Diagnostic Performance of Coronary Tomography Angiography and Serial Measurements of Sensitive Cardiac Troponin in Patients With Chest Pain and Intermediate Risk for Cardiovascular Events

Abstract

Background

Coronary tomography angiography (CTA) has been mainly used for chest pain evaluation in low-risk patients, and few data exist regarding patients at intermediate risk.

Objective

To evaluate the performance of serial measures of sensitive troponin and CTA in intermediate-risk patients.

Methods

A total of 100 patients with chest pain, TIMI risk scores of 3 or 4, and negative troponin were prospectively included. All patients underwent CTA and those with coronary stenosis ≥ 50% were referred to invasive coronary angiography. Patients with coronary lesions <50% were discharged and contacted 30 days later by a telephone call to assess clinical outcomes. Outcomes were hospitalization, death, and myocardial infarction at 30 days. The comparison between methods was performed by Kappa agreement test. The performance of troponin measures and CTA for detecting significant coronary lesions and clinical outcomes was calculated. Results were considered statistically significant when p < 0.05.

Results

Coronary stenosis ≥ 50% on CTA was found in 38% of patients and significant coronary lesions on coronary angiography were found in 31 patients. Two clinical events were observed. Kappa agreement analysis showed low agreement between troponin measures and CTA in the detection of significant coronary lesions (kappa = 0.022, p = 0.78). The performance of CTA for detecting significant coronary lesions on coronary angiography or for predicting clinical events at 30 days was better than sensitive troponin measures (accuracy of 91% versus 60%).

Conclusion

CTA performed better than sensitive troponin measures in the detection of significant coronary disease in patients with chest pain and intermediate risk for cardiovascular events.

Cardiovascular Diseases; Risk Factors; Risk Management; Chest Pain; Tomography, X-Ray Computed/methods; Troponin T; Troponin I; Angiotomography Coronary/methods

Resumo

Fundamento

A angiotomografia coronária (ATC) tem sido usada para avaliação de dor torácica principalmente em pacientes de baixo risco, e poucos dados existem com pacientes em risco intermediário.

Objetivo

Avaliar o desempenho de medidas seriadas de troponinas sensíveis e de ATC em pacientes de risco intermediário.

Métodos

Um total de 100 pacientes com dor torácica, TIMI score 3 ou 4 e troponina negativa foram prospectivamente incluídos. Todos os pacientes foram submetidos à ATC, e aqueles com obstruções ≥ 50% foram encaminhados à cineangiocoronariografia. Pacientes com lesões < 50% recebiam alta hospitalar, receberam alta e foram contatados 30 dias depois por telefonema para avaliação dos desfechos clínicos. Os desfechos foram hospitalização, morte, e infarto agudo do miocárdio em 30 dias. A comparação entre os métodos foi realizada pelo teste de concordância kappa. O desempenho das medidas de troponina e da ATC na detecção de lesões coronárias significativas e desfechos clínicos foi calculado. Os resultados foram considerados estatisticamente significativos quando p <0,05.

Resultados

Estenose coronária ≥ 50% na ATC foi encontrada em 38% dos pacientes e lesões coronárias significativas na angiografia coronária foram encontradas em 31 pacientes. Dois eventos clínicos foram observados. A análise de concordância Kappa mostrou baixa concordância entre as medidas de troponina e ATC na detecção de lesões coronárias significativas (kappa = 0,022, p = 0,78). O desempenho da ATC para detectar lesões coronárias significativas na angiografia coronária ou para prever eventos clínicos em 30 dias foi melhor que as medidas de troponina sensível (acurácia de 91% versus 60%).

Conclusão

ATC teve melhor desempenho que as medidas seriadas de troponina na detecção de doença coronariana significativa em pacientes com dor torácica e risco intermediário para eventos cardiovasculares.

Doenças Cardiovasculares; Fatores de Risco; Controle de Riscos; Dor no Peito; Tomografia Computadorizada por Imagem Raios X/métodos; Troponina T; Troponina I; Angiotomografia Coronária/métodos

Introduction

Chest pain is one of the most common complaints in emergency rooms worldwide. Great advances in clinical practice have been achieved with the use of coronary tomography angiography (CTA) and high-sensitivity troponin in the diagnosis of acute coronary syndrome (ACS).¹ - ⁴

Sensitive and high-sensitivity troponin T and I assays have detection thresholds for myocardial injury 10 to 100 times lower than conventional troponins. These assays have better accuracy for the diagnosis of ACS, particularly in patients with short-term chest pain. Most studies evaluating the accuracy of repeated troponin measures in ruling out ACS included patients with low risk for cardiovascular events as assessed by the TIMI (thrombolysis in myocardial infarction), HEART or GRACE risk scores.⁵ , ⁶

