Original Research
Adverse Plaque Characteristics Relate More Strongly With Hyperemic Fractional Flow Reserve and Instantaneous Wave-Free Ratio Than With Resting Instantaneous Wave-Free Ratio

https://doi.org/10.1016/j.jcmg.2019.06.013Get rights and content
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Abstract

Objectives

The current substudy of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial explores the impact of computed tomography (CT)–derived unfavorable plaque features on both hyperemic and non-hyperemic flow indices.

Background

Next to lesion severity, plaque vulnerability as assessed using coronary CT angiography affects fractional flow reserve (FFR), which is associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator-free assessment with iFR is associated with plaque stability similarly as FFR.

Methods

Of 120 patients (62% men, age 58.3 ± 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice coronary CT angiography to assess stenosis severity and plaque features (positive remodeling [PR], low attenuation plaque [LAP], spotty calcification [SC], and napkin ring sign [NRS]), as well as intracoronary pressure measurements (FFR, iFR, Pd/Pa, and pressure ratio during adenosine within the wave-free period [iFRa]). CT-derived plaque characteristics were related to these invasive pressure measurements.

Results

Atherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was significantly associated with impaired FFR, iFR, Pd/Pa, and iFRa. Multivariable analysis revealed that FFR and iFR were independently related to ≥70% stenosis (−0.10, p < 0.001 and −0.09, p = 0.003, respectively) and plaque volume (-0.02, p = 0.020 and -0.02, p = 0.030, respectively). Additionally, PR and SC were also independent predictors of an impaired FFR (−0.10, p < 0.001 and −0.07, p = 0.021, respectively), but adverse plaque characteristics were not independently related to the vasodilator-free iFR.

Conclusions

CT-derived vulnerable plaque characteristics are independently associated with hyperemic flow indices as assessed with FFR and iFRa, but not with non-hyperemic indices such as iFR and Pd/Pa. These findings suggest that the effects of hyperemia on pressure-derived indices might depend not only on hemodynamic stenosis severity but also on plaque characteristics.

Key Words

adverse plaque characteristics
coronary artery disease
coronary computed tomography angiography
fractional flow reserve
instantaneous wave-free ratio

Abbreviations and Acronyms

AUC
area under the receiver-operating characteristic curves
CAD
coronary artery disease
CFR
coronary flow reserve
CT
computed tomography
FFR
fractional flow reserve
ICA
invasive coronary angiography
iFR
instantaneous wave-free ratio
iFRa
instantaneous wave-free ratio during adenosine
LAD
left anterior descending
LAP
low attenuation plaque
LCX
left circumflex
MBF
myocardial blood flow
MI
myocardial infarction
NRS
napkin ring sign
PET
positron emission tomography
Pd/Pa
distal coronary artery pressure/aortic pressure
PR
positive remodeling
RCA
right coronary artery
SC
spotty calcification
SPECT
single-photon emission computed tomography

Cited by (0)

Dr. Min has served as a consultant to Abbott Vascular; has served on the Scientific Advisory Board of Arineta and GE Healthcare; has received funding from the Dalio Foundation, the National Institutes of Health, and GE Healthcare; and has an equity interest in MDDX and Cleerly. Dr. Leipsic has received research grants from GE Healthcare; and has served as a consultant to and holds stock options in Circle CVI and HeartFlow. Dr. Davies holds patents pertaining to the iFR technology; has served as a consultant for Philips Volcano; and has received research grants from Philips Volcano. Dr. van Royen has received research grants from Abbott, AstraZeneca, Biotronik, and Philips Healthcare; and has served on the Advisory Board of Boston Scientific, Medtronic, and Amgen. Dr. Knaapen received unrestricted research grants from HeartFlow. Dr. Knuuti has been a study consultant for GE Healthcare and AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Todd Villines, MD, served as Guest Editor for this paper.