Relationship Between Physiological Parameters and Acute Coronary Syndrome in Patients Presenting to the Emergency Department With Undifferentiated Chest Pain.

UNLABELLED: The investigators of this study sought to examine whether abnormal physiological parameters are associated with increased risk for acute coronary syndrome (ACS) in patients presenting to the emergency department (ED) with chest pain. METHODS: We used prospectively collected data on adult patients presenting with suspected ACS in 2 EDs in Australia and New Zealand. Trained research nurses collected physiological data including temperature, respiratory rate, heart rate, and systolic blood pressure (SBP) on presentation to the ED. The primary endpoint was ACS within 30 days of presentation, as adjudicated by cardiologists using standardized guidelines. The prognostic utility of physiological parameters for ACS was examined using risk ratios. RESULTS: Acute coronary syndrome was diagnosed in 384 of the 1951 patients (20%) recruited. Compared with patients whose SBP was between 100 and 140 mm Hg, patients with an SBP of lower than 100 mm Hg or higher than 140 mm Hg were 1.4 times (95% confidence interval, 1.2-1.7) more likely to have ACS. Similarly, compared with patients whose temperature was between 36.5°C and 37.5°C, patients with temperature of lower than 36.5°C or higher than 37.5°C were 1.4 times (95% confidence interval, 1.1-1.6) more likely to have ACS. Heart rate and respiratory rate were not predictors of ACS. CONCLUSIONS: Patients with abnormal temperature or SBP were slightly more likely to have ACS, but such risk was of too small a magnitude to be useful in clinical decision making. Other physiological parameters (heart rate and respiratory rate) had no prognostic value. The use of physiological parameters cannot reliably confirm or rule out ACS.

Limited utility of exercise stress testing in the evaluation of suspected acute coronary syndrome in patients aged less than 40 years with intermediate risk features.

OBJECTIVE: National guidelines for management of intermediate risk patients with suspected acute coronary syndrome, in whom AMI has been excluded, advocate provocative testing to final risk stratify these patients into low risk (negative testing) or high risk (positive testing suggestive of unstable angina). Adults less than 40 years have a low pretest probability of acute coronary syndrome. The utility of exercise stress testing in young adults with chest pain suspected of acute coronary syndrome who have National Heart Foundation intermediate risk features was evaluated. METHODS: A retrospective analysis of exercise stress testing performed on patients less than 40 years was evaluated. Patients were enrolled on a chest pain pathway and had negative serial ECGs and cardiac biomarkers before exercise stress testing to rule-out acute coronary syndrome. Chart review was completed on patients with positive stress tests. RESULTS: The 3987 patients with suspected intermediate risk acute coronary syndrome underwent exercise stress testing. One thousand and twenty-seven (25.8%) were aged less than 40 years (age 33.3 ± 4.8 years). Four of these 1027 patients had a positive exercise stress test (0.4% incidence of positive exercise stress testing). Of those, three patients had subsequent non-invasive functional testing that yielded a negative result. One patient declined further investigations. Assuming this was a true positive exercise stress test, the incidence of true positive exercise stress testing would have been 0.097% (95% confidence interval: 0.079-0.115%) (one of 1027 patients). CONCLUSIONS: Routine exercise stress testing has limited value in the risk stratification of adults less than 40 years with suspected intermediate risk of acute coronary syndrome.

Validation of an accelerated high-sensitivity troponin T assay protocol in an Australian cohort with chest pain.

OBJECTIVES: To validate an accelerated biomarker strategy using a high-sensitivity cardiac troponin T (hs-cTnT) assay for diagnosing acute myocardial infarction (AMI) in patients presenting to the emergency department with chest pain; and to validate this strategy in combination with the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand risk stratification model. DESIGN, SETTING AND PATIENTS: Single-centre, prospective, observational cohort study of 764 adults presenting to a tertiary hospital with symptoms of possible acute coronary syndrome between November 2008 and February 2011. MAIN OUTCOME MEASURES: AMI or cardiac death within 24 hours of presentation (primary), and major adverse cardiac events within 30 days (secondary). RESULTS: An elevated hs-cTnT assay result above the 99th percentile at either the 0 h or 2 h time points had sensitivity of 96.4% (95% CI, 87.9%-99.0%), specificity of 82.6% (95% CI, 79.7%-85.2%), negative predictive value of 99.7% (95% CI, 98.8%-99.9%) and positive predictive value of 30.5% (95% CI, 24.2%-37.6%) for diagnosing AMI. Compared with a traditional 6 h cardiac troponin testing strategy, the accelerated strategy led to reclassification of risk in only two patients with adverse cardiac outcomes, with no net effect on appropriate management. CONCLUSIONS: In patients presenting with chest pain, an accelerated biomarker strategy using the hs-cTnT assay performed well in the initial diagnosis of AMI. The accelerated strategy was also effective when incorporated into a comprehensive strategy of risk stratification that included clinical and demographic factors. The time saved by this approach could have a major impact on health service delivery. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000053022.

