1. Is it time to ADAPT?

2. Background By far, the most promising of the publications to yet emerge from the ADAPT cohort – 1,974 patients evaluated for acute chest pain in the Emergency Department – is this re-analysis and decision instrument. The original ADAPT publication, despite over 80% of the patients having no major cardiac event at 30 days, was only able to identify 20% of patients as “low-risk”. The HEART Score and the Vancouver Chest Pain Rule improve on this, but only incrementally. This publication, however, improves the identification of a low-risk cohort to nearly 50%. By incorporating and weighting 37 different predictor variables, then adding a layer of expert review and acceptability evaluation, these authors ultimately arrive at the “Emergency Department Assessment of Chest Pain Score (EDACS)”. Using age, gender, history, and symptoms, when combined with negative ECG and 0 and 2 hour troponins, a score of 16 constitutes a breakpoint for a decision instrument with ~99% sensitivity and ~55% specificity for MACE at 30 days. As far as decision instruments go, it’s relatively reasonable – although, certainly, nothing you’d be able to keep in your head. Scores for age range from +2 to +20, while four different symptoms and signs have varying positive and negative values. However, in the age of computerized decision-support, at least, mildly complex rules are not as burdensome as they once were. I would like to see, at least, prospective validation in a North American population – but this appears to be a lovely step forward. “Development and validation of the Emergency Department Assessment of Chest pain Score and 2 h accelerated diagnostic protocol“ http://onlinelibrary.wiley.com/doi/10.1111/1742-6723.12164/abstract http://onlinelibrary.wiley.com/doi/10.1111/1742-6723.12164/abstract

3. ACEP Another strategy is to use negative myoglobin in conjunction with a negative CK-MB mass or negative TnI measured at baseline and at 90 minutes in patients presenting less than 8 hours after symptom onset. A third approach is to use a negative 2-hour delta CK-MB in conjunction with a negative 2-hour delta TnI in patients presenting less than 8 hours after symptom onset.

4. NH trop – characteristics SSU – NSTEMI rate

5. St Emlyn’s take We looked at the ADAPT trial by Martin Than and colleagues. Essentially they assessed the diagnostic utility of an accelerated protocol using Timi risk score, 0 & 2 hour troponin I measurements for rapid exclusion of cardiac pathology in patients attending the ED with chest pain. I was rubbing my hands on this one. “think of the bed days we can save on the decision unit. Say goodbye to all the 12 hour boredom of the ‘rule out’ MI admission.”ADAPT So what did they actually do? Well, over 2 sites in Oz and NZ they assessed 1975 patients attending with chest pain of suspected cardiac origin. They performed baseline and 2 hour Troponin I measurements that were unavailable to clinicians. They performed usual diagnostic protocols and followed patients up for 3 months. Then an adjudication panel apportioned the diagnosis of Major Adverse Cardiac Events at the end of the study period. They subsequently looked back to ask 2 main questions: Firstly, what was the sensitivity of their accelerated diagnostic protocol (did it catch all the true positives)? Secondly, if we assume the ADP is highly sensitive and therefore ‘safe’ how many patients would have been potentially dischargeable directly from the ED within 4 hours? The methodology was pretty sound. Pretest probability for MACE was a little on the low side (15.3%) compared to our prevalence (20%) or other studies (30%). But their use of MACE is in keeping with much of the literature on the topic. The adjudication committee was not independent but we had a long discussion about this and concluded that actually, if they were blind to the Trop I assay, they couldn’t introduce much bias here even if they wanted to. If they underestimated MACE based on some of the more subjective aspects for example, they could potentially heighten the sensitivity of the diagnostic protocol – but this would worsen specificity and consequent diagnostic utility. Thus they would be shooting themselves in the foot. And what did they find? An excellent sensitivity of 99.7% (95% CI 98.1 – 99.9) A dischargeable proportion of 20% using the ADP, with 1 MACE event in this group only (0.25%). These are very interesting findings from a large, methodologically robust diagnostic study from 2 countries with a distinguished author list. So, are we going to start applying the findings in practice? I’m not so sure. The findings must be taken in context with other concerns about the paper. We only had a few issues, but here they are: There was no mention of symptom duration at presentation in the cohort. Thus we don’t know how long these patients had had symptoms for prior to presentation. This is important: if most of the 1975 presented at 10 hours then actually, your 2 hour Troponin is predominately a 12 hour Troponin if you use time from symptom onset for your exclusion. We do Troponins 12 hours after symptom onset, but other systems (for example in many American papers) a measure of 12 hours after ED presentation is used. Their findings have not yet been externally validated. The sensitivity especially is likely to be slightly overestimated in a tightly controlled exploratory cohort. Something to be cautious of. They used Trop I rather than one of the new all reaching brand new spanking best in show highly sensitive troponin assays. This might mean that the findings are more immediately relevant if you’re not using a high sensitivity assay, but for us in Europe this is a concern. The proportion of patients who could be discharged is likely to be lower with a high sensitivity assay. The proportion of dischargeable patients using this rule was actually not huge at 20%. In the UK, this may be even less (only 7.4% of our patients had a TIMI risk score of 0/7 in previous work). It follows that the others all end up admitted to some sort of inpatient service. This is a fairly self fulfilling prophecy in terms of investigations and therapeutics, as noted by their figures of 74% ADP negative patients receiving further investigations and 14% recieving therapy of some form. There are risks with this. And remember, the actual prevalence is only 15.3% (increased to 18-19% if we discount the ADP positive patients). 60% are still getting a raw deal (full inpatient investigation and treatment with no clear diagnosis at the end) Are we potentially therefore doing more harm by using a strict diagnostic protocol such as this one that will no doubt encourage admission due to the limited specificity?our patients The accompanying editorial to this paper can be found here and is a really nice summary of how far we have come and how much work still needs to be done on this topic. It also highlights the recent work looking atundetectable HsTnT to exclude MI at the door by a certain Dr Body (who?) and Professor Carley (never heard of him). This kind of work interests me a little more if I am honest.editorial to this paper can be found here undetectable HsTnT to exclude MI at the door I want a test which I can use immediately on the young patient with low risk chest pain that will rapidly reassure me about an absence of cardiac pathology. I am happy that Troponin is not this test in the elderly and will often manage them as ACS irrespective of initial trop results.