The anatomic evaluation of the coronary tree using CTA has a special role in the exclusion of ACS in patients at low-to-intermediate risk for coronary artery disease. CTA findings correlated well with invasive coronary angiography in a study that included 230 patients with chest pain. High sensitivity and specificity, and negative predictive values were seen when lesions greater than 50% were found in CTA. In the ROMICAT-II trial, the CTA strategy was as safe as the usual care strategy with respect to major cardiovascular events at 28 days. Therefore, CTA is an accurate non-invasive method for detecting ACS in patients with acute chest pain. However, its validation was mainly done in patients with low-risk profiles.⁷ The present study aims to evaluate the performance of sensitive troponin assays and CTA in the detection of significant coronary lesions on coronary angiography and clinical events in patients with chest pain and intermediate risk for cardiovascular events.

Methods

Study Patients

The study design is presented in Figure 1 . We prospectively included a total of 100 patients presenting with chest pain at the Emergency Department of the Heart Institute, InCor, University of Sao Paulo Medical School, Sao Paulo, Brazil. To be included, patients had to be aged between 40 and 75 years old, present with chest pain for at least two hours before arrival and have a TIMI risk score of 3 or 4. Additionally, a new or probable new deviation of ST of at least 0.5 mV and/or T wave inversion of at least 0.2 mV should not be present on the electrocardiogram, and their first measure of sensitive troponin should be < 99 percentile for trial inclusion. Exclusion criteria comprised: pregnancy, hemodynamic instability, serum creatinine > 1.5 mg/dL, intolerance to beta-blockers, allergy to iodine contrast, asthma, thoracic trauma in the previous 30 days, body mass index > 40 kg/m2, previous coronary artery bypass graft surgery, and known coronary lesion > 50%. Our Institutional Review Board for human subject studies approved this study, and all participants provided written informed consent prior to enrolment. There is no conflict of interest of any author.

Figure 1
– Study design and flowchart; CABG: coronary artery bypass grafting.

Sensitive troponin assay

Blood samples were drawn for sensitive troponin I measurement at two time points: at presentation and three hours later. The investigators were blinded to the second measurement until the end of the study period. Quantitative determination of troponin I was made by a sandwich-type immunoassay performed in three stages that uses direct chemiluminescence technology and constant quantities of two monoclonal antibodies. A reagent was added for detection of non-specific bindings. The commercial kit ADVIA Centaur^®TnI-Ultra (Siemens Healthcare Diagnostics, Tarrytown, NY, USA) was used for this in an automated equipment of the same brand. The 99th percentile value was 0.04 ng/ml. Sensitive troponin assays was donated by Siemens Healthcare Diagnostics.

Coronary tomography angiography

After trial inclusion, all patients underwent CTA. CTA images were acquired using a 320 detector-row scanner (Aquilion ONE, Canon Medical Systems, Japan) and a standard scanning protocol. To reach a heart rate lower than 65 bpm during acquisition, patients received oral metoprolol (50-100 mg).

Study outcomes

Two subgroups were studied: a) patients who underwent coronary angiography when CTA showed coronary stenosis ≥ 50%; and b) patients whose CTA showed no lesions or lesions < 50% and were discharged and contacted 30 days later by a telephone call to assess clinical outcomes. Coronary lesions > 70% at coronary angiography were considered significant. Clinical outcomes of interest were hospitalization, death and myocardial infarction.

Statistical analysis

Data were analyzed with the SAS Statview 5.0 software. Descriptive analysis of baseline characteristics was performed using means and standard deviations when a normal distribution of data was assumed, and median and interquartile intervals were used in non-normal distribution. The Kolmogorov-Smirnov test was used to assess the normality of distribution of continuous variables. Comparison of the time from patient arrival to the second troponin test versus time from patient arrival to CTA was made using the unpaired T-test.

The comparison between diagnostic methods was performed through Kappa agreement analysis. We compared the agreement between troponin measures and significant coronary lesions on coronary angiography or clinical outcomes. The results were considered statistically significant when p < 0.05. We calculated the sensitivity, specificity, positive predictive values, negative predictive values and accuracy of sensitive troponin or CTA in the detection of significant coronary lesions in coronary angiography or clinical events in the whole population (N=100). We also calculated the performance of troponin measures in the detection of significant coronary lesions in the subpopulation who underwent coronary angiography (N=38). Performance was calculated using as positivity a second troponin result above the 99th percentile and the percentage variation of the method in relation to the first measurement, identifying the best cutoff point by the ROC curve. Complementary analysis was made by calculating the area under the ROC curve and the cut-off score of troponin percentage increase and significant coronary lesions determined by coronary angiography and clinical events or by coronary angiography alone.

