ACCELERATED STRATEGIES IN THE ASSESSMENT OF EMERGENCY PATIENTS WITH POSSIBLE ACUTE CORONARY SYNDROMES Louise Cullen MBBS (Hons) FACEM Submitted in (partial) fulfilment of the requirements for the degree of Doctor of Philosophy by publication School of Public Health Faculty of Health Queensland University of Technology 2015 Keywords Acute coronary syndrome (ACS), Accelerated diagnostic protocols (ADP), Acute myocardial infarction (AMI), Chest pain, Emergency Department (ED) Abstract This PhD by publication assesses strategies aimed at improving the assessment process of patients presenting to the Emergency Department with symptoms of possible acute coronary syndrome The aim is to determine if more refined biomarker analysis and risk stratification processes may identify patients at low risk who may safely be able to be discharged from the Emergency Department The strategies are focused on accelerated protocols that maintain clinical safety whist improving the efficiency of the assessment process In addition to this, the thesis focuses on clinical implications of the differences in clinical management strategies based on different biomarkers and in particular troponin assays Troponin is the key cardiac biomarker detected in myocardial necrosis, and therefore is elevated in patients who have had a myocardial infarction; however the performance and accuracy of different troponin assays vary This variation in the precision of the assay to detect low concentrations may impact the clinical care of patients presenting to Emergency Department with symptoms of possible ACS This is a thesis by publication that compiles the research outcomes of a cohesive program of research This program was conducted by an international consortium within which the author was a joint leader and in particular led the research conducted at the Royal Brisbane and Women’s hospitals and all sites in China, Indonesia, Korea, and Thailand involved in the ASPECT trial She was the joint principal researcher in the ASPECT (Chapter 4), ADAPT (Chapter 5) and modified ADAPT (Chapter 6) studies Additionally the candidate obtained research funding through granting bodies including Queensland Emergency Medicine Research Foundation and the Royal Brisbane and Women’s Foundation to conduct the research, and contracted with private companies to allow investigation of preclinical assays The objective of this program of research was to contribute the evidence base for improved guidelines for the management of Acute Coronary Syndrome by documenting the significance, safety and effectiveness of rapid use of existing troponin assays and use of highly sensitive assays for troponin, in addition to novel accelerated risk assessment processes The outcomes of this program have been extensively published by the international consortium The candidate has contributed to more than 50 published papers (12 as first author) in peer reviewed journals over the last six years in very high ranking journals including one paper published in Lancet Further articles remain under consideration Additionally she has authored four book chapters (two as first author) and has had over 22 conference abstracts published The research reported in this thesis address the core concepts, data collection and analytical methods, safety and clinical effectiveness of enhanced use of troponin testing, accelerated diagnostic protocols and the practical application of rapid assessment processes in clinical care The publications chosen for inclusion in this thesis are those that speak to the core principles of ACS evaluation and which tests the clinical effectiveness of new analytical methods Chapter provides an overview of the clinical issue and of the research program and introduces the aims, objectives and research questions An overview of the clinical context and literature provides the ground work for the design of the research and the methods used Chapter (Publication one) defines the current process of assessment and outcomes in the assessment of ED patients based on the current National Heart Foundation and Cardiac Society of Australia and New Zealand (NHF/CSANZ) Society Guidelines This paper aims to establish a baseline by which improved strategies can be measured in terms of their safety, efficiency and costs Chapter (Publication two) provides a robust description of data elements and their definitions combined into a standardised dataset for use in ED-based research of patients with possible ACS This provides the framework for consistent reporting in ED-based publications investigating patients with chest pain Chapter (Publication three) investigates the safety of an accelerated diagnostic protocol (ADP), using a multi-marker approach in a prospective, international multi-centred observational trial evaluation involving 3582 patients from nine countries Chapter (Publication four) assesses the safety of the ADP for the assessment of ED patients with chest pain, however in this project, the multi-marker approach was replaced with a single cardiac biomarker, troponin, measured by sensitive troponin assays This study drew participants (n= 1975) from a subset of the cohort used in Chapter It involved only patients recruited in Brisbane, Australia and Christchurch, New Zealand Chapter (Publication five) refined the ADAPT accelerated diagnostic pathway replacing the troponin results from sensitive troponin assays with troponin results from a new high sensitivity troponin I assay At the time of this study, the new assay did not have TGA approval for clinical use in Australia The results were obtained from the analysis of stored samples collected during the ASPECT study outlined in Chapter and involved 1635 patients In addition, this chapter also describes the first independent validation of the Modified ADAPT ADP in a welldescribed geographically distinct cohort from the Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) Study led by Prof Christian Mueller in Basel, Switzerland (n=909) Chapter (Publication six) reports on the translation of research described in Chapter into clinical practice, with the implementation of the ADAPT ADP at the Nambour General Hospital, Queensland, Australia Chapter aims to draw together the findings of the program of research and to express the implications and application of those findings to clinical practice Accelerated diagnostic protocols for the assessment of patients presenting to the Emergency Department with symptoms of possible ACS are safe and effective at identifying low risk patients who can be managed in an outpatient setting It is estimated that over 20% of patients presenting to the ED with chest pain could be safely discharged significantly reducing the health system cost This important finding will inform clinicians and health services about improvements that can be made at this current time in the process of care of ED patients Key areas of investigation that still require research have been uncovered during this study The true implication of the analytical differences in troponin assays on actual patient care and outcomes requires additional examination Recently there has been much interest in point-of-care analysers, which have the benefit over labbased assays in that the time that results are available to clinicians is more rapid In addition they not require the infrastructure of a laboratory to run the tests, making them most useful in rural and regional areas The analytical characteristics of theses assays though are significantly different to most lab assays and the true implications of their use, including safety and patient flow issues in the setting of an ADP are currently unknown Notes Permission has been granted by all co-authors for the inclusion of the papers in this manuscript Additionally the publishers of the relevant Journals have all provided approval for the incorporation of the articles used in this thesis Table of Contents Keywords Abstract .3 List of Abbreviations 11 Statement of Original Authorship 13 Preamble 15 Chapter Introduction 17 Chapter Paper One 31 Chapter Paper Two .61 Chapter Paper Three 107 Chapter Paper Four 143 Chapter Paper Five 177 Chapter Paper Six .215 Chapter Summary and Conclusions 231 Acknowledgements .241 References .243 List of publications by Candidate 248 10 List of publications by Candidate Published Journal Papers Louise Cullen, John French, Tom Briffa, Julie Redfern, Christopher Hammett, David