Abstract 16705: Abnormal Atrial Substrate Underlies Atrial Fibrillation in Rats With Heart Failure With Preserved Ejection Fraction

Introduction: Atrial fibrillation (AF) is common in patients with heart failure with preserved ejection fraction (HFpEF), and heralds a poor prognosis, but the underlying mechanisms are not well studied. Hypothesis: We tested the hypothesis that prolonged atrial effective refractory period (AERP) and slow conduction predispose to AF in HFpEF rats. Methods: Dahl salt-sensitive rats were fed a high-salt diet from 7 weeks of age to induce HFpEF (n=32). Normal-salt fed rats were used as controls (n=26). Echocardiograms at 14-15 weeks of age were used to verify diastolic dysfunction and to assess left atrial size. Electrical phenotype was probed by electrocardiography (P wave duration, PR interval) and in vivo provocative electrophysiological testing (using a 1.5 French catheter) in echo-verified HFpEF and control rats. Optical mapping was performed to measure action potential duration (APD) and conduction velocity (CV) in ex vivo HFpEF and control hearts. Results: High-salt fed rats showed decreased E/E’ ratio with preserved ejection fraction (60-70%), hence were diagnosed with HFpEF. Left atrial size was increased in rats with HFpEF compared to controls (29.1±0.8 vs. 19.5±1.1 mm 2 , p<0.001). P waves were prolonged in HFpEF rats compared to controls (17.8±0.5 vs. 13.5±0.6 ms, p<0.001), as was the PR interval (57.8±1.1 vs. 48.8±1.3 ms, p<0.001). AF induction after burst pacing was much easier in HFpEF rats (27/32 HFpEF rats compared to 5/26 controls, 84.4 vs. 19.2%, p<0.001). Atrial effective refractory period (AERP) was prolonged in HFpEF rats compared to controls (37.8±1.7 vs. 30.6±1.8 ms, p<0.01). During optical mapping, APD was prolonged in left atrium of HFpEF rats compared to controls (APD90 42.3±3.6 vs. 30.9±2.2 ms, p<0.05), atrial CV was slower in HFpEF rats compared to controls (0.31±0.03 vs. 0.46±0.02 mm/ms, p<0.01). Conclusions: Rats with HFpEF were at increased risk of inducible AF after burst pacing. Decreased atrial conduction velocity and prolonged AERP contribute to the pathogenesis of AF in HFpEF.