ijcs International Journal of Cardiovascular Sciences Int. J. Cardiovasc. Sci. 2359-4802 2359-5647 Sociedade Brasileira de Cardiologia W7DyjTRhgSdyQZRsdWppjFj S2359-56472018000100033 10.5935/2359-4802.20170086 Original Articles Overview with Meta-analysis of Systematic Reviews of the Diagnostic and Prognostic Value of Coronary Computed Tomography Angiography in the Emergency Department Tavares Irlaneide da Silva 1 Matos Carlos José Oliveira de 1 Nunes Marco Antonio Prado 1 Sousa Antonio Carlos Sobral 1 2 Lyra Divaldo Pereira de Júnior 1 Oliveira Joselina Luzia Menezes 1 2 Universidade Federal de Sergipe Brazil Universidade Federal de Sergipe (UFS); Universidade Federal de Sergipe Rede e Hospital Primavera Centro de Imagem Aracaju SE Brazil Rede e Hospital Primavera - Centro de Imagem – Aracaju, SE - Brazil. Mailing Address: Carlos José Oliveira de Matos, Rua Orlando Magalhães Maia, 1330, Res. Eduardo Abreu, apto, 802. Postal Code: 49025-530, Jardins, Aracaju, SE - Brazil. E-mail: cjomatos@gmail.com; cjomatos@yahoo.com.br

Author contributions

Conception and design of the research: Tavares IS, Matos CJO, Lyra Júnior DP, Oliveira JLM. Acquisition of data: Tavares IS, Matos CJO, Oliveira JLM. Analysis and interpretation of the data: Tavares IS, Matos CJO, Nunes MAP, Sousa ACS, Lyra Júnior DP, Oliveira JLM. Statistical analysis: Tavares IS, Matos CJO, Nunes MAP, Sousa ACS, Oliveira JLM. Writing of the manuscript: Tavares IS, Matos CJO, Sousa ACS, Oliveira JLM. Critical revision of the manuscript for intellectual content: Tavares IS, Matos CJO, Sousa ACS, Lyra Júnior DP, Oliveira JLM. Supervision / as the major investigador: Tavares IS, Matos CJO, Oliveira JLM.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

 23 10 2017 Jan-Feb 2018 31 1 33 46 04 03 2017 01 07 2017 07 07 2017 This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 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).1 North American statistics show that in 2011 coronary artery disease (CAD) was responsible for about 1 of every 7 deaths, totaling 375,295 deaths.2 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%.3 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.4 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.5,6

Systematic reviews (SR) are studies with the highest level of evidence (higher in the hierarchy of evidence-based research) and rigorous methodological quality.7 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),8 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.9 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.10

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.11 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,25-28 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.

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.

Primary studies included and their clinical characteristics
Authors Type of study Year Type of CCTA (Channels) Centers Patients (N) Age(Mean ± SD) Men (%) BMI, (kg/m2± DP) HTNN (%) HLN (%) DMN (%) FH of premature CAD N (%) Smoker N (%)
Goldstein et al. 12 RCT 2007 64 Single center 197 50 ± 12 50 29 ± 5 75/38 70(36) 20(10) 82(42) 35(18)
CT-STAT 13 RCT 2011 64 a 320 Multicenter 699 50 ± 10 46 28 ± 5 259/37 234(33) 48(7) 212(30) 157(22)
ACRIN-PA 14 RCT 2012 ≥ 64 Multicenter 1370 49 ± 9 47 - 695/51 367(27) 194(14) 394(29) 447(33)
ROMICAT II 15 RCT 2011 64 Single center 1000 54 ± 8 53 29 ± 5 541/54 454(45) 173(17) 271(27) 492(49)
Rubinstein et al. 16 Cohort 2007 64 Single center 58 56 ± 10 64 - 33/57 32(55) 12(21 9(16) 22(38)
Gallagher et al. 17 Cohort 2007 64 Single center 85 49 ± 11 53 - 31(36,5) 23(27) 8(9) 50(59) 22(25,9)
Hollander et al. 18 Cohort 2009 64 Single center 568 47 ± 9 44 - 251(44) 108(19) 77(14) 104(18) 200(35)
Ueno et al. 19 Cohort 2009 64 Single center 36 66 ± 12 53 - 17(47) 19(53) 9(25) 8(22) 13(36)
Hoffmann et al. 20 Cohort 2009 64 Multicenter 368 53 ± 12 61 29 ± 6 145(39) 135(37) 40(11) 180(49)
Johnson et al. 21 Cohort 2007 64 Single center 55 67 ± 10 64 - - - - - -
Johnson et al. 22 Cohort 2008 64 Single center 109 63 ± 14 72 - - - - - -
Takakuwa et al. 23 Cohort 2008 64 Single center 197 49 ± 11 72 - 92(46,7) 53(26,9) 29(15) 62(31) 62(31,5)
Hansen et al. 24 Cohort 2010 64 Single center 89 56 ± 9 63 - 35(39) 37(42) 7(8) 29(33) 39(44)

CCTA: coronary computed tomography angiography; SD: standard deviation; BMI, body mass index; HTN: hypertension; HL: hyperlipidemia; DM: diabetes mellitus; FH: family history; CAD: coronary artery disease; RCT: randomized clinical trial

The studies were conducted in patients at low and intermediate risk for CAD (except Ueno et al.,19 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.16 reported the highest sensitivity (S = 98%), while the study by Johnson et al.22 reported the highest specificity (E = 100%). The largest study was that by Hollander et al.,18 2009, which included 568 patients, and reported a 94% sensitivity and a 92% specificity.