Based on an alpha error of 0.05 and using a power of 0.8 for primary outcomes, the number of individuals needed for this study was at least 71 according to previous studies, considering the incidence of coronary lesions with stenosis greater than or equal to 50% in patients at intermediate risk (TIMI risk), use of CTA in around 24% of patients,⁸ and diagnosis of ACS by the use of sensitive troponin in 11.4% of patients undergoing chest pain protocols.⁶ These data were used to evaluate the hypothesis of an existing difference in performance between these methods.

Results

Study population

A total of 100 patients with acute chest pain and TIMI risk scores of 3 or 4 were consecutively included. Clinical characteristics are presented in Table 1 . Inclusion and follow-up of patients were performed between April 2016 and March 2019 when the previously estimated sample size was reached. Overall, mean age was 62.9 ± 10.5 years and 58% were female. Most of the study population (81%) had a TIMI risk score of 3. Sensitive troponin variations of 20% were observed in 29 patients. Coronary stenosis ≥ 50% on CTA was found in 38% of patients (≥ 70% in 25 patients), and all of them underwent coronary angiography. Significant coronary lesions at coronary angiography were found in 31 patients.

Table 1
– Baseline characteristics of study patients (n=100)

Demographic characteristics
Age (years)	62.9 (± 10.5)
Male sex	42 (42%)
Comorbidities/risk factors
Hypertension	87 (87%)
Diabetes	49 (49%)
Dyslipidemia	79 (79%)
Previous stroke/TIA	5 (5%)
Previous acute MI	18 (18%)
Previous PCI	16 (16%)
Smoking (current or previous)	52 (52%)
Family history of CAD	44 (44%)
Clinical presentation
Systolic blood pressure (mmHg)	144.9 (± 23.7)
Heart rate (bpm)	71.9 (± 13.0)
TIMI risk 3	81 (81%)
TIMI risk 4	19 (19%)
Laboratory results
Hemoglobin (g/dL)	13.8 (± 1.5)
Creatinine (mg/dL)	0.92 (± 0.3)

• CAD: coronary artery disease; MI: myocardial infarction; PCI: percutaneous coronary intervention; SD: standard deviation; TIA: transient ischemic attack; TIMI: thrombolysis in myocardial infarction.

Clinical Events

All patients were alive at 30 days. In patients discharged without coronary angiography, two new hospitalizations were observed at 30 days. There were no observed deaths or myocardial infarctions in the follow-up.

Agreement analysis in the overall population

Agreement between sensitive troponin and CTA findings

This analysis included all patients of the study (N=100). The kappa agreement test showed a slight agreement between the second measure of positive troponin and CTA in the detection of significant coronary lesions (kappa = 0.022, p = 0.78). The time between patient arrival and the result of the second troponin was 312.08 ± 82.39 minutes versus 256.70 ± 83.91 minutes between patient arrival and CTA (p < 0.0001). The mean time between CTA to discharge was 6,837.10 ± 8,068.17 minutes, and all patients were submitted to coronary angiography in the first 24 hours of admission. Five patients showed a positive troponin result in the second measurement but were discharged as they did not present significant lesions on CTA.

Agreement between sensitive troponin variations and the presence of significant coronary lesions at coronary angiography or the occurrence of clinical events

Using the presence of significant coronary lesions at coronary angiography or the occurrence of clinical events at 30 days as the gold standard, the Kappa agreement test with a positive troponin result in the second measurement showed a slight agreement (kappa = 0.002, p = 0.979). The best cut-off for troponin variation from baseline to the second measure regarding the presence of significant coronary lesions on coronary angiography or the occurrence of clinical events at 30 days was 20%. The area under the ROC curve for the 20% variation in sensitive troponin was 0.508 (CI 95%: 0.386 – 0.629) ( Figure 2 ).

Figure 2
– ROC curve for 20% variation in sensitive troponin and detection of (A) significant coronary lesions at coronary angiography and the occurrence of clinical events and (B) significant coronary lesions at coronary angiography only. AUC: area under curve; CI: confidence interval

Performance of sensitive troponin measures or coronary lesions ≥ 50% on CTA in the detection of significant coronary lesions on coronary angiography or the occurrence of clinical events

The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of a) a positive troponin result in the second measure; b) troponin variations of 20%; and c) coronary lesions ≥ 50% on CTA for detection of lesions ≥ 70% on coronary angiography or for prediction of clinical events at 30 days are presented in Table 2 . The overall performance of CTA for detecting the composed outcome was better than troponin measures.

