TY  - JOUR
A1  - Petritsch, B.
A1  - Köstler, H.
A1  - Weng, A. M.
A1  - Horn, M.
A1  - Gassenmaier, T.
A1  - Kunz, A. S.
A1  - Weidemann, F.
A1  - Wanner, C.
A1  - Bley, T. A.
A1  - Beer, M.
T1  - Myocardial lipid content in Fabry disease: a combined \(^1\)H-MR spectroscopy and MR imaging study at 3 Tesla
JF  - BMC Cardiovascular Disorders
N2  - Background

Fabry disease is characterized by a progressive deposition of sphingolipids in different organ systems, whereby cardiac involvement leads to death. We hypothesize that lysosomal storage of sphingolipids in the heart as occurring in Fabry disease does not reflect in higher cardiac lipid concentrations detectable by \(^1\)H magnetic resonance spectroscopy (MRS) at 3 Tesla.

Methods

Myocardial lipid content was quantified in vivo by \(^1\)H-MRS in 30 patients (12 male, 18 female; 18 patients treated with enzyme replacement therapy) with genetically proven Fabry disease and in 30 healthy controls. The study protocol combined \(^1\)H-MRS with cardiac cine imaging and LGE MRI in a single examination.

Results

Myocardial lipid content was not significantly elevated in Fabry disease (p = 0.225). Left ventricular (LV) mass was significantly higher in patients suffering from Fabry disease compared to controls (p = 0.019). Comparison of patients without signs of myocardial fibrosis in MRI (LGE negative; n = 12) to patients with signs of fibrosis (LGE positive; n = 18) revealed similar myocardial lipid content in both groups (p > 0.05), while the latter showed a trend towards elevated LV mass (p = 0.076).

Conclusions

This study demonstrates the potential of lipid metabolic investigation embedded in a comprehensive examination of cardiac morphology and function in Fabry disease. There was no evidence that lysosomal storage of sphingolipids influences cardiac lipid content as measured by \(^1\)H-MRS. Finally, the authors share the opinion that a comprehensive cardiac examination including three subsections (LGE; \(^1\)H-MRS; T\(_1\) mapping), could hold the highest potential for the final assessment of early and late myocardial changes in Fabry disease.
KW  - late gadolinium enhancement
KW  - myocardial lipid content
KW  - magnetic resonance spectroscopy
KW  - Morbus Fabry
KW  - rare diseases
KW  - lysosomal storage disease
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146693
VL  - 16
IS  - 205
ER  - 
TY  - JOUR
A1  - Weidemann, F.
A1  - Niemann, M.
A1  - Stork, S.
A1  - Breunig, F.
A1  - Beer, M.
A1  - Sommer, C.
A1  - Herrmann, S.
A1  - Ertl, G.
A1  - Wanner, C.
T1  - Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications
JF  - Journal of Internal Medicine
N2  - The long-term effects of enzyme-replacement therapy (ERT) in Fabry disease are unknown. Thus, the aim of this study was to determine whether ERT in patients with advanced Fabry disease affects progression towards 'hard' clinical end-points in comparison with the natural course of the disease.

METHODS:
A total of 40 patients with genetically proven Fabry disease (mean age 40 ± 9 years; n = 9 women) were treated prospectively with ERT for 6 years. In addition, 40 subjects from the Fabry Registry, matched for age, sex, chronic kidney disease stage and previous transient ischaemic attack (TIA), served as a comparison group. The main outcome was a composite of stroke, end-stage renal disease (ESRD) and death. Secondary outcomes included changes in myocardial left ventricular (LV) wall thickness and replacement fibrosis, change in glomerular filtration rate (GFR), new TIA and change in neuropathic pain.

RESULTS:
During a median follow-up of 6.0 years (bottom and top quartiles: 5.1, 7.2), 15 events occurred in 13 patients (n = 7 deaths, n = 4 cases of ESRD and n = 4 strokes). Sudden death occurred (n = 6) only in patients with documented ventricular tachycardia and myocardial replacement fibrosis. The annual progression of myocardial LV fibrosis in the entire cohort was 0.6 ± 0.7%. As a result, posterior end-diastolic wall thinning was observed (baseline, 13.2 ± 2.0 mm; follow-up, 11.4 ± 2.1 mm; P < 0.01). GFR decreased by 2.3 ± 4.6 mL min(-1) per year. Three patients experienced a TIA. The major clinical symptom was neuropathic pain (n = 37), and this symptom improved in 25 patients. The event rate was not different between the ERT group and the untreated (natural history) group of the Fabry Registry.

CONCLUSION:
Despite ERT, clinically meaningful events including sudden cardiac death continue to develop in patients with advanced Fabry disease.
KW  - Fabry disease
KW  - α-galactosidase A
KW  - dialysis
KW  - prognosis
KW  - stroke
KW  - sudden cardiac death
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132075
VL  - 247
IS  - 4
ER  -