Early diagnosis of acute myocardial infarction based on assay for subforms of creatine kinase-MB.

Thrombolytic therapy for patients with acute myocardial infarction (AMI) has produced the need for an accurate early diagnostic marker. We previously developed and assessed an assay for the creatine kinase (CK)-MB subforms; assay time is 25 minutes. Plasma MB2 (tissue subform) activity, MB1 (plasma-modified subform) activity, and MB2/MB1 ratio in 56 healthy individuals were 0.61 +/- 0.33 units/l, 0.63 +/- 0.33 units/l, and 0.94 +/- 0.39, respectively. Only one individual had both an MB2 activity greater than 1.0 units/l and an MB2/MB1 ratio of more than 1.5. Similar results were obtained in 50 hospitalized patients without cardiac disease; two of these patients had both an MB2 activity and an MB2/MB1 ratio greater than the cutoff values. Among 49 patients with AMI, MB2 activity and the MB2/MB1 ratio began to increase 2 hours after AMI; the ratio reached a plateau of 3.1 by 4-6 hours. The first available plasma sample was abnormal by the subform assay in 67% of patients and by a conventional MB assay in 27% of patients. Assay sensitivities in samples collected at 2-4, 4-6, and 6-8 hours after AMI were 59%, 92%, and 100% for the subform assay and 23%, 50%, and 71% for the conventional assay (p less than 0.03 versus subform assay at each time interval). False-negative results were obtained by the subform and conventional assays in 15 and 45 samples at a mean of 2.3 and 5.8 hours, respectively. Subform assay provides rapid and reliable diagnosis of AMI within 4-6 hours after the onset of symptoms, which is 6 hours before conventional CK-MB assays are accurate.

[1]  M. Christensen,et al.  Optimal Diagnosis in Acute Myocardial Infarction: A Cost‐effectiveness Study , 1980, Circulation.

[2]  E. Veys,et al.  HL-A AND INFECTIVE SACROILEITIS , 1974 .

[3]  J. Coromilas,et al.  Left ventricular function and rapid release of creatine kinase MB in acute myocardial infarction. Evidence for spontaneous reperfusion. , 1983, The New England journal of medicine.

[4]  R. Roberts,et al.  Creatine kinase isoform analysis in the detection and assessment of thrombolysis in man. , 1987, Circulation.

[5]  R. Roberts,et al.  Sensitive, rapid assay of subforms of creatine kinase MB in plasma. , 1989, Clinical chemistry.

[6]  B. Sobel,et al.  Rapid separation of plasma creatine kinase isoenzymes by batch adsorption on glass beads. , 1975, Clinical chemistry.

[7]  M. Joseph.  Sensitivity of routine clinical criteria for diagnosing myocardial infarction within 24 hours of hospitalization , 1987 .

[8]  E. Grenadier,et al.  Acute myocardial infarction and MB creatine phosphokinase. , 1981, Archives of internal medicine.

[9]  R. Roberts,et al.  Purification and characterization of naturally occurring and in vitro induced multiple forms of MM creatine kinase. , 1984, The Journal of biological chemistry.

[10]  S. Rosalki.  An improved procedure for serum creatine phosphokinase determination. , 1967, The Journal of laboratory and clinical medicine.

[11]  E F Cook,et al.  Sensitivity of routine clinical criteria for diagnosing myocardial infarction within 24 hours of hospitalization. , 1987, Annals of internal medicine.

[12]  T. Schnitzer,et al.  MM subisoenzymes of creatine kinase as an index of disease activity in polymyositis. , 1985, Clinical chemistry.

[13]  E. Rapaport,et al.  Serum Creatine Kinase MM Isoenzyme Sub–bands After Acute Myocardial Infarction in Man , 1983, Circulation.

[14]  A. Wu.  Creatine kinase isoforms in ischemic heart disease. , 1989, Clinical chemistry.

[15]  M. Cohen,et al.  Late thrombolytic therapy preserves left ventricular function in patients with collateralized total coronary occlusion: primary end point findings of the Second Mount Sinai-New York University Reperfusion Trial. , 1989, Journal of the American College of Cardiology.

[16]  P. Clarkson,et al.  Creatine kinase isoforms following isometric exercise , 1987, Muscle & nerve.

[17]  R. Roberts,et al.  Carboxypeptidase-catalyzed hydrolysis of C-terminal lysine: mechanism for in vivo production of multiple forms of creatine kinase in plasma. , 1984, Clinical chemistry.

[18]  Gruppo Italiano per lo Studio della Soprawivenza nell'Inf Miocardico.,et al.  EFFECTIVENESS OF INTRAVENOUS THROMBOLYTIC TREATMENT IN ACUTE MYOCARDIAL INFARCTION , 1986, The Lancet.

[19]  P. Ludbrook,et al.  Specificity of elevated serum MB creatine phosphokinase activity in the diagnosis of acute myocardial infarction. , 1975, The American journal of cardiology.

[20]  D. Abendschein,et al.  Characterization of MB creatine kinase isoform conversion in vitro and in vivo in dogs. , 1989, The Journal of clinical investigation.

[21]  F. Van de Werf,et al.  Intravenous tissue plasminogen activator and size of infarct, left ventricular function, and survival in acute myocardial infarction. , 1988, BMJ.

[22]  F. Cobb,et al.  Acute myocardial infarction and MB creatine phosphokinase. Relationship between onset of symptoms of infarction and appearance and disappearance of enzyme. , 1980, Archives of internal medicine.

[23]  A. Wu,et al.  Early diagnosis of acute myocardial infarction by rapid analysis of creatine kinase isoenzyme-3 (CK-MM) sub-types. , 1987, Clinical chemistry.

[24]  R. Roberts.  Enzymatic diagnosis of acute myocardial infarction. , 1988, Chest.

[25]  L. Goldman,et al.  Candidates for thrombolysis among emergency room patients with acute chest pain. Potential true- and false-positive rates. , 1989, Annals of internal medicine.

[26]  L. Bolognese,et al.  RANDOMISED TRIAL OF INTRAVENOUS STREPTOKINASE, ORAL ASPIRIN, BOTH, OR NEITHER AMONG 17 187 CASES OF SUSPECTED ACUTE MYOCARDIAL INFARCTION: ISIS-2 , 1988, The Lancet.

[27]  R. Califf,et al.  Hemorrhagic complications associated with the use of intravenous tissue plasminogen activator in treatment of acute myocardial infarction. , 1988, The American journal of medicine.

[28]  F. Apple,et al.  Creatine kinase isoenzyme MM variants in skeletal muscle and plasma from marathon runners. , 1986, Clinical chemistry.

[29]  A. Jaffe,et al.  Diagnostic changes in plasma creatine kinase isoforms early after the onset of acute myocardial infarction. , 1986, Circulation.

[30]  R. Wevers,et al.  A study on the dimeric structure of creatine kinase (EC 2.7.3.2). , 1977, Clinica chimica acta; international journal of clinical chemistry.