Apoptosis as a prognostic indicator of long-term mortality and sudden cardiac death in patients with dilated cardiomyopathy undergoing palliative surgical treatment

Abstract

Background: Cardiomyocyte apoptosis has been described in dilated cardiomyopathies, but its clinical relevance remains unclear. In this study, we investigated if preoperative clinical variables and if the presence of cellular apoptosis in left ventricle fragments resected during partial left ventriculectomy had any influence on long-term survival after this palliative surgical procedure. Methods: Partial left ventriculectomy, associated when necessary with mitral insufficiency correction, was performed in 43 patients with idiopathic dilated cardiomyopathy. Eighteen patients were in NYHA functional class III and 25 in class IV. Left ventricular apoptotic cardiomyocytes and apoptotic interstitial cells were quantified using the Tunel assay. Multivariable Cox proportional-hazards analysis was performed with respect to three outcome end points: all deaths, deaths due to heart failure progression and deaths due to arrhythmia related events. Results: Nine patients (20.9%) died during the hospital period and the surviving patients were followed up for a mean of 43 32 months. Other 24 patients died at late follow-up. Causes of late deaths were equally divided between heart failure progression and arrhythmia related events. Actuarial survival rates were 58 7% at 1 year, 48 7% at 2 years, 39 7% at 4 years and 23 6% at 6 years of follow-up. Preoperative NYHA class IV and cardiomyocyte apoptosis were identified as independent predictors of poor long term survival (p 0.003). Functional class IV and elevated nor epinephrine levels were associated with heart failure progression (p 0.002), while arrhythmia related deaths were only predicted by the level of cardiomyocyte apoptosis (p 0.009). Conclusion: The results of palliative surgical treatment of dilated cardiomyopathies are limited by patients’ preoperative clinical condition and by the occurrence of sudden cardiac death, which may be associated with myocardial cells intrinsic compromise.