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Overview with Meta-analysis of Systematic Reviews of the Diagnostic and Prognostic Value of Coronary Computed Tomography Angiography in the Emergency Department

Abstract

Background:

The high prevalence of CAD, as well as your impact on health expenditure and the various treatment options to reduce morbidity and mortality related to CAD, comes to develop a diagnostic tool precis and with important findings in the Emergency Department.

Objetive:

To conduct an overview with meta-analysis to compile evidence from multiple systematic reviews (SR) on the diagnostic and prognostic value of coronary computed tomography angiography (CCTA) to assess acute chest pain in the emergency department (ED).

Methods:

We included SR of primary studies that evaluated the diagnostic and prognostic value of CCTA ≥ 64 channels in the ED. The studies were conducted in patients at low and intermediate risk for coronary artery disease (CAD). Quality assessment was performed using PRISMA and approved reviews that scored ≥ 80%. Two authors independently extracted data using a standardized form. Spearman correlation test, Chi-square test, Cochran's Q test or Higgins and Thompson statistical I2 were used. For meta-analysis, "mada" package statistical software R Core Team, 2015, was used. The significance level adopted was 95%.

Results:

Four reviews were eligible for inclusion in this overview, resulting in 13 articles after applying the exclusion criteria, and only 10 of these were used for meta-analysis, adding up to a total of 4831 patients (mean age, 54 ± 6 years; 51% male), of whom 46% were hypertensive, 32% had dyslipidemia, 13% had diabetes and 26% had a family history of premature CAD. In the meta-analysis, 9 studies defined CCTA positive in the presence of luminal lesions ≥ 50%, while 1 study defined it as luminal lesions ≥ 70%. Sensitivity ranged from 77% to 98%, and specificity, from 73% to 100%. The univariate analysis showed homogeneity of diagnostic odds ratio (DOR) [Q = 8.5 (df = 9), p = 0.48 and I2 = 0%]. The pooled mean DOR for CCTA in primary analyses was 4.33 (95% CI: 3.47 - 5.18). The area under the curve (AUC) was 0.982 (95% CI: 0.967 - 0.999). There was no death, 29 (0.6%) infarcts, 92 (1.9%) revascularizations and 312 (6.4%) invasive coronary angiographies. The diagnosis of acute coronary syndrome occurred in 7.3% of the 1655 patients included in the meta-analysis.

Conclusions:

The use of CCTA as a tool for stratification of patients at low or intermediate cardiovascular risk, who are in the ED with chest pain, has high accuracy, safety, reduces length of hospital stay and probably the costs, producing an early diagnosis and more effective decision making. (Int J Cardiovasc Sci. 2017; [online].ahead print, PP.0-0)

Keywords:
Coronary Artery Disease; Tomography, X-Ray Computed; Chest Pain; Emergency Medicine; Meta-Analysis as Topic

Resumo

Fundamento:

A alta prevalência de DAC, bem como seu impacto sobre as despesas de saúde e as várias opções de tratamento para reduzir a morbidade e mortalidade relacionados a DAC, vem desenvolver uma ferramenta de diagnóstico precisa e com resultados importantes no departamento de emergência.

Objetivo:

Fornecer visão geral com meta-análise para compilar evidência a partir de múltiplas revisões sistemáticas (RS) sobre o valor diagnóstico e prognóstico da angiotomografia computadorizada de artérias coronárias (ATCC) na avaliação da dor torácica aguda no setor de emergência (SE).

Métodos:

Incluímos RS de estudos primários avaliando o valor diagnóstico e prognóstico da ATCC ≥ 64 canais no SE. Os estudos foram conduzidos em pacientes de risco baixo e intermediário para doença arterial coronariana (DAC). Realizou-se avaliação qualitativa usando PRISMA, e aquelas que pontuaram ≥ 80% foram aprovadas. Dois autores extraíram dados independentemente usando um formulário padrão. Os testes de correlação de Spearman, do qui-quadrado, Q de Cochran ou a estatística I2 de Higgins e Thompson foram usados, assim como o pacote estatístico "mada" (R Core Team, 2015) para meta-análise. Adotou-se o nível de significância de 95%.

