Myocardial infarction: why can’t we get the diagnosis right?

Cheuk-Kit Wonga and Harvey D. Whiteb,*

a Cardiology Department, Dunedin Hospital, Dunedin, New Zealand
b Cardiology Department, Green Lane Hospital, Auckland, New Zealand

* Corresponding author. Professor Harvey White, Cardiology Department, Green Lane Hospital, Private Bag 92189, Auckland 1030, New Zealand. Tel.: +64-9-630 9992; fax:+64-9-630 9915
E-mail address: harveyw{at}adhb.govt.nz

Received 14 May 2003; accepted 16 May 2003

See doi:10.1016/S1095-668X(03)00204-5 for the article to which this editorial refers

A joint consensus statement redefining acute myocardial infarction (MI) was published on 4 September 2000 by the European Society of Cardiology (ESC) and the American College ofCardiology (ACC).1The new definition of MI relies heavily upon measurements of sensitive and specific markers of myocardial injury (primarily the troponins) in the appropriate clinical context. In this issue of the journal, Hasdai et al. present an analysis of data collected in the prospective Euro-Heart Survey of Acute Coronary Syndromes, which included 10 484 patients treated in 103 hospitals in 25 European and Mediterranean-basin countries between September 2000 and May 2001.2There were three major findings. First, cardiac troponin assays were performed in only 63.3% of patients, and the promulgation of the new definition in September 2000 had no impact on the usage of troponin assays over the subsequent 9 months. Second, of the 4398 patients with a discharge diagnosis of unstable angina, 28.1% had documented rises in troponin levels and 23.4% had rises in creatine kinase (CK) levels, suggesting that some of these patients were given an inaccurate diagnosis. Third, about a quarter of the 6086 patients with a discharge diagnosis of MI had normal troponin levels, normal CK levels, or both.

This is an interesting study, and it illustrates the lack of consensus as to how MI should be diagnosed in patients presenting with an acute coronary syndrome. This is rather surprising given the widespread dissemination of the new MI definition, especially considering the importance of accurate diagnosis in determining the choice of management strategy and providing prognostic advice for the patient.

Troponin testing has various advantages over CK-MB testing. The troponins are more sensitive markers of myocyte necrosis than CK-MB is.3Multiple micro-infarctions can occur due to platelet embolization from an ulcerated plaque with ongoing thrombosis, causing slow leakage of troponins which then accumulate in the blood due totheir long half lives. Cumulative small releases of troponins are therefore more likely to reach the threshold for detection than cumulative small releases of CK-MB, which has a shorter half-life. In addition to being a more sensitive marker of minor necrosis, elevated troponin levels have greater prognostic significance than elevated CK-MB levels, and have been shown to be associated with complex and thrombus-rich stenoses on coronaryangiography.4This pathophysiological association explains why patients with elevated troponin levels may benefit more from antithrombotic therapy5and revascularization than patients with normal troponin levels.6Because elevated troponin levels may persist in the blood for up to two weeks after MI, they can be useful for diagnosing MI in patients who present late, but cannot be used to diagnose early reinfarction, which is better detected by CK-MB testing.

As acknowledged by Hasdai et al., there are some limitations with the collection andinterpretation of data accrued from this survey across 25 countries. Nevertheless, the data are important in that they reflect clinical practice across a spectrum of European hospitals (both academic and non-academic) following the publication of the ESC/ACC consensus statement. The survey results indicate that many clinicians have not yet taken on board the message put out by the ESC/ACC—namely, that any amount of myocardial necrosis caused by ischaemia constitutes MI—and suggest that many continue to diagnose MI only when a substantial rise in cardiac marker levels occurs. This observation was consistent across the spectrum of academic and non-academic hospitals. However, it should not be assumed that all patients in the survey who tested positive for troponins but received diagnoses other than MI were wrongly diagnosed. Some might have had an MI within two weeks prior to their initial admission, and been diagnosed with postinfarction angina on the basis that their elevated troponin levels were due to that recent MI rather than to ongoing myocardial necrosis at the time of admission. Other patients might have presented with unstable angina without myocardial necrosis, but subsequently tested positive for troponins or creatine kinase after undergoing revascularisation procedures—a situation in which the interpretation of minor cardiac marker elevations is particularly problematic. It should be noted, however, that there was a 23.7% incidence of elevated troponin levels among patients who had no revascularization procedures and were discharged with a diagnosis of unstable angina.



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Fig. 1 Increasing risk in different clinical scenarios with the same troponin level. ACS=acute coronary syndrome, CABG=coronary artery bypass grafting, LAD=left anterior descending coronary artery, LV=left ventricular, PCI=percutaneous coronary intervention, ULRR=upper limit of the reference range. [Reproduced with permission from: White HD. Things ain’t what they used to be: implication of a new definition of myocardial infarction [editorial]. Am Heart J 2002; 144: 933-7].

