Diagnostic performance of exercise stress testing findings and coronary microvascular dysfunction in patients with angina with non-obstructive coronary artery disease

Background: Coronary microvascular dysfunction (CMD) is common among patients with angina with non-obstructive coronary artery disease (ANOCA) and leads to poorer clinical outcomes. Exercise stress testing (EST) was shown to have a high specificity for detecting CMD. However, the relationship between diagnosing CMD using different invasive physiological parameters and thresholds and the association between EST findings and the endotype of CMD remains unknown. Methods: This multicentre, prospective cohort study enrolled 117 patients with ANOCA who underwent EST prior to invasive coronary angiography with functional assessment to measure coronary flow reserve (CFR), the index of microvascular resistance (IMR) and microvascular resistance reserve (MRR)=(CFR/FFR)×(Pa rest/Pa hyper). CMD was classified using multiple criteria, including MRR <3.0, CFR <2.5 and CFR <2.0 or IMR ≥25. Diagnostic sensitivity and specificity and the accuracy of EST findings (exercise-induced chest discomfort, ischaemic ECG changes and exercise intolerance) for diagnosing CMD were assessed. Results: The prevalence of CMD was similar under all three definitions. However, structural CMD was more common using MRR <3.0. Ischaemic ECG changes during EST showed an excellent diagnostic accuracy of 86.3% (78.7-92.0%) for detecting CMD, with a sensitivity and specificity of 86.2% (68.3-96.1%) and 86.4% (77.4-92.8%), respectively. Exercise-induced chest discomfort also had a good diagnostic accuracy of 76.1% (95% CI 67.3% to 83.5%); however, it offered no additional value when added to ischaemic ECG changes. EST preferentially identified structural CMD, while functional CMD was more frequently missed. Conclusions: Ischaemic ECG changes during EST performed immediately before invasive functional assessment demonstrated excellent diagnostic accuracy for identifying patients with CMD, particularly the structural endotype. Trial registration number: NCT05841485.