Brieger, William Parsonage, Jeff Lefkovits, Chris Ellis, Tom David, Carolyn Astley, Tegwen Howell, John Elliott, Derek P Chew Association of highly sensitive troponin assays availability and ACS care: Insights from the SNAPSHOT registry Medical Journal of Australia 2015 Jan 19;202(1):36-9 Meller B, Cullen L, Parsonage WA, Greenslade JH, Aldous S, Reichlin T, Wildi K, Twerenbold R, Jaeger C, Hillinger P, Haaf P, Puelacher C, Kern V, Rentsch K, Stallone F, Gimenez MR, Ballarino P, Basseti S, Walukiewicz A, Troughton R, Pemberton CJ, Richards AM, Chu K, Reid CM, Than M, Mueller C Accelerated diagnostic protocol using high-sensitivity cardiac troponin T in acute chest pain patients International Journal of Cardiology 2015;184, 208-215 Greenslade JH, Kavsak P, Parsonage W, Shortt C, Than M, Pickering JW, Aldous S, and Cullen, L Combining presentation high-sensitivity cardiac troponin I and glucose measurements to rule-out an acute myocardial infarction in patients presenting to emergency department with chest pain Clinical Biochemistry 2014; 48(4-5) 288-291 Hickman PE, Lindahl B, Cullen L, Koerbin G, Tate J and Potter JM Decision limits and the reporting of cardiac troponin: Meeting the needs of 249 both the cardiologist and the ED physician Critical Reviews in Clinical Laboratory Sciences 2014; 52(1) 28-44 Gardner LS, Nguyen-Pham S, Greenslade J, Parsonage W, D’Emden M, Than M, Aldous S, Brown AFT, Cullen L Admission glycaemia and its association with acute coronary syndrome in Emergency Department patients with chest pain Emergency Medicine Journal 2014;0:1-5 Aldous S, Richards AM, George PM, Cullen L, Parsonage WA, Flaws D, Florkowski CM, Troughton RW, O’Sullivan JW, Reid CM, Banniester L,Than M Comparison of new point-of-care troponin assay with high sensitivity troponin in diagnosing myocardial infarction International Journal of Cardiology 2014;177(1)182-186 Derek P B Chew and Louise Cullen The promise of high-sensitivity troponin testing Med J Aust 2014; 201 (3): 125-126 Than M, Flaws D, Sanders S, Doust J, Glaziou P, Kline J, Aldous S, Troughton R, Reid, C, Parsonage WP, Frampton C, Greenslade JH, Deely JM, Hess E, Sadiq AB, Singleton R, Shopland R, Vercoe L, WoolhouseWilliams M, Ardagh M, Bossuyt, P, Bannister L, Cullen L Development and validation of the Emergency Department Assessment of Chest pain Score and 2h accelerated diagnostic protocol EMA 2014 26(1) 33-44 Simpson AJ, Potter JM, Koerbin G, Oakman C, Cullen L, Wilkes GJ, Scanlan SL, Parsonage W, Hickman PE Observed Within-Person Variation of Cardiac Troponin in Emergency Department Patients for Determination of Biological Variation and Percentage and Absolute Reference Change Values Clin Chem 2014 60 (6):848-54 250 10 Cullen L, Parsonage W Acute assessment of possible cardiac chest pain Medicine Today 2013; 14(12X): 41-44 11 Saunders M, Cullen L Re: Review article: Elevated troponin: Diagnostic gold or fool's gold? Emergency Medicine Australasia 2014 26 (4):414 12 Pretorius CJ, Cullen L, Parsonage WA, Greenslade JH, Tate, JR, Wilgen U, Ungerere JPJ Towards a consistent definition of a significant delta troponin with Z-scores: A way out of chaos? Eur Heart J Acute Cardiovasc Care 2014;3(2):149-57 13 Cullen L, Aldous S, Than M, Greenslade J, Tate J, George PM, Hammett CJ, Richards AM, Ungerer JPJ, Troughton RW, Brown AFT, Flaws DF, Lamanna A, Pemberton CJ, Florkowski C, Pretorius CJ, Chu K, Parsonage WA 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 Clin Biochem 2014;47(6):321-6 14 Cullen L, Greenslade JH, Than M, Brown AFT, Hammett CJ, Lamanna A, Flaws DF, Chu K, Fowles LF, Parsonage WA The new Vancouver Chest Pain Rule using troponin as the only biomarker: An external validation study Am J Emerg Med 2014; Feb;32(2):129-34 15 Cullen L, Greenslade J, Than M, Tate J, Ungerer JPJ, Pretorius C, Hammett CJ, Lamanna A, Chu K, Brown AFT, Parsonage WA Performance of risk stratification for acute coronary syndrome with hour sensitive troponin assay results Heart Lung Circ 2014;23(5):428-34 251 16 Parsonage WA, Tate JR, Greenslade JH, Hammett CJ, Ungerer JP, Pretorius CJ, Cullen L Effect of recalibration of the hs-TnT assay on diagnostic performance Clin Chem Lab Med 2014;52(2):e25-e7 17 Parsonage