Dapagliflozin but not empagliflozin prevents atrial fibrillation in an experimental whole-heart model

Abstract Background The SGLT2 inhibitors dapagliflozin and empagliflozin have an evolving role in heart failure therapy. Observational data suggest a lower risk of atrial fibrillation (AF) for patients on inhibitors. So far, it is unclear whether this related to direct antiarrhythmic potential or just marker improved function. Experimental the impact SGTL2 electrophysiology scarce. Purpose This study aimed at evaluating effects two electrophysiology. Methods 25 rabbit hearts were explanted retrogradely perfused employing Langendorff-setup. Two catheters placed both atria record monophasic action potentials. Hearts paced three different cycle lengths (350ms, 250ms, 150ms), thereby obtaining cycle-length dependent durations (aAPD90) effective refractory periods (aERP). Atrial post-repolarization (aPRR) refractoriness was determined by difference between aERP aAPD90. AF induced presence acetylcholine (ACh, 1μM) isoproterenol (Iso, 1μM). Thereafter, treated with (n=13, 3 μM) (n=12, μM). Results Ach/Iso abbreviated aAPD90, prolonged aPRR groups (dapagliflozin group: aAPD90: −49 ms, p<0.01; aERP: −33 aPRR: +18 p=0.06; −40 −25 p<0.05; p=0.05). Further treatment increased aAPD90 (+13 p<0.01), (+34 p<0.05) (+6 p=ns). Additional administration had no significant effect (−8 p=ns), (−1 p=ns) (+9 Vulnerability assessed standardized protocol consisting several trains burst pacing. vulnerability episodes 71 vs. 1 under baseline conditions, 27 2 p=0.08). perfusion significantly reduced occurrence (to 30 episodes, while additional (32 Conclusion Dapagliflozin opposing aERP, preventing AF. In contrast, did not change resulting effect. Our findings hint benefit dapagliflozin. Funding Acknowledgement Type funding sources: Private grant(s) and/or Sponsorship. Main source(s): Hans Gertie Fischer-Foundation C.E.)