Louise Cullen

2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial.

OBJECTIVES The purpose of this study was to determine whether a new accelerated diagnostic protocol (ADP) for possible cardiac chest pain could identify low-risk patients suitable for early discharge (with follow-up shortly after discharge). BACKGROUND Patients presenting with possible acute coronary syndrome (ACS), who have a low short-term risk of adverse cardiac events may be suitable for early discharge and shorter hospital stays. METHODS This prospective observational study tested an ADP that included pre-test probability scoring by the Thrombolysis In Myocardial Infarction (TIMI) score, electrocardiography, and 0 + 2 h values of laboratory troponin I as the sole biomarker. Patients presenting with chest pain due to suspected ACS were included. The primary endpoint was major adverse cardiac event (MACE) within 30 days. RESULTS Of 1,975 patients, 302 (15.3%) had a MACE. The ADP classified 392 patients (20%) as low risk. One (0.25%) of these patients had a MACE, giving the ADP a sensitivity of 99.7% (95% confidence interval [CI]: 98.1% to 99.9%), negative predictive value of 99.7% (95% CI: 98.6% to 100.0%), specificity of 23.4% (95% CI: 21.4% to 25.4%), and positive predictive value of 19.0% (95% CI: 17.2% to 21.0%). Many ADP negative patients had further investigations (74.1%), and therapeutic (18.3%) or procedural (2.0%) interventions during the initial hospital attendance and/or 30-day follow-up. CONCLUSIONS Using the ADP, a large group of patients was successfully identified as at low short-term risk of a MACE and therefore suitable for rapid discharge from the emergency department with early follow-up. This approach could decrease the observation period required for some patients with chest pain. (An observational study of the diagnostic utility of an accelerated diagnostic protocol using contemporary central laboratory cardiac troponin in the assessment of patients presenting to two Australasian hospitals with chest pain of possible cardiac origin; ACTRN12611001069943).

A 2-Hour Diagnostic Protocol for Possible Cardiac Chest Pain in the Emergency Department: A Randomized Clinical Trial

IMPORTANCE Patients with chest pain represent a high health care burden, but it may be possible to identify a patient group with a low short-term risk of adverse cardiac events who are suitable for early discharge. OBJECTIVE To compare the effectiveness of a rapid diagnostic pathway with a standard-care diagnostic pathway for the assessment of patients with possible cardiac chest pain in a usual clinical practice setting. DESIGN, SETTING, AND PARTICIPANTS A single-center, randomized parallel-group trial with blinded outcome assessments was conducted in an academic general and tertiary hospital. Participants included adults with acute chest pain consistent with acute coronary syndrome for whom the attending physician planned further observation and troponin testing. Patient recruitment occurred from October 11, 2010, to July 4, 2012, with a 30-day follow-up. INTERVENTIONS An experimental pathway using an accelerated diagnostic protocol (Thrombolysis in Myocardial Infarction score, 0; electrocardiography; and 0- and 2-hour troponin tests) or a standard-care pathway (troponin test on arrival at hospital, prolonged observation, and a second troponin test 6-12 hours after onset of pain) serving as the control. MAIN OUTCOMES AND MEASURES Discharge from the hospital within 6 hours without a major adverse cardiac event occurring within 30 days. RESULTS Fifty-two of 270 patients in the experimental group were successfully discharged within 6 hours compared with 30 of 272 patients in the control group (19.3% vs 11.0%; odds ratio, 1.92; 95% CI, 1.18-3.13; P = .008). It required 20 hours to discharge the same proportion of patients from the control group as achieved in the experimental group within 6 hours. In the experimental group, 35 additional patients (12.9%) were classified as low risk but admitted to an inpatient ward for cardiac investigation. None of the 35 patients received a diagnosis of acute coronary syndrome after inpatient evaluation. CONCLUSIONS AND RELEVANCE Using the accelerated diagnostic protocol in the experimental pathway almost doubled the proportion of patients with chest pain discharged early. Clinicians could discharge approximately 1 of 5 patients with chest pain to outpatient follow-up monitoring in less than 6 hours. This diagnostic strategy could be easily replicated in other centers because no extra resources are required. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12610000766011.

The HEART score for the assessment of patients with chest pain in the emergency department: a multinational validation study.

