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

Area of Science:

• Hematology
• Cardiovascular Medicine
• Genetics

Background:

• Clonal hematopoiesis of indeterminate potential (CHIP) is a recognized risk factor for hematologic malignancies and cardiovascular diseases.
• Understanding CHIP's impact on cardiovascular health in specific patient populations, like those with acute myeloid leukemia (AML), is crucial.

Purpose of the Study:

• To investigate the association between CHIP-related mutations and the development of symptomatic heart failure (HF) in patients newly diagnosed with AML.
• To identify specific CHIP mutations that correlate with increased HF risk in AML patients.

Main Methods:

• Retrospective analysis of 563 newly diagnosed AML patients who underwent pre-treatment bone marrow DNA sequencing.
• Utilized Cox proportional hazard and Fine and Gray's subdistribution hazard regression models to assess the relationship between CHIP mutations and symptomatic HF.
• Evaluated the incidence and cumulative incidence of symptomatic HF in relation to specific CHIP mutations, including DNMT3A, ASXL1, and TET2.

Main Results:

• A high prevalence of CHIP was observed, with 79.0% of patients harboring at least one CHIP-related mutation (DNMT3A, ASXL1, TET2 most frequent).
• Symptomatic HF developed in 9.1% of patients; incidence was significantly higher in those with DNMT3A mutations (1-year cumulative incidence 11.4% vs. 3.9%).
• DNMT3A mutations were independently associated with a twofold increased risk of symptomatic HF (HR 2.32, 95% CI 1.26-4.29), even after adjusting for age and anthracycline dose.

Conclusions:

• In AML patients, the presence of DNMT3A mutations is linked to a significantly elevated risk of developing symptomatic heart failure.
• This association persists regardless of patient age or anthracycline treatment, underscoring DNMT3A as a potential biomarker for cardiovascular risk in AML.
• Further research is warranted to elucidate the mechanisms underlying the link between DNMT3A mutations and HF in AML.