134 Chapter 4 this occurs mainly from the fifth decade onwards and for women from the sixth decade onwards [8, 33]. At the same time, there is evidence that early treatment (as early as dolescence in male patients with classical FD) is needed to prevent development of disease manifestations [10, 34]. Thus, evaluation of therapeutic effectiveness based on clinical cardiac endpoints can only be done after approximately two decades of treatment. In this study we show that serial measurements of echocardiographic parameters reflecting both morphological and functional changes can be used to determine whether or not new treatments prevent cardiac disease development. IVSd, RWT, LVMi, LAVI and E/e’ all show a greater increase in men and women with FD compared to healthy control subjects. The goal of new therapies should be to normalize the rate of change of the parameters to that of healthy control subjects. A second limitation of the current study is the fact that the echocardiograms of the FD patients and the healthy control subjects have been performed on different ultrasound systems and obtained by different technicians in two different centers. In addition, the calculated slopes cannot be used to predict the exact course for the different echocardiography parameters in individual FD patients, because of the non-uniform linear course of some of the parameters and, the retrospective nature of the study prevented the analysis of some of the parameters on the older images. Lastly, the analysis examining the association between echo markers and future AF development did not correct for the age of AF development because the number of events was too low to allow for multiple determinants in the model. Patients who developed AF were significantly older than patients who did not (49.7 vs 33.6 years), which represents the effect of age, but also an effect of longer exposure to the genetic condition. Conclusion In FD, echocardiography parameters reflecting LV and atrial morphology and LV diastolic function can be used to document cardiac disease progression over time. In the first decades of adult life, the absolute values for IVSd and RWT in all classical FD patients and E/e’ in male patients are significantly different from those of healthy individuals. During adult life IVSd, RWT, LVMi, LAVI and E/e’ increase at a higher rate in FD patients compared to healthy individuals. Assessing the absolute values (compared to a matched control cohort) and increment of these echocardiographic features can be used to determine the presence of early cardiac involvement, monitor disease progression, estimate the risk of development of atrial fibrillation and evaluate the effect of new and/ or earlier therapeutic interventions.
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