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

    European heart journal, 2024-Mar-07, 2024-03-07, 20240307, Letnik: 45, Številka: 10
    Journal Article

    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.