Test performance characteristics of CCTA in the studies included
Year Authors N TP FN FP TN S IC95% E IC95%
2007 Goldstein et al.12 99 8 0 24 67 0.94 0.63 - 0.99 0.73 0.64 - 0.81
2007 Rubinstein et al.16 58 20 0 3 35 0.98 0.81 - 1.00 0.91 0.78 - 0.97
2007 Gallagher et al.17 85 6 1 3 72 0.81 0.47 - 0.96 0.95 0.88 - 0.98
2009 Hollander et al.18 568 7 0 47 508 0.94 0.60 - 0.99 0.92 0.89 - 0.94
2009 Ueno et al.19 36 11 1 4 20 0.89 0.62 - 0.97 0.82 0.63 - 0.92
2009 Hoffmann et al.20 368 24 7 44 293 0.77 0.60 - 0.88 0.87 0.83 - 0.90
2007 Johnson et al.21 55 16 1 3 35 0.92 0.71 - 0.98 0.91 0.78 - 0.97
2008 Johnson et al.22 109 13 0 0 96 0.96 0.73 - 1.00 1.00 0.95 - 1.00
2008 Takakuwa et al.23 197 6 1 16 174 0.81 0.47 - 0.96 0.91 0.87 - 0.95
2010 Hansen et al.24 89 3 0 1 85 0.88 0.40 - 0.99 0.98 0.93 - 1.00

CCTA: coronary computed tomography angiography; TP: true positive; FN: false negative; FP: false positive; TN: true negative; S: sensibility; CI: confidence interval; E: specificity.

 Descriptive analysis of the likelihood ratio
Year Authors posLR Minimum Maximum negLR Minimum Maximum
2007 Goldstein et al.12 3.546 2.439 5.157 0.076 0.005 1.123
2007 Rubinstein et al.16 10.878 3.995 29.620 0.026 0.002 0.405
2007 Gallagher et al.17 17.643 6.015 51.746 0.197 0.046 0.832
2009 Hollander et al.18 10.974 7.925 15.196 0.068 0.005 1.001
2009 Ueno et al.19 4.915 2.081 11.607 0.141 0.031 0.641
2009 Hoffmann et al.20 5.815 4.163 8.123 0.270 0.144 0.506
2007 Johnson et al.21 10.214 3.723 28.022 0.092 0.020 0.425
2008 Johnson et al.22 187.071 11.763 2974.950 0.036 0.002 0.546
2008 Takakuwa et al.23 9.405 5.325 16.611 0.205 0.048 0.869
2010 Hansen et al.24 50.750 9.952 258.792 0.127 0.010 1.700

posLR: positive likelihood ratios; negLR: negative likelihood ratios.

All studies showed high positive likelihood ratio (the highest in the study by Johnson et al.,22 2008), and low negative likelihood ratio (the lowest in the study by Rubinstein et al.,16 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).

Forest plot for sensitivity of CCTA for diagnosing ACS.

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.

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).

Clinical outcomes of the individual studies
Author Year Type of Study Number of patients Age(Mean ± SD) Male % CAD Risk Follow-up (months) Outcomes
Goldstein et al.12 2007 RCT 99 50 ± 12 50 Very low 6 CABG and ICA
CT-STAT13 2011 RCT 361 50 ± 10 46 Low 6 CABG and ICA
ACRIN-PA14 2012 RCT 908 49 ± 09 47 Low and intermediary 1 MI, CABG and ICA
ROMICAT II15 2011 RCT 501 56 ± 10 53 Low and intermediary 1 MI, ICA and PCI
Rubinstein et al.16 2007 Prospective cohort 58 54 ± 8.0 64 Intermediary 15 MI, Death, CABG
Gallagher et al.17 2007 Prospective cohort 85 49 ± 11 53 Low 1 Diagnosis ACS
Hollander et al.18 2009 Observational cohort 568 47 ± 8.9 44 Low 1 Absence of death and MI
Ueno et al.19 2009 Prospective cohort 36 66 ± 12 53 High 1 -
Hoffmann et al.20 2009 Observational cohort 368 52.7 ± 12 61 Low and intermediary 6 Chest pain, UAP, readmission
Johnson et al.21 2007 Prospective cohort 55 67 ± 10 64 Low and intermediary ≥ 5 Focus on further tests and contrast-induced nephropathy
Johnson et al.22 2008 Prospective cohort 109 63 ± 14 71 Low and intermediary 6 Arrhythmia; Pleural effusion (pleurisy); Readmission
Takakuwa et al.23 2008 Prospective cohort 197 49 ± 11 72 Low and intermediary 1 There were no events (not specified which events)
Hansen et al.24 2010 Prospective cohort 89 56,3 ± 8,6 63 Low and intermediary 12 There were no events (Death and MI)

SD: standard deviation; CAD: coronary artery disease; CABG: coronary artery bypass graft; ICA: invasive coronary angiography percutaneous; MI: myocardial infarction; PCI: percutaneous coronary intervention; UAP: unstable angina pectoris

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.

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

SROC curve for CCTA ≥ 64 channels

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.29 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 Tomography30 and Focused Update of the Guidelines for the Management of Patients With Unstable Angina/ Non-ST-Elevation Myocardial Infarction.31

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).32 It may aid in the differential diagnosis of diseases, such as pulmonary embolism, aortic aneurysm, among others.33

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.34

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 randomized12-15 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.35 found in an observational cohort (2005-2008) an increase of costs and incidence of cardiac catheterization using CCTA. Three of the four RCT12,13,15 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,36 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.37

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.

