Aldosterone blockade attenuates development of an electrophysiological substrate associated with ventricular tachyarrhythmias in heart failure

Background Aldosterone blockade reduces sudden cardiac death in heart failure, but the underlying mechanism is unclear. Objective This study's aim was to determine whether chronic eplerenone treatment protects against detrimental ventricular electrical remodeling and development of an arrhythmogenic substrate in a rapid ventricular pacing (RVP)–induced heart failure model. Methods Dogs were assigned randomly to oral placebo or eplerenone treatment and divided into 4 groups: 2 sham-operated (no RVP) and 2 RVP groups. After 5 weeks of no RVP or RVP along with concurrent placebo or eplerenone treatment, dogs underwent echocardiographic assessments of systolic function and chamber size and electrophysiologic measurements of ventricular repolarization, refractoriness, conduction, tachyarrhythmia inducibility, and myocardial activation delays after premature stimulation. Results Eplerenone failed to prevent left ventricular systolic dysfunction or chamber enlargement in RVP dogs. Eplerenone attenuated prolongation of ventricular repolarization and refractoriness, increases in dispersion of repolarization and refractoriness, fractionation of ventricular electrograms, and delays in myocardial activation after premature stimulation at short coupling intervals and improved arrhythmia vulnerability score in RVP dogs with heart failure. Ventricular tachyarrhythmia inducibility in heart failure dogs was predicted by activation delays after premature stimulation at short coupling intervals, which were prevented by eplerenone. Eplerenone did not alter electrophysiological parameters in no-RVP dogs without heart failure. Conclusions Eplerenone attenuates heart failure–related ventricular electrical remodeling and tachyarrhythmia vulnerability. Inhibition of myocardial activation delays during premature excitation may contribute to preventing development of an arrhythmogenic ventricular substrate in heart failure.