combining coronary artery calcium scanning with spect/pet ... · noninvasive imaging for cad...

Daniel S. Berman, MDDirector, Cardiac ImagingCedars-Sinai Heart Institute

Combining Coronary Artery Calcium Scanningwith SPECT/PET Myocardial Perfusion Imaging

Cedars-Sinai Heart InstituteProfessor of Medicine and ImagingCedars-Sinai

Controversies 2018Beverly Hills

DISCLOSURESDaniel S. Berman, M.D.

declares the following relationships:

Software royalties from CSMC

MG 72 M 09/98

• 70 y/o male physician tennis player

• Asymptomatic

• Total cholesterol: 220 mg/dL; LDL 152

• Recent exercise thallium scan was normal

MG 72 M 09/98

• After normal thallium:

–No changes

MG 72 M 09/98

• After normal thallium:

–No changes

• Offered a coronary calcium scan• Offered a coronary calcium scan

MG 72 M 09/98

CAC Results

Location # CalcifiedLesions

Calcified Plaque

Volume (mm3)

Calcium Score

LAD 2 806 1063LAD 2 806 1063

LCX 4 645 782

RCA 2 830 1101

Total 8 2282 2946*

* 97th percentile

MG 72 M 09/98

• After CAC scan:

– Started statin and aspirin

– Changed eating habits– Changed eating habits

– Lost 10-15 lbs within one month

– Increased exercise

– Alive and well 17 years later

Value of an Imaging Test

Does the testresult in

improvedoutcomes or

reduce costs?

Does the testPREDICT risk?

reduce costs?

Value of an Imaging Test

Does the testresult in

improvedoutcomes or

reduce costs?

Does the testPREDICT risk?

reduce costs?

Must affect patient management

Coronary Artery Calcium (CAC)

• CAC: a marker of CAD

– Burden of coronary atherosclerosis

• Integrated lifetime effect of all risk factors– Overcomes the limitations of global risk scores– Overcomes the limitations of global risk scores

– Improves risk stratification

<1 mSv(~ mammogram)Single breathNo contrast

0 (n=11,044)

1-10 (n=3,567)

11-100 (n=5,032)

101-299 (n=2,616)

300-399 (n=561)

Cum

ula

tive

Surv

ival

0.90

0.95

1.00

All Cause Mortality and CAC Scores:

Long Term Prognosis in 25,253 patients

300: 10.4 xincreased

risk

Time to FollowTime to Follow--up (Years)up (Years)

400-699 (n=955)

700-999 (n=514)

1,000+ (n=964)2=1363, p<0.0001 for variable overall and for each category subset.

Cum

ula

tive

Surv

ival

0.0 2.0 4.0 6.0 8.0 10.0 12.0

0.70

0.75

0.80

0.85

Budoff, et al. JACC 2007; 49: 1860-70

0 (n=11,044)

1-10 (n=3,567)

11-100 (n=5,032)

101-299 (n=2,616)

300-399 (n=561)

Cum

ula

tive

Surv

ival

0.90

0.95

1.00

All Cause Mortality and CAC Scores:

Long Term Prognosis in 25,253 patients

300: 10.4 xincreased

risk

Time to FollowTime to Follow--up (Years)up (Years)

400-699 (n=955)

700-999 (n=514)

1,000+ (n=964)2=1363, p<0.0001 for variable overall and for each category subset.

Cum

ula

tive

Surv

ival

0.0 2.0 4.0 6.0 8.0 10.0 12.0

0.70

0.75

0.80

0.85

Budoff, et al. JACC 2007; 49: 1860-70

Consistent findings in multiple large registries andpopulation-based studies

• More targeted preventive treatment

• Upscale or downscale

• Improvement in risk factor profile1

• Intensification of Rx2

• Better adherence to Rx3,5

CAC leads to better treatment / lifestyle

• Better adherence to Rx3,5

• Dietary modifications4

• Increased exercise4

1 Rozanski et al, JACC 2011 (EISNER Study)2 Nasir K et al, Circ Cardiovasc Qual Outcomes 2010 (MESA)3 Kalia NK et al, Atherosclerosis. 20064 Orakzai RH et al, Am J Cardiol 20085 Taylor A t al, JACC 2008

