Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis.

PubMed

Damman, Kevin; Valente, Mattia A E; Voors, Adriaan A; O'Connor, Christopher M; van Veldhuisen, Dirk J; Hillege, Hans L

2014-02-01

Chronic kidney disease (CKD) and worsening renal function (WRF) have been associated with poor outcome in heart failure (HF). Articles were identified by literature search of MEDLINE (from inception to 1 July 2012) and Cochrane. We included studies on HF patients and mortality risk with CKD and/or WRF. In a secondary analysis, we selected studies investigating predictors of WRF. We retrieved 57 studies (1,076,104 patients) that investigated CKD and 28 studies (49,890 patients) that investigated WRF. The prevalence of CKD was 32% and associated with all-cause mortality: odds ratio (OR) 2.34, 95% confidence interval (CI) 2.20-2.50, P < 0.001). Worsening renal function was present in 23% and associated with unfavourable outcome (OR 1.81, 95% CI 1.55-2.12, P < 0.001). In multivariate analysis, moderate renal impairment: hazard ratio (HR) 1.59, 95% CI 1.49-1.69, P < 0.001, severe renal impairment, HR 2.17, 95% CI 1.95-2.40, P < 0.001, and WRF, HR 1.95, 95% CI 1.45-2.62, P < 0.001 were all independent predictors of mortality. Across studies, baseline CKD, history of hypertension and diabetes, age, and diuretic use were significant predictors for the occurrence of WRF. Across all subgroups of patients with HF, CKD, and WRF are prevalent and associated with a strongly increased mortality risk, especially CKD. Specific conditions may predict the occurrence of WRF and thereby poor prognosis.

Cardiac Ablation of Rheb1 Induces Impaired Heart Growth, Endoplasmic Reticulum-Associated Apoptosis and Heart Failure in Infant Mice

PubMed Central

Cao, Yunshan; Tao, Lichan; Shen, Shutong; Xiao, Junjie; Wu, Hang; Li, Beibei; Wu, Xiangqi; Luo, Wen; Xiao, Qi; Hu, Xiaoshan; Liu, Hailang; Nie, Junwei; Lu, Shuangshuang; Yuan, Baiyin; Han, Zhonglin; Xiao, Bo; Yang, Zhongzhou; Li, Xinli

2013-01-01

Ras homologue enriched in brain 1 (Rheb1) plays an important role in a variety of cellular processes. In this study, we investigate the role of Rheb1 in the post-natal heart. We found that deletion of the gene responsible for production of Rheb1 from cardiomyocytes of post-natal mice resulted in malignant arrhythmias, heart failure, and premature death of these mice. In addition, heart growth impairment, aberrant metabolism relative gene expression, and increased cardiomyocyte apoptosis were observed in Rheb1-knockout mice prior to the development of heart failure and arrhythmias. Also, protein kinase B (PKB/Akt) signaling was enhanced in Rheb1-knockout mice, and removal of phosphatase and tensin homolog (Pten) significantly prolonged the survival of Rheb1-knockouts. Furthermore, signaling via the mammalian target of rapamycin complex 1 (mTORC1) was abolished and C/EBP homologous protein (CHOP) and phosphorylation levels of c-Jun N-terminal kinase (JNK) were increased in Rheb1 mutant mice. In conclusion, this study demonstrates that Rheb1 is important for maintaining cardiac function in post-natal mice via regulation of mTORC1 activity and stress on the endoplasmic reticulum. Moreover, activation of Akt signaling helps to improve the survival of mice with advanced heart failure. Thus, this study provides direct evidence that Rheb1 performs multiple important functions in the heart of the post-natal mouse. Enhancing Akt activity improves the survival of infant mice with advanced heart failure. PMID:24351823

Iloprost improves ventricular function in the hypertrophic and functionally impaired right heart by direct stimulation.

PubMed

Holmboe, Sarah; Andersen, Asger; Vildbrad, Mads D; Nielsen, Jan M; Ringgaard, Steffen; Nielsen-Kudsk, Jens E

2013-12-01

Right heart function is an important predictor of morbidity and mortality in patients suffering from pulmonary arterial hypertension and congenital heart diseases. We investigated whether the prostacyclin analog iloprost has a direct inotropic effect in the pressure-overloaded hypertrophic and dysfunctional right ventricle (RV). Rats were randomized to monocrotaline injection (60 mg/kg; [Formula: see text]), pulmonary trunk banding (PTB; [Formula: see text]), or a sham operation ([Formula: see text]). RV function was evaluated with magnetic resonance imaging, echocardiography, and invasive pressure measurements at baseline, after intravenous administration of placebo, iloprost 10 ng/kg/min, or iloprost 100 ng/kg/min (Ilo100). Infusion of Ilo100 induced a [Formula: see text] ([Formula: see text]) increase in stroke volume in the sham group and a [Formula: see text] ([Formula: see text]) increase in the PTB group. RV [Formula: see text] was elevated by [Formula: see text] ([Formula: see text]) in the sham group and by [Formula: see text] ([Formula: see text]) in the PTB group. An elevation in cardiac output of [Formula: see text] ([Formula: see text]) and an [Formula: see text] ([Formula: see text]) increase in RV systolic pressure were found in the PTB group. Iloprost caused a decrease in mean arterial blood pressure (MAP) in all groups of animals. An equal reduction in MAP induced by the arterial vasodilator nitroprusside did not improve any of the measured parameters of RV function. We conclude that iloprost has inotropic properties directly improving ventricular function in the hypertrophic and dysfunctional right heart of the rat.

How Do Cognitive Function and Knowledge Affect Heart Failure Self-Care?

ERIC Educational Resources Information Center

Dickson, Victoria Vaughan; Lee, Christopher S.; Riegel, Barbara

2011-01-01

Despite extensive patient education, few heart failure (HF) patients master self-care. Impaired cognitive function may explain why patient education is ineffective. A concurrent triangulation mixed methods design was used to explore how knowledge and cognitive function influence HF self-care. A total of 41 adults with HF participated in interviews…

Regular physical exercise improves endothelial function in heart transplant recipients.

PubMed

Schmidt, Alice; Pleiner, Johannes; Bayerle-Eder, Michaela; Wiesinger, Günther F; Rödler, Suzanne; Quittan, Michael; Mayer, Gert; Wolzt, Michael

2002-04-01

Impaired endothelial function is detectable in heart transplant (HTX) recipients and regarded as risk factor for coronary artery disease. We have studied whether endothelial function can be improved in HTX patients participating in a regular physical training program as demonstrated in patients with chronic heart failure, hypertension and coronary artery disease. Male HTX patients and healthy, age-matched controls were studied. Seven HTX patients (age: 60 +/- 6 yr; 6 +/- 2 yr of HTX) participated in an outpatient training program, six HTX patients (age: 63 +/- 8 yr; 7 +/- 1 yr of HTX) maintained a sedentary lifestyle without regular physical exercise since transplantation. A healthy control group comprised six subjects (age: 62 +/- 6 yr). Vascular function was assessed by flow-mediated dilation of the brachial artery (FMD). Systemic haemodynamic responses to intravenous infusion of the endothelium independent vasodilator sodium nitroprusside (SNP) and to NG-monomethyl-L-arginine (L-NMMA), an inhibitor of constitutive nitric oxide synthase, were also measured. Resting heart rate was significantly lower (p < 0.05) in healthy controls (66 +/- 13) than in the HTX training group (83 +/- 11) and in non-training HTX patients (91 +/- 9), baseline blood pressure also tended to be lower in healthy subjects and in the training HTX patients. FMD was significantly higher (p < 0.05) in the control group (8.4 +/- 2.2%) and in the training group (7.1 +/- 2.4%), compared with non-training HTX patients (1.4 +/- 0.8%). The response of systolic blood pressure (p = 0.08) and heart rate (p < 0.05) to L-NMMA was reduced in sedentary HTX patients compared with healthy controls and heart rate response to SNP was also impaired in sedentary HTX patients. Regular aerobic physical training restores vascular function in HTX patients, who are at considerable risk for developing vascular complications. This effect is demonstrable in conduit and systemic resistance arteries.

Genome-wide compendium and functional assessment of in vivo heart enhancers

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

Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of > 35 epigenomic data sets from mouse and human pre-and postnatal hearts we created a comprehensive reference of > 80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs ofmore » two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function.« less

Genome-wide compendium and functional assessment of in vivo heart enhancers

DOE PAGES

Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen; ...

2016-10-05

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of > 35 epigenomic data sets from mouse and human pre-and postnatal hearts we created a comprehensive reference of > 80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs ofmore » two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function.« less

Genome-wide compendium and functional assessment of in vivo heart enhancers

PubMed Central

Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen; Fukuda-Yuzawa, Yoko; Osterwalder, Marco; Mannion, Brandon J.; May, Dalit; Spurrell, Cailyn H.; Plajzer-Frick, Ingrid; Pickle, Catherine S.; Lee, Elizabeth; Garvin, Tyler H.; Kato, Momoe; Akiyama, Jennifer A.; Afzal, Veena; Lee, Ah Young; Gorkin, David U.; Ren, Bing; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.

2016-01-01

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of >35 epigenomic data sets from mouse and human pre- and postnatal hearts we created a comprehensive reference of >80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs of two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function. PMID:27703156

Cognitive impairment in heart failure patients

PubMed Central

Leto, Laura; Feola, Mauro

2014-01-01

Cognitive damage in heart failure (HF) involves different domains thus interfering with the ability for single patient to self-care and to cope with treatment regimens, modifying symptoms and health behaviours. Many cerebral and functional changes were detected in brain imaging, involving areas of both grey and white matter deputed to cognition. Although various instruments are available to explore cognition, no consensus was obtained on better tools to be used in HF population. Reduction in cerebral blood flow, decreased cardiac output, alterations of cerebrovascular reactivity and modification of blood pressure levels are the main features involved in the etiopathogenetic mechanisms of cognitive deficit. Several cardiac variables, laboratory parameters, demographic and clinical elements were studied for their possible relation with cognition and should be properly evaluated to define patients at increased risk of impairment. The present review gathers available data pointing out assured information and discussing possible areas of research development. PMID:25593581

B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction.

PubMed

Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

2013-10-01

Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6C(hi) monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell-selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction.

B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction

PubMed Central

Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

2014-01-01

Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6Chi monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell–selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction. PMID:24037091

Reversible heart rhythm complexity impairment in patients with primary aldosteronism

NASA Astrophysics Data System (ADS)

Lin, Yen-Hung; Wu, Vin-Cent; Lo, Men-Tzung; Wu, Xue-Ming; Hung, Chi-Sheng; Wu, Kwan-Dun; Lin, Chen; Ho, Yi-Lwun; Stowasser, Michael; Peng, Chung-Kang

2015-08-01

Excess aldosterone secretion in patients with primary aldosteronism (PA) impairs their cardiovascular system. Heart rhythm complexity analysis, derived from heart rate variability (HRV), is a powerful tool to quantify the complex regulatory dynamics of human physiology. We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that underwent adrenalectomy and 25 patients with essential hypertension (EH). The heart rate data were analyzed by conventional HRV and heart rhythm complexity analysis including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We found APA patients had significantly decreased DFAα2 on DFA analysis and decreased area 1-5, area 6-15, and area 6-20 on MSE analysis (all p < 0.05). Area 1-5, area 6-15, area 6-20 in the MSE study correlated significantly with log-transformed renin activity and log-transformed aldosterone-renin ratio (all p < = 0.01). The conventional HRV parameters were comparable between PA and EH patients. After adrenalectomy, all the altered DFA and MSE parameters improved significantly (all p < 0.05). The conventional HRV parameters did not change. Our result suggested that heart rhythm complexity is impaired in APA patients and this is at least partially reversed by adrenalectomy.

Impaired chronotropic response to physical activities in heart failure patients.

PubMed

Shen, Hong; Zhao, Jianrong; Zhou, Xiaohong; Li, Jingbo; Wan, Qing; Huang, Jing; Li, Hui; Wu, Liqun; Yang, Shungang; Wang, Ping

2017-05-25

While exercise-based cardiac rehabilitation has a beneficial effect on heart failure hospitalization and mortality, it is limited by the presence of chronotropic incompetence (CI) in some patients. This study explored the feasibility of using wearable devices to assess impaired chronotropic response in heart failure patients. Forty patients with heart failure (left ventricular ejection fraction, LVEF: 44.6 ± 5.8; age: 54.4 ± 11.7) received ECG Holter and accelerometer to monitor heart rate (HR) and physical activities during symptom-limited treadmill exercise testing, 6-min hall walk (6MHW), and 24-h daily living. CI was defined as maximal HR during peak exercise testing failing to reach 70% of age-predicted maximal HR (APMHR, 220 - age). The correlation between HR and physical activities in Holter-accelerometer recording was analyzed. Of 40 enrolled patients, 26 were able to perform treadmill exercise testing. Based on exercise test reports, 13 (50%) of 26 patients did not achieve at least 70% of APMHR (CI patients). CI patients achieved a lower % APMHR (62.0 ± 6.3%) than non-CI patients who achieved 72.0 ± 1.2% of APMHR (P < 0.0001). When Holter-accelerometer recording was used to assess chronotropic response, the percent APMHR achieved during 6MHW and physical activities was significantly lower in CI patients than in non-CI patients. CI patients had a significantly shorter 6MHW distance and less physical activity intensity than non-CI patients. The study found impaired chronotropic response in 50% of heart failure patients who took treadmill exercise testing. The wearable Holter-accelerometer recording could help to identify impaired chronotropic response to physical activities in heart failure patients. ClinicalTrials.gov ID NCT02358603 . Registered 16 May 2014.

Resting handgrip force and impaired cardiac function at rest and during exercise in COPD patients.

PubMed

Cortopassi, Felipe; Divo, Miguel; Pinto-Plata, Victor; Celli, Bartolome

2011-05-01

Cardiac function measured as the oxygen pulse (O(2) pulse) is impaired during exercise (CPET) in patients with COPD. We investigated the relationship between handgrip force and O(2) pulse in COPD and controls. We measured anthropometrics, lung function, respiratory muscle force, handgrip (HG) force and fat free mass (FFM) at rest in 18 men with COPD (FEV(1)%=45±20) and 15 controls. We then performed a symptom limited cardiopulmonary exercise test (CPET) with similar load and used heart rate, and oxygen pulse (VO(2)/HR) to express cardiac function at rest and during exercise. We corrected the O(2) pulse by FFM. Patients and controls were similar in BMI and FFM. COPD patients had lower handgrip (37.8±7 vs. 55±2) kg. O(2) pulse and HG were associated (r=0.665). At rest, COPD patients had faster heart rate (76±11 vs. 61±5) and lower oxygen pulse. COPD patients had lower oxygen pulse mL/beat at exercise isotime (10.6±3.7 vs. 14.3±2.7), even adjusted by muscle mass. Handgrip is associated with impaired heart function at rest and during exercise in COPD patients even adjusting for muscle mass differences. Lower handgrip may be a marker of impaired cardiac function in COPD patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Echocardiographic assessment of right heart function in heart transplant recipients and the relation to exercise hemodynamics.

PubMed

Clemmensen, Tor Skibsted; Eiskjaer, Hans; Løgstrup, Brian Bridal; Andersen, Mads Jønsson; Mellemkjaer, Søren; Poulsen, Steen Hvitfeldt

2016-08-01

This study aimed to characterize right heart function in heart transplantation (HTx) patients using advanced echocardiographic assessment and simultaneous right heart catheterization (RHC). Comprehensive two-dimensional (2D) and three-dimensional (3D) echocardiographic assessment of right heart function was performed in 105 subjects (64 stable HTx patients and 41 healthy controls). RHC was performed at rest and during semi-supine maximal exercise test. Compared with controls, in conclusion, HTx patients had impaired right ventricle (RV) systolic function in terms of decreased RV-free wall (FW) global longitudinal strain (GLS) (-20 ± 5% vs. -28 ± 5%, P < 0.0001) and 3D-ejection fraction (EF) (50 ± 8% vs. 60 ± 6%, P < 0.0001). In HTx patients, echocardiographic RV systolic function was significantly correlated with NYHA-class (3D-RVEF: r = -0.62, P < 0.0001; RV-FW-GLS: r = -0.41, P = 0.0009) and cardiac allograft vasculopathy (3D-RVEF: r = -0.42, P = 0.0005; RV-FW-GLS: r = -0.25, P = 0.0444). RHC demonstrated a good correlation between invasively assessed resting RV-stroke volume index and exercise capacity (r = 0.58, P < 0.0001) and NYHA-class (r = -0.41, P = 0.0009). RV systolic function is reduced in HTx patients compared with controls. 3D RVEF and 2D longitudinal deformation analyses are associated with clinical performance in stable HTx patients and seem suitable in noninvasive routine right heart function evaluation after HTx. Invasively assessed RV systolic reserve was strongly associated with exercise capacity. © 2016 Steunstichting ESOT.

Impaired heart rate variability and altered cardiac sympathovagal balance after antidepressant overdose.

PubMed

Waring, W S; Rhee, J Y; Bateman, D N; Leggett, G E; Jamie, H

2008-11-01

Antidepressant overdose may be associated with significant cardiotoxicity, and recent data have shown that acute toxic effects are associated with impaired heart rate variability. This study was designed to examine the feasibility of non-invasive heart rate variability recording in patients that present to hospital after deliberate antidepressant ingestion. This was a prospective study of 72 consecutive patients attending the Emergency Department after deliberate antidepressant overdose and 72 age-matched patients that ingested paracetamol, as a control group. Single time-point continuous electrocardiographic recordings were used to allow spectral analyses of heart rate variability determined in low-frequency (LF) and high-frequency (HF) domains. The LF:HF ratio was used to represent overall sympathovagal cardiac activity. Antidepressant overdose was associated with reduced overall heart rate variability: 1329 vs. 2018 ms(2) (P = 0.0239 by Mann-Whitney test). Variability in the LF domain was higher (64.8 vs. 49.8, P = 0.0006), whereas that in the HF domain was lower (24.3 vs. 36.4, P = 0.0001), and the LF:HF ratio was higher in the antidepressant group (2.4 vs. 1.2, P = 0.0003). Antidepressant overdose is associated with impaired heart rate variability in a pattern consistent with excess cardiac sympathetic activity. Further work is required to establish the significance of these findings and to explore whether the impairment of heart rate variability may be used to predict the development of arrhythmia in this patient group.

PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats.

PubMed

Kurtz, Melisa; Capobianco, Evangelina; Martinez, Nora; Roberti, Sabrina Lorena; Arany, Edith; Jawerbaum, Alicia

2014-10-01

In maternal diabetes, the fetal heart can be structurally and functionally affected. Maternal diets enriched in certain unsaturated fatty acids can activate the nuclear receptors peroxisome proliferator-activated receptors (PPARs) and regulate metabolic and anti-inflammatory pathways during development. Our aim was to investigate whether PPARα expression, lipid metabolism, lipoperoxidation, and nitric oxide (NO) production are altered in the fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPAR activation on these parameters. We found decreased PPARα expression in the hearts of male but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARα ligand leukotriene B4 upregulated the expression of PPARα and target genes involved in fatty acid oxidation in the fetal hearts. Increased concentrations of triglycerides, cholesterol, and phospholipids were found in the hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented with 6% olive oil or 6% safflower oil, enriched in unsaturated fatty acids that can activate PPARs, led to few changes in lipid concentrations, but up-regulated PPARα expression in fetal hearts. NO production, which was increased in the hearts of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the hearts of male fetuses in the diabetic group, was reduced by the maternal treatments supplemented with safflower oil. In conclusion, impaired PPARα expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a gender-dependent manner by treatments enriched with PPAR ligands. © 2014 Society for Endocrinology.

Heart rhythm complexity impairment in patients undergoing peritoneal dialysis

NASA Astrophysics Data System (ADS)

Lin, Yen-Hung; Lin, Chen; Ho, Yi-Heng; Wu, Vin-Cent; Lo, Men-Tzung; Hung, Kuan-Yu; Liu, Li-Yu Daisy; Lin, Lian-Yu; Huang, Jenq-Wen; Peng, Chung-Kang

2016-06-01

Cardiovascular disease is one of the leading causes of death in patients with advanced renal disease. The objective of this study was to investigate impairments in heart rhythm complexity in patients with end-stage renal disease. We prospectively analyzed 65 patients undergoing peritoneal dialysis (PD) without prior cardiovascular disease and 72 individuals with normal renal function as the control group. Heart rhythm analysis including complexity analysis by including detrended fractal analysis (DFA) and multiscale entropy (MSE) were performed. In linear analysis, the PD patients had a significantly lower standard deviation of normal RR intervals (SDRR) and percentage of absolute differences in normal RR intervals greater than 20 ms (pNN20). Of the nonlinear analysis indicators, scale 5, area under the MSE curve for scale 1 to 5 (area 1-5) and 6 to 20 (area 6-20) were significantly lower than those in the control group. In DFA anaylsis, both DFA α1 and DFA α2 were comparable in both groups. In receiver operating characteristic curve analysis, scale 5 had the greatest discriminatory power for two groups. In both net reclassification improvement model and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of SDRR, pNN20, and pNN50. In conclusion, PD patients had worse cardiac complexity parameters. MSE parameters are useful to discriminate PD patients from patients with normal renal function.

The Missing Link in the Pathophysiology of Vascular Cognitive Impairment: Design of the Heart-Brain Study

PubMed Central

Hooghiemstra, Astrid M.; Bertens, Anne Suzanne; Leeuwis, Anna E.; Bron, Esther E.; Bots, Michiel L.; Brunner-La Rocca, Hans-Peter; de Craen, Anton J.M.; van der Geest, Rob J.; Greving, Jacoba P.; Kappelle, L. Jaap; Niessen, Wiro J.; van Oostenbrugge, Robert J.; van Osch, Matthias J.P.; de Roos, Albert; van Rossum, Albert C.; Biessels, Geert Jan; van Buchem, Mark A.; Daemen, Mat J.A.P.; van der Flier, Wiesje M.

2017-01-01

Background Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol. Methods The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz­heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines. Results and Conclusions The

Knockout of Eva1a leads to rapid development of heart failure by impairing autophagy

PubMed Central

Zhang, Shu; Lin, Xin; Li, Ge; Shen, Xue; Niu, Di; Lu, Guang; Fu, Xin; Chen, Yingyu; Cui, Ming; Bai, Yun

2017-01-01

EVA1A (Eva-1 homologue A) is a novel lysosome and endoplasmic reticulum-associated protein that can regulate cell autophagy and apoptosis. Eva1a is expressed in the myocardium, but its function in myocytes has not yet been investigated. Therefore, we generated inducible, cardiomyocyte-specific Eva1a knockout mice with an aim to determine the role of Eva1a in cardiac remodelling in the adult heart. Data from experiments showed that loss of Eva1a in the adult heart increased cardiac fibrosis, promoted cardiac hypertrophy, and led to cardiomyopathy and death. Further investigation suggested that this effect was associated with impaired autophagy and increased apoptosis in Eva1a knockout hearts. Moreover, knockout of Eva1a activated Mtor signalling and the subsequent inhibition of autophagy. In addition, Eva1a knockout hearts showed disorganized sarcomere structure and mitochondrial misalignment and aggregation, leading to the lack of ATP generation. Collectively, these data demonstrated that Eva1a improves cardiac function and inhibits cardiac hypertrophy and fibrosis by increasing autophagy. In conclusion, our results demonstrated that Eva1a may have an important role in maintaining cardiac homeostasis. PMID:28151473

[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.

Lamina-associated polypeptide 2alpha loss impairs heart function and stress response in mice.

PubMed

Gotic, Ivana; Leschnik, Michael; Kolm, Ursula; Markovic, Mato; Haubner, Bernhard J; Biadasiewicz, Katarzyna; Metzler, Bernhard; Stewart, Colin L; Foisner, Roland

2010-02-05

Lamina-associated polypeptide (LAP)2alpha is a mammalian chromatin-binding protein that interacts with a fraction of A-type lamins in the nuclear interior. Because mutations in lamins and LAP2alpha lead to cardiac disorders in humans, we hypothesized that these factors may play important roles in heart development and adult tissue homeostasis. We asked whether the presence of LAP2alpha was required for normal cardiac function. To study the molecular mechanisms of the disease, we analyzed heart structure and function in complete and conditional Lap2alpha(-/-) mice as well as Lap2alpha(-/-)/Mdx mutants. Unlike conditional deletion of LAP2alpha in late embryonic striated muscle, its complete knockout caused systolic dysfunction in young mice, accompanied by sporadic fibrosis in old animals, as well as deregulation of major cardiac transcription factors GATA4 and myocyte enhancer factor 2c. Activation of compensatory pathways, including downregulation of beta-adrenergic receptor signaling, resulted in reduced responsiveness of the myocardium to chronic beta-adrenergic stimulation and stalled the progression of LAP2alpha-deficient hearts from hypertrophy toward cardiac failure. Dystrophin deficiency in an Mdx background resulted in a transient rescue of the Lap2alpha(-/-) phenotype. Our data suggest a novel role of LAP2alpha in the maintenance of cardiac function under normal and stress conditions.

Heart and brain interaction in patients with heart failure: overview and proposal for a taxonomy. A position paper from the Study Group on Heart and Brain Interaction of the Heart Failure Association.

PubMed

Doehner, Wolfram; Ural, Dilek; Haeusler, Karl Georg; Čelutkienė, Jelena; Bestetti, Reinaldo; Cavusoglu, Yuksel; Peña-Duque, Marco A; Glavas, Duska; Iacoviello, Massimo; Laufs, Ulrich; Alvear, Ricardo Marmol; Mbakwem, Amam; Piepoli, Massimo F; Rosen, Stuart D; Tsivgoulis, Georgios; Vitale, Cristiana; Yilmaz, M Birhan; Anker, Stefan D; Filippatos, Gerasimos; Seferovic, Petar; Coats, Andrew J S; Ruschitzka, Frank

2018-02-01

Heart failure (HF) is a complex clinical syndrome with multiple interactions between the failing myocardium and cerebral (dys-)functions. Bi-directional feedback interactions between the heart and the brain are inherent in the pathophysiology of HF: (i) the impaired cardiac function affects cerebral structure and functional capacity, and (ii) neuronal signals impact on the cardiovascular continuum. These interactions contribute to the symptomatic presentation of HF patients and affect many co-morbidities of HF. Moreover, neuro-cardiac feedback signals significantly promote aggravation and further progression of HF and are causal in the poor prognosis of HF. The diversity and complexity of heart and brain interactions make it difficult to develop a comprehensive overview. In this paper a systematic approach is proposed to develop a comprehensive atlas of related conditions, signals and disease mechanisms of the interactions between the heart and the brain in HF. The proposed taxonomy is based on pathophysiological principles. Impaired perfusion of the brain may represent one major category, with acute (cardio-embolic) or chronic (haemodynamic failure) low perfusion being sub-categories with mostly different consequences (i.e. ischaemic stroke or cognitive impairment, respectively). Further categories include impairment of higher cortical function (mood, cognition), of brain stem function (sympathetic over-activation, neuro-cardiac reflexes). Treatment-related interactions could be categorized as medical, interventional and device-related interactions. Also interactions due to specific diseases are categorized. A methodical approach to categorize the interdependency of heart and brain may help to integrate individual research areas into an overall picture. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Cognitive impairment and cardiovascular diseases in the elderly. A heart-brain continuum hypothesis.

PubMed

Abete, Pasquale; Della-Morte, David; Gargiulo, Gaetano; Basile, Claudia; Langellotto, Assunta; Galizia, Gianluigi; Testa, Gianluca; Canonico, Vincenzo; Bonaduce, Domenico; Cacciatore, Francesco

2014-11-01

The aging population is increasing and, therefore, a higher prevalence of cardiac disease is emerging; including hypertension, coronary artery disease, atrial fibrillation and chronic heart failure. Large cohort studies have revealed a relationship among increased risk for cognitive impairment and dementia in cardiovascular diseases probably due to embolic stroke or chronic cerebral hypoperfusion. Thus, the aim of the present review is to overview the studies that investigate the presence and/or the development of cognitive impairments and dementia in patients with varied types of cardiovascular disease. Finally, a continuum among hypertension, coronary artery disease, atrial fibrillation and chronic heart failure with to the development of cognitive impairment and progression to dementia has been hypothesized. Copyright © 2014 Elsevier B.V. All rights reserved.

Renal impairment and heart failure with preserved ejection fraction early post-myocardial infarction

PubMed Central

Jorapur, Vinod; Lamas, Gervasio A; Sadowski, Zygmunt P; Reynolds, Harmony R; Carvalho, Antonio C; Buller, Christopher E; Rankin, James M; Renkin, Jean; Steg, Philippe Gabriel; White, Harvey D; Vozzi, Carlos; Balcells, Eduardo; Ragosta, Michael; Martin, C Edwin; Srinivas, Vankeepuram S; Wharton III, William W; Abramsky, Staci; Mon, Ana C; Kronsberg, Shari S; Hochman, Judith S

2010-01-01

AIM: To study if impaired renal function is associated with increased risk of peri-infarct heart failure (HF) in patients with preserved ejection fraction (EF). METHODS: Patients with occluded infarct-related arteries (IRAs) between 1 to 28 d after myocardial infarction (MI) were grouped into chronic kidney disease (CKD) stages based on estimated glomerular filtration rate (eGFR). Rates of early post-MI HF were compared among eGFR groups. Logistic regression was used to explore independent predictors of HF. RESULTS: Reduced eGFR was present in 71.1% of 2160 patients, with significant renal impairment (eGFR < 60 mL/min every 1.73 m2) in 14.8%. The prevalence of HF was higher with worsening renal function: 15.5%, 17.8% and 29.4% in patients with CKD stages 1, 2 and 3 or 4, respectively (P < 0.0001), despite a small absolute difference in mean EF across eGFR groups: 48.2 ± 10.0, 47.9 ± 11.3 and 46.2 ± 12.1, respectively (P = 0.02). The prevalence of HF was again higher with worsening renal function among patients with preserved EF: 10.1%, 13.6% and 23.6% (P < 0.0001), but this relationship was not significant among patients with depressed EF: 27.1%, 26.2% and 37.9% (P = 0.071). Moreover, eGFR was an independent correlate of HF in patients with preserved EF (P = 0.003) but not in patients with depressed EF (P = 0.181). CONCLUSION: A significant proportion of post-MI patients with occluded IRAs have impaired renal function. Impaired renal function was associated with an increased rate of early post-MI HF, the association being strongest in patients with preserved EF. These findings have implications for management of peri-infarct HF. PMID:20885993

Heart-Rate Recovery Index Is Impaired in Behçet's Disease

PubMed Central

Kaya, Ergun Baris; Yorgun, Hikmet; Akdogan, Ali; Ates, Ahmet Hakan; Canpolat, Ugur; Sunman, Hamza; Aytemir, Kudret; Tokgozoglu, Lale; Kabakci, Giray; Calguneri, Meral; Ozkutlu, Hilmi; Oto, Ali

2009-01-01

Behçet's disease, a multisystemic inflammatory disorder, has been associated with a number of cardiovascular dysfunctions, including ventricular arrhythmias and sudden cardiac death. Heart-rate recovery after exercise can provide both an estimate of impaired parasympathetic tone and a prognosis in regard to all-cause and cardiovascular death. The aim of our study was to evaluate heart-rate recovery in Behçet's disease From January through July 2008, we examined at our outpatient clinic and prospectively enrolled 30 consecutive patients with Behçet's disease and 50 healthy control participants who were matched for age and sex. Basal electrocardiography, echocardiography, and treadmill exercise testing were performed in all patients and control participants. The heart-rate recovery index was calculated in the usual manner, by subtracting the 1st-minute (Rec1), 2nd-minute (Rec2), and 3rd-minute (Rec3) recovery heart rates from the maximal heart rate after exercise stress testing. Patients with Behçet's disease exhibited significantly lower heart-rate recovery numbers, compared with healthy control participants: Rec1, 24.28 ± 8.2 vs 34.4 ± 7.6, P = 0.002; Rec2, 49.28 ± 11.2 vs 57.5 ± 7.0, P < 0.05; and Rec3, 56.2 ± 12.11 vs 67.4 ± 8.7, P = 0.014. To our knowledge, this is the 1st study that shows an impaired heart-rate recovery index (indicative of reduced parasympathetic activity) among patients with Behçet's disease. Given the independent prognostic value of the heart-rate recovery index, our results may explain the increased occurrence of arrhythmias and sudden cardiac death in Behçet's patients. Therefore, this index may be clinically useful in the identification of high-risk patients. PMID:19693299

Sexual function after heart transplantation.

PubMed

Mulligan, T; Sheehan, H; Hanrahan, J

1991-01-01

To define sexual interest, ability, and activity before and after heart transplantation, we surveyed all discharged, male heart transplant recipients from our institution. Of the 115 potential subjects, 71 (62%) responded. Respondents were predominantly (89%) white, had a mean age of 47.9 years (24 to 64 years), and most (74%) were living with their spouses. Pretransplant libido was strong and remained unchanged after heart transplantation. Transplant recipients reported their partner's libido to be strong, and even stronger after transplantation than before (p = 0.033). In contrast, erectile rigidity and orgasmic ability were impaired before, and declined further after, the transplant procedure. Respondents perceived this gap between libido and sexual ability to be a problem, and interest in evaluation and treatment was high.

Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

PubMed

Cheung, Carlos Chun Ho; Soon, Choong Yee; Chuang, Chia-Lin; Phillips, Anthony R J; Zhang, Shaoping; Cooper, Garth J S

2015-09-01

Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P < 0.0001) at concentrations that only moderately impaired function of control hearts. To our knowledge, this is the first report describing the acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease

Peak oxygen uptake and left ventricular ejection fraction, but not depressive symptoms, are associated with cognitive impairment in patients with chronic heart failure

PubMed Central

Steinberg, Gerrit; Lossnitzer, Nicole; Schellberg, Dieter; Mueller-Tasch, Thomas; Krueger, Carsten; Haass, Markus; Ladwig, Karl Heinz; Herzog, Wolfgang; Juenger, Jana

2011-01-01

Background The aim of the present study was to assess cognitive impairment in patients with chronic heart failure (CHF) and its associations with depressive symptoms and somatic indicators of illness severity, which is a matter of controversy. Methods and results Fifty-five patients with CHF (mean age 55.3 ± 7.8 years; 80% male; New York Heart Association functional class I–III) underwent assessment with an expanded neuropsychological test battery (eg, memory, complex attention, mental flexibility, psychomotor speed) to evaluate objective and subjective cognitive impairment. Depressive symptoms were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) and a self-report inventory (Hospital Anxiety and Depression Scale [HADS]). A comprehensive clinical dataset, including left ventricular ejection fraction, peak oxygen uptake, and a 6-minute walk test, was obtained for all patients. Neuropsychological functioning revealed impairment in 56% of patients in at least one measure of our neuropsychological test battery. However, the Mini Mental State Examination (MMSE) could only detect cognitive impairment in 1.8% of all patients, 24% had HADS scores indicating depressive symptoms, and 11.1% met SCID criteria for a depressive disorder. No significant association was found between depressive symptoms and cognitive impairment. Left ventricular ejection fraction was related to subjective cognitive impairment, and peak oxygen uptake was related to objective cognitive impairment. Conclusion Cognitive functioning was substantially reduced in patients with CHF and should therefore be diagnosed and treated in routine clinical practice. Caution is advised when the MMSE is used to identify cognitive impairment in patients with CHF. PMID:22267941

Peak oxygen uptake and left ventricular ejection fraction, but not depressive symptoms, are associated with cognitive impairment in patients with chronic heart failure.

PubMed

Steinberg, Gerrit; Lossnitzer, Nicole; Schellberg, Dieter; Mueller-Tasch, Thomas; Krueger, Carsten; Haass, Markus; Ladwig, Karl Heinz; Herzog, Wolfgang; Juenger, Jana

2011-01-01

The aim of the present study was to assess cognitive impairment in patients with chronic heart failure (CHF) and its associations with depressive symptoms and somatic indicators of illness severity, which is a matter of controversy. Fifty-five patients with CHF (mean age 55.3 ± 7.8 years; 80% male; New York Heart Association functional class I-III) underwent assessment with an expanded neuropsychological test battery (eg, memory, complex attention, mental flexibility, psychomotor speed) to evaluate objective and subjective cognitive impairment. Depressive symptoms were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) and a self-report inventory (Hospital Anxiety and Depression Scale [HADS]). A comprehensive clinical dataset, including left ventricular ejection fraction, peak oxygen uptake, and a 6-minute walk test, was obtained for all patients. Neuropsychological functioning revealed impairment in 56% of patients in at least one measure of our neuropsychological test battery. However, the Mini Mental State Examination (MMSE) could only detect cognitive impairment in 1.8% of all patients, 24% had HADS scores indicating depressive symptoms, and 11.1% met SCID criteria for a depressive disorder. No significant association was found between depressive symptoms and cognitive impairment. Left ventricular ejection fraction was related to subjective cognitive impairment, and peak oxygen uptake was related to objective cognitive impairment. Cognitive functioning was substantially reduced in patients with CHF and should therefore be diagnosed and treated in routine clinical practice. Caution is advised when the MMSE is used to identify cognitive impairment in patients with CHF.

Coronary heart disease and risk for cognitive impairment or dementia: Systematic review and meta-analysis.

PubMed

Deckers, Kay; Schievink, Syenna H J; Rodriquez, Maria M F; van Oostenbrugge, Robert J; van Boxtel, Martin P J; Verhey, Frans R J; Köhler, Sebastian

2017-01-01

Accumulating evidence suggests an association between coronary heart disease and risk for cognitive impairment or dementia, but no study has systematically reviewed this association. Therefore, we summarized the available evidence on the association between coronary heart disease and risk for cognitive impairment or dementia. Medline, Embase, PsycINFO, and CINAHL were searched for all publications until 8th January 2016. Articles were included if they fulfilled the inclusion criteria: (1) myocardial infarction, angina pectoris or coronary heart disease (combination of both) as predictor variable; (2) cognition, cognitive impairment or dementia as outcome; (3) population-based study; (4) prospective (≥1 year follow-up), cross-sectional or case-control study design; (5) ≥100 participants; and (6) aged ≥45 years. Reference lists of publications and secondary literature were hand-searched for possible missing articles. Two reviewers independently screened all abstracts and extracted information from potential relevant full-text articles using a standardized data collection form. Study quality was assessed with the Newcastle-Ottawa Scale. We pooled estimates from the most fully adjusted model using random-effects meta-analysis. We identified 6,132 abstracts, of which 24 studies were included. A meta-analysis of 10 prospective cohort studies showed that coronary heart disease was associated with increased risk of cognitive impairment or dementia (OR = 1.45, 95%CI = 1.21-1.74, p<0.001). Between-study heterogeneity was low (I2 = 25.7%, 95%CI = 0-64, p = 0.207). Similar significant associations were found in separate meta-analyses of prospective cohort studies for the individual predictors (myocardial infarction, angina pectoris). In contrast, meta-analyses of cross-sectional and case-control studies were inconclusive. This meta-analysis suggests that coronary heart disease is prospectively associated with increased odds of developing cognitive impairment or dementia

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.

Aging Impairs Myocardial Fatty Acid and Ketone Oxidation and Modifies Cardiac Functional and Metabolic Responses to Insulin in Mice

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

Hyyti, Outi M.; Ledee, Dolena; Ning, Xue-Han

2010-07-02

Aging presumably initiates shifts in substrate oxidation mediated in part by changes in insulin sensitivity. Similar shifts occur with cardiac hypertrophy and may contribute to contractile dysfunction. We tested the hypothesis that aging modifies substrate utilization and alters insulin sensitivity in mouse heart when provided multiple substrates. In vivo cardiac function was measured with microtipped pressure transducers in the left ventricle from control (4–6 mo) and aged (22–24 mo) mice. Cardiac function was also measured in isolated working hearts along with substrate and anaplerotic fractional contributions to the citric acid cycle (CAC) by using perfusate containing 13C-labeled free fatty acidsmore » (FFA), acetoacetate, lactate, and unlabeled glucose. Stroke volume and cardiac output were diminished in aged mice in vivo, but pressure development was preserved. Systolic and diastolic functions were maintained in aged isolated hearts. Insulin prompted an increase in systolic function in aged hearts, resulting in an increase in cardiac efficiency. FFA and ketone flux were present but were markedly impaired in aged hearts. These changes in myocardial substrate utilization corresponded to alterations in circulating lipids, thyroid hormone, and reductions in protein expression for peroxisome proliferator-activated receptor (PPAR)α and pyruvate dehydrogenase kinase (PDK)4. Insulin further suppressed FFA oxidation in the aged. Insulin stimulation of anaplerosis in control hearts was absent in the aged. The aged heart shows metabolic plasticity by accessing multiple substrates to maintain function. However, fatty acid oxidation capacity is limited. Impaired insulin-stimulated anaplerosis may contribute to elevated cardiac efficiency, but may also limit response to acute stress through depletion of CAC intermediates.« less

Impaired post exercise heart rate recovery in anabolic steroid users.

PubMed

dos Santos, M R; Dias, R G; Laterza, M C; Rondon, M U P B; Braga, A M F W; de Moraes Moreau, R L; Negrão, C E; Alves, M-J N N

2013-10-01

Previous study showed that muscle sympathetic nerve activity (MSNA) was augmented in anabolic steroids users (AASU). In the present study, we tested the hypothesis that the heart rate (HR) responses after maximal exercise testing would be reduced in AASU. 10 male AASU and 10 AAS nonusers (AASNU) were studied. Cardiopulmonary exercise was performed to assess the functional capacity and heart rate recovery. MSNA was recorded directly from the peroneal nerve by microneurography technique. Peak oxygen consumption (VO₂) was lower in AASU compared to AASNU (43.66±2.24 vs. 52.70±1.68 ml/kg/min, P=0.005). HR recovery (HRR) at first and second minute was lower in AASU than AASNU (21±2 vs. 27±2 bpm, P=0.02 and 37±4 vs. 45±2 bpm, P=0.05, respectively). MSNA was higher in AASU than AASNU (29±3 vs. 20±1 bursts/min, P=0.01). Further analysis showed a correlation between HRR and MSNA (r=- 0.64, P=0.02), HRR at first minute and peak VO₂ (r=0.70, P=0.01) and HRR at second minute and peak VO₂ (r=0.62, P=0.02). The exacerbated sympathetic outflow associated with a lower parasympathetic activation after maximal exercise, which impairs heart rate recovery, strengthens the idea of autonomic imbalance in AASU. © Georg Thieme Verlag KG Stuttgart · New York.

Chronic Hypoxemia in Children With Congenital Heart Defect Impairs Airway Epithelial Sodium Transport.

PubMed

Kaskinen, Anu K; Helve, Otto; Andersson, Sture; Kirjavainen, Turkka; Martelius, Laura; Mattila, Ilkka P; Rautiainen, Paula; Pitkänen, Olli M

2016-01-01

Ambient hypoxia impairs the airway epithelial Na transport, which is crucial in lung edema reabsorption. Whether chronic systemic hypoxemia affects airway Na transport has remained largely unknown. We have therefore investigated whether chronic systemic hypoxemia in children with congenital heart defect affects airway epithelial Na transport, Na transporter-gene expression, and short-term lung edema accumulation. Prospective, observational study. Tertiary care medical center responsible for nationwide pediatric cardiac surgery. Ninety-nine children with congenital heart defect or acquired heart disease (age range, 6 d to 14.8 yr) were divided into three groups based on their level of preoperative systemic hypoxemia: 1) normoxemic patients (SpO2% ≥ 95%; n = 44), 2) patients with cyanotic congenital heart defect and moderate hypoxemia (SpO2 86-94%; n = 16), and 3) patients with cyanotic congenital heart defect and profound systemic hypoxemia (SpO2 ≤ 85%; n = 39). Nasal transepithelial potential difference served as a surrogate measure for epithelial Na transport of the respiratory tract. Profoundly hypoxemic patients had 29% lower basal nasal transepithelial potential difference (p = 0.02) and 55% lower amiloride-sensitive nasal transepithelial potential difference (p = 0.0003) than normoxemic patients. In profoundly hypoxemic patients, nasal epithelial messenger RNA expressions of two airway Na transporters (amiloride-sensitive epithelial Na channel and β1- Na-K-ATPase) were not attenuated, but instead α1-Na-K-ATPase messenger RNA levels were higher (p = 0.03) than in the normoxemic patients, indicating that posttranscriptional factors may impair airway Na transport. The chest radiograph lung edema score increased after congenital cardiac surgery in profoundly hypoxemic patients (p = 0.0004) but not in patients with normoxemia or moderate hypoxemia. The impaired airway epithelial amiloride-sensitive Na transport activity in profoundly hypoxemic children with

Sleep-disordered breathing, impaired cardiac adrenergic innervation and prognosis in heart failure.

PubMed

Scala, Oriana; Paolillo, Stefania; Formisano, Roberto; Pellegrino, Teresa; Rengo, Giuseppe; Gargiulo, Paola; De Michele, Fausto; Starace, Antonio; Rapacciuolo, Antonio; Parisi, Valentina; Prastaro, Maria; Piscopo, Valentina; Dellegrottaglie, Santo; Bruzzese, Dario; De Martino, Fabiana; Parente, Antonio; Leosco, Dario; Trimarco, Bruno; Cuocolo, Alberto; Perrone-Filardi, Pasquale

2016-06-23

Unfavourable effects of sleep-disordered breathing (SDB) in heart failure (HF) are mainly mediated by impaired sympathetic activity. Few data are available on SDB and cardiac adrenergic impairment evaluated at myocardial level. The aim of the study was to assess the relationship between SDB, cardiac sympathetic innervation assessed by 123 I-metaiodobenzylguanidine ( 123 I-MIBG) imaging and prognosis in HF. Observational, prospective study enrolling patients with HF and reduced systolic function. Patients underwent nocturnal cardiorespiratory monitoring to assess SDB presence by apnoea/hypopnoea index (AHI), and 123 I-MIBG imaging to calculate heart-to-mediastinum (H/M) ratios and washout rate. Patients were prospectively followed for 29±18 months for the combined endpoint of cardiovascular death and HF hospitalisation. Ninety-four patients (66.1±9.8 years; left ventricular ejection fraction 32±7%) were enrolled; 72 (77%) showed SDB and, compared with non-SDB, significantly reduced early (1.67±0.22 vs 1.77±0.13; p=0.019) and late H/M ratios (1.50±0.22 vs 1.61±0.23; p=0.038). Dividing patients into two groups according to SDB severity, patients with a moderate-severe disturbance (AHI >15; n=43) showed significantly worse survival for the composite study outcome (log-rank test, p=0.001) with respect to patients with mild or no disorder (AHI ≤15; n=51). Adding SDB variables to the already known prognostic role of 123 I-MIBG imaging, we observed a worse survival in patients with both SDB and H/M impairment. Patients with systolic HF and SDB show more impaired cardiac adrenergic innervation assessed by 123 I-MIBG imaging, and more adverse prognosis compared with HF patients without SDB. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Assessment of cardiac autonomic functions by heart rate recovery, heart rate variability and QT dynamicity parameters in patients with acromegaly.

PubMed

Dural, Muhammet; Kabakcı, Giray; Cınar, Neşe; Erbaş, Tomris; Canpolat, Uğur; Gürses, Kadri Murat; Tokgözoğlu, Lale; Oto, Ali; Kaya, Ergün Barış; Yorgun, Hikmet; Sahiner, Levent; Dağdelen, Selçuk; Aytemir, Kudret

2014-04-01

Cardiovascular complications are the most common causes of morbidity and mortality in acromegaly. However, there is little data regarding cardiac autonomic functions in these patients. Herein, we aimed to investigate several parameters of cardiac autonomic functions in patients with acromegaly compared to healthy subjects. We enrolled 20 newly diagnosed acromegalic patients (55% female, age:45.7 ± 12.6 years) and 32 age- and gender-matched healthy subjects. All participants underwent 24 h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting 1st, 2nd and 3rd minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV) and QT dynamicity analysis. Baseline characteristics were similar except diabetes mellitus and hypertension among groups. Mean HRR1 (29.2 ± 12.3 vs 42.6 ± 6.5, p = 0.001), HRR2 (43.5 ± 15.6 vs 61.1 ± 10.8, p = 0.001) and HRR3 (46.4 ± 16.2 vs 65.8 ± 9.8, p = 0.001) values were significantly higher in control group. HRV parameters as, SDNN [standard deviation of all NN intervals] (p = 0.001), SDANN [SD of the 5 min mean RR intervals] (p = 0.001), RMSSD [root square of successive differences in RR interval] (p = 0.001), PNN50 [proportion of differences in successive NN intervals >50 ms] (p = 0.001) and high-frequency [HF] (p = 0.001) were significantly decreased in patients with acromegaly; but low frequency [LF] (p = 0.046) and LF/HF (p = 0.001) were significantly higher in acromegaly patients. QTec (p = 0.009), QTac/RR slope (p = 0.017) and QTec/RR slope (p = 0.01) were significantly higher in patients with acromegaly. Additionally, there were significant negative correlation of disease duration with HRR2, HRR3, SDNN, PNN50, RMSSD, variability index. Our study results suggest that cardiac autonomic functions are impaired in patients with acromegaly. Further large scale studies are needed to exhibit the prognostic significance of impaired autonomic functions in patients with

Experimental Evolution and Heart Function in Drosophila.

PubMed

Shahrestani, Parvin; Burke, Molly K; Birse, Ryan; Kezos, James N; Ocorr, Karen; Mueller, Laurence D; Rose, Michael R; Bodmer, Rolf

Drosophila melanogaster is a good model species for the study of heart function. However, most previous work on D. melanogaster heart function has focused on the effects of large-effect genetic variants. We compare heart function among 18 D. melanogaster populations that have been selected for altered development time, aging, or stress resistance. We find that populations with faster development and faster aging have increased heart dysfunction, measured as percentage heart failure after electrical pacing. Experimental evolution of different triglyceride levels, by contrast, has little effect on heart function. Evolved differences in heart function correlate with allele frequency changes at many loci of small effect. Genomic analysis of these populations produces a list of candidate loci that might affect cardiac function at the intersection of development, aging, and metabolic control mechanisms.

Health literacy and global cognitive function predict e-mail but not internet use in heart failure patients.

PubMed

Schprechman, Jared P; Gathright, Emily C; Goldstein, Carly M; Guerini, Kate A; Dolansky, Mary A; Redle, Joseph; Hughes, Joel W

2013-01-01

Background. The internet offers a potential for improving patient knowledge, and e-mail may be used in patient communication with providers. However, barriers to internet and e-mail use, such as low health literacy and cognitive impairment, may prevent patients from using technological resources. Purpose. We investigated whether health literacy, heart failure knowledge, and cognitive function were related to internet and e-mail use in older adults with heart failure (HF). Methods. Older adults (N = 119) with heart failure (69.84 ± 9.09 years) completed measures of health literacy, heart failure knowledge, cognitive functioning, and internet use in a cross-sectional study. Results. Internet and e-mail use were reported in 78.2% and 71.4% of this sample of patients with HF, respectively. Controlling for age and education, logistic regression analyses indicated that higher health literacy predicted e-mail (P < .05) but not internet use. Global cognitive function predicted e-mail (P < .05) but not internet use. Only 45% used the Internet to obtain information on HF and internet use was not associated with greater HF knowledge. Conclusions. The majority of HF patients use the internet and e-mail, but poor health literacy and cognitive impairment may prevent some patients from accessing these resources. Future studies that examine specific internet and email interventions to increase HF knowledge are needed.

Deletion of neurturin impairs development of cholinergic nerves and heart rate control in postnatal mouse hearts.

PubMed

Downs, Anthony M; Jalloh, Hawa B; Prater, Kayla J; Fregoso, Santiago P; Bond, Cherie E; Hampton, Thomas G; Hoover, Donald B

2016-05-01

The neurotrophic factor neurturin is required for normal cholinergic innervation of adult mouse heart and bradycardic responses to vagal stimulation. Our goals were to determine effects of neurturin deletion on development of cardiac chronotropic and dromotropic functions, vagal baroreflex response, and cholinergic nerve density in nodal regions of postnatal mice. Experiments were performed on postnatal C57BL/6 wild-type (WT) and neurturin knockout (KO) mice. Serial electrocardiograms were recorded noninvasively from conscious pups using an ECGenie apparatus. Mice were treated with atenolol to evaluate and block sympathetic effects on heart rate (HR) and phenylephrine (PE) to stimulate the baroreflex. Immunohistochemistry was used to label cholinergic nerves in paraffin sections. WT and KO mice showed similar age-dependent increases in HR and decreases in PR interval between postnatal days (P) 2.5 and 21. Treatment with atenolol reduced HR significantly in WT and KO pups at P7.5. PE caused a reflex bradycardia that was significantly smaller in KO pups. Cholinergic nerve density was significantly less in nodal regions of P7.5 KO mice. We conclude that cholinergic nerves have minimal influence on developmental changes in HR and PR, QRS, and QTc intervals in mouse pups. However, cholinergic nerves mediate reflex bradycardia by 1 week postnatally. Deletion of neurturin impairs cholinergic innervation of the heart and the vagal efferent component of the baroreflex early during postnatal development. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Functional impairment and mental health functioning among Vietnamese children.

PubMed

Dang, Hoang-Minh; Weiss, Bahr; Trung, Lam T

2016-01-01

Functional impairment is a key indicator of need for mental health services among children and adolescents, often a stronger predictor of service usage than mental health symptoms themselves. Functional impairment may be of particular importance in low- and middle-income countries (LMIC) because of its potential to focus policy on treatment of child mental health problems which is generally given low priority in LMIC. However, few studies have assessed functional impairment in LMIC. The present study assessed rates of functional impairment among children in Vietnam, as a case example of an LMIC, as well as effects of other risk/protective factors of particular relevance to LMIC (e.g., whether the family lived in an urban or rural area; family structure variables such as grandparents living with the family). 1314 parents of children 6-16 years old from 10 Vietnamese provinces were interviewed. The overall rate of functional impairment among Vietnamese children was 20 %, similar to rates in high-income countries such as Germany and the United States, suggesting that LMIC status may not be associated with dramatic increases in functional impairment in children. Functional impairment was significantly greater among mental health cases than non-cases, with increases of over 550 % associated with mental health caseness. A number of other risk factors (e.g., marital status) had smaller but significant effects. Mental health problems are a major but not the sole contributor to functional impairment among Vietnamese children. The pragmatic significance of this research lies in its potential to affect public awareness and policy related to child mental health in LMIC.

Human G109E-Inhibitor-1 Impairs Cardiac Function and Promotes Arrhythmias

PubMed Central

Haghighi, Kobra; Pritchard, Tracy J.; Liu, Guan-Sheng; Singh, Vivek P.; Bidwell, Philip; Lam, Chi Keung; Vafiadaki, Elizabeth; Das, Parthib; Ma, Jianyong; Kunduri, Swati; Sanoudou, Despina; Florea, Stela; Vanderbilt, Erica; Wang, Hong-Shang; Rubinstein, Jack; Hajjar, Roger J.; Kranias, Evangelia G.

2015-01-01

A hallmark of human and experimental heart failure is deficient sarcoplasmic reticulum (SR) Ca-uptake reflecting impaired contractile function. This is at least partially attributed to dephosphorylation of phospholamban by increased protein phosphatase 1 (PP1) activity. Indeed inhibition of PP1 by transgenic overexpression or gene-transfer of constitutively active inhibitor-1 improved Ca-cycling, preserved function and decreased fibrosis in small and large animal models of heart failure, suggesting that inhibitor-1 may represent a potential therapeutic target. We recently identified a novel human polymorphism (G109E) in the inhibitor-1 gene with a frequency of 7% in either normal or heart failure patients. Transgenic mice, harboring cardiac-specific expression of G109E inhibitor-1, exhibited decreases in contractility, Ca-kinetics and SR Ca-load. These depressive effects were relieved by isoproterenol stimulation. Furthermore, stress conditions (2 Hz +/− Iso) induced increases in Ca-sparks, Ca-waves (60% of G109E versus 20% in wild types) and after-contractions (76% of G109E versus 23% of wild types) in mutant cardiomyocytes. Similar findings were obtained by acute expression of the G109E variant in adult cardiomyocytes in the absence or presence of endogenous inhibitor-1. The underlying mechanisms included reduced binding of mutant inhibitor-1 to PP1, increased PP1 activity, and dephosphorylation of phospholamban at Ser16 and Thr17. However, phosphorylation of the ryanodine receptor at Ser2808 was not altered while phosphorylation at Ser2814 was increased, consistent with increased activation of Ca/calmodulin-dependent protein kinase II (CaMKII), promoting aberrant SR Ca-release. Parallel in vivo studies revealed that mutant mice developed ventricular ectopy and complex ventricular arrhythmias (including bigeminy, trigeminy and ventricular tachycardia), when challenged with isoproterenol. Inhibition of CaMKII activity by KN-93 prevented the increased propensity

Functional impairment and mental health functioning among Vietnamese children

PubMed Central

Dang, Hoang-Minh; Weiss, Bahr; Trung, Lam T.

