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

JAMES E. TISDALE, HEATHER A. JAYNES, BRIAN R. OVERHOLSER, KEVIN M. SOWINSKI, MARK D. FISCH, JO E. RODGERS, AHMED ALDEMERDASH, CHIA H.I.A.C.H.I. HSU, N. A.N. WANG, ELENA TOMASELLI MUENSTERMAN, VIJAY U. RAO, RICHARD J. KOVACS

Research output: Contribution to journalArticle

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 vs time curves, and baseline Fridericia-corrected QT (QTF) (417 ± 14 vs 413 ± 15 ms, P =.54) were similar in the HFpEF and control groups. Area under the effect (QTFvs time) curve (AUEC) from 0 to 1.17 hours during and following the ibutilide infusion was greater in the HFpEF group (519 ± 19 vs 497 ± 18 ms·h, P=.04), as was AUEC from 0 to 8.17 hours (3576 ± 125 vs 3428 ± 161 ms·h, P =.03) indicating greater QTF interval exposure. Maximum QTF (454 ± 15 vs 443 ± 22 ms, P =.18) and maximum percent increase in QTF from baseline (8.2 ± 2.1 vs 6.7 ± 1.9%, P =.10) in the 2 groups were not significantly different. Conclusions: HFpEF is associated with enhanced response to drug-induced QT interval lengthening.

Original languageEnglish (US)
Pages (from-to)781-785
Number of pages5
JournalJournal of Cardiac Failure
Volume26
Issue number9
DOIs
StatePublished - Sep 2020

Keywords

  • Drug-induced
  • QT interval
  • electrocardiography
  • heart failure with preserved ejection fraction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    TISDALE, JAMES. E., JAYNES, HEATHER. A., OVERHOLSER, BRIAN. R., SOWINSKI, KEVIN. M., FISCH, MARK. D., RODGERS, JO. E., ALDEMERDASH, AHMED., HSU, CHIA. H. I. A. C. H. I., WANG, N. A. N., MUENSTERMAN, ELENA. TOMASELLI., RAO, VIJAY. U., & KOVACS, RICHARD. J. (2020). Enhanced Response to Drug-Induced QT Interval Lengthening in Patients with Heart Failure with Preserved Ejection Fraction. Journal of Cardiac Failure, 26(9), 781-785. https://doi.org/10.1016/j.cardfail.2020.06.008