Conventional and promising new markers of myocardial injury have become an important diagnostic tool and their prognostic significance is also recognized. In addition, they help identify patients who will derive the most benefit from therapeutic interventions. The literature was searched from the websites of the National Library of Medicine (http://www.ncbi.nlm.nih.gov/) and PubMed Central, the U.S. National Library of Medicine’s digital archive of life sciences journal literature (http://www.pubmedcentral.nih.gov/). The data were accessed from books and journals that published relevant articles in this field. The diagnosis of acute myocardial infarction (AMI) has traditionally relied on the combination of chest pain, ECG features, and elevation in serum markers. However, chest symptoms are frequently atypical or absent and ECG changes may be nonspecific or absent. Hence, the diagnosis of acute coronary syndromes has become increasingly dependent on serum markers of cardiac injury. Among them, creatine kinase (CK) is an effective and widely used test, with the recent CKMB assay offering greater specificity and sensitivity. Cardiac troponins facilitate early and rapid diagnosis, enable effective risk stratification in patients with AMI (with or without traditional criteria for MI), and identify those who will benefit from aggressive medical or surgical intervention. Recent data suggest the potential of myoglobin and CKMB isoforms as sensitive markers in the early hours after symptom onset. Cardiac-specific troponins help in rapid diagnosis, prognostication, and treatment of AMI. Troponins also facilitate early detection of recent infarction owing to their prolonged diagnostic window and also aid in the detection of “microinfarction.” CKMB is used to detect reinfarction or infarct extension, if levels rise again after declining. Finally, novel biochemical markers are receiving attention in ongoing trials. They may prove to be more effective in diagnosis and prognosis than their existing counterparts.
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References
1.
Myocardial infarction redefined—a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Eur Heart J21:1502-1513, 2000.
2.
Lee TH, Goldman L: Serum enzyme assays in the diagnosis of acute myocardial infarction. Ann Intern Med105:221-233, 1986.
3.
Gehman EM, Ehsani AA, Campbell MK, et al: The influence of location and extent of myocardial infarction on long-term ventricular dysrhythmia and mortality. Circulation60:805-814, 1979.
4.
Karmen A, Wroblewski F, Ladne JS: Transaminase activity in human blood. J Clin Invest34:126-133, 1954.
5.
Vasudevan G, Mercer DW, Varat MA: Lactic dehydrogenase isoenzyme determination in the diagnosis of acute myocardial infarction. Circulation55:1055-1057, 1978.
6.
van der Veen KJ, Willebrands AF: Isoenzymes of creatine phosphokinase in tissue extracts and in normal and pathological sera. Clin Chim Acta13:312-316, 1966.
7.
Newby LK, Goldmann BU, Ohman EM: Troponin: An important prognostic marker and risk stratification tool in acute coronary syndromes. J Am Coll Cardiol41(4 suppl S):31S-36S, 2003.
8.
Adams JE III, Abendschein DR, Jaffe AS: Biochemical markers of myocardial injury. Is MB creatine kinase the choice for the 1990s? Circulation88:750-763, 1993.
9.
Katus HA, Remppis A, Scheffold T, et al: Intracellular compartmentation of cardiac troponin T and its release kinetics in patients with reperfused and nonreperfused myocardial infarction. Am J Cardiol67:1360-1367, 1991.
10.
Adams JE III, Bodor GS, Davila-Roman VG, et al: Cardiac troponin I: A marker with high specificity for cardiac injury. Circulation88:101-106, 1993.
11.
Katus HA, Looser S, Hallermayer K: Development and in vitro characterization of a new immunoassay of cardiac troponin I. Clin Chem38:386-393, 1992.
12.
Baum H, Braun S, Gerhardt W: Multicenter evaluation of a second generation assay for cardiac troponin T. Clin Chem43:1877-1884, 1997.
13.
Fitzmaurice TF, Brown C, Rifai N, et al: False increase of cardiac troponin I with heterophilic antibodies. Clin Chem44:2212-2214, 1998.
