Long-Term Clinical Outcomes of Nonhyperemic Pressure Ratios: Resting Full-Cycle Ratio, Diastolic Pressure Ratio, and Instantaneous Wave-Free Ratio

Abstract

Background Nonhyperemic pressure ratios (NHPRs) such as instantaneous wave-free ratio, resting full-cycle ratio, or diastolic pressure ratio have emerged as invasive physiologic indices precluding the need for hyperemic agents. The current study sought to evaluate the long-term prognostic implications of NHPRs compared with fractional flow reserve (FFR). Methods and Results NHPRs were calculated from resting pressure tracings by an independent core laboratory in 1024 vessels (435 patients). The association between NHPRs and the risk of 5-year vessel-oriented composite outcomes (VOCO, a composite of cardiac death, vessel-related myocardial infarction, and ischemia-driven revascularization) were analyzed among 864 deferred vessels. Lesions with positive NHPRs (instantaneous wave free ratio, resting full-cycle ratio, and diastolic pressure ratio ≤0.89) or FFR (≤0.80) showed significantly higher risk of VOCO at 5 years than those with negative NHPRs or FFR, respectively. Discriminant ability for 5-year VOCO was not different among NHPRs and FFR (C-index: 0.623-0.641, P for comparison=0.215). In comparison of VOCO among the groups with deferred concordant negative (NHPRs-/FFR-), deferred discordant (NHPRs+/FFR- or NHPRs-/FFR+), and revascularized vessels, the cumulative incidence of VOCO were 7.5%, 14.4%, and 14.8% (log-rank P<0.001), respectively. The deferred discordant group showed similar risk of VOCO with the revascularized vessel group (hazard ratio, 0.981; 95% CI 0.434-2.217, P=0.964). Conclusions Currently available invasive pressure-derived indices showed similar prognostic implications for vessel-related events at 5 years. Deferred lesions with discordant results between NHPRs and FFR did not show higher risk of vessel-related events at 5 years than revascularized vessels. Registration URL: https://www.clini​caltr​ials.gov; Unique identifiers: NCT01621438, NCT01621438.

Keywords: coronary artery disease; diastolic pressure ratio; fractional flow reserve; instantaneous wave-free ratio; ischemia; prognosis; resting full-cycle ratio.

Conflict of interest statement

Dr Joo Myung Lee received a research grant from St. Jude Medical (Abbott Vascular) and Philips Volcano. Dr Joo‐Yong Hahn received a research grant from St. Jude Medical (Abbott Vascular). Dr Bon‐Kwon Koo received an institutional research grant from St. Jude Medical (Abbott Vascular) and Philips Volcano. The remaining authors have no disclosures to report.

Figures

Figure 1. Comparison of vessel‐oriented composite outcome at 5 years according to invasive physiologic indices.

Comparison of the risk of VOCO at 5 years between positive vs negative (A) iFR, (B) RFR, (C) dPR, or (D) FFR according to their cut‐off values. dPR indicates diastolic pressure ratio; FFR, fractional flow reserve; HR, hazard ratio; iFR, instantaneous wave‐free ratio; and RFR, resting full‐cycle ratio.

Figure 2. Association and discrimination ability of invasive physiologic indices with estimated risk of VOCO at 5 years.

A, The association between 5‐year VOCO risk and invasive physiologic indices (iFR, RFR, dPR, or FFR). All physiologic indices showed significant association with 5‐year VOCO risk as continuous values. Blue, orange, black, and red lines represent regression lines for iFR, RFR, dPR, and FFR as continuous values, respectively. Blue, orange, black, and red circles represent each patient's iFR, RFR, dPR, and FFR values and estimated VOCO rates according to their values, respectively. The marginal Cox proportional hazard regression models to calculate hazard ratio and 95% CI with adjustment for the clustered data. B, Discriminant ability (Harrell's c‐index) of invasive physiologic indices for the occurrence of VOCO at 5 years. Blue, orange, black, and red lines represent receiver‐operating curve for iFR, RFR, dPR, and FFR, respectively, as continuous values. dPR indicates diastolic pressure ratio; FFR, fractional flow reserve; HR, hazard ratio; iFR, instantaneous wave‐free ratio; RFR, resting full‐cycle ratio; and VOCO, vessel‐oriented composite outcomes.

Figure 3. Subgroup analysis for prognostic meaning of invasive physiologic indices in deferred patients.

Subgroup analysis according to patient and lesion characteristics in comparing the risk of VOCO between positive and negative NHPRs or FFR. The higher risk of VOCO in lesions with positive NHPRs or FFR than negative lesions was observed across all subgroups without significant interaction P values and across all invasive physiologic indices including iFR, RFR, dPR, and FFR. dPR indicates diastolic pressure ratio; FFR, fractional flow reserve; iFR, instantaneous wave‐free ratio; NHPR, nonhyperemic pressure ratios; Pint, interaction P value; RFR, resting full‐cycle ratio; and VOCO, vessel‐oriented composite outcomes.

Figure 4. Comparison of 5‐year clinical outcomes classified by NHPRs and FFR.

The cumulative incidence of VOCO at 5 years are compared among revascularized vessels, deferred vessel with concordant negative results in both NHPRs and FFR, and deferred vessel with discordant results between NHPRs and FFR (NHPRs−/FFR+ or NHPRs+/FFR−). FFR indicates fractional flow reserve; HR, hazard ratio; NA, not available; NHPRs, nonhyperemic pressure ratios; and VOCO, vessel‐oriented composite outcomes.