Expert Consensus Proposes Multiparametric Cardiac Assessment System for Fabry Disease Management

Fabry disease (FD) is a rare inborn error of metabolism caused by deficient alpha-galactosidase A activity, leading to lysosomal accumulation of globotriaosylceramide in various organs, notably the heart. Fabry cardiomyopathy is the primary cause of morbidity and mortality. While ECG, echocardiography, CMR, troponin, and NT-proBNP are used for diagnosis and monitoring, definitive guidelines for follow-up, treatment initiation, and switching therapies are lacking. Current recommendations suggest starting treatment upon evidence of left ventricular hypertrophy but before fibrosis develops, highlighting a critical gap in standardized clinical pathways.

A panel of ten experts on Fabry disease, selected for their extensive contributions to the literature, convened in Milan on March 8, 2024. The group deliberated on appropriate parameters for comprehensive cardiac assessment at diagnosis and during patient follow-up. Their discussions focused on developing a multiparametric cardiac assessment system, integrating ECG, laboratory biomarkers (e.g., troponin, NT-proBNP), echocardiographic parameters, and CMR imaging. The experts defined the requirements for such a system and advocated for the necessary research to build and validate it. They also proposed a multiparametric clinical pathway to guide routine clinical decisions regarding cardiac assessment, treatment initiation, and ongoing follow-up.

The expert panel established a conceptual framework for a comprehensive multiparametric cardiac assessment system, designed to integrate existing diagnostic tools for Fabry disease. This system aims to standardize patient evaluation at diagnosis and throughout long-term follow-up, providing clearer, evidence-informed guidance for clinicians navigating this complex rare disease. The consensus highlighted the importance of early detection of cardiac involvement to prevent irreversible damage, such as myocardial fibrosis. The panel also emphasized the need for a structured approach to monitor treatment response and guide therapy adjustments. They acknowledged that while general guidance is crucial, management must be tailored to individual patient characteristics, reflecting the broad clinical spectrum of Fabry disease. The experts specifically called for further research to build and validate the proposed system, ensuring its clinical utility and efficacy in improving patient outcomes. This includes developing robust algorithms for interpreting multiparametric data and defining clear thresholds for intervention. The proposed clinical pathway is intended to support routine clinical decisions, offering a structured approach from initial assessment to ongoing management.