Abstract 15710: Myocardial Ischaemia in Cardiac Amyloidosis, Changing Perspectives

Abstract

Introduction: Cardiac involvement determines outcome in systemic amyloidosis, but the relationship between amyloid deposits and outcomes is poorly understood. Many clinical observations are not explained by the simple concept of physical, mechanical replacement of the interstitium by amyloid material. Hypothesis: Preliminary studies in patients with cardiac amyloidosis (CA) support the hypothesis that myocardial ischaemia contributes to cell damage. This study assesses the presence and mechanisms of myocardial ischaemia using CMR with multiparametric mapping and histopathological assessment. Methods: 92 patients with CA (41 AL, 51 ATTR) and 73 without CA (26 with unobstructed coronary arteries; 47 with 3VD) underwent CMR with T1, T2, Extracellular volume (ECV) mapping and adenosine stress with myocardial blood flow (MBF) mapping. 25 cardiac biopsies and 3 explanted hearts with CA were analysed histopathologically. Results: CA patients had severe reductions in stress MBF and myocardial perfusion reserve (MPR)- (1.03ml/g/min±0.50;1.54±0.59 ) compared to patients with unobstructed coronary arteries (2.82 ml/g/min±0.53; 2.94±0.59, p<0.001), and comparable only to 3VD (1.32±0.47ml/g/min, p=0.04;1.49±0.44, p=1.00). Myocardial perfusion abnormalities correlated with amyloid burden, systolic function and blood biomarkers (p<0.001). Biopsies showed evidence of diffuse hypoxia with abnormal VEGF staining in cardiomyocytes and endothelial cells. Amyloid infiltration in intramural arteries was associated with severe lumen reduction in 20% of vessels, with severe reduction in capillary density in areas with and without amyloid deposits. Conclusion: CA is associated with severe myocardial ischaemia demonstrable by histology and CMR perfusion mapping. Histological evaluation indicates a complex pathophysiology, where direct disruption of the vessels by amyloid deposits and reduction in epicardial flow contribute to myocardial ischaemia.