Clinical relevance of functionally insignificant moderate coronary artery stenosis assessed by 3-vessel fractional flow reserve measurement

Background--Understanding of the risk conferred by functionally insignificant lesions in multiple coronary vessels is limited. We investigated the prognostic implications of coronary artery disease (CAD) based on 3-vessel fractional flow reserve (FFR). Methods and Results--A total of 1,136 patients underwent FFR measurement in the 3 major epicardial arteries. We defined vessels with "Moderate CAD" as vessels with FFR, 0.81 to 0.87. Patients were classified into Group 1: No apparent CAD (FFR > 0.87 in all 3-vessels); Group 2: Single-vessel moderate CAD; Group 3: Multivessel moderate CAD; and Group 4: Functionally significant CAD (FFR=0.80) in any vessel. The primary end point was 2-year major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. Forty-three percent of patients had moderate CAD (Group 2: 403/1136, 35.5%; Group 3: 84/1136, 7.4%). The 2-year risk of major adverse cardiac events was not significantly different between patients with singlevessel moderate CAD and no apparent CAD (2.6 versus 2.6%; HR, 1.1; 95% confidence interval, 0.4%-2.8%; P=0.89). However, patients with multivessel moderate CAD were at significantly higher risk than Group 1 (7.4 versus 2.6%; hazard ratio, 3.3; 95% confidence interval, 1.1%-9.8%; P=0.03). The risk of major adverse cardiac events in patients with multivessel moderate CAD was comparable to that of patients with functionally significant CAD (hazard ratio, 1.2; 95% confidence interval, 0.5%-3.0%; P=0.67). In a multivariable regression model, multivessel moderate CAD was an independent predictor of greater risk of 2-year major adverse cardiac events. Conclusions--Global physiologic assessment with FFR measurement of 3 vessels can identify multivessel moderate CAD. The prognostic implication of multivessel moderate CAD appears comparable to that of functionally significant CAD. Clinical Trial Registration--URL: http://www.clinicaltrials.gov. Unique identifier: NCT01621438.