Presentation by Dr Chan Wan Xian Cardiologist, Echocardiologist, Heart Failure Specialist Asian Heart & Vascular Centre www.ahvc.com.sg

1. CT coronary angiogram vs
Cardiac stress tests
Dr Chan Wan Xian
Consultant Cardiologist
Heart Failure Specialist
Echocardiologist

2. CT Coronary Angiogram Cardiac Stress Tests

3. CT coronary angiogram

4. Advances in Cardiac CT
• High quality images of the heart
• Improved tissue and material characterization
• Advances in radiation dose reduction techniques
• Accuracy of cardiac CT in depicting coronary artery anatomy compared to
invasive coronary angiography has now been established
• High accuracy and negative predictive value make CT well suited to exclude
obstructive coronary artery disease in the low to intermediate risk population
• Myocardial perfusion CT option available to obtain functional information from
CT. It has higher specificity (68–98%) and PPV (55–94%) in the diagnosis of
myocardial ischemia compared to conventional CT
• Large multicenter trials have also established the role of CT in predicting major
cardiovascular events which helps in prognostication and early initiation of
preventive therapy at subclinical stage
Cardiovasc Diagn Ther 2017;7(5):429-431

5. National Institute of Health and Care Excellence (NICE)
guideline

6. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS
guideline

7. European Society of Cardiology 2013 non-invasive
testing in
patients with suspected stable coronary artery disease
Class IIa recommendation for CTA in patients
in the lower range to intermediate pre-test
probability as an alternative to stress
imaging, or after an inconclusive stress test,
or for patients who have contraindications

9. Pro: NICE guidelines represent a NICE evolution
• Computed tomography angiography offers improved
accuracy
• Computed tomography angiography offers improved
outcomes
• Computed tomography angiography is associated with less
non-obstructive invasive coronary angiography,
downstream testing, and angina and increased quality of life
and medical therapy
• Computed tomography angiography should improve
compliance with appropriate use criteria (AUC)

10. Meta-analyses of the diagnostic performance of functional imaging and
CCTA with ICA >50% Diameter Stenosis as reference standard
CCTA, stress MRI, and PET emerge as the most sensitive and specific modalities,
compared with single-photon emission computed tomography (SPECT) and stress echo
imaging

11. • With invasive FFR ≤0.80 as the reference, CCTA, and stress MRI and PET prove to be the most
sensitive, and the latter two to be the most specific
• Coronary CT angiography is the least specific but CT derived FFR and CT perfusion (CTP) increase the
specificity and positive likelihood ratio closer to the level of MRI and PET imaging without loss of sensitivity

12. Pooled results of the shorter-term trials revealed significantly fewer myocardial infarctions with CTA (3.8% vs.
5.6%, P= 0.038), as well as higher rates of revascularization (49% vs. 21%, P= 0.01) compared with UC.
There were no differences in death, ICA, or chest pain readmission
Circ Cardiovasc Imaging. 2016;9:e004419.

13. Calcium imaging and selective computed tomography angiography in comparison to functional
testing for suspected coronary artery disease: the multicentre, randomized CRESCENT trial
• 350 patients randomised in a
2:1 ratio to CAC+CTA if CAC 1–
400 vs. functional testing (ETT
50%, SPECT 29%, SE 7%, ICA
11%) with a median 1.2-year
followup.
• It reported significant
reductions for CTA in major
adverse cardiac events (3% vs.
10%, P= 0.004) with an event
free hazard ratio of 0.36,
(96.7% vs. 89.8%, P= 0.01)
compared with UC, as well as a
significant cost reduction (P <
0.0001) without change in ICA
frequency.
European Heart Journal (2016)
37, 1232–1243
Downstream testing.
Proportion of patients
requiring further non-
invasive and/or
invasive testing.
Kaplan–Meier curves of event-free survival

14. Functional Testing or Coronary Computed Tomography Angiography in
Patients With Stable Coronary Artery Disease
• The Danish National Registry compared 53 744 stable CAD patients evaluated by functional testing (80%
treadmill testing, 20% MPI) and 32 961 patients evaluated by CTA, with a 3.6 year follow-up period
• There was a lower risk of myocardial infarction following CTA (hazard ratio 0.71; 95% confidence interval 0.61–0.82) and
comparable all-cause mortality (hazard ratio 0.96; 95% confidence interval 0.88-1.05)
Jørgensen, M.E. et al. J Am Coll Cardiol. 2017;69(14):1761–70.

