Brief ReportEnhanced Response to Drug-Induced QT Interval Lengthening in Patients with Heart Failure with Preserved Ejection Fraction
Section snippets
Methods
Two groups of volunteers ≥18 years of age were enrolled. One group had HFpEF, defined as7 (1) a diagnosis of symptomatic HF, (2) left ventricular ejection fraction of ≥50% documented on echocardiogram within the previous 2 years, and (3) ≥1 of the following echocardiographic findings8: E/E’ > 15; E/A < 0.5; maximum left atrial volume index of >40 mL/m2; and diastolic dysfunction grade 2 or greater. Patients with HFpEF were recruited from HF clinics at Indiana University (IU) Health in
Results
Recruitment was suspended in October 2018 after enrollment of 10 patients per group, due to an inability to enroll the targeted sample size, owing primarily to the stringent HFpEF inclusion criteria and safety-oriented exclusion criteria. Of 2214 patients screened, 2081 met ≥1 exclusion criterion or declined to participate; 43 consented, of whom 23 were subsequently withdrawn due to exclusion criteria (Supplementary Figure S1). Although potential patients were recruited and screened from all
Discussion
This is the first study to investigate whether patients with HFpEF demonstrate enhanced response to drug-induced QT lengthening. Based on higher postibutilide AUECs at 1 and 8 hours in the HFpEF group, indicating greater and more prolonged QT interval exposure, and significantly longer QT intervals during the first 2 hours after ibutilide administration, our findings indicate that patients with HFpEF exhibit a heightened response to drug-induced QT lengthening compared with a matched group of
Conclusions
Patients with HFpEF demonstrate enhanced response to drug-induced QT lengthening. Further study is required to confirm these findings in a larger population and to determine if patients with HFpEF are at increased risk of drug-induced torsade de pointes.
Sources of Funding
Supported by a grant from the Cardiovascular Section of the IU Health-IU School of Medicine Strategic Research Initiative (Center of Excellence in Cardiovascular Research [CECARE] award). This investigation was also supported in part with support from the Indiana Clinical and Translational Sciences Institute funded, in part, by grant number UL1TR001108 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. In
Disclosures
Dr Rodgers serves as a consultant, advisory board member, and recipient of research grants for/from Novartis. Dr Rao serves as an advisory board member for Bristol-Myers Squibb, Pfizer, and CryoLife, and on speakers bureaus for Novartis, Boehringer-Ingelheim, Eli Lilly, Bristol-Myers Squibb, and Pfizer. The remaining authors have no relationships with industry.
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Emerging risk factors for QT interval prolongation and torsades de pointes
2022, Torsades de PointesChinese expert consensus on the application of intensive care big data (2022)
2023, National Medical Journal of China
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Present address: Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
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Present address: ZS Associates, Princeton, New Jersey.
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Present address: AbbVie Inc, North Chicago, Illinois.