The diagnostic performance of EST in identifying CMD in patients with ANOCA: insights into endotypes and clinical implications

Abstract Background Coronary microvascular dysfunction (CMD) is a prevalent condition among patients with angina and non-obstructive coronary artery disease (ANOCA), contributing to persistent symptoms and adverse clinical outcomes. Exercise stress testing (EST) has been shown to exhibit high specificity for detecting CMD (1). However, the relationship between EST findings and the diagnosis of CMD using various invasive physiological parameters and thresholds, as well as the association between EST results and different CMD endotypes, remains poorly understood. Methods This multicentre, prospective cohort study included 117 ANOCA patients who underwent EST followed by invasive coronary angiography with functional assessment. Key parameters measured included coronary flow reserve (CFR), the index of microvascular resistance (IMR), and microvascular resistance reserve (MRR), calculated as (CFR/FFR) × (Pa rest/Pa hyper). CMD was defined using multiple criteria: MRR 3.0, CFR 2.5, and CFR 2.0 or IMR ≥ 25. The diagnostic sensitivity, specificity, and accuracy of EST findings—such as exercise-induced chest discomfort, ischemic ECG changes, and exercise tolerance—were evaluated for their ability to identify CMD. Results The prevalence of CMD was consistent across all three diagnostic definitions. However, structural CMD was more frequently identified using the MRR 3.0 criterion. Ischemic ECG changes during EST demonstrated excellent diagnostic accuracy for detecting CMD, with an accuracy of 86.3% (95% CI: 78.7–92.0%), sensitivity of 86.2% (95% CI: 68.3–96.1%), and specificity of 86.4% (95% CI: 77.4–92.8%). Exercise-induced chest discomfort also showed good diagnostic accuracy (76.1%; 95% CI: 67.3–83.5%) but did not provide additional diagnostic value when combined with ischemic ECG changes. EST was more effective in identifying structural CMD, whereas functional CMD was often missed. Conclusions Ischemic ECG changes observed during EST, performed immediately before invasive functional assessment, demonstrated excellent diagnostic accuracy for identifying CMD, particularly the structural endotype. These findings highlight the potential utility of EST in the diagnostic evaluation of ANOCA patients, especially for detecting structural CMD. The study also underscores the need for further research to integrate EST into the diagnostic workflow for ANOCA patients, as it may help guide therapeutic decisions and improve outcomes.