15. Coronary CT Angiography and 5-Year Risk
of Myocardial Infarction
The SCOT-HEART Investigators
N Engl J Med 2018;379:924-33
• CTA compared with UC for the primary endpoint of
death from CAD or non-fatal myocardial (2.3% [48
patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95%
confidence interval [CI], 0.41 to 0.84; P = 0.004).
• More preventive therapies were initiated in patients in the CTA
group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more
antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54).

16. • In three studies, there was significantly more non-obstructive ICA following UC than CTA
• Downstream testing was significantly lower for CTA in the two trials in which it was reported
• Significantly improved quality of life following CTA was reported by CAPP and decreased angina frequency
following CTA was noted in CRESCENT
• In the two trials that reported changes in medical therapy, CTA was more effective than UC
European Heart Journal (2019) 40, 1440–1453

17. CT coros likely to improve compliance with
appropriate use criteria (AUC)?
• In the United States, the number of stress tests has increased from
1.6 million annually in 1993–1995, to 3.8 million per year in 2008-
2010, and the accompanied imaging tests increasing from 59% to
87%, respectively
• However, the increased utilization has not been associated with an
increase in their appropriate use application
• A meta-analysis of 59 reports of 103 567 tests, published from 2000
to 2012 appropriate use of CTA increased from 37% in 2006 to 55% in
2010 but no significant change for stress echo and MPI use

19. Anatomic approaches for stable chest pain
miss the mark?
• Approach of using non-invasive stress test to assess for presence and
severity of ischemia has been the main stay of clinical management
for patients with stable CAD for more than three decades
• It remains a valuable means to guide therapeutic decision-making
(initiation and intensification of anti-ischaemic therapies)
• Use of stress imaging to determine demand ischemia and to identify
functionally significant obstructive CAD has been a core means of
defining CAD treatment and has been the focus of many prior trials

20. Initial diagnostic management of patients with suspected
stable coronary artery disease
Stepwise approach
• Clinical assessment
• Determine pretest
probability
• Non-invasive test to
establish the diagnosis of
stable CAD/ non ob
atherosclerosis
• Management post stress
test
- Medical
- Revascularisation
• Risk stratification

22. Determine pretest probability
Analysis of probability as an aid in the clinical
diagnosis of
coronary-artery disease. N Engl J Med. 1979;
• Type of pain and age and sex of the patient can provide a
reasonable estimate of the likelihood of IHD
• 50-yo man with atypical angina, the probability of CAD is ~50%
• Diagnostic testing is most valuable in INTERMEDIATE pre-test
probability of Ischemic heart disease
• Duke Databank incorporated electrocardiographic
findings (Q waves or ST-T changes) and information
about risk factors (smoking, diabetes mellitus,
hyperlipidemia)
• Key contribution is the value of incorporating data
about risk factors into the probability estimate.

23. • Groups in white boxes have a PTP <15% and hence can be managed without further testing.
• Groups in blue boxes have a PTP of 15–65%. They could have an exercise ECG if feasible as the initial test. However, if local
expertise and availability permit a non-invasive imaging based test for ischaemia this would be preferable given the superior
diagnostic capabilities of such tests. In young patients radiation issues should be considered.
• Groups in light red boxes have PTPs between 66–85% and hence should have a non-invasive imaging functional test for making a
diagnosis of SCAD.
• In groups in dark red boxes the PTP is >85% and one can assume that SCAD is present. They need risk stratification only

