Fabry’s Disease Cardiomyopathy: Echocardiographic Detection of Endomyocardial Glycosphingolipid Compartmentalization

Fabry’s Disease Cardiomyopathy: Echocardiographic Detection of Endomyocardial Glycosphingolipids Compartmentalization

Maurizio Pieroni, Cristina Chimenti, Francesco De Cobelli, Emanuela Morgante, Alessandro Del Maschio, Carlo Gaudio, Matteo Antonio Russo, Andrea Frustaci

Non-invasive differential diagnosis between Fabry’s disease cardiomyopathy (FC) and other forms of left ventricular hypertrophy (LVH) is often difficult and frequently relies on invasive studies or molecular and gene analysis. In the present study we identified a specific echocardiographic feature of FC represented by a binary appearance of left ventricular endocardial border, reflecting endomyocardial compartmentalization of glycosphingolipids observed in endomyocardial biopsies. This echocardiographic hallmark is characterized by high specificity and sensitivity and may represent a useful tool for differentiating FC from other forms of LVH.

Objectives

We sought to identify echocardiographic hallmarks of Fabry’s disease cardiomyopathy (FC).

Background

The recognition of FC from other forms of left ventricular hypertrophy (LVH) by noninvasive imaging techniques is not yet available, and diagnosis, mostly in the absence of systemic manifestations, still relies on genetic and invasive studies.

Methods

Forty consecutive patients (mean age 39 ± 15 years, 22 men and 18 women) with an established diagnosis of Fabry’s disease were submitted to echocardiographic evaluation. Control population consisted of 40 consecutive patients with hypertrophic cardiomyopathy (HCM), 40 hypertensive patients with echocardiographic evidence of LVH, and 40 age- and gender-matched healthy subjects with no LVH. All HCM patients and FC with LVH and/or cardiac symptoms underwent cardiac catheterization with left ventricular endomyocardial biopsy.

Results

Echocardiography showed in 83% of FC patients (95% of FC patients with LVH) a binary appearance of endocardial border absent in all HCM, hypertensive, and healthy subjects. The sensitivity and specificity of this echocardiographic feature in detecting Fabry patients in study population were 94% and 100%, respectively. Comparison of echocardiographic with histologic and ultrastructural findings showed the binary appearance to reflect an endomyocardial glycosphingolipids compartmentalization, consisting of thickened glycolipid-rich endocardium, free glycosphingolipid subendocardial storage, and an inner severely affected myocardial layer with a clear subendocardial-midwall layer gradient of disease severity.

Conclusions

Echocardiographic binary appearance of left ventricular endocardial border, reflecting endomyocardial glycosphingolipids compartmentalization, represents a sensitive and specific diagnostic hallmark of Fabry’s disease cardiomyopathy.