title: Prognostic value of fractional flow reserve: linking physiologic severity to clinical outcomes.
abstract: BACKGROUND
  Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.
  
  
  OBJECTIVE
  The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.
  
  
  METHODS
  Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.
  
  
  RESULTS
  A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.
  
  
  CONCLUSIONS
  FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.
authors.affiliation: Weatherhead PET Center For Preventing and Reversing Atherosclerosis, Division of Cardiology, Department of Medicine, University of Texas Medical School and Memorial Hermann Hospital, Houston, Texas. Electronic address: Nils.Johnson@uth.tmc.edu.
authors.forename: Nils P
authors.initials: NP
authors.lastname: Johnson
authors.affiliation: Cardiovascular Center Aalst, Aalst, Belgium.
authors.forename: Gábor G
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authors.lastname: Tóth
authors.affiliation: Division of Biostatistics, University of Texas School of Public Health, Houston, Texas.
authors.forename: Dejian
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authors.affiliation: Division of Biostatistics, University of Texas School of Public Health, Houston, Texas.
authors.forename: Hongjian
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authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Kartal Kosuyolu High Speciality Education and Research Hospital, Istanbul, Turkey.
authors.forename: Göksel
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authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Pierfrancesco
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authors.affiliation: Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Yolande
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authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Fatih
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authors.affiliation: Cardiovascular Center Aalst, Aalst, Belgium.
authors.forename: Emanuele
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authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing City, China.
authors.forename: Shao-Liang
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authors.affiliation: Department of Cardiology, Presidio Ospedaliero (P.O.) Di Venere, Bari, Italy.
authors.forename: Luigi
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authors.affiliation: Unidad de Gestión Clínica del Corazón, Hospital Clínico Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Málaga, Spain.
authors.forename: Antonio J
authors.initials: AJ
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authors.affiliation: Pôle Cardiovasculaire Interventionnel, Hôpital Privé d'Antony, Antony, France.
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authors.affiliation: Department of Cardiology, Kartal Kosuyolu High Speciality Education and Research Hospital, Istanbul, Turkey.
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authors.affiliation: Department of Cardiology, Memorial Hospital, Istanbul, Turkey.
authors.forename: Ozlem B
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authors.affiliation: Department of Cardiology, University Hospital of Heraklion, Crete, Greece.
authors.forename: Michalis
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authors.affiliation: Department of Cardiology, Okayama Kyokuto Hospital, Okayama, Japan.
authors.forename: Kohichiro
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authors.affiliation: Department of Cardiology, Odense University Hospital, Odense, Denmark.
authors.forename: Lisette O
authors.initials: LO
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authors.affiliation: Unidad de Gestión Clínica del Corazón, Hospital Clínico Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga (UMA), Málaga, Spain.
authors.forename: Manuel F
authors.initials: MF
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authors.affiliation: Department of Cardiology, Athens Euroclinic, Athens, Greece.
authors.forename: Demosthenes G
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authors.affiliation: Department of Cardiology, Gazi University School of Medicine, Ankara, Turkey.
authors.forename: Sinan A
authors.initials: SA
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authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Bon-Kwon
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authors.forename: Ramón
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authors.initials: JD
authors.lastname: Lorin
authors.affiliation: Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, New York.
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.affiliation: Department of Cardiology, University of Lausanne Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: Olivier
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authors.lastname: Muller
authors.affiliation: Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, South Korea.
authors.forename: Chang-Wook
authors.initials: CW
authors.lastname: Nam
authors.affiliation: Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Niels
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authors.affiliation: Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Etienne
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authors.affiliation: Clinic for Cardiology and Internal Intensive Care Medicine, Klinikum Bogenhausen, Munich, Germany.
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authors.affiliation: Interventional Cardiology Department, Hospices Civils de Lyon and CARMEN INSERM 1060, France.
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authors.affiliation: Québec Heart and Lung Institute, Laval University, Québec City, Canada.
authors.forename: Josep
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authors.affiliation: VA New York Harbor Health Care System, New York University School of Medicine, New York, New York.
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authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
authors.affiliation: Department of Cardiology, Catharina Hospital, Eindhoven, the Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
authors.forename: Pim A L
authors.initials: PA
authors.lastname: Tonino
authors.affiliation: Department of Cardiology, University Hospital, and EA2693, Lille-II-University, Lille, France.
authors.forename: Eric
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authors.lastname: Van Belle
authors.affiliation: Department of Cardiology, Ospedale di Circolo e Fondazione Macchi, University Hospital, Varese, Italy.
authors.forename: Edoardo
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authors.affiliation: Klinikum Darmstadt, Darmstadt, Germany.
authors.forename: Gerald S
authors.initials: GS
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authors.affiliation: Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, California.
authors.forename: William F
authors.initials: WF
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authors.affiliation: Department of Cardiology, Catharina Hospital, Eindhoven, the Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
authors.forename: Nico H J
authors.initials: NH
authors.lastname: Pijls
authors.affiliation: Cardiovascular Center Aalst, Aalst, Belgium.
authors.forename: Bernard
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authors.lastname: De Bruyne
authors.affiliation: Weatherhead PET Center For Preventing and Reversing Atherosclerosis, Division of Cardiology, Department of Medicine, University of Texas Medical School and Memorial Hermann Hospital, Houston, Texas.
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mesh_terms: D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology*; D053805:Fractional Flow Reserve, Myocardial / Q000502:physiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D012720:Severity of Illness Index; D016896:Treatment Outcome
keywords: fractional flow reserve; meta-analysis; prognosis; threshold