WA, Greenslade JH, Hammett CJ, Lamanna A, Tate J, Ungerer JPJ, Chu K, Than M, Brown AFT, Cullen L Validation of an accelerated high sensitivity troponin T assay protocol in an Australian cohort with chest pain Med J Aust 2014; 200(3):161-5 18 Than M, Aldous S, Lord SJ, Goodacre S, Frampton CM, Troughton R, George P, Florkowski CM, Ardagh M, Smyth D, Jardine DL, Peacock WF, Young J, Hamilton G, Deely JM, Cullen L, Richards AM A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: A randomized clinical trial JAMA Intern Med 2013:174 (1): 51-8 19 Scott AC, Bilesky J, Lamanna A, Cullen L, Brown AFT, Denaro C, Parsonage WA 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 Emerg Med Australas 2014 26(2):170-6 20 Scott AC, O’Dwyer K, Cullen L, Brown AFT, Denaro C, Parsonage WA Implementation of a chest pain management service improves patient care and reduces length of stay Crit Pathw Cardiol 2013 13(1): 9-13 21 Parsonage WA, Tate JR, Greenslade JH, Hammett CJ, Ungerer JP, Pretorius CJ, Brown AF, Cullen L Effect of recalibration of the hs-TnT assay on diagnostic performance Clin Chem Lab Med 2014 52(2): e25-7 252 22 Cullen L, Mueller C, Parsonage WA, Wildi K, Greenslade JH, Twerenbold R, Aldous S, Meller B, Tate JR, Reichlin T, Hammett CJ, Zellweger C, Ungerer JP, Rubini Gimenez M, Troughton R, Murray K, Brown AF, Mueller M, George P, Mosimann T, Flaws DF, Reiter M, Lamanna A, Haaf P, Pemberton CJ, Richards AM, Chu K, Reid CM, Peacock WF, Jaffe AS, Florkowski C, Deely JM, Than M 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 J Am Coll Cardiol 2013;62:1242-1249 23 Cullen L, Parsonage WA, Greenslade J, Lamanna A, Hammett CJ, Than M, Tate J, Kalinowski L, Ungerer JP, Chu K, Brown A Delta troponin for the early diagnosis of AMI in emergency patients with chest pain Int J Cardiol 2013;168:2602-2608 24 Cullen L, Greenslade J, Hammett CJ, Brown AF, Chew DP, Bilesky J, Than M, Lamanna A, Ryan K, Chu K, Parsonage WA Comparison of three risk stratification rules for predicting patients with acute coronary syndrome presenting to an Australian emergency department Heart Lung Circ 2013;22:844-851 25 George T, Ashover S, Cullen L, Larsen P, Gibson J, Bilesky J, Coverdale S, Parsonage W Introduction of an accelerated diagnostic protocol in the assessment of emergency department patients with possible acute coronary syndrome: the Nambour Short Low-Intermediate Chest pain project Emerg Med Australas 2013;25:340-344 26 Greenslade JH, Cullen L, Than M, Aldous S, Chu K, Brown AF, Richards AM, Pemberton CJ, George P, Parsonage WA Validation of the Vancouver 253 Chest Pain Rule using troponin as the only biomarker: a prospective cohort study Am J Emerg Med 2013;31:1103-1107 27 Greenslade JH, Cullen L, Kalinowski L, Parsonage W, Palmer S, Aldous S, Richards M, Chu K, Brown AF, Troughton R, Pemberton C, Than M Examining renal impairment as a risk factor for acute coronary syndrome: A prospective observational study Ann Emerg Med 2013;62:38-46 28 Parsonage WA, Cullen L, Younger JF The approach to patients with possible cardiac chest pain Med J Aust 2013;199:30-34 29 Peacock WF, Cullen L, Mueller C, Than M Troponin testing: End of an era? Clin Biochem 2013;46:1627-1628 30 Six AJ, Cullen L, Backus BE, Greenslade J, Parsonage W, Aldous S, Doevendans PA, Than M The HEART score for the assessment of patients with chest pain in the emergency department: a multinational validation study Crit Pathw Cardiol 2013;12:121-126 31 Than M, Herbert M, Flaws D, Cullen L, Hess E, Hollander JE, Diercks D, Ardagh MW, Kline JA, Munro Z, Jaffe A What is an acceptable risk of major adverse cardiac event in chest pain patients soon after discharge from the Emergency Department?: A clinical survey Int J Cardiol 2013;166:752754 32 Than M, Flaws D, Cullen L, Deely J Cardiac Risk Stratification Scoring Systems for Suspected Acute Coronary Syndromes in the Emergency Department Current 2013;1(1):53-63 254 Emergency and Hospital Medicine Reports 33 Aldous SJ, Richards M, Cullen L, Troughton R, Than M Diagnostic and prognostic utility of early measurement with high-sensitivity troponin T assay in patients presenting with chest pain CMAJ 2012;184:260-268 34 Aldous SJ, Richards M, Cullen L, Troughton