Enalapril effects on atrial remodeling and atrial fibrillation in experimental congestive heart failure

OBJECTIVE: Atrial remodeling contributes to the maintenance of atrial fibrillation (AF) in several cardiac disorders. There is evidence that angiotensin-converting enzyme (ACE) inhibitors reduce the prevalence of AF in patients with congestive heart failure (CHF). There have been no studies performed to assess the effects of ACE inhibitors on atrial dimensions and emptying function in relationship to vulnerability to AF in the setting of experimental CHF. METHODS: CHF was produced in 20 dogs by rapid right ventricular pacing during 5 weeks. The dogs were randomized to enalapril (EN) therapy (2 mg/kg/day, n=10) or to a control group (n=10). Echocardiography was performed at baseline and weekly thereafter. At the 5-week electrophysiological study, AF was induced by burst pacing and AF duration was measured. RESULTS: Atrial areas increased significantly with CHF. Left atrial (LA) fractional area shortening (FAS) decreased by 42% (P=0.0001) in controls but by 9% (P=NS) in the EN group (P=0.01, EN vs. controls). Similar findings were observed for right atrial (RA) changes (P=0.02). Atrial fibrosis was highly correlated with the decrease in LA FAS (r=0.85, P<0.01) and was reduced by EN (from 11.2+/-1.6 to 8.3+/-0.7%, P=0.008). AF duration was 720+/-461 s for controls and 138+/-83 s for EN (P=0.001). LA and RA areas and FAS at 5 weeks correlated with AF duration (P< or =0.001 for all). FAS decrease in both atria also correlated with AF duration at follow-up (r=0.78 and 0.77 for LA and RA, P< or =0.001 for both). CONCLUSIONS: Experimental CHF causes structural and functional abnormalities in both atria, which are correlated with AF duration. ACE inhibition attenuates CHF-induced atrial fibrosis and remodeling and reduces associated AF promotion. These results indicate a role for the renin-angiotensin system in arrhythmogenic atrial structural remodeling in CHF.