24. Interpretation of non-invasive cardiac tests
requires a Bayesian approach to diagnosis
• Uses clinicians’ pre-test estimates[termed pre-test probability (PTP)]
of disease along with the results of diagnostic tests to generate
individualized post-test disease probabilities for a given patient
• The probability of a new event, or ‘true’ positive stress test, depends
on the pre-test risk of the patient which have been derived from
empiric data
• PTP is influenced by the prevalence of the disease in the population
studied, as well as clinical features (including the presence of CV risk
factors) of an individual

25. Approach in selection of diagnostic tests
• Functional or stress testing to detect inducible ischemia has been the
“gold standard” and is the most common noninvasive test used to
diagnose SIHD
• All functional tests are designed to provoke cardiac ischemia by using
exercise or pharmacological stress agents either to increase
myocardial work and oxygen demand or to induce vasodilation-
elicited heterogeneity in induced coronary flow
• Production of ischemia, however, depends on the severity of stress
imposed (i.e., submaximal exercise can fail to produce ischemia) and
the severity of the flow disturbance

26. Principles within the ischemic cascade

27. Cardiac Stress Tests to provoke Ischemia
Patient CAN exercise Patient canNOT exercise
Exercise stress tests Pharmacological stress tests
1. Treadmill
2. Treadmill + Echo
3. Treadmill + SPECT nuclear stress test
4. Exercise + MRI scan
Vasodilator
- Dipyridamole
- Adenosine
- Regadenosone
Beta-agonist
- Dobutamine
1. SPECT Nuclear stress test
2. PET Nuclear stress test
3. Cardiac MRI perfusion scan
4. CT perfusion scan
1. Dobutamine stress Echo
2. Dobutamine stress MRI
Increase Myocardial Work
and Oxygen Demand
Induce Vasodilator-elicited
heterogeneity in induced coronary flow

29. Treadmill Exercise Stress Test
1918 - Bousfield noted ST depressions during angina
1929 - Masters and Oppenheimer developed a standardized exercise test
Target HR: 220 - patient’s age (SD: 10-12 beats/min) x 0.85
End-Point: Heart Rate, Blood Pressure, Exercise Capacity, ECG, Symptoms
↑ Cardiac Output, ↑ Stroke Volume
↑ Sympathetic discharge ↓ Parasympathetic
discharge ↑ Epinephrine/NE ↑ Skeletal blood
flow, ↓ PVR ↑ SBP, ↓/= DBP
• Achieve 85% max predicted HR (220‐age), for an optimal test
Advantages - Widely available - Least expensive - Provides a good
measure of functional capacity
Limitations - Non-diagnostic with abnormal baseline ECG: - LBBB, paced
rhythm, LVH, ST-segment depressions 0.5 mm - Lower sensitivity and
specificity than imaging - Non-localizing (unless ST segment elevations)

30. Baseline ECG

31. Peak Exercise ECG

32. Treadmill+ Echo
End-Point: HR, BP, Exercise Capacity, ECG, Symptoms, ECHO images, Wall motion abnormalities and POST peak LVEF
Target HR: 220 - patient’s age (SD: 10-12 beats/min) x 0.85
Advantages
- Readily available
- Provides direct visualization of wall motion, LV function, and
anatomy
- Can localize region of abnormality
- May detect valvular abnormalities
- Higher specificity than perfusion imaging (77-89% vs 70-88%)
- Higher sensitivity than Treadmill alone (70-85% vs 61-68%)
- No radiation
Limitations
- Technically difficult with poor acoustic windows
- Requires an experienced sonographer
- Less sensitive than myocardial perfusion imaging (requires
ischemia)
- Fewer clinical data than perfusion imaging
- Interpretation is subjective
- Interpretable image quality may be obtained during submaximal HR

33. Dobutamine Stress Echo
End-Point: HR, ECG, Symptoms and ECHO images, Wall motion abnormalities (demand state), PEAK stress LVEF
Dobutamine: Beta-agonist: ↑ Heart Rate, ↑ Inotropy
Target HR: 220 - patient’s age (SD: 10-12 beats/min) x 0.85
Application:
- Reactive airway disease, severe
COPD
- Second degree AV block
- Caffeine consumption within 24 h
Advantages:
- Used for risk-stratifying patients prior to
vascular surgery
- Preferred over vasodilator nuclear test
for assessment of regional wall motion
- At low-dose stages allows viability and
ischemia assessment in segments with
abnormal function at rest
- No radiation
Disadvantages:
- Small risk of drug-specific adverse
events: VT/VF and MI (1:2,000)
- Poor image quality (patients with
advanced lung disease)
- May need Atropine (max 2mg) to
augment HR
- Intolerable symptoms: palpitations,
nausea, headache, tremor, anxiety

