| BACKGROUNDSAcute non-traumatic chest pain is one of the most common reasons for emergency department(ED)evaluation.According to the data collected in the 2016 National Hospital Ambulatory Medical Care Survey in the United States,more than 7.5 million patients with chest pain and related symptoms visited the ED,accounting for 5.2%of the total number of ED visits.A cross-sectional study in Beijing in 2009 showed that patients with acute chest pain accounted for 4.7%of all ED visits.Chest pain can be caused by an extensive variety of conditions ranging from life-threatening chest pain such as acute coronary syndrome(ACS),pulmonary embolism,acute aortic syndrome,tension pneumothorax to disorders relatively harmless,such as costochondritis,pleuritis,and so on.ACS is the most common cause of life-threatening conditions.The first priority in the evaluation of patients with acute chest pain is to assess the likelihood of ACS and the likelihood of major adverse cardiac events(MACE).Previous studies have indicated that between 2.1%and 4.6%of patients with acute myocardial infarction(AMI)in the ED were discharged mistakenly,3.7%of patients were discharged mistakenly and presented with MACE within 60 days.Meanwhile,only 10%-20%of patients with suspected ACS received a final diagnosis of ACS.Thus,it is still a challenge for emergency physicians to identify patients with high-risk chest pain efficiently and reliably and triage patients with low-risk chest pain safely and reasonablyCurrent guidelines recommend the use of structured risk stratification tools to assess and triage patients with suspected ACS presenting to the ED.Previous studies have indicated that the performance of the History,Electrocardiogram(ECG),Age,Risk factors,Troponin(HEART)score seems superior to other risk scores.It has been recommended that patients with a HEART score ?3 should be discharged without further diagnostic testing,including no second cardiac troponin(cTn)measurement.But risk stratification scores currently used merely focus on one cross-section of the timeline during an ED stay.It takes time to observe changes of a patient's clinical condition.To solve this problem,many triage pathways,such as the HEART pathway,ASia-Pacific Evaluation of Chest pain Trial(ASPECT),2-hour Accelerated Diagnostic protocol to Assess Patients with chest pain symptoms using contemporary Troponins as the only biomarker(ADAPT),based on a clinical score and two serial cardiac biomarkers tests have been developed and evaluated.Only the change in biomarkers over time is considered.Triage decisions for acute chest pain patients using usual care are based on a comprehensive strategy which performed in the physician's mind.Therefore,it remains controversial whether simple,structured risk evaluation strategies can surpass real,complex judgments in usual care.Cardiac biomarkers play an important role in the identification and diagnosis of ACS,cTn is the preferred biomarker.With the development of detection technology,the sensitivity of cTn to detect myocardial injury has increased,while the specificity has decreased.More sensitive troponin assays have the potential to better evaluate the patients with suspected ACS presenting to the ED,allowing for earlier safe discharge of low-risk chest pain and earlier recognition of AMI.Conventional troponin assays could lead to an inappropriate discharge,while the more sensitive troponin assays may result in avoidable diagnostic testing.Published data about the impact of the use of more sensitive cTn assays compared with the conventional ones on the actual managements and outcomes of chest pain patients presenting to the ED are inconclusive.More researches are needed to test whether the clinical consequences are altered when the more sensitive cTn assays are used.In this study,we aimed to evaluate the performance of triage stratigies.We compared the efficacy and safety of usual care with HEART score and pathway to identify patients for direct discharge in a tertiary hospital and evaluated whether the HEART score was superior to usual care at this institution.Meanwhile,we decided to investigate the clinical influence of different troponin assays.We evaluated the influence of a more sensitive cTn assay on patient triage,diagnosis,management and prognosis in actual medical practiceMETHODS1.Research designThis study was a retrospective analysis of data which were collected prospectively.We identified all consecutive patients presenting to the ED with acute chest pain or equivalent ischemic symptoms suggestive of ACS in Qilu Hospital of Shandong University between August 24,2015 and September 30,2017.The study was approved by the ethics committee of the hospital,and all patients enrolled provided written informed consent.Study populationPatients were included if they were(1)18 years and older,(2)presenting to the ED,(3)with chest pain or other ischemic symptoms suggestive of ACS;(4)with symptoms occurred or peaked within the last 24 hours,(5)with cTn level measured and(6)signed an informed consent.Patients were excluded