title: Impact of hyperaemic microvascular resistance on fractional flow reserve measurements in patients with stable coronary artery disease: insights from combined stenosis and microvascular resistance assessment.
abstract: BACKGROUND
  Fractional flow reserve (FFR) aims to identify the extent of epicardial disease, but may be obscured by involvement of the coronary microvasculature. We documented the impact of hyperaemic stenosis resistance (HSR) and hyperaemic microvascular resistance (HMR) on FFR, and its relationship with myocardial ischaemia in patients with stable coronary artery disease.
  
  
  RESULTS
  We evaluated 255 coronary arteries with stenoses of intermediate severity by means of intracoronary pressure and flow measurements to determine FFR, HSR and HMR. Myocardial perfusion scintigraphy (MPS) was performed to identify inducible myocardial ischaemia. In 178 patients, HMR was additionally determined in a reference coronary artery. Target vessel HMR was stratified according to reference vessel HMR tertiles. The diagnostic OR for inducible ischaemia on MPS of a positive compared with a negative FFR was significantly higher only in the presence of a high HMR (at the 0.75 and 0.80 FFR cut-off). Among stenoses with a positive FFR, the prevalence of ischaemia was significantly higher when HMR was high despite equivalent FFR across the HMR groups. This was paralleled by a concomitant significant increase in HSR with increasing HMR across groups. The relation between FFR and HSR (r(2)=0.54, p<0.001) was modulated by the magnitude of HMR, and improved substantially after adjustment for HMR (adjusted-r(2)=0.73, p<0.001), where, for epicardial disease of equivalent severity, FFR increased with increasing HMR.
  
  
  CONCLUSIONS
  Identification of epicardial disease severity by FFR is partly obscured by the microvascular resistance, which illustrates the necessity of combined pressure and flow measurements in daily practice.
authors.affiliation: AMC Heartcentre, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Department of Biomedical Engineering and Physics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Hospital Clínico San Carlos and Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Tim P
authors.initials: TP
authors.lastname: van de Hoef
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Froukje
authors.initials: F
authors.lastname: Nolte
authors.affiliation: Hospital Clínico San Carlos and Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Mauro
authors.initials: M
authors.lastname: EchavarrÍa-Pinto
authors.affiliation: AMC Heartcentre, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Martijn A
authors.initials: MA
authors.lastname: van Lavieren
authors.affiliation: AMC Heartcentre, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Damman
authors.affiliation: Department of Cardiology, University Medical Centre, Utrecht, The Netherlands.
authors.forename: Steven A J
authors.initials: SA
authors.lastname: Chamuleau
authors.affiliation: Department of Cardiology, University Medical Centre, Utrecht, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Voskuil
authors.affiliation: Department of Nuclear Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Hein J
authors.initials: HJ
authors.lastname: Verberne
authors.affiliation: AMC Heartcentre, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: José P S
authors.initials: JP
authors.lastname: Henriques
authors.affiliation: Department of Nuclear Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Berthe L F
authors.initials: BL
authors.lastname: van Eck-Smit
authors.affiliation: AMC Heartcentre, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Karel T
authors.initials: KT
authors.lastname: Koch
authors.affiliation: AMC Heartcentre, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: de Winter
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jos A E
authors.initials: JA
authors.lastname: Spaan
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Siebes
authors.affiliation: AMC Heartcentre, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jan G P
authors.initials: JG
authors.lastname: Tijssen
authors.affiliation: Department of Cardiology, Amphia Hospital, Breda, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Meuwissen
authors.affiliation: AMC Heartcentre, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
mesh_terms: D000241:Adenosine; D000368:Aged; D001783:Blood Flow Velocity; D001794:Blood Pressure; D006328:Cardiac Catheterization; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000503:physiopathology*; D023921:Coronary Stenosis / Q000175:diagnosis / Q000503:physiopathology*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D053805:Fractional Flow Reserve, Myocardial; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014655:Vascular Resistance; D014665:Vasodilator Agents
chemical_list: D014665:Vasodilator Agents; D000241:Adenosine