Browsing by Subject "Drug-induced"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Arrhythmias in Patients With Heart Failure Prescribed Dofetilide or Sotalol
    (Elsevier, 2024-11-07) Huang, Chien-Yu; Overholser, Brian R.; Sowinski, Kevin M.; Jaynes, Heather A.; Kovacs, Richard J.; Tisdale, James E.; Medicine, School of Medicine
    Background: Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced arrhythmias. It is unknown whether HF with preserved ejection fraction (HFpEF) also increases the risk. Objectives: The purpose of this study was to determine if the risk of ventricular tachycardia (VT) and sudden cardiac arrest (SCA) is increased in patients with HFpEF prescribed dofetilide or sotalol. Methods: Using Medicare claims and pharmacy benefits from 2014 to 2016, we identified patients taking dofetilide or sotalol and non-dofetilide/sotalol users among 3 groups: HFrEF (n = 26,176), HFpEF (n = 33,304), and no HF (n = 580,249). Multinomial propensity score matching was performed. We compared baseline characteristics using Cochran-Mantel-Haenszel statistics and standardized differences, and tested associations of VT and SCA among dofetilide/sotalol users and those with HFpEF, HFrEF, or no HF using a generalized Cox proportional hazards model. Results: VT and SCA occurred 166 (10.68%) and 16 (1.03%) of 1,554 dofetilide/sotalol users with HFpEF, 543 (38.76%) and 40 (2.86%) of 1,401 dofetilide/sotalol users with HFrEF, and 245 (5.06%) and 13 (0.27%) of 4,839 dofetilide/sotalol users without HF. Overall VT risk was increased in HFrEF and HFpEF patients (HR: 7.00 [95% CI: 6.10-8.02] and 1.99 [95% CI: 1.70-2.32], respectively). The risk of VT in patients prescribed dofetilide/sotalol was increased in HFrEF and HFpEF patients (1.53 [95% CI: 1.07-2.20] and 2.34 [95% CI: 1.11-4.95], respectively). While the overall SCA risk was increased in HFrEF and HFpEF patients (5.19 [95% CI: 4.10-6.57] and 2.53 [95% CI: 1.98-3.23], respectively), dofetilide/sotalol use was not associated with an increased SCA risk. Conclusions: In patients with HF who are prescribed dofetilide or sotalol, the risk of VT, but not SCA, was increased.
  • Thumbnail Image
    Item
    Enhanced Response to Drug-Induced QT Interval Lengthening in Patients with Heart Failure with Preserved Ejection Fraction
    (Elsevier, 2020-09) Tisdale, James E.; Jaynes, Heather A.; Overholser, Brian R.; Sowinski, Kevin M.; Fisch, Mark D.; Rodgers, Jo E.; Aldemerdash, Ahmed; Hsu, Chia-Chi; Wang, Nan; Tomaselli Muensterman, Elena; Rao, Vijay U.; Kovacs, Richard J.; Medicine, School of Medicine
    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.