Abstract. Patients presenting with symptoms suggestive of an acute coronary syndrome (ACS) and without ST-segment elevation in the ECG, constitute a diagnostic, prognostic and therapeutic challenge. These patients encompass a broad spectrum of diagnoses with different prognosis, from relatively large myocardial infarction (MI) over minor MI or UA to chest pain of noncardiac causes, but must be considered to have an ACS until otherwise is proven. In relation to ST-elevation MI the proportion of patients with non-ST elevation MI (nonSTEMI) is increasing. In the Swedish Coronary Care registry the proportion of nonSTEMI increased from 49 %, in year1995-96, to 58 %, in year 2001-02.

Key events for the development of ACS are in most cases a disruption of an atherosclerotic plaque and thrombus formation, leading to abrupt and unpredictable reductions in coronary blood flow, causing myocardial ischemia at rest or decreasing levels of exertion. If the ischemia is prolonged enough to cause myocardial necrosis, the patient will, by definition, have an acute myocardial infarction.

Myocardial necrosis can be recognized by several different methods. The most sensitive method in clinical practice is measurement in the blood of different biochemical markers of myocardial necrosis (proteins and enzymes) released into the circulation from the damaged myocytes. Currently, the most sensitive and specific markers are the cardiac troponins I and T (cTnT and cTnI). The troponins are proteins that regulate calcium mediated muscle contraction. When the myocardial cell is damaged and the cell membrane loses its integrity, troponins from a small unbound cytosolic pool can immediately diffuse into the interstitium and, from there, into the circulation. However, most of the troponin in the cell is structurally bound and is continuously released as the necrotic cell disintegrates. This explains the long period of elevated levels of the troponins after myocardial injury, starting after 3-6 hours and remaining 1-2 weeks, although the troponin molecules have a short plasma half-life.

The development of these very sensitive and almost 100 % specific methods for detecting myocardial necrosis have prompted a redefinition of myocardial infarction. Previously, the widely accepted and used, WHO criteria defined MI by a combination of “two out of three characteristics”, i.e. typical symptoms, enzyme rise and a typical ECG pattern. Recently, the joint ESC/ACC committee on redefinition of myocardial infarction suggested “one plus one out of two characteristics” for the clinical definition of acute MI. An elevation of a specific marker of myocardial necrosis (preferably cTnT or cTnI) is a prerequisite for the diagnosis of acute myocardial infarction. However, it is important to remember that an elevated level of troponin in blood only signals that myocardial damaged has occurred, not the cause or the location of the damage. Beside ischemia due to a thrombotic or embolic occlusion of a coronary artery, there are several other possible causes of myocardial necrosis, such as inflammation (e.g. myocarditis), toxic effects (e.g. chemotherapeutic drugs) and mechanical damage (e.g. cardiac trauma). Therefore, in establishing the cause of the damage, an interpretation of the clinical circumstances must always be performed. Accordingly, in addition to the elevation of a marker of myocardial damage ischemic symptoms and/or electrocardiographic evidence of ischemia is the second prerequisite to establish the diagnosis of AMI. ECG changes, in the absence of QRS confounders, indicative of myocardial ischemia, but not necessarily of necrosis, are ST-segment elevation, ST-segment depression and T wave abnormalities. For the diagnosis of acute, evolving or recent MI, an elevation of a specific marker of myocardial necrosis is required even when pathologic Q-waves are developed. However, the development of new pathologic Q waves on serial ECGs is in itself enough for the diagnosis of established MI according to the new criteria. In the Swedish coronary care registry some 14 % of patients with acute MI have “normal” ECG on admission. Using a much more stringent definition of normal ECG we found in one study that of all patients with a final diagnosis of nonSTEMI 10 % had normal ECG at presentation (which means about 5 % of all MIs).

The joint ESC/ACC committee further proposed that the 99th percentile value of the marker in a reference control population should be used as the decision level for AMI diagnosis, on the condition that the imprecision (CV%) of the particular assay at that level is below 10 %. So far, no commercial troponin assay has been able to match this tough demand. Therefore, for use in clinical practice, a slightly higher decision level than the 99th percentile value of healthy controls is used. Nevertheless, the use of these low decision levels for the troponins will lead to a substantial increase of 20-30 % in the number of AMI diagnoses (i.e. nonSTEMI). Almost all of these “new” AMI patients have previously received a diagnosis of unstable angina.

There is a strong association between the short- and long-term risk for new cardiac events and myocardial necrosis in patients with non-ST elevation ACS. The increase in risk seems to appear as soon as any elevation of troponin is possible to demonstrate, i.e. well below the former decision levels for acute MI. Multivariate analyses have shown that the troponin level adds independent prognostic information to that of clinical variables, ECG findings, echocardiographic findings and C-reactive protein level. In the above mentioned study, 11% of those with perfectly normal ECG on admission and tnT elevation within 6 hours died or had a nonfatal MI during a mean follow-up of 6 months, compared to only 1.5 % of those with normal ECG and no tnT elevation (p<0.05). Its association with the extent of CAD, occurrence of intra coronary thrombus and left ventricular function might explain the prognostic value of the troponin level.

An increasing number of therapeutic options are now available for the management of patients with non-ST elevation ACS. Many of these are rather costly and some have potential serious side effects. Therefore, identification of those who benefit most from a particular therapy has become important in the management of non-ST elevation ACS patients. The beneficial effects of antithrombotic treatment with l.m.w heparins, antiplatelet therapy with GPIIb/IIIa receptor inhibitors and an invasive approach with early revascularization have been shown to be predominantly present in patients with evidence of myocardial necrosis (i.e. elevated troponin).