Chest Pain Controversies: Coronary CTA Use (Part 2)

Authors: Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC, USAF) and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital) // Edited by: Jamie Santistevan, MD (@Jamie_Rae_EMdoc, Admin and Quality Fellow at UW, Madison, WI)

A 53-year-old female presents with 5 hours of chest pain and diffuse weakness. She denies dyspnea, nausea/vomiting, and diaphoresis. Her vital signs, ECG, chest X-ray, and initial labs are completely normal, including troponin and TSH. You have low suspicion of PE, dissection, and other life-threatening diseases. Your center excels with coronary computed tomography angiogram (CCTA). Should you use this modality?

This is the second of a two-part series evaluating chest pain controversies in the ED. The American Heart Association (AHA) supports noninvasive cardiac imaging for further evaluation before or within 72 hours of discharge, which may consist of stress testing, CCTA, or no further testing at all.1 As discussed previously, a nonischemic ECG with negative cardiac biomarkers at 0 hr and 3 hr is associated with low risk of major cardiac adverse event (MACE).2,3 This post will examine the use of CCTA in the ED. Are there benefits? What are the adverse effects? 

Coronary computed tomography angiogram (CCTA)

CCTA has risen to the forefront of chest pain evaluation, providing an anatomical evaluation of coronary artery vasculature. This means that the test is asking one question: is there disease within the coronary arteries? It is important to note that unlike coronary angiogram, CCTA is unable to evaluate coronary blood flow.4-7 However, this test does have the potential to provide a safe, noninvasive measure that allows for a better means to diagnose CAD when compared to history, physical exam, ECG, and biomarkers.4-7

Current Guidelines

The American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) and the European Society of Cardiology (ESC) guidelines list CCTA for use in patients with low or intermediate risk.4,5

Guideline Use of CCTA
ACCF/AHA – Low to intermediate risk patients, exercise capable: Class III, level of evidence C for patients with interpretable ECG. For patients with uninterpretable ECG, Class IIb, level of evidence B for CCTA.

Low to intermediate risk patients, exercise incapable: Class IIa, level of evidence C for CCTA.

– In patients with symptoms at high risk for disease, CCTA assumes a Class IIb, level of evidence C recommendation. Coronary angiogram possesses a Class I, level of evidence C recommendation.

*High risk categorized as presence of classic cardiovascular risk factors: advanced age, hypertension, diabetes mellitus, smoking, male.

ESC – Class IIa, level of evidence C recommendation for CCTA use in patients with lower range of intermediate risk as alternative to stress imaging or non-conclusive exercise ECG or stress imaging.

*Prerequisite of obtaining good imaging quality.

No role for CCTA in symptomatic patients with high pretest probability of disease.

Table 1: Current guidelines for the use of CCTA

The evidence surrounding CCTA 

The evidence for CCTA has shown a low rate of ACS/AMI within 30 days of testing, as well as decreased ED length of stay (LOS).4-10

In 2001, de Filippi et al. randomized 248 patients with normal ECG, negative biomarkers, and ages 20-65 years old to CCTA or exercise testing.8 Positive CCTA was defined by stenosis greater than 50%. Patients with negative CCTA had fewer returns (decreased by 20%) and hospital admissions (3% versus 16%) than patients with negative stress tests. The study revealed no death or MI in both groups at one year.8

The 2012 ACRIN-PA trial randomized 1,370 patients with TIMI score 0-2, ECG without ischemia, and negative first biomarker to CCTA versus standard stress test.9,11 Approximately 50% of patients in CCTA could be discharged, versus 22.7% in the stress arm, decreasing ED LOS.9

The ROMICAT-II trial evaluated CCTA and found that no coronary disease on imaging effectively ruled out ACS. However, if the CT revealed stenosis >/= 50%, sensitivity was reduced to 78.4% for ACS.12 In this population,  length of stay was 7.6 hours in the CCTA group, with a rate of ED discharge 47% in the CCTA group versus 12% in the standard evaluation arm. No difference in the rate of adverse cardiovascular events between groups was found.12

Chang et al. evaluated 32 patients who underwent repeat CCTA imaging at two years after their first imaging evaluation. No patient with less than the 50% stenosis threshold demonstrated > 50% stenosis on second imaging.13

Four large trials randomized low-risk patients to standard workup with stress testing or CCTA following ED evaluation with negative ECG and troponin.9,14-16 These studies in addition to a meta-analysis by Hulten et al. suggest decreased ED LOS, with negative predictive values approaching 99% with CCTA.17 However, no difference in MACE is found based on these large studies.9,14-17

