Shaw - Anatomic vs. Functional Stress Testing · COronary CTA EvaluatioN For Clinical Outcomes: An...
Transcript of Shaw - Anatomic vs. Functional Stress Testing · COronary CTA EvaluatioN For Clinical Outcomes: An...
Anatomic vs. Functional Stress Testing – It’s Complicated!
Anatomic vs. Functional Stress Testing – It’s Complicated!
Leslee J. Shaw, PhD, MASNC, FACC, FAHA, FSCCTProfessor of MedicineCo-Director, Emory Clinical CV Research InstitutePresident SCCTEmory University School of MedicineAtlanta, GeorgiaE-mail: [email protected]
Leslee J. Shaw, PhD, MASNC, FACC, FAHA, FSCCTProfessor of MedicineCo-Director, Emory Clinical CV Research InstitutePresident SCCTEmory University School of MedicineAtlanta, GeorgiaE-mail: [email protected]
Trends in CV ImagingTrends in CV Imaging
Imaging is Essential for CV Disease Diagnosis & Management
Technologic Innovation in Imaging Has Been Dramatic!
Sharp Decline in Utilization -Nuclear, Echo, & CMR Downward pressure on CV imaging AUC, RBM/SBM, Choosing Wisely
Campaign, Reduced Reimbursement (Technical Component) & High Deductibles…
0.0
0.5
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Card
iac C
T Us
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1,00
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Source: David Levin, MD (ACR), Ferrari J Am Coll Cardiol Img 2014;7:324-332.
A Means to Ensure that the Health of our Population isEnhanced by Health Reform Efforts
Intelligent Cost Containment Can Promote Change Through Quality-Guided Revisions in
Healthcare Financing, Organization, & Delivery
Source: Mushlin NEJM 2010;362:e6
Comparative Evidence from Trials & Registries:
The Optimal Approach to Evaluation of CADBoth Anatomy and Physiology
Evaluation of Integrated CAD Imaging in Ischemic Heart Disease (EVINCI) Trial
Source: Neglia Circ CV Imaging 2015 Mar;8(3).
Diagnostic Accuracy Estimating Obstructive CAD (N=475 from 14 Centers)
• CCTA Plus 1+ Stress Test
• Patients with Abnormal Findings Underwent Invasive Angiography
90%80%
74%
57%45%
93% 89%
66%
96%90%
0%
25%
50%
75%
100%
CCTA PET SPECT CMR Echo
Sensitivity Specificity
Wall MotionPerfusion
(N=475)(N=475) (n=96)(n=96) (n=293)(n=293) (n=85)(n=85) (n=263)(n=263)
Strong Correlation Between Tests of Anatomy is Expected
Anatomic Test Anatomic Test=
Mild-Moderate Correlation Between Functional & Anatomic Tests
Functional Test Anatomic Test≠
Cascade of Mechanisms & Manifestations of Ischemia
Exposure Time of Mismatch in Myocardial Oxygen Supply / DemandNear Term Prolonged
Prog
ress
ive M
anife
stat
ions
of I
sche
mia
Micro-Infarction/ Fibrosis
Diastolic Dysfunction
Decreased Segmental Perfusion
Regional Wall Motion
↓ Subendocardial Perfusion
Systolic Dysfunction
Endothelial & Microvascular Dysfxn
Altered Metabolism/Abnml ST response
Source: Douglas NEJM 2015;372:1291-1300.
78% Atypical CP / Only 12% Typical CP
Much Lower Risk Than Designed!
Stress Nuclear (67%)Stress Echo (23%)
Ex ECG (10%)
Functional Testing Strategy (n=5,007)
CCTA Testing Strategy (n=4,996)
Randomized (N=10,003; 193 NA sites)
Randomized (N=10,003; 193 NA sites)
Source: Hoffmann AHA 2015
Site-based Test Reports were Classified as Normal, Mildly, Moderately, or Severely Abnormal
*Death, MI, or UA. (27 m)
Normal CCTA=0.9%Normal Stress Test=2.2%HR 0.47 (p=0.009)…but not significantly different for other test strata
PROMISE: CCTA in Women
Source: Pagidipati JACC 2016
HR 5.86, p<0.001 HR 2.27, p=0.011
• Women w/ Positive CTA More Likely to Have an Event vs.Those with Positive Stress Test (p=0.028)
• Men No Difference in Hazard for Events Following PositiveStress Test or CCTA (p=0.17)
Source: Steg JAMA Intern Med 2014;174:1651-9.
