Infiltrative Cardiomyopathies

Infiltrative cardiomyopathy refers to a heterogeneous group of disorders which involves infiltration of the myocardium with various molecules. Some infiltrative cardiomyopathies, such as Fabry disease (FD), cause a hypertrophic phenotype, while others, such as iron-overload cardiomyopathy (IOC), cause a dilated phenotype. FD is an X-linked recessive lysosomal storage disorder characterized by deficient α-galactosidase A activity and gradual accumulation of glycosphingolipids, resulting in dermatological, gastrointestinal, ocular, neurological, renal, and cardiac manifestations. Cardiovascular disease, including left-ventricular hypertrophy and diastolic dysfunction, is the most significant cause of morbidity and mortality in FD. Biomarkers and cardiac imaging play a crucial role in diagnosis and following disease progression. Enzyme replacement reduces glycosphingolipid levels in the heart and vasculature, leading to slowed progression of cardiac disease. Iron overload can be caused by both inherited and acquired etiologies, leading to IOC, including left ventricular dilatation and decreased ejection fraction, as well as extracardiac manifestations. Therapy for iron overload differs based upon the underlying etiology and typically involves either therapeutic phlebotomy or iron chelation therapy, preventing disease progression. Echocardiography and cardiac MRI provide useful prognostic and diagnostic information. This chapter discusses the cardiac manifestations of Fabry disease and iron-overload cardiomyopathy.