CAC in Guiding Treatmentin Patients with 5-20% ASCVD Risk

Modified from Hecht, et al JCCT 2017

Primary Prevention:Emphasize Adherence to Healthy Lifestyle

Age 40-75y and LDL-C ≥70 - <190 mg/dL without diabetes mellitus

10-year ASCVD risk percentbegins risk discussion

7.5% - <20%

If risk decision is uncertain:Consider measuring CAC in selected adults:

CAC Consideration

0 Consider no statin

22018 Cholesterol Clinical Practice Guidelines

7.5% - <20%“Intermediate risk”

Risk discussion:If risk estimate + risk

enhancers favor statin,initiate moderate-intensity statin to

reduce LDL-C by 30% -49% (Class I)

1-99 Favors statin

(especially >age 55)

100+ or ≥75th

percentile

Initiate statin therapy

Grundy SM, et al. Circulalation 2018

Noninvasive Imaging for CADSuspected CAD

Pre-test likelihood of CAD

Intermediate to High (50-100%)

Ischemia Testing

log

Haza

rdR

atio

34

56

Medical Rx*

Post-SPECT Cardiac Mortality and Rx GivenEarly Revascularization vs Medical Therapy

N=10,627F/U: 1.9 ± 0.6 yrs

Risk adjusted

log

Haza

rdR

atio

01

2

% Myocardium Ischemic

0 12.5% 25% 32.5% 50%

Revasc*

*p<0.001

Hachamovitch, et al. (Cedars-Sinai) Circulation 2003

log

Haza

rdR

atio

34

56

Medical Rx*

Post-SPECT Cardiac Mortality and Rx GivenEarly Revascularization vs Medical Therapy

N=10,627F/U: 1.9 ± 0.6 yrs

Risk adjusted

log

Haza

rdR

atio

01

2

% Myocardium Ischemic

0 12.5% 25% 32.5% 50%

Revasc*

*p<0.001

Hachamovitch, et al. (Cedars-Sinai) Circulation 2003

Fundamental limitation of SPECT/PET MPIDoes not detect subclinical atherosclerosis

Noninvasive Imaging for CADSuspected CAD

Pre-test likelihood of CAD

Intermediate to High (50-100%)

Ischemia Testing + CAC

Noninvasive Imaging for CADSuspected CAD

Pre-test likelihood of CAD

Intermediate to High (50-100%)

Ischemia Testing + CAC

• Could be performed with hybrid imaging or add on CACPotential of SPECT/PET+CAC vs CCTAhas not been tested in RCT

Hybrid SPECT/CT and PET/CT

GE SPECT/CT Siemens PET/CT

• Attenuation correction• Coronary artery calcium scoring

Hybrid SPECT/CT and PET/CT

GE SPECT/CT Siemens PET/CT

• Attenuation correction• Coronary artery calcium scoring

CAC: Routine with hybrid or low-cost separate add-on procedure

• Detects subclinical atherosclerosis

• Improves risk assessment

• Increases diagnostic certainty

CAC in Patients Undergoing SPECT/PET-MPI

• Increases diagnostic certainty

• Improves identification of patients at highest risk

• Leads to greater change in patient management

0 11%16%

CACscore

He et alBerman et al

CAC Distribution in Normal SPECT-MPI Patients

1-9

10-99

100-399

≥400

23%

6%

39%

23%

3%

17%

26%

37%

JACC 2004 Circulation 2000

0 11%16%

CACscore

He et alBerman et al

CAC Distribution in Normal SPECT-MPI Patients

1-9

10-99

100-399

≥400

23%

6%

39%

23%

3%

17%

26%

37%

JACC 2004 Circulation 2000

• Detects subclinical atherosclerosis

• Improves risk assessment

• Increases diagnostic certainty

CAC in Patients Undergoing SPECT/PET-MPI

• Increases diagnostic certainty

• Improves identification of patients at highest risk

• Leads to greater change in patient management

Added Prognostic Value of CAC in Rb-PET MPI

Schenker et al. Circulation 2008;117:1693-700

PET/CT:N=695FU 6-28 monthsAdjusted:

age, sex, symptoms and RF

Event Rates by CAC in Normal and Abnormal Scan

Added Prognostic Value of CAC in SPECT MPI

Engbers, et al: Circ Imaging 2016

Years to event Years to event

• N=4897 symptomatic patients• F/u: median 940 days• MACE (278): MI, ACD, late revascularization (>90 days)• MACE rate: 2.3%/year

Highest category: >1000

CAC+MPS: Multivariable Predictors of MACE

• Age +10 y 1.40 <0.001

• Male 1.32 0.04

• CAC score category

– 100-399 3.31 <0.001

– 400-999 4.87 <0.001– 400-999 4.87 <0.001

– ≥1000 7.57 <0.001

• SPECT findings

– Small 1.64 0.001

– Moderate 2.21 <0.001

– Large 3.74 <0.001

Engbers, et al: Circ Imaging 2016• N=4897 symptomatic patients• F/u: median 940 days

• Detects subclinical atherosclerosis

• Improves risk assessment

• Increases diagnostic certainty

CAC in Patients Undergoing SPECT/PET-MPI

• Increases diagnostic certainty

• Improves identification of patients at highest risk

• Leads to greater change in patient management

63

44

29

16

20

18

13

21

36

8

14

18

CAC 100-399

CAC 400-999

CAC≥1000

CONFIRM Patients with no prior CADPrevalence of Obstructive CAD with any CP symptom

CAC: Aid in Pre-test Likelihood of Coronary Stenosis

97

85

63

2

9

16

1

5

13

1

2

8

0 20 40 60 80 100

CAC 0

CAC 1-99

CAC 100-399

%

0-49% 50-69% ≥70% ≥70% prox LAD or ≥50% LM

CONFIRM: UnpublishedN=8,660

63

44

29

16

20

18

13

21

36

8

14

18

CAC 100-399

CAC 400-999

CAC≥1000

CONFIRM Patients with no prior CADPrevalence of Obstructive CAD with any CP symptom

CAC: Aid in Pre-test Likelihood of Coronary Stenosis

97

85

63

2

9

16

1

5

13

1

2

8

0 20 40 60 80 100

CAC 0

CAC 1-99

CAC 100-399

%

0-49% 50-69% ≥70% ≥70% prox LAD or ≥50% LM

CONFIRM: UnpublishedN=8,660

63

44

29

16

20

18

13

21

36

8

14

18

CAC 100-399

CAC 400-999

CAC≥1000

CONFIRM Patients with no prior CADPrevalence of Obstructive CAD with any CP symptom

CAC: Aid in Pre-test Likelihood of Coronary Stenosis

97

85

63

2

9

16

1

5

13

1

2

8

0 20 40 60 80 100

CAC 0

CAC 1-99

CAC 100-399

%

0-49% 50-69% ≥70% ≥70% prox LAD or ≥50% LM

CONFIRM: Unpublished 2017N=8,660

63

44

29

16

20

18

13

21

36

8

14

18

CAC 100-399

CAC 400-999

CAC≥1000

CONFIRM Patients with no prior CADPrevalence of Obstructive CAD with any CP symptom