CCTA provides sensitivities ranging from 81% to 99%, specificity 64% to 93%, positive predictive value (PPV) 64% to 92%, and negative predictive value (NPV) 83% to 99%.17-21 Obtaining these results requires an experienced reader and optimal imaging quality. A study in Canada found high variability in diagnostic capability and accuracy across four centers, questioning reproducibility when not interpreted by an experienced radiologist.21 Results demonstrate sensitivity 50% to 93%, specificity 92% to 100%, PPV 85% to 100%, and NPV 43% to 95%.21 Fractional flow reserve assessment with CCTA is a newer modality, with sensitivity 84% to 94% and NPV 72% to 80%.20-23

PROMISE

Two recent large studies have evaluated the use of CCTA in patients with chest pain. The PROMISE study randomized 10,003 patients to standard noninvasive testing or CCTA.24 This study recruited patients from outpatient settings, rather than ED, with new onset chest pain and negative biomarkers and ECG changes. No difference in death, MI, major procedural complications, or hospitalization for unstable angina between the CCTA and standard groups (3.3% versus 3.0%) was found. Patients in the CCTA group underwent more testing and intervention, 12.2% versus 8.1% for catheterization. An overall low mortality rate, 1.5%, and low rate of MI, 0.7%, were found in the population studied.24

SCOT-HEART

The SCOT-HEART trial enrolled 4,146 patients in Scotland, comparing exercise stress test versus evaluation with CCTA.25 Over 85% of patients underwent stress testing. After initial patient assessment, the physician estimated baseline risk of CAD and recommended further testing. Patients were then randomized to CCTA or standard testing only. After 6 weeks, physicians again estimated risk of CAD based on study results. In this trial, CCTA improved physician confidence in diagnosis of CAD and angina, and more patients were diagnosed with CAD in the CCTA group (23% versus 11%). This lead to more cardiac catheterizations. However, the rate of adverse cardiovascular outcomes during the follow up period of 1.7 years was not statistically different, 1.3% versus 2.0%. Patient outcomes were not affected, though physicians felt more comfortable.25

CCTA has repeatedly demonstrated the ability to decrease ED LOS. The majority of these studies incorporate low risk patients, who, with negative ECG and biomarkers, have a risk of less than 1%.2,3,26 CCTA is associated with increased rate of invasive angiography and downstream testing. The meta-analysis by Hulten et al. revealed more downstream testing, including invasive angiography.17

Muhlestein et al. evaluated close to 900 patients with diabetes type I and II, using CCTA for screening of CAD.27 Patients in the CCTA group underwent more catheterizations (13.3% versus 5.1%), more percutaneous interventions (6.0% versus 1.8%), and more bypass operations (2.9% versus 1.3%), with no change in adverse cardiac events.27 Given the increased rate of invasive testing without decreasing adverse events, use of CCTA in low risk patients is questionable.26

What is identified on CCTA?

CCTA detects coronary artery calcium and the degree of obstruction to the artery lumen. Non-obstructive CAD is that which causes <50% arterial stenosis, whereas stenosis of 50% or more defines significant CAD. Calcium plaques can be further characterized based on visual appearance and are considered at high risk for causing thrombosis if any of the following features are present: spotty calcium, remodeling of vasculature, low Housfield Units attenuation, large plaque volume and the napkin-ring sign.12 These radiographic features are based on histologic features of plaques that demonstrate high risk for rupture such as the presence of a necrotic, lipid-rich core, a thin-cap fiberatheroma and vascular remodeling.

napkin-ring

Figure 1: Cross-sectional CT showing coronary plaque with napkin-ring sign.37 a). Non-enhanced image b). Contrast-enhanced image c). Histopathology showing thin-cap fiberoatheroma with a necrotic core*.

Patient selection for CCTA

Patient selection to undergo CCTA is key for optimal imaging. Morbidly obese patients present challenges due to chest wall thickness, which interferes with imaging quality. Patients with known disease, heavy coronary calcifications, and prior coronary revascularization do not benefit. Studies demonstrate high risk patients should undergo angiogram rather than CCTA, which has better assessment of real-time coronary flow, presence of thrombotic material, and collateral circulation.28 Control of heart rate and rhythm is essential, as direct correlation exists with heart rate and ability to evaluate vasculature.29 Over 95% of coronary vasculature is evaluable with a heart rate less than 60 bpm. This decreases to 80% to 90% with rates of 60-65 bpm. As rates approach 70-80 bpm, 70% of the vasculature is evaluable.29 Patients with irregular rhythm, frequent premature atrial or ventricular ectopy, and uncontrolled tachycardia cannot be evaluated.29

Complications of CCTA

CCTA is associated increased radiation exposure, though this has decreased with improved technology. A 320-slice detector reduces radiation to 2-6 mSv.29-34 Despite this, cumulative radiation exposure increases with CCTA use due to increased downstream testing. Chronic kidney disease also warrants caution, as this test can lead to contrast nephropathy.35

