title: Repeatability of Fractional Flow Reserve Despite Variations in Systemic and Coronary Hemodynamics.
abstract: OBJECTIVE
  This study classified and quantified the variation in fractional flow reserve (FFR) due to fluctuations in systemic and coronary hemodynamics during intravenous adenosine infusion.
  
  
  BACKGROUND
  Although FFR has become a key invasive tool to guide treatment, questions remain regarding its repeatability and stability during intravenous adenosine infusion because of systemic effects that can alter driving pressure and heart rate.
  
  
  METHODS
  We reanalyzed data from the VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice) study, which enrolled consecutive patients who were infused with intravenous adenosine at 140 μg/kg/min and measured FFR twice. Raw phasic pressure tracings from the aorta (Pa) and distal coronary artery (Pd) were transformed into moving averages of Pd/Pa. Visual analysis grouped Pd/Pa curves into patterns of similar response. Quantitative analysis of the Pd/Pa curves identified the "smart minimum" FFR using a novel algorithm, which was compared with human core laboratory analysis.
  
  
  RESULTS
  A total of 190 complete pairs came from 206 patients after exclusions. Visual analysis revealed 3 Pd/Pa patterns: "classic" (sigmoid) in 57%, "humped" (sigmoid with superimposed bumps of varying height) in 39%, and "unusual" (no pattern) in 4%. The Pd/Pa pattern repeated itself in 67% of patient pairs. Despite variability of Pd/Pa during the hyperemic period, the "smart minimum" FFR demonstrated excellent repeatability (bias -0.001, SD 0.018, paired p = 0.93, r(2) = 98.2%, coefficient of variation = 2.5%). Our algorithm produced FFR values not significantly different from human core laboratory analysis (paired p = 0.43 vs. VERIFY; p = 0.34 vs. RESOLVE).
  
  
  CONCLUSIONS
  Intravenous adenosine produced 3 general patterns of Pd/Pa response, with associated variability in aortic and coronary pressure and heart rate during the hyperemic period. Nevertheless, FFR - when chosen appropriately - proved to be a highly reproducible value. Therefore, operators can confidently select the "smart minimum" FFR for patient care. Our results suggest that this selection process can be automated, yet comparable to human core laboratory analysis.
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: 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.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Johnson
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.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Kirkeeide
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; West of Scotland Regional Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, United Kingdom.
authors.forename: Colin
authors.initials: C
authors.lastname: Berry
authors.affiliation: Cardiovascular Center Aalst, Aalst, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: De Bruyne
authors.affiliation: Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, California.
authors.forename: William F
authors.initials: WF
authors.lastname: Fearon
authors.affiliation: West of Scotland Regional Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, United Kingdom.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Oldroyd
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: NHJ
authors.lastname: Pijls
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.
authors.forename: K Lance
authors.initials: KL
authors.lastname: Gould
mesh_terms: D000241:Adenosine / Q000008:administration & dosage; D000465:Algorithms; D062186:Arterial Pressure; D006328:Cardiac Catheterization; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000503:physiopathology; D023921:Coronary Stenosis / Q000175:diagnosis* / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D005060:Europe; D053805:Fractional Flow Reserve, Myocardial / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007262:Infusions, Intravenous; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D012815:Signal Processing, Computer-Assisted; D013997:Time Factors; D014481:United States; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D014665:Vasodilator Agents; D000241:Adenosine
keywords: adenosine; algorithm; fractional flow reserve; repeatability