Resultados:

Quatro RS foram elegíveis para inclusão neste estudo, resultando em 13 artigos após aplicação dos critérios de exclusão, sendo apenas 10 usados para a meta-análise, num total de 4831 pacientes (idade média, 54 ± 6 anos; 51% homens), dos quais 46% tinham hipertensão, 32% dislipidemia, 13% diabetes e 26% história familiar de DAC prematura. Na meta-análise, 9 estudos definiram ATCC positiva na presença de lesões luminais ≥ 50%, enquanto 1 estudo definiu ATCC positiva na presença de lesões luminais ≥ 70%. A sensibilidade variou de 77% a 98%, e a especificidade, de 73% a 100%. A análise univariada mostrou homogeneidade do odds ratio diagnóstico (DOR) [Q = 8,5 (df = 9), p = 0,48 and I(2) = 0%]. A estimativa sumária da DOR para ATCC nas análises primárias foi de 4,33 (IC95%: 3,47 - 5,18). A área sob a curva foi 0,982 (IC95%: 0,967 - 0,999). Houve 29 (0.6%) infartos, 92 (1,9%) revascularizações, 312 (6,4%) angiografias coronarianas invasivas e nenhuma morte. Síndrome coronariana aguda foi diagnosticada em 7,3% dos 1655 pacientes incluídos na meta-análise.

Conclusões:

O uso de ATCC como ferramenta para estratificação de pacientes de risco cardiovascular baixo e intermediário, que procuraram o SE com dor torácica, tem alta acurácia e segurança, reduz a permanência no hospital e provavelmente os custos, produzindo diagnóstico precoce e uma tomada de decisão mais efetiva. (Int J Cardiovasc Sci. 2017; [online].ahead print, PP.0-0)

Palavras-chave:
Doença da Artéria Coronariana; Tomografia Computadorizada por Raios X; Dor no Peito; Medicina de Emergência; Metanálise como Assunto

Introduction

In 2010, in the United States of America, nearly 6 million patients with chest pain visited the emergency departments (ED); this is the second most frequent reason for visits to this unit, although only a minority receives the diagnosis of acute coronary syndrome (ACS).11 Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29-322. doi: 10.1161/CIR.0000000000000152. Erratum in: Circulation. 2016;133(8):e417. Circulation. 2015;131(24):e535.
https://doi.org/10.1161/CIR.000000000000...
North American statistics show that in 2011 coronary artery disease (CAD) was responsible for about 1 of every 7 deaths, totaling 375,295 deaths.22 National Center for Health Statistics. Mortality Multiple Cause Micro-data Files, 2011. Public-use data file and documentation. NHLBI tabulations. [Accessed on 2014, July 03]. Available from: http://www.cdc.gov/nchs/data_access/Vitalstatsonline.htm#Mortality_Multiple
http://www.cdc.gov/nchs/data_access/Vita...
Coronary artery disease is responsible for a substantial impact on the use of health care, with an estimated cost of US$ 21.9 billion in 2011. Between 2013 and 2030 the costs are estimated to increase ≈ 100%.33 Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, et al; American Heart Association Advocacy Coordinating Committee; Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Clinical Cardiology; Council on Epidemiology and Prevention; Council on Arteriosclerosis; Thrombosis and Vascular Biology; Council on Cardiopulmonary; Critical Care; Perioperative and Resuscitation; Council on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Disease; Council on Cardiovascular Surgery and Anesthesia, and Interdisciplinary Council on Quality of Care and Outcomes Research. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 2011;123(8):933-44. doi: 10.1161/CIR.0b013e31820a55f5.
https://doi.org/10.1161/CIR.0b013e31820a...
Due to the high prevalence of CAD, as well as its impact on health expenditure and the various treatment options to reduce morbidity and mortality related to CAD, accurate diagnosis is essential.

