Continuum of Vasodilator Stress From Rest to Contrast Medium to Adenosine Hyperemia for Fractional Flow Reserve Assessment.
OBJECTIVE
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.
Weatherhead PET Center, Division of Cardiology, Department of Medicine, McGovern Medical School at UTHealth and Memorial Hermann Hospital, Houston, Texas. Electronic address: Nils.Johnson@uth.tmc.edu.
Nils P
NP
Johnson
Division of Cardiovascular Medicine, Stony Brook University Medical Center, Stony Brook, New York; Cardiovascular Research Foundation (CRF), New York, New York.
Allen
A
Jeremias
Department of Cardiology, Catharina Hospital, Eindhoven, the Netherlands.
Frederik M
FM
Zimmermann
Cardiovascular Center, OLV Clinic, Aalst, Belgium.
Julien
J
Adjedj
Karolinska Institutet, Department of Clinical Science and Education, Division of Cardiology, Södersjukhuset, Stockholm, Sweden.
Nils
N
Witt
West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank, Scotland; British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland.
Barry
B
Hennigan
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
Bon-Kwon
BK
Koo
Cardiovascular Research Foundation (CRF), New York, New York; Department of Medicine, Columbia University Medical Center, New York, New York.
Akiko
A
Maehara
Cardiovascular Research Foundation (CRF), New York, New York.
Mitsuaki
M
Matsumura
Cardiovascular Center, OLV Clinic, Aalst, Belgium; Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy.
Emanuele
E
Barbato
Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy.
Giovanni
G
Esposito
Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy.
Bruno
B
Trimarco
Department of Interventional Cardiology, Hospices Civils de Lyon and CARMEN, INSERM 1060, Lyon, France.
Gilles
G
Rioufol
Heart Institute, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Seung-Jung
SJ
Park
Stanford University Medical Center and the Palo Alto VA Health Care Systems, Stanford and Palo Alto, California; Department of Cardiology, Ajou University School of Medicine, Suwon, South Korea.
Hyoung-Mo
HM
Yang
Fernando da Fonseca Hospital, Amadora, Portugal.
Sérgio B
SB
Baptista
Department of Cardiology, INTEGRIS Baptist Medical Center, Oklahoma City, Oklahoma.
George S
GS
Chrysant
Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy.
Antonio M
AM
Leone
West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank, Scotland; British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland.
Colin
C
Berry
Cardiovascular Center, OLV Clinic, Aalst, Belgium.
Bernard
B
De Bruyne
Weatherhead PET Center, Division of Cardiology, Department of Medicine, McGovern Medical School at UTHealth and Memorial Hermann Hospital, Houston, Texas.
K Lance
KL
Gould
Weatherhead PET Center, Division of Cardiology, Department of Medicine, McGovern Medical School at UTHealth and Memorial Hermann Hospital, Houston, Texas.
Richard L
RL
Kirkeeide
West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank, Scotland.
Keith G
KG
Oldroyd
Department of Cardiology, Catharina Hospital, Eindhoven, the Netherlands; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Nico H J
NHJ
Pijls
Stanford University Medical Center and the Palo Alto VA Health Care Systems, Stanford and Palo Alto, California.
William F
WF
Fearon
D000241:Adenosine / Q000008:administration & dosage*; D000368:Aged; D019540:Area Under Curve; D062186:Arterial Pressure; D006328:Cardiac Catheterization / Q000379:methods*; D003287:Contrast Media / Q000008:administration & dosage*; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000628:therapy; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005260:Female; D053805:Fractional Flow Reserve, Myocardial; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage*
D003287:Contrast Media; D014665:Vasodilator Agents; D000241:Adenosine
adenosine; contrast medium; fractional flow reserve; hyperemia; instantaneous wave-free ratio