Cardiac Dysfunction in β-Thalassemia: A Narrative Review

Iron overload is the primary driver of heart problems. Patients with β-thalassemia major require lifelong blood transfusions to survive.Early detection is critical because symptoms appear late. Cardiac dysfunction often remains hidden (subclinical) until the disease is advanced.Management focuses on iron chelation and monitoring. Since the body cannot naturally remove excess iron, the primary treatment to prevent or reverse cardiac damage is iron chelation therapy.

β-thalassemia, particularly the major form, is associated with significant morbidity, as it requires lifelong maintenance transfusion therapy to manage the condition. This transforms thalassemia from a fatal childhood disease into a chronic disorder. Nonetheless, this therapeutic approach presents challenges due to its pathological adverse effects on cardiac health, including heart failure and arrhythmias.

Multiple lifelong transfusions, combined with the pathological effects of thalassemia-such as hemolysis and ineffective erythropoiesis-exacerbate excessive iron deposition, primarily in the liver but most critically in the heart. This creates a vicious cycle between iron overload and cardiac dysfunction. Due to their high dependence on blood transfusions, thalassemia major patients are predisposed to left-sided heart failure, resulting from both dilated and restrictive cardiomyopathy, as well as life-threatening arrhythmias and electrical disturbances. These complications arise from the heart's overwhelmed capacity to clear free radicals. Cardiac dysfunction represents a critical complication requiring early detection and prompt intervention, underscoring the limitations of conventional echocardiography in diagnosing subclinical and systolic dysfunction-the latter often appearing only in advanced disease. Earlier risk stratification is essential, with recent studies highlighting the role of genetic predisposition, biomarkers, and advanced noninvasive imaging (MRI) in facilitating timely treatment initiation, such as iron-chelating therapy, to improve survival outcomes.

Iron overload is an inevitable consequence for thalassemia major patients requiring transfusions, as the human body lacks mechanisms to eliminate excess iron. These patients require careful observation, monitoring, and timely diagnosis according to standard guidelines to facilitate chelation therapy and prevent its harmful effects. This review examines the complex interplay between symptomatic management of thalassemia, subsequent iron overload, and cardiac dysfunction in treated patients, with the goal of promoting early detection of therapeutic complications and timely intervention.