LETTER TO THE EDITOR
Redefinition of myocardial infarction by a consensus dissenter: reply
Joseph S. Alpert, MD, FACC, FESCa and
Kristian Thygesen, MD, FACC, FESCa
a Department of Internal Medicine, University of Arizona, 1501 North Campbell Avenue, Tucson, Arizona, USA 85724
We would like to thank Dr. Tunstall-Pedoe for his comments. Controversy is the soul of all intellectual activities, and we welcome Dr. Tunstall-Pedoe’s minority opinion concerning the recently published consensus statement on the definition of myocardial infarction. Unfortunately, Dr. Tunstall-Pedoe has seriously misunderstood and misinterpreted both the nature of the European Society of Cardiology/American College of Cardiology (ESC/ACC) conference and the published document.
Dr. Tunstall-Pedoe was invited to participate in the meeting to provide context for our discussions given his many years of involvement with the original and subsequent modified World Health Organization (WHO) definitions of myocardial infarction. The conference was conceived as a joint project of the ESC and the ACC with the hope that it would help to standardize the definition of myocardial infarction in clinical studies, patient care and health care statistics.
Procedure followed. The original participants at the first meeting at the European Heart House created a first draft of the document. Because of the large number of individuals involved (50) at this first conference, a smaller number (6) were selected for further work on the manuscript and its eventual report. It was never our expectation that everyone in the medical community nor even everyone at the original conference would be in total agreement with the final report. We sought, therefore, to create a document that would be accepted by most clinicians, investigators and epidemiologists.
A first draft was sent to all participants, including Dr. Tunstall-Pedoe. Anyone who responded to the first draft was sent subsequent drafts. Indeed, anyone who requested the then current draft of the document received it by e-mail. The report went through 13 versions before the document was published. Dr. Tunstall-Pedoe did not respond to the first draft that contained approximately 70% of the material that was eventually published. Three other recognized and widely published epidemiologists received all subsequent drafts of the document and all their suggestions were incorporated into the published report. The final manuscript was read and critiqued by the Scientific and Clinical Initiative Committee of the ESC, the Board of the ESC, selected leaders of the ACC and selected reviewers.
Dr. Tunstall-Pedoe suggests that we should have sought input from interest groups involved with rehabilitation, health promotion (whatever this refers to), employment and insurance. Indeed, such individuals were invited to the conference as well as individuals representing government, industry, and even the WHO. Many of these groups responded and had input into the final document.
Content of the revised definition of myocardial infarction. Dr. Tunstall-Pedoe misinterprets the final document. In the report, the definition of myocardial infarction rests on elevated blood troponin or CK-MB levels in an appropriate clinical setting. Patients who arrive at the hospital 24 or 48 h after the onset of their infarct will still have an elevated troponin level that remains abnormal for 3 to 14 days following the onset of myocardial necrosis. Therefore, such late-arriving patients as described by Dr. Tunstall-Pedoe will meet the new definition of myocardial infarction. Patients with infarction who are first seen many days, weeks or months after their infarction can still meet the diagnosis for "established infarction" as noted in the published ESC/ACC document.
The patient who dies shortly after arriving in the coronary care unit represents a problem for diagnosis of myocardial infarction. This is true today and will remain true in the future. As pointed out by the pathology group in the published ESC/ACC document, infarction cannot be recognized pathologically until at least 6 h has passed since the onset of ischemia/infarction. Thus, there is currently a window of "blindness" for the diagnosis of infarction that lasts for approximately 6 h after the onset of myocardial necrosis. Abnormal CK-MB levels may be seen as early as 3 to 4 h after the onset of necrosis and abnormal blood myoglobin levels may be observed even earlier. Perhaps, subsequent revised editions of the ESC/ACC report will contain suggestions about diagnosis of infarction in the early few hours after the onset of myocardial necrosis. Further data will be needed before any such suggestion can be made. In addition, patients with unequivocal ECG evidence (pathologic Q-waves) for infarction but no serological assays can still be labeled as having had an infarct based on the criteria for "established infarction."
Even though the enzyme assays are not standardized in the original WHO and derived MONICA criteria, Dr. Tunstall-Pedoe vigorously defends the MONICA definition for the diagnosis of myocardial infarction (1). This is understandable, but may be ill-advised given the recent report of Porela et al. (2) that failed to document prognostic significance associated with this method for diagnosing infarction. Indeed, Dr. Tunstall-Pedoe states that the MONICA investigators have been seriously considering revising their own definition of myocardial infarction. This is commendable given the recently published data cited above.
We welcome Dr. Tunstall-Pedoe’s suggestion that the new definition be "field tested," and indeed, a number of investigators are already proceeding with such studies. As noted already, the data of Porela et al. (2) support the concept of myocardial infarction defined by means of abnormal blood levels of a myocardial enzyme, CK-MB. These same investigators failed to find similar supportive data for the MONICA definition of infarction. We anxiously await the results of further "field testing."
The unfortunate fact is that the "new" definition of myocardial infarction was already being widely used before our meeting in Nice, France, took place. Indeed, many hospitals and many clinicians around the world already define myocardial infarction based on an abnormal blood troponin value. It was this fact, and the resulting confusion created between hospitals and physicians who used the new sensitive and specific cardiac markers versus those who did not, that led us to organize the ESC/ACC consensus conference. Thus, the "confusion and chaos" referred to by Dr. Tunstall-Pedoe were already present when we began sending out invitations to the meeting at the European Heart House.
In conclusion, we believe that the process as well as the product that led to the ESC/ACC new definition for myocardial infarction were both fair, reasonable and represented the opinion of most of the participants at the ESC/ACC conference as well as a variety of experts who subsequently examined the manuscript and made useful comments. We look forward to further work in this area that will undoubtedly result in revisions to the currently recommended definition for myocardial infarction.
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References
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1. Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, Arveiler D, Rajakangas AM, Pajak A. Myocardial infarction and coronary deaths in the World Health Organization MONICA Project: Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation. 1994;90:583–612[Abstract/Free Full Text]
2. Porela P, Helenius H, Pulkki K, Voipio-Pulkki L-M. Epidemiological classification of acute myocardial infarction: time for a change? Eur Heart J. 1999;20:1459–1464[Abstract/Free Full Text]
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