Editor's Note: This is the Pro article of a two-part Pro/Con Expert Analysis. Click here for the Con article.

The evaluation of adults with stable chest pain concerning for possible coronary artery disease (CAD) is one of the most commonplace and costly evaluations in all of medicine. Given the number of available, well-studied, and prognostically useful noninvasive tests for CAD, there remains much debate over optimal evaluation pathways to improve clinical and cost outcomes in patients with chest pain. Current US stable ischemic heart disease guidelines favor noninvasive functional testing for myocardial ischemia in most patients, reserving anatomic testing using coronary computed tomography angiography (CTA) for patients without established CAD who have already undergone functional testing (inconclusive results or ongoing symptoms) or are unable to undergo functional testing.¹ However, coronary CTA has undergone remarkable technological advancements in safety and image quality that, when paired with results from recent comparative effectiveness trials, has led many to conclude that it should be more broadly performed and serve as the first test in many patients with stable chest pain.² For example, in 2016, the National Institute for Health and Care Excellence (NICE), the evidence-based organization that guides healthcare in the United Kingdom, updated its chest pain guideline and made coronary CTA the first test for all patients without established CAD who present with typical or atypical angina or with non-anginal chest pain plus an abnormal resting electrocardiogram (ECG).³ Stress imaging studies were recommended in patients with known CAD, and exercise stress ECG testing was not recommended for the diagnosis of CAD due to its low accuracy and high rates of subsequent testing. It was estimated that broad adoption of this strategy would save the UK National Health Service £16 million annually.

As discussed below, there are several reasons why NICE made these sweeping recommendations and why we in the United States should accordingly more broadly utilize coronary CTA as the preferred test for patients without known CAD who present with stable chest pain.

Coronary CTA Improves Important Patient Outcomes Compared With Functional Testing: The Value of Nonobstructive CAD to Guide Post-Test Management

Numerous large-scale randomized, controlled comparative effectiveness trials, such as PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain; n = 10,003) and SCOT-HEART (Scottish Computed Tomography of the Heart; n = 4,146), have established that coronary CTA is at least as effective as strategies that do not utilize coronary CTA for all studied cardiovascular outcomes.^4,5 In fact, among randomized controlled imaging-guided trials, coronary CTA has been consistently associated with reduced incident myocardial infarction (MI) in both acute and stable chest pain populations.⁶ In a meta-analysis of randomized trials, stable chest pain patients who underwent coronary CTA were noted to have a 31% lower risk for MI (pooled risk ratio 0.69; 95% confidence interval, 0.49-0.98), a finding that was consistent across the 3 included trials, including PROMISE and SCOT-HEART (I-squared = 0%).⁷

Because tests themselves do not improve outcomes, a closer look at these trials reveals the impact that visualized coronary atherosclerosis on CTA had on subsequent utilization of preventive therapies, such as aspirin and statins. For example, in SCOT-HEART, not only did coronary CTA improve diagnostic certainty for patients and providers regarding the etiology of the patients' presenting symptoms (primary outcome), but also patients who underwent coronary CTA had a fourfold increase in the use of aspirin or statin therapy.⁸ These test-driven changes in post-test management related primarily to visualization of nonobstructive CAD resulted in a 50% reduction in incident MIs within fewer than 2 years of follow-up.

In addition to CAD location and stenosis severity, plaque composition and morphology may further enhance the prognostic yield from coronary CTA. In a recent analysis of the PROMISE trial, the presence of high-risk plaque (positive remodeling, low computed tomography [CT] attenuation, or napkin ring sign) was associated with significantly increased risk of major adverse cardiac events (adjusted hazard ratio 1.73; 95% confidence interval, 1.13-2.62), even after adjustment for risk factors and stenosis severity.⁹ The prognostic importance of high-risk plaque was especially apparent among subjects with nonobstructive CAD on CTA (adjusted hazard ratio 4.31 vs. 2.64) among this low-intermediate risk cohort (33% with 10-year atherosclerotic cardiovascular disease risk <7.5%).

These findings remind us that although functional tests attempt to detect flow limiting CAD, only coronary CTA can accurately quantify the presence, extent, angiographic severity, and composition of coronary atherosclerosis (Figure 1). Importantly, these well-proven measures of CAD have been shown to consistently outperform risk factors for predicting long-term cardiovascular outcomes and may better identify patients most likely to benefit from aggressive preventive medications and lifestyle interventions.