for(1)chest pain caused by trauma,(2)an initial impression of ST-segment elevation myocardial infarction(STEMI),(3)being transferred from another hospital,(4)being transferred to other hospitals,(5)leaving against medical advice,(6)dying in the ED,(7)without ECG and(8)being lost to follow up.Three troponin assays were used in the study.Point-of-care testing(POCT)was often used for patients directly entered the first-aid room,and blood samples of other patients were sent to the laboratory.On May 10,2016,the laboratory cTn assay was changed from Access AccuTnI to Access AccuTnI+3,which increased the sensitivity.It gave us the opportunity to evaluate the clinical value of different troponin assays.The study cohort was allocated to two groups according to the cTn assay used:(1)conventional cTn group(from August 24,2015 to May 9,2016,using Access AccuTnI);(2)sensitive cTn group(from August 24,2016 to May 9,2017,using Access AccuTnI+3).Patients presenting at other times were not considered,to alleviate the effects of seasonal variation.2.Data collection2.1 Data collectionThe data included pre-hospital information,ED datasets,hospitalization information(inpatients)and follow-up information.All data were collected on standardized case report forms(CRF)using clinical data standards by trained research assistants.Follow-up after 30 days was conducted to acquire information about adverse events,hospital revisits,and readmission over the telephone.The relevant medical records were obtained if a hospital admission was reported during the follow-up period.Local death registry data were checked to ensure whether patients lost to contact were deceased.The electronic data acquisition(EDC)system was used to record and manage the data.Meanwhile,quality control personnel reviewed the data to ensure the integrity and authenticity of the data.2.2 Decision strategiesThe triage of patients in the study was determined by usual care of emergency physicians,and was categorized into discharged and undischarged.Discharged means going home directly from ED.Undischarged included hospitalization and referral to a cardiologist.Hospitalization was defined as admission to an inpatient unit or to an observation room in the ED for at least 24 hours.Every subject in this study was managed by usual care(discharged or undischarged)and retrospectively evaluated to be low or high risk according to the HEART score(?3 or>3).Patients with low risk were eligible for hospital discharge,while patients with high risk were not eligible for hospital discharge.Usual care was defined as the clinical practice of the physicians on duty.Direct discharge of a patient indicated stratifying the patient as low risk.Physicians assessed the risk of MACE in patients with suspected ACS by integrating patients' history;the results of a dynamic evaluation of symptoms,signs,ECG,and laboratory measurements;and their clinical expertise or intuition.No quantitative assessment approach was used.The length of stay(LOS)in the ED was calculated as the interval between discharge and presentation.The HEART score consisted of five elements:history,ECG,age,risk factors,and cTn.Each variable was assigned a score of 0,1 or 2,respectively.The overall HEART scores were retrospectively determined by the SAS program to guarantee their veracity and consistency.Patients with a HEART score of 0 to 3 were categorized as low-risk of developing MACE and considered eligible for direct discharge from the ED without further diagnostic testing.Since the use of the HEART score would have indicated discharge immediately after the low-risk score was assigned,the LOS in the ED was calculated as the interval between the time of the initial cTn report and presentation.The HEART pathway(-)indicated patients were low risk if their HEART score was ?3 and two cTn tests were both ?99th percentile upper reference limit(URL)(the first and second cTn values after presentation).2.3 Troponin assaysPatients in the conventional cTn group underwent testing of cTnI levels by Access AccuTnI.It had a 99th percentile URL of 0.04 ng/mL with a median imprecision of 14%coefficient of variation(CV),and a 10%CV at 0.06 ng/mL.Our central laboratory used 0.06 ng/mL suggested by the manufacturer as the diagnostic threshold.Patients in the sensitive cTn group underwent testing using Access AccuTnI+3.The 10%CV was at 40 ng/L.The 99th percentile URL was at 30 ng/L,and this was used as the diagnostic threshold.2.4 Observation indexes1)The LOS in the ED(time spent in the ED,covering time spent in the emergency observation room)at the index episode,it was calculated as the interval between discharge and presentation;2)Hospitalization rate,hospitalization was defined as admission to an inpatient unit or to an observation room in the ED for at least 24 hours according to the 2013 American College of Cardiology Foundation/American Heart Association(ACCF/AHA)data standards;3)The use of echocardiography,coronary computed tomography angiography(CCTA),coronary angiography(CAG)and percutaneous coronary intervention(PCI),medication in the