Table 2
– Performance of the second measure of positive troponin, troponin variation of 20%, and coronary lesions ≥ 50% at computed tomography angiography in detecting lesions ≥ 70% at coronary angiography or to predict clinical events at 30 days

	Sensitivity	Specificity	Positive predictive value	Negative predictive value	Accuracy
Second positive troponin result	12.1%	88.1%%	33.3%	67.0%	63.0%
Troponin variation ≥ 20%	33.3%	73.1%	37.9%	69.0%	60.0%
Coronary lesions ≥ 50% at CTA	93.9%	89.6%	81.6%	96.8%	91.0%

• CTA: computed tomography angiography.

Agreement analysis in patients who underwent coronary angiography

Agreement between sensitive troponin variations and the presence of significant coronary lesions on coronary angiography

This analysis included only patients who underwent coronary angiography (N=38). Using the presence of significant coronary lesions on coronary angiography as the gold standard, the Kappa agreement test with a positive troponin result in the second measure showed slight agreement (kappa = 0.006, p = 0.922). The best cut-off for troponin variation regarding the presence of significant coronary lesions on coronary angiography was 20%. Area under ROC curve for the 20% variation in sensitive troponin was 0.465 (CI 95%: 0.230 – 0.701) ( Figure 2 ).

Performance of sensitive troponin measures in the detection of significant coronary lesions on coronary angiography

The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of a) a positive troponin result in the second measure, and b) troponin variations of 20% in the detection of lesions ≥ 70% at coronary angiography are presented in Table 3 .z Significant coronary lesions were detected by coronary angiography in 81.6% of patients with lesions ≥ 50% on CTA. This proportion was higher than the one for positive troponin in the second measure or its variations. High specificities were found for a positive troponin result in the second measure and troponin variations of 20% - 85.7% and 71.4%, respectively.

Table 3
– Performance of the second positive troponin result or troponin variation of 20% in detecting lesions ≥ 70% on coronary angiography

	Sensitivity	Specificity	Positive predictive value	Negative predictive value	Accuracy
Second measure of positive troponin	12.9%	85.7%%	80%	18.2%	26.3%
Troponin variation ≥ 20%	32.3%	71.4%	83.3%	19.2%	39.5%

Discussion

Our study presents the performance of sensitive troponin measures or CTA in the detection of significant coronary lesions on coronary angiography and/or clinical events in patients with chest pain and intermediate risk for cardiovascular events. Sensitive troponin measures agreed poorly with the detection of significant coronary lesions on CTA or coronary angiography and with the occurrence of clinical events. CTA was superior to the measure of serial troponin, with better sensitivity and negative predictive value in the detection of coronary artery disease. In clinical practice, patients with acute chest pain are often discharged from the hospital according to chest pain protocols based only on the serial measurement of troponins. Our findings suggest that intermediate risk patients without ischemic alterations on the electrocardiogram should preferably be stratified at admission by CTA. This strategy may reduce the chance of erroneous hospital discharge in these situations. We emphasize the fact that the assessment of clinical events becomes secondary in this context due to the sample size, and hence the agreement with the diagnosis of coronary heart disease was the most relevant finding.

It is not uncommon that patients with chest pain are released from emergency rooms after initial evaluation and develop ischemic events in the following hours. These individuals do not receive an adequate treatment at the appropriate time.³ , ⁹ It is estimated that one in eight patients with unstable angina will suffer an acute myocardial infarction (AMI) in the next two weeks. Mortality in patients with AMI admitted or mistakenly released from the emergence departments ranges from 6% to 25%,³ which leads to lawsuits related to medical malpractice.⁴ The incidence of adverse outcomes in patients with TIMI risk score of 3 and 4 can reach up to 11.1%.¹⁰ , ¹¹ However, studies exploring diagnostic strategies for chest pain evaluation in this specific population are scarce and come mostly from secondary analyses.

In 2006, Morris et al.⁸ conducted a study including 1,000 consecutive patients with acute chest pain to explore whether the use of TIMI risk score could help predict combined events at 30 days in this population. The AUC was 0.79 (CI 95%: 0.75 - 0.84), which showed a good applicability of the score. Since then, studies have suggested that patients with intermediate scores (3 and 4) should have troponin measured and a provocative ischemic test performed, when possible.⁸ , ¹² Our findings also suggest that it is important to better evaluate the presence of coronary heart disease in this population using a non-invasive test in addition to troponin measures.

