Microvascular dysfunction in patients with non-obstructive coronary artery disease

Abstract Background Non-obstructive coronary artery disease (NOCAD) is increasingly recognized as a major contributor to ischemic heart disease. Coronary microvascular dysfunction (CMD) plays a critical role in NOCAD, yet its precise pathophysiological mechanisms and prognostic significance remain incompletely understood. This study aimed to assess CMD using invasive and non-invasive measures and evaluate its impact on cardiovascular outcomes. Methods We conducted a prospective study of 228 patients (mean age: 59.3 ± 8.7 years; 62.3% female) with angina and no significant epicardial coronary stenosis (≥50% luminal narrowing). CMD was assessed using coronary flow reserve (CFR) via transthoracic Doppler echocardiography and index of microcirculatory resistance (IMR) during invasive coronary physiology testing. Patients were categorized into CMD-positive (CFR <2.5 or IMR >25 U, n=148) and CMD-negative groups (n=80). Biomarkers, endothelial function (via flow-mediated dilation, FMD), and cardiac magnetic resonance imaging (CMR) with stress perfusion were analyzed. Results CMD-positive patients exhibited lower CFR (1.96 ± 0.43 vs. 2.87 ± 0.36, p<0.001), higher IMR (29.7 ± 4.9 vs. 17.3 ± 3.1, p<0.001), and reduced FMD (4.8% ± 1.9% vs. 7.2% ± 2.1%, p=0.002). High-sensitivity troponin (hs-TnT) and NT-proBNP were significantly elevated in CMD patients (p<0.01). Multivariate logistic regression identified CMD as an independent predictor of major adverse cardiovascular events (MACE) at 12 months (HR=2.47, 95% CI: 1.68–3.62, p<0.001). ROC analysis of CFR for predicting MACE yielded an AUC of 0.81 (95% CI: 0.74–0.88, p<0.001). Conclusion CMD is prevalent in NOCAD and is associated with impaired endothelial function, elevated biomarkers, and increased MACE risk. CFR and IMR provide robust prognostic utility. Further studies should explore targeted therapies for CMD to improve patient outcomes.

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