Does left ventricular assist device implantation modulate the cardiac cell apoptosis in end-stage heart failure?

Purpose: In heart failure (HF), the balance between pro- and anti-apoptotic factors has a key role in cardiac cell apoptosis. Appropriate treatments, such as Left Ventricular Assist Devices (LVAD) implantation, could be able to modulate the apoptotic process. Aim of this study was to assess the expression of apoptosis biomarkers in cardiac tissue of severe HF patients with mechanical ventricular support compared to patients submitted to cardiac transplant. Methods: Seven end-stage HF patients (NYHA class III-IV; age 57±11 yrs; LVEF<20) undergoing LVAD implantation, as bridge to heart transplantation, and seven patients directly driven towards heart transplantation (Tx) were studied. Cardiac tissue biopsies were collected both from left (LV) and right ventricle (RV) and mRNA expression of Caspase (Casp)-3, Casp-9 and their regulatory systems, Bcl-2 and Hsp72, were determined by semi-quantitative RT-PCR analysis. Nitric oxide (NO) expression was also studied. The eEF1A was used as reference gene. Results: Lower expression levels of Casp-9, associated to higher expression of Hsp72 and Bcl-2, were observed in LVAD compared to Tx, both in RV and LV. The figure shows data relative to LV. In RV Casp-9 0.49±0.12 vs 0.73±0.07, p=ns; Hsp72 2.01±0.72 vs 1.08±0.04 p=ns; Bcl-2 2.88±0.74 vs 1.13±0.42 *p=0.02, LVAD vs Tx. No significant difference in Casp-3 and NO expression was found in all situations. Conclusions: These findings suggest that, in end-stage HF, LVAD implant may modulate the apoptotic pathway. The lower expression of Casp-9 and the higher expression of the apoptosis control systems found in LVAD compared to transplant hearts suggest a more favourable balance between pro-apoptotic and antiapoptotic factors in this condition.