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Developing a Marker of Ischemia

Clinical and Research Challenges
  • Robert L. Jesse
Part of the Contemporary Cardiology book series (CONCARD)

Abstract

Assessment of the patient with suspected acute coronary syndrome (ACS) has remained challenging despite the growing armamentarium of both diagnostic and prognostic tests. Inadvertent discharge of patients thought to be at low risk of ischemia but later found to have an ACS remains unacceptably high. Present tools (history, clinical examination, electrocardiogram, and biomarkers of necrosis) are not optimally sensitive for the identification of patients with unstable angina. Technetium-based myocardial perfusion imaging is sensitive and specific and provides proof of principle that myocardial ischemia is both detectable and actionable. However, this technology is expensive and requires significant technical expertise. Biochemical tests have historically proven to be fast, accurate, simple to perform, relatively easy to interpret, and inexpensive. All of these characteristics provide a strong argument toward development of biochemical markers of myocardial ischemia. Nevertheless, there are many challenges to this effort. The physiology is complex, and it is complicated by the issues of chronicity, timing, and severity. The absence of a “gold standard” for diagnosis of unstable angina makes comparative analyses difficult to interpret. However, if successful, the potential payback is tremendous in terms of improved clinical management and outcomes.

Key Words

Unstable angina ischemia biomarkers diagnosis 

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References

  1. 1.
    Pope JH, Aufderheide TP, Ruthazer R, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 2000;342:1163–1170.CrossRefPubMedGoogle Scholar
  2. 2.
    Gibler WB, Runyon JP, Levy RC, et al. A rapid diagnostic and treatment center for patients with chest pain in the emergency department. Ann Emerg Med 1995;25:1–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Graff LG, Dallara J, Ross MA, et al. Impact on the care of the emergency department chest pain patient from the chest pain evaluation registry (CHEPER) study. Am J Cardiol 1997;80:563–568.CrossRefPubMedGoogle Scholar
  4. 4.
    Jesse RL, Kontos MC, Roberts CS. Diagnostic strategies for the evaluation of the patient presenting with chest pain. Prog Cardiovasc Dis 2004;46:417–437.CrossRefPubMedGoogle Scholar
  5. 5.
    Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—summary article: 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 2002;40: 1366–1374.CrossRefPubMedGoogle Scholar
  6. 6.
    Pollack CVJ, Roe MT, Peterson ED. 2002 update to the ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: implications for emergency department practice. Ann Emerg Med 2003;41:355–369.CrossRefPubMedGoogle Scholar
  7. 7.
    Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary. A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol 2004;44:671–719.CrossRefPubMedGoogle Scholar
  8. 8.
    Gomez MA, Anderson JL, Karagounis LA, Muhlestein JB, Mooers FB. An emergency department-based protocol for rapidly ruling out myocardial ischemia reduces hospital time and expense: results of a randomized study (ROMIO). J Am Coll Cardiol 1996;28:25–33.CrossRefPubMedGoogle Scholar
  9. 9.
    Roberts RR, Zalenski RJ, Mensah EK, et al. Costs of an emergency department-based accelerated diagnostic protocol vs hospitalization in patients with chest pain: a randomized controlled trial. JAMA 1997;278:1670–1676.CrossRefPubMedGoogle Scholar
  10. 10.
    Farkouh ME, Smars PA, Reeder GS, et al. A clinical trial of a chest-pain observation unit for patients with unstable angina. Chest Pain Evaluation in the Emergency Room (CHEER) Investigators. N Engl J Med 1998;339:1882–1888.CrossRefPubMedGoogle Scholar
  11. 11.
    Joseph AJ, Cohen AG, Bahr RD. A formal, standardized and evidence-based approach to Chest Pain Center development and process improvement: the Society of Chest Pain Centers and Providers accreditation process. J Cardiovasc Manage 2003;14:11–14.Google Scholar
  12. 12.
    Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes (1). N Engl J Med 1992;326:242–250.PubMedGoogle Scholar
  13. 13.
    Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes (2). N Engl J Med 1992;326:310–318.PubMedCrossRefGoogle Scholar
  14. 14.