first 24 hours in the ED(aspirin,P2Y12 inhibitors,low molecular weight heparin[LMWH],statins,etc);2.5 Clinical outcome2.5.1 The outcome of comparison of two stragegies for triaging patientsThe primary outcome included death from all causes,AMI,revascularization,and CAG revealing significant stenosis(>50%)with conservative treatment within 30 days after initial presentation.The secondary outcome was the composite of death,AMI and emergency revascularization within 30 days.AMI referred to a type 1 myocardial infarction,and included index(being the cause for the initial presentation)and subsequent(occurring during the follow-up)AMI.Revascularization included emergency and non-emergency revascularization.2.5.2 The outcome of analysis of clinical impact of different troponin assaysThe outcome was the incidence of MACE at 30 days,including all-cause death,new or recurrent AMI,emergency revascularization,stroke,cardiogenic shock,and cardiac arrest.AMI referred to myocardial necrosis caused by acute myocardial ischemia,all 5 clinical types were included.Index AMI was not included.Each event in MACE was adjudicated by two cardiologists for all patients according to the definitions following a review of all available clinical records.In case of disagreement,a third cardiologist decided.3.Statistical analysisContinuous variables were described as means and standard deviations or medians(with 25th and 75th percentiles),and t test or Wilcoxon test were used to compare the differences when appropriate.Categorical variables were presented as numbers and percentages.When comparing the differences,x2 or Fisher's exact test were used.Diagnostic accuracy with a 95%confidence interval(CI)for usual care and HEART score or pathway for MACE were determined,including sensitivity,specificity,negative predictive value(NPV),and positive predictive value(PPV).The efficacy(proportion of patients identified as low risk),sensitivity,and specificity were compared using the McNemar test based on paired 4-fold tables.The NPV,PPV and the clinical outcome rates were compared using x2 tests for the respective proportions.Prediction performance of differenct troponin assays for usual care and HEART score for MACE and the diagnostic performance of different troponin assays for AMI were determined,including sensitivity,specificity,NPV,and PPV.When comparing the differences,x2 or Fisher's exact test were used.Receiver operating characteristic(ROC)curves were constructed to assess the diagnostic accuracy of different troponin assays to diagnose AMI.The comparison of areas under the ROC curves(AUC)was performed by z test.Multivariable stepwise logistic regression analysis was used to investigate the association between the type of cTnI assays and the LOS in the ED,hospital admission rate,the use of echocardiography/CCTA/CAG/PCI,and the incidence of MACE.Age,sex,previous coronary artery disease(CAD),heart failure,hypertension,dyslipidemia,previous stroke,tobacco smoking,diabetes mellitus,family history of premature CAD,and ischemic ECG were included in the model.A P value less than 0.05(two-sided significance testing)was considered statistically significant.All analyses were performed using SAS V.9.4(SAS Institute Inc.,Cary,North Carolina,USA)or MedCalc V.18.11.3(MedCalc Software,Ostend,Belgium).RESULTS1.Study populationA total of 3939 patients with acute chest pain presented to the ED of Qilu Hospital of Shandong University from August 24,2015 to September 30,2017,of which 1754 patients did not meet the inclusion criteria.There were 2185 patients involved in the final analysis.2.Comparison of usual care and the HEART risk score2.1 OutcomesA total of 615(28.1%)patients had 30-day primary outcome among these 2185 patients.The primary outcome rate in patients directly discharged by usual care was 2.2%(20/926),and the rate would have been 5.2%(27/524)in those with HEART score ?3(P=0.002).The incidence of the composite of death,AMI,and emergency revascularization was similar in patients directly discharged by usual care and in patients with HEART score ?3(0.5%vs 1.5%,P=0.079).2.2 Efficacy of usual care vs the HEART scoreUsual care triaged 926(42.4%)patients to be discharged without further testing.If the HEART score was used,524(24.0%)patients would have been identified to be directly discharged.The difference between these two percentages was significant(P<0.001).The specificity of usual care to identify primary outcome was 0.577(0.553,0.602),which was superior to the HEART score with 0.317(0.294,0.340)(P<0.001).The median LOS of patients directly discharged by usual care was 5.5(1.7,8.7)hours,which was longer than the time using a HEART score,1.5(1.4,1.7)hours(P<0.001).For the secondary outcome,the specificity of usual care at 0.527(0.504,0.551)still outperformed the HEART score at 0.295(0.274,0.317)(P<0.001).2.3.Safety of usual care vs the HEART scoreFor the primary outcome,the sensitivity of usual care was similar with the HEART score.The difference in NPV was significant(P=0.003)between usual care at 0.978(0.969,0.988)and the HEART score