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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Gallagher MJ Ross MA Raff GL Goldstein JA O&Neill WW O&Neil B The diagnostic accuracy of 64-slice computed tomography coronary angiography compared with stress nuclear imaging in emergency department low-risk chest pain patients Ann Emerg Med 2007 49 2 125 136 10.1016/j.annemergmed.2006.06.043 18 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. 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 10.1016/j.annemergmed.2008.09.025 19 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. Ueno K Anzai T Jinzaki M Yamada M Kohno T Kawamura A Diagnostic capacity of 64-slice multidetector computed tomography for acute coronary syndrome in patients presenting with acute chest pain Cardiology 2009 112 3 211 218 10.1159/000149630 20 Hoffmann U, Bamberg F, Chae CU, Nichols JH, Rogers IS, Seneviratne SK, et al. Coronary computed tomography angiography for early triage of patients with acute chest pain. The ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) trial. J Am Coll Cardiol. 2009;53(18):1642-50. Hoffmann U Bamberg F Chae CU Nichols JH Rogers IS Seneviratne SK Coronary computed tomography angiography for early triage of patients with acute chest pain. The ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) trial J Am Coll Cardiol 2009 53 18 1642 1650 21 Johnson TR, Nikolaou K, Wintersperger BJ, Knez A, Boekstegers P, Reiser MF, et al. ECG-gated 64-MDCT Angiography in the Differential Diagnosis of Acute Chest Pain. AJR Am J Roentgenol. 2007;188(1):76-82. doi: 10.2214/AJR.05.1153. Johnson TR Nikolaou K Wintersperger BJ Knez A Boekstegers P Reiser MF ECG-gated 64-MDCT Angiography in the Differential Diagnosis of Acute Chest Pain AJR Am J Roentgenol 2007 188 1 76 82 10.2214/AJR.05.1153 22 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. Johnson TR Nikolaou K Becker A Leber AW Rist C Wintersperger BJ Dual-source CT for chest pain assessment Eur Radiol 2008 18 4 773 780 10.1007/s00330-007-0803-y 23 Takakuwa KM, Halpern EJ. Evaluation of a "Triple Rule-Out" Coronary CT angiography protocol: use of 64-section CT in low-to-moderate risk emergency departament patients suspected of having acute coronary syndrome. Radiology. 2008;248(2):438-46. doi: 10.1148/radiol.2482072169. Takakuwa KM Halpern EJ Evaluation of a "Triple Rule-Out" Coronary CT angiography protocol: use of 64-section CT in low-to-moderate risk emergency departament patients suspected of having acute coronary syndrome Radiology 2008 248 2 438 446 10.1148/radiol.2482072169 24 Hansen M, Ginns J, Seneviratne S, Slaughter R, Premaranthe M, Samardhi H, et al. The value of dual-source 64-slice CT coronary angiography in the assessment of patients presenting to an acute chest pain service. Hear Lung Circ. 2010;19(4):213-8. doi: 10.1016/j.hlc.2010.01.004. Hansen M Ginns J Seneviratne S Slaughter R Premaranthe M Samardhi H The value of dual-source 64-slice CT coronary angiography in the assessment of patients presenting to an acute chest pain service Hear Lung Circ 2010 19 4 213 218 10.1016/j.hlc.2010.01.004 25 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. Hulten E Pickett C Bittencourt MS Villines TC Petrillo S Carli MF 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 8 880 892 10.1016/j.jacc.2012.11.061 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. Samad Z Hakeem A Mahmood SS Pieper K Patel MR Simel DL 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 2 364 376 10.1007/s12350-012-9520-2 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. 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 1528 10.1007/.s12350-012-9520-2 28 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. 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 3 307 316 10.1007/s11606-010-1556-x 29 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. Fihn SD Gardin JM Abrams J Berra K Blankenship JC Dallas AP 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 10.1016/j.jacc.2012.07.013 30 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. Taylor AJ Cerqueira M Hodgson JM Mark D Min J O'Gara PAmerican 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 1894 10.1016/j.jacc.2010.07.005 31 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. Wright RS Anderson JL Adams CD Bridges CR Casey DE Ettinger SM 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 e367 10.1016/j.jacc.2011.02.011 32 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. 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 13 255 255 10.21037/atm.2016.06.30 33 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. Sara L Szarf G Tachibana A Schiozaki AA Villa AV de Oliveira AC 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 10.5935/abc.2014S006 34 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. 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 6 562 569 10.5935/abc.20130208 35 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. 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 2136 10.1001/jama.2011.1652 36 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. Shaw LJ Hausleiter J Achenbach S Al-Mallah M Berman DS Budoff MJ 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 2114 10.1016/j.jacc.2012.05.062 37 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. 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 1187 10.3348/kjr.2015.16.6.1175 Artigos Visão Geral com Meta-Análise de Revisões Sistemáticas sobre o Valor Diagnóstico e Prognóstico da Angiotomografia de Coronárias na Emergência Tavares Irlaneide da Silva 1 Matos Carlos José Oliveira de 1 Nunes Marco Antonio Prado 1 Sousa Antonio Carlos Sobral 1 2 Lyra Divaldo Pereira de Júnior 1 Oliveira Joselina Luzia Menezes 1 2 Universidade Federal de Sergipe (UFS) Rede e Hospital Primavera - Centro de Imagem – Aracaju, SE - Brazil. Correspondência para: Carlos José Oliveira de Matos, Rua Orlando Magalhães Maia, 1330, Res. Eduardo Abreu, apto, 802. CEP: 49025-530, Jardins, Aracaju, SE - Brasil. E-mail: cjomatos@gmail.com; cjomatos@yahoo.com.br

Contribuição dos autores

Concepção e desenho da pesquisa: Tavares IS, Matos CJO, Lyra Júnior DP, Oliveira JLM. Obtenção de dados: Tavares IS, Matos CJO, Oliveira JLM. Análise e interpretação dos dados: Tavares IS, Matos CJO, Nunes MAP, Sousa ACS, Lyra Júnior DP, Oliveira JLM. Análise estatística: Tavares IS, Matos CJO, Nunes MAP, Sousa ACS, Oliveira JLM. Redação do manuscrito: Tavares IS, Matos CJO, Sousa ACS, Oliveira JLM. Revisão crítica do manuscrito quanto ao conteúdo intelectual importante: Tavares IS, Matos CJO, Sousa ACS, Lyra Júnior DP, Oliveira JLM. Supervisão / como investigador principal: Tavares IS, Matos CJO, Oliveira JLM.

