Divergent electrophysiologic profile of dapagliflozin and empagliflozin in isolated rabbit hearts

Julian Wolfes (Münster)1, J. Uphoff (Münster)1, S. Kemena (Münster)1, F. K. Wegner (Münster)1, B. Rath (Münster)1, L. Eckardt (Münster)1, G. Frommeyer (Münster)1, C. Ellermann (Münster)1

1Universitätsklinikum Münster Klinik für Kardiologie II - Rhythmologie Münster, Deutschland




The use of SGLT-2 inhibitors has revolutionized heart failure therapy. Evidence suggests a reduced incidence of ventricular and atrial arrhythmias in patients with dapagliflozin or empagliflozin treatment. Here, it is unclear to what extent the reduced arrhythmia burden is due to direct effects of the SGLT2 inhibitors or is solely a marker of improved cardiac function. 

Therefore, the ventricular and atrial electrophysiologic effects of dapagliflozin and empagliflozin were investigated in an established whole-heart model. 




105 hearts of New Zealand White rabbits were allocated to eight groups (groupsize: 12-17 hearts) and retrogradely perfused, employing a Langendorff setup. Cycle-length dependent action potential duration at 90% of repolarization (APD90), QT intervals, effective refractory periods, conduction velocity, and dispersion of repolarization were obtained with monophasic action potential catheters. 

A long-QT model was established with erythromycin, a short-QT model with pinacidil, and an atrial fibrillation model with isoproterenol and acetylcholine. 


With increasing concentrations of both SGLT2 inhibitors, reductions in QT intervals and APD90 were observed, accompanied by a slight increase in ventricular arrhythmia episodes. During drug-induced LQTS, empagliflozin succeeded in decreasing QT intervals, APD90, and VT burden. Dapagliflozin had no significant effect in this regard. During pinacidil-induced SQTS, neither SGLT2 inhibitor had a significant impact on cardiac electrophysiology.


In the atrial fibrillation model, perfusion with dapagliflozin showed significant suppression of atrial fibrillation episodes in the course of restitution of electrophysiological parameters. In contrast, empagliflozin showed no significant effect on atrial fibrillation incidence.  




In this model, empagliflozin showed effective arrhythmia suppression in a long-QT model, whereas dapagliflozin showed effective suppression of atrial arrhythmias.



SGLT2i; dapagliflozin; empagliflozin; Langendorff; atrial fibrillation; short QT syndrome; long QT syndrome; arrhythmia; sudden cardiac death;

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