Plaque assessment on coronary CT Angiography: Is there clinical value ?

Damini.Dey@cshs.org

Damini Dey, PhD, FSCCT

Associate Professor and Research Scientist Director, Quantitative Image Analysis Lab

Biomedical Imaging Research Institute Cedars-Sinai Medical Center

Normal coronary CTA

43-y/o woman, family history of CAD

Normal CCTA. HR 65 bpm

100 kVp, Prospective

Radiation Dose 1.5 mSv

Warranty period for normal CTA: at least 8 years

Coronary CTA – with Atherosclerosis

Noncalcified, low-density non-calcified plaque Calcified plaque

Dangerous plaques: healing the heart National Geographic 2007

Coronary plaque

Plaque assessment from coronary CTA

• High-risk plaque features - Low-attenuation < 30 HU - Positive remodeling - Napkin-ring sign • Quantitative plaque Characterization - Low-attenuation NCP - Plaque composition, burden - Positive remodeling - Stenosis & luminal features

Motoyama et al JACC 2009 Otsuka et al JACC imaging 2013

Hell et al EHJ-CI 2017, Doris et al JCCT 2017

Quantitative plaque characterization from coronary CTA

• Standardized semi-automated software - Total plaque - Non-calcified plaque (NCP) - Calcified plaque - Low-attenuation NCP - Plaque composition - Positive outward remodeling - Stenosis

Hell et al EHJ-Cardiovascular Imaging 2017 Per-lesion, per-vessel and per-patient

Total coronary plaque volume: IVUS

Matsumoto, …,Dey et al European Radiology 2019

118 plaques in 77 patients with IVUS

R = 0.943, p<0.001

Lumen intima border

External elastic membrane

Coronary CTA

IVUS

NCP volume – blinded comparison to IVUS

Dey et al Radiology 2010

NCP volume measurement

Dey et al Radiology 2010

NCP volume measurement

116.6100.8105.9

0

50

100

150

200

IVUS Manual CCTA

APQ

NCP Volume

P=NS P=NS

Volu

me

(mm

3 )

Dey et al Radiology 2010

Comparison with IVUS: Qangio CT

Park et al Eur Radiol 2015

142 patients

with IVUS

Stenosis, MLA,

plaque volume

and burden

R = 0.91 expert R=0.84 automated

Plaque and Lesion-specific ischemia

from prospective, multicenter studies

Park et al JACC Cardiovascular Imaging 2015 Diaz Zamudio et al Radiology 2015

Gaur et al European Heart Journal 2016

Plaque composition and Lesion-specific ischemia: prospective, multicenter NXT trial

254 patients

Does plaque composition add to stenosis to predict FFR ?

Gaur et al European Heart Journal 2016

• Multicenter NXT trial • 254 patients (64% male) • 484 vessels with FFR

• NXT trial N=254 (484 vessels) analyzed for stenosis, plaque and scan findings • Highest predictive value for contrast density difference and low attenuation plaque

Machine learning for integrating plaque features to predict ischemia Machine learning for decision-making

Dey et al European Radiology 2018

*

Machine learning ischemia risk score from CTA Invasive FFR LAD = 0.73

Dey et al Artificial intelligence in Cardiovascular Imaging JACC 2019

• 2748 patients, no prior CAD • Followup of 5 ± 2 years • 32 patients with cardiac death compared to controls matched by age, gender, risk factors and symptoms • Plaque analysis by Autoplaque

Quantitative plaque: prediction of future cardiac death

Hell et al EHJ Cardiovascular Imaging 2017

Quantitative plaque: prediction of future cardiac death

Michaela Hell et al EHJ Cardiovascular Imaging 2017

Quantitative plaque: prediction of future cardiac death

Among quantitative global plaque characteristics, low-density NCP, NCP and total plaque volume as well

as CDD predict future cardiac death Michaela Hell et al EHJ Cardiovascular Imaging 2017

• ICONIC: nested case control study within CONFIRM registry (13 sites)

