Tasneem Z Naqvi, MD, FRCP (UK), RVT, MMM

Director Non-invasive Cardiology and Echocardiography

Professor of Medicine and Clinical Scholar

Keck School of Medicine

University of Southern California, Los Angeles

LATEST DEVELOPMENTS IN NON-INVASIVE IMAGING OF ATHEROSCLEROSIS USING

CAROTID ULTRASOUND (CIMT AND PLAQUE) IN THE NEW ERA OF PCIPreventive Cardiovascular Imaging

DISCLOSURE

I personally perform carotid IMT and plaque assessment for CV risk

assessment in my patients(often free of charge!)

PCI (IMT) IS IN THE GUIDELINES!

For CAD risk assessment in asymptomatic adults at intermediate

risk (Level of Evidence B)

2010 ACCF/AHA Guidelines

IIa “a Reasonable Test” Benefit >> Risk

CAROTID ARTERY WALL LAYERS

• IMT is a normal structure, made up of about 80% media and 20% intima• Atherosclerosis is largely an intimal process

Noninvasive, no radiation

Internal carotid artery

Carotid bifurcation

Common carotid artery

TransducerExternal

carotid artery

Tip of the flow divider

Far wall

Near wall

(10 mm) (10 mm) (10 mm)

CCA

ICA

ECA

CCAbulbbulb

CAROTID ARTERY INTIMA MEDIA THICKNESS ASSESSMENT, MEASUREMENT & REPORTING

• Varying comprehensivenss– single vs. multiple segments, single vs. multiple angles, far wall only, far and near wall, plaque inclusive vs. plaque exclusive

• Phase of cardiac cycle, single vs. multiple frames

• IMT measure - average mean, mean max, max, caliper vs. automated

CAROTID ARTERY INTIMA MEDIA THICKNESS ASSESSMENT, MEASUREMENT & REPORTING

• 75th percentile, standard deviation, upper and lower quartile or tertile, >0.9 mm

• ASE and ACC/AHA recommend 75th percentile

• Differences in Pixel resolution among US systems and transducers

PLAQUE DEFINITION AND ASSESSMENT IN CLINICAL STUDIES

Focal thickening of the carotid wall that is at least 0.5 mm or 50% of surrounding IMT value Focal region with CIMT 1.5 mm that is distinct from adjacent boundary and protrudes into the lumenQuantitative AssessmentCategorical: Yes and No

Quantitative Plaque BurdenNumber of plaques, Plaque thickness, Area, Plaque volume, Vessel volume

Qualitative Assessment• Plaque heterogeneity, irregularity, plaque vascularity, plaque calcification

PLAQUE MORPHOLOGY

PREDICTIVE VALUE OF IMT VS. PLAQUE IN POPULATION BASED STUDIES - FUTURE MI

Inaba Y et al Atherosclerosis Volume 220,2012 128 - 133

SROC Curve

Meta-analysis,11studies, 54,336 patients

Sensitivity

1-specificity

Prediction of Clinical Cardiovascular Events with Carotid Intima-media Thickness

Lorenz M W et al. Circulation 2007;115:459-467

*Adjusted for age, sex, body mass index, systolic and diastolic blood pressure, LDL cholesterol, smoking and diabetes. †Adjusted for age, sex, systolic and diastolic blood pressure, smoking, and diabetes. ‡Adjusted for age, sex, BMI, systolic and diastolic blood pressure, total and HDL cholesterol, smoking, and diabetes. §Adjusted for age, sex, systolic and diastolic blood pressure, total and HDL cholesterol, smoking, diabetes, and cardiovascular disease.

