This website is intended for healthcare professionals only.

Hospital Healthcare Europe
Hospital Pharmacy Europe     Newsletter    Login            

Chest pain at the emergency department

Point-of-care testing has the potential to reduce admission rates, associated bed use and hospital costs for patients presenting with acute chest pain at the emergency department
Ulf Martin Schilling MD PhD
Department of Clinical and Experimental Medicine,
Faculty of Health Science,
Linköpings University, Sweden;
Department of Accidents and Emergencies,
University Hospital of Linköping, Sweden
Patients with chest pain and dyspnoea contribute to 8.5% of emergency department (ED) visits, and comprise 25% of patients attending the ED due to problems related to internal medicine. In these patients, one of the major goals in the ED is the identification or the exclusion of acute coronary syndromes (ACS), that is, acute myocardial infarction (AMI) and unstable angina pectoris (UAP). 
Classically, the identification of these syndromes has been made by medical history, estimation of the patient’s individual risk for ACS, physical examination, ECG and repetitive blood sampling, and eventually some form of cardiac stress test or cardiac catheterisation. Yet, literature reports that up to 5% of AMI are missed by emergency physicians, and 25% of malpractice losses for emergency physicians were a result of such misses. 
With cardiovascular death being the main cause of death worldwide according to the World Health Organization, and the possibility of medical or early invasive intervention to prevent fatal outcome, the early identification of patients at risk is not only of paramount importance for the patient but also of economic interest for the hospital.
Simultaneously, the majority of patients attending for chest pain and dyspnoea will be discharged with a diagnosis of non-cardiac causes of their symptoms. Beside the use of limited resources for the exclusion of potentially underlying disease, these patients tend to contribute to a major part to the overcrowding problem encountered in the majority of EDs.   
Thus, major efforts have been made to early identify patients at risk, and to identify patients at low or no risk of ACS. 
Currently, several models exist to process the diagnostic workup of these patients.
ST-elevation myocardial infarction
By means of an ECG, patients with ST-elevation myocardial infarction (STEMI) are immediately identified as suffering from AMI. These patients are at immediate risk for life and tend to be subjected to invasive revascularisation procedures. These patients are admitted to hospital and blood samples are taken. The common therapeutic options are percutaneous coronary intervention (PCI) with balloon dilatation and/or extraction of the intravascular thrombus, often combined with the implantation of a stent, open bypass surgery and thrombolysis.
Patients with a non-ST-elevation myocardial infarction (NSTEMI) comprise the majority of those attending the hospital due to ACS. These patients tend to be elderly and multimorbid. They are defined as patients at high risk of suffering ACS by current scoring systems; however, final diagnosis is often made by repeated positive testing for elevated troponin levels because 15–30% of all ACS are missed on the ECG.(1) Patients with NSTEMI will either be diagnosed at the ED during prolonged stay and thereby contribute to overcrowding, or they will be admitted accordingly to the ward for repeated sampling and cardiac monitoring. 
One of the major problems in these patients is the existence of chronically elevated troponin levels owing to renal failure and severe cardiovascular disease. Elevated baseline troponin levels correlate with the long-term prognosis in these patients, who are commonly admitted to the hospital, thereby contributing to bed shortages and overcrowding problems at the ED. Therapy for NSTEMI is often conservative because some of these patients might not be eligible for further invasive procedures, which can impact on the hospital’s reimbursement. 
The strategy most appropriate for the single hospital handling a patient with chest pain or dyspnoea is heavily dependant upon the local possibilities, the reimbursement system and potential obstructions in the patient flow.
Local possibilities include the staffing and competence at the ED, the use of scoring systems, the availability of the relevant laboratory analysis and the related turnaround time for blood samples, the availability of hospital beds and/or a chest pain unit (CPU), and the internal policy regarding the acceptance of emergency patients into the wards.
The ED
The ED is one of the main ways of admission to the hospital and the number of ED patients has been increasing continuously in the majority of countries. In Sweden, more than 50% of all hospital admissions are through the ED, and approximately 25% of the population attends the ED every year. As a result, EDs have increasingly developed into high-flow, high-risk units that require extensive staffing to meet the demand, especially if patient time at the ED is related to reimbursement, as in the UK and Sweden. Next to staffing, stringent clinical pathways and first-line competence of the attending physicians are of utmost importance to optimise in-department, ED flow. Further factors are rapid turnaround times of blood samples, and minimising obstacles to admission to the CPU or hospital wards.
