Heart failure in patients with acute myeloid leukemia (AML) treated with anthracycline agents during remission induction therapy: a systematic review and meta-analysis.

Abstract

Patients with acute myeloid leukemia (AML) are at increased risk of cardiovascular disease, particularly heart failure. Anthracyclines are integral to remission induction therapy in patients eligible for intensive treatment and well-known for their association with cardiotoxicity. However, the incidence of heart failure and other cardiovascular adverse events (CVAEs), as well as differences across various anthracycline agents, has not been comprehensively assessed. We systematically searched PubMed and EMBASE for studies conducted in AML patients treated with anthracyclines during remission induction. Forty-one studies (5995 patients), primarily clinical trials, published between February 1991 and March 2024 were included. The pooled proportion of heart failure was 3.2% (95% CI 1.0-6.2) overall and 2.3% (95% CI 1.4-3.3), 5.0% (95% CI 0.3-14.1) and 10.2% (95% CI 2.4-21.7) for patients treated with daunorubicin, idarubicin or mitoxantrone respectively. Cardiac function was infrequently monitored, and CVAE reporting was generally poor. Since current adverse event grading systems primarily rely on clinical symptoms to assign severity, significant asymptomatic declines in cardiac function will remain undetected. Enhanced CVAE monitoring and reporting, along with revisions to established grading systems, is needed to better identify subclinical cardiotoxicity in AML patients, enabling timely intervention to prevent progression to more advanced heart failure stages.