Quantification of Diffuse Myocardial Iron Overload Related Interstitial Fibrosis With Cardiac Magnetic Resonance Imaging in Patients With Transfusion-Dependent Anemias

Cardiac failure is the major cause of death in patients with transfusion-related iron overload. Histopathologic studies indicate that patients with myocardial siderosis have diffuse interstitial fibrosis. Cardiac MR assessment of the extracellular volume (ECV) fraction in other disease processes has been shown to accurately characterize diffuse myocardial fibrosis and to correlate with changes in diastolic function. No prior studies have assessed for diffuse interstitial myocardial fibrosis in patients with iron overload utilizing the proposed imaging techniques.

In this study, the investigators will assess the presence and extent of interstitial fibrosis in patients with transfusion-dependent anemias using cardiac MR techniques of T1 mapping and determination of ECV fraction. ECV values will be correlated with the severity of myocardial iron deposition determined by multi-echo T2*-weighted imaging, systolic ventricular function as determined by cardiac MR and diastolic function assessed by echocardiography. The investigators will recruit 35 patients with transfusion-related iron overload. Ten age-matched healthy subjects will be included as controls, to establish baseline values of myocardial T1 and ECV values. A modified Look-Locker with inversion recovery (MOLLI) sequence will be used to determine T1 values pre-, and post-administration of a gadolinium-based contrast agent (GBCA) at 1.5 Tesla. Calculated ECV values will be compared between iron-overload subjects and healthy controls, and will be correlated with left ventricular ejection fraction, measures of diastolic dysfunction and T2* values.

Detection of myocardial fibrosis in patients with iron overload would allow for improved prognostication and risk stratification. Elucidation of the relationship between myocardial fibrosis and myocardial iron deposition as well as cardiac functional parameters would provide valuable mechanistic insights and improved pathophysiological understanding of the disease. The results of the proposed study have the potential to significantly impact patient management including recommendations for earlier or more aggressive chelation therapy based on changes in ECV values.