at 0.948(0.930,0.967).For the secondary outcome,the sensitivity and NPV were similar between usual care and the HEART score.2.4 Performance of usual care vs the HEART pathwayAmong 340 patients who received serial cTn tests,the proportion of low-risk chest pain noted by usual care was 25.9%(88/340),whereas use of the HEART pathway would have identified only 11.5%(39/340)of patients as low risk(P<0.001).The primary outcome rate in discharged patients was similar to that would have been in the HEART pathway(-)group(3.4%vs 7.7%,P=0.370).The specificities of these two strategies were 0.445(0.375,0.516)and 0.188(0.133,0.244)(P<0.001).The sensitivities and NPV showed no difference.3.Analysis of clinical impact of different troponin assays3.1 Clinical characteristicsA total of 1161 patients were included(conventional cTn group:618 visits;sensitive cTn group:543 visits).The proportion of smoker and obesity in the conventional cTn group was higher than that in the sensitive cTn group,and the proportion of patients with coronary artery bypass grafting(CABG)was lower.Compared with the use of conventional cTnI,the use of the more sensitive cTn assay decreased the proportion of patients with negative cTn of the first measurement(91.4%vs 82.7%,P<0.001).The median time from chest pain onset to presentation was later in sensitive cTn group(3.4h vs 4.5h,P=0.002),however,there was no statistically significant difference in the proportion of patients in each time period,and the median time from chest pain onset to the first sample collection.3.2 Final clinical diagnosesCompared with the conventional cTn group,more patients were considered to have AMI in the sensitive cTn group(9.5%vs 15.1%,P=0.004),while the proportion of patients who were diagnosed with UA did not change significantly(23.1%vs 23.2%,P=0.979).3.3 The influence of different troponin assays for triage strategiesAfter the application of sensitive cTn,the proportion of low-risk chest pain noted by usual care reduced significantly(61.5%vs 53.8%,P=0.008).The prediction performance of usual care for primary outcome was not affected significantly.The NPV of the HEART risk score was decreased(0.979 vs 0.928,P=0.032)and the PPV was increased(0.223 vs 0.292,P=0.024)when sensitive cTn was used,but there was no significant difference in the proportion of low-risk cheat pain,sensitivity or specificity.3.4 The performance of different troponin assays to diagnose AMIAfter applying the sensitive cTn,the sensitivity of the baseline cTn for AMI diagnosis increased(0.763 vs 0.890,P=0.043),but the specificity reduced(0.986 vs 0.954,P=0.003).There was no significant difference in AUC(0.972 vs 0.961,P=0.583).3.5 The impact of clinical outcomesThe proportions of patients who received aspirin,P2Y12 inhibitors,LMWH,and statins in the first 24 hours in the ED were not statistically different between these two groups.The median LOS in the ED did not decrease significantly(7.9 vs 7.1 hours,P=0.233)after applying the more sensitive cTn assay.For patients discharged home,the median LOS in the ED was shorter in the sensitive cTn group than in the conventional cTn group(6.0 vs 2.4 hours,P<0.001).The proportion of patients hospitalized increased when the sensitive assay was used(35.1%vs 42.7%,P=0.008).More patients in the sensitive cTn group received echocardiography(23.5%vs 32.2%,P=0.001),CAG(12.1%vs 18.4%0,P=0.003),and PCI(6.5%vs 11.6%,P=0.002).The proportion of patients received CCTA increased,but there was no statistical difference(4.0%vs 6.4%,P=0.065).The incidences of MACE were not significantly different in these two groups(2.6%vs 1.7%,P=0.275).Among patients without ACS,no difference was found in the proportions of patients who underwent echocardiography,CCTA or CAG,and the incidence of MACE remained similar in two groups,too.Following multivariable adjustment for potential confounders,the median ED LOS decreased in sensitive cTn group regarding patients discharged home(odds ratio[OR]0.395,95%CI 0.280-0.558,P<0.001).The hospitalization rate(OR 1.364,95%CI 1.053-1.768,P=0.019),the use of echocardiography(OR 1.520,95%CI 1.161-1.992,P=0.002),CAG(OR 1.626,95%CI 1.153-2.294,P=0.006)and PCI(OR 1.795,95%CI 1.161-2.774,P=0.009)were increased,while the incidence of MACE did not decrease significantly(OR 0.658,95%CI 0.284-1.524,P=0.328).CONCLUSIONS1.Compared to a physician's dynamic and comprehensive assessment of each patient's individual information,application of the HEART score would not appear to provide helpful risk stratification.2.Different troponin assays had no significant effect on the safety of triage strategies for the primary outcome.3.There was no significant difference in the diagnostic accuracy of AMI between conventional baseline cTn and sensitive baseline cTn.4.The introduction of the more sensitive cTn assay appeared to result in less time spent in the ED regarding patients discharged home directly,and prompted more hospitalizations and procedures without impacting the incidence of MACE at 30 days significantly. |
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