The presence and extent of coronary microvascular dysfunction is associated to the severity of cardiomyopathy in patients with Fabry disease

Abstract

Funding Acknowledgements Type of funding sources: None. Background Coronary microvascular dysfunction (CMD) occurs before left ventricular hypertrophy (LVH) in Anderson Fabry Disease (AFD). Few data exist about the role of CMD in Fabry cardiomyopathy, when overt LVH has already established. Purpose Aim of our study was to assess the relationship between CMD and clinical and echocardiographic features in a cohort of Fabry cardiomyopathy patients. Methods We performed coronary CT scan to exclude epicardial coronary artery disease (CAD) in 27 AFD cardiomyopathy patients with angina and/or evidence of silent ischemia at treadmill stress test. All consenting patients with no CAD (n = 17) were submitted to resting and stress 13N-Ammonia myocardial perfusion PET/CT to assess the presence of CMD. All patients also underwent complete echocardiography. Patients were followed-up for 17.3 ± 12.5 months. Results Global coronary flow reserve (CFR) resulted <2.5 in 7 (41%) patients. Global stress myocardial blood flow (MBF) was <1.85 mL/min/g in 5 (29%) patients. Global transmural perfusion gradient (TPG, subendocardial MBF/subepicardial MBF) during stress was <1.0 in 13/17 (76.5%) patients. Resting global TPG was ≥1 in 16 (94%) patients. Patients with CFR < 2.5 were older (p = 0.02), had more severe LVH (maximal wall thickness p = 0.04), worst global longitudinal strain (p = 0.03) and E/e’ (p = 0.04) and higher troponin levels (p = 0.002) as compared to patients with CFR ≥ 2.5. They also performed less at treadmill stress (METs p = 0.045). No variables were associated to major cardiovascular events at multivariable analysis. Conclusions In Fabry cardiomyopathy patients with angina and/or evidence of silent ischemia, the prevalence of CMD is high and it is associated to a more severe cardiac phenotype, including cardiac biomarker and functional capacity. We are not able to draw any conclusion on the possible prognostic role of CMD in Fabry cardiomyopathy.

Inflammation in Fabry disease: stages, molecular pathways, and therapeutic implications

“…Endomyocardial biopsy has revealed disorganised and hypertrophied cardiomyocytes, evidence of apoptosis, nitric oxide synthase and accumulation of glycosphingolipids ( 49 ). Furthermore, the hypertrophy seen in FD has been linked to ischaemia of the heart tissue ( 50 , 51 ) , however, more recent advances have highlighted that ischaemia in FD is more likely associated with coronary microvascular dysfunction ( 52 ) and some limited evidence that early assessment of coronary flow reserve using cardiac MRI may be an important step in the assessment of the disease; although use of this for prognostication purposes is currently limited due to lack of large scale evidence ( 53 ).…”