36. 3RPL 75-80% stented with Orsiro 3.0 x 22mm. pLAD 75% stented with Orsiro 4.0 x 18mm. D1 ostium 75% treated wlth Magic Touch 2.0 x 15mm DEB.
LCx disease for medical therapy

37. Treadmill Exercise + SPECT Nuclear Myocardial Perfusion Scan
End-Point: HR, BP, Exercise Capacity, ECG, Symptoms and coronary flow
Possible vasodilator conversion if submaximal HR
Advantages
- Can be used in patients with moderate to high
pre-test probability
- Perfusion and function
- Can localize disease
- Can risk stratify
- Pharmacologic stress may be performed
- Higher sensitivity than stress echo (flow
heterogeneity)
Limitations
- Relatively expensive
- Decreased specificity (attenuation artifact)
- Radiation exposure
Target HR: 220 - patient’s age (SD: 10-12 beats/min) x 0.85

38. Pharmacological Nuclear Myocardial Perfusion Scan
Indications:
• Abnormal baseline ECG : Atrial
fibrillation, LBBB, paced, LVH etc
• Unable to exercise adequately
• Patients with prior revascularization
• Patients with a higher likelihood for
disease
• Poor Echo acoustic window
Advantages:
-After successful PCI, to evaluate
symptoms suggesting new disease
-Ischemia assessment after CABG
-Prior to intermediate or high risk non-
cardiac surgery
-PET has higher sensitivity for CAD
detection, in women and obese
Disadvantages:
-Risk of drug-specific adverse events:
bronchospasm in COPD, AV block
-Global reductions in myocardial perfusion
(i.e. left main or 3V CAD), can result in
balanced reduction ischemic burden
-Radiation

40. Large, severe, reversible defect involving the anterior wall, septum, apex and inferior wall
-> Cath confirmed 85% mid LAD stenosis

41. Large-sized area of severely decreased uptake in the inferior wall.
This defect is almost fully reversible on rest images, EF 44%.

42. Cardiac MRI perfusion scan
First-pass perfusion study with a
saturation-recovery-prepared
gradient echo sequence covering
four sections during each heartbeat
The graph shows signal
intensity (SI) changes in
anterior and inferior
myocardial sectors, with the
latter showing reduced
myocardial enhancement

43. A, Stress and, B, rest first-pass
perfusion images show ischemia in
anterolateral wall and a fixed defect in
the inferolateral walls (no stenosis)
(arrows).
C, D, Late gadolinium enhancement
images show a nearly transmural
myocardial infarction in the inferolateral
wall (arrow) and viable myocardium
everywhere else.

44. E, F, Subsequent coronary angiograms ordered at the discretion of the referring
physician show, E, critical luminal narrowing (arrow, >70%) in left anterior descending
coronary artery and, F, no critical stenosis in the right coronary artery.

45. Illustration of the sequence of protocol components in a cardiac MR examination, which includes assessment of myocardial perfusion at rest and
during vasodilator stress. The stress perfusion examination is generally performed before rest perfusion imaging to minimize a confounding
effect of late gadolinium enhancement on the diagnostically most valuable part of the perfusion examination (vasodilator perfusion).

46. CT Myocardial Perfusion Imaging
A, Curved multiplanar reformatted view of left anterior descending artery shows noncalcified plaque (arrow)
with critical stenosis in proximal segment. B and C, Long-axis (B) and four-chamber (C) views show
hypoattenuation of anterior and apical subendocardial myocardium (arrowheads) consistent with acute
infarction.

