James E Tisdale1, Heather A Jaynes2, Brian R Overholser3, Kevin M Sowinski3, Mark D Fisch4, Jo E Rodgers5, Ahmed Aldemerdash5, Chia-Chi Hsu5, Nan Wang5, Elena Tomaselli Muensterman2, Vijay U Rao6, Richard J Kovacs7. 1. Department of Pharmacy Practice, College of Pharmacy, Purdue University, Indianapolis, Indiana; Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana. Electronic address: jtisdale@purdue.edu. 2. Department of Pharmacy Practice, College of Pharmacy, Purdue University, Indianapolis, Indiana. 3. Department of Pharmacy Practice, College of Pharmacy, Purdue University, Indianapolis, Indiana; Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana. 4. Indiana University Health North, Carmel, Indiana. 5. Division of Pharmacotherapy and Experimental Therapeutics, Eshelmen School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 6. Franciscan Health, Division of Cardiology, Indianapolis, IN, Indiana. 7. Krannert Institute of Cardiology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana.
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.
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.
Authors: James E Tisdale; Brian R Overholser; Heather A Wroblewski; Kevin M Sowinski; Kwadwo Amankwa; Steven Borzak; Joanna R Kingery; Rita Coram; Douglas P Zipes; David A Flockhart; Richard J Kovacs Journal: J Clin Pharmacol Date: 2011-11-01 Impact factor: 3.126
Authors: Jane E Wilcox; Jonathan Rosenberg; Ajay Vallakati; Mihai Gheorghiade; Sanjiv J Shah Journal: Am J Cardiol Date: 2011-09-10 Impact factor: 2.778
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Authors: James E Tisdale; Heather A Jaynes; Joanna R Kingery; Noha A Mourad; Tate N Trujillo; Brian R Overholser; Richard J Kovacs Journal: Circ Cardiovasc Qual Outcomes Date: 2013-05-28