Abstract
IntroductionPatients with heart failure with reduced ejection fraction demonstrate enhanced response to drug-induced QT interval lengthening and are at increased risk for drug-induced torsades de pointes. The influence of heart failure with preserved ejection fraction (HFpEF) on response to drug-induced QT interval lengthening is unknown.HypothesisPatients with HFpEF demonstrate enhanced response to drug-induced QT interval lengthening.MethodsWe prospectively enrolled n=10 subjects with HFpEF (symptomatic heart failure, left ventricular ejection fraction > 50%, and ≥1 of the following on echocardiogramE/E’ > 15; E/A < 0.5; maximum left atrial volume index > 40 mL/m; diastolic dysfunction > grade 2) and a control group (n=10) without heart failure matched to the HFpEF group by age (±10 years) and sex. Subjects received a single intravenous dose of the QT interval-lengthening drug ibutilide 0.003 mg/kg over 10 minutes, after which 12-lead electrocardiograms (ECGs) were obtained serially for measurement of Fridericia-corrected QT (QTF) intervals.ResultsThere were no significant differences between the HFpEF and control groups in demographics, maximum serum ibutilide concentrations, or pre-ibutilide QTFintervals. During the 8-hour period following ibutilide infusion, QTFintervals were significantly longer in the HFpEF group (Figure). Area under the effect (QTF) curve during and one hour following ibutilide administration (AUEC0-1.17) and for 8 hours after ibutilide administration (AUEC0-8.17) were significantly larger in the HFpEF group (Table).ConclusionsHFpEF is associated with enhanced response to drug-induced QT interval lengthening