N=32,105 Stable CAD Outpatients from 45 countries w/ 2-year follow-up
Eligibility: – Site-defined Ischemia – ECG, Echo, or Nuc– No Differentiation by Severity or Extent, Ex
Duration, etc.
Most stable CAD patients did not have angina or ischemia Combination of Angina & Presence of Myocardial Ischemia on noninvasive
Testing - Most PredictiveIschemia alone was not!
Source: SCOT-HEART Lancet 2015;385:2383-2391.
• 35% Typical Angina• ~17% Est. CHD Risk• 85% Stress ECG, 10%
Stress Nuclear
Index Stress ECG in 85% of Patients
Source: SCOT-HEART Lancet 2015;385:2383-2391.
Kaplan-Meier curves for A. CHD Death & MI (p=0.053)B. CHD Death, MI, & Stroke (p=0.056)
…. in patients assigned to CCTA (Blue) and Standard Care (SC) (Red)
CHD Death & MI (p=0.053)
CHD Death, MI, & Stroke(p=0.056)
CCTA
SC
SC
CCTA
Cumulative Fatal & Nonfatal MI
Source: Williams J Am Coll Cardiol 2016;67(15):1759-1768.
CCTA (n=17)
SC (n=34)
HR: 0.50, 95% CI: 0.28-0.88(p= 0.02)
Initiation of New Preventive TherapiesAntiplatelet Therapy
SC
CCTA
CCTA
SC
Statin Therapy
>50 days (median time to rx initiation)
SCOT-HEART Trial
12.2-fold > Use(p<0.0001)
3.5-fold > Use(p<0.0001)
Source: Williams J Am Coll Cardiol 2016;67(15):1759-1768.
CCTA: • Improved Diagnostic Accuracy• Greater MD Confidence
→ Define Extent & Severity of Obstructive / Nonobstructive CAD -Guide Management
Source: Blankstein Am J Cardiol 2010;105:1246-53.
Stress Testing: • Reduced Diagnostic Accuracy• Reduced Patient Satisfaction
→ High Rate of Inadequate Stress, ETT Challenging for Most Patients, ? Quality Imaging…
Does CCTA Provide the Link To Improve Patient Outcomes?
Source: Hachamovitch JACC 2012;59:462-74., Cheezum JACC CV Imag 2013;6:574-81., Shaw Circulation 2011;124:1239-49.
Stress Testing: ~50% of Moderate-Severely Abnormal Studies → ICA– Diminished Confidence /
Diagnostic UncertaintyCCTA: Patients with Nonobstructive / Obstructive CAD - Significant– Intensification in Statin, BP, &
Aspirin Rx (all p<0.001), – Improvements in:
Total Cholesterol (p=0.008)LDL Cholesterol (p=0.001) SBP (p=0.002) / DBP (p=0.012)
CAC + Selective CCTA vs. Exercise Testing in Suspected Coronary Artery Disease
(CRESCENT) Trial
10 Endpoint: All-cause Mortality, NFMI,Major Stroke, UA with Objective Ischaemiaor Requiring Revascularization, UnplannedCAD Evaluation, & Late Revascularization
CAC>0(n=141)
89.8% 96.7%
*No events for CAC=0.
Source: Lubbers Eur Heart J 2016; Apr 14;37(15):1232-43.
Angina Status 1-year Post-Randomization Downstream Testing
Source: Lubbers Eur Heart J 2016; Apr 14;37(15):1232-43.
CRESCENT Trial
€369 v. €44016% Cost Savings
(p<0.0001)
Target Appropriate Growth in Stable Ischemic Heart Disease
Ex ECG is the Most Common Procedure
RCT Evidence Supports That CCTA Improves Outcomes, Reduces Symptom Burden, & Saves $ CAPP Trial CRESCENT Trial
Source: Lubbers EHJ 2016;37:1232-43.; McKavanagh EHJ CV Imaging.2015;16:441-8.
Diagnostic Yield By Randomized Test Strategy:
CCTA vs. Standard of Care or Stress Testing
71% of 1,047
72%of 609
69%of 409
72%of 29
53% of 819
48% of 406
57%of 401
58%of 12
0.0%
20.0%
40.0%
60.0%
80.0%
100.0%
Pooled PROMISE SCOT-HEART CRESCENTCCTA SC or Stress Test
Source: Shaw JACC CV Imaging (in press).
