Symptom phenotypes and coronary microvascular function in non-obstructive coronary artery disease: Insights beyond epicardial ischemia

Study objective To examine the relationship between coronary microvascular dysfunction (CMD) indices and chest pain presentation in patients with non-obstructive coronary artery disease (NOCA). Design and setting Retrospective, single-center observational study. Participants Patients with angiographically intermediate left anterior descending artery (LAD) stenosis and preserved epicardial physiology (fraction flow reserve, FFR >0.80), with no significant stenosis in vessels other than the LAD. Interventions Invasive CMD assessment using coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and myocardial resistance reserve (MRR). Main outcome measures Associations between symptom phenotypes and physiological indices, and the diagnostic performance of symptom-based assessment for detecting CMD. Results Among 59 patients (mean age 69.2 years; 71 % male), CFR and MRR differed significantly across symptom phenotypes (both p < 0.001), whereas IMR did not. Patients with typical angina exhibited the lowest CFR and MRR, indicating impaired microvascular vasodilatory reserve despite preserved epicardial physiology. Conversely, patients with atypical symptoms had the highest CFR and MRR, whereas asymptomatic patients had intermediate values. FFR was comparable across groups (median 0.89, p = 0.21). In age-adjusted analyses, symptom severity was inversely associated with CFR (β = −1.085, p = 0.004) and MRR (β = −1.062, p = 0.003), but not with IMR. Symptom-based assessment showed higher specificity than sensitivity across CMD definitions and performed best for impaired MRR (sensitivity 60.9 %, specificity 80.6 %). Functional CMD was observed even in asymptomatic patients. Conclusion In patients with NOCA, coronary microvascular vasodilatory reserve varies according to symptom phenotype, highlighting the limited reliability of symptom assessment alone and underscoring the importance of objective physiological evaluation for characterizing CMD.