title: Baseline instantaneous wave-free ratio as a pressure-only estimation of underlying coronary flow reserve: results of the JUSTIFY-CFR Study (Joined Coronary Pressure and Flow Analysis to Determine Diagnostic Characteristics of Basal and Hyperemic Indices of Functional Lesion Severity-Coronary Flow Reserve).
abstract: BACKGROUND
  Coronary flow reserve has extensive validation as a prognostic marker in coronary disease. Although pressure-only fractional flow reserve (FFR) improves outcomes compared with angiography when guiding percutaneous coronary intervention, it disagrees with coronary flow reserve classification 30% of the time. We evaluated whether baseline instantaneous wave-free ratio (iFR) could provide an improved pressure-only estimation of underlying coronary flow reserve.
  
  
  RESULTS
  Invasive pressure and flow velocity were measured in 216 stenoses from 186 patients with coronary disease. The diagnostic relationship between pressure-only indices (iFR and FFR) and coronary flow velocity reserve (CFVR) was compared using correlation coefficient and the area under the receiver operating characteristic curve. iFR showed a stronger correlation with underlying CFVR (iFR-CFVR, ρ=0.68 versus FFR-CFVR, ρ=0.50; P<0.001). iFR also agreed more closely with CFVR in stenosis classification (iFR area under the receiver operating characteristic curve, 0.82 versus FFR area under the receiver operating characteristic curve, 0.72; P<0.001, for a CFVR of 2). The closer relationship between iFR and CFVR was found for different CFVR cutoffs and was particularly marked in the 0.6 to 0.9 FFR range. Hyperemic FFR flow was similar to baseline iFR flow in functionally significant lesions (FFR ≤0.75; mean FFR flow, 25.8±13.7 cm/s versus mean iFR flow, 21.5±11.7 cm/s; P=0.13). FFR flow was higher than iFR flow in nonsignificant stenoses (FFR >0.75; mean FFR flow, 42.3±22.8 cm/s versus mean iFR flow, 26.1±15.5 cm/s; P<0.001).
  
  
  CONCLUSIONS
  When compared with FFR, iFR shows stronger correlation and better agreement with CFVR. These results provide physiological evidence that iFR could potentially be used as a functional index of disease severity, independently from its agreement with FFR.
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Ricardo
authors.initials: R
authors.lastname: Petraco
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Tim P
authors.initials: TP
authors.lastname: van de Hoef
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Sukhjinder
authors.initials: S
authors.lastname: Nijjer
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Sayan
authors.initials: S
authors.lastname: Sen
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Martijn A
authors.initials: MA
authors.lastname: van Lavieren
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Foale
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Martijn
authors.initials: M
authors.lastname: Meuwissen
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Christopher
authors.initials: C
authors.lastname: Broyd
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Mauro
authors.initials: M
authors.lastname: Echavarria-Pinto
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Foin
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Iqbal S
authors.initials: IS
authors.lastname: Malik
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Ghada W
authors.initials: GW
authors.lastname: Mikhail
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Alun D
authors.initials: AD
authors.lastname: Hughes
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Jamil
authors.initials: J
authors.lastname: Mayet
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Carlo
authors.initials: C
authors.lastname: Di Mario
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Javier
authors.initials: J
authors.lastname: Escaned
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.).
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
authors.affiliation: From the International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (R.P., S.N., S.S., R.A.F., C.B., N.F., I.S.M., G.W.M., A.D.H., D.P.F., J.M., C.D.M., J.E.D.); Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands (T.P.v.d.H., M.A.v.L., J.J.P.); Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain (M.E.-P., J.E.); Amphia Hospital, Breda, The Netherlands (M.M.); and Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, United Kingdom (C.D.M.). justin.davies@imperial.ac.uk.
authors.forename: Justin E
authors.initials: JE
authors.lastname: Davies
mesh_terms: D000368:Aged; D023921:Coronary Stenosis / Q000175:diagnosis*; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D003935:Diagnostic Techniques, Cardiovascular; D018450:Disease Progression; D005260:Female; D053805:Fractional Flow Reserve, Myocardial / Q000502:physiology*; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011312:Pressure; D011379:Prognosis; D015203:Reproducibility of Results; D012720:Severity of Illness Index
keywords: coronary disease; fractional flow reserve, myocardial