combining coronary artery calcium scanning with spect/pet ... · noninvasive imaging for cad...
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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
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DISCLOSURESDaniel S. Berman, M.D.
declares the following relationships:
Software royalties from CSMC
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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
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MG 72 M 09/98
• After normal thallium:
–No changes
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MG 72 M 09/98
• After normal thallium:
–No changes
• Offered a coronary calcium scan• Offered a coronary calcium scan
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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
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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
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Value of an Imaging Test
Does the testresult in
improvedoutcomes or
reduce costs?
Does the testPREDICT risk?
reduce costs?
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Value of an Imaging Test
Does the testresult in
improvedoutcomes or
reduce costs?
Does the testPREDICT risk?
reduce costs?
Must affect patient management
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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
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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
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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
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• 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
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CAC in Guiding Treatmentin Patients with 5-20% ASCVD Risk
Modified from Hecht, et al JCCT 2017
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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
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Noninvasive Imaging for CADSuspected CAD
Pre-test likelihood of CAD
Intermediate to High (50-100%)
Ischemia Testing
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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
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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
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Noninvasive Imaging for CADSuspected CAD
Pre-test likelihood of CAD
Intermediate to High (50-100%)
Ischemia Testing + CAC
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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
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Hybrid SPECT/CT and PET/CT
GE SPECT/CT Siemens PET/CT
• Attenuation correction• Coronary artery calcium scoring
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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
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• 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
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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
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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
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• 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
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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
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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
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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
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• 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
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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
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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
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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
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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
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WIZMAL (2018) 65 F SOB; Abnl ECGChol, DM, HTN; Regadenoson
STRESS
REST
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WIZMAL (2018) 65 F SOB; Abnl ECGChol, DM, HTN; Regadenoson
STRESS
REST
CAC0
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STRESS
REST
STARIC (2018) 73 M Chol, HTN, FHNo walk regadenoson
REST
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STRESS
REST
STARIC (2018) 73 M Chol, HTN, FHNo walk regadenoson
REST
CAC3056
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STRESS
REST
STARIC (2018) 73 M Chol, HTN, FHNo walk regadenoson
REST
Staged PCIof LAD and LCX
CAC3056
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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)
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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)
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• 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
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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
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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
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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
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STRESS
RJ 75 F ATA/SOB, DM, no walk regadenosonRJ 75 F ATA/SOB, DM, no walk regadenoson
REST
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STRESS
RJ 75 F ATA/SOB, DM, no walk regadenosonRJ 75 F ATA/SOB, DM, no walk regadenoson
REST
CAC 1463
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STRESS
RJ 75 F ATA/SOB, DM, no walk regadenosonRJ 75 F ATA/SOB, DM, no walk regadenoson
REST
CAC 1463
LM: CABG
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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
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• 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
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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
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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)
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• 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
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• 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
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Thank you very much
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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]
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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
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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
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Prevalence of Abnormal SPECT by CAC Score
Engbers, et al: Circ Imaging 20164897 symptomatic patients
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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
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Impact of CAC on Lifestyle Changes
Gupta et al; JACCi 2017
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Impact of CAC on Preventive Medications
Gupta et al; JACCi 2017
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Prevalence of Abnormal SPECT by CAC Score
Engbers, et al: Circ Imaging 2016
4897 symptomatic patients referred for SPECT-MPI
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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
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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
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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