14.
Wu AHB, Feng YJ, Moore R: Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparisons of assay for troponin T and I. Clin Chem44:1198-1208, 1998.
15.
Wu AH, Apple FS, Gibler WE, et al: National Academy of Clinical Biochemistry standards of laboratory practice: Recommendations for the use of cardiac markers in coronary artery diseases. Clin Chem45:1104-1121, 1999.
16.
Apple FS, Quist HE, Doyle PJ, et al: Plasma 99th percentile reference limits for cardiac troponin and creatine kinase MB mass for use with European Society of Cardiology/American College of Cardiology consensus recommendations. Clin Chem49:1331-1336, 2003.
17.
McLaurin MD, Apple FS, Voss EM, et al: Cardiac troponin T and creatine kinase MB in dialysis patients without ischemic heart disease: Evidence of cardiac troponin T expression in skeletal muscle. Clin Chem43:976-982, 1997.
18.
Ricchiuti V, Voss EM, Wey A, et al: Cardiac troponin-T isoforms expressed in renal diseased skeletal muscle will not cause false-positive results by the second-generation cardiac troponin-T assay by Boehringer Mannheim. Clin Chem44:1919-1924, 1998.
19.
Bodor GS, Porterfield D, Voss EM, et al: Cardiac troponin-I is not expressed in fetal and healthy or diseased adult human skeletal muscle tissue. Clin Chem41:1710-1716, 1995.
20.
Santalo Bel M, Guido Soldevila J, Ordonez Llanos J: Biological markers of myocardial necrosis. Rev Esp Cardiol56:703-720, 2003.
21.
Wiviott SD, Cannon CP, Murphy SA, et al: Differential expression of cardiac biomarkers in patients with unstable angina/non-ST-elevation myocardial infarction: A TACTICS-TIMI 18 substudy. Circulation109:565-567, 2004.
22.
Hasdai D, Behar S, Boyko V, et al: Cardiac biomarkers and acute coronary syndromes—the Euro Heart Survey of Acute Coronary Syndromes Experience. Eur Heart J24:1189-1194, 2003.
23.
Del Carlo CH, Pereira AC, Cassaro C, et al: Serial measure of cardiac troponin-T levels for prediction of clinical events in congestive heart failure. J Card Fail10:43-48, 2004.
24.
Wu AHB (ed.): Cardiac Markers. Totowa, NJ: Humana Press, 1998, p 300.
25.
Fink FM, Genser N, Fink C, et al: Cardiac troponin T and creatine kinase MB mass concentrations in children receiving anthracycline chemotherapy. Med Pediatr Oncol25:185-189, 1995.
26.
Spies C, Hande V, Fitzner R, et al: Serum cardiac troponin T as prognostic marker in early sepsis. Chest113:1055-1063, 1998.
27.
Alehan D, Ayabakan C, Hallioglu O: Role of serum cardiac troponin T in the diagnosis of acute rheumatic fever and rheumatic carditis. Heart90:689-690, 2004.
28.
Lauer B, Niederau C, Kuhl U, et al: Cardiac troponin T in patients with clinically suspected myocarditis. J Am Coll Cardiol30:1354-1359, 1997.
29.
Scirica BM, Morrow DA: Troponins in acute coronary syndromes. Semin Vasc Med3:363-374, 2003.
30.
Mockel M, Danne O, Schmidt A, et al: Reference values for cardiac troponin T and I in goal-oriented concept of health. Clin Chim Acta342:83-86, 2004.
31.
Muller Bardorff M, Hallermayer K, Schroeder A, et al: Improved troponin T ELISA specific for cardiac troponin T isoform: Assay development and analytical and clinical validation. Clin Chem43:458-466, 1997.
32.
De Zoysa JR: Cardiac troponins and renal disease. Nephrology9:83-88, 2004.
33.
Hetland O, Dickstein K: Cardiac troponins I and T in patients with suspected acute coronary syndrome: A comparative study in a routine setting. Clin Chem44:1430-1436, 1998.
