Function In Heart Failure Research Articles

Abstract 17091: High Saturated Fat Intake Improves Survival in Genetic Cardiomyopathy Compared to a High Polyunsaturated Fat Diet or a Low Fat Diet

Surprisingly, a high fat diet comprised mainly of saturated fatty acids improves LV function and survival in rat models of heart failure induced by hypertension or myocardial infarction. The mechanism for this effect is not clear, nor is it known if a similar effect occurs with a high fat diet composed of plant derived polyunsaturated fatty acids (PUFA), or in genetic cardiomyopathies. We determined if survival in cardiomyopathic hamsters (Bio TO-2 strain) is prolonged by a high fat diet compared to a low fat diet (see table). Further, we compared the effect of high fat diets enriched with either saturated fat (palmitate and stearate), or PUFAs from plant sources(primarily linoleic and α-linolenic acids). Cardiomyopathic hamsters (6 wks old) were fed either a Low Fat diet; a High PUFA diet, or a High Saturated Fat diet. Survival was assessed (n=30/group), and subgroups were evaluated at 30 wks of age (n=12/group) for LV and mitochondrial function. The diet has no effect on LV function as assessed by echocardiography, and there was no difference in body weight or LV mass. Since there is impaired mitochondrial function in heart failure and dietary lipid composition might positively impact mitochondrial function, isolated mitochondria were assessed. Respiration and Ca 2+ -induced mitochondrial permeability transition were unaffected by diet. On the other hand, the high PUFA diet increased fat pad mass compared with the two other cardiomyopathic groups and elevated plasma free fatty acid concentration (p<0.05). Importantly, there was a significant increase in survival in the high saturated sat group compared to the either the low fat or the high PUFA groups after 16 months of treatment (p<0.0001). These results show that a high fat diet comprised largely of long chain saturated fatty acids increase survival in cardiomyopathic hamsters compared to either a low fat diet or a high fat diet comprised of PUFA from plant sources. The effect was independent of improved mitochondrial function.

POSTER PRESENTATIONS

POSTER PRESENTATIONS

Myocyte Changes in Heart Failure

Structural remodeling is a major feature of heart failure and typically precedes the development of symptomatic disease. Structural remodeling of the heart reflects changes in myocyte morphology. Disproportional myocyte growth is observed in pathologic concentric hypertrophy (myocyte thickening) and in eccentric dilated hypertrophy (myocyte lengthening). Alterations in myocyte shape lead to changes in chamber geometry and wall stress. Human and animal studies indicate that changes in myocyte morphology are reversible. Normalization or reversal of maladaptive cardiomyocyte remodeling should be a therapeutic aim that can prevent deterioration or improve cardiac function in heart failure.

Mitochondrial Dynamics in Heart Failure

Mitochondria have been widely studied for their critical role in cellular metabolism, energy production, and cell death. New developments in research on mitochondria derived from studies in yeast have led to the discovery of entirely new mitochondrial processes that have implications for mitochondrial function in heart failure. Recent studies have identified that maintaining normal mitochondrial morphology and function depends on the dynamic balance of mitochondrial fusion and fission (division). Mitochondrial fusion and fission are constant ongoing processes, which are essential for the maintenance of normal mitochondrial function. Studies in heart failure have been limited but suggest a possible reduction in mitochondrial fusion. As mitochondrial fusion and fission have important links to apoptosis, a key mechanism of loss of cardiac myocytes in heart failure, there are many implications for both heart failure research and treatment.

Study of quantitative assessment of left ventricular systolic function by tissue motion annular displacement in heart failure patients

ObjectiveTo evaluate the ability of tissue motion annular displacement (TMAD) for assessment of global left ventricular systolic function in heart failure patients.MethodsThe HF group and the control group were composed...

