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The Fourth Edition of the Universal Definition of Myocardial Infarction

  • Joseph S. Alpert
    Correspondence
    Requests for reprints should be addressed to Joseph S. Alpert, MD, University of Arizona College of Medicine, 1501 North Campbell Avenue, Sarver Heart Center Room #5133, Tucson, Arizona 85724-5037.
    Affiliations
    The American Journal of MedicineUniversity of Arizona College of Medicine, Tucson
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      Recently, the American College of Cardiology, the American Heart Association, the European Society of Cardiology, and the World Heart Federation simultaneously published the fourth document in the universal definition of myocardial infarction series.

      Thygesen KA, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction. J Am Coll Cardiol, in press.

      The first document proposing a universal definition was published in 2000 in the European Heart Journal and the Journal of the American College of Cardiology. The American Heart Association and the World Heart Federation became cosponsors of subsequent editions of these guidelines starting with the second document in 2007.
      • Thygesen K
      • Alpert JS
      • White HD
      Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction
      Universal definition of myocardial infarction.
      • Thygesen K
      • Mair J
      • Giannitsis E
      • et al.
      How to use high-sensitivity cardiac troponins in acute cardiac care.
      The current and fourth document contains substantial quantities of new material based on scientific reports that have been published since the development of the third document in 2012. In this commentary, I will briefly highlight the changes in the new document that I believe deserve the attention of clinicians involved in the care of patients with acute myocardial infarction and the ever-increasing number of individuals who have elevated blood troponin levels but have not had a myocardial infarction.
      The definition of myocardial infarction still depends on the presence of an elevated troponin blood test together with clinical evidence of ischemia (eg, ischemic patterns in the electrocardiogram [ECG]). The 5 subtypes of myocardial infarction have been retained in the new document with some modest revision in the wording of these categories to improve understanding.

      Thygesen KA, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction. J Am Coll Cardiol, in press.

      • Thygesen K
      • Alpert JS
      • White HD
      Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction
      Universal definition of myocardial infarction.
      • Thygesen K
      • Mair J
      • Giannitsis E
      • et al.
      How to use high-sensitivity cardiac troponins in acute cardiac care.
      Type 1 myocardial infarction is the result of an atherosclerotic plaque fissure, erosion, or rupture with subsequent coronary arterial thrombosis. Type 1 myocardial infarction patients can have an ST elevation or a non-ST elevation myocardial infarction and are usually treated with medication and stenting of the culprit lesion in the coronary artery. Type 2 myocardial infarction is the result of ischemia, but there has not been an atherosclerotic plaque erosion, fissuring, or disruption. Rather, there is an imbalance of myocardial oxygen supply and demand, such as may occur in a patient with hypotension (decreased supply) or a tachyarrhythmia (increased demand). Type 3 myocardial infarction is seen in a patient with a classic presentation of myocardial infarction, such as with a typical ST elevation ECG, but a troponin blood test was not performed. This is an unusual situation in economically advantaged countries. Type 4 myocardial infarction occurs in the setting of a percutaneous coronary intervention in the catheterization laboratory, usually as the result of a complication of the procedure being performed. Type 5 is comparable to type 4 but occurs at the time of coronary bypass surgery.
      Patients with elevated blood troponin levels but without clinical evidence of ischemia are said to have had a ‘myocardial injury.’

      Thygesen KA, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction. J Am Coll Cardiol, in press.

