Accepted Manuscript

Non-invasive fractional flow reserve in vessels without severe obstructive stenosis is

associated with coronary plaque burden

Mhairi K. Doris, Yuka Otaki, Yoav Arnson, Balaji Tamarappoo, Markus Goeller,
Heidi Gransar, Frances Wang, Sean Hayes, John Friedman, Louise Thomson, Piotr
Slomka, Damini Dey, Daniel Berman
PII: S1934-5925(18)30095-9
DOI: 10.1016/j.jcct.2018.05.003
Reference: JCCT 1096

To appear in: Journal of Cardiovascular Computed Tomograph

Received Date: 15 February 2018

Revised Date: 13 April 2018
Accepted Date: 3 May 2018

Please cite this article as: Doris MK, Otaki Y, Arnson Y, Tamarappoo B, Goeller M, Gransar H, Wang
F, Hayes S, Friedman J, Thomson L, Slomka P, Dey D, Berman D, Non-invasive fractional flow reserve
in vessels without severe obstructive stenosis is associated with coronary plaque burden, Journal of
Cardiovascular Computed Tomograph (2018), doi: 10.1016/j.jcct.2018.05.003.

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 ACCEPTED MANUSCRIPT

Non-invasive fractional flow reserve in vessels without severe obstructive

stenosis is associated with coronary plaque burden

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*Mhairi K Doris1,2, *Yuka Otaki1, Yoav Arnson1, Balaji Tamarappoo1, Markus

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Goeller1, Heidi Gransar1, Frances Wang1, Sean Hayes1, John Friedman1,

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Louise Thomson1, Piotr Slomka1, Damini Dey1, Daniel Berman1.

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Department of Imaging and Medicine and Biomedical Sciences, Cedars-Sinai
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Medical Center, Los Angeles, CA, USA.

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Centre for Cardiovascular Science, University of Edinburgh, Scotland, UK
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Authors:
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* Mhairi Doris: Mhairi.Doris@ed.ac.uk

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* Yuka Otaki: Yuka.Otaki@cshs.org

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Balaji Tamarappoo: Balaji.Tamarappoo@cshs.org

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Yoav Arnson: Yoav.Arnson@cshs.org

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Markus Goeller: markus.goeller@cshs.org

Heidi Gransar: Heidi.Gransar@cshs.org

Frances Wang: Frances.Wang@cshs.org

Sean Hayes: Sean.Hayes@cshs.org

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John Friedman: John.Friedman@cshs.org

Louise Thomson: Louise.Thomson@cshs.org

Piotr J. Slomka: Piotr.Slomka@cshs.org

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Damini Dey: Damini.Dey@cshs.org

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Daniel S. Berman: Daniel.Berman@cshs.org

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Word count: 4089 AN
Brief title:

* Authors contributed equally

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Address for correspondence

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Daniel S. Berman
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Cedars-Sinai Medical Center, Los Angeles, California USA

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8700 Beverly Boulevard, Los Angeles, California 90048

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Tel: +1- 310-423-4223

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Email: Daniel S. Berman: Daniel.Berman@cshs.org

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ABSTRACT

Aims

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Non-invasive fractional flow reserve derived from coronary CT angiography

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(FFRCT) has been shown to be predictive of lesion-specific ischemia as

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assessed by invasive fractional flow reserve (FFR). However, in practice,

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clinicians are often faced with an abnormal distal FFRCT in the absence of a
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discrete obstructive lesion. Using quantitative plaque analysis, we sought to

determine the relationship between an abnormal whole vessel FFRCT (V-FFRCT)

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and quantitative measures of whole vessel atherosclerosis in coronary arteries

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without obstructive stenosis.

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Methods
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FFRCT was calculated in 155 consecutive patients undergoing coronary CTA

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with ≥25% but less than 70% stenosis in at least one major epicardial vessel.
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Semi-automated software was used to quantify plaque volumes (total plaque

[TP], calcified plaque [CP], non-calcified plaque [NCP], low-density non-calcified

plaque [LD-NCP]), remodeling index [RI], maximal contrast density difference

[CDD] and percent diameter stenosis [%DS]. Abnormal V-FFRCT was defined as

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a minimum value of ≤0.75 across the vessel (at the most distal region where

FFRCT was computed).