Hemodynamic and Neurochemical Determinates of Renal Function in Heart Failure

In patients with chronic heart failure (HF) abnormalities in renal function are common and have a strong negative impact on prognosis. The etiology of renal dysfunction in HF is poorly understood. We measured systemic blood pressure, central hemodynamics, GFR (inulin), renal plasma flow (RPF, para-amino hippurate) and renal sympathetic activity (radiotracer assessment of transrenal norepineprine gradient corrected for extraction) in 62 patients with NYHA class II-III HF secondary to LV systolic dysfunction. Mean age was 58±11 years and the mean EF was 25±7%. Regression analysis revealed that GFR was systematically related to RPF, right atrial pressure and mean arterial BP but not to mean pulmonary artery pressure, wedge pressure cardiac output, EF or measures of renal sympathetic activity. Multiple regression analysis revealed that the only independent predictor of GFR was RPF. Further regression analysis revealed that RPF was systematically related to renal sympathetic activity, right atrial pressure, and wedge pressure but not mean arterial BP, cardiac output or EF. Multiple regression analysis revealed that only right atrial independently predicted RPF. Hemodynamic, neurochemical and renal function responses to Dobutamine (n=13) and Nitroprusside (n=23) were evaluated. Changes in GFR in response to these interventions were closely correlated with changes in right atrial, mean pulmonary artery and wedge pressure but not to changes in cardiac output, systemic arterial BP or renal sympathetic activity. In this case the multiple regression analysis revealed that decreases in right atrial and wedge pressures were both independent predictors of increases in GFR. These data support the concept that GFR is strongly dependent on RPF, which, in turn, is independently related to right atrial pressure. Further, reductions in right and left heart filling pressures in response to therapeutic interventions independently predict increases in GFR. These findings suggest that reductions in cardiac filling pressure should continue to be an important goal in the management of chronic HF while modifications of cariac output and systemic arterial pressure appear to have less impact on renal function.

Selective and specific If inhibition with ivabradine: new perspectives for the treatment of cardiovascular disease

Heart rate is a major determinant of myocardial oxygen demand and supply, and increased heart rate adversely affects the pathophysiology of myocardial ischemia. High resting heart rate is a risk factor in cardiovascular disease. The development of the heart rate-lowering agent ivabradine showed that heart rate was also an important treatment target, notably in coronary artery disease and heart failure. Indeed, heart rate reduction with ivabradine, a selective and specific If inhibitor, reduces myocardial oxygen demand, increases diastolic perfusion time and improves energetics in ischemic myocardium. Ivabradine protects the myocardium during ischemia, improves left ventricular function in heart failure and reduces remodeling following myocardial infarction. It improves prognosis in patients with coronary artery disease, left ventricular dysfunction and heart rate ≥70 beats per minute, as well as in patients with heart failure and left ventricular dysfunction. Ivabradine is safe, well tolerated and can be used in combination with the main drugs for cardiovascular disease.

Changes in myofilament proteins, but not Ca2+ regulation, are associated with a high-fat diet-induced improvement in contractile function in heart failure

Pathological conditions such as diabetes, insulin resistance, and obesity are characterized by elevated plasma and myocardial lipid levels and have been reported to exacerbate the progression of heart failure (HF). Alterations in cardiomyocyte Ca(2+) regulatory properties and myofilament proteins have also been implicated in contractile dysfunction in HF. However, our prior studies reported that high saturated fat (SAT) feeding improves in vivo myocardial contractile function, thereby exerting a cardioprotective effect in HF. Therefore, we hypothesized that SAT feeding improves contractile function by altering Ca(2+) regulatory properties and myofilament protein expression in HF. Male Wistar rats underwent coronary artery ligation (HF) or sham surgery (SH) and were fed normal chow (SHNC and HFNC groups) or a SAT diet (SHSAT and HFSAT groups) for 8 wk. Contractile properties were measured in vivo [echocardiography and left ventricular (LV) cannulation] and in isolated LV cardiomyocytes. In vivo measures of contractility (peak LV +dP/dt and -dP/dt) were depressed in the HFNC versus SHNC group but improved in the HFSAT group. Isolated cardiomyocytes from both HF groups were hypertrophied and had decreased percent cell shortening and a prolonged time to half-decay of the Ca(2+) transient versus the SH group; however, SAT feeding reduced in vivo myocyte hypertrophy in the HFSAT group only. The peak velocity of cell shortening was reduced in the HFNC group but not the HFSAT group and was positively correlated with in vivo contractile function (peak LV +dP/dt). The HFNC group demonstrated a myosin heavy chain (MHC) isoform switch from fast MHC-α to slow MHC-β, which was prevented in the HFSAT group. Alterations in Ca(2+) transients, L-type Ca(2+) currents, and protein expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase and phosphorylated phospholamban could not account for the changes in the in vivo contractile properties. In conclusion, the cardioprotective effects associated with SAT feeding in HF may occur at the level of the isolated cardiomyocyte, specifically involving changes in myofilament function but not sarcoplasmic reticulum Ca(2+) regulatory properties.

Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium

Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P < 0.01) and end-systolic (8.6 ± 0.5 vs. 9.6 ± 0.6 mm, P < 0.01) dimensions and attenuated MI-induced increases in LV end-diastolic pressure. Cross-sectional areas of cardiomyocytes were smaller in ST rats and associated with a significant reduction in myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.

Systemic arterial and venous determinants of renal hemodynamics in congestive heart failure

Heart and kidney interactions are fascinating, in the sense that failure of the one organ strongly affects the function of the other. In this review paper, we analyze how principal driving forces for glomerular filtration and renal blood flow are changed in heart failure. Moreover, renal autoregulation and modulation of neurohumoral factors, which can both have repercussions on renal function, are analyzed. Two paradigms seem to apply. One is that the renin-angiotensin system (RAS), the sympathetic nervous system (SNS), and extracellular volume control are the three main determinants of renal function in heart failure. The other is that the classical paradigm to analyze renal dysfunction that is widely applied in nephrology also applies to the pathophysiology of heart failure: pre-renal, intra-renal, and post-renal alterations together determine glomerular filtration. At variance with the classical paradigm is that the most important post-renal factor in heart failure seems renal venous hypertension that, by increasing renal tubular pressure, decreases GFR. When different pharmacological strategies to inhibit the RAS and SNS and to assist renal volume control are considered, there is a painful lack in knowledge about how widely applied drugs affect primary driving forces for ultrafiltration, renal autoregulation, and neurohumoral control. We call for more clinical physiological studies.

SERCA2a Gene Transfer Decreases Sarcoplasmic Reticulum Calcium Leak and Reduces Ventricular Arrhythmias in a Model of Chronic Heart Failure

Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) gene therapy improves mechanical function in heart failure and is under evaluation in a clinical trial. A critical question is whether SERCA2a gene therapy predisposes to increased sarcoplasmic reticulum calcium (SR Ca(2+)) leak, cellular triggered activity, and ventricular arrhythmias in the failing heart. We studied the influence of SERCA2a gene therapy on ventricular arrhythmogenesis in a rat chronic heart failure model. ECG telemetry studies revealed a significant antiarrhythmic effect of SERCA2a gene therapy with reduction of both spontaneous and catecholamine-induced arrhythmias in vivo. SERCA2a gene therapy also reduced susceptibility to reentry arrhythmias in ex vivo programmed electrical stimulation studies. Subcellular Ca(2+) homeostasis and spontaneous SR Ca(2+) leak characteristics were measured in failing cardiomyocytes transfected in vivo with a novel AAV9.SERCA2a vector. SR Ca(2+) leak was reduced after SERCA2a gene therapy, with reversal of the greater spark mass observed in the failing myocytes, despite normalization of SR Ca(2+) load. SERCA2a reduced ryanodine receptor phosphorylation, thereby resetting SR Ca(2+) leak threshold, leading to reduced triggered activity in vitro. Both indirect effects of reverse remodeling and direct SERCA2a effects appear to underlie the antiarrhythmic action. SERCA2a gene therapy stabilizes SR Ca(2+) load, reduces ryanodine receptor phosphorylation and decreases SR Ca(2+) leak, and reduces cellular triggered activity in vitro and spontaneous and catecholamine-induced ventricular arrhythmias in vivo in failing hearts. SERCA2a gene therapy did not therefore predispose to arrhythmias and may represent a novel antiarrhythmic strategy in heart failure.