Randomized Clinical Trial Evidence
4 Controlled Clinical Trials Report High Diagnostic Accuracy
3 Randomized Clinical Trials (RCT) in Acute Imaging of Low Risk Chest Pain
4 RCT in Suspected Stable Ischemic Heart Disease (SIHD)
Source: Litt NEJM 2012;366:1393-403.; Hoffmann NEJM 2012;367:299-308., Goldstein JACC 2011;58:1414-22.; Shaw JACC CVImag (in press).
Death, MI, Unstable Angina, Procedural
Complications
CHD Death or MI
CAD Events + ED Leading to Unplanned Hospitalization
Trials: NNear-Term Δ
CostLong-Term Δ
CostOverall Cost
FindingsPROMISE 9,504 Δ$254 @ 3-m
(p=NS)Δ$627 @ 3-yrs
(p=NS)Minimal Cost
Difference (p=NS)SCOT-HEART 4,146 Index Cost
$342 ↑ for CCTA (p<0.001)
Δ$89 @ 6-m No Difference
(p=0.27)
No Difference: Δ$89 (p=0.27)
CRESCENT 350 Index Cost €164 ↑ for
Selective CCTA
Δ€71 @ 1-yr ↓ for CCTA (p<0.0001)
1-Yr Costs=€369 for CCTA vs. €440 for Ex
ECG (p<0.0001)
Economic Evidence in SIHD Trials: CCTA vs. Standard of Care or Stress Testing
No or Minimal Difference in Cost! • Index CCTA Costs Higher But Offset By
Subsequent Savings• CAC + Selective CCTA Reduces CostsSource: Shaw JACC CV Imaging (in press).
1) Efficacious
2) Effective
3) Efficient
Early Detection with CCTA
What other modality detects nonobstructiveCAD Targeted Intensive Lifestyle & Preventive Therapies
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
SCOT-HEART CONFIRM
Source: Shaw JACC CV Imaging (in press).
NormalNon-Obstructive
p<0.0001
1-Vessel CADp<0.0001
2-Vessel CADp<0.001
3-Vessel/Left Main p<0.0001
Surv
ival P
roba
bilit
y
Survival Time (Years)Source: Min JACC 2011 Aug 16;58(8):849-60.
CONFIRM Registry: COronary CTA EvaluatioN For Clinical Outcomes: An InteRnational Multicenter Registry
Dynamic registry of >32,000 consecutive pts1) 12 sites (US, Canada, Germany, Switzerland, Italy, & S. Korea)2) +6 sites (Miami, California, Vancouver, NY, Innsbruck, Seoul)3) +3 sites (Italy, Portugal, Poland)
Risk Associated with a Normal CCTA
Left Anterior Descending Artery
Left Circumflex Artery
Right Coronary Artery
0.22% 0.26% 0.0% 0.24%0
2
4
6
8
10
CONFIRM Ostrom Andreini Hadamitzky
• Min (ACM): 1,000 patients, >4 yr f/u, >64-row CT• Ostrom (ACM): 2,538 patients, 6.5 yr f/u, EBT• Andreini (MACE): 1,304 patients, 4.3 yr f/u, 64-row CT • Hadamitzky (MACE): 1,584 patients, 5.6 yr f/u, 16- / 64-row CT
Source: Min J Am Coll Cardiol 2011 Aug 16;58(8):849-60 ; Ostrom J Am Coll Cardiol 2008 Oct 14;52(16):1335-43.; Andreini JACC Imaging 2012 Jul;5(7):690-701; Hadamitzky J Am Coll Cardiol 2013 Jul 30;62(5):468-76.
Long-term Annualized Prognosis For Normal CT
“Warranty Period” of Normal CCTA – At least 5 years
6,426 patients, ~5.5 yr f/u
Annu
alize
d Eve
nt Ra
te
0
5
10
15
1VD 2VD 3VD
>6-fold higher mortality for patients with 3-vessel mild CAD
HR 1.93 HR 2.74 HR 6.09
Source: Lin J Am Coll Cardiol 2011 Jul 26;58(5):510-9.
Mild Nonobstructive Stenosis & Adverse Events2,583 patients with CCTA <50% stenosis (Follow-up: 3.1 years)
Source: Motoyama JACC 2009 Jun 30;54(1):49-57., JACC 2015.