R, Than M A 2-hour thrombolysis in myocardial infarction score outperforms other risk stratification tools in patients presenting with possible acute coronary syndromes: comparison of chest pain risk stratification tools Am Heart J 2012;164:516-523 35 Aldous SJ, Richards MA, Cullen L, Troughton R, Than M A new improved accelerated diagnostic protocol safely identifies low-risk patients with chest pain in the emergency department Acad Emerg Med 2012;19:510-516 36 Cullen L, Parsonage WA, Greenslade J, Lamanna A, Hammett CJ, Than M, Ungerer JP, Chu K, O'Kane S, Brown AF 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 Emerg Med Australas 2012;24:595-603 37 Greenslade JH, Cullen L, Parsonage W, Reid CM, Body R, Richards M, Hawkins T, Lim SH, Than M Examining the signs and symptoms experienced by individuals with suspected acute coronary syndrome in the Asia-Pacific region: a prospective observational study Ann Emerg Med 2012;60:777-785.e773 38 Parsonage WA, Cullen L, Younger JF, Than M The role of cardiac computed tomography in assessment of acute chest pain Heart Lung Circ 2012;21:763; author reply 763-764 255 39 Scott IA, Cullen L, Tate JR, Parsonage W Highly sensitive troponin assays-a two-edged sword? Med J Aust 2012;197:320-323 40 Backus BE, Six AJ, Cullen L, Greenslade J, Than M The HEART score for chest pain patients at the emergency department validated in a multi centre Asia-Pacific population Eur Heart J 2012;33:6-7 41 Than M, Cullen L, Aldous S, Parsonage WA, Reid CM, Greenslade J, Flaws D, Hammett CJ, Beam DM, Ardagh MW, Troughton R, Brown AF, George P, Florkowski CM, Kline JA, Peacock WF, Maisel AS, Lim SH, Lamanna A, Richards AM 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;59:2091-2098 42 Aldous SJ, Richards AM, Cullen L, Than MP Early dynamic change in high-sensitivity cardiac troponin T in the investigation of acute myocardial infarction Clin Chem 2011;57:1154-1160 43 Aldous S, Richards AM, Cullen L, Than M Early dynamic change in highsensitivity cardiac troponin T in the investigation of acute myocardial infarction Clin Chem 2011;58:author reply 313-314 44 Cullen L Troponin: a risk-defining biomarker for emergency department physicians Emerg Med Australas 2011;23:391-394 45 Mangleson FI, Cullen L, Scott AC The evolution of chest pain pathways Crit Pathw Cardiol 2011;10:69-75 46 Than M, Cullen L, Reid CM, Lim SH, Aldous S, Ardagh MW, Peacock WF, Parsonage WA, Ho HF, Ko HF, Kasliwal RR, Bansal M, Soerianata S, Hu D, Ding R, Hua Q, Seok-Min K, Sritara P, Sae-Lee R, Chiu TF, Tsai KC, Chu 256 FY, Chen WK, Chang WH, Flaws DF, George PM, Richards AM A 2-h diagnostic protocol to assess patients with chest pain symptoms in the AsiaPacific region (ASPECT): a prospective observational validation study Lancet 2011;377:1077-1084 47 Than M, Cullen L, Reid CM, Lim SH, Richards M Rapid diagnositic protocol for patients with chest pain: Reply Lancet 2011;378:398-399 48 Brown AFT, Cullen L, Than M Future developments in chest pain diagnosis and management Medical Clinics of North America 2010;94:375-400 49 Cullen L, Than M, Brown AFT, Richards M, Parsonage W, Flaws D, Hollander JE, Christenson RH, Kline JA, Goodacre S, Jaffe AS Comprehensive standardized data definitions for acute coronary syndrome research in emergency departments in Australasia Emergency Medicine Australasia 2010;22:35-55 50 Cullen L, Taylor D, Taylor S, Chu K Nebulized lidocaine decreases the discomfort of nasogastric tube insertion: a randomized, double-blind trial Ann Emerg Med 2004;44:131-137 Book Chapters Cullen L, Than M, White HD, Jaffe AS The reporting and interpretation of troponin results - laboratory and clinical aspects; in Tate JR, Johnson R, Jaffe AS, Panteghini M (eds): The Clinical Biochemist monograph: Laboratory and clinical issues affecting the measurement and reporting of cardiac troponins: a guide for clinical laboratories Alexandria, NSW, AACB, 2012 257 Than M, Cullen L The challenges of sensitive and highly sensitive troponin assay use in the emergency department - the emergency physician's perspective; in Tate JR, Johnson R, Jaffe AS, Panteghini M (eds): The Clinical Biochemist monograph: Laboratory and clinical issues affecting the measurement and reporting