Abstract Body (Do not enter title and authors here): Background:
Approximately 50% of patients with angina who undergo invasive coronary angiography (ICA) do not exhibit obstructive epicardial coronary artery disease. A significant subset of these patients has coronary microvascular dysfunction (CMD). The current gold standard for diagnosing CMD is the invasive Index of Microcirculatory Resistance (IMR), which requires administration of adenosine and pressure wire instrumentation, carrying procedural risks. Angiography-derived IMR (Angio-IMR) is a novel, non-invasive, machine learning-based method that applies computational fluid dynamics to standard ICA images to emulate hyperemic microvascular assessment.

Hypothesis:
Angio-IMR is an accurate predictor of CMD when compared with invasively measured IMR.

Methods:
This prospective, multicentre study was conducted across three tertiary Australian hospitals. Patients undergoing ICA were assessed using both invasive IMR and Angio-IMR. Angio-IMR analyses were performed centrally and blinded, using manual frame counting with Medis QFR software (version 3.1). Patients were stratified into derivation and validation cohorts. Diagnostic performance of Angio-IMR was assessed using ROC analysis, with invasive IMR > 25 was used as the threshold for significant CMD.

Results:
A total of 335 patients (63 ± 10.6 years; 56% male), encompassing 394 vessels, were included. In the derivation (n = 124) and validation (n = 124) cohorts, significant CMD (IMR > 25) was present in 27% and 23% of vessels respectively. Angio-IMR showed moderate correlation with invasive IMR (r = 0.47 in derivation; r = 0.33 in validation). Angio-IMR predicted significant CMD with an area under the ROC curve (AUC) of 0.82 and 0.76 (both p < 0.001) in the derivation and validation cohorts, respectively. An Angio-IMR threshold of > 21 optimized sensitivity and specificity. At this cutoff, sensitivity and negative predictive value (NPV) were 94.9% and 95.9% in the derivation cohort, and 89.0% and 92.0% in the validation cohort, respectively.

Conclusion:
Angio-IMR is a promising non-invasive tool for the detection of CMD, demonstrating strong diagnostic performance, particularly in ruling out disease. Its high sensitivity and NPV support its use as a gatekeeper to invasive IMR, potentially reducing need for pressure wire-based assessments in low-risk patients. This study establishes Angio-IMR as a clinically valuable adjunct in the assessment of microvascular coronary disease.