Effect of clonal hematopoiesis of indeterminate potential on long-term survival in patients with arrhythmias
5 affiliations
- 1Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100037 China
- 2Department of Medical Genetics, Center for Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing, 100191 China
- 3Neuroscience Research Institute, Key Laboratory for Neuroscience, Peking University, Ministry of Education of China & National Health Commission of China, Beijing, 100191 China
- 4Autism Research Center, Peking University Health Science Center, Beijing, 100191 China
- 5Centre for Statistics in Medicine and NIHR Biomedical Research Centre Oxford, NDORMS, University of Oxford, Windmill Rd, Oxford, OX3 7LD Oxfordshire UK
Abstract
Background: Clonal hematopoiesis of indeterminate potential(CHIP), defined by somatic mutations within hematopoietic clones, has emerged as a novel risk factor for cardiovascular disease. While cardiac arrhythmias are a major global health concern, the factors contributing to outcome variability remain unclear. The study aimed to investigate the association between CHIP and mortality in patients with arrhythmias.
Methods: This study analyzed UK Biobank participants hospitalized with arrhythmias who had whole-exome sequencing data. Arrhythmia subtypes were classified using ICD-10 codes. Outcomes, including all-cause, cardiovascular, and cancer-related mortality, were obtained from national registries. CHIP was defined as any CHIP as variant allele fraction(VAF) ≥ 2%, large CHIP as VAF ≥ 10%. Cox regression models adjusted for confounders were used.
Results: Among 53,149 individuals (median age 69 years), 3,315 carried CHIP mutations. Both any and large CHIP were independently associated with higher mortality: adjusted hazard ratios (HRs) for all-cause mortality were 1.26 (1.19–1.34) and 1.44 (1.33–1.55), respectively; for cardiovascular mortality, 1.14 (1.02–1.27) and 1.31 (1.14–1.52); and for cancer-related mortality, 1.36 (1.23–1.51) and 1.65 (1.45–1.87). Associations persisted across arrhythmia subtypes, with the strongest effects in ventricular arrhythmias. In gene-specific analyses, TET2, TP53 and spliceosome genes appeared to be the strongest deleterious genes for all-cause mortality [large TET2 CHIP: HR 1.63 (1.40–1.90); large TP53 CHIP: 1.83 (1.18–2.84); large spliceosome CHIP: HR 1.85 (1.32–2.59)].
Conclusions: CHIP is independently associated with increased mortality in patients with arrhythmias across different subtypes. These findings suggest that CHIP may serve as a potential prognostic marker and therapeutic target.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12967-026-08748-0.
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BibTeX
@article{ding2026effect,
title = {{Effect of clonal hematopoiesis of indeterminate potential on long-term survival in patients with arrhythmias}},
author = {Lei Ding and Panhui Tian and Fengyuan Yu and Zihan Jiang and Yingjie Qi and Aikai Zhang and Yuandong Liu and Yujing Shen and Hongda Zhang and Min Tang and Tianyun Wang and Junqing Xie},
journal = {Journal of Translational Medicine},
year = {2026},
month = aug,
doi = {10.1186/s12967-026-08748-0},
url = {https://doi.org/10.1186/s12967-026-08748-0},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Effect of clonal hematopoiesis of indeterminate potential on long-term survival in patients with arrhythmias
AU - Lei Ding
AU - Panhui Tian
AU - Fengyuan Yu
AU - Zihan Jiang
AU - Yingjie Qi
AU - Aikai Zhang
AU - Yuandong Liu
AU - Yujing Shen
AU - Hongda Zhang
AU - Min Tang
AU - Tianyun Wang
AU - Junqing Xie
PY - 2026
DA - 2026/08/08
JO - Journal of Translational Medicine
DO - 10.1186/s12967-026-08748-0
UR - https://doi.org/10.1186/s12967-026-08748-0
AB - Background: Clonal hematopoiesis of indeterminate potential(CHIP), defined by somatic mutations within hematopoietic clones, has emerged as a novel risk factor for cardiovascular disease. While cardiac arrhythmias are a major global health concern, the factors contributing to outcome variability remain unclear. The study aimed to investigate the association between CHIP and mortality in patients with arrhythmias. Methods: This study analyzed UK Biobank participants hospitalized with arrhythmias who had whole-exome sequencing data. Arrhythmia subtypes were classified using ICD-10 codes. Outcomes, including all-cause, cardiovascular, and cancer-related mortality, were obtained from national registries. CHIP was defined as any CHIP as variant allele fraction(VAF) ≥ 2%, large CHIP as VAF ≥ 10%. Cox regression models adjusted for confounders were used. Results: Among 53,149 individuals (median age 69 years), 3,315 carried CHIP mutations. Both any and large CHIP were independently associated with higher mortality: adjusted hazard ratios (HRs) for all-cause mortality were 1.26 (1.19–1.34) and 1.44 (1.33–1.55), respectively; for cardiovascular mortality, 1.14 (1.02–1.27) and 1.31 (1.14–1.52); and for cancer-related mortality, 1.36 (1.23–1.51) and 1.65 (1.45–1.87). Associations persisted across arrhythmia subtypes, with the strongest effects in ventricular arrhythmias. In gene-specific analyses, TET2, TP53 and spliceosome genes appeared to be the strongest deleterious genes for all-cause mortality [large TET2 CHIP: HR 1.63 (1.40–1.90); large TP53 CHIP: 1.83 (1.18–2.84); large spliceosome CHIP: HR 1.85 (1.32–2.59)]. Conclusions: CHIP is independently associated with increased mortality in patients with arrhythmias across different subtypes. These findings suggest that CHIP may serve as a potential prognostic marker and therapeutic target. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12967-026-08748-0.
SN - 1479-5876
ER -