Anne-Maree KellyDirector, Joseph Epstein Centre for Emergency Medicine Research@Western Health, Melbourne

No relationships with cardiac diagnostic or imaging companies

Co-author of National Heart Foundation (Australia) guidelines for the management of ACS (and addenda)

Supervisor of PhDs in CTCA’s role in chest pain

Editorial boards of:◦ Annals of Emergency Medicine◦ Emergency Medicine Australasia◦ Hong Kong Journal of Emergency Medicine

To explore the role of CTCA in ED chest pain patients, with a focus on those that ‘rule out’ for ACS in ED

To explore the cost-benefit of a CTCA compared to alternatives

To provoke debate about the rational place of CTCA in ED chest pain work-up!

From Schussler JM. Cardiac computed tomography:Emergeing cardiac devices and technology. Asian Hospital and Healthcare Management. http://www.asianhhm.com/diagnostics/cardiac_computed_tomography.htm

• Non-invasive• Nice pictures• Can ‘see’ if there are lesions

or not

Three major studies have suggested that CTCA for ED chest pain patients:

• Reduces ED length of stay

• Reduces admissions

• That negative scans have good prognostic performance

• That CTCA may be more ‘accurate’ in identification of CAD than alternatives

ROMICAT II

ACRIN-PA

CT-STAT

ACRIN-PA ROMICAT II

50% reduction in admissions (23% vs. 50%)

25% reduction in LOS (18 hours vs. 25 hours)

67% reduction in median LOS (9 hours vs. 27 hours)

19% reduction in ED costs

Litt HI et al. N Engl J Med 2012; 366:1393-403. Hoffmann U et al. NEJM 2012; 367:299-308

CT-STAT

54% reduction in time to diagnosis (3 hours vs. 6 hours)

38% reduction in costs

No difference in events

Goldstein et al. J Am Coll Cardiol 2011;58:1414-22

In Victoria, estimated 40,000 patients undergo ACS rule out in ED annually

The ‘rule in’ rate for ACS is ~15-20%◦ Depends how you count

About 32,000 have ACS ruled out and (according to ACS guidelines) need a further assessment strategy to rule out clinically significant CAD

Based on Dept Health Victoria data and estimates of chest pain presentations by Goodacre (UK): Goodacre et al. Heart. 2005; 91: 229–230.

Victoria, Australia

Population 5.6 million

Highly variable

Options◦ Exercise test◦ Nuclear medicine studies◦ CTCA◦ GP or cardiologist can decide!◦ Nothing (active choice)

TIMI score Demographics

0 33% 1 18% 2 18% 3 11% 4 11% 5+ ~9%

Male =60%

Average age=62

Known CAD = 33%

Based on data from cohort study @ WH 2009

Is CTCA sensitive for the detection of CAD?

Is CTCA suitable for the ED chest pain patient cohort?

Does a negative CTCA have good prognostic performance for future ACS events?

Does CTCA improve outcomes for patients?

How does CTCA perform in comparison to alternative investigation strategies?

Which patients should have this test rather than an alternative?

Depends on whether analysis is at patient level or segment level◦ Patient level is of prime importance in the ED context

Simple answer is ‘YES’

In a recent systematic review/ meta-analysis, CTCA had 94% (61-99%) sensitivity and 87% (16-100%) specificity for CAD.

Another meta-analysis of 64-slice +, reports sensitivity of 99% (95% CI 97-99%)

BUT about 9% of tests are non-diagnostic/ inconclusive

•Goodacre et al. Health Technol Assess 2013;17:1-188 •Mowatt et al. Technol Assess. 2008; 12:iii-iv, ix-143.

Remember, the question being asked is “Is there CAD”?