OBJECTIVE The HEART score for the early risk stratification of patients presenting to the emergency department with chest pain contains 5 elements: history, electrocardiogram, age, risk factors, and troponin. It has been validated in The Netherlands. The purpose of this investigation was to perform an external validation of the HEART score in an Asia-Pacific population. METHODS Data were used from 2906 patients presenting with chest pain to the emergency departments of 14 hospitals. HEART scores were determined retrospectively. Three risk groups were composed based on previous research. The predictive values for the occurrence of 30-day major adverse coronary events (MACE) were assessed. A comparison was made with the Thrombolysis in Myocardial Infarction (TIMI) score in terms of the value of C-statistics. RESULTS The low-risk group, HEART score ≤ 3, consisted of 820/2906 patients (28.2%). Fourteen (1.7%) patients were incorrectly defined as low risk (false negatives). The high-risk population, HEART score 7-10, consisted of 464 patients (16%) with a risk of MACE of 43.1%. The C-statistics were 0.83 (0.81-0.85) for HEART and 0.75 (0.72-0.77) for TIMI (P < 0.01). CONCLUSIONS Utilization of the HEART score provided excellent determination of risk for 30-day MACE, comparing well with the Thrombolysis in Myocardial Infarction score. This study externally validates previous findings that HEART is a powerful clinical tool in this setting. It quickly identifies both a large proportion of low-risk patients, in whom early discharge without additional testing goes with a risk of MACE of only 1.7%, and high-risk patients who are potential candidates for early invasive strategies.

Diagnostic and prognostic utility of early measurement with high-sensitivity troponin T assay in patients presenting with chest pain

Background: High-sensitivity troponin assays are now available for clinical use. We investigated whether early measurement with such an assay is superior to a conventional assay in the evaluation of acute coronary syndromes. Methods: Patients presenting to an emergency department with chest pain who did not have ST-segment elevation were prospectively recruited from November 2007 to December 2010. Patients underwent serial testing with a conventional cardiac troponin I assay. Samples were also obtained at presentation and two hours later for measurement of troponin T levels using a high-sensitivity assay. The primary outcome was diagnosis of myocardial infarction on admission; secondary outcomes were death, myocardial infarction and heart failure at one year. Results: Of the 939 patients enrolled in the study, 205 (21.8%) had myocardial infarction. By two hours after presentation, the high-sensitivity troponin T assay at the cut-off point of the 99th percentile of the general population (14 ng/L) had a sensitivity of 92.2% (95% confidence interval [CI] 88.1%–95.0%) and a specificity of 79.7% (95% CI 78.6%–80.5%) for the diagnosis of non–ST-segment myocardial infarction. The sensitivity of the assay at presentation was 100% among patients who presented four to six hours after symptom onset. By one year, the high-sensitivity troponin T assay was found to be superior than the conventional assay in predicting death (hazard ratio [HR] 5.4, 95% CI 2.7–10.7) and heart failure (HR 27.8, 95% CI 6.6–116.4), whereas the conventional assay was superior in predicting nonfatal myocardial infarction (HR 4.0, 95% CI 2.4–6.7). Interpretation: The high-sensitivity troponin T assay at the cut-off point of the 99th percentile was highly sensitive for the diagnosis of myocardial infarction by two hours after presentation and had prognostic utility beyond that of the conventional assay. To rule out myocardial infarction, the optimal time to test a second sample using the high-sensitivity troponin T level may be four to six hours after symptom onset, but this finding needs verification in future studies before it can become routine practice.

Development and validation of the Emergency Department Assessment of Chest pain Score and 2 h accelerated diagnostic protocol

Risk scores and accelerated diagnostic protocols can identify chest pain patients with low risk of major adverse cardiac event who could be discharged early from the ED, saving time and costs. We aimed to derive and validate a chest pain score and accelerated diagnostic protocol (ADP) that could safely increase the proportion of patients suitable for early discharge.

Diagnosis of Myocardial Infarction Using a High-Sensitivity Troponin I 1-Hour Algorithm.

