The diagnostic performance of exercise stress testing findings and coronary microvascular dysfunction in ANOCA patients

Background Coronary microvascular dysfunction (CMD) is common among patients with angina with non-obstructive coronary artery disease (ANOCA) and leads to poorer clinical outcomes. Recently, Sinha et al. demonstrated high specificity of exercise stress testing (EST) for CMD. However, the relationship between CMD diagnosis under different physiological thresholds and the association between EST findings and the endotype of CMD remains unknown. Methods This is a multicentre, prospective cohort of 117 ANOCA patients 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, specificity and accuracy of EST findings (EST-induced angina, ischemic ECG changes, and exercise tolerance) for diagnosing CMD were assessed. Results The prevalence of CMD was similar under all three definitions (Figure 1), however structural CMD was more common under MRR<3.0. Ischemic ECG changes during EST showed an excellent diagnostic accuracy of 86.3% (95% CI:78.7-92.0%) for detecting CMD, with a sensitivity and specificity of 86.2% (95% CI:68.3-96.1%) and 86.4% (95% CI:77.4-92.8%), respectively. Exercise-induced chest discomfort also had a good diagnostic accuracy of 76.1% (95%CI:67.3-83.5%) but offered no additional diagnostic value to ischemic ECG changes. (Figure2) EST preferentially identified structural CMD, while functional CMD was more frequently missed. Conclusions Ischemic ECG changes during EST performed immediately before invasive functional assessment demonstrated excellent diagnostic accuracy for identifying CMD, particularly the structural endotype.