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Enhanced Sensitivity to Drug-Induced QT Interval Lengthening in Patients With Heart Failure Due to Left Ventricular Systolic Dysfunction.
- Source :
-
Journal of Clinical Pharmacology . Sep2012, Vol. 52 Issue 9, p1296-1305. 10p. - Publication Year :
- 2012
-
Abstract
- Patients with heart failure (HF) are at increased risk for drug-induced torsades de pointes (TdP) due to unknown mechanisms. Our objective was to determine if sensitivity to drug-induced QT interval lengthening is enhanced in patients with HF. In this multicenter, prospective study, 15 patients with atrial fibrillation or flutter requiring conversion to sinus rhythm were enrolled: 6 patients with New York Heart Association class II to III HF (mean ejection fraction [EF], 30% ± 9%), and 9 controls (mean EF, 53% ± 6%). Patients received ibutilide 1 mg intravenously. Blood samples and 12-lead electrocardiograms were obtained prior to and during 48 hours postinfusion. Serum ibutilide concentrations at 50% maximum effect on Fridericia-corrected QT (QTF) intervals (EC50) were determined, and areas under the effect (QTF interval vs time) curves (AUECs) were calculated. Ibutilide concentration–QTF relationships were best described by a sigmoidal Emax model with a hypothetical effect compartment. Median [interquartile range] AUEC from 0 to 4 hours was larger in the HF group than in controls (1.86 [1.86-1.93] vs 1.82 [1.81-1.84] s·h; P = .04). Median EC50 was lower in the HF group (0.48 [0.46-0.49] vs 1.85 [1.10-3.23] μg/L; P = .008). Sensitivity to drug-induced QT interval lengthening is enhanced in patients with systolic HF, which may contribute to the increased risk of drug-induced TdP. [ABSTRACT FROM PUBLISHER]
- Subjects :
- *ACADEMIC medical centers
*ARRHYTHMIA
*ATRIAL fibrillation
*CARDIAC output
*ELECTROCARDIOGRAPHY
*FISHER exact test
*LEFT heart ventricle
*HEART beat
*HEART failure
*LONGITUDINAL method
*MEDICAL cooperation
*MYOCARDIAL depressants
*RESEARCH
*RESEARCH funding
*STATISTICS
*SULFONAMIDES
*T-test (Statistics)
*ATRIAL flutter
*VENTRICULAR tachycardia
*DATA analysis
*LONG QT syndrome
*DATA analysis software
*DESCRIPTIVE statistics
*DISEASE complications
*PHARMACODYNAMICS
*THERAPEUTICS
*DISEASE risk factors
SULFONAMIDE drugs
Subjects
Details
- Language :
- English
- ISSN :
- 00912700
- Volume :
- 52
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 79772675
- Full Text :
- https://doi.org/10.1177/0091270011416939