Comparison of high sensitivity troponin T and I assays in the diagnosis of non-ST elevation acute myocardial infarction in emergency patients with chest pain.

OBJECTIVES: Concentrations of troponin measured with high sensitivity troponin assays are raised in a number of emergency department (ED) patients; however many are not diagnosed with acute myocardial infarction (AMI). Clinical comparisons between the early use (2h after presentation) of high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) assays for the diagnosis of AMI have not been reported. DESIGN AND METHODS: Early (0 h and 2 h) hs-cTnT and hs-cTnI assay results in 1571 ED patients with potential acute coronary syndrome (ACS) without ST elevation on electrocardiograph (ECG) were evaluated. The primary outcome was diagnosis of index AMI adjudicated by cardiologists using the local cTnI assay results taken ≥6 h after presentation, ECGs and clinical information. Stored samples were later analysed with hs-cTnT and hs-cTnI assays. RESULTS: The ROC analysis for AMI (204 patients; 13.0%) for hs-cTnT and hs-cTnI after 2h was 0.95 (95% CI: 0.94-0.97) and 0.98 (95% CI: 0.97-0.99) respectively. The sensitivity, specificity, PLR, and NLR of hs-cTnT and hs-cTnI for AMI after 2h were 94.1% (95% CI: 90.0-96.6) and 95.6% (95% CI: 91.8-97.7), 79.0% (95% CI: 76.8-81.1) and 92.5% (95% CI: 90.9-93.7), 4.48 (95% CI: 4.02-5.00) and 12.86 (95% CI: 10.51-15.31), and 0.07 (95% CI: 0.04-0.13) and 0.05 (95% CI:0.03-0.09) respectively. CONCLUSIONS: Exclusion of AMI 2h after presentation in emergency patients with possible ACS can be achieved using hs-cTnT or hs-cTnI assays. Significant differences in specificity of these assays are relevant and if using the hs-cTnT assay, further clinical assessment in a larger proportion of patients would be required.

The new Vancouver Chest Pain Rule using troponin as the only biomarker: an external validation study.

OBJECTIVES: To externally evaluate the accuracy of the new Vancouver Chest Pain Rule and to assess the diagnostic accuracy using either sensitive or highly sensitive troponin assays. METHODS: Prospectively collected data from 2 emergency departments (EDs) in Australia and New Zealand were analysed. Based on the new Vancouver Chest Pain Rule, low-risk patients were identified using electrocardiogram results, cardiac history, nitrate use, age, pain characteristics and troponin results at 2 hours after presentation. The primary outcome was 30-day diagnosis of acute coronary syndrome (ACS), including acute myocardial infarction, and unstable angina. Sensitivity, specificity, positive predictive values and negative predictive values were calculated to assess the accuracy of the new Vancouver Chest Pain Rule using either sensitive or highly sensitive troponin assay results. RESULTS: Of the 1635 patients, 20.4% had an ACS diagnosis at 30 days. Using the highly sensitive troponin assay, 212 (13.0%) patients were eligible for early discharge with 3 patients (1.4%) diagnosed with ACS. Sensitivity was 99.1% (95% CI 97.4-99.7), specificity was 16.1 (95% CI 14.2-18.2), positive predictive values was 23.3 (95% CI 21.1-25.5) and negative predictive values was 98.6 (95% CI 95.9-99.5). The diagnostic accuracy of the rule was similar using the sensitive troponin assay. CONCLUSIONS: The new Vancouver Chest Pain Rule should be used for the identification of low risk patients presenting to EDs with symptoms of possible ACS, and will reduce the proportion of patients requiring lengthy assessment; however we recommend further outpatient investigation for coronary artery disease in patients identified as low risk.

Performance of risk stratification for acute coronary syndrome with two-hour sensitive troponin assay results.

BACKGROUND: Risk stratification processes for patients with possible acute coronary syndrome (ACS) recommend the use of serial sensitive troponin testing over at least 6h. Troponin assays vary in their analytical performance. Utility in accurate risk stratification at 2h post-presentation is unknown. METHODS: A diagnostic accuracy study of patients presenting to the emergency department (ED) with symptoms of ACS was performed. Troponin was measured at 0, 2 and 6h post-presentation. Acute myocardial infarction (AMI) was adjudicated by cardiologists and incorporated the 0 and 6h troponin values measured by a sensitive troponin assay. Results were described using standard measures of test accuracy. RESULTS: Of the 685 patients, 51 (7.4%) had 30-day AMI or cardiac death, and 76 (11.1%) had secondary outcomes (all cause death, ACS and revascularisation procedures). There was no significant difference in the diagnostic accuracy of early versus late biomarker strategies when used with the current risk stratification processes. Incorporation of a significant delta did not improve the stratification at 2h post-presentation. CONCLUSIONS: Accelerated risk stratification of patients with ACS symptoms may occur at 2h post-presentation using troponin results measured by a sensitive assay. Incorporation of such a strategy could support improvements in patient flow within EDs.

