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: leslee.shaw@emory.edu

Leslee J. Shaw, PhD, MASNC, FACC, FAHA, FSCCTProfessor of MedicineCo-Director, Emory Clinical CV Research InstitutePresident SCCTEmory University School of MedicineAtlanta, GeorgiaE-mail: leslee.shaw@emory.edu

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

1.0

1.5

2.0

2.5

Card

iac C

T Us

e Per

1,00

0

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