A high precision effective diagnostic test to exclude acute CAD could reduce the cost of the USA health care system by billions of dollars. The advent of coronary computed tomography angiography (CCTA), a noninvasive method to study the coronary anatomy, with tomography scanner ≥ 64 channels, reducing artifacts as well as increasing spatial and temporal resolution, has given rise to a quick test, effective to reliably exclude ACS.44 Auseon AJ, Advani SS, Bush CA, Raman SV. Impact of 64-slice Multidetector Computed Tomography on Other Diagnostic Studies for Coronary Artery Disease. Am J Med. 2009;122(4):387-91. doi: 10.1016/j.amjmed.2008.10.031.
https://doi.org/10.1016/j.amjmed.2008.10...
Although invasive coronary angiography (ICA) is the "gold standard" for CAD detection, it is not appropriate for extensive use because it is invasive, not routinely available, and has high cost and increased risk of complications. Furthermore, the immediate and future probability of cardiac events in patients without CAD or with minimal CAD is low for patients with chest pain in the ED.55 Min JK, Shaw LJ, Devereux RB, Okin PM, Weinsaft JW, Russo DJ, et al. Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality. J Am Coll Cardiol. 2007;50(12):1161-70. doi: 10.1016/j.jacc.2007.03.067.
https://doi.org/10.1016/j.jacc.2007.03.0...
,66 Hulten EA, Carbonaro S, Petrillo SP, Mitchell JD, Villines TC. Prognostic value of cardiac computed tomography angiography: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;57(10):1237-47. doi: 10.1016/j.jacc.2010.10.011.
https://doi.org/10.1016/j.jacc.2010.10.0...

Systematic reviews (SR) are studies with the highest level of evidence (higher in the hierarchy of evidence-based research) and rigorous methodological quality.77 Evans D. Hierarchy of evidence: a framework for ranking evidence evaluating healthcare interventions. J Clin Nurs. 2003;12(1):77-84. PMID: 12519253. Due to the rapid expansion of the literature and the presence of a relatively high number of SR on this topic, the purpose of this study was to conduct an overview of meta-analyses to compile evidence from multiple SR related to the diagnostic and prognostic value of CCTA in the assessment of acute chest pain in the ED.

Methods

Literature search

The search was conducted from January 2005 (the first year of published studies from 64-slice scanners) to July 2015. The strategy was developed through the Medical Subject Heading (MeSH) terms: "coronary artery disease", "computed tomography", "chest pain" and "emergency department". The electronic databases researched were MEDLINE and COCHRANE LIBRARY. This overview included SR on the diagnostic and prognostic value of CCTA in the ED. Only studies reported in English were eligible and had their references checked.

We analyzed all studies of SR, excluding duplicates, performed with CCTA < 64 channels, with at least 30 patients. In the presence of more than one study with the same database, the oldest was deleted.

Ethics approval was not required for this overview.

Quality assessment

All eligible SR were assessed using the PRISMA quality assessment tool (Preferred Reporting Items for Systematic Reviews and Meta-Analysis),88 Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1-34. doi: 10.1016/j.jclinepi.2009.06.006.
https://doi.org/10.1016/j.jclinepi.2009....
and those scoring ≥ 80% were approved.

Data extraction

Two authors independently extracted data using a standardized data extraction form including study characteristics (design, inclusion and exclusion criteria), characteristics of the intervention (at least 64-slice computed tomography, use and timing of cardiac enzymes relative to CCTA, follow-up duration), patients characteristics (age, sex, cardiac risk factors), outcomes [death, nonfatal myocardial infarction (MI), repeated ED chest pain evaluation, repeated hospitalization for ACS, ICA, revascularization by percutaneous coronary intervention (PCI)/coronary artery bypass graft (CABG)], hospital length of stay (LOS), and cost. Disagreements were resolved by consensus or consultation with a third individual.

Data synthesis and statistical analysis

Numerical variables were described as mean and standard deviation and categorical variables, as simple and relative frequencies. The sensitivity and specificity were described as estimates with 95% confidence interval (CI), rounded to the nearest integer. Using true positive (TP), false positive (FP), true negative (TN), and false negative (FN), we derived sensitivity, specificity, positive and negative likelihood ratios (posLR and negLR, respectively), and positive and negative predictive values (VP+ and VP-, respectively) for each study.