IMPORTANCE Rapid and accurate diagnosis of acute myocardial infarction (AMI) currently constitutes an unmet need. OBJECTIVE To test a 1-hour diagnostic algorithm to diagnose AMI using a high-sensitivity troponin I assay with a new cutoff level of 6 ng/L. DESIGN, SETTING, AND PARTICIPANTS The Biomarkers in Acute Cardiac Care study is a prospective study that investigated the application of the troponin I assay for the diagnosis of AMI in 1040 patients presenting to the emergency department with acute chest pain from July 19, 2013, to December 31, 2014. Results were validated in 2 independent cohorts of 4009 patients. Final follow-up was completed on July 1, 2015, and data were assessed from July 2 to December 15, 2015. EXPOSURE Acute chest pain suggestive of AMI. MAIN OUTCOMES AND MEASURES Accurate diagnosis or exclusion of AMI and 12-month mortality in patients with acute chest pain. RESULTS Of the 1040 patients included from the study cohort, 673 (64.7%) were male and had a median age of 65 (interquartile range, 52-75) years. With application of a low troponin I cutoff value of 6 ng/L, the rule-out algorithm showed a high negative predictive value of 99.8% (95% CI, 98.6%-100.0%) after 1 hour for non-ST-segment elevation MI type 1. The 1-hour approach was comparable to a 3-hour approach. Similarly, a rule-in algorithm based on troponin I levels provided a high positive predictive value with 82.8% (95% CI, 73.2%-90.0%). Moreover, application of the cutoff of 6 ng/L resulted in lower follow-up mortality (1.0%) compared with the routinely used 99th percentile (3.7%) for this assay. Two independent cohorts further validated the performance of this algorithm with high negative and positive predictive values. CONCLUSIONS AND RELEVANCE Patients with possible AMI can be triaged within 1 hour after admission with no loss of safety compared with a 3-hour approach, when a low and sensitive cutoff is applied. This concept enables safe discharge or rapid treatment initiation after 1 hour.

High-Sensitivity Cardiac Troponin T Concentrations below the Limit of Detection to Exclude Acute Myocardial Infarction: A Prospective Evaluation

BACKGROUND Initial reports suggest that concentrations of high-sensitivity cardiac troponin T (hs-cTnT) (Roche Diagnostics Elecsys(®)) below the limit of blank (LoB) (3 ng/L) or limit of detection (LoD) (5 ng/L) of the assay have almost 100% negative predictive value (NPV) for acute myocardial infarction (AMI), particularly among patients without electrocardiograph (ECG) evidence of ischemia. We aimed to prospectively validate those findings. METHODS We included adults presenting to the emergency department with suspected cardiac chest pain. Standard troponin T (cTnT) and hs-cTnT (both Roche Elecsys) were tested in samples drawn on arrival. The primary outcome was AMI, adjudicated by 2 investigators on the basis of clinical data and ≥12-h cTnT testing. We also evaluated diagnostic performance when AMI was readjudicated on the basis of hs-cTnT (≥12-h) concentrations. RESULTS Of 463 patients included, 79 (17.1%) had AMI. Twenty-four patients (5.2%) had hs-cTnT concentrations below the LoB, although none had AMI. Ninety-six patients (20.7%) had hs-cTnT concentrations below the LoD, 1 of whom had AMI. Thus, diagnostic sensitivity was 98.7% (95% CI 87.5%-98.6%) and NPV was 99.0% (95% CI 94.3%-100.0%). Of the 17.3% (n = 80) patients with hs-cTnT below the LoD and no ECG ischemia, none had AMI. Thus, diagnostic sensitivity was 100.0% (95% CI 95.4%-100.0%) and NPV was 100.0% (95% CI 95.5%-100.0%). Sensitivity and NPV were maintained when AMI was readjudicated on the basis of hs-cTnT. CONCLUSIONS Our findings confirm that patients with nonischemic ECG and undetectable hs-cTnT at presentation have a very low probability of AMI, although the proportion of patients affected was smaller than in previous research.

Early Dynamic Change in High-Sensitivity Cardiac Troponin T in the Investigation of Acute Myocardial Infarction

