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Schuermans A, Vlasschaert C, Nauffal V, Cho SMJ, Uddin MM, Nakao T, Niroula A, Klarqvist MDR, Weeks LD, Lin AE, Saadatagah S, Lannery K, Wong M, Hornsby W, Lubitz SA, Ballantyne C, Jaiswal S, Libby P, Ebert BL, Bick AG, Ellinor PT, Natarajan P, Honigberg MC
Eur. Heart J. 45 (10) 791-805 [2024-03-07; online 2023-11-12]
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. 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. 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. CHIP may represent a novel risk factor for incident arrhythmias, indicating a potential target for modulation towards arrhythmia prevention and treatment.
PubMed 37952204
DOI 10.1093/eurheartj/ehad670
Crossref 10.1093/eurheartj/ehad670
pmc: PMC10919923
pii: 7320137