CT Coronary Angiogram VS Cardiac Stress Test

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 H igh 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 for ‘Chest Pain of Recent Onset Assessment and Diagnosis’ 2016

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

8. 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)

9. 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

10. 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

11. 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.

12. 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

13. 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.

14. 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).

15. 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

16. 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

17. 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

18. 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

19. Determine pretest probability Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med. 1979; 300:1350–8. Forrester and Diamond 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.

20. 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

21. 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

22. 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

23. Principles within the ischemic cascade

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

25. 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)

26. Baseline ECG

27. Peak Exercise ECG

28. 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

29. 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

30. 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

31. 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

32. 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

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

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

35. 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

36. 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.

37. 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.

38. 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).

39. 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.

40. 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.

41. 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 resulting n 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.

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

43. 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

44. 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

45. 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).

46. 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

47. 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

48. Coronary angiogram FFR

49. 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, FFR angio  report showing the 3-dimensional left coronary system with color-coded FFR angio  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 FFR angio  (0.70) measurements. FFR indicates fractional flow reserve

50. CT coronary angiogram FFR Determination of FFR CT 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.

51. The balanced view…

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

53. 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

54. 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

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

56. MRI and PET perfusion scans

57. 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

58. 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, P=0.04)

59. Objectives- Coronary artery diesase Improved diagnosis Improve prognosis assessment

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

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

62. 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