Coronary CTA Should Be the Initial Test in Most Patients With Stable Chest Pain: CON
Editor's Note: This is the Con article of a two-part Pro/Con Expert Analysis. Click here for the Pro article.
Appropriate risk stratification of patients presenting with stable chest pain is crucial not only for the individual but also for health care systems across the world. Despite the development of several well-established clinical pathways, it is difficult to define a singular approach applicable to all patients due to heterogeneity of clinical presentations and comorbid conditions. In fact, some of the current approaches seem to have significant limitations, as evidenced by the low prevalence of obstructive coronary artery disease (CAD) found on invasive coronary angiography (ICA) even after noninvasive testing.1,2 Yet, the future is promising given recent advances in testing modalities including coronary computed tomography angiography (CTA). Coronary CTA has experienced a sharp rise in development over recent years based on robust data demonstrating its diagnostic and prognostic utility in the detection of CAD. However, although coronary CTA may be a suitable test in some patients, it is not the appropriate initial test for most patients with stable chest pain.
Coronary CTA certainly has excellent sensitivity to detect underlying CAD. Several cohort studies and randomized clinical trials have studied the diagnostic accuracy of coronary CTA with respect to ICA. For example, the ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial studying 230 patients and a pooled analysis report by the European Society of Cardiology and European Council of Nuclear Cardiology studying 800 patients reported a sensitivity of 94% and 89% for a stenosis ≥70% and ≥50%, respectively.3,4 These findings are generally representative of several other cohort data. Furthermore, a meta-analysis of 16 studies including 1,119 patients found a sensitivity of 96% to detect significant coronary stenoses in the setting of stable ischemic heart disease.5 Despite the high correlation of coronary CTA and ICA, these comparisons provide only anatomic correlation and do not address the physiologic significance of coronary disease nor provide an estimation of the ischemic burden, a key component of outcome and therapeutic planning.
The sensitivity to detect anatomic CAD should not be the sole basis upon which to decide the appropriateness of an initial test for stable chest pain. The ideal initial test should be practical, generalizable, and safe while also demonstrating an ability to diagnose significant CAD, define prognosis, and plot a course of treatment. In fact, the appropriate evaluation for most patients is simply a comprehensive clinical assessment with determination of the pre-test probability of CAD. The Diamond-Forrester Criteria and the two CAD consortium scores can effectively risk stratify patients while both avoiding unnecessary testing in up to 1/3 of patients and identifying those who should proceed directly to ICA.6,7 Multiple studies have found that even the most recent models overestimate the pre-test likelihood of CAD given that approximately 60% of elective ICAs found no obstructive CAD.1,8 Optimal pre-test prediction models are actively being investigated to assist in refining our clinical acumen.1,8 The PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) minimal risk tool can result in avoidance of noninvasive testing in over 25% of patients with no difference in outcomes (Table 1).9 In addition, PROMISE demonstrated that coronary CTA also increased the rate of ICA by almost 50% compared with routine provocative testing.9,10 Several meta-analyses have confirmed that coronary CTA increases downstream ICA and revascularization rates with a small decrease in myocardial infarction but of unclear etiology and significance, thus underscoring the need for improved management strategies after coronary CTA results.11,12 Thus, coronary CTA may result in unnecessary ICA and subsequent intervention without improvement in mortality.
