Clinical Features, Diagnosis, and Management of Patients With Anderson-Fabry Cardiomyopathy

Yogasundaram, Haran; Kim, Daniel; Oudit, Omar; Thompson, Richard B.; Weidemann, Frank; Oudit, Gavin Y.

doi:10.1016/j.cjca.2017.04.015

Cited by 39 publications

(34 citation statements)

References 135 publications

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“…Accelerated vascular disease with progressive renal failure, cardiomyopathy and occlusive cerebro-vascular events are associated with early mortality in subjects with Fabry disease 26 . Whilst some clinical and experimental studies have shown that accumulation of globotriaosylceramide in endothelial cells may contribute to vascular dysfunction 27 , 28 , others have not 29 . Additionally, activation of innate immunity via dendritic cells has been associated with renal and cardiac inflammation in Fabry disease 30 – 32 .…”

Section: Introductionmentioning

confidence: 99%

Corneal confocal microscopy detects corneal nerve damage and increased dendritic cells in Fabry disease

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Malik

et al. 2018

Sci Rep

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Fabry disease is characterised by neuropathic pain and accelerated vascular disease. This study evaluates the utility of corneal confocal microscopy (CCM) to non-invasively quantify corneal nerve and endothelial cell morphology and dendritic cell (DC) density in relation to disease severity in subjects with Fabry disease. Seventeen consecutive participants with Fabry disease and 17 healthy control subjects were included in this cross-sectional study. Fabry disease severity was measured using the Mainz Severity Score Index (MSSI). Central corneal sensitivity was assessed with a contact corneal esthesiometer. There was a significant reduction in the corneal sensitivity (5.75 [5.25–6.00] vs. 6.00 [6.00-6.00] cm, P = 0.014), nerve fiber density (NFD) (26.4 ± 10.1 vs. 33.7 ± 7.9 fibers/mm2, P = 0.025) and nerve fiber length (NFL) (15.9 ± 3.4 vs. 19.5 ± 4.4 mm/mm2, P = 0.012) and an increase in DC density (38.3 [17.5–97.3] vs. 13.5 [0–29.4] cells/mm2, P = 0.004) in subjects with Fabry disease compared to the healthy control subjects. The total MSSI score correlated with NFD (ρ = −0.686; P = 0.006), NFL (ρ = −0.692; P = 0.006), endothelial cell density (ρ = −0.511; P = 0.036), endothelial cell area (ρ = 0.514; P = 0.036) and α-galactosidase A enzyme activity (ρ = −0.723; P = 0.008). This study demonstrates reduced corneal sensitivity, corneal nerve fiber damage and increased DCs in subjects with Fabry disease.

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Section: Introductionmentioning

confidence: 99%

Corneal confocal microscopy detects corneal nerve damage and increased dendritic cells in Fabry disease

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Türkmen

Malik

et al. 2018

Sci Rep

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“…In those with atrial fibrillation (AF), no established disease-specific guidelines are present, but in general, the threshold for anticoagulation is lower even with short paroxysms of AF given the increased risk of thromboembolism in the setting of structural or valvular heart disease (January et al 2014 ; Yogasundaram et al 2017 ). Antiarrhythmics such as sotalol or amiodarone may be used in Fabry patients although general principles of avoiding bradycardia and care with QTc prolongation are necessary.…”

Section: Treatment Of Cardiac Disease In Afdmentioning

confidence: 99%

Anderson-Fabry disease in heart failure

Akhtar

Elliott

2018

Biophys Rev

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Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene that result in deficiency of the enzyme alpha-galactosidase A. The worldwide incidence of Fabry’s disease is reported to be in the range of 1 in 40,000–117,000, although this value may be a significant underestimate given under recognition of symptoms and delayed or missed diagnosis. Deficiency in alpha-galactosidase A causes an accumulation of neutral glycosphingolipids such as globotriaosylceramide (Gb3) in lysosomes within various tissues including the vascular endothelium, kidneys, heart, eyes, skin and nervous system. Gb3 accumulation induces pathology via the release of pro-inflammatory cytokines, growth-promoting factors and by oxidative stress, resulting in myocardial extracellular matrix remodelling, left ventricular hypertrophy (LVH), vascular dysfunction and interstitial fibrosis. Cardiac involvement manifesting as ventricular hypertrophy, systolic and diastolic dysfunction, valvular abnormalities and conduction tissue disease is common in AFD and is associated with considerable cardiovascular morbidity and mortality from heart failure, sudden cardiac death and stroke-related death.

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“…The accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3), involves all cardiac tissues, including cardiomyocytes, vessels, cardiac valves, nerves and conduction system 6 . The ventricular hypertrophy in FD is usually concentric and frequently involves the right ventricle 7 .…”

Section: Pathological Differential Diagnosis Of Hcmmentioning

confidence: 99%

Histopathology in HCM

Tejado

Jou

2018

gcsp

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[first paragraph of article]Histopathology in patients with HCM is characterized by disarray of the overall architecture of the hypertrophied myocytes, which appear branched and may be intermingled with a variable amount of interstitial fibrosis. These changes may be patched and must be distinguished from the non-specific physiological disarrangement of the junctional area of the septum and the apex. The myocardial cell diameter is another important indicator of hypertrophy. Under normal conditions it ranges from 5–12 μm in diameter. Anything up to 20 μm may be indicative of mild hypertrophy. In moderate hypertrophy cardiocyte diameter is up to 25 μm and moderate to severe hypertrophy is usually between 25-30 μm. For diameters greater than 30 μm severe hypertrophy must be suspected.

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Clinical Features, Diagnosis, and Management of Patients With Anderson-Fabry Cardiomyopathy

Cited by 39 publications

References 135 publications

Corneal confocal microscopy detects corneal nerve damage and increased dendritic cells in Fabry disease

Corneal confocal microscopy detects corneal nerve damage and increased dendritic cells in Fabry disease

Anderson-Fabry disease in heart failure

Histopathology in HCM

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