Results

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Vessels with abnormal V-FFRCT had higher per-vessel TP (554 vs 331 mm3),

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CP (59 vs 25 mm3), NCP (429 vs 295 mm3), LD-NCP (65 vs 35 mm3) volume

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and maximum CDD (21 vs 14%) than those with normal V-FFRCT (median,

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p<0.05 for all). Using a multivariate analysis to adjust for CDD and %DS, all
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measures of plaque volume were predictive of abnormal V-FFRCT (OR 2.09,

1.36, 1.95, 1.95 for TP, CP, NCP and LD-NCP volume, respectively; p<0.05 for
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all).
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Conclusion
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Abnormal V-FFRCT in vessels without obstructive stenosis is associated with

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multiple markers of diffuse non-obstructive atherosclerosis, independent of

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stenosis severity. Whole vessel FFRCT may represent a novel measure of

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diffuse coronary plaque burden.

Keywords

Fractional flow reserve; plaque characteristics; diffuse atherosclerosis.

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Abbreviations

CTA = Computed tomography angiography

FFRCT = coronary CT angiography -derived fractional flow reserve

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V-FFRCT = whole vessel FFRCT

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NCP = non-calcified plaque

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LD-NCP = low-density non-calcified plaque

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CP = calcified plaque AN
CDD = contrast density difference

SD = standard deviation
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TP = total plaque
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RI = remodeling index
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%DS = percent diameter stenosis

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INTRODUCTION

The emergence of non-invasive FFR, derived from coronary computed

tomography angiography (FFRCT), has been an important advance in combining

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detailed information regarding anatomy and physiology using coronary CT

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angiography (CTA) in a single standard examination.

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FFRCT has been demonstrated to predict invasive FFR (1-3) and improve

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diagnostic specificity for the detection of hemodynamically significant coronary
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lesions compared to coronary computed tomography angiography (CTA) alone.

(3)
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Quantitative plaque analysis from coronary CTA can allow the measurement of
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plaque volume and composition in specific lesions and whole vessels, providing
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detailed information about plaque burden and adverse plaque characteristics.

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Such methods have been used to investigate the impact of adverse plaque
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characteristics on FFRCT and myocardial ischemia, demonstrating that the

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presence of large plaque volume and adverse plaque characteristics, such as

positive remodeling and a lipid core, can allow the identification of ischemia-

inducing lesions, independent of the degree of stenosis. (4-6) There has been

uncertainty regarding the anatomical location where FFRCT should be computed

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relative to a stenosis (7), although studies have evaluated the role of FFRCT in

detecting functionally significant lesions just distal to a stenosis as an alternative

to invasive FFR (8). The relationship between per-vessel FFRCT values and

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diffuse epicardial disease, however, is unknown. We hypothesized that whole

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vessel FFRCT (V-FFRCT) may reflect whole vessel plaque burden in vessels

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without severe stenosis.

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METHODS

Study population
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One hundred and fifty-five patients who underwent clinically indicated coronary
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CTA at Cedars Sinai Medical Centre between February and October 2016 with
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at least 25% stenosis in one major epicardial vessel were included. FFRCT was
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calculated as previously described (Heartflow, Inc; Redwood City, CA, USA). (9)
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Patients with prior coronary stent implantation, coronary artery bypass surgery
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or inadequate CTA image quality for FFRCT processing were excluded from the

analysis. The study protocol was approved by the Cedars-Sinai Institutional

Review Board and all patients provided written informed consent.

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Coronary computed tomography angiography acquisition

Coronary CTA was performed on a dual-source CT scanner (Somatom,

Siemens Medical Solutions, Forchheim, Germany). When necessary, oral

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and/or intravenous metoprolol was administered to achieve a target heart rate

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of ≤70 beats/min (bpm). (10) Immediately prior to CTA, 0.4 or 0.8 mg of

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sublingual nitroglycerin (ScielePharma, Alpharetta, Georgia) was administered.

