189 Summary and general discussion course that is comparable to the general population. At the same time, some women carry a cardiac phenotype resembling that of men with a severe classical phenotype. Ideally, within this group, we should select individual patients at risk for developing cardiac complications so that we can treat them with Fabryspecific or supportive therapy earlier, as multiple studies have shown that initiating therapy at the onset of cardiac fibrosis is less effective than in patients in whom therapy is started prior to fibrosis [14]. Studies that have examined the therapeutic effect of ERT suggest that the application of ERT can stabilize left ventricular mass (LVM) or septal thickness or even cause a reduction of LV mass in both men and women with cFD. Other studies claim that patients receiving ERT show a longer median survival time compared to untreated patients [15]. These findings, in our opinion, should be interpreted with great caution because of following three main reasons: 1) The conducted studies often have a retrospective design with relatively short follow-up periods and do not consider the significant differences in the diagnosis’s timing and treatment initiation among FD patients. For example, a patient diagnosed at 50 years of age through family screening and treated because of subtle cardiac manifestations will have a very different cardiac outcome compared to a patient who is diagnosed at the same age and has already experienced multiple cardiac events with significant cardiac damage. In our opinion it is invalid to compare two groups of patients who have not been treated with ERT and who have vastly different baseline conditions. 2) Retrospective studies with short follow-up periods and, for example, only two measurements of LV mass are difficult to interpret because of the high variability in the measures, especially if echocardiography is used. In studies that show a stabilizing effect on LVM, it is still being determined whether this stable LVM is simply an age-related effect within the general population, as control groups from the general population are often lacking. 3) Studies in women with cFD often focus on the effect of ERT on cardiac mass, however women with cFD can develop cardiac complications and fibrosis in absence of an increased LV mass [8]. Therefore, LVM is not an ideal marker for response to therapy, especially in women with cFD. Fabry cardiomyopathy and ERT: use of clinical markers As mentioned above, previously published data shows that early treatment with ERT, i.e. before irreversible damage has occurred, may improve renal and cardiac outcomes [16, 17]. Males with classical FD over 45 years of age invariably suffer a cardiovascular event [2]. For this reason, there is, again, no debate about the need for Fabry-specific treatment in the classically affected male group. On the other hand, we have shown in chapter 2 that only a subset of women with classical FD (cFD) developed cardiovascular events, with a highly variable age 6
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