CT High Risk Atherosclerotic Plaque& Acute Coronary Syndromes
• 1,059 pts Examined for Positive Remodeling (PR) & Low Attenuation Plaque (LAP)
• All Events in Patients with <75% Stenosis• Limited Number of Wew ACS (n=14)
- 2-Feature + Plaque (22.2%)- 1-Feature + Plaque(3.7%)- 0-No Plaque(0.5%)
Advancing Our Understanding of The Relationship of Atherosclerotic
Plaque with Myocardial Ischemia
Source: Ahmadi et alJAMA Cardiology
Amir Ahmadi et al.
0"0.1"0.2"0.3"0.4"0.5"0.6"0.7"0.8"0.9"1"
0"10"20"30"40"50"60"70"80"90"
100"
FFR/" FFR+" FFR/" FFR+" FFR/" FFR+"
ICA/"Luminal"Stenosis"<30"
ICA/Luminal"Stenosis"30/50"
ICA/"Luminal"Stenosis"50/70"
ICA" LAP"Volume"mm3" FFR"
"
National Institute of Health & Care Excellence (NICE) Guidance - Stable Chest Pain Pathway
Source: Lee Open Heart 2015;2:e000151.
£0
£100
£200
£300
£400
Pre-CG95 Post-CG95
8.7% Cost Savings
16.3% Require Testing
31.7% Require Testing
Matched Cohort: 3,006 Pre- & Post-
Be NICE to Patients…do CTA 1st
(if any testing is needed at all)
Why CCTA?
Underuse of CT vs. Functional Testing Yet,
Safe Timely CAD Diagnosis High Diagnostic Yield High Diagnostic Certainty Effective Risk Stratification - Uniquely, for
Nonobstructive CAD Patient Satisfaction
Smart Selection of Imaging Candidates
Low / Intermediate Risk =– ↓ CAD Prevalence– Nonobstructive CAD
Detection– Stress Testing = High Rate of
Inadequate / False Positives– CCTA: 18% – SPECT: 29%– ETT: 54%
– Expected Low Rate of Follow-up In The Few w/ CAD
Source: Nielsen Int J CV Imag 2011;27:813-23., Shaw JACC 2009;54:1561-75.; Shaw Circ 2008;117:1787-801.; Diamond NEJM 1987;641.; Cheng Circ2011;124: 2423-32., Nielsen EHJ CV Imag 2014;15:961-71., Zeb Atherosclerosis 2014;234:426-35.
12% 11%
19%
13%
25%
19%
40%
29%
0%
10%
20%
30%
40%
50%
NonanginalCP
AtypicalAngina
TypicalAngina
Dyspnea
Women (n=6,329) Men (n=7,719)
CONFIRM Registry: CCTA Obstructive CAD Prevalence
Can We ∆ Paradigm of Stress First?De Novo Symptom Evaluation
-- +
CCTA
+-- - - +- - -
--
+-- +- -
+ + + +----Negatives Positives
Induce Unwarranted Test Utilization
+ Invasive Testing
+ 1 or more Diagnostic Tests
+ Serial / Annual Testing
Nonobstructive
Care – Not To Drive Unnecessary Costs But to Target Effective Anti-
Ischemic Strategies
Source: Foy JAMA IM 2015;175:428-36., Shreibati JAMA 2011;306:2128-36.Source: Fihn JACC 2012;60:e44-e164.
Shaw JACC 2012;60:2103-14.
Multiparametric CMR: Balanced Steady-State Free
Precession Cine Imaging Stress / Rest Perfusion 3D coronary MRA Late Gadolinium Enhancement
CV Magnetic Resonance and SPECT For Diagnosis of CHD (CE-MARC) Trial (N=752)
Source: Greenwood Lancet 2012;379:453-60., Greenwood Circulation 2014;129:1129-38.
DesignN=1,200 - RCT of 3T CMR Stress-Guided Care vs. Standard of Care for Suspected CADHypothesis: CMR-Guided Management is Superior to the Standard of Care Avoiding Unnecessary Coronary Angiography & Reducing Clinical Outcomes
Source: Ripley Am Heart J 2015;169:17–24. Completed in 2018
Utilization of CCTA & Outpatient Invasive Coronary Angiography in Ontario, Canada
CCTA Growth - “Slow & Steady”
Elective Invasive Angiography & Revascularization Significantly Reduced post-CCTA Initiation 1,044 Fewer Invasive Angiograms /
Year
Source: Roifman JCCT 2015;9:567-571.
