Long-term Patient Prognostication by Coronary Flow Reserve and Index of Microcirculatory Resistance: International Registry of Comprehensive Physiologic Assessment

Abstract

Background and objectives: Recent guideline recommends evaluation using of coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with functionally insignificant stenosis. We evaluated clinical implications of CFR and IMR in patients with high fractional flow reserve (FFR) and deferred revascularization.

Methods: A total of 867 patients (1,152 vessels) consigned to deferred revascularization who underwent comprehensive physiologic assessments were enrolled. Patients with high FFR (>0.80) were categorized by CFR (≤2) and IMR (≥23 U). Clinical outcome was assessed by patient-oriented composite outcome (POCO), a composite of any death, myocardial infarction (MI), and revascularization at 5 years.

Results: Patients with low CFR (≤2) showed significantly greater risk of POCO than those with high CFR (>2) in both high-FFR (p=0.024) and low-FFR (p=0.034) groups. In patients with high FFR, those with low CFR and high IMR (overt microvascular disease) displayed the greatest risk of POCO overall (p=0.015), surpassing those with high CFR and low IMR (HR, 2.873; 95% CI, 1.476-5.594; p=0.002) and showing significantly greater risk of cardiac death or MI (HR, 5.662; 95% CI, 1.984-16.154; p=0.001). Overt microvascular disease was independently associated with POCO in the high-FFR population (HR, 2.282; 95% CI, 1.176-4.429; p=0.015).

Conclusion: Among patients with deferred revascularization, those with low CFR showed significantly greater risk of POCO than those with high CFR, regardless of FFR. In patients with high FFR, those with overt microvascular disease showed significantly greater risk of POCO and cardiac death or MI at 5-year, compared with the others.

Trial registration: ClinicalTrials.gov Identifier: NCT03690713.

Keywords: Coronary artery disease; Coronary flow reserve; Fractional flow reserve; Index of microcirculatory resistance; Myocardial ischemia; Percutaneous coronary intervention.

Conflict of interest statement

Dr. Joo Myung Lee received a research grant from St. Jude Medical (Abbott Vascular) and Philips Volcano. Dr. Bon-Kwon Koo received an Institutional Research Grant from St. Jude Medical (Abbott Vascular) and Philips Volcano. Dr. Escaned received personal fees from Philips Volcano, Boston Scientific, and Abbott/St. Jude Medical outside the submitted work. All other authors declare that there is no conflict of interest relevant to the submitted work.

Copyright © 2020. The Korean Society of Cardiology.

Figures

Figure 1. Distribution of deferred patients according to FFR and CFR.

Distribution of patients with deferred revascularization is presented according to FFR and CFR. Red dots indicate high index of microcirculatory resistance (IMR, ≥23 U). All IMR values corrected by Yong's formula (Pa × Tmn × ([1.35 × Pd/Pa] − 0.32). CFR = coronary flow reserve; FFR = fractional flow reserve; IMR = index of microcirculatory resistance.

Figure 2. Impact of coronary flow reserve on cumulative incidence of clinical outcomes.

Cumulative incidence POCO in patients with (A) low FFR (≤0.80) and (B) high FFR (>0.80), shown by CFR values. CFR = coronary flow reserve; CI = confidence intervals; FFR = fractional flow reserve; HR = hazard ratio; MI = myocardial infarction; POCO = patient-oriented composite outcome.

Figure 3. Distribution of deferred patients with high fractional flow reserve (>0.80) by CFR and IMR.

Since there was weak correlation between CFR and IMR and agreement between the 2 indices was low, therefore, 4 different patterns were observed. CFR = coronary flow reserve; IMR = index of microcirculatory resistance.

Figure 4. Clinical outcomes by microvascular status, based on CFR and IMR in deferred patients with high fractional flow reserves (>0.80).

Cumulative incidences of (A) patient-oriented composite outcomes and (B) cardiac death or myocardial infarction in 4 patient groups divided by CFR and IMR in patients with deferred revascularization based on high fractional flow reserve (>0.80). CFR = coronary flow reserve; CI = confidence intervals; HR = hazard ratio; IMR = index of microcirculatory resistance; NA = not applicable; PCI = percutaneous intervention.