دورية أكاديمية
Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction.
| العنوان: | Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction. |
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| المؤلفون: | Pascual-Figal, Domingo A, Bayes-Genis, Antoni, Díez-Díez, Miriam, Hernández-Vicente, Álvaro, Vázquez-Andrés, David, de la Barrera, Jorge, Vazquez, Enrique, Quintas, Ana, Zuriaga, María A, Asensio-López, Mari C, Dopazo, Ana, Sánchez-Cabo, Fátima, Fuster, José J |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2021 |
| المجموعة: | REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII) |
| مصطلحات موضوعية: | Heart Failure, Ventricular Dysfunction, Left, Aged, Cause of Death, Clonal Hematopoiesis, DNA (Cytosine-5-)-Methyltransferases, DNA Methyltransferase 3A, DNA-Binding Proteins, Dioxygenases, Disease Progression, Female, Hospitalization, Humans, Male, Mortality, Mutation, Prognosis, Prospective Studies, Proto-Oncogene Proteins, Spain |
| الوصف: | 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1558-3597 |
| العلاقة: | J Am Coll Cardiol. 2021 Apr 13;77(14):1747-1759.; http://hdl.handle.net/20.500.12105/18207Test; Journal of the American College of Cardiology |
| DOI: | 10.1016/j.jacc.2021.02.028 |
| الإتاحة: | https://doi.org/20.500.12105/18207Test https://doi.org/10.1016/j.jacc.2021.02.028Test https://hdl.handle.net/20.500.12105/18207Test |
| حقوق: | http://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; Attribution-NonCommercial-NoDerivatives 4.0 Internacional ; open access |
| رقم الانضمام: | edsbas.5D73A6CB |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15583597 |
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| DOI: | 10.1016/j.jacc.2021.02.028 |