Peter R. Puleo

Use of a Rapid Assay of Subforms of Creatine Kinase MB to Diagnose or Rule Out Acute Myocardial Infarction

BACKGROUND Ruling out myocardial infarction in patients coming to the emergency room with chest pain is hindered by the lack of a specific early diagnostic marker. Less than 30 percent of patients admitted to coronary care units have infarction, resulting in substantial unnecessary expenditures. We developed a rapid assay of the subforms of creatine kinase MB (CK-MB) and prospectively analyzed its sensitivity and specificity in diagnosing myocardial infarction in the first six hours after the onset of chest pain. METHODS In 1110 consecutive patients who came to the emergency room with chest pain, blood samples were collected every 30 to 60 minutes until at least 6 hours after the onset of symptoms; in patients who were then admitted to the hospital, samples were collected every 4 hours for up to 48 hours. The samples were analyzed for CK-MB subforms, and the diagnosis of myocardial infarction was confirmed by conventional CK-MB analysis. RESULTS Of the 1110 patients evaluated, 121 had myocardial infarction. The sensitivity of the assay of CK-MB subforms to detect myocardial infarction in the first six hours after the onset of symptoms was 95.7 per cent, as compared with only 48 percent for the conventional CK-MB assay; the specificity was 93.9 percent among patients hospitalized without myocardial infarction and 96.2 percent among those sent home. Among the patients with myocardial infarction, definitive results of the subform assay were available a mean (+/- SD) of 1.22 +/- 1.17 hours after their arrival in the emergency room. CONCLUSIONS The assay of CK-MB subforms reliably detected myocardial infarction within the first six hours after the onset of symptoms, and its use could reduce admission to the coronary care unit by 50 to 70 percent, thereby reducing costs.

Return of atrial mechanical function following electrical conversion of atrial dysrhythmias

The return of atrial mechanical function and its relationship to embolic events following cardioversion of atrial arrhythmias is controversial. Fourteen patients with atrial arrhythmias were evaluated with pulsed Doppler echocardiography before and after direct current (DC) cardioversion. The atrial filling fraction increased significantly: 1.14 +/- 4.3% at baseline versus 14.9 +/- 13.3%, 13.4 +/- 11.4%, and 21.9 +/- 13.5% at 5 minutes, 30 minutes, and 24 hours, respectively, following cardioversion. Absent atrial mechanical activity was noted in four patients immediately after cardioversion. Mechanical activity resumed by 30 minutes in one patient and at 24 hours in two others. Those with delayed atrial function had lower stroke volumes and atrial filling fractions following cardioversion. An embolic event occurred in one patient who had immediate return of atrial mechanical activity. This patient also had the largest atrial filling fraction of any patient at 24 hours (41%). These data suggest that the degree of atrial mechanical activity following cardioversion is variable and that embolic episodes are not necessarily related to delayed return of atrial mechanical activity following cardioversion.

NONINVASIVE DETECTION OF REPERFUSION IN ACUTE MYOCARDIAL INFARCTION BASED ON PLASMA ACTIVITY OF CREATINE KINASE MB SUBFORMS

Successful thrombolytic therapy is associated with an accelerated release of creatine kinase (CK) MB from necrotic myocardium. With use of a previously validated assay, the plasma kinetics of the myocardial subform (MB2) and the plasma-modified subform (MB1) were determined in blood samples obtained from 56 patients with acute Q wave myocardial infarction: 33 patients who received thrombolytic therapy (group A) and 23 patients managed conservatively (group B). Plasma MB2 activity increased more rapidly in the group A patients, but there was substantial overlap with group B. Plasma MB1 activity did not differ significantly between the two groups. The MB2/MB1 ratio was significantly higher in group A patients than in group B patients between 2 and 10 h after the onset of infarction. Among group A patients, the ratio increased from 2.4 +/- 1.6 to 4.6 +/- 2.0 in the 1st h after therapy (p less than 0.001). The peak ratio was 6.3 +/- 2.5 in group A patients and 3.1 +/- 1.2 in group B patients. Twenty-seven of the 33 group A patients had a peak ratio greater than 3.8 versus 5 of the 23 group B patients (p less than 0.001). In seven group A patients, the ratio was greater than 3.8 before plasma CK MB activity was out of the normal range. Angiography was performed at 5.0 +/- 3.5 days in 39 patients. Eighteen (90%) of 20 patients with a patent infarct-related artery had a peak ratio greater than 3.8; 17 (89.5%) of 19 patients with an occluded infarct-related artery had a ratio less than 3.8 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Time course of creatine kinase release after termination of sustained ventricular dysrhythmias

