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Imaging assessment of Fabry cardiomyopathy and its clinical implications

An article from the E-Journal of the ESC Council for Cardiology Practice

Cardiac involvement of Fabry patients is usually recognised by the presence of left ventricular hypertrophy, valve disorders or rhythm disturbances. Early diagnosis is important because it will prevent cardiac complications. We recently reported that Tissue Doppler abnormalities, by means of lower tissue velocities, can be present in some patients with Fabry cardiac disease. These changes can be seen even before of the appearence of left ventricular hypertrophy and therefore may be considered as an early manifestation of the disease.

Myocardial Disease

I - Background

The Anderson - Fabry disease is a rare X-linked lysosomal storage disorder caused by a-galactosidase A deficiency. The disease leads to a progressive accumulation of globotriaosylceramide in various organ systems [1] and a wide variety of signs and symptoms including acroparaesthesiae, pain crisis, heat intolerance, hypohydrosis, gastrointestinal symptoms, angiokeratomas, corneal dystrophy, renal impairment, cerebrovascular disease and cardiomyopathy.

Heterozygous female patients are not only carriers of the disease they may also show a wide range of disease severity, ranging from a relatively benign course to manifestations comparable with those of hemizygous men [2].
Life expectancy in men is reported to be reduced by about 20 years from that of the general population and the most frequent cause of death in males is end-stage renal failure followed by cardiac involvement [3] which is characterised by a progressive left ventricular hypertrophy (LVH) mimicking the clinical phenotype of hypertrophic cardiomyopathy [4].

Interestingly, Fabry disease has been reported as the cause of left ventricular hypertrophy in 6% of men with a late-onset of hypertrophic cardiomyopathy. Concentric hypertrophy patterns are most frequent but asymmetric septal hypertrophy occurs in 5% of cases and dynamic left ventricular outflow obstructions are rare. As the disease progresses, interstitial abnormalities and replacement myocardial fibrosis become important. Other cardiac manifestations are valve infiltration with regurgitation and a wide variety of rhythm abnormalities.

II - Diagnosis

Diagnosis is confirmed by biochemical demonstration of a reduction in the activity of α- Galatosidase A in peripheral blood cells and the detection of casual mutation.  The standard non-invasive tools for identifying patients with Fabry and heart involvement clearly are ECG, conventional 2D-echocardiography and cardiovascular magnetic resonance.  ECG provides information about electrical alterations or the presence of LVH. Echo offers an estimate LV mass and assessment of LV function and possible Valvular alterations  MRI can detect the preence of late enhancement with gadolinium that can be a sign of fibrosis in patients with cardiac FAbry manifestations.

This image diagnostic approach is useful in patients with established cardiomyopathy but it is not suitable to detect impaired myocardial function early in the course of the disease or sensitive enough for the screening of Fabry relatives. For early detection, tissue Doppler imaging (TDI) has emerged as a sensitive and non-invasive tool for detecting impaired contraction and relaxation myocardial function in several forms of inherited cardiomyopathies [5-8]. 

III - Treatment

The advent of enzyme replacement treatment (ERT) by recombinant α-galactosiadase A has increased the need for early recognition to help treatment and delay or prevent complications. Most published studies have focused on Fabry patients with advanced organ involvement which probably explains the variation in response to ERT seen in a number of them [9-10]. Current guidelines indicate that all males over the age of 16 years should be offered ERT as a strategy that would ensure the initiation of ERT before major organ damage has progressed to irreversible stages, however the recommendations for women are less clear [11]. Further studies are needed to assess the prognostic implications of ERT in patients without established cardiomyopathy and usefulness of TDI and TDI-derived techniques in clinical decision making.

Figure 1 shows slightly reduced systolic TDI velocities (7 cm/sec) in a Fabry male patient with normal parietal thickness.


















Figure 2 represents the typical phenotype of concentric LVH in a Fabry male patient.


[1]. Desnick RJ, Ionnaou YA, Eng CM. α-Galactosidase A deficiency: Fabry disease. In: Scriver CR, Beaudet AL, Sly SW, Valle D, editors. The metabolic and molecular bases of inherited disease. 8th ed. New York, NY: Mc Graw-Hill; 2001. p.3733-74
[2]. MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of the disease in a cohort of  98 hemizygous males. J Med Genet 2001;38:750-60.
[3]. Linhart A, Kampmann C, Zamorano JL, et al. Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. Eur Heart J 2007;28:1228-35.
[4]. Weidemann F, Breunig F, Beer M, Sandstede J, Stork S, Voelker W, Ertl G, Knoll A, Wanner C, Strotmann JM. The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease. Eur Heart J. 2005;26:1221-7.
[5]. Nagueh SF, Bachinski LL, Meyer D, Hill R, Zoghbi WA, Tam JW, Quinones MA, Roberts R, Marian AJ. Tissue Doppler imaging consistently detects myocardial abnormalities in patients with hypertrophic cardiomyopathy and provides a novel means for an early diagnosis before and independently of hypertrophy. Circulation. 2001;104:128-30.
[6]. De Backer J, Matthys D, Gillebert TC, De Paepe A, De Sutter J. The use of Tissue Doppler Imaging for the assessment of changes in myocardial structure and function in inherited cardiomyopathies. Eur J Echocardiogr. 2005;6:243-50.
[7] Pieroni M, Chimenti C, Ricci R, Sale P, Russo MA, Frustaci A. Early detection of Fabry cardiomyopathy by tissue doppler imaging. Circulation. 2003;107:1978-84.
 [8]. Toro R, Pérez-Isla L, Doxataquis G, Barba MA, Rivera Gallego A, Pintos G, Barbados FJ, Mangas A, Zamorano JL. Clinical usefulness of tissue Doppler imaging in predicting preclinical Fabry cardiomyopathy. Int J Cardiol (2008);doi: 10.1016/j.ijcard.2008.04.075.
[9]. Beer M, Weidemann F, Breunig F, Knoll A, Koeppe S, Machann W, Hahn D, Wanner C, Strotmann J, Sandstede J. Impact of enzyme replacement therapy on cardiac morphology and function and late enhancement in Fabry's cardiomyopathy. Am J Cardiol. 2006;97:1515-18.
[10]. Hughes DA, Elliott PM, Shah J, Zuckerman J, Coughlan G, Brookes J, Mehta AB. Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomized, double-blind, placebo-controlled clinical trial of agalsidase-alfa. Heart. 2008;94:153-158.
[11]. Eng CM, Germain DP, Banikazemi M, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 2006;8:539-48.


Vol7 N°21

Notes to editor

Viviana Serra, Eloy Domínguez, *José Luis Zamorano.
Secretary of the ESC and President of the Association of Echography (EAE).

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.