Association between angiography-derived index of microcirculatory resistance and the progression of coronary artery disease defined by fractional flow reserve

Abstract Background The progression of coronary artery disease (CAD) is influenced by multiple risk factors. While coronary microvascular dysfunction (CMD) is known to be associated with adverse cardiovascular outcomes, its role in CAD progression remains unclear. The angiography-derived index of microcirculatory resistance (angio-IMR) is a novel, non-invasive metric that estimates IMR without the need for guidewire insertion and hyperemia induction. However, reports on the relationship between angio-IMR and CAD progression are limited. Purpose This study aimed to investigate the association between angio-IMR and lesion progression, defined by fractional flow reserve (FFR) assessment over time. Methods We retrospectively analyzed patients who underwent coronary angiography (CAG) and FFR measurements at our institution between 2016 and 2025. Among them, 105 patients who had undergone serial CAG and FFR assessments at an interval of more than one year were included. To ensure reliable measurement of angio-IMR, only lesions in the left anterior descending artery (LAD) were analyzed. Patients who underwent percutaneous coronary intervention (PCI) between the two evaluations, those without LAD-FFR assessment, or those with a history of coronary artery bypass grafting (CABG) were excluded. Angio-IMR was derived from angiography at the initial evaluation. The association between a change in FFR over time and A-IMR was assessed. Results The median age was 68.0 years (interquartile range (IQR): 65.0, 74.0), and 76.2% (80/105) of patients were male. The median time interval of the serial FFR assessments was 29.7 IQR: 18.3, 48.5 months. The difference between the initial and following FFR was 0.01 IQR: -0.01, 0.04. Patients were divided into two groups based on the median value of the change in FFR (0.01). The progression group exhibited significantly higher initial angio-IMR values compared to the non-progression group (33.71 IQR 22.03, 47.61 vs. 23.98 IQR 17.39, 33.78, p=0.011). A significant correlation was observed between angio-IMR and the change in FFR over time (r=0.286, P=0.003). Multivariable linear regression analysis identified male gender, lower estimated glomerular filtration rate, and higher angio-IMR as independently associated factors with a change in FFR over time. Multivariable logistic regression analysis revealed that angio-IMR was an independent predictor of the progression after adjusting for confounding factors (adjusted odds ratio: 1.03 95% confidence interval: 1.00, 1.05, P=0.04). Conclusion Higher angio-IMR values were associated with CAD progression as assessed by serial FFR measurements. These findings suggest that microvascular dysfunction, as reflected by angio-IMR, may contribute to the identification of potentially progressive epicardial coronary lesions. Non-invasive assessment of microcirculatory function could provide valuable insights into CAD progression and aid in risk stratification.