CLIN. CHEM. 28/2, 277-283 (1982) CLINICAL CHEMISTRY, Vol. 28, No. 2, 1982 277 Creatine Kinaseand CreatineKinaseB-SubunitActivityin Serum in Cases of SuspectedMyocardialInfarction W. Gerhardt,’ J. WaldenstrOm,2 M. HOrder,3 S. Hofvendahl,4 R. BIIIstrOrn,4R. Ljungdahl,4 H. Bernlng,5 and P. Bagger1 We evaluated a diagnostic strategy by studying 481 pa- tients suspected of having had an acute myocardial in- farction; the prevalence of infarction by independent cri- teria was 0.43. This strategy is based on the sequential application of: (a) clinical criteria; (b) total creatine kinase determinations In two serum samples drawn within 10 to 20 h of the onset of acute symptoms; and (C) creatine ki- nase B-subunit (S-CK B) determinations after immunoin- hibition with antibodiesto creatine kinase M-subunit inthe reaction medium inallsamples found to have increased total creatine kinase activity.Discriminationlimitsof 150 U/L totalcreatine kinase for women and 200 U/L for men gave a diagnostic sensitivity of 0.99. Activities less than these limits in samples identified 68% of the 274 non- infarctcases (posteriorprobability of a negative result of 0.99) within 20 h. Subsequent determination of S-CK B in 292 patients who were positive by the discrimination limits for total creatine kinase verified myocardial infarction in 99% of 207 cases for which S-CK B exceeded the dis- crimination limit of 12 U/L. The strategy excluded 98% of all non-infarct cases at a posterior probability of 0.99. Addftlonal Keyphrases: enzyme activity . immunoinhi- bitlon . isoenzymes . electrophoresis, agarose gel Rational utilization of enzyme tests, such as measurement of S-CK and S-CK B subunit activity, for the early exclusion and diagnosis of AMI requires a strictly defined diagnostic strategy based on sampling in the time interval during which S-CK and S-CK B are most likely to be increased.6 Several studies have demonstrated that this is 10 to 20 h after the onset of acute symptoms (1-7). It follows that earlier emer- gency determinations of these enzymes carry a considerable risk of falsely negative results (8), and in fact, may instill a The first three authors are the Working Group of the Scandinavian Committee on Enzymes, the next three are clinical consultants, and the last two are statistical consultants. An expanded version of this study was published as a booklet by the Nordic Clinical Chemistry Project (NORDKEM, Sibeliusgatan 12, Helsinki 26, Finland) in 1981 (26 pp., $1) 1 Department of Clinical Chemistry, Nya Lasarettet, Helsingborg, Sweden. 2 Department of Clinical Chemistry, Sahlgren’s Hospital, Gothenburg, Sweden. 3Department of Clinical Chemistry, University Hospital, Odense, Denmark. Coronary Care Unit, Nya Lasarettet, Helsingborg, Sweden. 5Department of Clinical Chemistry, Herlev Sygehus, Copenhagen, Denmark. 6Nonstandard abbreviations: S-CK, total creatine kinase (ATP: creatine N-phosphotransferase; EC 2.7.3.2) activity in serum; S-CK B, creatine kinase B-subunit activity in serum; SCE, Scandinavian Committee on Enzymes; S-ASAT, aspartate aminotransferase (EC 2.6.1.1) activity in serum; S-ALAT, alanine aminotransferase (EC 2.6.1.2) activity in serum; S-LD, L-lacthte:NAD oxidoreductase (EC 1.1.1.27) activity in serum; AMI, acute myocardial infarction. Received July 21, 1981; accepted Oct. 6, 1981. false feeling of security in the clinician, leading to erroneous decisions. Because AM! can be definitely excluded by means of these enzyme tests only in the 10- to 20-h interval after onset of symptoms, it is rational to obtain samples only within this time period. On the other hand, S-CK and S-CK B may be increased in some patients earlier than 10 h after onset of symptoms. However, it would appear irresponsible to deny a patient adequate care until a laboratory verification of an AM! has been obtained, especially because the risk of dangerous ar- rhythmias is greater during the initial phase of an AMI. Under Scandinavian hospital policy a patient suspected of having an AMI is rapidly transferred to the best possible monitoring facility, preferably a coronary care unit, and remains under supervision until an AMI can be definitely disproved. We have previously described an analytically specific rou- tine method for S-CK B determinations with use of the Scandinavian-recommended (SCE) CK reagent and complete immunoinhibition of CK M-subunit activity (9). As a working group of the Scandinavian Committee on Enzymes we here evaluate a three-stage diagnostic strategy comprising the se- quential application of clinical criteria, 10- to 20-h S-CK, and S-CK B measured in all S-CK positive samples from 481 AMI-suspect patients. Materials and Methods Patients We studied a total of 481 AMI-suspect patients admitted to our emergency ward and coronary care unit during 1977-1978 and part of 1979. The patients included in the study all presented with symptoms indicative of their having had an AM! (10) within the previous 24 h. Most had localized or irradiating chest pain lasting more than 20 mm and often characterized by nonresponsiveness to nitroglycerin. Some presented with pulmonary edema or cardiogenic shock but no chest pain. A few patients had atypical symptoms, including cardiac failure, cardiac arrest, or severe arrhythmias with or without a history of previous coronary disease, indicating the possibility of an AM!. Of the AM! suspect patients 85% were transferred to the coronary care unit upon admission. The prevalence of AM! (by independent criteria, see below) in this group was 0.47. For various reasons, such as only very slight suspicion of AM!, other severe complicating disease, or extreme old age, about 15% of the cases remained in the general-observation ward. The prevalence of AM! in this group was 0.15. The prevalence of AMI in the total patient population was thus 0.43. Sampling S-CK and S-CK B: From each patient two specimens were drawn within 10 to 20 h after onset of the acute symptoms, preferably after 10 and after 16 h. The samples were centri- fuged within 1 h of collection. Samples not analyzed within about 2 h after centrifugation were stored at -80 #{176}C until the next series was run. S-ASAT, S-ALAT, and S-LD: Specimens for use in these assays were drawn daily for three days after admission.