BACKGROUND The definition of acute myocardial infarction (AMI) requires a rise and/or fall in troponin with 1 or more results ≥99th percentile of the reference range. How much troponin must change has not been specified. We ascertained whether dynamic changes (δ) in high-sensitivity troponin T (hs-TnT) improved diagnostic and prognostic test performance in the emergency department. METHODS We recruited 939 patients with symptoms suggestive of acute coronary syndrome (without ST elevation). hs-cTnT was measured at 0 h and 2 h after presentation. End-points were admission diagnosis of AMI and 1-year adverse events (composite of death, AMI, revascularization). RESULTS Diagnostic specificity of 0-2-h hs-cTnT for AMI (incurred by 200 patients) improved from 79.8% (78.8%-80.5%) by using the 99th percentile alone to 94.2% (92.9%-95.4%) when we also included a δ ≥20%, but diagnostic sensitivity decreased from 94.5% (90.7%-96.9%) to 49.5% (44.6%-53.9%). With the inclusion of those patients with a δ ≥20% when 0-2-h hs-cTnT was <99th percentile, in addition to any with concentrations ≥99th percentile, diagnostic sensitivity increased to 97.5% (94.4%-98.9%). hs-cTnT ≥99th percentile predicted adverse events (incurred by 111 patients), adjusted hazard ratio 1.9 (1.2-2.8), whereas a δ ≥20% did not, hazard ratio 1.1 (0.7-1.7). CONCLUSIONS Diagnostic specificity of hs-cTnT improved with the use of a δ ≥20% in those patients with concentrations ≥99th percentile, but at a cost of a large reduction in sensitivity. Diagnostic sensitivity improved with the use of a δ ≥20% in patients with 0-2-h concentrations <99th percentile. Both approaches may be required for optimum rule-in and rule-out strategies, respectively. The δ criteria seem to be less useful for medium-term risk stratification.

Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis

Background High-sensitivity assays for cardiac troponin T (hs-cTnT) are sometimes used to rapidly rule out acute myocardial infarction (AMI). Purpose To estimate the ability of a single hs-cTnT concentration below the limit of detection (<0.005 µg/L) and a nonischemic electrocardiogram (ECG) to rule out AMI in adults presenting to the emergency department (ED) with chest pain. Data Sources EMBASE and MEDLINE without language restrictions (1 January 2008 to 14 December 2016). Study Selection Cohort studies involving adults presenting to the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT measurements were obtained and AMI outcomes adjudicated during initial hospitalization. Data Extraction Investigators of studies provided data on the number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements <0.005 µg/L) and the number who had AMI during hospitalization (primary outcome) or a major adverse cardiac event (MACE) or death within 30 days (secondary outcomes), by risk classification (low or not low risk). Two independent epidemiologists rated risk of bias of studies. Data Synthesis Of 9241 patients in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%) low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7% (95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%; pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died. Limitation Few studies, variation in timing and methods of reference standard troponin tests, and heterogeneity of risk and prevalence of AMI across studies. Conclusion A single hs-cTnT concentration below the limit of detection in combination with a nonischemic ECG may successfully rule out AMI in patients presenting to EDs with possible emergency acute coronary syndrome. Primary Funding Source Emergency Care Foundation.

National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand: Australian Clinical Guidelines for the Management of Acute Coronary Syndromes 2016.

Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 897 Key Evidence-Based Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 898 1 Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901 1.1 Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901 1.2 Contemporary Outcomes of ACS and Chest Pain in Australia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901 1.3 The Process of Developing the 2016 ACS Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901 1.4 Conflicts of Interest Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 902 1.5 Development of Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 903 2 Assessment of Possible Cardiac Chest Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 904 2.1 Initial Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 904 2.1.1 Outpatient Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 904 2.1.2 Emergency Department Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 904 2.1.3 Initial ECG and Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 904 2.2 Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 905 2.3 Initial Clinical Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 905 2.4 Risk Scores and Clinical Assessment Protocols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 907 2.5 Biomarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 909 2.6 Further Diagnostic Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 915 2.7 Representation with Symptoms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 916 2.8 Discharge Advice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 916 3 Diagnostic Considerations and Risk Stratification of Acute Coronary Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 917 3.1 Diagnostic Considerations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 917 3.2 Risk Stratification for Patients with Confirmed ACS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 917 4 Acute Reperfusion and Invasive Management Strategies in Acute Coronary Syndromes. . . . . . . . . . . . . . . . . . . . . . . 919 4.1 Reperfusion for STEMI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 919 4.2 Ongoing Management of Fibrinolytic-Treated Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921 4.3 Early Invasive Management for NSTEACS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921 5 Pharmacotherapy of Acute Coronary Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 926 5.1 Acute Anti-Ischaemic Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 926 5.2 Antiplatelet Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 926 5.3 Anticoagulant Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 930 5.4 Duration of Cardiac Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 931