Assessment of systolic and diastolic function in heart failure using ambulatory monitoring with acoustic cardiography

Introduction. The circadian variation of heart function and heart sounds in patients with and without heart failure (HF) is poorly understood. We hypothesized HF patients would exhibit less circadian variation with worsened cardiac function and sleep apnea. Methods. We studied 67 HF patients (age 67.4 ± 8.2 years; 42% acute HF) and 63 asymptomatic control subjects with no history of HF (age 61.6 ± 7.7 years). Subjects wore a heart sound/ECG/respiratory monitor. The data were analyzed for sleep apnea, diastolic heart sounds, and systolic time intervals. Results. The HF group had significantly greater prevalence of the third heart sound and prolongation of electro-mechanical activation time, while the control group had an age-related increase in the prevalence of the fourth heart sound. The control group showed more circadian variation in cardiac function. The HF subjects had more sleep apnea and higher occurrence of heart rate non-dipping. Conclusions. The control subjects demonstrated an increasing incidence of diastolic dysfunction with age, while systolic function was mostly unchanged with aging. Parameters related to systolic function were significantly worse in the HF group with little diurnal variation, indicating a constant stimulation of sympathetic tone in HF and reduction of diurnal regulation.

Bioelectrical impedance vector analysis (BIVA) in stable and non-stable heart failure patients: A pilot study

Heart failure (HF) patients have a high morbidity and mortality and often require numerous visits and hospital readmissions related to fluid retention [ [1] Gonseth J. Guallar-Castillon P. Banegas J.R. Rodriguez-Artalejo F. The effectiveness of disease management programmes in reducing hospital re-admission in older patients with heart failure: a systematic review and meta-analysis of published reports. Eur Heart J. 2004; 18: 1570-1595 Crossref Scopus (366) Google Scholar ]. Biompedance is a method of body composition analysis studied in HF in different ways such as impedance cardiography [ [2] Thompson B. Drazner M.H. Dries D.L. Yancy C.W. Systolic time ratio by impedance cardiography to distinguish preserved vs impaired left ventricular systolic function in heart failure. Congest Heart Fail. 2008; 14: 261-265 Crossref PubMed Scopus (16) Google Scholar ] or as a home monitoring method in telemedicine systems [ [3] Radai M.M. Arad M. Zlochiver S. Krief H. Engelman T. Abboud S. A novel telemedicine system for monitoring congestive heart failure patients. Congest Heart Fail. 2008; 14: 239-244 Crossref PubMed Scopus (8) Google Scholar ], but little data exist about the analysis of the components of the impedance vector (BIVA-Bioimpedance Vector Analysis-) in HF. The result of a measurement using bioelectrical impedance is a vector (Z vector) in which the opposition of an alternating current flow through intra- and extra-cellular ionic solutions is resistance (R), and the capacitance of biological tissues, is reactance (Xc). The arc tangent of the vector is the phase angle (PA) [ [4] Grimnes S. Martinsen Ø.G. Bioimpedance and bioelectricity basics. in: Academic Press, London2000: 114-115 Google Scholar ]. BIVA is a validated method where the components of the impedance vector are normalized by the height (H) of the subjects (R/H and Xc/H) [ [5] Piccoli A. Pastori G. BIVA software. Department of Medical and Surgical Sciences, University of Padova, Italy2002 Google Scholar ]. They are represented on confidence and tolerance ellipses in an RXc-graph [ [6] Piccoli A. Rossi B. Pillon L. Bucciante G. A new method for monitoring body fluid variation by bioimpedance analysis: the RXc graph. Kidney Int. 1994; 46: 534-539 Crossref PubMed Scopus (502) Google Scholar ] separated by gender [ 7 Piccoli A. Nigrelli S. Caberlotto A. Bivariate normal values of the bioelectrical impedance vector in adult and elderly populations. Am J Clin Nutr. 1995; 61: 269-270 PubMed Google Scholar , 8 Piccoli A. Pillon L. Dumler F. Impedance vector distribution by sex, race, body mass index, and age in the United States: standard reference intervals as bivariate Z scores. Nutrition. 2002; 18: 156-170 Google Scholar ]. Many populations have already been characterized by BIVA [ 7 Piccoli A. Nigrelli S. Caberlotto A. Bivariate normal values of the bioelectrical impedance vector in adult and elderly populations. Am J Clin Nutr. 1995; 61: 269-270 PubMed Google Scholar , 8 Piccoli A. Pillon L. Dumler F. Impedance vector distribution by sex, race, body mass index, and age in the United States: standard reference intervals as bivariate Z scores. Nutrition. 2002; 18: 156-170 Google Scholar , 9 Piccoli A. Fanos V. Peruzzi L. et al. Reference values of the bioelectical impedance vector in neonates in the first week after birth. Nutrition. 2002; 18: 17-21 Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar , 10 De Palo T. Messina G. Edefonti A. et al. Normal values of the bioelectrical impedance vector in childhood and puberty. Nutrition. 2000; 16: 417-424 Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar , 11 Piccoli A. Brunani A. Savia G. Discriminating between body fat and fluid changes in the obese adult using bioimpedance vector analysis. Int J Obes. 1998; 22: 97-104 Crossref PubMed Scopus (128) Google Scholar , 12 Nescolarde L. Piccoli A. Doñate T. Rosell J. Bioelectrical impedance vector analysis in haemodialysis patients: relation between oedema and mortality. Physiol Meas. 2004; 25: 1271-1280 Crossref PubMed Scopus (63) Google Scholar , 13 Nescolarde L. Doñate T. Piccoli A. Rosell J. Comparison of segmental with whole-body impedance measurements in peritoneal dialysis patients Med. Eng Phys. 2008; 30: 817-824 Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar , 14 Toso S. Piccoli A. Gusella M. Menon D. Bononi A. Crepaldi G. Altered tissue electric properties in lung cancer patients as detected by bioelectric impedance vector analysis. Nutrition. 2000; 16: 120-124 Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar ], but little data exist in HF. The aim of this pilot study was to assess the usefulness of BIVA in assessing the hydration state in stable and non-stable HF patients.

