Advanced imaging to understand the relation between coronary microvascular dysfunction, coronary plaque burden, and vascular remodeling
Y Ding, R Heok, P Kamila, I Danad, N S Nurmohamed, R A Jukema, P G Raijmakers, R S Driessen, P A van Diemen, A D Choi, J Knuuti, P Knaapen, H Liu, J J Bax, A van RosendaelAbstract
Background
Chronic coronary syndromes frequently occur in the absence of flow-limiting epicardial stenosis. Coronary microvascular dysfunction (CMD) is a key mechanism underlying angina with non-obstructive coronary arteries, yet its relationship with epicardial atherosclerosis remains incompletely understood. Emerging evidence suggests a potential interplay between plaque development, arterial remodeling, and microvascular impairment.
Purpose
To investigate the association between epicardial atherosclerotic characteristics assessed by quantitative coronary CT angiography (CCTA) and coronary microvascular dysfunction, integrating invasive fractional flow reserve (FFR), positron emission tomography (PET)–derived myocardial blood flow, and microvascular resistance reserve (MRR).
Methods
This post hoc analysis included 599 vessels from 208 patients with suspected coronary artery disease enrolled in the PACIFIC-1 trial. All patients underwent [15O]H2O PET, CCTA with AI-based quantitative plaque analysis, and invasive coronary angiography with routine FFR. Vessels were classified as non-ischemic (normal FFR and hyperemic myocardial blood flow [hMBF]), CMD (normal FFR, impaired hMBF), or epicardial flow-limiting (FFR ≤0.80). MRR was calculated as (CFR/FFR) × (Pa,rest/Pa,hyper). Vessel-level associations were analyzed using generalized estimating equations.
Results
Of 599 vessels, 352 (58.8%) were non-ischemic, 88 (14.7%) CMD, and 159 (26.5%) epicardial flow-limiting. Atherosclerotic burden increased progressively across groups. CMD vessels demonstrated intermediate plaque volume and percentage atheroma volume compared with non-ischemic and epicardial flow-limiting vessels (all P<0.001) (Figure 1). Notably, CMD vessels exhibited the largest lumen volume and area, consistent with pronounced positive remodeling. Among 508 vessels with complete physiological data, CMD vessels had significantly lower MRR than non-ischemic and epicardial flow-limiting vessels (median 2.22 vs. 3.86 and 3.40; P<0.001). In multivariable analysis within CMD vessels, higher remodeling index was independently associated with higher MRR (Table 1). In non-ischemic vessels, greater non-calcified plaque burden was associated with lower MRR, whereas in epicardial flow-limiting vessels, hypertension was independently associated with reduced MRR.
Conclusion
CMD vessels demonstrate a distinct structural–functional phenotype characterized by intermediate plaque burden and marked positive remodeling. The independent association between remodeling and preserved MRR suggests a potential adaptive epicardial response in the presence of microvascular dysfunction. These findings highlight a complex interplay between early atherosclerosis and CMD and may indicate a clinically relevant window for early detection and intervention in coronary artery disease.