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Eur Heart J. 2018 Mar 14;39(11):945-951. doi: 10.1093/eurheartj/ehx458.

Clinical implications of three-vessel fractional flow reserve measurement in patients with coronary artery disease.

Author information

Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, 50, Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.
Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, 101 Daehang-ro, Chongno-gu, Seoul 110-744, Korea.
Institute on Aging, Seoul National University, 50, Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.
Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.
Department of Medicine, Keimyung University Dongsan Medical Center, Daegu, South Korea.
Department of Medicine, Inje University Ilsan Paik Hospital, Goyang, South Korea.
Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, China.
Division of Biostatistics, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD, USA.
Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
Department of Cardiology, Tokyo Medical University, Tokyo, Japan.
Kokura Memorial Hospital, Kitakyuku, Japan.
Department of Cardiology, Gifu Heart Center, Gifu, Japan.
Department of Cardiology, Aichi Medical University, Nagakute, Japan.
Wakayama Medical University, Wakayama, Japan.



There are limited data on the clinical implications of total physiologic atherosclerotic burden assessed by invasive physiologic studies in patients with coronary artery disease. We investigated the prognostic implications of total physiologic atherosclerotic burden assessed by total sum of fractional flow reserve (FFR) in three vessels (3V-FFR).

Methods and results:

A total of 1136 patients underwent FFR measurement in three vessels (3V FFR-FRIENDS study, NCT01621438). The patients were classified into high and low 3V-FFR groups according to the median value of 3V-FFR (2.72). The primary endpoint was major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction and ischaemia-driven revascularization) at 2 years. Mean angiographic percent diameter stenosis and FFR were 43.7 ± 19.3% and 0.90 ± 0.08, respectively. There was a negative correlation between 3V-FFR and estimated 2-year MACE rate (P < 0.001). The patients in low 3V-FFR group showed a higher risk of 2-year MACE than those in the high 3V-FFR group [(7.1% vs. 3.8%, hazard ratio (HR) 2.205, 95% confidence interval (CI) 1.201-4.048, P = 0.011]. The higher 2-year MACE rate was mainly driven by the higher rate of ischaemia-driven revascularization in the low 3V-FFR group (6.2% vs. 2.7%, HR 2.568, 95% CI 1.283-5.140, P = 0.008). In a multivariable adjusted model, low 3V-FFR was an independent predictor of MACE (HR 2.031, 95% CI 1.078-3.830, P = 0.029).


Patients with high total physiologic atherosclerotic burden assessed by 3V-FFR showed higher risk of 2-year clinical events than those with low total physiologic atherosclerotic burden. The difference was mainly driven by ischaemia-driven revascularization for both functionally significant and insignificant lesions at baseline. Three-vessel FFR might be used as a prognostic indicator in patients with coronary artery disease.

Clinical trial registration:

3V FFR-FRIENDS study (, NCT01621438).


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