Risk scores
Clinically validated risk scores help the attending clinician to estimate the patient’s individual risk for suffering and ACS. Risk scores are often implemented in the clinical guidelines to help in discharge, admission to the CPU, admission to the medical ward or to cardiac intensive care. 
Examples of clinically applied scoring systems are the TIMI score or the HEART score.(2,3) Interestingly, both scoring systems include the measurement of cardiac biomarkers for risk assessment, and the current definition of MI includes elevated cardiac markers, that is, troponins, for all non-fatal MI as recommended by the consensus guidelines of the American College of Cardiology and the European Society of Cardiology. 
Current biomarkers
A number of biomarkers are used in the diagnosis of ACS. The classical biomarkers (lactate dehydrogenase, creatine kinase and its MB isoenzyme and myoglobin) have essentially been replaced by the troponins, and their use is currently recommended in special circumstances only. The primacy of cardiac troponin measurement has been recognised by redefinition of AMI in the universal definition of myocardial infarction.
This redefinition includes cardiac troponin elevation as one of the diagnostic criteria and the measurement of cardiac troponin renders the measurement of other cardiac biomarkers unnecessary. Early studies suggested that the optimal time to measure cardiac troponin was 10–12 hours from hospital presentation and this recommendation was incorporated into initial clinical guidelines. More recent evidence recommended that six to nine hours from presentation was suitable.(4) The development of progressively more sensitive methods of troponin measurement has suggested that a much shorter interval (three to six hours) from presentation can be used.(5)
Among cardiologists, an intense debate is ongoing about the most appropriate protocols for the use of the different types of troponin tests, and the benefits of the different tests. While high-sensitivity troponin assays might potentially detect AMI earlier than current troponin essays, they will be positive in a major group of patients with disease other than AMI, resulting in potential overdiagnosis. Both current troponins and high-sensitivity troponins detect myocardial necrosis reliably, and the actual guidelines are based on current generation troponin assays. Criteria for diagnosis of MI include a change in markers of myocardial necrosis, that is positive troponin, a change in the levels of serial troponins or a diagnosis by autopsy,(5,6) combined with symptoms of ischaemia, ECG-changes suggestive of AMI, or imaging evidence of AMI, troponins are essential in the diagnosis of AMI.
Point-of-care testing
Point-of-care testing (POCT) offers a number of advantages that will reduce turnaround time. Samples are measured in close proximity to the patient, so do not have to be taken to the laboratory (which may cause a significant delay). The methods use whole blood, so samples do not require laboratory pre-processing before analysis. Finally, results are immediately available to the healthcare practitioner without having to be obtained elsewhere. 
Current guidelines still recommend a serial draw on arrival at the ED and 12 hours after symptom onset combined with serial ECG.(7)
Due to the fact that the majority of patients presenting with chest pain at the ED do not suffer ACS, safe, rapid rule-out protocols offer the opportunity to enhance early discharge of patients, and to reduce the costs of the diagnosis of ACS. In combination with rapid turnaround times provided by the use of contemporary point of care platforms, the potential benefits of rapid rule out protocols might be realised.
Recently, shortened protocols have been published based on both current generation troponins and high sensitivity troponins.(8–13)
Beside more sensitive tests, new biomarkers are also being tested for clinical use in the early identification and exclusion of ACS. The biomarkers under current investigation are heart-type fatty acid-binding protein (HFABP), copeptin, matrix metalloproteinase (MMP) and ischaemia-modified albumin (IMA).
HFABP is a relatively specific marker of cardiac ischaemia and is released into the blood before myocardial necrosis is established in AMI. HFABP levels rise earlier than troponin levels in cardiac ischaemia, and might facilitate earlier diagnosis of AMI. Currently, the clinical value of HFABP in ACS is under investigation.(14–16)
Copeptin is a precursor protein of the stress hormone, arginine vasopressin. It has been shown to be elevated in patients with acute severe disease, such as severe sepsis and AMI, and is considered to correlate with the patient’s prognosis. In several trials, the value of copeptin combined with troponin assays in the early diagnosis and exclusion has been tested. To date, no final conclusion has been reached as the views regarding copeptin vary widely. In one study, for example, AMI (but not UA) was excluded with a single sampling of troponin combined with copeptin; in another study, however, no additional value of copeptin in addition to troponin could be found.(17–19)
Matrix metalloproteinases (including MMP subtype 9) have recently come under discussion as markers for the development of artherosclerotic plaques, their modulation, their rupture and resulting inflammation. Levels have been shown to be higher in patients with UA than in patients with stable angina, and in the late stage of AMI compared with the early stages.(20)
The clinical value of MMP9 is yet to be determined, especially as other inflammatory markers such as high-sensitivity C-reactive protein have been shown to be of prognostic rather than diagnostic value in ACS.(21)
IMA is a form of albumin that is altered by tissue ischaemia. In ACS, it can be detected before myocardial necrosis occurs, that is, in patients with UA but not AMI. Although IMA is non-specific, it might prove to be of diagnostic value in patients with chest pain due to UA and negative troponin. The clinical value of IMA has yet to be determined. 