Spearman correlation test was used to analyze the correlation between sensitivity and the ratio of FP. Chi-square test (χ2) was used to assess the heterogeneity of sensitivity and specificity and, in both cases, the null hypothesis was the same (or homogeneity). Potential heterogeneity among studies was assessed using the Cochran's Q test or Higgins and Thompson statistical I2. Cochran's Q test calculates a measure of the overall variation among the studies, stating, as the null hypothesis, that the studies that make up the meta-analysis are homogeneous. The I2 evaluates the estimate of the variance due to heterogeneity, rather than chance, and is based on traditional statistical variance defined as Cochran's Q.99 Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557-60. doi: 10.1136/bmj.327.7414.557.
https://doi.org/10.1136/bmj.327.7414.557...
Significant heterogeneity was set to I2 > 50%. Data were used with a significance level of 95%. Data analysis was performed with R-package "mada" for meta-analysis (R Core Team, 2015) that presents some approaches for diagnostic studies, such as descriptive statistics and graphs. In the data analysis, in 2 x 2 tables, cells with zeros often lead to statistical artifacts, since certain reasons can 'not exist'; so the package "mada" uses the value of 0.5 as a correction of continuity "standard". This package does not calculate the aggregated value of sensitivity and specificity. It is not appropriate analytical indicator.1010 Gatsonis C, Paliwal P. Meta-analysis of diagnostic and screening test accuracy evaluations: methodologic primer. AJR Am J Roentgenol. 2006;187(2):271-81. doi: 10.2214/AJR.06.0226.
https://doi.org/10.2214/AJR.06.0226...

In presence of publication bias, the funnel plot, method known to assess publication bias, is unlikely to be useful to detect the effect of sample size because these parameters will vary depending on the cut-off values and random error.1111 Brasil. Ministério da Saúde. Diretrizes Metodológicas: elaboração de revisão sistemática e metanálise de estudos de acurácia diagnóstica. Brasília; 2014. Meta-regression was not performed, since its purpose is to evaluate the causes of heterogeneity and the diagnostic odds ratio (DOR) was homogeneous.

Results

The literature search generated a total of 4 SR that evaluated the diagnostic and prognostic value of CCTA ≥ 64 channels in the ED,2525 Hulten E, Pickett C, Bittencourt MS, Villines TC, Petrillo S, Carli MF, 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. doi: 10.1016/j.jacc.2012.11.061.
https://doi.org/10.1016/j.jacc.2012.11.0...

26 Samad Z, Hakeem A, Mahmood SS, Pieper K, Patel MR, Simel DL, et al. A meta-analysis and systematic review of computed tomography angiography as a diagnostic triage tool for patients with chest pain presenting to the emergency department. J Nucl Cardiol. 2012;19(2):364-76. doi: 10.1007/s12350-012-9520-2.
https://doi.org/10.1007/s12350-012-9520-...

27 Takakuwa KM, Keith SW, Estepa AT, Shofer FS. A meta-analysis of 64-section coronary CT angiography findings for predicting 30-day major adverse cardiac events in patients presenting with symptoms suggestive of acute coronary syndrome. Acad Radiol. 2011;18(12):1522-8. doi: 10.1007/.s12350-012-9520-2.
https://doi.org/10.1007/.s12350-012-9520...
-2828 Ollendorf DA, Kuba M, Pearson SD. The diagnostic performance of multi-slice coronary computed tomographic angiography: a systematic review. J Gen Intern Med. 2011;26(3):307-16. doi: 10.1007/s11606-010-1556-x.
https://doi.org/10.1007/s11606-010-1556-...
containing 91 primary studies. From these, 13 articles meeting the inclusion criteria were included in the qualitative analysis. Due to absence of quantitative dates, only 10 studies were used in the meta-analysis. The main reasons for exclusion of the primary studies were: not performed in the ED; duplicated studies; and CCTA of 4 or 16 channels. Figure 1 shows a flow chart of study exclusion.

Figure 1
Flow diagram describing the process of study inclusion

A total of 4831 patients were included (mean age of 54 ± 6 years, 51% male), of whom 46% were hypertensive, 32% had dyslipidemia, 13% had diabetes and 26% had a family history of premature CAD. The primary studies included and their clinical characteristics are outlined in Table 1. In general, patients with atrial fibrillation, ventricular arrhythmias, enzymatic changes, renal failure, hemodynamic instability, allergy to contrast, and pregnant women were excluded from studies.

Table 1
Primary studies included and their clinical characteristics

The studies were conducted in patients at low and intermediate risk for CAD (except Ueno et al.,1919 Ueno K, Anzai T, Jinzaki M, Yamada M, Kohno T, Kawamura A, et al. Diagnostic capacity of 64-slice multidetector computed tomography for acute coronary syndrome in patients presenting with acute chest pain. Cardiology. 2009;112(3):211-8. doi: 10.1159/000149630.
https://doi.org/10.1159/000149630...
2009, that includes high-risk patients) with normal cardiac enzymes and nonischemic initial ECG.