6. JACC editorial Emergency department (ED) overcrowding is a national health problem. From 1997 to 2007, the annual number of ED visits in the United States increased from 95 to 117 million, whereas the number of EDs decreased by 10% (1). This increased volume has put demands for acute care services at more than can be provided: 50% of urban hospitals and 31% of rural hospitals continuously operate at or over capacity (2). ED overcrowding is associated with adverse cardiovascular outcomes (3), reduced use of guideline-recommended therapies, and a higher risk of recurrent myocardial infarction (4).1234 Given that chest pain is the second most common reason patients present to EDs across the United States (1), rapidly identifying patients with acute coronary syndrome (ACS) and efficiently identifying low-risk patients who can be safely evaluated in the outpatient setting is a critical issue. A key to facilitating the care of these patients is early risk stratification, proper use of sensitive and specific markers (e.g., cardiac troponin [cTn]), and comprehensive follow-up. This effort for low-risk patients is what has been evaluated by Than et al. in this issue of the Journal (5).15 A total of 1,975 consenting adults presenting with symptoms suggestive of ACS were prospectively enrolled from 2 urban EDs. The investigators identified a low-risk group using an accelerated diagnostic protocol (ADP) that included patients with a Thrombolysis In Myocardial Infarction (TIMI) risk score of 0 at presentation, no new ischemic changes on the initial electrocardiogram (ECG), and cardiac troponin I (cTnI) concentrations at 0 and 2 h after arrival below the institutional cutoff for cTn elevation. The investigators were confident that close short-term follow-up with primary care physicians would occur in their local setting. Patients were prospectively followed to ascertain the occurrence of major adverse cardiac events (MACE), including ruling in for acute myocardial infarction (AMI) on the 12-h blood sample. The remainder of events included a composite of cardiac death, cardiac arrest, emergency revascularization, cardiogenic shock, ventricular arrhythmia requiring intervention, high-degree atrioventricular block requiring intervention, and AMI within 30 days of ED presentation. Overall, of the 1,975 patients, there were 302 (15%) patients who had a MACE within 30 days. However, only 1 of these occurred in the 392 patients (20% of the cohort) who were ADP negative, giving the ADP a sensitivity of 99.7% and specificity of 23.4%. If this protocol were implemented in clinical practice, it could potentially identify 20% of ED patients who could be safely discharged within 2 to 3 h of presentation. However, there are very significant limitations to this investigation. Specifically, 18% of ADP negative patients underwent therapeutic and 2% underwent procedural interventions during their initial presentation or within 30 days of the ED visit, introducing the risk of outcome misclassification due to cointervention. Moreover, 74% of these patients had additional investigations, 81% of which were cardiac stress tests, suggesting that further risk stratification after the ED visit was deemed essential in the majority of ADP negative patients. Thus, it could be argued that the results obtained reflect the design of the study, with more prolonged observation of some of the patients and aggressive follow-up in the others. Although this approach would be helpful to EDs, it would be ideal if the results did not depend so heavily on follow-up evaluations. This may work well in the 2 centers involved, but may not be the case in some others. Thus, there is room for improvement in the proximate elements of the evaluation, including the risk score and how cTn was used. The TIMI risk score was originally developed to predict risk in hospitalized high-risk ACS patients. A recent meta-analysis of 17,265 patients from 10 prospective ED cohort studies (6) observed statistical heterogeneity among studies related to differences in the prevalence of cardiac events between cohorts. This would lead to anticipation of variability in the performance of the ADP among practice settings based on the baseline prevalence of MACE in a given population.6 Several prediction models have been developed that may be better tailored for use in the ED setting. The North American Chest Pain Rule incorporates the clinician's assessment of chest pain etiology as well as readily available data from the initial ECG, cTn, and cardiovascular history. It had a sensitivity of 100% and a