Author + information
- Stavros Kounas, MD and
- Perry Elliott, MD, FACC, FESC* ()
- ↵*The Heart Hospital, University College London, 16-18 Westmoreland Street, London, W1G 8PH, United Kingdom
We thank Drs. Pieroni and Crea for their comments on our recent paper (1). Our study was originally conceived as a response to an article by one of the authors suggesting that the presence of a binary endocardial appearance on 2-dimensional echocardiography is 100% specific for the diagnosis of Anderson-Fabry disease (AFD) (2). Because our clinical experience suggested that the sign was unreliable, we set out to prospectively test their findings in a small, blinded study of patients with genetically proven AFD. The results confirmed our clinical impression that the sign is not specific and that it is poorly reproducible.
Drs. Pieroni and Crea argue that a weakness of our paper (1) is the lack of endomyocardial biopsy data to confirm the presence of cardiac involvement. This argument is spurious for a number of reasons. Although it could be argued that endomyocardial biopsy is necessary for proving the presence of cardiac involvement, it is not the gold standard for the diagnosis of Anderson-Fabry disease, which requires the demonstration of mutation in the gene encoding alpha-galactosidase A. Second, most evidence suggests that glycosphingolipid accumulation is present from a very early age (3), whereas clinical evidence of organ involvement occurs much later (4). One can assume, therefore, that most adult patients presenting with signs and symptoms of AFD will have histological evidence of cardiac involvement, making the need for routine cardiac biopsy in patients with biochemically and genetically proven AFD unnecessary. Finally, knowledge of the histology does not improve the ability of the binary sign to reliably distinguish patients with sarcomeric protein gene mutations from AFD, irrespective of the degree of hypertrophy.
Drs. Pieroni and Crea suggest that the lack of biopsy data is a particular problem in female patients because hypertrophy is rare in women with AFD and, when present, might be the result of hypertension caused by renal involvement. These comments are not supported by data from a large international registry of patients with AFD that has shown that hypertrophy is common and severe renal involvement rare in female patients (4).
In conclusion, we disagree strongly with Drs. Pieroni and Crea's suggestion that the binary sign could be used as a “first filter” in screening large unselected populations with left ventricular hypertrophy before moving to dedicated genetic and enzymatic tests. Screening tests should be reproducible and highly specific to avoid exclusion of false-negative cases from further diagnostic testing. In our experience, reliance on the binary sign would result in a substantial number of misdiagnoses.
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