Heart Failure in Anthracycline Cardiotoxicity: From Mechanisms to Clinical Management.

Anthracyclines remain a cornerstone therapy for haematological malignancies and solid tumours, but their use is limited by cardiotoxicity, ranging from asymptomatic left ventricular dysfunction to overt heart failure (HF). The risk increases with cumulative doxorubicin-equivalent exposure exceeding 250-300 mg/m2, although susceptibility varies substantially according to patient characteristics, pre-existing cardiovascular disease, genetic predisposition, and modifiable risk factors. Clinically overt HF occurs in ∼6-9% of patients, while subclinical cardiac dysfunction develops in up to 18%. The pathophysiology is multifactorial, involving interconnected mechanisms that disrupt cardiomyocyte homeostasis and promote endothelial dysfunction, inflammation, fibrosis, and adverse remodelling. Yet evidence connecting molecular mechanisms with long-term HF outcomes in humans remains incomplete. Risk stratification, incorporating clinical variables, cardiac biomarkers, echocardiography and, when appropriate, cardiac magnetic resonance enables earlier recognition of cardiac dysfunction. Trials of preventive neurohormonal treatment and statins have produced heterogeneous results, often relying on imaging rather than clinical HF endpoints. Once cardiac dysfunction develops, prompt initiation of foundational HF treatment and multidisciplinary decisions on cancer therapy are essential. Early detection and prompt initiation of HF therapies may reverse myocardial dysfunction, whereas delayed recognition is associated with a poorer treatment response and prognosis. This narrative review integrates current evidence on the mechanisms, risk stratification, surveillance, prevention, and management of anthracycline cardiotoxicity and HF, while highlighting gaps in knowledge, emerging therapeutic strategies, and future directions for clinically meaningful, risk-guided research.