Clarification of Myocardial Infarction Types
In 1999, the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC) Committee, the forerunner of the Universal Definition of Myocardial Infarction Task Force, assembled at the European Heart House to develop a clinical set of criteria that could be used consistently to redefine the diagnosis of myocardial infarction (MI).1 Prior to that time, there had been many disparate approaches that were variations of the World Health Organization (WHO) criteria based on a combination of two of three characteristics (i.e., typical symptoms, the electrocardiographic pattern, and enzyme rises). The WHO criteria were originally developed for epidemiological studies, but over time the complex variety of criteria made it difficult to compare clinical studies of MI. By the time of the Joint ESC/ACC Committee meeting in 1999, it was clear that cardiac troponin (cTn) had emerged as the biomarker of choice for the detection of myocardial injury/necrosis. That biomarker, together with symptoms and electrocardiographic findings of myocardial ischemia criteria, which were unchanged from the WHO criteria, became the main components of the MI definition. The new definition also retained the need for a rise and/or fall of cardiac biomarkers (preferably cTn).1,2 The increased sensitivity and specificity of cTn and the choice of the 99th percentile upper reference limit3 markedly facilitated the diagnosis of MI and provided a template for a consistent definition going forward.1,2
The Joint ESC/ACC Committee comprised representatives from the ESC and the ACC who examined the scientific and societal implications of the new definition of MI from seven points of view: pathology, biochemistry, electrocardiography, imaging, clinical trials, epidemiology and public policy.1 A concerted attempt was made to ensure that all of the points of view were taken into account and that a clinical definition that would work across the entire world could be developed.
Given the considerable advances in the diagnosis and management of MI since the original document was published, the leadership of the ESC, the ACC, the American Heart Association (AHA), and the World Heart Federation (WHF) convened a Global Task Force, later renamed the Universal Definition of Myocardial Infarction Task Force, that comprised members from all over the world. Many of the features of the original definition of MI have been retained or amplified. New MI types 1-5 were added in 2007 to enable a pathophysiologic distinction among MI categories.4 One controversial area of the original definition of MI was the situation of an elevated cTn following percutaneous coronary intervention. The original document also offered no criteria for diagnosing an MI following coronary bypass surgery. The subsequent 2007 ESC/ACC/AHA/WHF documents proposed criteria for both of these situations, although it should be emphasized that these criteria resulted from consensus among task force members based on the best scientific information available at the time the document was written.4 The WHO endorsed the ESC/ACC/AHA/WHF definition of MI to be applied to settings with no resource constraints as a category A recommendation and added categories B and C to be applied whenever incomplete information on cardiac biomarkers is available or delayed access to medical services or the unavailability of electrocardiography or laboratory assays exist.5
The concept of MI typing has remained unchanged, with minor modifications through additional iterations of the Universal Definition of Myocardial Infarction document in 2012 and 2018.6 Not surprisingly, the boundaries among the suggested different MI types have been debated, in particular that between types 1 and 2 MI.7 Type 1 MI is the traditional clinical picture of a heart attack. The underlying pathophysiology involves acute atherosclerotic plaque disruption complicated by intraluminal thrombosis that results in decreased oxygen and nutrient delivery to heart muscle. On the other hand, the oxygen deprivation in type 2 MI is not caused by atherosclerotic plaque rupture in a coronary artery but rather by an acute stressor such as an acute gastrointestinal bleed with a precipitous drop in hemoglobin or a sustained tachyarrhythmia with clinical manifestations of myocardial ischemia. Most often, abnormalities in both supply and demand are present.6,7 Each of these settings and many others may result in a supply/demand imbalance of myocardial oxygen and nutrient supply, leading to ischemia and myocardial injury. The ischemic thresholds may vary substantially from one patient to another depending on the magnitude of the stressor, the presence of non-cardiac comorbidities, the extent of underlying coronary artery disease (CAD), and cardiac structural abnormalities. Coronary atherosclerosis is commonly seen in patients with type 2 MI who undergo coronary angiography.7 However, atherosclerotic plaque rupture with accompanying thrombosis is not seen.6
This distinction among and the features of types 1 and 2 MI have recently been questioned by a group who think that the presence or absence of coronary obstruction and the use of angiography should be the first step to determine the type of MI.8 They argue that any acute coronary obstruction, including spontaneous coronary dissection, coronary embolism, or vasospasm whether epicardial or microvascular, should be included as subtypes of type 1 MI. Presumably, aortic dissection with coronary involvement would fit as well. Type 2 MI events would comprise supply-demand mismatch with or without CAD but without "acute coronary obstruction," although criteria were not outlined.8 The essence of this advocacy is to rely on coronary angiography as a first step when acute MI is suspected, which would facilitate the way they want clinical care to proceed. This may be an understandable course of action in centers with no resource constraints where one can categorize comprehensively the coronary anatomy that may be involved in any given event. It is less applicable, however, to sites that may not have coronary angiography, including many resource-constrained countries, which would then limit their ability to make the diagnosis of MI and/or to categorize the type of MI present.9 This is obviously an important consideration for many parts of the global community. One could argue that using coronary computer tomographic angiography as an alternative is a reasonable consideration, but available data on that are far from consistent and reassuring.10 In addition, there are limitations due to differences in scanner precision, varying levels of interpreter expertise, and variation in interpretation criteria. In addition, there are substantial concerns about costs and risks, and 24/7 availability may not be possible at many centers.
