Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction.
J Am Coll Cardiol
; 77(14): 1747-1759, 2021 04 13.
Article
em En
| MEDLINE
| ID: mdl-33832602
ABSTRACT
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
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Disfunção Ventricular Esquerda
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DNA (Citosina-5-)-Metiltransferases
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Proteínas de Ligação a DNA
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Hematopoiese Clonal
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Insuficiência Cardíaca
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
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Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
J Am Coll Cardiol
Ano de publicação:
2021
Tipo de documento:
Article