2015-01-01

Purpose Functional impairment is a key indicator of need for mental health services among children and adolescents, often a stronger predictor of service usage than mental health symptoms themselves. Functional impairment may be of particular importance in low and middle income countries (LMIC) because of its potential to focus policy on treatment of child mental health problems which is generally given low priority in LMIC. However, few studies have assessed functional impairment in LMIC. The present study assessed rates of functional impairment among children in Vietnam, as a case example of an LMIC, as well as effects of other risk/protective factors of particular relevance to LMIC (e.g., whether the family lived in an urban or rural area; family structure variables such as grandparents living with the family). Methods 1,314 parents of children 6–16 years old from 10 Vietnamese provinces were interviewed. Results The overall rate of functional impairment among Vietnamese children was 20%, similar to rates in high income countries such as Germany and the United States, suggesting that LMIC status may not be associated with dramatic increases in functional impairment in children. Functional impairment was significantly greater among mental health cases than non-cases, with increases of over 550% associated with mental health caseness. A number of other risk factors (e.g., marital status) had smaller but significant effects. Conclusions Mental health problems are a major but not the sole contributor to functional impairment among Vietnamese children. The pragmatic significance of this research lies in its potential to affect public awareness and policy related to child mental health in LMIC. PMID:26315942

Exercise training in Tgαq*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism.

PubMed

Grassi, Bruno; Majerczak, Joanna; Bardi, Eleonora; Buso, Alessia; Comelli, Marina; Chlopicki, Stefan; Guzik, Magdalena; Mavelli, Irene; Nieckarz, Zenon; Salvadego, Desy; Tyrankiewicz, Urszula; Skórka, Tomasz; Bottinelli, Roberto; Zoladz, Jerzy A; Pellegrino, Maria Antonietta

2017-08-01

Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgα q *44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age). Forty-eight Tgα q *44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype [myosin heavy chain (MHC) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5'-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor-γ coactivator-α (PGC-1α)]. In the untrained Tgα q *44 mice functional impairments of exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK, and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased percentage of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance. NEW & NOTEWORTHY Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration

Lung Function Abnormalities in Smokers with Ischemic Heart Disease.

PubMed

Franssen, Frits M E; Soriano, Joan B; Roche, Nicolas; Bloomfield, Paul H; Brusselle, Guy; Fabbri, Leonardo M; García-Rio, Francisco; Kearney, Mark T; Kwon, Namhee; Lundbäck, Bo; Rabe, Klaus F; Raillard, Alice; Muellerova, Hana; Cockcroft, John R

2016-09-01

The aim of the ALICE (Airflow Limitation in Cardiac Diseases in Europe) study was to investigate the prevalence of airflow limitation in patients with ischemic heart disease and the effects on quality of life, healthcare use, and future health risk. To examine prebronchodilator and post-bronchodilator spirometry in outpatients aged greater than or equal to 40 years with clinically documented ischemic heart disease who were current or former smokers. This multicenter, cross-sectional study was conducted in 15 cardiovascular outpatient clinics in nine European countries. Airflow limitation was defined as post-bronchodilator FEV1/FVC less than 0.70. Among the 3,103 patients with ischemic heart disease who were recruited, lung function was defined for 2,730 patients. Airflow limitation was observed in 30.5% of patients with ischemic heart disease: 11.3% had mild airflow limitation, 15.8% moderate airflow limitation, 3.3% severe airflow limitation, and 0.1% very severe airflow limitation. Most patients with airflow limitation (70.6%) had no previous spirometry testing or diagnosed pulmonary disease. Airflow limitation was associated with greater respiratory symptomatology, impaired health status, and more frequent emergency room visits (P < 0.05). Airflow limitation compatible with chronic obstructive pulmonary disease affects almost one-third of patients with ischemic heart disease. Although airflow limitation is associated with additional morbidity and societal burden, it is largely undiagnosed and untreated. Clinical trial registered with www.clinicaltrials.gov (NCT 01485159).

Association between socioeconomic deprivation and functional impairment after stroke: the South London Stroke Register.

PubMed

Chen, Ruoling; Crichton, Siobhan; McKevitt, Christopher; Rudd, Anthony G; Sheldenkar, Anita; Wolfe, Charles D A

2015-03-01

Previous findings of the association between socioeconomic deprivation and functional impairment after stroke are inconsistent. There is a lack of data on long-term association. We assessed the association and differences by age, sex, prestroke comorbidities, and stroke phenotypes. We examined data from the South London Stroke Register cohort of 1995 to 2011, recording all first-ever strokes in patients of all ages in South London. A total of 2104 patients were alive at 3 months after stroke. Socioeconomic deprivation was measured using the index of multiple deprivation based on patient postcodes, and functional impairment after stroke was defined as a Barthel index of <15. At 3 months after stroke, 643 patients had functional impairment (30.6%; 95% confidence interval, 28.6%-32.5%). Compared with the first quartile of index of multiple deprivation (the least deprived), multivariate-adjusted odds ratios for functional impairment in patients with the second, third, and fourth quartiles were 1.29 (95% confidence interval, 0.94-1.76), 1.33 (0.97-1.82), and 1.78 (1.31-2.43), overall P=0.004. The association was significant in patients aged ≥65 years (corresponding odds ratios were 1.49 [1.02-2.17], 1.21 [0.83-1.75], and 1.94 [1.34-2.81]; P=0.003); in women, P=0.008, in patients who do not have prestroke comorbidities, P=0.009, and in patients with ischemic stroke, P<0.001, but not significant in their counterpart patients. There were similar patterns of the associations of socioeconomic deprivation with impairment at 3 years after stroke. There are significant inequalities in short- and long-term functional recovery after stroke. General socioeconomic improvement, targeting groups at high risk of functional impairment is likely to reduce inequality in functional recovery after stroke. © 2015 American Heart Association, Inc.

Renal denervation in male rats with heart failure improves ventricular sympathetic nerve innervation and function

PubMed Central

Pinkham, Maximilian I.; Loftus, Michael T.; Amirapu, Satya; Guild, Sarah-Jane; Quill, Gina; Woodward, William R.; Habecker, Beth A.

2017-01-01

Heart failure is characterized by the loss of sympathetic innervation to the ventricles, contributing to impaired cardiac function and arrhythmogenesis. We hypothesized that renal denervation (RDx) would reverse this loss. Male Wistar rats underwent myocardial infarction (MI) or sham surgery and progressed into heart failure for 4 wk before receiving bilateral RDx or sham RDx. After additional 3 wk, left ventricular (LV) function was assessed, and ventricular sympathetic nerve fiber density was determined via histology. Post-MI heart failure rats displayed significant reductions in ventricular sympathetic innervation and tissue norepinephrine content (nerve fiber density in the LV of MI+sham RDx hearts was 0.31 ± 0.05% vs. 1.00 ± 0.10% in sham MI+sham RDx group, P < 0.05), and RDx significantly increased ventricular sympathetic innervation (0.76 ± 0.14%, P < 0.05) and tissue norepinephrine content. MI was associated with an increase in fibrosis of the noninfarcted ventricular myocardium, which was attenuated by RDx. RDx improved LV ejection fraction and end-systolic and -diastolic areas when compared with pre-RDx levels. This is the first study to show an interaction between renal nerve activity and cardiac sympathetic nerve innervation in heart failure. Our findings show denervating the renal nerves improves cardiac sympathetic innervation and function in the post-MI failing heart. PMID:28052866

Double jeopardy: the influence of excessive daytime sleepiness and impaired cognition on health-related quality of life in adults with heart failure

PubMed Central

Riegel, Barbara; Ratcliffe, Sarah J.; Weintraub, William S.; Sayers, Steven L.; Goldberg, Lee R.; Potashnik, Sheryl; Weaver, Terri E.; Pressler, Susan J.

2012-01-01

Aims To determine how excessive daytime sleepiness (EDS) and impaired cognition contribute to health-related quality of life (HRQL) in heart failure (HF). Methods and results Adults with chronic HF were enrolled into a prospective cohort study. Data were obtained from 280 subjects enrolled from three sites in the northeastern USA; 242 completed the 6-month study. At baseline, cohorts with and without EDS were identified using the Epworth Sleepiness Scale. Each EDS group was further subdivided into those with and without impaired cognition using a battery of five neuropsychological tests. Two disease-specific measures, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Functional Outcomes of Sleep Questionnaire (FOSQ), were used to measure HRQL. General linear modelling of square-transformed variables was used to test the hypothesis that cohort membership was a significant predictor of HRQL. At 6 months the remaining sample was 62.5 [standard deviation (SD) 12] years old, mostly male (63%), white (65%), and functionally compromised [72% New York Heart Association (NYHA) class III/IV]. The cohort with both EDS and impaired cognition had the lowest KCCQ overall summary score (60.5 ± 22.5) compared with the cohort without EDS or impaired cognition (74.6 ± 17.4, P ≤ 0.001). A similar effect was seen on the FOSQ (16.0 ± 2.8 vs. 18.5 ± 2.2, P < 0.001). Conclusion Impaired cognition alone did not explain poor HRQL, but the addition of EDS poses a significant risk for poor HRQL. Interventions designed to influence EDS may improve HRQL in this population. PMID:22510422

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.

Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer's Disease.

PubMed

Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard

2015-01-01

The temporal relationship of cognitive deficit and functional impairment in Alzheimer's disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process.

[Functional impairment associated with cognitive impairment in hospitalised elderly].

PubMed

Ocampo-Chaparro, José Mauricio; Mosquera-Jiménez, José Ignacio; Davis, Annabelle S; Reyes-Ortiz, Carlos A

The aim of this study was to analyse the effect of cognitive impairment on functional decline in hospitalised patients aged ≥60 years. Measurements at admission included demographic data, Charlson's comorbidity index, and cognitive impairment (according to education level). Data were also collected on hospital length of stay, depression, and delirium developed during hospitalisation. The outcome, Barthel Index (BI), was measured at admission, discharge, and 1-month post-discharge. Patients with BI≤75 at admission (n=54) or with a missing BI value were excluded (n=1). Multivariate logistic regression analyses were conducted to explore predictive factors with functional decline (BI≤75) from admission to discharge, and 1-month later. Of the 133 patients included, 24.8% and 19.6% had a BI≤75 at discharge and at 1-month, respectively. Compared with men, women had more than double risk for functional decline at discharge and 1-month (P<.05). Compared with those without delirium and without cognitive impairment, those with delirium and cognitive impairment had an increased risk for functional decline (BI≤75) at discharge (OR 5.15, 95% CI; 1.94-13.67), and at 1-month (OR 6.26, 95% CI; 2.30-17.03). Similarly, those with comorbidity (≥2) had increased functional decline at discharge (OR 2.36, 95% CI; 1.14-4.87), and at 1-month after discharge (OR 2.71, 95% CI; 1.25-5.89). Delirium during hospitalisation, together with cognitive impairment on admission, was a strong predictor of functional decline. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Associations of Subjective Sleep Quality and Daytime Sleepiness With Cognitive Impairment in Adults and Elders With Heart Failure.

PubMed

Byun, Eeeseung; Kim, Jinyoung; Riegel, Barbara

2017-01-01

This study examined the association of subjective nighttime sleep quality and daytime sleepiness with cognitive impairment in 105 adults (< 60 years old) and 167 elders (≥ 60 years old) with heart failure. Nighttime sleep quality and daytime sleepiness were measured by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. Cognitive impairment was assessed using a neuropsychological battery measuring attention, memory, and processing speed. Multivariate logistic regression was used. In adults, daytime sleepiness was associated with cognitive impairment, whereas poor nighttime sleep quality was associated with cognitive impairment in elders. Age may play an important role in how sleep impacts cognition in persons with heart failure. Improving nighttime sleep quality and daytime sleepiness in this population may improve cognition.

Human G109E-inhibitor-1 impairs cardiac function and promotes arrhythmias.

PubMed

Haghighi, Kobra; Pritchard, Tracy J; Liu, Guan-Sheng; Singh, Vivek P; Bidwell, Philip; Lam, Chi Keung; Vafiadaki, Elizabeth; Das, Parthib; Ma, Jianyong; Kunduri, Swati; Sanoudou, Despina; Florea, Stela; Vanderbilt, Erica; Wang, Hong-Shang; Rubinstein, Jack; Hajjar, Roger J; Kranias, Evangelia G

2015-12-01

A hallmark of human and experimental heart failure is deficient sarcoplasmic reticulum (SR) Ca-uptake reflecting impaired contractile function. This is at least partially attributed to dephosphorylation of phospholamban by increased protein phosphatase 1 (PP1) activity. Indeed inhibition of PP1 by transgenic overexpression or gene-transfer of constitutively active inhibitor-1 improved Ca-cycling, preserved function and decreased fibrosis in small and large animal models of heart failure, suggesting that inhibitor-1 may represent a potential therapeutic target. We recently identified a novel human polymorphism (G109E) in the inhibitor-1 gene with a frequency of 7% in either normal or heart failure patients. Transgenic mice, harboring cardiac-specific expression of G109E inhibitor-1, exhibited decreases in contractility, Ca-kinetics and SR Ca-load. These depressive effects were relieved by isoproterenol stimulation. Furthermore, stress conditions (2Hz +/- Iso) induced increases in Ca-sparks, Ca-waves (60% of G109E versus 20% in wild types) and after-contractions (76% of G109E versus 23% of wild types) in mutant cardiomyocytes. Similar findings were obtained by acute expression of the G109E variant in adult cardiomyocytes in the absence or presence of endogenous inhibitor-1. The underlying mechanisms included reduced binding of mutant inhibitor-1 to PP1, increased PP1 activity, and dephosphorylation of phospholamban at Ser16 and Thr17. However, phosphorylation of the ryanodine receptor at Ser2808 was not altered while phosphorylation at Ser2814 was increased, consistent with increased activation of Ca/calmodulin-dependent protein kinase II (CaMKII), promoting aberrant SR Ca-release. Parallel in vivo studies revealed that mutant mice developed ventricular ectopy and complex ventricular arrhythmias (including bigeminy, trigeminy and ventricular tachycardia), when challenged with isoproterenol. Inhibition of CaMKII activity by KN-93 prevented the increased propensity to

hnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function.

PubMed

Ye, Junqiang; Beetz, Nadine; O'Keeffe, Sean; Tapia, Juan Carlos; Macpherson, Lindsey; Chen, Weisheng V; Bassel-Duby, Rhonda; Olson, Eric N; Maniatis, Tom

2015-06-09

We report that mice lacking the heterogeneous nuclear ribonucleoprotein U (hnRNP U) in the heart develop lethal dilated cardiomyopathy and display numerous defects in cardiac pre-mRNA splicing. Mutant hearts have disorganized cardiomyocytes, impaired contractility, and abnormal excitation-contraction coupling activities. RNA-seq analyses of Hnrnpu mutant hearts revealed extensive defects in alternative splicing of pre-mRNAs encoding proteins known to be critical for normal heart development and function, including Titin and calcium/calmodulin-dependent protein kinase II delta (Camk2d). Loss of hnRNP U expression in cardiomyocytes also leads to aberrant splicing of the pre-mRNA encoding the excitation-contraction coupling component Junctin. We found that the protein product of an alternatively spliced Junctin isoform is N-glycosylated at a specific asparagine site that is required for interactions with specific protein partners. Our findings provide conclusive evidence for the essential role of hnRNP U in heart development and function and in the regulation of alternative splicing.

Impairment of pulmonary diffusion correlates with hypoxemic burden in central sleep apnea heart failure patients.

PubMed

Fox, Henrik; Koerber, Britta; Bitter, Thomas; Horstkotte, Dieter; Oldenburg, Olaf

2017-09-01

Central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR) are highly prevalent in heart failure (HF) and are linked to increased mortality. Impaired pulmonary diffusion capacity [DLCO] and [KCO]) have been suggested to play a key role in CSA-CSR pathophysiology. This study investigated the relationship between HF, CSR, DLCO and KCO in well-characterized HF patients. This prospective study included HF patients with CSR, all patients underwent full overnight polysomnography (PSG) and lung function testing. A total of 100 patients were included (age 70.7±9.7years, 95% male, body mass index 28.9±5.3kg/m 2 , left ventricular ejection fraction 33.5±7.7%, New York Heart Association class III 65%. DLCO and oxygenation were significantly correlated with hypoxemic burden (p<0.05). Mean oxygen saturation, oxygen desaturation, C-reactive protein level and pH were significantly associated with CSA-CSR severity (p<0.05). The finding that lung diffusion capacity is significantly associated with hypoxemic burden in HF patients with CSA-CSR highlights the important of lung function in HF patients. Copyright © 2017. Published by Elsevier B.V.

Telomeres and Mitochondria in the Aging Heart

PubMed Central

Moslehi, Javid; DePinho, Ronald A.; Sahin, Ergün

2013-01-01

Studies in humans and in mice have highlighted the importance of short telomeres and impaired mitochondrial function in driving age-related functional decline in the heart. Although telomere and mitochondrial dysfunction have been viewed mainly in isolation, recent studies in telomerase-deficient mice have provided evidence for an intimate link between these two processes. Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and PGC-1β in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging. PMID:22539756

ON THE BIOMECHANICS OF HEART VALVE FUNCTION

PubMed Central

Sacks, Michael S.; Merryman, W. David; Schmidt, David E.

2009-01-01

Heart valves (HVs) are fluidic control components of the heart that ensure unidirectional blood flow during the cardiac cycle. However, this description does not adequately describe the biomechanical ramifications of their function in that their mechanics are multi-modal. Moreover, they must replicate their cyclic function over an entire lifetime, with an estimated total functional demand of least 3×109 cycles. The focus of the present review is on the functional biomechanics of heart valves. Thus, the focus of the present review is on functional biomechanics, referring primarily to biosolid as well as several key biofluid mechanical aspects underlying heart valve physiological function. Specifically, we refer to the mechanical behaviors of the extra-cellular matrix structural proteins, underlying cellular function, and their integrated relation to the major aspects of valvular hemodynamic function. While we focus on the work from the author’s laboratories, relevant works of other investigators have been included whenever appropriate. We conclude with a summary of important future trends. PMID:19540499

Assessment of Diastolic Function in Congenital Heart Disease

PubMed Central

Panesar, Dilveer Kaur; Burch, Michael

2017-01-01

Diastolic function is an important component of left ventricular (LV) function which is often overlooked. It can cause symptoms of heart failure in patients even in the presence of normal systolic function. The parameters used to assess diastolic function often measure flow and are affected by the loading conditions of the heart. The interpretation of diastolic function in the context of congenital heart disease requires some understanding of the effects of the lesions themselves on these parameters. Individual congenital lesions will be discussed in this paper. Recently, load-independent techniques have led to more accurate measurements of ventricular compliance and remodeling in heart disease. The combination of inflow velocities and tissue Doppler measurements can be used to estimate diastolic function and LV filling pressures. This review focuses on diastolic function and assessment in congenital heart disease. PMID:28261582

Neurocognition, functional competence and self-reported functional impairment in psychometrically defined schizotypy.

PubMed

Xavier, Shannon; Best, Michael W; Schorr, Emily; Bowie, Christopher R

2015-01-01

Schizotypy is phenologically and genetically related to schizophrenia-spectrum illness. Previous studies find cognitive function to be mildly impaired, but specific impairments and their relationship to functioning are not well understood. In this study, we sought to examine how cognitive load affects performance in schizotypy and to examine whether impairments might manifest in functional capacity and quality of life. Undergraduate students were screened for abnormally high levels of schizotypy (N = 72) and compared to those without psychopathology (N = 80) on a standard battery of neuropsychological tests, cognitive tests with varying cognitive load, functional capacity measures and quality of life. The high schizotypy group did not differ from controls on traditional measures of neuropsychological functioning, but an interaction of group by cognitive load was observed, where those with schizotypy manifested a greater decline in performance as information processing load was parametrically increased. Differences in functioning were observed and cognitive impairment was associated with impaired functioning. Cognitive and functional impairment can be observed in those with high schizotypal traits who are non-treatment seeking. The sensitivity of cognitive tests to impairment in this population might be a function of their ability to parametrically increase cognitive load.

Obesity is associated with lack of inhibitory control and impaired heart rate variability reactivity and recovery in response to food stimuli.

PubMed

Spitoni, Grazia Fernanda; Ottaviani, Cristina; Petta, Anna Maria; Zingaretti, Pietro; Aragona, Massimiliano; Sarnicola, Antonio; Antonucci, Gabriella

2017-06-01

Recent theories compare obesity with addiction in terms of lack of inhibitory control in both clinical populations. The present study hypothesized impaired inhibition in obese patients reflected both in executive functions and reduced vagal tone (indexed by a decrease in heart rate variability; HRV) in response to food stimuli. Twenty-four inpatients with obesity (19 women) and 37 controls (24 women) underwent ECG monitoring during baseline, food stimuli viewing, and a recovery phase. Tests and questionnaires assessing inhibitory control and psychopathological dispositions were also administered. As hypothesized, patients were characterized by deficits in all the tests measuring inhibitory capacities. Results also show greater HRV reduction and impaired HRV recovery in response to food stimuli in obese patients compared to controls. The drive to eat experienced by obese patients in the absence of caloric need may rely on impairments in inhibitory and vagal functioning. Results are discussed in terms of implications for therapy. Copyright © 2017. Published by Elsevier B.V.

Medication self-management skills and cognitive impairment in older adults hospitalized for heart failure: A cross-sectional study.

PubMed

Howell, Erik H; Senapati, Alpana; Hsich, Eileen; Gorodeski, Eiran Z

2017-01-01

Cognitive impairment is highly prevalent among older adults (aged ≥65 years) hospitalized for heart failure and has been associated with poor outcomes. Poor medication self-management skills have been associated with poor outcomes in this population as well. The presence and extent of an association between cognitive impairment and poor medication self-management skills in this population has not been clearly defined. We assessed the cognition of consecutive older adults hospitalized for heart failure, in relation to their medication self-management skills. We conducted a cross-sectional study of older adults (aged ≥65 years) who were hospitalized for heart failure and were being discharged home. Prior to discharge, we assessed cognition using the Mini-Cog. We also tested patients' ability to read a pill bottle label, open a pill bottle safety cap, and allocate mock pills to a pill box. Pill allocation performance was assessed quantitatively (counts of errors of omission and commission) and qualitatively (patterns suggestive of knowledge-based mistakes, rule-based mistakes, or skill-based slips). Of 55 participants, 22% were found to have cognitive impairment. Patients with cognitive impairment tended to be older as compared to those without cognitive impairment (mean age = 81 vs 76 years, p = NS). Patients with cognitive impairment had a higher prevalence of inability to read pill bottle label (prevalence ratio = 5.8, 95% confidence interval = 3.2-10.5, p = 0.001) and inability to open pill bottle safety cap (prevalence ratio = 3.3, 95% confidence interval = 1.3-8.4, p = 0.03). While most patients (65%) had pill-allocation errors regardless of cognition, those patients with cognitive impairment tended to have more errors of omission (mean number of errors = 48 vs 23, p = 0.006), as well as more knowledge-based mistakes (75% vs 40%, p = 0.03). There is an association between cognitive impairment and poor

Is endothelial microvascular function equally impaired among patients with chronic Chagas and ischemic cardiomyopathy?

PubMed

Borges, Juliana Pereira; Mendes, Fernanda de Souza Nogueira Sardinha; Lopes, Gabriella de Oliveira; Sousa, Andréa Silvestre de; Mediano, Mauro Felippe Felix; Tibiriçá, Eduardo

2018-08-15

Chronic Chagas cardiomyopathy (CCC) and cardiomyopathies due to other etiologies involve differences in pathophysiological pathways that are still unclear. Systemic microvascular abnormalities are associated with the pathogenesis of ischemic heart disease. However, systemic microvascular endothelial function in CCC remains to be elucidated. Thus, we compared the microvascular endothelial function of patients presenting with CCC to those with ischemic cardiomyopathy disease. Microvascular reactivity was assessed in 21 patients with cardiomyopathy secondary to Chagas disease, 21 patients with cardiomyopathy secondary to ischemic disease and 21 healthy controls. Microvascular blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh). Peak increase in forearm blood flow with ACh iontophoresis in relation to baseline was greater in healthy controls than in patients with heart disease (controls: 162.7 ± 58.4% vs. ischemic heart disease: 74.1 ± 48.3% and Chagas: 85.1 ± 68.1%; p < 0.0001). Patients with Chagas and ischemic cardiomyopathy presented similar ACh-induced changes from baseline in skin blood flow (p = 0.55). Endothelial microvascular function was equally impaired among patients with CCC and ischemic cardiomyopathy. Copyright © 2018 Elsevier B.V. All rights reserved.

Impaired Mitochondrial Biogenesis Precedes Heart Failure in Right Ventricular Hypertrophy in Congenital Heart Disease

PubMed Central

Karamanlidis, Georgios; Bautista-Hernandez, Victor; Fynn-Thompson, Francis; Nido, Pedro del; Tian, Rong

2011-01-01

Background The outcome of the surgical repair in congenital heart disease (CHD) correlates with the degree of myocardial damage. In this study we determined whether mitochondrial DNA depletion is a sensitive marker of right ventricular (RV) damage and whether impaired mitochondrial DNA (mtDNA) replication contributes to the transition from compensated hypertrophy to failure. Methods and Results RV samples obtained from 31 patients undergoing cardiac surgery were compared to 5 RV samples from non-failing hearts (control). Patients were divided into compensated hypertrophy and failure groups based on preoperative echocardiography, catheterization and/or MRI data. Mitochondrial enzyme activities (citrate synthase and succinate dehydrogenase) were maintained during hypertrophy and decreased by ~40% (p<0.05 vs. control) at the stage of failure. In contrast, mtDNA content was progressively decreased in the hypertrophied RV through failure (by 28±8% and 67±11% respectively, p<0.05 for both), whereas mtDNA encoded gene expression was sustained by increased transcriptional activity during compensated hypertrophy but not in failure. MtDNA depletion was attributed to reduced mtDNA replication in both hypertrophied and failing RV and it was independent of PGC-1 down-regulation but was accompanied by reduced expression of proteins constituting the mtDNA replication fork. Decreased mtDNA content in compensated hypertrophy was also associated with pathological changes of mitochondria ultrastructure. Conclusions Impaired mtDNA replication causes early and progressive depletion of mtDNA in the RV of the CHD patients during the transition from hypertrophy to failure. Decreased mtDNA content is likely a sensitive marker of mitochondrial injury in this patient population. PMID:21840936

Involvement of systemic venous congestion in heart failure.

PubMed

Rubio Gracia, J; Sánchez Marteles, M; Pérez Calvo, J I

2017-04-01

Systemic venous congestion has gained significant importance in the interpretation of the pathophysiology of acute heart failure, especially in the development of renal function impairment during exacerbations. In this study, we review the concept, clinical characterisation and identification of venous congestion. We update current knowledge on its importance in the pathophysiology of acute heart failure and its involvement in the prognosis. We pay special attention to the relationship between abdominal congestion, the pulmonary interstitium as filtering membrane, inflammatory phenomena and renal function impairment in acute heart failure. Lastly, we review decongestion as a new therapeutic objective and the measures available for its assessment. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Methods to assess Drosophila heart development, function and aging

PubMed Central

Ocorr, Karen; Vogler, Georg; Bodmer, Rolf

2014-01-01

In recent years the Drosophila heart has become an established model of many different aspects of human cardiac disease. This model has allowed identification of disease-causing mechanisms underlying congenital heart disease and cardiomyopathies and has permitted the study underlying genetic, metabolic and age-related contributions to heart function. In this review we discuss methods currently employed in the analysis of the Drosophila heart structure and function, such as optical methods to infer heart function and performance, electrophysiological and mechanical approaches to characterize cardiac tissue properties, and conclude with histological techniques used in the study of heart development and adult structure. PMID:24727147

suPAR level is associated with myocardial impairment assessed with advanced echocardiography in patients with type 1 diabetes with normal ejection fraction and without known heart disease or end-stage renal disease.

PubMed

Theilade, Simone; Rossing, Peter; Eugen-Olsen, Jesper; Jensen, Jan S; Jensen, Magnus T

2016-06-01

Heart disease is a common fatal diabetes-related complication. Early detection of patients at particular risk of heart disease is of prime importance. Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker for development of cardiovascular disease. We investigate if suPAR is associated with early myocardial impairment assessed with advanced echocardiographic methods. In an observational study on 318 patients with type 1 diabetes without known heart disease and with normal left ventricular ejection fraction (LVEF) (biplane LVEF >45%), we performed conventional, tissue Doppler and speckle tracking echocardiography, and measured plasma suPAR levels. Associations between myocardial function and suPAR levels were studied in adjusted models including significant covariates. Patients were 55±12 years (mean±s.d.) and 160 (50%) males. Median (interquartile range) suPAR was 3.4 (1.7) ng/mL and LVEF was 58±5%. suPAR levels were not associated with LVEF (P=0.11). In adjusted models, higher suPAR levels were independently associated with both impaired systolic function assessed with global longitudinal strain (GLS) and tissue velocity s', and with impaired diastolic measures a' and e'/a' (all P=0.034). In multivariable analysis including cardiovascular risk factors and both systolic and diastolic measures (GLS and e'/a'), both remained independently associated with suPAR levels (P=0.012). In patients with type 1 diabetes with normal LVEF and without known heart disease, suPAR is associated with early systolic and diastolic myocardial impairment. Our study implies that both suPAR and advanced echocardiography are useful diagnostic tools for identifying patients with diabetes at risk of future clinical heart disease, suited for intensified medical therapy. © 2016 European Society of Endocrinology.

Evolution of association between renal and liver functions while awaiting heart transplant: An application using a bivariate multiphase nonlinear mixed effects model.

PubMed

Rajeswaran, Jeevanantham; Blackstone, Eugene H; Barnard, John

2018-07-01

In many longitudinal follow-up studies, we observe more than one longitudinal outcome. Impaired renal and liver functions are indicators of poor clinical outcomes for patients who are on mechanical circulatory support and awaiting heart transplant. Hence, monitoring organ functions while waiting for heart transplant is an integral part of patient management. Longitudinal measurements of bilirubin can be used as a marker for liver function and glomerular filtration rate for renal function. We derive an approximation to evolution of association between these two organ functions using a bivariate nonlinear mixed effects model for continuous longitudinal measurements, where the two submodels are linked by a common distribution of time-dependent latent variables and a common distribution of measurement errors.

Iron Status in Chronic Heart Failure: Impact on Symptoms, Functional Class and Submaximal Exercise Capacity.

PubMed

Enjuanes, Cristina; Bruguera, Jordi; Grau, María; Cladellas, Mercé; Gonzalez, Gina; Meroño, Oona; Moliner-Borja, Pedro; Verdú, José M; Farré, Nuria; Comín-Colet, Josep

2016-03-01

To evaluate the effect of iron deficiency and anemia on submaximal exercise capacity in patients with chronic heart failure. We undertook a single-center cross-sectional study in a group of stable patients with chronic heart failure. At recruitment, patients provided baseline information and completed a 6-minute walk test to evaluate submaximal exercise capacity and exercise-induced symptoms. At the same time, blood samples were taken for serological evaluation. Iron deficiency was defined as ferritin < 100 ng/mL or transferrin saturation < 20% when ferritin is < 800 ng/mL. Additional markers of iron status were also measured. A total of 538 heart failure patients were eligible for inclusion, with an average age of 71 years and 33% were in New York Heart Association class III/IV. The mean distance walked in the test was 285 ± 101 meters among those with impaired iron status, vs 322 ± 113 meters (P=.002). Symptoms during the test were more frequent in iron deficiency patients (35% vs 27%; P=.028) and the most common symptom reported was fatigue. Multivariate logistic regression analyses showed that increased levels of soluble transferrin receptor indicating abnormal iron status were independently associated with advanced New York Heart Association class (P < .05). Multivariable analysis using generalized additive models, soluble transferrin receptor and ferritin index, both biomarkers measuring iron status, showed a significant, independent and linear association with submaximal exercise capacity (P=.03 for both). In contrast, hemoglobin levels were not significantly associated with 6-minute walk test distance in the multivariable analysis. In patients with chronic heart failure, iron deficiency but not anemia was associated with impaired submaximal exercise capacity and symptomatic functional limitation. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species

PubMed Central

Wythe, Joshua D.; Liu, Jiandong; Cartry, Jerome; Vogler, Georg; Mohapatra, Bhagyalaxmi; Otway, Robyn T.; Huang, Yu; King, Isabelle N.; Maillet, Marjorie; Zheng, Yi; Crawley, Timothy; Taghli-Lamallem, Ouarda; Semsarian, Christopher; Dunwoodie, Sally; Winlaw, David; Harvey, Richard P.; Fatkin, Diane; Towbin, Jeffrey A.; Molkentin, Jeffery D.; Srivastava, Deepak; Ocorr, Karen; Bruneau, Benoit G.

2011-01-01

Unraveling the gene regulatory networks that govern development and function of the mammalian heart is critical for the rational design of therapeutic interventions in human heart disease. Using the Drosophila heart as a platform for identifying novel gene interactions leading to heart disease, we found that the Rho-GTPase Cdc42 cooperates with the cardiac transcription factor Tinman/Nkx2-5. Compound Cdc42, tinman heterozygous mutant flies exhibited impaired cardiac output and altered myofibrillar architecture, and adult heart–specific interference with Cdc42 function is sufficient to cause these same defects. We also identified K+ channels, encoded by dSUR and slowpoke, as potential effectors of the Cdc42–Tinman interaction. To determine whether a Cdc42–Nkx2-5 interaction is conserved in the mammalian heart, we examined compound heterozygous mutant mice and found conduction system and cardiac output defects. In exploring the mechanism of Nkx2-5 interaction with Cdc42, we demonstrated that mouse Cdc42 was a target of, and negatively regulated by miR-1, which itself was negatively regulated by Nkx2-5 in the mouse heart and by Tinman in the fly heart. We conclude that Cdc42 plays a conserved role in regulating heart function and is an indirect target of Tinman/Nkx2-5 via miR-1. PMID:21690310

Reproducibility of onset and recovery oxygen uptake kinetics in moderately impaired patients with chronic heart failure

PubMed Central

De Vries, Wouter R.; Hoogeveen, Adwin R.; Zonderland, Maria L.; Thijssen, Eric J. M.; Schep, Goof

2007-01-01

Oxygen (O2) kinetics reflect the ability to adapt to or recover from exercise that is indicative of daily life. In patients with chronic heart failure (CHF), parameters of O2 kinetics have shown to be useful for clinical purposes like grading of functional impairment and assessment of prognosis. This study compared the goodness of fit and reproducibility of previously described methods to assess O2 kinetics in these patients. Nineteen CHF patients, New York Heart Association class II–III, performed two constant-load tests on a cycle ergometer at 50% of the maximum workload. Time constants of O2 onset- and recovery kinetics (τ) were calculated by mono-exponential modeling with four different sampling intervals (5 and 10 s, 5 and 8 breaths). The goodness of fit was expressed as the coefficient of determination (R2). Onset kinetics were also evaluated by the mean response time (MRT). Considering O2 onset kinetics, τ showed a significant inverse correlation with peak- \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} $$ \\ifmmode\\expandafter\\dot\\else\\expandafter\\.\\fi{V}{\\text{O}}_{2} $$\\end{document} (R = −0.88, using 10 s sampling intervals). The limits of agreement of both τ and MRT, however, were not clinically acceptable. O2 recovery kinetics yielded better reproducibility and goodness of fit. Using the most optimal sampling interval (5 breaths), a change of at least 13 s in τ is needed to exceed normal test-to-test variations. In conclusion, O2 recovery kinetics are more reproducible for clinical purposes than O2 onset kinetics in moderately impaired patients with CHF. It should be recognized that this observation cannot be assumed to be generalizable to more severely impaired CHF patients. PMID:17277937

Sensory Impairments and Cognitive Function in Middle-Aged Adults.

PubMed

Schubert, Carla R; Cruickshanks, Karen J; Fischer, Mary E; Chen, Yanjun; Klein, Barbara E K; Klein, Ronald; Pinto, A Alex

2017-08-01

Hearing, visual, and olfactory impairments have been associated with cognitive impairment in older adults but less is known about associations with cognitive function in middle-aged adults. Sensory and cognitive functions were measured on participants in the baseline examination (2005-2008) of the Beaver Dam Offspring Study. Cognitive function was measured with the Trail Making tests A (TMTA) and B (TMTB) and the Grooved Peg Board test. Pure-tone audiometry, Pelli-Robson letter charts, and the San Diego Odor Identification test were used to measure hearing, contrast sensitivity, and olfaction, respectively. There were 2,836 participants aged 21-84 years with measures of hearing, visual, olfactory, and cognitive function at the baseline examination. Nineteen percent of the cohort had one sensory impairment and 3% had multiple sensory impairments. In multivariable adjusted linear regression models that included all three sensory impairments, hearing impairment, visual impairment, and olfactory impairment were each independently associated with poorer performance on the TMTA, TMTB, and Grooved Peg Board (p < .05 for all sensory impairments in all models). Participants with a sensory impairment took on average from 2 to 10 seconds longer than participants without the corresponding sensory impairment to complete these tests. Results were similar in models that included adjustment for hearing aid use. Hearing, visual and olfactory impairment were associated with poorer performance on cognitive function tests independent of the other sensory impairments and factors associated with cognition. Sensory impairments in midlife are associated with subtle deficits in cognitive function which may be indicative of early brain aging. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Renal function assessment in heart failure.

PubMed

Pérez Calvo, J I; Josa Laorden, C; Giménez López, I

Renal function is one of the most consistent prognostic determinants in heart failure. The prognostic information it provides is independent of the ejection fraction and functional status. This article reviews the various renal function assessment measures, with special emphasis on the fact that the patient's clinical situation and response to the heart failure treatment should be considered for the correct interpretation of the results. Finally, we review the literature on the performance of tubular damage biomarkers. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Executive functions deficit in mild cognitive impairment.

PubMed

Traykov, Latchezar; Raoux, Nadine; Latour, Florence; Gallo, Livia; Hanon, Olivier; Baudic, Sophie; Bayle, Catherine; Wenisch, Emilie; Remy, Philippe; Rigaud, Anne-Sophie

2007-12-01

To investigate whether patients diagnosed with amnestic mild cognitive impairment (MCI) have also impairment in attention/executive functions, and therefore to clarify whether all subcomponents of executive control are equally affected in MCI. MCI refers to the transitional state between normal aging and dementia. Amnestic MCI is characterized by impaired episodic memory, although subtle impairment of executive functions has been noted on neuropsychologic tests. We investigated 20 MCI patients and 20 normal controls using episodic memory, attention/executive functions, language, and praxis tests. MCI patients had significantly lower scores on all measures of the Free and Cued Selective Reminding Test (P<0.05 to 0.01) than controls. Furthermore, MCI had a greater number of perseverations (P<0.01) on Modified Card Sorting Test and the lowest performance on the Stroop Test (P<0.02). Our findings showed impairment in episodic memory performance in MCI as compared with that of controls. In addition, MCI patients had problems with response inhibition, switching, and cognitive flexibility, which encompass various aspects of executive functions. This suggests that MCI may be identified by using a more detailed procedure for the assessment of cognitive decline than the evaluation of memory alone.

High-fat diet induces protein kinase A and G-protein receptor kinase phosphorylation of β2 -adrenergic receptor and impairs cardiac adrenergic reserve in animal hearts.

PubMed

Fu, Qin; Hu, Yuting; Wang, Qingtong; Liu, Yongming; Li, Ning; Xu, Bing; Kim, Sungjin; Chiamvimonvat, Nipavan; Xiang, Yang K

2017-03-15

Patients with diabetes show a blunted cardiac inotropic response to β-adrenergic stimulation despite normal cardiac contractile reserve. Acute insulin stimulation impairs β-adrenergically induced contractile function in isolated cardiomyocytes and Langendorff-perfused hearts. In this study, we aimed to examine the potential effects of hyperinsulinaemia associated with high-fat diet (HFD) feeding on the cardiac β 2 -adrenergic receptor signalling and the impacts on cardiac contractile function. We showed that 8 weeks of HFD feeding leads to reductions in cardiac functional reserve in response to β-adrenergic stimulation without significant alteration of cardiac structure and function, which is associated with significant changes in β 2 -adrenergic receptor phosphorylation at protein kinase A and G-protein receptor kinase sites in the myocardium. The results suggest that clinical intervention might be applied to subjects in early diabetes without cardiac symptoms to prevent further cardiac complications. Patients with diabetes display reduced exercise capability and impaired cardiac contractile reserve in response to adrenergic stimulation. We have recently uncovered an insulin receptor and adrenergic receptor signal network in the heart. The aim of this study was to understand the impacts of high-fat diet (HFD) on the insulin-adrenergic receptor signal network in hearts. After 8 weeks of HFD feeding, mice exhibited diabetes, with elevated insulin and glucose concentrations associated with body weight gain. Mice fed an HFD had normal cardiac structure and function. However, the HFD-fed mice displayed a significant elevation of phosphorylation of the β 2 -adrenergic receptor (β 2 AR) at both the protein kinase A site serine 261/262 and the G-protein-coupled receptor kinase site serine 355/356 and impaired adrenergic reserve when compared with mice fed on normal chow. Isolated myocytes from HFD-fed mice also displayed a reduced contractile response to

Marital Conflict, Depressive Symptoms, and Functional Impairment

ERIC Educational Resources Information Center

Choi, Heejeong; Marks, Nadine F

2008-01-01

Guided by a stress process perspective, we investigated (a) whether marital conflict might directly lead to changes in depression and functional impairment, (b) whether marital conflict might indirectly lead to changes in functional impairment via depression, and (c) whether marital conflict might indirectly lead to changes in depression via…

What is your patient’s cognitive profile? Three distinct subgroups of cognitive function in persons with heart failure

PubMed Central

Hawkins, Misty A.W.; Schaefer, Julie T.; Gunstad, John; Dolansky, Mary A.; Redle, Joseph D.; Josephson, Richard; Moore, Shirley M.; Hughes, Joel W.

2014-01-01

Purpose To determine whether patients with heart failure (HF) have distinct profiles of cognitive impairment. Background Cognitive impairment is common in HF. Recent work found three cognitive profiles in HF patients— (1) intact, (2) impaired, and (3) memory-impaired. We examined the reproducibility of these profiles and clarified mechanisms. Methods HF patients (68.6±9.7years; N=329) completed neuropsychological testing. Composite scores were created for cognitive domains and used to identify clusters via agglomerative-hierarchical cluster analysis. Results A 3-cluster solution emerged. Cluster 1 (n=109) had intact cognition. Cluster 2 (n=123) was impaired across all domains. Cluster 3 (n=97) had impaired memory only. Clusters differed in age, race, education, SES, IQ, BMI, and diabetes (ps ≤.026) but not in mood, anxiety, cardiovascular, or pulmonary disease (ps≥.118). Conclusions We replicated three distinct patterns of cognitive function in persons with HF. These profiles may help providers offer tailored care to patients with different cognitive and clinical needs. PMID:25510559

Evaluating the role of functional impairment in personality psychopathology.

PubMed

Boland, Jennifer K; Damnjanovic, Tatjana; Anderson, Jaime L

2018-03-22

DSM-5's Section III Alternative Model for Personality Disorder (AMPD) model states that an individual must show impairment in self and interpersonal functioning for PD diagnosis. The current study investigated dimensional personality trait associations with impairment, including differential patterns of impairment across specific PDs, and whether traits have improved our assessment of functional impairment in PDs. Two-hundred and seventy-seven participants were administered measures of Antisocial PD, Avoidant PD, Borderline PD, Narcissistic PD, Obsessive-Compulsive PD, and Schizotypal PD from the perspectives of Section II (PDQ-4) and Section III (PID-5) PD models, as well as measures of functional impairment in interpersonal and intrapersonal domains. Pearson correlations showed associations between ratings of impairment and most Section II and Section III PDs and trait facets, with the exception of narcissistic PD. Hierarchical regression analyses revealed that Section III PDs added predictive validity beyond Section II PDs in predicting impairment, except narcissistic PD. These findings provide support both for the impairment criterion in the AMPD and for the association between trait-based PDs and impairment, and suggest that this trait-based measurement adds uniquely to the understanding of functional impairment. Copyright © 2018. Published by Elsevier B.V.

Inadequate consultation behavior modulates the relationship between type D personality and impaired health status in chronic heart failure.

PubMed

Pelle, Aline J; Schiffer, Angélique A; Smith, Otto R; Widdershoven, Jos W; Denollet, Johan

2010-06-25

Psychological risk factors for impaired health outcomes have been acknowledged in chronic heart failure (CHF), with Type D personality being such a risk factor. Inadequate consultation behavior, a specific aspect of self-management, might be one mechanism in explaining the adverse effect of Type D on health outcomes. In this study we examined the relationship between Type D personality, impaired disease-specific health status, and inadequate consultation behavior. CHF outpatients (n=313) completed the Type D Scale (DS14) at baseline, and the European Heart Failure Self-care Behaviour Scale (EHFScBS) and the Minnesota Living with Heart Failure Questionnaire (MLWHFQ) at 6-month follow-up. Type D personality independently predicted inadequate consultation behavior (OR=1.80, 95%CI [1.03-3.16], p=.04) and impaired health status (OR=3.61, 95%CI [1.93-6.74], p<.001) at 6-month follow-up, adjusting for demographic and clinical variables. Inadequate consultation behavior (OR=1.80, 95%CI [1.11-2.94], p=.02) and NYHA-class (OR=2.83, 95%CI [1.17-4.71], p<.001) were associated with impaired health status, after controlling for demographics, clinical variables, and Type D personality. Post-hoc multivariable analysis pointed out that Type D patients who displayed inadequate consultation behavior were at a 6-fold increased risk of reporting impaired health status, compared to the reference group of non-Type D patients who displayed adequate consultation behavior (OR=6.06, 95%CI [2.53-14.52], p<.001). These findings provide evidence for inadequate behavior as a mechanism that may explain the link between Type D personality and impaired health status. Future studies are warranted to elaborate on these findings. Copyright 2008 Elsevier Ireland Ltd. All rights reserved.

Computational analysis of microRNA function in heart development.

PubMed

Liu, Ganqiang; Ding, Min; Chen, Jiajia; Huang, Jinyan; Wang, Haiyun; Jing, Qing; Shen, Bairong

2010-09-01

Emerging evidence suggests that specific spatio-temporal microRNA (miRNA) expression is required for heart development. In recent years, hundreds of miRNAs have been discovered. In contrast, functional annotations are available only for a very small fraction of these regulatory molecules. In order to provide a global perspective for the biologists who study the relationship between differentially expressed miRNAs and heart development, we employed computational analysis to uncover the specific cellular processes and biological pathways targeted by miRNAs in mouse heart development. Here, we utilized Gene Ontology (GO) categories, KEGG Pathway, and GeneGo Pathway Maps as a gene functional annotation system for miRNA target enrichment analysis. The target genes of miRNAs were found to be enriched in functional categories and pathway maps in which miRNAs could play important roles during heart development. Meanwhile, we developed miRHrt (http://sysbio.suda.edu.cn/mirhrt/), a database aiming to provide a comprehensive resource of miRNA function in regulating heart development. These computational analysis results effectively illustrated the correlation of differentially expressed miRNAs with cellular functions and heart development. We hope that the identified novel heart development-associated pathways and the database presented here would facilitate further understanding of the roles and mechanisms of miRNAs in heart development.

Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction.

PubMed

Borlaug, Barry A; Melenovsky, Vojtech; Russell, Stuart D; Kessler, Kristy; Pacak, Karel; Becker, Lewis C; Kass, David A

2006-11-14

Nearly half of patients with heart failure have a preserved ejection fraction (HFpEF). Symptoms of exercise intolerance and dyspnea are most often attributed to diastolic dysfunction; however, impaired systolic and/or arterial vasodilator reserve under stress could also play an important role. Patients with HFpEF (n=17) and control subjects without heart failure (n=19) generally matched for age, gender, hypertension, diabetes mellitus, obesity, and the presence of left ventricular hypertrophy underwent maximal-effort upright cycle ergometry with radionuclide ventriculography to determine rest and exercise cardiovascular function. Resting cardiovascular function was similar between the 2 groups. Both had limited exercise capacity, but this was more profoundly reduced in HFpEF patients (exercise duration 180+/-71 versus 455+/-184 seconds; peak oxygen consumption 9.0+/-3.4 versus 14.4+/-3.4 mL x kg(-1) x min(-1); both P<0.001). At matched low-level workload, HFpEF subjects displayed approximately 40% less of an increase in heart rate and cardiac output and less systemic vasodilation (all P<0.05) despite a similar rise in end-diastolic volume, stroke volume, and contractility. Heart rate recovery after exercise was also significantly delayed in HFpEF patients. Exercise capacity correlated with the change in cardiac output, heart rate, and vascular resistance but not end-diastolic volume or stroke volume. Lung blood volume and plasma norepinephrine levels rose similarly with exercise in both groups. HFpEF patients have reduced chronotropic, vasodilator, and cardiac output reserve during exercise compared with matched subjects with hypertensive cardiac hypertrophy. These limitations cannot be ascribed to diastolic abnormalities per se and may provide novel therapeutic targets for interventions to improve exercise capacity in this disorder.

Mitochondria and heart failure.

PubMed

Murray, Andrew J; Edwards, Lindsay M; Clarke, Kieran

2007-11-01

Energetic abnormalities in cardiac and skeletal muscle occur in heart failure and correlate with clinical symptoms and mortality. It is likely that the cellular mechanism leading to energetic failure involves mitochondrial dysfunction. Therefore, it is crucial to elucidate the causes of mitochondrial myopathy, in order to improve cardiac and skeletal muscle function, and hence quality of life, in heart failure patients. Recent studies identified several potential stresses that lead to mitochondrial dysfunction in heart failure. Chronically elevated plasma free fatty acid levels in heart failure are associated with decreased metabolic efficiency and cellular insulin resistance. Tissue hypoxia, resulting from low cardiac output and endothelial impairment, can lead to oxidative stress and mitochondrial DNA damage, which in turn causes dysfunction and loss of mitochondrial mass. Therapies aimed at protecting mitochondrial function have shown promise in patients and animal models with heart failure. Despite current therapies, which provide substantial benefit to patients, heart failure remains a relentlessly progressive disease, and new approaches to treatment are necessary. Novel pharmacological agents are needed that optimize substrate metabolism and maintain mitochondrial integrity, improve oxidative capacity in heart and skeletal muscle, and alleviate many of the clinical symptoms associated with heart failure.

Impact of Variations in Kidney Function on Nonvitamin K Oral Anticoagulant Dosing in Patients With Atrial Fibrillation and Recent Acute Heart Failure.

PubMed

Andreu-Cayuelas, José M; Pastor-Pérez, Francisco J; Puche, Carmen M; Mateo-Martínez, Alicia; García-Alberola, Arcadio; Flores-Blanco, Pedro J; Valdés, Mariano; Lip, Gregory Y H; Roldán, Vanessa; Manzano-Fernández, Sergio

2016-02-01

Renal impairment and fluctuations in renal function are common in patients recently hospitalized for acute heart failure and in those with atrial fibrillation. The aim of the present study was to evaluate the hypothetical need for dosage adjustment (based on fluctuations in kidney function) of dabigatran, rivaroxaban and apixaban during the first 6 months after hospital discharge in patients with concomitant atrial fibrillation and heart failure. An observational study was conducted in 162 patients with nonvalvular atrial fibrillation after hospitalization for acute decompensated heart failure who underwent creatinine determinations during follow-up. The hypothetical recommended dosage of dabigatran, rivaroxaban and apixaban according to renal function was determined at discharge. Variations in serum creatinine and creatinine clearance and consequent changes in the recommended dosage of these drugs were identified during 6 months of follow-up. Among the overall study population, 44% of patients would have needed dabigatran dosage adjustment during follow-up, 35% would have needed rivaroxaban adjustment, and 29% would have needed apixaban dosage adjustment. A higher proportion of patients with creatinine clearance < 60 mL/min or with advanced age (≥ 75 years) would have needed dosage adjustment during follow-up. The need for dosage adjustment of nonvitamin K oral anticoagulants during follow-up is frequent in patients with atrial fibrillation after acute decompensated heart failure, especially among older patients and those with renal impairment. Further studies are needed to clarify the clinical importance of these needs for drug dosing adjustment and the ideal renal function monitoring regime in heart failure and other subgroups of patients with atrial fibrillation. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. 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

Cognitive Function Before and After Left Heart Catheterization.

PubMed

Scott, David A; Evered, Lisbeth; Maruff, Paul; MacIsaac, Andrew; Maher, Sarah; Silbert, Brendan S

2018-03-10

Hospital procedures have been associated with cognitive change in older patients. This study aimed to document the prevalence of mild cognitive impairment in individuals undergoing left heart catheterization (LHC) before the procedure and the incidence of cognitive decline to 3 months afterwards. We conducted a prospective, observational, clinical investigation of elderly participants undergoing elective LHC. Cognition was assessed using a battery of written tests and a computerized cognitive battery before the LHC and then at 3 months afterwards. The computerized tests were also administered at 24 hours (or discharge) and 7 days after LHC. A control group of 51 community participants was recruited to calculate cognitive decline using the Reliable Change Index. Of 437 participants, mild cognitive impairment was identified in 226 (51.7%) before the procedure. Computerized tests detected an incidence of cognitive decline of 10.0% at 24 hours and 7.5% at 7 days. At 3 months, written tests detected an incidence of cognitive decline of 13.1% and computerized tests detected an incidence of 8.5%. Cognitive decline at 3 months using written tests was associated with increasing age, whereas computerized tests showed cognitive decline was associated with baseline amnestic mild cognitive impairment, diabetes mellitus, and prior coronary stenting. More than half the patients aged >60 years presenting for LHC have mild cognitive impairment. LHC is followed by cognitive decline in 8% to 13% of individuals at 3 months after the procedure. Subtle cognitive decline both before and after LHC is common and may have important clinical implications. URL: www.anzctr.org.au. Unique identifier: ACTRN12607000051448. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Treatment of Functional Impairment in Patients with Bipolar Disorder.

PubMed

Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Vieta, Eduard

2017-01-01

Traditionally, functional impairment has received little attention in bipolar disorder, despite the fact that many patients experience significant impairments in daily life. In the last decade, research has changed its focus from clinical remission to functional recovery in bipolar patients as a priority. A literature review of this topic will allow us provide an overview of the relevance of functional impairment as well as the potential factors that can predict or contribute to low functioning in bipolar disorder (BD). Treatment approaches should consider not only euthymia as a goal but also cognitive and functional improvement of patients with such a complex disorder. Functional remediation and psychoeducation among psychological interventions may help to enhance functioning. The combination of cognitive enhancers and cognitive/functional remediation programs may help in improving cognitive and functional impairments. Early interventions are essential to prevent cognitive deficits and disability.

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

High‐fat diet induces protein kinase A and G‐protein receptor kinase phosphorylation of β2‐adrenergic receptor and impairs cardiac adrenergic reserve in animal hearts

PubMed Central

Hu, Yuting; Wang, Qingtong; Liu, Yongming; Li, Ning; Xu, Bing; Kim, Sungjin; Chiamvimonvat, Nipavan

2017-01-01

Key points Patients with diabetes show a blunted cardiac inotropic response to β‐adrenergic stimulation despite normal cardiac contractile reserve.Acute insulin stimulation impairs β‐adrenergically induced contractile function in isolated cardiomyocytes and Langendorff‐perfused hearts.In this study, we aimed to examine the potential effects of hyperinsulinaemia associated with high‐fat diet (HFD) feeding on the cardiac β2‐adrenergic receptor signalling and the impacts on cardiac contractile function.We showed that 8 weeks of HFD feeding leads to reductions in cardiac functional reserve in response to β‐adrenergic stimulation without significant alteration of cardiac structure and function, which is associated with significant changes in β2‐adrenergic receptor phosphorylation at protein kinase A and G‐protein receptor kinase sites in the myocardium.The results suggest that clinical intervention might be applied to subjects in early diabetes without cardiac symptoms to prevent further cardiac complications. Abstract Patients with diabetes display reduced exercise capability and impaired cardiac contractile reserve in response to adrenergic stimulation. We have recently uncovered an insulin receptor and adrenergic receptor signal network in the heart. The aim of this study was to understand the impacts of high‐fat diet (HFD) on the insulin–adrenergic receptor signal network in hearts. After 8 weeks of HFD feeding, mice exhibited diabetes, with elevated insulin and glucose concentrations associated with body weight gain. Mice fed an HFD had normal cardiac structure and function. However, the HFD‐fed mice displayed a significant elevation of phosphorylation of the β2‐adrenergic receptor (β2AR) at both the protein kinase A site serine 261/262 and the G‐protein‐coupled receptor kinase site serine 355/356 and impaired adrenergic reserve when compared with mice fed on normal chow. Isolated myocytes from HFD‐fed mice also displayed a

Absolute and Functional Iron Deficiency Is a Common Finding in Patients With Heart Failure and After Heart Transplantation.