34.
Zimmerman J, Fromm R, Meyer D, et al: Diagnostic Marker Co-operative Study for the diagnosis of myocardial infarction. Circulation91:1671-1677, 1999.
35.
Antman EM, Tanasijevic MJ, Thompson B, et al: Cardiac specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med335:1342-1349, 1996.
36.
Ottani F, Galvani M, Nicolini FA, et al: Elevated cardiac troponin levels predict the risk of adverse outcome in patients with acute coronary syndromes. Am Heart J140:917-927, 2000.
37.
Ohman EM, Armstrong PW, Christenson RH, et al: Cardiac troponin T levels for risk stratification in acute myocardial ischemia GUSTO II Investigators. N Engl J Med335:1333-1341, 1996.
38.
Lindahl B, Diderholm E, Lagerqvist B, et al: Mechanisms behind the prognostic value of troponin T in unstable coronary artery disease: A FRISC (Fragmin in unstable coronary artery disease) II substudy. J Am Coll Cardiol38:979-983, 2001.
39.
Heidenreich PA, Alloggiamento T, Melsop K, et al: The prognostic value of troponin in patients with non-ST elevation acute coronary syndromes: A meta-analysis. J Am Coll Cardiol38:478-490, 2001.
40.
Antman EM, Sacks DB, Rifai N, et al: Time to positivity of a rapid bedside assay for cardiac specific troponin T predicts prognosis in acute coronary syndromes: A Thrombolysis in Myocardial Infarction (TIMI) 11A substudy. J Am Coll Cardiol31:326-330, 1998.
41.
Solymoss BC, Bourassa MG, Cernacek P, et al: Classification and risk stratification of patients with acute chest pain using cardiac troponin T. Clin Cardiol27:130-136, 2004.
42.
Okamatsu K, Takano M, Sakai S, et al: Elevated troponin T levels and lesion characteristics in non-ST-elevation acute coronary syndromes. Circulation109:465-470, 2004.
43.
Carrier M, Pellerin M, Perrault LP, et al: Troponin levels in patients with myocardial infarction after coronary artery bypass graftingAnn Thorac Surg69:435-440, 2000.
44.
Kim LJ, Martinez EA, Faraday N, et al: Cardiac troponin I predicts short-term mortality in vascular surgery patients. Circulation106:2366-2369, 2002.
45.
Bessman S, Carpenter C: The creatine-creatine phosphate energy shuttle. Annu Rev Biochem54:831-840, 1985.
46.
Wolf PL: Abnormalities in serum enzymes in skeletal muscle diseases. Am J Clin Pathol95:293-298, 1991.
47.
Lott JA, Stang JM: Differential diagnosis of patients with abnormal creatinine kinase isoenzymes. Clin Lab Med9:627-642, 1989.
48.
Gibler WB, Lewis LM, Erb RE, et al: Early detection of acute myocardial infarction in patients presenting with chest pain and nondiagnostic electrocardiograms: Serial CK-MB sampling in the emergency department. Ann Emerg Med19:1359-1366, 1990.
49.
Hedges JR, Young GP, Hentel GF, et al: Serial ECGs are less accurate than serial CK-MB results for emergency department diagnosis of myocardial infarction. Ann Emerg Med21:1445-1450, 1992.
50.
Collinson PO: Troponin T or I or CK-MB (or none?). Eur Heart J19(suppl N):N16-N24, 1998.
51.
Wevers RA, Delsing M, Klein Gebbink JA, et al: Postsynthetic changes in creatine kinase isoenzymes. Clin Chim Acta86:323-327, 1978.
52.
Prager NP, Suzuki T, Jaffe AS, et al: The nature and time course of generation of isoforms of MB creatine kinase in vivo. J Am Coll Cardiol20:414-420, 1992.
53.
Puleo PR, Meyer D, Wathen C, et al: Use of a rapid assay of subforms of creatine kinase-MB to diagnose or rule out acute myocardial infarction. N Engl J Med331:561-566, 1994.
