Clinical Outcomes of Deferred Lesions With Angiographically Insignificant Stenosis But Low Fractional Flow Reserve

Joo Myung Lee, Bon-Kwon Koo, Eun-Seok Shin, Chang-Wook Nam, Joon-Hyung Doh, Xinyang Hu, Fei Ye, Shaoliang Chen, Junqing Yang, Jiyan Chen, Nobuhiro Tanaka, Hiroyoshi Yokoi, Hitoshi Matsuo, Hiroaki Takashima, Yasutsugu Shiono, Doyeon Hwang, Jonghanne Park, Kyung-Jin Kim, Takashi Akasaka, Jianan Wang, Joo Myung Lee, Bon-Kwon Koo, Eun-Seok Shin, Chang-Wook Nam, Joon-Hyung Doh, Xinyang Hu, Fei Ye, Shaoliang Chen, Junqing Yang, Jiyan Chen, Nobuhiro Tanaka, Hiroyoshi Yokoi, Hitoshi Matsuo, Hiroaki Takashima, Yasutsugu Shiono, Doyeon Hwang, Jonghanne Park, Kyung-Jin Kim, Takashi Akasaka, Jianan Wang

Abstract

Background: Data are limited regarding outcomes of deferred lesions in patients with angiographically insignificant stenosis but low fractional flow reserve (FFR). We investigated the natural history of angiographically insignificant stenosis with low FFR among patients who underwent routine 3-vessel FFR measurement.

Methods and results: From December 2011 to March 2014, 1136 patients with 3298 vessels underwent routine 3-vessel FFR measurement (3V FFR-FRIENDS study, ClinicalTrials.gov identifier NCT01621438), and this study analyzed the 2-year clinical outcomes of 1024 patients with 2124 lesions with angiographically insignificant stenosis (percentage of diameter stenosis <50%), in which revascularization was deferred. All lesions were classified according to FFR values, using a cutoff of 0.80 (high FFR >0.80 versus low FFR ≤0.80). The primary end point was outcome of major adverse cardiovascular events (a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization) at 2 years. Mean angiographic percentage of diameter stenosis and FFR of total lesions were 32.5±10.3% and 0.91±0.08%, respectively. Among the total lesions with angiographically insignificant stenosis, 8.7% showed low FFR (185 lesions). The incidence of lesions with low FFR was 2.5%, 3.8%, 9.0%, and 15.1% in categories of percentage of diameter stenosis <20%, 20% to 30%, 30% to 40%, and 40% to 50%, respectively. At 2-year follow-up, the low-FFR group showed a significantly higher risk of major adverse cardiovascular events compared with the high FFR group (3.3% versus 1.2%, hazard ratio: 3.371; 95% CI, 1.346-8.442; P=0.009). In multivariable analysis, low FFR was the most powerful independent predictor of future MACE in deferred lesions with angiographically insignificant stenosis (adjusted hazard ratio: 2.617; 95% CI, 1.026-6.679; P=0.044).

Conclusions: In deferred angiographically insignificant stenosis, lesions with low FFR showed significantly higher event rates than those with high FFR. FFR was an independent predictor of future major adverse cardiovascular events in lesions with angiographically insignificant stenosis.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01621438.

Keywords: coronary artery disease; discordance; fractional flow reserve; prognosis; reverse mismatch; stents.

© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
Distribution of lesions according to angiographic percentage of diameter stenosis (%DS) and FFR. A, Distributions of total lesions are presented according to %DS and FFR values. The incidence of lesions with low FFR was 2.5%, 3.8%, 9.0%, and 15.1% in %DS categories <20%, 20% to 30%, 30% to 40%, and 40% to 50%, respectively. B, The proportions of lesions with low FFR are presented according to target vessels. LM and LAD showed the highest proportions of lesions with low FFR compared with non‐LM or non‐LAD. FFR indicates fractional flow reserve; LAD, left anterior descending artery; LCX, left circumflex artery; LM, left main vessel; RCA, right coronary artery.
Figure 2
Figure 2
Comparison of 2‐year clinical outcomes of deferred angiographically insignificant lesions classified according to fractional flow reserve. Kaplan–Meier curves are shown for deferred angiographically insignificant lesions, classified according to FFR values. HRs were calculated from a marginal Cox proportional hazards regression model. CI indicates confidence interval; FFR, fractional flow reserve; HR, hazard ratio.
Figure 3
Figure 3
Representative case examples of angiographically insignificant stenosis with low FFR. Two representative cases of angiographically insignificant stenosis with low FFR are presented. The limitations of coronary angiography, such as hidden focal stenosis (A) and angiographically underestimated diffuse atherosclerosis (B), can cause the low FFR, despite angiographically insignificant stenosis. In both cases, N13‐ammonia positron emission tomography showed a reversible perfusion defect in stress imaging (arrow), low‐stress myocardial blood flow, and coronary flow reserve in LAD territory. CFR indicates coronary flow reserve; FFR, fractional flow reserve; LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery.

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