The Association between β-Thalassemia Major (β-TM) and Cardiac Complications: Recent Insights

β-thalassemia Major (β-TM) is a severe hereditary disorder characterized by insufficient synthesis of β-globin chains, resulting in chronic anemia and lifelong dependence on regular blood transfusions. Despite advancements in therapeutic modalities, cardiac complications, including atrial fibrillation, cardiomyopathy, and pulmonary hypertension, continue to be significant contributors to morbidity and mortality among β-TM patients. These persistent cardiovascular risks underscore the urgent need for early, accurate detection and the implementation of personalized assessment strategies to improve patient outcomes. The prevalence of cardiac complications is notably high, with studies reporting affected individuals in up to 71% of the β-TM population. This highlights cardiac pathology as a predominant clinical concern in this population. The primary underlying mechanism is iron overload, predominantly resulting from chronic transfusional therapy. Excess iron accumulates in the myocardium, leading to myocardial siderosis, the development of dilated cardiomyopathy, and an increased risk of life-threatening arrhythmias. Cardiac magnetic resonance imaging (cMR), particularly T2* imaging, remains the gold standard for quantifying myocardial iron deposition and guiding therapeutic interventions. Emerging biomarkers, such as Growth Differentiation Factor-15 (GDF-15) and galectin-3, have shown potential for early detection of cardiac involvement and risk stratification, with the prospect of improving clinical outcomes through timely and targeted interventions. This review aims to discuss the prevalence and pathophysiology of cardiac complications in β-thalassemia major (β-TM), delineate risk factors, including serum ferritin levels, iron chelation therapy, age, genetic predispositions, and splenectomy, and evaluate current diagnostic and monitoring strategies. Furthermore, the utility of novel biomarkers, including follistatin and other emerging candidates, for early detection and prognosis is discussed, highlighting their potential to facilitate personalized management approaches that may reduce cardiac morbidity and mortality. In conclusion, integrating advanced imaging modalities such as cMR, novel biomarker profiling, and individualized risk stratification, considering ferritin levels, genetic factors, and splenectomy status, may significantly enhance early detection and intervention strategies, ultimately mitigating the burden of cardiac complications in β-TM.