CAC: Aid in Pre-test Likelihood of Coronary Stenosis

97

85

63

2

9

16

1

5

13

1

2

8

0 20 40 60 80 100

CAC 0

CAC 1-99

CAC 100-399

%

0-49% 50-69% ≥70% ≥70% prox LAD or ≥50% LM

CONFIRM: Unpublished 2017CAC ≥400: 35-54% have ≥70% stenosisN=8,660

WIZMAL (2018) 65 F SOB; Abnl ECGChol, DM, HTN; Regadenoson

STRESS

REST

WIZMAL (2018) 65 F SOB; Abnl ECGChol, DM, HTN; Regadenoson

STRESS

REST

CAC0

STRESS

REST

STARIC (2018) 73 M Chol, HTN, FHNo walk regadenoson

REST

STRESS

REST

STARIC (2018) 73 M Chol, HTN, FHNo walk regadenoson

REST

CAC3056

STRESS

REST

STARIC (2018) 73 M Chol, HTN, FHNo walk regadenoson

REST

Staged PCIof LAD and LCX

CAC3056

PET-MPI + CAC: Improved Prediction of Obstructive CAD*

Per-vessel CAD by Ischemic TPD (ITPD) and CAC category

Brodov….Slomka, JNM, 2015

* ≥70% stenosis

Per-vessel analysis 456 (152 patients)

PET-MPI + CAC: Improved Prediction of Obstructive CAD*

Per-vessel CAD by Ischemic TPD (ITPD) and CAC category

Brodov….Slomka, JNM, 2015

* ≥70% stenosis

Per-vessel analysis 456 (152 patients)

• Detects subclinical atherosclerosis

• Improves risk assessment

• Increases diagnostic certainty

CAC in Patients Undergoing SPECT/PET-MPI

• Increases diagnostic certainty

• Improves identification of patients at highest risk

• Leads to greater change in patient management

Underestimation of the Extent of CAD by SPECT MPIUnderestimation of the Extent of CAD by SPECT MPI

101 consecutive SPECT-MPI ptswith LM CAD (50% stenosis)

Berman et al,Berman et al,JNC 2007JNC 2007

Underestimation of the Extent of CAD by SPECT MPIUnderestimation of the Extent of CAD by SPECT MPI

101 consecutive SPECT-MPI ptswith LM CAD (50% stenosis)

Berman et al,Berman et al,JNC 2007JNC 2007

Underestimation of the Extent of CAD by SPECT MPIUnderestimation of the Extent of CAD by SPECT MPI

101 consecutive SPECT-MPI ptswith LM CAD (50% stenosis)

Berman et al,Berman et al,JNC 2007JNC 2007

STRESS

RJ 75 F ATA/SOB, DM, no walk regadenosonRJ 75 F ATA/SOB, DM, no walk regadenoson

REST

STRESS

RJ 75 F ATA/SOB, DM, no walk regadenosonRJ 75 F ATA/SOB, DM, no walk regadenoson

REST

CAC 1463

STRESS

RJ 75 F ATA/SOB, DM, no walk regadenosonRJ 75 F ATA/SOB, DM, no walk regadenoson

REST

CAC 1463

LM: CABG

STRESS

RJ 75 F ATA/SOB, DM, no walk regadenosonRJ 75 F ATA/SOB, DM, no walk regadenoson

REST

CAC 1463

LM: CABGCAC : Aids in identification of patients at high risk

• Detects subclinical atherosclerosis

• Improves risk assessment

• Increases diagnostic certainty

CAC in Patients Undergoing SPECT/PET-MPI

• Increases diagnostic certainty

• Improves identification of patients at highest risk

• Leads to greater change in patient management

Impact of CAC Score on Preventive Medication UsePatients with Normal SPECT-MPI

1033 stable symptomatic patients*Adjusted for risk factors and baseline medication use

Engbers, et al: Am Heart J 2017

20%

25%

30%

35%

40%

45%

%P

re

va

len

ce

Yearly Prevalence of Abnormal and Ischemic SPECT MyocardialPerfusion Imaging Studies between 1991 and 2009

0%

5%

10%

15%

1991 1993 1995 1997 1999 2001 2003 2005 2007 2009

%P

re

va

len

ce

Year

% Ischemia % Abnormal SPECTN=39, 515 Rozanski, et al JACC 2012 (Cedars-Sinai)