Valvular and aortic diseases in osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is an inheritable connective tissue disorder caused by defective collagen synthesis with the principal manifestations of bone fragility. OI has been associated with left sided valvular regurgitation and aortic dilation. Valve and aortic surgery are technically feasible in patients with OI but are inherently high risk due to the underlying connective tissue defect. This report reviews the valvular and aortic pathology associated with OI and their management. We describe two cases of patients with OI who have significant aortic and mitral valve regurgitation, one of whom has been managed conservatively and the other who has undergone successful mitral valve repair and aortic valve replacement. The latter case represents the fifth case of mitral valve repair in a patient with OI reported in the medical literature.

Comparison of three risk stratification rules for predicting patients with acute coronary syndrome presenting to an Australian emergency department.

OBJECTIVES: To compare the predictive ability of three risk stratification tools used to assess patients presenting to the ED with potential acute coronary syndrome. DESIGN: Pre-planned analysis of an observational study. SETTING: A single tertiary referral hospital. PARTICIPANTS: 1495 patients presented with chest pain. 948 patients were screened and enrolled. Patients with at least 5 min of chest pain suggestive of ACS were eligible. INTERVENTIONS: Subjects were risk categorised using the Heart Foundation of Australia/Cardiac Society of Australia and New Zealand guidelines (HFA/CSANZ), the TIMI score and the GRACE score. Three strata of the TIMI and GRACE score were used to compare to the HFA/CSANZ risk categories. MAIN OUTCOME MEASUREMENT: 30-Day cardiac event rates including cardiac death, acute myocardial infarction and unstable angina. RESULTS: There were 152 events in 91 patients (9.6%). The discriminatory ability of the scores determined by the AUC was 0.83 (95% CI 0.79-0.87) for the GRACE score, 0.79 (95% CI 0.74-0.83) for TIMI score and 0.75 (95% CI 0.70-0.80) for HFA/CSANZ. The AUCs with three strata of the GRACE and TIMI scores were 0.76 (95% CI 0.72-0.81) and 0.68 (95% CI 0.62-0.73) respectively. CONCLUSIONS: All three scores were similar in performance in quantifying risk in ED patients with possible ACS. The GRACE score identified a sizable low risk cohort with high sensitivity and NPV but complexity of this tool may limit its utility. Improved scores are needed to allow early identification of low- and high-risk patients to support improvements in patient flow and ED overcrowding.

Delta troponin for the early diagnosis of AMI in emergency patients with chest pain.

OBJECTIVES: In patients presenting to the Emergency Department (ED) with potential acute myocardial infarction (AMI), elevated cardiac troponin (cTn) levels are indicative of myocardial necrosis. We assessed the accuracy of 'delta cTn' at 2h or 6h compared to the cTn concentration above the 99th percentile reference value for AMI in a prospective study of adult patients presenting to ED with symptoms suggestive of possible acute coronary syndrome. METHODS: Blood was sampled for cardiac troponin I (cTnI) on presentation, and at 2h and 6h following presentation using a sensitive assay (Beckman AccuTnI). All clinical endpoints were adjudicated by a cardiologist who was blinded to the 2h cTn assay result. RESULTS: Of the 874 patients, 70 (8%) were diagnosed with an AMI during their index presentation. The area under the ROC curve for diagnosing AMI at 2h was 0.89 [95%CI, 0.84-0.95] for absolute delta cTn versus 0.79 [95%CI 0.73-0.85] for the relative change. Specificity and PPV at 2h were optimized using a delta cTnI ≥ 0.03 µg/L (95.8% [95%CI 94.1-97.0] and 61.4% [95%CI 50.9-70.9] respectively). Sensitivity and NPV for AMI were optimized using the 99th percentile with the addition of a delta of<0.03 µg/L (97.1% [95%CI 90.2-99.2] and 99.7% [95%CI 99-99.9] respectively). CONCLUSIONS: An algorithm incorporating cTnI concentration and delta cTn values with a sensitive troponin assay allows accurate diagnosis of AMI within 2h from presentation and earlier rule-out of AMI in the majority of patients.

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.