54.
Abendschein D, Seacord LM, Nohara R, et al: Prompt detection of myocardial injury by assay of creatine kinase isoforms in initial plasma samples. Clin Cardiol11:661-666, 1988.
55.
Alexander JH, Sparapani RA, Mahaffey KW, et al: Association between minor deviations of creatinine kinase MB level and mortality in patients with acute coronary syndromes without ST segment elevation. PURSUIT Steering Committee. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor suppression using Integrilin therapy. JAMA283:347-363, 2000.
56.
Savonitto S, Granger CB, Ardissino D, et al, on behalf of the GUSTO IIb investigators: The prognostic value of creatine kinase elevation extends across the whole spectrum of acute coronary syndromes. J Am Coll Cardiol39:22-30, 2002.
57.
Kagen LJ: Myoglobin: Biochemical, Physiological and Clinical Aspects. New York: Columbia University press, 1973.
58.
Ohman EM, Casey C, Bengston JR, et al: Early detection of acute myocardial infarction: Additional diagnostic information from serum concentrations of myoglobin in patients without ST elevation. Br Heart J63:335-338, 1990.
59.
Mair J, Artner-Dworzak E, Lechleitner P, et al: Early diagnosis of acute myocardial infarction by a newly developed rapid immunoturbidimetric assay for myoglobin. Br Heart J68:462-468, 1992.
60.
Montagne C, Kircher T: Myoglobin in the early evaluation of acute chest pain. Am J Clin Pathol104:472-476, 1995.
61.
Luscher MS, Ravikilde J, Thygesen K, et al: Clinical application of two novel rapid bedside tests for the detection of cardiac troponin T and creatine kinase—MB mass/myoglobin in whole blood in acute myocardial infarction. Cardiology89:222-228, 1998.
62.
Kontos MC, Anderson FP, Hanburg CM, et al: Use of the combination of myoglobin and CK-MB mass for rapid diagnosis of acute myocardial infarction. Am J Emerg Med15:14-19, 1997.
63.
Laperche T, Steg PG, Benessiano J: Patterns of myoglobin and MM-creatine kinase isoforms release early after intravenous thrombolysis or direct percutaneous transluminal coronary angioplasty for acute myocardial infarction and implication for the early noninvasive diagnosis of reperfusion. Am J Cardiol70:1129-1134, 1992.
64.
de Lemons JA, Morrow DA, Gibson CM, et al: The prognostic value of serum myoglobin in patients with non-ST-segment elevation acute coronary syndromes. Results from the TIMI IIB and TACTICS-TIMI 18 studies. J Am Coll Cardiol40:238-244, 2002.
65.
Zaninotto Plebani M: Diagnostic strategies in myocardial infarction using myoglobin measurement. Eur Heart J19(suppl N):N12-N15, 1998.
66.
Marshall T, Williams J, Willams KM: Electrophoresis of serum proteins and enzymes following acute myocardial infarction. J Chromatogr569:323-327, 1991.
67.
Mortelmans L, Vanheacke J, Lesaffre E, et al: Evaluation of the effect of thrombolytic treatment on infarct size and left ventricular function by enzymatic, scintigraphic and angiographic methods: The European Co-operative Study Group for Recombinant Tissue Type Plasminogen Activator. Am Heart J119:1231-1237, 1990.
68.
Van Nieuwenhoven FA, Kleine AH, Wodzing WH, et al: Discrimination between myocardial and skeletal muscle injury by assessment of the plasma ratio of myoglobin over fatty binding protein. Circulation92:2848-2852, 1995.
69.
Chen SH, Gilbett ER: Enolase: Human tissue distribution and evidence for three different loci. Ann Hum Genet39:277-280, 1976.
70.
Kato K, Ishiguro Y, Ariyoshi Y: Enolase isozymes as disease markers: Distribution of three enolase subunits (α, β, and γ) in various human tissues. Dis Markers1:213-220, 1983.
