Clonal Haematopoiesis of Indeterminate Potential Predicts Incident Cardiac Arrhythmias

Authors

• Art Schuermans
• Caitlyn Vlasschaert
• Victor Nauffal
• So Mi Jemma Cho
• Md Mesbah Uddin
• Tetsushi Nakao
• Abhishek Niroula
• Marcus D R Klarqvist
• Lachelle D Weeks
• Amy E Lin
• Seyedmohammad Saadatagah
• Kim Lannery
• Megan Wong
• Whitney Hornsby
• Steven A Lubitz
• Christie Ballantyne
• Siddhartha Jaiswal
• Peter Libby
• Benjamin L Ebert
• Alexander G Bick
• Patrick T Ellinor
• Pradeep Natarajan
• Michael C Honigberg

Language

English

Publication Date

3-7-2024

Journal

European Heart Journal

DOI

10.1093/eurheartj/ehad670

PMID

37952204

PMCID

PMC10919923

PubMedCentral® Posted Date

11-11-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Background and aims: Clonal haematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutations, is associated with atherosclerotic cardiovascular disease and heart failure. This study aimed to test the association of CHIP with new-onset arrhythmias.

Methods: UK Biobank participants without prevalent arrhythmias were included. Co-primary study outcomes were supraventricular arrhythmias, bradyarrhythmias, and ventricular arrhythmias. Secondary outcomes were cardiac arrest, atrial fibrillation, and any arrhythmia. Associations of any CHIP [variant allele fraction (VAF) ≥ 2%], large CHIP (VAF ≥10%), and gene-specific CHIP subtypes with incident arrhythmias were evaluated using multivariable-adjusted Cox regression. Associations of CHIP with myocardial interstitial fibrosis [T1 measured using cardiac magnetic resonance (CMR)] were also tested.

Results: This study included 410 702 participants [CHIP: n = 13 892 (3.4%); large CHIP: n = 9191 (2.2%)]. Any and large CHIP were associated with multi-variable-adjusted hazard ratios of 1.11 [95% confidence interval (CI) 1.04-1.18; P = .001] and 1.13 (95% CI 1.05-1.22; P = .001) for supraventricular arrhythmias, 1.09 (95% CI 1.01-1.19; P = .031) and 1.13 (95% CI 1.03-1.25; P = .011) for bradyarrhythmias, and 1.16 (95% CI, 1.00-1.34; P = .049) and 1.22 (95% CI 1.03-1.45; P = .021) for ventricular arrhythmias, respectively. Associations were independent of coronary artery disease and heart failure. Associations were also heterogeneous across arrhythmia subtypes and strongest for cardiac arrest. Gene-specific analyses revealed an increased risk of arrhythmias across driver genes other than DNMT3A. Large CHIP was associated with 1.31-fold odds (95% CI 1.07-1.59; P = .009) of being in the top quintile of myocardial fibrosis by CMR.

Conclusions: CHIP may represent a novel risk factor for incident arrhythmias, indicating a potential target for modulation towards arrhythmia prevention and treatment.

Keywords

Humans, Clonal Hematopoiesis, Bradycardia, Atrial Fibrillation, Heart Arrest, Heart Failure, Arrhythmia, Aging, Atrial fibrillation, Cardiac arrest, Genomics, Prevention

Published Open-Access

yes

Recommended Citation

Schuermans, Art; Vlasschaert, Caitlyn; Nauffal, Victor; et al., "Clonal Haematopoiesis of Indeterminate Potential Predicts Incident Cardiac Arrhythmias" (2024). Faculty, Staff and Students Publications. 6681.
https://digitalcommons.library.tmc.edu/baylor_docs/6681