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Images were acquired with prospective ECG-gating following the administration
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of 85ml intravenous contrast (Omnipaque or Visipaque, GE Healthcare,

Princeton, New Jersey). In the event of suboptimal heart rate control, helical
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images were acquired with dose modulation. Acquisition and reconstruction

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parameters included: tube voltage of 120 or 100 kVp (the latter used in patients
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with weight <200 pounds or BMI < 30 kg/m²), 0.6-mm slice thickness, 0.3-mm
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slice increment, 250-mm field-of-view, and 512 × 512 matrix.

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Quantitative coronary plaque analysis

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Coronary segments with a luminal diameter ≥2 mm and with visible plaque were

analyzed along the entire length of the coronary arteries using semi-automated

software (AutoPlaque version 2.0, Cedars-Sinai Medical Center, Los Angeles,

CA, USA). Four experienced readers (Y.O, M.D, Y.A and B.K.T) who were

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blinded to the coronary CTA findings and FFRCT values analyzed 365 vessels

with visible coronary plaque using multiplanar coronary CTA images. Percent

diameter stenosis (%DS) was calculated by dividing the narrowest lumen

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diameter by the mean of two non-diseased reference points. Attenuation

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thresholds for non-calcified, calcified plaque and lumen were computed from a

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standardized region-of-interest placed on the aorta, as previously described.

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(11,12) Low-density non-CP (LD-NCP) was defined as plaque with attenuation
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<30 Hounsfield units. Plaque components were quantified within the manually

designated areas using adaptive algorithms. (12) Remodeling index was

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determined as the ratio of maximum vessel area to that at the proximal normal
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reference point. (13) The measure of plaque length was provided by the semi-
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automated software and includes the diseased cross-sections measured in

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millimetres from the beginning to distal boundaries of the quantified plaque in

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millimetres. Contrast density difference across the lesion was computed as

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follows: the luminal contrast density, defined as attenuation per unit area,

similar to area gradient, (14) was computed over 1-mm cross sections of the

arterial segment. The contrast density difference was defined as the maximum

percent difference in contrast density compared to a proximal reference cross

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section without atherosclerotic disease. Manual adjustments of vessel contours

were made if necessary. For each artery, whole vessel plaque volume

measurements were obtained by the sum of plaque volumes in each segment

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of the three major epicardial coronary vessels (left anterior descending, left

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circumflex and right coronary arteries).

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Plaque analysis was performed on a per-vessel basis after excluding vessels

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with severe obstructive stenosis (%DS ≥70), as the V-FFRCT values would be
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expected to be dominated by the presence of obstructive stenosis in these

patients. The time required for whole vessel quantitative plaque analysis was
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approximately 10 minutes per vessel.

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Computation of fractional flow reserve derived from coronary computed

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tomography angiography
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Computation of FFRCT was performed centrally by independent blinded analysts

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(Autoplaque version 2.0). The FFRCT computation process has previously been

described in detail. (3,9) Briefly, non-invasive fractional flow reserve (FFRCT)

applies computational fluid dynamics to calculate the drop in coronary pressure

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across a stenosis as a ratio to pressure in a non-diseased artery, thereby acting

as a surrogate measure of ischaemia.

In each subject, FFRCT was computed throughout the coronary tree. The distal

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minimum values for each entire coronary vessel (V-FFRCT) were included in the

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analysis. A whole vessel FFRCT ≤0.75 was considered abnormal. If the FFRCT

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could not be calculated due to small vessel caliber or poor image quality, the

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vessel was excluded from analysis. A case example illustrating quantitative
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plaque analysis and V-FFRCT is shown in Figure 1.

Statistical analysis
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Continuous variables were presented as mean +/- standard deviation (SD) or

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median (interquartile range) as appropriate, after being assessed for normality

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using the Shapiro-Wilks test. Categorical variables were expressed as numbers

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and percentages. Quantitative plaque parameters across >2 groups were

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compared using the Kruskal-Wallis test; categorical variables were compared

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across groups using Pearson Chi-square test or Fisher Exact test for cell counts

< 6. The relationship between qunatitative plaque measures (TP, CP, NCP and

LD-NCP volumes, CDD, diameter stenosis, remodeling index, and plaque

length) and abnormal V-FFRCT was evaluated by univariate and multivariate

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logistic regression analysis after adjusting for contrast density difference, and

diameter stenosis. In logistic regression anlaysis, quantitative plaque measures

were log-transformed. To account for collinearity in measurements of plaque

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volume, different multivariate models were used to assess the relationship

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between V-FFRCT and TP, CP, NCP and LD-NCP. Four different multivariable

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analyses were performed using logistic regression adjusted for CDD and

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diameter stenosis to investigate the association between abnormal V-FFRCT
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and TP, CP, NCP and LD-NCP volumes, respectively. Because up to three

coronary arteries were examined per patient, intraclass coefficients were

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calculated to assess the within-patient correlations, as previously described.

