An impaired renal function: a predictor of ventricular arrhythmias and mortality in patients with nonischemic cardiomyopathy and heart failure.

BACKGROUND: This study investigated the overall mortality and the incidence of ventricular tachyarrhythmia (VT) in 99 patients with nonischemic cardiomyopathy (NICM) and with an implantable cardioverter defibrillator (ICD) suffering from heart failure. METHODS: We performed a stepwise regression model to identify independent risk factors for the occurrence of ventricular arrhythmias. Using a Cox regression model, independent risk factors for total mortality were evaluated and, subsequently, a Kaplan-Meier analysis was applied. The primary endpoint of this study was the identification of independent predictors of overall mortality and the incidence of malignant arrhythmias. RESULTS: One hundred twenty-five VT (≥310 ms), 51 fast VT (between 310 ms and 240 ms), and 48 episodes of ventricular fibrillation (≤240 ms) were documented in 32 patients. Independent predictors of arrhythmias detected and treated by the ICD included female gender (odds ratio [OR] 3.4), lack of statin therapy (OR 3.5), and increased serum creatinine (OR 3.7). The Kaplan-Meier analysis showed no difference in survival between participants with or without VT. Total mortality was predicted by increased age (OR 2.3) and an impaired renal function (OR 1.9), independently. CONCLUSIONS: In this cohort of NICM patients with heart failure, female gender, lack of statin therapy, and increased creatinine represented independent risk factors for the incidence of malignant arrhythmias. Furthermore, renal insufficiency and age favored total mortality. Considering these results, impaired renal function might represent a valuable noninvasive tool to identify NICM patients who, despite ICD implantation, have the highest risk of mortality and therefore require a particularly thorough follow-up.

Isoform-specific downregulation of peroxiredoxin in human failing myocardium.

Peroxiredoxins (Prx) are a family of antioxidant thioredoxin or glutathione dependent peroxidases. The major functions of Prx comprise modulation of signalling cascades that apply hydrogen peroxide (H(2)O(2)) and cellular protection against oxidative stress. Nothing is known about Prx isoforms in human myocardium. We investigated the protein expression of Prx isoforms 1-6 in human non-failing (NF, donor hearts, n=6, male, age: 53.3+/-2.1 years) and failing myocardium (DCM, orthotopic heart transplantation, dilated cardiomyopathy, n=15, male, 57.0+/-1.7 years). In addition, we performed immunohistochemical stainings and measured Prx 4 mRNA expression levels (RNAse protection assay). The protein expression of Prx 1-2 was similar in NF and DCM. The protein expression of Prx 3-6 and the mRNA-expression of Prx 4 were decreased in DCM. Immunohistochemical analyses provided evidence that all Prx isoforms are present in cardiomyocytes and endothelial cells. Whereas Prx 1-5 staining was more pronounced in endothelial cells, Prx6 staining was more evident in cardiomyocytes. This study provides evidence that Prx are differentially regulated in DCM. The selective downregulation of peroxiredoxin 3-6 isoforms may point towards a subcellular specific dysregulation of the antioxidative defence during the development of DCM.

[Reverse remodeling of the intracellular Ca(2+)-homeostasis: new concepts of pathophysiology and therapy of heart failure]. / Reverses Remodeling der intrazellulären Ca(2+)-Homöostase: Neue Konzepte zur Pathophysiologie und Therapie der Herzinsuffizienz.

Cardiac contraction is dependent on a rapid alteration of the intracellular Ca(2+) concentration, especially the Ca(2+) released during systole. In end-stage heart failure, cardiac contractility is depressed due to alterations in the structure and function of proteins or protein complexes. Over recent years, new insights have been obtained regarding the regulation of the intracellular Ca(2+) homeostasis and its pathophysiological alteration in end-stage heart failure. This review focuses on the mechanisms involved in the release of Ca(2+) from the sarcoplasmic reticulum (SR) during systole via the ryanodine receptors and the Ca(2+)-uptake into the SR by the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA 2a). In addition, new therapeutic options will be introduced which may be of importance for the treatment of heart failure patients.