Impairment of sympathetic activity in Fabry disease cardiomyopathy: A further challenge for cardiac imaging

Excerpt

Fabry disease (FD) (OMIM #301500) is a rare, X-linked, lysosomal storage disorder due to mutation in the GLA gene that encodes for α-galactosidase A enzyme. The consequent enzymatic deficiency causes progressive lysosomal accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in capillary endothelial cells and in in several organ specific cellular types and tissues, leading to major renal, cardiac and cerebrovascular clinical manifestations and to a significant reduction in life expectancy.¹ Cardiac involvement is characterized by biventricular hypertrophy, myocardial fibrosis, left ventricular filling abnormalities and systolic dysfunction and represents the primary cause of the reduced life expectancy.² A growing understanding of FD related cardiomyopathy has developed during the last two decades, with cardiac imaging playing a main role in highlighting features of cardiac involvement and improving diagnosis and staging. Since FD is a rare disease, most of the studies offered insights into only small cohorts of patients. However, both echocardiography and cardiac magnetic resonance (MR) contributed to detail morphologic and functional aspects of heart in FD, namely: left ventricular concentric hypertrophy, preserved ejection fraction, disproportionate hypertrophy of papillary muscles and, often, right ventricular hypertrophy. Gadolinium enhanced cardiac MR has allowed to decipher interstitial expansion and fibrosis as prominent pathological features of FD, with a curious predilection for the basal inferolateral segments of the left ventricle³ and sometimes occurring before left ventricular hypertrophy, mainly in women.⁴ …