In 2000, the First Global MI Task Force presented a new definition of myocardial infarction (MI), which implied that any necrosis in the setting of myocardial ischemia should be labeled as MI.¹ These principles were further refined by the Second Global MI Task Force, leading to the first Universal Definition of MI Consensus Document in 2007, which emphasized the different conditions that might lead to an MI. Even more sensitive assays for markers of myocardial necrosis mandated further revision, particularly when such necrosis occurs in three settings: critical illness, after percutaneous coronary procedures, or after cardiac surgery.

On August 25, 2012 at the ESC Congress in Munich, the Third Global MI Task Force released a document with an updated definition of MI which recognizes that very small amounts of myocardial injury or necrosis can be detected by biochemical markers and/or imaging, but should not be considered an MI.

Apples Versus Oranges

The need for a universally understood and applied definition of MI was addressed in 2006 in an editorial by Joseph S. Alpert, MD, and Kristian A. Thygesen, MD, DSc, who have co-chaired all three of the Global MI Task Force committees.² Over the many years that clinical research had been performed on patients with acute MI, they noted in their editorial, different definitions using contemporary diagnostic tools were utilized and consequently it was often a challenge to compare the "apples" in one study to the "oranges" in another. Similar problems arose in the arena of public health statistics because physicians used different algorithms to define MI in the clinical setting, leading to inaccuracies when public health data were collated from discharge summaries. Thus, studies involving large databases that use hospital discharge diagnoses could—and usually did—contain significant inaccuracies because different physicians used different definitions of MI.

Once a new definition for MI was proposed in the 2000 joint ESC/ACC document, most of the subsequent studies using the definition demonstrated that the new biomarker-based definition of MI resulted in an increased number of patients identified as having had an MI. This is, of course, not surprising because the new biomarker used, troponin, is considerably more sensitive and more specific than total creatine kinase (CK) and its isoform, CKMB, which had been used routinely before the advent of troponin assays.

Today, the need for an update remains and the drivers are still ever more sensitive markers of myocardial necrosis, especially troponin, and more refined imaging techniques. According to Dr. Alpert, troponin assays typically used in the U.S. are 20-times more sensitive and specific than CKMB; in Europe, the high-sensitivity troponin tests used are 30-, 40- or 50-times more sensitive and specific. Because the new troponin assay identifies smaller infarcts than did CKMB, it was predicted early on that the short-term prognosis for patients with such troponin-positive, CKMB-negative infarcts would be better than that for patients with both positive troponin and positive CKMB measurements.

The overall pathological definition of MI remains myocardial cell death as a result of prolonged ischemia, with the definition applicable in any of five types:

• Type 1, spontaneous MI
• Type 2, MI secondary to ischemic imbalance
• Type 3, MI resulting in death when biomarkers are unavailable
• Type 4, MI related to PCI (with 4b related to stent thrombosis)
• Type 5, related to CABG

According to Dr. Thygesen, "We have always had to go for a more biochemical approach. Biomarkers could detect necrosis, which was always difficult with an ECG. So in this latest definition, the concept of MI has not changed but the diagnosis is now based on patient symptoms, ECG changes, highly sensitive biochemical markers, and information gleaned from various imaging techniques."

Additions in the third edition have been made in relation to PCI, CABG, cardiac and noncardiac surgery, and clinical trials.³

Sorting Through the Confusion

What has been confusing to clinicians and to clinical investigators in the past is that a patient, with or without coronary disease, may develop a very serious illness—for example one that drops their blood pressure—and decreased blood flow to the heart produces a small MI. But, as Dr. Alpert points out, it's not the same as the heart attack that brings people to the emergency room clutching their chest where there is a blood clot in the artery, a type 1 MI. What we're talking about in the setting of critical illness is a type 2 MI because there was no event in the coronary arteries but there was an event that affected the heart. 

"You can imagine that is sometimes difficult to distinguish from these other injuries that go on and so there is a lot of confusion in the hospital," said Dr. Alpert. "Whenever I'm on the consult service that is one of the most common things they are asking me: Did this patient have a type 2 MI? Is this myocardial injury? What should we do about it? Do we need to do an evaluation? Do we need to do therapy? Tell us what to do. The truth is, we still don't have all the answers there. But for many of these patients, you do not have to do anything except treat their underlying illness. So, a lot of time in the document is spent on that."

The third universal definition document tightens up the language and adds many new references to recent work, but the work is not done yet. "We just met today (at ESC), and there's going to be ongoing work that has to deal with this whole question of myocardial injury and type 2 MI," said Dr. Alpert. "That is continuing to be a big problem and we are going to try to put together a position paper on it; there needs to be a lot more research to help the clinician and also the clinical investigator."

References

1. Alpert JS, et al. J Am Coll Cardiol. 2000;36:959-69. http://content.onlinejacc.org/article.aspx?articleid=1126658
2. Alpert JS, Thygesen K. Circulation. 2006;114:757-8.
3. Thygesen K, et al. J Am Coll Cardiol. 2012 August 25. [Epub ahead of print] http://www.cardiosource.org/~/media/Files/Science%20and%20Quality/Guidelines/Clinical_Documents/UniversalDefMI.ashx

To listen to an interview with Kristian A. Thygesen, MD, about the changing definition of MI, visit youtube.cswnews.org. The interview was conducted by Benjamin M. Scirica, MD, MPH.

Keywords: Prognosis, Myocardial Infarction, Myocardial Ischemia, Creatine Kinase, Biomarkers, Critical Illness, Coronary Disease, Blood Pressure, Necrosis, Troponin

< Back to Listings