Prevalence, endotypes, and clinical implications of CMD in STEMI patients

Abstract Background Coronary microvascular dysfunction (CMD) is increasingly recognized as a contributor to adverse outcomes in patients with ST-elevation myocardial infarction (STEMI). However, the prevalence, endotypes, and clinical implications of CMD endotype in this population remain poorly understood. This study aimed to characterize CMD in STEMI patients, focusing on its structural and functional endotypes, and to explore its association with demographic, clinical, and outcome profiles. Methods This multicenter, prospective cohort study enrolled 210 STEMI patients with multivessel disease who underwent successful revascularization. At 3 months post-revascularization, patients returned for coronary physiology assessments using bolus thermodilution to measure microvascular resistance reserve (MRR) and the index of microvascular resistance (IMR). CMD was classified into functional CMD (MRR 3 and IMR 25) and structural CMD (MRR 3 and IMR ≥ 25). The prevalence of these endotypes and their association with major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months were investigated. Baseline demographic and clinical characteristics were compared across CMD endotypes, and Kaplan-Meier analysis was used to evaluate MACCE-free survival. Results CMD was identified in 27% (n = 56) of STEMI patients, with structural CMD being the predominant endotype (24%, n = 51), compared to functional CMD (3%, n = 5). Female patients were significantly overrepresented in the structural CMD group (68.63% vs. 32.47% in the no CMD group, p 0.001). Diabetes mellitus was notably more prevalent in the structural CMD group (43.14%) compared to the no CMD group (18.83%) and was absent in the functional CMD group (p = 0.001). Smoking was more common in the structural CMD group (58.82%) but did not differ significantly between the overall CMD and no CMD groups, suggesting a multifactorial etiology. Age, body mass index (BMI), and body surface area (BSA) did not differ significantly across groups. Kaplan-Meier analysis revealed a trend toward lower MACCE-free survival in structural CMD patients compared to functional CMD patients, though this did not reach statistical significance (log-rank p = 0.054), likely due to the small sample size of the functional CMD group. Conclusions Structural CMD is the predominant endotype in STEMI patients and is associated with a higher prevalence of female sex and diabetes mellitus. While smoking may contribute to structural CMD, it is not the sole determinant, indicating a multifactorial pathophysiology. The trend toward worse outcomes in structural CMD patients highlights the need for further research into targeted therapeutic strategies. Future studies with larger cohorts are warranted to validate these findings and explore the long-term impact of CMD endotypes on clinical outcomes in STEMI patients.CMD Endotypes in STEMI Patients STEMI Patients by CMD Endotypes