Clinical Research Directory

Therapeutic Implications of CMR Low Native T1 in Non-treated Non-hypertrophic Females With Fabry Disease (FD)

Sponsor: University Hospital, Bordeaux

Summary

Females with Fabry disease are characterized by variable phenotypes regarding time of onset, severity of symptoms and progression of disease due to the random inactivation of X chromosome leading to a cellular mosaic of mutated and wild genotypes. Left ventricular hypertrophy (LVH) is a relatively late manifestation, appearing typically after the third decade in men and the fourth decade in women. Cardiac involvement progresses throughout life in Fabry females and is the first cause of death but in contrast to males, the loss of myocardial function and the development of fibrosis do not necessarily require myocardial hypertrophy in female with FD. The presence of overt LVH and myocardial fibrosis has been shown to negatively affect treatment outcome, suggesting the importance of early initiation of treatment. Multiparametric cardiac magnetic resonance (CMR) is able to detect sphingolipid infiltration by identifying a pre-LVH phase of cardiac FD defined by a low myocardial native T1, occurring in up to 60% of FD patients, with a concomitant slight elevated LV ejection fraction and electrocardiographic (ECG) changes. Low myocardial T1 values are independently associated with FD progression and are risk factors for clinical worsening. Normal native T1 value is known to be higher in healthy young women than in men but prevalence of low native T1 in Fabry females has not been correctly assessed so far. Treating Fabry females at the appropriate time is still a major issue and remains questionable as therapeutic and financial burden has to be balanced with severity status. However, low native myocardial T1 in CMR is an early marker of cardiac impairment in FD that could justify adapting the therapeutic initiation notably in women. This is of paramount importance as early treatment may provide more benefit before occurrence of irreversible lesions such as LVH and fibrosis.

Official title: Therapeutic Implications of CMR Low Native T1 in Non-treated Non-hypertrophic Females With a Genetically Confirmed Diagnosis of Fabry Disease (FD)

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