In the meta-analysis, 9 studies defined positive CCTA when in the presence of luminal lesions ≥ 50%, while 1 study defined it when luminal lesion ≥ 70%. A total of 1655 patients were included. Descriptive statistics for diagnostic test (CCTA) performance are described in Tables 2 and 3. The study by Rubinstein et al.1616 Rubinshtein R, Halon DA, Gaspar T, Jaffe R, Karkabi B, Flugelman MY, et al. Usefulness of 64-slice cardiac computed tomographic angiography for diagnosing acute coronary syndromes and predicting clinical outcome in emergency department patients with chest pain of uncertain origin. Circulation. 2007;115(13):1762-8. doi: 10.1161/CIRCULATIONAHA.106.618389.
https://doi.org/10.1161/CIRCULATIONAHA.1...
reported the highest sensitivity (S = 98%), while the study by Johnson et al.2222 Johnson TR, Nikolaou K, Becker A, Leber AW, Rist C, Wintersperger BJ, et al. Dual-source CT for chest pain assessment. Eur Radiol. 2008;18(4):773-80. doi: 10.1007/s00330-007-0803-y.
https://doi.org/10.1007/s00330-007-0803-...
reported the highest specificity (E = 100%). The largest study was that by Hollander et al.,1818 Hollander JE, Chang AM, Shofer FS, McCusker CM, Baxt WG, Litt HI. Coronary computed tomographic angiography for rapid discharge of low-risk patients with potential acute coronary syndromes. Ann Emerg Med. 2009;53(3):295-304. doi: 10.1016/j.annemergmed.2008.09.025.
https://doi.org/10.1016/j.annemergmed.20...
2009, which included 568 patients, and reported a 94% sensitivity and a 92% specificity.

Table 2
Test performance characteristics of CCTA in the studies included
Table 3
Descriptive analysis of the likelihood ratio

All studies showed high positive likelihood ratio (the highest in the study by Johnson et al.,2222 Johnson TR, Nikolaou K, Becker A, Leber AW, Rist C, Wintersperger BJ, et al. Dual-source CT for chest pain assessment. Eur Radiol. 2008;18(4):773-80. doi: 10.1007/s00330-007-0803-y.
https://doi.org/10.1007/s00330-007-0803-...
2008), and low negative likelihood ratio (the lowest in the study by Rubinstein et al.,1616 Rubinshtein R, Halon DA, Gaspar T, Jaffe R, Karkabi B, Flugelman MY, et al. Usefulness of 64-slice cardiac computed tomographic angiography for diagnosing acute coronary syndromes and predicting clinical outcome in emergency department patients with chest pain of uncertain origin. Circulation. 2007;115(13):1762-8. doi: 10.1161/CIRCULATIONAHA.106.618389.
https://doi.org/10.1161/CIRCULATIONAHA.1...
2007).

To assess the effect of different cut-offs for "significant" luminal obstruction on analysis, we performed diagnostic threshold analyses. We found a Spearman correlation coefficient of 0.045, p > 0.05 (95% CI -0.602 to 0.656), which means 'very weak' correlation or no significant correlation.

The equality test for sensitivity showed homogeneity across studies [χ2 = 8.4 (df = 9), p = 0.5] and heterogeneity for specificity [χ2 = 55.5 (df = 9), p < 0.001], confirmed with the forest plot (Figures 2 and 3).

Figure 2
Forest plot for sensitivity of CCTA for diagnosing ACS.

Figure 3
Forest plot for specificity of CCTA for diagnosing ACS.

The univariate analysis showed homogeneity of DOR [Q = 8.5 (df = 9), p = 0.48 and I2 = 0%]. Figure 4 shows estimate of the synthesis.

Figure 4
Forest plot for diagnostic odds ratio (DOR).

The χ2 test did not reject the hypothesis of homogeneity for the model [χ2 = 10.14 (df = 1), p = 0.34, θ(theta) = 0.018 (CI95%: 0.0014 to 0,0246)] and so we opted for the fixed effects model. The area under the curve (AUC) was 0.982 (95% CI: 0.967-0.999).