specificity of 20.9% among 2,718 patients enrolled from 3 centers (7). The HEART (History, ECG, Age, Risk Factors, and Troponin) score has also been developed (8) in ED chest pain patients as well as the Vancouver chest pain rule (9). This growing literature suggests that additional investigations will provide the needed refinements to identify low-risk ACS patients.789 In addition, although the cTn assays used were reasonable fourth-generation cTnI assays, they were used at a higher cutoff value than suggested by the guidelines (10). Thus, by definition, they might have missed more patients than would be ideal. With more sensitive assays, such an approach may be improved, but it is unclear, especially in patients who present very early, that 2 h will provide a robust ability to exclude all AMIs. However, there are approaches that may help. Recently, Body et al. (11) reported that patients with an initial highly sensitive cTnI value below the level of detection had negligible rates of MACE over a 30-day period. If a group that had chest pain >6 h before presentation without intercurrent symptoms were added, this group might be as high as 40% of the ED cohort. If so, it might be that many patients could have AMI excluded at the time of admission. This would still leave some patients with possible unstable angina, but as assay sensitivity improves, this group would be smaller and smaller. The tension, however, is clear. There will be a much larger number of cTn elevations with these assays, both due to chronic diseases and acute diseases such as sepsis, stroke, and pulmonary embolism (12).101112 Where do we go from here? Is there a safe and efficient way out of the jungle? For the short term, an effective solution to the dilemma of ED overcrowding is, of necessity, collaborative. Although we anticipate improvements in our ability to define a low-risk cohort and in metrics necessary to optimally use high sensitivity cTn assays, a multidisciplinary team approach with good follow-up is needed to provide consistent, high-quality health care for possible ACS patients in the context of an emergency care system at its breaking point. References 1 Niska R., Bhuiya F., Xu J.; National Hospital Ambulatory Medical Care Survey: 2007 emergency department summary. Natl Health Stat Report. 2010:1-31. 2 American Hospital Association Rapid Response Survey, Telling the Hospital Story. Chicago, IL: Health Forum; 2010. 3 Pines J.M., Pollack C.V. Jr., Diercks D.B., Chang A.M., Shofer F.S., Hollander J.E.; The association between emergency department crowding and adverse cardiovascular outcomes in patients with chest pain. Acad Emerg Med. 16 2009:617-625. CrossRef | PubMed CrossRefPubMed 4 Diercks D.B., Roe M.T., Chen A.Y.; Prolonged emergency department stays of non-ST-segment-elevation myocardial infarction patients are associated with worse adherence to the American College of Cardiology/American Heart Association Guidelines for Management and Increased Adverse Events. Ann Emerg Med. 50 2007:489-496. CrossRef | PubMed CrossRefPubMed 5 Than M., Cullen L., Aldous S.; A 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. 59 2012:2091-2098. CrossRef | PubMed CrossRefPubMed 6 Hess E.P., Agarwal D., Chandra S.; Diagnostic accuracy of the TIMI risk score in patients with chest pain in the emergency department: a meta-analysis. CMAJ. 182 2010:1039-1044. CrossRef | PubMed CrossRefPubMed 7 Hess E.P., Brison R.J., Perry J.J.; Development of a clinical prediction rule for 30-day cardiac events in emergency department patients with chest pain and possible acute coronary syndrome. Ann Emerg Med. 59 2012:115-125. CrossRef | PubMed CrossRefPubMed 8 Backus B.E., Six A.J., Kelder J.C.; Chest pain in the emergency room: a multicenter validation of the HEART Score. Crit Pathw Cardiol. 9 2010:164-169. CrossRef | PubMed CrossRefPubMed 9 Christenson J., Innes G., McKnight D.; A clinical prediction rule for early discharge of patients with chest pain. Ann Emerg Med. 47 2006:1-10. CrossRef | PubMed CrossRefPubMed 10 Jaffe A.S.; The 10 commandments of troponin, with special reference to high sensitivity assays. Heart. 97 2011:940-946. CrossRef | PubMed CrossRefPubMed 11 Body R., Carley S., McDowell G.; Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a high-sensitivity assay. J Am Coll Cardiol. 58 2011:1332-1339. CrossRef | PubMed CrossRefPubMed 12 Hammarsten O., Fu M.L., Sigurjonsdottir R.; Troponin T percentiles from a random population sample, emergency room patients and patients with myocardial infarction. Clin Chem. 58 2012:628-637. CrossRef | PubMed CrossRefPubMed

