European Heart Journal Advance Access originally published online on February 13, 2006
European Heart Journal 2006 27(6):759; doi:10.1093/eurheartj/ehi779
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Markers of myocardial ischaemia: reply
Universitätsklinikum Heidelberg
Abteilung Innere Medizin III
Im Neuenheimer Feld 410
69120 Heidelberg
Germany
Universitätsklinikum Heidelberg
Abteilung Innere Medizin III
Im Neuenheimer Feld 410
69120 Heidelberg
Germany
Tel: +49 6221 8670
E-mail address: hugo_katus{at}med.uni-heidelberg.de
We thank Sinha and coworkers for their very interesting comments. We appreciate the overview on the evidence available for ischaemia-modified albumin (IMA). In fact, our editorial1 did not primarily focus on IMA but used IMA as an example to point to some inconsistencies and shortcomings of a flood of new biomarkers claiming early and sensitive detection of myocardial ischaemia before or in the absence of myonecrosis such as heart fatty-acid-binding protein or DNase I activity. Sinha highlights elegantly by listing conditions with elevated IMA in the absence of myocardial ischaemia that IMA lacks absolute cardiospecificity and that the clear mechanism for the generation of IMA is still illusive. A recent publication of this research group supports the hypothesis that reactive oxygen species after reperfusion injury may be responsible for the generation of IMA.2
With respect to the superior sensitivity for IMA compared with cardiac troponin, the use of an inappropriately high cTnT cutpoint >0.05 µg/L in representative trials3,4 may have contributed to the low diagnostic sensitivity of cTnT, thus improving the sensitivity of IMA.
Concerns on the inappropriate use of cardiac troponins due to the use of high cut-off values, or the use of insensitive assays or only the initial sample of analysis have been raised in an editorial by Jaffe and Katus.5 Given a very unreflected use of new biomarkers, we feel that there is a need for an authoritative and scholastic reminder for emergency and other physicians that the FDA has only approved IMA for use in low-risk patients with chest pain suggestive of acute coronary syndrome (ACS), and only in conjunction with a 12-lead ECG and cardiac troponin. Thus, a negative IMA result together with a normal ECG and cardiac troponin test may only help to rule out ACS in patients with a low pre-test probability for coronary artery disease and an ACS, respectively. Although such a constellation may be frequent in an interdisciplinary emergency department, only a small fraction of cases presenting to an internal medicine emergency department or to a specialized chest pain centre has such a low pre-test probability for ACS.
An even more controversial area emerging is the use of IMA to rule in and risk stratify patients with ischaemic heart disease. Given the relatively low cardiospecificity of IMA, a high prevalence of suspected disease is required for this purpose.
Whether IMA or other new biomarkers will be able to complement or even to compete with the well-established diagnostic and risk-predicting tools such as the ECG, cardiac troponins, natriuretic peptides, and inflammatory markers remains uncertain at present.
References
- Giannitsis E, Katus HA. Mirror, mirror on the wall: the quest for the earliest marker of myocardial ischaemia. Eur Heart J 2005;26:2349–2350.
[Free Full Text] - Roy D, Quiles J, Gaze DC, Collinson P, Kaski JC, Baxter GF. Role of reactive oxygen species on the formation of the novel diagnostic marker ischaemia modified albumin. Heart 2006;92:113–114.
[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, Aldama G, Sinha M, Avanzas P, Arroyo-Espliguero R, Gaze D, Collinson P, Carlos Kaski J. Ischemia modified albumin for the assessment of patients presenting to the emergency department with acute chest pain but normal or non-diagnostic 12-lead electrocardiograms and negative cardiac troponin T. Int J Cardiol 2004;97:297–301.[CrossRef][Web of Science][Medline]
- Jaffe AS, Katus H. Acute coronary syndrome biomarkers: the need for more adequate reporting. Circulation 2004;110:104–106.
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