Enhanced Response to Drug-Induced QT Interval Lengthening in Patients with Heart Failure with Preserved Ejection Fraction.

ABSTRACT Background Patients with heart failure (HF) with reduced ejection fraction demonstrate enhanced response to drug-induced QT interval lengthening and are at increased risk for torsades de pointes. The influence of HF with preserved ejection fraction (HFpEF) on response to drug-induced QT lengthening is unknown. Methods and Results We administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex- matched control subjects without HF. Serial 12-lead electrocardiograms were obtained for determination of QT intervals. Demographics, maximum serum ibutilide concentrations, area under the serum ibutilide concentration versus time curves, and baseline Fridericia-corrected QT (QTF) (417±14 vs 413±15 ms, p=0.54) were similar in the HFpEF and control groups. Area under the effect (QTF versus time) curve (AUEC) from 0-1.17 hours during and following the ibutilide infusion was greater in the HFpEF group (519±19 vs 497±18 ms•h, p = 0.04), as was AUEC from 0-8.17 hours (3576±125 vs 3428 ± 161 ms•h, p=0.03) indicating greater QTF interval exposure. Maximum QTF (454±15 vs 443±22 ms, p=0.18) and maximum percent increase in QTF from baseline (8.2±2.1 vs 6.7±1.9%, p=0.10) in the two groups were not significantly different. Conclusions HFpEF is associated with enhanced response to drug-induced QT interval lengthening.