P899Long-term evolution of Fabry cardiomyopathy under enzyme replacement therapy in the Swiss Fabry cohort. An echocardiographic study

Abstract

Abstract Introduction Fabry cardiomyopathy may present with left ventricular hypertrophy (LVH) and enzyme replacement therapy (ERT) aims to slow its progression in affected patients. LVH progression may be observed despite ERT and the aim of this study was to identify predictors of adverse LV remodeling under treatment. Methods This multicentric study included consecutive Fabry patients receiving ERT and for whom a clinical follow-up (FU) with echocardiography (TTE) of at least 5 years was available. The first TTE was performed at the time of ERT start and disease progression was defined as an increase in LV mass index between the first and the last available FU TTE. Results Sixty-one patients (median age 35 years [23–48] and 40 (66%) men) were included with a median FU of 10.5 years [7.2–12.2]. Progression was seen in 33 (54%) patients with an annual increase in LV mass index of 1.8 g/m2/year [0.7–3.2] (vs −0.8 g/m2/year [−1.6 to 0.4] in the non-progression group). Presence of LVH (>95 g/m2 in women or >115 g/m2 in men) at the start of ERT was the only morphological baseline parameter significantly associated with progression after adjustment for age, gender and baseline arterial hypertension (OR 22.5, 95% CI 2.7–188.3, p=0.004). Over the FU duration, patients with baseline LVH (n=22) had higher increase in LV diastolic diameter (2.3±4.9 mm vs 0.9±4.1, p=0.009), a lower increase in relative wall thickness (−1.7±14.1% vs 4.6±9.8%, p=0.04), and a higher increase in LV mass index (22±22 g/m2 vs 0±17 g/m2, p=0.001), as compared with patients with no baseline LVH. While no difference was seen in the evolution of the LV ejection fraction, a faster decline in diastolic function was observed in patients with baseline LVH, with a higher increase in E/e' ratio (5.9±7.4 vs 1.1±2.8, p=0.001) and in left atrial diameter (4.7±5.4 mm vs 1.8±5.2 mm). Baseline characteristics All (n=61) No LVH (n=39) LVH (n=22) p Age (years) 35 [23–48] 17 [21–36] 50 [44–54] <0.001 Male gender 40 (66%) 22 (56%) 18 (82%) 0.79 Arterial hypertension 10 (17%) 3 (8%) 7 (31%) 0.03 LV mass index (g/m2) 105±43 79±18 150±38 <0.001 Mitral E/e' ratio 7.8±5.0 6.7±2.0 9.9±7.8 0.02 Conclusion Over a median FU of over 10 years, LV wall thickness, LV mass and LV diastolic function remained stable under ERT, providing the treatment was started, early, i.e. before development of LVH. If LVH is already present at baseline, ERT appears to be less effective, with significant progression in LV mass and significantly faster decrease in diastolic function.