As for the events, there was great variability between studies in the outcomes assessed. A summary of the compound events in all studies, with their specific characteristics, is described in Table 4. In most studies, the events investigated were death, MI, CABG and ICA. Others evaluated the diagnosis of ACS, and, in three studies, the technique of "triple rule-out" was used (in addition to investigating CAD, pulmonary embolism and aortic dissection).

Table 4
Clinical outcomes of the individual studies

Figure 7 shows the main events: 29 (0.6%) MI, 92 (1.9%) CRM, and 312 (6.4%) ICA. There was no death. The diagnosis of ACS occurred in 7.3% of the 1655 patients included in the meta-analysis.

Figure 5
SROC curve with θ (theta) estimative and confidence interval.

Figure 6
SROC curve for CCTA ≥ 64 channels

Figure 7
Events in the follow-up.

Although analyzed heterogeneously, the four randomized clinical trials (RCTs) also evaluated the hospital LOS and costs. Compared to usual care, the use of CCTA reduced the hospital LOS in all studies, and the costs, in three studies.

Discussion

This study had the purpose to evaluate the diagnostic and prognostic value of CCTA in the evaluation of acute chest pain in the ED. We included 4 SR, totaling 13 studies. After primary analysis of the exclusion criteria, we used 10 studies for quantitative analysis (meta-analysis).

We found that CCTA has high sensitivity and specificity for CAD detection in patients with chest pain in the ED in all studies, and showed high positive likelihood ratio and low negative likelihood ratio. The distribution of sensitivity was homogeneous, while that of specificity was heterogeneous. We found weak correlation on the effect of the different cut-offs for the diagnosis of significant luminal obstruction. The DOR was homogeneous and significant. There was variability on the number and type of events between the studies. The clinical trials reported decreased LOS and costs.

The quality of cardiac image by CCTA is directly related to the evolution of tomography. Current technical developments of CT scanners and the software are intended to improve the spatial and temporal resolution of cardiac CT images while reducing the radiation dose received from a typical examination. They include wider detector arrays that allow a higher number of simultaneously acquired image slices, faster x-ray tube rotation, and use of alternative image reconstruction techniques.2929 Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, et al; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; American College of Physicians; American Association for Thoracic Surgery; Preventive Cardiovascular Nurses Association; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons. 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(24):e44-164. doi: 10.1016/j.jacc.2012.07.013.
https://doi.org/10.1016/j.jacc.2012.07.0...
Its use in patients with early biomarkers and negative ECG for myocardial ischemia is already included in the algorithm of chest pain evaluation in several emergency centers, a strategy that is supported by the current Appropriate Use Criteria for Cardiac Computed Tomography3030 Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O'Gara P, et al; American College of Cardiology Foundation Appropriate Use Criteria Task Force; Society of Cardiovascular Computed Tomography; American College of Radiology; American Heart Association; American Society of Echocardiography; American Society of Nuclear Cardiology; North American Society for Cardiovascular Imaging; Society for Cardiovascular Angiography and Interventions; Society for Cardiovascular Magnetic Resonance. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. J Am Coll Cardiol. 2010;56(22):1864-94. doi: 10.1016/j.jacc.2010.07.005.
https://doi.org/10.1016/j.jacc.2010.07.0...
and Focused Update of the Guidelines for the Management of Patients With Unstable Angina/ Non-ST-Elevation Myocardial Infarction.3131 Wright RS, Anderson JL, Adams CD, Bridges CR, Casey DE, Ettinger SM, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;57(19):e215-367. doi: 10.1016/j.jacc.2011.02.011.
https://doi.org/10.1016/j.jacc.2011.02.0...

The CCTA has the unique ability to noninvasively depict the coronary anatomy, not only allowing visualization of the arterial lumen to detect severe stenosis or occlusion responsible for myocardial ischemia, but also allows the assessment of the coronary artery wall by demonstrating the presence or absence of CAD and characteristics of the plaque (can identify predictors of plaque rupture).3232 De Filippo M, Capasso R. Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) imaging in the assessment of patients presenting with chest pain suspected for acute coronary syndrome. Ann Transl Med. 2016;4(13):255. doi: 10.21037/atm.2016.06.30.
https://doi.org/10.21037/atm.2016.06.30...
It may aid in the differential diagnosis of diseases, such as pulmonary embolism, aortic aneurysm, among others.3333 Sara L, Szarf G, Tachibana A, Schiozaki AA, Villa AV, de Oliveira AC, et al; Sociedade Brasileira de Cardiologia; Colégio Brasileiro de Radiologia. [II Guidelines on Cardiovascular Magnetic Resonance and Computed Tomography of the Brazilian Society of Cardiology and the Brazilian College of Radiology]. Arq Bras Cardiol. 2014;103(6 Suppl 3):1-86. doi: 10.5935/abc.2014S006.
https://doi.org/10.5935/abc.2014S006...

