Author + information
- Received November 6, 2015
- Revision received December 28, 2015
- Accepted December 29, 2015
- Published online April 25, 2016.
- Nils P. Johnson, MD, MSa,∗ (, )
- Allen Jeremias, MD, MScb,c,
- Frederik M. Zimmermann, MDd,
- Julien Adjedj, MDe,
- Nils Witt, MD, PhDf,
- Barry Hennigan, MB BCh BAO, BMedScig,h,
- Bon-Kwon Koo, MD, PhDi,
- Akiko Maehara, MDc,j,
- Mitsuaki Matsumura, BSc,
- Emanuele Barbato, MD, PhDe,k,
- Giovanni Esposito, MD, PhDk,
- Bruno Trimarco, MDk,
- Gilles Rioufol, MD, PhDl,
- Seung-Jung Park, MD, PhDm,
- Hyoung-Mo Yang, MD, PhDn,o,
- Sérgio B. Baptista, MDp,
- George S. Chrysant, MDq,
- Antonio M. Leone, MD, PhDr,
- Colin Berry, MBChB, PhDg,h,
- Bernard De Bruyne, MD, PhDe,
- K. Lance Gould, MDa,
- Richard L. Kirkeeide, PhDa,
- Keith G. Oldroyd, MBChB, MDg,
- Nico H.J. Pijls, MD, PhDd,s and
- William F. Fearon, MDn
- aWeatherhead PET Center, Division of Cardiology, Department of Medicine, McGovern Medical School at UTHealth and Memorial Hermann Hospital, Houston, Texas
- bDivision of Cardiovascular Medicine, Stony Brook University Medical Center, Stony Brook, New York
- cCardiovascular Research Foundation (CRF), New York, New York
- dDepartment of Cardiology, Catharina Hospital, Eindhoven, the Netherlands
- eCardiovascular Center, OLV Clinic, Aalst, Belgium
- fKarolinska Institutet, Department of Clinical Science and Education, Division of Cardiology, Södersjukhuset, Stockholm, Sweden
- gWest of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank, Scotland
- hBritish Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland
- iDepartment of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
- jDepartment of Medicine, Columbia University Medical Center, New York, New York
- kDivision of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
- lDepartment of Interventional Cardiology, Hospices Civils de Lyon and CARMEN, INSERM 1060, Lyon, France
- mHeart Institute, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
- nStanford University Medical Center and the Palo Alto VA Health Care Systems, Stanford and Palo Alto, California
- oDepartment of Cardiology, Ajou University School of Medicine, Suwon, South Korea
- pFernando da Fonseca Hospital, Amadora, Portugal
- qDepartment of Cardiology, INTEGRIS Baptist Medical Center, Oklahoma City, Oklahoma
- rInstitute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy
- sDepartment of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
- ↵∗Reprint requests and correspondence:
Dr. Nils P. Johnson, Weatherhead PET Center, McGovern Medical School at UTHealth at Houston, 6431 Fannin Street, Room MSB 4.256, Houston, Texas 77030.
Objectives This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) ≤0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure (Pa), and the instantaneous wave-free ratio (iFR).
Background FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR.
Methods We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion.
Results A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 ± 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias <0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR ≤0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p < 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR.
Conclusions cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to simplify invasive coronary physiological assessments. Yet FFR remains the reference standard for diagnostic certainty as even cFFR reached only ∼85% agreement.
Dr. Johnson has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; and significant institutional research support from St. Jude Medical (for this study [NCT02184117]) and Volcano/Philips Corporation (for NCT02328820), makers of intracoronary pressure and flow sensors. Dr. Jeremias has served as a consultant and member of the Speakers’ Bureau for Volcano/Philips Corporation. Dr. Koo has received institutional research support from St. Jude Medical. Dr. Maehara has received research grants from Boston Scientific. Dr. Barbato has received institutional consultancy fees and research support from St. Jude Medical. Dr. Park has received consultancy fees and research support from Abbott Vascular, Boston Scientific, and Medtronic; and has equity in the CardioVascular Research Foundation. Dr. Baptista has received institutional research support from St. Jude Medical, Medtronic, Cordis Johnson & Johnson, AstraZeneca, and Merck Sharp & Dohme; and receives consultancy fees from St. Jude Medical. Dr. Chrysant is a consultant for Abbott Vascular, The Medicines Company, and St. Jude Medical. Dr. Leone has received speaker honoraria from St. Jude Medical. Dr. Berry has received institutional research grant support and serves as a consultant for St. Jude Medical. Dr. De Bruyne has received institutional consultancy fees and research support from St. Jude Medical and Boston Scientific. Dr. Gould has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis and is the 510(k) applicant for CFR Quant (K113754) and HeartSee (K143664), software packages for cardiac positron emission tomography image processing and analysis, including absolute flow quantification. Dr. Kirkeeide has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis. 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; has served as a consultant for St. Jude Medical, Boston Scientific, and Opsens; and has equity in Philips, GE, ASML, and HeartFlow. Dr. Fearon has received institutional research support from St. Jude Medical and Medtronic; has received honoraria from Medtronic; and has served as a consultant to HeartFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 6, 2015.
- Revision received December 28, 2015.
- Accepted December 29, 2015.
- 2016 American College of Cardiology Foundation