112 Chapter 4 Abstract Background Morphological and functional abnormalities that can be detected by echocardiography in Fabry disease (FD) include left ventricular (LV) hypertrophy, left atrial dilatation and parameters of LV systolic and diastolic dysfunction. Currently, the progression of echocardiographic features of FD over long periods of follow-up in larger cohorts of FD patients is unknown. Methods In this study the two echocardiograms, with the longest follow-up period per patient, of 92 patients with classical FD (cFD) were re-assessed and analyzed (34 men, echo’s, median 12 years apart, 92% treated with ERT). Results were compared to data from 147 echocardiograms of healthy individuals (age and sex matched on a group level, cross-sectional data). Linear mixed-effect models (GLM) were used to analyze the effect of FD, age and sex on five echocardiographic parameters: 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’). The regression slope and absolute values per decade for each echocardiographic parameter were compared between FD patients and healthy control subjects. A Cox proportionalhazard model studied the relationship between the first echocardiogram and subsequent development of Atrial fibrillation (AF). Results The absolute values for IVSd and RWT in both men and women and E/e’ in men were significantly different between FD patients and healthy individuals (p<0.05) from age 18 onwards. Rate of change, rather than absolute values of other echocardiographic parameters were different in FD patients compared to healthy controls (p<0.05 for all comparisons). Increased IVSd, RWT and E/e’ on the first echocardiogram were associated with an increased hazard ratio for AF later on (HRs: 1.31, 1.50 and 1.20, respectively, p<0.001). Conclusions The earliest signs of cardiac involvement of FD on echocardiography are increased values for IVSd and RWT in all cFD patients and E/e’ in men. Early detection of cardiac disease is especially important in women with cFD, since not all of them will develop cardiac symptoms of the disease. During adult life IVSd, RWT, LVMi, LAVI and E/e’ increase at a significantly higher rate in FD patients compared to healthy individuals. These parameters may be used for treatment decisions, monitoring disease progression and evaluating the effect of new therapeutic interventions.
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