Patterns of left ventricular remodeling and outcomes in fabry disease

Abstract Background The development of progressive left ventricular hypertrophy (LVH) is the hallmark of Fabry cardiomyopathy. In patients with Fabry disease (FD), the presence and degree of LVH are well-known prognostic markers, however the implications of different patterns of left ventricular (LV) remodeling have never been examined in outcomes studies. Purpose In the present study, we aimed to investigate the prevalence of different patterns of LV remodeling in a large population of FD patients and to assess their prognostic implications. Methods Patients with FD from 5 Italian referral centers were classified based on LV remodeling patterns. LVH was defined as left ventricular mass index (LVMi)>95g/m2 for females and 115 g/m2 for males and was categorized as concentric hypertrophy (cLVH) if the RWT >42% or eccentric hypertrophy (eLVH) if the RWT ≤42%. Patients with normal LVMi were classified as patients having concentric remodeling if RWT>42% or normal LV geometry if the RWT ≤42%. The study endpoint was the composite of all-cause death, admission for heart failure, new-onset atrial fibrillation, major brady- or tachy-arrhythmias and ischemic stroke. Results A total of 347 patients with FD were included. Normal geometry was found in 143 (41%) patients, concentric remodeling in 43 (12%) patients, cLVH in 129 (36%) patients and eLVH in 32 (9%) patients. The comparison of baseline features between groups is illustrated in Figure 1. Patients with normal geometry were younger than those with concentric remodeling, while patients with cLVH or eLVH were older as compared to patients with concentric remodeling. Women were more prevalent among patients with normal geometry and, interestingly, with eLVH. Patients with cLVH and eLVH showed an increased risk of meeting the composite endpoint at 8 years (46% and 34%, respectively), in comparison with patients with concentric remodeling (3%) and patients with normal geometry (1%) (log-rank p< 0.001; Figure 2). At multivariable Cox regression analysis, either cLVH and eLVH were independently associated with the study endpoint (HR=12.30, 95% CI: 1.51-97.23, p=0.017 and HR=13.52, 95% CI: 1.64-111.38, p=0.016, respectively), after adjustment for age, sex, NYHA class, estimated glomerular filtration rate and exposure to disease-specific therapy. Conclusions LV remodeling patterns affect prognosis in FD. cLVH and eLVH emerge as independent predictors of cardiovascular events, while concentric remodeling is associated with favourable long-term prognosis, similarly to normal LV geometry.Comparison of baseline features LV remodeling patterns and outcomes