7. Rapid Exclusion of Acute Myocardial Infarction in Patients With Undetectable Troponin Using a High-Sensitivity Assay Richard Body, MB, ChB, PhD ? ; Simon Carley, MD † ; Garry McDowell, PhD ? ; Allan S. Jaffe, MD ‡ ; Michael France, MB BS † ; Kennedy Cruickshank, MB, MD ? ; Christopher Wibberley, PhD § ; Michelle Nuttall † ; Kevin Mackway-Jones, BM, BCh, MA † ? † ? ‡ † ? § † J Am Coll Cardiol. 2011;58(13):1332-1339. doi:10.1016/j.jacc.2011.06.026 Objectives This paper sought to evaluate whether high sensitivity troponin (hs-cTnT) can immediately exclude acute myocardial infarction (AMI) at a novel ‘rule out' cut-off. Background Subgroup analysis of recent evidence suggests that undetectable hs-cTnT may exclude AMI at presentation. Methods In a cohort study, we prospectively enrolled patients with chest pain, evaluating them with standard troponin T and testing for hs-cTnT (Roche Diagnostics, Basel, Switzerland) at presentation. The primary outcome was a diagnosis of AMI. We also followed up patients for adverse events within 6 months. After subsequent clinical implementation of hs-cTnT, we again evaluated whether initially undetectable hs-cTnT ruled out a subsequent rise. Results Of 703 patients in the cohort study, 130 (18.5%) had AMI, none of whom initially had undetectable hs-cTnT (sensitivity: 100.0%, 95% confidence interval [CI]: 95.1% to 100.0%, negative predictive value: 100.0%, 95% CI: 98.1% to 100.0%). This strategy would rule out AMI in 27.7% of patients, 2 (1.0%) of whom died or had AMI within 6 months (1 periprocedural AMI, 1 noncardiac death). We evaluated this approach in an additional 915 patients in clinical practice. Only 1 patient (0.6%) with initially undetectable hs-cTnT had subsequent elevation (to 17 ng/l), giving a sensitivity of 99.8% (95% CI: 99.1% to 100.0%) and a negative predictive value of 99.4% (95% CI: 96.6% to 100.0%). Conclusions Undetectable hs-cTnT at presentation has very high negative predictive value, which may be considered to rule out AMI, identifying patients at low risk of adverse events. Pending further validation, this strategy may reduce the need for serial testing and empirical treatment, enabling earlier reassurance for patients and fewer unnecessary evaluations and hospital admissions.

