Cardiac Involvement in Pompe Disease: From Pathophysiology to Multimodality Cardiovascular Assessment and Therapeutic Perspectives

Pompe disease, also known as glycogen storage disease type II or acid maltase deficiency, is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in the GAA gene encoding lysosomal acid α-glucosidase. Deficient enzyme activity results in progressive intralysosomal glycogen accumulation, particularly in skeletal, respiratory, and, in the classic infantile phenotype, cardiac muscle. Cardiac involvement is most prominent in classic infantile-onset Pompe disease, in which severe myocardial hypertrophy, ventricular remodeling, diastolic dysfunction, and electrical abnormalities may develop early in life. In contrast, clinically significant cardiac disease is uncommon in late-onset Pompe disease, although subtle abnormalities have occasionally been identified using sensitive cardiovascular imaging techniques. Cardiovascular assessment therefore needs to be adapted to the clinical phenotype and age of onset. Electrocardiography and echocardiography remain the principal first-line investigations, whereas speckle-tracking echocardiography and cardiac magnetic resonance may provide complementary information in selected patients. Cardiac magnetic resonance allows accurate assessment of ventricular volumes and mass and provides tissue characterization, although current evidence remains limited and heterogeneous. Enzyme replacement therapy has substantially changed the natural history of classic infantile Pompe disease, with regression of myocardial hypertrophy and improvement in cardiac function when treatment is initiated early. The cardiovascular response in late-onset disease appears considerably less pronounced. This review summarizes the mechanisms of cardiac involvement in Pompe disease, its clinical and electrocardiographic manifestations, the contribution of multimodality cardiovascular imaging, practical diagnostic considerations for cardiologists, and current and emerging therapeutic perspectives. Particular emphasis is placed on the role of the cardiologist in recognizing atypical cardiac phenotypes and participating in multidisciplinary long-term management.