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ASNC 2011: The Prognostic Value of CTA: The Evidence is Expanding
Does Coronary Artery Calcium Scoring Improve the Prognostic Value
of Stress MPI?
John J. Mahmarian, MD, FACC, FASNC, FSCCT
Professor of Medicine Department of Cardiology, Weill Cornell Medical College
Medical Director, Nuclear Cardiology and CT ServicesMethodist DeBakey Heart & Vascular Center
The Methodist HospitalHouston, Texas
ASNC 2011 Presenter Disclosure Information
“Does Coronary Artery Calcium Scoring Improve the Prognostic Value of Stress MPI?”
Disclosure Information:The following relationships exist to this presentation:
John J. Mahmarian, MD – None
Does CACS Improve the Prognostic Value of MPI?
“I am not one of those who in expressing opinions confine themselves to facts”
-- Mark Twain
An All Too Common Scenario
Integrating CACS and MPI
Anatomy: CACS 1362 Physiology: Apical Ischemia
Fundamental Basis for this Approach: To better clarify CAD extent and severity than by either test alone and thereby
Improve risk stratification and patient management decisions.
The Asymptomatic Patient Without Known CADScreening for Subclinical Coronary Atherosclerosis
SymptomaticPatients
Those Not FarBehind!
CT Coronary Artery Calcium ScoringAdvantages For Use In Screening
• Rapid, Simple Imaging Test to Diagnose
Early Atherosclerosis (10 sec breathhold)
• No Patient Preparation
• Readily Available: Performed on conventional MDCT (> 4 slice) and no contraindications
• No risk & relatively low radiation exposure (1-2 mSv)
• Reproducible and Easily Interpretable(semi-automated analysis)
• Inexpensive
CACS for Defining Low Risk All-Cause MortalityImplications in Clinical Decision-making
Blaha M et al. J Am Coll Cardiol Img 2009;2:692-700
44,052 Asymptomatic individuals mean age 54 yrs. without CHD referred for CACS study
Men (54% of subjects) Women (46% of subjects)
Mean followup 5.6 years
All cause mortality 1000 person-years CACS=0 0.87 (0.72-1.05)CACS1-10 1.92 (1.48-2.48)CACS >10 7.48 (6.95-8.04)
“In non-high risk patients, the absence of CAC could be used as a rationale to emphasize lifestyle changes, scale back on costly preventative pharmacotherapy and refrain from frequent cardiac imaging”
The value of a CACS of Zero!
Warranty Period for a Normal CACS of 0
422 subjects with CACS=0 who had annual scans up to 5 years.
25% with CAC at 4.1±0.9 years (6.1%/year)
Conversion associated with age>40, diabetes and smoking (all p<0.001) with a mean CACS at
the time of conversion of 19±19
Min et al JACC 2010;55:1110
2948 subjects with CACS=0 who had serial imaging at mean 2.4 years*
16.1% with CAC at 2.4 years (6.6%/year)
Conversion associated with age, diabetes male sex, BMI and hyperlipidemia
*Kronmal et al. Circ 2007;115:2722
Asymptomatic PatientsWhy Not MPI as the Initial Test?
3,664 patients without known CAD followed for 1.9years
Zellwenger et al. J Nucl Cardiol 2009;16:193
6.0% of patients
SPECT MPI DOES NOT DETECT EARLY CORONARY ATHEROSCLEROSIS!
Change in Progression of IVUS Percent Atheroma Volume vs. LDL-C in IVUS Trials
-1.2
-0.6
0
0.6
1.2
1.8
50 60 70 80 90 100 110 120Med
ian
Ch
ang
e In
Per
cen
t Ath
ero
ma
Volu
me
(%)
REVERSALpravastatin
REVERSALatorvastatin
CAMELOTplacebo
A-Plusplacebo
ACTIVATEplacebo
ASTEROIDrosuvastatin
r2= 0.95p<0.001
On-Treatment LDL-C (mg/dL)
JAMA 2006;295:1556-1565; Cleve Clin J Med 2006;73:937-944
Detrano R et al. N Engl J Med 2008;358:1336-1345
CACS and Cardiac Events AmongDifferent Ethnic Groups: MESA (6722 pts.)
