Emergency Departments (ED) are facing a difficult task: to identify patients presenting with symptoms of heart disease and to rapidly rule out acute myocardial infarction (AMI). The problem is enhanced by the exponential growth of the ageing population. Up to 80% of patients in the ED who present with symptoms consistent with acute coronary syndrome (ACS) are actually suffering from other problems and not ACS, specifically AMI [1]. Consequently, it is important to quickly rule out AMI to enable rapid and appropriate treatment. For patients in the ED not suffering from an AMI, this process can be both costly and time consuming [2].
by Marco Witteveen
In a clinical setting, the term AMI applies when there is evidence of myocardial myocyte necrosis consistent with myocardial ischaemia. The rise and/or fall of cardiac biomarkers with at least one value above the 99th percentile of the upper reference limit (URL), together with evidence of myocardial ischaemia with at least one of the following indicates a diagnosis of AMI: symptoms of ischaemia; ECG changes indicative of new ischaemia (new ST-T changes, or new or presumed new left bundle branch block [LBBB]); development of pathological Q waves in the ECG; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.
Although a common diagnostic tool, the use of ECG alone has been shown to be non-diagnostic for AMI in up to 50% of patients presenting with ACS symptoms [3]. The pitfalls of ECG are the false positives of benign early repolarisation; left bundle branch block (LBBB); pre-excitation; pulmonary embolism; and metabolic disturbances. The false negatives can be defined as the prior Q waves and/or persistent ST-elevation, paced rhythm and LBBB.
Taking this into account, clinicians have an absolute need for cardiac biomarkers which are sensitive and specific, not only to rule in, but more importantly to rule out AMI. Such biomarkers should enable rapid results using a systematic approach. A confident buy-in by all stakeholders (Emergency Department, Cardiology, Administration, the Cardiac Catherisation Lab and Laboratory) is needed, and a process which facilitates timely clinical-decision making to improve clinical, as well as economic and operational outcomes is required. The use of ECG and cardiac biomarkers would provide supportive evidence, together with clinical history, physical assessment and other parameters that physicians utilise in their clinical-decision making process.
Cardiac biomarkers
The US National Academy of Clinical Biochemistry (NACB) recommendations specify that cardiac biomarker assays should be available on an immediate basis 24 hours per day, seven days per week, with a turnaround time (TAT) of one hour, and a preferred time of less than 30 minutes [4]. TAT is defined as the period from when the patient arrives in the ED and undergoes phlebotomy until the time the Emergency Physician is aware of the test result so as to include it in the full clinical picture. However, a TAT of one hour is currently very challenging for many hospitals. Transport, sample handling, delays with data management systems, shortage of staff, location of the laboratory and informing the emergency physician of the result are all logistical hurdles that make a TAT of one hour or less difficult to accomplish within a centralised laboratory set-up [2].
One alternative is the use of a rapid 90 minute rule-out method [2,5]. The use of a combined myoglobin with creatine kinase-MB (CK-MB), as well as a cardiac troponin I, assay may enable rapid exclusion of AMI and thus discharge of patients who do not require observation [2]. Myoglobin appears as early as one to three hours after the onset of symptoms and has a high sensitivity for detection of AMI within the first few hours of presentation [6] [Figure 1]. Measurement of this combination of biomarkers gives a sensitivity and negative predictive value of 100% for myocardial infarction, and as a result can reduce coronary care unit (CCU) admissions by 40%, and reduce the need for a dedicated observation unit [5]. The method is particularly useful for patients with non-diagnostic ECGs.
Additionally, a single measurement of B-Type Natriuretic Peptide (BNP), obtained in the first few days after the onset of ischaemic symptoms, provides predictive information for use in risk stratification across the spectrum of acute coronary syndromes. Cardiac neuro-hormonal activation may be a unifying feature among patients at high risk of death after an acute coronary syndrome [7].