 
Another interesting finding of this survey is that MI was often diagnosed even when cardiac marker levels were normal. This was permissible under the previous World Health Organization definition of MI, which required only two out of three criteria to be met, thus the diagnosis of myocardial infarction could be made on the basis of chest pain with electrocardiographic changes even when cardiac marker assays were performed at appropriate times and returned normal results. The paper does not give details regarding the timing of troponin or creatine kinase assays in relation to the onset of ischaemia, and it is unclear how many patients had elevated troponin levels in the presence of normal creatine kinase levels or vice versa.

There are various reasons why not all patients diagnosed with MI in this survey would necessarily have tested positive for troponins. In cases of prolonged ischaemia, the release of cardiac markers following myocyte necrosis occurs relatively slowly, hence troponin levels take several hours to reach the detection threshold. Thus any patients who died within the first 6h after the onset of MI would most likely have had normal troponin levels. Other patients might have presented with a history of prolonged ischaemia and marked ST-segment elevation on their electrocardiogram, and received reperfusion therapy promptly enough to resolve the ST-segment elevation before their cardiac marker levels had time to rise. There are no clear guidelines as to how to diagnose an aborted MI, and some clinicians might diagnose such patients as having an MI might.7Other patients could have been diagnosed with MI after developing new Q waves on their electrocardiogram.

It is not clear why clinicians are not using troponin tests more widely. It is over 12 years since troponins were shown to be useful for the diagnosis of myocardial infarction,8and 11 years since they were shown to be prognostically important.9One of the major pitfalls of diagnosing MI on the basis of a rise in troponin levels is the poor performance of the current tests. The Joint ESC/ACC Committee recognised this issue, and recommended in their consensus statement that the precision of troponin assays should meet the specification of <10% coefficient of variation at the 99th percentile of the reference control group. Few of the assays currently available fulfil this standard. Standardization of troponin assays should be a priority for the cardiological community, and indeed a call has been made for any troponin assays that fail this requirement by September 2003 (ie 3 years after the publication of the ESC/ACC consensus statement) to be abandoned.3

Elevated troponin levels are only one of many prognostic factors to be considered when assessing a patient, and their significance varies in different clinical scenarios. Different patients with the same magnitude of troponin elevation may have quite different prognoses (Fig. 1).

The redefinition of MI will continue to have broad implications, not just for patient care, but also for epidemiological research and government policies, including driving and rehabilitation guidelines. It must surely be possible to get the diagnosis right, and to know what we mean when we diagnose a patient with myocardial infarction.

The time is now ripe for national and international cardiological organizations (including the World Health Organization) to revisit the definition of MI, so that a consensus as to just what constitutes an MI can be reached and implemented worldwide in a more coordinated fashion.

References

  1. The Joint European Society of Cardiology/American College of Cardiology Committee. 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 J. 2000;21:1502–1513.[Abstract/Free Full Text]
  2. 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 J. 2003;24:1189–1194.[Abstract/Free Full Text]
  3. White HD. Things ain’t what they used to be: impact of a new definition of myocardial infarction. Am Heart J. 2002;144:933–937.[CrossRef][Medline]
  4. Hamm CW, Heeschen C, Goldmann B et al. Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. N Engl J Med. 1999;340:1623–1629.[Abstract/Free Full Text]
  5. Lindahl B, Venge P, Wallentin L, for the Fragmin in Unstable Coronary Artery Disease (FRISC) Study Group. Troponin T identifies patients with unstable coronary artery disease who benefit from long-term antithrombotic protection. J Am Coll Cardiol. 1997;29:43–48.[CrossRef][Medline]
  6. Morrow DA, Cannon CP, Rifai N et al. Ability of minor elevations of troponins I or T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction. JAMA. 2001;286:2405–2412.[Abstract/Free Full Text]
  7. Lamfers EJP, Hooghoudt TEH, Hertzberger DP et al. Abortion of acute ST segment elevation myocardial infarction after reperfusion: incidence, patients’ characteristics, and prognosis. Heart. 2003;89:496–501.[Abstract/Free Full Text]
  8. Katus HA, Remppis A, Neumann FJ et al. Diagnostic efficiency of troponin T measurements in acute myocardial infarction. Circulation. 1991;83:902–912.[Abstract]
  9. Hamm CW, Ravkilde J, Gerhardt W et al. The prognostic value of serum troponin T in unstable angina. N Engl J Med. 1992;327:146–150.[Abstract]

Related articles in EHJ:

Cardiac biomarkers and acute coronary syndromes — The Euro Heart Survey of Acute Coronary Syndromes Experience
David Hasdai, Solomon Behar, Valentina Boyko, Nicholas Danchin, Jean-Pierre Bassand, and Alexander Battler
EHJ 2003 24: 1189-1194. [Abstract] [Full Text]