The microvascular resistance reserve (MRR) was introduced as a means to characterize the vasodilator reserve capacity of the coronary microcirculation while accounting for the influence of concomitant epicardial disease and the impact of administration of potent vasodilators on aortic pressure. This study aimed to evaluate the diagnostic and prognostic performance of MRR. A total of 1481 patients with stable symptoms and a clinical indication for coronary angiography were included from the global ILIAS Registry. MRR was derived as a function of the coronary flow reserve (CFR) divided by the fractional flow reserve (FFR) and corrected for driving pressure. The median MRR was 2.97 [Q1–Q3: 2.32–3.86] and the overall relationship between MRR and CFR was good [correlation coefficient (R_s) = 0.88, P < 0.005]. The difference between CFR and MRR increased with decreasing FFR [coefficient of determination (R²) = 0.34; Coef.—2.88, 95% confidence interval (CI): -3.05–−2.73; P < 0.005]. MRR was independently associated with major adverse cardiac events (MACE) at 5-year follow-up [hazard ratio (HR) 0.78; 95% CI 0.63–0.95; P = 0.024] and with target vessel failure (TVF) at 5-year follow-up (HR 0.83; 95% CI 0.76–0.97; P = 0.047). The optimal cut-off value of MRR was 3.0. Based on this cut-off value, only abnormal MRR was significantly associated with MACE and TVF at 5-year follow-up in vessels with functionally significant epicardial disease (FFR <0.75). MRR seems a robust indicator of the microvascular vasodilator reserve capacity. Moreover, in line with its theoretical background, this study suggests a diagnostic advantage of MRR over other indices of vasodilatory capacity in patients with hemodynamically significant epicardial coronary artery disease. Diagnostic and prognostic value of the microvascular resistance reserve (MRR).The MRR is a novel index of the coronary vasodilatory capacity. The MMR is an index that corrects the assessment of the vasodilatory capacity for concomitant epicardial disease and the administration of vasodilatory indices. The MRR shows an excellent correlation with the coronary flow reserve (CFR), which decreases with decreasing fractional flow reserve (FFR) values. The MRR is an independent and significant predictor of both major adverse cardiac events (MACE) and target vessel failure (TVF) at 5-year follow-up.

Background: Despite the significant decline in cardiovascular mortality in women over the past several decades, sex differences in the underlying pathology of acute coronary syndromes remain poorly understood. Previous postmortem studies have demonstrated sex differences in coronary plaque morphology with a higher prevalence of plaque erosion in young women and more plaque rupture in older women after menopause, whereas men showed no increase in prevalence of plaque rupture with age. However, in vivo data are limited. Methods: This study included patients who presented with acute coronary syndrome and underwent preintervention optical coherence tomography imaging of the culprit lesion. The culprit plaque was categorized as plaque rupture, plaque erosion or culprit plaque with calcification, and stratified by age. Features of plaque vulnerability at culprit lesion were also analyzed. Results: In 1368 patients (women=286), women and men had a similar distribution of culprit plaque morphology (plaque rupture versus plaque erosion). However, significant sex differences were found in the underlying mechanisms of acute coronary syndrome among different age groups: women showed a significant ascending trend with age in plaque rupture ( P <0.001) and the features of plaque vulnerability such as lipid plaque ( P <0.001), thin-cap fibroatheroma ( P =0.005), and microstructures including macrophages, cholesterol crystals, and calcification ( P =0.026). No trend was observed in men. Conclusions: Age related sex differences in culprit plaque morphology and vulnerability were identified in patients with acute coronary syndrome: prevalence of plaque rupture and vulnerability increased with age in women but not in men. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01110538 and NCT03479723.

Background: In the absence of obstructive coronary stenoses, abnormality of noninvasive stress tests (NIT) in patients with chronic coronary syndromes may indicate myocardial ischemia of nonobstructive coronary arteries (INOCA). The differential prognosis of INOCA according to the presence of coronary microvascular dysfunction (CMD) and incremental prognostic value of CMD with intracoronary physiologic assessment on top of NIT information remains unknown. Methods and Results: From the international multicenter registry of intracoronary physiologic assessment (ILIAS [Inclusive Invasive Physiological Assessment in Angina Syndromes] registry, N=2322), stable patients with NIT and nonobstructive coronary stenoses with fractional flow reserve >0.80 were selected. INOCA was diagnosed when patients showed positive NIT results. CMD was defined as coronary flow reserve ≤2.5. According to the presence of INOCA and CMD, patients were classified into 4 groups: group 1 (no INOCA nor CMD, n=116); group 2 (only CMD, n=90); group 3 (only INOCA, n=41); and group 4 (both INOCA and CMD, n=40). The primary outcome was major adverse cardiovascular events, a composite of all‐cause death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 5 years. Among 287 patients with nonobstructive coronary stenoses (fractional flow reserve=0.91±0.06), 81 patients (38.2%) were diagnosed with INOCA based on positive NIT. By intracoronary physiologic assessment, 130 patients (45.3%) had CMD. Regardless of the presence of INOCA, patients with CMD showed a significantly lower coronary flow reserve and higher hyperemic microvascular resistance compared with patients without CMD ( P <0.001 for all). The cumulative incidence of major adverse cardiovascular events at 5 years were 7.4%, 21.3%, 7.7%, and 34.4% in groups 1 to 4. By documenting CMD (groups 2 and 4), intracoronary physiologic assessment identified patients at a significantly higher risk of major adverse cardiovascular events at 5 years compared with group 1 (group 2: adjusted hazard ratio [HR _adjusted ], 2.88; 95% CI, 1.52–7.19; P =0.024; group 4: HR _adjusted , 4.00; 95% CI, 1.41–11.35; P =0.009). Conclusions: In stable patients with nonobstructive coronary stenoses, a diagnosis of INOCA based only on abnormal NIT did not identify patients with higher risk of long‐term cardiovascular events. Incorporating intracoronary physiologic assessment to NIT information in patients with nonobstructive disease allowed identification of patient subgroups with up to 4‐fold difference in long‐term cardiovascular events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04485234.