Transition From Left Ventricular Hypertrophy to Massive Fibrosis in the Cardiac Variant of Fabry Disease
A 43-year-old male patient with cardiac Fabry disease was followed up by single-photon emission computed tomography (SPECT) and 18F-deoxyglucose (FDG) positron emission tomography (PET) examinations from 1992 onward. At first, he was thought to have concentric left ventricular (LV) hypertrophy, as determined by echocardiography (LV apex wall thickness, 21 mm; diastolic interventricular septum wall thickness, 25 mm; diastolic LV posterior wall thickness, 29 mm; ejection fraction, 76%); however, a diagnosis of cardiac Fabry disease was defined by endomyocardial biopsy and decreased α-galactosidase A activity of the peripheral lymphocyte in 1996. Extracardiac signs of Fabry disease were not detected at that time.
In 1992, a PET study after overnight fasting showed increased uptakes of FDG at the apical and lateral walls, whereas PET scanning after oral glucose loading showed a mildly reduced uptake of FDG. The uptakes of FDG were reduced in the apical and lateral walls of the LV on glucose loading images (Figure 1A, lower panel), whereas the uptakes of FDG were increased in the same regions on the fasting images (Figure 1A, upper panel). This mirror-image pattern of uptakes suggested myocardial ischemia at the apical and lateral walls. In 1996, SPECT and PET studies showed that no perfusion was evident in the apical region of the LV, suggesting that the myocardial tissue of the apex had been replaced by fibrous tissue (Figure 1B and Figure 2A). However, coronary angiography revealed no lesions in the coronary arteries. In 2004, echocardiography showed a moderate reduction in LV contractility (ejection fraction, 42%). Although the interventricular septum and LV posterior wall were hypertrophic (wall thicknesses, 24 and 28 mm, respectively), the apical and lateral wall thicknesses of the LV were remarkably decreased (wall thickness, 9 mm), and dyskinetic motion was recognized at the apex. SPECT and PET scans revealed that the size of the fibrotic region had expanded from 1996 to 2004 (Figures 1C and 2⇓B). Coronary angiography revealed no obstructive lesions, and the extent of the fibrotic region did not coincide with segments of the coronary arteries (Figure 2C). These findings indicated that the hypertrophied myocardium in the apical and lateral regions of the LV had been replaced by massive fibrosis.
Although myocardial fibrosis associated with Fabry disease has been recently reported,1–3 the extent of fibrosis was mild and restricted to the interstitium. In our patient, replacement of hypertrophied myocardium by massive fibrosis gradually progressed during a long follow-up period. Although vascular changes due to vascular accumulation of globotriaosylceramide cause thrombotic events,4 the extent of the fibrotic region did not coincide with the segments of coronary arteries in our case. Because globotriaosylceramide accumulates in endothelial cells and vascular smooth cells in Fabry disease, the microcirculation of the heart might be impaired in the cardiac variant of Fabry disease. Therefore, there is a possibility that massive fibrosis was induced by cardiomyocyte death through a decrease in myocardial perfusion at the microcirculatory level. To our knowledge, this is the first report of the progressive replacement of hypertrophied myocardium by massive fibrosis as a manifestation of Fabry disease. Because massive fibrosis induces cardiac dysfunction and heart failure, early diagnosis of Fabry disease and early initiation of enzyme replacement therapy are warranted.5
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