Microvascular resistance reserve: diagnostic and prognostic performance in the ILIAS registry

Abstract

Aims: 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.

Methods and results: 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 (Rs) = 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).

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT0448523.

Keywords: Coroanry artery disease; Coronary microvascular dysfunction; Coronary physiology; Microvascular resistance reserve.

Structured Graphical Abstract

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.

Figure 1

Correlation between CFR and MRR in the whole study population. Scatter plot of individual coronary flow reserve (CFR) and microvascular resistance reserve (MRR) values, and the corresponding linear correlation between CFR and MRR (A), as well as the corresponding Bland–Altman plot (B) and a modified Bland–Altman plot with the effect of fractional flow reserve (FFR) on the difference between CFR and MRR (C). Upper limit of agreement (ULA), lower limit of agreement (LLA).

Figure 2

Cumulative incidence curves for MACE (A) and TVF (B) according to normal and abnormal MRR. Cumulative incidence curves for major adverse cardiac events (MACE) (A) and target vessel failure (TVF) (B) up to 5-year follow-up according to normal or abnormal microvascular resistance reserve (MRR) (cut-off value: 3.0). Hazard ratio (HR) with 95% confidence interval (CI) presented based on proportional hazards analysis corrected for confounders and accounting for the competing risk of death using the Fine-Gray model for TVF.

Figure 3

Hazard ratios for the risk of MACE (A) and TVF (B) at 5-year follow-up according to different indices of CMD. Plot showing hazard ratios with 95% confidence intervals associated with major adverse cardiac events (MACE) and target vessel failure (TVF) at 5-year follow-up based on multivariate proportional hazards analysis for indices of CMD (as binary variables). HR was adjusted for the competing risk of death for TVF using the Fine and Gray method. MR [minimal resistance (HMR >2.5; IMR >25)].