristová, Viera; Snirc, Vladimír; Nosál'ová, Viera; Sotníková, Ruzena

2006-12-01

In the present study, the relationship between diabetes-induced hyperglycemia, reactive oxygen species production and endothelium-mediated arterial function was examined. The effect of antioxidant on the reactive oxygen species induced damage was tested. Diabetes was induced by streptozotocin (STZ), 3 x 30 mg/kg i.p., administered on three consecutive days. After 10 weeks of diabetes, the functional state of the endothelium of the aorta was tested, endothelemia evaluation was performed and systolic blood pressure was measured. Reactive oxygen species (ROS) formation in blood and the aorta was measured using luminol-enhanced chemiluminescence (CL). Levels of reduced glutathione (GSH) were determined in the aorta, kidney, and plasma. To study the involvement of hyperglycemia in functional impairment of the endothelium, aortal rings incubated in solution with high glucose concentration were tested in in vitro experiments. After 10 weeks of diabetes, endothelial injury was observed, exhibited by diminished endothelium-dependent relaxation of the aorta, increased endothelemia and by elevated systolic blood pressure. Using luminol-enhanced CL, a significant increase of ROS production was found in arterial tissue and blood. GSH levels were significantly increased in the kidney, while there were no GSH changes in plasma and the aorta. Incubation of aortic rings in solution with high glucose concentration led to impairment of endothelium-dependent relaxation. The synthetic antioxidant SMe1EC2 was able to restore reduced endothelium-mediated relaxation. Our results suggest an important role of hyperglycemia-induced ROS production in mediating endothelial dysfunction in experimental diabetes, confirmed by CL and the protective effect of the antioxidant SMe1EC2.

Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)

PubMed Central

Yu, Xichun; Tesiram, Yasvir A; Towner, Rheal A; Abbott, Andrew; Patterson, Eugene; Huang, Shijun; Garrett, Marion W; Chandrasekaran, Suresh; Matsuzaki, Satoshi; Szweda, Luke I; Gordon, Brian E; Kem, David C

2007-01-01

Background Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI) and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes. Methods Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19–25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks) in diabetic mice and age-matched controls. Results After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV) wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction. Conclusion Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy. PMID:17309798

Evaluation of Echocardiographic Abnormalities in HIV Positive Patients Treated with Antiretroviral Medications.

PubMed

Badie, Sina M; Rasoulinejad, Mehrnaz; Salehi, Mohammad R; Kochak, Hamid E; Alinaghi, Seyed A S; Manshadi, Seyed A D; Abad, Fatemeh J A; Badie, Banafsheh M

2017-01-01

Echocardiography is a reliable means for the diagnosis of functional and valvular diseases of the heart in HIV positive and HIV negative patients. The current study was to evaluate echocardiographic abnormalities in HIV positive patients under an antiretroviral therapy (ART) program in Tehran, Imam Khomeini Hospital, Iran. This is a descriptive cross-sectional study, conducted among 231 HIV-1 positive patients under ART. All HIV positive patients including 150 men (65%) and 81 women (35%) (mean age of 41 years) were assessed by trans-thoracic echocardiography (TTE) in Imam Khomeini Hospital, over the period from 2013 to 2014. The mean CD4 count was 408 cell/μl, and the average left ventricular ejection fraction (LVEF) was 59.5%. There was an inverse correlation between age and LVEF level. Nevirapine users showed a significantly higher LVEF than non-users. Left ventricular systolic dysfunction (LVSD) was diagnosed in 5.6% along with the increase in age, while left ventricular diastolic dysfunction (LVDD) was reported in 19.5% of patients associated with age and smoking. Here, the mean systolic pulmonary arterial pressure (SPAP) was only 20 mmHg and just four percent of the patients suffered pulmonary hypertension. Almost 44% had a heart valve disorder among which mitral valve prolapse is the most common problem. Pericardial effusion was not found in any patients. It seems that heart disorders with no suggestive symptoms in HIV positive patients, and mainly older adults who have traditional risk factors for heart diseases, should be seriously considered by health providers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.