Prognostic Implications of Resistive Reserve Ratio in Patients With Coronary Artery Disease

Abstract

Background Resistive reserve ratio is a thermodilution-based index which integrates both coronary flow and pressure. Resistive reserve ratio represents the vasodilatory capacity of interrogated vessels including both epicardial coronary artery and microvascular circulation. We evaluated the prognostic potential of resistive reserve ratio compared with pressure-derived index (fractional flow reserve [FFR]) or flow-derived index (coronary flow reserve [CFR]). Methods and Results A total of 1245 patients underwent coronary pressure and flow measurement using pressure-temperature wire. Resistive reserve ratio was calculated by CFR adjusted using the ratio between resting and hyperemic distal coronary pressure ([resting mean transit time/hyperemic mean transit time]×[resting distal coronary pressure/hyperemic distal coronary pressure]). Clinical outcome was assessed by patient-oriented composite outcome (POCO), a composite of any death, myocardial infarction, and revascularization at 5 years. At 5 years, the cumulative incidence of POCO was significantly different according to quartiles of resistive reserve ratio (9.9%, 11.3%, 17.2%, and 22.7% in quartiles 1 to 4, respectively, log rank P<0.001). Among patients with deferred revascularization, those with depressed resistive reserve ratio (<3.5) showed a significantly higher risk of POCO than those with preserved resistive reserve ratio (≥3.5) in patients with FFR>0.80 or patients with CFR>2.0. (FFR>0.80 group: 14.8% versus 6.0%; log rank P=0.001; CFR>2.0 group: 13.5% versus 7.1%; log rank P=0.045). Adding resistive reserve ratio into the model for 5-year POCO showed significantly higher global Chi square value than FFR or CFR (P<0.001, respectively, for FFR and CFR). Resistive reserve ratio <3.5 was significantly associated with the risk of POCO at 5 years in multivariable model (adjusted hazard ratio 1.597, 95% CI, 1.098-2.271, P=0.014). Conclusions Resistive reserve ratio, which integrated both coronary flow and pressure, showed incremental prognostic implications in patients with coronary artery disease undergoing elective percutaneous coronary intervention guided by invasive physiologic evaluation. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03690713.

Keywords: coronary artery disease; coronary flow reserve; fractional flow reserve; prognosis; resistive reserve ratio.

Figures

Figure 1. Concept of resistive reserve ratio.

In assessment of coronary circulatory function, coronary flow reserve can be calculated by ratio between resting and hyperemic mean transit time which is a surrogate marker of coronary flow. Fractional flow reserve is calculated as the ratio between hyperemic distal coronary pressure and hyperemic aortic pressure which is also surrogate marker of coronary flow at hyperemia. Resistive reserve ratio is an integrated index of both thermodilution‐measured coronary flow reserve and distal coronary pressure measured during resting and hyperemic status and represents vasodilatory capacity of the coronary circulation and reflects cumulative functional disease burden throughout the interrogated vessel. Pa indicates aortic pressure; Pd, distal coronary pressure; and Tmn, mean transit time.

Figure 2. Comparison of patient‐oriented composite outcome according to quartiles of resistive reserve ratio.

The cumulative incidence of patient‐oriented composite outcome at 5 years is compared according to quartile of resistive reserve ratio. There was a significant trend of higher RRR and lower risk of patient‐oriented composite outcome, and vice versa. HR indicates hazard ratio; Q1 to Q4, quartile 1 to 4; and RRR, resistive reserve ratio.

Figure 3. Comparison of patient‐oriented composite outcome between preserved or depressed resistive reserve ratio, among high fractional flow reserve or high coronary flow reserve population with deferred revascularization.

The cumulative incidence of patient‐oriented composite outcome at 5 years is compared between preserved (≥3.5) and depressed resistive reserve ratio (A) high fractional flow reserve (>0.80) or (B) high coronary flow reserve (>2.0) among patients with deferred revascularization. CFR indicates coronary flow reserve; FFR, fractional flow reserve; HR, hazard ratio; and RRR, resistive reserve ratio.

Figure 4. Association of resistive reserve ratio with estimated risk of patient‐oriented composite outcome at 5 years among patients with deferred revascularization.

The non‐linear relationship between resistive reserve ratio and the estimated risk of patient‐oriented composite outcome at 5 years was plotted after adjustment with (A) percent diameter stenosis (%DS), (B) fractional flow reserve, or (C) multivariable adjustment. Adjusted covariates in the multivariable model are age, sex, hypertension, diabetes mellitus, hyperlipidemia, acute coronary syndrome, multivessel disease, fractional flow reserve, and % diameter stenosis. %DS indicates percent diameter stenosis; FFR, fractional flow reserve; and RRR, resistive reserve ratio.

Figure 5. Comparison of additive prognostic impact of FFR, CFR, and RRR for risk of patient‐oriented composite outcome at 5 years among patients with deferred revascularization.

In addition to model with clinical variables, additive prognostic impact of fractional flow reserve, coronary flow reserve, or resistive reserve ratio was compared. Model 4 (clinical variables with resistive reserve ratio) showed significantly higher global Chi square value than Model 2 (clinical variables with fractional flow reserve) or Model 3 (clinical variables with coronary flow reserve). Included clinical variables were age, sex, hypertension, diabetes mellitus, hyperlipidemia, acute coronary syndrome, multivessel disease, and % diameter stenosis. CFR indicates coronary flow reserve, FFR, fractional flow reserve; and RRR, resistive reserve ratio.