of cardiac troponins: a guide for clinical laboratories Alexandria, NSW, AACB, 2012 Tate JR, Panteghini M, Cullen L, Jaffe AS An overview of clinical and laboratory issues affecting the laboratory measurement and reporting of troponin; in Tate JR, Johnson R, Jaffe AS, Panteghini M (eds): The Clinical Biochemist monograph: Laboratory and clinical issues affecting the measurement and reporting of cardiac troponins: a guide for clinical laboratories Alexandria, NSW, AACB, 2012: 9-14 Cullen L, Fleming J Biomarkers in Emergency Medicine; in David S (ed): The Textbook of Emergency Medicine India, Wolters Kluwer, 2012 Published Abstracts Parsonage W, Cullen L, Greenslade J, Tate J, Ungerer J, Hammett C, Pretorius C, Chu K, Brown AFT Comparison of highly sensitive Troponin I and T results in the diagnosis of acute myocardial infarction J Am Coll Cardiol 2013;61:E228 Carlton EW, Cullen L, Than M, Greaves K A modified Goldman Risk Score in combination with high-sensitivity troponin proves superior to TIMI in the evaluation of suspected acute cardiac chest pain Journal of the American College of Cardiology 2014;63(12_S) 258 George T, Cullen L, Parsonage W, Larsen P, Coverdale S, Ashover S, et al Use of an Accelerated Diagnostic Protocol in the Assessment of Emergency Department Patients with Possible Acute Coronary Syndrome Heart, Lung and Circulation 2013;22:S53-S Parsonage W, Cullen L, Greenslade J, Aldous S, George P, Lamanna A, et al A Study Comparing Diagnostic Accuracy of High Sensitivity Assays of Troponin I and Troponin T for Myocardial Infarction Within Two Hours of Presentation to the Emergency Room Heart, Lung and Circulation 2013;22:S207-S8 Parsonage W, Greenslade J, Ungerer J, Tate J, Pretorius C, Hammett C, Cullen L A Study of the Effect of the Manufacturers Advised Recalculation of the High Sensitivity Troponin T Assay on the Early Detection of Acute Myocardial Infarction in Patients Presenting to the Emergency Department Heart, Lung and Circulation 2013;22:S208-S Meller B, Cullen L, Parsonage W, Greenslade J, Aldous S, Reichlin T, et al Accelerated diagnostic protocol using high-sensitivity cardiac troponin T in acute chest pain patients European Heart Journal 2013;34(suppl 1):21 Cullen L, Parsonage W, Greeenslade J, Aldous S, George P, Hammett C, et al Diagnosis of Acute Myocardial Infarction in Emergency Patients with Chest Pain Using a Two Hour Algorithm with Highly Sensitive Troponin I Assay Results Heart, Lung and Circulation 2013;22:S35-S6 Cullen L, Parsonage W, Greenslade J, Aldous S, George P, Lamanna A, et al Diagnosis of AMI Using Sex-Specific Cut-Off Values of a Highly Sensitive 259 Troponin I Assay in Emergency Department Patients With Chest Pain Heart, Lung and Circulation 2013;22:S36-S Cullen L, Greenslade J, Than M, Aldous S, George P, Hawkins T, et al Identification of Low Risk Emergency Patients with Symptoms of Possible Acute Coronary Syndrome: External Validation of the Vancouver Chest Pain Rule Heart, Lung and Circulation 2013;22:S42-S 10 Bilesky J, Younger J, Parsonage W, Greenslade J, Lamanna A, Hammett C, Brown A, Chu K, Cullen L Suitability of Emergency Department (ED) Patients with Undifferentiated Chest Pain for CT Coronary Angiography (CTCA) Heart Lung Circ 2012;21, Supplement 1:S260 11 Carr L, Bilesky J, Younger J, Parsonage W, Greenslade J, Brown A, Cullen L Utility of a Six-Hour TIMI Risk Score (TIMI-6) to Improve Risk Stratification in Intermediate Risk Chest Pain Patients Heart Lung and Circ 2012;21, Supplement 1:S264 12 Cullen L, Brazil V, Dooris M, Baldwin M, Muller H ‘Stemi-sim’ – A ‘Process of Care’ Simulation can Help Improve Door to Balloon Times for Patients with ST Elevation Myocardial Infarction Heart Lung Circ 2012;21, Supplement 1:S50 13 Bilesky J, Cullen L, Greenslade J, Lamanna A, Hammett C, Brown A, et al Prospective Observational Validation of the Heart Foundation of Australia (HF)/Cardiac Society of Australian and New Zealand (CSANZ) Risk Stratification Tool in Patients Presenting to the Emergency Department with Acute Chest Pain Heart, Lung and Circulation 2012;21:S49 260 14 Cullen L, Parsonage W, Greenslade J, Lamanna A, Hammett C, Than M, Ungerer JPJ, Chu K, O’Kane S, Brown AFT Comparison of