• Followup: 3.4 ± 2.1 years • 234 patients with ACS matched

to 234 controls – risk factors and CTA stenosis

• Plaque analysis by core lab with QAngio CT software

Quantitative plaque composition: as precursor of ACS

Chang et al JACC 2018; 71(22):2511-22

• NCP components - Necrotic core NC (-30, 30) HU - Fibrofatty FF (31-130) HU - Fibrous (131-350) HU

• High-risk noncalcified plaque – precursor of ACS

Quantitative plaque composition: as precursor of ACS

Chang et al JACC 2018; 71(22):2511-22

Quantitative plaque burden: beneficial changes with therapy ?

Plaque changes with statins

• PARADIGM cohort (13-center)

• 1255 patients serial CTA ≥ 2 years apart

• Plaque measurement by core lab QAngio CT

Lee et al JACC Cardiovascular Imaging 2018

Plaque changes with statins

Lee et al JACC Cardiovascular Imaging 2018

• PARADIGM cohort (13-center)

• 1255 patients serial CTA ≥ 2 years apart

• Plaque volume: 21% reduction

• HRP: 35% reduction

Plaque changes with statins

Lee et al JACC Cardiovascular Imaging 2018 Lee et al Circ Cardiovascular Imaging 2018

• Statins were associated with slower progression of total plaque volume, with increased plaque calcification and reduction of high-risk plaque features.

• Statins did not affect the progression of percent stenosis but induced changes in plaque composition.

• Both baseline plaque burden and its change improved prediction of MACE

Baseline Follow-up

LDL-C (mg/dl) 164 80

Plaque volume(mm3) Total plaque 581.6 408.0

Calcified plaque 67.8 63.6

Non-calcified plaque 513.9 344.3

Low-density non-calcified plaque 42.2 12.0

Baseline Follow-up

CTA plaque changes with LDL decrease ≥ 10% over 1 year 52 y.o. male with family history of CAD on statin

LAD

CP

NCP

Tamarappoo, Otaki,…, Dey, Berman et al, JCCT 2018

Otaki, Tamarappoo,…, Dey, Berman Otaki et al Atherosclerosis 2019

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20

40

60

80

100

h t tih ti tih ff ti h f ti h d ti

Annu

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hang

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pla

que

volu

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(mm

3 ) p<0.0001

p=0.0001* p=0.0001* p=0.0005* p=0.60

Plaque volume change with LDL decrease and increase All plaque components

Medium attenuation

Total plaque

Calcified plaque

Low attenuation

Medium-low attenuation

Patients with LDL decrease Patients with no LDL decrease

154 patients with serial CTA time interval 4±2 years

Non-calcified plaque

Reduction in LDL (≥10%) related to beneficial changes in plaque composition ( all components of NCP)

• CTA allows plaque characterization over the coronary tree

• Quantitative CTA measures improves prediction of lesion-specific ischemia beyond stenosis

– Low-density noncalcified plaque

– Noncalcified plaque

– Positive remodeling

– Contrast density difference

Summary: quantitative CTA

Adverse cardiac events

• More automation and standardization necessary - for faster accurate analysis

• Adverse plaque thresholds needed

• Noninvasive quantitative plaque characterization

• Improves identification of patients at risk of ischemia and cardiac events

• Improves prognostication

• Allows assessment of serial therapy: emphasis on prevention

Summary

Thank you very much

Quantitative plaque burden predict ischemia in intermediate coronary lesions ?

Diaz-Zamudio et al Radiology 2015

CTA

Automated quantification in a 65-y-o male patient. FFR (at arrow)= 0.78

DS= 34%

TP= 43%

CP= 13%

NCP= 30%

LDNCP= 2%

Quantitative plaque burden predict ischemia in intermediate coronary lesions ?

Diaz-Zamudio et al Radiology 2015

Quantitative plaque burden predict ischemia in intermediate coronary lesions ?

Diaz-Zamudio et al Radiology 2015