Will serum enzymes and other proteins find a clinical application in the early diagnosis of myocardial infarction?

Until recently there was little interest in the early diagnosis of myocardial infarction because the duration of symptoms had little impact on the hospital management strategy. Attitudes changed after the publication of the major mortality studies of thrombolytic therapy which showed not only that treatment improves prognosis but also that the earlier it is given after the onset of symptoms the greater is the benefit.l1 This stimulated a review of the three diagnostic methods used clinically for the diagnosis of acute myocardial infarction (electrocardiogram, enzyme analysis, non-invasive imaging) to determine which could provide the earliest diagnosis.5 There is no doubt that in terms of cost, practicality, and accuracy the presenting electrocardiogram remains the best method for early diagnosis. Regional ST elevation occurs within seconds of the onset of coronary occlusion67 and its diagnostic specificity for acute infarction is close to 100%. 8 9 Nevertheless, its sensitivity may be as low as 60%, reflecting the significant minority of patients who present with non-diagnostic changes such as left bundle branch block, ST depression, or T wave inversion: occasionally, the presenting electrocardiogram is entirely normal.89 In the past, serum enzyme analysis has proved useful for retrospective confirmation of infarction in these patients, but the timing of enzyme release and until recently the logistics of the method effectively ruled it out as a means of early diagnosis. Now, however, kits are available for the rapid analysis of creatine kinase and its MB isoenzyme and a myoglobin assay can be diagnostic within 4 h of the onset of symptoms. '012 If these serum markers of myocardial infarction provide early diagnosis when the electrocardiogram is non-diagnostic will they save lives by allowing increased application of thrombolytic therapy and other interventions aimed at reducing mortality? 12 Though serum markers of myocardial infarction may permit early diagnosis in cases where the electrocardiogram is unhelpful, this is unlikely to improve outcome. Indeed, there is real concern that it may have the opposite effect by leading to the use of thrombolytic agents in a group of patients in which the risk of treatment exceeds the potential benefit. If serum markers of myocardial infarction are to be useful in early diagnosis it will be in patients who present with chest pain and left bundle branch block. In those in whom infarction is confirmed mortality is high and there is much to gain from successful thrombolysis. "3 However, it is questionable whether this role will be realised because most cardiologists would not wish to wait for laboratory data before starting treatment of these high risk patients. Patients with chest pain and other non-diagnostic electrocardiogram patterns have a much better prognosis and do not require such early diagnosis and treatment. Thus Yusuf et al found that only 1 2% of patients entered into the ISIS-1 (International Study of Infarct Survival) trial developed cardiac arrest or died when the presenting electrocardiogram was nondiagnostic compared with 11% when it showed ST elevation.9 Of course, these were selected, low risk patients not all of whom had a definite infarct. Nevertheless, the database of > 1000 consecutive patients with acute infarction treated at Newham General Hospital confirms that patients without ST elevation have a hospital mortality of < 5%, which is about one third that seen in patients with ST elevation. Clearly, therefore, hospital outcome in these patients with non-diagnostic electrocardiograms is good compared with patients with ST elevation, and this must diminish the potential value of thrombolytic therapy and other interventions designed to improve survival. Indeed, subgroup analysis of the ISIS-2 trial, indicated that mortality reduction in response to treatment was greatest in subgroups at greatest risk of death (for example, women, older patients, patients with previous infarction or anterior infarction), and no apparent benefit for either streptokinase or aspirin could be demonstrated in patients with normal electrocardiograms or ST depression.2 In this latter respect, the finding accorded with the GISSI subgroup analysis. ' Only the LATE study has suggested a small benefit in outcome for patients without ST elevation randomised to thrombolytic therapy, but it is not clear to what extent patients with left bundle branch block confounded the mortality statistic. '4 The balance of evidence from subgroup analyses of the randomised trials of thrombolytic therapy, therefore, tends to strengthen the hypothesis that patients with non-diagnostic electrocardiograms may not show the same benefit from thrombolytic therapy as patients with ST elevation. If true, this calls into question the need for early diagnosis by rapid analysis of enzymes or other proteins Department of Cardiology, London Chest Hospital, London E2 9JX AD Timmis Accepted for publication 19 October 1993 309