BPS2026 - Electrophysiological effects of testosterone in a rabbit model of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is frequently associated with anabolic hormone deficiency, which may influence repolarization reserve and arrhythmogenesis. Female (but not male) rabbits treated with a high-cholesterol (HC) diet. To evaluate the EP effects of testosterone in a rabbit model of HFpEF induced by an HC diet. Female rabbits were assigned to the HC diet ( n = 6) or the HC diet plus testosterone ( n = 6) for 8 weeks. Optical mapping was performed in Langendorff-perfused isolated hearts to assess action potential duration (APD). Ventricular fibrillation (VF) inducibility and phase singularities (PSs) during VF were analyzed under isoproterenol stimulation. Data are presented as median [interquartile range], and group comparisons were performed using the Mann-Whitney U test. At baseline, no significant differences in APD or VF inducibility were observed between groups. Under isoproterenol stimulation, testosterone significantly shortened APD 80-25 (HC diet 67.7 [63.1–72.3] ms vs. HC diet + testosterone 61.5 [56.2–66.8] ms; p = 0.005), reduced VF inducibility (HC diet 7.5 [7.0–8.0] vs. HC diet + testosterone 4.9 [3.5–6.3] episodes/10 stimulations; p = 0.047), and decreased PSs/VF (HC diet 10.9 [9.5–12.3] vs. HC diet + testosterone 7.6 [7.4–7.9]; p = 0.014). Chronic testosterone treatment did not affect baseline APD but had significant EP and antiarrhythmic effects during isoproterenol infusion in a rabbit model of HFpEF. The reduced APD 80-25 and the reduced PSs/VF can be explained by testosterone’s effects on I Ca,L and I KS . These findings also suggest that testosterone may reduce arrhythmogenic risk in females with HFpEF.