CT coronary angiography is a relatively new modality for identifying coronary artery disease. What is its place in ED chest pain assessment. See the evidence -and the evidence gaps- and judge for yourself where it might fit!

1. Anne-Maree Kelly
Director, Joseph Epstein Centre for Emergency Medicine
Research@Western Health, Melbourne

2.  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

3.  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!

4. From Schussler JM. Cardiac computed tomography:Emergeing
cardiac devices and technology. Asian Hospital and Healthcare
Management.
http://www.asianhhm.com/diagnostics/cardiac_computed_tomograp
hy.htm
• Non-invasive
• Nice pictures
• Can ‘see’ if there are lesions
or not

5. 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

6. 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

7. 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

8.  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

9.  Highly variable
 Options
◦ Exercise test
◦ Nuclear medicine studies
◦ CTCA
◦ GP or cardiologist can decide!
◦ Nothing (active choice)

10. 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

11.  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?

12.  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.

13.  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

14.  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

15.  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

16.  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. S
Schlett CA et al. JACC Cardiovasc Imaging. 2011;4: 481–491.

17.  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%.

18.  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.

19.  CTCA asks “Is there plaque”?
 I am not sure that is the right question

20.  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?

21.  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.

22. 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

23.  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. S
Schlett CA et al. JACC Cardiovasc Imaging. 2011;4:481–491.

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

25.  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!

26.  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.

27. 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.

28. 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

29. 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

30.  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

31.  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!

32.  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

33.  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.

34.  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

35.  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?

36.  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