Using two serial measurements of sensitive troponin with short time intervals is a good approach to rule out acute coronary syndromes in low-risk patients, which allows the implementation of rapid chest pain assessment protocols.⁵ , ⁶ , ¹³ , ¹⁴ - ³¹ A study on patients with suspected ACS showed that a 20% increase in high-sensitivity troponin levels were associated with greater probability of ACS, with an area under the ROC curve of 0.785. Other studies observed that variations in high-sensitivity troponin T over a few hours also had high negative predictive values.³² However, it is worth noting that the population included in most studies that showed a very high accuracy of ultrasensitive troponin had a low risk. The negative predictive value of a 20% variation in sensitive troponin in our study was 69%, an index below what the literature has shown, which may be justified by the inclusion of patients at intermediate risk.

In ROMICAT study, the use of CTA in addition to the TIMI risk score increased the accuracy for event prediction.³³ The ROMICAT-II study included 1000 patients with chest pain and first negative troponin result, who were randomized to perform CTA or follow the usual chest pain protocol.³⁴ During the 2-year follow-up including 333 patients, it was observed that CTA had high predictive power with an AUC of 0.61 for combined cardiovascular events. When associated with the TIMI score, the AUC reached 0.84. In this study, only 5.4% of patients had TIMI risk between 3 and 4.³⁵ , ³⁶ We believe our findings add to these results as we showed that, in intermediate risk patients, CTA performed better than serial measures of sensitive troponin.

When compared to traditional chest pain protocols, CTA does not alter outcomes such as death or AMI, however it reduces length of hospital stay and the number of unnecessary hospital admissions.⁵ , ⁷ , ³⁷ - ⁵⁶ Litt et al.⁷ showed that the use of CTA, compared with the traditional chest pain evaluation protocol, had an excellent safety profile in low-risk patients, as no death or AMI occurred at 30 days. Additionally, CTA promoted a higher number of hospital discharges (49.6% vs. 22.7%) and shorter hospital stay (18 hours vs. 24.8 hours, p < 0.001). The agreement between CTA and cardiac catheterization findings also seems to be strong.⁴⁴ , ⁴⁵ In ROMICAT-II, hospital stay was 7.6 hours shorter in the CTA group compared to the usual care group. In our study, we also observed that the time interval between patient arrival and CTA was approximately one hour shorter than the time between patient arrival and the result of the second troponin.

Our results should be interpreted in light of some limitations. This was a single center study, with a relatively small sample size, and the number of clinical events was low. Therefore, larger studies should be performed to validate our findings. Intermediate risk patients were rarely represented in previous studies investigating strategies for chest pain evaluation. We believe our findings add to the existing literature and suggest that CTA may have an important role in ruling out acute coronary syndromes in this population.

Conclusions

CTA performed better than sensitive troponin measures in the detection of significant coronary disease in patients with chest pain and intermediate risk for cardiovascular events.

