Apical hypertrophic cardiomyopathy: could it be Fabry?

Abstract Background Fabry disease is a lysosomal storage disorder with multisystemic effects, due to glycosphingolipid deposition, particularly involving heart, kidneys and brain. Although an X-linked disorder, it is recognised that female heterozygotes can express clinical manifestations. Left ventricular hypertrophy (LVH) is a key manifestation of Fabry disease, mimicking hypertrophic cardiomyopathy (HCM). Although often described as an asymmetrical or concentric pattern, with inferolateral scar, in clinical practice we observed an apical pattern in some patients. We therefore set out to establish the prevalence and features of apical hypertrophic phenotype in our Fabry cohort. Methods Data was collected retrospectively from our cohort of genetically confirmed Fabry patients, with evidence of cardiomyopathy. This data included the presence of LVH on cardiac MRI, distribution of late-gadolinium enhancement (LGE), and high-sensitivity troponin I. Results Of 140 patients in our Fabry cohort (48 males, 92 females), 59 were diagnosed with Fabry cardiomyopathy, 52 displaying LVH on cardiac MRI, 7 patients displayed LGE-only. Of these 52 patients with LVH, 30 were males, 22 females (Table 1). 30 patients (57.7%) demonstrated concentric LVH pattern, 14 (26.9%) asymmetrical, 8 (15.4%) had an apical hypertrophic pattern (Figure 1). Apical Subgroup (8 patients): 4 patients were identified by HCM gene panel, 2 following low alpha-galactosidase level tested in cardiology clinics, and 2 from cascade genetic testing. No specific genotype was associated with apical hypertrophy. Median age of onset 47.5 years; 5 males, 3 females. 7 patients with apical hypertrophy had LGE on cardiac MRI, with LGE distributed in an apical pattern in 6 patients. The remaining patient had a diffuse-extensive pattern. One patient had apical hypertrophy, but no LGE. All 7 patients with both apical hypertrophy and LGE demonstrated an elevated high-sensitivity troponin I (>40ng/L), with the median 212ng/L (IQR 114 - 1196). T1 value was available in 5 patients, and reduced in the basal septum, remote from the apical scar. T1 was not performed in one patient, two patients were excluded due to pacemakers. Conclusion This study demonstrates that Fabry cardiomyopathy can manifest as an apical hypertrophic phenotype. It is therefore important to include Fabry disease within the differential diagnosis in patients presenting with apical hypertrophic cardiomyopathy.