PubMed

Przybylowski, P; Wasilewski, G; Golabek, K; Bachorzewska-Gajewska, H; Dobrzycki, S; Koc-Zorawska, E; Malyszko, J

2016-01-01

Anemia is relatively common in patients with heart failure and heart transplant recipients. Both absolute and functional iron deficiency may contribute to the anemia in these populations. Functional iron deficiency (defined as ferritin greater than 200 ng/mL with TSAT (Transferrin saturation) less than 20%) is characterized by the presence of adequate iron stores as defined by conventional criteria, but with insufficient iron mobilization to adequately support. The aim of this study was to determine prevalence of absolute and functional iron deficiency in patients with heart failure (n = 269) and after heart transplantation (n = 130) and their relation to parameters of iron status and inflammation. Iron status, complete blood count, and creatinine levels were assessed using standard laboratory methods. C-reactive protein, hepcidin and hemojuvelin were measured using commercially available kits. Absolute iron deficiency was present in 15% of patients with heart failure and 30% in heart transplant recipients, whereas functional iron deficiency was present in 18% of patients with heart failure and 17% in heart transplant recipients. Functional iron deficiency was associated with significantly higher C-reactive protein and hepcidin levels in heart failure patients, and higher hepcidin and lower estimate glomerular filtration rates in heart transplant recipients. Prevalence of anemia (according to the World Health Organization) was significantly higher in heart transplant recipients (40% vs 22%, P < .001), they were also younger, but with worse kidney function than patients with heart failure. Both absolute and functional iron deficiency were present in a considerable group of patients. This population should be carefully screened for possible reversible causes of inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

Memory loss and decreased executive function are associated with limited functional capacity in patients with heart failure compared to patients with other medical conditions.

PubMed

Kim, JinShil; Shin, Mi-Seung; Hwang, Seon Young; Park, Eunok; Lim, Young-Hyo; Shim, Jae Lan; Kim, Sun Hwa; Kim, Yeon Hee; An, Minjeong

There is limited evidence on the degree of cognitive impairment and its association with physical functional capacity among patients with heart failure (HF) in Korea. In this study, we compared cognitive impairment between patients with HF and community-dwelling participants with non-HF medical conditions (medical participants) and its association with physical functional capacity. We conducted a cross-sectional comparative study and assessed the neuropsychological cognitive status (Seoul Neuropsychological Screening Battery) and physical functional capacity (Duke Activity Status Index) of patients with HF and medical participants using face-to-face interviews. One hundred and eighteen patients with HF (age, 65.45 ± 9.38 years; men, 57.6%; left ventricular ejection fraction, 34.93 ± 8.72%) and 83 medical participants (age, 66.02 ± 8.28 years; men, 47.0%) were included. Using seventh-percentile medical participant Z-scores as cutoffs, memory and executive function were worse in patients with HF than in medical participants: immediate (35.0% vs. 6.0%) and delayed recall memory (34.5% vs. 8.4%), and executive function (28.6% vs. 6.0%). Independent of age, sex, education, comorbidity, and HF status, executive function was a significant predictor of physical functional capacity (b = 1.82, p = .021). More patients with HF had impaired memory and executive function, which were associated with their physical functional capacities. Copyright © 2017 Elsevier Inc. All rights reserved.

Restoration of heart functions using human embryonic stem cells derived heart muscle cells.

PubMed

Gepstein, Lior; Kehat, Izhak

2005-02-01

Extract: Recent advances in molecular and cellular biology and specifically in the areas of stem cell biology and tissue engineering have paved the way for the development of a new field in biomedicine, regenerative medicine. This exciting approach seeks to develop new biological solutions, using the mobilization of endogenous stem cells or delivery of exogenous cells to replace or modify the function of diseased, absent, or malfunctioning tissue. The adult heart represents an attractive candidate for these emerging technologies, since adult cardiomyocytes have limited regenerative capacity. Thus, any significant heart cell loss or dysfunction, such as occurs during heart attack, is mostly irreversible and may lead to the development of progressive heart failure, one of the leading causes of world-wide morbidity and mortality. Similarly, dysfunction of the specialized electrical conduction system within the heart may result in inefficient rhythm initiation or impulse conduction, leading to significant slowing of the heart rate, usually requiring the implantation of a permanent electronic pacemaker. Replacement of the dysfunctional myocardium (heart muscle) by implantation of external heart muscle cells is emerging as a novel paradigm for restoration of the myocardial electromechanical properties, but has been significantly hampered by the paucity of cell sources for human heart cells and by the relatively limited evidence for functional integration between grafted and host cells. The recently described human embryonic stem cell (hESC) lines may provide a possible solution for the aforementioned cell sourcing problem.

The association between disease severity, functional status, depression and daily quality of life in congestive heart failure patients.

PubMed

Carels, Robert A

2004-02-01

Congestive heart failure significantly compromises quality of life by contributing to severe physical, role, and social functioning impairment as well as increased psychological distress. Previous research examining quality of life in CHF patients has typically been conducted using global self-report instruments that may exceed a patient's ability to accurately recall their experiences. This investigation examines the impact of disease severity, functional status, and level of depression on daily quality of life (i.e., mean level and variability) in CHF patients during a 2-week monitoring period. Indices of quality of life included emotional and physical quality of life, social support and conflict, positive and negative mood, and coping responses. Fifty-eight patients with CHF participated in the investigation. Depressive symptoms were positively associated with a number of quality of life indices (i.e., physical and emotional quality of life, social support and conflict, mood, and coping behaviours). Left ventricular ejection fraction and functional impairment had a much weaker association with quality of life. These findings suggest that depressive symptoms may have a greater impact on quality of life in CHF patients than severity of cardiac dysfunction or functional impairment.

Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

PubMed

Harjola, Veli-Pekka; Mullens, Wilfried; Banaszewski, Marek; Bauersachs, Johann; Brunner-La Rocca, Hans-Peter; Chioncel, Ovidiu; Collins, Sean P; Doehner, Wolfram; Filippatos, Gerasimos S; Flammer, Andreas J; Fuhrmann, Valentin; Lainscak, Mitja; Lassus, Johan; Legrand, Matthieu; Masip, Josep; Mueller, Christian; Papp, Zoltán; Parissis, John; Platz, Elke; Rudiger, Alain; Ruschitzka, Frank; Schäfer, Andreas; Seferovic, Petar M; Skouri, Hadi; Yilmaz, Mehmet Birhan; Mebazaa, Alexandre

2017-07-01

Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Reduced Mastication Impairs Memory Function.

PubMed

Fukushima-Nakayama, Y; Ono, Takehito; Hayashi, M; Inoue, M; Wake, H; Ono, Takashi; Nakashima, T

2017-08-01

Mastication is an indispensable oral function related to physical, mental, and social health throughout life. The elderly tend to have a masticatory dysfunction due to tooth loss and fragility in the masticatory muscles with aging, potentially resulting in impaired cognitive function. Masticatory stimulation has influence on the development of the central nervous system (CNS) as well as the growth of maxillofacial tissue in children. Although the relationship between mastication and cognitive function is potentially important in the growth period, the cellular and molecular mechanisms have not been sufficiently elucidated. Here, we show that the reduced mastication resulted in impaired spatial memory and learning function owing to the morphological change and decreased activity in the hippocampus. We used an in vivo model for reduced masticatory stimuli, in which juvenile mice were fed with powder diet and found that masticatory stimulation during the growth period positively regulated long-term spatial memory to promote cognitive function. The functional linkage between mastication and brain was validated by the decrease in neurons, neurogenesis, neuronal activity, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. These findings taken together provide in vivo evidence for a functional linkage between mastication and cognitive function in the growth period, suggesting a need for novel therapeutic strategies in masticatory function-related cognitive dysfunction.

Functional requirements of a mathematical model of the heart.

PubMed

Palladino, Joseph L; Noordergraaf, Abraham

2009-01-01

Functional descriptions of the heart, especially the left ventricle, are often based on the measured variables pressure and ventricular outflow, embodied as a time-varying elastance. The fundamental difficulty of describing the mechanical properties of the heart with a time-varying elastance function that is set a priori is described. As an alternative, a new functional model of the heart is presented, which characterizes the ventricle's contractile state with parameters, rather than variables. Each chamber is treated as a pressure generator that is time and volume dependent. The heart's complex dynamics develop from a single equation based on the formation and relaxation of crossbridge bonds. This equation permits the calculation of ventricular elastance via E(v) = partial differentialp(v)/ partial differentialV(v). This heart model is defined independently from load properties, and ventricular elastance is dynamic and reflects changing numbers of crossbridge bonds. In this paper, the functionality of this new heart model is presented via computed work loops that demonstrate the Frank-Starling mechanism and the effects of preload, the effects of afterload, inotropic changes, and varied heart rate, as well as the interdependence of these effects. Results suggest the origin of the equivalent of Hill's force-velocity relation in the ventricle.

IQGAP1 regulates ERK1/2 and AKT signalling in the heart and sustains functional remodelling upon pressure overload

PubMed Central

Sbroggiò, Mauro; Carnevale, Daniela; Bertero, Alessandro; Cifelli, Giuseppe; De Blasio, Emanuele; Mascio, Giada; Hirsch, Emilio; Bahou, Wadie F.; Turco, Emilia; Silengo, Lorenzo; Brancaccio, Mara; Lembo, Giuseppe; Tarone, Guido

2011-01-01

Aims The Raf-MEK1/2-ERK1/2 (ERK1/2—extracellular signal-regulated kinases 1/2) signalling cascade is crucial in triggering cardiac responses to different stress stimuli. Scaffold proteins are key elements in coordinating signalling molecules for their appropriate spatiotemporal activation. Here, we investigated the role of IQ motif-containing GTPase-activating protein 1 (IQGAP1), a scaffold for the ERK1/2 cascade, in heart function and remodelling in response to pressure overload. Methods and results IQGAP1-null mice have unaltered basal heart function. When subjected to pressure overload, IQGAP1-null mice initially develop a compensatory hypertrophy indistinguishable from that of wild-type (WT) mice. However, upon a prolonged stimulus, the hypertrophic response develops towards a thinning of left ventricular walls, chamber dilation, and a decrease in contractility, in an accelerated fashion compared with WT mice. This unfavourable cardiac remodelling is characterized by blunted reactivation of the foetal gene programme, impaired cardiomyocyte hypertrophy, and increased cardiomyocyte apoptosis. Analysis of signalling pathways revealed two temporally distinct waves of both ERK1/2 and AKT phosphorylation peaking, respectively, at 10 min and 4 days after aortic banding in WT hearts. IQGAP1-null mice show strongly impaired phosphorylation of MEK1/2-ERK1/2 and AKT following 4 days of pressure overload, but normal activation of these kinases after 10 min. Pull-down experiments indicated that IQGAP1 is able to bind the three components of the ERK cascade, namely c-Raf, MEK1/2, and ERK1/2, as well as AKT in the heart. Conclusion These data demonstrate, for the first time, a key role for the scaffold protein IQGAP1 in integrating hypertrophy and survival signals in the heart and regulating long-term left ventricle remodelling upon pressure overload. PMID:21493702

Inferential functioning in visually impaired children.

PubMed

Puche-Navarro, Rebeca; Millán, Rafael

2007-01-01

The current study explores the inferential abilities of visually impaired children in a task presented in two formats, manipulative and verbal. The results showed that in the group of visually impaired children, just as with children with normal sight, there was a wide range of inference types. It was found that the visually impaired children perform slightly better in the use of inductive and relational inferences in the verbal format, while in the manipulative format children with normal sight perform better. These results suggest that in inferential functioning of young children, and especially visually impaired children, the format of the task influences performance more than the child's visual ability.

Chamber identity programs drive early functional partitioning of the heart.

PubMed

Mosimann, Christian; Panáková, Daniela; Werdich, Andreas A; Musso, Gabriel; Burger, Alexa; Lawson, Katy L; Carr, Logan A; Nevis, Kathleen R; Sabeh, M Khaled; Zhou, Yi; Davidson, Alan J; DiBiase, Anthony; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Zon, Leonard I

2015-08-26

The vertebrate heart muscle (myocardium) develops from the first heart field (FHF) and expands by adding second heart field (SHF) cells. While both lineages exist already in teleosts, the primordial contributions of FHF and SHF to heart structure and function remain incompletely understood. Here we delineate the functional contribution of the FHF and SHF to the zebrafish heart using the cis-regulatory elements of the draculin (drl) gene. The drl reporters initially delineate the lateral plate mesoderm, including heart progenitors. Subsequent myocardial drl reporter expression restricts to FHF descendants. We harnessed this unique feature to uncover that loss of tbx5a and pitx2 affect relative FHF versus SHF contributions to the heart. High-resolution physiology reveals distinctive electrical properties of each heart field territory that define a functional boundary within the single zebrafish ventricle. Our data establish that the transcriptional program driving cardiac septation regulates physiologic ventricle partitioning, which successively provides mechanical advantages of sequential contraction.

Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart

PubMed Central

Wang, Jingying; Ma, Heng; Tong, Chao; Zhang, Hanying; Lawlis, Gavin B.; Li, Yuanda; Zang, Mengwei; Ren, Jun; Nijland, Mark J.; Ford, Stephen P.; Nathanielsz, Peter W.; Li, Ji

2010-01-01

Maternal obesity in pregnancy predisposes offspring to insulin resistance and associated cardiovascular disease. Here, we used a well-established sheep model to investigate the effects of maternal obesity on cardiac functions. Multiparous ewes were assigned to a control (CON) diet [100% of National Research Council (NRC) recommendations] or an obesogenic (OB) diet (150% of NRC recommendations) from 60 d before conception to necropsy on d 135 of pregnancy. Fetal blood glucose and insulin were increased (P<0.01, n=8) in OB (35.09±2.03 mg/dl and 3.40±1.43 μU/ml, respectively) vs. CON ewes (23.80±1.38 mg/dl and 0.769±0.256 μU/ml). Phosphorylation of AMP-activated protein kinase (AMPK), a cardioprotective signaling pathway, was reduced (P<0.05), while the stress signaling pathway, p38 MAPK, was up-regulated (P<0.05) in OB maternal and fetal hearts. Phosphorylation of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) at Ser-307 were increased (P<0.05) in OB fetal heart associated with lower downstream PI3K-Akt activity (P<0.05), indicating impaired cardiac insulin signaling. Although OB fetal hearts exhibited a normal contractile function vs. CON fetal hearts during basal perfusion, they developed an impaired heart-rate-left-ventricular-developed pressure product in response to high workload stress. Taken together, fetuses of OB mothers demonstrate alterations in cardiac PI3K-Akt, AMPK, and JNK-IRS-1 signaling pathways that would predispose them to insulin resistance and cardiac dysfunction.—Wang, J., Ma, H., Tong, C., Zhang, H., Lawlis, G. B., Li, Y., Zang, M., Ren, J., Nijland, M. J., Ford, S. P., Nathanielsz, P. W., Li, J. Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart. PMID:20110268

Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy

PubMed Central

Fillmore, N; Mori, J; Lopaschuk, G D

2014-01-01

Heart disease is a leading cause of death worldwide. In many forms of heart disease, including heart failure, ischaemic heart disease and diabetic cardiomyopathies, changes in cardiac mitochondrial energy metabolism contribute to contractile dysfunction and to a decrease in cardiac efficiency. Specific metabolic changes include a relative increase in cardiac fatty acid oxidation rates and an uncoupling of glycolysis from glucose oxidation. In heart failure, overall mitochondrial oxidative metabolism can be impaired while, in ischaemic heart disease, energy production is impaired due to a limitation of oxygen supply. In both of these conditions, residual mitochondrial fatty acid oxidation dominates over mitochondrial glucose oxidation. In diabetes, the ratio of cardiac fatty acid oxidation to glucose oxidation also increases, although primarily due to an increase in fatty acid oxidation and an inhibition of glucose oxidation. Recent evidence suggests that therapeutically regulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation can improve cardiac function of the ischaemic heart, the failing heart and in diabetic cardiomyopathies. In this article, we review the cardiac mitochondrial energy metabolic changes that occur in these forms of heart disease, what role alterations in mitochondrial fatty acid oxidation have in contributing to cardiac dysfunction and the potential for targeting fatty acid oxidation to treat these forms of heart disease. LINKED ARTICLES This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24147975

Relationships Among Cognitive Function and Cerebral Blood Flow, Oxidative Stress, and Inflammation in Older Heart Failure Patients.

PubMed

Kure, Christina E; Rosenfeldt, Franklin L; Scholey, Andrew B; Pipingas, Andrew; Kaye, David M; Bergin, Peter J; Croft, Kevin D; Wesnes, Keith A; Myers, Stephen P; Stough, Con

2016-07-01

The mechanisms for cognitive impairment in heart failure (HF) are unclear. We investigated the relative contributions of cerebral blood flow velocity (BFV), oxidative stress, and inflammation to HF-associated cognitive impairment. Thirty-six HF patients (≥60 years) and 40 healthy controls (68 ± 7 vs 67 ± 5 years, P > .05; 69% vs 50% male, P > .05) completed the Cognitive Drug Research computerized assessment battery and Stroop tasks. Common carotid (CCA) and middle cerebral arterial BFV were obtained by transcranial Doppler. Blood samples were collected for oxidant (diacron-reactive oxygen metabolites; F2-isoprostanes), antioxidant (coenzyme Q10; CoQ10), and inflammatory markers (high-sensitivity C-reactive protein). Compared with controls, patients exhibited impaired attention (Cognitive Drug Research's Power of Attention domain, congruent Stroop) and executive function (incongruent Stroop). Multiple regression modeling showed that CCA-BFV and CoQ10 but not group predicted performance on attention and executive function. Additionally, in HF patients, CCA-BFV and CoQ10 (β = -0.34 vs β = -0.35) were significant predictors of attention, and CCA-BFV (β = -0.34) was a predictor of executive function. Power of Attention and executive function is impaired in older HF patients, and reduced CCA-BFV and CoQ10 are associated with worse cognition. Interventions addressing these mechanisms may improve cognition in older HF patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Metaiodobenzylguanidine (/sup 131/I) scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure

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

Rabinovitch, M.A.; Rose, C.P.; Rouleau, J.L.

1987-12-01

In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine (/sup 131/I) to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine (/sup 131/I) and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4more » hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine (/sup 131/I) scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine (/sup 123/I) scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients.« less

Merits of Non-Invasive Rat Models of Left Ventricular Heart Failure

EPA Science Inventory

Heart failure (HF) is defined primarily by the impairment of cardiac function and consequent inability of the heart to supply tissues with ample oxygen. To study HF etiology, investigators have applied many different techniques to elicit this condition in animals, with varying de...

Family factors, emotional functioning, and functional impairment in juvenile fibromyalgia syndrome.

PubMed

Kashikar-Zuck, Susmita; Lynch, Anne M; Slater, Shalonda; Graham, T Brent; Swain, Nicole F; Noll, Robert B

2008-10-15

Family factors and emotional functioning can play an important role in the ability of adolescents with juvenile primary fibromyalgia syndrome (JPFS) to cope with their condition and function in their everyday lives. The primary objectives of this study were to determine 1) whether adolescents with JPFS and their caregivers differed from healthy age-matched comparison peers and their caregivers in terms of emotional distress and functional impairment; 2) whether there were any differences in the family environment of adolescents with JPFS compared with healthy comparison peers; and 3) which individual-, caregiver-, and family-level variables were associated with functional impairment in adolescents with JPFS. Participants were 47 adolescents with JPFS recruited from a pediatric rheumatology clinic and 46 comparison peers without chronic illness matched for age, sex, and race. Participants and their caregivers (all mothers) completed a battery of standardized measures administered in their homes. Adolescents with JPFS had greater internalizing and externalizing symptoms than healthy comparison peers. Mothers of adolescents with JPFS reported twice as many pain conditions and significantly greater depressive symptoms than mothers of comparison peers. The JPFS group also had poorer overall family functioning and more conflicted family relationships. In adolescents with JPFS, maternal pain history was associated with significantly higher functional impairment. Increased distress and chronic pain are evident in families of adolescents with JPFS, and family relationships are also impacted. Implications for child functional impairment and the need for inclusion of caregivers in treatment are discussed.

Loss of Mitochondrial Function Impairs Lysosomes.

PubMed

Demers-Lamarche, Julie; Guillebaud, Gérald; Tlili, Mouna; Todkar, Kiran; Bélanger, Noémie; Grondin, Martine; Nguyen, Angela P; Michel, Jennifer; Germain, Marc

2016-05-06

Alterations in mitochondrial function, as observed in neurodegenerative diseases, lead to disrupted energy metabolism and production of damaging reactive oxygen species. Here, we demonstrate that mitochondrial dysfunction also disrupts the structure and function of lysosomes, the main degradation and recycling organelle. Specifically, inhibition of mitochondrial function, following deletion of the mitochondrial protein AIF, OPA1, or PINK1, as well as chemical inhibition of the electron transport chain, impaired lysosomal activity and caused the appearance of large lysosomal vacuoles. Importantly, our results show that lysosomal impairment is dependent on reactive oxygen species. Given that alterations in both mitochondrial function and lysosomal activity are key features of neurodegenerative diseases, this work provides important insights into the etiology of neurodegenerative diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Metabolic support for the heart: complementary therapy for heart failure?

PubMed

Heggermont, Ward A; Papageorgiou, Anna-Pia; Heymans, Stephane; van Bilsen, Marc

2016-12-01

The failing heart has an increased metabolic demand and at the same time suffers from impaired energy efficiency, which is a detrimental combination. Therefore, therapies targeting the energy-deprived failing heart and rewiring cardiac metabolism are of great potential, but are lacking in daily clinical practice. Metabolic impairment in heart failure patients has been well characterized for patients with reduced ejection fraction, and is coming of age in patients with 'preserved' ejection fraction. Targeting cardiomyocyte metabolism in heart failure could complement current heart failure treatments that do improve cardiovascular haemodynamics, but not the energetic status of the heart. In this review, we discuss the hallmarks of normal cardiac metabolism, typical metabolic disturbances in heart failure, and past and present therapeutic targets that impact on cardiac metabolism. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Association between renal function and cardiovascular structure and function in heart failure with preserved ejection fraction.

PubMed

Gori, Mauro; Senni, Michele; Gupta, Deepak K; Charytan, David M; Kraigher-Krainer, Elisabeth; Pieske, Burkert; Claggett, Brian; Shah, Amil M; Santos, Angela B S; Zile, Michael R; Voors, Adriaan A; McMurray, John J V; Packer, Milton; Bransford, Toni; Lefkowitz, Martin; Solomon, Scott D

2014-12-21

Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR) >30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only low eGFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall fractional shortening (MWFS) (P = 0.009), and higher NT-proBNP (P = 0.006). Compared with patients without renal dysfunction, those with low eGFR and no albuminuria had a higher prevalence of abnormal LV geometry (P = 0.032) and lower MWFS (P < 0.01), as opposed to those with only albuminuria. Conversely, albuminuria alone was associated with greater LV dimensions (P < 0.05). Patients with combined renal impairment had mixed abnormalities (higher LV wall thicknesses, NT-proBNP; lower MWFS). Renal dysfunction, as determined by both eGFR and albuminuria, is highly prevalent in HFpEF, and associated with cardiac remodelling and subtle systolic dysfunction. The observed differences in cardiac structure/function between each type of renal damage suggest that both parameters of kidney function might play a distinct role in HFpEF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

PubMed

Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

2015-08-24

Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

Vascular Cognitive Impairment.

PubMed

Dichgans, Martin; Leys, Didier

2017-02-03

Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts. © 2017 American Heart Association, Inc.

Glucose Homeostasis, Pancreatic Endocrine Function, and Outcomes in Advanced Heart Failure.

PubMed

Melenovsky, Vojtech; Benes, Jan; Franekova, Janka; Kovar, Jan; Borlaug, Barry A; Segetova, Marketa; Tura, Andrea; Pelikanova, Tereza

2017-08-07

The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (HF) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF. In total, 140 advanced HF patients without known diabetes mellitus and 21 sex-, age-, and body mass index-matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucose-regulating hormones to model pancreatic β-cell secretory response. Compared with controls, HF patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing HF severity, there was a reduction in glucose, insulin, and insulin/glucagon ratio-a signature of starvation. The insulin/C-peptide ratio was decreased in HF, indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449 days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome ( P =0.01). Patients in the lowest quartile of fasting plasma glucose (3.8-5.1 mmol·L -1 , 68-101 mg·dL -1 ) had 3-times higher event risk than in the top quartile (6.0-7.9 mmol·L -1 , 108-142 mg·dL -1 ; relative risk: 3.05 [95% confidence interval, 1.46-6.77]; P =0.002). Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced HF. Pancreatic insulin secretion is preserved in advanced HF, but levels decrease with increasing HF severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia. © 2017 The Authors. Published on behalf of the American Heart Association, Inc

Decreased frequencies and impaired functions of the CD31+ subpopulation in Treg cells associated with decreased FoxP3 expression and enhanced Treg cell defects in patients with coronary heart disease.

PubMed

Huang, L; Zheng, Y; Yuan, X; Ma, Y; Xie, G; Wang, W; Chen, H; Shen, L

2017-03-01

Coronary heart disease (CHD) is one of the most common types of organ lesions caused by atherosclerosis, in which CD4 + CD25 + forkhead box protein 3 (FoxP3 + ) regulatory T cells (T reg ) play an atheroprotective role. However, T reg cell numbers are decreased and their functions are impaired in atherosclerosis; the underlying mechanisms remain unclear. CD31 plays an important part in T cell response and contributes to maintaining T cell tolerance. The immunomodulatory effects of CD31 are also implicated in atherosclerosis. In this study, we found that decreased frequencies of the CD31 + subpopulation in T reg cells (CD31 + Tr cells) correlated positively with decreased FoxP3 expression in CHD patients. Cell culture in vitro demonstrated CD31 + Tr cells maintaining stable FoxP3 expression after activation and exhibited enhanced proliferation and immunosuppression compared with the CD31 - subpopulation in T reg cells (CD31 - Tr cells). We also confirmed impaired secretion of transforming growth factor (TGF)-β1 and interleukin (IL)-10 in CD31 + Tr cells of CHD patients. Further analysis revealed reduced phospho-SHP2 (associated with CD31 activation) and phospho-signal transducer and activator of transcription-5 (STAT-5) (associated with FoxP3 transcription) levels in CD31 + Tr cells of CHD patients, suggesting that decreased FoxP3 expression in CD31 + Tr cells might be because of attenuated SHP2 and STAT-5 activation. These data indicate that decreased frequencies and impaired functions of the CD31 + Tr subpopulation associated with decreased FoxP3 expression give rise, at least in part, to T reg cell defects in CHD patients. Our findings emphasize the important role of the CD31 + Tr subpopulation in maintaining T reg cell normal function and may provide a novel explanation for impaired immunoregulation of T reg cells in CHD. © 2016 British Society for Immunology.

Lungs in Heart Failure

PubMed Central

Apostolo, Anna; Giusti, Giuliano; Gargiulo, Paola; Bussotti, Maurizio; Agostoni, Piergiuseppe

2012-01-01

Lung function abnormalities both at rest and during exercise are frequently observed in patients with chronic heart failure, also in the absence of respiratory disease. Alterations of respiratory mechanics and of gas exchange capacity are strictly related to heart failure. Severe heart failure patients often show a restrictive respiratory pattern, secondary to heart enlargement and increased lung fluids, and impairment of alveolar-capillary gas diffusion, mainly due to an increased resistance to molecular diffusion across the alveolar capillary membrane. Reduced gas diffusion contributes to exercise intolerance and to a worse prognosis. Cardiopulmonary exercise test is considered the “gold standard” when studying the cardiovascular, pulmonary, and metabolic adaptations to exercise in cardiac patients. During exercise, hyperventilation and consequent reduction of ventilation efficiency are often observed in heart failure patients, resulting in an increased slope of ventilation/carbon dioxide (VE/VCO2) relationship. Ventilatory efficiency is as strong prognostic and an important stratification marker. This paper describes the pulmonary abnormalities at rest and during exercise in the patients with heart failure, highlighting the principal diagnostic tools for evaluation of lungs function, the possible pharmacological interventions, and the parameters that could be useful in prognostic assessment of heart failure patients. PMID:23365739

Cross-Sectional Associations of Flow Reversal, Vascular Function, and Arterial Stiffness in the Framingham Heart Study.

PubMed

Bretón-Romero, Rosa; Wang, Na; Palmisano, Joseph; Larson, Martin G; Vasan, Ramachandran S; Mitchell, Gary F; Benjamin, Emelia J; Vita, Joseph A; Hamburg, Naomi M

2016-12-01

Experimental studies link oscillatory flow accompanied by flow reversal to impaired endothelial cell function. The relation of flow reversal with vascular function and arterial stiffness remains incompletely defined. We measured brachial diastolic flow patterns along with vasodilator function in addition to tonometry-based central and peripheral arterial stiffness in 5708 participants (age 47±13 years, 53% women) in the Framingham Heart Study Offspring and Third Generation cohorts. Brachial artery diastolic flow reversal was present in 35% of the participants. In multivariable regression models, the presence of flow reversal was associated with lower flow-mediated dilation (3.9±0.2 versus 5.0±0.2%; P<0.0001) and reactive hyperemic flow velocity (50±0.99 versus 57±0.93 cm/s; P<0.0001). The presence of flow reversal (compared with absence) was associated with higher central aortic stiffness (carotid-femoral pulse wave velocity 9.3±0.1 versus 8.9±0.1 m/s), lower muscular artery stiffness (carotid-radial pulse wave velocity 9.6±0.1 versus 9.8±0.1 m/s), and higher forearm vascular resistance (5.32±0.03 versus 4.66±0.02 log dyne/s/cm 5 ; P<0.0001). The relations of diastolic flow velocity with flow-mediated dilation, aortic stiffness, and forearm vascular resistance were nonlinear, with a steeper decline in vascular function associated with increasing magnitude of flow reversal. In our large, community-based sample, brachial artery flow reversal was common and associated with impaired vasodilator function and higher aortic stiffness. Our findings are consistent with the concept that flow reversal may contribute to vascular dysfunction. © 2016 American Heart Association, Inc.

Cardiac Metabolism in Heart Failure - Implications beyond ATP production

PubMed Central

Doenst, Torsten; Nguyen, T. Dung; Abel, E. Dale

2013-01-01

The heart has a high rate of ATP production and turnover which is required to maintain its continuous mechanical work. Perturbations in ATP generating processes may therefore affect contractile function directly. Characterizing cardiac metabolism in heart failure revealed several metabolic alterations termed metabolic remodeling, ranging from changes in substrate utilization to mitochondrial dysfunction, ultimately resulting in ATP deficiency and impaired contractility. However, ATP depletion is not the only relevant consequence of metabolic remodeling during heart failure. By providing cellular building blocks and signaling molecules, metabolic pathways control essential processes such as cell growth and regeneration. Thus, alterations in cardiac metabolism may also affect the progression to heart failure by mechanisms beyond ATP supply. Our aim is therefore to highlight that metabolic remodeling in heart failure not only results in impaired cardiac energetics, but also induces other processes implicated in the development of heart failure such as structural remodeling and oxidative stress. Accordingly, modulating cardiac metabolism in heart failure may have significant therapeutic relevance that goes beyond the energetic aspect. PMID:23989714

Cardiac-specific overexpression of sarcolipin inhibits sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2a) activity and impairs cardiac function in mice

PubMed Central

Asahi, Michio; Otsu, Kinya; Nakayama, Hiroyuki; Hikoso, Shungo; Takeda, Toshihiro; Gramolini, Anthony O.; Trivieri, Maria G.; Oudit, Gavin Y.; Morita, Takashi; Kusakari, Yoichiro; Hirano, Shuta; Hongo, Kenichi; Hirotani, Shinichi; Yamaguchi, Osamu; Peterson, Alan; Backx, Peter H.; Kurihara, Satoshi; Hori, Masatsugu; MacLennan, David H.

2004-01-01

Sarcolipin (SLN) inhibits the cardiac sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2a) by direct binding and is superinhibitory if it binds through phospholamban (PLN). To determine whether overexpression of SLN in the heart might impair cardiac function, transgenic (TG) mice were generated with cardiac-specific overexpression of NF-SLN (SLN tagged at its N terminus with the FLAG epitope). The level of NF-SLN expression (the NF-SLN/PLN expression ratio) was equivalent to that which induces profound superinhibition when coexpressed with PLN and SERCA2a in HEK-293 cells. In TG hearts, the apparent affinity of SERCA2a for Ca2+ was decreased compared with non-TG littermate control hearts. Invasive hemodynamic and echocardiographic analyses revealed impaired cardiac contractility and ventricular hypertrophy in TG mice. Basal PLN phosphorylation was reduced. In isolated papillary muscle subjected to isometric tension, peak amplitudes of Ca2+ transients and peak tensions were reduced, whereas decay times of Ca2+ transients and relaxation times of tension were increased in TG mice. Isoproterenol largely restored contractility in papillary muscle and stimulated PLN phosphorylation to wild-type levels in intact hearts. No compensatory changes in expression of SERCA2a, PLN, ryanodine receptor, and calsequestrin were observed in TG hearts. Coimmunoprecipitation indicated that overexpressed NF-SLN was bound to both SERCA2a and PLN, forming a ternary complex. These data suggest that NF-SLN overexpression inhibits SERCA2a through stabilization of SERCA2a–PLN interaction in the absence of PLN phosphorylation and through the inhibition of PLN phosphorylation. Inhibition of SERCA2a impairs contractility and calcium cycling, but responsiveness to β-adrenergic agonists may prevent progression to heart failure. PMID:15201433

Correlates of impaired function in older women.

PubMed

Ensrud, K E; Nevitt, M C; Yunis, C; Cauley, J A; Seeley, D G; Fox, K M; Cummings, S R

1994-05-01

To determine the factors associated with impaired function in older women. Cross-sectional analysis of baseline data collected for a multicenter, prospective study of risk factors for osteoporotic fractures. Four clinical centers in Portland, Oregon, Minneapolis, Minnesota, Baltimore, Maryland, and the Monongahela Valley, Pennsylvania. A total of 9,704 ambulatory, non-black women, aged 65 years and older, recruited from population-based listings. Independent variables, including demographic and historical information (medical conditions, health habits, and medications) and physiologic measures (anthropometry, blood pressure, mental status, vision, and neuromuscular performance) were obtained from a baseline questionnaire, interview, and examination. Measurement of function was assessed by self-reported ability to perform six physical and instrumental activities of daily living (ADL) and impaired function (dependent variable) was defined as difficulty performing three or more physical and instrumental ADLs. In order of decreasing strength of association, hip fracture, osteoarthritis, parkinsonism, slower walking speed, lower hip abduction force, back pain, greater Quetelet index, osteoporosis, former alcohol use, stroke, never drinking alcohol, lower mental status, use of anxiolytics and/or sleeping medications, inability to hold the tandem position, postural dizziness, cataracts, greater waist to hip ratio, lower physical activity in the past year, greater lifetime cigarette consumption, and lower grip strength were independently associated with impaired function in multivariate analyses. Age, low educational level, diabetes, current heavy alcohol use, postural hypotension, depth perception, and contrast sensitivity were not independent predictors. A combination of neuromuscular performance measures, including decreased muscle strength and impaired balance and gait, appeared to account for the effect of age on disability. A combination of many factors, including

Sleep Apnea and Left Atrial Phasic Function in Heart Failure With Reduced Ejection Fraction.

PubMed

Haruki, Nobuhiko; Tsang, Wendy; Thavendiranathan, Paaladinesh; Woo, Anna; Tomlinson, George; Logan, Alexander G; Bradley, T Douglas; Floras, John S

2016-12-01

The study aim was to determine whether phasic left atrial (LA) function of patients with heart failure with reduced ejection fraction differs between those with obstructive sleep apnea (OSA) and central sleep apnea (CSA). Participation in the Adaptive Servo Ventilation for Therapy of Sleep Apnea in Heart Failure (ADVENT-HF) trial requires 2-dimensional echocardiographic documentation of left ventricular ejection fraction ≤ 45% and a polysomnographic apnea hypopnea index (AHI) ≥ 15 events per hour. Of initial enrollees, we identified 132 patients in sinus rhythm (82 with predominantly OSA and 50 with CSA). To determine LA reservoir (expansion index; EI), conduit (passive emptying index; PEI), and booster function (active emptying index), we blindly quantified maximum and minimum LA volume and LA volume before atrial contraction. Each of EI (P = 0.004), PEI (P < 0.001), and active emptying index (P = 0.045) was less in participants with CSA compared with those with OSA, whereas average left ventricular ejection fraction and LA and left ventricular volumes were similar. Multivariable analysis identified an independent relationship between central AHI and LA EI (P = 0.040) and PEI (P = 0.005). In contrast, the obstructive AHI was unrelated to any LA phasic index, and slopes relating central AHI to EI and PEI differed significantly from corresponding relationships with obstructive AHI (P = 0.018; P = 0.006). In these ADVENT-HF patients with heart failure with reduced ejection fraction, all 3 components of LA phasic function (reservoir, conduit, and contractile) were significantly reduced in those with CSA compared with participants with OSA. The severity of CSA, but not OSA associated inversely and independently with LA reservoir and conduit function. Impaired LA phasic function might be consequent to or could exacerbate CSA. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

One year of high-intensity interval training improves exercise capacity, but not left ventricular function in stable heart transplant recipients: a randomised controlled trial.

PubMed

Rustad, Lene A; Nytrøen, Kari; Amundsen, Brage H; Gullestad, Lars; Aakhus, Svend

2014-02-01

Heart transplant recipients have lower exercise capacity and impaired cardiac function compared with the normal population. High-intensity interval training (HIIT) improves exercise capacity and cardiac function in patients with heart failure and hypertension, but the effect on cardiac function in stable heart transplant recipients is not known. Thus, we investigated whether HIIT improved cardiac function and exercise capacity in stable heart transplant recipients by use of comprehensive rest- and exercise-echocardiography and cardiopulmonary exercise testing. Fifty-two clinically stable heart transplant recipients were randomised either to HIIT (4 × 4 minutes at 85-95% of peak heart rate three times per week for eight weeks) or to control. Three such eight-week periods were distributed throughout one year. Echocardiography (rest and submaximal exercise) and cardiopulmonary exercise testing were performed at baseline and follow-up. One year of HIIT increased VO 2peak from 27.7 ± 5.5 at baseline to 30.9 ± 5.0 ml/kg/min at follow-up, while the control group remained unchanged (28.5 ± 7.0 vs. 28.0 ± 6.7 ml/kg per min, p < 0.001 for difference between the groups). Systolic and diastolic left ventricular functions at rest and during exercise were generally unchanged by HIIT. Whereas HIIT is feasible in heart transplant recipients and effectively improves exercise capacity, it does not alter cardiac systolic and diastolic function significantly. Thus, the observed augmentation in exercise capacity is best explained by extra-cardiac adaptive mechanisms.

Cardiac telomere length in heart development, function, and disease.

PubMed

Booth, S A; Charchar, F J

2017-07-01

Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. Copyright © 2017 the American Physiological Society.

Structural equation modeling of motor impairment, gross motor function, and the functional outcome in children with cerebral palsy.

PubMed

Park, Eun-Young; Kim, Won-Ho

2013-05-01

Physical therapy intervention for children with cerebral palsy (CP) is focused on reducing neurological impairments, improving strength, and preventing the development of secondary impairments in order to improve functional outcomes. However, relationship between motor impairments and functional outcome has not been proved definitely. This study confirmed the construct of motor impairment and performed structural equation modeling (SEM) between motor impairment, gross motor function, and functional outcomes of regarding activities of daily living in children with CP. 98 children (59 boys, 39 girls) with CP participated in this cross-sectional study. Mean age was 11 y 5 mo (SD 1 y 9 mo). The Manual Muscle Test (MMT), the Modified Ashworth Scale (MAS), range of motion (ROM) measurement, and the selective motor control (SMC) scale were used to assess motor impairments. Gross motor function and functional outcomes were measured using the Gross Motor Function Measure (GMFM) and the Functional Skills domain of the Pediatric Evaluation of Disability Inventory (PEDI) respectively. Measurement of motor impairment was consisted of strength, spasticity, ROM, and SMC. The construct of motor impairment was confirmed though an examination of a measurement model. The proposed SEM model showed good fit indices. Motor impairment effected gross motor function (β=-.0869). Gross motor function and motor impairment affected functional outcomes directly (β=0.890) and indirectly (β=-0.773) respectively. We confirmed that the construct of motor impairment consist of strength, spasticity, ROM, and SMC and it was identified through measurement model analysis. Functional outcomes are best predicted by gross motor function and motor impairments have indirect effects on functional outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cardiorespiratory functional assessment after pediatric heart transplantation.

PubMed

Pastore, E; Turchetta, A; Attias, L; Calzolari, A; Giordano, U; Squitieri, C; Parisi, F

2001-12-01

Limited data are available on the exercise capacity of young heart transplant recipients. The aim of this study was therefore to assess cardiorespiratory responses to exercise in this group of patients. Fourteen consecutive heart transplant recipients (six girls and eight boys, age-range 5-15 yr) and 14 healthy matched controls underwent a Bruce treadmill test to determine: duration of test; resting and maximum heart rates; maximum systolic blood pressure; peak oxygen consumption (VO2 peak); and cardiac output. Duration of test and heart rate increase were then compared with: time since transplantation, rejections per year, and immunosuppressive drugs received. The recipients also underwent the following lung function tests: forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). When compared with healthy controls, transplant recipients had tachycardia at rest (126 +/- 3.7 beats/min; p < 0.001); significantly reduced tolerance (9.3 +/- 0.4 min; p < 0.001), a maximum heart rate of 169 +/- 5.4 beats/min (p < 0.05); a cardiac output of 5.65 +/- 0.6 L/min (p < 0.05); and a lower heart-rate increase from rest to peak exercise (p < 0.001) but a similar VO2 peak. The heart-rate increase correlated significantly with time post-transplant (r = 0.55; p < 0.05), number of rejection episodes per year (r = - 0.63; p < 0.05), and number of immunosuppressive drugs (r = - 0.60; p < 0.05). The recipients had normal FVC and FEV1 values. After surgery, few heart transplant recipients undertake physical activity, possibly owing to over-protective parents and teachers and to a lack of suitable supervised facilities. The authors stress the importance of a cardiorespiratory functional evaluation for assessment of health status and to encourage recipients, if possible, to undertake regular physical activity.

Paraoxonase 2 prevents the development of heart failure.

PubMed

Li, Wei; Kennedy, David; Shao, Zhili; Wang, Xi; Kamdar, Andre Klaassen; Weber, Malory; Mislick, Kayla; Kiefer, Kathryn; Morales, Rommel; Agatisa-Boyle, Brendan; Shih, Diana M; Reddy, Srinivasa T; Moravec, Christine S; Tang, W H Wilson

2018-05-02

Mitochondrial oxidation is a major source of reactive oxygen species (ROS) and mitochondrial dysfunction plays a central role in development of heart failure (HF). Paraoxonase 2 deficient (PON2-def) mitochondria are impaired in function. In this study, we tested whether PON2-def aggravates HF progression. Using qPCR, immunoblotting and lactonase activity assay, we demonstrate that PON2 activity was significantly decreased in failing hearts despite increased PON2 expression. To determine the cardiac-specific function of PON2, we performed heart transplantations in which PON2-def and wild type (WT) donor hearts were implanted into WT recipient mice. Beating scores of the donor hearts, assessed at 4 weeks post-transplantation, were significantly decreased in PON2-def hearts when compared to WT donor hearts. By using a transverse aortic constriction (TAC) model, we found PON2 deficiency significantly exacerbated left ventricular remodeling and cardiac fibrosis post-TAC. We further demonstrated PON2 deficiency significantly enhanced ROS generation in heart tissues post-TAC. ROS generation was measured through dihydroethidium (DHE) using high-pressure liquid chromatography (HPLC) with a fluorescent detector. By using neonatal cardiomyocytes treated with CoCl 2 to mimic hypoxia, we found PON2 deficiency dramatically increased ROS generation in the cardiomyocytes upon CoCl 2 treatment. In response to a short CoCl 2 exposure, cell viability and succinate dehydrogenase (SDH) activity assessed by MTT assay were significantly diminished in PON2-def cardiomyocytes compared to those in WT cardiomyocytes. PON2-def cardiomyocytes also had lower baseline SDH activity. By using adult mouse cardiomyocytes and mitochondrial ToxGlo assay, we found impaired cellular ATP generation in PON2-def cells compared to that in WT cells, suggesting that PON2 is necessary for proper mitochondrial function. Our study suggests a cardioprotective role for PON2 in both experimental and human heart

Pediatric heart failure and worsening renal function: association with outcomes after heart transplantation.

PubMed

Rajagopal, Satish K; Yarlagadda, Vamsi V; Thiagarajan, Ravi R; Singh, Tajinder P; Givertz, Michael M; Almond, Christopher S D

2012-03-01

Renal function deteriorates in some children awaiting heart transplantation. This study was initiated to assess the effects of worsening renal function (WRF) on post-heart transplantation outcomes and to determine the effect of waiting-list associated WRF on survival after heart transplantation. All children aged <18 years who underwent their first heart transplantation between 1999 and 2009, had reported plasma creatinine concentrations at listing and at transplantation, and were free of renal replacement therapy at listing were identified using the Organ Procurement and Transplant Network database. The independent effects of WRF on in-hospital mortality and post-discharge survival were assessed using logistic regression and log-rank analyses, respectively. Of the 2,216 children included in the analysis, WRF occurred in 334 (15%) awaiting heart transplantation: WRF was mild (stage 1) in 210 (63%), moderate (stage 2) in 40 (12%), and severe (stage 3) in 84 (25%). All WRF stages were independently associated with in-hospital, post-transplant mortality: mild WRF with adjusted odds ratio (AOR) of 2.1 (95% confidence interval [CI], 1.2-3.5); moderate WRF, 2.7 (95% CI, 1.1-6.7); and severe WRF, 3.6 (95% CI, 2.0-6.5). WRF was not associated with death after discharge (hazard ratio, 1.2; 95% CI, 0.9-1.7) at a median follow-up of 2.7 years. WRF occurs in 15% of children awaiting heart transplantation and is associated with early but not late post-transplant mortality. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Association of Central Sleep Apnea with Impaired Heart Structure and Cardiovascular Hemodynamics in Patients with Chronic Heart Failure.

PubMed

Kazimierczak, Anna; Krzesiński, Paweł; Gielerak, Grzegorz; Uziębło-Życzkowska, Beata; Smurzyński, Paweł; Ryczek, Robert; Cwetsch, Andrzej; Skrobowski, Andrzej

2016-08-25

BACKGROUND Advanced heart failure (HF) is commonly accompanied by central sleep apnea (CSA) with Cheyne-Stokes respiration (CSR). The aim of this study was to evaluate the relationship between CSA/CSR and other clinical features of HF, with particular emphasis on cardiovascular hemodynamics. MATERIAL AND METHODS In 161 stable HF patients with left ventricular ejection fraction (LVEF) ≤45% (NYHA class I-III; mean LVEF 32.8%) the clinical evaluation included: LVEF; left and right ventricular end-diastolic diameter (LVDd, RVDd); ratio of early transmitral flow velocity to early diastolic septal mitral annulus velocity (E/e') assessed by echocardiography; stroke index (SI); heart rate (HR); cardiac index (CI); and systemic vascular resistance index (SVRI) assessed by impedance cardiography (ICG). The comparison was performed between 2 subgroups: one with moderate/severe CSA/CSR - CSR_ [+] (n=51), and one with mild or no CSA/CSR - CSR_ [-] (n=110). RESULTS CSR_ [+] patients presented more advanced NYHA class (p<0.001) and more frequently had permanent atrial fibrillation (p=0.018). Moreover, they had: lower LVEF (p<0.0001); higher LVDd (p<0.0001), RVDd (p<0.001), and E/e' (p<0.001); lower SI (p<0.001) and CI (p=0.009); and higher HR (p=0.044) and SVRI (p=0.016). The following predictors of CSR_ [+] were identified: NYHA class (OR=3.34 per class, p<0.001, which was the only independent predictor); atrial fibrillation (OR=2.29, p=0.019); RV enlargement (OR=2.75, p=0.005); LVEF<35% (OR=3.38, p=0.001); E/e' (OR=3.15; p=0.003); and SI<35 ml/m2 (OR=2.96, p=0.003). CONCLUSIONS Presence of CSA/CSR in HF is associated with NYHA class, atrial fibrillation and more advanced impairment of cardiovascular structure and hemodynamics. Patient functional state remains the main determinant of CSR.

Superoxide Dismutase 1 In Vivo Ameliorates Maternal Diabetes Mellitus-Induced Apoptosis and Heart Defects Through Restoration of Impaired Wnt Signaling.

PubMed

Wang, Fang; Fisher, Steven A; Zhong, Jianxiang; Wu, Yanqing; Yang, Peixin

2015-10-01

Oxidative stress is manifested in embryos exposed to maternal diabetes mellitus, yet specific mechanisms for diabetes mellitus-induced heart defects are not defined. Gene deletion of intermediates of Wingless-related integration (Wnt) signaling causes heart defects similar to those observed in embryos from diabetic pregnancies. We tested the hypothesis that diabetes mellitus-induced oxidative stress impairs Wnt signaling, thereby causing heart defects, and that these defects can be rescued by transgenic overexpression of the reactive oxygen species scavenger superoxide dismutase 1 (SOD1). Wild-type (WT) and SOD1-overexpressing embryos from nondiabetic WT control dams and nondiabetic/diabetic WT female mice mated with SOD1 transgenic male mice were analyzed. No heart defects were observed in WT and SOD1 embryos under nondiabetic conditions. WT embryos of diabetic dams had a 26% incidence of cardiac outlet defects that were suppressed by SOD1 overexpression. Insulin treatment reduced blood glucose levels and heart defects. Diabetes mellitus increased superoxide production, canonical Wnt antagonist expression, caspase activation, and apoptosis and suppressed cell proliferation. Diabetes mellitus suppressed Wnt signaling intermediates and Wnt target gene expression in the embryonic heart, each of which were reversed by SOD1 overexpression. Hydrogen peroxide and peroxynitrite mimicked the inhibitory effect of high glucose on Wnt signaling, which was abolished by the SOD1 mimetic, tempol. The oxidative stress of diabetes mellitus impairs Wnt signaling and causes cardiac outlet defects that are rescued by SOD1 overexpression. This suggests that targeting of components of the Wnt5a signaling pathway may be a viable strategy for suppression of congenital heart defects in fetuses of diabetic pregnancies. © 2015 American Heart Association, Inc.

Potential mechanisms for chemotherapy-induced impairments in cognitive function.

PubMed

Jansen, Catherine; Miaskowski, Christine; Dodd, Marilyn; Dowling, Glenna; Kramer, Joel

2005-11-03

To review the domains of cognitive function and their corresponding neuroanatomic structures as well as present current evidence for neurotoxicity associated with specific chemotherapeutic agents and potential mechanisms for chemotherapy-induced cognitive impairments. Published research articles, review articles, and textbooks. Chemotherapy does not appear to cross the blood-brain barrier when given in standard doses; however, many chemotherapy drugs have the potential to cause cognitive impairments through more than one mechanism. In addition, patient factors may be protective or place individuals at higher risk for cognitive impairments. Although evidence of chemotherapy-induced impairments in cognitive function exists, no clinical studies have attempted to elucidate the mechanisms for chemotherapy-induced impairments in cognitive function. In addition, further studies are needed to determine predictive factors, potential biomarkers, and relevant assessment parameters. The ability to identify high-risk patients has important implications for practice in regard to informed consent, patient education about the effects of treatment, and preventive strategies.

Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function.

PubMed

Przybylowski, P; Koc-Zorawska, E; Malyszko, J S; Kozlowska, S; Mysliwiec, M; Malyszko, J

2011-10-01

Mammalian intracellular fatty-acid-binding proteins (FABPs), a large multigene family, encode 14-kD proteins that are members of a superfamily of lipid-binding proteins. FABPs are tissue specific. Liver-type FABP (L-FABP) can be filtered through the glomerulus owing to its small molecular size, similar to cystatin C, but it is reabsorbed by proximal tubule epithelial cells like other small proteins. In the human kidney, L-FABP is expressed predominantly in proximal tubules. It had been suggested that the presence of L-FABP in urine reflects hypoxic conditions resulting from decreased peritubular capillary flow, serving as a marker of acute kidney injury. The aim of this study was to assess urinary L-FABP in 111 heart and 76 kidney transplant recipients in relation to kidney function. Complete blood count, urea, fasting glucose, creatinine, and the N-terminal fragment of brain natriuretic protein were studied by standard laboratory methods; L-FABP and cystatin C, by ELISA using commercially available kits. Kidney transplant recipients displayed significantly higher L-FABP than heart recipients. Upon univariate analysis, urinary L-FABP correlated, with serum creatinine, cystatin C and estimated glomerular filtration ratio (eGFR) in kidney allograft recipients. However, in heart transplant recipients it was not related to kidney function, as reflected by creatinine or eGFR; was strongly related to cystatin C (r=0.34; P<.001) and urinary creatinine (r=-0.29; P<.01), and NGAL (r=0.29; P<.01). Upon multiple regression analysis, the best predictor of urinary L-FABP in kidney allograft recipients, was eGFR whereas in heart recipients, no parameter independently predicted L-FABP. Successful heart transplantation is associated with kidney injury as reflected by a reduced eGFR; however, in this population, L-FABP did not serve as a marker of kidney function. In contrast, in kidney allograft recipients, L-FABP may be a potential early marker for impaired kidney function

Reduced Gray Matter Volume Is Associated With Poorer Instrumental Activities of Daily Living Performance in Heart Failure.

PubMed

Alosco, Michael L; Brickman, Adam M; Spitznagel, Mary Beth; Narkhede, Atul; Griffith, Erica Y; Cohen, Ronald; Sweet, Lawrence H; Josephson, Richard; Hughes, Joel; Gunstad, John

2016-01-01

Heart failure patients require assistance with instrumental activities of daily living in part because of the high rates of cognitive impairment in this population. Structural brain insult (eg, reduced gray matter volume) is theorized to underlie cognitive dysfunction in heart failure, although no study has examined the association among gray matter, cognition, and instrumental activities of daily living in heart failure. The aim of this study was to investigate the associations among gray matter volume, cognitive function, and functional ability in heart failure. A total of 81 heart failure patients completed a cognitive test battery and the Lawton-Brody self-report questionnaire to assess instrumental activities of daily living. Participants underwent magnetic resonance imaging to quantify total gray matter and subcortical gray matter volume. Impairments in instrumental activities of daily living were common in this sample of HF patients. Regression analyses controlling for demographic and medical confounders showed that smaller total gray matter volume predicted decreased scores on the instrumental activities of daily living composite, with specific associations noted for medication management and independence in driving. Interaction analyses showed that reduced total gray matter volume interacted with worse attention/executive function and memory to negatively impact instrumental activities of daily living. Smaller gray matter volume is associated with greater impairment in instrumental activities of daily living in persons with heart failure, possibly via cognitive dysfunction. Prospective studies are needed to clarify the utility of clinical correlates of gray matter volume (eg, cognitive dysfunction) in identifying heart failure patients at risk for functional decline and determine whether interventions that target improved brain and cognitive function can preserve functional independence in this high-risk population.

Functional impairment in elderly patients with mild cognitive impairment and mild Alzheimer's disease

PubMed Central

Brown, Patrick J.; Devanand, D.P.; Liu, Xinhua; Caccappolo, Elise

2013-01-01

CONTEXT The original mild cognitive impairment (MCI) criteria exclude substantial functional deficits, but recent reports suggest otherwise. Identifying the extent, severity, type, and correlates of functional deficits that occur in MCI and mild Alzheimer’s disease (AD) can aid in early detection of incipient dementia and identify potential mechanistic pathways to disrupted instrumental activities of daily living (IADLs). OBJECTIVES To examine the number, type, and severity of functional impairments and identify the clinical characteristics associated with functional impairment across individuals with amnestic MCI (aMCI) and those with mild AD. DESIGN The study uses baseline data from the Alzheimer’s Disease Neuroimaging Initiative. SETTING Data from the Alzheimer’s Disease Neuroimaging Initiative was collected at multiple research sites in the US and Canada. PATIENTS The samples included 229 controls, 394 aMCI, and 193 AD patients. MAIN OUTCOME MEASURE The 10-item Pfeffer Functional Activities Questionnaire (FAQ) assessed function. RESULTS Informant-reported FAQ deficits were common in patients with aMCI (72.3%) and AD (97.4%) but were rarely self-reported by controls (7.9%). The average severity per FAQ deficit did not differ between patients with aMCI and controls; both were less impaired than patients with AD (P < .001). Two FAQ items (remembering appointments, family occasions, holidays, and medications; assembling tax records, business affairs, or other papers) were specific (0.95) in differentiating controls from the combined aMCI and AD groups (only 34.0% of patients with aMCI and 3.6% of patients with AD had no difficulty with these 2 items). The severity of FAQ deficits in the combined aMCI and AD group was associated with worse Trailmaking Test A scores and smaller hippocampal volumes (P < .001). Within the aMCI group, functionally intact individuals had greater hippocampal volumes and better Auditory Verbal Learning Test 30-minute delay and

Functional impairment in elderly patients with mild cognitive impairment and mild Alzheimer disease.

