Coronary microvascular dysfunction is an early feature of cardiac involvement in patients with Anderson–Fabry disease

Abstract

AimsMale patients with Anderson-Fabry disease (AFD) often exhibit cardiac involvement, characterized by LV hypertrophy (LVH), associated with severe coronary microvascular dysfunction (CMD). Whether CMD is present in patients without LVH, particularly when female, remains unresolved. The aim of the study was to investigate the presence of CMD by positron emission tomography (PET) in AFD patients of both genders, with and without evidence of LVH. Methods and resultsWe assessed myocardial blood flow following dipyridamole infusion (Dip-MBF) with 13 N-labelled ammonia by PET in 30 AFD patients (age 51 + 13 years; 18 females) and in 24 healthy controls. LVH was defined as echocardiographic maximal LV wall thickness ≥13 mm. LVH was present in 67% of patients (n ¼ 20; 10 males and 10 females). Dip-MBF was reduced in all patients compared with controls (1.8 + 0.5 and 3.2 + 0.5 mL/min/g, respectively, P , 0.001). For both genders, flow impairment was most severe in patients with LVH (1.4 + 0.5 mL/min/g in males and 1.9 + 0.5 mL/min/g in females), but was also evident in those without LVH (1.8 + 0.3 mL/min/g in males and 2.1 + 0.4 mL/min/g in females; overall P ¼ 0.064 vs. patients with LVH). Analysis of variance (ANOVA) for the 17 LV segments showed marked regional heterogeneity of MBF in AFD (F ¼ 4.46, P , 0.01), with prevalent hypoperfusion of the apical region. Conversely, controls showed homogeneous LV perfusion (F ¼ 1.25, P ¼ 0.23). ConclusionsCoronary microvascular function is markedly impaired in AFD patients irrespective of LVH and gender. CMD may represent the only sign of cardiac involvement in AFD patients, with potentially important implications for clinical management.--

Coronary Microvascular Dysfunction Is Related to Abnormalities in Myocardial Structure and Function in Cardiac Amyloidosis

“…Rest MBF, peak stress MBF and CFR per unit LV mass was significantly lower in the amyloid compared to the LVH group (Figure 2), suggesting differences independent of LV mass. The myocardial extracellular volume fraction may be expanded and the functioning myocardial mass as estimated by echocardiography may thus be lower in the amyloid compared to control subjects (22). Hence, we performed sensitivity analysis assuming a functioning myocardial mass of 0.50 and 0.75; the stress MBF was significantly lower at LV mass 0.75 (trend to lower stress MBF at LV mass 0.5) and CFR values remain significantly lower in the amyloid subjects.…”

“…The magnitude of the microvascular dysfunction in our amyloid patients is not only more severe than those seen in hypertensive disease, but are also more severe to previously reported data in dilated cardiomyopathy (21) and in Fabry’s disease. (20,22)…”

Role of PET to evaluate coronary microvascular dysfunction in non-ischemic cardiomyopathies

“…A seminal cardiac pathology in Fabry’s cardiomyopathy is globotriaosylceramide deposition in myocytes with vacuolization[32]. These deposits may activate a variety of signaling pathways leading to hypertrophy, apoptosis, necrosis and fibrosis, which increase coronary vascular resistance, myocardial oxygen demand, and cause CMD[33]. CMD has the potential to cause myocardial fibrosis in Fabry’s Disease[34].…”

“…CMD has the potential to cause myocardial fibrosis in Fabry’s Disease[34]. Although CMD is more severe among those with LV hypertrophy, it is also seen in women and among individuals without LV hypertrophy[33]; these authors thus, propose that in addition to capillary rarefaction, and microvascular compression, pathologies related to LV hypertrophy, endothelial dysfunction from the storage of glycosphingolipids, dysregulation of the nitric oxide pathway, and microvascular remodeling may contribute to CMD in Fabry’s disease[33]. Also, on intravascular ultrasound imaging patients with Fabry’s disease demonstrate diffuse hypoechoic coronary plaques with greater lipid cores compared to control individuals[35].…”

Update on Coronary Involvement in Fabry Disease

“…However, Tomberli et al demonstrated that the microvascular coronary involvement could be present even without LVH, suggesting that it could be an early damage of the disease. 19 The population included in this study consisted of 30 patients with FDconfirmed diagnosis, where 12 (40%) of them were male. The analysis of the mutations showed that 10 were related to the disease classic phenotype, whereas the remaining (p.Asn215-Ser) were associated with a milder form of the disease of later onset (fourth to fifth decade).…”