2026-08-25T14:08:59Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/182072024-09-27T08:56:48Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Pascual-Figal, Domingo A author Bayes-Genis, Antoni author Díez-Díez, Miriam author Hernández-Vicente, Álvaro author Vázquez-Andrés, David author de la Barrera, Jorge author Vazquez, Enrique author Quintas, Ana author Zuriaga, María A author Asensio-López, Mari C author Dopazo, Ana author Sanchez-Cabo, Fatima author Fuster, José J author 2021-04-13 BACKGROUND Clonal hematopoiesis driven by somatic mutations in hematopoietic cells, frequently called clonal hematopoiesis of indeterminate potential (CHIP), has been associated with adverse cardiovascular outcomes in population-based studies and in patients with ischemic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Yet, the impact of CHIP on HF progression, including nonischemic etiology, is unknown. OBJECTIVES The purpose of this study was to assess the clinical impact of clonal hematopoiesis on HF progression irrespective of its etiology. METHODS The study cohort comprised 62 patients with HF and LVEF <45% (age 74 ± 7 years, 74% men, 52% nonischemic, and LVEF 30 ± 8%). Deep sequencing was used to detect CHIP mutations with a variant allelic fraction >2% in 54 genes. Patients were followed for at least 3.5 years for various adverse events including death, HF-related death, and HF hospitalization. RESULTS CHIP mutations were detected in 24 (38.7%) patients, without significant differences in all-cause mortality (p = 0.151). After adjusting for risk factors, patients with mutations in either DNA methyltransferase 3 alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) exhibited accelerated HF progression in terms of death (hazard ratio [HR]: 2.79; 95% confidence interval [CI]: 1.31 to 5.92; p = 0.008), death or HF hospitalization (HR: 3.84; 95% CI: 1.84 to 8.04; p < 0.001) and HF-related death or HF hospitalization (HR: 4.41; 95% CI: 2.15 to 9.03; p < 0.001). In single gene-specific analyses, somatic mutations in DNMT3A or TET2 retained prognostic significance with regard to HF-related death or HF hospitalization (HR: 4.50; 95% CI: 2.07 to 9.74; p < 0.001, for DNMT3A mutations; HR: 3.18; 95% CI: 1.52 to 6.66; p = 0.002, for TET2 mutations). This association remained significant irrespective of ischemic/nonischemic etiology. CONCLUSIONS Somatic mutations that drive clonal hematopoiesis are common among HF patients with reduced LVEF and are associated with accelerated HF progression regardless of etiology. J Am Coll Cardiol. 2021 Apr 13;77(14):1747-1759. 10.1016/j.jacc.2021.02.028 1558-3597 Journal of the American College of Cardiology 33832602 http://hdl.handle.net/20.500.12105/18207 Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction.