Heart Failure Differentially Modulates the Effects of Ivabradine on the Electrical Activity of the Sinoatrial Node and Pulmonary Veins

Abstract Background: Ivabradine increases the risk of atrial fibrillation (AF). Heart failure (HF) or sinoatrial node (SAN) dysfunction increases the risk of AF, and pulmonary veins (PVs) play a critical role in the pathophysiology of AF. This study investigated the electrophysiologic effects of ivabradine on SANs and PVs in a rabbit model of HF. Methods and Results: Conventional microelectrodes were used to simultaneously record the electrical activities and conduction properties of control and HF rabbit SAN-PV preparations before and after perfusion with ivabradine (0.1, 1, or 10 μmol/L), either alone or with isoproterenol (1 μmol/L). HF SANs exhibited a lower beating rate than the control SANs. SAN automaticity exit blocks and SAN-PV conduction blocks were observed in 25% and 50% of samples, respectively, with P Conclusions: HF differentially modulates the effects of ivabradine on the electrical activities of SAN and PVs, which may increase PV arrhythmogenesis and contribute to the risk of AF in HF patients.