AMI and Cardiac Death Any Coronary Event
A similar increase in risk among all ethnic groupsCACS added significantly to traditional RF’s for predicting cardiac events and in all ethnic groups ---- Adds to >70,000 patients worth of prognostic data
Integrating SPECT After CACS to Assess RiskDetecting Asymptomatic Ischemia
1.5% 0 1.8%
11.3%
17.6%
12%
5.2%
46%45%
41%
13%
0
10
20
30
40
50
<100 101-399 >400
He et al (N=411)
Anand et al (N=220)
Moser (N=102)Berman (N=1195)
N = 657Overall 1.7%
N = 669Overall 26%
N = 602Overall 10%
% Pts
CACS
~10% of subjects
Wong ND et al. Diabetes Care 2005;28:1445
Ischemia by SPECT Across CACS Categories Metabolic Syndrome
1043 subjects without known CAD, 313 (30%) with metabolic abnormalities
Multivariate Predictors of SPECT Ischemia
Log CACS: RR 4.30 (2.70-6.86),
p<0.001
Chest Pain Symptoms:RR 2.88 (1.67-4.97) p<0.001
Metabolic Abnormality:RR 1.98 ( 1.20-3.28)
p=0.008
Enhanced Risk StratificationCACS After SPECT in Patients Without CAD
• Rosanski et al. JACC 2007; 49:1352
• Anand et al. Eur Heart J 2006; 27:71
• Schenker et al. Circulation 2008; 117:1693
• Chang et al. JACC 2009; 54:1872
Enhanced Risk Stratification in DiabeticsCombining CT CACS and SPECT
Anand et al. Eur Heart J 2006;27:713-721
Interaction P=0.003 (unadjusted) and <0.0001 (adjusted for United Kingdom Prospective Diabetes Study risk score [Stevens RJ et al. Clin Sci 2001;101:671-679]). Event-free survival estimates are from a stratified Cox model
% of Myocardium
CAC 0–100
CAC 101–400
CAC 401–1000
CAC >1000
0% 100% 98% 96% 90%
1–5% 100% 92% 83%77%
RR=9.20 (1.48, 57.19), P=0.017
>5% 100%80%
RR=8.30 (1.35, 50.99), P=0.022
64%RR=12.64 (2.97, 53.84), P=0.001
48%RR=24.43 (5.59, >100), P<0.0001
p = 0.003
Improved Risk Stratification Based on CACS/PET Results
Schenker et al. Circulation 2008;117:1693
Annual CV Event Rates : PET/CACS
621 patients without CAD Mean age 60.9yrs Pre test Likelihood CAD: 59.4 (29.9)
Improved Risk Stratification: CACS With SPECT
Log rank p <0.001 Log rank p <0.001
Time point analysis: P value 0.03 at year 3
Time point analysis: P value 0.01 at year 5
Patients With Normal SPECT
1126 patients followed up to 12 years (median 6.9), 84% FRS> Intermediate
Chang SM et al. J Am Coll Cardiol 2009;54:1872
CACS=0 Total Events 0.5%/year Death/MI 0.15%/year
A Total Cardiac Events
Eve
nt-
free
Su
rviv
al
Eve
nt-
free
Su
rviv
al
B All Cause Death/MI
Normal<15% LV PDS>15% LV PDS
Log rank p <0.001
Log rank p <0.001
Years to Cardiac Event Years to Death/MI
Normal<15% LV PDS>15% LV PDS
Chang SM et al. J Am Coll Cardiol 2009;54:1872
Improved Risk Stratification: CACS and SPECTEvent Rates Based on Total Perfusion Defect Size
