tasneem z naqvi, md, frcp (uk), rvt, mmm director non-invasive cardiology and echocardiography...
TRANSCRIPT
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
adj
uste
d pr
obab
ility
of fi
rst
coro
nary
eve
ntN
on a
djus
ted
prob
abili
ty o
f firs
t co
rona
ry e
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
Cu
mu
lati
ve p
rob
abil
ity
of
myo
card
ial
infa
rcti
on
C
um
ula
tive
pro
bab
ilit
y o
f m
yoc
ard
ial
infa
rcti
on
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
Cu
mu
lati
ve
pro
ba
bil
ity
of
my
oc
ard
ial
infa
rcti
on
C
um
ula
tiv
e p
rob
ab
ilit
y o
f m
yo
ca
rdia
l in
farc
tio
n
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
Per
cen
t P
atie
nts
with
out
or w
ithC
arot
id A
rter
y P
laqu
e o
n U
ltras
ound
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
cen
t P
atie
nts
with
out
or w
ith
IMT
>75
th C
entil
e o
n U
ltras
ound
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