9. J Am Coll Cardiol.J Am Coll Cardiol. 2013 Oct 1;62(14):1242-9. doi: 10.1016/j.jacc.2013.02.078. Epub 2013 Apr 10. 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. Cullen L et al.. Cullen L Abstract 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).

10. TIMI scores? Antman EM, Cohen M, Bernink PJ, et. al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. 2000 Aug 16;284(7):835-42. Age >= 65 ( 3 or more CAD risk factors (1 point) Known CAD with more than 50% stenosis (1 point) Aspirin use in the past 7 days (1 point) Severe angina in the preceeding 24 hours (1 point) Elevated cardiac markers (1 point) ST deviation greater than 0.5 mm (1 point)

11. JAMA Intern Med.JAMA Intern Med. 2014 Jan;174(1):51-8. doi: 10.1001/jamainternmed.2013.11362. A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: a randomized clinical trial. Than M Than M 1, Aldous S 1, Lord SJ 2, Goodacre S 3, Frampton CM 4, Troughton R 4, George P 1, Florkowski CM 5, Ardagh M 4, Smyth D 1, Jardine DL 1, Peacock WF 6,Young J 1, Hamilton G 7, Deely JM 7, Cullen L 8, Richards AM 4.Aldous SLord SJGoodacre SFrampton CMTroughton RGeorge PFlorkowski CMArdagh MSmyth DJardine DLPeacock WFYoung JHamilton GDeely JMCullen LRichards AM Author information Abstract 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.

12. NH Troponin Not all troponin ‘I’s or ‘T’s are the same. high sensitivity sensitive not particularly sensitive at all super sensitive Using the 10% CV cutoff identified, an additional 12% more cases were identified relative to the WHO acute MI cutoff. The 99th percentile cutoff identified an additional 10% of cases relative to the 10% CV cutoff, as well as a 22% increase in the number of cases over the WHO acute MI cutoff. Nevertheless, the odds ratios for the adverse cardiac event rates of death or MI at 30 days were similar for all 3 cutoffs, suggesting that the lower cutoffs detected more patients with cardiovascular risk without sacrificing specificity. [12, 13] The National Academy of Clinical Biochemistry (NACB) working with the ACC/ESC guidelines has recommended adoption of the 99th percentile upper reference limit as the recommended cutoff for a positive troponin result. Ideally, the precision of the assay at this cutoff level should be measured by a CV that is less than 10%. However, most TnI assays are imprecise at the 99th percentile reference limit. [14] Some have therefore recommended that the cutoff level be raised to the slightly higher 10% CV level instead of the 99th percentile reference limit to ensure adequate assay precision. In addition, studies have shown that populations within the 99th percentile reference limit include patients with low troponin levels who nevertheless have an elevated cardiac risk, and that the true 99th percentile cutoff for a healthy patient population is actually a factor of 10-50 lower. Accordingly, these investigations suggest that higher sensitivity or ultrasensitive troponin assays are necessary. [13] The advantage of ultrasensitive troponins is based on the premise that lower cutoff levels achieve higher sensitivity that will allow earlier diagnosis, often within 90 minutes of presentation. To optimize the assay’s use in the ED, it is important to be familiar with the particular troponin assay available in the laboratory and to know whether the cutoff is set at the 10% CV level or the 99th percentile upper reference limit.

13. POC? Point-of-care assays NACB recommendations specify that cardiac markers be available on an immediate basis 24 h/d, 7 d/wk, with a turnaround time of 1 hour. [15] Point-of-care (POC) devices that provide rapid results should be considered in hospitals whose laboratories cannot meet these guidelines. POC assays for CK-MB, myoglobin, and the cardiac troponins TnI and TnT are available. Only qualitative TnT assays are available as POC tests, but both quantitative and qualitative POC TnI assays are currently marketed. In a multicenter trial, the time to positivity was significantly faster for the POC device than for the local laboratory (2.5 h vs 3.4 h). [16] In another multicenter study, which evaluated the i-STAT POC TnI assay in comparison with the central laboratory in 2000 patients with suspected ACS, POC testing reduced the length of stay by approximately 25 minutes for patients who were discharged from the ED. [17, 18] The sensitivity of current POC assays coupled with the benefit of rapid turnaround time make the POC assays attractive clinical tools in the ED.

