Heterogeneity of coronary microvascular dysfunction: endotype-specific characteristics, symptoms, and outcomes

Background Coronary vasomotor dysfunction is the main cause of angina and no obstructive coronary artery disease (ANOCA), involving epicardial and/or microvascular vasospasm and coronary microvascular dysfunction (CMD). Invasive coronary function testing enables classification of CMD into structural, functional, and compensated structural endotypes. This study aims to improve understanding of CMD heterogeneity by comparing endotypes with respect to patient characteristics, healthcare burden and patient-reported symptoms and quality of life. Purpose This prospective, single center registry is part of a nationwide program and systematically collects data on ANOCA patients undergoing CFT at a University Medical Center. Methods Patients without obstructive coronary artery disease and with angina pectoris underwent liberal CFT with or without spasm provocation testing. Participants were classified into four CMD endotypes: 1) Normal physiology (CFR>2.5 and IMR <25); 2) Structural CMD (CFR ≤2.5 and IMR ≥25); 3) Functional CMD (CFR ≤2.5 and IMR <25); and 4) Compensated Structural CMD (CFR>2.5 and IMR ≥25). Participants had a baseline, one-year and if available two years follow-up. Throughout the follow-up period, 60 participants completed questionnaires to assess their symptoms, healthcare utilization, and quality of life at baseline and one year post-CFT. Results A total of 227 participants were included (mean age 66.1 ± 9.7, 53% women). Of these, 59% had normal physiology, 14% structural CMD, 12% functional CMD, and 15% compensated structural CMD. No sex-related differences were observed between these endotypes. Among 56 patients undergoing spasm provocation, 50% showed epicardial spasm. Participants with CMD were significantly older. Medical history, risk factors, and baseline medication were comparable, calcium-channel blockers use significantly increased post-CFT in the CMD-groups. Patients with an abnormal CFR (structural- & functional CMD) showed worse 2-year clinical outcomes. Overall, CFT improved patient-reported angina symptoms and quality of life, however patients with only an abnormal IMR (compensated structural CMD) reported poorer 1-year outcomes. Conclusions This study showed a high prevalence of CMD for both men and women. Participants with an abnormal CFR showed worse 2-years clinical outcomes and higher healthcare utilization, whereas those with isolated IMR abnormalities reported more angina symptoms and lower quality of life.