    Alpert JS, Thygesen K, Bassand JP, et al. Myocardial infarction redefined—a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of Myocardial Infarction. J Am Coll Cardiol 2000;36:959–969.CrossRefPubMedGoogle Scholar
  15. 15.
    Goldman L, Cook EF, Brand DA, et al. A computer protocol to predict myocardial infarction in emergency department patients with chest pain. N Engl J Med 1988;318:797–803.PubMedCrossRefGoogle Scholar
  16. 16.
    Selker HP, Beshansky JR, Griffith JL, et al. Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia: a multicenter, controlled clinical trial. Ann Intern Med 1998;129:845–855.PubMedGoogle Scholar
  17. 17.
    Pozen MW, D’Agostino RB, Mitchell JB, et al. The usefulness of a predictive instrument to reduce inappropriate admissions to the coronary care unit. Ann Intern Med 1980;92:238–242.PubMedGoogle Scholar
  18. 18.
    Lee TH, Rouan GW, Weisberg MC, et al. Clinical characteristics and natural history of patients with acute myocardial infarction sent home from the emergency room. Am J Cardiol 1987;60:219–224.CrossRefPubMedGoogle Scholar
  19. 19.
    Karcz A, Korn R, Burke MC, et al. Malpractice claims against emergency physicians in Massachusetts: 1975–1993. Am J Emerg Med 1996;14:341–345.CrossRefPubMedGoogle Scholar
  20. 20.
    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 Med 1996;335:1342–1349.CrossRefPubMedGoogle Scholar
  21. 21.
    Lee TH, Cook EF, Weisberg M, Sargent RK, Wilson C, Goldman L. Acute chest pain in the emergency room: identification and examination of low-risk patients. Arch Intern Med 1985;145:65–69.CrossRefPubMedGoogle Scholar
  22. 22.
    Fesmire FM, Percy RF, Bardoner JB, Wharton DR, Calhoun FB. Usefulness of automated serial 12-lead ECG monitoring during the initial emergency department evaluation of patients with chest pain. Ann Emerg Med 1998;31:3–11.CrossRefPubMedGoogle Scholar
  23. 23.
    Zalenski RJ, Cooke D, Rydman R, Sloan EP, Murphy DG. Assessing the diagnostic value of an ECG containing leads V4R, V8, and V9: the 15-lead ECG. Ann Emerg Med 1993;22:786–793.CrossRefPubMedGoogle Scholar
  24. 24.
    Kornreich F, Montague TJ, Rautaharju PM. Body surface potential mapping of ST segment changes in acute myocardial infarction: implications for ECG enrollment criteria for thrombolytic therapy. Circulation 1993;87:773–782.PubMedGoogle Scholar
  25. 25.
    Amsterdam EA, Kirk JD, Diercks DB, Lewis WR, Turnipseed SD. Immediate exercise testing to evaluate low-risk patients presenting to the emergency department with chest pain. J Am Coll Cardiol 2002;40: 251–256.CrossRefPubMedGoogle Scholar
  26. 26.
    Klocke FJ, Baird MG, Lorell BH, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). Circulation 2003;108:1404–1418.CrossRefPubMedGoogle Scholar
  27. 27.
    Kontos MC, Jesse RL, Anderson FP, Schmidt KL, Ornato JP, Tatum JL. Comparison of myocardial perfusion imaging and cardiac troponin I in patients admitted to the emergency department with chest pain. Circulation 1999;99:2073–2078.PubMedGoogle Scholar
  28. 28.
    Heller GV, Stowers SA, Hendel RC, et al. Clinical value of acute rest technetium-99m tetrofosmin tomographic myocardial perfusion imaging in patients with acute chest pain and nondiagnostic electrocardiograms. J Am Coll Cardiol 1998;31:1011–1017.CrossRefPubMedGoogle Scholar
  29. 29.
    Hilton TC, Thompson RC, Williams HJ, Saylors R, Fulmer H, Stowers SA. Technetium-99m sestamibi myocardial perfusion imaging in the emergency room evaluation of chest pain. J Am Coll Cardiol 1994;23:1016–1022.PubMedCrossRefGoogle Scholar
  30. 30.
    Tatum JL, Jesse RL, Kontos MC, et al. Comprehensive strategy for the evaluation and triage of the chest pain patient. Ann Emerg Med 1997;29:116–123.CrossRefPubMedGoogle Scholar
  31. 31.
    Kontos MC, Jesse RL, Schmidt KL, Ornato JP, Tatum JL. Value of acute rest sestamibi perfusion imaging for evaluation of patients admitted to the emergency department with chest pain. J Am Coll Cardiol 1997;30:976–982.CrossRefPubMedGoogle Scholar
  32. 32.
    Fintel DJ, Ledley GS. Management of patients with non-ST-segment elevation acute coronary syndromes: insights from the PURSUIT trial. Clin Cardiol 2000;23:1–12.CrossRefGoogle Scholar
  33. 33.
    Stocker R, Keaney JF Jr. Role of oxidative modifications in atherosclerosis. Physiol Rev 2004;84(4): 1381–1478.Google Scholar
  34. 34.
    Holvoet P, Collen D, Van de Werf F. Malondialdehyde-modified LDL as a marker of acute coronary syndromes. JAMA 1999;281:1718–1721.CrossRefPubMedGoogle Scholar
  35. 35.
