Combining Coronary Artery Calcium Scanning with SPECT/PET ... · Noninvasive Imaging for CAD...
Transcript of 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