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Clonal haematopoiesis of indeterminate potential predicts incident cardiac arrhythmias

Schuermans, Art ; Vlasschaert, Caitlyn ; Nauffal, Victor ; Cho, So Mi Jemma ; Uddin, Md Mesbah ; Nakao, Tetsushi ; Niroula, Abhishek LU ; Klarqvist, Marcus D.R. ; Weeks, Lachelle D. and Lin, Amy E. , et al. (2024) In European Heart Journal 45(10). p.791-805
Abstract

Background and Clonal haematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutaAims tions, 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... (More)

Background and Clonal haematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutaAims tions, 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.

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publication status
published
subject
keywords
Aging, Arrhythmia, Atrial fibrillation, Cardiac arrest, Genomics, Prevention
in
European Heart Journal
volume
45
issue
10
pages
15 pages
publisher
Oxford University Press
external identifiers
  • pmid:37952204
  • scopus:85187197656
ISSN
0195-668X
DOI
10.1093/eurheartj/ehad670
language
English
LU publication?
yes
id
3c25f5b7-a438-4384-8bfc-7fa1793baa3d
date added to LUP
2024-04-10 14:43:41
date last changed
2024-04-24 18:25:34
@article{3c25f5b7-a438-4384-8bfc-7fa1793baa3d,
  abstract     = {{<p>Background and Clonal haematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutaAims tions, 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.</p>}},
  author       = {{Schuermans, Art and Vlasschaert, Caitlyn and Nauffal, Victor and Cho, So Mi Jemma and Uddin, Md Mesbah and Nakao, Tetsushi and Niroula, Abhishek and Klarqvist, Marcus D.R. and Weeks, Lachelle D. and Lin, Amy E. and Saadatagah, Seyedmohammad and Lannery, Kim and Wong, Megan and Hornsby, Whitney and Lubitz, Steven A. and Ballantyne, Christie and Jaiswal, Siddhartha and Libby, Peter and Ebert, Benjamin L. and Bick, Alexander G. and Ellinor, Patrick T. and Natarajan, Pradeep and Honigberg, Michael C.}},
  issn         = {{0195-668X}},
  keywords     = {{Aging; Arrhythmia; Atrial fibrillation; Cardiac arrest; Genomics; Prevention}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{10}},
  pages        = {{791--805}},
  publisher    = {{Oxford University Press}},
  series       = {{European Heart Journal}},
  title        = {{Clonal haematopoiesis of indeterminate potential predicts incident cardiac arrhythmias}},
  url          = {{http://dx.doi.org/10.1093/eurheartj/ehad670}},
  doi          = {{10.1093/eurheartj/ehad670}},
  volume       = {{45}},
  year         = {{2024}},
}