Early Biomarker Strategies with the Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines (HFA/CS-ANZ) for Risk Stratification of Emergency Department Patients Presenting with Chest Pain Heart Lung Circ 2012;21, Supplement 1:S33-S34 15 Cullen L, Parsonage WA, Greenslade J, Lamanna A, Hammett C, Than M, Tate J, Kalinowski L, Ungerer J, Chu K, Brown AFT Delta Troponin for the Diagnosis of AMI: Comparison of and 6h Metrics Using a Contemporary Troponin Assay for Emergency Department Patients with Chest Pain Heart Lung Circ 2012;21, Supplement 1:S35-S36 16 Lamanna A, Scott A, Bilesky J, Cullen L, Greenslade J, Brown A, Denaro C, Parsonage W The Utility of Exercise Stress Test in the Risk Stratification of Women Aged 40–54 Years with Suspected Intermediate Risk Acute Coronary Syndrome Heart Lung Circ 2012;21, Supplement 1:S51 17 Hunter J, Hammett C, Cullen L, Greenslade J, Brown AFT, Chu K, Parsonage W Indeterminate Troponin Elevations Have Poor Positive Predictive Value for Acute Coronary Syndrome in an Emergency Department population Heart Lung Circ 2011;20S:S1–S155 18 Lamanna A, Scott A, Bilesky J, Greenslade J, Cullen L, Denaro C, Brown AFT, Parsonage W Limited Utility of Exercise Stress Test in the Evaluation of Suspected Acute Coronary Syndrome in Patients Aged Less Than 40 Years with Intermediate Risk Features Heart Lung Circ 2011;20S: S156-S251 261 19 Cullen LA, Greenslade JH, Brown AFT, Hammett C, Than M, Chu K, Ungerer J, Parsonage WA Comparison of and hour time intervals in the diagnosis of acute myocardial infarction Eur Heart J 2011;32:725 20 Cullen LA, Than MP, Reid CM, Lim SH, Aldous S, Ardagh M, Richards AM The ASia-Pacific Evaluation of Chest pain Trial (ASPECT): two-hour emergency department rule-out evaluation for chest pain Eur Heart J 2011;32:723 21 Camuglia A, Gibson J, Hammett C, Brown AFT, Cullen L, Parsonage WA Positive Predictive Value of Exercise Electrocardiography in Patients Referred from a Brisbane Emergency Department with Chest Pain Heart Lung Circ 2010;19: S33 22 Dooris M, Muller H, Cullen L Factors affecting time to mechanical reperfusion for ST elevation myocardial infarction Heart Lung Circ 2009;18: S211 In press Reichlin T, Cullen L, Parsonage WA, Greenslade JH, Twerenbold R, Reiter M, Moehring B, Wildi K, Mueller S, Zellweger C, Mosimann T, Giminez MR, Haaf P, Rentsch K, Osswald S, and Mueller C Two hour algorithm for triage towards rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac Troponin T American Journal of Medicine 2014 In Press Accepted Manuscript Greenslade JH, Beamish D, Parsonage W, Hawkins T, Schluter J, Dalton E, Parker K, Than M, Hammett C, Lamanna A, Cullen L Relationship between 262 physiological parameters and acute coronary syndrome in patients presenting to the Emergency Department with undifferentiated chest pain Journal of Cardiovascular Nursing 2015; February Online ahead of print Louise Cullen, Jaimi H Greenslade, Katharina Merollini, Nicholas Graves, Christopher J Hammett, Tracey Hawkins, Martin Than, Anthony Brown, Christopher Bryan Huang, Seyed Ehsan Panahi, Emily Dalton, William A Parsonage Process, cost and outcomes in the assessment of patients presenting to an Australian Emergency Department with symptoms of possible cardiac chest pain Accepted January 2015 by the the Medical Journal of Australia Submitted Kimberley Ryan, Jaimi Greenslade, Emily Dalton, Kevin Chu, Anthony FT Brown, Louise Cullen Factors influencing triage assignment of Emergency Department patients ultimately diagnosed with acute myocardial infarction Submitted to the Australian Emergency Nursing Journal July 2014 263 ... context and clinical assessment including electrocardiograph (ECG) recordings International guidelines utilising troponin testing in the assessment of patients with possible ACS emerged in the early... together the findings of the program of research and to express the implications and application of those findings to clinical practice Accelerated diagnostic protocols for the assessment of patients. .. a change in concentration over time being the basis for the diagnosis of AMI and underpinning the importance of the serial measurement of troponin International guidelines, including the recommendations