Background: Patients with heart failure have a high prevalence of serious arrhythmias and sudden cardiac-death.
Methods and results: Male patients aged 18-75 years with chronic heart failure were randomized to enalapril or hydralazine-isosorbide dinitrate. Short-term (4-hour to 8-hour) Holter tape recordings were performed before randomization, at 3 months, at 1 year, and yearly thereafter. Of 804 patients randomized to therapy, 715 had Holters at baseline. Couplets were noted in 56% versus 60% and ventricular tachycardia (VT) (three or more consecutive ventricular premature beats) in 27% versus 29% of patients randomized to enalapril versus hydralazine-isosorbide dinitrate, respectively. The presence of VT at 3 months, 1 year, and 2 years predicted significantly higher mortality during the subsequent year (p < 0.0001, p < 0.001, and p < 0.037, respectively). In the enalapril group, VT prevalence decreased by 27% at 1 year (p < 0.02). A decrease in prevalence of VT was not seen in the hydralazine-isosorbide dinitrate group. New VT was seen in 11% of enalapril patients versus 24% of hydralazine-isosorbide dinitrate patients at 1 year (p < 0.002). When compared with hydralazine-isosorbide dinitrate at 1 and 2 years, there was a 52% and 49% reduction, respectively, in sudden deaths in the enalapril group. Thus, at 1 and 2 years, the decrease in sudden deaths in the enalapril group coincided with the decrease in VT prevalence and the decrease in new VT emergence.
Conclusions: In patients with heart failure, VT and couplets predict increased mortality. When compared with hydralazine-isosorbide dinitrate, enalapril decreases both the persistence of baseline VT at 3 months and the emergence of new VT at 1 and 2 years. The reduction in VT prevalence parallels a reduction in sudden death. The effect of enalapril on survival over hydralazine-isosorbide dinitrate may be related to its ability to reduce prevalence of ventricular arrhythmia.