Just over 50% of the patient cohort is suitable for CTCA

About 30-40% of patients already have known CAD◦ Other investigation pathways are more suitable in most of these

Other ‘contra-indications’: 10-15%◦ Metformin ◦ Inability to control rate adequately◦ Renal failure/ impairment◦ Thyroid disease◦ Irregular rhythms

Hamid S et al. Am J Emerg Med. 2010;28:494-8

Safety◦ Short term adverse events related to the scan are very rare◦ Contrast allergy at expected rate (1/2,500-1/25,000)◦ Adverse effects due to rate control-usually minor◦ Radiation risk

Feasibility◦ Limited by access to scanner and availability of experienced readers◦ ‘In hours’ only availability does not match ED 24/7 patient flow◦ ‘Competition’ with other patients needing CT scan

In meta-analysis: I death from 1334 patients No PCI, MI etc Rate = 0.07% (95% CI

0.01% to 0.4%)

Goodacre et al. Health Technol Assess 2013;17:1-188

In cohort study: No PCI, MI, deaths in 508

patients at median 47 month follow-up

Rate = 0% (95% CI 0% to 0.07%)

Simple answer is ‘YES’

Nasis et al. Radiol 2014; April 14

In meta-analysis: 39 events in 332 cases 12 MI Two thirds of events were revascularisations Rate 12% (95% CI 9-16%) Only one study was blinded to CTCA results:

◦ Showed CTCA result (presence of stenosis) was independently associated with MACE (HR 17)

Goodacre et al. Health Technol Assess 2013;17:1-188. SSchlett CA et al. JACC Cardiovasc Imaging. 2011;4: 481–491.

A growing literature with several points of view

Focus is the sub-population without known CAD◦ 65-70% of cohort (about 25,000 patients annually in Victoria)

Available data suggests background rate of asymptomatic CAD ~5-8%.

Cost benefit depends on:◦ Sensitivity of the tests being compared◦ Prevalence of clinically relevant CAD, especially in low risk

subgroups◦ Relative costs in the healthcare system in question◦ Patterns of investigation/ intervention especially for

intermediate or indeterminate tests◦ The risk of adverse events associated with CAD ◦ The time period of follow-up◦ The community’s willingness to pay (e.g. $ per QALY)◦ Any negative impact of CT delay for other patients e.g. acute

stroke, head injury, etc.

CTCA asks “Is there plaque”?

I am not sure that is the right question

What is the risk of MACE in patients without known CAD, with non-diagnostic ECG and normal serial biomarkers in ED?◦ This prognostic information is still evolving◦ Complicated (and simplified) by new higher sensitivity

biomarkers

At what MACE risk level is ‘routine’ testing indicated?

What is the risk of MACE in patients without known CAD, with non-diagnostic ECG and normal serial biomarkers in ED?

A. 5%

B. 2%

C. 1%

D. 0.5%Fitzgerald P et al. Acad Emerg Med 2011;18:488–95.

Test Sensitivity NPV (MACE)

CTCA 94-99% >99%

MPS 87% 97.2%

Exercise ECG (EST) 20-30% As low as 86%

Conti et al. Nucl Med Commun 2011 32;1223

Varying study design, populations and outcomes studied

In meta-analysis Rate of MACE for negative EST 0.7% (95% CI 0.5-

1.2%) But sensitivity questionable

◦ Some studies around 30% sensitivity for occlusive CAD

Goodacre et al. Health Technol Assess 2013;17:1-188. SSchlett CA et al. JACC Cardiovasc Imaging. 2011;4:481–491.

Not enough data in the specific population of interest to draw conclusions

Positive predictive value for CAD at segment level is only moderate (78%)◦ False positives: over-estimation of lesion severity in presence

of calcified plaques

Scanning 15,000 patients in Victoria/year will pose access issues for CT scanners!

An ‘elephant in the room’

Retrospectively gated protocols, risk estimated at:◦ 0.11 to 0.13% for men◦ 0.27-0.37% for women

Prospectively gated protocols, risk estimated at:◦ 0.014-0.017% for men◦ 0.035-0.06% for women

Risk is inversely related to age

Significant ethnic variation

Huang et al. Br J Radiol.  2010;83(986):152-8.