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(15) For logistic regression analyses, the standard errors were then adjusted
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using the clustered sandwich estimator to take into account the within-group
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correlations of up to 3 coronary arteries per patient. (16) Statistical analyses

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were performed with Stata software version 13 (StataCorp, College Station, TX,
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USA) and SPSS version 22 (IBM Corp, USA). Two-sided P-values <0.05 were

considered statistically significant.

Results

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Patient characteristics and vessels analyzed

Baseline characteristics of the study population are shown in Table 1. From a

total of 465 vessels in 155 patients, 168 vessels were excluded from the

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analysis. This included 100 vessels with no visible plaque, 54 vessels with

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quantitative diameter stenosis >70%, and 25 vessels in which FFRCT could not

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be processed due to small vessel caliber. Of the remaining 297 vessels

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included in the analysis, 122 (41%) comprised the left anterior descending
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coronary artery, 80 (27%) the left circumflex coronary artery, and 95 (32%) the

right coronary artery.

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Relationship between coronary quantitative diameter stenosis severity

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and V-FFRCT
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There were 32 vessels with abnormal V-FFRCT and 265 vessels with normal V-
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FFRCT. Maximum quantitative diameter stenosis was significantly higher in

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vessels with abnormal V-FFRCT than in vessels with normal V-FFRCT (diameter

stenosis [median, IQR]: 40%, 26-47% in abnormal V-FFRCT vs. 26%, 14-37% in

normal V-FFRCT, p=0.003, Figure 2B). There was no difference in the frequency

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of vessels with 50-69% stenosis between the groups with normal and abnormal

V-FFRCT (16% in abnormal V-FFRCT vs. 12% in normal V-FFRCT, p=0.61).

Relationship between plaque characteristics and V-FFRCT

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Total plaque volume, CP volume, NCP volume, and LD-NCP volume were

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higher in vessels with abnormal V-FFRCT than in vessels with normal V-FFRCT

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(p<0.005 for all, Figure 2A). Moreover, vessels with abnormal V-FFRCT had

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higher maximal CDD and plaque length compared to vessels with normal V-
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FFRCT (p<0.005 for both, Figure 2B). There was no significant difference in

remodeling index between vessels with normal and abnormal V-FFRCT (Figure
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2C).
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Plaque characteristics to predict abnormal V-FFRCT in univariate and

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multivariate analysis
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In univariate analysis to predict abnormal V-FFRCT, all measures of plaque

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volume (TP, CP, NCP, and LD-NCP), CDD, plaque length and diameter
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stenosis were independent predictors of an impaired V-FFRCT (Table 2). In

multivariate analysis adjusting for CDD and diameter stenosis, the results

demonstrated a significant association between abnormal V-FFRCT and log-

transformed TP, CP, NCP and LD-NCP volumes (Odds ratio of TP volume:

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2.09, 95% CI: 1.09 to 4.01, p=0.03, odds ratio for CP volume: 1.36, 95% CI:

1.01 to 1.84, p=0.04, odds ratio of NCP volume: 1.95, 95% CI: 1.02 to 3.75,

p=0.04, odds ratio of LD-NCP volume: 1.95, 95%CI: 1.06 to 3.57, p=0.03, Table

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3 Model 1-4). CDD was a significant predictor of an abnormal V-FFRCT in all

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multivariate models (Table 3 Model 1-4).