Potencial Conflito de Interesse

Declaro não haver conflito de interesses pertinentes.

 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 Introdução

Em 2010, nos Estados Unidos da América, quase 6 milhões de pacientes procuraram o setor de emergência (SE) com dor torácica, que é a segunda causa mais frequente de visitas a esse setor, embora apenas uma minoria seja diagnosticada com síndrome coronariana aguda (SCA).1 As estatísticas norte-americanas mostram que em 2011 a doença arterial coronariana (DAC) foi responsável por cerca de 1 em cada 7 mortes, no total de 375.295 mortes.2 A DAC é responsável por um substancial impacto no uso dos cuidados de saúde, com um custo estimado de 21,9 bilhões de dólares em 2011. Entre 2013 e 2030, espera-se que esse gasto aumente em ≈ 100%.3 Devido à alta prevalência de DAC, assim como ao seu impacto nos gastos em saúde e às várias opções de tratamento para reduzir a morbimortalidade a ela relacionada, um diagnóstico preciso é essencial.

Um teste diagnóstico efetivo e de alta precisão para excluir DAC aguda poderia reduzir o custo do sistema de saúde norte-americano em bilhões de dólares. O advento da angiotomografia computadorizada de artérias coronárias (ATCC), um método não invasivo para estudar a anatomia das coronárias, com um scanner tomográfico de pelo menos 64 canais, reduzindo artefatos e incrementando a resolução espacial e temporal, deu origem a um exame rápido e efetivo para excluir com segurança a SCA.4 Embora a angiografia coronariana invasiva (ACI) seja o "padrão ouro" para detecção de DAC, não é adequado para uso extenso por ser invasivo, não estar disponível rotineiramente e ter alto custo e elevado risco de complicações. Além disso, a probabilidade imediata e futura de eventos cardíacos em pacientes sem DAC ou com DAC mínima é baixa para aqueles que se apresentam no SE com dor torácica.5,6

Revisões sistemáticas (RS) são estudos com o mais alto nível de evidência (o mais alto na hierarquia da pesquisa baseada em evidência) e rigorosa qualidade metodológica.7 Devido à rápida expansão da literatura e à presença de um número relativamente grande de RS sobre esse tópico, este estudo visou a fornecer uma visão geral com meta-análise para compilar evidência a partir de múltiplas RS relacionadas ao valor diagnóstico e prognóstico da ATCC na avaliação da dor torácica aguda no SE.

 Métodos Busca na literatura

A busca na literatura foi conduzida de janeiro de 2005 (o primeiro ano da publicação de estudos com scanners de 64 canais) a julho de 2015. A estratégia consistiu na busca dos seguintes termos no Medical Subject Heading (MeSH): "coronary artery disease", "computed tomography", "chest pain" e "emergency department". As bases de dados eletrônicos pesquisadas foram MEDLINE e COCHRANE LIBRARY. Essa pesquisa incluiu RS sobre o valor diagnóstico e prognóstico da ATCC no SE. Apenas estudos redigidos em inglês foram elegíveis e tiveram suas referências checadas.

Analisamos todos os estudos de RS, excluindo os duplicados e os realizados com ATCC com menos de 64 canais, com pelo menos 30 pacientes. Na presença de mais de um estudo utilizando a mesma base de dados, o mais antigo foi descartado.

Aprovação de comitê de ética não foi necessária para esta pesquisa.

 Avaliação qualitativa

Todas as RS foram avaliadas usando a ferramenta de avaliação qualitativa PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis),8 e aquelas que obtiveram um escore ≥ 80% foram aprovadas.

 Extração de dados

Dois autores extraíram os dados independentemente usando um formulário padrão de extração de dados, incluindo as características do estudo (design, critérios de inclusão e exclusão), características da intervenção (tomografia computadorizada de pelo menos 64 canais, uso e tempo das enzimas cardíacas em relação à ATCC, duração do seguimento), características dos pacientes (idade, sexo, fatores de risco cardíaco), desfechos [morte, infarto do miocárdio (IM) não fatal, avaliação repetida de dor torácica no SE, re-hospitalização por SCA, ACI, revascularização miocárdica por intervenção coronariana percutânea (ICP)/cirurgia de revascularização miocárdica (CRM)], tempo de permanência hospitalar e custo. As discordâncias foram resolvidas por consenso ou consulta de uma terceira parte.

 Síntese dos dados e análise estatística

As variáveis numéricas foram descritas como média e desvio-padrão, e as variáveis categóricas, como frequências simples e relativas. A sensibilidade e a especificidade foram descritas como estimativas com intervalo de confiança (IC) de 95%, arredondado para o inteiro mais próximo. Usando verdadeiro positivo (VP), falso positivo (FP), verdadeiro negativo (VN), e falso negativo (FN), derivaram-se sensibilidade, especificidade, razões de verossimilhança positiva e negativa (LR+ e LR-, respectivamente), e valores preditivos positivo e negativo (VP+ e VP-, respectivamente) para cada estudo.