14. When do we start he clock? (a) When the patient arrives in the hospital, or (b) When the patient says their peak symptoms occurred? In Australia/ UK the clock starts at (b) Elsewhere, the clock starts at (a) Either approach is totally acceptable according to international guidelines

15. MIA 2012: Than M 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. BOTTOM LINE [1][1] For ED patients presenting with undifferentiated chest pain, a TIMI score of 0, together with a non-ischemic EKG, and a negative cTnI at 0 hours and 2 hours, can identify patients at very low-risk for having a major adverse cardiac event (MACE) in 30 days. WHY IT’S IMPORTANT FOR EMERGENCY MEDICINE No ED physician wants to miss the diagnosis of ACS, but with over 6 million visits each year for chest pain, that’s a boat load of “rule-out ACS” admissions – the vast majority (85%) of whom do not end up having ACS at all. This trial tests the performance of an accelerated diagnostic protocol (ADP) – which combines clinical data (TIMI score) + a conventional biomarker (rather than using an expensive coronary CT angiogram or a scarce high-sensitivity cardiac biomarker) – to identify patients at very low risk for MACE in 30 days, and thus suitable for discharge. And it misses only 0.25%. That’s pretty good… MAJOR POINTS Only 1 out of 392 patient who met the ADP had an adverse outcome, meaning the ADP had a sensitivity of 99.7%. TIMI score 0 without the 2-hr cTnI missed 5 patients (3.2%). TIMI score 1, negative EKG, negative 0+2hr cTnI had sensitivity of 97%. DESIGN & RESULTS Prospective observational cohort from 2 urban EDs in Australia and New Zealand. Patients were >18y/o, had >5mins of symptoms consistent with ACS, and the ED physician planned on serial cTn testing. 2168 patients eligible; 1975 patients evaluated with the ADP. No patients lost to follow-up. 392 patients were ADP-negative; 1 patient with 30-day MACE CRITICISMS Although only 1 patient had a MACE, 7 patients (2%) in the ADP-negative group had “nonemergent” revasculariztion, and 18.3% had some other therapeutic intervention within those 30 days. The interventions may have affected these patient probability of developing a MACE. Reviewed by V.Nguyen MIA 2012 = Most Interesting Articles series of 2012 References M. Than, L. Cullen, S. Aldous, W.A. Parsonage, C.M. Reid, J. Greenslade, D. Flaws, C.J. Hammett, D.M. Beam, M.W. Ardagh, R. Troughton, A.F.T. Brown, P. George, C.M. Florkowski, J.A. Kline, W.F. Peacock, A.S. Maisel, S.H. Lim, A. Lamanna, and A.M. Richards, "2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial.", Journal of the American College of Cardiology, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22578923http://www.ncbi.nlm.nih.gov/pubmed/22578923