PubMed

Brown, Patrick J; Devanand, D P; Liu, Xinhua; Caccappolo, Elise

2011-06-01

The original mild cognitive impairment (MCI) criteria exclude substantial functional deficits, but recent reports suggest otherwise. Identifying the extent, severity, type, and correlates of functional deficits that occur in MCI and mild Alzheimer disease (AD) can aid in early detection of incipient dementia and can identify potential mechanistic pathways to disrupted instrumental activities of daily living (IADLs). To examine the number, type, and severity of functional impairments and to identify the clinical characteristics associated with functional impairment across patients with amnestic MCI (aMCI) and those with mild AD. Study using baseline data from the Alzheimer's Disease Neuroimaging Initiative. Multiple research sites in the United States and Canada. Patients Samples included 229 control individuals, 394 patients with aMCI, and 193 patients with AD. The 10-item Pfeffer Functional Activities Questionnaire (FAQ) assessed function. Informant-reported FAQ deficits were common in patients with aMCI (72.3%) and AD (97.4%) but were rarely self-reported by controls (7.9%). The average severity per FAQ deficit did not differ between patients with aMCI and controls; both were less impaired than patients with AD (P < .001). Two FAQ items (remembering appointments, family occasions, holidays, and medications and assembling tax records, business affairs, or other papers) were specific (specificity estimate, 0.95) in differentiating the control group from the combined aMCI and AD groups (only 34.0% of patients with aMCI and 3.6% of patients with AD had no difficulty with these 2 items). The severity of FAQ deficits in the combined aMCI and AD group was associated with worse Trail Making Test, part A scores and smaller hippocampal volumes (P < .001 for both). Within the aMCI group, functionally intact individuals had greater hippocampal volumes and better Auditory Verbal Learning Test 30-minute delay and Trail Making Test, part A (P < .001 for each) scores compared

Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial.

PubMed

Holman, Rury R; Coleman, Ruth L; Chan, Juliana C N; Chiasson, Jean-Louis; Feng, Huimei; Ge, Junbo; Gerstein, Hertzel C; Gray, Richard; Huo, Yong; Lang, Zhihui; McMurray, John J; Rydén, Lars; Schröder, Stefan; Sun, Yihong; Theodorakis, Michael J; Tendera, Michal; Tucker, Lynne; Tuomilehto, Jaakko; Wei, Yidong; Yang, Wenying; Wang, Duolao; Hu, Dayi; Pan, Changyu

2017-11-01

The effect of the α-glucosidase inhibitor acarbose on cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance is unknown. We aimed to assess whether acarbose could reduce the frequency of cardiovascular events in Chinese patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of type 2 diabetes could be reduced. The Acarbose Cardiovascular Evaluation (ACE) trial was a randomised, double-blind, placebo-controlled, phase 4 trial, with patients recruited from 176 hospital outpatient clinics in China. Chinese patients with coronary heart disease and impaired glucose tolerance were randomly assigned (1:1), in blocks by site, by a centralised computer system to receive oral acarbose (50 mg three times a day) or matched placebo, which was added to standardised cardiovascular secondary prevention therapy. All study staff and patients were masked to treatment group allocation. The primary outcome was a five-point composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospital admission for unstable angina, and hospital admission for heart failure, analysed in the intention-to-treat population (all participants randomly assigned to treatment who provided written informed consent). The secondary outcomes were a three-point composite outcome (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), death from any cause, cardiovascular death, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, hospital admission for unstable angina, hospital admission for heart failure, development of diabetes, and development of impaired renal function. The safety population comprised all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT00829660, and the International Standard Randomised Controlled Trial Number registry, number ISRCTN91899513. Between March 20, 2009

Lamin and the heart.

PubMed

Captur, Gabriella; Arbustini, Eloisa; Bonne, Gisèle; Syrris, Petros; Mills, Kevin; Wahbi, Karim; Mohiddin, Saidi A; McKenna, William J; Pettit, Stephen; Ho, Carolyn Y; Muchir, Antoine; Gissen, Paul; Elliott, Perry M; Moon, James C

2018-03-01

Lamins A and C are intermediate filament nuclear envelope proteins encoded by the LMNA gene. Mutations in LMNA cause autosomal dominant severe heart disease, accounting for 10% of dilated cardiomyopathy (DCM). Characterised by progressive conduction system disease, arrhythmia and systolic impairment, lamin A/C heart disease is more malignant than other common DCMs due to high event rates even when the left ventricular impairment is mild. It has several phenotypic mimics, but overall it is likely to be an under-recognised cause of DCM. In certain clinical scenarios, particularly familial DCM with early conduction disease, the pretest probability of finding an LMNA mutation may be quite high.Recognising lamin A/C heart disease is important because implantable cardioverter defibrillators need to be implanted early. Promising oral drug therapies are within reach thanks to research into the mitogen-activated protein kinase (MAPK) and affiliated pathways. Personalised heart failure therapy may soon become feasible for LMNA , alongside personalised risk stratification, as variant-related differences in phenotype severity and clinical course are being steadily elucidated.Genotyping and family screening are clinically important both to confirm and to exclude LMNA mutations, but it is the three-pronged integration of such genetic information with functional data from in vivo cardiomyocyte mechanics, and pathological data from microscopy of the nuclear envelope, that is properly reshaping our LMNA knowledge base, one variant at a time. This review explains the biology of lamin A/C heart disease (genetics, structure and function of lamins), clinical presentation (diagnostic pointers, electrocardiographic and imaging features), aspects of screening and management, including current uncertainties, and future directions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless

Residential Proximity to Major Roadways Is Not Associated with Cardiac Function in African Americans: Results from the Jackson Heart Study.

PubMed

Weaver, Anne M; Wellenius, Gregory A; Wu, Wen-Chih; Hickson, DeMarc A; Kamalesh, Masoor; Wang, Yi

2016-06-13

Cardiovascular disease (CVD), including heart failure, is a major cause of morbidity and mortality, particularly among African Americans. Exposure to ambient air pollution, such as that produced by vehicular traffic, is believed to be associated with heart failure, possibly by impairing cardiac function. We evaluated the cross-sectional association between residential proximity to major roads, a marker of long-term exposure to traffic-related pollution, and echocardiographic indicators of left and pulmonary vascular function in African Americans enrolled in the Jackson Heart Study (JHS): left ventricular ejection fraction, E-wave velocity, isovolumic relaxation time, left atrial diameter index, and pulmonary artery systolic pressure. We examined these associations using multivariable linear or logistic regression, adjusting for potential confounders. Of 4866 participants at study enrollment, 106 lived <150 m, 159 lived 150-299 m, 1161 lived 300-999 m, and 3440 lived ≥1000 m from a major roadway. We did not observe any associations between residential distance to major roads and these markers of cardiac function. Results were similar with additional adjustment for diabetes and hypertension, when considering varying definitions of major roadways, or when limiting analyses to those free from cardiovascular disease at baseline. Overall, we observed little evidence that residential proximity to major roads was associated with cardiac function among African Americans.

Inappropriate Prescription and Renal Function Among Older Patients with Cognitive Impairment.

PubMed

Sönnerstam, Eva; Sjölander, Maria; Gustafsson, Maria

2016-12-01

Older people are more sensitive to drugs and adverse drug reactions than younger people because of age-related physiological changes such as impaired renal function. As people with dementia are particularly vulnerable to the effects of drugs, it is especially important to evaluate the dosages of renally cleared medications in this group. The aim of this study was to estimate the prevalence of impaired renal function and inappropriate prescriptions on the basis of renal function among older patients with dementia or cognitive impairment. The medical records of 428 patients aged ≥65 years who were admitted to two hospitals in northern Sweden were reviewed and renally cleared medications were identified. The Cockcroft-Gault equation was used to evaluate renal function. Doses were evaluated according to the Geriatric Dosage Handbook. Renal function was impaired (estimated glomerular filtration rate <60 ml/min) in 65.4 % of the study population. Impaired renal function was associated with increasing age. Among 547 prescriptions identified as renally cleared medications, 9.1 % were inappropriate based on the patient's renal function; 13.5 % of the 326 patients prescribed renally cleared medications had inappropriate prescriptions. Inappropriate prescriptions were more common among patients living in nursing homes. Impaired renal function is common and inappropriate prescription is prevalent among old people with cognitive impairment in northern Sweden. Continuous consideration of renal function is important when prescribing medications to this group.

Arthritis and Risk of Cognitive and Functional Impairment in Older Mexican Adults.

PubMed

Veeranki, Sreenivas P; Downer, Brian; Jupiter, Daniel; Wong, Rebeca

2017-04-01

This study investigated the risk of cognitive and functional impairment in older Mexicans diagnosed with arthritis. Participants included 2,681 Mexicans, aged ≥60 years, enrolled in the Mexican Health and Aging Study cohort. Participants were categorized into arthritis and no arthritis exposure groups. Primary outcome included participants categorized into "cognitively impaired" or "cognitively normal" groups. Secondary outcomes included participants categorized into Normal, Functionally Impaired only, Cognitively Impaired only, or Dementia (both cognitively and functionally impaired) groups. Multivariable logistic and multinomial regression models were used to assess the relationships. Overall, 16% or 7% were diagnosed with cognitive impairment or dementia. Compared with older Mexicans without arthritis, those who were diagnosed with arthritis had significantly increased risk of functional impairment (adjusted odds ratio [OR] 1.82, 95% confidence interval [CI] = [1.45, 2.29]), but not of dementia. Arthritis is associated with increased risk of functional impairment, but not with dementia after 11 years in older Mexicans.

Functional impairment and the economic consequences of female breast cancer.

PubMed

Chirikos, Thomas N; Russell-Jacobs, Anita; Jacobsen, Paul B

2002-01-01

Recent trends in breast cancer diagnosis and mortality suggest that long-term survivors are now more likely to be functionally impaired and, hence, more likely to experience adverse economic outcomes. This study tests whether women who have survived breast cancer for at least five years exhibit more, or more severe, functional impairments than otherwise similar women without breast cancer. It also tests whether women with more severe impairments experience poorer economic outcomes attributable to their functional status. A group of 105 breast cancer survivors was interviewed to obtain data on health and economic changes in the five-year period since diagnosis and initial treatment. An age- and work-matched group of 105 women without cancer was also interviewed to obtain the same data over the same time period. Key changes in the functional status of the subjects as well as economic outcomes such as changes in market earnings, household income, and insurance coverage were measured. Whether impairment is more severe in the breast cancer group than the comparison group was then tested statistically; whether economic outcomes are more adverse in more impaired than less impaired women regardless of their breast cancer status was also tested. The analysis turned up statistically significant evidence in regard to each of these relationships. Breast cancer survivors were more likely than controls to be functionally impaired at the five-year benchmark. Impaired women, in turn, were more likely to reduce work effort and experience downturns in market earnings, among other things. Policy and research implications are discussed.

The Living Heart Project: A robust and integrative simulator for human heart function.

PubMed

Baillargeon, Brian; Rebelo, Nuno; Fox, David D; Taylor, Robert L; Kuhl, Ellen

2014-11-01

The heart is not only our most vital, but also our most complex organ: Precisely controlled by the interplay of electrical and mechanical fields, it consists of four chambers and four valves, which act in concert to regulate its filling, ejection, and overall pump function. While numerous computational models exist to study either the electrical or the mechanical response of its individual chambers, the integrative electro-mechanical response of the whole heart remains poorly understood. Here we present a proof-of-concept simulator for a four-chamber human heart model created from computer topography and magnetic resonance images. We illustrate the governing equations of excitation-contraction coupling and discretize them using a single, unified finite element environment. To illustrate the basic features of our model, we visualize the electrical potential and the mechanical deformation across the human heart throughout its cardiac cycle. To compare our simulation against common metrics of cardiac function, we extract the pressure-volume relationship and show that it agrees well with clinical observations. Our prototype model allows us to explore and understand the key features, physics, and technologies to create an integrative, predictive model of the living human heart. Ultimately, our simulator will open opportunities to probe landscapes of clinical parameters, and guide device design and treatment planning in cardiac diseases such as stenosis, regurgitation, or prolapse of the aortic, pulmonary, tricuspid, or mitral valve.

Early differentiation of dementia with Lewy bodies and Alzheimer's disease: Heart rate variability at mild cognitive impairment stage.

PubMed

Kim, Min Seung; Yoon, Jung Han; Hong, Ji Man

2018-05-29

Our study aimed to investigate whether heart rate variability (HRV) could be a useful diagnostic screening tool at MCI (mild cognitive impairment) stage of Dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). This retrospective study used a selected sample from Ajou neurological registry. We identified MCI patients who underwent HRV testing at baseline, and who developed probable DLB (MCI-DLB: n = 23) or AD (MCI-AD: n = 32). The MCI-DLB group exhibited significantly lower levels of almost all HRV parameters compared with the MCI-AD group. Fronto-executive function and visuospatial abilities were poorer in the MCI-DLB group, whereas the extent of verbal memory impairment was greater in the MCI-AD. Verbal memory score was negatively correlated with overall HRV parameters, and visuospatial function was positively correlated with the frequency domain of HRV. Receiver operating curve area under the curve (AUC) analysis revealed that the low frequency component was the best potential diagnostic marker (AUC = 0.88). MCI-DLB patients exhibited greater cardiac autonomic dysfunction (as measured by HRV) and greater fronto-executive and visuospatial deficit compared with MCI-AD patients. HRV may be useful method to differentiate DLB from AD in patients with MCI; this would facilitate early disease-specific intervention. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Cognitive Function in Ambulatory Patients with Systolic Heart Failure: Insights from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

PubMed Central

Graham, Susan; Ye, Siqin; Qian, Min; Sanford, Alexandra R.; Di Tullio, Marco R.; Sacco, Ralph L.; Mann, Douglas L.; Levin, Bruce; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Mohr, J. P.; Labovitz, Arthur J.; Lip, Gregory Y. H.; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.; Thompson, John L. P.; Homma, Shunichi

2014-01-01

We sought to determine whether cognitive function in stable outpatients with heart failure (HF) is affected by HF severity. A retrospective, cross-sectional analysis was performed using data from 2, 043 outpatients with systolic HF and without prior stroke enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial. Multivariable regression analysis was used to assess the relationship between cognitive function measured using the Mini-Mental Status Exam (MMSE) and markers of HF severity (left ventricular ejection fraction [LVEF], New York Heart Association [NYHA] functional class, and 6-minute walk distance). The mean (SD) for the MMSE was 28.6 (2.0), with 64 (3.1%) of the 2,043 patients meeting the cut-off of MMSE <24 that indicates need for further evaluation of cognitive impairment. After adjustment for demographic and clinical covariates, 6-minute walk distance (β-coefficient 0.002, p<0.0001), but not LVEF or NYHA functional class, was independently associated with the MMSE as a continuous measure. Age, education, smoking status, body mass index, and hemoglobin level were also independently associated with the MMSE. In conclusion, six-minute walk distance, but not LVEF or NYHA functional class, was an important predictor of cognitive function in ambulatory patients with systolic heart failure. PMID:25426862

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

Impact of Sensory Impairments on Functional Disability in Adults With Arthritis

PubMed Central

Fisher, Diana E.; Ward, Michael M.; Hoffman, Howard J.; Li, Chuan-Ming; Cotch, Mary Frances

2015-01-01

Introduction Mobility is reduced in people with sensory impairments and those with arthritis. The joint impact of these conditions may be underappreciated. This study examines the associations between impairments in vision, hearing, and balance and functional ability in adults with versus without arthritis. Methods Using National Health and Nutrition Examination Survey data from 1999–2004, arthritis status, functional ability, and sensory impairments (vision, hearing, and balance) were assessed from self-reported responses by 6,654 individuals aged ≥50 years (mean age, 63.4 years; 46.3% male). Multivariable regression analyses, conducted in 2014, assessed the associations between sensory impairment and arthritis on functional ability and mobility. Results Among study participants, 41.8% reported having arthritis; of these, 27.1%, 44.9%, and 35.1% reported impaired vision, hearing, or balance, respectively. Having multiple sensory impairments was significantly associated with reduced functional ability in people with arthritis; individuals with three sensory impairments reported the highest levels of disability for all functional domains (compared with no impairment; lower extremity mobility, 80.2% vs 39.1%; general physical activities, 94.7% vs 75.9%; activities of daily living, 69.7% vs 27.2%; instrumental activities of daily living, 77.2% vs 37.4%; leisure and social activities, 66.3% vs 30.6%; impaired gait speed, 48.1% vs 16.3%; all p<0.001). Importantly, visual deficits, in combination with arthritis, had the greatest impact on mobility, with odds of impaired mobility at least twice as high as for individuals without arthritis. Conclusions Addressing sensory deficits, especially difficulties with vision, may improve functional ability, which may be particularly helpful for adults with arthritis. PMID:26410186

Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I.

PubMed

Kruse, Martin; Schulze-Bahr, Eric; Corfield, Valerie; Beckmann, Alf; Stallmeyer, Birgit; Kurtbay, Güven; Ohmert, Iris; Schulze-Bahr, Ellen; Brink, Paul; Pongs, Olaf

2009-09-01

Progressive familial heart block type I (PFHBI) is a progressive cardiac bundle branch disease in the His-Purkinje system that exhibits autosomal-dominant inheritance. In 3 branches of a large South African Afrikaner pedigree with an autosomal-dominant form of PFHBI, we identified the mutation c.19G-->A in the transient receptor potential cation channel, subfamily M, member 4 gene (TRPM4) at chromosomal locus 19q13.3. This mutation predicted the amino acid substitution p.E7K in the TRPM4 amino terminus. TRPM4 encodes a Ca2+-activated nonselective cation (CAN) channel that belongs to the transient receptor potential melastatin ion channel family. Quantitative analysis of TRPM4 mRNA content in human cardiac tissue showed the highest expression level in Purkinje fibers. Cellular expression studies showed that the c.19G-->A missense mutation attenuated deSUMOylation of the TRPM4 channel. The resulting constitutive SUMOylation of the mutant TRPM4 channel impaired endocytosis and led to elevated TRPM4 channel density at the cell surface. Our data therefore revealed a gain-of-function mechanism underlying this type of familial heart block.

Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I

PubMed Central

Kruse, Martin; Schulze-Bahr, Eric; Corfield, Valerie; Beckmann, Alf; Stallmeyer, Birgit; Kurtbay, Güven; Ohmert, Iris; Schulze-Bahr, Ellen; Brink, Paul; Pongs, Olaf

2009-01-01

Progressive familial heart block type I (PFHBI) is a progressive cardiac bundle branch disease in the His-Purkinje system that exhibits autosomal-dominant inheritance. In 3 branches of a large South African Afrikaner pedigree with an autosomal-dominant form of PFHBI, we identified the mutation c.19G→A in the transient receptor potential cation channel, subfamily M, member 4 gene (TRPM4) at chromosomal locus 19q13.3. This mutation predicted the amino acid substitution p.E7K in the TRPM4 amino terminus. TRPM4 encodes a Ca2+-activated nonselective cation (CAN) channel that belongs to the transient receptor potential melastatin ion channel family. Quantitative analysis of TRPM4 mRNA content in human cardiac tissue showed the highest expression level in Purkinje fibers. Cellular expression studies showed that the c.19G→A missense mutation attenuated deSUMOylation of the TRPM4 channel. The resulting constitutive SUMOylation of the mutant TRPM4 channel impaired endocytosis and led to elevated TRPM4 channel density at the cell surface. Our data therefore revealed a gain-of-function mechanism underlying this type of familial heart block. PMID:19726882

Pharmacokinetic profile of nifedipine GITS in hypertensive patients with chronic renal impairment.

PubMed

Schneider, R; Stolero, D; Griffel, L; Kobelt, R; Brendel, E; Iaina, A

1994-01-01

25 hypertensive patients with normal or impaired renal function underwent pharmacokinetic and safety studies after single and multiple dose administration of nifedipine GITS (Gastro-Intestinal Therapeutic System) 60mg tablets. Complete pharmacokinetic data were obtained from 23 of these patients. Blood pressure and heart rate changes were compatible with the known properties of the drug. Impaired renal function did not affect the maximum plasma concentrations or bioavailability of nifedipine after single or multiple dose administration of nifedipine GITS, nor was there any evidence of excessive drug accumulation in the presence of renal impairment.

Renal Function Recovery with Total Artificial Heart Support.

PubMed

Quader, Mohammed A; Goodreau, Adam M; Shah, Keyur B; Katlaps, Gundars; Cooke, Richard; Smallfield, Melissa C; Tchoukina, Inna F; Wolfe, Luke G; Kasirajan, Vigneshwar

2016-01-01

Heart failure patients requiring total artificial heart (TAH) support often have concomitant renal insufficiency (RI). We sought to quantify renal function recovery in patients supported with TAH at our institution. Renal function data at 30, 90, and 180 days after TAH implantation were analyzed for patients with RI, defined as hemodialysis supported or an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m. Between January 2008 and December 2013, 20 of the 46 (43.5%) TAH recipients (age 51 ± 9 years, 85% men) had RI, mean preoperative eGFR of 48 ± 7 ml/min/1.73 m. Renal function recovery was noted at each follow-up interval: increment in eGFR (ml/min/1.73 m) at 30, 90, and 180 days was 21 ± 35 (p = 0.1), 16.5 ± 18 (p = 0.05), and 10 ± 9 (p = 0.1), respectively. Six patients (30%) required preoperative dialysis. Of these, four recovered renal function, one remained on dialysis, and one died. Six patients (30%) required new-onset dialysis. Of these, three recovered renal function and three died. Overall, 75% (15 of 20) of patients' renal function improved with TAH support. Total artificial heart support improved renal function in 75% of patients with pre-existing significant RI, including those who required preoperative dialysis.

Comparison of the effects of penbutolol and propranolol on glomerular filtration rate in hypertensive patients with impaired renal function.

PubMed Central

van der Meulen, J; Reijn, E; Heidendal, G A; Oe, P L; Donker, A J

1986-01-01

Penbutolol and propranolol were administered orally in a dosage of 40 mg once daily and 80 mg twice daily, respectively to 12 patients with hypertension and impaired renal function. Both drugs caused a significant decrease in mean arterial pressure and heart rate. Serum creatinine concentration increased significantly by 10% during therapy with propranolol without concomitant decrease in creatinine clearance. No such effect was seen with penbutolol. GFR measured with [125I]-iothalamate showed no significant changes with both drugs. PMID:3533129

Arthritis and Risk of Cognitive and Functional Impairment in Older Mexican Adults

PubMed Central

Veeranki, Sreenivas P.; Downer, Brian; Jupiter, Daniel; Wong, Rebeca

2016-01-01

Objective This study investigated the risk of cognitive and functional impairment in older Mexicans diagnosed with arthritis. Participants included 2,681 Mexicans, aged ≥60 years, enrolled in the Mexican Health and Aging Study cohort. Method Participants were categorized into arthritis and no arthritis exposure groups. Primary outcome included participants categorized into “cognitively impaired” or “cognitively normal” groups. Secondary outcomes included participants categorized into Normal, Functionally Impaired only, Cognitively Impaired only, or Dementia (both cognitively and functionally impaired) groups. Multivariable logistic and multinomial regression models were used to assess the relationships. Results Overall, 16% or 7% were diagnosed with cognitive impairment or dementia. Compared with older Mexicans without arthritis, those who were diagnosed with arthritis had significantly increased risk of functional impairment (adjusted odds ratio [OR] 1.82, 95% confidence interval [CI] = [1.45, 2.29]), but not of dementia. Conclusion Arthritis is associated with increased risk of functional impairment, but not with dementia after 11 years in older Mexicans. PMID:26965081

Methylene Blue Partially Rescues Heart Defects in a Drosophila Model of Huntington's Disease.

PubMed

Heidari, Raheleh; Monnier, Véronique; Martin, Elodie; Tricoire, Hervé

2015-01-01

Huntington's disease (HD) is a Polyglutamine disease caused by the presence of CAG repeats in the first exon of Huntingtin (Htt), a large protein with multiple functions. In addition to neurodegeneration of specific brain regions, notably the striatum, HD also shows alterations in peripheral tissues, such as the heart, skeletal muscles or peripheral endocrine glands. Mutant Huntingtin (mHtt)-driven mitochondrial impairment may underlie some of the CNS and peripheral tissues dysfunctions, especially in tissues with high energy demand such as the heart. The aim of this study is to characterize two new inducible Drosophila HD heart models and to assay the therapeutic potential of methylene blue in these HD models. We report the construction of inducible Drosophila HD heart models, expressing two Nter fragments of the protein encompassing either exon 1 or the first 171 amino acids and the characterization of heart phenotypes in vivo. We show that both mHtt fragments are able to impair fly cardiac function with different characteristics. Additionally, expression of mHtt, which was limited to adulthood only, leads to mild heart impairment, as opposed to a strong and age-dependent phenotype observed when mHtt expression was driven during both developmental and adult stages. We report that treatment with methylene blue (MB), a protective compound in mitochondria-related diseases, partially protects the fly's heart against mHtt-induced toxicity, but does not rescue neuronal or glial phenotypes in other fly models of HD. This may be linked to its low penetration through the fly's blood-brain barrier. Our data suggest that improvement of mitochondrial function by MB, or related compounds, could be an efficient therapeutic strategy to prevent cardiac failure in HD patients.

Normalization of NAD+ Redox Balance as a Therapy for Heart Failure.

PubMed

Lee, Chi Fung; Chavez, Juan D; Garcia-Menendez, Lorena; Choi, Yongseon; Roe, Nathan D; Chiao, Ying Ann; Edgar, John S; Goo, Young Ah; Goodlett, David R; Bruce, James E; Tian, Rong

2016-09-20

Impairments of mitochondrial function in the heart are linked intricately to the development of heart failure, but there is no therapy for mitochondrial dysfunction. We assessed the reduced/oxidized ratio of nicotinamide adenine dinucleotide (NADH/NAD(+) ratio) and protein acetylation in the failing heart. Proteome and acetylome analyses were followed by docking calculation, mutagenesis, and mitochondrial calcium uptake assays to determine the functional role of specific acetylation sites. The therapeutic effects of normalizing mitochondrial protein acetylation by expanding the NAD(+) pool also were tested. Increased NADH/NAD(+) and protein hyperacetylation, previously observed in genetic models of defective mitochondrial function, also are present in human failing hearts as well as in mouse hearts with pathologic hypertrophy. Elevation of NAD(+) levels by stimulating the NAD(+) salvage pathway suppressed mitochondrial protein hyperacetylation and cardiac hypertrophy, and improved cardiac function in responses to stresses. Acetylome analysis identified a subpopulation of mitochondrial proteins that was sensitive to changes in the NADH/NAD(+) ratio. Hyperacetylation of mitochondrial malate-aspartate shuttle proteins impaired the transport and oxidation of cytosolic NADH in the mitochondria, resulting in altered cytosolic redox state and energy deficiency. Furthermore, acetylation of oligomycin-sensitive conferring protein at lysine-70 in adenosine triphosphate synthase complex promoted its interaction with cyclophilin D, and sensitized the opening of mitochondrial permeability transition pore. Both could be alleviated by normalizing the NAD(+) redox balance either genetically or pharmacologically. We show that mitochondrial protein hyperacetylation due to NAD(+) redox imbalance contributes to the pathologic remodeling of the heart via 2 distinct mechanisms. Our preclinical data demonstrate a clear benefit of normalizing NADH/NAD(+) imbalance in the failing hearts

Type 2 Diabetes Mellitus and Impaired Renal Function Are Associated With Brain Alterations and Poststroke Cognitive Decline.

PubMed

Ben Assayag, Einor; Eldor, Roy; Korczyn, Amos D; Kliper, Efrat; Shenhar-Tsarfaty, Shani; Tene, Oren; Molad, Jeremy; Shapira, Itzhak; Berliner, Shlomo; Volfson, Viki; Shopin, Ludmila; Strauss, Yehuda; Hallevi, Hen; Bornstein, Natan M; Auriel, Eitan

2017-09-01

Type 2 diabetes mellitus (T2DM) is associated with diseases of the brain, kidney, and vasculature. However, the relationship between T2DM, chronic kidney disease, brain alterations, and cognitive function after stroke is unknown. We aimed to evaluate the inter-relationship between T2DM, impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. The TABASCO (Tel Aviv brain acute stroke cohort) is a prospective cohort of stroke/transient ischemic attack survivors. The volume and white matter integrity, ischemic lesions, and brain and hippocampal volumes were measured at baseline using 3-T MRI. Cognitive tests were performed on 507 patients, who were diagnosed as having mild cognitive impairment, dementia, or being cognitively intact after 24 months. At baseline, T2DM and impaired renal function (estimated creatinine clearance [eCCl] <60 mL/min) were associated with smaller brain and hippocampal volumes, reduced cortical thickness, and worse white matter microstructural integrity. Two years later, both T2DM and eCCl <60 mL/min were associated with poorer cognitive scores, and 19.7% of the participants developed cognitive decline (mild cognitive impairment or dementia). Multiple analysis, controlling for age, sex, education, and apolipoprotein E4, showed a significant association of both T2DM and eCCl <60 mL/min with cognitive decline. Having both conditions doubled the risk compared with patients with T2DM or eCCl <60 mL/min alone and almost quadrupled the risk compared with patients without either abnormality. T2DM and impaired renal function are independently associated with abnormal brain structure, as well as poorer performance in cognitive tests, 2 years after stroke. The presence of both conditions quadruples the risk for cognitive decline. T2DM and lower eCCl have an independent and additive effect on brain atrophy and the risk of cognitive decline. URL: http://www.clinicaltrials.gov. Unique identifier: NCT

Impaired endothelial function in patients with mild primary hyperparathyroidism improves after parathyroidectomy.

PubMed

Tuna, Mazhar M; Doğan, Berçem A; Arduç, Ayşe; Imga, Narin Nasiroğlu; Tütüncü, Yasemin; Berker, Dilek; Güler, Serdar

2015-12-01

Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity; however, data on the reversibility of cardiovascular disease in mild primary hyperparathyroidism are conflicting. The aim of this study was to assess endothelial function in patients with mild PHPT before and after parathyroidectomy (Ptx). We prospectively evaluated 53 patients with mild PHPT (Group 1; 45 women, eight men; aged 52 ± 3·1 years) and 46 healthy control subjects (Group 2; 38 women, eight men; aged 46 ± 9·5 years). Endothelial function was measured as flow-mediated dilation (FMD) and carotid intima-media thickness (CIMT) using Doppler ultrasonography. Patients with diabetes mellitus, coronary heart disease, impaired renal function, hyperthyroidism, hypothyroidism and a history of smoking were excluded from the study. Patients were studied at baseline and 6-12 months after the first evaluation. There were no differences with respect to age, gender and BMI between the two groups. Hypertension prevalence was three times higher in group 1 than in controls. % FMD was lower in group 1 than in group 2 (2·6 ± 1·2 vs 14·8 ± 9·6, P < 0·001). CIMT was higher in patients with PHPT than controls (0·69 ± 0·18 vs 0·61 ± 0·12, P = 0·045). This significance remained when hypertensive patients were excluded from the analysis. While FMD and CIMT improved significantly after Ptx, there were no differences in mild PHPT patients who followed without parathyroidectomy. FMD and CIMT are impaired in patients with mild PHPT compared to controls and improved significantly after a successful Ptx. Ptx improves endothelial function in patients with mild PHPT that may lead to decreased cardiovascular morbidity and mortality. © 2014 John Wiley & Sons Ltd.

Psychosocial functioning in pediatric heart transplant recipients and their families.

PubMed

Cousino, Melissa K; Schumacher, Kurt R; Rea, Kelly E; Eder, Sally; Zamberlan, Mary; Jordan, Jessica; Fredericks, Emily M

2018-03-01

Across pediatric organ transplant populations, patient and family psychosocial functioning is associated with important health-related outcomes. Research has suggested that pediatric heart transplant recipients and their families are at increased risk for adverse psychosocial outcomes; however, recent investigation of psychosocial functioning in this population is lacking. This study aimed to provide a contemporary characterization of psychosocial functioning in pediatric heart transplant recipients and their families. Associations between psychosocial function, demographic variables, and transplant-related variables were investigated. Fifty-six parents/guardians of pediatric heart transplant recipients completed a comprehensive psychosocial screening measure during transplant follow-up clinic visits. Descriptive statistics, correlational analyses, and independent samples t tests were performed. Forty percent of pediatric heart transplant recipients and their families endorsed clinically meaningful levels of total psychosocial risk. One-third of patients presented with clinically significant psychological problems per parent report. Psychosocial risk was unassociated with demographic or transplant-related factors. Despite notable improvements in the survival of pediatric heart transplant recipients over the past decade, patients and families present with sustained psychosocial risks well beyond the immediate post-transplant period, necessitating mental health intervention to mitigate adverse impact on health-related outcomes. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

HSF1 deficiency accelerates the transition from pressure overload-induced cardiac hypertrophy to heart failure through endothelial miR-195a-3p-mediated impairment of cardiac angiogenesis.

PubMed

Wang, Shijun; Wu, Jian; You, Jieyun; Shi, Hongyu; Xue, Xiaoyu; Huang, Jiayuan; Xu, Lei; Jiang, Guoliang; Yuan, Lingyan; Gong, Xue; Luo, Haiyan; Ge, Junbo; Cui, Zhaoqiang; Zou, Yunzeng

2018-05-01

Heat shock transcription factor 1 (HSF1) deficiency aggravates cardiac remodeling under pressure overload. However, the mechanism is still unknown. Here we employed microRNA array analysis of the heart tissue of HSF1-knockout (KO) mice to investigate the potential roles of microRNAs in pressure overload-induced cardiac remodeling under HSF-1 deficiency, and the profiles of 478 microRNAs expressed in the heart tissues of adult HSF1-KO mice were determined. We found that the expression of 5 microRNAs was over 2-fold higher expressed in heart tissues of HSF1-KO mice than in those of wild-type (WT) control mice. Of the overexpressed microRNAs, miR-195a-3p had the highest expression level in HSF1-null endothelial cells (ECs). Induction with miR-195a-3p in ECs significantly suppressed CD31 and VEGF, promoted AngII-induced EC apoptosis, and impaired capillary-like tube formation. In vivo, the upregulation of miR-195a-3p accentuated cardiac hypertrophy, increased the expression of β-MHC and ANP, and compromised systolic function in mice under pressure overload induced by transverse aortic constriction (TAC). By contrast, antagonism of miR-195a-3p had the opposite effect on HSF1-KO mice. Further experiments confirmed that AMPKα2 was the direct target of miR-195a-3p. AMPKα2 overexpression rescued the reduction of eNOS and VEGF, and the impairment of angiogenesis that was induced by miR-195a-3p. In addition, upregulation of AMPKα2 in the myocardium of HSF1-null mice by adenovirus-mediated gene delivery enhanced CD31, eNOS and VEGF, reduced β-MHC and ANP, alleviated pressure overload-mediated cardiac hypertrophy and restored cardiac function. Our findings revealed that the upregulation of miR-195a-3p due to HSF1 deficiency impaired cardiac angiogenesis by regulating AMPKα2/VEGF signaling, which disrupted the coordination between the myocardial blood supply and the adaptive hypertrophic response and accelerated the transition from cardiac hypertrophy to heart failure in

Treatment Concerns and Functional Impairment in Pediatric Anxiety.

PubMed

Wu, Monica S; Salloum, Alison; Lewin, Adam B; Selles, Robert R; McBride, Nicole M; Crawford, Erika A; Storch, Eric A

2016-08-01

Although there are efficacious, evidence-based treatments for anxiety disorders, youth often experience delays in seeking therapy. Myriad reasons may contribute to this lag in treatment initiation, with some youth possessing concerns about therapy. Treatment concerns are broadly characterized by worries/ambivalence about seeking treatment, including concerns about the negative reactions, consequences, and inconvenience of treatment. As no studies exist for youth with anxiety disorders, this study examined the phenomenology of treatment concerns in 119 treatment-seeking, anxious youth and utilized a structural equation model to examine the relationship between child anxiety, depressive symptoms, treatment concerns, and anxiety-related functional impairment. Over 90 % of the children positively endorsed some type of treatment-related fear, with the most frequently expressed concern being that therapy would take too much time (50.4 %). Based on the model, both child anxiety and depressive symptoms predicted functional impairment, and treatment concerns mediated the relationship between child anxiety and functional impairment.

Mitochondrial Metabolism in Aging Heart

PubMed Central

Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

2016-01-01

Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

Self-care and quality of life of heart failure patients at a multidisciplinary heart function clinic.

PubMed

Seto, Emily; Leonard, Kevin J; Cafazzo, Joseph A; Masino, Caterina; Barnsley, Jan; Ross, Heather J

2011-01-01

Multidisciplinary heart function clinics aim to improve self-care through patient education and to provide clinical management. The objectives of the present study were to investigate the self-care and quality of life of patients attending a multidisciplinary heart function clinic and to explore the relationship between self-care and quality of life. One hundred outpatients attending a multidisciplinary heart function clinic were asked to complete a questionnaire. The questionnaire included the Self-care of Heart Failure Index (SCHFI) and the Minnesota Living With Heart Failure Questionnaire, which were used to assess self-care behavior and quality of life, respectively. Self-care practices and perceived barriers were also assessed through semistructured interviews with each patient. : The returned questionnaires (n = 94) were used to compute the following SCHFI maintenance, management, and confidence scores: 60.8 (SD, 19.3), 62.0 (SD, 20.7), and 55.9 (SD, 19.7), respectively. Higher SCHFI scores indicate better self-care. None of the self-care dimensions reached the self-care adequacy cut point of 70. The average score on the Minnesota Living With Heart Failure Questionnaire was 49.9 (SD, 25.4), indicating a moderate health-related quality of life. Lower ejection fraction, older age, and better quality of life were associated with better self-care. Determinants of better quality of life were older age, better functional capacity, higher self-care confidence, and fewer comorbidities. The patient interviews revealed that better quality of life is associated with higher self-care confidence and barriers to self-care caused anxiety to the patients. The self-care barriers were found to include lack of self-care education, financial constraints, lack of perceived benefit, and low self-efficacy. Patients attending a large multidisciplinary Canadian heart failure clinic do not perform adequate self-care as measured with the SCHFI and report only a moderate quality of life

PATHOPHYSIOLOGICAL CONSEQUENCES OF TAT-HKII PEPTIDE ADMINISTRATION ARE INDEPENDENT OF IMPAIRED VASCULAR FUNCTION AND ENSUING ISCHEMIA

PubMed Central

Nederlof, Rianne; Xie, Chaoqin; Eerbeek, Otto; Koeman, Anneke; Milstein, Dan MJ; Hollmann, Markus W; Mik, Egbert G; Warley, Alice; Southworth, Richard; Akar, Fadi G.; Zuurbier, Coert J

2013-01-01

Rationale We have shown that partial dissociation of HKII from mitochondria in the intact heart using low dose (200 nM) TAT-HKII prevents the cardioprotective effects of ischemic preconditioning (IPC) whereas high-dose (10 μM) TAT-HKII administration results in rapid myocardial dysfunction, mitochondrial depolarization and disintegration. In this issue of Circulation Research, Pasdois et al argue that the deleterious effects of TAT-HKII administration on cardiac function are likely due to vasoconstriction and ensuing ischemia. Objective To investigate whether altered vascular function and ensuing ischemia recapitulate the deleterious effects of TAT-HKII in intact myocardium. Methods and Results Using a variety of complementary techniques, including mitochondrial membrane potential (ΔΨm) imaging, high-resolution optical action potential (AP) mapping, analysis of lactate production, NADH epifluorescence, lactate dehydrogenase (LDH) release, and electron microscopy, we provide direct evidence that refutes the notion that acute myocardial dysfunction by high-dose TAT-HKII peptide administration is a consequence of impaired vascular function. Moreover, we demonstrate that low-dose TAT-HKII treatment, which abrogates the protective effects of IPC, is not associated with ischemia or ischemic-injury. Conclusions Our findings challenge the notion that the effects of TAT-HKII are attributable to impaired vascular function and ensuing ischemia; thereby, lending further credence to the role of mitochondria bound HKII as a critical regulator of cardiac function, ischemia-reperfusion (IR) injury, and cardioprotection by IPC. PMID:23329797

Decreased Mitochondrial Pyruvate Transport Activity in the Diabetic Heart

PubMed Central

Vadvalkar, Shraddha S.; Matsuzaki, Satoshi; Eyster, Craig A.; Giorgione, Jennifer R.; Bockus, Lee B.; Kinter, Caroline S.; Kinter, Michael

2017-01-01

Alterations in mitochondrial function contribute to diabetic cardiomyopathy. We have previously shown that heart mitochondrial proteins are hyperacetylated in OVE26 mice, a transgenic model of type 1 diabetes. However, the universality of this modification and its functional consequences are not well established. In this study, we demonstrate that Akita type 1 diabetic mice exhibit hyperacetylation. Functionally, isolated Akita heart mitochondria have significantly impaired maximal (state 3) respiration with physiological pyruvate (0.1 mm) but not with 1.0 mm pyruvate. In contrast, pyruvate dehydrogenase activity is significantly decreased regardless of the pyruvate concentration. We found that there is a 70% decrease in the rate of pyruvate transport in Akita heart mitochondria but no decrease in the mitochondrial pyruvate carriers 1 and 2 (MPC1 and MPC2). The potential role of hyperacetylation in mediating this impaired pyruvate uptake was examined. The treatment of control mitochondria with the acetylating agent acetic anhydride inhibits pyruvate uptake and pyruvate-supported respiration in a similar manner to the pyruvate transport inhibitor α-cyano-4-hydroxycinnamate. A mass spectrometry selective reactive monitoring assay was developed and used to determine that acetylation of lysines 19 and 26 of MPC2 is enhanced in Akita heart mitochondria. Expression of a double acetylation mimic of MPC2 (K19Q/K26Q) in H9c2 cells was sufficient to decrease the maximal cellular oxygen consumption rate. This study supports the conclusion that deficient pyruvate transport activity, mediated in part by acetylation of MPC2, is a contributor to metabolic inflexibility in the diabetic heart. PMID:28154187

Performance of the Automated Neuropsychological Assessment Metrics (ANAM) in detecting cognitive impairment in heart failure patients.

PubMed

Xie, Susan S; Goldstein, Carly M; Gathright, Emily C; Gunstad, John; Dolansky, Mary A; Redle, Joseph; Hughes, Joel W

2015-01-01

Evaluate capacity of the Automated Neuropsychological Assessment Metrics (ANAM) to detect cognitive impairment (CI) in heart failure (HF) patients. CI is a key prognostic marker in HF. Though the most widely used cognitive screen in HF, the Mini-Mental State Examination (MMSE) is insufficiently sensitive. The ANAM has demonstrated sensitivity to cognitive domains affected by HF, but has not been assessed in this population. Investigators administered the ANAM and MMSE to 57 HF patients, compared against a composite model of cognitive function. ANAM efficiency (p < .05) and accuracy scores (p < .001) successfully differentiated CI and non-CI. ANAM efficiency and accuracy scores classified 97.7% and 93.0% of non-CI patients, and 14.3% and 21.4% with CI, respectively. The ANAM is more effective than the MMSE for detecting CI, but further research is needed to develop a more optimal cognitive screen for routine use in HF patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Autonomic Impairment in Severe Traumatic Brain Injury: A Multimodal Neuromonitoring Study.

PubMed

Sykora, Marek; Czosnyka, Marek; Liu, Xiuyun; Donnelly, Joseph; Nasr, Nathalie; Diedler, Jennifer; Okoroafor, Francois; Hutchinson, Peter; Menon, David; Smielewski, Peter

2016-06-01

Autonomic impairment after acute traumatic brain injury has been associated independently with both increased morbidity and mortality. Links between autonomic impairment and increased intracranial pressure or impaired cerebral autoregulation have been described as well. However, relationships between autonomic impairment, intracranial pressure, impaired cerebral autoregulation, and outcome remain poorly explored. Using continuous measurements of heart rate variability and baroreflex sensitivity we aimed to test whether autonomic markers are associated with functional outcome and mortality independently of intracranial variables. Further, we aimed to evaluate the relationships between autonomic functions, intracranial pressure, and cerebral autoregulation. Retrospective analysis of a prospective database. Neurocritical care unit in a university hospital. Sedated patients with severe traumatic brain injury. Waveforms of intracranial pressure and arterial blood pressure, baseline Glasgow Coma Scale and 6 months Glasgow Outcome Scale were recorded. Baroreflex sensitivity was assessed every 10 seconds using a modified cross-correlational method. Frequency domain analyses of heart rate variability were performed automatically every 10 seconds from a moving 300 seconds of the monitoring time window. Mean values of baroreflex sensitivity, heart rate variability, intracranial pressure, arterial blood pressure, cerebral perfusion pressure, and impaired cerebral autoregulation over the entire monitoring period were calculated for each patient. Two hundred and sixty-two patients with a median age of 36 years entered the analysis. The median admission Glasgow Coma Scale was 6, the median Glasgow Outcome Scale was 3, and the mortality at 6 months was 23%. Baroreflex sensitivity (adjusted odds ratio, 0.9; p = 0.02) and relative power of a high frequency band of heart rate variability (adjusted odds ratio, 1.05; p < 0.001) were individually associated with mortality, independently

Oil Exposure Impairs In Situ Cardiac Function in Response to β-Adrenergic Stimulation in Cobia (Rachycentron canadum).

PubMed

Cox, Georgina K; Crossley, Dane A; Stieglitz, John D; Heuer, Rachael M; Benetti, Daniel D; Grosell, Martin

2017-12-19

Aqueous crude oil spills expose fish to varying concentrations of dissolved polycyclic aromatic hydrocarbons (PAHs), which can have lethal and sublethal effects. The heart is particularly vulnerable in early life stages, as PAH toxicity causes developmental cardiac abnormalities and impaired cardiovascular function. However, cardiac responses of juvenile and adult fish to acute oil exposure remain poorly understood. We sought to assess cardiac function in a pelagic fish species, the cobia (Rachycentron canadum), following acute (24 h) exposure to two ecologically relevant levels of dissolved PAHs. Cardiac power output (CPO) was used to quantify cardiovascular performance using an in situ heart preparation. Cardiovascular performance was varied using multiple concentrations of the β-adrenoceptor agonist isoproterenol (ISO) and by varying afterload pressures. Oil exposure adversely affected CPO with control fish achieving maximum CPO's (4 mW g -1 Mv) greater than that of oil-exposed fish (1 mW g -1 Mv) at ISO concentrations of 1 × 10 -6 M. However, the highest concentration of ISO (1 × 10 -5 M) rescued cardiac function. This indicates an interactive effect between oil-exposure and β-adrenergic stimulation and suggests if animals achieve very large increases in β-adrenergic stimulation it could play a compensatory role that may mitigate some adverse effects of oil-exposure in vivo.

Executive Functioning and School Performance Among Pediatric Survivors of Complex Congenital Heart Disease

PubMed Central

Gerstle, Melissa; Beebe, Dean W.; Drotar, Dennis; Cassedy, Amy; Marino, Bradley S.

2016-01-01

Objective To investigate the presence and severity of real-world impairments in executive functioning– responsible for children’s regulatory skills (metacognition, behavioral regulation) – and its potential impact on school performance among pediatric survivors of complex congenital heart disease (CHD). Study design Survivors of complex CHD aged 8–16 years (n=143)and their parents/guardians from a regional CHD survivor registry participated (81% participation rate). Parents completed proxy measures of executive functioning, school competency, and school-related quality of life (QOL). Patients also completed a measure of school QOL and underwent IQ testing. Patients were categorized into two groups based on heart lesion complexity: two-ventricle or single-ventricle. Results Survivors of complex CHD performed significantly worse than norms for executive functioning, IQ, school competency, and school QOL. Metacognition was more severely affected than behavioral regulation, and metacognitive deficits were more often present in older children. Even after taking into account demographic factors, disease severity, and IQ, metacognition uniquely and strongly predicted poorer school performance. In exploratory analyses, patients with single-ventricle lesions were rated as having lower school competency and school QOL, and patients with two-ventricle lesions were rated as having poorer behavioral regulation. Conclusions Survivors of complex CHD experience greater executive functioning difficulties than healthy peers, with metacognition particularly impacted and particularly relevant for day-to-day school performance. Especially in older children, clinicians should watch for metacognitive deficits, such as problems with organization, planning, self-monitoring, and follow-through on tasks. PMID:26875011

Association of Central Sleep Apnea with Impaired Heart Structure and Cardiovascular Hemodynamics in Patients with Chronic Heart Failure

PubMed Central

Kazimierczak, Anna; Krzesiński, Paweł; Gielerak, Grzegorz; Uziebło-Życzkowska, Beata; Smurzyński, Paweł; Ryczek, Robert; Cwetsch, Andrzej; Skrobowski, Andrzej

2016-01-01

Background Advanced heart failure (HF) is commonly accompanied by central sleep apnea (CSA) with Cheyne-Stokes respiration (CSR). The aim of this study was to evaluate the relationship between CSA/CSR and other clinical features of HF, with particular emphasis on cardiovascular hemodynamics. Material/Methods In 161 stable HF patients with left ventricular ejection fraction (LVEF) ≤45% (NYHA class I–III; mean LVEF 32.8%) the clinical evaluation included: LVEF; left and right ventricular end-diastolic diameter (LVDd, RVDd); ratio of early transmitral flow velocity to early diastolic septal mitral annulus velocity (E/e’) assessed by echocardiography; stroke index (SI); heart rate (HR); cardiac index (CI); and systemic vascular resistance index (SVRI) assessed by impedance cardiography (ICG). The comparison was performed between 2 subgroups: one with moderate/severe CSA/CSR - CSR_ [+] (n=51), and one with mild or no CSA/CSR – CSR_ [−] (n=110). Results CSR_ [+] patients presented more advanced NYHA class (p<0.001) and more frequently had permanent atrial fibrillation (p=0.018). Moreover, they had: lower LVEF (p<0.0001); higher LVDd (p<0.0001), RVDd (p<0.001), and E/e’ (p<0.001); lower SI (p<0.001) and CI (p=0.009); and higher HR (p=0.044) and SVRI (p=0.016). The following predictors of CSR_ [+] were identified: NYHA class (OR=3.34 per class, p<0.001, which was the only independent predictor); atrial fibrillation (OR=2.29, p=0.019); RV enlargement (OR=2.75, p=0.005); LVEF<35% (OR=3.38, p=0.001); E/e’ (OR=3.15; p=0.003); and SI<35 ml/m2 (OR=2.96, p=0.003). Conclusions Presence of CSA/CSR in HF is associated with NYHA class, atrial fibrillation and more advanced impairment of cardiovascular structure and hemodynamics. Patient functional state remains the main determinant of CSR. PMID:27558771

Displacement as a predictor of functional impairment in tsunami-exposed children.

PubMed

Lee, Christopher; Du, Ye Beverly; Christina, Desy; Palfrey, Judith; O'Rourke, Edward; Belfer, Myron

2015-01-01

Thirty months after the Indian Ocean tsunami of 26 December 2004, thousands of families in Aceh Province, Indonesia, remained in temporary barracks while sanitation conditions and non-governmental organisation support deteriorated. This study sought to determine the factors associated with functional impairment in a sample of 138 displaced and non-displaced Acehnese children. Using multivariate linear regression models, it was found that displacement distance was a consistent predictor of impairment using the Brief Impairment Scale. Exposure to tsunami-related trauma markers was not significantly linked with impairment in the model. Paternal employment was a consistent protective factor for child functioning. These findings suggest that post-disaster displacement and the subsequent familial economic disruption are significant predictors of impaired functioning in children's daily activities. Post-disaster interventions should consider the disruption of familiar environments for families and children when relocating vulnerable populations to avoid deleterious impacts on children's functioning. © 2014 The Author(s). Disasters © Overseas Development Institute, 2014.

Insulin Signaling and Heart Failure

PubMed Central

Riehle, Christian; Abel, E. Dale

2016-01-01

Heart failure is associated with generalized insulin resistance. Moreover, insulin resistant states such as type 2 diabetes and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes alters the systemic and neurohumoral milieu leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead (FOXO) transcriptional signaling or glucose transport which may also impair cardiac metabolism, structure and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed. PMID:27034277

Reduced Physical Fitness in Patients With Heart Failure as a Possible Risk Factor for Impaired Driving Performance

PubMed Central

Alosco, Michael L.; Penn, Marc S.; Spitznagel, Mary Beth; Cleveland, Mary Jo; Ott, Brian R.

2015-01-01

OBJECTIVE. Reduced physical fitness secondary to heart failure (HF) may contribute to poor driving; reduced physical fitness is a known correlate of cognitive impairment and has been associated with decreased independence in driving. No study has examined the associations among physical fitness, cognition, and driving performance in people with HF. METHOD. Eighteen people with HF completed a physical fitness assessment, a cognitive test battery, and a validated driving simulator scenario. RESULTS. Partial correlations showed that poorer physical fitness was correlated with more collisions and stop signs missed and lower scores on a composite score of attention, executive function, and psychomotor speed. Cognitive dysfunction predicted reduced driving simulation performance. CONCLUSION. Reduced physical fitness in participants with HF was associated with worse simulated driving, possibly because of cognitive dysfunction. Larger studies using on-road testing are needed to confirm our findings and identify clinical interventions to maximize safe driving. PMID:26122681

Analysis of left ventricular function of the mouse heart during experimentally induced hyperthyroidism and recovery.

PubMed

Hübner, Neele Saskia; Merkle, Annette; Jung, Bernd; von Elverfeldt, Dominik; Harsan, Laura-Adela

2015-01-01

Many of the clinical manifestations of hyperthyroidism are due to the ability of thyroid hormones to alter myocardial contractility and cardiovascular hemodynamics, leading to cardiovascular impairment. In contrast, recent studies highlight also the potential beneficial effects of thyroid hormone administration for clinical or preclinical treatment of different diseases such as atherosclerosis, obesity and diabetes or as a new therapeutic approach in demyelinating disorders. In these contexts and in the view of developing thyroid hormone-based therapeutic strategies, it is, however, important to analyze undesirable secondary effects on the heart. Animal models of experimentally induced hyperthyroidism therefore represent important tools for investigating and monitoring changes of cardiac function. In our present study we use high-field cardiac MRI to monitor and follow-up longitudinally the effects of prolonged thyroid hormone (triiodothyronine) administration focusing on murine left ventricular function. Using a 9.4 T small horizontal bore animal scanner, cinematographic MRI was used to analyze changes in ejection fraction, wall thickening, systolic index and fractional shortening. Cardiac MRI investigations were performed after sustained cycles of triiodothyronine administration and treatment arrest in adolescent (8 week old) and adult (24 week old) female C57Bl/6 N mice. Triiodothyronine supplementation of 3 weeks led to an impairment of cardiac performance with a decline in ejection fraction, wall thickening, systolic index and fractional shortening in both age groups but with a higher extent in the group of adolescent mice. However, after a hormonal treatment cessation of 3 weeks, only young mice are able to partly restore cardiac performance in contrast to adult mice lacking this recovery potential and therefore indicating a presence of chronically developed heart pathology. Copyright © 2014 John Wiley & Sons, Ltd.

American Heart Association's Life's Simple 7: Avoiding Heart Failure and Preserving Cardiac Structure and Function.

PubMed

Folsom, Aaron R; Shah, Amil M; Lutsey, Pamela L; Roetker, Nicholas S; Alonso, Alvaro; Avery, Christy L; Miedema, Michael D; Konety, Suma; Chang, Patricia P; Solomon, Scott D

2015-09-01

Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association's Life's Simple 7 guidelines—on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose—is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults ages 45-64 years in 1987-1989. From the 1987-1989 risk factor measurements, we created a Life's Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4855 participants free of clinical cardiovascular disease in 2011-2013, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. One in four participants (25.5%) developed heart failure through age 85 years. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life's Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life's Simple 7 score, compared with an inadequate score. Greater achievement of American Heart Association's Life's Simple 7 in middle age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function. Copyright © 2015 Elsevier Inc. All rights reserved.

Nonlinearities of heart rate variability in animal models of impaired cardiac control: contribution of different time scales.