• Detects subclinical atherosclerosis

• Improves risk assessment

• Increases diagnostic certainty

CAC in Patients Undergoing SPECT/PET-MPI

• Improves identification of patients at highest risk

• Leads to greater change in patient management

JNC 2016

• Detects subclinical atherosclerosis

• Improves risk assessment

• Increases diagnostic certainty

CAC in Patients Undergoing SPECT/PET-MPI

• Improves identification of patients at highest risk

• Leads to greater change in patient management

JNC 2016Berman, Rozanski JNC 2016

Should be considered in all patients without known CADreferred for SPECT/PET MPI

Thank you very much

During follow-up, patients assigned to CTA were morelikely than patients assigned to standard care alone to

have commenced preventive therapies

Preventive therapies

Antianginal therapies

CCTA Standard care Odds ratio

Preventive therapies 19.4% (402/2037) 14.7% (305/2037) 1.40 [1.19, 1.65]

Antianginal therapies 13.2% (273/2037) 10.7% (221/2037) 1.27 [1.05, 1.54]

Adapted from Newby et al, Engl J Med 2018

0.5 1 1.5 2

Antianginal therapies

Odds ratio (95% CI)

CCTA Standard care Odds ratio

Preventive therapies 19.4% (402/2037) 14.7% (305/2037) 1.40 [1.19, 1.65]

Antianginal therapies 13.2% (273/2037) 10.7% (221/2037) 1.27 [1.05, 1.54]

0 11%16%

CACscore

He et alBerman et al

CAC Distribution in Normal SPECT-MPI Patients

OPTION 1

0.50

Engberg et al (AHJ 2017)

1-9

10-99

100-399

≥400

23%

6%

39%

23%

3%

17%

26%

37%

JACC 2004 Circulation 2000

0.32 0.32

0.20

0.16

0.00

0.10

0.20

0.30

0.40

0 1-99 100-399 ≥400

Pat

ien

ts(%

)

CAC distribution in normal SPECT-MPI patients

CAC Distribution in Normal SPECT-MPI PatientsOPTION 2

0.30

0.40

0.50

Pat

ien

ts(%

)

0.00

0.10

0.20

0 1-99 100-399 ≥400

Pat

ien

ts(%

)

CAC score

Berman et al JACC 2000 He et al Circ 2004 Engberg et al AHJ 2017

Prevalence of Abnormal SPECT by CAC Score

Engbers, et al: Circ Imaging 20164897 symptomatic patients

Impact of CAC on Prevention

• Increased exercise

• Dietary change

• Aspirin initiation

• Lipid lowering medications• Lipid lowering medications

• Blood pressure lowering medication

Gupta et al JACCi 2017Meta-anlaysis

Impact of CAC on Lifestyle Changes

Gupta et al; JACCi 2017

Impact of CAC on Preventive Medications

Gupta et al; JACCi 2017

Prevalence of Abnormal SPECT by CAC Score

Engbers, et al: Circ Imaging 2016

4897 symptomatic patients referred for SPECT-MPI

0 11%16%

CACscore

He et alBerman et al

CAC Distribution in Normal SPECT-MPI Patients

OPTION 1

0.50

Engberg et al (AHJ 2017)

1-9

10-99

100-399

≥400

23%

6%

39%

23%

3%

17%

26%

37%

JACC 2004 Circulation 2000

0.32 0.32

0.20

0.16

0.00

0.10

0.20

0.30

0.40

0 1-99 100-399 ≥400

Pat

ien

ts(%

)

CAC distribution in normal SPECT-MPI patients

CAC Score Increases Certainty ofInterpretation of MPI

• N=151 SPECT/CT• No prior MI• Major interpretation change

• N=39• N=39• ICA ≥70% standard

• 24 correct change• 15 incorrect change

Mouden, et al: J Nucl Card 2014

CAC Score Increases Certainty ofInterpretation of MPI

• N=151 SPECT/CT• No prior MI• Major interpretation change

• N=39• N=39• ICA ≥70% standard

• 24 correct change• 15 incorrect change

Mouden, et al: J Nucl Card 2014