The CCTA allows the identification of non-obstructive CAD in patients with acute chest pain improving substantially the therapeutic management in this group of patients by allowing a previous clinical decision, more effectively targeting the treatment.3434 Prazeres CE, Cury RC, Carneiro AC, Rochitte CE. Coronary computed tomography angiography in the assessment of acute chest pain in the emergency room. Arq Bras Cardiol. 2013;101(6):562-9. doi: 10.5935/abc.20130208.
https://doi.org/10.5935/abc.20130208...

In face of the epidemiology of chest pain in the ED, the evaluation of these patients is a major challenge, both from the point of view of diagnosis and the optimization of time (to start treatment or discharge) and in the correct direction of resources. The use of serum biomarkers does not allow a rapid exclusion of myocardial ischemia, resulting in early discharge from the ED. Thus, there are limited tools available for fast triage of patients with chest pain. It is with this idea that the four clinical trials randomized1212 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(8):863-71. doi: 10.1016/j.jacc.2006.08.064
https://doi.org/10.1016/j.jacc.2006.08.0...

13 Goldstein JA, Chinnaiyan KM, Abidov A, Achenbach S, Berman DS, Hayes SW, et al; CT-STAT Investigators. The CT-STAT (Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment) trial. J Am Coll Cardiol. 2011;58(14):1414-22. doi: 10.1016/j.jacc.2011.03.068.
https://doi.org/10.1016/j.jacc.2011.03.0...

14 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;366(15):1393-403. doi: 10.1056/NEJMoa1201163.
https://doi.org/10.1056/NEJMoa1201163...
-1515 Hoffmann U, Truong QA, Schoenfeld DA, Chou ET, Woodard PK, Nagurney JT, et al; ROMICAT-II Investigators. Coronary CT angiography versus standard evaluation in acute chest pain. N Engl J Med. 2012;367(4):299-308. doi: 10.1056/NEJMoa1201161.
https://doi.org/10.1056/NEJMoa1201161...
investigated the reduction in hospital LOS and concluded that the use of emergency CCTA in patients at low to intermediate risk of CAD reduces the hospital LOS.

Shreibati et al.3535 Shreibati JB, Baker LC, Hlatky MA. Association of coronary CT angiography or stress testing with subsequent utilization and spending among medicare beneficiaries. JAMA. 2011;306(19):2128-36. doi: 10.1001/jama.2011.1652.
https://doi.org/10.1001/jama.2011.1652...
found in an observational cohort (2005-2008) an increase of costs and incidence of cardiac catheterization using CCTA. Three of the four RCT1212 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(8):863-71. doi: 10.1016/j.jacc.2006.08.064
https://doi.org/10.1016/j.jacc.2006.08.0...
,1313 Goldstein JA, Chinnaiyan KM, Abidov A, Achenbach S, Berman DS, Hayes SW, et al; CT-STAT Investigators. The CT-STAT (Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment) trial. J Am Coll Cardiol. 2011;58(14):1414-22. doi: 10.1016/j.jacc.2011.03.068.
https://doi.org/10.1016/j.jacc.2011.03.0...
,1515 Hoffmann U, Truong QA, Schoenfeld DA, Chou ET, Woodard PK, Nagurney JT, et al; ROMICAT-II Investigators. Coronary CT angiography versus standard evaluation in acute chest pain. N Engl J Med. 2012;367(4):299-308. doi: 10.1056/NEJMoa1201161.
https://doi.org/10.1056/NEJMoa1201161...
showed a reduction in hospital costs. However, to assess the impact of new technologies on health costs requires the use of specific methodology that allows the evaluation of cost-effectiveness.

