Author + information
- Received December 5, 2014
- Accepted January 15, 2015
- Published online July 1, 2015.
- Nils P. Johnson, MD, MS∗∗ (, )
- Daniel T. Johnson, MSc∗,
- Richard L. Kirkeeide, PhD∗,
- Colin Berry, MB ChB, PhD†,‡,
- Bernard De Bruyne, MD, PhD§,
- William F. Fearon, MD‖,
- Keith G. Oldroyd, MB ChB, MD‡,
- Nico H.J. Pijls, MD, PhD¶,# and
- K. Lance Gould, MD∗
- ∗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
- †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
- §Cardiovascular Center Aalst, Aalst, Belgium
- ‖Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, California
- ¶Department of Cardiology, Catharina Hospital, Eindhoven, the Netherlands
- #Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
- ↵∗Reprint requests and correspondence:
Dr. Nils P. Johnson, Weatherhead PET Center, University of Texas Medical School at Houston, 6431 Fannin Street, Room MSB 4.256, Houston, Texas 77030.
Objectives 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, r2 = 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.
Dr. Nils P. Johnson received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; and has received significant institutional research support from St. Jude Medical (for NCT02184117) and Volcano Corporation (for NCT02328820), makers of intracoronary pressure and flow sensors. Dr. Kirkeeide has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; and has signed nonfinancial, nondisclosure agreements with St. Jude Medical and Volcano Corporation to discuss coronary physiology projects. Dr. Berry has received institutional research grant support and consultancy agreements from St. Jude Medical. Dr. De Bruyne has received institutional consultancy fees and research support from St. Jude Medical. Dr. Fearon has received institutional research support from St. Jude Medical; and has served as an advisor to HeartFlow Inc. Dr. Oldroyd has received speaker fees from St. Jude Medical, AstraZeneca, and Volcano Corporation. Dr. Pijls has received institutional grant support from St. Jude Medical; serves as a consultant for St. Jude Medical, HeartFlow Inc., and Boston Scientific; and possesses equity in Philips, ASML, and Heartflow. Dr. Gould has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; and he is the 510(k) applicant for cfrQuant, a software package for quantifying absolute flow using cardiac positron emission tomography. All royalties will go to a University of Texas scholarship fund. The University of Texas has a commercial, nonexclusive agreement with Positron Corporation to distribute and market cfrQuant in exchange for royalties. However, Dr. Gould retains the ability to distribute cost-free versions to selected collaborators for research. Dr. Daniel T. Johnson has reported that he has no relationships relevant to the contents of this paper to disclose.
- Received December 5, 2014.
- Accepted January 15, 2015.
- 2015 American College of Cardiology Foundation