Utility of CCTA

CCTA likely causes more harm than benefit in low risk patients, as it can lead to a greater number of false-positive results and further testing and increased radiation exposure.7,26  Utility of CCTA  exists for patients who may have difficulty obtaining further testing or lack of follow-up.4-8 A patient with no disease found on CCTA possesses an extremely low risk of ACS (less than 1%) and these patients can be safely discharged. No disease is found in one third to one half of low to intermediate risk patients.17 If follow-up is in place, CCTA benefit is controversial.7,17,26

If CAD of >50% stenosis is present or if there are high risk plaque features at any degree of stenosis, the patient may require aggressive medical management and should be admitted for further testing with stress test or angiography. In these cases, decision-making with a cardiologist about recommended medical or invasive management is recommended. If any degree of CAD is detected, these patients may also benefit from cardiology consult as further management should include shared decision-making with consideration of the risks and benefits of therapies and patient preferences.

Patients with intermediate risk based on history and other comorbidities may be candidates for further risk stratification with CCTA, as no disease on imaging lowers the risk of MACE.36 Further studies on the utility of CCTA for intermediate risk patients is required. Use in high risk patients should be avoided, as coronary artery disease is likely to be present on CCTA.7,26,36

Summary

– Missed ACS is a concern for patients and emergency providers. Nonischemic ECG and negative biomarker at 0 and 3 hours reduces risk of MACE to less than 1%.

– Stress testing and CCTA are commonly used for further evaluation of these patients, but their ability to further risk stratify low risk patients further is controversial.

– Use of CCTA has increased, with the goal to evaluate anatomical coronary artery disease.

– CCTA is associated with decreased ED LOS. However, CCTA is also associated with further downstream testing, with no evidence of improved outcome in low risk patients.

Intermediate risk patients, or those with difficulty obtaining follow up, may benefit from CCTA, though further studies are required in this patient subset.