In addition, one of the issues to which many have been sensitive is the possibility that relying heavily on angiography as an initial step could lead to increases in the frequency with which interventions are done. Overall, nonischemic myocardial injury is much more common than acute MI as an etiology for an increased cTn value,11 and many such patients may have incidental CAD. An upfront approach with angiography could in some instances lead to an excessive number of invasive procedures with inherent risk that may not be in the best interest of all patients. It can also be difficult to distinguish acute obstruction from more chronic disease without the use of highly sophisticated imaging. In the future, it may be that cardiac magnetic resonance imaging may be useful in this regard when used to explain increased high-sensitivity cTn concentrations as an upfront strategy.12 As noted, however, except for selected referral or tertiary centers, limitations exist in availability, ability, and expertise for broader use of advanced imaging. Finally, even if an invasive coronary angiography is preferred for acute diagnosis, it takes a highly sophisticated cardiac catheterization laboratory that incorporates intracoronary imaging such as intravascular ultrasound or optical coherence tomography, invasive coronary physiology, and provocative testing to comprehensively evaluate all of the potential mechanisms leading to acute MI. Thus, even if an angiographic facility is available, the expertise to do what is needed may or may not be available.
Therefore, we have advocated the use of clinical criteria to define MI types; it is a strategy that has been utilized in almost all of the studies validating MI types. Perhaps with additional studies there will be other criteria predicated on angiography or other imaging to facilitate diagnoses and management, and such studies are ongoing. However, such criteria are lacking at present. This approach, contrary to advocacy of the broad use of angiography,7 should not preclude in any way categorization of patients, collecting of data regarding the types of presentations that occur, or the need for specific sorts of interventions, be they medical or invasive.5 Such an approach also takes advantage of the ability to have a standardized definition for type 1 MI (i.e., acute atherothrombotic plaque disruption) as opposed to subsuming a large and heterogeneous number of potential etiologies for coronary obstruction. We suggest that this approach, in which type 1 MI can be relied on to be relatively homogeneous and type 2 MI can be where a heterogeneity of etiologies reside, is preferable to accommodating the biases of a small percentage of our colleagues who would like the definitions to fit their practices.
- Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959-69.
- Jaffe AS, Ravkilde J, Roberts R, et al. It's time for a change to a troponin standard. Circulation 2000;102:1216-20.
- Sandoval Y, Apple FS, Saenger AK, Collinson PO, Wu AHB, Jaffe AS. 99th 99th Percentile Upper-Reference Limit of Cardiac Troponin and the Diagnosis of Acute Myocardial Infarction. Clin Chem 2020;66:1167-80.
- Thygesen K, Alpert JS, White HD; Joint ESC/ACC/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Circulation 2007;116:2634-53.
- Mendis S, Thygesen K, Kuulasmaa K, et al. World Health Organization definition of myocardial infarction: 2008-09 revision. Int J Epidemiol 2011;40:139-46.
- Thygesen K, Alpert JS, Jaffe AS, et al. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol 2018;72:2231-64.
- Sandoval Y, Jaffe AS. Type 2 Myocardial Infarction: JACC Review Topic of the Week. J Am Coll Cardiol 2019;73:1846-60.
- de Lemos JA, Newby LK, Mills NL. A Proposal for Modest Revision of the Definition of Type 1 and Type 2 Myocardial Infarction. Circulation 2019;140:1773-5.
- Sandoval Y, Thygesen K, Jaffe AS. The Universal Definition of Myocardial Infarction: Present and Future. Circulation 2020;141:1434-6.
- Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med 2015;372:1291-300.
- Melki D, Lugnegård J, Alfredsson J, et al. Implications of Introducing High-Sensitivity Cardiac Troponin T Into Clinical Practice: Data From the SWEDEHEART Registry. J Am Coll Cardiol 2015;65:1655-64.
- Smulders MV, Kietselaer BLJH, Wildberger JE, et al. Initial Imaging-Guided Strategy Versus Routine Care in Patients With Non-ST-Segment Elevation Myocardial Infarction. J Am Coll Cardiol 2019;74:2466-77.
Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), ACS and Cardiac Biomarkers, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Heart Failure and Cardiac Biomarkers, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Magnetic Resonance Imaging, Nuclear Imaging
Keywords: Acute Coronary Syndrome, American Heart Association, Consensus, Leadership, Electrocardiography, Myocardial Ischemia, World Health Organization, Biomarkers, Pharmacological, Percutaneous Coronary Intervention, Troponin, Public Policy, Coronary Artery Bypass, Myocardial Infarction, Epidemiologic Studies, Tomography, Optical Coherence, Plaque, Atherosclerotic, Coronary Artery Disease, Coronary Angiography, Embolism, Oxygen, Myocardium, Tachycardia, Coronary Occlusion, Hemoglobins, Thrombosis, Magnetic Resonance Imaging, Chronic Disease
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