Point-of-Care assessment
Point-of-care (POC) testing of cardiac biomarkers within the ED, using technology such as the Biosite Triage Meter (Inverness Medical Inc.), enables results to be known within about 15 minutes of testing patients during assessment, and can potentially reduce the time to diagnosis. It has been shown that AMI can be rapidly excluded in the ED by the use of POC measurements of myoglobin and troponin I during the first 90 minutes after presentation [2]. POC testing of cardiac biomarkers avoids any unnecessary transportation to the central laboratory and shortens the TAT from blood being drawn to a physicians’ clinical decision by up to 84.5% [Figure 2]. However, it is important that POC testing is an extension of the central laboratory service and that all tests are controlled, recorded and verified through the Laboratory Information System (LIS) and/or Hospital Information System (HIS).
The Triage meter is a portable fluorometer which offers a POC multimarker panel with tests for cardiovascular biomarkers includingmyoglobin, CK-MB and troponin I, as well as assays for B-Type Natriuretic Peptide (BNP) and D-dimer in various configurations. Additionally, a Neutrophil Gelatinase Associated Lipocalin (NGAL) test is available for the early detection of Acute Kidney Injury; this biomarker may have a role in assessing this patient population for renal complications.
The diagnostic capabilities of the Triage meter are supported by the Census data management software system, which makes it possible to connect the Triage meter to the LIS or HIS in order for the laboratory to validate the results and control decentralised testing. It has been shown that rapid, quantitative measurement of myoglobin, CK-MB, troponin I and BNP using the Triage meter enables simultaneous results of biomarker levels in about 15 minutes. In a comparative study, the diagnostic accuracy of the POC Triage meter was tested against a lab-based platform and it was found to provide similar diagnostic performance to contemporary lab-based assays [4]. There were no performance differences between the lab-based and POC tests when comparing patients with and without non-ST segment MI. Additionally, the Triage meter allows triage decisions in under two hours when used with accelerated protocols [5]; rapid, accurate rule out of AMI and faster triage decisions to care pathways are enabled [2,5].
Summary
Studies have shown that POC testing with cardiac biomarkers is an essential component of acute chest pain assessment in the ED. A rapid 90 minute rule out method for patients presenting with chest pain suggestive of AMI, involving POC serial testing of myoglobin, CK-MB and troponin I, can reduce CCU admissions, reduce costs and provide effective assessment of patients with acute chest pain [8]. The use of a multimarker testing initiative at 90 minutes following patient arrival offers 100% sensitivity, unlike single and dual biomarker testing algorithms [Figure 3]. This strategy used at the POC, with test results delivered rapidly and made available to emergency physicians, could improve the efficiency of chest pain assessment, triage and treatment [9].
References
1. Braunwald E et al. ACC/AHA Guideline Update for the Management of Patients with UA and NSTE-ACS.
2. McCord J et al. Ninety-minute exclusion of acute myocardial infarction by use of quantitative point of care testing of myoglobin and Troponin I. Circulation 2001; 104:1483.
3. Karlson BW et al. Early prediction of AMI from clinical history, examination, and electrocardiogram in the emergency room. Am J Cardiol. 1991; 68:171-175.
4. Peacock WF et al. Acad Emerg Med. 2004; 1(5):569–570.
5. Ng S et al. Ninety minute accelerated critical pathway for chest pain evaluation. Am J Cardiol 2001; 88: 611–17.
6. Brogan GX et al. Evaluation of a new rapid quantitative immunoassay for serum myoglobin versus CK-MB for ruling out AMI in the emergency department. Ann Emerg Med 1994; 24:665-671.
7. de Lemos JA et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 2001; 345: 1014-21.
8. Dunn F et al. Are chest pain observation units essential for rapid and effective emergency care in the UK? Emergency Medicine Journal 2006; 23:487-488.
9. Newby LK et al. Bedside multimarker testing for risk stratification in chest pain units. Circulation 2001; 103:1832-1837.
The author
Marco Witteveen
Inernational Marketing Manager Cardiology
Biosite International SARL
An Inverness Medical company
Switzerland
email: info.cardiology@invmed.com
www.invernessmedical.com
