Abstract
Introduction
Somatic mutations in hematopoietic cells are associated with age and have been associated with higher mortality in apparently healthy adults, especially due to atherosclerotic disease. In animal models, somatic mutations are associated with atherosclerosis progression and myocardial dysfunction, especially when gene TET2 is affected. Preliminary clinical data, referred to ischemic heart failure (HF), have associate the presence of these acquired mutations with impaired prognosis.
Purpose
To study the prevalence of somatic mutations in patients with heart failure with reduced ejection fraction (HFrEF) and their impact on long-term prognosis.
Methods
We studied a cohort of elderly patients (more than 60 years old) hospitalized with HFrEF (LVEF<45%). The presence of somatic mutations was assessed using next generation sequencing (Illumina HiSeq 2500), with a mutated allelic fraction of at least 2% and a panel of 55 genes related with clonal hematopoiesis. Patients were followed-up for a median of three years. The study endpoint was a composite of death or readmission for worsening HF. Kaplan-Meier analysis (log-rank test) and Cox proportional hazards regression models were performed adjusting for age, sex and LVEF.
Results
A total of 62 patients (46 males (74.2%), age 74±7.5 years) with HFrEF (LVEF 29.7±7.8%) were enrolled in the study. The ischemic etiology was present in 54% of patients. Somatic mutations in Dnmt3a or Tet2 were present in 11 patients (17.7%). No differences existed in baseline characteristics except for a higher prevalence of atrial fibrillation in patients with somatic mutations (70% vs. 40%, p=0.007). During the follow-up period, 40 patients (64.5%) died and 38 (61.3%) had HF re-admission. The KM survival analysis for the combined event is shown in Figure 1. Compared with patients without somatic mutations and after adjusting for covariates, there was an increased risk of adverse outcomes when the somatic mutations were present (HR 3.6, 95% CI [1.6, 7.8], p=0.0014). This results remains considering death as a competing risk (Gray's test p=0.0097) and adjusting for covariates (HR = 2.21 95% CI [0.98, 5], p=0.0556).
Conclusions
Somatic mutation are present in patients with HFrEF and determine a higher risk of adverse events in the follow-up. Further studies are needed to assess the clinical implications of these findings.
Figure 1
Funding Acknowledgement
Type of funding source: None
Prognostic impact of hospital‐acquired disability in elderly patients with heart failure
