Use of a Rapid Assay of Subforms of Creatine Kinase MB to Diagnose or Rule Out Acute Myocardial Infarction
Peter R. Puleo, Denise Meyer, Cheryl Wathen, Cyril B. Tawa, Susan Wheeler, Robert J. Hamburg, Nadir Ali, Steven D. Obermueller, Fernando J. Triana, Janice L. Zimmerman, M. Benjamin Perryman, and Robert Roberts
Background Ruling out myocardial infarction in patients comingto the emergency room with chest pain is hindered by the lackof a specific early diagnostic marker. Less than 30 percentof patients admitted to coronary care units have infarction,resulting in substantial unnecessary expenditures. We developeda rapid assay of the subforms of creatine kinase MB (CK-MB)and prospectively analyzed its sensitivity and specificity indiagnosing myocardial infarction in the first six hours afterthe onset of chest pain.
Methods In 1110 consecutive patients who came to the emergencyroom with chest pain, blood samples were collected every 30to 60 minutes until at least 6 hours after the onset of symptoms;in patients who were then admitted to the hospital, sampleswere collected every 4 hours for up to 48 hours. The sampleswere analyzed for CK-MB subforms, and the diagnosis of myocardialinfarction 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 myocardialinfarction in the first six hours after the onset of symptomswas 95.7 percent, as compared with only 48 percent for the conventionalCK-MB assay; the specificity was 93.9 percent among patientshospitalized without myocardial infarction and 96.2 percentamong 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 arrivalin the emergency room.
Conclusions The assay of CK-MB subforms reliably detected myocardialinfarction within the first six hours after the onset of symptoms,and its use could reduce admission to the coronary care unitby 50 to 70 percent, thereby reducing costs. .
Source Information
From the Department of Medicine, Section of Cardiology, Christ Hospital, Cincinnati (P.R.P.); and the Department of Medicine, Sections of Cardiology (D.M., C.W., C.B.T., S.W., R.J.H., N.A., S.D.O., J.F.T., M.B.P., R.R.) and Critical Care (J.L.Z.), Baylor College of Medicine, Houston.
Address reprint requests to Dr. Roberts at Baylor College of Medicine, 6535 Fannin, MS F905, Houston, TX 77030.
NACB WRITING GROUP MEMBERS, , Morrow, D. A., Cannon, C. P., Jesse, R. L., Newby, L. K., Ravkilde, J., Storrow, A. B., Wu, A. H.B., Christenson, R. H.
(2007). National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes. Circulation
115: e356-e375
[Full Text]
NACB WRITING GROUP MEMBERS, , Morrow, D. A., Cannon, C. P., Jesse, R. L., Newby, L. K., Ravkilde, J., Storrow, A. B., Wu, A. H.B., Christenson, R. H., NACB COMMITTEE MEMBERS, , Christenson, R. H., Apple, F. S., Cannon, C. P., Francis, G., Jesse, R. L., Morrow, D. A., Newby, L. K., Ravkilde, J., Storrow, A. B., Tang, W., Wu, A. H.B.
(2007). National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes. Clin. Chem.
53: 552-574
[Full Text]
Rajappa, M., Sharma, A.
(2005). Biomarkers of Cardiac Injury: An Update. ANGIOLOGY
56: 677-691
[Abstract]
Hayashida, K., Kume, N., Murase, T., Minami, M., Nakagawa, D., Inada, T., Tanaka, M., Ueda, A., Kominami, G., Kambara, H., Kimura, T., Kita, T.
(2005). Serum Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels Are Elevated in Acute Coronary Syndrome: A Novel Marker for Early Diagnosis. Circulation
112: 812-818
[Abstract][Full Text]
Abadie, J. M., Blassingame, C. L., Bankson, D. D.
(2005). Albumin Cobalt Binding Assay to Rule Out Acute Coronary Syndrome. Annals of Clinical & Laboratory Science
35: 66-72
[Abstract][Full Text]
Kemp, M., Donovan, J., Higham, H., Hooper, J.
(2004). Biochemical markers of myocardial injury. Br J Anaesth
93: 63-73
[Abstract][Full Text]
Alhadi, H.A., Fox, K.A.A.
(2004). Do we need additional markers of myocyte necrosis: the potential value of heart fatty-acid-binding protein. QJM
97: 187-198
[Abstract][Full Text]
Wakai, A, Gleeson, A, Winter, D
(2003). Role of fibrin D-dimer testing in emergency medicine. Emerg. Med. J.
20: 319-325
[Abstract][Full Text]
Erhardt, L., Herlitz, J., Bossaert, L., Halinen, M., Keltai, M., Koster, R., Marcassa, C., Quinn, T., van Weert, H.
(2002). Task force on the management of chest pain. Eur Heart J
23: 1153-1176
[Full Text]
Deykin, A., Massaro, A. F., Drazen, J. M., Israel, E.