Differentiation between primary and secondary (caused by acute myocardial infarction) ventricular fibrillation has important therapeutic and prognostic implications. The diagnosis of myocardial infarction is based on clinical, ECG, and creatine kinase MB isoenzyme (MBCK) activity. Enzymatic criteria might not be able to confirm the diagnosis of myocardial infarction after recent cardioversion. The routine use of electrophysiologic studies involving the induction and termination of ventricular dysrhythmias provides a setting in which enzyme release as a result of cardioversion alone can be examined. Therefore a systematic investigation of the magnitude and time course of creatine kinase (CK) and MBCK release was performed after termination of ventricular dysrhythmias in 57 patients undergoing electrophysiologic studies. Of patients requiring external cardioversion, only 50% had an elevation in CK and MBCK activity. Elevation when present corrected with the number of shocks and cumulative energy delivered. The magnitude of MBCK release exceeded 10% of the total CK activity in 9% of observations. Pace-termination of ventricular tachycardia did not result in enzyme release. Arrhythmia characteristics, coronary artery disease, and left ventricular function did not affect the magnitude of the time course of enzyme release. These data suggest that cardioversion with multiple shocks may result in a component of MBCK release, and thus a false positive diagnosis of primary acute myocardial infarction may be made by relying exclusively on the enzyme release pattern.

Prostaglandin E1 does not accelerate rTPA-induced thrombolysis in acute myocardial infarction☆

Fifteen patients who arrived between 6 and 24 hours after the onset of acute myocardial infarction and who were found to have totally occluded coronary arteries, received aspirin, heparin, and tissue plasminogen activator given over 3 hours. Eight patients were randomly assigned to receive intravenous prostaglandin E1, 20 ng/kg/min for 6 hours, while seven patients received placebo infusion. Coronary arteriography begun immediately before the start of tissue plasminogen activator and repeated every 15 minutes revealed restoration of antegrade flow in two of eight (25%) patients treated with prostaglandin E1 and in two of seven (28%) patients receiving placebo. Pharmacologic sampling of tissue plasminogen activator levels were performed at baseline and 30, 45, 60, 75, 90, 135, 180, 190, 210, and 240 minutes afterwards for assessment of tissue plasminogen activator antigen. There was no difference in fibrinogen levels and no difference in tissue plasminogen activator antigen levels at these time periods. Clearance values of tissue plasminogen activator were calculated and were not different between the two groups. These data do not support the use of prostaglandin E1 for the acceleration of reperfusion in patients receiving tissue plasminogen activator for acute myocardial infarction.

Determining Reperfusion and Myocardial Infarct Size Using Serum Enzymes

Interventions implemented to date in the clinical setting of acute myocardial infarction to salvage ischemic myocardium were aimed primarily at decreasing myocardial oxygen demands. Attempts to increase coronary flow have been relatively unsuccessful with drug therapy. Reperfusion, although shown in experimental infarction to be the most effective means of increasing coronary flow, was until recently not feasible in man. The recent demonstration that transmural myocardial infarction is associated with a coronary thrombus (1) which can be lysed with thrombolytic therapy (2) has drastically changed our thinking in both the assessment and treatment of acute myocardial infarction. Intracoronary streptokinase was very quickly approved by the Food and Drug Administration for routine use in acute myocardial infarction, perhaps too quickly. The impetus for this therapy has been enhanced by the recent demonstration that coronary thrombolysis could be achieved by the intravenous administration of streptokinase and, more recently, the relatively clot-selective, naturally occurring tissue plasminogen activator (rt-PA) (3). Given the safety and ease whereby the recombinant form of rt-PA can be given, it is conceivable that it could be administered to patients with suspected acute myocardial infarction at home or in transit to the hospital. Documentation of coronary thrombolysis is exciting, but should the present, ongoing, multicentered trial show coronary lysis with rt-PA to be effective in salvaging myocardium and reducing mortality, it could indeed revolutionize the care of the patient with acute myocardial infarction and change the overall thrust in the coronary care unit (4).