      Acute myocardial injury (eg, from sternal trauma) is associated with a rising and falling pattern of troponin elevation when serial testing is performed. This is a similar pattern to what is seen with types 1, 2, 4, and 5 myocardial infarction. All patients with an elevated blood troponin level are said to have a form of myocardial injury, but only patients with a myocardial injury AND clinical evidence of ischemia are said to have myocardial infarction. The new document discusses at length the various forms of nonischemic myocardial injury. For example, a young diabetic patient with gram-negative sepsis but without hypotension or marked tachycardia but with an elevated blood troponin level would be called a patient with a myocardial injury that likely occurred because of damage to myocardial cells secondary to increased levels of circulating catecholamines and cytokines.
      • Vestergaard KR
      • Jespersen CB
      • Arnadottir A
      • et al.
      Prevalence and `significance of troponin elevations in patients without acute coronary disease.
      • White HD
      Pathobiology of troponin elevations: do elevations occur with myocardial ischemia as well as necrosis?.
      • Giannitsis E
      • Katus HA
      Cardiac troponin level elevations not related to acute coronary syndromes.
      Another form of myocardial injury occurs in patients with myocarditis or with chemotherapy-induced myocardial necrosis.
      Some individuals with advanced renal failure or severe heart failure have low-grade, chronic elevations in blood troponin levels. There is no evidence of chronic ischemia in these patients; rather, structural changes in the myocardium and probably elevated levels of circulating catecholamines and cytokines cause this form of chronic, ongoing form of myocardial injury. The prognosis for patients with severe illnesses and concomitant myocardial injury without ischemia is worse than for an identical patient with a normal blood troponin value.
      The new document also contains material concerning an unusual form of myocardial infarction: myocardial infarction with nonobstructed coronary arteries (MINOCA).
      • Lindahl B
      • Baron T
      • Erlinge D
      • et al.
      Medical therapy for secondary prevention and long-term outcome in patients with myocardial infarction with nonobstructive coronary artery disease.
      Clinical research studies of MINOCA have yet to completely reveal the pathophysiology of this syndrome. A variety of mechanisms have been proposed, such as coronary arterial vasospasm, coronary embolism, and a hypercoagulable state. It appears likely that a variety of pathophysiological events can result in MINOCA. Because these patients usually have some modest degree of coronary atherosclerosis, secondary antiatherosclerotic therapy is indicated (eg, daily ingestion of a statin). In addition, there is new material on the takotsubo or stress-related syndrome of myocardial injury that can mimic an ST elevation myocardial infarction.
      The syndrome of perioperative myocardial infarction is identified when blood troponin values are elevated following a surgical procedure.
      • Devereaux PJ
      • Biccard BM
      • Sigamani A
      • et al.
      Association of postoperative high-sensitivity troponin levels with myocardial injury and 30-day mortality among patients undergoing noncardiac surgery.
      Perioperative myocardial infarction is a condition that is usually difficult to diagnose because patients are anesthetized and cannot therefore relate a history of chest discomfort or sudden onset of dyspnea. Nonspecific ECG changes are often seen in the perioperative period, which also makes the diagnosis of myocardial ischemia difficult. This form of myocardial infarction is usually the result of supply-demand imbalances occurring during the operative procedure and is associated with increased postoperative morbidity and mortality. At this time, the best therapeutic approach for these patients is unknown. However, statins, beta blockers, and antiplatelet agents are often administered. Because these patients have had a recent invasive procedure, considerable thought and consultation with the surgeons involved is needed when cardiac interventions requiring anticoagulation are being considered.
      The fourth edition of the universal definition of myocardial infarction also contains new material on the use of high-sensitivity troponin assays in the diagnosis of myocardial infarction and an expanded section on the indications for and uses of noninvasive imaging in patients with myocardial infarction. Finally, there is new material on regulatory issues involving individuals with a recent or old myocardial infarction. It is of considerable interest that all 5 subtypes of myocardial infarction and nonischemic myocardial injury now have associated International Classification of Diseases, 10th Revision codes for billing and epidemiologic purposes.
      As always, I welcome comments and discussion concerning this commentary at [email protected] or on our blog at www.amjmed.org.

      References

      1. Thygesen KA, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction. J Am Coll Cardiol, in press.

        • Thygesen K
        • Alpert JS
        • White HD
        • Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction
        Universal definition of myocardial infarction.
        Eur Heart J. 2007; 28 (Circulation. 2007;116:2634-2653): 2525-2538;
        • Thygesen K
        • Mair J
        • Giannitsis E
        • et al.
        How to use high-sensitivity cardiac troponins in acute cardiac care.
        Eur Heart J. 2012; 33: 2252-2257
        • Vestergaard KR
        • Jespersen CB
        • Arnadottir A
        • et al.
        Prevalence and `significance of troponin elevations in patients without acute coronary disease.
        Int J Cardiol. 2016; 222: 819-825
        • White HD
        Pathobiology of troponin elevations: do elevations occur with myocardial ischemia as well as necrosis?.
        J Am Coll Cardiol. 2011; 57: 2406-2408
        • Giannitsis E
        • Katus HA
        Cardiac troponin level elevations not related to acute coronary syndromes.
        Nat Rev Cardiol. 2013; 10: 623-634
        • Lindahl B
        • Baron T
        • Erlinge D
        • et al.
        Medical therapy for secondary prevention and long-term outcome in patients with myocardial infarction with nonobstructive coronary artery disease.
        Circulation. 2017; 135: 1481-1489
        • Devereaux PJ
        • Biccard BM
        • Sigamani A
        • et al.
        Association of postoperative high-sensitivity troponin levels with myocardial injury and 30-day mortality among patients undergoing noncardiac surgery.
        JAMA. 2017; 317: 1642-1651