CPUs are hospital units, or sometimes specialised units at the ED, dedicated to ruling out ACS in patients with low-to-moderate risk of ACS. CPUs have been shown to be cost efficient because of the rapid turnaround times for patients, and owing to the standardised work-up of patients attending for chest pain without obstructing the ED or cardiac intensive care with patients with low probability of ACS.
In those units, patients will usually be monitored for arrhythmia, and undergo repetitive sampling of cardiac biomarkers. As soon as the patient is deemed not to be suffering ACS, discharge is possible. Some CPUs offer the possibility of cardiac stress testing, further condensing the process of ruling out ACS; however, standards between different countries vary.
Minimal standards for CPUs in Germany have been defined by the German Society of Cardiology as following: integration into an emergency unit led by cardiologists; at least four beds for continuous surveillance, available 24/7 with immediate access to cardiac catheterisation; monitoring on all beds; transthoracic and transesophageal echocardiography available 24/7; and with a recommendation of the unit being a separate unit in the hospital with at least one additional bed per 50,000 population and continuous education. The extensive criteria and recommendations were published in 2008.(22)
The ESCAPE trial in the UK required an immediate cardiac stress test (treadmill testing) for all patients with negative series of cardiac markers but no cardiologist surveillance.(23) As a result of these criteria, CPUs are expensive because of the level and the expertise of staffing required, and because of the technology required. However, they are cheaper than patient admissions, and offer the potential of rapid patient turnover because the diagnostic process can be reduced to a minimal amount of time (in the ESCAPE trial 83% of admitted patients were discharged directly from the CPU, and economic analysis was in favour of the CPU(24)). 
In an Italian analysis of different strategies in the evaluation of acute chest pain, a strategy using pharmacological stress echocardiography was estimated to be the most cost efficient; however, significant differences in costs for each strategy have been found in different national studies.(25) 
Acceptance to the ward
Acceptance of emergency patients to the ward is a political rather than a medical issue. However, in several countries, restrictions are applied regarding the time a patient should be waiting at the ED (the four-hour limit), and reimbursement by the authorities or insurance companies will be related to the limit. As prolonged waiting times at the ED tend to be connected to overcrowding, which, in turn, has been shown to be an independent risk-factor of elevated mortality and morbidity, and connected to prolonged length of stay at the hospital ward after admission, any obstacles to medically motivated acceptance of an emergency patient to the ward are expensive for the hospital. To minimise such obstacles, the identification of the underlying reasons is money well invested.
Novel imaging methods
Cardiac CT scans
Recently, the use of cardiac CT scans has been introduced in clinical practice to visualise the coronary arteries and to exclude significant coronary arterial stenosis in patients at low risk of acute coronary syndromes (<30%), which reduces costs for admission, stress test and invasive investigations.(7,26) More expensive functional imaging, that is, stress-echocardiography, functional MRI or myocard-scintigraphy is recommended as an investigation in patients at moderate risk (30–60%), with invasive coronary angiography recommended for patients at greater than 60% risk for ACS.(7)
Several pathways to rule out ACS are applied clinically. At the current level, three major diagnostic strategies to rule out myocardial infarction can be found in the literature: i) admission of the patient for serial testing, re-evaluation and stress-test in selected cases; ii) rapid serial testing and stress-test; and iii), combination with novel biomarkers. CPUs have been shown to reduce the length of stay at the hospital for chest pain patients, and are cost efficient. However, through the use of novel protocols, such as rapid serial testing, a significant number of admissions can be avoided, potentially questioning the need of CPUs. Novel biomarkers, in turn, might facilitate the exclusion of coronary syndromes at the emergency department on first-line testing and result in even greater reductions in the number of admissions (and thus costs), but yet have to prove their practical value.
