Symptomatic Heart Failure and Clonal Hematopoiesis–Related Mutations in Patients With Acute Myeloid Leukemia

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is a common risk factor for both hematological malignancies and cardiovascular (CV) diseases. The purpose of this study was to investigate the association between CHIP-related mutations and symptomatic heart failure in patients diagnosed with acute myeloid leukemia (AML). A total of 563 patients with newly-diagnosed AML who underwent DNA sequencing of bone marrow before treatment were retrospectively investigated. Cox proportional hazard regression models and Fine and Gray's subdistribution hazard regression models were used to assess the association between CHIP-related mutations and symptomatic heart failure (HF). 79.0% patients had at least 1 CHIP-related mutation; the most frequent mutations were DNMT3A, ASXL1 and TET2. Fifty-one patients (9.1%) developed symptomatic HF. The incidence of symptomatic HF was more frequent in patients with DNMT3A mutations (P<0.01), with a 1-year cumulative incidence of symptomatic HF in patients with DNMT3A mutations of 11.4%, compared to 3.9% in wild-type DNMT3A patients (P<0.01). After adjustment for age and anthracyclines dose, DNMT3A mutations remained independently correlated with HF (HR: 2.32, 95% CI: 1.26-4.29, P=0.01). In conclusion, in patients with AML, the presence of DNMT3A mutations was associated with a 2-fold increased risk for symptomatic HF irrespective of age and anthracyclines use.