16. Troponin LITFL | Education | Critical Care Compendium | Troponin LITFLEducationCritical Care Compendium Troponin OVERVIEW Troponin abnormality is set at the 99th percentile in the healthy population As the tests become more and more sensitive, the absolute cutoff value for “abnormal” has become lower and lower and the test has become less specific for myocardial infarction From 1995 to 2007, the limit of troponin detection fell from 0.5 ng/mL to 0.006 ng/mL often raised in the critically unwell (medical ICU, surgical ICU, trauma ICU, sepsis and septic shock, hypovolaemic shock) PATHOPHYSIOLOGY cardiac TNI and TNT are regulatory proteins that control the calcium-mediated interaction of actin and myosin, producing myocardial contraction myocardial injury, including but not limited to ischemia, causes release of these proteins into blood CAUSES OF ELEVATION Myocardial infarction Type 1 (due to atheromatous plaque rupture) Type 2 (due to other precipitant, e.g. hypotension, anaemia, vasospasm) Other cardiac causes Acute and chronic heart failure Myocarditis Cardiac contusion from trauma Cardioversion Endomyocardial biopsy Aortic dissection Hypertrophic cardiomyopathy Aortic valve disease (aortic stenosis or regurgitation) Cardiotoxic drugs Tachyarrhythmia (SVT, V-tach, atrial fibrillation) Bradyarrhythmia or heart block Cardiac surgery Cardioversion Tako-tsubo cardiomyopathy Rhabdomyolysis Stenting or angioplasty (percutaneous coronary intervention/PCI) Irukandji syndrome Non-cardiac causes Renal failure Pulmonary embolism Severe pulmonary hypertension Sepsis Severe critical illness Burns Extreme exertion Amyloidosis or other infiltrative diseases Stroke Subarachnoid hemorrhage TIME COURSE Myocardial infarction distinct rise and fall typically rise 4-8 hours post onset of symptoms in MI peaks at 18-24 hours levels stay elevated for 10 days (allows late diagnosis of MI, may detect re-infarction with serial testing) IMPLICATIONS IN CRITICAL ILLNESS length of stay: associated with increased LOS mortality: increased in ACS: increased mortality TEST CHARACTERISTICS greater specificity than CK-MB as this is also found in skeletal muscle, gut, and uterus PROS AND CONS AND A CARDIAC BIOMARKER Advantages widely available high familiarity rises over 4-8 hours, peaks at 10-24 hours, declines over 10 days can be used to detect reinfarction predicts outcome/ mortality (if negative, then low risk 30 day outcomes) area under the curve of troponin elevation correlates with infarct size new assays are highly sensitive Disadvantages low specificity: multiple causes of raised troponin other than infarction e.g. PE and RV strain (see above) different reference ranges for different assays elevated baseline troponin in renal failure diagnosis of infarction often requires repeated tests leading to a delay in diagnosis ‘washout’ occurs after reperfusion unclear significance of raised troponin post-cardiac surgery APPROACH TO MI DIAGNOSIS IN CHEST PAIN History ECG — Specific (97%) but not aensitivity (28%) Lower sensitivity troponin requires at least 6 hours between time of initial lab and repeat troponin to see a conclusive increase to rule in AMI Serial sampling of high sensitivity tropining at 0 and 2 hours can safely rule-out of AMI (can be discharged if TIMI 0 or 1, and normal ECG)

17. Why Low Risk Chest Pain Management is totally Screwed with David Newman and Ashley Shreves The management of low risk chest pain in the US is founded on a number of tenets: If low risk chest pain patients are sent home and they have unstable angina, they will do worse than if we admitted them Provocative testing will identify patients who are safe for discharge A positive stress test identifies patients who will have benefit from PCI PCI is the standard of care for UA/NSTEMI as it reduces patient important adverse events The problem is that all of these are false. But I wouldn’t expect you to believe me

18. Issue 4 (Vol. 25)Issue 4 (Vol. 25) of Emergency Medicine Australasia Accelerated diagnostic protocol in the assessment of ED patients with possible acute coronary syndrome (ACS) Accelerated diagnostic protocol in the assessment of ED patients with possible acute coronary syndrome (ACS) George and colleagues short report on the Nambour Short Low-Intermediate Chest (SLIC) pain project outlined a trial implementation of the ADAPT accelerated diagnostic protocol (ADP) on a cohort of ED patients with undifferentiated chest pain and possible ACS, in the context of facilitating the current time-critical access targets (NEAT) in these patients. This SLIC trial demonstrated that the ADAPT ADP can be safely and effectively implemented in standard local clinical practice. The ADAPT protocol facilitated the early discharge of approximately 20% of ED patients with undifferentiated chest pain, with no adverse events reported within 30 day follow up. This was achieved with a significant reduction in ED LOS and improvement in NEAT performance. The findings suggest that with appropriately validated protocols, safe high quality care can be provided in an environment of increasing demand, performance indicators and cost containment.ADAPT accelerated diagnostic protocolNEAT

19. Other: BNP/Trop I ratio NEW BIOMARKER STRATEGY “BRAIN NATRIURETIC PEPTIDE /TROPONIN I- RATIO” FOR DETECTING ACUTE MYOCARDIAL INFARCTION FROM PATIENTS WITH CHEST SYMPTOMS AT EMERGENCY DEPARTMENT Nobutaka Ikeda; Hisao Hara J Am Coll Cardiol. 2013;61(10_S):. doi:10.1016/S0735-1097(13)60237-5