    Eisen A, Fisman EZ, Rubenfire M, et al. Ischemic preconditioning: nearly two decades of research: a comprehensive review. Atherosclerosis 2004;172:201–210.CrossRefPubMedGoogle Scholar
  36. 36.
    Bar-Or D, Lau E, Rao N, Bampos N, Winkler JV, Curtis CG. Reduction in the cobalt binding capacity of human albumin with myocardial ischemia [abstract]. Ann Emerg Med 1999;34:4.Google Scholar
  37. 37.
    Christenson RH, Duh SH, Sanhai WR, et al. Characteristics of an albumin cobalt binding test for assessment of acute coronary syndrome patients: a multicenter study. Clin Chem 2001;47(3):464–470.Google Scholar
  38. 38.
    Sinha MK, Gaze DC, Tippins JR, Collinson PO, Kaski JC. Ischemia modified albumin is a sensitive marker of myocardial ischemia after percutaneous coronary intervention. Circulation 2003;107:2403–2405.CrossRefPubMedGoogle Scholar
  39. 39.
    deFilippi C, Yoon S, Bounds C, et al. Early detection of myocardial ischemia by a novel blood-based biomarker: the kinetics of ischemia modified albumin. J Am Coll Cardiol 2003;41(6)(Suppl A):402A.Google Scholar
  40. 40.
    Reinhardt CP, Weinstein H, Leppo JA. Comparison of iodine-125-BMIPP and thallium-201 in myocardial hypoperfusion. J Nucl Med 1995;36(9):1645–1653.PubMedGoogle Scholar
  41. 41.
    Takeda K, Saito K, Makino K, et al. Iodine-123-BMIPP myocardial washout and cardiac work during exercise in normal and ischemic hearts. J Nucl Cardiol 1997;38(4):559–563.Google Scholar
  42. 42.
    Naruse H, Arii T, Kondo T, et al. Clinical usefulness of iodine 123-labeled fatty acid imaging in patients with acute myocardial infarction. J Nucl Cardiol 1998;5(3):275–284.CrossRefGoogle Scholar
  43. 43.
    Kawai Y, Tsukamoto E, Nozaki Y, Morita K, Sakurai M, Tamaki N. Significance of reduced uptake of iodinated fatty acid analogue for the evaluation of patients with acute chest pain. J Am Coll Cardiol 2001;38(7):1888–1894.CrossRefPubMedGoogle Scholar
  44. 44.
    Kleinfeld AM, Prothro D, Brown DL, Davis RC, Richieri GV, DeMaria A. Increases in serum unbound free fatty acid levels following coronary angioplasty. Am J Cardiol 1996;78:1350–1354.CrossRefPubMedGoogle Scholar
  45. 45.
    Katus HA, Remppis A, Neumann FJ, et al. Diagnostic efficiency of troponin T measurements in acute myocardial infarction. Circulation 1991;83:902–912.PubMedGoogle Scholar
  46. 46.
    Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined—a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. J Am Coll Cardiol 2000;36:959–969.CrossRefPubMedGoogle Scholar
  47. 47.
    Rosalki SB, Roberts R, Katus HA, Giannitsis E, Ladenson JH. Cardiac biomarkers for detection of myocardial infarction: perspectives from past to present. Clin Chem 2004;50(11):2205–2213.CrossRefPubMedGoogle Scholar
  48. 48.
    Apple FS, Kleinfeld AM, Adams J III. Unbound free fatty acid concentrations are increased in cardiac ischemia. Clin Proteomics 2004;1:41–44.CrossRefGoogle Scholar
  49. 49.
    Abadie JM, Blassingame CL, Bankson DD. Albumin cobalt binding assay to rule out acute coronary syndrome. Ann Clin Lab Sci 2005;35:66–72.PubMedGoogle Scholar
  50. 50.
    Armstrong PW, Fu Y, Chang WC, et al. Acute coronary syndromes in the GUSTO-IIb trial: prognostic insights and impact of recurrent ischemia. The GUSTO IIb Investigators. Circulation 1998;98:1860–1868.PubMedGoogle Scholar
  51. 51.
    Galvani M, Ottani F, Ferrini D, et al. Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina. Circulation 1997;95:2053–2059.PubMedGoogle Scholar
  52. 52.
    Selker HP, Griffith JL, Dorey FJ, D’Agostino RB. How do physicians adapt when the coronary care unit is full? A prospective multicenter study. JAMA 1987;257:1181–1185.CrossRefPubMedGoogle Scholar
  53. 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 Med 1994;331:561–566.CrossRefPubMedGoogle Scholar
  54. 54.
    Rouan GW, Hedges JR, Toltzis R, Goldstein-Wayne B, Brand D, Goldman L. A chest pain clinic to improve the follow-up of patients released from an urban university teaching hospital emergency department. Ann Emerg Med 1987;16:1145–1150.CrossRefPubMedGoogle Scholar
  55. 55.
    Tierney WM, Fitzgerald J, McHenry R, et al. Physicians’ estimates of the probability of myocardial infarction in emergency room patients with chest pain. Med Decis Making 1986;6:12–17.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Robert L. Jesse
    • 1
    • 2
  1. 1.Acute Cardiac Care, Coronary ICUVirginia Commonwealth University Health SystemRichmond
  2. 2.Cardiology SectionDepartment of Veterans Affairs Medical CenterRichmond

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