Usou-se o teste de correlação de Spearman para analisar a correlação entre sensibilidade e taxa de FP. O teste do qui-quadrado (χ2) foi usado para avaliar a heterogeneidade da sensibilidade e da especificidade, sendo que, nos dois casos, a hipótese nula foi igual (homogeneidade). Avaliou-se a potencial heterogeneidade entre os estudos usando-se o teste Q de Cochran ou a estatística I2 de Higgins e Thompson. O teste Q de Cochran calcula a medida da variação geral entre os estudos, apresentando, como hipótese nula, a afirmação de que os estudos que compõem a meta-análise são homogêneos. A estatística I2 avalia a estimativa da variância devida à heterogeneidade, mais do que ao acaso, sendo baseada na variância estatística tradicional definida como Q de Cochran.9 Estabeleceu-se como heterogeneidade significativa se I2 > 50%. Adotou-se o nível de significância de 95%. A análise dos dados foi realizada com o pacote "mada" para meta-análise (R Core Team, 2015) com algumas abordagens para estudos diagnósticos, como estatística descritiva e gráficos. Na análise dos dados, em tabelas 2 x 2, células com zeros, com frequência, levaram a artefatos estatísticos, pois certas razões podem não existir; portanto, o pacote "mada" usa o valor de 0,5 como uma correção de continuidade "padrão". Esse pacote não calcula o valor agregado de sensibilidade e especificidade. Não se trata de indicador analítico adequado.10

Na presença de viés de publicação, é pouco provável que "funnel plot", o método conhecido para avaliar viés de publicação, seja útil para detectar o efeito do tamanho da amostra, pois tal parâmetro varia dependendo dos valores de corte e o erro randômico.11 Não se realizou meta-regressão, pois seu propósito é avaliar as causas de heterogeneidade e o odds ratio diagnóstico (DOR) foi homogêneo.

 Resultados

A busca na literatura resultou em um total de 4 RS sobre o valor diagnóstico e prognóstico da ATCC ≥ 64 canais no SE,25-28 contendo 91 estudos primários. Desses, 13 artigos atenderam aos critérios de inclusão, sendo, portanto, incluídos na análise qualitativa. Devido à falta de dados quantitativos, apenas 10 estudos foram usados na meta-análise. As principais causas de exclusão dos estudos primários foram: não realização no SE; duplicação de estudos; e ATCC com 4 ou 16 canais. A Figura 1 mostra o fluxograma de exclusão do estudo.

Fluxograma descrevendo o processo de inclusão no estudo. RS: revisões sistemáticas; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analysis.

Um total de 4831 pacientes foram incluídos (idade média, 54 ± 6 anos; 51% eram do sexo masculino), dos quais 46% tinham hipertensão, 32% dislipidemia, 13% diabetes e 26% história familiar de DAC prematura. A Tabela 1 apresenta os estudos primários incluídos e suas características clínicas. Em geral, pacientes com fibrilação atrial, arritmias ventriculares, alterações enzimáticas, insuficiência renal, instabilidade hemodinâmica, alergia a contraste, e grávidas foram excluídos dos estudos.

Estudos primários incluídos e suas características clínicas
Autores Tipo de estudo Ano Tipo de ATCC (canais) Centros Pacientes (N) Idade (média ± DP) Homens (%) IMC, (kg/m2± DP) HTNN (%) HLN (%) DMN (%) HF de DAC prematura N (%) TabagismoN (%)
Goldstein et al. 12 ECR 2007 64 Unicêntrico 197 50 ± 12 50 29 ± 5 75/38 70(36) 20(10) 82(42) 35(18)
CT-STAT 13 ECR 2011 64 a 320 Multicêntrico 699 50 ± 10 46 28 ± 5 259/37 234(33) 48(7) 212(30) 157(22)
ACRIN-PA 14 ECR 2012 ≥64 Multicêntrico 1370 49 ± 9 47 - 695/51 367(27) 194(14) 394(29) 447(33)
ROMICAT II 15 ECR 2011 64 Unicêntrico 1000 54 ± 8 53 29 ± 5 541/54 454(45) 173(17) 271(27) 492(49)
Rubinstein et al. 16 Coorte 2007 64 Unicêntrico 58 56 ± 10 64 - 33/57 32(55) 12(21 9(16) 22(38)
Gallagher et al. 17 Coorte 2007 64 Unicêntrico 85 49 ± 11 53 - 31(36,5) 23(27) 8(9) 50(59) 22(25,9)
Hollander et al. 18 Coorte 2009 64 Unicêntrico 568 47 ± 9 44 - 251(44) 108(19) 77(14) 104(18) 200(35)
Ueno et al. 19 Coorte 2009 64 Unicêntrico 36 66 ± 12 53 - 17(47) 19(53) 9(25) 8(22) 13(36)
Hoffmann et al. 20 Coorte 2009 64 Multicêntrico 368 53 ± 12 61 29 ± 6 145(39) 135(37) 40(11) 180(49)
Johnson et al. 21 Coorte 2007 64 Unicêntrico 55 67 ± 10 64 - - - - - -
Johnson et al. 22 Coorte 2008 64 Unicêntrico 109 63 ± 14 72 - - - - - -
Takakuwa et al. 23 Coorte 2008 64 Unicêntrico 197 49 ± 11 72 - 92(46,7) 53(26,9) 29(15) 62(31) 62(31,5)
Hansen et al. 24 Coorte 2010 64 Unicêntrico 89 56 ± 9 63 - 35(39) 37(42) 7(8) 29(33) 39(44)

ATCC: angiotomografia computadorizada de artérias coronárias; DP: desvio-padrão; IMC: índice de massa corporal; HTN: hipertensão; HL: hiperlipidemia; DM: diabetes mellitus; HF: história familiar; DAC: doença arterial coronariana; ECR: ensaio clínico randomizado.

