Abstract 1086: Angiotensin-II Receptor Blockade Accelerates the Recovery of Atrial Remodeling
Background: Renin-angiotensin system (RAS) inhibitors prevent AF recurrence in structurally-normal hearts, but the mechanism remains mysterious, particularly since they don’t prevent atrial-tachycardia remodeling (ATR). The effects of RAS inhhibitors on recovery from remodeling have not been evaluated. Hence, we assessed effects of the angiotensin-II receptor blocker candesartan on recovery and redevelopment of ATR.
Methods: Dogs were subjected to atrial tachypacing (ATP, 400 bpm) with AV block and ventricular pacing at 80 bpm for 4 wks, followed by 1-wk recovery. An additional 1-wk ATP was then applied to assess remodeling redevelopment. The dynamics of ATR were evaluated by serial closed chest electrophysiological studies. Candesartan (CSN)-treated dogs (10 mg/kg/day, N=6) were compared to no-drug controls (CTLs, N=6). To mimic clinical treatment initiation during AF, CSN was started 3 weeks after ATP onset (when ATR was well-developed) and continued thereafter.
Results: ATP significantly increased mean duration of induced AF within 4 days (Figure⇓) and decreased atrial effective refractory period (ERP, e.g. at basic cycle length 300 ms from 139±7 to 82±5 ms, p<0.01 at 4-week ATP). These responses were unaffected by CSN. Recovery from ATR required 4 days in CTL, but occurred within 1 day in CSN dogs (Figure⇓). The redevelopment of ATR upon ATP re-initiation was accelerated in CTL dogs compared to the initial remodeling period, a phenomenon not significantly altered by CSN.
Conclusion: CSN accelerates the recovery from ATR. This dynamic effect constitutes a potential explanation of angiotensin receptor blocker efficacy in clinical AF without structural heart disease.