Anderson-Fabry disease management: role of the cardiologist

Graphical Abstract Role of the cardiologist in the management of patients with AFD. The cardiologist plays a central role in the decision-making and management of AFD patients. He represents one of the leading figures in the multidisciplinary teams responsible for therapeutic decisions and proper monitoring of AFD patients. The role of the cardiologist is essential for early differential diagnosis and treatment decisions, particularly when dealing with non-classic AFD. As current AFD-specific therapies may be of limited efficacy on cardiac damage, prevention and management of cardiovascular complications according to specific and general guidelines are mandatory. The increasing identification of newborns and children carrying variants associated with late-onset disease requires a prolonged cardiological follow-up, including an appropriate transition of care from paediatric to adult cardiologists. Increased awareness of AFD among cardiologists and continuing cardiological research are of utmost importance to improve the outcomes of AFD patients. International networks between research centres are of utmost importance to further address the clinical and research unmet needs. AFD, Anderson-Fabry disease; CV, cardiovascular; FD, Fabry disease; AI, artificial intelligence; PROM, patient-reported outcome measure. Figure in part created with Biorender officially licenced to M.P. Anderson-Fabry disease (AFD) is a lysosomal storage disorder characterized by glycolipid accumulation in cardiac cells, associated with a peculiar form of hypertrophic cardiomyopathy (HCM). Up to 1% of patients with a diagnosis of HCM indeed have AFD. With the availability of targeted therapies for sarcomeric HCM and its genocopies, a timely differential diagnosis is essential. Specifically, the therapeutic landscape for AFD is rapidly evolving and offers increasingly effective, disease-modifying treatment options. However, diagnosing AFD may be difficult, particularly in the non-classic phenotype with prominent or isolated cardiac involvement and no systemic red flags. For many AFD patients, the clinical journey from initial clinical manifestations to diagnosis and appropriate treatment remains challenging, due to late recognition or utter neglect. Consequently, late initiation of treatment results in an exacerbation of cardiac involvement, representing the main cause of morbidity and mortality, irrespective of gender. Optimal management of AFD patients requires a dedicated multidisciplinary team, in which the cardiologist plays a decisive role, ranging from the differential diagnosis to the prevention of complications and the evaluation of timing for disease-specific therapies. The present review aims to redefine the role of cardiologists across the main decision nodes in contemporary AFD clinical care and drug discovery.