Microvascular Resistance Reserve and Outcomes in Angina and Nonobstructive Coronary Artery Disease

Importance: Coronary microvascular dysfunction (CMD) is highly prevalent in patients with angina and nonobstructive coronary arteries (ANOCA). Microvascular resistance reserve (MRR) is a novel index to assess CMD independently of epicardial disease and driving pressures, but the long-term prognostic value of continuous thermodilution-derived MRR in patients with ANOCA is unknown. Objective: To assess the prognostic value of continuous thermodilution-derived MRR and its association with clinical outcomes and symptom burden in patients with ANOCA. Design, Setting, and Participants: This prospective, multicenter cohort study within the Netherlands Registry of Invasive Coronary Vasomotor Function Testing (NL-CFT) included patients between July 2020 and June 2025 in 4 clinical centers in the Netherlands. Follow-up for clinical events and patient-reported symptoms was completed for up to 3 years. Clinical events were adjudicated by investigators blinded to CFT results. Consecutive patients with ANOCA who underwent continuous thermodilution were included. Exposure: Abnormal MRR (CMD) was defined as less than 2.1, gray zone as 2.1 to 2.7, and normal microvascular function as 2.7 or greater. Main Outcomes and Measures: The primary clinical outcome was a composite of all-cause death, acute coronary syndrome, stroke, clinically indicated revascularization, repeat angiography without intervention, and unplanned hospital admittance or emergency department visit due to angina or heart failure. Secondary outcomes included angina at baseline and follow-up. Symptoms were assessed using the patient-reported Seattle Angina Questionnaire (SAQ) scores. Results: Among 553 included patients (mean [SD] age, 59.1 [9.6] years; 459 female [83.0%]) with a mean (SD) follow-up of 27.5 (16.1) months, CMD was observed in 94 patients (17.0%). The main composite outcome did not differ across the 3 MRR categories (18 of 94 patients with abnormal [19.1%] vs 21 of 98 patients with gray zone [21.4%] vs 76 of 361 patients with normal [21.1%] MRR; log-rank P = .85). Individual outcomes did not differ between groups. There was no overall longitudinal interaction between MRR and SAQ summary scores. While low MRR (abnormal vs normal groups) was not associated with an increased symptom burden at baseline, it was associated with worse angina at follow-up (mean [SD] SAQ summary score, 53.0 [16.7] vs 60.1 [16.6]; P = .04) and less clinically relevant improvement (9 of 30 patients [30.0%] vs 52 of 88 patients [59.1%]; P = .02). Conclusions and Relevance: In this study, CMD assessed by continuous thermodilution-derived MRR was not associated with clinical outcomes.