In 293 patients with Fabry disease, there was a consistent absence of systolic anterior motion (SAM) in all cases, attributed to restricted mitral leaflet mobility.
In patients with Fabry disease and mitral regurgitation, the absence of systolic anterior motion suggests that regurgitation is driven by leaflet restriction rather than the mechanisms typically seen in hypertrophic cardiomyopathy.
Absolute Event Rate: 0% vs 0%
Abstract Introduction Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, resulting in α-galactosidase deficiency. Cardiac involvement is characterized by myocardial and papillary muscle hypertrophy, thickening of the subvalvular apparatus, and increased rigidity of the mitral valve. Mitral regurgitation (MR) is more prevalent in patients with FD compared to the general population (1). Purpose In patients with Fabry disease-related cardiac involvement, MR and left ventricular outflow tract obstruction (LVOTO) are more frequently observed. Considering the structural similarities to hypertrophic cardiomyopathy (HCM), where systolic anterior motion (SAM) of the mitral leaflet occurs in 25–50% of cases (2,3,4,5), we hypothesized that SAM might similarly contribute to MR in a subset of FD patients. We know that any distance 2.75 cm implies a relative anterior displacement of the coaptation point and, hence, susceptibility to SAM (6). Methods We conducted a retrospective analysis of echocardiographic data from 293 patients with genetically confirmed Fabry disease, selecting those with at least moderate mitral regurgitation, collected between 2003 and 2023. In addition to standard echocardiographic measurements, we assessed the coaptation distance between the mitral valve leaflets and the interatrial septum (C-sept distance) (Img1). We also measured the distance between the open anterior mitral leaflet and the interatrial septum during diastole. Results The cohort comprised 42 symptomatic patients (14%), all exhibiting at least NYHA class II symptoms and diagnosed with moderate to severe mitral regurgitation. Enzyme replacement therapy (ERT) was administered to all patients with severe mitral regurgitation (SMR) and to 69% of those with moderate mitral regurgitation (MMR). Six patients presented with left ventricular outflow tract obstruction (LVOTO), three of whom underwent percutaneous transluminal septal myocardial ablation; none of these patients had SMR. Notably, no cases of systolic anterior motion (SAM) were observed in either group. The measurements showed a median C-sept value of 2.8 cm, with a standard deviation of 0.5 cm, and interquartile range from 2.6 cm (Q1) to 3.1 cm (Q3). The primary cause of mitral regurgitation was leaflet restriction. Additionally, leaflet length in Fabry disease remains within normal ranges, with only slight dilation of the annulus observed in both groups (Tab 1). Conclusion Our findings demonstrate a consistent absence of systolic anterior motion (SAM) in all patients with Fabry disease, which appears to be attributable to restricted mitral leaflet mobility. This mechanistic distinction differentiates Fabry cardiomyopathy from hypertrophic cardiomyopathy in some cases. We hypothesize that the absence of SAM is due to increased stiffness of the anterior leaflet caused by storage disease, which prevents it from bowing into the outflow tract.C-sept distance Echocardiographic measurements
Večeřová et al. (Thu,) reported a other. In 293 patients with Fabry disease, there was a consistent absence of systolic anterior motion (SAM) in all cases, attributed to restricted mitral leaflet mobility.