Spatial heterogeneity of coronary vasomotor dysfunction in ANOCA demonstrated by systematic multivessel assessment in the Nationwide J-CMD Registry

Background Diagnostic protocols for angina with non-obstructive coronary arteries (ANOCA) traditionally rely on single-vessel interrogation—predominantly the left anterior descending artery (LAD)—based on the assumption that microvascular pathology is a diffuse phenomenon. However, emerging evidence suggests that vasomotor dysfunction may be territory-specific. Thus, we aimed to examine possible heterogeneity of coronary vasomotor dysfunction by systematic multivessel assessment in the nationwide J-CMD Registry in Japan. Methods We prospectively analyzed 213 patients from the J-CMD registry who underwent physiological and vasomotor assessment of both the LAD and the right coronary artery (RCA). Protocols included pharmacological spasm provocation and thermodilution-derived measurements of coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). Spatial concordance was assessed for epicardial vasospasm (EVS), microvascular spasm (MVS), and coronary microvascular dysfunction (CMD; CFR <2.5). CMD was further categorized into structural (IMR ≥25) or functional (IMR <25) subtypes. Mixed-type CMD was defined as inter-territory discordance in CMD subtype. Misclassification was defined as any diagnostic discrepancy between LAD-only strategy and a multivessel approach. Results At the patient level, EVS was present in 46.9%, MVS in 16.0%, and CMD in 41.3% (structural 26.3%, functional 8.0%, mixed-type 7.0%). Importantly, pronounced diagnostic discordance was observed between territories. Kappa statistics revealed poor agreement for EVS (κ=0.28) and negligible agreement for structural (κ=0.10) and functional CMD (κ=0.05). Although MVS showed moderate concordance (κ=0.59), overall diagnostic discordance (any parameter) affected 58.7% of patients. Consequently, LAD-only approach would have misclassified 28.6% of the cohort. In contrast, multivessel assessment reduced the proportion of patients with no identifiable dysfunction from 38.0% to 27.2%. Conclusions Coronary vasomotor dysfunction in ANOCA is characterized by significant spatial heterogeneity. Reliance on single-vessel evaluation could result in misclassification and incomplete phenotyping. Systematic multivessel interrogation is essential to demonstrate the full complexity of coronary vascular pathology and to facilitate precise and tailored therapeutic management.