New clinical staging proposal applied to a Fabry cardiomyopathy cohort

Abstract Background Fabry disease (FD) is a rare cause of hypertrophic cardiomyopathy (HCM), and early diagnosis is important considering the response to enzyme replacement or chaperone therapies. Recently, a practical clinical staging for Fabry cardiomyopathy was proposed by Olivotto et al 2023, considering several features, being potentially useful for standardizing the criteria for initiation and response assessment to therapy. Imaging characterization of hypertrophy and fibrosis are critical key items to determine stages. This new proposal suggested 4 main stages (0, I, II, III) according to these parameters. Stages 0 and I are further divided in 2 sub-stages according to minor findings and hypertrophy severity, respectively. Unfortunately, not all patients with Fabry cardiomyopathy are identified early in the disease, limiting the response to treatment. Aim Our study aimed to evaluate retrospectively the staging of Fabry cardiomyopathy at first imaging cardiac evaluation according to the recent proposal (1), in a cohort of 35 patients with FD at a reference centre of Fabry disease. Results At the first cardiac evaluation, the group of patients had a median age of 46 years (28-68 years), 69% were female and 5% were already under enzymatic therapy. The majority of Fabry patients (66%) were in non-hypertrophic stage 0: 4 patients in 0A with no detected cardiac involvement and 19 patients in 0B with subclinical cardiac findings (17% presenting diastolic dysfunction, 14% impaired global longitudinal strain, 6% hypertrabeculation, 6% reduced native T1, 3% short PR duration, 3% cardiac symptoms). In hypertrophic stage I, 14% of patients were classified according to the presence and severity of LVH: 3 in IA (12-15 mm) and 2 in IB (>15mm). All patients (n=3, 9%) in hypertrophic fibrotic stage II presented non-extensive late enhancement (< 3 LV segments) in the first CMR. Patients with overt dysfunction or stage III (n=4; 11%), presented diffuse myocardial fibrosis (> 3 LV segments) or impaired systolic function (LVEF < 50%). Conclusion In our cohort patients, the new staging scheme allows us to identify and classify the different stages of FD cardiomyopathy. The majority of patients were unexpectedly identified in early disease stages, but that could be related to diagnosis in the context of familial screening. This proposal seems useful for clinical staging standardization to facilitate the evaluation of responses to treatments and to predict outcomes, however, needs to be validated in larger and prospective studies.