184 Chapter 6 Summary Although the exact pathophysiological mechanism is still not completely understood, it is widely accepted that Globotriaosylceramide (Gb3) accumulation in cardiac tissue is the culprit leading to progressive cardiac dysfunction and ultimately early death in Fabry disease (FD). Following the launch of enzyme replacement therapies, an increasing number of studies has been published describing the cardiac manifestations of FD. However, extensive longitudinal studies that reveal the exact clinical course of Fabry cardiomyopathy in distinct groups divided by phenotype and sex were lacking. The hypothesis is that in FD gradual alterations in electrophysiological, echocardiographic and biochemical markers arise with increasing age of the patient, some of which will be present prior to clinical manifestations. Once we know which and when these biomarkers start to change in different patient groups and how they are related to the occurrence of cardiac events, it will be possible to: 1) Early identify and treat FD patients at risk for developing cardiac events, which may delay irreversible myocardial damage and improve prognosis. 2) Identify clinically relevant electrophysiological, echocardiographic and biochemical markers that help clinicians in the evaluation of Fabry specific and supportive treatment effects. 3) Develop tailored follow-up protocols taking these prognostic markers into account, in combination with sex, phenotype and age of the patient. The studies performed within this thesis included observational longitudinal retrospective studies in a group of well-phenotyped FD patients followed at the Amsterdam University Medical Centre (Amsterdam UMC), the Netherlands. Data on cardiac outcomes, electrophysiological, imaging (cardiac MRI (CMR) and echocardiography) and biochemical parameters were collected. For comparison to the general population, data from healthy population cohorts (the Healthy Life in an Urban Setting (HELIUS) and Rotterdam Navigator cohort) were used. By comparing the electrophysiological and echocardiographic characteristics of FD patients, to those of healthy individuals cardiac features that are typical for FD, at both an early and late disease stage, could be recognized. In chapter 2, we recorded the prevalence and timing of cardiac events from birth to the last outpatient clinic visit in a large cohort of 213 FD patients with classical and non-classical FD (average follow-up time: 50 years). In men with classical FD, events occurred mainly from the fifth decade of life onwards. In women with classical FD and men with non-classical FD, events were observed on average one decade later, with a larger variation in the age of complications’ onset and in a smaller proportion of patients.
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