N=37,197FU 5.5 yrs

RR MI & stroke 1.26 & 1.32 per 1 SD CCA IMT difference 1.15 & 1.18 per 0.10-mm CCA IMT difference

Common Carotid Intima-Media Thickness Measurements in Cardiovascular Risk Prediction:  A Meta-analysis

Ruizter H et al. JAMA. 2012;308(8):796-803

N=45,828, FU 11 yrsFRS C statistic 0.757FRS and CIMT 0.759

NRI with common CIMT was 0.8%In Intermediate risk, NRI improvement 3.6%

ARIC STUDY - EVALUATION OF PREDICTIVE ROLE OF IMT AND PLAQUE

Nambi V, et al. JACC 2010;55:1600-1607

At each category of CIMT the presence of plaque is associated with higher incidence of CHD

n=13145 (5682 men, 7463 women

n=13145 (5682 men, 7463 women)

Model Overall Men Women

NRI (%)

Clinical NRI (%)

NRI (%)

Clinical NRI (%)

NRI (%)

Clinical NRI (%)

TRF vs. TRF+CIMT 7.1 16.1 8.9 15.7 6.1 15.9

TRF vs. TRF + plaque 7.7 17.7 4.2 10.5 10.2 25.6

TRF vs. TRF+CIMT+ plaque

9.9 21.7 8.9 16.3 9.7 25.4

ARIC Study Net Reclassification Index Using Various Models

Nambi V, et al. JACC 2010;55:1600-1607

Predictive Role of Carotid Plaque and IMT in Older Adults

No PlaquePlaques at 1 sitePlaques at 2 sites or more

Non

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vent

<0.61mm0.61-0.67mm0.67-0.73mm0.73-0.81mm>0.81mm

Follow- up (Months)

Follow- up (Months)

p= <.001

p= 0.30

Celermajerc D et al Atherosclerosis Volume 219, 2011 917 - 924

5895 CHD-free adults aged 65–85years, FU 5.4 yrs

HR IMT: 0.8

HR plaques: 1 site = 1.5 plaques at ≥2 sites = 2.2

ROC curve - 0.728 to 0.745NRI =13.7%

Proportion of MI According to Total Plaque Area

Johnsen S H et al. Stroke 2007;38:2873-2880

No Plaque1. tertile2. tertile3. tertile

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Follow-up time, years

Follow-up time, years

No Plaque1. tertile2. tertile3. tertile

Men

WomenAdj. RR highest plaque tertile vs. no plaque

N=6226, FU 6 yrs, age 25-84

HR 1.56

HR 3.95

Proportion of MI According to IMT

Johnsen S H et al. Stroke 2007;38:2873-2880

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Follow-up time, years

Follow-up time, years

1. quartile2. quartile3. quartile4. quartile

1. quartile2. quartile3. quartile4. quartile

0 1 2 3 4 5 6

0 1 2 3 4 5 6

Men

Women Adj. RR highest vs. lowest IMT quartile No predictive value if bulb IMT excluded

HR 1.73

HR 2.86

Mathiesen E B et al. Stroke 2011;42:972-978

Proportion of Ischemic Stroke According to Total Plaque Area

Hazard Ratio highest quartile vs. no plaque

1.73, p, 0.04

1.62, p, 0.03

Mathiesen E B et al. Stroke 2011;42:972-978

Proportion of Ischemic Stroke According to IMT

No diff in stroke risk across quartiles of IMT

HR 1 SD IMT 8%

HR 1 SD IMT 24%

Internal Carotid Artery IMT and Plaque and not CCA IMT Predicts Probability of New Onset CVD

Polak et al N Engl J Med 2011; 365:213-221

2965 Framingham Offspring Study FU 7.2 yrs

NRI max , mean CCA IMT 0%, Max ICA IMT 7.6%, plaque presence 7.3%

HR 1SD IMTMn CCA IMT 1.13Max ICA IMT 1.21

EFFECT OF PLAQUE THICKNESS ON VASCULAR EVENTS

Rundek T et al. Neurology 2008 ;70(14):1200-7

N=2189FU 6.9 yrsHR: 2.844% of low FRSHad 18% risk if plaque present

Carotid intima-media Thickness Progression to Predict Cardiovascular Events in the

General Population

Lorenz M et al The Lancet Volume 379, Issue 9831 2012 2053 - 2062

16 studies, 36 984 participants, FU 7 yrs

CAROTID PLAQUE MORPHOLOGY IMPROVES STROKE RISK PREDICTION

Prati P et al Cerebrovasc Dis 2011;31(3):300-

TPRS• Stenosis degree• Plaque surface

irregularity• Echolucency• Texture

N=1,348 FU 12 yr

...

