42 Chapter 2 and may thus not be fully accurate. The contribution of enrollment bias on the observed outcomes between sexes remains unknown. In theory, more women could have been identified through family screening and more men because of clinical manifestations, which could have contributed to the observed differences in the occurrence of cardiac events. The influence of chronic kidney disease on MACE occurrence, which may have increased the risk, was not analyzed as the sample size and differences in follow-up duration between patients did not allow for this analysis. Although, a GFR below 60 ml/min was only present in 20% of classically affected male patients and only in a single patient from other groups (supplemental table 4). In addition, the effect of ERT on the occurrence of cardiac events was not analyzed, because of the same reasons, as well as variability in the age of therapy initiation and indication bias for start of treatment. An important strength of the study is the fact that it was a long-term longitudinal study on a large FD cohort, and the detailed data on predefined clinical cardiac events, in contrast to earlier studies which often used composites for cardiac involvement in Fabry disease including symptoms of angina pectoris, palpitations, and microscopic Gb3 storage [22, 23]. Conclusions This large longitudinal study confirms that men with classical FD develop severe cardiac events, mainly from the fifth decade of life onwards. For women with classical FD and men with non-classical FD, cardiac events occur approximately a decade later and in a smaller proportion of patients. None of the non-classically affected women in this cohort developed a major cardiac event. More than half of the first observed sustained ventricular arrhythmias occurred in the context of either an MI or HF, and HF was the most common cause of death. These findings shed new light on the clinical course and cardiac outcomes in FD cardiomyopathy and emphasize the need for new treatments, primarily to prevent heart failure in FD.
RkJQdWJsaXNoZXIy MTk4NDMw