Cardiac involvement in Fabry disease

Abstract

Cardiac involvement is frequent in Fabry disease and is the most important cause of disease-related death and reduced life expectancy. The intracellular accumulation of glycosphingolipids occurs within the myocytes, valves and vascular endothelium of the heart. The main manifestation of cardiac involvement is cardiomyopathy with echocardiographic and clinical features resembling those of hypertrophic cardiomyopathy. In its early stages Fabry cardiomyopathy is characterized by left ventricular hypertrophy and diastolic dysfunction but with progression of the disease the ventricular hypertrophy increases and is accompanied by the development of myocardial replacement fibrosis (detectable by late gadolinium-enhanced cardiac magnetic resonance) and ultimately systolic dysfunction. Clinical manifestations include symptoms of heart failure, angina pectoris and arrhythmias. The differential and early diagnosis are mainly based on the recognition of systemic noncardiological manifestations and specific cardiological features. Newer techniques like cardiac magnetic resonance with T1 mapping may further improve its early diagnosis, which is crucial for early treatment. The management of Fabry cardiomyopathy, besides early institution of enzyme replacement therapy (ERT), requires comprehensive clinical management including concomitant cardiological therapies, mostly in the advanced stages of the disease. A cardiologist together with the other involved disciplines should define the indication for ERT. Before and during ERT it is important to initiate additional therapy in almost every Fabry patient.