Figure 1

Coronary CTA: High Diagnostic Accuracy; Rarely Misses Severe, High-Risk CAD

Coronary CTA has been shown to have the highest diagnostic accuracy compared with all available noninvasive tests for the detection of angiographically significant stenosis on invasive coronary angiography (ICA). In the CORE-320 (Combined Non-invasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography) trial (n = 391), sensitivity to identify patients with stenosis ≥50% on ICA was greater for CTA than single-photon emission computed tomography (SPECT) myocardial perfusion imaging (0.92 vs. 0.62, respectively; p < 0.001).¹⁰ Similarly, in the EVINCI (Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease) trial, coronary CTA had sensitivity and specificity of 91% and 92%, respectively, compared with myocardial perfusion imaging with SPECT/ positron emission tomography (PET) (sensitivity 74%, specificity 73%) for detection of significant CAD (>50% left main, >70% non-left main or fractional flow reserve [FFR] <0.80) on ICA.¹¹ It is not surprising that coronary CTA, an anatomic test, correlates more strongly with ICA. When using invasive FFR as the reference, coronary CTA again demonstrates very high per-patient sensitivity. In the recent PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial, 208 patients with suspected CAD underwent coronary CTA, SPECT, [15O]H2O PET, and ICA with FFR of all coronary arteries.¹² The sensitivity for FFR <0.80 was 90% for coronary CTA, 57% for SPECT, and 87% for PET. Not surprisingly, the specificity of coronary CTA (60%) was lower compared with SPECT (94%) and PET (84%). It is well-documented that coronary CTA has lower diagnostic accuracy in patients with significant coronary artery calcium and patients unable to achieve optimal heart rate control. These findings suggest that further efforts to improve the specificity of coronary CTA, such as selective utilization of CT-derived FFR, CT perfusion, or post-CTA functional testing, may be warranted in patients with a stenosis of intermediate severity in a proximal location. However, given the relatively low prevalence of obstructive CAD among patients with stable symptoms, a test with higher sensitivity (to rule out CAD quickly and definitively), such as coronary CTA, may be preferred by patients and providers, consistent with the approach by NICE.

Coronary CTA Slightly Increases Catheterization Rates but may Better Select Patients Who Might Benefit From Revascularization

The use of noninvasive functional tests, especially SPECT and exercise treadmill tests, in selecting patients for ICA is also remarkably imprecise. For example, regardless of the noninvasive functional test utilized, less than 50% of patients referred for ICA in the United States are found to have obstructive CAD.¹³ Although numerous factors, including patient recidivism and provider concerns despite low-risk testing results, undoubtedly influence post-testing referrals to ICA, we must also recognize that test accuracy, as discussed above, and its relationship with post-test provider confidence is not ideal for many noninvasive modalities with low sensitivity, such as SPECT.

Introduced above, PROMISE randomized 10,003 symptomatic patients without known CAD to either coronary CTA or functional testing (68% nuclear stress imaging) and evaluated for incident major adverse cardiac events (death, MI, unstable angina, and major procedural complications) over a median of 25 months.⁴ There was no significant difference in the primary endpoint between coronary CTA and functional testing (3.3 vs. 3.0%, p = 0.75) or in costs, solidifying the role of coronary CTA as a valid alternative to more established functional testing strategies. Like SCOT-HEART, PROMISE also highlighted significant differences in how patients who undergo coronary CTA are managed following testing.¹⁴ For example, more patients were referred to ICA (12.1 vs. 8.1%) and underwent revascularization (6.2 vs. 3.2%) following CTA compared with functional testing. However, the percentage of patients with obstructive CAD on ICA was markedly higher in the CTA arm (72.1 vs. 47.5%), suggesting that CTA improved patient selection for ICA to patients most likely to have high-grade coronary artery stenosis and perhaps more likely to benefit from revascularization (Table 1).

Table 1: Proportion of Obstructive CAD on ICA

Conclusions

Based on its high per-patient accuracy, characterization of subclinical and flow-limiting CAD, and the results from numerous large-scale, randomized comparative effectiveness trials, coronary CTA should be considered as the test of choice in most symptomatic patients without known CAD. Unfortunately, the utilization of coronary CTA has markedly lagged behind the evidence. For example, more than 40 SPECT examinations are done for every coronary CTA in the United States, and current private payer coverage for coronary CTA is quite limited in large parts of the country.¹⁵ The choice of noninvasive tests should always be individualized, accounting for local expertise, results of prior testing, and patient factors that influence test appropriateness and accuracy, but coronary CTA should at least always be an option available to patients and providers. That would be a NICE step forward to improving the value of noninvasive testing pathways in patients with stable chest pain.