Referências

• ¹
  Czarnecki A, Chong A, Lee DS, Schull MJ, Tu JV, Lau C, et al. Association between physician follow-up and outcomes of care after chet pain assesment in high-risk patient. Circulation. 2013;127:1386-94.
• ²
  Cannon CP. Acute coronary syndromes: risk stratification and initial management. Cardiol Clin. 2005;23(4):401-9.
• ³
  Herren KR, Mackway-Jones K. Emergency management of cardiac chest pain: a review. Emerg Med J. 2001;18(1):6-10.
• ⁴
  Haasenritter J, Aerts M, Bosner S, Buntinx F, Burnand B, Herzig L, et al. Coronary heart disease in primary care: accuracy of medical history and physical findings in patients with chest pain – a study protocol for a systematic review with individual patient data. BMC Family Practice. 2012 Ago 9;13:81.
• ⁵
  Hamm CW, Bassand J, Agewall S, Bax J, Boersma E, Bueno H, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J.2011;32(23):2999–3054.
• ⁶
  Jaffe AS. Use of biomarkers in the emergency department and chest pain unit. Cardiol Clin.2005;23(4):453-65.
• ⁷
  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.
• ⁸
  Conway Morris A, Caesar D, Gray S, Gray A. TIMI risk score accurately risk stratifies patients with undifferentiated chest pain presenting to an emergency department. Heart. 2006 Sep;92(9):1333-4.
• ⁹
  Fernandez JB, Ezquerra EA, Genover XB, O’Callaghan AC, Gárriz II, Jimenez JJ, et al. Chest pain units. Organization and protocol for the diagnosis of acute coronary syndromes. Rev Esp Cardiol. 2002;55(2):143-54.
• ¹⁰
  Holly J, Fuller M, Hamilton D, Mallin M, Black K, Robbins R, et al. Prospective evaluation of the use of the thrombolysis in myocardial infarction score as a risk stratification tool for chest pain patients admitted to an ED observation unit. Am J Emerg Med. 2013 Jan;31(1):185-9.
• ¹¹
  Alderwish E, Schultz E, Kassam Z, Poon M, Coplan N. Evaluation of Acute Chest Pain: Evolving Paradigm of Coronary Risk Scores and Imaging. Rev Cardiovasc Med. 2019 Dec 30;20(4):231-44. doi: 10.31083/j.rcm.2019.04.589.
• ¹²
  Levsky JM, Haramati LB, Spevack DM, Menegus MA, Chen T, Mizrachi S, et al. Coronary Computed Tomography Angiography Versus Stress Echocardiography in Acute Chest Pain: A Randomized Controlled Trial. JACC Cardiovasc Imaging. 2018 Sep;11(9):1288-97. doi: 10.1016/j.jcmg.2018.03.024. Epub 2018 Jun 13.
• ¹³
  Cullen L, Mueller C, Parsonage WA, Wildi K, Greenslade JH, Twerenbold R, et al. Validation of high-sensitivity troponin I in a 2-hour diagnostic strategy to assess 30-day outcomes in emergency department patients with possible acute coronary syndrome. J Am Coll Cardiol. 2013 Oct 1;62(14):1242-9.
• ¹⁴
  Januzzi JL, Bamberg F, Lee H, Truong QA, Nichols JH, Karakas M, et al. High-sensitivity troponin T concentrations in acute chest pain patients evaluated with cardiac computed tomography. Circulation.2010;121(10):1227-34.
• ¹⁵
  Lippi G. Biomarkers of myocardial ischemia in the emergency room: cardiospecific troponin and beyond. Eur J of Intern Med.2013;24(2):97-9.
• ¹⁶
  Thygesen K, Mair J, Giannitsis E, Mueller C, Lindahl B, Blankenberg S, et al. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J.2012;21(18):1-7.
• ¹⁷
  Sonel A, Sasseen BM, Fineberg N, Bang N, Wilensky RL. Prospective study correlating fibrinopeptide A, troponin I, myoglobin and myosin light chain levels with early and late ischemic events in consecutive patients presenting to the emergency department with chest pain. Circulation.2000;102(10):1107-13.
• ¹⁸
  Dadkhah S, Sharain K, Sharain R, Kiabayan H, Foschi A, Zonta C, et al. The value of bedside cardiac multibiomarker assay in rapid and accurate diagnosis of acute coronay syndromes. Crit Pathways Cardiol.2007;6(2):76-84.
• ¹⁹
  Chan D, Ng LL. Biomarkers in acute myocardial infarction. BMC Med.2010;8:34.
• ²⁰
  Gravning J1, Smedsrud MK, Omland T, Eek C, Skulstad H, Aaberge L, et al. Sensitive troponin assays and N-terminal pro-B-type natriuretic peptide in acute coronary syndrome: prediction of significant coronary lesions and long-term prognosis. Am Heart J. 2013 May;165(5):716-24.
• ²¹
  Mohammed AA, Januzzi JL Jr. Clinical applications of highly sensitive troponin assays. Cardiol Rev. 2010 Jan-Feb;18(1):12-9.
• ²²
  Omland T. Sensitive cardiac troponin assays: sense and sensibility. Eur Heart J. 2012 Apr;33(8):944-6.
