BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is associated with enhanced response to drug-induced QT interval lengthening. We determined the influence of HFpEF on drug-induced lengthening of dispersion of repolarization, a measure of proarrhythmic risk. MethodsWe administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched controls without HF. 12‑lead electrocardiograms were obtained prior to, during, and serially for 8 h post-ibutilide. Tpeak-Tend, a measure of dispersion of ventricular repolarization, and heart rate-corrected J-Tpeak, representing early repolarization, were measured by an investigator blinded to study groups. ResultsBaseline (pre-ibutilide) Tpeak-Tend and J-Tpeakc were not significantly different in the HFpEF and control groups. Maximum Tpeak-Tend was longer in the HFpEF group than in the control group (85 ± 10 vs 73 ± 8 ms, p = 0.01). Additionally, % change from baseline in Tpeak-Tend was longer in the HFpEF group [median (IQR) 17 (11) vs 8 (3)%, p = 0.03]. The area under the effect curve (AUEC) for Tpeak-Tend was also larger in the HFpEF group (600 ± 42 vs. 543 ± 49 ms•hr, p = 0.03). Maximum J-Tpeakc, % change from baseline in J-Tpeakc and AUEC for J-Tpeakc in the two groups were not significantly different. ConclusionHFpEF is associated with enhanced response to drug-induced increases in dispersion of repolarization.