Heart Fatty Acid Binding Protein and cardiac troponin: development of an optimal rule-out strategy for acute myocardial infarction

Background: Improved ability to rapidly rule-out Acute Myocardial Infarction (AMI) in patients presenting with chest pain will promote decongestion of the Emergency Department (ED) and reduce unnecessary hospital admissions. We assessed a new commercial Heart Fatty Acid Binding Protein (H-FABP) assay for additional diagnostic value when combined with cardiac troponin (using a high sensitivity assay). Methods: H-FABP and high-sensitivity troponins I (hs-cTnI) and T (hs-cTnT) were measured in samples taken on-presentation from patients, attending the ED, with symptoms triggering investigation for possible acute coronary syndrome. The optimal combination of H-FABP with each hs-cTn was defined as that which maximized the proportion of patients with a negative test (low-risk) whilst maintaining at least 99 % sensitivity for AMI. A negative test comprised both H-FABP and hs-cTn below the chosen threshold in the absence of ischemic changes on the ECG. Results: One thousand seventy-nine patients were recruited including 248 with AMI. H-FABP 99 % sensitivity for AMI whilst classifying 40.9 % of patients as low-risk. The combination of H-FABP < 3.9 ng/mL and hs-cTnT < 7.6 ng/L with a negative ECG maintained the same sensitivity whilst classifying 32.1 % of patients as low risk. Conclusions: In patients requiring rule-out of AMI, the addition of H-FABP to hs-cTn at presentation (in the absence of new ischaemic ECG findings) may accelerate clinical diagnostic decision making by identifying up to 40 % of such patients as low-risk for AMI on the basis of blood tests performed on presentation. If implemented this has the potential to significantly accelerate triaging of patients for early discharge from the ED

Effectiveness of EDACS Versus ADAPT Accelerated Diagnostic Pathways for Chest Pain: A Pragmatic Randomized Controlled Trial Embedded Within Practice

Study objective A 2-hour accelerated diagnostic pathway based on the Thrombolysis in Myocardial Infarction score, ECG, and troponin measures (ADAPT-ADP) increased early discharge of patients with suspected acute myocardial infarction presenting to the emergency department compared with standard care (from 11% to 19.3%). Observational studies suggest that an accelerated diagnostic pathway using the Emergency Department Assessment of Chest Pain Score (EDACS-ADP) may further increase this proportion. This trial tests for the existence and size of any beneficial effect of using the EDACS-ADP in routine clinical care. Methods This was a pragmatic randomized controlled trial of adults with suspected acute myocardial infarction, comparing the ADAPT-ADP and the EDACS-ADP. The primary outcome was the proportion of patients discharged to outpatient care within 6 hours of attendance, without subsequent major adverse cardiac event within 30 days. Results Five hundred fifty-eight patients were recruited, 279 in each arm. Sixty-six patients (11.8%) had a major adverse cardiac event within 30 days (ADAPT-ADP 29; EDACS-ADP 37); 11.1% more patients (95% confidence interval 2.8% to 19.4%) were identified as low risk in EDACS-ADP (41.6%) than in ADAPT-ADP (30.5%). No low-risk patients had a major adverse cardiac event within 30 days (0.0% [0.0% to 1.9%]). There was no difference in the primary outcome of proportion discharged within 6 hours (EDACS-ADP 32.3%; ADAPT-ADP 34.4%; difference −2.1% [−10.3% to 6.0%], P=.65). Conclusion There was no difference in the proportion of patients discharged early despite more patients being classified as low risk by the EDACS-ADP than the ADAPT-ADP. Both accelerated diagnostic pathways are effective strategies for chest pain assessment and resulted in an increased rate of early discharges compared with previously reported rates

2-Hour Accelerated Diagnostic Protocol to Assess Patients With Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker

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

Personalized diagnosis in suspected myocardial infarction

Background: In suspected myocardial infarction (MI), guidelines recommend using high-sensitivity cardiac troponin (hscTn)- based approaches. These require fixed assay-specific thresholds and timepoints, without directly integrating clinical information. Using machine-learning techniques including hs-cTn and clinical routine variables, we aimed to build a digital tool to directly estimate the individual probability of MI, allowing for numerous hs-cTn assays. Methods: In 2,575 patients presenting to the emergency department with suspected MI, two ensembles of machine-learning models using single or serial concentrations of six different hs-cTn assays were derived to estimate the individual MI probability ( ARTEMIS model). Discriminative performance of the models was assessed using area under the receiver operating characteristic curve (AUC) and logLoss. Model performance was validated in an external cohort with 1688 patients and tested for global generalizability in 13 international cohorts with 23,411 patients. Results: Eleven routinely available variables including age, sex, cardiovascular risk factors, electrocardiography, and hs-cTn were included in the ARTEMIS models. In the validation and generalization cohorts, excellent discriminative performance was confirmed, superior to hs-cTn only. For the serial hs-cTn measurement model, AUC ranged from 0.92 to 0.98. Good calibration was observed. Using a single hs-cTn measurement, the ARTEMIS model allowed direct rule-out of MI with very high and similar safety but up to tripled efficiency compared to the guideline- recommended strategy. Conclusion We developed and validated diagnostic models to accurately estimate the individual probability of MI, which allow for variable hs-cTn use and flexible timing of resampling. Their digital application may provide rapid, safe and efficient personalized patient care

A Clinical Decision Rule to Identify Emergency Department Patients at Low Risk for Acute Coronary Syndrome Who Do Not Need Objective Coronary Artery Disease Testing: The No Objective Testing Rule

Study objective We derive a clinical decision rule for ongoing investigation of patients who present to the emergency department (ED) with chest pain. The rule identifies patients who are at low risk of acute coronary syndrome and could be discharged without further cardiac testing. Methods This was a prospective observational study of 2,396 patients who presented to 2 EDs with chest pain suggestive of acute coronary syndrome and had normal troponin and ECG results 2 hours after presentation. Research nurses collected clinical data on presentation, and the primary endpoint was diagnosis of acute coronary syndrome within 30 days of presentation to the ED. Logistic regression analyses were conducted on 50 bootstrapped samples to identify predictors of acute coronary syndrome. A rule was derived and diagnostic accuracy statistics were computed. Results Acute coronary syndrome was diagnosed in 126 (5.3%) patients. Regression analyses identified the following predictors of acute coronary syndrome: cardiac risk factors, age, sex, previous myocardial infarction, or coronary artery disease and nitrate use. A rule was derived that identified 753 low-risk patients (31.4%), with sensitivity 97.6% (95% confidence interval [CI] 93.2% to 99.5%), negative predictive value 99.6% (95% CI 98.8% to 99.9%), specificity 33.0% (95% CI 31.1% to 35.0%), and positive predictive value 7.5% (95% CI 6.3% to 8.9%) for acute coronary syndrome. This was referred to as the no objective testing rule. Conclusion We have derived a clinical decision rule for chest pain patients with negative early cardiac biomarker and ECG testing results that identifies 31% at low risk and who may not require objective testing for coronary artery disease. A prospective trial is required to confirm these findings

Validation of the Vancouver Chest Pain Rule using troponin as the only biomarker: a prospective cohort study

Objectives The objective of this study is to evaluate the accuracy of the Vancouver Chest Pain Rule using troponin as the only biomarker in an emergency department (ED) setting. Methods This is an analysis of prospectively collected data from 2 EDs in Australia and New Zealand. Trained research nurses collected clinical data using a customised case report form. Based on a modified Vancouver Chest Pain Rule using troponin as the only biomarker, low-risk patients were identified using clinical history, age, pain characteristics, electrocardiography, and troponin results at 0 and 2 hours after presentation. The primary outcome was diagnosis of acute coronary syndrome (ACS) within 30 days of presentation as adjudicated by 2 independent cardiologists. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to assess the accuracy of the rule. Results There were 1635 patients, and 20.4% had ACS. One hundred twenty-one patients (7.4%) were assigned to the low-risk group on presentation, and a further 418 (25.6%) were assigned low risk after 2-hour electrocardiography and troponin testing. Of the 539 patients (33%) who were eligible for early discharge, 30 (5.6%) had ACS. Sensitivity was 91.0% (95% confidence interval [CI], 85.7%-93.6%), negative predictive value was 94.4% (95% CI, 92.2-96.1), specificity was 39.1% (95% CI, 36.5-41.8), and positive predictive value was 27.7% (95% CI, 25.2-30.5). Conclusions The Vancouver Chest Pain Rule with troponin as the only biomarker identified a sizable low-risk cohort. However, sensitivity was lower than that identified in the original derivation study and was considered insufficient to enable safe early discharge. Modifications to the tool would be required if troponin was incorporated as the only biomarker