• ²³
  Meune C, Reichlin T, Irfan A, Schaub N, Twerenbold R, Meissner J, et al. How safe is the outpatient management of patients with acute chest pain and mildly increased cardiac troponin concentrations? Clin Chem. 2012 May;58(5):916-24.
• ²⁴
  Bohula May EA, Bonaca MP, Jarolim P, Antman EM, Braunwald E, Giugliano RP, et al. Prognostic performance of a high-sensitivity cardiac troponin I assay in patients with non-ST-elevation acute coronary syndrome. Clin Chem. 2014 Jan;60(1):158-64.
• ²⁵
  Correia LC, Sodré FL, Lima JC, Sabino M, Brito M, Garcia G, et al. Prognostic value of high-sensitivity troponin I versus troponin T in acute coronary syndromes. Arq Bras Cardiol. 2012 May;98(5):406-12.
• ²⁶
  Wu AH, Jaffe AS. The clinical need for high-sensitivity cardiac troponin assays for acute coronary syndromes and the role for serial testing. Am Heart J. 2008 Feb;155(2):208-14.
• ²⁷
  Than M, Aldous S, Lord SJ, Goodacre S, Frampton CM, Troughton R, et al. A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: a randomized clinical trial. JAMA Intern Med. 2014 Jan;174(1):51-8.
• ²⁸
  Tanindi A, Cemri M. Troponin elevation in conditions other than acute coronary syndromes. Vasc Health Risk Manag.2011;7:597-603.
• ²⁹
  Than M, Cullen L, Reid CM, Lim SH, Aldous S, Ardagh MW, et al. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet. 2011 Mar 26;377(9771):1077-84.
• ³⁰
  Than M, Cullen L, Aldous S, Parsonage WA, Reid CM, Greenslade J, et al. 2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial. J Am Coll Cardiol. 2012 Jun 5;59(23):2091-8.
• ³¹
  Reiter M, Twerenbold R, Reichlin T, Benz B, Haaf P, Meissner J, et al. Early diagnosis of acute myocardial infarction in patients with pre-existing coronary artery disease using more sensitive cardiac troponin assays. Eur Heart J. 2012 Apr;33(8):988-97.
• ³²
  Biener M, Mueller M, Vafaie M, Jaffe AS, Widera C, Katus HA, et al. Diagnostic performance of rising, falling, or rising and falling kinetic changes of high-sensitivity cardiac troponin T in an unselected emergency department population. Eur Heart J Acute Cardiovasc Care. 2013 Dec;2(4):314-22.
• ³³
  Ferencik M, Schlett CL, Bamberg F, Truong QA, Nichols JH, Pena AJ, et al. Comparison of traditional cardiovascular risk models and coronary atherosclerotic plaque as detected by computed tomography for prediction of acute coronary syndrome in patients with acute chest pain. Acad Emerg Med. 2012 Aug;19(8):934-42.
• ³⁴
  Hoffmann U, Truong QA, Schoenfeld DA, Chou ET, Woodard PK, Nagurney JT, et al. Coronary CT angiography versus standard evaluation in acute chest pain. N Engl J Med. 2012 Jul 26;367(4):299-308.
• ³⁵
  Singer AJ, Domingo A, Thode HC Jr, Daubert M, Vainrib AF, Ferraro S, et al. Utilization of coronary computed tomography angiography for exclusion of coronary artery disease in ED patients with low- to intermediate-risk chest pain: a 1-year experience. Am J Emerg Med. 2012 Nov;30(9):1706-11.
• ³⁶
  Schlett CL, Banerji D, Siegel E, Bamberg F, Lehman SJ, Ferencik M, et al. Prognostic value of CT angiography for major adverse cardiac events in patients with acute chest pain from the emergency department: 2-year outcomes of the ROMICAT trial. JACC Cardiovasc Imaging. 2011 May;4(5):481-91.
• ³⁷
  Amsterdam EA, Kirk JD, Bluemke DA, Diercks D, Farkouh ME, Garvey JL, et al. Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association. Circulation. 2010 Oct 26;122(17):1756-76.
• ³⁸
  Pferfeman E, Forlenza LMA. Estrutura da unidade de dor torácica. In:Serrano Jr. CV, Timerman A, Stefanini E. Tratado de cardiologia SOCESP – 2° ed – Barueri – SP: Manole,2009: 844-60.
• ³⁹
  Lau J, Ioannidis JP, Balk EM, Milch C, Terrin N, Chew PW, et al. Diagnosing acute cardiac ischemia in the emergency department: a systematic review of the accuracy and clinical effect of current technologies. Ann Emerg Med.2001;37:453-60.
• ⁴⁰
  Cury RC, Feutchner G, Pena CS, Janowitz WR, Katzen BT, Ziffer JA. Acute chest pain imaging in the emergency department with cardiac computed tomography angiography. J Nucl Cardiol.2008;15(4):564-75.
• ⁴¹
  Limkakeng AT, Halpern E, Takakuwa KM. Sixty-four-slice multidetector computed tomography: the future of ED cardiac care. Am J Emerg Med.2007;25(4):450-8.
• ⁴²