References/Further Reading

  1. Amsterdam EA, Kirk JD, Bluemke DA, et al; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology, Council on Cardiovascular Nursing, and Interdisciplinary Council on Quality of Care and Outcomes Research. Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association. Circulation 2010;122(17):1756-1776.
  2. Pope JH, Aufderheide TP, Ruthazer R, Woolard RH, Feldman JA, Beshansky JR, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 2000; 342:1163–70.
  3. Weinstock MB, Weingart S, Orth F, VanFossen D, Kaide C, Anderson J, Newman DH. Risk for Clinically Relevant Adverse Cardiac Events in Patients With Chest Pain at Hospital Admission. JAMA Intern Med 2015 Jul;175(7):1207-12.
  4. Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013;34:2949–3003.
  5. Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, et al; American College of Cardiology Foundation/American Heart Association Task Force. 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. Circulation 2012;126:e354–e471.
  6. Achenbach S. Can coronary computed tomography angiography replace invasive angiography? Yes: it is all about finding the right test for the right person at the right time. Circulation 2015 Jan 27;131(4):410-6; discussion 417.
  7. Stefanini GG, Windecker S. Can coronary computed tomography angiography replace invasive angiography? Coronary computed tomography angiography cannot replace invasive angiography. Circulation 2015 Jan 27;131(4):418-25; discussion 426.
  8. deFilippi CR, Rosanio S, Tocchi M, Parmar RJ, Potter MA, Uretsky BF, Runge MS. Randomized comparison of a strategy of predischarge coronary angiography versus exercise testing in low-risk patients in a chest pain unit: in-hospital and long-term outcomes. J Am Coll Cardiol 2001 Jun 15;37(8):2042-9.
  9. Litt HI, Gatsonis C, Snyder B, Singh H, Miller CD, Entrikin DW, et al. CT angiography for safe discharge of patients with possible acute coronary syndromes. N Engl J Med 2012 Apr 12;366(15):1393-403.
  10. Redberg RF. Coronary CT angiography for acute chest pain. N Engl J Med 2012;367:375–376.
  11. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, et. al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA 2000 Aug 16;284(7):835-42.
  12. Puchner SB, Liu T, Mayrhofer T, et al. High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial. J Am Coll Cardiol 2014;64(7):684-92.
  13. Chang SA, Choi SI, Choi EK, Kim HK, Jung JW, Chun EJ, et al. Usefulness of 64-slice multidetector computed tomography as an initial diagnostic approach in patients with acute chest pain. Am Heart J 2008;156:375– 383
  14. 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.
  15. Goldstein JA, Chinnaiyan KM, Abidov A, et al. The CT-STAT (Coronary Computed Tomographic Angiography for Systematic Tri- age of Acute Chest Pain Patients to Treatment) trial. J Am Coll Cardiol 2011;58:1414–22.
  16. Hoffmann U, Truong QA, Schoenfeld DA, et al. Coronary CT angiography versus standard evaluation in acute chest pain. N Engl J Med 2012;367:299–308.
  17. Hulten E, Pickett C, Bittencourt MS, et al. Outcomes after coronary computed tomography angiography in the emergency department: a systematic review and meta-analysis of randomized, controlled trials. J Am Coll Cardiol 2013;61:(8)880-92.
  18. Miller JM, Rochitte CE, Dewey M, Arbab-Zadeh A, Niinuma H, Gottlieb I, et al. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med 2008;359:2324–2336.
  19. Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, 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 Nov 18;52(21):1724-32.
  20. Meijboom W, Meijs ML, Schuijf JD, et al. Diagnostic Accuracy of 64-Slice Computed Tomography Coronary Angiography: A Prospective, Multicenter, Multivendor Study. J Am Coll Cardiol 2008;52(25):2135-2144.
  21. Chow BW, Freeman MR, Bowen JM, et al. Ontario Multidetector Computed Tomographic Coronary Angiography Study: Field Evaluation of Diagnostic Accuracy. Arch Intern Med 2011;171(11):1021-1029.
  22. Min JK, Leipsic J, Pencina MJ, et al. Diagnostic Accuracy of Fractional Flow Reserve From Anatomic CT Angiography. JAMA 2012;308(12):1237-1245.
  23. Koo BK, Erglis A, Doh JH, Daniels DV, Jegere S, Kim HS, et al. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol 2011 Nov 1;58(19):1989-97.
  24. Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of Anatomical versus Functional Testing for Coronary Artery Disease. N Engl J Med 2015;372(14):1291-1300.
  25. 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 Jun 13;385(9985):2383-91.
  26. Radecki RP. CT coronary angiography: new risks for low-risk chest pain. Emerg Med J 2013;30:856-857.
  27. Muhlestein JB, Lappé DL, Lima JA, Rosen BD, May HT, Knight S, et al. Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes: the FACTOR-64 randomized clinical trial. JAMA 2014 Dec 3;312(21):2234-43.
  28. De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PA, Piroth Z, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med 2012 Sep 13;367(11):991-1001.
  29. Achenbach S, Ropers U, Kuettner A, Anders K, Pflederer T, et al. Randomized comparison of 64-slice single- and dual-source computed tomography coronary angiography for the detection of coronary artery disease. JACC Cardiovasc Imaging 2008;1:177–186.
  30. Hirai N, Horiguchi J, Fujioka C, Kiguchi M, Yamamoto H, Matsuura N, et al. Prospective versus retrospective ECG-gated 64-detector coronary CT angiography: assessment of image quality, stenosis, and radiation dose. Radiology 2008;248:424–430.
  31. Bischoff B, Hein F, Meyer T, Hadamitzky M, Martinoff S, Schömig A, Hausleiter J. Impact of a reduced tube voltage on CT angiography and radiation dose: results of the PrOTECTIOn I study. JACC Cardiovasc Imaging 2009;2:940–946.
  32. Achenbach S, Marwan M, ropers D, Schepis T, P Ederer T, Anders K, Kuettner A, et al. Coronary computed tomography angiography with a consistent dose below 1 mSv using prospectively electrocardiogram-triggered high-pitch spiral acquisition. Eur Heart J 2010;31:340–346.
  33. Scheffel H, Alkadhi H, Leschka S, Plass A, Desbiolles l, Guber I, et al. Low- dose CT coronary angiography in the step-and-shoot mode: diagnostic performance. Heart 2008;94:1132–1137.
  34. Dewey M, Zimmermann E, Deissenrieder F, laule M, Dübel HP, Schlattmann P, Knebel F, rutsch W, Hamm B. Noninvasive coronary angiography by 320-row computed tomography with lower radiation exposure and maintained diagnostic accuracy: comparison of results with cardiac catheterization in a head-to-head pilot investigation. Circulation 2009;120:867–875.
  35. Eckardt KU, Coresh J, Devuyst O, Johnson RJ, Köttgen A, et al. Evolving importance of kidney disease: from subspecialty to global health burden. Lancet 2013;382:158–169.
  36. Bittencourt MS, Hulten EA, Veeranna V, Blankstein R. Coronary computed tomography angiography in the evaluation of chest pain of suspected cardiac origin. Circulation 2016; 133:1963-1968.
  37. Maurovich-Horat P, Ferencik M, Voros S, et al. Comprehensive plaque assessment by coronary CT angiography. Nat Rev Cardiol. 2014 Jul;11(7):390-402.

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