Table 1: Components of PROMISE Minimal Risk Tool
Ever Smoked Tobacco
Family History of Premature CAD
Symptoms Related to Physical/Mental Stress
High-Density Lipoprotein Value (mg/dL)
When clinical assessment is inadequate, noninvasive testing should be considered. Several options are available depending on specific patient factors, such as exercise capacity, electrocardiogram (ECG) interpretability, and known cardiac disease. Although coronary CTA is not dependent on exercise or ECG interpretability, this technique is limited by its inability to provide physiologic information. Therefore, in the United States, exercise stress electrocardiography (graded exercise testing [GXT]) remains the recommended initial diagnostic test for patients with low to intermediate pre-test probability of CAD with an interpretable ECG and who are able to exercise maximally.13,14 GXT has a substantial ability to predict future cardiac events, and more technologically advanced diagnostic tools have not yet been able to supplant the prognostic power of exercise.15,16
Coronary CTA does not routinely involve a physiologic assessment and, therefore, does not address the ischemic cascade like other provocative modalities.17 Coronary CTA also does not yield a key prognostic variable: the presence and extent of inducible myocardial ischemia. Decades of data from noninvasive trials have revealed that ischemic burden is a key predictor of cardiac-event-free survival and helps to stratify patients and plan therapeutic interventions.18-22 More recently, the invasive assessment of coronary physiology through fractional flow reserve and instantaneous wave-free ratio determinations has been shown to identify hemodynamically significant stenoses, assist in planning revascularization to improve cardiovascular outcomes, and avoid unnecessary interventional procedures.23-26 Because physiology-guided revascularization results in improved cardiovascular outcomes compared with angiography-guided revascularization, the next step in coronary CTA evaluation seems to involve the determination of fractional flow reserve by computed tomography (FFRCT). FFRCT has been shown to alter management in over 1/3 of patients and reduce the need for ICA in patients without obstructive disease.27,28 Interestingly, several of these management changes involved stenoses at the extremes; 30% of vessels with >90% stenosis were surprisingly found to be functionally insignificant, and 10% of stenoses <50% were actually found to be significant.27
Despite the promise of coronary CTA (with and without FFRCT), technique and patient-related limitations exist for the widespread application of this technology. Multiple patient-specific factors may result in suboptimal images, including a body mass index greater than 40 kg/m2, frequent ectopy, atrial fibrillation, tachycardia, and an inability to receive beta-blockers or nitroglycerin.29,30 Additionally, patients with renal insufficiency or an allergy to contrast agents are unable to undergo coronary CTA. Interpretation of images, even in expert centers, is difficult in the presence of coronary stents, small vessels <2 mm, severe calcification, and bypass grafts in relation to their insertion points.29 The aforementioned limitations may therefore exclude over 1/3 of patients and/or can result in non-diagnostic studies.29,31 Furthermore, the excellent diagnostic results have been reported only from highly skilled centers, raising the question of how this will translate to institutions with less-experienced readers and protocol managers.32-34 The availability of at least 64-slice scanners remains limited, and the negative effects of radiation are still considerations despite improved technology.29,35,36 Finally, extracardiac incidental findings such as pulmonary nodules may be found in up to 1/3 of cases, and although such secondary findings may not confer a profound change in a patient's prognosis, they can affect mental stress and lead to further testing and a potential increase health care costs.10,37
An alternative to the use of coronary CTA in the setting of stable chest pain may be with the use of coronary artery calcium scoring (CACS) because this appears to have adequate value as an initial test after clinical assessment in the intermediate risk population. CACS determination is a rapid test and does not require contrast or an intricate protocol. CACS has demonstrated reclassification rates of over 50% when added to clinical and exercise variables with cutoffs that are well-validated for event-free survival.38 Moreover, coronary CTA may not provide incremental risk stratification when compared with CACS alone.39 Additionally, coronary CTA appears unable to exclude high-grade CAD when the Agatston score is >287 and does not add value if the Agatston score is zero, essentially representing an extremely low likelihood of CAD.40
At the current time, most clinical practice guidelines do not support coronary CTA as the initial test in the majority of patients with stable chest pain. The American College of Cardiology guidelines for stable ischemic heart disease include coronary CTA as an option if there are contraindications to stress testing or for patients who are unable to exercise.13,14 The appropriate use criteria guidelines note that it is "rarely appropriate" to use coronary CTA in low-risk populations that can exercise, thus restricting the use of this method.41 The recently published National Institute for Health and Care Excellence (NICE) guidelines that strongly support coronary CTA as a diagnostic choice for chest pain patients do emphasize clinical assessment first, with coronary CTA recommended only if this clinical stratification suggests underlying CAD.42 However, there is significant concern regarding widespread implementation of the NICE guidelines due to the requirement of a much larger specialist workforce and coronary CTA-capable scanners.43
Although practical issues and a lack of physiologic information limits its widespread use, coronary CTA and its variations can enhance our diagnostic and prognostic abilities for some patients when the presence and severity of CAD remains in doubt. However, when considering the strength of clinical assessment with newer clinical risk models that may eliminate the need for noninvasive testing in several patient populations and the shortcomings of coronary CTA regarding an increased cost with downstream ICA and revascularization without clinical benefit, lack of physiologic data, and patient- and technique-related limitations including high coronary artery calcium, coronary CTA cannot be recommended as an appropriate initial test in many patients presenting with stable chest pain.
- Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med 2010;362:886-95.
- Ladapo JA, Blecker S, Douglas PS. Physician decision making and trends in the use of cardiac stress testing in the United States: an analysis of repeated cross-sectional data. Ann Intern Med 2014;161:482-90.
- Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol 2008;52:1724-32.
- Schroeder S, Achenbach S, Bengel F, et al. Cardiac computed tomography: indications, applications, limitations, and training requirements: report of a Writing Group deployed by the Working Group Nuclear Cardiology and Cardiac CT of the European Society of Cardiology and the European Council of Nuclear Cardiology. Eur Heart J 2008;29:531-56.
- Athappan G, Habib M, Ponniah T, Jeyaseelan L. Multi-detector computerized tomography angiography for evaluation of acute chest pain--a meta analysis and systematic review of literature. Int J Cardiol 2010;141:132-40
- Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med 1979;300:1350-8.
- Bittencourt MS, Hulten E, Polonsky TS, et al. European Society of Cardiology-Recommended Coronary Artery Disease Consortium Pretest Probability Scores More Accurately Predict Obstructive Coronary Disease and Cardiovascular Events Than the Diamond and Forrester Score: The Partners Registry. Circulation 2016;134:201-11.
- Greenwood JP, Ripley DP, Berry C, et al. Effect of Care Guided by Cardiovascular Magnetic Resonance, Myocardial Perfusion Scintigraphy, or NICE Guidelines on Subsequent Unnecessary Angiography Rates: The CE-MARC 2 Randomized Clinical Trial. JAMA 2016;316:1051-60.
- Fordyce CB, Douglas PS, Roberts RS, et al. Identification of Patients With Stable Chest Pain Deriving Minimal Value From Noninvasive Testing: The PROMISE Minimal-Risk Tool, A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol 2017;2:400-8.
- 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.
- 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.
- Nielsen LH, Ortner N, Nørgaard BL, Achenbach S, Leipsic J, Abdulla J. The diagnostic accuracy and outcomes after coronary computed tomography angiography vs. conventional functional testing in patients with stable angina pectoris: a systematic review and meta-analysis. Eur Heart J Cardiovasc Imaging 2014;15:961-71.
- 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.
- Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2014;130:1749-67.
- Bourque JM, Beller GA. Value of Exercise ECG for Risk Stratification in Suspected or Known CAD in the Era of Advanced Imaging Technologies. JACC Cardiovasc Imaging 2015;8:1309-21.
- Rozanski A, Gransar H, Hayes SW, et al. Temporal trends in the frequency of inducible myocardial ischemia during cardiac stress testing: 1991 to 2009. J Am Coll Cardiol 2013;61:1054-65.
- Nesto RW, Kowalchuk GJ. The ischemic cascade: temporal sequence of hemodynamic, electrocardiographic and symptomatic expressions of ischemia. Am J Cardiol 1987;59:23C-30C.
- Cassar A, Holmes DR Jr, Rihal CS, Gersh BJ. Chronic coronary artery disease: diagnosis and management. Mayo Clin Proc 2009;84:1130-46.
- Iwasaki K. Myocardial ischemia is a key factor in the management of stable coronary artery disease. World J Cardiol 2014;6:130-9.
- Bourque JM, Patel CA, Ali MM, Perez M, Watson DD, Beller GA. Prevalence and predictors of ischemia and outcomes in outpatients with diabetes mellitus referred for single-photon emission computed tomography myocardial perfusion imaging. Circ Cardiovasc Imaging 2013;6:466-77.
- Zellweger MJ, Hachamovitch R, Kang X, et al. Prognostic relevance of symptoms versus objective evidence of coronary artery disease in diabetic patients. Eur Heart J 2004;25:543-50.
