Investigator-reported ventricular arrhythmias and mortality in heart failure with mildly reduced or preserved ejection fraction

Curtain, J. P. et al. (2023) Investigator-reported ventricular arrhythmias and mortality in heart failure with mildly reduced or preserved ejection fraction. European Heart Journal, 44(8), pp. 668-677. (doi: 10.1093/eurheartj/ehac801) (PMID:36632831)

Abstract

Aims: Few reports have examined the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) or their relationship with mortality in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF). Methods and results: Data from the PARAGON-HF, TOPCAT, I-Preserve, and CHARM-Preserved trials were merged. VT/VF, reported as adverse events, were identified. Patients who experienced VT/VF were compared with patients who did not. The relationship between VT/VF and mortality was examined in time-updated Cox proportional hazard regression models. Variables associated with VT/VF were examined in Cox proportional hazard regression models. The rate of VT/VF in patients with HFmrEF compared with patients with HFpEF was examined in a Cox proportional hazards regression model. Of 13 609 patients, over a median follow-up of 1170 days (interquartile range: 966–1451), 146 (1.1%) experienced an investigator-reported VT/VF (incidence rate 0.3 per 100 person-years). Patients who experienced VT/VF were more likely to be male, have had a myocardial infarction, poorer renal function, more adverse left ventricular remodelling, and higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) than patients who did not. Occurrence of VT/VF was associated with NT-proBNP, history of atrial fibrillation/flutter, male sex, lower ejection fraction, and history of hypertension. VT/VF was associated with all-cause death [adjusted hazard ratio (HR): 3.95, 95% confidence interval (CI): 2.80–5.57; P < 0.001] and cardiovascular death, driven by death from heart failure and not sudden death. Patients with HFmrEF had a higher rate of VT/VF than patients with HFpEF (adjusted HR: 2.19, 95% CI: 1.77–2.71). Conclusion: VT/VF was uncommon in patients with HFmrEF and HFpEF. However, such events were strongly associated with mortality and appear to be a marker of disease severity rather than risk of sudden death. Clinical trial registration: ClinicalTrials.gov unique identifier: NCT01920711(PARAGON-HF); NCT00094302 (TOPCAT); NCT00095238 (I-Preserve); NCT00634712 (CHARM-Preserved).

• Item Type: Articles
• Additional Information: The PARAGON-HF trial was funded by Novartis. The TOPCAT trial was funded by the 2 National Heart, Lung and Blood Institute. The I-Preserve trial was supported by Bristol 3 Myers Squibb and Sanofi-Aventis. The CHARM-Preserved trial was supported by 4 AstraZeneca. CA, MCP, PSJ and JJVM are supported by a British Heart Foundation Centre 5 of Research Excellence Grant RE/18/6/34217.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Butt, Mr Jawad and Curtain, Dr James and Jhund, Professor Pardeep and Petrie, Professor Mark and Kober, Professor Lars and Adamson, Dr Carly and Kondo, Dr Toru and McMurray, Professor John
• Authors: Curtain, J. P., Adamson, C., Kondo, T., Butt, J., Desai, A. S., Zannad, F., Rouleau, J. L., Rohde, L. E., Kober, L., Anand, I. S., van Veldhuisen, D. J., Zile, M. R., Lefkowitz, M. P., Solomon, S. D., Packer, M., Petrie, M. C., Jhund, P. S., and McMurray, J. J.V.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: European Heart Journal
• Publisher: Oxford University Press
• ISSN: 0195-668X
• ISSN (Online): 1522-9645
• Published Online: 12 January 2023
• Copyright Holders: Copyright © 2023 Oxford University Press
• First Published: First published in European Heart Journal 44(8): 668-677
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303944		BHF Centre of Excellence	Colin Berry	British Heart Foundation (BHF)	RE/18/6/34217	CAMS - Cardiovascular Science