ACRIN-PA

50% reduction in admissions (23% vs. 50%)

25% reduction in LOS (18 hours vs. 25 hours)

No patient with negative CTCA had death, MI within 30 days

Only 2/1357 (0.15%) of patients not diagnosed with MI at index visit had MI within 30 days

Trial conditions re CT availability

TIMI 0-2◦ >85% TIMI 0 or 1

Litt HI et al. N Engl J Med 2012; 366:1393-403.

CT-STAT

54% reduction in time to diagnosis (3 hours vs. 6 hours)

38% reduction in costs

Only included ED costs

Trial conditions re CT availability

Highly selected cohort

In CTCA cohort, 6 times greater rate of additional non-invasive tests after ED discharge◦ Cost◦ Radiation, etc

Goldstein et al. J Am Coll Cardiol 2011;58:1414-22

ROMICAT II

67% reduction in median LOS (9 hours vs. 27 hours)

19% reduction in ED costs

Eventual hospital costs actually 50% higher in CTCA group

Higher rate of additional testing (27% vs.12%)

No difference in events

Trial conditions re CT availability

Selected population ◦ 40-74◦ No AF or renal disease or BMI<40Hoffmann U et al. NEJM 2012; 367:299-308

Data from administrative dataset◦ Age 66+◦ Non-emergent, non-invasive test for ?CAD◦ No known CAD

Compared CTCA vs. stress myocardial perfusion scan Results:

Outcome CTCA MPS

Cardiac catheter 23% 12%

PCI 7.8% 3.4%

CABG 3.7% 1.3%

All cause mortality 180 days

1.05% 1.28%

Hospitalization for MI 180 days

0.19% 0.43%

Schreibati et al. JAMA 2011; 306:2128-36

1. That a test to rule out CAD before discharge is needed in ED chest pain patients◦ This is unproven!◦ The rationale for any test (compared to no test) is that it improves

outcome◦ Event rates are so low (<1%) in all arms that it is impossible to tell if

CTCA provided benefit 2. All lesions found were cause of symptoms

◦ 5% rate of occlusive lesions found in screening of asymptomatic patients

With risk of dye, radiation, extra tests etc. harm is likely to seriously compete with any benefit!

In Australasia:

◦ ~75% of patients are discharged from ED/SSU

◦ Most do not have additional testing before discharge

◦ Median LOS of the order of 6-10 hours, depending on centre and protocol (some much shorter)

◦ LOS likely to reduce as accelerated diagnostic biomarker pathways are implemented

SCCT/AHA/ACC:◦ Symptomatic patients without known CAD with ‘intermediate’

pre-test probability◦ Symptomatic patients without known CAD with ‘low’ pre-test

probability who cannot perform a functional test or with equivocal functional test results

◦ Not suitable for high pre-test probability patients due to: High likelihood of plaques Limited spatial and temporal resolution These should have CA or functional test

Taylor AJ et al. J Am Coll Cardiol 2010:56:1864-94.

CTCA is not indicated as a ‘routine’ test in ED patients with chest pain without known CAD and with normal biomarkers and ECG

It may be useful in a subgroup based on risk, but how this risk might be defined in unclear

There is a reasonable case for no further testing in significant proportion of ED chest pain patients who have had ACS ruled out by clinical evaluation, ECG and biomarkers

Comparison of DM, ‘metabolic syndrome’ and other (MPS study)

Metabolic syndrome defined as at least 3 of:◦ Fasting glucose >110mg/dl◦ High BP◦ Low HDL◦ High triglicerides◦ High waist circumference

Rate of MACE at 1 year ◦ DM 30%◦ Metabolic syndrome 26%◦ Others 15%

Conti et al. Nucl Med Commun 2008; 29:1106-12.

Could similar parameters identify a subgroup of patients who might benefit from CTCA?

CTCA is a test looking for its role in the ED chest pain population

More data regarding patient selection and patient-centred outcomes is needed before its place can be better defined