(2002). Exhaled Nitric Oxide as a Diagnostic Test for Asthma: Online versus Offline Techniques and Effect of Flow Rate. Am. J. Respir. Crit. Care Med.
165: 1597-1601
[Abstract][Full Text]
Futterman, L. G., Lemberg, L.
(2002). Novel Markers in the Acute Coronary Syndrome: BNP, IL-6, PAPP-A. Am J Crit Care
11: 168-172
[Full Text]
Douketis, J. D., Crowther, M. A., Stanton, E. B., Ginsberg, J. S.
(2002). Elevated Cardiac Troponin Levels in Patients With Submassive Pulmonary Embolism. Arch Intern Med
162: 79-81
[Abstract][Full Text]
Bayes-Genis, A., Conover, C. A., Overgaard, M. T., Bailey, K. R., Christiansen, M., Holmes, D. R. Jr., Virmani, R., Oxvig, C., Schwartz, R. S.
(2001). Pregnancy-Associated Plasma Protein A as a Marker of Acute Coronary Syndromes. NEJM
345: 1022-1029
[Abstract][Full Text]
Braunwald, E., Antman, E. M., Beasley, J. W., Califf, R. M., Cheitlin, M. D., Hochman, J. S., Jones, R. H., Kereiakes, D., Kupersmith, J., Levin, T. N., Pepine, C. J., Schaeffer, J. W., Smith, E. E. III, Steward, D. E., Theroux, P., Gibbons, R. J., Alpert, J. S., Eagle, K. A., Faxon, D. P., Fuster, V., Gardner, T. J., Gregoratos, G., Russell, R. O., Smith, S. C. Jr
(2000). ACC/AHA guidelines for the management of patients with unstable angina and non-st-segment elevation myocardial infarction: A report of the american college of cardiology/ american heart association task force on practice guidelines (committee on the management of patients with unstable angina). J Am Coll Cardiol
36: 970-1062
[Full Text]
Lee, T. H., Goldman, L.
(2000). Evaluation of the Patient with Acute Chest Pain. NEJM
342: 1187-1195
[Full Text]
Roger, V. L., Farkouh, M. E., Weston, S. A., Reeder, G. S., Jacobsen, S. J., Zinsmeister, A. R., Yawn, B. P., Kopecky, S. L., Gabriel, S. E.
(2000). Sex Differences in Evaluation and Outcome of Unstable Angina. JAMA
283: 646-652
[Abstract][Full Text]
Hillis, G S, Zhao, N, Taggart, P, Dalsey, W C, Mangione, A
(1999). Utility of cardiac troponin I, creatine kinase-MBmass, myosin light chain 1, and myoglobin in the early in-hospital triage of "high risk" patients with chest pain. Heart
82: 614-620
[Abstract][Full Text]
Porela, P., Helenius, H., Pulkki, K., Voipio-Pulkki, L.-M.
(1999). Epidemiological classification of acute myocardial infarction: time for a change?. Eur Heart J
20: 1459-1464
[Abstract]
Wu, A. H.B., Apple, F. S., Gibler, W. B., Jesse, R. L., Warshaw, M. M., Valdes, R. Jr.
(1999). National Academy of Clinical Biochemistry Standards of Laboratory Practice: Recommendations for the Use of Cardiac Markers in Coronary Artery Diseases. Clin. Chem.
45: 1104-1121
[Abstract][Full Text]
Zimmerman, J., Fromm, R., Meyer, D., Boudreaux, A., Wun, C.-C. C., Smalling, R., Davis, B., Habib, G., Roberts, R.
(1999). Diagnostic Marker Cooperative Study for the Diagnosis of Myocardial Infarction. Circulation
99: 1671-1677
[Abstract][Full Text]
Roberts, R., Fromm, R. E.
(1998). Management of Acute Coronary Syndromes Based on Risk Stratification by Biochemical Markers : An Idea Whose Time Has Come. Circulation
98: 1831-1833
[Full Text]
Lakkis, N. M., Nagueh, S. F., Kleiman, N. S., Killip, D., He, Z.-X., Verani, M. S., Roberts, R., Spencer, W. H. III
(1998). Echocardiography-Guided Ethanol Septal Reduction for Hypertrophic Obstructive Cardiomyopathy. Circulation
98: 1750-1755
[Abstract][Full Text]
Christenson, R. H., Azzazy, H. M. E.
(1998). Biochemical markers of the acute coronary syndromes. Clin. Chem.
44: 1855-1864
[Abstract][Full Text]
Nagueh, S. F., Lakkis, N. M., He, Z.-X., Middleton, K. J., Killip, D., Zoghbi, W. A., Quinones, M. A., Roberts, R., Verani, M. S., Kleiman, N. S., Spencer, W. H. III
(1998). Role of myocardial contrast echocardiography during nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol
32: 225-229
[Abstract][Full Text]
Stahmer, S. A
(1998). Recent advances: Accident and emergency medicine. BMJ
316: 1071-1074
[Full Text]
Hamm, C. W., Goldmann, B. U., Heeschen, C., Kreymann, G., Berger, J., Meinertz, T.