Os estudos foram conduzidos em pacientes de risco baixo e intermediário para DAC (exceto o de Ueno et al.,19 que incluiu pacientes de alto risco) com enzimas cardíacas normais e sem isquemia no ECG inicial.

Na meta-análise, 9 estudos definiram ATCC positiva quando havia lesões luminais ≥ 50%, enquanto 1 estudo definiu ATCC positiva quando havia lesão luminal ≥ 70%. Foram incluídos 1655 pacientes. As Tabelas 2 e 3 mostram a estatística descritiva para o desempenho do teste diagnóstico (ATCC). O estudo de Rubinstein et al.16 relatou a mais alta sensibilidade (S = 98%), enquanto o de Johnson et al.,22 a mais alta especificidade (E = 100%). O maior estudo, incluindo 568 pacientes, foi realizado por Hollander et al.,18 que reportou sensibilidade de 94% e especificidade de 92%.

Características de desempenho do exame de ATCC nos estudos incluídos
Ano Autores N VP FN FP VN S IC95% E IC95%
2007 Goldstein et al.12 99 8 0 24 67 0,94 0,63 - 0,99 0,73 0,64 - 0,81
2007 Rubinstein et al.16 58 20 0 3 35 0,98 0,81 - 1,00 0,91 0,78 - 0,97
2007 Gallagher et al.17 85 6 1 3 72 0,81 0,47 - 0,96 0,95 0,88 - 0,98
2009 Hollander et al.18 568 7 0 47 508 0,94 0,60 - 0,99 0,92 0,89 - 0,94
2009 Ueno et al.19 36 11 1 4 20 0,89 0,62 - 0,97 0,82 0,63 - 0,92
2009 Hoffmann et al.20 368 24 7 44 293 0,77 0,60 - 0,88 0,87 0,83 - 0,90
2007 Johnson et al.21 55 16 1 3 35 0,92 0,71 - 0,98 0,91 0,78 - 0,97
2008 Johnson et al.22 109 13 0 0 96 0,96 0,73 - 1,00 1,00 0,95 - 1,00
2008 Takakuwa et al.23 197 6 1 16 174 0,81 0,47 - 0,96 0,91 0,87 - 0,95
2010 Hansen et al.24 89 3 0 1 85 0,88 0,40 - 0,99 0,98 0,93 - 1,00

ATCC: angiotomografia computadorizada de artérias coronárias; VP: verdadeiro positivo; FN: falso negativo; FP: falso positivo; VN: verdadeiro negativo; S: sensibilidade; IC: intervalo de confiança; E: especificidade.

 Análise descritiva da razão de verossimilhança
Ano Autores LR+ Mínima Máxima LR- Mínima Máxima
2007 Goldstein et al.12 3,546 2,439 5,157 0,076 0,005 1,123
2007 Rubinstein et al.16 10,878 3,995 29,620 0,026 0,002 0,405
2007 Gallagher et al.17 17,643 6,015 51,746 0,197 0,046 0,832
2009 Hollander et al.18 10,974 7,925 15,196 0,068 0,005 1,001
2009 Ueno et al.19 4,915 2,081 11,607 0,141 0,031 0,641
2009 Hoffmann et al.20 5,815 4,163 8,123 0,270 0,144 0,506
2007 Johnson et al.21 10,214 3,723 28,022 0,092 0,020 0,425
2008 Johnson et al.22 187,071 11,763 2974,950 0,036 0,002 0,546
2008 Takakuwa et al.23 9,405 5,325 16,611 0,205 0,048 0,869
2010 Hansen et al.24 50,750 9,952 258,792 0,127 0,010 1,700

LR+: razão de verossimilhança positiva; LR-: razão de verossimilhança negativa.

Todos os estudos mostraram alta razão de verossimilhança positiva (a maior, no estudo de Johnson et al.22), e baixa razão de verossimilhança negativa (a mais baixa, no estudo de Rubinstein et al.16).

Para avaliar o efeito de diferentes pontos de corte para obstrução luminal "significativa" na análise, realizamos análises de limiar de diagnóstico. Encontramos coeficiente de correlação de Spearman de 0,045, p > 0,05 (IC95%: -0,602 - 0,656), indicando correlação muito fraca ou não significativa.

O teste de igualdade mostrou homogeneidade nos estudos para sensibilidade [χ2 = 8,4 (df = 9), p = 0,5] e heterogeneidade nos estudos para especificidade [χ2 = 55,5 (df = 9), p < 0,001], o que foi confirmado com "forest plot" (Figuras 2 e 3).

Forest plot para sensibilidade (S) de ATCC para diagnosticar síndrome coronariana aguda.

Forest plot para especificidade (E) de ATCC para diagnosticar síndrome coronariana aguda.

A análise univariada mostrou homogeneidade de DOR [Q = 8,5 (df = 9), p = 0,48 e I2 = 0%]. A Figura 4 mostra a estimativa da síntese.

Forest plot para odds ratio diagnóstico (DOR).

O teste do χ2 não rejeitou a hipótese de homogeneidade para o modelo [χ2 = 10,14 (df = 1), p = 0,34, θ (teta) = 0,018 (IC95%: 0,0014-0,0246)], portanto, optamos pelo modelo de efeitos fixos. A área sob a curva (AUC) foi 0,982 (IC95%: 0,967-0,999).

