Author + information
- Guus De Waard1,
- Maurits Hollander2,
- Elisa Meinster3,
- Jeroen Belien3,
- Hans Niessen3 and
- Niels van Royen4
Inducible myocardial ischemia is influenced by contributions of both the epicardial coronary artery and the coronary microcirculation. Experimental studies in porcine models suggest that downstream adverse structural remodeling of the microcirculation occurs in response to a stenosis of the epicardial coronary artery. Findings in patients contradict these experimental studies, as the minimal microvascular resistance remains unchanged in the presence of a epicardial stenosis. We aimed to investigate whether downstream remodeling of the microcirculation occurs in patients.
37 deceased patients with both a pathological examination as well as invasive coronary angiography within 2 years prior to death were included. Quantitative coronary angiography was performed for 88 coronary arteries without total angiographic occlusion. Immunohistological examination of myocardium corresponding to each coronary was performed using an anti-smooth muscle actin-α and an anti-CD31 staining. The outcome parameters: arteriolar density, percentage arteriolar area of total myocardial area and capillary density, were obtained by image analysis. Additional outcome parameters were the ratio between lumen area and wall thickness area, and the ratio between lumen diameter and wall thickness diameter which were analyzed for 10 randomly selected arterioles of <40 μm, 40-100 μm and 100-200 μm diameter.
28 pairs of both an angiographic stenosis in one of the coronary arteries and an unobstructed artery within the same patient were formed. In this paired analysis, no statistically significant differences were found for any of the outcome parameters between the stenotic and unobstructed vessel. A second unpaired analysis involving all 88 coronary arteries classified into three groups (<30%, 30-65% and >65% diameter stenosis) also showed no significant differences between any of three groups for each of the outcome parameters.
Our findings demonstrate that downstream remodeling of the microcirculation distal to a coronary stenosis does not occur in clinical patients encountered in the catheterization laboratory. These findings are clinically important, since they support the theoretical framework of the fractional flow reserv and FFR - CT.
OTHER: Pre-Clinical/First In-Human Studies