The Fabry Cardio Prediction Study

Fabry Disease (FD) is a rare, X- linked inherited lysosomal storage disease leading to cardiac, renal and/ or cerebrovascular complications. In 50-70% of the Fabry patients there is cardiac involvement. Common cardiac manifestations of Fabry disease are: left ventricular hypertrophy, myocardial fibrosis, conduction disturbances, microvascular disease and heart valve diseases. Clinically this manifests itself in chronic heart failure, angina pectoris (with absence of significant stenosis on coronary angiography) and/ or arrhythmias.

Background

Cardiovascular death and acute cardiac death are the most common cause of death in patients with Fabry disease. Given that cardiac fibrosis and malignant arrhythmias within Fabry cardiomyopathy contribute strongly to morbidity and mortality, it is important to counteract its development. Enzyme replacement therapy has been available since 2001 in the form of agalsidase-alpha (Replagal) or agalsidase-beta (Fabrazyme), but the right moment to initiate treatment is still uncertain. If treatment is initiated when advanced myocardial fibrosis is already present, it does not prevent  the occurrence of severe cardiac complications.  Ideally, a set of  pre- symptomatic electrophysiological, imaging and/or biochemical parameters known to predict cardiac complications should guide the decision to start treatment. Currently these predictive parameters have either not been identified or not been validated.  

Objectives of the study

1. Identifying early pre- symptomatic electrophysiological, imaging and biochemical parameters that predict the occurrence of cardiac dysfunction and complications.

2. Establish the 'sequence of events' in the development of Fabry cardiomyopathy for men and women.

Methods

This is a longitudinal retrospective study, in a cohort of Fabry patients that is under follow up at the  the Amsterdam UMC (location AMC) and of which long-term follow-up data are available. Data on clinical, electrophysiological, imaging (cardiac MRI/echocardiography), biochemical parameters  and cardiac complications will be collected.

Inclusion criteria

The study will include all adult AMC patients with a certain diagnosis of Fabry disease and a minimum follow-up period of 1 year.

Start date/expected completion

Start date: 06-2018

Expected completion: 06-2019

Expected number of patients

70 male patients

110 female patients

Study type

Single center. Retrospective cohort.

Contact

Mr. M. El Sayed, Msc. PhD Student- Dept of Internal Medicine, div of Endocrinology and Metabolism, F5-165
Academic Medical Center
Meibergdreef 9
1105 AZ Amsterdam
T +31 205667672 E m.elsayed@amc.uva.nl