  Poon M, Cortegiano M, Abramowicz AJ, Hines M, Singer AJ, Henry MC, et al. Associations between routine coronary computed tomography angiography and reduced unnecessary hospital admissions, length of stay, recidivism rates, and invasive coronary angigraphy in the emergency department triage of chest pain. J Am Coll Cardiol.2013;62(6):543-52.
• ⁴³
  Truong QA, Hayden D, Woodard PK, Kirby R, Chou ET, Nagurney JT, et al. Sex differences in the effectiveness of early coronary computed tomography angiographiy compared with standard emergency department evaluation for acute chest pain: the rule-out myocardial infarction with computer-assisted tomography (ROMICAT)-II Trial. Circulation.2013;127(25):2494-502.
• ⁴⁴
  Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008 Nov 18;52(21):1724-32.
• ⁴⁵
  Petcherski O, Gaspar T, Halon DA, Peled N, Jaffe R, Molnar R, et al. Diagnostic accuracy of 256-row computed tomographic angiography for detection of obstructive coronary artery disease using invasive quantitative coronary angiography as reference standard. Am J Cardiol. 2013 Feb 15;111(4):510-5.
• ⁴⁶
  Goldstein JA, Chinnaiyan KM, Abidov A, Achenbach S, Berman DS, Hayes SW, et al. The CT-STAT (Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment) trial. J Am Coll Cardiol. 2011 Sep 27;58(14):1414-22.
• ⁴⁷
  Puchner SB, Liu T, Mayrhofer T, Truong QA, Lee H, Fleg JL, et al. High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial. J Am Coll Cardiol. 2014 Aug 19;64(7):684-92.
• ⁴⁸
  Hulten E, Goehler A, Bittencourt MS, Bamberg F, Schlett CL, Truong QA, et al. Cost and resource utilization associated with use of computed tomography to evaluate chest pain in the emergency department: the Rule Out Myocardial Infarction using Computer Assisted Tomography (ROMICAT) study. Circ Cardiovasc Qual Outcomes. 2013 Sep 1;6(5):514-24.
• ⁴⁹
  Blankstein R, Ahmed W, Bamberg F, Rogers IS, Schlett CL, Nasir K, et al. Comparison of exercise treadmill testing with cardiac computed tomography angiography among patients presenting to the emergency room with chest pain: the Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) study. Circ Cardiovasc Imaging. 2012 Mar;5(2):233-42.
• ⁵⁰
  Hoffmann U, Truong QA, Fleg JL, Goehler A, Gazelle S, Wiviott S, et al. Design of the Rule Out Myocardial Ischemia/Infarction Using Computer Assisted Tomography: a multicenter randomized comparative effectiveness trial of cardiac computed tomography versus alternative triage strategies in patients with acute chest pain in the emergency department. Am Heart J. 2012 Mar;163(3):330-8, 338.e1.
• ⁵¹
  Staniak HL, Bittencourt MS, Sharovsky R, Benseñor I, Olmos RD, Lotufo PA. Calcium score to evaluate chest pain in the emergency room. Arq Bras Cardiol. 2013 Jan;100(1):90-3.
• ⁵²
  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 Apr 3;115(13):1762-8.
• ⁵³
  Cury RC, Budoff M, Taylor AJ. Coronary CT angiography versus standard of care for assessment of chest pain in the emergency department. J Cardiovasc Comput Tomogr. 2013 Mar-Apr;7(2):79-82.
• ⁵⁴
  Nasis A, Meredith IT, Nerlekar N, Cameron JD, Antonis PR, Mottram PM, et al. Acute chest pain investigation: utility of cardiac CT angiography in guiding troponin measurement. Radiology. 2011 Aug;260(2):381-9.
• ⁵⁵
  Kargoli F, Levsky J, Bulcha N, Mustehsan MH, Brown-Manhertz D, Furlani A, et al. Comparison Between Anatomical and Functional Imaging Modalities for Evaluation of Chest Pain in the Emergency Department. Am J Cardiol. 2020 Apr 4;S0002-9149(20)30273-3.doi: 10.1016/j.amjcard.2020.03.024.
  » https://doi.org/10.1016/j.amjcard.2020.03.024
• ⁵⁶
  Yang S, Manjunath L, Willemink MJ, Nieman K. The role of coronary CT angiography for acute chest pain in the era of high-sensitivity troponins. J Cardiovasc Comput Tomogr. 2019 Sep-Oct;13(5):267-73. doi: 10.1016/j.jcct.2019.05.007. Epub 2019 Jun 15.

• Registration
  NCT02772991 – CONECTTIN trial
• Study Association
  This study is not associated with any thesis or dissertation work.

• Sources of Funding: This study was partially funded by Siemens Healthcare Diagnósticos and Canon Medical Systems.

Publication Dates

• Publication in this collection
  13 May 2022
• Date of issue
  May 2022

History

• Received
  05 Jan 2021
• Reviewed
  30 May 2021
• Accepted
  16 June 2021