Cardiac Resynchronization Therapy for Treatment of Heart Failure

Conduction abnormalities, commonly seen in systolic heart failure, lead to delayed activation of the myocardium as the electrical impulse spreads slowly without the aid of healthy conduction tissue. The resulting dyssynchronous ventricular contraction is mechanically less efficient, reducing systolic function and impairing diastolic filling. Simultaneous pacing of the right and left ventricles (i.e., biventricular pacing) reduces ventricular dyssynchronous contraction, overcoming these consequences of conduction delay. An important role for implantable rhythm-management devices providing cardiac resynchronization therapy has emerged in the optimization of ventricular function in heart failure. Long-term benefits in patient outcomes have been well established. With increasing use, understanding of cardiac resynchronization therapy devices and the principles behind the therapy are important for physicians providing perioperative and intensive care for patients with heart failure.

The use of recombinant human B-type natriuretic peptide for the protection of cardiac and renal functions in heart failure patients with acute anterior myocardial infarction in peri-operative period of primary percutaneous coronary intervention

To evaluate the protective effect of recombinant human B-type natriuretic peptide (rhBNP) on cardiac and renal functions in heart failure (HF) patients as a result of acute anterior myocardial infarction (AAMI) in peri-operative period of primary percutaneous coronary intervention (pPCI). One hundred and twenty-six patients with AAMI-HF were enrolled into this study. All patients undertaken pPCI were randomly assigned to the rhBNP group (n=62) or the control group (n=64). rhBNP or nitroglycerin was intravenously administered on the basis of conventional treatment from first day of admission to 24 hours after pPCI in both groups. Heart rate (HR), systolic blood pressure (SBP), B-type natriuretic peptide (BNP), estimated glomerular filtration rate (eGFR) and heart function were observed. All patients were followed up for 30 days for the observation of main adverse cardiac events (MACE). The HR was significantly decreased compared with that at admission in rhBNP group, but such condition was not found in the control group. The SBP was reduced obviously in both groups. The plasma level of BNP, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic dimension (LVEDD) were improved significantly at different time points compared with those before administration in both groups. The improvement of above parameters in rhBNP group was more significant than that in the control group [BNP (ng/L) 30 hours after pPCI: 303.5±128.4 vs. 354.0±133.6, 14 days after pPCI: 157.8±78.6 vs. 201.1±91.7; LVEF 1 day after pPCI: 0.420±0.052 vs. 0.378±0.055, 14 days after pPCI : 0.444±0.050 vs. 0.393±0.055, 30 days after pPCI: 0.469±0.053 vs. 0.413±0.052; LVEDD (mm) 1 day after pPCI: 53.5±4.4 vs. 57.6±4.4, 14 days after pPCI : 49.6±5.1 vs. 53.4±4.6, 30 days after pPCI: 46.5±4.4 vs. 50.2±4.8, P<0.05 or P<0.01]. The eGFR was reduced obviously 1 day after pPCI than that at admission in both groups, and eGFR recovered to baseline 3 days after pPCI. The level of eGFR was significantly increased 7 days and 14 days after pPCI than that at admission, but there was no difference between rhBNP group and control group. The incidence of contrast-induced nephropathy showed a lowering tendency in the rhBNP group than that in the control group [19.4% (12/62) vs. 29.7% (19/64), P=0.178]. The incidence of ventricular arrhythmias was obviously lowered 7 days after pPCI in the rhBNP group than that in the control group [48.4% (30/62) vs. 75.0% (48/64), P<0.01]. The rate of MACE was lower in rhBNP group than that in control group in 30 days [12.9% (8/62) vs. 26.6% (17/64), P<0.05]. Administration of rhBNP can effectively improve the heart function in AAMI-HF patients undergoing pPCI, and it lowered the incidence of MACE in 30 days, without influence on renal function, and it can reduce the incidence of contrast-induced nephropathy.

Improvement in Right Ventricular Systolic Function after Cardiac Resynchronization Therapy Correlates with Left Ventricular Reverse Remodeling

Cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function in heart failure (HF). However, the effects of CRT on right ventricular (RV) systolic function are not fully understood. We aimed to determine echocardiographic correlates of improvement in RV systolic function after CRT. Fifty-four patients (61.9 ± 10.5 years; 43 men; LV ejection fraction 24.6 ± 4.0%; QRS duration > 120 ms) with HF were enrolled. Standard echocardiography, strain rate (SR), and tissue Doppler imaging were performed in all patients before and 6 months after CRT. Pulsed-wave TDI-derived systolic indices of RV included systolic (RV(S) ) and isovolumic velocity (RV(IVV)) and isovolumic acceleration (RV(IVA)). Response to CRT was defined as decline in LV end-systolic volume (LVESV) ≥ 10%. When indices of RV systolic function were assessed between responders and nonresponders, in responders (38 patients, 70.4%) RV end-diastolic diameters (RVD1-3), mid-RV strain, and mid-RV SR improved significantly (P < 0.01, for all). RV(S) (10.77 ± 4.29 vs 12.62 ± 4.10 cm/sec, P = 0.005), RV(IVV) (14.71 ± 5.88 vs 18.52 ± 6.62 cm/sec, P < 0.001), and RV(IVA) (1.69 ± 0.70 vs 2.39 ± 0.77 m/sec(2) , P < 0.001) significantly increased among responders. There was no significant change in these parameters among nonresponders. Pearson's analyses revealed moderate positive correlations between reduction of LVESV and ΔRV(IVV) (r = 0.467, P = 0.001) and ΔRV(IVA) (r = 0.473, P = 0.001), respectively. RV diameters and systolic indices after CRT improved only in the responder group. Improvement in RV systolic performance after CRT is correlated with the reduction of LVESV.

Therapeutic effect and safety of drug eluting stent for patients with acute ST-elevation anterior wall myocardial infarction by left anterior descending artery occluded abruptly