1126 asymptomatic followed up to 12 years (median 6.9), 84% FRS> Intermediate
Annualized Event Rates Based on CACS and SPECT Results
Total Deaths 87 (33 cardiac, 31 non-cardiac, 23 unknown), NFMI 22, Revascularization 90
p =0.01 for increasing CACS (normal SPECT)
An
nu
aliz
ed E
ven
t R
ate
(%)
CACS
p <0.001 for CACS >100abnormal vs normalSPECT
p =0.01 for increasing CACS (normal SPECT)
CACS
p <0.001 for CACS >100abnormal vs normal SPECT
A Total Cardiac Events B All Cause Death/MI
An
nu
aliz
ed E
ven
t R
ate
(%)
0-10 11-100 101-400 >400
5.35
6.08
0.7 0.971.3
2.97
0
2
4
6
8Normal SPECTAbnormal SPECT
0-10 11-100 101-400 >400
2.44
3.89
0.591.1 1.25
2.05
0
2
4
6
8Normal SPECT
Abnormal SPECT
Chang SM et al. J Am Coll Cardiol 2009;54:1872
Improved Risk Stratification: Combining CACS With SPECT
Log rank p <0.001 Log rank p <0.001
Time point analysis: P value 0.03 at year 3
Time point analysis: P value 0.01 at year 5
Patients With Normal SPECT
1126 patients followed up to 12 years (median 6.9), 84% FRS> Intermediate
Chang SM et al. J Am Coll Cardiol 2009;54:1872
Exercise SPECT Results : SACALE
65 year old M.D. with a history of hypertension, hyperlipidemia, cigarette smoking and recent onset atypical chest pain
ETT Results:Exercise Time:8.5minMaximal HR:125bpm (80% target)AsymptomaticNo ST changesDuke TS: 8.5 (low risk)
CT CACS Following a Normal SPECT
CACS = 740
CACS With Normal PET MPITherapeutic Considerations
• 760 consecutive patients without known CAD who had CACS and normal Rb-82 PET
Bybee KA et al J Nucl Cardiol 2009
CACS Distribution
Agatston Score =0
Agatston Score 1-100
Agatston Score >100
Low FR Score Intermediate FRScore
High FR Score~30%
Bybee KA et al. J Nucl Cardiol 2009
Change in Therapy based on CACS
760 consecutive patients without prior CAD who had CACS and normal Rb-82 PET
CACS With Normal PET MPITherapeutic Considerations
p<0.001 vs. CACS=0 (odds ratio 3.05; 95% CI 2.30 to 4.05).
Taylor AJ et al. J Am Coll Cardiol 2008;51:1337
p < 0.001 vs. CACS=0 (odds ratio 3.53; 95% CI 2.66 to 4.69).
CACS Results: Do They Alter Therapy?
Statin Use Based On CACS Results Aspirin Use Based On CACS Results
1640 asymptomatic men, active army duty, 40-50 years old, 10-year FRS 4.6 (2.6)CACS of 0: 1263 (77.6%); TChol: 204 (36); LDL:128 (32); HDL: 50 (13) mg/dl
JUPITER: Cardiovascular EventsThe New Clinical Paradigm
Primary End Point: RR 0.56 (.46-.69), p<.00001
To prevent 1 primary event: treat 95 patients for 2 years or 25 patients for 5 years
MI, Stroke, CV Death: RR .53(0.4-0.69), p<.0001
At a median of 1.9 years in a clinically low risk group, but reclassified as high risk by CRP, the incidence of major CV events was significantly reduced with rosuvastatin.
