Internal Medicine Journal 37 (2007) 737738

E D I TO R I A L

Non-STEMI or no NSTEMI?

The assessment and management of patients with acute coronary syndromes (ACS) have been revolutionized in the last decade by the use of assays for the cardiac troponins, T and I. The levels of these cardiac biomarkers, which are very sensitive indicators of myocyte necrosis, are important for patient diagnosis, triage and prognosis. Indeed the redenition of myocardial infarction (MI) has emphasized cardiac troponins as the preferred biomarkers, which in turn has led to the acronym for non-ST elevation MI, NSTEMI, becoming an important term in the cardiological lexicon.1,2 While there is one cardiac troponin T assay, there are multiple assays and manufacturers of Troponin I and creatine kinase (CK) MB, which has resulted in clinician confusion over reference ranges in the last decade. Although troponins are now the preferred cardiac biomarker, CK-MB has had an important role in the diagnosis of reinfarction, particularly after percutaneous coronary interventions and coronary artery bypass grafting, and as a clinical trial end-point.2 Many of these MI events occur soon after the initial presentation, when troponin levels from the index event are still elevated. However, increases in troponin levels above the baseline of >20% are gaining acceptance as an MI end-point criteria.1 Increased levels of troponins T and I above the upper limit of the reference ranges suggest myocardial damage from any cause and do not necessarily mean critical obstruction to either epicardial coronary arteries or the coronary microvasculature, unless they have occurred in the context of spontaneous or procedure-related ischaemia. There are several other causes of increased troponin levels other than an ACS because of plaque rupture or ssuring.2 These include (i) other cardiac causes including postcardiac surgery and congestive heart failure (without infarction), (ii) systemic inammatory disorders, (iii) inltrative disorders, (iv) respiratory illnesses and severe sepsis, (v) renal failure and severe hypertension (including pheochromocytoma) and (vi) miscellaneous causes including trauma and various causes of brain injury. The pattern of release of troponins into the blood stream usually claries whether the myocyte injury is the result of an ACS. Serial measurements of troponin levels are especially useful in patients with chronic renal failure, and continuing increases in troponin T levels often suggest the aetiology as an ACS.
2007 The Authors Journal compilation 2007 Royal Australasian College of Physicians

Levels of cardiac biomarkers are traditionally measured by enzyme-linked immunosorbant assays, which take 4590 min, whereas point of care, qualitative or semi-quantitative troponin assays facilitate the early identication of myocardial infarction by triage nurses in emergency departments. The widespread use of this cardiac biomarker testing method could aid prompt admission of patients with denite ACS, allowing emergency department (ED) medical staff to concentrate on their assessment of patients who are initially troponin negative. The results of The Australian Acute Coronary Syndromes Prospective Audit (ACACIA) study by Chew et al. are reported in this issue of Internal Medicine Journal and describe current patterns of ACS care in a variety of metropolitan, regional and rural centres of Australia.3 Among the patients with non-ST elevation ACS (NSTEACS), approximately 50% of those patients considered high risk did not have an increased troponin level. Such patients included those with at least one of the following characteristics: 1 mm of T-wave inversion in two contiguous leads; diabetes mellitus; and prior coronary surgery. Inclusion was predicated by a history of symptoms suggestive of ischaemia. As cardiologists, we nd that a patients history of ischaemic symptoms may be variably assessed by nonspecialist staff in ED. This may in part explain higher than usual frequencies of both diabetes mellitus and prior coronary surgery in patients in the high-risk ACS group in ACACIA. Thus, many of the high-risk but troponinnegative patients are likely to have been of somewhat heterogeneous risk, and a proportion may have symptoms that led to hospital presentation, which were of low likelihood of having been due to plaque instability. These patients were unlikely to derive benet from a treatment strategy aimed at lesion passivation including aggressive antiplatelet therapy, early coronary angiography and, where indicated, revascularization. The ACACIA study poses many questions regarding the spectrum of management options for ACS in Australia. Although classication between NSTEACS high risk and intermediate risk was centrally adjudicated, based on electrocardiogram and biomarker ndings, perhaps the important confounding issue affecting interpretation of these ndings is the likely variability in the functioning of

737

Editorial

chest pain pathways between hospitals. This probably led to variability in the rates of hospitalisation of troponinnegative patients, and thus variability in eligibility for inclusion in ACACIA. These patients may have been admitted in one hospital, whereas many similar patients at another hospital may have been managed by an early discharge strategy and thus not included. At our institution, a proportion of patients are classied as high risk in the ED based on at least one of the following characteristics: diabetes, prior coronary surgery and renal dysfunction or often have a history quite atypical of unstable myocardial ischaemia, on cardiological review. Thus, some of these patients in ACACIA may appropriately have not been commenced on clopidogrel therapy or have undergone early angiography. Registries or cohort studies such as ACACIA usually report patients with higher risk proles (such as older age or more cardiogenic shock) than those patients recruited in concurrently conducted randomized trials. However, the age of STEMI patients in ACACIA, for example, was the same as in concurrently conducted Assessment of Pexelizumab in Myocardial Infarction trial (the largest primary percutaneous coronary interventions trial thus far conducted), but the rate of cardiogenic shock in ACACIA was lower;3,4 the usual rate of cardiogenic shock complicating MI in routine practice has been consistently ;8% over recent decades.5 Thus, concerns are raised by these low reported rates in ACACIA STEMI patients that these were not unselected patients perhaps because informed consent was required. In conclusion, current clinical practice often does not extend to the routine collection of information of sufcient quality to accurately assess key performance indicators in patients with ACS; collection of information in the ACACIA study was made possible by industry support. However, whether the kinetic proles of the increase in cardiac marker levels, particularly troponin T, were sufcient to differentiate plaque instability from other causes of marker increases, is unclear. In future studies, to clarify several issues raised by the ACACIA study, it would be desirable to obtain and report results from the high-risk NSTEACS group separately from those meeting the revised

denition of NSTEMI, thus allowing clarication of the appropriateness of rates of use of an early invasive strategy, clopidogrel and glycoprotein IIb/IIIa antagonists. Obtaining insights into management differences of intermediate and high-risk NSTEACS patients is also likely to require examination of inter-institutional differences in the functioning of chest pain pathways. Finally, it would be necessary to obtain limited data about patients who die soon after hospital arrival but prior to obtaining consent, to determine whether there are time-dependent changes in the risk prole and outcomes in unselected STEMI patients in Australia.
Received 14 August 2007; accepted 15 August 2007. doi:10.1111/j.1445-5994.2007.01515.x

J. Gohil C. Juergens J. French

Department of Cardiology, Liverpool Hospital and South West Sydney Clinical School (UNSW), Sydney New South Wales, Australia

References
1 Thygesen K, Alpert JS, White HD on behalf of The Joint ESCACC-AHA-WHF Task Force for the Redenition of Myocardial Infarction. Universal denition of myocardial infarction. Eur Heart J (in press). 2 French JK, White HD. Clinical implications of the new denition of myocardial infarction. Heart 2004; 90: 99106. 3 Chew D, Amerana J, Rankin J, Astley C, Brieger D. Current management of acute coronary syndromes in Australia: observations from the Acute Coronary Syndromes prospective Audit (ACACIA). Intern Med J 2007; 37: 7418. 4 The APEX MI Investigators. Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial. JAMA 2007; 297: 4351. 5 Babaev A, Frederick PD, Pasta DJ, Every N, Sichrovsky T, Hochman JS et al. Trends in management and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock. JAMA 2005; 294: 44854.

738

2007 The Authors Journal compilation 2007 Royal Australasian College of Physicians