PubMed

Silva, Luiz Eduardo Virgilio; Lataro, Renata Maria; Castania, Jaci Airton; Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar; Fazan, Rubens; Porta, Alberto

2017-08-01

Heart rate variability (HRV) has been extensively explored by traditional linear approaches (e.g., spectral analysis); however, several studies have pointed to the presence of nonlinear features in HRV, suggesting that linear tools might fail to account for the complexity of the HRV dynamics. Even though the prevalent notion is that HRV is nonlinear, the actual presence of nonlinear features is rarely verified. In this study, the presence of nonlinear dynamics was checked as a function of time scales in three experimental models of rats with different impairment of the cardiac control: namely, rats with heart failure (HF), spontaneously hypertensive rats (SHRs), and sinoaortic denervated (SAD) rats. Multiscale entropy (MSE) and refined MSE (RMSE) were chosen as the discriminating statistic for the surrogate test utilized to detect nonlinearity. Nonlinear dynamics is less present in HF animals at both short and long time scales compared with controls. A similar finding was found in SHR only at short time scales. SAD increased the presence of nonlinear dynamics exclusively at short time scales. Those findings suggest that a working baroreflex contributes to linearize HRV and to reduce the likelihood to observe nonlinear components of the cardiac control at short time scales. In addition, an increased sympathetic modulation seems to be a source of nonlinear dynamics at long time scales. Testing nonlinear dynamics as a function of the time scales can provide a characterization of the cardiac control complementary to more traditional markers in time, frequency, and information domains. NEW & NOTEWORTHY Although heart rate variability (HRV) dynamics is widely assumed to be nonlinear, nonlinearity tests are rarely used to check this hypothesis. By adopting multiscale entropy (MSE) and refined MSE (RMSE) as the discriminating statistic for the nonlinearity test, we show that nonlinear dynamics varies with time scale and the type of cardiac dysfunction. Moreover, as

Human cardiomyocyte calcium handling and transverse tubules in mid-stage of post-myocardial-infarction heart failure.

PubMed

Høydal, Morten Andre; Kirkeby-Garstad, Idar; Karevold, Asbjørn; Wiseth, Rune; Haaverstad, Rune; Wahba, Alexander; Stølen, Tomas L; Contu, Riccardo; Condorelli, Gianluigi; Ellingsen, Øyvind; Smith, Godfrey L; Kemi, Ole J; Wisløff, Ulrik

2018-06-01

Cellular processes in the heart rely mainly on studies from experimental animal models or explanted hearts from patients with terminal end-stage heart failure (HF). To address this limitation, we provide data on excitation contraction coupling, cardiomyocyte contraction and relaxation, and Ca 2+ handling in post-myocardial-infarction (MI) patients at mid-stage of HF. Nine MI patients and eight control patients without MI (non-MI) were included. Biopsies were taken from the left ventricular myocardium and processed for further measurements with epifluorescence and confocal microscopy. Cardiomyocyte function was progressively impaired in MI cardiomyocytes compared with non-MI cardiomyocytes when increasing electrical stimulation towards frequencies that simulate heart rates during physical activity (2 Hz); at 3 Hz, we observed almost total breakdown of function in MI. Concurrently, we observed impaired Ca 2+ handling with more spontaneous Ca 2+ release events, increased diastolic Ca 2+ , lower Ca 2+ amplitude, and prolonged time to diastolic Ca 2+ removal in MI (P < 0.01). Significantly reduced transverse-tubule density (-35%, P < 0.01) and sarcoplasmic reticulum Ca 2+ adenosine triphosphatase 2a (SERCA2a) function (-26%, P < 0.01) in MI cardiomyocytes may explain the findings. Reduced protein phosphorylation of phospholamban (PLB) serine-16 and threonine-17 in MI provides further mechanisms to the reduced function. Depressed cardiomyocyte contraction and relaxation were associated with impaired intracellular Ca 2+ handling due to impaired SERCA2a activity caused by a combination of alteration in the PLB/SERCA2a ratio and chronic dephosphorylation of PLB as well as loss of transverse tubules, which disrupts normal intracellular Ca 2+ homeostasis and handling. This is the first study that presents these mechanisms from viable and intact cardiomyocytes isolated from the left ventricle of human hearts at mid-stage of post-MI HF. © 2018 The Authors. ESC Heart

Ten-Year Review of Rating Scales, VII: Scales Assessing Functional Impairment

ERIC Educational Resources Information Center

Winters, Nancy C.; Collett, Brent R.; Myers, Kathleen M.

2005-01-01

Objective: This is the seventh in a series of 10-year reviews of rating scales. Here the authors present scales measuring functional impairment, a sequela of mental illness. The measurement of functional impairment has assumed importance with the recognition that symptom resolution does not necessarily correlate with functional improvement.…

Cardiac structure and function across the glycemic spectrum in elderly men and women free of prevalent heart disease: the Atherosclerosis Risk In the Community study.

PubMed

Skali, Hicham; Shah, Amil; Gupta, Deepak K; Cheng, Susan; Claggett, Brian; Liu, Jiankang; Bello, Natalie; Aguilar, David; Vardeny, Orly; Matsushita, Kunihiro; Selvin, Elizabeth; Solomon, Scott

2015-05-01

Individuals with diabetes mellitus and pre-diabetes mellitus are at particularly high risk of incident heart failure or death, even after accounting for known confounders. Nevertheless, the extent of impairments in cardiac structure and function in elderly individuals with diabetes mellitus and pre-diabetes mellitus is not well known. We aimed to assess the relationship between echocardiographic measures of cardiac structure and function and dysglycemia. We assessed measures of cardiac structure and function in 4419 participants without prevalent coronary heart disease or heart failure who attended the Atherosclerosis Risk In the Community (ARIC) visit 5 examination (2011-2013) and underwent transthoracic echocardiography (age, 75±6 years; 61% women, 23% black). Subjects were grouped across the dysglycemia spectrum as normal (39%), pre-diabetes mellitus (31%), or diabetes mellitus (30%) based on medical history, antidiabetic medication use, and glycated hemoglobin levels. Glycemic status was related to measures of cardiac structure and function. Worsening dysglycemia was associated with increased left ventricular mass, worse diastolic function, and subtle reduction in left ventricular systolic function (P≤0.01 for all). For every 1% higher glycated hemoglobin, left ventricular mass was higher by 3.0 g (95% confidence interval, 1.5-4.6 g), E/E' by 0.5 (95% confidence interval, 0.4-0.7), and global longitudinal strain by 0.3% (95% confidence interval, 0.2-0.4) in multivariable analyses. In a large contemporary biracial cohort of elderly subjects without prevalent cardiovascular disease or heart failure, dysglycemia was associated with subtle and subclinical alterations of cardiac structure, and left ventricular systolic and diastolic function. It remains unclear whether these are sufficient to explain the heightened risk of heart failure in individuals with diabetes mellitus. © 2015 American Heart Association, Inc.

Impaired Skeletal Muscle Vasodilation during Exercise in Heart Failure with Preserved Ejection Fraction

PubMed Central

Lee, Joshua F.; Barrett-O’Keefe, Zachary; Nelson, Ashley D.; Garten, Ryan S.; Ryan, John J.; Nativi-Nicolau, Jose N.; Richardson, Russell S.; Wray, D. Walter

2016-01-01

Background Exercise intolerance is a hallmark symptom of heart failure patients with preserved ejection fraction (HFpEF), which may be related to an impaired ability to appropriately increase blood flow to the exercising muscle. Methods We evaluated leg blood flow (LBF, ultrasound Doppler), heart rate (HR), stroke volume (SV), cardiac output (CO), and mean arterial blood pressure (MAP, photoplethysmography) during dynamic, single leg knee-extensor (KE) exercise in HFpEF patients (n = 21; 68 ± 2 yrs) and healthy controls (n = 20; 71 ± 2 yrs). Results HFpEF patients exhibited a marked attrition during KE exercise, with only 60% able to complete the exercise protocol. In participants who completed all exercise intensities (0-5-10-15W; HFpEF, n = 13; Controls, n = 16), LBF was not different at 0W and 5W, but was 15-25% lower in HFpEF compared to controls at 10W and 15W (P < 0.001). Likewise, leg vascular conductance (LVC), an index of vasodilation, was not different at 0W and 5W, but was 15-20% lower in HFpEF compared to controls at 10W and 15W (P < 0.05). In contrast to these peripheral deficits, exercise-induced changes in central variables (HR, SV, CO), as well as MAP, were similar between groups. Conclusions These data reveal a marked reduction in LBF and LVC in HFpEF patients during exercise that cannot be attributed to a disease-related alteration in central hemodynamics, suggesting that impaired vasodilation in the exercising skeletal muscle vasculature may play a key role in the exercise intolerance associated with this patient population. PMID:26970959

Chemosensory interaction: acquired olfactory impairment is associated with decreased taste function.

PubMed

Landis, Basile N; Scheibe, Mandy; Weber, Cornelia; Berger, Robert; Brämerson, Annika; Bende, Mats; Nordin, Steven; Hummel, Thomas

2010-08-01

Olfaction, taste and trigeminal function are three distinct modalities. However, in daily life they are often activated concomitantly. In health and disease, it has been shown that in two of these senses, the trigeminal and olfactory senses, modification of one sense leads to changes in the other sense and vice versa. The objective of the study was to investigate whether and (if so) how, the third modality, taste, is influenced by olfactory impairment. We tested 210 subjects with normal (n = 107) or impaired (n = 103) olfactory function for their taste identification capacities. Validated tests were used for olfactory and gustatory testing (Sniffin' Sticks, Taste Strips). In an additional experiment, healthy volunteers underwent reversible olfactory cleft obstruction to investigate short-time changes of gustatory function after olfactory alteration. Mean gustatory identification (taste strip score) for the subjects with impaired olfaction was 19.4 +/- 0.6 points and 22.9 +/- 0.5 points for those with normal olfactory function (t = 4.6, p < 0.001). The frequencies of both, smell and taste impairments interacted significantly (Chi(2), F = 16.4, p < 0.001), and olfactory and gustatory function correlated (r (210) = 0.30, p < 0.001). Neither age nor olfactory impairment cause effects interfered with this olfactory-gustatory interaction. In contrast, after short-lasting induced olfactory decrease, gustatory function remained unchanged. The present study suggests that longstanding impaired olfactory function is associated with decreased gustatory function. These findings seem to extend previously described mutual chemosensory interactions also to smell and taste. It further raises the question whether chemical senses in general decrease mutually after acquired damage.

Functional MRI detects perfusion impairment in renal allografts with delayed graft function.

PubMed

Hueper, Katja; Gueler, Faikah; Bräsen, Jan Hinrich; Gutberlet, Marcel; Jang, Mi-Sun; Lehner, Frank; Richter, Nicolas; Hanke, Nils; Peperhove, Matti; Martirosian, Petros; Tewes, Susanne; Vo Chieu, Van Dai; Großhennig, Anika; Haller, Hermann; Wacker, Frank; Gwinner, Wilfried; Hartung, Dagmar

2015-06-15

Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with noninvasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4-11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labeling technique. Renal function was assessed by estimated glomerular filtration rate (eGFR), and renal biopsies were performed when indicated within 5 days of MRI. Twenty-six of 46 patients had DGF. Of these, nine patients had acute rejection (including borderline), and eight had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF group compared with the group with good allograft function (231 ± 15 vs. 331 ± 15 ml·min(-1)·100 g(-1), P < 0.001). Living donor allografts exhibited significantly higher perfusion values compared with deceased donor allografts (P < 0.001). Renal perfusion significantly correlated with eGFR (r = 0.64, P < 0.001), resistance index (r = -0.57, P < 0.001), and cold ischemia time (r = -0.48, P < 0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, noninvasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF. Copyright © 2015 the American Physiological Society.

Physiological Stress Elicits Impaired Left Ventricular Function in Preterm-Born Adults.

PubMed

Huckstep, Odaro J; Williamson, Wilby; Telles, Fernando; Burchert, Holger; Bertagnolli, Mariane; Herdman, Charlotte; Arnold, Linda; Smillie, Robert; Mohamed, Afifah; Boardman, Henry; McCormick, Kenny; Neubauer, Stefan; Leeson, Paul; Lewandowski, Adam J

2018-03-27

Experimental and clinical studies show that prematurity leads to altered left ventricular (LV) structure and function with preserved resting LV ejection fraction (EF). Large-scale epidemiological data now links prematurity to increased early heart failure risk. The authors performed echocardiographic imaging at prescribed exercise intensities to determine whether preterm-born adults have impaired LV functional response to physical exercise. We recruited 101 normotensive young adults born preterm (n = 47; mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) for detailed cardiovascular phenotyping. Full clinical resting and exercise stress echocardiograms were performed, with apical 4-chamber views collected while exercising at 40%, 60%, and 80% of peak exercise capacity, determined by maximal cardiopulmonary exercise testing. Preterm-born individuals had greater LV mass (p = 0.015) with lower peak systolic longitudinal strain (p = 0.038) and similar EF to term-born control subjects at rest (p = 0.62). However, by 60% exercise intensity, EF was 6.7% lower in preterm subjects (71.9 ± 8.7% vs 78.6 ± 5.4%; p = 0.004) and further declined to 7.3% below the term-born group at 80% exercise intensity (69.8 ± 6.4% vs 77.1 ± 6.3%; p = 0.004). Submaximal cardiac output reserve was 56% lower in preterm-born subjects versus term-born control subjects at 40% of peak exercise capacity (729 ± 1,162 ml/min/m 2 vs. 1,669 ± 937 ml/min/m 2 ; p = 0.021). LV length and resting peak systolic longitudinal strain predicted EF increase from rest to 60% exercise intensity in the preterm group (r = 0.68, p = 0.009 and r = 0.56, p = 0.031, respectively). Preterm-born young adults had impaired LV response to physiological stress when subjected to physical exercise, which suggested a reduced myocardial functional reserve that might help explain their increased risk of early heart failure. (Young Adult Cardiovascular Health sTudy [YACHT]; NCT02103231

Differential Regenerative Capacity of Neonatal Mouse Hearts after Cryoinjury

PubMed Central

Darehzereshki, Ali; Rubin, Nicole; Gamba, Laurent; Kim, Jieun; Fraser, James; Huang, Ying; Billings, Joshua; Mohammadzadeh, Robabeh; Wood, John; Warburton, David; Kaartinen, Vesa; Lien, Ching-Ling

2015-01-01

Neonatal mouse hearts fully regenerate after ventricular resection similar to adult zebrafish. We established cryoinjury models to determine if different types and varying degrees of severity in cardiac injuries trigger different responses in neonatal mouse hearts. In contrast to ventricular resection, neonatal mouse hearts fail to regenerate and show severe impairment of cardiac function post transmural cryoinjury. However, neonatal hearts fully recover after non-transmural cryoinjury. Interestingly, cardiomyocyte proliferation does not significantly increase in neonatal mouse hearts after cryoinjuries. Epicardial activation and new coronary vessel formation occur after cryoinjury. The profibrotic marker PAI-1 is highly expressed after transmural but not non-transmural cryoinjuries, which may contribute to the differential scarring. Our results suggest that regenerative medicine strategies for heart injuries should vary depending on the nature of the injury. PMID:25555840

Targeting Inflammation in Heart Failure with Histone Deacetylase Inhibitors

PubMed Central

McKinsey, Timothy A

2011-01-01

Cardiovascular insults such as myocardial infarction and chronic hypertension can trigger the heart to undergo a remodeling process characterized by myocyte hypertrophy, myocyte death and fibrosis, often resulting in impaired cardiac function and heart failure. Pathological cardiac remodeling is associated with inflammation, and therapeutic approaches targeting inflammatory cascades have shown promise in patients with heart failure. Small molecule histone deacetylase (HDAC) inhibitors block adverse cardiac remodeling in animal models, suggesting unforeseen potential for this class of compounds for the treatment of heart failure. In addition to their beneficial effects on myocardial cells, HDAC inhibitors have potent antiinflammatory actions. This review highlights the roles of HDACs in the heart and the potential for using HDAC inhibitors as broad-based immunomodulators for the treatment of human heart failure. PMID:21267510

Functional role of AMP-activated protein kinase in the heart during exercise.

PubMed

Musi, Nicolas; Hirshman, Michael F; Arad, Michael; Xing, Yanqiu; Fujii, Nobuharu; Pomerleau, Jason; Ahmad, Ferhaan; Berul, Charles I; Seidman, Jon G; Tian, Rong; Goodyear, Laurie J

2005-04-11

AMP-activated protein kinase (AMPK) plays a critical role in maintaining energy homeostasis and cardiac function during ischemia in the heart. However, the functional role of AMPK in the heart during exercise is unknown. We examined whether acute exercise increases AMPK activity in mouse hearts and determined the significance of these increases by studying transgenic (TG) mice expressing a cardiac-specific dominant-negative (inactivating) AMPKalpha2 subunit. Exercise increased cardiac AMPKalpha2 activity in the wild type mice but not in TG. We found that inactivation of AMPK did not result in abnormal ATP and glycogen consumption during exercise, cardiac function assessed by heart rhythm telemetry and stress echocardiography, or in maximal exercise capacity.

Structural Equation Modeling of Motor Impairment, Gross Motor Function, and the Functional Outcome in Children with Cerebral Palsy

ERIC Educational Resources Information Center

Park, Eun-Young; Kim, Won-Ho

2013-01-01

Physical therapy intervention for children with cerebral palsy (CP) is focused on reducing neurological impairments, improving strength, and preventing the development of secondary impairments in order to improve functional outcomes. However, relationship between motor impairments and functional outcome has not been proved definitely. This study…

Annual Research Review: Conceptualising Functional Impairment in Children and Adolescents

ERIC Educational Resources Information Center

Rapee, Ronald M.; Bogels, Susan M.; van der Sluis, Cathy M.; Craske, Michelle G.; Ollendick, Thomas

2012-01-01

Functional impairment is a key factor in the clinical importance of mental health problems in children. Yet, the nature of impairment and criteria for defining and assessing impairment in childhood disorders has been surprisingly overlooked in much of the literature. The current article examines the extant literature on the conceptualisation,…

Assessing functional impairment in siblings living with children with disability.

PubMed

Goudie, Anthony; Havercamp, Susan; Jamieson, Barry; Sahr, Timothy

2013-08-01

The purpose of this study was to empirically test if siblings of children with disability had higher levels of parent-reported behavioral and emotional functional impairment compared with a peer group of siblings residing with only typically developing children. This was a retrospective secondary analysis of data from the Medical Expenditure Panel Survey. We included only households with at least 2 children to ensure sibling relationships. Two groups of siblings were formed: 245 siblings resided in households with a child with disability and 6564 siblings resided in households with typically developing children. Parents responded to questions from the Columbia Impairment Scale to identify functional impairment in their children. On the basis of parent reports and after adjusting for sibling demographic characteristics and household background, siblings of children with disability were more likely than siblings residing with typically developing children to have problems with interpersonal relationships, psychopathological functioning, functioning at school, and use of leisure time (P < .05). The percentage of siblings of children with disability classified with significant functional impairment was 16.0% at the first measurement period and 24.2% at the second (P < .001). For siblings of typically developing children there was a smaller percentage increase from 9.5% to 10.3% (P < .001). Functional impairment is a key indicator for the need of mental health services and, as such, early assessment and interventions to limit increasing severity and short- to long-term consequences need to be addressed. Health care professionals need to consider a family-based health care approach for families raising children with disability.

Cognitive and motor function of neurologically impaired extremely low birth weight children.

PubMed

Bernardo, Janine; Friedman, Harriet; Minich, Nori; Taylor, H Gerry; Wilson-Costello, Deanne; Hack, Maureen

2015-01-01

Rates of neurological impairment among extremely low birth weight children (ELBW [<1 kg]) have decreased since 2000; however, their functioning is unexamined. To compare motor and cognitive functioning of ELBW children with neurological impairment, including cerebral palsy and severe hypotonia/hypertonia, between two periods: 1990 to 1999 (n=83) and 2000 to 2005 (n=34). Measures of function at 20 months corrected age included the Mental and Psychomotor Developmental Indexes of the Bayley Scales of Infant Development and the Gross Motor Functional Classification System as primary outcomes and individual motor function items as secondary outcomes. Analysis failed to reveal significant differences for the primary outcomes, although during 2000 to 2005, sitting significantly improved in children with neurological impairment (P=0.003). Decreases in rates of neurological impairment among ELBW children have been accompanied by a suggestion of improved motor function, although cognitive function has not changed.

Illness severity, trait anxiety, cognitive impairment and heart rate variability in bipolar disorder.

PubMed

Levy, Boaz

2014-12-30

Numerous studies have documented a significant association between symptom severity and cognitive functioning in bipolar disorder (BD). These findings advanced speculations about a potential link between the physiological stress associated with illness severity and cognitive dysfunction. To explore this hypothesis, the current study employed heart rate variability (HRV) as a physiological measure that is sensitive to the effects of chronic stress, and a scale of trait anxiety for assessing a psychological condition that is correlated with hyper sympathetic arousal. Analyses indicated that BD patients with High Illness Severity reported more symptoms of trait-anxiety (i.e., State Trait Anxiety Inventory), performed more poorly on a computerized neuropsychological battery (i.e., CNS Vital Signs), and exhibited a more constricted HRV profile (i.e., lower SDNN with elevated LF/HF ratio) than patients with Low Illness Severity. Illness severity was determined by a history of psychosis, illness duration, and number of mood episodes. A third group of healthy controls (n=22) performed better on the neuropsychological battery and exhibited a healthier HRV profile than the BD groups. This study provides preliminary evidence that illness severity and cognitive impairment in BD may be associated with state anxiety and neuro-cardiac alterations that are sensitive to physiological stress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Role of sialic acid loss in the myocardium in depressing the contractile function of the heart muscle during stress].

PubMed

Meerson, F Z; Saulia, A I; Gudumak, V S

1985-01-01

Under conditions of stress a time-dependent decrease in content of sialic acids was found in adult rats; within 9 hrs of the animal immobilization the sialic acid content was decreased by 40% as compared with controls. At the same time, activities of trypsin and LDHI were increased in blood serum. The data obtained suggest that activation of proteases occurring during the stress led to increased hydrolysis of base components of glycocalyx and to impairment of the cardiomyocyte sarcolemma. These phenomena appear to be responsible for the post-stress deterioration of heart muscle contractile functions.

Serial optical coherence scanning reveals an association between cardiac function and the heart architecture in the aging rodent heart

PubMed Central

Castonguay, Alexandre; Lefebvre, Joël; Pouliot, Philippe; Avti, Pramod; Moeini, Mohammad; Lesage, Frédéric

2017-01-01

Normal aging is accompanied by structural changes in the heart architecture. To explore this remodeling, we used a serial optical coherence tomography scanner to image entire mouse hearts at micron scale resolution. Ex vivo hearts of 7 young (4 months) and 5 old (24 months) C57BL/6 mice were acquired with the imaging platform. OCT of the myocardium revealed myofiber orientation changing linearly from the endocardium to the epicardium. In old mice, this rate of change was lower when compared to young mice while the average volume of old mice hearts was significantly larger (p<0.05). Myocardial wall thickening was also accompanied by extracellular spacing in the endocardium, resulting in a lower OCT attenuation coefficient in old mice endocardium (p<0.05). Prior to serial sectioning, cardiac function of the same hearts was imaged in vivo using MRI and revealed a reduced ejection fraction with aging. The use of a serial optical coherence tomography scanner allows new insight into fine age-related changes of the heart associated with changes in heart function. PMID:29188099

Beyond Type D personality: reduced positive affect (anhedonia) predicts impaired health status in chronic heart failure.

PubMed

Pelle, Aline J; Pedersen, Susanne S; Szabó, Balázs M; Denollet, Johan

2009-08-01

Type D personality has been associated with impaired health status in chronic heart failure (CHF), but other psychological factors may also be important. To determine whether non-Type D patients with low positive affect and Type D patients report lower health status, compared with non-Type D patients with high positive affect at 12-month follow-up in chronic heart failure. Consecutive CHF outpatients (n = 276) filled out the Short Form-12 (health status) and Health Complaints Scale (disease-specific complaints) at inclusion and 12-month follow-up, and the DS14 (Type D personality) and positive affect (Global Mood Scale) at inclusion. Three groups were composed: non-Type D patients without anhedonia, non-Type D patients with anhedonia, and Type D patients. After controlling for demographic and clinical confounders, and scores at inclusion, anhedonic non-Type D patients reported lower mental health status (beta = -.19, P < .004), and more feelings of disability (beta = .10, P = .04), marginally lower physical health status (beta = -.11, P = .07), and equal levels of cardiac symptoms (beta = .04, P = .43), when compared with non-Type D's without anhedonia. Type D patients reported lower levels of impaired mental health status, more cardiac symptoms and feelings of disability (-.31 < beta < .17, all Ps < .05). A trend was shown for physical health status (beta = -.11, P = .09). Non-Type D patients low on positive affect and Type D patients report lower levels of health status in CHF, compared with non-Type D patients with high positive affect. Future studies need to determine whether lack of positive affect is associated with impaired clinical outcome.

Structure and function of the hearts of lizards and snakes.

PubMed

Jensen, Bjarke; Moorman, Antoon F M; Wang, Tobias

2014-05-01

With approximately 7000 species, snakes and lizards, collectively known as squamates, are by far the most species-rich group of reptiles. It was from reptile-like ancestors that mammals and birds evolved and squamates can be viewed as phylogenetically positioned between them and fishes. Hence, their hearts have been studied for more than a century yielding insights into the group itself and into the independent evolution of the fully divided four-chambered hearts of mammals and birds. Structurally the heart is complex and debates persist on rudimentary issues such as identifying structures critical to understanding ventricle function. In seeking to resolve these controversies we have generated three-dimensional (3D) models in portable digital format (pdf) of the anaconda and anole lizard hearts ('typical' squamate hearts) and the uniquely specialized python heart with comprehensive annotations of structures and cavities. We review the anatomy and physiology of squamate hearts in general and emphasize the unique features of pythonid and varanid lizard hearts that endow them with mammal-like blood pressures. Excluding pythons and varanid lizards it is concluded that the squamate heart has a highly consistent design including a disproportionately large right side (systemic venous) probably due to prevailing pulmonary bypass (intraventricular shunting). Unfortunately, investigations on rudimentary features are sparse. We therefore point out gaps in our knowledge, such as the size and functional importance of the coronary vasculature and of the first cardiac chamber, the sinus venosus, and highlight areas with implications for vertebrate cardiac evolution. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

Paralysis and heart failure precede ion balance disruption in heat-stressed European green crabs.

PubMed

Jørgensen, Lisa B; Overgaard, Johannes; MacMillan, Heath A

2017-08-01

Acute exposure of ectotherms to critically high temperatures causes injury and death, and this mortality has been associated with a number of physiological perturbations including impaired oxygen transport, loss of ion and water homeostasis, and neuronal failure. It is difficult to discern which of these factors, if any, is the proximate cause of heat injury because, for example, loss of ion homeostasis can impair neuromuscular function (including cardiac function), and conversely impaired oxygen transport reduces ATP supply and can thus reduce ion transport capacity. In this study we investigated if heat stress causes a loss of ion homeostasis in marine crabs and examined if such loss is related to heart failure. We held crabs (Carcinus maenas) at temperatures just below their critical thermal maximum and measured extracellular (hemolymph) and intracellular (muscle) ion concentrations over time. Analysis of Arrhenius plots for heart rates during heating ramps revealed a breakpoint temperature below which heart rate increased with temperature, and above which heart rate declined until complete cardiac failure. As hypothesised, heat stress reduced the Nernst equilibrium potentials of both K + and Na + , likely causing a depolarization of the membrane potential. To examine whether this loss of ion balance was likely to cause disruption of neuromuscular function, we exposed crabs to the same temperatures, but this time measured ion concentrations at the individual-specific times of complete paralysis (from which the crabs never recovered), and at the time of cardiac failure. Loss of ion balance was observed only after both paralysis and complete heart failure had occurred; indicating that the loss of neuromuscular function is not caused by a loss of ion homeostasis. Instead we suggest that the observed loss of ion balance may be linked to tissue damage related to heat death. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metoprolol impairs resistance artery function in mice

PubMed Central

El Beheiry, Mostafa H.; Heximer, Scott P.; Voigtlaender-Bolz, Julia; Mazer, C. David; Connelly, Kim A.; Wilson, David F.; Beattie, W. Scott; Tsui, Albert K. Y.; Zhang, Hangjun; Golam, Kabir; Hu, Tina; Liu, Elaine; Lidington, Darcy; Bolz, Steffen-Sebastian

2011-01-01

Acute β-blockade with metoprolol has been associated with increased mortality by undefined mechanisms. Since metoprolol is a relatively high affinity blocker of β2-adrenoreceptors, we hypothesized that some of the increased mortality associated with its use may be due to its abrogation of β2-adrenoreceptor-mediated vasodilation of microvessels in different vascular beds. Cardiac output (CO; pressure volume loops), mean arterial pressure (MAP), relative cerebral blood flow (rCBF; laser Doppler), and microvascular brain tissue Po2 (G2 oxyphor) were measured in anesthetized mice before and after acute treatment with metoprolol (3 mg/kg iv). The vasodilatory dose responses to β-adrenergic agonists (isoproterenol and clenbuterol), and the myogenic response, were assessed in isolated mesenteric resistance arteries (MRAs; ∼200-μm diameter) and posterior cerebral arteries (PCAs ∼150-μm diameter). Data are presented as means ± SE with statistical significance applied at P < 0.05. Metoprolol treatment did not effect MAP but reduced heart rate and stroke volume, CO, rCBF, and brain microvascular Po2, while concurrently increasing systemic vascular resistance (P < 0.05 for all). In isolated MRAs, metoprolol did not affect basal artery tone or the myogenic response, but it did cause a dose-dependent impairment of isoproterenol- and clenbuterol-induced vasodilation. In isolated PCAs, metoprolol (50 μM) impaired maximal vasodilation in response to isoproterenol. These data support the hypothesis that acute administration of metoprolol can reduce tissue oxygen delivery by impairing the vasodilatory response to β2-adrenergic agonists. This mechanism may contribute to the observed increase in mortality associated with acute administration of metoprolol in perioperative patients. PMID:21799135

Carbon dioxide field flooding reduces neurologic impairment after open heart surgery.

PubMed

Martens, Sven; Neumann, Katrin; Sodemann, Christian; Deschka, Heinz; Wimmer-Greinecker, Gerhard; Moritz, Anton

2008-02-01

Air emboli released from incompletely deaired cardiac chambers may cause neurocognitive decline after open heart surgery. Carbon dioxide (CO2) field flooding is reported to reduce residual intracavital air during cardiac surgery. A protective effect of carbon dioxide insufflation on postoperative brain function remains unproven in clinical trials. Eighty patients undergoing heart valve operations by median sternotomy were randomly assigned to either CO2 insufflation (group I, n = 39) or unprotected controls (group II, n = 41). Preoperative evaluation included neurocognitive test batteries consisting of six different tests, and objective measurements of brain function by means of P300 wave auditory-evoked potentials (peak latencies, ms). Neurocognitive testing and P300 measurements were repeated on postoperative day 5. Neurocognitive deficit (ND) was defined as a 20% decrement in two or more tests. Preoperatively, P300 peak latencies did not differ between groups (374 +/- 75 vs 366 +/- 72 ms, not significant [n.s.]). Five days after surgery, P300 peak latencies were significantly shorter with CO2 protection as compared with the unprotected control group (group I: 390 +/- 68 ms, group II: 429 +/- 75 ms, p = 0.02). Clinical outcome was comparable as for mortality (group I: 1 patient; group II: 2 patients) and cerebrovascular events or confusional syndromes (group I: 5 patients; group II: 4 patients) or other clinical variables as intubation time or hospital stay. Neurocognitive test batteries did not reveal differences between groups. Shorter P300 peak latencies after surgery indicate less brain damage in patients who underwent heart valve operations with CO2 flooding of the thoracic cavity. Even if these findings were not supported by clinical results or neurocognitive test batteries in our cohort, carbon dioxide field flooding has proven efficiency and should be advocated for all patients undergoing open heart surgery.

Acquired deficiency of tafazzin in the adult heart: Impact on mitochondrial function and response to cardiac injury.

PubMed

Szczepanek, Karol; Allegood, Jeremy; Aluri, Hema; Hu, Ying; Chen, Qun; Lesnefsky, Edward J

2016-04-01

The content and composition of cardiolipin (CL) is critical for preservation of mitochondrial oxidative phosphorylation (OXPHOS) and inner membrane integrity. Tafazzin (Taz) is an enzyme responsible for remodeling of immature CL containing mixed acyl groups into the mature tetralinoleyl form (C18:2)4-CL. We hypothesized that acquired defects in Taz in the mature heart would impact remodeling of CL and augment cardiac injury. The role of acquired Taz deficiency was studied using the inducible Taz knockdown (TazKD) mouse. Taz-specific shRNA is induced by doxycycline (DOX). One day of DOX intake decreased Taz mRNA in the heart to 20% vs. DOX-treated WT. Knockdown was initiated at an adult age and was stable during long term feeding. CL phenotype was assessed by (C18:2)4-CL content and was reduced 40% vs. WT at two months of DOX. TazKD showed increased production of reactive oxygen species and increased susceptibility to permeability transition pore opening at baseline. However, OXPHOS measured using the rate of oxygen consumption was unchanged in the setting of acquired Taz deficiency. Infarct size, measured in isolated buffer-perfused Langendorff hearts following 25min. Stop flow ischemia and 60min. Reperfusion was not altered in TazKD hearts. Thus, impaired Taz-function with onset at adult age does not enhance susceptibility to ischemia-reperfusion injury. Published by Elsevier B.V.

Left atrial phasic function and heart rate variability in asymptomatic diabetic patients.

PubMed

Tadic, Marijana; Vukomanovic, Vladan; Cuspidi, Cesare; Suzic-Lazic, Jelena; Stanisavljevic, Dejana; Celic, Vera

2017-03-01

We evaluated left atrial (LA) phasic function and heart rate variability (HRV) in asymptomatic diabetic patients, and the relationship between HRV indices and LA phasic function assessed by volumes and speckle tracking imaging. This cross-sectional study included 55 asymptomatic patients with type 2 diabetes and 50 healthy controls without cardiovascular risk factors. All study subjects underwent laboratory analyses, complete two-dimensional echocardiography examination (2DE) and 24-h Holter monitoring. Maximum, minimum LA and pre-A LA volumes and volume indexes are significantly higher in diabetic patients. Total and passive LA emptying fractions (EF), representing the LA reservoir and conduit function, are significantly lower in diabetic subjects. Active LA EF, the parameter of the LA booster pump function, is compensatory increased in diabetic patients. Similar results were obtained by 2DE strain analysis. Cardiac autonomic function, assessed by HRV, is significantly deteriorated in diabetic patients. Time and frequency-domain HRV measures are significantly lower in diabetic subjects than in controls. HbA1c, LV mass index and HRV are associated with total LA EF and longitudinal LA strain independently of age, body mass index and LV diastolic function in the whole study population. LA phasic function and cardiac autonomic nervous system assessed by HRV are impacted by diabetes. HbA1c and HRV are independently associated with LA reservoir function evaluated by volumetric and strain methods in the whole study population. This study emphasizes the importance of determination of LA function and HRV as important markers of preclinical cardiac damage and autonomic function impairment in diabetic patients.

Assessing Functional Impairment in Siblings Living With Children With Disability

PubMed Central

Havercamp, Susan; Jamieson, Barry; Sahr, Timothy

2013-01-01

OBJECTIVE: The purpose of this study was to empirically test if siblings of children with disability had higher levels of parent-reported behavioral and emotional functional impairment compared with a peer group of siblings residing with only typically developing children. METHODS: This was a retrospective secondary analysis of data from the Medical Expenditure Panel Survey. We included only households with at least 2 children to ensure sibling relationships. Two groups of siblings were formed: 245 siblings resided in households with a child with disability and 6564 siblings resided in households with typically developing children. Parents responded to questions from the Columbia Impairment Scale to identify functional impairment in their children. RESULTS: On the basis of parent reports and after adjusting for sibling demographic characteristics and household background, siblings of children with disability were more likely than siblings residing with typically developing children to have problems with interpersonal relationships, psychopathological functioning, functioning at school, and use of leisure time (P < .05). The percentage of siblings of children with disability classified with significant functional impairment was 16.0% at the first measurement period and 24.2% at the second (P < .001). For siblings of typically developing children there was a smaller percentage increase from 9.5% to 10.3% (P < .001). CONCLUSIONS: Functional impairment is a key indicator for the need of mental health services and, as such, early assessment and interventions to limit increasing severity and short- to long-term consequences need to be addressed. Health care professionals need to consider a family-based health care approach for families raising children with disability. PMID:23897909

Capturing structure and function in an embryonic heart with biophotonic tools

PubMed Central

Karunamuni, Ganga H.; Gu, Shi; Ford, Matthew R.; Peterson, Lindsy M.; Ma, Pei; Wang, Yves T.; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

2014-01-01

Disturbed cardiac function at an early stage of development has been shown to correlate with cellular/molecular, structural as well as functional cardiac anomalies at later stages culminating in the congenital heart defects (CHDs) that present at birth. While our knowledge of cellular and molecular steps in cardiac development is growing rapidly, our understanding of the role of cardiovascular function in the embryo is still in an early phase. One reason for the scanty information in this area is that the tools to study early cardiac function are limited. Recently developed and adapted biophotonic tools may overcome some of the challenges of studying the tiny fragile beating heart. In this chapter, we describe and discuss our experience in developing and implementing biophotonic tools to study the role of function in heart development with emphasis on optical coherence tomography (OCT). OCT can be used for detailed structural and functional studies of the tubular and looping embryo heart under physiological conditions. The same heart can be rapidly and quantitatively phenotyped at early and again at later stages using OCT. When combined with other tools such as optical mapping (OM) and optical pacing (OP), OCT has the potential to reveal in spatial and temporal detail the biophysical changes that can impact mechanotransduction pathways. This information may provide better explanations for the etiology of the CHDs when interwoven with our understanding of morphogenesis and the molecular pathways that have been described to be involved. Future directions for advances in the creation and use of biophotonic tools are discussed. PMID:25309451

Testing a Model of Functional Impairment in Telephone Crisis Support Workers.

PubMed

Kitchingman, Taneile A; Wilson, Coralie J; Caputi, Peter; Wilson, Ian; Woodward, Alan

2017-11-01

It is well known that helping professionals experience functional impairment related to elevated symptoms of psychological distress as a result of frequent empathic engagement with distressed others. Whether telephone crisis support workers are impacted in a similar way is not currently reported in the literature. The purpose of this study was to test a hypothesized model of factors contributing to functional impairment in telephone crisis support workers. A national sample of 210 telephone crisis support workers completed an online survey including measures of emotion regulation, symptoms of general psychological distress and suicidal ideation, intentions to seek help for symptoms, and functional impairment. Structural equation modeling was used to test the fit of the data to the hypothesized model. Goodness-of-fit indices were adequate and supported the interactive effects of emotion regulation, general psychological distress, suicidal ideation, and intentions to seek help for ideation on functional impairment. These results warrant the deliberate management of telephone crisis support workers' impairment through service selection, training, supervision, and professional development strategies. Future research replicating and extending this model will further inform the modification and/or development of strategies to optimize telephone crisis support workers' well-being and delivery of support to callers.

Depressive Symptoms and Impaired Physical Function after Acute Lung Injury

PubMed Central

Colantuoni, Elizabeth; Mendez-Tellez, Pedro A.; Dinglas, Victor D.; Shanholtz, Carl; Husain, Nadia; Dennison, Cheryl R.; Herridge, Margaret S.; Pronovost, Peter J.; Needham, Dale M.

2012-01-01

Rationale: Survivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear. Objectives: To evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions. Methods: This prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 (“depressive symptoms”) in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living (“impaired physical function”) in patients without baseline impairment. Measurements and Main Results: During 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms. Conclusions: Incident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors’ long-term outcomes. PMID:22161158

Effectiveness of the second-stage rehabilitation in stroke patients with cognitive impairment.

PubMed

Milinavičienė, Eglė; Rastenytė, Daiva; Kriščiūnas, Aleksandras

2011-01-01

The aim of this study was to evaluate the recovery of functional status and effectiveness of the second-stage rehabilitation depending on the degree of cognitive impairment in stroke patients. The study sample comprised 226 stroke patients at the Viršužiglis Hospital of rehabilitation, Hospital of Lithuanian University of Health Sciences. Functional status was evaluated with the Functional Independence Measure, cognitive function with the Mini-Mental Status Examination scale, and severity of neurologic condition with the National Institutes of Health Stroke Scale. The patients were divided into 4 study groups based on cognitive impairment: severe, moderate, mild, or no impairment. More than half (53%) of all cases were found to have cognitive impairment, while patients with different degree of cognitive impairment were equally distributed: mild impairment (18%), moderate impairment (17%), and severe impairment (18%). Improvement of functional status was observed in all study groups (P<0.001). In the patients with moderate and severe cognitive impairment, cognitive recovery was significantly more expressed than in other study groups (P<0.001). Insufficient recovery of functional status was significantly associated with hemiplegia (OR, 11.15; P=0.015), urinary incontinence (OR, 14.91; P<0.001), joint diseases (OR, 5.52; P=0.022), heart diseases (OR, 4.10; P=0.041), and severe cognitive impairment (OR, 15.18; P<0.001), while moderate and mild cognitive impairment was not associated with the recovery of functional status. During the second-stage rehabilitation of stroke patients, functional status as well as cognitive and motor skills were improved both in patients with and without cognitive impairment; however, the patients who were diagnosed with severe or moderate cognitive impairment at the beginning of second-stage rehabilitation showed worse neurological and functional status during the whole second-stage rehabilitation than the patients with mild or no

Early administration of tolvaptan preserves renal function in elderly patients with acute decompensated heart failure.

PubMed

Kimura, Kazuhiro; Momose, Tomoyasu; Hasegawa, Tomoya; Morita, Takehiro; Misawa, Takuo; Motoki, Hirohiko; Izawa, Atsushi; Ikeda, Uichi

2016-05-01

Loop diuretics used in the treatment of heart failure often induce renal impairment. This study was conducted in order to evaluate the renal protective effect of adding tolvaptan (TLV), compared to increasing the furosemide (FRM) dose, for the treatment of acute decompensated heart failure (ADHF) in a real-world elderly patient population. This randomized controlled trial enrolled 52 consecutive hospitalized patients (age 83.4±9.6 years) with ADHF. The patients were assigned alternately to either the TLV group (TLV plus conventional treatment, n=26) or the FRM group (increasing the dose of FRM, n=26). TLV was administered within 24h from admission. The incidence of worsening renal function (WRF) within 7 days from admission was significantly lower in the TLV group (26.9% vs. 57.7%, p=0.025). Furthermore, the rates of occurrence of persistent and late-onset (≥5 days from admission) WRF were significantly lower in the TLV group. Persistent and late-onset WRF were significantly associated with a higher incidence of cardiac death or readmission for worsening heart failure in the 90 days following discharge, compared to transient and early-onset WRF, respectively. Early administration of TLV, compared to increased FRM dosage, reduces the incidence of WRF in real-world elderly ADHF patients. In addition, it reduces the occurrence of 'worse' WRF-persistent and late-onset WRF-which are associated with increased rates of cardiac death or readmission for worsening heart failure in the 90 days after discharge. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Electrohypersensitivity: a functional impairment due to an inaccessible environment.

PubMed

Johansson, Olle

2015-01-01

In Sweden, electrohypersensitivity is recognized as a functional impairment which implies only the environment as the culprit. The Swedish view provides persons with this impairment a maximal legal protection, it gives them the right to get accessibility measures for free, as well as governmental subsidies and municipality economic support, and to provide them with special Ombudsmen (at the municipality, the EU, and the UN level, respectively), the right and economic means to form disability organizations and allow these to be part of national and international counterparts, all with the simple and single aim to allow persons with the functional impairment electrohypersensitivity to live an equal life in a society based on equality. They are not seen as patients, the do not have an overriding medical diagnosis, but the 'patient' is only the inferior and potentially toxic environment. This does not mean that a subjective symptom of a functionally impaired can not be treated by a physician, as well as get sick-leave from their workplace as well as economic compensation, and already in the year 2000 such symptoms were identified in the Internal Code of Diagnoses, version 10 (ICD-10; R68.8/now W90), and have been since. But the underlying cause still remains only the environment.

Narcissistic Personality Disorder: Relations with distress and functional impairment

PubMed Central

Miller, Joshua D.; Campbell, W. Keith; Pilkonis, Paul A.

2007-01-01

This study examined the construct validity of Narcissistic Personality Disorder (NPD) by examining the relations between NPD and measures of psychological distress and functional impairment both concurrently and prospectively across two samples. In particular, the goal was to address whether NPD typically “meets” Criterion C of the DSM-IV definition of Personality Disorder, which requires that the symptoms lead to clinically significant distress or impairment in functioning. Sample 1 (N =152) was composed of individuals receiving psychiatric treatment, while Sample 2 (N=151) was composed of both psychiatric patients (46%) and individuals from the community. NPD was linked to ratings of depression, anxiety, and several measures of impairment both concurrently and at 6-month follow-up. However, the relations between NPD and psychological distress were (a) small, especially in concurrent measurements, and (b) largely mediated by impaired functioning. NPD was most strongly related to causing pain and suffering to others, and this relationship was significant even when other Cluster B personality disorders were controlled. These findings suggest that NPD is a maladaptive personality style which primarily causes dysfunction and distress in interpersonal domains. The behavior of narcissistic individuals ultimately leads to problems and distress for the narcissistic individuals and for those with whom they interact. PMID:17292708

Associations of smoking and alcohol consumption with impaired β-cell function in Chinese men.

PubMed

Xu, Min; Zhou, Yulin; Xu, Baihui; Sun, Jichao; Wang, Tiange; Lu, Jieli; Lai, Shenghan; Bi, Yufang; Wang, Weiqing; Ning, Guang

2016-05-01

The aims of the present study were to examine the association of cigarette smoking and alcohol consumption with impaired β-cell function in Chinese men, particularly the interaction of smoking and alcohol consumption on impaired insulin secretion. A population-based cross-sectional study was performed in 3957 Chinese men aged ≥40 years. The homeostatic model assessment of β-cell function (HOMA-β) was calculated, and impaired β-cell function was defined as less than the lowest quartile HOMA-βcut-off point. The prevalence of impaired β-cell function in current smokers and heavy drinkers (≥200 g/week) was significantly higher than in non-smokers and non-drinkers, respectively. Compared with non-smoking, current smoking had an exacerbating relationship with impaired β-cell function (odds ratio [OR] 1.78; 95% confidence interval [CI] 1.47-2.15; P < 0.001). No significant association was found between impaired β-cell function and former smoking (P = 0.21), although low and heavy drinking were associated with an increased risk of impaired β-cell function (OR 1.40 [95% CI 1.07-1.81] and 2.14 [95% CI 1.77-2.58], respectively) compared with non-drinking. The combination of current smoking and heavy drinking was associated with the highest risk of impaired β-cell function (OR 3.16; 95% CI 2.43-4.12; P < 0.0001) after adjustment for confounders. We did not detect an additive interaction between current smoking and heavy drinking on the association with impaired β-cell function. Cigarette smoking and alcohol consumption were significantly and independently associated with impaired β-cell function in Chinese men. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Heart rate turbulence.

PubMed

Cygankiewicz, Iwona

2013-01-01

Heart rate turbulence (HRT) is a baroreflex-mediated biphasic reaction of heart rate in response to premature ventricular beats. Heart rate turbulence is quantified by: turbulence onset (TO) reflecting the initial acceleration of heart rate following premature beat and turbulence slope (TS) describing subsequent deceleration of heart rate. Abnormal HRT identifies patients with autonomic dysfunction or impaired baroreflex sensitivity due to variety of disorders, but also may reflect changes in autonomic nervous system induced by different therapeutic modalities such as drugs, revascularization, or cardiac resynchronization therapy. More importantly, impaired HRT has been shown to identify patients at high risk of all-cause mortality and sudden death, particularly in postinfarction and congestive heart failure patients. It should be emphasized that abnormal HRT has a well-established role in stratification of postinfarction and heart failure patients with relatively preserved left ventricular ejection fraction. The ongoing clinical trials will document whether HRT can be used to guide implantation of cardioverter-defibrillators in this subset of patients, not covered yet by ICD guidelines. This review focuses on the current state-of-the-art knowledge regarding clinical significance of HRT in detection of autonomic dysfunction and regarding the prognostic significance of this parameter in predicting all-cause mortality and sudden death. © 2013.

Brain natriuretic peptide and right heart dysfunction after heart transplantation.

PubMed

Talha, Samy; Charloux, Anne; Piquard, François; Geny, Bernard

2017-06-01

Heart transplantation (HT) should normalize cardiac endocrine function, but brain natriuretic peptide (BNP) levels remain elevated after HT, even in the absence of left ventricular hemodynamic disturbance or allograft rejection. Right ventricle (RV) abnormalities are common in HT recipients (HTx), as a result of engraftment process, tricuspid insufficiency, and/or repeated inflammation due to iterative endomyocardial biopsies. RV function follow-up is vital for patient management as RV dysfunction is a recognized cause of in-hospital death and is responsible for a worse prognosis. Interestingly, few and controversial data are available concerning the relationship between plasma BNP levels and RV functional impairment in HTx. This suggests that infra-clinical modifications, such as subtle immune system disorders or hypoxic conditions, might influence BNP expression. Nevertheless, due to other altered circulating molecular forms of BNP, a lack of specificity of BNP assays is described in heart failure patients. This phenomenon could exist in HT population and could explain elevated BNP plasmatic levels despite a normal RV function. In clinical practice, intra-individual change in BNP over time, rather than absolute BNP values, might be more helpful in detecting right cardiac dysfunction in HTx. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Active inhibitor-1 maintains protein hyper-phosphorylation in aging hearts and halts remodeling in failing hearts.

PubMed

Pritchard, Tracy J; Kawase, Yoshiaki; Haghighi, Kobra; Anjak, Ahmad; Cai, Wenfeng; Jiang, Min; Nicolaou, Persoulla; Pylar, George; Karakikes, Ioannis; Rapti, Kleopatra; Rubinstein, Jack; Hajjar, Roger J; Kranias, Evangelia G

2013-01-01

Impaired sarcoplasmic reticulum calcium cycling and depressed contractility are key characteristics in heart failure. Defects in sarcoplasmic reticulum function are characterized by decreased SERCA2a Ca-transport that is partially attributable to dephosphorylation of its regulator phospholamban by increased protein phosphatase 1 activity. Inhibition of protein phosphatase 1 through activation of its endogenous inhibitor-1 has been shown to enhance cardiac Ca-handling and contractility as well as protect from pathological stress remodeling in young mice. In this study, we assessed the long-term effects of inducible expression of constitutively active inhibitor-1 in the adult heart and followed function and remodeling through the aging process, up to 20 months. Mice with inhibitor-1 had normal survival and similar function to WTs. There was no overt remodeling as evidenced by measures of left ventricular end-systolic and diastolic diameters and posterior wall dimensions, heart weight to tibia length ratio, and histology. Higher phosphorylation of phospholamban at both Ser16 and Thr17 was maintained in aged hearts with active inhibitor-1, potentially offsetting the effects of elevated Ser2815-phosphorylation in ryanodine receptor, as there were no increases in arrhythmias under stress conditions in 20-month old mice. Furthermore, long-term expression of active inhibitor-1 via recombinant adeno-associated virus type 9 gene transfer in rats with pressure-overload induced heart failure improved function and prevented remodeling, associated with increased phosphorylation of phospholamban at Ser16 and Thr17. Thus, chronic inhibition of protein phosphatase 1, through increases in active inhibitor-1, does not accelerate age-related cardiomyopathy and gene transfer of this molecule in vivo improves function and halts remodeling in the long term.

Functional impairment in patients with major depressive disorder: the 2-year PERFORM study.

PubMed

Hammer-Helmich, Lene; Haro, Josep Maria; Jönsson, Bengt; Tanguy Melac, Audrey; Di Nicola, Sylvie; Chollet, Julien; Milea, Dominique; Rive, Benoît; Saragoussi, Delphine

2018-01-01

The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study describes the course of depressive symptoms, perceived cognitive symptoms, and functional impairment over 2 years in outpatients with major depressive disorder (MDD) and investigates the patient-related factors associated with functional impairment. This was a 2-year observational study in 1,159 outpatients with MDD aged 18-65 years who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Functional impairment was assessed by the Sheehan Disability Scale and the Work Productivity and Activity Impairment questionnaire. Patients assessed depression severity using the nine-item Patient Health Questionnaire and severity of perceived cognitive symptoms using the five-item Perceived Deficit Questionnaire. To investigate which patient-related factors were associated with functional impairment, univariate analyses of variance were performed to identify relevant factors that were then included in multivariate analyses of covariance at baseline, month 2, months 6 and 12 combined, and months 18 and 24 combined. The greatest improvement in depressive symptoms, perceived cognitive symptoms, and functional impairment was seen immediately (within 2 months) following initiation or switch of antidepressant therapy, followed by more gradual improvement and long-term stabilization. Improvement in perceived cognitive symptoms was less marked than improvement in depressive symptoms during the acute treatment phase. Functional impairment in patients with MDD was not only associated with severity of depressive symptoms but also independently associated with severity of perceived cognitive symptoms when adjusted for depression severity throughout the 2 years of follow-up. These findings highlight the burden of functional impairment in MDD and the importance of recognizing and managing cognitive symptoms in daily practice.

Telephone Crisis Support Workers' Intentions to Use Recommended Skills While Experiencing Functional Impairment.

PubMed

Kitchingman, Taneile A; Wilson, Coralie J; Woodward, Alan; Caputi, Peter; Wilson, Ian

2018-05-01

Empathic engagement with distressed others can lead to elevated symptoms of psychological distress and functional impairment, which preclude helping professionals' delivery of optimal patient care. Whether telephone crisis support workers are impacted in a similar way is not currently reported in the literature. This study examined the relationship between functional impairment and intentions to use recommended support skills in a representative national sample of 210 telephone crisis support workers. Participants completed an online survey including measures of functional impairment and intentions to use recommended telephone crisis support skills with callers reporting suicidal ideation, symptoms of depression, and anxiety. As a group, participants who experienced greater functional impairment during the past month reported significantly lower intentions to use recommended support skills with callers than those who reported lower functional impairment. Future research is needed to clarify the extent to which results generalize to telephone crisis support workers from other organizations. Results warrant further research to (a) identify determinants of telephone crisis support workers' functional impairment, and (b) for the deliberate management of telephone crisis support workers' functional impairment through developing and/or modifying existing service strategies to optimize workers' psychological well-being and delivery of support to callers.

Obesity suppresses circulating level and function of endothelial progenitor cells and heart function

PubMed Central

2012-01-01

Background and aim This study tested the hypothesis that obesity suppresses circulating number as well as the function of endothelial progenitor cells (EPCs) and left ventricular ejection fraction (LVEF). Methods High fat diet (45 Kcal% fat) was given to 8-week-old C57BL/6 J mice (n = 8) for 20 weeks to induce obesity (group 1). Another age-matched group (n = 8) were fed with control diet for 20 weeks as controls (group 2). The animals were sacrificed at the end of 20 weeks after obesity induction. Results By the end of study period, the heart weight, body weight, abdominal fat weight, serum levels of total cholesterol and fasting blood sugar were remarkably higher in group 1 than in group 2 (all p<0.01). The circulating level of EPCs (C-kit/CD31, Sca-1/KDR, CXCR4/CD34) was significantly lower in group 1 than in group 2 (p<0.03) at 18 h after critical limb ischemia induction. The angiogenesis and migratory ability of bone marrow-derived EPCs was remarkably impaired in group 1 compared to that in group 2 (all p<0.01). The repair ability of aortic endothelium damage by lipopolysaccharide was notably attenuated in group 1 compared with that in group 2 (p<0.01). Collagen deposition (Sirius red staining) and fibrotic area (Masson's Trichrome staining) in LV myocardium were notably increased in group 1 compared with group 2 (p<0.001). LVEF was notably lower, whereas LV end-diastolic and end-systolic dimensions were remarkably higher in group 1 than in group 2 (all p<0.001). Conclusions Obesity diminished circulating EPC level, impaired the recovery of damaged endothelium, suppressed EPC angiogenesis ability and LVEF, and increased LV remodeling. PMID:22747715

A patient with heart failure and worsening kidney function.

PubMed

Sarnak, Mark J

2014-10-07

There is high prevalence of CKD, defined by reduced GFR, in patients with heart failure. Reduced kidney function is associated with increased morbidity and mortality in this patient population. The cardiorenal syndrome (CRS) involves a bidirectional relationship between the heart and kidneys whereby dysfunction in either may exacerbate the function of the other, but this syndrome has been difficult to precisely define because it has many complex physiologic, biochemical, and hormonal abnormalities. The pathophysiology of CRS is not completely understood, but potential mechanisms include reduced kidney perfusion due to decreased forward flow, increased right ventricular and venous pressure, and neurohormonal adaptations. Treatment options include inotropic medications; diuretics; ultrafiltration; and medications, such as β-blockers, inhibitors of the renin-angiotensin-aldosterone system, and more novel treatments that focus on unique aspects of the pathophysiology. Recent observational studies suggest that treatments that result in a decrease in venous pressure and lead to hemoconcentration may be associated with improved outcomes. Patients with CRS that is not responsive to medical interventions should be considered for ventricular assist devices, heart transplantation, or combined heart and kidney transplantation. Copyright © 2014 by the American Society of Nephrology.