  1. Meune C et al. Patients with acute coronary syndrome and normal high-sensitive troponin. Am J Med 2011;124:1151–7. 
  2. Antman EM et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA 2000;284(7):835–42.
  3. Six AJ, Backus BE, Kelder JC. Chest pain in the emergency room: value of the HEART score. Neth Heart J 2008;16(6):191–6.
  4. Schilling UM. POCT in the emergency department: a review. Hosp Healthcare Eur 2013;99–102.
  5. Raphael Twerenbold R et al. High-sensitive troponin T measurements: what do we gain and what are the challenges? Eur Heart J 2012;33(5): 579–86.
  6. Korley FK, Jaffe Allan S. Preparing the United States for high-sensitivity cardiac troponin assays. J Am Coll Cardiol 2013;61:1753–8.
  7. National Institute for Health and Care Excellence. Chest pain of recent onset. Assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. NICE clinical guideline 95. (accessed 13 February 2014).
  8. Thygesen K et al. Study Group on Biomarkers in Cardiology of ESC Working Group on Acute Cardiac Care. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J 2012;33(18):2252–7. 
  9. Fesmire FM et al. The Erlanger chest pain evaluation protocol: a one-year experience with serial 12-lead ECG monitoring, two-hour delta serum marker measurements, and selective nuclear stress testing to identify and exclude acute coronary syndromes. Ann Emerg Med 2002;40(6):584–94.
  10. Cullen L et al. 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(14):1242–9. 
  11. Soremekun OA et al. Safety of a rapid diagnostic protocol with accelerated stress testing. Am J Emerg Med 2013;S0735-6757(13)00691-8.
  12. Than M et al. A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: A randomized clinical trial. JAMA Intern Med 2013;doi: 10.1001/jamainternmed.2013.11362.
  13. 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;59(23):2091–8. 
  14. Colli A et al. Heart fatty acid binding protein in the diagnosis of myocardial infarction: where do we stand today?” Cardiology 2007;108(1):4–10. 
  15. Collinson PO. Randomised Assessment of Treatment using Panel Assay of Cardiac markers – Contemporary Biomarker Evaluation (RATPAC CBE). Health Technol Assess 2013;17(15):v-vi, 1-122.
  16. Reiter M et al. Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial infarction. Heart 2013;99(10):708–14.
  17. Lotze U et al. Combined determination of highly sensitive Troponin T and copeptin for the early exclusion of acute myocardial infarction: first experiences in an emergency department of a general hospital. Vasc Health Risk Manage 2011;7:509–15. 
  18. Keller T et al. Copeptin improves early diagnosis of acute myocardial infarction. J Am Coll Cardiol 2010;55(19):2096–106. 
  19. National Institute for Health and Care Excellence. BRAHMS copeptin assay to rule out myocardial infarction in patients with acute chest pain. NICE medical technology guidance 4; 2011. 
  20. Xu S et al. Clinical significance of leukotriene b4 and extracellular matrix metalloproteinase inducer in acute coronary syndrome. Clin Invest Med. 2013;36(6):E282.
  21. Koenig W. High-sensitivity C-reactive protein and atherosclerotic disease: from improved risk prediction to risk-guided therapy. Int J Cardiol 2013;168(6):5126–34. 
  22. Breuckmann F et al. Kriterien der Deutschen Gesellschaft für Kardiologie – Herz- und Kreislaufforschung für “Chest-Pain-Units. Kardiologe 2008:1–6.
  23. Arnold J, Goodacre S, Morris F. Structure, process and outcome of chest pain units established in the ESCAPE Trial. Emerg Med J 2007;24(7)462–6.
  24. Goodacre S, Dixon S. Is a chest pain observation unit likely to be cost effective at my hospital? Extrapolation of data from a randomized controlled trial. Emerg Med J 2005;22(6)418–22.
  25. Bedetti G et al. Economic analysis including long-term risks and costs of alternative diagnostic strategies to evaluate patients with chest pain. Cardiovasc Ultrasound 2008;6:21. 
  26. Priest VL et al. Cost-effectiveness of coronary computed tomography and cardiac stress imaging in the emergency department: a decision analytic model comparing diagnostic strategies for chest pain in patients at low risk of acute coronary syndromes. JACC Cardiovasc Imaging 2011;4(5):549–56.