47. A, Curved multiplanar reformatted view of left circumflex artery shows mixed plaque (arrow) with
intermediate-to-severe stenosis. B and C, At stress, dual-energy iodine distribution map (B) shows well-
demarcated area of decreased myocardial iodine content (arrowheads) in lateral wall of left ventricle, which
is reversible on rest image (C). Findings are thus consistent with lateral wall ischemia.

48. A, Three-dimensional volume-rendered reconstruction of coronary CTA shows stent (arrow) in first obtuse
marginal branch of left circumflex artery.
B, Curved multiplanar reformatted view of coronary CTA shows area of marked hypoattenuation proximal to
stent (dotted arrow), suggesting intimal hyperplasia resultingn severe restenosis.
C, Parametric map of myocardial blood flow derived from stress dynamic CT myocardial perfusion imaging
shows well-demarcated area of decreased myocardial blood flow to lateral wall of left ventricle (arrowheads),
corresponding to territory of first obtuse marginal branch.

49. Combined dynamic rest and stress CT perfusion studies can require radiation exposure of
approximately 18 mSv

50. Con: anatomic approaches for stable chest
pain miss the mark
• Computed tomography angiography is a relatively new procedure and
standards of care have yet to be put forth from recent randomized trials
• CTA-guided therapeutic strategy not been defined
• Index anatomic procedure leads to a higher rate of downstream ICA and
revascularization when compared with index functional testing
• Coronary revascularisation has failed to demonstrate a benefit in terms of
risk reduction in stable CAD (difficulty in risk stratification without stress
induced ischemia to guide treatment approach)
• CTA approach eliminates functional testing and information on ischemia in
patients with intermediate-high grade stenosis

51. Optimal Medical Therapy with or without PCI
for Stable Coronary Disease
- COURAGE TRIAL
• Randomized trial involving 2287 patients who had
objective evidence of myocardial ischemia and
significant coronary artery disease at 50 U.S. and
Canadian centers between 1999 and 2004
• 1149 patients to undergo PCI with optimal medical
therapy (PCI group) vs 1138 to receive optimal medical
therapy alone(medical-therapy group)
N Engl J Med 2007;356:1503-16

52. There were no significant differences
between the PCI group and the
medical-therapy group in
• 4.6-year cumulative primary-
event rates were 19.0% in the PCI
group and 18.5% in the medical-
therapy group (hazard ratio for
the PCI group, 1.05; 95%
confidence interval [CI], 0.87 to
1.27; P = 0.62).
• the composite of death,
myocardial infarction, and stroke
(20.0% vs. 19.5%; hazard ratio,
1.05; 95% CI, 0.87 to 1.27; P =
0.62)
• hospitalization for acute coronary
syndrome (12.4% vs. 11.8%;
hazard ratio, 1.07; 95% CI, 0.84 to
1.37; P = 0.56)
• myocardial infarction (13.2% vs.
12.3%; hazard ratio, 1.13; 95% CI,
0.89 to 1.43; P = 0.33).

53. A Randomized Trial of Therapies for Type 2 Diabetes and
Coronary Artery Disease
The BARI 2D Study Group
• There was no significant difference in rates of survival between the revascularization group and
the medical-therapy group
• The rates of major cardiovascular events (death, myocardial infarction, or stroke) also did not differ
significantly between the revascularization group and the medical-therapy group

54. Advances in Cardiac CT
• CT-FFR is an advanced post-processing technique. FFR is obtained
non-invasively from a routine coronary CTA.
• Provides functional information of coronary artery stenoses
Cardiovasc Diagn Ther 2017;7(5):429-431

55. Coronary angiogram FFR

56. Accuracy of Fractional Flow Reserve Derived From Coronary Angiography, Volume: 139, Issue: 4, Pages: 477-484, DOI: (10.1161/CIRCULATIONAHA.118.037350)
A, Coronary angiograms showing a moderate lesion in the left anterior descending artery. B, FFRangio report showing the 3-
dimensional left coronary system with color-coded FFRangio measured along the vessels shown in 2 views with overlay on the 2-
dimensional angiogram (top) and with lumen contours (bottom). C, Location of the pressure sensor for FFR measurement. D,
Corresponding pressure wire–derived FFR including the equalization (top), resting (middle), and hyperemic (bottom) recordings,
with similar FFR (0.72) and FFRangio (0.70) measurements. FFR indicates fractional flow reserve