Resting heart rate and the risk of developing impaired fasting glucose and diabetes: the Kailuan prospective study

PubMed Central

Wang, Liang; Cui, Liufu; Wang, Yanxue; Vaidya, Anand; Chen, Shuohua; Zhang, Caifeng; Zhu, Ying; Li, Dongqing; Hu, Frank B; Wu, Shouling; Gao, Xiang

2015-01-01

Background: To investigate the association between resting heart rate and the risk of developing impaired fasting glucose (IFG), diabetes and conversion from IFG to diabetes. Methods: The prospective analysis included 73 357 participants of the Kailuan cohort (57 719 men and 15 638 women). Resting heart rate was measured via electrocardiogram in 2006. Incident diabetes was defined as either the fasting blood glucose (FBG) ≥ 7.0 mmol/l or new active use of diabetes medications during the 4-year follow-up period. IFG was defined as a FBG between 5.6 and 6.9 mmol/l. A meta-analysis including seven published prospective studies focused on heart rate and diabetes risk, and our current study was then conducted using random-effects models. Results: During 4 years of follow-up, 17 463 incident IFG cases and 4 649 incident diabetes cases were identified. The corresponding adjusted hazard ratios (HRs) for each 10 beats/min increase in heart rate were 1.23 [95% confidence interval (CI): 1.19, 1.27] for incident diabetes, 1.11 (95% CI: 1.09, 1.13) for incident IFG and 1.13 (95% CI: 1.08, 1.17) for IFG to diabetes conversion. The risks of incident IFG and diabetes were significantly higher among participants aged < 50 years than those aged ≥ 50 years (P-interaction < 0.02 for both). A meta-analysis confirmed the positive association between resting heart rate and diabetes risk (pooled HR for the highest vs lowest heart rate quintile = 1.59, 95% CI:1.27, 2.00; n = 8). Conclusion: Faster resting heart rate is associated with higher risk of developing IFG and diabetes, suggesting that heart rate could be used to identify individuals with a higher future risk of diabetes. PMID:26002923

[Impaired renal function: be aware of exogenous factors].

PubMed

van der Meijden, Wilbert A G; Smak Gregoor, Peter J H

2013-01-01

Renal function is currently estimated using the Modification of Diet in Renal Disease (MDRD) formula, which is partly based on the serum creatinine level. Patients with impaired renal function are referred to nephrologists in accordance with the Dutch national transmural agreement for 'Chronic renal impairment'. A 54-year-old woman without significant history was referred to analyse a coincidentally found decline in the estimated glomerular filtration rate (eGFR). The patient had no complaints and used no medication except creatine supplements. Additional diagnostic testing showed no abnormalities. After cessation of creatine supplementation, the calculated renal function normalized. Serum creatinine is a reflection of muscle mass. The use of creatine-containing dietary supplements, such as creatine ethyl ester, can influence serum creatinine levels and therefore the eGFR as calculated with the MDRD formula. The use of supplements deserves attention when taking the history.

Comprehensive Functional Assessment of Right-Sided Heart Using Speckle Tracking Strain for Patients with Pulmonary Hypertension.

PubMed

Fukuda, Yuko; Tanaka, Hidekazu; Ryo-Koriyama, Keiko; Motoji, Yoshiki; Sano, Hiroyuki; Shimoura, Hiroyuki; Ooka, Junichi; Toki, Hiromi; Sawa, Takuma; Mochizuki, Yasuhide; Matsumoto, Kensuke; Emoto, Noriaki; Hirata, Ken-Ichi

2016-07-01

Right ventricular (RV) systolic function is one of the most important determinants of outcome for pulmonary hypertension (PH) patients, but the factors influencing prognosis vary widely. Elevated right atrial (RA) pressure is reported to be one of these prognostic factors, but its functional importance has scarcely been assessed. Eighty-two PH patients, all of whom underwent echocardiography and right heart catheterization, were recruited. RV function was assessed by two-dimensional speckle tracking longitudinal strain from RV-focused apical four-chamber view and calculated by averaging the three regional peak strains from the RV free wall (RV-free). RA function was determined as the sum of three peak strain values comprising reservoir, conduit, and contractile function (sum of RA strain). Sum of RA strain correlated significantly with hemodynamic parameters such as mean right atrial pressure (r = -0.35, P = 0.002) and end-diastolic RV pressure (r = -0.29, P = 0.008). Patients with sum of RA strain ≥30.2% experienced more favorable outcomes than those with sum of RA strain <30.2% (log-rank P = 0.001). Furthermore, patients with impaired RV systolic function (RV-free <20%) and RA function (sum of RA strain <30.2%) showed the worst outcome (P = 0.001). A sequential Cox model based on clinical variables (χ(2) = 5.8) was improved by addition of RV-free (χ(2) = 8.7; P < 0.05) and further improved by addition of sum of RA strain (χ(2) = 12.0; P < 0.01). Right atrial strain appears to be a valuable additive factor for predicting outcomes for PH patients, and comprehensive functional assessment of right-sided heart using speckle tracking strain may have potential clinical implications for better management of PH patients. © 2016, Wiley Periodicals, Inc.

High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

PubMed

Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

2015-01-01

The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

Progressively Disrupted Brain Functional Connectivity Network in Subcortical Ischemic Vascular Cognitive Impairment Patients.

PubMed

Sang, Linqiong; Chen, Lin; Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Li, Chuanming; Qiu, Mingguo

2018-01-01

Cognitive impairment caused by subcortical ischemic vascular disease (SIVD) has been elucidated by many neuroimaging studies. However, little is known regarding the changes in brain functional connectivity networks in relation to the severity of cognitive impairment in SIVD. In the present study, 20 subcortical ischemic vascular cognitive impairment no dementia patients (SIVCIND) and 20 dementia patients (SIVaD) were enrolled; additionally, 19 normal controls were recruited. Each participant underwent a resting-state functional MRI scan. Whole-brain functional networks were analyzed with graph theory and network-based statistics (NBS) to study the functional organization of networks and find alterations in functional connectivity among brain regions. After adjustments for age, gender, and duration of formal education, there were significant group differences for two network functional organization indices, global efficiency and local efficiency, which decreased (NC > SIVCIND > SIVaD) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, p  < 0.01) mainly involved the orbitofrontal, parietal, and temporal cortices, as well as the basal ganglia. The brain connectivity network was progressively disrupted as cognitive impairment worsened, with an increased number of decreased connections between brain regions. We also observed more reductions in nodal efficiency in the prefrontal and temporal cortices for SIVaD than for SIVCIND. These findings indicated a progressively disrupted pattern of the brain functional connectivity network with increased cognitive impairment and showed promise for the development of reliable biomarkers of network metric changes related to cognitive impairment caused by SIVD.

Obesity's Effects on the Onset of Functional Impairment among Older Adults

ERIC Educational Resources Information Center

Jenkins, Kristi Rahrig

2004-01-01

Purpose: This study has two purposes. First, it determines if there is a relationship between body weight and the onset of functional impairment across time among this sample of older adults. More specifically, it examines if obese older adults are more likely to experience the onset of functional impairment. Second, it explores how health…

Predictors of heart failure self-care in patients who screened positive for mild cognitive impairment.

PubMed

Davis, Karen K; Himmelfarb, Cheryl R Dennison; Szanton, Sarah L; Hayat, Matthew J; Allen, Jerilyn K

2015-01-01

Heart failure (HF) is associated with cognitive impairment, which could negatively affect a patient's abilities to carry out self-care, potentially resulting in higher hospital readmission rates. Factors associated with self-care in patients experiencing mild cognitive impairment (MCI) are not known. This descriptive correlation study aimed to assess levels of HF self-care and knowledge and to determine the predictors of self-care in HF patients who screen positive for MCI. The Montreal Cognitive Assessment was used to screen for MCI. In 125 patients with MCI hospitalized with HF, self-care (Self-care of Heart Failure Index) and HF knowledge (Dutch Heart Failure Knowledge Scale) were assessed. We used multiple regression analysis to test a model of variables hypothesized to predict self-care maintenance, management, and confidence. Mean (SD) HF knowledge scores (11.24 [1.84]) were above the level considered to be adequate (defined as >10). Mean (SD) scores for self-care maintenance (63.57 [19.12]), management (68.35 [20.24]), and confidence (64.99 [16.06]) were consistent with inadequate self-care (defined as scores <70). In multivariate analysis, HF knowledge, race, greater disease severity, and social support explained 22% of the variance in self-care maintenance (P < .001); age, education level, and greater disease severity explained 19% of the variance in self-care management (P < .001); and younger age and higher social support explained 20% of the variance in self-care confidence scores (P < .001). Blacks, on average, scored significantly lower in self-care maintenance (P = .03). In this sample, patients who screened positive for MCI, on average, had adequate HF knowledge yet inadequate self-care scores. These models show the influence of modifiable and nonmodifiable predictors for patients who screened positive for MCI across the domains of self-care. Health professionals should consider screening for MCI and identifying interventions that address HF

Functional impairment in patients with major depressive disorder: the 2-year PERFORM study

PubMed Central

Hammer-Helmich, Lene; Haro, Josep Maria; Jönsson, Bengt; Tanguy Melac, Audrey; Di Nicola, Sylvie; Chollet, Julien; Milea, Dominique; Rive, Benoît; Saragoussi, Delphine

2018-01-01

Background The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study describes the course of depressive symptoms, perceived cognitive symptoms, and functional impairment over 2 years in outpatients with major depressive disorder (MDD) and investigates the patient-related factors associated with functional impairment. Methods This was a 2-year observational study in 1,159 outpatients with MDD aged 18–65 years who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Functional impairment was assessed by the Sheehan Disability Scale and the Work Productivity and Activity Impairment questionnaire. Patients assessed depression severity using the nine-item Patient Health Questionnaire and severity of perceived cognitive symptoms using the five-item Perceived Deficit Questionnaire. To investigate which patient-related factors were associated with functional impairment, univariate analyses of variance were performed to identify relevant factors that were then included in multivariate analyses of covariance at baseline, month 2, months 6 and 12 combined, and months 18 and 24 combined. Results The greatest improvement in depressive symptoms, perceived cognitive symptoms, and functional impairment was seen immediately (within 2 months) following initiation or switch of antidepressant therapy, followed by more gradual improvement and long-term stabilization. Improvement in perceived cognitive symptoms was less marked than improvement in depressive symptoms during the acute treatment phase. Functional impairment in patients with MDD was not only associated with severity of depressive symptoms but also independently associated with severity of perceived cognitive symptoms when adjusted for depression severity throughout the 2 years of follow-up. Conclusion These findings highlight the burden of functional impairment in MDD and the importance of recognizing and managing

Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart following hypoxia/reoxygenation

PubMed Central

Mansor, Latt S.; Sousa Fialho, Maria da Luz; Yea, Georgina; Coumans, Will A.; West, James A.; Kerr, Matthew; Carr, Carolyn A.; Luiken, Joost J.F.P.; Glatz, Jan F.C.; Evans, Rhys D.; Griffin, Julian L.; Tyler, Damian J.; Clarke, Kieran

2017-01-01

Aims The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress. Methods and results Hearts from type 2 diabetic and control male Wistar rats were perfused in normoxia, hypoxia and reoxygenation, with the FAT/CD36 inhibitor sulfo-N-succinimidyl oleate (SSO) infused 4 min before hypoxia. SSO infusion into diabetic hearts decreased the fatty acid oxidation rate by 29% and myocardial triglyceride concentration by 48% compared with untreated diabetic hearts, restoring fatty acid metabolism to control levels following hypoxia-reoxygenation. SSO infusion increased the glycolytic rate by 46% in diabetic hearts during hypoxia, increased pyruvate dehydrogenase activity by 53% and decreased lactate efflux rate by 56% compared with untreated diabetic hearts during reoxygenation. In addition, SSO treatment of diabetic hearts increased intermediates within the second span of the Krebs cycle, namely fumarate, oxaloacetate, and the FAD total pool. The cardiac dysfunction in diabetic hearts following decreased oxygen availability was prevented by SSO-infusion prior to the hypoxic stress. Infusing SSO into diabetic hearts increased rate pressure product by 60% during hypoxia and by 32% following reoxygenation, restoring function to control levels. Conclusions Diabetic hearts have limited metabolic flexibility and cardiac dysfunction when stressed, which can be rapidly rectified by reducing fatty acid uptake with the FAT/CD36 inhibitor, SSO. This novel

Angina pectoris severity among coronary heart disease patients is associated with subsequent cognitive impairment.

PubMed

Weinstein, Galit; Goldbourt, Uri; Tanne, David

2015-01-01

The relationship between coronary heart disease (CHD) and cognitive function is not completely elucidated. We examined the association between severity of angina pectoris (AP) in mid-life and subsequent cognitive impairment among CHD patients. Severity of AP according to the Canadian Cardiovascular Society angina classification was assessed in a subgroup of people with chronic CHD, who previously participated in a secondary prevention trial. Cognitive performance was evaluated 15±3 years later, using a validated set of computerized cognitive tests (Neurotrax Computerized Cognitive Battery; computing index scores summarizing performance in each cognitive domain and a global cognitive score). We compared the risk of cognitive deficits in participants with AP class >2 to those with AP≤2, adjusting for vascular risk factors, common carotid-intima media thickness (CC-IMT), and presence of carotid plaques. Among 535 participants (mean age at baseline 57.9±6.6 y; 95% males), AP class >2 was associated with subsequent poorer performance on tests of memory and attention compared to those with AP class ≤2 (β=-4.3±1.8; P=0.016 and β=-3.6±1.7; P=0.029, respectively) and with a higher risk of having impairment in these domains [odds ratio (95% confidence interval)=1.83 (1.11-3.02); P=0.019 and 2.36 (1.34-4.16); P=0.003, for memory and attention, respectively]. These results were similar after controlling for vascular risk factors; however, the association of AP with memory domain attenuated after adjustment for CC-IMT or presence of carotid plaques. In people with preexisting CHD, severity of AP is associated with late-life poorer cognitive performance, independent of other vascular risk factors.

Activation of PPAR-α in the early stage of heart failure maintained myocardial function and energetics in pressure-overload heart failure.

PubMed

Kaimoto, Satoshi; Hoshino, Atsushi; Ariyoshi, Makoto; Okawa, Yoshifumi; Tateishi, Shuhei; Ono, Kazunori; Uchihashi, Motoki; Fukai, Kuniyoshi; Iwai-Kanai, Eri; Matoba, Satoaki

2017-02-01

Failing heart loses its metabolic flexibility, relying increasingly on glucose as its preferential substrate and decreasing fatty acid oxidation (FAO). Peroxisome proliferator-activated receptor α (PPAR-α) is a key regulator of this substrate shift. However, its role during heart failure is complex and remains unclear. Recent studies reported that heart failure develops in the heart of myosin heavy chain-PPAR-α transgenic mice in a manner similar to that of diabetic cardiomyopathy, whereas cardiac dysfunction is enhanced in PPAR-α knockout mice in response to chronic pressure overload. We created a pressure-overload heart failure model in mice through transverse aortic constriction (TAC) and activated PPAR-α during heart failure using an inducible transgenic model. After 8 wk of TAC, left ventricular (LV) function had decreased with the reduction of PPAR-α expression in wild-type mice. We examined the effect of PPAR-α induction during heart failure using the Tet-Off system. Eight weeks after the TAC operation, LV construction was preserved significantly by PPAR-α induction with an increase in PPAR-α-targeted genes related to fatty acid metabolism. The increase of expression of fibrosis-related genes was significantly attenuated by PPAR-α induction. Metabolic rates measured by isolated heart perfusions showed a reduction in FAO and glucose oxidation in TAC hearts, but the rate of FAO preserved significantly owing to the induction of PPAR-α. Myocardial high-energy phosphates were significantly preserved by PPAR-α induction. These results suggest that PPAR-α activation during pressure-overloaded heart failure improved myocardial function and energetics. Thus activating PPAR-α and modulation of FAO could be a promising therapeutic strategy for heart failure. NEW & NOTEWORTHY The present study demonstrates the role of PPAR-α activation in the early stage of heart failure using an inducible transgenic mouse model. Induction of PPAR-α preserved heart

Optimizing donor heart outcome after prolonged storage with endothelial function analysis and continuous perfusion.

PubMed

Poston, Robert S; Gu, Junyan; Prastein, Deyanira; Gage, Fred; Hoffman, John W; Kwon, Michael; Azimzadeh, Agnes; Pierson, Richard N; Griffith, Bartley P

2004-10-01

By minimizing tissue ischemia, continuous perfusion (CP) during organ transport may increase the safety of "marginal donors." My colleagues and I investigated whether an analysis of donor heart viability predicts recovery of grafts challenged with a 24-hour preservation interval. Dog hearts underwent cold static storage (CS) for 8 hours (n = 8) or 24 hours (n = 2) or CP for 24 hours with cold asanguinous, oxygenated solution (n = 8). Myocardial systolic and diastolic function and oxygen and lactate consumption were assessed at base line, during CP, and after Langendorff blood reperfusion. Base line endothelial function was evaluated by the percentage transcoronary change ([coronary sinus - aorta]/aorta) in myeloperoxidase and by platelet function and coronary flow reserve after 20 seconds of coronary artery occlusion. During CP, the endothelium was assessed by transcoronary protein release and coronary resistance. Edema was assessed by weight gain and histology. Base line systolic and metabolic functions showed no relation to post-Langendorff function. Compared with CS, CP resulted in a greater recovery in systolic function (87% +/- 35% vs 65% +/- 15% of baseline; p = 0.05) and a shorter interval required for lactate consumption to exceed production (7.0 +/- 6.8 minutes vs 15.0 +/- 8.9 minutes; p = 0.06). Endothelial function was heterogeneous: coronary flow reserve, 2.7 +/- 0.7; percentage change in myeloperoxidase, -8.4% +/- 6.8%; and change in platelet function, 4.3% +/- 3.5%, as determined by thromboelastography angle at base line. Protein release during CP for 24 hours was 8.3 +/- 7.1 g. Two factors predicted more than 75% systolic pressure generation recovery: use of CP and normal endothelial function (p = 0.05; Fisher's exact test). However, CP led to edema according to histology, weight gain (72 +/- 29 g), and impaired diastolic function versus CS (end-diastolic pressure-volume relationship, 1.4 +/- 0.4 mm Hg/mL vs 0.8 +/- 0.3 mm Hg/mL; p = 0.08). Better

Post-tuberculous lung function impairment in a tuberculosis reference clinic in Cameroon.

PubMed

Mbatchou Ngahane, Bertrand Hugo; Nouyep, Junior; Nganda Motto, Malea; Mapoure Njankouo, Yacouba; Wandji, Adeline; Endale, Mireille; Afane Ze, Emmanuel

2016-05-01

After completion of treatment, a proportion of pulmonary TB (pTB) patients experience lung function impairment which can influence their quality of life. This study aimed to determine the prevalence of lung function impairment in patients treated for pTB and investigate its associated factors. A cross-sectional study was conducted in TB clinic of the Douala Laquintinie Hospital in Cameroon. Patients aged 15 and above who were treated for pTB between 2008 and 2012 were included in the study. Demographic data, respiratory symptoms prior TB diagnosis, comorbidities and chest radiography findings prior to TB treatment were collected. All participants underwent spirometric measurements. Airflow obstruction was defined as a post-bronchodilation FEV1/FVC <70% with FVC >80%, restrictive defects as an FEV1/FVC ratio of ≥70% with an FVC <80% predicted, and mixed defects as FVC of <80% predicted and an FEV1/FVC ratio of <70%. Lung function impairment was defined by the presence of at least one of these three abnormalities. Logistic regression analysis was employed to investigate risk factors of lung function impairment. Of a total of 269 participants included in the study, 146 (54.3%) were male. The median age of participants was 33 years. The median duration of symptoms before diagnosis of TB was 4 weeks [interquartile range (IQR) 3-8]. The prevalence of lung function impairment was 45.4% (95% CI 39-51). The multivariate analysis identified duration of symptoms [OR 1.08; 95% CI (1.01-1.15)] and fibrotic pattern [OR 3.54; 95% CI (1.40-8.95)] as independent risk factors for lung function impairment. Post-tuberculous pulmonary function impairment is frequent in Douala. Sensitization of patient with symptoms of pulmonary TB for an earlier visit to healthcare facilities could reduce the impact of pTB on lung function of patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exercise Training Reverses Extrapulmonary Impairments in Smoke-exposed Mice.

PubMed

Bowen, T Scott; Aakerøy, Lars; Eisenkolb, Sophia; Kunth, Patricia; Bakkerud, Fredrik; Wohlwend, Martin; Ormbostad, Anne Marie; Fischer, Tina; Wisloff, Ulrik; Schuler, Gerhard; Steinshamn, Sigurd; Adams, Volker; Bronstad, Eivind

2017-05-01

Cigarette smoking is the main risk factor for chronic obstructive pulmonary disease and emphysema. However, evidence on the extrapulmonary effects of smoke exposure that precede lung impairments remains unclear at present, as are data on nonpharmacological treatments such as exercise training. Three groups of mice, including control (n = 10), smoking (n = 10), and smoking with 6 wk of high-intensity interval treadmill running (n = 11), were exposed to 20 wk of fresh air or whole-body cigarette smoke. Exercise capacity (peak oxygen uptake) and lung destruction (histology) were subsequently measured, whereas the heart, peripheral endothelium (aorta), and respiratory (diaphragm) and limb (extensor digitorum longus and soleus) skeletal muscles were assessed for in vivo and in vitro function, in situ mitochondrial respiration, and molecular alterations. Smoking reduced body weight by 26% (P < 0.05) without overt airway destruction (P > 0.05). Smoking impaired exercise capacity by 15% while inducing right ventricular dysfunction by ~20%, endothelial dysfunction by ~20%, and diaphragm muscle weakness by ~15% (all P < 0.05), but these were either attenuated or reversed by exercise training (P < 0.05). Compared with controls, smoking mice had normal limb muscle and mitochondrial function (cardiac and skeletal muscle fibers); however, diaphragm measures of oxidative stress and protein degradation were increased by 111% and 65%, respectively (P < 0.05), but these were attenuated by exercise training (P < 0.05). Prolonged cigarette smoking reduced exercise capacity concomitant with functional impairments to the heart, peripheral endothelium, and respiratory muscle that preceded the development of overt emphysema. However, high-intensity exercise training was able to reverse these smoke-induced extrapulmonary impairments.

American Heart Association’s Life’s Simple 7: Avoiding Heart Failure and Preserving Cardiac Structure and Function

PubMed Central

Folsom, Aaron R.; Shah, Amil M.; Lutsey, Pamela L.; Roetker, Nicholas S.; Alonso, Alvaro; Avery, Christy L.; Miedema, Michael D.; Konety, Suma; Chang, Patricia P.; Solomon, Scott D.

2015-01-01

BACKGROUND Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association’s Life’s Simple 7 guidelines -- on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose -- is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. METHODS We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults aged 45-64 years in 1987-89. From the 1987-89 risk factor measurements, we created a Life’s Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2,218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4,855 participants free of clinical cardiovascular disease in 2011-13, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. RESULTS One in four participants (25.5%) developed heart failure through age 85. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life’s Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life’s Simple 7 score compared with an inadequate score. CONCLUSIONS Greater achievement of American Heart Association’s Life’s Simple 7 in middle-age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function. PMID:25908393

Disagreement between Parent and Adolescent Reports of Functional Impairment

ERIC Educational Resources Information Center

Kramer, Teresa L.; Phillips, Susan D.; Hargis, Michael B.; Miller, Terri L.; Burns, Barbara J.; Robbins, James M.

2004-01-01

Objective: Adolescents' functional impairment has become increasingly important as a criterion for diagnosis and service eligibility as well as a target of therapeutic intervention in mental health settings. This study examines three critical issues in measuring functioning: 1) agreement between parent and adolescent reports of functioning, 2)…

Body Dysmorphic Symptoms, Functional Impairment, and Depression: The Role of Appearance-Based Teasing.

PubMed

Weingarden, Hilary; Renshaw, Keith D

2016-01-01

Body dysmorphic disorder is associated with elevated social and occupational impairment and comorbid depression, but research on risk factors for body dysmorphic symptoms and associated outcomes is limited. Appearance-based teasing may be a potential risk factor. To examine the specificity of this factor, the authors assessed self-reported appearance-based teasing, body dysmorphic, and obsessive-compulsive symptom severity, functional impairment (i.e., social, occupational, family impairment), and depression in a nonclinical sample of undergraduates. As hypothesized, appearance-based teasing was positively correlated with body dysmorphic symptoms. The correlation between teasing and body dysmorphic symptoms was stronger than that between teasing and obsessive-compulsive symptom severity. Last, body dysmorphic symptom severity and appearance-based teasing interacted in predicting functional impairment and depression. Specifically, appearance-based teasing was positively associated with depression and functional impairment only in those with elevated body dysmorphic symptoms. When a similar moderation was tested with obsessive-compulsive, in place of body dysmorphic, symptom severity, the interaction was nonsignificant. Findings support theory that appearance-based teasing is a specific risk factor for body dysmorphic symptoms and associated functional impairment.

Let's think in alkaline phosphatase at heart function.

PubMed

Martins, Maria João; Azevedo, Isabel

2010-10-08

In their recent paper, Cheung et al [B.M. Cheung, K.L. Ong, L.Y. Wong, Elevated serum alkaline phosphatase and peripheral arterial disease in the United States National Health and Nutrition Examination Survey 1999-2004. Int J Cardiol 2008 (Electronic publication ahead of print)] described a significant association between serum alkaline phosphatase levels and low ankle-brachial blood pressure index, a risk factor for cardiovascular pathology. We had verified that alkaline phosphatase is present at the rat heart, showing a distribution compatible with cardiomyocyte sarcoplasmic reticulum. Moreover, several drugs with cardiac effect were shown to interfere with heart alkaline phosphatase activity. We therefore propose that alkaline phosphatase may be a local regulator at heart function and a putative target for therapeutic interventions. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

The effects of heart failure on renal function.

PubMed

Udani, Suneel M; Koyner, Jay L

2010-08-01

Heart-kidney interactions have been increasingly recognized by clinicians and researchers who study and treat heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of concomitant cardiac and renal dysfunction remains unclear; however, evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. 2010 Elsevier Inc. All rights reserved.

The Effects of Heart Failure on Renal Function

PubMed Central

Udani, Suneel M; Koyner, Jay L

2010-01-01

Summary Heart-kidney interactions have been increasingly recognized by clinicians and researchers involved in the study and treatment of heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Recent work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of the concomitant cardiac and renal dysfunction remains unclear; however, increasing evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. PMID:20621250

Risk factors for psychosis: impaired social and role functioning.

PubMed

Cornblatt, Barbara A; Carrión, Ricardo E; Addington, Jean; Seidman, Larry; Walker, Elaine F; Cannon, Tyronne D; Cadenhead, Kristin S; McGlashan, Thomas H; Perkins, Diana O; Tsuang, Ming T; Woods, Scott W; Heinssen, Robert; Lencz, Todd

2012-11-01

Risk for psychosis is currently defined primarily on the basis of attenuated positive symptoms (APS), with no inclusion of the functional deficits characteristic of schizophrenia. Impaired social and role functioning have been of interest for reflecting poor outcome but far less is known about the developmental impact of these deficits as vulnerability or risk factors. Age-appropriate social and role functioning were prospectively assessed in 100 individuals at clinical high risk (CHR) for psychosis included in the 8-site North American Prodromal Longitudinal Study database. A nested case-control design was used to compare changes in social and role functioning in 26 individuals converting to psychosis shortly after baseline assessment and 24 converting over a year later. Individuals in each converter subgroup were directly matched to a non-converter at the same site, controlling for time to conversion, age, gender, and severity of baseline symptoms. At baseline, CHR subjects who later became psychotic were significantly more likely to be impaired socially than matched non-converters. Onset of psychosis did not further disrupt social difficulties. Role functioning showed some of the same trends, but the overall pattern was not as consistent as for the social domain. Controlling for neurocognition did not change the pattern of group differences. Early impaired social functioning appears to be a risk factor for psychosis and, added to APS, could potentially contribute to accurate identification of CHR individuals and provide a new direction for early intervention to reduce long-term disability.

Dipeptidyl peptidase-4 independent cardiac dysfunction links saxagliptin to heart failure.

PubMed

Koyani, Chintan N; Kolesnik, Ewald; Wölkart, Gerald; Shrestha, Niroj; Scheruebel, Susanne; Trummer, Christopher; Zorn-Pauly, Klaus; Hammer, Astrid; Lang, Petra; Reicher, Helga; Maechler, Heinrich; Groschner, Klaus; Mayer, Bernd; Rainer, Peter P; Sourij, Harald; Sattler, Wolfgang; Malle, Ernst; Pelzmann, Brigitte; von Lewinski, Dirk

2017-12-01

Saxagliptin treatment has been associated with increased rate of hospitalization for heart failure in type 2 diabetic patients, though the underlying mechanism(s) remain elusive. To address this, we assessed the effects of saxagliptin on human atrial trabeculae, guinea pig hearts and cardiomyocytes. We found that the primary target of saxagliptin, dipeptidyl peptidase-4, is absent in cardiomyocytes, yet saxagliptin internalized into cardiomyocytes and impaired cardiac contractility via inhibition of the Ca 2+ /calmodulin-dependent protein kinase II-phospholamban-sarcoplasmic reticulum Ca 2+ -ATPase 2a axis and Na + -Ca 2+ exchanger function in Ca 2+ extrusion. This resulted in reduced sarcoplasmic reticulum Ca 2+ content, diastolic Ca 2+ overload, systolic dysfunction and impaired contractile force. Furthermore, saxagliptin reduced protein kinase C-mediated delayed rectifier K + current that prolonged action potential duration and consequently QTc interval. Importantly, saxagliptin aggravated pre-existing cardiac dysfunction induced by ischemia/reperfusion injury. In conclusion, our novel results provide mechanisms for the off-target deleterious effects of saxagliptin on cardiac function and support the outcome of SAVOR-TIMI 53 trial that linked saxagliptin with the risk of heart failure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Key neurological impairments influence function-related group outcomes after stroke.

PubMed

Han, Lu; Law-Gibson, Diane; Reding, Michael

2002-07-01

The function-related group (FRG) classification is based on functional assessment and has been assumed to encompass the effects of different patterns and severity of neurological impairments. This assumption may not be correct. It has been proposed as a means of comparing rehabilitation outcome across institutions. If neurological impairments significantly affect FRG outcome, then higher FRG outcome scores may reflect selection bias favoring patients with fewer neurological impairments rather than better quality of rehabilitation care. The goal of this study was to assess the influence of motor, somatosensory, and hemianopic visual impairments on FRG outcomes after stroke. All 288 consecutive stroke patients discharged in 1999 from an acute rehabilitation hospital were assigned to 1 of 5 FRGs on the basis of their Functional Independence Measure (FIM) mobility subscore and age. Each FRG was also stratified into 1 of 4 cohorts on the basis of the presence or absence of key neurological impairments: motor impairment only (M), motor plus either somatosensory or hemianopic visual impairment (MS/MV), motor plus somatosensory plus hemianopic visual impairment (MSV), and other combinations of impairments. FIM scores were available every 10 days for all patients from admission to discharge. The effect of impairment group on outcome was assessed within each FRG category through repeated-measures analysis of variance to assess differences in serial FIM scores across the 4 impairment groups. The distribution of each of the 4 impairment groups across the 5 FRGs was assessed with chi2 analysis. The numbers of patients in each of the 5 FRGs from the lowest level, FRG-11, to the highest, FRG-15, were as follows: 78 (27%), 47 (16%), 75 (26%), 55 (19%), and 33 (11%). Different neurological impairments were associated with significantly different mean+/-SD discharge FIM scores as follows: for FRG-11, MSV=63+/-16, MS/MV=68+/-19, and M=81+/-13 (P=0.04); for FRG-12, MSV=47+/-14, MS

Functional Literacy for Students with Visual Impairments and Significant Cognitive Disabilities: The Perspective of Teachers of Students with Visual Impairments

ERIC Educational Resources Information Center

Zebehazy, Kim T.

2014-01-01

This study reports opinions and practices of teachers of students with visual impairments (TSVIs) in 34 states regarding functional literacy for students with visual impairments (VIs) and significant cognitive disabilities (SCDs). The survey asked TSVIs to select a definition of functional literacy, indicate agreement with a series of literacy…

Visual impairment, visual functioning, and quality of life assessments in patients with glaucoma.

PubMed Central

Parrish, R K

1996-01-01

BACKGROUND/PURPOSE: To determine the relation between visual impairment, visual functioning, and the global quality of life in patients with glaucoma. METHODS: Visual impairment, defined with the American Medical Association Guides to the Evaluation of Permanent Impairment; visual functioning, measured with the VF-14 and the Field Test Version of the National Eye Institute-Visual Functioning Questionnaire (NEI-VFQ); and the global quality of life, assessed with the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), were determined in 147 consecutive patients with glaucoma. RESULTS: None of the SF-36 domains demonstrated more than a weak correlation with visual impairment. The VF-14 scores were moderately correlated with visual impairment. Of the twelve NEI-VFQ scales, distance activities and vision specific dependency were moderately correlated with visual impairment. Of the twelve NEI-VFQ scales, distance activities and vision specific dependency were moderately correlated with visual field impairment; vision specific social functioning, near activities, vision specific role difficulties, general vision, vision specific mental health, color vision, and driving were modestly correlated; visual pain was weakly correlated; and two were not significantly correlated. Correcting for visual actuity weakened the strength of the correlation coefficients. CONCLUSIONS: The SF-36 is unlikely to be useful in determining visual impairment in patients with glaucoma. Based on the moderate correlation between visual field impairment and the VF-14 score, this questionnaire may be generalizable to patients with glaucoma. Several of the NEI-VFQ scales correlate with visual field impairment scores in patients with a wide range of glaucomatous damage. PMID:8981717

Uncovering the Rare Variants of DLC1 Isoform 1 and Their Functional Effects in a Chinese Sporadic Congenital Heart Disease Cohort

PubMed Central

Wang, Zhen; Tan, Huilian; Kong, Xianghua; Shu, Yang; Zhang, Yuchao; Huang, Yun; Zhu, Yufei; Xu, Heng; Wang, Zhiqiang; Wang, Ping; Ning, Guang; Kong, Xiangyin; Hu, Guohong; Hu, Landian

2014-01-01

Congenital heart disease (CHD) is the most common birth defect affecting the structure and function of fetal hearts. Despite decades of extensive studies, the genetic mechanism of sporadic CHD remains obscure. Deleted in liver cancer 1 (DLC1) gene, encoding a GTPase-activating protein, is highly expressed in heart and essential for heart development according to the knowledge of Dlc1-deficient mice. To determine whether DLC1 is a susceptibility gene for sporadic CHD, we sequenced the coding region of DLC1 isoform 1 in 151 sporadic CHD patients and identified 13 non-synonymous rare variants (including 6 private variants) in the case cohort. Importantly, these rare variants (8/13) were enriched in the N-terminal region of the DLC1 isoform 1 protein. Seven of eight amino acids at the N-terminal variant positions were conserved among the primates. Among the 9 rare variants that were predicted as “damaging”, five were located at the N-terminal region. Ensuing in vitro functional assays showed that three private variants (Met360Lys, Glu418Lys and Asp554Val) impaired the ability of DLC1 to inhibit cell migration or altered the subcellular location of the protein compared to wild-type DLC1 isoform 1. These data suggest that DLC1 might act as a CHD-associated gene in addition to its role as a tumor suppressor in cancer. PMID:24587289

Eating disorder severity and functional impairment: moderating effects of illness duration in a clinical sample.

PubMed

Davidsen, Annika Helgadóttir; Hoyt, William T; Poulsen, Stig; Waaddegaard, Mette; Lau, Marianne

2017-09-01

The aim was to examine duration of illness and body mass index as possible moderators of the relationship between eating disorder severity and functional impairment, as well as psychological distress as a possible mediator of this relationship. The study included 159 patients diagnosed with bulimia nervosa, binge eating disorder or eating disorder not otherwise specified. Regression analysis was applied to assess the effect of the hypothesized moderators and mediators. Eating disorder severity was measured with the Eating Disorder Examination Questionnaire, functional impairment was measured with the Sheehan Disability Scale, and psychological distress was measured with the Symptom Check List-90-R. Duration of illness and body mass index were assessed clinically. Duration of illness significantly moderated the relationship between eating disorder severity and functional impairment; the relationship was strongest for patients with a shorter duration of illness. Psychological distress partly mediated the relationship between eating disorder severity and functional impairment. Duration of illness significantly moderated the relationship between psychological distress and functional impairment; the strongest relationship was seen for patients with a shorter duration of illness. Body mass index was not a significant moderator of the relationship between ED severity and functional impairment. Overall, this study established a link between ED severity, psychological distress and functional impairment indicating that both eating disorder severity and psychological distress are more strongly related to impaired role functioning for patients with more recent onset of an eating disorder. More research in the complex relationship between ED severity and functional impairment is needed.

Can the Nerve Growth Factor promote the reinnervation of the transplanted heart?

PubMed

Galli, Alessio

2014-02-01

The activity of the heart is widely regulated by the autonomous nervous system. This important mechanism of control may be impaired in chronic diseases such as heart failure or lost in those patients who undergo heart transplantation, owing to the surgical interruption of cardiac nerves in the transplanted heart. It has been demonstrated that spontaneous reinnervation can occur in transplanted hearts and is associated with an improvement in cardiac function. However, this process may require many years and the restoration of a proper cardiac innervation and functioning during exercise is never complete. In this perspective, the Nerve Growth Factor (NGF) and other neurotrophic hormones might ameliorate cardiac innervation in the transplanted heart and should be tried in animal models. Endothelial cells engineered with a viral vector to overexpress the NGF might be engrafted in the heart and integrate into cardiac small vessels, thus providing a source of neurotrophic factors which might promote and direct regrowth and axonal sprouting of cardiac nerves. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cardiac haemangioma associated with a duct-dependent congenital heart disease in a newborn infant.

PubMed

Djordjevic, Stefan A; Glumac, Sofija; Kalanj, Jasna

2017-07-01

Cardiac haemangiomas are exceedingly rare; however, they can cause significant haemodynamic impairment and disturbances in heart rhythm. Rarely, cardiac tumours may also coexist with congenital heart lesions. We present an extremely unusual case of a cardiac haemangioma in the setting of complex transposition of the great arteries that caused functional tricuspid atresia. To our knowledge, this is the first such case described in the literature.

8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish

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

Yan, Lifeng; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029; Zhou, Yong

Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes andmore » nkx2.5{sup +} cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits. - Highlights: • A key DNA repair enzyme ogg1 is expressed in the embryonic heart in zebrafish. • We found that ogg1 is essential for normal cardiac morphogenesis in zebrafish. • The production of embryonic cardiomyocytes requires appropriate ogg1 expression. • Ogg1 critically regulated proliferation of cardiac progenitor cells in zebrafish. • foxh1 is a partner of ogg1 in the cardiac development in response to DNA damage.« less

A new twist on an old idea part 2: cyclosporine preserves normal mitochondrial but not cardiomyocyte function in mini‐swine with compensated heart failure

PubMed Central

Hiemstra, Jessica A.; Gutiérrez‐Aguilar, Manuel; Marshall, Kurt D.; McCommis, Kyle S.; Zgoda, Pamela J.; Cruz‐Rivera, Noelany; Jenkins, Nathan T.; Krenz, Maike; Domeier, Timothy L.; Baines, Christopher P.; Emter, Craig A.

2014-01-01

Abstract We recently developed a clinically relevant mini‐swine model of heart failure with preserved ejection fraction (HFpEF), in which diastolic dysfunction was associated with increased mitochondrial permeability transition (MPT). Early diastolic function is ATP and Ca2+‐dependent, thus, we hypothesized chronic low doses of cyclosporine (CsA) would preserve mitochondrial function via inhibition of MPT and subsequently maintain normal cardiomyocyte Ca2+ handling and contractile characteristics. Left ventricular cardiomyocytes were isolated from aortic‐banded Yucatan mini‐swine divided into three groups; control nonbanded (CON), HFpEF nontreated (HF), and HFpEF treated with CsA (HF‐CsA). CsA mitigated the deterioration of mitochondrial function observed in HF animals, including functional uncoupling of Complex I‐dependent mitochondrial respiration and increased susceptibility to MPT. Attenuation of mitochondrial dysfunction in the HF‐CsA group was not associated with commensurate improvement in cardiomyocyte Ca2+ handling or contractility. Ca2+ transient amplitude was reduced and transient time to peak and recovery (tau) prolonged in HF and HF‐CsA groups compared to CON. Alterations in Ca2+ transient parameters observed in the HF and HF‐CsA groups were associated with decreased cardiomyocyte shortening and shortening rate. Cellular function was consistent with impaired in vivo systolic and diastolic whole heart function. A significant systemic hypertensive response to CsA was observed in HF‐CsA animals, and may have played a role in the accelerated the development of heart failure at both the whole heart and cellular levels. Given the significant detriment to cardiac function observed in response to CsA, our findings suggest chronic CsA treatment is not a viable therapeutic option for HFpEF. PMID:24963034

Functional abilities in older adults with mild cognitive impairment.

PubMed

Burton, Catherine L; Strauss, Esther; Bunce, David; Hunter, Michael A; Hultsch, David F

2009-01-01

A classification scheme and general set of criteria for diagnosing mild cognitive impairment (MCI) were recently proposed by a multidisciplinary group of experts who met at an international symposium on MCI. One of the proposed criteria included preserved basic activities of daily living and minimal impairment in complex instrumental activities of daily living (IADLs). To investigate whether older adults with MCI classified according to the subtypes identified by the Working Group (i.e. amnestic, single non-memory domain, and multiple domain with or without a memory component) differed from cognitively intact older adults on a variety of measures indexing IADLs and to examine how well measures of IADL predict concurrent MCI status. Two hundred and fifty community-dwelling older adults, ranging in age from 66 to 92, completed self-report measures of IADLs (Lawton and Brody IADL Scale, Scales of Independent Behaviour-Revised--SIB-R) and a measure of everyday problem solving indexing IADLs (Everyday Problems Test--EPT). Ratings of participants' IADL functioning were also obtained from informants (e.g. spouse, adult child and friend). Older adults with multiple-domain MCI demonstrated poorer IADL functioning than older adults with no cognitive impairment on the EPT and the SIB-R (both self- and informant-report versions). The multiple-domain MCI participants also demonstrated poorer IADLs than MCI participants with impairments in a single cognitive domain on the self-reported SIB-R and EPT. The single-domain MCI groups demonstrated poorer IADLs than older adults without cognitive impairment on the informant-reported SIB-R and EPT. No significant group differences were found on the Lawton and Brody IADL Scale. Using the EPT and SIB-R as predictors in a multinomial regression analysis, MCI group status was reliably predicted, but the classification rate was poor. Individuals with MCI demonstrated poorer IADL functioning compared to cognitively intact older adults

[Heart functions in monkeys during a 2-week antiorthostatic hypokinesia

NASA Technical Reports Server (NTRS)

Krotov, V. P.; Convertino, V.; Korol'kov, V. I.; Latham, R.; Trambovetskii, E. V.; Fanton, J.; Crisman, R.; Truzhennikov, A. N.; Evert, D.; Nosovskii, A. M.;

Insulin resistance is associated with impaired cardiac sympathetic innervation in patients with heart failure.

PubMed

Paolillo, S; Rengo, G; Pellegrino, T; Formisano, R; Pagano, G; Gargiulo, P; Savarese, G; Carotenuto, R; Petraglia, L; Rapacciuolo, A; Perrino, C; Piscitelli, S; Attena, E; Del Guercio, L; Leosco, D; Trimarco, B; Cuocolo, A; Perrone-Filardi, P

2015-10-01

Insulin resistance (IR) represents, at the same time, cause and consequence of heart failure (HF) and affects prognosis in HF patients, but pathophysiological mechanisms remain unclear. Hyperinsulinemia, which characterizes IR, enhances sympathetic drive, and it can be hypothesized that IR is associated with impaired cardiac sympathetic innervation in HF. Yet, this hypothesis has never been investigated. Aim of the present observational study was to assess the relationship between IR and cardiac sympathetic innervation in non-diabetic HF patients. One hundred and fifteen patients (87% males; 65 ± 11.3 years) with severe-to-moderate HF (ejection fraction 32.5 ± 9.1%) underwent iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy to assess sympathetic innervation and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) evaluation to determine the presence of IR. From (123)I-MIBG imaging, early and late heart to mediastinum (H/M) ratios and washout rate were calculated. Seventy-two (63%) patients showed IR and 43 (37%) were non-IR. Early [1.68 (IQR 1.53-1.85) vs. 1.79 (IQR 1.66-1.95); P = 0.05] and late H/M ratio [1.50 (IQR 1.35-1.69) vs. 1.65 (IQR 1.40-1.85); P = 0.020] were significantly reduced in IR compared with non-IR patients. Early and late H/M ratio showed significant inverse correlation with fasting insulinemia and HOMA-IR. Cardiac sympathetic innervation is more impaired in patients with IR and HF compared with matched non-IR patients. These findings shed light on the relationship among IR, HF, and cardiac sympathetic nervous system. Additional studies are needed to clarify the pathogenetic relationship between IR and HF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

The aftermath of terrorism: posttraumatic stress and functional impairment after the 2011 Oslo bombing

PubMed Central

Solberg, Øivind; Blix, Ines; Heir, Trond

2015-01-01

Objective: In the present study we wanted to investigate the link between exposure, posttraumatic stress symptomatology, and functional impairment in the aftermath of terrorism. Method: Posttraumatic stress symptomatology and functional impairment related to the Oslo bombing 22nd of July, 2011, in directly and indirectly exposed individuals (N = 1927) were assessed together with demographics, exposure, peri-traumatic reactions, and event centrality approximately 1 year after the attack. Results: Directly and indirectly exposed individuals qualifying for posttraumatic stress disorder (PTSD) reported similar peri-traumatic reactions, event centrality, and functional impairment. However, clusters within the PTSD symptomatology were differentially associated with impairment as a function of their exposure. In the directly exposed group, all clusters within the PTSD symptomatology were associated with impairment in function, while only emotional numbing was associated with impairment within the indirectly exposed group. Conclusion: Considering that terror attacks frequently involve directly exposed individuals and a larger population of indirectly exposed individuals, this finding is of importance, especially in the design of intervention programs and the development of treatment policies. PMID:26300833

Exploring Heart and Lung Function in Space: ARMS Experiments

NASA Technical Reports Server (NTRS)

Kuipers, Andre; Cork, Michael; LeGouic, Marine

2002-01-01

The Advanced Respiratory Monitoring System (ARMS) is a suite of monitoring instruments and supplies used to study the heart, lungs, and metabolism. Many experiments sponsored by the European Space Agency (ESA) will be conducted using ARMS during STS-107. The near-weightless environment of space causes the body to undergo many physiological adaptations, and the regulation of blood pressure is no exception. Astronauts also experience a decrease in blood volume as an adaptation to microgravity. Reduced blood volume may not provide enough blood pressure to the head during entry or landing. As a result, astronauts often experience light-headedness, and sometimes even fainting, when they stand shortly after returning to Earth. To help regulate blood pressure and heart rate, baroreceptors, sensors located in artery walls in the neck and near the heart, control blood pressure by sending information to the brain and ensuring blood flow to organs. These mechanisms work properly in Earth's gravity but must adapt in the microgravity environment of space. However, upon return to Earth during entry and landing, the cardiovascular system must readjust itself to gravity, which can cause fluctuation in the control of blood pressure and heart rate. Although the system recovers in hours or days, these occurrences are not easily predicted or understood - a puzzle investigators will study with the ARMS equipment. In space, researchers can focus on aspects of the cardiovascular system normally masked by gravity. The STS-107 experiments using ARMS will provide data on how the heart and lungs function in space, as well as how the nervous system controls them. Exercise will also be combined with breath holding and straining (the Valsalva maneuver) to test how heart rate and blood pressure react to different stresses. This understanding will improve astronauts' cardiopulmonary function after return to Earth, and may well help Earthbound patients who experience similar effects after long

The Brief Impairment Scale (Bis): A Multidimensional Scale of Functional Impairment for Children and Adolescents.

ERIC Educational Resources Information Center

Bird, Hector R.; Canino, Glorisa J.; Davies, Mark; Ramirez, Rafael; Chavez, Ligia; Duarte, Cristiane; Shen, Sa

2005-01-01

Objective: This article provides the results of the psychometric testing of the Brief Impairment Scale (BIS). The BIS is a 23-item instrument that evaluates three domains of functioning: interpersonal relations, school/work functioning, and self-care/self-fulfilment. It capitalizes on the strengths of existing global measures while addressing some…

Functional Impairment and Changes in Depression Subtypes for Women in STAR*D: A Latent Transition Analysis

PubMed Central

Rothschild, Anthony J.; Lapane, Kate L.

2016-01-01

Abstract Objective: To characterize the association between functional impairment and major depression subtypes at baseline and to characterize changes in subtypes by functional impairment level in women receiving citalopram in level 1 of the Sequenced Treatment Alternatives to Relieve Depression trial. Method: Women who completed baseline and week 12 study visits were included. Items from the self-reported Quick Inventory of Depressive Symptomatology were used to define the latent depression subtypes. The Work and Social Adjustment Scale was used to classify baseline functional impairment. A latent transition analysis model provided estimates of the prevalence of subtype membership and transition probabilities by functional impairment level. Results: Of the 755 women included, 69% had major functional impairment at baseline. Regardless of functional impairment level, the subtypes were differentiated by depression severity, appetite changes, psychomotor disturbances, and insomnia. Sixty-seven percent of women with normal/significant functional impairment and 60% of women with major impairment were likely to transition to a symptom resolution subtype at week 12. Women with baseline major impairment who were in the severe with psychomotor agitation subtype at the beginning of the study were least likely to transition to the symptom resolution subtype (4% chance). Conclusions: Functional impairment level was related to both the baseline depression subtype and the likelihood of moving to a different subtype. These results underscore the need to incorporate not only depression symptoms but also functioning in the assessment and treatment of depression. PMID:26488110

Neurocognitive and executive functioning in adult survivors of congenital heart disease.

PubMed

Klouda, Leda; Franklin, Wayne J; Saraf, Anita; Parekh, Dhaval R; Schwartz, David D

2017-01-01

Congenital heart disease (CHD) can affect the developing central nervous system, resulting in neurocognitive and behavioral deficits. Preoperative neurological abnormalities as well as sequelae of the open heart operations required to correct structural abnormalities of the heart contribute to these deficits. There are few studies examining the neurocognitive functioning of adults with CHD. This study sought to investigate multiple domains of neurocognitive functioning in adult survivors of CHD who had childhood cardiac surgery with either moderate or severe disease complexity. A total of 48 adults (18-49 years of age) who had undergone cardiac surgery for CHD prior to five years of age participated in the study. CHD severity was classified as moderate or severe according to the 32nd Bethesda Guidelines. A computerized battery of standardized neurocognitive tests (CNS-Vital Signs), a validated rating scale of executive functioning, and demographic questionnaires were administered. There were no significant differences between the moderate CHD group and normative data on any cognitive measure. In contrast, the severe CHD group differed from norms in multiple domains: psychomotor speed, processing speed, complex attention, reaction time, and on the overall neurocognitive index. Number of surgeries was strongly related to worse executive functioning. There was no association between age at first surgery or time since last surgery and neuropsychological functioning. Number of surgeries was also unrelated to neurocognitive test performance. Patients with severe CHD performed significantly worse on measures of processing speed, attention, and executive functioning. These findings may be useful in the long-term care of adults with congenital heart disease. © 2016 Wiley Periodicals, Inc.

Heart Rate Recovery, Physical Activity Level, and Functional Status in Subjects With COPD.

PubMed

Morita, Andrea A; Silva, Laís K O; Bisca, Gianna W; Oliveira, Joice M; Hernandes, Nidia A; Pitta, Fabio; Furlanetto, Karina C

2018-05-15

A normal heart rate reflects the balance between the sympathetic and parasympathetic autonomic nervous system. When the difference between heart rate at the end of an exercise test and after 1 min of recovery, known as the 1-min heart rate recovery, is ≤ 12 beats/min, this may indicate an abnormal delay. We sought to compare physical activity patterns and subjects' functional status with COPD with or without delayed 1-min heart rate recovery after the 6-min walk test (6MWT). 145 subjects with COPD (78 men, median [interquartile range (IQR)] age 65 [60-73] y, body mass index 25 [21-30] kg/m 2 , FEV 1 45 ± 15% predicted) were underwent the following assessments: spirometry, 6MWT, functional status, and physical activity in daily life (PADL). A delayed heart rate recovery of 1 min was defined as ≤ 12 beats/min. Subjects with delayed 1-min heart rate recovery walked a shorter distance in the 6MWT compared to subjects without delayed heart rate recovery (median [IQR] 435 [390-507] m vs 477 [425-515] m, P = .01; 81 [71-87] vs 87 [79-98]% predicted, P = .002). Regarding PADL, subjects with delayed heart rate recovery spent less time in the standing position (mean ± SD 185 ± 89 min vs 250 ± 107 min, P = .002) and more time in sedentary positions (472 ± 110 min vs 394 ± 129 min, P = .002). Scores based on the self-care domain of the London Chest Activity of Daily Living questionnaire and the activity domain of the Pulmonary Functional Status and Dyspnea questionnaire were also worse in the group with delayed heart rate recovery (6 ± 2 points vs 5 ± 2 points; P = .039 and 29 ± 24 points vs 19 ± 17 points; P = .037, respectively). Individuals with COPD who exhibit delayed 1-min heart rate recovery after the 6MWT exhibited worse exercise capacity as well as a more pronounced sedentary lifestyle and worse functional status than those without delayed heart rate recovery. Despite its assessment simplicity, heart rate recovery after the 6MWT can be further explored

Neural origins of psychosocial functioning impairments in major depression.

PubMed

Pulcu, Erdem; Elliott, Rebecca

2015-09-01

Major depressive disorder, a complex neuropsychiatric condition, is associated with psychosocial functioning impairments that could become chronic even after symptoms remit. Social functioning impairments in patients could also pose coping difficulties to individuals around them. In this Personal View, we trace the potential neurobiological origins of these impairments down to three candidate domains-namely, social perception and emotion processing, motivation and reward value processing, and social decision making. We argue that the neural basis of abnormalities in these domains could be detectable at different temporal stages during social interactions (eg, before and after decision stages), particularly within frontomesolimbic networks (ie, frontostriatal and amygdala-striatal circuitries). We review some of the experimental designs used to probe these circuits and suggest novel, integrative approaches. We propose that an understanding of the interactions between these domains could provide valuable insights for the clinical stratification of major depressive disorder subtypes and might inform future developments of novel treatment options in return. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of thyroid hormones on the heart.

PubMed

Vargas-Uricoechea, Hernando; Bonelo-Perdomo, Anilsa; Sierra-Torres, Carlos Hernán

2014-01-01

Thyroid hormones have a significant impact on heart function, mediated by genomic and non-genomic effects. Consequently, thyroid hormone deficiencies, as well as excesses, are expected to result in profound changes in cardiac function regulation and cardiovascular hemodynamics. Thyroid hormones upregulate the expression of the sarcoplasmic reticulum calcium-activated ATPase and downregulate the expression of phospholamban. Overall, hyperthyroidism is characterized by an increase in resting heart rate, blood volume, stroke volume, myocardial contractility, and ejection fraction. The development of "high-output heart failure" in hyperthyroidism may be due to "tachycardia-mediated cardiomyopathy". On the other hand, in a hypothyroid state, thyroid hormone deficiency results in lower heart rate and weakening of myocardial contraction and relaxation, with prolonged systolic and early diastolic times. Cardiac preload is decreased due to impaired diastolic function. Cardiac afterload is increased, and chronotropic and inotropic functions are reduced. Subclinical thyroid dysfunction is relatively common in patients over 65 years of age. In general, subclinical hypothyroidism increases the risk of coronary heart disease (CHD) mortality and CHD events, but not of total mortality. The risk of CHD mortality and atrial fibrillation (but not other outcomes) in subclinical hyperthyroidism is higher among patients with very low levels of thyrotropin. Finally, medications such as amiodarone may induce hypothyroidism (mediated by the Wolff-Chaikoff), as well as hyperthyroidism (mediated by the Jod-Basedow effect). In both instances, the underlying cause is the high concentration of iodine in this medication. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

The association between atrial fibrillation and cognitive function in patients with heart failure.

