title: Relative flow reserve derived from quantitative perfusion imaging may not outperform stress myocardial blood flow for identification of hemodynamically significant coronary artery disease.
abstract: BACKGROUND
  Quantitative myocardial perfusion imaging is increasingly used for the diagnosis of coronary artery disease. Quantitative perfusion imaging allows to noninvasively calculate fractional flow reserve (FFR). This so-called relative flow reserve (RFR) is defined as the ratio of hyperemic myocardial blood flow (MBF) in a stenotic area to hyperemic MBF in a normal perfused area. The aim of this study was to assess the value of RFR in the detection of significant coronary artery disease.
  
  
  RESULTS
  From a clinical population of patients with suspected coronary artery disease who underwent oxygen-15-labeled water cardiac positron emission tomography and invasive coronary angiography, 92 patients with single- or 2-vessel disease were included. Intermediate lesions (diameter stenosis, 30%-90%; n=75) were interrogated by FFR. Thirty-eight (41%) vessels were deemed hemodynamically significant (>90% stenosis or FFR≤0.80). Hyperemic MBF, coronary flow reserve, and RFR were lower for vessels with a hemodynamically significant lesion (2.01±0.78 versus 2.90±1.16 mL·min(-1)·g(-1); P<0.001, 2.27±1.03 versus 3.10±1.29; P<0.001, and 0.67±0.23 versus 0.93±0.15; P<0.001, respectively). The correlation between RFR and FFR was moderate (r=0.54; P<0.01). Receiver operator characteristic curve analysis showed an area under the curve of 0.82 for RFR, which was not significantly higher compared with that for hyperemic MBF and coronary flow reserve (0.76; P=0.32 and 0.72; P=0.08, respectively).
  
  
  CONCLUSIONS
  Noninvasive estimation of FFR by quantitative perfusion positron emission tomography by calculating RFR is feasible, yet only a trend toward a slight improvement of diagnostic accuracy compared with hyperemic MBF assessment was determined.
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Wijnand J
authors.initials: WJ
authors.lastname: Stuijfzand
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Valtteri
authors.initials: V
authors.lastname: Uusitalo
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Tanja
authors.initials: T
authors.lastname: Kero
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Danad
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Mischa T
authors.initials: MT
authors.lastname: Rijnierse
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Pieter G
authors.initials: PG
authors.lastname: Raijmakers
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Harms
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Martijn W
authors.initials: MW
authors.lastname: Heymans
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Marc C
authors.initials: MC
authors.lastname: Huisman
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Koen M
authors.initials: KM
authors.lastname: Marques
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Sami A
authors.initials: SA
authors.lastname: Kajander
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Mikko
authors.initials: M
authors.lastname: Pietilä
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Jens
authors.initials: J
authors.lastname: Sörensen
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Niels
authors.initials: N
authors.lastname: van Royen
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.).
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.affiliation: From the Departments of Cardiology (W.J.S., I.D., M.T.R., K.M.M., N.v.R., P.K.), Radiology and Nuclear Medicine (P.G.R., A.A.L, H.J.H., M.C.H.), Department of Epidemiology and Biostatistics (M.W.H.), VU University Medical Center, Amsterdam, The Netherlands; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland (V.U., A.S., S.A.K, M.P., J.K.); and Department of Nuclear Medicine and PET, Institution of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden (T.K., J.S.). p.knaapen@vumc.nl.
authors.forename: Paul
authors.initials: P
authors.lastname: Knaapen
mesh_terms: D000241:Adenosine; D000368:Aged; D019540:Area Under Curve; D001783:Blood Flow Velocity; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000503:physiopathology; D023921:Coronary Stenosis / Q000175:diagnosis* / Q000503:physiopathology; D005060:Europe; D005240:Feasibility Studies; D005260:Female; D053805:Fractional Flow Reserve, Myocardial; D006439:Hemodynamics; D006801:Humans; D006940:Hyperemia / Q000175:diagnosis / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D014665:Vasodilator Agents
chemical_list: D014665:Vasodilator Agents; D000241:Adenosine
keywords: coronary angiography; coronary artery disease; fractional flow reserve, myocardial; positron-emission tomography