57. CT coronary angiogram FFR
Determination of FFRCT by using computational fluid dynamics principles
Acquisition of standard
coronary CT angiography
data
Creation of a 3D
model of the coronary
artery anatomy
Determination of a
physiologic model of the
coronary microcirculation
derived from patient-
specific boundary
conditions
Application of computational fluid
dynamics for the computation of
coronary blood flow
Color-coded three-dimensional
mesh representing FFRCT
values for each point
throughout the coronary tree.

58. The balanced view…

59. What is the clinical question???
1. The presence of CAD (of any degree)
2. High-risk plaque that portends hard events
3. Stenosis of a certain anatomic/physiologic severity
4. Stenosis that compromises myocardial blood flow significantly
(ischaemia)
5. Stenosis that needs intervention with varying urgency
6. Stenosis that can and should be fixed to reduce adverse outcomes
7. Re-stenosis/ ischemia in previous PCI / CABG patients

60. • To answer different clinical questions,
different diagnostic strategies are needed
• Not realistic to think that one test will
adequately answer all the questions
• Anginal symptoms are often, but not
always, a consequence of lumen
compromise
• Prognostic risk, on the other hand, is
predicated on the amount of plaque and
the nature of the arterial wall (plaque
morphology and local dynamics) and can
be high in asymptomatic patients who are
not typically seen or offered non-invasive
testing at all by the cardiology community
• Different non-invasive tests provide
different clinical information
• Availability of techniques and tests

61. What should be the future approach to
evaluation of stable CAD?
• Establish goal of testing in patient with suspected CAD and plan our
diagnostic strategies based on the answer to that question
• Fundamentally, we need more robust data to determine that detecting any
of these endpoints is meaningful and, more importantly, intervention
based on these endpoints changes outcomes
• It is evident that one test may not answer all these questions in many
patients
• Layered/ tiered testing in intermediate probability patients if the first test is
not conclusive
• Newer techniques of non invasive testing that are available easily and cost
effective
• It is good to keep an open mind about the role of testing for CAD

62. Thank you
6 Napier Road # 04-13
Gleneagles Annex Block
Singapore 258499
38 Irrawaddy Road #08-58
Mount Elizabeth Novena
Specialist Centre
Singapore 329563

63. MRI and PET perfusion scans

64. Talk outline
• Chest pain approach guidelines
• Management of stable IHD/ angina guidelines
• Ischemic cascade/ controversy
• Introduce cardiac stress tests, purpose
• Introduce CT coros , current radiation and accuracies
• What is the controversy?
• - CT coros better than stress echo- anatomical infor- no functional infor
• Stress tests better than CT coros, earlier in the ischemic cascade- no anatomical infor
• Recent studies- CT coros better- cost effective, better outcomes driven by better management
• Pros and cons of CT coros and cardiac stress tests
• UK NICE guidelines vs ACC and ESC
• Advances in CT coros- CT FFR

65. • 10 000 symptomatic patients were randomized to CTA or functional testing (SPECT 67.5%, SE
22.4%, ETT 10.2%) and followed for a mean of 25months
• There were no outcome differences, very likely because of the low incidence of events and obstructive
disease or ischaemia, but CTA had better prognostic value than functional testing (c-index 0.72 vs. 0.64,

66. Objectives- Coronary artery diesase
• Improved diagnosis
• Improve prognosis assessment

67. CT coronary angiogram
• Can identify both nonobstructive and obstructive coronary artery
disease (CAD)

68. • Not so much which test but Importance of an approach- not studied
or trialed- difficult- logistics and expenses

70. Cardiac Stress Tests to provoke Ischemia
• Treadmill exercise stress test
• Echocardiography stress test
• Myocardial Perfusion stress test
• CT perfusion stress test
• MRI perfusion stress test