PubMed

Yang, Huifeng; Niu, Weihua; Zang, Xiaoying; Lin, Mei; Zhao, Yue

2017-02-01

Atrial fibrillation (AF) is associated with cognitive impairment in heart failure (HF). The purpose of this study was to examine whether AF independently predicted cognitive function in HF patients after controlling for more demographic, medical and psychological characteristics, and whether the timing of AF onset in relation to HF diagnosis independently contributed to cognitive function in HF patients with AF. A total of 188 hospitalized HF patients (62.8% male, age 66.3±10.6 years) completed cognitive function assessment with the Montreal Cognitive Assessment (MoCA). A history of AF, along with other medical characteristics, was ascertained through a review of participants' medical charts. The timing of AF onset in relation to HF diagnosis was categorized into AF occurring prior to HF diagnosis (i.e. prior AF) and AF developing after HF diagnosis (i.e. incident AF). Altogether 72 participants had a positive diagnostic history of AF. Specifically, 41 had prior AF, and 31 developed AF subsequently. In HF patients, AF was associated with poorer performance on cognitive function after controlling for more confounders (β=-0.112, ΔR 2 =0.010, p=0.046). Among HF patients with AF, incident AF independently predicted poorer cognitive function (β=-0.238, ΔR 2 =0.027, p=0.047). AF independently contributes to cognitive function in HF patients after adjusting for more confounding variables. The timing of AF onset in relation to HF diagnosis independently predicts cognitive function in HF patients with AF. Prospective studies are needed to elucidate possible mechanisms for the association between AF and cognitive function in HF populations.

Restoring heart function and electrical integrity: closing the circuit

NASA Astrophysics Data System (ADS)

Monteiro, Luís Miguel; Vasques-Nóvoa, Francisco; Ferreira, Lino; Pinto-do-Ó, Perpétua; Nascimento, Diana Santos

2017-04-01

Cardiovascular diseases are the main cause of death in the world and are often associated with the occurrence of arrhythmias due to disruption of myocardial electrical integrity. Pathologies involving dysfunction of the specialized cardiac excitatory/conductive tissue are also common and constitute an added source of morbidity and mortality since current standard therapies withstand a great number of limitations. As electrical integrity is essential for a well-functioning heart, innovative strategies have been bioengineered to improve heart conduction and/or promote myocardial repair, based on: (1) gene and/or cell delivery; or (2) conductive biomaterials as tools for cardiac tissue engineering. Herein we aim to review the state-of-art in the area, while briefly describing the biological principles underlying the heart electrical/conduction system and how this system can be disrupted in heart disease. Suggestions regarding targets for future studies are also presented.

Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment.

PubMed

Löwe, Bernd; Spitzer, Robert L; Williams, Janet B W; Mussell, Monika; Schellberg, Dieter; Kroenke, Kurt

2008-01-01

To determine diagnostic overlap of depression, anxiety and somatization as well as their unique and overlapping contribution to functional impairment. Two thousand ninety-one consecutive primary care clinic patients participated in a multicenter cross-sectional survey in 15 primary care clinics in the United States (participation rate, 92%). Depression, anxiety, somatization and functional impairment were assessed using validated scales from the Patient Health Questionnaire (PHQ) (PHQ-8, eight-item depression module; GAD-7, seven-item Generalized Anxiety Disorder Scale; and PHQ-15, 15-item somatic symptom scale) and the Short-Form General Health Survey (SF-20). Multiple linear regression analyses were used to investigate unique and overlapping associations of depression, anxiety and somatization with functional impairment. In over 50% of cases, comorbidities existed between depression, anxiety and somatization. The contribution of the commonalities of depression, anxiety and somatization to functional impairment substantially exceeded the contribution of their independent parts. Nevertheless, depression, anxiety and somatization did have important and individual effects (i.e., separate from their overlap effect) on certain areas of functional impairment. Given the large syndrome overlap, a potential consideration for future diagnostic classification would be to describe basic diagnostic criteria for a single overarching disorder and to optionally code additional diagnostic features that allow a more detailed classification into specific depressive, anxiety and somatoform subtypes.

Functional Impairment: An Unmeasured Marker of Medicare Costs for Postacute Care of Older Adults.

PubMed

Greysen, S Ryan; Stijacic Cenzer, Irena; Boscardin, W John; Covinsky, Kenneth E

2017-09-01

To assess the effects of preadmission functional impairment on Medicare costs of postacute care up to 365 days after hospital discharge. Longitudinal cohort study. Health and Retirement Study (HRS). Nationally representative sample of 16,673 Medicare hospitalizations of 8,559 community-dwelling older adults from 2000 to 2012. The main outcome was total Medicare costs in the year after hospital discharge, assessed according to Medicare claims data. The main predictor was functional impairment (level of difficulty or dependence in activities of daily living (ADLs)), determined from HRS interview preceding hospitalization. Multivariable linear regression was performed, adjusted for age, race, sex, income, net worth, and comorbidities, with clustering at the individual level to characterize the association between functional impairment and costs of postacute care. Unadjusted mean Medicare costs for 1 year after discharge increased with severity of impairment in a dose-response fashion (P < .001 for trend); 68% had no functional impairment ($25,931), 17% had difficulty with one ADL ($32,501), 7% had dependency in one ADL ($39,928), and 8% had dependency in two or more ADLs ($45,895). The most severely impaired participants cost 77% more than those with no impairment; adjusted analyses showed attenuated effect size (33% more) but no change in trend. Considering costs attributable to comorbidities, only three conditions were more expensive than severe functional impairment (lymphoma, metastatic cancer, paralysis). Functional impairment is associated with greater Medicare costs for postacute care and may be an unmeasured but important marker of long-term costs that cuts across conditions. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Effect of Methamphetamine Dependence on Heart Rate Variability

PubMed Central

Henry, Brook L.; Minassian, Arpi; Perry, William

2010-01-01

Background Methamphetamine (METH) is an increasing popular and highly addictive stimulant associated with autonomic nervous system (ANS) dysfunction, cardiovascular pathology, and neurotoxicity. Heart rate variability (HRV) has been used to assess autonomic function and predict mortality in cardiac disorders and drug intoxication, but has not been characterized in METH use. We recorded HRV in a sample of currently abstinent individuals with a history of METH dependence compared to age- and gender-matched drug-free comparison subjects. Method HRV was assessed using time domain, frequency domain, and nonlinear entropic analyses in 17 previously METH-dependent and 21 drug-free comparison individuals during a 5 minute rest period. Results The METH-dependent group demonstrated significant reduction in HRV, reduced parasympathetic activity, and diminished heartbeat complexity relative to comparison participants. More recent METH use was associated with increased sympathetic tone. Conclusion Chronic METH exposure may be associated with decreased HRV, impaired vagal function, and reduction in heart rate complexity as assessed by multiple methods of analysis. We discuss and review evidence that impaired HRV may be related to the cardiotoxic or neurotoxic effects of prolonged METH use. PMID:21182570

Functional Hubs in Mild Cognitive Impairment

NASA Astrophysics Data System (ADS)

Navas, Adrián; Papo, David; Boccaletti, Stefano; Del-Pozo, F.; Bajo, Ricardo; Maestú, Fernando; Martínez, J. H.; Gil, Pablo; Sendiña-Nadal, Irene; Buldú, Javier M.

We investigate how hubs of functional brain networks are modified as a result of mild cognitive impairment (MCI), a condition causing a slight but noticeable decline in cognitive abilities, which sometimes precedes the onset of Alzheimer's disease. We used magnetoencephalography (MEG) to investigate the functional brain networks of a group of patients suffering from MCI and a control group of healthy subjects, during the execution of a short-term memory task. Couplings between brain sites were evaluated using synchronization likelihood, from which a network of functional interdependencies was constructed and the centrality, i.e. importance, of their nodes was quantified. The results showed that, with respect to healthy controls, MCI patients were associated with decreases and increases in hub centrality respectively in occipital and central scalp regions, supporting the hypothesis that MCI modifies functional brain network topology, leading to more random structures.

Comparison of residual depressive symptoms and functional impairment between fully and partially remitted patients with major depressive disorder: a multicenter study.

PubMed

Xiao, Le; Feng, Lei; Zhu, Xue-Quan; Feng, Yuan; Wu, Wen-Yuan; Ungvari, Gabor S; Ng, Chee H; Xiang, Yu-Tao; Wang, Gang

2018-03-01

This study compared residual depressive and somatic symptoms and functional impairment between remitted and partially remitted patients with major depressive disorder (MDD), and explored the associations of functioning with demographic and clinical characteristics including residual depressive symptoms. Altogether, 1503 outpatients with MDD formed the study sample. Residual symptoms and psychosocial functioning were measured using standardized instruments. Approximately half (51.2%) of the patients who responded to antidepressant treatment achieved remission ('remitters'), while the rest who responded to treatment achieved only partial remission ('non-remitters'). Residual mood symptoms in remitters included sleep disturbances (66.6%), fatigue (32.3%), decreased concentration (31.3%), appetite/weight disturbances (28.8%), psychomotor changes (23.2%), sad mood (21.9%) and loss of interest (21.1%) measured by the Quick Inventory of Depressive Symptomatology-Self-Report. Residual somatic symptoms included headache (31.9%), intestinal complaints (31.3%), heart pounding/racing (26.3%), gastric complaints (22.3%), dizziness (22.2%) and stomach pain (20.6%) measured by the Patient Health Questionnaire-15. Such residual symptoms were even more frequent in the 'non-remitters' group. Residual symptoms of fatigue, psychomotor changes, sleep disturbance and appetite/weight disturbance contributed to impairment of all functional domains. Given the negative impact of residual symptoms on psychosocial functioning, more attention needs to be paid to the assessment and treatment of residual depressive symptoms. Copyright © 2018 Elsevier B.V. All rights reserved.

Impaired Kidney Function and Associated Factors Among Rural Adults With Disabilities in Taiwan.

PubMed

Chen, Chu-Yeh; Chiu, Wen-Nan; Lin, Yu-Chen; Jane, Sui-Hwi; Chiang, Hsin-Hung; Chen, Mei-Yen

2017-04-01

The results of numerous studies indicate that people with disabilities seek more healthcare than those who are not disabled, particularly for conditions such as chronic kidney disease, cardiovascular disease, and obesity. However, little is known about the incidence of impaired kidney function and its associated factors among adults with disabilities in Taiwan. The aim of this study was to explore the prevalence and factors associated with impaired kidney function among adults with disabilities. This descriptive study was nurse led and was conducted as part of a health promotion program for disadvantaged rural adults with disabilities in Chiayi County, Taiwan. Health screening and a health needs survey were conducted between July and December 2013. Kidney function, physiological biomarkers, health-related behaviors, and demographic characteristics were examined. Eight hundred ten rural adults with disabilities were enrolled. The most common disabilities included physical-related disability (33.1%), intellectual-related disability (26.7%), and hearing and vision impairment (18.6%). The prevalence of impaired kidney function in this population was 85%. According to classification for chronic kidney disease, 68.6% were in Stages 1-2, and 16.8% were in Stages 3-4. Univariate analysis showed that impaired kidney function was significantly associated with lower educational level (p < .001), hearing or vision impairment (p < .001), being overweight or obese (p < .05), high systolic blood pressure (p < .01), fasting blood glucose (p < .001), total cholesterol (p < .001), total triglyceride (p < .05), older age (p < .001), smoking (p < .05), chewing betel nuts (p = .001), and low levels of participation in social activities (p < .05). The final logistic regression model showed that residents with disabilities who were older or had less education, high fasting blood glucose, and high total cholesterol tended to have impaired kidney function after adjustment for other

Obesity and functional impairment: influence of comorbidity, joint pain, and mental health.

PubMed

Heo, Moonseong; Pietrobelli, Angelo; Wang, Dan; Heymsfield, Steven B; Faith, Myles S

2010-10-01

To examine the relationship between obesity and functional impairment and the influence of comorbidity, joint pain, and mental health on this association, we used US adult respondents (N = 430,912) to the 2007 Behavioral Risk Factor Surveillance Survey (BRFSS-07). Functional impairment was indicated if a respondent was either (i) limited in any way or in any activities because of physical, mental, or emotional problems, or (ii) had any health problem that required using special equipment such as a cane, wheelchair, special bed, or special telephone. Approximately 62.8% of respondents were overweight or obese and 20.3% were functionally impaired. The unadjusted relationship between obesity and functional impairment revealed a classical J-shaped pattern with odds ratios (95% confidence interval) compared to the normal weight group: 1.63 (1.54-1.73), 1.22 (1.20-1.25), 1.77 (1.73-1.81), 2.43 (2.36-2.51), and 4.12 (3.97-4.27) for underweight, overweight, obesity class I, II, and III, respectively. Although inclusion of different combinations of sociodemographic and medical covariates substantially attenuated the unadjusted association, the collective inclusion of all covariates in a single model did not eliminate the significant J-shaped association resulting in the following corresponding adjusted odds ratios: 1.19 (1.13-1.25), 1.01 (0.99-1.04), 1.23 (1.19-1.27), 1.38 (1.32-1.44), and 1.92 (1.82-2.02). The attenuation was mostly influenced by medical comorbidity. In conclusion, functional impairment is associated with obesity, primarily due to medical comorbidity conditions. The significant residual association highlights the importance of sustainable obesity prevention and treatment at both the individual and public level as functional impairment can create burdens at individual, familial, and societal levels.

A novel 'splice site' HCN4 Gene mutation, c.1737+1 G>T, causes familial bradycardia, reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability.

PubMed

Hategan, Lidia; Csányi, Beáta; Ördög, Balázs; Kákonyi, Kornél; Tringer, Annamária; Kiss, Orsolya; Orosz, Andrea; Sághy, László; Nagy, István; Hegedűs, Zoltán; Rudas, László; Széll, Márta; Varró, András; Forster, Tamás; Sepp, Róbert

2017-08-15

The most important molecular determinant of heart rate regulation in sino-atrial pacemaker cells includes hyperpolarization-activated, cyclic nucleotide-gated ion channels, the major isoform of which is encoded by the HCN4 gene. Mutations affecting the HCN4 gene are associated primarily with sick sinus syndrome. A novel c.1737+1 G>T 'splice-site' HCN4 mutation was identified in a large family with familial bradycardia which co-segregated with the disease providing a two-point LOD score of 4.87. Twelve out of the 22 investigated family members [4 males, 8 females average age 36 (SD 6) years] were considered as clinically affected (heart rate<60/min on resting ECG). Minimum [36 (SD 7) vs. 47 (SD 5) bpm, p=0.0087) and average heart rates [62 (SD 8) vs. 73 (SD 8) bpm, p=0.0168) were significantly lower in carriers on 24-hour Holter recordings. Under maximum exercise test carriers achieved significantly lower heart rates than non-carrier family members, and percent heart rate reserve and percent corrected heart rate reserve were significantly lower in carriers. Applying rigorous criteria for chronotropic incompetence a higher number of carriers exhibited chronotropic incompetence. Parameters, characterizing short-term variability of heart rate (i.e. rMSSD and pNN50%) were increased in carrier family members, even after normalization for heart rate, in the 24-hour ECG recordings with the same relative increase in 5-minute recordings. The identified novel 'splice site' HCN4 gene mutation, c.1737+1 G>T, causes familial bradycardia and leads to reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability in the mutation carriers. Copyright © 2017 Elsevier B.V. All rights reserved.

Cognitive impairments associated with CFS and POTS.

PubMed

Shanks, Lindzi; Jason, Leonard A; Evans, Meredyth; Brown, Abigail

2013-01-01

Chronic fatigue syndrome (CFS) is characterized by fatigue, sleep dysfunction, and cognitive deficits (Fukuda et al., 1994). Research surrounding cognitive functioning among patients with CFS has found difficulty with memory, attention, and information processing. A similar disorder, postural tachycardia syndrome (POTS), is characterized by increased heart rate, fatigue, and mental cloudiness (Raj et al., 2009). Potential implications of cognitive deficits for patients with CFS and/or POTS are discussed, including difficulties with school and/or employment. A few biological theories (i.e., kindling, impairments in the central nervous system, and difficulty with blood flow) have emerged as potential explanations for the cognitive deficits reported in both CFS and POTS Future research should continue to examine possible explanations for cognitive impairments in CFS and POTS, and ultimately use this information to try and reduce cognitive impairments for these patients.

Reduced global brain metabolism but maintained vascular function in amnestic mild cognitive impairment.

PubMed

Thomas, Binu P; Sheng, Min; Tseng, Benjamin Y; Tarumi, Takashi; Martin-Cook, Kristen; Womack, Kyle B; Cullum, Munro C; Levine, Benjamin D; Zhang, Rong; Lu, Hanzhang

2017-04-01

Amnestic mild cognitive impairment represents an early stage of Alzheimer's disease, and characterization of physiological alterations in mild cognitive impairment is an important step toward accurate diagnosis and intervention of this condition. To investigate the extent of neurodegeneration in patients with mild cognitive impairment, whole-brain cerebral metabolic rate of oxygen in absolute units of µmol O 2 /min/100 g was quantified in 44 amnestic mild cognitive impairment and 28 elderly controls using a novel, non-invasive magnetic resonance imaging method. We found a 12.9% reduction ( p = 0.004) in cerebral metabolic rate of oxygen in mild cognitive impairment, which was primarily attributed to a reduction in the oxygen extraction fraction, by 10% ( p = 0.016). Global cerebral blood flow was not found to be different between groups. Another aspect of vascular function, cerebrovascular reactivity, was measured by CO 2 -inhalation magnetic resonance imaging and was found to be equivalent between groups. Therefore, there seems to be a global, diffuse diminishment in neural function in mild cognitive impairment, while their vascular function did not show a significant reduction.

TRPV2 is critical for the maintenance of cardiac structure and function in mice

PubMed Central

Katanosaka, Yuki; Iwasaki, Keiichiro; Ujihara, Yoshihiro; Takatsu, Satomi; Nishitsuji, Koki; Kanagawa, Motoi; Sudo, Atsushi; Toda, Tatsushi; Katanosaka, Kimiaki; Mohri, Satoshi; Naruse, Keiji

2014-01-01

The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca2+ handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca2+-dependent intracellular Ca2+ increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function. PMID:24874017

TRPV2 is critical for the maintenance of cardiac structure and function in mice.

PubMed

Katanosaka, Yuki; Iwasaki, Keiichiro; Ujihara, Yoshihiro; Takatsu, Satomi; Nishitsuji, Koki; Kanagawa, Motoi; Sudo, Atsushi; Toda, Tatsushi; Katanosaka, Kimiaki; Mohri, Satoshi; Naruse, Keiji

2014-05-29

The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca(2+) handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca(2+)-dependent intracellular Ca(2+) increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function.

Executive Function and Internalizing Symptoms in Adolescents and Young Adults With Congenital Heart Disease: The Role of Coping.

PubMed

Jackson, Jamie L; Gerardo, Gina M; Monti, Jennifer D; Schofield, Kyle A; Vannatta, Kathryn

2018-01-10

Executive functioning deficits have been documented among congenital heart disease (CHD) survivors and may contribute to emotional distress. Little research has investigated the role of coping in this association. This study examined the role of coping in accounting for the association between self-reported executive function problems and internalizing symptoms among adolescents and emerging adults (AEAs), as well as young adults (YAs) with CHD. Participants included 74 AEA ( M age  = 19.32  ±  3.47 years, range 15-25 years) and 98 YA CHD survivors ( M age  = 32.00  ±  3.69 years, range 26-39 years), recruited from pediatric and adult outpatient cardiology clinics. Participants completed self-report measures of executive function problems, coping (primary control, secondary control, and disengagement coping), and internalizing symptoms. Lesion severity classification and functional impairment due to symptoms of heart failure were determined from medical chart review. Significant problems in executive function were reported by 5% of AEA and 13% of YA. Coping was not associated with executive function problems or internalizing symptoms for AEA. However, among YA, less use of adaptive coping strategies and more maladaptive coping responses was associated with both more executive function problems and internalizing symptoms. An indirect effect of executive function problems on internalizing symptoms via secondary control coping emerged for YA. Executive function problems may disrupt the ability to use important adaptive coping skills, such as cognitive reappraisal, positive thinking, and acceptance, thereby resulting in greater emotional distress among YA CHD survivors. © The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth.

PubMed

Alphonse, Rajesh S; Vadivel, Arul; Fung, Moses; Shelley, William Chris; Critser, Paul John; Ionescu, Lavinia; O'Reilly, Megan; Ohls, Robin K; McConaghy, Suzanne; Eaton, Farah; Zhong, Shumei; Yoder, Merv; Thébaud, Bernard

2014-05-27

Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or alveolar destruction. Both conditions lack effective therapies. Angiogenic growth factors promote alveolar growth and contribute to alveolar maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating and resident endothelial cells capable of self-renewal and de novo vessel formation. We hypothesized that resident ECFCs exist in the developing lung, that they are impaired during arrested alveolar growth in experimental bronchopulmonary dysplasia, and that exogenous ECFCs restore disrupted alveolar growth. Human fetal and neonatal rat lungs contain ECFCs with robust proliferative potential, secondary colony formation on replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In contrast, human fetal lung ECFCs exposed to hyperoxia in vitro and neonatal rat ECFCs isolated from hyperoxic alveolar growth-arrested rat lungs mimicking bronchopulmonary dysplasia proliferated less, showed decreased clonogenic capacity, and formed fewer capillary-like networks. Intrajugular administration of human cord blood-derived ECFCs after established arrested alveolar growth restored lung function, alveolar and lung vascular growth, and attenuated pulmonary hypertension. Lung ECFC colony- and capillary-like network-forming capabilities were also restored. Low ECFC engraftment and the protective effect of cell-free ECFC-derived conditioned media suggest a paracrine effect. Long-term (10 months) assessment of ECFC therapy showed no adverse effects with persistent improvement in lung structure, exercise capacity, and pulmonary hypertension. Impaired ECFC function may contribute to arrested alveolar growth. Cord blood-derived ECFC therapy may offer new therapeutic options for lung diseases characterized by alveolar damage. © 2014 American Heart Association, Inc.

Comparison of Spontaneously Elicited Language Patterns in Specific Language Impairment and High-Functioning Autism.

PubMed

Craig, Megan; Trauner, Doris

2018-02-01

We aimed to characterize differences in the use of language in children with specific language impairment and high-functioning autism by analyzing verbal responses on standardized tests. The overall goal was to provide clinicians with additional tools with which to aid in distinguishing the two neurodevelopmental disorders. This study included 16 children with specific language impairment, 28 children with high-functioning autism, and 52 typically developing participants between the ages of six and 14. Groups were matched for age, and specific language impairment and high-functioning autism groups were matched on verbal and performance IQ. Responses from standardized tests were examined for response length, grammatical errors, filler words, perseverations, revisions (repeated attempts to begin or continue a sentence), off-topic attention shifts (lapses in attention to the task), and rambling. Data were analyzed using parametric and nonparametric methods. Specific language impairment responses were longer and contained more filler words than did those of the other two groups, whereas high-functioning autism responses exhibited more grammatical errors, off-topic attention shifts, and rambling. Specific language impairment and high-functioning autism responses showed higher rates of perseveration compared with controls. There were no significant differences in revisions among the three groups. Differences in language patterns of participants with specific language impairment and high-functioning autism may be useful to the clinician in helping to differentiate isolated language impairment from high-functioning autism. The results also support the conclusion that the two conditions are separable, and each exhibits a different pattern of language dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

Hypothyroidism-induced myocardial damage and heart failure: an overlooked entity.

PubMed

Shuvy, Mony; Shifman, Oshrat E Tayer; Nusair, Samir; Pappo, Orit; Lotan, Chaim

2009-01-01

Hypothyroid state may induce cardiac muscle impairment such as diastolic dysfunction and abnormal relaxation time. Advanced heart failure in hypothyroid patients has been described only in severe symptomatic cases, mostly during myxedematous coma. We describe an unusual case of asymptomatic patient with hypothyroidism who presented with severely reduced cardiac function with elevated cardiac enzymes reflecting significant myocardial injury. Comprehensive evaluation for heart failure was suggestive only for long-standing untreated hypothyroidism. Endomyocadial biopsy demonstrated unique histological findings of mucopolysaccharide accumulation attributed to hypothyroid state. Asymptomatic hypothyroidism may cause severe reduction in cardiac function accompanied with elevated cardiac enzymes. To our knowledge, this is the first description of human myocardial biopsy revealing mucopolysaccharide accumulation attributed to hypothyroid state.

How Does Subclinical Hyperthyroidism Affect Right Heart Function and Mechanics?

PubMed

Tadic, Marijana; Celic, Vera; Cuspidi, Cesare; Ilic, Sanja; Zivanovic, Vladimir; Marjanovic, Tamara

2016-02-01

Right heart function and mechanics have not been investigated in patients with subclinical hyperthyroidism. Our aim was to investigate right ventricular (RV) and right atrial (RA) function and deformation as evaluated by 3-dimensional echocardiography (3DE) and speckle-tracking 2-dimensional echocardiography (2DE) in these individuals. We included 39 untreated women with endogenous subclinical hyperthyroidism and 39 healthy women matched by age. All participants underwent laboratory analyses that included thyroid hormone levels and comprehensive 2DE and 3DE examinations. Three-dimensional echocardiographic RV volumes were significantly elevated in the patients with subclinical hyperthyroidism (P < .05), whereas the 3DE RV ejection fraction was reduced in this group, but with borderline significance. Two-dimensional echocardiographic longitudinal RV and RA strain were significantly reduced in the patients with subclinical hyperthyroidism. Two-dimensional echocardiographic RV systolic and early diastolic strain rates were reduced, whereas late diastolic strain rates were increased in the patients with subclinical hyperthyroidism. The same changes were detected in RA mechanics among the patients with subclinical hyperthyroidism. The thyrotropin (TSH) level correlated with the left ventricular mass index, transmitral early diastolic peak flow velocity (E)/late diastolic flow velocity (A) ratio, tricuspid E/A ratio, 2DE RV global strain, 2DE RA, strain, and 3DE RV end-diastolic volume. A multivariate regression analysis showed that the mitral E/A ratio, 2DE RV global strain, and 3DE RV end-diastolic volume were independently associated with the TSH level. Right ventricular and RA function as evaluated by 3DE and speckle-tracking 2DE is significantly impaired in patients with subclinical hyperthyroidism. The TSH level correlated with parameters for RV function and mechanics in the whole study population. © 2016 by the American Institute of Ultrasound in Medicine.

Levomilnacipran Extended-Release Treatment in Patients With Major Depressive Disorder: Improvements in Functional Impairment Categories

PubMed Central

Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Ruth, Adam

2015-01-01

Objective: In this post hoc analysis, improvement in functional impairment in patients with major depressive disorder (MDD) treated with levomilnacipran extended release (ER) was evaluated by assessing shifts from more severe to less severe functional impairment categories on individual Sheehan Disability Scale (SDS) subscales. Method: SDS data were pooled from 5 phase II/III studies conducted between December 2006 and March 2012 of levomilnacipran ER versus placebo in adult patients with MDD (DSM-IV-TR criteria). Proportions of patients shifting from moderate-extreme baseline impairment (score ≥ 4) to mild-no impairment (score ≤ 3) at end of treatment were assessed for each SDS subscale. Proportions of patients shifting from marked-extreme (score ≥ 7) baseline impairment to moderate-no (score ≤ 6) or mild-no impairment (score ≤ 3) at end of treatment, and shifts in which patients worsened from moderate-no to marked-extreme impairment, were also evaluated. Results: A significantly higher proportion of patients treated with levomilnacipran ER than placebo-treated patients improved from more severe categories of functional impairment at baseline to less severe impairment categories across all SDS subscales: work/school, social life, and family life/home responsibilities (P < .01). Depending on the SDS subscale, 48%–55% of levomilnacipran ER–treated patients with moderate-extreme impairment at baseline improved to mild or no impairment, compared with no more than 40% of placebo patients on any subscale. Almost half (42%–47%) of levomilnacipran ER–treated patients versus only about one-third (29%–34%) of placebo patients improved from marked-extreme to mild or no impairment across functional domains. Conclusions: These results suggest that functional improvement was observed across the SDS functional domains. To our knowledge, this is the first such categorical analysis of functional improvement, as measured by the SDS, for an antidepressant. Trial

Insulin receptor substrate signaling controls cardiac energy metabolism and heart failure.

PubMed

Guo, Cathy A; Guo, Shaodong

2017-06-01

The heart is an insulin-dependent and energy-consuming organ in which insulin and nutritional signaling integrates to the regulation of cardiac metabolism, growth and survival. Heart failure is highly associated with insulin resistance, and heart failure patients suffer from the cardiac energy deficiency and structural and functional dysfunction. Chronic pathological conditions, such as obesity and type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodeling metabolic pathways, modulating cardiac energetics and impairing cardiac contractility. Recent studies demonstrated that insulin receptor substrates 1 and 2 (IRS-1,-2) are major mediators of both insulin and insulin-like growth factor-1 (IGF-1) signaling responsible for myocardial energetics, structure, function and organismal survival. Importantly, the insulin receptor substrates (IRS) play an important role in the activation of the phosphatidylinositide-3-dependent kinase (PI-3K) that controls Akt and Foxo1 signaling cascade, regulating the mitochondrial function, cardiac energy metabolism and the renin-angiotensin system. Dysregulation of this branch in signaling cascades by insulin resistance in the heart through the endocrine system promotes heart failure, providing a novel mechanism for diabetic cardiomyopathy. Therefore, targeting this branch of IRS→PI-3K→Foxo1 signaling cascade and associated pathways may provide a fundamental strategy for the therapeutic and nutritional development in control of metabolic and cardiovascular diseases. In this review, we focus on insulin signaling and resistance in the heart and the role energetics play in cardiac metabolism, structure and function. © 2017 Society for Endocrinology.

Functionality of albumin-derived perfluorocarbon-based artificial oxygen carriers in the Langendorff-heart †.

PubMed

Wrobeln, Anna; Schlüter, Klaus D; Linders, Jürgen; Zähres, Manfred; Mayer, Christian; Kirsch, Michael; Ferenz, Katja B

2017-06-01

The aim of this study was to prove whether albumin-derived perfluorocarbon-based nanoparticles (capsules) can operate as a novel artificial oxygen carrier in a rat Langendorff-heart perfusion model. Hearts perfused with capsules showed increased left ventricular pressure and rate pressure product compared to hearts perfused with pure Krebs-Henseleit (KH)-buffer. The capsules prevented the myocardium from functional fail when in their absence a noxious ischemia was observed. Capsules did not change rheological properties of KH-buffer and could repeatedly reload with oxygen. This albumin-derived perfluorocarbon-based artificial oxygen carrier preserved the function of rat hearts due to the transport of oxygen in a satisfactory manner. Because of these positive results, the functionality of the applied capsules should be verified in living animals.

Acute impact of conventional and eccentric cycling on platelet and vascular function in patients with chronic heart failure.

PubMed

Haynes, Andrew; Linden, Matthew D; Chasland, Lauren C; Nosaka, Kazunori; Maiorana, Andrew; Dawson, Ellen A; Dembo, Lawrence H; Naylor, Louise H; Green, Daniel J

2017-06-01

Evidence-based guidelines recommend exercise therapy for patients with chronic heart failure (CHF). Such patients have increased atherothrombotic risk. Exercise can transiently increase platelet activation and reactivity and decrease vascular function in healthy participants, although data in CHF are scant. Eccentric (ECC) cycling is a novel exercise modality that may be particularly suited to patients with CHF, but the acute impacts of ECC cycling on platelet and vascular function are currently unknown. Our null hypothesis was that ECC and concentric (CON) cycling, performed at matched external workloads, would not induce changes in platelet or vascular function in patients with CHF. Eleven patients with heart failure with reduced ejection fraction (HFrEF) took part in discrete bouts of ECC and CON cycling. Before and immediately after exercise, vascular function was assessed by measuring diameter and flow-mediated dilation (FMD) of the brachial artery. Platelet function was measured by the flow cytometric determination of glycoprotein IIb/IIIa activation and granule exocytosis in the presence and absence of platelet agonists. ECC cycling increased baseline artery diameter (pre: 4.0 ± 0.8 mm vs. post: 4.2 ± 0.7 mm; P = 0.04) and decreased FMD%. When changes in baseline artery diameter were accounted for, the decrease in FMD post-ECC cycling was no longer significant. No changes were apparent after CON. Neither ECC nor CON cycling resulted in changes to any platelet-function measures (all P > 0.05). These results suggest that both ECC and CON cycling, at a moderate intensity and short duration, can be performed by patients with HFrEF without detrimental impacts on vascular or platelet function. NEW & NOTEWORTHY This is the first evidence to indicate that eccentric (ECC) cycling can be performed relatively safely by patients with chronic heart failure (CHF), as it did not result in impaired vascular or platelet function compared with conventional cycling

[Experts consensus on the management of the right heart function in critically ill patients].

PubMed

Wang, X T; Liu, D W; Zhang, H M; Long, Y; Guan, X D; Qiu, H B; Yu, K J; Yan, J; Zhao, H; Tang, Y Q; Ding, X; Ma, X C; Du, W; Kang, Y; Tang, B; Ai, Y H; He, H W; Chen, D C; Chen, H; Chai, W Z; Zhou, X; Cui, N; Wang, H; Rui, X; Hu, Z J; Li, J G; Xu, Y; Yang, Y; Ouyan, B; Lin, H Y; Li, Y M; Wan, X Y; Yang, R L; Qin, Y Z; Chao, Y G; Xie, Z Y; Sun, R H; He, Z Y; Wang, D F; Huang, Q Q; Jiang, D P; Cao, X Y; Yu, R G; Wang, X; Chen, X K; Wu, J F; Zhang, L N; Yin, M G; Liu, L X; Li, S W; Chen, Z J; Luo, Z

2017-12-01

To establish the experts consensus on the right heart function management in critically ill patients. The panel of consensus was composed of 30 experts in critical care medicine who are all members of Critical Hemodynamic Therapy Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 52 experts to reassess all the statements. (1) Right heart function is prone to be affected in critically illness, which will result in a auto-exaggerated vicious cycle. (2) Right heart function management is a key step of the hemodynamic therapy in critically ill patients. (3) Fluid resuscitation means the process of fluid therapy through rapid adjustment of intravascular volume aiming to improve tissue perfusion. Reversed fluid resuscitation means reducing volume. (4) The right ventricle afterload should be taken into consideration when using stroke volume variation (SVV) or pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload alone could lead to septal displacement and damage the diastolic function of the left ventricle. (6) The Starling curve of the right ventricle is not the same as the one applied to the left ventricle,the judgement of the different states for the right ventricle is the key of volume management. (7) The alteration of right heart function has its own characteristics, volume assessment and adjustment is an important part of the treatment of right ventricular dysfunction (8) Right ventricular enlargement is the prerequisite for increased cardiac output during reversed fluid resuscitation; Nonetheless, right heart enlargement does not mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance induced by a variety of factors could affect right heart function by obstructing the blood flow. (10) When pulmonary hypertension was detected in clinical scenario, the differentiation of

Sleep in heart failure.

PubMed

Naughton, Matthew T; Lorenzi-Filho, Geraldo

2009-01-01

Sleep plays a large role in patients with heart failure. In normal subjects, sleep is usually in a supine position with reduced sympathetic drive, elevated vagal tone and as such a relatively lower cardiac output and minute ventilation, allowing for recuperation. Patients with heart failure may not experience the same degree of autonomic activity change and the supine position may place a large strain on the pulmonary system. More than half of all heart failure patients have one of two types of sleep apnea: either obstructive or central sleep apnea. Some patients have both types. Obstructive sleep apnea is likely to be a cause of heart failure due to large negative intrathoracic pressures, apnea related hypoxemia and hypercapnia, terminated by an arousal and surge in systemic blood pressure associated with endothelial damage and resultant premature atherosclerosis. Reversal of obstructive sleep apnea improves blood pressure, systolic contraction and autonomic dysfunction however mortality studies are lacking. Central sleep apnea with Cheyne Stokes pattern of respiration (CSA-CSR) occurs as a result of increased central controller (brainstem driving ventilation) and plant (ventilation driving CO2) gain in the setting of a delayed feed back (i.e., low cardiac output). It is thought this type of apnea is a result of moderately to severely impaired cardiac function and is possibly indicative of high mortality. Treatment of CSA-CSR is best undertaken by treating the underlying cardiac condition which may include with medications, pacemakers, transplantation or continuous positive airway pressure (CPAP). In such patients CPAP exerts unique effects to assist cardiac function and reduce pulmonary edema. Whether CPAP improves survival in this heart failure population remains to be determined.

Executive function, but not memory, associates with incident coronary heart disease and stroke.

PubMed

Rostamian, Somayeh; van Buchem, Mark A; Westendorp, Rudi G J; Jukema, J Wouter; Mooijaart, Simon P; Sabayan, Behnam; de Craen, Anton J M

2015-09-01

To evaluate the association of performance in cognitive domains executive function and memory with incident coronary heart disease and stroke in older participants without dementia. We included 3,926 participants (mean age 75 years, 44% male) at risk for cardiovascular diseases from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) with Mini-Mental State Examination score ≥24 points. Scores on the Stroop Color-Word Test (selective attention) and the Letter Digit Substitution Test (processing speed) were converted to Z scores and averaged into a composite executive function score. Likewise, scores of the Picture Learning Test (immediate and delayed memory) were transformed into a composite memory score. Associations of executive function and memory were longitudinally assessed with risk of coronary heart disease and stroke using multivariable Cox regression models. During 3.2 years of follow-up, incidence rates of coronary heart disease and stroke were 30.5 and 12.4 per 1,000 person-years, respectively. In multivariable models, participants in the lowest third of executive function, as compared to participants in the highest third, had 1.85-fold (95% confidence interval [CI] 1.39-2.45) higher risk of coronary heart disease and 1.51-fold (95% CI 0.99-2.30) higher risk of stroke. Participants in the lowest third of memory had no increased risk of coronary heart disease (hazard ratio 0.99, 95% CI 0.74-1.32) or stroke (hazard ratio 0.87, 95% CI 0.57-1.32). Lower executive function, but not memory, is associated with higher risk of coronary heart disease and stroke. Lower executive function, as an independent risk indicator, might better reflect brain vascular pathologies. © 2015 American Academy of Neurology.

Hemodynamics of a functional centrifugal-flow total artificial heart with functional atrial contraction in goats.

PubMed

Shiga, Takuya; Shiraishi, Yasuyuki; Sano, Kyosuke; Taira, Yasunori; Tsuboko, Yusuke; Yamada, Akihiro; Miura, Hidekazu; Katahira, Shintaro; Akiyama, Masatoshi; Saiki, Yoshikatsu; Yambe, Tomoyuki

2016-03-01

Implantation of a total artificial heart (TAH) is one of the therapeutic options for the treatment of patients with end-stage biventricular heart failure. There is no report on the hemodynamics of the functional centrifugal-flow TAH with functional atrial contraction (fCFTAH). We evaluated the effects of pulsatile flow by atrial contraction in acute animal models. The goats received fCFTAH that we created from two centrifugal-flow ventricular assist devices. Some hemodynamic parameters maintained acceptable levels: heart rate 115.5 ± 26.3 bpm, aortic pressure 83.5 ± 10.1 mmHg, left atrial pressure 18.0 ± 5.9 mmHg, pulmonary pressure 28.5 ± 9.7 mmHg, right atrial pressure 13.6 ± 5.2 mmHg, pump flow 4.0 ± 1.1 L/min (left) 3.9 ± 1.1 L/min (right), and cardiac index 2.13 ± 0.14 L/min/m(2). fCFTAH with atrial contraction was able to maintain the TAH circulation by forming a pulsatile flow in acute animal experiments. Taking the left and right flow rate balance using the low internal pressure loss of the VAD pumps may be easier than by other pumps having considerable internal pressure loss. We showed that the remnant atrial contraction effected the flow rate change of the centrifugal pump, and the atrial contraction waves reflected the heart rate. These results indicate that remnant atria had the possibility to preserve autonomic function in fCFTAH. We may control fCFTAH by reflecting the autonomic function, which is estimated with the flow rate change of the centrifugal pump.

Impairment in Occupational Functioning and Adult ADHD: The Predictive Utility of Executive Function (EF) Ratings Versus EF Tests

PubMed Central

Barkley, Russell A.; Murphy, Kevin R.

2010-01-01

Attention deficit hyperactivity disorder (ADHD) is associated with deficits in executive functioning (EF). ADHD in adults is also associated with impairments in major life activities, particularly occupational functioning. We investigated the extent to which EF deficits assessed by both tests and self-ratings contributed to the degree of impairment in 11 measures involving self-reported occupational problems, employer reported workplace adjustment, and clinician rated occupational adjustment. Three groups of adults were recruited as a function of their severity of ADHD: ADHD diagnosis (n = 146), clinical controls self-referring for ADHD but not diagnosed with it (n = 97), and community controls (n = 109). Groups were combined and regression analyses revealed that self-ratings of EF were significantly predictive of impairments in all 11 measures of occupational adjustment. Although several tests of EF also did so, they contributed substantially less than did the EF ratings, particularly when analyzed jointly with the ratings. We conclude that EF deficits contribute to the impairments in occupational functioning that occur in conjunction with adult ADHD. Ratings of EF in daily life contribute more to such impairments than do EF tests, perhaps because, as we hypothesize, each assesses a different level in the hierarchical organization of EF as a meta-construct. PMID:20197297

Effects of propranolol treatment on left ventricular function and intracellular calcium regulation in rats with postinfarction heart failure

PubMed Central

Litwin, Sheldon E; Katz, Sarah E; Morgan, James P; Douglas, Pamela S

1999-01-01

Chronic treatment with beta-adrenergic blocking agents can improve survival in patients with heart failure. The mechanisms underlying the beneficial effects and whether these effects are generalizable to ischaemic heart failure are unresolved.We performed echocardiographic-Doppler examinations in rats (n=28) 1 and 6 weeks after myocardial infarction (MI) or sham surgery. Rats were randomized to no treatment or propranolol (500 mg/l in drinking water) after the first echocardiogram. Isometric contractions and intracellular Ca transients were recorded simultaneously in noninfarcted left ventricular (LV) papillary muscles.Untreated MI rats had significant LV dilatation (10.6±0.4* vs 8.9±0.3 mm, MI vs control), impaired systolic function (fractional shortening=11±2* vs 38±2%), and a restrictive LV diastolic filling pattern. MI rats receiving propranolol had similar LV chamber sizes (10.6±0.5 mm) and systolic function (13±2%). The propranolol treated animals had higher LV end-diastolic pressures (27±2* vs 20±3 mmHg) and a more restricted LV diastolic filling pattern (increased ratio of early to late filling velocities and more rapid E wave deceleration rate). Contractility of papillary muscles from untreated MI rats was depressed (1.6±0.3 vs 2.4±0.5 g mm−2). In addition, Ca transients were prolonged and the inotropic response to isoproterenol was blunted. Propranolol treatment did not improve force development (1.6±0.3 g mm−2) or the duration of Ca transients during isoproterenol stimulation.Chronic propranolol treatment in rats with postinfarction heart failure did not improve LV remodeling or systolic function. LV diastolic pressures and filling patterns were worsened by propranolol. Treatment also did not produce appreciable improvement in contractility, intracellular Ca regulation or beta-adrenergic responsiveness in the noninfarcted myocardium. PMID:10455325

Functional Impairment and Occupational Outcome in Adults with ADHD

ERIC Educational Resources Information Center

Gjervan, Bjorn; Torgersen, Terje; Nordahl, Hans M.; Rasmussen, Kirsten

2012-01-01

Objective: ADHD is associated with poor functional outcomes. The objectives were to investigate the prevalence of functional impairment and occupational status in a clinically referred sample of adults with ADHD and explore factors predicting occupational outcome. Method: A sample of 149 adults with a confirmed diagnosis of ADHD participated in…

Left ventricular performance in various heart diseases with or without heart failure:--an appraisal by quantitative one-plane cineangiocardiography.

PubMed

Lien, W P; Lee, Y S; Chang, F Z; Chen, J J; Shieh, W B

1978-01-01

Quantitative one-plane cineangiocardiography in right anterior oblique position for evaluation of LV performance was carried out in 62 patients with various heart diseases and in 13 subjects with normal LV. Parameters for evaluating both pump and muscle performances were derived from volume and pressure measurements. Of 31 patients with either systolic hypertension or LV myocardial diseases (coronary artery disease or idiopathic cardiomyopathy), 14 had clinical evidence of LV failure before the study. It was found that mean VCF and EF were most sensitive indicators of impaired LV performance among the various parameters. There was a close correlation between mean VCF and EF, yet discordant changes of both parameters were noted in some patients. Furthermore, wall motion abnormalities were not infrequently observed in patients with coronary artery disease or primary cardiomyopathy. Therefore, assessment of at least three ejection properties (EF, mean VCF and wall motion abnormalities) are considered to be essential for full understanding of derangement of LV function in heart disease. This is especially true of patients with coronary artery disease. LV behavior in relation to different pathological stresses or lesions, such as chronic pressure or volume load, myocardial disease and mitral stenosis, was also studied and possible cause of impaired LV myocardial function in mitral stenosis was discussed.

Right ventricular systolic function in hypertensive heart failure.

PubMed

Oketona, O A; Balogun, M O; Akintomide, A O; Ajayi, O E; Adebayo, R A; Mene-Afejuku, T O; Oketona, O T; Bamikole, O J

2017-01-01

Heart failure (HF) is a major cause of cardiovascular admissions and hypertensive heart failure (HHF) is the most common cause of HF admissions in sub-Saharan Africa, Nigeria inclusive. Right ventricular (RV) dysfunction is being increasingly recognized in HF and found to be an independent predictor of adverse outcomes in HF. This study aimed to determine the prevalence of RV systolic dysfunction in HHF by several echocardiographic parameters. One hundred subjects with HHF were recruited consecutively into the study along with 50 age and sex-matched controls. All study participants gave written informed consent, and had a full physical examination, blood investigations, 12-lead electrocardiogram, and transthoracic echocardiography. RV systolic function was assessed in all subjects using different methods based on the American Society of Echocardiography guidelines for echocardiographic assessment of the right heart in adults. This included tricuspid annular plane systolic excursion (TAPSE), RV myocardial performance index (MPI), and RV systolic excursion velocity by tissue Doppler (S'). RV systolic dysfunction was found in 53% of subjects with HHF by TAPSE, 56% by RV MPI, and 48% by tissue Doppler systolic excursion S'. RV systolic dysfunction increased with reducing left ventricular ejection fraction (LVEF) in subjects with HHF. A high proportion of subjects with HHF were found to have RV systolic functional abnormalities using TAPSE, RV MPI, and RV S'. Prevalence of RV systolic dysfunction increased with reducing LVEF.

Hypertrophied tonsils impair velopharyngeal function after palatoplasty.

PubMed

Abdel-Aziz, Mosaad

2012-03-01

When tonsillar hypertrophy obstructing the airway is encountered in a child with a repaired cleft palate and velopharyngeal insufficiency, the surgeon may opt for tonsillectomy to relieve the airway obstruction, with possible effects on velopharyngeal closure. The aim of this study was to assess the impact of hypertrophied tonsils on velopharyngeal function in children with repaired cleft palate and to measure the effect of tonsillectomy on velopharyngeal closure and speech resonance. Case series. Twelve children with repaired cleft palate and tonsillar hypertrophy underwent tonsillectomy to relieve airway obstruction. Preoperative and postoperative evaluation of velopharyngeal function was performed. Auditory perceptual assessment of speech and nasalance scores were measured, and velopharyngeal closure was evaluated by flexible nasopharyngoscopy. Preoperative impairment of velopharyngeal function was detected. However, significant postoperative improvement of speech parameters (hypernasality, nasal emission of air, and weak pressure consonants measured with auditory perceptual assessment) was achieved, and the overall postoperative nasalance score was improved significantly for nasal and oral sentences. Reduction of velopharyngeal gap size was detected after removal of hypertrophied tonsils. Although the improvement of velopharyngeal closure was not significant, three cases demonstrated complete postoperative closure with no gap. Hypertrophied tonsils may impair velopharyngeal function in children with repaired cleft palate, and tonsillectomy is beneficial for such patients as it can improve the velopharyngeal closure and speech resonance. Secondary corrective surgery may be avoided in some cases after tonsillectomy. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

The cardiokine story unfolds: ischemic stress-induced protein secretion in the heart.

PubMed

Doroudgar, Shirin; Glembotski, Christopher C

2011-04-01

Intercellular communication depends on many factors, including proteins released via the classical or non-classical secretory pathways, many of which must be properly folded to be functional. Owing to their adverse effects on the secretion machinery, stresses such as ischemia can impair the folding of secreted proteins. Paradoxically, cells rely on secreted proteins to mount a response designed to resist stress-induced damage. This review examines this paradox using proteins secreted from the heart, cardiokines, as examples, and focuses on how the ischemic heart maintains or even increases the release of select cardiokines that regulate important cellular processes in the heart, including excitation-contraction coupling, hypertrophic growth, myocardial remodeling and stem cell function, in ways that moderate ischemic damage and enhance cardiac repair. Copyright © 2010 Elsevier Ltd. All rights reserved.

Accelerating cine-MR Imaging in Mouse Hearts Using Compressed Sensing

PubMed Central

Wech, Tobias; Lemke, Angela; Medway, Debra; Stork, Lee-Anne; Lygate, Craig A; Neubauer, Stefan; Köstler, Herbert; Schneider, Jürgen E

2011-01-01

Purpose To combine global cardiac function imaging with compressed sensing (CS) in order to reduce scan time and to validate this technique in normal mouse hearts and in a murine model of chronic myocardial infarction. Materials and Methods To determine the maximally achievable acceleration factor, fully acquired cine data, obtained in sham and chronically infarcted (MI) mouse hearts were 2–4-fold undersampled retrospectively, followed by CS reconstruction and blinded image segmentation. Subsequently, dedicated CS sampling schemes were implemented at a preclinical 9.4 T magnetic resonance imaging (MRI) system, and 2- and 3-fold undersampled cine data were acquired in normal mouse hearts with high temporal and spatial resolution. Results The retrospective analysis demonstrated that an undersampling factor of three is feasible without impairing accuracy of cardiac functional parameters. Dedicated CS sampling schemes applied prospectively to normal mouse hearts yielded comparable left-ventricular functional parameters, and intra- and interobserver variability between fully and 3-fold undersampled data. Conclusion This study introduces and validates an alternative means to speed up experimental cine-MRI without the need for expensive hardware. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc. PMID:21932360

Chronic mercury exposure impairs the sympathovagal control of the rat heart.

PubMed

Simões, M R; Azevedo, B F; Fiorim, J; Jr Freire, D D; Covre, E P; Vassallo, D V; Dos Santos, L

2016-11-01

Mercury is known to cause harmful neural effects affecting the cardiovascular system. Here, we evaluated the chronic effects of low-dose mercury exposure on the autonomic control of the cardiovascular system. Wistar rats were treated for 30 days with HgCl 2 (1st dose 4.6 μg/kg followed by 0.07 μg/kg per day, intramuscular) or saline. The femoral artery and vein were then cannulated for evaluation of autonomic control of the hemodynamic function, which was evaluated in awake rats. The following tests were performed: baroreflex sensitivity, Von Bezold-Jarisch reflex, heart rate variability (HRV) and pharmacological blockade with methylatropine and atenolol to test the autonomic tone of the heart. Exposure to HgCl 2 for 30 days slightly increased the mean arterial pressure and heart rate (HR). There was a significant reduction in the baroreflex gain of animals exposed to HgCl 2 . Moreover, haemodynamic responses to the activation of the Von Bezold-Jarisch reflex were also reduced. The changes in the spectral analysis of HRV suggested a shift in the sympathovagal balance toward a sympathetic predominance after mercury exposure, which was confirmed by autonomic pharmacological blockade in the HgCl 2 group. This group also exhibited reduced intrinsic HR after the double block suggesting that the pacemaker activity of the sinus node was also affected. These findings suggested that the autonomic modulation of the heart was significantly altered by chronic mercury exposure, thus reinforcing that even at low concentrations such exposure might be associated with increased cardiovascular risk. © 2016 John Wiley & Sons Australia, Ltd.

Impaired Right, Left, or Biventricular Function and Resting Oxygen Saturation Are Associated With Mortality in Eisenmenger Syndrome: A Clinical and Cardiovascular Magnetic Resonance Study.

PubMed

Jensen, Annette S; Broberg, Craig S; Rydman, Riikka; Diller, Gerhard-Paul; Li, Wei; Dimopoulos, Konstantinos; Wort, Stephen J; Pennell, Dudley J; Gatzoulis, Michael A; Babu-Narayan, Sonya V

2015-12-01

Patients with Eisenmenger syndrome (ES) have better survival, despite similar pulmonary vascular pathology, compared with other patients with pulmonary arterial hypertension. Cardiovascular magnetic resonance (CMR) is useful for risk stratification in idiopathic pulmonary arterial hypertension, whereas it has not been evaluated in ES. We studied CMR together with other noninvasive measurements in ES to evaluate its potential role as a noninvasive risk stratification test. Between 2003 and 2005, 48 patients with ES, all with a post-tricuspid shunt, were enrolled in a prospective, longitudinal, single-center study. All patients underwent a standardized baseline assessment with CMR, blood test, echocardiography, and 6-minute walk test and were followed up for mortality until the end of December 2013. Twelve patients (25%) died during follow-up, mostly from heart failure (50%). Impaired ventricular function (right or left ventricular ejection fraction) was associated with increased risk of mortality (lowest quartile: right ventricular ejection fraction, <40%; hazard ratio, 4.4 [95% confidence interval, 1.4-13.5]; P=0.01 and left ventricular ejection fraction, <50%; hazard ratio, 6.6 [95% confidence interval, 2.1-20.8]; P=0.001). Biventricular impairment (lowest quartile left ventricular ejection fraction, <50% and right ventricular ejection fraction, <40%) conveyed an even higher risk of mortality (hazard ratio, 8.0 [95% confidence interval, 2.5-25.1]; P=0.0004). No other CMR or noninvasive measurement besides resting oxygen saturation (hazard ratio, 0.90 [0.83-0.97]/%; P=0.007) was associated with mortality. Impaired right, left, or biventricular systolic function derived from baseline CMR and resting oxygen saturation are associated with mortality in adult patients with ES. CMR is a useful noninvasive tool, which may be incorporated in the risk stratification assessment of ES during lifelong follow-up. © 2015 American Heart Association, Inc.

Brief Exposure to Secondhand Smoke Reversibly Impairs Endothelial Vasodilatory Function

PubMed Central

2014-01-01

Introduction: We sought to determine the effects of brief exposures to low concentrations of tobacco secondhand smoke (SHS) on arterial flow-mediated dilation (FMD, a nitric oxide-dependent measure of vascular endothelial function), in a controlled animal model never before exposed to smoke. In humans, SHS exposure for 30min impairs FMD. It is important to gain a better understanding of the acute effects of exposure to SHS at low concentrations and for brief periods of time. Methods: We measured changes in FMD in rats exposed to a range of real-world levels of SHS for durations of 30min, 10min, 1min, and 4 breaths (roughly 15 s). Results: We observed a dose-response relationship between SHS particle concentration over 30min and post-exposure impairment of FMD, which was linear through the range typically encountered in smoky restaurants and then saturated at higher concentrations. One min of exposure to SHS at moderate concentrations was sufficient to impair FMD. Conclusions: Brief SHS exposure at real-world levels reversibly impairs FMD. Even 1min of SHS exposure can cause reduction of endothelial function. PMID:24302638

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

The pathophysiology of heart failure.

PubMed

Kemp, Clinton D; Conte, John V

2012-01-01

Heart failure is a clinical syndrome that results when the heart is unable to provide sufficient blood flow to meet metabolic requirements or accommodate systemic venous return. This common condition affects over 5 million people in the United States at a cost of $10-38 billion per year. Heart failure results from injury to the myocardium from a variety of causes including ischemic heart disease, hypertension, and diabetes. Less common etiologies include cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs. As the heart fails, patients develop symptoms which include dyspnea from pulmonary congestion, and peripheral edema and ascites from impaired venous return. Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function. These include increasing cardiac output via the Frank-Starling mechanism, increasing ventricular volume and wall thickness through ventricular remodeling, and maintaining tissue perfusion with augmented mean arterial pressure through activation of neurohormonal systems. Although initially beneficial in the early stages of heart failure, all of these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Treatment strategies have been developed based upon the understanding of these compensatory mechanisms. Medical therapy includes diuresis, suppression of the overactive neurohormonal systems, and augmentation of contractility. Surgical options include ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation. Despite significant understanding of the underlying pathophysiological mechanisms in heart failure, this disease causes significant morbidity and carries a 50% 5-year mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

The treatment with pyridostigmine improves the cardiocirculatory function in rats with chronic heart failure.

