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 single‐vessel 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.