title: A Prospective Natural History Study of Coronary Atherosclerosis Using Fractional Flow Reserve.
abstract: In patients with coronary artery disease, clinical outcome depends on the extent of reversible myocardial ischemia. Whether the outcome also depends on the severity of the stenosis as determined by fractional flow reserve (FFR) remains unknown.
  
  
  
  This study sought to investigate the relationship between FFR values and vessel-related clinical outcome.
  
  
  
  We prospectively studied major adverse cardiovascular events (MACE) at 2 years in 607 patients in whom all stenoses were assessed by FFR and who were treated with medical therapy alone. The relationship between FFR and 2-year MACE was assessed as a continuous function. Logistic and Cox proportional hazards regression models were used to calculate the average decrease in the risk of MACE per 0.05-U increase in FFR.
  
  
  
  MACE occurred in 272 (26.5%) of 1,029 lesions. Target lesions with diameter stenosis ≥70% were more often present in the MACE group (p < 0.01). Median FFR was significantly lower in the MACE group versus the non-MACE group (0.68 [interquartile range: 0.54 to 0.77] vs. 0.80 [interquartile range: 0.70 to 0.88]; p < 0.01). The cumulative incidence of MACE significantly increased with increasing FFR quartiles. An average decrease in MACE per 0.05-unit increase in FFR was statistically significant even after adjustment for all clinical and angiographic features (odds ratio: 0.81; 95% confidence interval: 0.76 to 0.86]). The strongest increase in MACE occurred for FFR values between 0.80 and 0.60. In multivariable Cox regression analysis, FFR was significantly associated with MACE up to 2 years (hazard ratio: 0.87; 95% confidence interval: 0.83 to 0.91]).
  
  
  
  In patients with stable coronary disease, stenosis severity as assessed by FFR is a major and independent predictor of lesion-related outcome. (FAME II - Fractional Flow Reserve [FFR] Guided Percutaneous Coronary Intervention [PCI] Plus Optimal Medical Treatment [OMT] Verses OMT; NCT01132495).
authors.affiliation: Cardiovascular Research Center Aalst OLV Hospital, Aalst, Belgium; Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy. Electronic address: emanuele.barbato@olvz-aalst.be.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Barbato
authors.affiliation: Department of Cardiology, University Heart Center Graz, Graz, Austria.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Toth
authors.affiliation: Division of Cardiology, Department of Medicine, University of Texas Medical School, Houston, Texas.
authors.forename: Nils P
authors.initials: NP
authors.lastname: Johnson
authors.affiliation: Department of Cardiology, Catharina Hospital, Eindhoven, the Netherlands.
authors.forename: Nico H J
authors.initials: NH
authors.lastname: Pijls
authors.affiliation: Stanford University Medical Center, Stanford, California.
authors.forename: William F
authors.initials: WF
authors.lastname: Fearon
authors.affiliation: Department of Cardiology, Catharina Hospital, Eindhoven, the Netherlands.
authors.forename: Pim A L
authors.initials: PA
authors.lastname: Tonino
authors.affiliation: Department of Cardiology, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Curzen
authors.affiliation: Gottsegen Gyorgy Hungarian Institute of Cardiology, Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Piroth
authors.affiliation: Interventional Cardiology Department, Hospices Civils de Lyon, Claude Bernard University Lyon 1 and CARMEN INSERM, Bron, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Rioufol
authors.affiliation: Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada; Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Jüni
authors.affiliation: Cardiovascular Research Center Aalst OLV Hospital, Aalst, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: De Bruyne
mesh_terms: D050197:Atherosclerosis / Q000175:diagnosis / Q000503:physiopathology* / Q000601:surgery; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000503:physiopathology* / Q000601:surgery; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D053805:Fractional Flow Reserve, Myocardial / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors
keywords: clinical outcome; fractional flow reserve; stable angina; vessel related