References

1. Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2012;60:e44-e164.
2. Villines TC, Shaw LJ. Coronary Computed Tomographic Angiography-The First Test for Evaluating Patients With Chest Pain? JAMA Intern Med 2017;177:1631-2.
3. National Institute for Health and Care Excellence. Clinical guideline CG95 "Chest pain of recent onset: assessment and diagnosis." London, England: NICE; March 24, 2010.
4. Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med 2015;372:1291-300.
5. SCOT-HEART investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet 2015;385:2383-91.
6. Foy AJ, Dhruva SS, Peterson B, Mandrola JM, Morgan DJ, Redberg RF. Coronary Computed Tomography Angiography vs Functional Stress Testing for Patients With Suspected Coronary Artery Disease: A Systematic Review and Meta-analysis. JAMA Intern Med 2017;177:1623-31.
7. Bittencourt MS, Hulten EA, Murthy VL, et al. Clinical Outcomes After Evaluation of Stable Chest Pain by Coronary Computed Tomographic Angiography Versus Usual Care: A Meta-Analysis. Circ Cardiovasc Imaging 2016;9:e004419.
8. Williams MC, Hunter A, Shah ASV, et al. Use of Coronary Computed Tomographic Angiography to Guide Management of Patients With Coronary Disease. J Am Coll Cardiol 2016;67:1759-68.
9. Ferencik M, Mayrhofer T, Bittner DO, et al. Use of High-Risk Coronary Atherosclerotic Plaque Detection for Risk Stratification of Patients With Stable Chest Pain: A Secondary Analysis of the PROMISE Randomized Clinical Trial. JAMA Cardiol 2018;3:144-52.
10. Arbab-Zadeh A, Di Carli MF, Cerci R, et al. Accuracy of Computed Tomographic Angiography and Single-Photon Emission Computed Tomography-Acquired Myocardial Perfusion Imaging for the Diagnosis of Coronary Artery Disease. Circ Cardiovasc Imaging 2015;8:e003533.
11. Neglia D, Rovai D, Caselli C, et al. Detection of significant coronary artery disease by noninvasive anatomical and functional imaging. Circ Cardiovasc Imaging 2015;8:e002179.
12. Danad I, Raijmakers PG, Driessen RS, et al. Comparison of Coronary CT Angiography, SPECT, PET, and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve. JAMA Cardiol 2017;2:1100-7.
13. Patel MR, Dai D, Hernandez AF, et al. Prevalence and predictors of nonobstructive coronary artery disease identified with coronary angiography in contemporary clinical practice. Am Heart J 2014;167:846-52.e2.
14. Mark DB, Douglas PS, Daniels MR. Economic Outcomes With Anatomical Versus Functional Diagnostic Testing for Coronary Artery Disease. Ann Intern Med 2016;165:891.
15. Levin DC, Parker L, Halpern EJ, Rao VM. Recent Trends in Imaging for Suspected Coronary Artery Disease: What Is the Best Approach? J Am Coll Radiol 2016;13:381-6.

Clinical Topics: Arrhythmias and Clinical EP, Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Computed Tomography, Nuclear Imaging, Hypertension

Keywords: Angina Pectoris, Angina, Unstable, Angiography, Aspirin, Atrial Fibrillation, Body Mass Index, Calcium, Catheterization, Chest Pain, Cohort Studies, Constriction, Pathologic, Coronary Angiography, Coronary Artery Disease, Coronary Stenosis, Critical Pathways, Diabetes Mellitus, Diagnostic Tests, Routine, Disease-Free Survival, Dyslipidemias, Electrocardiography, Exercise Test, Exercise Test, Follow-Up Studies, Health Care Costs, Heart Rate, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypersensitivity, Hypertension, Incidental Findings, Life Style, Lipoproteins, HDL, Myocardial Infarction, Myocardial Perfusion Imaging, National Health Programs, Nitroglycerin, Odds Ratio, Patient Selection, Positron-Emission Tomography, Prevalence, Prognosis, Prospective Studies, Referral and Consultation, Risk Factors, Renal Insufficiency, Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography, Stents, Tachycardia, Tomography, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed, Vascular Calcification, Diagnostic Imaging

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