To assess the therapeutic effect and safety of drug eluting stent for the patients with anterior wall myocardial infarction by left anterior descending artery occluded abruptly. From January 2004 to December 2008, 302 patients with anterior wall myocardial infarction in 12 hours from chest pain to treatment were treated. But only 189 patients were recruited and randomly divided into drug eluting stent group (n = 95) and bare metal stent group (n = 94). The occurrence of cardiac death, stent thrombosis, reinfarction, target vessel revascularization and re-hospitalization because of heart function failure was compared. There was no difference in cardiac death [3/95 (3%) vs 7/94 (7%), P = 0.206], reinfarction [1/95 (1%) vs 5/94 (5%), P = 0.112] and re-hospitalization because of heart function failure [8 (8%) vs 5 (5%), P = 0.434]. Compared with those in bare metal stent group, the patients in drug eluting stent group has a lower rate of target vessel revascularization [2 (2%) vs 13 (14%), P = 0.009] and composite therapeutic effect endpoints [12 (13%) vs 25 (27%), P = 0.011]. There was no difference in safety endpoint or stent thrombosis [1 (1%) vs 4 (4%), P = 0.204]. In patients with anterior wall myocardial infarction by left anterior descending artery occluded abruptly, drug eluting stent decreases the rate of target vessel revascularization. But it has no increased stent thrombosis.

Hemoglobin and Hematocrit Inversely Correlate With Systolic Function in Heart Failure

Hemoglobin and Hematocrit Inversely Correlate With Systolic Function in Heart Failure

Apoptosis-related factors p53, bcl-2 and the defects of force transmission in dilated cardiomyopathy

The etiology of heart failure in dilated cardiomyopathy involves multiple agents. The purpose of this study was to investigate the presence of apoptosis-related proteins p53, bcl-2, and the defects of force transmission in end-stage dilated cardiomyopathy. We studied myocardial samples from 20 hearts with histologic findings of dilated cardiomyopathy. Myocardial samples obtained from 10 normal hearts were used as controls. An immunohistochemical method was performed with the use of desmin, N-cadherin, p53, and bcl-2 antibodies. The expression of desmin and N-cadherin was much more pronounced in dilated cardiomyopathy, and both of them were arranged disorderly. On the other hand, increased expression of p53 is associated with progressive loss of myocytes by apoptosis in heart failure, and increased expression of bcl-2 represents a possible compensatory antiapoptotic mechanism. The increased amount and the irregular distribution of desmin and N-cadherin in dilated cardiomyopathy may compensate for the loss of cellular stability due to the loss of contractile material. These alterations contribute to the deterioration of contractile function in heart failure. Furthermore, the prevalence of an apoptotic or compensatory antiapoptotic mechanism may influence the evolution of heart failure in dilated cardiomyopathy.

Cardiac resynchronization therapy-induced left ventricular reverse remodelling is associated with reduced plasma annexin A5

Cardiac resynchronization therapy (CRT) diminishes cardiac apoptosis and improves systolic function in heart failure (HF) patients with ventricular dyssynchrony. Plasma annexin A5 (AnxA5), a protein related to cellular damage, is associated with systolic dysfunction. We investigated whether the response to CRT is associated with plasma AnxA5. We also studied AnxA5 overexpression effects in HL-1 cardiomyocytes. AnxA5 ELISA was performed in plasma from 57 patients with HF and ventricular dyssynchrony at baseline and after 1 year of CRT. Patients were categorized as responders if they presented both a reduction in left ventricular (LV) end-systolic volume index (LVESVi) >10% and an increase in LV ejection fraction (LVEF) >10%. HL-1 cells were transfected with human AnxA5 cDNA, and AnxA5, PKC, Akt, p38MAPK, Bcl-2, mitochondrial integrity, caspase-3, and ATP were assessed. At baseline, an increased plasma AnxA5 level was associated with decreased LVEF and increased LVEDVi values (P < 0.05). No differences in baseline AnxA5 were observed between responders and non-responders. After CRT, AnxA5 decreased (P = 0.001) in responders but remained unchanged in non-responders. Final values of AnxA5 were independently associated with LVEF (r = -0.387, P = 0.003) and LVESVi (r = 0.403, P = 0.004) in all patients. Compared with control cells, AnxA5-transfected cells exhibited AnxA5 overexpression, decreased PKC and Akt and increased p38MAPK and Bcl-2 phosphorylation, loss of mitochondrial integrity, caspase-3 activation, and decreased ATP. CRT-induced LV reverse remodelling is associated with reduction in plasma AnxA5. The excess of AnxA5 is detrimental for HL-1 cardiomyocytes. Collectively, these data suggest that the beneficial effects of CRT might be related to an AnxA5 decrease.