Carotid Plaque Burden as a Measure of Subclinical Atherosclerosis : Comparison With Other Tests for Subclinical Arterial Disease

Sillesen H et al. JACC Imag 2012;;5, 681 - 689

Chi Square: 450 Chi Square: 24

0

20

40

60

80

100

CAC 0 CAC 1-99 CAC =or>100

No Plaque Plaque

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Chi square=15.12, Pr=0.001

Naqvi TZ et al. J Am Soc Echocardiogr. 2010;23:809-15

High Prevalence of Carotid Atherosclerosis in Subjects with Low FRS

0

20

40

60

80

100

CAC 0 CAC 1-99 CAC =or>100

IMT <75% IMT>75%

Chi square=9.1, Pr=0.01

Per

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The Multi-Ethnic Study of Atherosclerosis (MESA)

• Prospective epidemiologic study• Study population: White (38%), African American (28%), Hispanic (22%), Chinese(12%)

• N=6698 (47.2% M), age 45-84 • Median follow up: 3.9 years

• HR for highest vs. lowest quartile:

-HR: 3.3 for maximal internal carotid IMT

-HR: 2.3 for maximal common carotid IMTFolsom, A. R. et al. Arch Intern Med 2008;168:1333-1339

Baseline Plaque Area & Plaque Progression

Predicts CV Events

Spence JD. Et al Stroke 2002 Dec;33(12):2916-22

5 yr risk 5.6% vs. 19.5%

5 yr risk 9.4% vs. 15.7%

N=1686

N=1085

3D Plaque Volume and Vessel Volume

Shai I et al. Circulation 2010;121:1200-1208Ainsworth C D et al. Stroke 2005;36:1904-1909

SUMMARY

• Lack of uniform definition of IMT and of plaque

• CCA IMT alone without plaque assessment does not appear to be clinically useful over and above FRS compared to IMT inclusive of bulb and ICA

• Plaque predicts CV events better than IMT

• Plaque burden assessment and assessment of plaque charateristics are better measures of atherosclerosis and CV risk than presence or absence of plaque

• Plaque progression and regression may be a powerful tool to evaluate effect of therapy

PLAQUE VS. IMT• The dynamic range of measurements varies by

100-fold for TPV compared to 2-fold for the ∼ ∼IMT

• The resolution of carotid ultrasound is 0.2 ∼mm, whereas the annual change of IMT is

0.15 mm, so change cannot be measured ∼within individuals in clinically meaningful time frames

• Carotid TPA changes on average by 10 mm∼ 2 allowing measurement of progression or regression within months

PLAQUE IS A GREAT EQUALIZER• 12, 576 individuals

• 15.2 yr mean follow up

• CHD end points, no stroke

• Mean IMT of CCA IMT vs All segment IMT mean

C statistic

• ACRS 0.741

• All IMT and plaque 0.754

• CCA mean and plaque 0.753

Nambi V et al. Eur eart H2012;33:183-90

Presence of Calcified Carotid Plaque Predicts Vascular Events: The Northern

Manhattan Study

Prabhakaran S et al Atherosclerosis 2007;195”e197 - e201

Common Carotid Intima-Media Thickness Measurements in Cardiovascular Risk

Prediction:  A Meta-analysis

Ruizter H et al. JAMA. 2012;308(8):796-803

HRP - BIOIMAGE STUDY - 63% > 2 RISK FACTORS

525MRI

1,085AdvancedImaging

6104Full Study

7,687CompletedEnrollment

9,866Met Eligibility

24,149Humana Members

Surveyed

865Survey Only

718Framingham

380CTA

180PET-CT

Am Heart J. 2010 Jul;160(1):49-57.e1.

No CVD or Significant Others

Control Phone

Control No Imaging

6104 4 Baseline Imag.

10853 Advanced Imag.

PREDICTIVE VALUE OF IMT VS. PLAQUE DIAGNOSTIC COHORT STUDIES - CAD

Metanalysis, 27 diagnostic cohort studies, 4,878 patients

SROC CurveSensitivity

1-specificity

Diagnostic accuracy of carotid ultrasound for the detection of CAD

Inaba Y et al Atherosclerosis Volume 220, Issue 1 2012 128 - 133

Definitions of the Carotid Segments

Lorenz M W et al. Circulation 2007;115:459-467