(1997). Emergency Room Triage of Patients with Acute Chest Pain by Means of Rapid Testing for Cardiac Troponin T or Troponin I. NEJM
337: 1648-1653
[Abstract][Full Text]
Hlatky, M. A.
(1997). Evaluation of Chest Pain in the Emergency Department. NEJM
337: 1687-1689
[Full Text]
Roberts, R. R., Zalenski, R. J., Mensah, E. K., Rydman, R. J., Ciavarella, G., Gussow, L., Das, K., Kampe, L. M., Dickover, B., McDermott, M. F., Hart, A., Straus, H. E., Murphy, D. G., Rao, R.
(1997). Costs of an Emergency Department--Based Accelerated Diagnostic Protocol vs Hospitalization in Patients With Chest Pain: A Randomized Controlled Trial. JAMA
278: 1670-1676
[Abstract]
Heden, B., Ohlin, H., Rittner, R., Edenbrandt, L.
(1997). Acute Myocardial Infarction Detected in the 12-Lead ECG by Artificial Neural Networks. Circulation
96: 1798-1802
[Abstract][Full Text]
Owa, M., Origasa, H., Saito, M., Owa, M.
(1997). Predictive Validity of the Braunwald Classification of Unstable Angina for Angiographic Findings, Short-Term Prognoses, and Treatment Selection. ANGIOLOGY
48: 663-671
[Abstract]
Randall, D. C., Jones, D. L.
(1997). Eliminating Unnecessary Lactate Dehydrogenase Testing: A Utilization Review Study and National Survey. Arch Intern Med
157: 1441-1444
[Abstract]
Zalenski, R. J., McCarren, M., Roberts, R., Rydman, R. J., Jovanovic, B., Das, K., Mendez, J., El-Khadra, M., Fraker, L., McDermott, M.
(1997). An Evaluation of a Chest Pain Diagnostic Protocol to Exclude Acute Cardiac Ischemia in the Emergency Department. Arch Intern Med
157: 1085-1091
[Abstract]
Ishikawa, Y., Saffitz, J. E., Mealman, T. L., Grace, A. M., Roberts, R.
(1997). Reversible myocardial ischemic injury is not associated with increased creatine kinase activity in plasma. Clin. Chem.
43: 467-475
[Abstract][Full Text]
Goldman, L., Cook, E. F., Johnson, P. A., Brand, D. A., Rouan, G. W., Lee, T. H.
(1996). Prediction of the Need for Intensive Care in Patients Who Come to Emergency Departments with Acute Chest Pain. NEJM
334: 1498-1504
[Abstract][Full Text]
Sgarbossa, E. B., Pinski, S. L., Barbagelata, A., Underwood, D. A., Gates, K. B., Topol, E. J., Califf, R. M., Wagner, G. S., The GUSTO-1 (Global Utilization of Streptokinase a, , Tissue Plasminogen Activator for Occluded Coronary,
(1996). Electrocardiographic Diagnosis of Evolving Acute Myocardial Infarction in the Presence of Left Bundle-Branch Block. NEJM
334: 481-487
[Abstract][Full Text]
Lewis, W. R., Amsterdam, E. A.
(1996). Evaluation of the Patient With 'Rule Out Myocardial Infarction'. Arch Intern Med
156: 41-45
[Abstract]
de Winter, R. J., Koster, R. W., Sturk, A., Sanders, G. T.
(1995). Value of Myoglobin, Troponin T, and CK-MBmass in Ruling Out an Acute Myocardial Infarction in the Emergency Room. Circulation
92: 3401-3407
[Abstract][Full Text]
Erdos, E. G., Skidgel, R. A., Wians, F.H.
(1995). More on Subforms of Creatine Kinase MB. NEJM
333: 390-391
[Full Text]
Antman, E. M., Grudzien, C., Sacks, D. B.
(1995). Evaluation of a Rapid Bedside Assay for Detection of Serum Cardiac Troponin T. JAMA
273: 1279-1282
[Abstract]
Keffer, J.H., Bhayana, V., Henderson, A. R., Propp, D. A., Lane, G. E., Gilson, G., Roberts, R., Puleo, P., Hamm, C. W.
(1995). Subforms of Creatine Kinase MB in the Diagnosis of Myocardial Infarction. NEJM
332: 608-610
[Full Text]
(1994). RAPID ASSAY OF CK-MB SUBFORMS MAY AID DIAGNOSIS OF MI. JWatch General
1994: 1-1
[Full Text]
Hamm, C. W.
(1994). New Serum Markers for Acute Myocardial Infarction. NEJM
331: 607-608
[Full Text]