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Association between plaque characteristics and abnormal V-FFRCT in
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vessel with <50% stenosis

In vessels with a maximum diameter stenosis <50% (n=259), there were 27

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vessels with abnormal V-FFRCT and 232 vessels with normal V- FFRCT.
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Multivariate analysis was performed using four models, as described above, to

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investigate the association between plaque volumes (TP, CP, NCP and LD-
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NCP) and abnormal V-FFRCT, adjusting for CDD and diameter stenosis.
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In vessels with a maximum diameter stenosis of less than 50%, the results also
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demonstrated a significant association between abnormal V-FFRCT and log-

transformed TP, CP, NCP and LD-NCP volumes (Odds ratio for TP volume:

2.89, 95% CI: 1.26 to 6.63, p=0.01, odds ratio for CP volume: 1.67, 95% CI:

1.14 to 2.46, p=0.009, odds ratio of NCP volume: 2.40, 95% CI: 1.06 to 5.45,

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p=0.04, and odds ratio of LD-NCP volume: 2.72, 95%CI: 1.33 to 5.58, p=0.006,

Table 3 Model 1-4). CDD remained a significant predictor for an abnormal V-

FFRCT in all four multivariate models (Table 3 Model 1-4).

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DISCUSSION

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Lesion-specific non-invasive fractional flow reserve have been demonstrated to

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correlate well with invasive FFR and predict lesion-specific ischemia. However,
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the relationship between a graded drop in non-invasive fractional flow reserve

and quantitative plaque characteristics on a whole vessel basis has, to our

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knowledge, not previously been examined. Using semi-automated quantitiave

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plaque analysis, we have shown that plaque volume and characteristics

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quantified on a per-vessel basis predict an abnormal FFRCT, suggesting that an

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abnormal V-FFRCT may reflect diffuse epicardial atherosclerosis.

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A previous study has investigated the influence of diffuse non-obstructive

atherosclerosis on distal FFR measured invasively and demonstrated that

vessels with diffuse but angiographically insignificant disease exhibit a gradual

and progressive decline in FFR across the length of the vessel. (17) This

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continuous drop in pressure on FFR was observed in half of the vessels with

luminal irregularities but no visual stenosis on invasive angiography, while there

was no distal decline in FFR in vessels without evidence of disease. Our results

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add further support to the finding that an impaired whole vessel fractional flow

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reserve may reflect diffuse atherosclerosis. Further, we have expanded these

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findings by evaluating plaque characteristics on CT and performing detailed

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plaque quantification. In our results, non-calcified plaque volume and low-
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density non-calcified plaque volume, a CT-identified surrogate measure of lipid

core, were independent predictors of an impaired distal FFRCT. Indeed, both

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non-calcified plaque volume and low-density non-calcified plaque volume were

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stronger predictors of abnormal V-FFRCT than calcified plaque volume. This

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relationship persisted even when all vessels with greater than 50% stenosis
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were excluded from analysis.

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Recent studies have highlighted that lesion-specific plaque characteristics can

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influence fractional flow reserve, and lipid density has consistently been

identified as a strong predictor of flow in lesion-specific analyses. (5,18,19) This

relationship was extended to entire vessels in our study as demonstrated in our

results which revealed lipid density to be an independent predictor of an

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abnormal whole vessel FFRCT in vessels without obstructive stenosis. This

suggests that distal FFRCT may be reflective of the presence of, not only diffuse

disease, but also adverse plaque features.

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Previous studies have utilized intravascular ulstrasound (IVUS) imaging to

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demonstrate that, in the early stages of atherosclerosis, endothelial dysfunction

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leads to abnormal endothelial reactivity and, even in minimal atherosclerosis,

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the presence of local endothelial dysfunction is closely associated with high-risk
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plaque characteristics including the presence of a lipid core. (20) The

pathophysiological explanation for this finding is considered to be a

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consequence of the pro-inflammatory and oxidative effect exerted by the

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necrotic core which results in reduced nitric oxide bioavailability and an increase
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in local vasoconstriction by mediators such as isoprostane. (21,22) It may

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therefore be hypothesized that an abnormal V-FFRCT relates to impaired

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vascular reactivity across the length of the vessel, although further studies are
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required to confirm this.

Our findings regarding the relationship between quantitative whole vessel

plaque characteristics and whole vessel FFRCT are similar to relationships

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observed with segmental plaque characteristics and lesion-specific FFRCT. In

patients with intermediate grade stenosis, we have previously shown that

plaque burden on a per-patient basis is predictive of an abnormal invasive FFR.