PubMed

Sabino, João Paulo J; da Silva, Carlos Alberto Aguiar; de Melo, Rubens Fernando; Fazan, Rubens; Salgado, Helio C

2013-01-01

Sympathetic hyperactivity and its outcome in heart failure have been thoroughly investigated to determine the focus of pharmacologic approaches targeting the sympathetic nervous system in the treatment of this pathophysiological condition. On the other hand, therapeutic approaches aiming to protect the reduced cardiac parasympathetic function have not received much attention. The present study evaluated rats with chronic heart failure (six to seven weeks after coronary artery ligation) and the effects of an increased parasympathetic function by pyridostigmine (an acetylcholinesterase inhibitor) on the following aspects: arterial pressure (AP), heart rate (HR), baroreceptor and Bezold-Jarisch reflex, pulse interval (PI) and AP variability, cardiac sympathetic and parasympathetic tonus, intrinsic heart rate (i-HR) and cardiac function. Conscious rats with heart failure exhibited no change in HR, Bezold-Jarisch reflex, PI variability and cardiac sympathetic tonus. On the other hand, these animals presented hypotension and reduced baroreflex sensitivity, power in the low frequency (LF) band of the systolic AP spectrum, cardiac parasympathetic tonus and i-HR, while anesthetized rats exhibited reduced cardiac performance. Pyridostigmine prevented the attenuation of all the parameters examined, except basal AP and cardiac performance. In conclusion, the blockade of acetylcholinesterase with pyridostigmine was revealed to be an important pharmacological approach, which could be used to increase parasympathetic function and to improve a number of cardiocirculatory parameters in rats with heart failure. Copyright © 2012 Elsevier B.V. All rights reserved.

American ginseng acutely regulates contractile function of rat heart.

PubMed

Jiang, Mao; Murias, Juan M; Chrones, Tom; Sims, Stephen M; Lui, Edmund; Noble, Earl G

2014-01-01

Chronic ginseng treatments have been purported to improve cardiac performance. However reports of acute administration of ginseng on cardiovascular function remain controversial and potential mechanisms are not clear. In this study, we examined the effects of acute North American ginseng (Panax quinquefolius) administration on rat cardiac contractile function by using electrocardiogram (ECG), non-invasive blood pressure (BP) measurement, and Langendorff isolated, spontaneously beating, perfused heart measurements (LP). Eight-week old male Sprague-Dawley rats (n = 8 per group) were gavaged with a single dose of water-soluble American ginseng at 300 mg/kg body weight. Heart rate (HR) and BP were measured prior to and at 1 and 24 h after gavaging (ECG and BP). Additional groups were used for each time point for Langendorff measurements. HR was significantly decreased (ECG: 1 h: 6 ± 0.2%, 24 h: 8 ± 0.3%; BP: 1 h: 8.8 ± 0.2%, 24 h: 13 ± 0.4% and LP: 1 h: 22 ± 0.4%, 24 h: 19 ± 0.4%) in rats treated with water-soluble ginseng compared with pre or control measures. An initial marked decrease in left ventricular developed pressure was observed in LP hearts but BP changes were not observed in BP group. A direct inhibitory effect of North American ginseng was observed on cardiac contractile function in LP rats and on fluorescence measurement of intracellular calcium transient in freshly isolated cardiac myocytes when exposed to ginseng (1 and 10 μg/ml). Collectively these data present evidence of depressed cardiac contractile function by acute administration of North American ginseng in rat. This acute reduction in cardiac contractile function appears to be intrinsic to the myocardium.

American ginseng acutely regulates contractile function of rat heart

PubMed Central

Jiang, Mao; Murias, Juan M.; Chrones, Tom; Sims, Stephen M.; Lui, Edmund; Noble, Earl G.

2014-01-01

Chronic ginseng treatments have been purported to improve cardiac performance. However reports of acute administration of ginseng on cardiovascular function remain controversial and potential mechanisms are not clear. In this study, we examined the effects of acute North American ginseng (Panax quinquefolius) administration on rat cardiac contractile function by using electrocardiogram (ECG), non-invasive blood pressure (BP) measurement, and Langendorff isolated, spontaneously beating, perfused heart measurements (LP). Eight-week old male Sprague–Dawley rats (n = 8 per group) were gavaged with a single dose of water-soluble American ginseng at 300 mg/kg body weight. Heart rate (HR) and BP were measured prior to and at 1 and 24 h after gavaging (ECG and BP). Additional groups were used for each time point for Langendorff measurements. HR was significantly decreased (ECG: 1 h: 6 ± 0.2%, 24 h: 8 ± 0.3%; BP: 1 h: 8.8 ± 0.2%, 24 h: 13 ± 0.4% and LP: 1 h: 22 ± 0.4%, 24 h: 19 ± 0.4%) in rats treated with water-soluble ginseng compared with pre or control measures. An initial marked decrease in left ventricular developed pressure was observed in LP hearts but BP changes were not observed in BP group. A direct inhibitory effect of North American ginseng was observed on cardiac contractile function in LP rats and on fluorescence measurement of intracellular calcium transient in freshly isolated cardiac myocytes when exposed to ginseng (1 and 10 μg/ml). Collectively these data present evidence of depressed cardiac contractile function by acute administration of North American ginseng in rat. This acute reduction in cardiac contractile function appears to be intrinsic to the myocardium. PMID:24672484

Predictors of impaired work functioning in employees with major depression in remission.

PubMed

de Vries, Gabe; Koeter, Maarten W J; Nieuwenhuijsen, Karen; Hees, Hiske L; Schene, Aart H

2015-10-01

This study aims to (i) assess work functioning in employees returning to work with a major depression in remission, (ii) study the predictors of impaired work functioning. Participants diagnosed with major depressive disorder (MDD), on long term sick leave (mean 27 weeks) and treated in a specialized mental healthcare setting, were selected from an intervention study sample. They were eligible for this study if they were remitted from their depression and had returned to work for at least 50% of their contract hours at 18 month follow-up. Work functioning was assessed with the Work Limitations Questionnaire (WLQ) and the Need For Recovery scale (NFR). Potential predictors of impaired work functioning were demographic characteristics (assessed at baseline), health characteristics (assessed at baseline, six and twelve month follow-up), and personality- and work characteristics (assessed at 18 month follow-up). After their return to work with MDD in remission, employees were on average still impaired in their work functioning. Personality characteristics were the strongest predictor of this impaired work functioning, followed by health and work characteristics. In the final prediction model, only a passive reaction coping style remained as predictor. We used self-report data with respect to work functioning and work characteristics and not an assessment by a supervisor. Personality trait, coping style, and ability to manage the work environment should be addressed in mental health and return-to-work interventions. Subsequent improved work functioning may be beneficial for mental health and may reduce societal costs. Copyright © 2015 Elsevier B.V. All rights reserved.

Structure and function of gap junction proteins: role of gap junction proteins in embryonic heart development.

PubMed

Ahir, Bhavesh K; Pratten, Margaret K

2014-01-01

Intercellular (cell-to-cell) communication is a crucial and complex mechanism during embryonic heart development. In the cardiovascular system, the beating of the heart is a dynamic and key regulatory process, which is functionally regulated by the coordinated spread of electrical activity through heart muscle cells. Heart tissues are composed of individual cells, each bearing specialized cell surface membrane structures called gap junctions that permit the intercellular exchange of ions and low molecular weight molecules. Gap junction channels are essential in normal heart function and they assist in the mediated spread of electrical impulses that stimulate synchronized contraction (via an electrical syncytium) of cardiac tissues. This present review describes the current knowledge of gap junction biology. In the first part, we summarise some relevant biochemical and physiological properties of gap junction proteins, including their structure and function. In the second part, we review the current evidence demonstrating the role of gap junction proteins in embryonic development with particular reference to those involved in embryonic heart development. Genetics and transgenic animal studies of gap junction protein function in embryonic heart development are considered and the alteration/disruption of gap junction intercellular communication which may lead to abnormal heart development is also discussed.

Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association.

PubMed

Gorelick, Philip B; Scuteri, Angelo; Black, Sandra E; Decarli, Charles; Greenberg, Steven M; Iadecola, Costantino; Launer, Lenore J; Laurent, Stephane; Lopez, Oscar L; Nyenhuis, David; Petersen, Ronald C; Schneider, Julie A; Tzourio, Christophe; Arnett, Donna K; Bennett, David A; Chui, Helena C; Higashida, Randall T; Lindquist, Ruth; Nilsson, Peter M; Roman, Gustavo C; Sellke, Frank W; Seshadri, Sudha

2011-09-01

This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment and dementia of later life are common. Definitions of vascular cognitive impairment (VCI), neuropathology, basic science and pathophysiological aspects, role of neuroimaging and vascular and other associated risk factors, and potential opportunities for prevention and treatment are reviewed. This statement serves as an overall guide for practitioners to gain a better understanding of VCI and dementia, prevention, and treatment. Writing group members were nominated by the writing group co-chairs on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council Scientific Statement Oversight Committee, the Council on Epidemiology and Prevention, and the Manuscript Oversight Committee. The writing group used systematic literature reviews (primarily covering publications from 1990 to May 1, 2010), previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulate recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. After peer review by the American Heart Association, as well as review by the Stroke Council leadership, Council on Epidemiology and Prevention Council, and Scientific Statements Oversight Committee, the statement was approved by the American Heart Association Science Advisory and Coordinating Committee. The construct of VCI has been introduced to capture the entire spectrum of cognitive disorders associated with all forms of cerebral vascular brain injury-not solely stroke-ranging from mild cognitive impairment through fully developed dementia. Dysfunction of the neurovascular

Clinical outcome of patients with heart failure and preserved left ventricular function.

PubMed

Gotsman, Israel; Zwas, Donna; Planer, David; Azaz-Livshits, Tanya; Admon, Dan; Lotan, Chaim; Keren, Andre

2008-11-01

Patients with heart failure have a poor prognosis. However, it has been presumed that patients with heart failure and preserved left ventricular function (LVF) may have a more benign prognosis. We evaluated the clinical outcome of patients with heart failure and preserved LVF compared with patients with reduced function and the factors affecting prognosis. We prospectively evaluated 289 consecutive patients hospitalized with a definite clinical diagnosis of heart failure based on typical symptoms and signs. They were divided into 2 subsets based on echocardiographic LVF. Patients were followed clinically for a period of 1 year. Echocardiography showed that more than one third (36%) of the patients had preserved systolic LVF. These patients were more likely to be older and female and have less ischemic heart disease. The survival at 1 year in this group was poor and not significantly different from patients with reduced LVF (75% vs 71%, respectively). The adjusted survival by Cox regression analysis was not significantly different (P=.25). However, patients with preserved LVF had fewer rehospitalizations for heart failure (25% vs 35%, P<.05). Predictors of mortality in the whole group by multivariate analysis were age, diabetes, chronic renal failure, atrial fibrillation, residence in a nursing home, and serum sodium < or = 135 mEq/L. The prognosis of patients with clinical heart failure with or without preserved LVF is poor. Better treatment modalities are needed in both subsets.

Therapeutic potential of functional selectivity in the treatment of heart failure.

PubMed

Christensen, Gitte Lund; Aplin, Mark; Hansen, Jakob Lerche

2010-10-01

Adrenergic and angiotensin receptors are prominent targets in pharmacological alleviation of cardiac remodeling and heart failure, but their use is associated with cardiodepressant side effects. Recent advances in our understanding of seven transmembrane receptor signaling show that it is possible to design ligands with "functional selectivity," acting as agonists on certain signaling pathways while antagonizing others. This represents a major pharmaceutical opportunity to separate desired from adverse effects governed by the same receptor. Accordingly, functionally selective ligands are currently pursued as next-generation drugs for superior treatment of heart failure. Copyright © 2010 Elsevier Inc. All rights reserved.

MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.

PubMed

Hsu, Ying-Han R; Yogasundaram, Haran; Parajuli, Nirmal; Valtuille, Lucas; Sergi, Consolato; Oudit, Gavin Y

2016-01-01

Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders.

Burden of impaired sleep quality on work productivity in functional dyspepsia.

PubMed

Matsuzaki, Juntaro; Suzuki, Hidekazu; Togawa, Koji; Yamane, Tsuyoshi; Mori, Hideki; Komori, Takahiro; Masaoka, Tatsuhiro; Kanai, Takanori

2018-04-01

Impaired sleep quality is common, and can reduce work productivity in patients with functional dyspepsia (FD). The objective of this article is to evaluate whether there is a direct association between the presence of FD and the severity of impaired sleep quality, and to calculate the economic loss due to the decreased work productivity associated with sleep quality. In Study 1, using a web-based survey completed by workers with and without FD, we evaluated impaired sleep quality, work and daily productivity, and the severity of reflux and bowel symptoms. In Study 2, the association between the presence of FD and the severity of impaired sleep quality was validated in a hospital-based cohort. In both Study 1 and 2, although impaired sleep quality was more frequent in participants with FD than in those without FD, the independent association between the presence of FD and the severity of impaired sleep quality was not observed after adjustment for the severity of reflux and bowel symptoms. FD participants with impaired sleep quality reported additional economic loss of 53,500 Japanese yen/month. Although the association between impaired sleep quality and FD was indirect, concomitant impaired sleep quality could worsen economic loss.

Heart rate variability regression and risk of sudden unexpected death in epilepsy.

PubMed

Galli, Alessio; Lombardi, Federico

2017-02-01

The exact mechanisms of sudden unexpected death in epilepsy remain elusive, despite there is consensus that SUDEP is associated with severe derangements in the autonomic control to vital functions as breathing and heart rate regulation. Heart rate variability (HRV) has been advocated as biomarker of autonomic control to the heart. Cardiac dysautonomia has been found in diseases where other branches of the autonomous nervous system are damaged, as Parkinson disease and multiple system atrophy. In this perspective, an impaired HRV not only is a risk factor for sudden cardiac death mediated by arrhythmias, but also a potential biomarker for monitoring a progressive decline of the autonomous nervous system. This slope may lead to an acute imbalance of the regulatory pathways of vital functions after seizure and then to SUDEP. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanisms Explaining the Influence of Subclinical Hypothyroidism on the Onset and Progression of Chronic Heart Failure.

PubMed

Triggiani, Vincenzo; Angelo Giagulli, Vito; De Pergola, Giovanni; Licchelli, Brunella; Guastamacchia, Edoardo; Iacoviello, Massimo

2016-01-01

Subclinical hypothyroidism can be associated with the onset and progression of chronic heart failure. We undertook a careful search of the literature aiming to review the possible pathogenetic mechanisms explaining the influence of subclinical hypothyroidism on the onset and progression of chronic heart failure. Thyroid hormones can influence the expression of genes involved in calcium handling and contractile properties of myocardiocytes. Subclinical hypothyroidism, therefore, can alter both cardiovascular morphology and function leading to changes in myocardiocytes shape and structure, and to alterations of both contractile and relaxing properties, impairing systolic as well as diastolic functions. Furthermore, it can favour dyslipidemia, endothelial dysfunction and diastolic hypertension, favouring atherogenesis and coronary heart disease, possibly evolving into chronic heart failure. Beside an influence on the onset of chronic heart failure, subclinical hypothyroidism can represent a risk factor for its progression, in particular hospitalization and mortality but the mechanisms involved need to be fully elucidated. Subclinical hypothyroidism can be associated with the onset of chronic heart failure, because it can favour two frequent conditions that can evolve in heart failure: coronary heart disease and hypertension; it can also alter both cardiovascular morphology and function leading to heart failure progression in patients already affected through mechanisms still not completely understood.

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest.

PubMed

Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M; Farrehi, Peter; Borjigin, Jimo

2018-01-01

Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO 2 -mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients.

Executive Function in Preschoolers with Primary Language Impairment

ERIC Educational Resources Information Center

Yang, Hui-Chun; Gray, Shelley

2017-01-01

Purpose: The purpose of this study was to evaluate whether preschoolers with primary language impairment (PLI) show deficits in executive function (EF) compared with their peers with typical development (TD) when inhibition, updating, and mental-set shifting are examined using both linguistically based and visually based tasks. Method: Twenty-two…

Diabetes mellitus induced impairment of male reproductive functions: a review.

PubMed

Jangir, Ram Niwas; Jain, Gyan Chand

2014-05-01

Diabetes mellitus (DM) represents one of the greatest threats to human health all over the world. The incidence of DM is rising rapidly also including children and young persons of reproductive age. Diabetes has been associated with reproductive impairment in both men and women. Diabetes may affect male reproductive functions at multiple levels as a result of its effects on the endocrine control of spermatogenesis, steroidogenesis, sperm maturation, impairment of penile erection and ejaculation. A large number of studies both on diabetic men and experimental diabetic animals have been published on the impact of DM on male reproductive functions during the past few years but many of them have conflicting results. The present review summarizes the research finding of a large number of research papers on the reproductive functions especially on hypothalmo-pituitary-gonadal axis, spermatogenesis, histopathology of testis, synthesis and secretion of testosterone, sperm quality, ejaculatory function and fertility both in diabetic men and experimental diabetic animals.

Assessment of the physiologic contribution of right atrial function to total right heart function in patients with and without pulmonary arterial hypertension.

PubMed

Sivak, Joseph A; Raina, Amresh; Forfia, Paul R

2016-09-01

Total right heart function requires normal function of both the right ventricle and the right atrium. However, the degree to which right atrial (RA) function and right ventricular (RV) function each contribute to total right heart function has not been quantified. In this study, we aimed to quantify the contribution of RA function to total right heart function in a group of pulmonary arterial hypertension (PAH) patients compared to a cohort of normal controls without cardiovascular disease. The normal cohort comprised 35 subjects with normal clinical echocardiograms, while the PAH cohort included 37 patients, of whom 31 had echocardiograms before and after initiation of PAH-specific therapy. Total right heart function was measured via tricuspid annular plane excursion (TAPSE). TAPSE was broken down into two components, the excursion occurring during RA contraction (TAPSERA) and that occurring before RA contraction (TAPSERV). RA fractional area change (RA-FAC) was also compared between the two groups. In the PAH cohort, more than half of the total TAPSE occurred during atrial systole, compared to less than one-third in the normal cohort (51.0% vs. 32.1%; P < 0.0001). There was a significant correlation between RA-FAC and TAPSE in the PAH cohort but not in the normal cohort. TAPSE improved significantly in the posttreatment cohort (1.7 vs. 2.1 cm), but TAPSERA continued to account for about half of the total TAPSE after treatment. RA function accounts for a significantly greater proportion of total right heart function in patients with PAH than in normal subjects.

Assessment of the physiologic contribution of right atrial function to total right heart function in patients with and without pulmonary arterial hypertension

PubMed Central

Sivak, Joseph A.; Raina, Amresh

2016-01-01

Abstract Total right heart function requires normal function of both the right ventricle and the right atrium. However, the degree to which right atrial (RA) function and right ventricular (RV) function each contribute to total right heart function has not been quantified. In this study, we aimed to quantify the contribution of RA function to total right heart function in a group of pulmonary arterial hypertension (PAH) patients compared to a cohort of normal controls without cardiovascular disease. The normal cohort comprised 35 subjects with normal clinical echocardiograms, while the PAH cohort included 37 patients, of whom 31 had echocardiograms before and after initiation of PAH-specific therapy. Total right heart function was measured via tricuspid annular plane excursion (TAPSE). TAPSE was broken down into two components, the excursion occurring during RA contraction (TAPSERA) and that occurring before RA contraction (TAPSERV). RA fractional area change (RA-FAC) was also compared between the two groups. In the PAH cohort, more than half of the total TAPSE occurred during atrial systole, compared to less than one-third in the normal cohort (51.0% vs. 32.1%; P < 0.0001). There was a significant correlation between RA-FAC and TAPSE in the PAH cohort but not in the normal cohort. TAPSE improved significantly in the posttreatment cohort (1.7 vs. 2.1 cm), but TAPSERA continued to account for about half of the total TAPSE after treatment. RA function accounts for a significantly greater proportion of total right heart function in patients with PAH than in normal subjects. PMID:27683609

Peak heart rates and sympathetic function in tetraplegic nonathletes and athletes.

PubMed

Currie, Katharine D; West, Christopher R; Hubli, Michéle; Gee, Cameron M; Krassioukov, Andrei V

2015-06-01

To examine differences in peak heart rate (HR) and measures of sympathetic function between nonathletes and athletes with chronic, motor-complete, cervical spinal cord injury (SCI). Eight nonathletic men with SCI (C4-C7; age 47 ± 9 yr, with injury duration of 16 ± 9 yr) and 13 athletic men with SCI (C5-C8; age 37 ± 8 yr, with injury duration of 16 ± 6 yr) participated in the study. Measures of sympathetic function included palmar sympathetic skin responses (SSR) to median nerve stimulation, and systolic (SBP) and diastolic (DBP) blood pressure responses to a passive sit-up test. Peak HR responses were assessed during a maximal exercise test. Compared to the athletic group, the nonathletic group exhibited lower peak HR (102 ± 34 vs 161 ± 20 bpm, P < 0.001) and average SSR scores (0.13 ± 0.35 vs 2.41 ± 1.97, P = 0.008), along with greater reductions in SBP and DBP in response to passive sit-up (SBP: -22 ± 10 vs -9 ± 12 mm Hg, P = 0.019; DBP: -18 ± 8 mm Hg vs -4 ± 9 mm Hg, P = 0.003). On the basis of the criteria for orthostatic hypotension (OH) (drop in SBP ≥ 20 mm Hg or DBP ≥ 10 mm Hg), 88% and 23% of nonathletes and athletes had OH. Attenuated peak HR in nonathletic individuals with tetraplegia may be secondary to impairments in sympathetic function including absent SSR and OH. Furthermore, the degree of preserved sympathetic function documented in tetraplegic athletes may suggest a predisposition to engage in high-performance sports. Collectively, our findings provide novel insight into the importance of the sympathetic nervous system for exercise performance.

Ultrasound functional imaging in an ex vivo beating porcine heart platform

NASA Astrophysics Data System (ADS)

Petterson, Niels J.; Fixsen, Louis S.; Rutten, Marcel C. M.; Pijls, Nico H. J.; van de Vosse, Frans N.; Lopata, Richard G. P.

2017-12-01

In recent years, novel ultrasound functional imaging (UFI) techniques have been introduced to assess cardiac function by measuring, e.g. cardiac output (CO) and/or myocardial strain. Verification and reproducibility assessment in a realistic setting remain major issues. Simulations and phantoms are often unrealistic, whereas in vivo measurements often lack crucial hemodynamic parameters or ground truth data, or suffer from the large physiological and clinical variation between patients when attempting clinical validation. Controlled validation in certain pathologies is cumbersome and often requires the use of lab animals. In this study, an isolated beating pig heart setup was adapted and used for performance assessment of UFI techniques such as volume assessment and ultrasound strain imaging. The potential of performing verification and reproducibility studies was demonstrated. For proof-of-principle, validation of UFI in pathological hearts was examined. Ex vivo porcine hearts (n  =  6, slaughterhouse waste) were resuscitated and attached to a mock circulatory system. Radio frequency ultrasound data of the left ventricle were acquired in five short axis views and one long axis view. Based on these slices, the CO was measured, where verification was performed using flow sensor measurements in the aorta. Strain imaging was performed providing radial, circumferential and longitudinal strain to assess reproducibility and inter-subject variability under steady conditions. Finally, strains in healthy hearts were compared to a heart with an implanted left ventricular assist device, simulating a failing, supported heart. Good agreement between ultrasound and flow sensor based CO measurements was found. Strains were highly reproducible (intraclass correlation coefficients  >0.8). Differences were found due to biological variation and condition of the hearts. Strain magnitude and patterns in the assisted heart were available for different pump action, revealing

Leptin concentration and risk of impaired physical function in older adults: the Seniors-ENRICA cohort.

PubMed

Lana, Alberto; Struijk, Ellen; Guallar-Castillón, Pilar; Martín-Moreno, Jose María; Rodríguez Artalejo, Fernando; Lopez-Garcia, Esther

2016-11-01

leptin resistance, which may develop during the ageing process, stimulates the production of pro-inflammatory cytokines and insulin resistance that could impair the muscle function. However, the role of leptin on physical functioning among older adults has not yet been elucidated. to examine the association between serum leptin levels and physical function impairment in older adults. prospective study of 1,556 individuals 60 years and older from the Seniors-ENRICA cohort, who were free of physical function limitation at baseline. serum leptin was measured in 2008-10, and incident functional limitation was assessed through 2012. Self-reported limitations in agility and mobility were assessed with the Rosow and Breslau scale, limitation in the lower extremity function was measured with the Short Physical Performance Battery, and impairment in the overall physical performance with the physical component summary of the SF-12. after adjustment for potential confounders and compared to individuals in the lowest quartile of leptin concentration, those in the highest quartile showed increased risk of impaired physical function; the odds ratio (95% confidence interval) and P-trend was: 1.95 (1.11-3.43), P = 0.006 for self-reported impaired mobility; 1.76 (1.08-2.87), P = 0.02 for self-reported impaired agility; 1.48 (1.02-2.15), P = 0.04 for limitation in the lower extremity function; and 1.97 (1.20-3.22), P = 0.01, for decreased overall physical performance. These associations were only modestly explained by C-reactive protein and insulin resistance. Moreover, the associations held across groups with varying health status and were independent of estimated total body fat. higher leptin concentration was associated with increased risk of impaired physical function. Preserving metabolic function during the old age could help delaying physical function decline. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All

Impairment in proverb interpretation as an executive function deficit in patients with amnestic mild cognitive impairment and early Alzheimer's disease.

PubMed

Leyhe, Thomas; Saur, Ralf; Eschweiler, Gerhard W; Milian, Monika

2011-01-01

Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain impairment by common neuropsychological testing. We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer's disease (EAD). The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD.

Taurine Supplementation Improves Functional Capacity, Myocardial Oxygen Consumption, and Electrical Activity in Heart Failure.

PubMed

Ahmadian, Mehdi; Dabidi Roshan, Valiollah; Ashourpore, Eadeh

2017-07-04

Taurine is an amino acid found abundantly in the heart in very high concentrations. It is assumed that taurine contributes to several physiological functions of mammalian cells, such as osmoregulation, anti-inflammation, membrane stabilization, ion transport modulation, and regulation of oxidative stress and mitochondrial protein synthesis. The objective of the current study was to evaluate the effectiveness of taurine supplementation on functional capacity, myocardial oxygen consumption, and electrical activity in patients with heart failure. In a double-blind and randomly designed study, 16 patients with heart failure were assigned to two groups: taurine (TG, n = 8) and placebo (PG, n = 8). TG received 500-mg taurine supplementation three times per day for two weeks. Significant decrease in the values of Q-T segments (p < 0.01) and significant increase in the values of P-R segments (p < 0.01) were detected following exercise post-supplementation in TG rather than in PG. Significantly higher values of taurine concentration, T wave, Q-T segment, physical capacities, and lower values of cardiovascular capacities were detected post-supplementation in TG as compared with PG (all p values <0.01). Taurine significantly enhanced the physical function and significantly reduced the cardiovascular function parameters following exercise. Our results also suggest that the short-term taurine supplementation is an effective strategy for improving some selected hemodynamic parameters in heart failure patients. Together, these findings support the view that taurine improves cardiac function and functional capacity in patients with heart failure. This idea warrants further study.

Echocardiographic predictors of change in renal function with intravenous diuresis for decompensated heart failure.

PubMed

Gannon, Stephen A; Mukamal, Kenneth J; Chang, James D

2018-06-14

The aim of this study was to identify echocardiographic predictors of improved or worsening renal function during intravenous diuresis for decompensated heart failure. Secondary aim included defining the incidence and clinical risk factors for acute changes in renal function with decongestion. A retrospective review of 363 patients admitted to a single centre for decompensated heart failure who underwent intravenous diuresis and transthoracic echocardiography was conducted. Clinical, echocardiographic, and renal function data were retrospectively collected. A multinomial logistic regression model was created to determine relative risk ratios for improved renal function (IRF) or worsening renal function (WRF). Within this cohort, 36% of patients experienced WRF, 35% had stable renal function, and 29% had IRF. Patients with WRF were more likely to have a preserved left ventricular ejection fraction compared with those with stable renal function or IRF (P = 0.02). Patients with IRF were more likely to have a dilated, hypokinetic right ventricle compared with those with stable renal function or WRF (P ≤ 0.01), although this was not significant after adjustment for baseline characteristics. Left atrial size, left ventricular linear dimensions, and diastolic function did not significantly predict change in renal function. An acute change in renal function occurred in 65% of patients admitted with decompensated heart failure. WRF was statistically more likely in patients with a preserved left ventricular ejection fraction. A trend towards IRF was noted in patients with global right ventricular dysfunction. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

A Circadian Clock Gene, Cry, Affects Heart Morphogenesis and Function in Drosophila as Revealed by Optical Coherence Microscopy

PubMed Central

Zeng, Xianxu; Tate, Rebecca E.; McKee, Mary L.; Capen, Diane E.; Zhang, Zhan; Tanzi, Rudolph E.; Zhou, Chao

2015-01-01

Circadian rhythms are endogenous, entrainable oscillations of physical, mental and behavioural processes in response to local environmental cues such as daylight, which are present in the living beings, including humans. Circadian rhythms have been related to cardiovascular function and pathology. However, the role that circadian clock genes play in heart development and function in a whole animal in vivo are poorly understood. The Drosophila cryptochrome (dCry) is a circadian clock gene that encodes a major component of the circadian clock negative feedback loop. Compared to the embryonic stage, the relative expression levels of dCry showed a significant increase (>100-fold) in Drosophila during the pupa and adult stages. In this study, we utilized an ultrahigh resolution optical coherence microscopy (OCM) system to perform non-invasive and longitudinal analysis of functional and morphological changes in the Drosophila heart throughout its post-embryonic lifecycle for the first time. The Drosophila heart exhibited major morphological and functional alterations during its development. Notably, heart rate (HR) and cardiac activity period (CAP) of Drosophila showed significant variations during the pupa stage, when heart remodeling took place. From the M-mode (2D + time) OCM images, cardiac structural and functional parameters of Drosophila at different developmental stages were quantitatively determined. In order to study the functional role of dCry on Drosophila heart development, we silenced dCry by RNAi in the Drosophila heart and mesoderm, and quantitatively measured heart morphology and function in those flies throughout its development. Silencing of dCry resulted in slower HR, reduced CAP, smaller heart chamber size, pupal lethality and disrupted posterior segmentation that was related to increased expression of a posterior compartment protein, wingless. Collectively, our studies provided novel evidence that the circadian clock gene, dCry, plays an essential

Functional Impairment in Latino Children with ADHD: Implications for Culturally Appropriate Conceptualization and Measurement

ERIC Educational Resources Information Center

Haack, Lauren Marie; Gerdes, Alyson C.

2011-01-01

Conceptualizing and measuring functional impairment related to childhood ADHD, particularly within the rapidly growing, yet underserved, Latino population, is an important area of research that is in its infancy in the field of psychology. The functional impairments related to academic achievement, social competence, and familial relations…

Heart rate response and functional capacity in patients with chronic heart failure with preserved ejection fraction.

PubMed

Domínguez, Eloy; Palau, Patricia; Núñez, Eduardo; Ramón, José María; López, Laura; Melero, Joana; Bellver, Alejandro; Santas, Enrique; Chorro, Francisco J; Núñez, Julio

2018-03-24

The mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF) are not yet elucidated. Chronotropic incompetence has emerged as a potential mechanism. We aimed to evaluate whether heart rate (HR) response to exercise is associated to functional capacity in patients with symptomatic HFpEF. We prospectively studied 74 HFpEF patients [35.1% New York Heart Association Class III, 53% female, age (mean ± standard deviation) 72.5 ± 9.1 years, and 59.5% atrial fibrillation]. Functional performance was assessed by peak oxygen consumption (peak VO 2 ). The mean (standard deviation) peak VO 2 was 10 ± 2.8 mL/min/kg. The following chronotropic parameters were calculated: Delta-HR (HR at peak exercise - HR at rest), chronotropic index (CI) = (HR at peak exercise - resting HR)/[(220 - age) - resting HR], and CI according to the equation developed by Keteyian et al. (CIK) (HR at peak exercise - HR at rest)/[119 + (HR at rest/2) - (age/2) - 5 - HR at rest]. In a bivariate setting, peak VO 2 was positively and significantly correlated with Delta-HR (r = 0.35, P = 0.003), CI (r = 0.27, P = 0.022), CIK (r = 0.28, P = 0.018), and borderline with HR at peak exercise (r = 0.22, P = 0.055). In a multivariable linear regression analysis that included clinical, analytical, echocardiographic, and functional capacity covariates, the chronotropic parameters were positively associated with peak VO 2 . We found a linear relationship between Delta-HR and peak VO 2 (β coefficient of 0.03; 95% confidence interval: 0.004-0.05; P = 0.030); conversely, the association among CIs and peak VO 2 was exponentially shaped. In patients with chronic HFpEF, the HR response to exercise was positively associated to patient's functional capacity. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Acute hypoglycemia impairs executive cognitive function in adults with and without type 1 diabetes.

PubMed

Graveling, Alex J; Deary, Ian J; Frier, Brian M

2013-10-01

Acute hypoglycemia impairs cognitive function in several domains. Executive cognitive function governs organization of thoughts, prioritization of tasks, and time management. This study examined the effect of acute hypoglycemia on executive function in adults with and without diabetes. Thirty-two adults with and without type 1 diabetes with no vascular complications or impaired awareness of hypoglycemia were studied. Two hyperinsulinemic glucose clamps were performed at least 2 weeks apart in a single-blind, counterbalanced order, maintaining blood glucose at 4.5 mmol/L (euglycemia) or 2.5 mmol/L (hypoglycemia). Executive functions were assessed with a validated test suite (Delis-Kaplan Executive Function). A general linear model (repeated-measures ANOVA) was used. Glycemic condition (euglycemia or hypoglycemia) was the within-participant factor. Between-participant factors were order of session (euglycemia-hypoglycemia or hypoglycemia-euglycemia), test battery used, and diabetes status (with or without diabetes). Compared with euglycemia, executive functions (with one exception) were significantly impaired during hypoglycemia; lower test scores were recorded with more time required for completion. Large Cohen d values (>0.8) suggest that hypoglycemia induces decrements in aspects of executive function with large effect sizes. In some tests, the performance of participants with diabetes was more impaired than those without diabetes. Executive cognitive function, which is necessary to carry out many everyday activities, is impaired during hypoglycemia in adults with and without type 1 diabetes. This important aspect of cognition has not received previous systematic study with respect to hypoglycemia. The effect size is large in terms of both accuracy and speed.

Intrinsic motivation as a mediator between metacognition deficits and impaired functioning in psychosis.

PubMed

Luther, Lauren; Firmin, Ruth L; Vohs, Jenifer L; Buck, Kelly D; Rand, Kevin L; Lysaker, Paul H

2016-09-01

Poor functioning has long been observed in individuals with psychosis. Recent studies have identified metacognition - one's ability to form complex ideas about oneself and others and to use that information to respond to psychological and social challenges-as being an important determinant of functioning. However, the exact process by which deficits in metacognition lead to impaired functioning remains unclear. This study first examined whether low intrinsic motivation, or the tendency to pursue novel experiences and to engage in self-improvement, mediates the relationship between deficits in metacognition and impaired functioning. We then examined whether intrinsic motivation significantly mediated the relationship when controlling for age, education, symptoms, executive functioning, and social cognition. Mediation models were examined in a cross-sectional data set. One hundred and seventy-five individuals with a psychotic disorder completed interview-based measures of metacognition, intrinsic motivation, symptoms, and functioning and performance-based measures of executive functioning and social cognition. Analyses revealed that intrinsic motivation mediated the relationship between metacognition deficits and impaired functioning (95% CI of indirect effect [0.12-0.43]), even after controlling for the aforesaid variables (95% CI of indirect effect [0.04-0.29]). Results suggest that intrinsic motivation may be a mechanism that underlies the link between deficits in metacognition and impaired functioning and indicate that metacognition and intrinsic motivation may be important treatment targets to improve functioning in individuals with psychosis. The findings of this study suggest that deficits in metacognition may indirectly lead to impaired functioning through their effect on intrinsic motivation in individuals with psychosis. Psychological treatments that target deficits in both metacognition and intrinsic motivation may help to alleviate impaired functioning in

Impaired Long Distance Functional Connectivity and Weighted Network Architecture in Alzheimer's Disease

PubMed Central

Liu, Yong; Yu, Chunshui; Zhang, Xinqing; Liu, Jieqiong; Duan, Yunyun; Alexander-Bloch, Aaron F.; Liu, Bing; Jiang, Tianzi; Bullmore, Ed

2014-01-01

Alzheimer's disease (AD) is increasingly recognized as a disconnection syndrome, which leads to cognitive impairment due to the disruption of functional activity across large networks or systems of interconnected brain regions. We explored abnormal functional magnetic resonance imaging (fMRI) resting-state dynamics, functional connectivity, and weighted functional networks, in a sample of patients with severe AD (N = 18) and age-matched healthy volunteers (N = 21). We found that patients had reduced amplitude and regional homogeneity of low-frequency fMRI oscillations, and reduced the strength of functional connectivity, in several regions previously described as components of the default mode network, for example, medial posterior parietal cortex and dorsal medial prefrontal cortex. In patients with severe AD, functional connectivity was particularly attenuated between regions that were separated by a greater physical distance; and loss of long distance connectivity was associated with less efficient global and nodal network topology. This profile of functional abnormality in severe AD was consistent with the results of a comparable analysis of data on 2 additional groups of patients with mild AD (N = 17) and amnestic mild cognitive impairment (MCI; N = 18). A greater degree of cognitive impairment, measured by the mini-mental state examination across all patient groups, was correlated with greater attenuation of functional connectivity, particularly over long connection distances, for example, between anterior and posterior components of the default mode network, and greater reduction of global and nodal network efficiency. These results indicate that neurodegenerative disruption of fMRI oscillations and connectivity in AD affects long-distance connections to hub nodes, with the consequent loss of network efficiency. This profile was evident also to a lesser degree in the patients with less severe cognitive impairment, indicating that the potential of resting

Resting-State Functional Connectivity Predicts Cognitive Impairment Related to Alzheimer's Disease.

PubMed

Lin, Qi; Rosenberg, Monica D; Yoo, Kwangsun; Hsu, Tiffany W; O'Connell, Thomas P; Chun, Marvin M

2018-01-01

Resting-state functional connectivity (rs-FC) is a promising neuromarker for cognitive decline in aging population, based on its ability to reveal functional differences associated with cognitive impairment across individuals, and because rs-fMRI may be less taxing for participants than task-based fMRI or neuropsychological tests. Here, we employ an approach that uses rs-FC to predict the Alzheimer's Disease Assessment Scale (11 items; ADAS11) scores, which measure overall cognitive functioning, in novel individuals. We applied this technique, connectome-based predictive modeling, to a heterogeneous sample of 59 subjects from the Alzheimer's Disease Neuroimaging Initiative, including normal aging, mild cognitive impairment, and AD subjects. First, we built linear regression models to predict ADAS11 scores from rs-FC measured with Pearson's r correlation. The positive network model tested with leave-one-out cross validation (LOOCV) significantly predicted individual differences in cognitive function from rs-FC. In a second analysis, we considered other functional connectivity features, accordance and discordance, which disentangle the correlation and anticorrelation components of activity timecourses between brain areas. Using partial least square regression and LOOCV, we again built models to successfully predict ADAS11 scores in novel individuals. Our study provides promising evidence that rs-FC can reveal cognitive impairment in an aging population, although more development is needed for clinical application.

Differential Item Functioning Comparisons on a Performance-Based Alternate Assessment for Students with Severe Cognitive Impairments, Autism and Orthopedic Impairments

ERIC Educational Resources Information Center

Laitusis, Cara Cahalan; Maneckshana, Behroz; Monfils, Lora; Ahlgrim-Delzell, Lynn

2009-01-01

The purpose of this study was to examine Differential Item Functioning (DIF) by disability groups on an on-demand performance assessment for students with severe cognitive impairments. Researchers examined the presence of DIF for two comparisons. One comparison involved students with severe cognitive impairments who served as the reference group…

Gender differences in associations between DSM-5 posttraumatic stress disorder symptom clusters and functional impairment in war veterans.

PubMed

Meyer, Eric C; Konecky, Brian; Kimbrel, Nathan A; DeBeer, Bryann B; Marx, Brian P; Schumm, Jeremiah; Penk, Walter E; Gulliver, Suzy Bird; Morissette, Sandra B

2018-05-01

Understanding the links between posttraumatic stress disorder (PTSD) symptoms and functional impairment is essential for assisting veterans in transitioning to civilian life. Moreover, there may be differences between men and women in the relationships between PTSD symptoms and functional impairment. However, no prior studies have examined the links between functional impairment and the revised symptom clusters as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5; American Psychiatric Association, 2013) or whether the associations between PTSD symptom clusters and functional impairment differ by gender. We examined the associations between the DSM-5 PTSD symptom clusters and functional impairment in 252 trauma-exposed Iraq and Afghanistan war veterans (79 females). Regression analyses included demographic factors and exposure to both combat and military sexual trauma as covariates. In the total sample, both the intrusions cluster (β = .18, p = .045) and the negative alterations in cognition and mood cluster (β = .45, p < .001) were associated with global functional impairment. Among male veterans, global functional impairment was associated only with negative alterations in cognition and mood (β = .52, p < .001). However, by contrast, among female veterans, only marked alterations in arousal and reactivity were associated with global functional impairment (β = .35, p = .027). These findings suggest that there may be important gender differences with respect to the relationship between PTSD symptoms and functional impairment. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Different Functional and Microstructural Changes Depending on Duration of Mild Cognitive Impairment in Parkinson Disease.

PubMed

Shin, N-Y; Shin, Y S; Lee, P H; Yoon, U; Han, S; Kim, D J; Lee, S-K

2016-05-01

The higher cortical burden of Lewy body and Alzheimer disease-type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. Fifty-nine patients with Parkinson disease with mild cognitive impairment were classified into 2 groups on the basis of shorter (<1 year, n = 16) and longer (≥1 year, n = 43) durations of parkinsonism before mild cognitive impairment. Fifteen drug-naïve patients with de novo Parkinson disease with intact cognition were included for comparison. Cortical thickness, Tract-Based Spatial Statistics, and seed-based resting-state functional connectivity analyses were performed. Age, sex, years of education, age at onset of parkinsonism, and levodopa-equivalent dose were included as covariates. The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased fractional anisotropy and increased mean and radial diffusivity values in the frontal areas compared with the group with longer duration of parkinsonism before mild cognitive impairment (corrected P < .05). The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity in the default mode network area when the left or right posterior cingulate was used as a seed, and in the dorsolateral prefrontal areas when the left or right caudate was used as a seed (corrected P < .05). The group with longer duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity mainly in the medial prefrontal cortex when the left or right

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

PubMed Central

Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M.; Farrehi, Peter; Borjigin, Jimo

2018-01-01

Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients. PMID:29487541

Treating Heart Failure with Preserved Ejection Fraction: A Challenge for Clinicians.

PubMed

Howard, Patricia A

2015-06-01

Despite a decline in many forms of cardiovascular disease, heart failure (HF) continues to increase. Heart failure with preserved ejection fraction (HFpEF) is common, especially among persons with multiple comorbidities. HFpEF presents many challenges for clinicians due to the incomplete understanding of the underlying mechanisms and lack of consensus on the most effective strategies for treatment. Angiotensin and beta receptor-blocking drugs, which form the cornerstone for the treatment of systolic HF, have failed to show similar benefits in patients with impaired diastolic function. This article provides an overview of drug therapy for HFpEF, including newer agents now under investigation.

Functional significance of cardiac reinnervation in heart transplant recipients.

PubMed

Schwaiblmair, M; von Scheidt, W; Uberfuhr, P; Ziegler, S; Schwaiger, M; Reichart, B; Vogelmeier, C

1999-09-01

There is accumulating evidence of structural sympathetic reinnervation after human cardiac transplantation. However, the functional significance of reinnervation in terms of exercise capacity has not been established as yet; we therefore investigated the influence of reinnervation on cardiopulmonary exercise testing. After orthotopic heart transplantation 35 patients (mean age, 49.1 +/- 8.4 years) underwent positron emission tomography with scintigraphically measured uptake of C11-hydroxyephedrine (HED), lung function testing, and cardiopulmonary exercise testing. Two groups were defined based on scintigraphic findings, indicating a denervated group (n = 15) with a HED uptake of 5.45%/min and a reinnervated group (n = 20) with a HED uptake of 10.59%/min. The two study groups did not show significant differences with regard to anthropometric data, number of rejection episodes, preoperative hemodynamics, and postoperative lung function data. The reinnervated group had a significant longer time interval from transplantation (1625 +/- 1069 versus 800 +/- 1316 days, p < .05). In transplant recipients with reinnervation, heart rate at maximum exercise (137 +/- 15 versus 120 +/- 20 beats/min, p = .012), peak oxygen uptake (21.0 +/- 4 versus 16.1 +/- 5 mL/min/kg, p = .006), peak oxygen pulse (12.4 +/- 2.9 versus 10.2 +/- 2.7 mL/min/beat, p = .031), and anaerobic threshold (11.2 +/- 1.8 versus 9.5 +/- 2.1 mL/min, p = .046) were significantly increased in comparison to denervated transplant recipients. Additionally, a decreased functional dead space ventilation (0.24 +/- 0.05 versus 0.30 +/- 0.05, p = .004) was observed in the reinnervated group. Our study results support the hypothesis that partial sympathetic reinnervation after cardiac transplantation is of functional significance. Sympathetic reinnervation enables an increased peak oxygen uptake. This is most probably due to partial restoration of the chronotropic and inotropic competence of the heart as well as an

Impaired work functioning due to common mental disorders in nurses and allied health professionals: the Nurses Work Functioning Questionnaire.

PubMed

Gärtner, F R; Nieuwenhuijsen, K; van Dijk, F J H; Sluiter, J K

2012-02-01

Common mental disorders (CMD) negatively affect work functioning. In the health service sector not only the prevalence of CMDs is high, but work functioning problems are associated with a risk of serious consequences for patients and healthcare providers. If work functioning problems due to CMDs are detected early, timely help can be provided. Therefore, the aim of this study is to develop a detection questionnaire for impaired work functioning due to CMDs in nurses and allied health professionals working in hospitals. First, an item pool was developed by a systematic literature study and five focus group interviews with employees and experts. To evaluate the content validity, additional interviews were held. Second, a cross-sectional assessment of the item pool in 314 nurses and allied health professionals was used for item selection and for identification and corroboration of subscales by explorative and confirmatory factor analysis. The study results in the Nurses Work Functioning Questionnaire (NWFQ), a 50-item self-report questionnaire consisting of seven subscales: cognitive aspects of task execution, impaired decision making, causing incidents at work, avoidance behavior, conflicts and irritations with colleagues, impaired contact with patients and their family, and lack of energy and motivation. The questionnaire has a proven high content validity. All subscales have good or acceptable internal consistency. The Nurses Work Functioning Questionnaire gives insight into precise and concrete aspects of impaired work functioning of nurses and allied health professionals. The scores can be used as a starting point for purposeful interventions.

Proportional Recovery From Lower Limb Motor Impairment After Stroke.

PubMed

Smith, Marie-Claire; Byblow, Winston D; Barber, P Alan; Stinear, Cathy M

2017-05-01

In people with preserved corticospinal tract (CST) function after stroke, upper limb impairment resolves by ≈70% within 3 months. This is known as the proportional recovery rule. Patients without CST function do not fit this rule and have worse upper limb outcomes. This study investigated resolution of motor impairment in the lower limb (LL). Patients with stroke and LL weakness were assessed 3 days and 3 months after stroke with the LL Fugl-Meyer. CST integrity was determined in a subset of patients using transcranial magnetic stimulation to test for LL motor-evoked potentials and magnetic resonance imaging to measure CST lesion load. Linear regression analyses were conducted to predict resolution of motor impairment (ΔFugl-Meyer) including factors initial impairment, motor-evoked potential status, CST lesion load, and LL therapy dose. Thirty-two patients completed 3-month follow-up and recovered 74% (95% confidence interval, 60%-88%) of initial LL motor impairment. Initial impairment was the only significant predictor of resolution of motor impairment. There was no identifiable cluster of patients who did not fit the proportional recovery rule. Measures of CST integrity did not predict proportional LL recovery. LL impairment resolves by ≈70% within 3 months after stroke. The absence of a nonfitter group may be because of differences in the neuroanatomical organization of descending motor tracts to the upper limb and LL. Proportional recovery of the LL is not influenced by therapy dose providing further evidence that it reflects a fundamental biological process. © 2017 American Heart Association, Inc.

The Reliability of the CVI Range: A Functional Vision Assessment for Children with Cortical Visual Impairment

ERIC Educational Resources Information Center

Newcomb, Sandra

2010-01-01

Children who are identified as visually impaired frequently have a functional vision assessment as one way to determine how their visual impairment affects their educational performance. The CVI Range is a functional vision assessment for children with cortical visual impairment. The purpose of the study presented here was to examine the…

Self-care confidence may be the key: A cross-sectional study on the association between cognition and self-care behaviors in adults with heart failure.

PubMed

Vellone, Ercole; Fida, Roberta; D'Agostino, Fabio; Mottola, Antonella; Juarez-Vela, Raul; Alvaro, Rosaria; Riegel, Barbara

2015-11-01

Self-care, a key element of heart failure care, is challenging for patients with impaired cognition. Mechanisms through which cognitive impairment affects self-care are not currently well defined but evidence from other patient populations suggests that self-efficacy, or task-specific confidence, mediates the relationship between cognitive functioning and patient behaviors such as self-care. The aim of this study was to test the mediating role of self-care confidence in the relationship between cognition and self-care behaviors. A secondary analysis of data from a cross-sectional study. Outpatient heart failure clinics in 28 Italian provinces. 628 Italian heart failure patients. We used the Self-Care of Heart Failure Index v.6.2 to measure self-care maintenance, self-care management, and self-care confidence. Cognition was assessed with the Mini Mental State Examination. Structural equation modeling was used to analyze the data. Participants were 73 years old on average (SD=11), mostly (58%) male and mostly (77%) in New York Heart Association functional classes II and III. The mediation model showed excellent fit (comparative fit index=1.0; root mean square error of approximation=0.02): Self-care confidence totally mediated the relationship between cognition and self-care maintenance and management. Cognition affects self-care behaviors indirectly, through self-care confidence. Interventions aimed at improving self-care confidence may improve self-care, even in heart failure patients with impaired cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Residual symptoms and specific functional impairments in euthymic patients with bipolar disorder.

PubMed

Samalin, Ludovic; de Chazeron, Ingrid; Vieta, Eduard; Bellivier, Frank; Llorca, Pierre-Michel

2016-03-01

The aims of the present study were to confirm the impact of residual symptoms on overall functioning in a large sample of euthymic patients with bipolar disorder in real-life conditions and to explore the relationship between residual symptoms and specific areas of functional impairment. This was a multicenter, cross-sectional, non-interventional study of euthymic outpatients with bipolar disorder. The Functioning Assessment Short Test was used to assess overall and specific domains of functioning (autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time). Various residual symptoms were assessed (residual mood symptoms, emotional dysregulation, sleep and sexual disorders, stigma, and perceived cognitive impairment). Logistic regression was used to determine the best model of association between functional domains and residual symptoms. Almost half of the 468 patients included (42%) had poor overall functioning. Residual depressive symptoms appeared to have an impact on overall functioning and in nearly all areas of functioning. In addition, specific residual symptoms had significantly more negative effects on some domains of functioning in euthymic patients with bipolar disorder (residual manic symptoms and occupational stigma on autonomy, emotional inhibition on occupational functioning, residual manic symptoms on financial issues, family stigma on interpersonal relationships, and sexual function and occupational stigma on leisure time). Our findings highlight the importance of evaluating overall functioning in clinical practice as well as functional domains. They also indicate that some residuals symptoms in patients with bipolar disorder should be targeted in personalized treatment plans, in order to improve functioning in the domains in which the patient is most impaired. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Renal function monitoring in heart failure - what is the optimal frequency? A narrative review.

PubMed

Al-Naher, Ahmed; Wright, David; Devonald, Mark Alexander John; Pirmohamed, Munir

2018-01-01

The second most common cause of hospitalization due to adverse drug reactions in the UK is renal dysfunction due to diuretics, particularly in patients with heart failure, where diuretic therapy is a mainstay of treatment regimens. Therefore, the optimal frequency for monitoring renal function in these patients is an important consideration for preventing renal failure and hospitalization. This review looks at the current evidence for optimal monitoring practices of renal function in patients with heart failure according to national and international guidelines on the management of heart failure (AHA/NICE/ESC/SIGN). Current guidance of renal function monitoring is in large part based on expert opinion, with a lack of clinical studies that have specifically evaluated the optimal frequency of renal function monitoring in patients with heart failure. Furthermore, there is variability between guidelines, and recommendations are typically nonspecific. Safer prescribing of diuretics in combination with other antiheart failure treatments requires better evidence for frequency of renal function monitoring. We suggest developing more personalized monitoring rather than from the current medication-based guidance. Such flexible clinical guidelines could be implemented using intelligent clinical decision support systems. Personalized renal function monitoring would be more effective in preventing renal decline, rather than reacting to it. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Impairment in Proverb Interpretation as an Executive Function Deficit in Patients with Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease

PubMed Central

Leyhe, Thomas; Saur, Ralf; Eschweiler, Gerhard W.; Milian, Monika

2011-01-01

Background/Aims Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain impairment by common neuropsychological testing. Methods We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer's disease (EAD). Results The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Conclusions Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD. PMID:22163233

Hypertension Severity Is Associated With Impaired Cognitive Performance.

PubMed

Muela, Henrique C S; Costa-Hong, Valeria A; Yassuda, Mônica S; Moraes, Natália C; Memória, Claudia M; Machado, Michel F; Macedo, Thiago A; Shu, Edson B S; Massaro, Ayrton R; Nitrini, Ricardo; Mansur, Alfredo J; Bortolotto, Luiz A

2017-01-11

Most evidence of target-organ damage in hypertension (HTN) is related to the kidneys and heart. Cerebrovascular and cognitive impairment are less well studied. Therefore, this study analyzed changes in cognitive function in patients with different stages of hypertension compared to nonhypertensive controls. In a cross-sectional study, 221 (71 normotensive and 150 hypertensive) patients were compared. Patients with hypertension were divided into 2 stages according to blood pressure (BP) levels or medication use (HTN-1: BP, 140-159/90-99 or use of 1 or 2 antihypertensive drugs; HTN-2: BP, ≥160/100 or use of ≥3 drugs). Three groups were comparatively analyzed: normotension, HTN stage 1, and HTN stage 2. The Mini-Mental State Examination, Montreal Cognitive Assessment, and a validated comprehensive battery of neuropsychological tests that assessed 6 main cognitive domains were used to determine cognitive function. Compared to the normotension and HTN stage-1, the severe HTN group had worse cognitive performance based on Mini-Mental State Examination (26.8±2.1 vs 27.4±2.1 vs 28.0±2.0; P=0.004) or Montreal Cognitive Assessment (23.4±3.7 vs 24.9±2.8 vs 25.5±3.2; P<0.001). On the neuropsychological tests, patients with hypertension had worse performance in language, processing speed, visuospatial abilities, and memory. Age, hypertension stage, and educational level were the best predictors of cognitive impairment in patients with hypertension in different cognitive domains. Cognitive impairment was more frequent in patients with hypertension, and this was related to hypertension severity. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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

PubMed

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

2017-03-01

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

Temporal cohesion of the structural, functional and molecular characteristics of the developing zebrafish heart.

PubMed

Matrone, Gianfranco; Wilson, Kathryn S; Mullins, John J; Tucker, Carl S; Denvir, Martin A

2015-06-01

Heart formation is a complex, dynamic and highly coordinated process of molecular, morphogenetic and functional factors with each interacting and contributing to formation of the mature organ. Cardiac abnormalities in early life can be lethal in mammals but not in the zebrafish embryo which has been widely used to study the developing heart. While early cardiac development in the zebrafish has been well characterized, functional changes during development and how these relate to architectural, cellular and molecular aspects of development have not been well described previously. To address this we have carefully characterised cardiac structure, function, cardiomyocyte proliferation and cardiac-specific gene expression between 48 and 120 hpf in the zebrafish. We show that the zebrafish heart increases in volume and changes shape significantly between 48 and 72 hpf accompanied by a 40% increase in cardiomyocyte number. Between 96 and 120 hpf, while external heart expansion slows, there is rapid formation of a mature and extensive trabecular network within the ventricle chamber. While ejection fraction does not change during the course of development other determinants of contractile function increase significantly particularly between 72 and 96 hpf leading to an increase in cardinal vein blood flow. This study has revealed a number of novel aspects of cardiac developmental dynamics with striking temporal orchestration of structure and function within the first few days of development. These changes are associated with changes in expression of developmental and maturational genes. This study provides important insights into the complex temporal relationship between structure and function of the developing zebrafish heart. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.