02468
101214161820
2011 2012 2013 2014
Stan
dard
ized
Rate
/ 100
,000
Cardiac CT Coverage
Begins
10.1 million Adults in Ontario
Target Appropriate Growth in the ED
RCT Evidence Supports CCTA Use in ED Evaluation of Low Risk Chest Pain Timely Diagnosis & Discharge in
Troponin Neg. Patients
UK’s National Institute of Health & Care Excellence (NICE) - Cost Effective
CT Use ↑ - 0.8% → 4.5% (p<0.001) from 2006-2013
Source: Litt NEJM 2012;366:1393-403.; Hoffmann NEJM 2012;367:299-308., Goldstein JACC 2011;58:1414-22.; Goodacre HTA 2013;17:1-188., Morris Acad Emerg Med 2016 May 7.
434%
-22% -11% -6%
-100%
0%
100%
200%
300%
400%
500%
CCTA ETT StressEcho
StressNuclear
Administrative Claims Analysis:
N=2,047,799 Testing ≤72 hrs
Comparative Trends of CCTA & Stress Testing in Emergency Department (ED) Patients with Chest Pain: Administrative Claims Analysis
N=2,047,799 ED Patients With CCTA or Stress Testing ≤72 hrs
CCTA Use ↑ from 0.8% to 4.5% (p<0.001) from 2006-2013
CCTA associated with higher rates of PCI (OR=1.25) and CABG (OR=1.47)
CCTA associated with more hospitalizations, return ED visits, & repeat noninvasive testing
Source: Morris Acad Emerg Med 2016 May 7.
434%
-22% -11% -6%
-100%
0%
100%
200%
300%
400%
500%
CCTA ETT StressEcho
StressNuclear
CCTA: Coronary Computed Tomographic Angiography; ETT: Exercise Tolerance Testing without Imaging; Echo: Echocardiography; Nuclear: PET or SPECT.
Patient-Centered Imaging
Right Patients + Right Rx Guidance = Optimal Patient Outcomes
Patient-Centered Imaging – To Optimally Guide Therapeutic Decision Making
High Quality CV Procedures
Right Patient Right Procedure Decision
Appropriate Use CriteriaGuidelines
Patient Preferences
Performance Measures
Quality MetricsPublic Reporting
Right Procedure Execution
Right Outcome
Ongoing Trials & Evidence
Value Equation for CV Procedures: Was Right Procedure Done Promptly in Right Way w/ Right Outcome?
To Identify Optimal Candidates for CV Procedures To Improve Safety - Reduce
Radiation Exposure / Complications Whenever Possible To Foster Efficiency - Eliminate
Unnecessary Testing – Induce Cost Savings
ACC Appropriate Use Criteria Taskforce
Standardize Communication of CCTA Findings & Facilitate OptimalPatient Management
CAD-RADS Classification - Recommendations for Management ofChest Pain Patients
CCTA-Guided Strategy of Care – Framework for Education &Quality Assurance to Facilitate Improve Quality of Care
Source: Cury JCCT 2016 (online).
Patient-Centered Imaging
Desired Patient
OutcomeCAD-RADSAUC
Focus on Patient-Centered Imaging
Quality Metrics in Your Practice – AUC, Structured Reporting, CAD/RADS, Timeliness Standards… Focus Use in Appropriate Patients Populations Establish Utilization in Areas w/ Established Comparative Effectiveness
Evidence in our Core Patient Populations
Institute Quality Assurance Programs – e.g., Cath Correlation Focused Patient & Referring MD Education of Radiation
Exposure & the Benefits of CCTA
Lab Accreditation, Physician Credentialing, Tech. Certification
Engage in Lifelong Learning – CCTA Experts
Value of Information: NICE Shared Learning Database
CCTA vs. Ex ECG in Low-Intermediate Risk Suspected SIHD PatientsJanuary 2012University Hospital Lewisham
CCTA Outperformed Ex ECGExcluding CAD– CCTA: 97.1%– Ex ECG: 72.9%
Fewer 2nd-Line Tests– 8.8%– 23.5%
Total Costs 20.3% Lower for CCTA
https://www.nice.org.uk/sharedlearning/ct-coronary-angiography#results
Legacy of Overuse in Imaging
Source: Lee Health Affairs 2012;31:1-9.
• Doctors Routinely Order Unnecessary Procedures• ~1/3 = Overuse / Duplication
Source: IOM; Stern Am J Med 2012;125:115-117., Phillips JNC (in press).
• Knowledge gap of ordering provider• Financial motivation ~$16b / y• Intolerance of diagnostic uncertainty• Defensive medicine, ~1 / 5 exams• Inaccessible prior exams, ~1 / 5 exams