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(5) In a study of 56 patients undergoing invasive coronary angiography and

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invasive FFR, total plaque burden was a significant predictor of impaired

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invasive FFR (Odds Ratio [OR] 1.15, P=0.007). (5) Further, in a study

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examining the relationship between plaque features and FFR, percent
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aggregate plaque volume (defined as the aggregate plaque volume divided by

the total vessel volume) provided incremental prediction of ischaemia by

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invasive FFR when added to adverse plaque characteristics and CTA-

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measured stenosis. (19)

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Another recent study examined the effects of diffuse atherosclerosis and,

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specifically, lesion length in all grades of stenosis and demonstrated that diffuse
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disease, as measured by lesion length, was an independent predictor of

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invasive FFR. (23) Our report, however, is the first to our knowledge to assess

the impact of quantitative plaque volume, burden and composition in vessels

with <70% stenosis on whole vessel FFRCT, and suggests that distal whole

vessel FFRCT is reflective of whole vessel plaque burden.

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We excluded severe stenosis in our analysis because we expected an

individual stenosis to impact on the distal FFRCT value. Nonetheless, even with

this exclusion, the maximum contrast density difference was predictive of

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abnormal V-FFRCT. Of importance, this relationship was observed even when

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vessels with 50-69% stenosis were excluded. This highlights that the abnormal

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distal V-FFRCT values were not observed only as a direct consequence of a

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single proximal obstructive lesion.AN
Further, we adopted a threshold of less than or equal to 0.75 as indicative of an

abnormal V-FFRCT. While this is lower than invasive FFR and FFRCT thresholds
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used in prior lesion-specific studies, (18,24) we wished to employ a value which

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would more reliably discriminate an abnormal distal pressure reserve. (25)

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Indeed, while previous studies have adopted a threshold of 0.80 as a ‘normal’

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FFRCT, FFRCT values between 0.75 and 0.80 are considered borderline, with
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45% of lesions causing no ischemia on invasive testing. The probability of

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inducible ischemia increases as FFRCT values fall, with 92% of lesions with an

FFRCT ≤0.75 demonstrating ischemia on invasive testing. (8)

Limitations

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While we have identified that diffuse non-obstructive disease and the presence

of high risk plaque characteristics predict an abnormal distal FFRCT, the

relationship between abnormal V-FFRCT and tissue ischemia has not yet been

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documented. Future studies should consider the relationship between abnormal

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V-FFRCT and non-invasive measures of coronary flow or ischemia, such as

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coronary flow reserve. Coronary flow reserve (CFR), measured by PET

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perfusion imaging, provides an integrated analysis of myocardial perfusion and
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the hemodynamic effects of both epicardial atherosclerosis and microvascular

dysfunction in combination and could provide insight in this regard, particularly

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as a means of further understanding the relationship between microvascular

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dysfunction and non-obstructive coronary atherosclerosis in patients

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manifesting evidence of myocardial ischemia without significant epicardial

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coronary stenosis.
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Conclusions
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Abnormal V-FFRCT in vessels without obstructive stenosis is associated with

multiple markers of diffuse non-obstructive atherosclerosis, independent of

stenosis severity. Whole vessel FFRCT may represent a novel measure of

diffuse coronary plaque burden.

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Funding Sources

This work was supported in part by the Cardiac Imaging Research Initiative

(Adelson Medical Research Foundation) and Heartflow.

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Conflict of Interest

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P.J.S., D.S.B., and D.D. received software royalties from Cedars-Sinai Medical

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Center and have a patent. All other authors have nothing to declare.

