P678 Late gadolinium enhancement cardiac magnetic resonance and layer-specific longitudinal strain in treatment naive Anderson Fabry disease

Abstract

Abstract Background In Anderson-Fabry disease (AFD), the accumulation of glycosphingolipids in cardiomyocytes causes inflammation, hypertrophy and interstitial fibrosis which is first limited to the mid-myocardial layers, then spreads to transmural fibrosis. Speckle tracking echocardiography allows the estimation of layer-specific strain, differentiating longitudinal strain (LS) at subendocardium and subepicardium (LSsubendo and LSsubepi, respectively). Purpose To investigate the matching of functional and structural abnormalities in newly diagnosed, never treated AFD patients by comparing multi-layer LS and late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR). Methods Twenty newly diagnosed, never treated AFD patients (age = 37 ± 13 years; F/M =10/10) and 20 healthy controls, matched for age and sex, underwent comprehensive evaluation of target organs and a standard echo-Doppler exam, including assessment of relative diastolic wall thickness (RWT) and left ventricular mass index (LVMI). Left ventricular hypertrophy (LVH) was defined as LVMi > 47 g/m^2.7 in women and >50 g/m^2.7 in men. Speckle tracking echocardiography derived left ventricular transmural global longitudinal strain (GLS), LSsubendo, LSsubepi and LS gradient (LSsubendo - LSsubpepi) were also determined. CMR sequences including assessment of LGE were also performed. Results AFD patients had normal renal function and comparable body mass index, blood pressure, heart rate, ejection fraction and diastolic indices with healthy controls. LVMi (p = 0.006) and RWT (p < 0.02) were greater in AFD patients than in controls. GLS (p = 0.006), LSsubendo (p = 0.005) and LSsubepi (p < 0.001) were lower in AFD patients. By CMR, only four patients (F/M = 3/1), 3 with LVH (75%), exhibited focal LGE, always localized in the midwall. LGE was detected at basal lateral wall in three patients and at the septal insertional points with the right ventricle in the remaining one. AFD patients with LGE had higher LVMi than those without LGE (47.2 ± 11.0 vs. 34.5 ± 11.6 g/m^2.7, p = 0.04). There was no correspondence of LGE with both regional LS and layer specific LS impairment (Figure). However, AFD patients with LGE had higher LS gradient compared to those without LGE (5.8 ± 0.65 vs. 4.8 ± 0.66, p < 0.02). Conclusions Treatment naïve AFD patients show a reduction of longitudinal deformation, which involves both subendocardial and subepicardial layers. Patients with LGE present higher LV mass and increased LS gradient, without a correspondence of LGE with both regional and layer specific LS impairment. Accordingly, this impairment might due to myocardial inflammation occurring in the early disease stages more than to myocardial fibrosis itself. Abstract P678 Figure. Multilayer bull"s eye and LGE-CMR in AFD