OBJECTIVES: The study objective was to validate a new high-sensitivity troponin I (hs-TnI) assay in a clinical protocol for assessing patients who present to the emergency department with chest pain. BACKGROUND: Protocols using sensitive troponin assays can accelerate the rule out of acute myocardial infarction in patients with low-risk (suspected) acute coronary syndrome (ACS). METHODS: This study evaluated 2 prospective cohorts of patients in the emergency department with ACS in an accelerated diagnostic pathway integrating 0- and 2-h hs-TnI results, Thrombolysis In Myocardial Infarction (TIMI) risk scores, and electrocardiography. Strategies to identify low-risk patients incorporated TIMI risk scores= 0 or ≤ 1. The primary endpoint was a major adverse cardiac event (MACE) within 30 days. RESULTS: In the primary cohort, 1,635 patients were recruited and had 30-day follow-up. A total of 247 patients (15.1%) had a MACE. The finding of no ischemic electrocardiogram and hs-TnI ≤ 26.2 ng/l with the TIMI = 0 and TIMI ≤ 1 pathways, respectively, classified 19.6% (n = 320) and 41.5% (n = 678) of these patients as low risk; 0% (n = 0) and 0.8% (n = 2) had a MACE, respectively. In the secondary cohort, 909 patients were recruited. A total of 156 patients (17.2%) had a MACE. The TIMI = 0 and TIMI ≤ 1 pathways classified 25.3% (n = 230) and 38.6% (n = 351), respectively, of these patients as low risk; 0% (n = 0) and 0.8% (n = 1) had a MACE, respectively. Sensitivity, specificity, and negative predictive value for TIMI = 0 in the primary cohort were 100% (95% confidence interval [CI]: 98.5% to 100%), 23.1% (95% CI: 20.9% to 25.3%), and 100% (95% CI: 98.8% to 100%), respectively. Sensitivity, specificity, and negative predictive value for TIMI ≤ 1 in the primary cohort were 99.2 (95% CI: 97.1 to 99.8), 48.7 (95% CI: 46.1 to 51.3), and 99.7 (95% CI: 98.9 to 99.9), respectively. Sensitivity, specificity, and negative value for TIMI ≤ 1 in the secondary cohort were 99.4% (95% CI: 96.5 to 100), 46.5% (95% CI: 42.9 to 50.1), and 99.7% (95% CI: 98.4 to 100), respectively. CONCLUSIONS: An early-discharge strategy using an hs-TnI assay and TIMI score ≤ 1 had similar safety as previously reported, with the potential to decrease the observation periods and admissions for approximately 40% of patients with suspected ACS. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study, NCT00470587; A 2 hr Accelerated Diagnostic Protocol to Assess patients with chest Pain symptoms using contemporary Troponins as the only biomarker [ADAPT]: a prospective observational validation study, ACTRN12611001069943).

Comparison of early biomarker strategies with the Heart Foundation of Australia/Cardiac Society of Australia and New Zealand guidelines for risk stratification of emergency department patients with chest pain.

OBJECTIVES: To compare cardiac risk stratification using a 0 and 2 h point-of-care (POC) cardiac troponin (cTn), 0 and 2 h POC multi-biomarkers against the 0 and 6 h laboratory cTn reference standard. METHODS: A prospective observational study of ED patients presenting with chest pain was performed. Patients were risk stratified and treated as per the Heart Foundation of Australia/Cardiac Society of Australia and New Zealand (HF-A/CS-ANZ) guidelines using the 0 and 6 h laboratory cTn (T6). Patients were further stratified using a 0 and 2 h POC cTn (T2) plus 0 and 2 h POC multi-biomarkers (cTn, creatine kinase-MB, myoglobin) (M2). The T6, T2 and M2 strategies were compared using the 30-day major adverse cardiac events as the primary outcome. RESULTS: Seven hundred and four patients (median age 54 years, male 62.1%) were enrolled. Using the T6 reference standard, 2%, 61% and 37% were stratified as low, intermediate and high risk, respectively. The 30-day event rates were 0%, 3.5% and 28.6%, respectively. The T2 strategy stratified 1.5%, 57% and 41% as low, intermediate and high risk, respectively, with 30-day event rates of 0%, 4.2% and 24.8%, respectively. The M2 strategy resulted in significantly different risk distribution with 1%, 40% and 59% stratified as low, intermediate and high risk, respectively, with 30-day event rates of 0%, 3.9% and 18.8%, respectively. CONCLUSION: Using a 2 h POC cTn-only biomarker strategy with the HF-A/CS-ANZ guidelines accurately identified a population at intermediate risk of 30-day events in whom further objective testing might be accelerated, allowing subsequent early discharge of the majority of this cohort. Within 2 h of presentation a high risk population could be identified in whom early management, including admission, was required.

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).