CACS! (MESA-Lancet 2011)
CTA in the Emergency DepartmentRecent Clinical Trial Experience
Hoffman et al Circulation 2006; 114:2251Rubinshtein et al. Circulation 2007; 115:1762Gallagher et al. Ann Emerg Med 2007; 49:125Goldstein et al JACC 2007; 49:863*Hoffmann et al (ROMICAT) JACC 2009; 53:1642*
Negative Predictive Values : 96-100% for excluding ACS
Patient Population: Low risk, No history CAD, Normal cardiac markers, Non-diagnostic ECG
~ 1/3 of screened patients with a contraindication to CTA*
24% randomized to CTA needed subsequent SPECT+
Time to Diagnosis Longer with SPECT (7.3h vs. 3.4h, p<.0001).*Median costs higher with SPECT ($1,872 vs. $1,586, p<.0001).*
However, diagnostic accuracy the same as CTA*
CP Evaluation: The Value of CACS
CT CACS= 0Normal coronary
arteries – the rule rather than the exception
Rapid (10-20 sec breathhold) No Patient Preparation/contrastPerformed on standard
MDCT scanners (> 16 slice)Relatively low radiation
exposure (1-2 mSv) Can identify non-coronary
causes of chest pain
The Methodist Hospital Experience
CACS In the ED:Identifying Which Patients With Chest Pain Can Be Safely Discharged Home
Prospective study in 1031 Consecutive Patients with ACP and no prior history of CAD admitted through the ED from
September 2006 to November 2007 (all had CACS and SPECT)
20% of all ED CP visits and 55% of those admitted with non-diagnostic CP, 99% TIMI Score <4
(99% with 6 month follow-up)
Nabi et al. Ann Emerg Med 2010; 56: 220-229
Relationship Between CACS & SPECT
5 Abnormal SPECT in CACS=0• 4/5 normal LHC• 1/5 (0.16%) treated medically without events
in follow-up
61% with CACS=0 and 96% with normal SPECT
Patients With CACS of ZeroClinical Implications (n=625)
0.8
0.3
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
CACS 0
Abnomal SPECTCV Events
Per
cen
tag
e
N= 5
N= 2
Abnormal SPECT (n=5)• 4/5 normal LHC
0.00
0.25
0.50
0.75
1.00
Sen
siti
vity
0.00 0.25 0.50 0.75 1.00
1-Specificity
TIMI 0.7639
TIMI+CACS 0.8403TIMI+SPECT 0.9033
TIMI+CACS+SPECT 0.9091
Area under ROC Curve
95% CI
0.68 to 0.84
0.84 to 0.97
0.78 to 0.90
0.85 to 0.97
ROC Curve Analysis Based on CACS and SPECT Results and in Relation to TIMI Risk Score
CACS and ACS in the ED Setting
Authors Year N CACS =0Sensitivity
(%)Specificity
(%)PPV (%) NPV (%)
Laudon et al 1999 105 59 (59%) 100 63 30 100
McLaughlin et al 1999 134 48 (36%) 100 38 8 100
Georgiou et al 2001 192 76 (40%) 97 55 48 97
Hoffman et al 2009 368 197 (54%) 97 59 18 99.5
Laudon et al 2010 263 133 (51%) 97 57 23 99
Nabi et al 2010 1031 625 (61%) 93.8 62.4 7.4 99.7
Fernandez-Freira 2011 225 133 (59%) 91 64 20 99
Total 2318 1271 (55%) 96.4 59.5 17.8 99.5
95% CI 92-99% 57-62% 15-20% 99-100%
ROMICAT: ACS 1/14 (7.1%)PTS with NCP BUT only 1/197 PTs.Without CAC (0.5%)
Does CACS Improvethe Prognostic Value of Stress MPI?
• CACS as initial test in asymptomatic patients at intermediate-high clinical risk (ATP/FRS) to:
• identify early atherosclerosis and“prevent progression”
• detect significant silent myocardial ischemia and initiate therapy
CACS as a subsequent test in intermediate-high risk symptomatic patients with a normal stress MPI to determine atherosclerotic burden and modify long-term risk.
• CACS in the ED setting for triaging low-intermediate risk patients with chest pain