71.
Nomura M, Kato K, Nagaska A, et al: Serum β-enolase in acute myocardial infarction. Br Heart J58:29-33, 1987.
72.
Herraez-Dominguez M, Goldberg D, Anderson A, et al: Serum enolase and pyruvate kinase activities in the diagnosis of myocardial infarction. Enzyme21:211-224, 1976.
73.
van L Andeghem AAJ, Soons JBJ, Wever RA, et al: Purification and determination of the modifying protein responsible for the post-synthetic modification of creatine kinase (EC 2.7.3.2) and enolase (EC4.2.1.11). Clin Chim Acta153:217-234, 1985.
74.
Collins JH, Thiebert JL, Libera LD: Amino acid sequence of rabbit ventricular myosin light chain-2: Identity with the slow skeletal muscle isoform. Biosci Rep6:655-671, 1986.
75.
Katus HA, Yasuda T, Gold H, et al: Diagnosis of acute myocardial infarction by detection of circulating cardiac myosin light chains. Am J Cardiol54:964-970, 1984.
76.
Hoberg E, Katus HA, Diedrich KW, et al: Myoglobin, creatine kinase-B isozyme and myosin light chain release in patients with unstable angina pectoris. Eur Heart J8:989-994, 1987.
77.
Segrin JR, Saussine M, Ferrierre M, et al: Myosin: A highly sensitive indicator of myocardial necrosis after cardiac operations. J Thorac Cardiovasc Surg98:397-401, 1989.
78.
Leger JOC, Larne C, Ming T, et al: Assay of serum cardiac myosin heavy chain fragments in patients with acute myocardial infarction: Determination of infarct size and long term follow up. Am Heart J120:781-790, 1990.
79.
Ridker P: Fibrinolytic and inflammatory markers for arterial occlusion: The evolving epidemiology of thrombosis and hemostasis. Thromb Hemostas78:53-59, 1997.
80.
Elgharib N, Chi DS, Younis W, et al: C-reactive protein as a novel biomarker and predictor of cardiac events. Postgrad Med114:39-44, 2003.
81.
Koenig W, Sund M, Frohlich M, et al: C-reactive protein, a sensitive marker of inflammation predicts future risk of coronary heart disease; results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation99:237-242, 1999.
82.
Kuller LH, Tracy RP, Shaten J, et al: Relation of C-reactive protein and the risk of coronary heart disease in the MRFIT nested case control study. Am J Epidemiol144:537-547, 1996.
83.
Morrow D, Ridker P: High sensitivity C-reactive protein (hs-CRP): A novel risk marker in cardiovascular disease. Preventive Cardiol1:13-16, 1999.
84.
Howard OM, Oppenheim JJ, Wang JM: Chemokines as molecular target for therapeutic intervention. J Clin Immunol19:280-292, 1999.
85.
Meune C, Martins E, Fulla Y, et al: New biological markers for acute coronary artery disease. J Mal Vasc28:251-257, 2003.
86.
Lindahl B, Venge P, Wallentin L, et al: Troponin T identifies patients with unstable coronary artery disease who benefit from long-term antithrombotic protection Fragmin in Unstable Coronary Artery Disease (FRISC) study group. J Am Coll Cardiol29:43-48, 1997.
87.
Hamn C, Heeschen C, Goldmann B, et al: Value of troponins in predicting therapeutic efficacy of abciximab in patients with unstable angina (abstract). JACC31:185A, 1998.
88.
Hamm C, Heeschen C, Goldmann B, et al: Troponin T predicts the benefit of abciximab in patients with unstable angina in the CAPTURE study (abstract). Eur Heart J19:117, 1998.
89.
Ridker PM, Cushman M, Stampfer MJ, et al: Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men. N Engl J Med336:973-979, 1997.
90.
Ridker P, Rifai N, Pfeffer M, et al: Inflammation, pravastatin and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Circulation98:939-944, 1998.
