Evidence of apoptosis in right ventricular dysfunction in rheumatic mitral valve stenosis.

BACKGROUND & OBJECTIVES: Right ventricular (RV) dysfunction is one of the causes of morbidity and mortality in valvular heart disease. The phenomenon of apoptosis, though rare in cardiac muscle may contribute to loss of its function. Role of apoptosis in RV in patients with rheumatic valvular heart disease is investigated in this study.

METHODS: Patients with rheumatic mitral valve stenosis formed two groups based on RV systolic pressure (RVSP) as RVSP <40 mmHg (group I, n=9) and RVSP ≥40 mmHg (group II, n=30). Patients having atrial septal defect (ASD) with RVSP <40 mmHg served as control (group III, n=15). Myocardial performance index was assessed for RV function. Real-time polymerase chain reaction was performed on muscle biopsy procured from RV to assess expression of pro-apoptotic genes (Bax, cytochrome c, caspase 3 and Fas) and anti-apoptotic genes (Bcl-2). Apoptosis was confirmed by histopathology and terminal deoxynucleotide-transferase-mediated dUTP nick end labelling.

RESULTS: Group II had significant RV dysfunction compared to group I (P=0.05) while caspase 3 (P=0.01) and cytochrome c (P=0.03) were expressed excessively in group I. When group I was compared to group III (control), though there was no difference in RV function, a highly significant expression of pro-apoptotic genes was observed in group I (Bax, P=0.02, cytochrome c=0.001 and caspase 3=0.01). There was a positive correlation between pro-apoptotic genes. Nuclear degeneration was present conforming to apoptosis in valve disease patients (groups I and II) while it was absent in patients with ASD.

INTERPRETATION & CONCLUSION: Our findings showed evidence of apoptosis in RV of patients with valvular heart disease. Apoptosis was set early in the course of rheumatic valve disease even with lower RVSP, followed by RV dysfunction; however, expression of pro-apoptotic genes regressed.