European Heart Journal Advance Access originally published online on February 13, 2006
European Heart Journal 2006 27(6):758; doi:10.1093/eurheartj/ehi778
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Markers of myocardial ischaemia
Division of Cardiac and Vascular Sciences
St George's University of London
London
UK
Division of Cardiac and Vascular Sciences
St George's University of London
London
UK
Division of Cardiac and Vascular Sciences
St George's University of London
Cranmer Terrace
London SW17 0RE
UK
Tel: +44 208 725 3963
Fax: +44 208 725 3328
E-mail address: jkaski{at}sgul.ac.uk
We read with interest the article by Giannitsis and Katus1 on markers of myocardial ischaemia. Although their comments are authoritative and scholarly, we feel that the authors failed to objectively summarize the evidence available for ischaemia-modified albumin (IMA) as a marker of myocardial ischaemia. Research from our unit has shown that IMA is an early marker of ischaemia in patients undergoing coronary angioplasty.2 We have also shown that IMA has a higher sensitivity than the 12-lead ECG and cardiac troponin (cTn) T levels for the diagnosis of acute coronary syndrome (ACS) in chest pain patients attending the emergency department within 3 h of the onset of pain.3 The combined use of IMA, cTn, and a negative ECG has a high negative predictive value for ACS, which may be extremely useful to rule out ACS in the emergency room. In fact, the FDA has recently approved the use of IMA for this indication.
The use of IMA as a marker of ischaemia in the clinical setting, however, has limitations at present. (i) IMA has a relatively low specificity for myocardial ischaemia as it may increase in patients with stroke, end-stage renal disease, liver disease, and some neoplasms. (ii) Increased endogenous lactate levels appear to reduce IMA concentrations, which raise concern about the true significance of a negative IMA result in patients with sepsis or renal failure where lactate may be present in the circulation. (iii) A further limitation is that the ACB test (the test currently used to measure IMA) is a colorimetric assay, and therefore an indirect measurement of IMA production. New assay platforms (i.e. immunoassays), however, are expected to be available in the near future, which may improve the specificity of IMA.
Despite these limitations, the high sensitivity of the test will drive a high negative predictive value in a population with low prevalence of coronary disease, thus making IMA measurement a good test to rule out ACS in acute chest pain patients with low to moderate pre-test probability of coronary disease presenting with normal cTn and ECG results.
Of importance, we have also reported that IMA levels raise after radiofrequency catheter ablation and direct current cardioversion,4,5 which could be due to the generation of reactive oxygen species following electrical and thermal myocardial injury. These data taken together suggest that increased IMA levels may be a marker of both myocardial ischaemia and oxidative stress. As oxidative stress not only occurs during myocardial ischaemia but develops also in other medical conditions, studies in large ‘real-life’ patient populations are required to assess the true role of IMA as a marker of transient myocardial ischaemia. Incorporating the ACB test into the decision-making process of a typical emergency room population may be a good way forward to ascertain whether IMA has a diagnostic and risk stratification role in the clinical setting. Importantly, however, as with other cardiac markers, IMA cannot be used effectively without fully considering the clinical circumstances of the patient.
References
- Giannitis E, Katus H. Mirror, mirror on the wall: the quest for the earliest marker of myocardial ischaemia. Eur Heart J 2005;26:2349–2350.
[Free Full Text] - 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.
[Abstract/Free Full Text] - Sinha MK, Roy D, Gaze DC, Collinson PO, Kaski JC. Role of ‘ischemia modified albumin’, a new biochemical marker of myocardial ischaemia, in the early diagnosis of acute coronary syndromes. Emerg Med J 2004;21:29–34.
[Abstract/Free Full Text] - Roy D, Quiles J, Sinha M, Aldama G, Gaze D, Kaski JC. Effect of direct current cardioversion on ischemia modified albumin levels in patients with atrial fibrillation. Am J Cardiol 2004;93:366–368.[CrossRef][Web of Science][Medline]
- Roy D, Quiles J, Sinha M, Floros D, Gaze D, Collinson P, Baxter GF, Kaski JC. The effect of radiofrequency catheter ablation on the biochemical marker ischemia modified albumin (IMA). Am J Cardiol 2004;94:234–236.[CrossRef][Web of Science][Medline]
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