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Objectives: The objective of the present study was to assess the relationship between the presence of left ventricular (LV) dyssynchrony and clinical outcome in patients with moderate systolic heart failure undergoing coronary artery bypass graft (CABG) surgery., Background: The presence of LV dyssynchrony is associated with poor prognosis in patients with LV dysfunction., Methods: The study consisted of 215 consecutive patients with ischemic cardiomyopathy and dyspnea (age 65 +/- 9 years, 81% male) undergoing CABG. Dyssynchrony was calculated by tissue Doppler imaging from regional time intervals in basal LV segments before and 1 month after CABG. Myocardial viability was assessed using single-photon emission computed tomography (SPECT) before CABG., Results: Twenty-five patients (11.6%) died within 30 days (in-hospital mortality) of CABG. The presence of pre-CABG dyssynchrony > or =119 ms had the highest predictive accuracy for in-hospital mortality, with a sensitivity of 84% and a specificity of 71%. During the median follow-up period of 359 days (interquartile range 219 to 561), an additional 19 patients (10.3%) died and 34 patients (18.5%) were hospitalized for worsening heart failure. At Cox regression analysis, post-CABG dyssynchrony > or =72 ms and > or =5 viable segments were identified as independent predictors of clinical events, with a hazard ratio (HR) of 5.02, 95% confidence interval (CI) 2.57 to 10.02 (p < 0.001), and an HR of 0.63, 95% CI 0.55 to 0.75 (p < 0.001), respectively. Patients without post-CABG dyssynchrony and with viable myocardium had excellent prognosis compared with patients with severe post-CABG dyssynchrony and nonviable myocardium (event rate 3% vs. 64%; p < 0.001)., Conclusions: The presence of severe LV dyssynchrony is associated with poor clinical outcomes despite revascularization. These results advocate a routine assessment of both LV dyssynchrony and viability to predict outcome in systolic heart failure patients undergoing CABG surgery.

Background: To assess whether hypoxia, as can be found in obstructive sleep apnea syndrome, is causally associated with the development of heart failure through a direct effect on calcium leakage from the sarcoplasmic reticulum. Methods: The impact of hypoxia on sarcoplasmic reticulum calcium leakage and expression of RyR2 (ryanodine receptor2) and SERC2a (sarcoplasmic reticulum Ca2+ATPase 2a) was investigated together with the outcomes of JTV-519 and S107 treatment. HL-1 cardiomyocytes were cultured for 7 days on gas-permeable cultureware under control (12% O2) or hypoxic (1% O2) conditions with or without JTV-519 or S107. SRCL was assessed using a Fluo-5N probe. Gene and protein expression was analyzed using qPCR and western blotting. Results: Hypoxic exposure increased sarcoplasmic reticulum calcium leakage by 39% and reduced RyR2 gene expression by 52%. No effect on RyR2 protein expression was observed. Treatment with 1µM JTV-519 reduced sarcoplasmic reticulum calcium leakage by 52% and 35% under control and hypoxic conditions, respectively. Administration of 1 µM JTV-519 increased RyR2 gene expression by 89% in control conditions. No effect on SRCL, RyR2, or SERC2a gene, or protein expression was observed with S107 treatment. Conclusion: Hypoxia increased sarcoplasmic reticulum calcium leakage which was ameliorated by JTV-519 treatment independently of gene or protein expression. JTV-519 represents a possible treatment for obstructive sleep apnea-associated HF. [ABSTRACT FROM AUTHOR]

Background. Apoptosis plays an important role in the myocardial injury after acute myocardial infarction and in the subsequent development of heart failure. Aim. To clarify serum kinetics of apoptotic markers TRAIL and sFas and their relation to left ventricular ejection fraction (LVEF) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Methods. In 101 patients with STEMI treated with pPCI, levels of TRAIL and sFas were measured in series of serum samples obtained during hospitalization and one month after STEMI. LVEF was assessed at admission and at one month. Major adverse cardiovascular events (MACE, i.e., death, re-MI, and hospitalization for heart failure and stroke) were analysed during a two-year followup. Results. Serum level of TRAIL significantly decreased one day after pPCI (50.5pg/mL) compared to admission (56.7pg/mL), subsequently increased on day 2 after pPCI (58.8pg/mL), and reached its highest level at one month (70.3pg/mL). TRAIL levels on days 1 and 2 showed a significant inverse correlation with troponin and a significant positive correlation with LVEF at baseline. Moreover, TRAIL correlated significantly with LVEF one month after STEMI (day 1: r=0.402, p<0.001; day 2: r=0.542, p<0.001). On the contrary, sFas level was significantly lowest at admission (5073pg/mL), increased one day after pPCI (6370pg/mL), and decreased on day 2 (5548pg/mL). Significantly highest sFas level was marked at one month (7024pg/mL). sFas failed to correlate with LVEF at baseline or at one month. Both TRAIL and sFas showed no ability to predict improvement of LVEF one month after STEMI or a 2-year MACE (represented by 3.29%). Conclusion. In STEMI treated with pPCI, TRAIL reaches its lowest serum concentration after reperfusion. Low TRAIL level is associated with worse LVEF in the acute phase of STEMI as well as one month after STEMI. Higher TRAIL level appears to be beneficial and thus TRAIL seems to represent a protective mediator of post-AMI injury. [ABSTRACT FROM AUTHOR]

Apoptosis plays an important role in the myocardial loss after acute myocardial infarction and participates in the process of subsequent left ventricular remodeling and development of symptomatic heart failure. Finding a sensitive apoptotic marker that would help in prognostic stratification of patients after acute myocardial infarction and offer new therapeutic strategies is thus of a great importance. Several studies suggest that tumor necrosis factor-related apoptosis inducing ligand (TRAIL) represents a very promising marker of prognosis in patients with acute myocardial infarction. This review article provides an overview of current knowledge on the role of apoptosis in ischemic heart disease and highlights potentially beneficial apoptotic markers in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Apoptosis plays an important role in the development of heart failure. The aim of the prospectively designed study was to assess whether the concentration of apoptotic markers apoptosis-stimulating fragment (Fas, CD95/APO-1) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can predict prognosis in patients with acute coronary syndromes. Methods: The concentrations of soluble Fas and TRAIL were determined in 295 patients with acute coronary syndromes. The status of all patients was evaluated at 6 months. The primary goal was a composite end-point of death and hospitalization for heart failure. The secondary end-points were re-MI, death alone and stroke alone. Results: During the median follow-up of 6 months, 26 patients experienced the composite end-point. Using multivariate logistic regression, the concentration of TRAIL was the strongest significant and independent predictor of composite end-point (OR 0.11 (95% CI 0.03–0.45), p = 0.002). Low concentration was associated with poor prognosis of patients. Other significant predictors of composite end-point were serum creatinine (OR 7.7 (95% CI 1.1–54.5, p = 0.041) and complete revascularization (OR 0.19 (95% CI 0.05–0.78, p = 0.02). Independent significant predictors of death in the multivariate analysis were the concentration of TRAIL (OR 0.053 (95% CI 0.004–0.744), p = 0.029), older age (OR 1.20 (95% CI 1.02–1.41, p = 0.026) and serum creatinine (OR 15.1 (95% CI 1.56–145.2), p = 0.0193). Re-MI or stroke could not be predicted by any combination of obtained parameters. Conclusions: Low concentrations of soluble TRAIL represent a strong predictor of a poor prognosis in patients with acute coronary syndrome. The predictive value of TRAIL concentration is independent of age, ejection fraction, index peak troponin level, concentration of BNP or serum creatinine. [ABSTRACT FROM AUTHOR]