Houve grande variabilidade nos eventos de desfecho entre os estudos. A Tabela 4 apresenta um resumo dos eventos compostos em todos os estudos, com suas características específicas. Na maioria dos estudos, os eventos investigados foram morte, IM, CRM e ACI. Alguns avaliaram o diagnóstico de SCA, sendo que três estudos usaram a técnica de 'triple rule-out', além de investigarem DAC, embolia pulmonar e dissecção aórtica.

Desfechos clínicos dos estudos individuais
Autor Ano Tipo de estudo Número de pacientes Idade(média ± DP) Masculino % Risco de DAC Seguimento (meses) Desfechos
Goldstein et al.12 2007 ECR 99 50 ± 12 50 Muito baixo 6 CRM e ACI
CT-STAT13 2011 ECR 361 50 ± 10 46 Baixo 6 CRM e ACI
ACRIN-PA14 2012 ECR 908 49 ± 09 47 Baixo e intermediário 1 IM, CRM e ACI
ROMICAT II15 2011 ECR 501 56 ± 10 53 Baixo e intermediário 1 IM, ACI e PCI
Rubinstein et al.16 2007 Coorte prospectiva 58 54 ± 8.0 64 Intermediário 15 IM, morte, CRM
Gallagher et al.17 2007 Coorte prospectiva 85 49 ± 11 53 Baixo 1 Diagnóstico de SCA
Hollander et al.18 2009 Coorte observacional 568 47 ± 8.9 44 Baixo 1 Ausência de morte e IM
Ueno et al.19 2009 Coorte prospectiva 36 66 ± 12 53 Alto 1 -
Hoffmann et al.20 2009 Coorte observacional 368 52.7 ± 12 61 Baixo e intermediário 6 Dor torácica, API, readmissão
Johnson et al.21 2007 Coorte prospectiva 55 67 ± 10 64 Baixo e intermediário ≥ 5 Foco em testes adicionais e nefropatia induzida por contraste
Johnson et al.22 2008 Coorte prospectiva 109 63 ± 14 71 Baixo e intermediário 6 Arritmia; derrame pleural (pleurite); readmissão
Takakuwa et al.23 2008 Coorte prospectiva 197 49 ± 11 72 Baixo e intermediário 1 Nenhum evento (ou não especificou os eventos)
Hansen et al.24 2010 Coorte prospectiva 89 56,3 ± 8,6 63 Baixo e intermediário 12 Nenhum evento (morte e IM)

DP: desvio-padrão; DAC: doença arterial coronariana; ECR: ensaio clínico randomizado; CRM: cirurgia de revascularização miocárdica; ACI: angiografia coronariana invasiva; IM: infarto do miocárdio; ICP: ntervenção coronariana percutânea; SCA: síndrome coronariana aguda; API: angina pectoris instável.

A Figura 7 mostra os principais eventos, que foram: 29 (0,6%) IM, 92 (1,9%) CRM e 312 (6,4%) ACI. Não houve morte. O diagnóstico de SCA ocorreu em 7,3% dos 1655 pacientes incluídos na meta-análise.

Curva SROC com θ (teta) estimado e intervalo de confiança.

Curva SROC para ATCC ≥ 64 canais.

Eventos no seguimento. IM: infarto do miocárdio; CRM: cirurgia de revascularização miocárdica; ACI: angiografia coronariana invasiva.

Embora analisados de maneira heterogênea, os quatro ensaios clínicos randomizados também avaliaram o tempo de permanência hospitalar e os custos. Em comparação ao cuidado padrão, o uso de ATCC reduziu o tempo de permanência hospitalar em todos os estudos, e, em três deles, também os custos.

 Discussão

Este estudo teve por objetivo avaliar o valor diagnóstico e prognóstico da ATCC na avaliação da dor torácica aguda no SE. Incluímos 4 RS, num total de 13 estudos. Após análise primária dos critérios de exclusão, usamos 10 estudos para análise quantitativa (meta-análise).

Descobrimos que a ATCC apresentou altas sensibilidade e especificidade para detecção de DAC em pacientes com dor torácica no SE em todos os estudos, assim como alta razão de verossimilhança positiva e baixa razão de verossimilhança negativa. A distribuição da sensibilidade foi homogênea, mas a da especificidade foi heterogênea. Observamos fraca correlação nos efeitos dos diferentes pontos de corte para diagnóstico de obstrução luminal significativa. O DOR foi homogêneo e significativo. Houve variabilidade no número e tipo de eventos entre os estudos. Os ensaios clínicos relataram redução dos custos e do tempo de permanência hospitalar.

A qualidade da imagem cardíaca na ATCC acha-se diretamente relacionada à evolução da tomografia. Os avanços técnicos atuais dos scanners e software de tomografia destinam-se a aprimorar a resolução espacial e temporal das imagens de tomografia computadorizada cardíaca, assim como a reduzir a dose de radiação recebida em um exame típico. Incluem faixas de detecção mais amplas, que permitem a aquisição simultânea de um maior número de cortes de imagem, rotação mais rápida do tubo de raio x, e aplicação de técnicas alternativas de reconstrução de imagem.29 Seu uso em pacientes com biomarcadores precoces e ECG negativo para isquemia miocárdica já está incluído no algoritmo de avaliação de dor torácica em vários centros de emergência, uma estratégia que encontra suporte nos atuais Critérios de Uso Adequado da Tomografia Cardíaca Computadorizada30 e na Atualização Focada das Diretrizes para Manejo de Pacientes Com Angina Instável/Infarto do Miocárdio Sem Elevação do Segmento ST.31

