Heart Fail Rev. 2026 Aug 7;31(1):91. doi: 10.1007/s10741-026-10663-x.
ABSTRACT
Iron overload cardiomyopathy (IOC) remains an important cause of morbidity and mortality in patients with hereditary haemochromatosis and transfusion-dependent conditions such as haemoglobinopathies. The condition arises when excess iron, due to increased intestinal iron absorption or repetitive transfusions, saturates transferrin-binding capacity, generating non-transferrin-bound iron. This form of iron enters cardiomyocytes through L-type and T-type calcium channels, divalent metal transporter 1, and ZIP14 and triggers oxidative stress via the Fenton reaction, mitochondrial dysfunction, calcium dysregulation, and ferroptosis. The resulting clinical spectrum ranges from diastolic dysfunction to overt heart failure and fatal arrhythmias. Cardiac magnetic resonance T2* has revolutionized diagnosis and risk stratification, enabling MRI-guided chelation strategies that have dramatically reduced cardiac mortality over the past decades. Phlebotomy remains the cornerstone of treatment in primary haemochromatosis, while iron chelators, including deferoxamine, deferiprone and deferasirox, is the standard for transfusion-dependent patients. Adjunctive amlodipine has also emerged as a strategy to reduce myocardial iron accumulation. Novel disease-modifying or curative treatments for thalassaemia, such as luspatercept, mitapivat and gene therapy offer the prospect of addressing the root cause of iron loading. This review provides an updated comprehensive, evidence-based overview of the pathophysiology, diagnosis, and management of IOC.
PMID:42566087 | DOI:10.1007/s10741-026-10663-x