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Table 1. Patient characteristics

Number of patients 155

Age, years (mean ± SD) 66±10

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Male, n (%) 113 (73)

Body mass index, kg/m2 (mean ± SD) 27±5

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Risk factors and history of coronary artery disease

Diabetes, n (%) 27 (17)

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Hypertension, n (%) 81 (52)

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Hyperlipidemia, n (%) 110 (71)
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Current smoker, n (%) 11 (7)

Previous myocardial infarction, n (%) 2 (1)

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Symptoms

Typical angina, n (%) 8 (5)

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Atypical angina, n (%) 12 (8)

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Nonanginal chest pain, n (%) 45 (29)

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Shortness of breath, n (%) 72 (46)

Asymptomatic, n (%) 55 (35)

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SD= standard deviation

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Table 2. Univariate logistic regression analysis of quantitative plaque

features for ischemia based on impaired whole vessel; FFRCT

Odds ratio (95% CI) p value

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TP volume 2.03 (1.32-3.10) 0.001

CP volume 1.36 (1.11-1.67) 0.004

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NCP volume 1.93 (1.26-2.94) 0.002

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LD-NCP volume 2.00 (1.35-2.96) 0.001

Contrast density difference 3.35 (1.76-6.35) <0.001

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Diameter stenosis 1.03 (1.01-1.05) 0.006
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Remodeling index 7.16 (0.99-51.50) 0.05

Plaque length 2.31 (1.40-3.79) 0.001

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TP=total plaque, CP=calcified plaque, NCP=non-calcified plaque, LD-NCP=

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low-density-non-calcified plaque, CI=confidence interval

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Table 3. Multivariate logistic regression analysis of quantitative plaque

features for ischemia based on impaired whole vessel FFRCT (297 vessles

with stenosis <70% and 259 vessels with <50% stenosis)

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Max Diameter Stenosis

Max Diameter Stenosis <50%
<70%
Odds Ratio pValu Odds Ratio p Value
(95% CI) e (95% CI)

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Model 1
2.09 2.89

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Total Plaque Volume 0.03 0.01
(1.09-4.01) (1.26-6.63)
Contrast Density 4.65 4.44
0.002 0.008
Difference (1.77-12.22) (1.46-13.44)

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1.70
Diameter stenosis … 0.29 0.20
(0.76-3.80)
Model 2
Calcified Plaque 1.36
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0.04 0.009
Volume (1.01-1.84) (1.14-2.46)
Contrast Density 3.90 4.11
0.007 0.01
Difference (1.45-10.47) (1.36-12.39)
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1.56 2.11
Diameter Stenosis 0.15 0.08
(0.85-2.89) (0.91-4.87)
Model 3
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Non-Calcified Plaque 1.95 2.40

0.04 0.04
volume (1.02-3.75) (1.06-5.45)
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Contrast Density 4.82 4.63

0.001 0.006
Difference (1.84-12.64) (1.55-13.85)
1.72
Diameter Stenosis … 0.29 0.18
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(0.77-3.82)
Model 4
Low Density Non-
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1.95 2.72
Calcified Plaque 0.03 0.006
(1.06-3.57) (1.33-5.58)
Volume
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Contrast Density 3.86 3.64

0.006 0.02
Difference (1.46-10.22) (1.27-10.43)
Diameter Stenosis … 0.33 … 0.21

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Figure 1. A case example of a 52 year old asymptomatic male with risk

factors for coronary artery disease.

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CCTA demonstrates diffuse plaque in the proximal to distal portions of the left
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anterior descending coronary artery (LAD) (A). FFRCT was computed in the LAD
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and the results demonstrate an FFRCT value of 0.80 across the region of

maximal stenosis and a distal V-FFRCT value (whole vessel FFRCT) of 0.73 (B).

Quantitative plaque analysis was performed using AutoPlaque (C & D: proximal

to mid LAD and E & F: mid to distal LAD) and demonstrated total non-calcified

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plaque (760 mm3, red), total calcified plaque (67mm3, yellow), total low-density

non-calcified plaque (48 mm3), maximum remodeling index 1.6, maximum

contrast density difference 30% and maximum diameter stenosis 47%.

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Figure 2. Differences in coronary plaque volume (A), contrast density

difference, diameter stenosis and plaque length (B) and remodeling index

(C) between vessels with normal and abnormal V-FFRCT.

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Distributions of plaque volume and plaque sub-components boxes indicate

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quartiles, and whiskers display adjacent values. V-FFRCT: whole vessel FFRCT,

NCP: non-calcified plaque, LD-NCP: low-density non-calcified plaque, CP:

calcified plaque, TP: total plaque, CDD: contrast density difference.

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