199 Summary and general discussion reach the necessary event rate to assess the predictive value of the parameters discussed above. Since heart failure with preserved ejection fraction (HFpEF) is the predominant cardiac phenotype in FD [37, 38], paying attention to the history and physical examination indicating chronic heart failure is essential. This is important because there is new supportive treatment. In HFpEF patients, regardless of the cause of heart failure, the administration of SGLT2 inhibitors in acute HF hospitalized patients led to reduced 90-day morbidity and mortality, compared to patients receiving a placebo (EMPULSE trial) [39]. Whether this treatment will also impact disease outcomes in patients with chronic HFpEF in the context of FD requires a randomized control trial, in which FD patients treated with an SGLT2 inhibitor on top of the regular recommended heart failure medication (diuretics) [40] will be compared with patients only receiving regular care. The majority of patients with FD report exercise intolerance. Patients describe this as (muscle) fatigue, lack of endurance capacity or breathlessness. These symptoms limit the patients’ ability to participate in work and daily activities, leading to reduced mobility and independence. Simultaneously, it is one of the features of FD that is most difficult to tackle, as the origin of the exercise intolerance is often not clear, limiting the possibility of giving individualized medical advice (e.g. early treatment of heart failure, training/exercise advice, rehabilitation programs and psychosocial interventions). Lack of interventions results in the persistence of the problem and more immobility, resulting in a vicious cycle. The relationship between complaints and cardiac dysfunction is not always apparent, especially in younger patients that show a structural and functionally normal or only subtly abnormal heart on routine clinical tests (e.g. ECG, echocardiography and blood tests). It is essential to note that these clinical tests are performed at rest, whereas the complaints occur during exercise. Exercise intolerance symptoms in FD can be related to cardiac dysfunction [41]. However, it may also result from lung or skeletal muscle function or deconditioning changes. Pulmonary dysfunction, especially bronchial obstruction, was frequently observed in FD [42, 43]. A histopathological study in 12 FD patients suggests that in skeletal muscle, accumulation of glycosphingolipids can occur, in both vascular endothelium and myocytes, resulting in skeletal myopathy [44]. Recent studies have shown that lysosomal storage disorders such as FD cause mitochondrial dysfunction [45-47]. Whether this also occurs in cardiac and skeletal muscle in FD and contributes to exercise intolerance in FD has not yet been determined. By performing incremental cardiopulmonary exercise (CPX) tests in our ongoing Fabry Exercise Intolerance STudy (FEISTY), more insight 6
RkJQdWJsaXNoZXIy MTk4NDMw