- Bourque JM, Holland BH, Watson DD, Beller GA. Achieving an exercise workload of > or = 10 metabolic equivalents predicts a very low risk of inducible ischemia: does myocardial perfusion imaging have a role? J Am Coll Cardiol 2009;54:538-45.
- Tonino PA, De Bruyne B, Pijls NH, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213-24.
- De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med 2012;367:991-1001.
- Götberg M, Christiansen EH, Gudmundsdottir IJ, et al. Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI. N Engl J Med 2017;376:1813-23.
- Davies JE, Sen S, Dehbi HM, et al. Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI. N Engl J Med 2017:376:1824-34.
- Curzen NP, Nolan J, Zaman AG, Nørgaard BL, Rajani R. Does the Routine Availability of CT-Derived FFR Influence Management of Patients With Stable Chest Pain Compared to CT Angiography Alone?: The FFRCT RIPCORD Study. JACC Cardiovasc Imaging 2016;9:1188-94.
- Douglas PS, De Bruyne B, Pontone G, et al. 1-Year Outcomes of FFRCT-Guided Care in Patients With Suspected Coronary Disease: The PLATFORM Study. J Am Coll Cardiol 2016;68:435-45.
- Hendel RC. Is computed tomography coronary angiography the most accurate and effective noninvasive imaging tool to evaluate patients with acute chest pain in the emergency department? CT coronary angiography is the most accurate and effective noninvasive imaging tool for evaluating patients presenting with chest pain to the emergency department: antagonist viewpoint. Circ Cardiovasc Imaging 2009;2:264-75.
- Bamberg F, Abbara S, Schlett CL, et al. Predictors of image quality of coronary computed tomography in the acute care setting of patients with chest pain. Eur J Radiol 2010;74:182-8.
- Goldstein JA, Gallagher MJ, O'Neill WW, Ross MA, O'Neil BJ, Raff GL. A randomized controlled trial of multi-slice coronary computed tomography for evaluation of acute chest pain. J Am Coll Cardiol 2007;49:863-71.
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- Budoff MJ, Cohen MC, Garcia MJ, et al. ACCF/AHA clinical competence statement on cardiac imaging with computed tomography and magnetic resonance: a report of the American College of Cardiology Foundation/American Heart Association/American College of Physicians Task Force on Clinical Competence and Training. J Am Coll Cardiol 2005;46:383-402.
- Budoff MJ, Achenbach S, Fayad Z, et al. Task Force 12: training in advanced cardiovascular imaging (computed tomography): endorsed by the American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Atherosclerosis Imaging and Prevention, and Society of Cardiovascular Computed Tomography. J Am Coll Cardiol 2006;47:915-20.
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- Vrachliotis TG, Bis KG, Haidary A, et al. Atypical chest pain: coronary, aortic, and pulmonary vasculature enhancement at biphasic single-injection 64-section CT angiography. Radiology 2007;243:368-76.
- Scholtz JE, Lu MT, Hedgire S, et al. Incidental pulmonary nodules in emergent coronary CT angiography for suspected acute coronary syndrome: Impact of revised 2017 Fleischner Society Guidelines. J Cardiovasc Comput Tomogr 2018;12:28-33.
- Chang SM, Nabi F, Xu J, et al. Value of CACS compared with ETT and myocardial perfusion imaging for predicting long-term cardiac outcome in asymptomatic and symptomatic patients at low risk for coronary disease: clinical implications in a multimodality imaging world. JACC Cardiovasc Imaging 2015;8:134-44.
- Cho I, Chang HJ, Sung JM, et al. Coronary computed tomographic angiography and risk of all-cause mortality and nonfatal myocardial infarction in subjects without chest pain syndrome from the CONFIRM Registry (coronary CT angiography evaluation for clinical outcomes: an international multicenter registry). Circulation 2012;126:304-13.
- Schuhbaeck A, Schmid J, Zimmer T, et al. Influence of the coronary calcium score on the ability to rule out coronary artery stenoses by coronary CT angiography in patients with suspected coronary artery disease. J Cardiovasc Comput Tomogr 2016;10:343-50.
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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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