186 Chapter 6 used to evaluate the effectiveness of treatment, with the current study providing reference data for comparison of new treatments. Chapter 4 describes the morphological and functional echocardiographic alterations in patients with classical FD versus healthy controls. We conducted this study because 1) the progression of echocardiographic features of FD over long follow-up periods was largely unknown, and 2) insight into the evolution of echocardiographic parameters and their relation with cardiac events may aid in therapeutic decision-making. The two echocardiograms, with the longest follow-up period between them, per patient were re- assessed and analyzed for 92 patients with classical FD (58 women, echo’s median 12 years apart, 92% treated with ERT). Results were compared to data from 147 echocardiograms of healthy individuals (age and sexmatched on a group level, cross-sectional data). The effect of FD, age and sex on end-diastolic interventricular septum thickness (IVSd), relative wall thickness (RWT), left ventricular mass index (LVMi), left atrium volume index (LAVI) and the ratio of early diastolic mitral inflow velocity/ early diastolic septal tissue mitral annulus velocity (E/e’) was analyzed. As a secondary study aim, the relation between the first echocardiogram and subsequent development of Atrial fibrillation (AF) in FD was tested. The earliest signs of cardiac involvement of classical FD on echocardiography were increased values for IVSd and RWT in all FD patients and E/e’ in men. Increased absolute values of these markers on the first echocardiogram were associated with an increased risk for AF later. During adult life, IVSd, RWT, LVMi, LAVI and E/e’ increase significantly in FD patients compared to healthy individuals. These findings suggest that echocardiographic parameters reflecting left ventricular (LV), atrial morphology and LV diastolic function can represent disease progression over time in classical FD patients. Comparing the absolute values of echocardiographic parameters in FD patients with age and sex-specific reference ranges or evaluating the increment over time can be used to determine the need for treatment initiation, monitor disease progression and evaluate the effect of therapeutic existing and new future interventions. Finding a biomarker with a substantial predictive value for disease course is crucial to establish the need for Fabry-specific treatment and the right follow-up frequency for an individual FD patient. In Chapter 5, we investigated whether levels of plasma Globotriaosylsphingosine (lysoGb3) were stable over time in untreated FD patients and how these levels relate to cardiac and non-cardiac FD manifestations by studying 237 untreated FD patients. Plasma lysoGb3 levels remained stable over time in these untreated FD patients, confirming its
RkJQdWJsaXNoZXIy MTk4NDMw