There was increased ICA in the group that underwent CCTA as opposed to standard monitoring, but the design of the studies provides no data to assess if there is an excess use of ICA in the group that underwent CCTA or underutilization in the group which did not use it. In the CONFIRM registry,3636 Shaw LJ, Hausleiter J, Achenbach S, Al-Mallah M, Berman DS, Budoff MJ, et al; CONFIRM Registry Investigators. Coronary computed tomographic angiography as a gatekeeper to invasive diagnostic and surgical procedures: results from the multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: an International Multicenter) registry. J Am Coll Cardiol. 2012;60(20):2103-14. doi: 10.1016/j.jacc.2012.05.062.
https://doi.org/10.1016/j.jacc.2012.05.0...
during follow-up, the rates of ICA were low in patients with no to mild CAD according to CCTA, revealing that, in clinical practice, physicians are accepting the results obtained by CCTA, and, in this case, the negative predictive value is high.

The rate of major cardiac events among patients involved in the studies was very low, it is concluded that these have excellent prognosis. However, the data is not sufficient to determine whether the use of CCTA brought some benefit in reducing major adverse cardiac events (death and heart attack) compared to standard of care.

The overall prevalence of CAD in most studies was low; therefore, the data cannot be extrapolated to high-risk patients. More studies are necessary to detect differences in clinical outcomes, given the nature of this low-risk population. The evaluation of patients in the ED did not show a fixed standard between studies, contrariwise, there was great variability in the behavior; in most studies, the attending physician decided the next "step" in the evaluation, even for RCT.

For the exclusion of ACS in patients with known coronary occlusions, the CCTA would have a less useful role as a screening test, since the identification of coronary obstruction in patients with known CAD does not explain the etiology of chest pain.

Limitations

A difficulty found was the heterogeneity of the studies published in the ED. There was a deficiency of standardization in the evidence of the evaluation method, and large differences in follow-up and outcome measures.

Even with a total number of 4831 patients, the "force" to detect differences in clinical events such as heart attack and death is still low, since these are rare in these groups of patients.

All studies may have verification bias, since it is impossible to "blind" the conduct (CCTA or standard of care) for physicians and patients.

The methodology used in diagnostic test accuracy studies is quite different from that of therapeutic/interventional studies and has been developed substantially in recent decades.3737 Kim KW, Lee J, Choi SH, Huh J, Park SH. Systematic review and meta-analysis of studies evaluating diagnostic test accuracy?: a practical review for clinical researchers - Part I. Korean J Radiol. 2015;16(6):1175-87. doi: 10.3348/kjr.2015.16.6.1175.
https://doi.org/10.3348/kjr.2015.16.6.11...

Conclusions

The use of CCTA as a tool for stratification of patients with low or intermediate cardiovascular risk, who are in the ED with chest pain, has high accuracy, safety, reduces hospital LOS and probably the costs, producing an early diagnosis and more effective decision making. To assess the value of CCTA in the prevention of future events, studies with more appropriate design and longer follow-up are necessary.

  • Sources of Funding
    There were no external funding sources for this study.
  • Study Association
    This article is part of the thesis of Doctoral submitted by Carlos José Oliveira de Matos, from Universidade Federal de Sergipe.
  • Ethics approval and consent to participate
    This article does not contain any studies with human participants or animals performed by any of the authors.
  • Erratum

    In the article “Overview with Meta-analysis of Systematic Reviews of the Diagnostic and Prognostic Value of Coronary Computed Tomography Angiography in the Emergency Department” by Irlaneide da Silva Tavares, Carlos José Oliveira de Matos, Marco Antonio Prado Nunes, Antonio Carlos Sobral Sousa, Divaldo Pereira de Lyra Júnior, and Joselina Luzia Menezes Oliveira, substitute the institution Centro de Ensino e Pesquisa e Laboratório de Ecocardiografia (ECOLAB) do Hospital e Fundação São Lucas2 with Rede e Hospital Primavera - Centro de Imagem2 – Aracaju, SE - Brazil.

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Publication Dates

  • Publication in this collection
    23 Oct 2017
  • Date of issue
    Jan-Feb 2018

History

  • Received
    04 Mar 2017
  • Reviewed
    01 July 2017
  • Accepted
    07 July 2017
Sociedade Brasileira de Cardiologia Avenida Marechal Câmara, 160, sala: 330, Centro, CEP: 20020-907, (21) 3478-2700 - Rio de Janeiro - RJ - Brazil
E-mail: revistaijcs@cardiol.br