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