Author + information
- Maurizio Pieroni, MD, PhD* ( and )
- Filippo Crea, MD, FACC
- ↵*Institute of Cardiology, Catholic University, Largo A. Gemelli 8, 00168, Rome, Italy
We read with interest the article by Kounas et al. (1), in which they reported a poor sensitivity and specificity of binary sign in discriminating Anderson-Fabry disease from familial hypertrophic cardiomyopathy compared with our findings previously published in the Journal(2).
The definition of specificity and sensitivity usually implies the identification of true and false positives as well as true and false negatives according to a diagnostic gold standard. In the settings of Anderson-Fabry cardiomyopathy, the gold standard to define the presence of cardiac involvement is represented by endomyocardial biopsy demonstrating glycosphingolipid accumulation in cardiac tissues. This finding is particularly true in female patients with borderline or mild left ventricular hypertrophy: in these patients, cardiac involvement can be absent in most cases (3), and cardiac wall thickening may be the result of concomitant hypertension often caused by initial renal involvement. Accordingly, in our study, we evaluated the specificity and sensitivity of the binary sign in patients with Fabry disease and biopsy-proven cardiac involvement. On the contrary, in the small population described by Kounas et al. (1), no clear demonstration of cardiac involvement is provided in the 5 (36%) female patients and in the 5 (36%) male patients with maximum wall thickness <15 mm included in the analysis to calculate specificity and sensitivity of the binary sign. Despite these methodological limitations, the overall specificity of the echocardiographic sign remained 79% with a positive predictive value (calculated from the published data) of 63%. From these considerations it emerges that, whatever its real specificity and sensitivity, both studies identify the binary sign as a useful additional feature to search for during echocardiographic evaluation of patients with unexplained cardiac wall thickening. In particular, it probably remains more sensitive and specific than other echocardiographic features, including concentric hypertrophy, right ventricular involvement, absence of outflow obstruction, and valve leaflet thickening, which usually are considered in the differential diagnosis. On this basis, in our study we suggested that binary appearance should be regarded not as an infallible diagnostic hallmark but rather as a first filter to focus the enzymatic and genetic tests in a more selected population in the settings of screening studies as well as of daily echocardiography laboratory activity. In fact, we would like to emphasize that the screening of large populations may be expensive and therefore available only in selected referral centers, thus potentially retarding the proper diagnosis and treatment. With this regard there is growing evidence (4) that early administration of enzyme replacement therapy is associated with better long-term results in terms of both cardiac and systemic symptoms improvement; thus, the early identification and treatment of this rare but potentially treatable cardiomyopathy is urgent.
Therefore, we believe that, even if obtained by adjusting image quality and gain settings, the binary sign should be included among the echocardiographic features, leading to a differential diagnosis between Anderson-Fabry cardiomyopathy and other forms of left ventricular hypertrophy.
- American College of Cardiology Foundation
- Kounas S.,
- Demetrescu C.,
- Pantazis A.A.,
- et al.
- Pieroni M.,
- Chimenti C.,
- De Cobelli F.,
- et al.