A ATCC tem a capacidade única de representar de maneira não invasiva a anatomia das coronárias, permitindo não apenas a visualização da luz arterial para detectar estenose ou oclusão grave responsável por isquemia miocárdica, mas ainda a avaliação da parede das artérias coronárias, demonstrando a presença ou ausência de DAC e as características da placa (pode identificar preditores de ruptura da placa).32 Pode auxiliar no diagnóstico diferencial de doenças, como embolia pulmonar e aneurisma aórtico.33

A ATCC permite a identificação de DAC não obstrutiva em pacientes com dor torácica aguda, aprimorando substancialmente o manejo terapêutico nesse grupo de pacientes ao permitir uma decisão clínica prévia, de modo a obter um tratamento mais efetivo.34

Ante a epidemiologia da dor torácica no SE, a avaliação desses pacientes é um grande desafio, tanto do ponto de vista de diagnóstico e otimização do tempo (começar tratamento ou dar alta) quanto do correto direcionamento dos recursos. O uso de biomarcadores séricos não permite uma rápida exclusão de isquemia miocárdica, resultando em alta precoce do SE. Portanto, as ferramentas disponíveis para uma rápida triagem dos pacientes com dor torácica são limitadas. Considerando isso, os quatro ensaios clínicos randomizados12-15 investigaram o tempo de permanência hospitalar e concluíram que o uso de ATCC no SE em pacientes de risco baixo e intermediário de DAC reduz a permanência hospitalar.

Shreibati et al.35 descobriram em uma coorte observacional (2005-2008) aumento dos custos e da incidência de cateterismo cardíaco usando ATCC. Três dos quatro ensaios clínicos randomizados12,13,15 mostraram redução nos custos hospitalares. Entretanto, a avaliação do impacto de novas tecnologias nos custos de saúde requer o uso de metodologia específica que permite análise de custo-efetividade.

Houve aumento de ACI no grupo submetido a ATCC em comparação àquele submetido a monitoração padrão, mas o desenho dos estudos não forneceu dados para se avaliar a existência de uso excessivo de ACI no grupo submetido a ATCC ou subutilização no grupo não submetido a ATCC. No Registro CONFIRM,36 durante seguimento, as taxas de ACI foram baixas em pacientes sem DAC ou com DAC leve segundo a ATCC, revelando que, na prática clínica, os médicos estão aceitando os resultados da ATCC, sendo, nesse caso, alto o valor preditivo negativo.

A taxa de eventos cardíacos maiores nos pacientes dos estudos foi muito baixa, concluindo-se que têm excelente prognóstico. Entretanto, os dados são insuficientes para determinar se o uso de ATCC, em comparação ao cuidado padrão, conferiu algum benefício quanto à redução na taxa de eventos cardíacos maiores (morte e IM).

A prevalência global de DAC na maioria dos estudos foi baixa; portanto, os dados não podem ser extrapolados para pacientes de alto risco. Mais estudos são necessários para detectar diferenças nos desfechos clínicos, considerando-se a natureza dessa população de baixo risco. A avaliação dos pacientes no SE não mostrou um padrão fixo entre os estudos; ao contrário, houve grande variação no comportamento. Na maioria dos estudos, o médico assistente decidiu o 'passo' seguinte na avaliação, mesmo para ensaios clínicos randomizados.

Para a exclusão de SCA em pacientes com oclusões coronarianas conhecidas, a ATCC seria menos útil como exame de triagem, pois a identificação de obstrução coronariana em pacientes com DAC conhecida não explica a etiologia da dor torácica.

Limitações

Uma dificuldade encontrada foi a heterogeneidade dos estudos publicados realizados no SE. Houve deficiência de padronização nos métodos de avaliação e grandes diferenças no seguimento e nas medidas de desfecho.

Até mesmo com um total de 4831 pacientes, o "poder" de detecção de diferenças nos eventos clínicos, como IM e morte, ainda é baixo, pois são raros nesse grupo de pacientes.

Todos os estudos podem apresentar viés de verificação, por ser impossível "cegar" a conduta (ATCC ou cuidado padrão) para médicos e pacientes.

A metodologia usada nos estudos de acurácia diagnóstica é bem diferente daquela dos estudos terapêuticos/intervencionais, tendo sido substancialmente desenvolvida nas décadas recentes.37

Conclusões

O uso de ATCC como ferramenta de estratificação de pacientes com risco cardiovascular baixo e intermediário, que se apresentam no SE com dor torácica, tem alta acurácia e segurança, reduz o tempo de permanência hospitalar e provavelmente os custos, produzindo diagnóstico precoce e uma tomada de decisão mais efetiva. Para avaliar o valor da ATCC na prevenção de eventos futuros, estudos com desenho mais apropriado e seguimento mais longo são necessários.

Fontes de Financiamento

O presente estudo não teve fontes de financiamento externas.

Vinculação Acadêmica

Este artigo é parte de tese de Doutorado de Carlos José Oliveira de Matos pela Universidade Federal de Sergipe.

Aprovação Ética e consentimento informado

Este artigo não contém estudos com humanos ou animais realizados por nenhum dos autores.

No artigo “Visão Geral com Meta-Análise de Revisões Sistemáticas sobre o Valor Diagnóstico e Prognóstico da Angiotomografia de Coronárias na Emergência” dos autores Irlaneide da Silva Tavares, Carlos José Oliveira de Matos, Marco Antonio Prado Nunes, Antonio Carlos Sobral Sousa, Divaldo Pereira de Lyra Júnior, Joselina Luzia Menezes Oliveira, retirar a instituição Centro de Ensino e Pesquisa e Laboratório de Ecocardiografia (ECOLAB) do Hospital e Fundação São Lucas2 e considerar correta a instituição Rede e Hospital Primavera - Centro de Imagem2 – Aracaju, SE - Brasil.