In Atlanta, Georgia during the spring of 1998, my good friend and colleague, Kristian Thygesen, professor of medicine at Aarhus University in Denmark, and I were having dinner together while attending the annual scientific sessions of the American College of Cardiology. The major topic of conversation that night was the confusing results of 2 therapeutic clinical trials in acute myocardial infarction. Both trials employed the same intervention but came up with opposite results: one trial reported a positive outcome while the second trial found no benefit. We kept asking ourselves that night what could have been the reason for the difference in outcomes? After much conjecture and study of the abstracts from these 2 studies, we realized that the protocols employed differed in the criteria used for entering patients into the trial. The 2 investigations had used different definitions for acute myocardial infarction and hence the patient populations in the 2 trials were not the same, even though the intervention was the same. It was another example of the problem of comparing apples with oranges.
During further discussion that night, we noted that a similar problem occurred every day in our own hospitals, where each cardiologist had his/her own idea as to the criteria for making a diagnosis of myocardial infarction. This difference in diagnostic criteria led to daily confusion among health care staff, patients, and families of patients. During rounds, patients often said, “Doctor, I don’t understand; you tell me that I had a heart attack, but the cardiologist I saw yesterday said that I did not have a heart attack!”
That night, the idea of a universal and globally applied definition for myocardial infarction arose out of our dinner conversation. At that time, I was a member of the Board of Directors of the American College of Cardiology, and Kristian was a member of the same entity in the European Society of Cardiology. We asked ourselves, why not bring these 2 organizations together to sponsor a meeting of experts to prepare a document containing criteria for a uniform definition of myocardial infarction? Over the next few months, we brought this idea to our respective professional societies, which resulted in a meeting at the European Heart House in France and the first publication from what later became known as the Task Force for the Universal Definition of Myocardial Infarction.1
The criteria for the diagnosis of acute myocardial infarction involved appropriately timed abnormal results for the sensitive and specific myocardial biomarker, troponin, in blood samples from patients with a recent clinical event suggestive of an acute myocardial infarction. Troponin elevation alone, however, was felt to be insufficient to establish the diagnosis of myocardial infarction. In addition, to make the diagnosis of myocardial infarction, there had to be supportive evidence from the patient’s history or electrocardiogram (ECG) or coronary arterial angiogram.1 Subsequent reports further refined the definition and clarified a number of entities related to or mimicking acute myocardial infarction such as a stress-induced (takotsubo) myocardial injury or a perioperative myocardial infarction.2, 3, 4 The second report from the Task Force also defined 5 subtypes of myocardial infarction, including the Type 1 myocardial infarction seen every day in emergency departments around the world.2
Type 1 myocardial infarction results from a coronary arterial atherosclerotic plaque rupture or erosion leading to activation of the clotting cascade and resulting in coronary arterial thrombosis, myocardial ischemia, and myocyte necrosis. A Type 2 myocardial infarction is also the result of ischemic myocardial cell necrosis, but the cause is not plaque rupture or erosion with subsequent coronary arterial thrombosis.2 Rather, myocardial ischemia in a Type 2 myocardial infarction is the result of an imbalance between myocardial blood supply and demand. For example, a patient with or without stable underlying coronary arterial disease might have a Type 2 myocardial infarction when this individual developed atrial fibrillation with a rapid ventricular response, possibly, a heart rate of 150 beats per minute. In such a situation, the delivery of oxygen and nutrients to the myocardium would be inadequate because of the increased metabolic demand from the tachycardia. A second example would be a patient with a gastrointestinal hemorrhage and hypotension that decreased the delivery of oxygen and nutrients to the myocardium, resulting in myocyte ischemia and necrosis.
Management of patients with Type 1 and Type 2 myocardial infarction are quite different. With Type 1 myocardial infarction, the goal is to restore myocardial blood flow while reducing myocardial metabolic demand. Therapy for Type 2 myocardial infarction has not been established, but common sense suggests that correction of the entity that led to the imbalance between supply and demand should be the primary approach. A common inpatient cardiology consultation question involves distinguishing a Type 1 from a Type 2 myocardial infarction, which can, at times, be challenging.
In this issue of The American Journal of Medicine, Pandey et al5 report on differences in the release kinetics of troponin and creatine kinase myocardial band (CK-MB) for Type 1 and Type 2 myocardial infarction. Type 1 myocardial infarctions tended to be larger than Type 2, based on peak blood troponin levels. In addition, there was a significantly higher mean percentage increase for both cardiac troponin T and CK-MB for Type 1, compared with Type 2, myocardial infarction. These investigators also noted that there was a trend toward a higher ratio of peak cardiac troponin T to peak CK-MB in Type 2 compared with Type 1 myocardial infarction. The authors suggest that these findings might assist clinicians in separating Type 1 from Type 2 myocardial infarction. Of course, the clinical scenario is also different in the 2 types of myocardial infarction, with Type 2 occurring commonly in older, female patients with comorbidities that are the actual reason for their admission to the hospital, for example, sepsis. Thus, typical Type 2 myocardial infarction patients are found in medical or surgical intensive care units with primary diagnoses such as acute respiratory failure with hypoxemia, tachycardia, or sepsis. Type 2 myocardial infarction patients usually demonstrate unremarkable or nonspecific findings on the ECG. Type 1 myocardial infarction patients are usually first seen in the emergency department complaining of chest discomfort, with ischemic changes present on the ECG. Most hospitals have discontinued CK-MB determination, however, the troponin patterns described in the report of Pandey et al5 add another diagnostic element that can assist clinicians in distinguishing Type 1 from Type 2 myocardial infarction.
To make things a bit more complicated, there are 2 other causes of elevated blood troponin values: nonischemic myocardial injury and chronic myocardial injury. Nonischemic injury is commonly seen in intensive care patients with marked activation of the immune and adrenocortical systems. These patients have high blood levels of cytokines and catecholamines that can directly injure myocardium, leading to elevated blood troponin levels. In addition, many of these patients also have myocardial supply/demand imbalances, so there may be an element of Type 2 myocardial infarction elevation of troponin added to the nonischemic troponin increase.
Chronic myocardial injuries occur in subsets of patients with advanced renal insufficiency or systolic heart failure with markedly reduced left ventricular function. These troponin elevations are due to chronic low-grade injury to the myocardium in the absence of ischemia. The pattern of the elevated blood troponin levels is flat rather than rising and falling, as is seen with acute ischemia.
As always, I am happy to hear from readers about this commentary at jalpert@shc.arizona.edu or on our blog at amjmed.org.
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-Joseph S. Alpert, MD
