Fourth Universal Definition of Myocardial Infarction (2018)

HomeCirculationVol. 138, No. 20Fourth Universal Definition of Myocardial Infarction (2018) Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBFourth Universal Definition of Myocardial Infarction (2018) Kristian Thygesen, Joseph S. Alpert, Allan S. Jaffe, Bernard R. Chaitman, Jeroen J. Bax, David A. Morrow, Harvey D. White and The Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction Kristian ThygesenKristian Thygesen *Corresponding authors. Kristian Thygesen, Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard, DK-8200 Aarhus N, Denmark. Tel: +45 78452262, Fax: +45 78452260, Email: E-mail Address: [email protected]; E-mail Address: [email protected]. Search for more papers by this author , Joseph S. AlpertJoseph S. Alpert Joseph S. Alpert, Department of Medicine, University of Arizona College of Medicine, 1501 N. Campbell Ave., P.O. Box 245037, Tucson AZ 85724-5037, USA. Tel: +1 5206262763, Email: E-mail Address: [email protected]. Search for more papers by this author , Allan S. JaffeAllan S. Jaffe Search for more papers by this author , Bernard R. ChaitmanBernard R. Chaitman Search for more papers by this author , Jeroen J. BaxJeroen J. Bax Search for more papers by this author , David A. MorrowDavid A. Morrow Search for more papers by this author , Harvey D. WhiteHarvey D. White Harvey D. White, Green Lane Cardiovascular Service, Auckland City Hospital, Private Bag 92024, 1030 Auckland, New Zealand. Tel: +64 96309992, Fax: 00 64 9 6309915, Email: E-mail Address: [email protected]. Search for more papers by this author and The Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction Search for more papers by this author Originally published24 Aug 2018https://doi.org/10.1161/CIR.0000000000000617Circulation. 2018;138:e618–e651is corrected byCorrection to: Fourth Universal Definition of Myocardial Infarction (2018)Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: August 25, 2018: Ahead of Print Abbreviations and AcronymsACCAmerican College of CardiologyACSAcute coronary syndromeAHAAmerican Heart AssociationARC-2Academic Research Consortium-2AUCArea under the curveCADCoronary artery diseaseCABGCoronary artery bypass graftingCKDChronic kidney diseaseCK-MBCreatine kinase MB isoformCMRCardiac magnetic resonanceCTCAComputed tomographic coronary angiographycTnCardiac troponincTnICardiac troponin IcTnTCardiac troponin TCTComputed tomographyCVCoefficient of variationEFEjection fractionECGElectrocardiogram or electrocardiographicHFHeart failurehs-cTnHigh-sensitivity cardiac troponinIFCCInternational Federation of Clinical Chemistry and Laboratory MedicineISFCInternational Society and Federation of CardiologyLADLeft anterior descending arteryLBBBLeft bundle branch blockLoDLimit of detectionLGELate gadolinium enhancementLGE-CMRLate gadolinium enhancement cardiac magnetic resonanceLVLeft ventricularLVHLeft ventricular hypertrophyMIMyocardial infarctionMINOCAMyocardial infarction with nonobstructive coronary arteriesMONICAMONItoring of trends and determinants in CArdiovascular diseaseMPSMyocardial perfusion scintigraphyNHLBINational Heart, Lung, and Blood InstituteNSTEMINon–ST-elevation myocardial infarctionPETPositron emission tomographyPCIPercutaneous coronary interventionPOCPoint of careRBBBRight bundle branch blockSPECTSingle photon emission computed tomographySTEMIST-elevation myocardial infarctionST-TST-segment–T waveTIMIThrombolysis in Myocardial InfarctionTTSTakotsubo syndromeUDMIUniversal Definition of Myocardial InfarctionURLUpper reference limitWHFWorld Heart FederationWHOWorld Health OrganizationTable of contentsAbbreviations and Acronyms e6191. What Is New in the Universal Definition of Myocardial Infarction? e6202. Universal Definitions of Myocardial Injury and Myocardial Infarction: Summary e6213. Introduction e6214. Pathological Characteristics of Myocardial Ischemia and Infarction e6225. Biomarker Detection of Myocardial Injury and Infarction e6236. Clinical Presentations of Myocardial Infarction e6237. Clinical Classification of Myocardial Infarction e6247.1. Myocardial Infarction Type 1 e6247.2. Myocardial Infarction Type 2 e6257.3. Myocardial Infarction Type 2 and Myocardial Injury e6267.4. Myocardial Infarction Type 3 e6268. Coronary Procedure–Related Myocardial Injury e6289. Myocardial Infarction Associated With Percutaneous Coronary Intervention (Type 4a Myocardial Infarction) e62910. Stent/Scaffold Thrombosis Associated With Percutaneous Coronary Intervention (Type 4b Myocardial Infarction) e62911. Restenosis Associated With Percutaneous Coronary Intervention (Type 4c Myocardial Infarction) e63012. Myocardial Infarction Associated With Coronary Artery Bypass Grafting (Type 5 Myocardial Infarction) e63013. Other Definitions of Myocardial Infarction Related to Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting e63114. Recurrent Myocardial Infarction e63115. Reinfarction e63116. Myocardial Injury and Infarction Associated With Cardiac Procedures Other Than Revascularization e63117. Myocardial Injury and Infarction Associated With Noncardiac Procedures e63118. Myocardial Injury or Infarction Associated With Heart Failure e63219. Takotsubo Syndrome e63220. Myocardial Infarction With Nonobstructive Coronary Arteries e63321. Myocardial Injury and/or Infarction Associated With Kidney Disease e63322. Myocardial Injury and/or Infarction in Critically Ill Patients e63423. Biochemical Approach for Diagnosing Myocardial Injury and Infarction e63424. Analytical Issues of Cardiac Troponins e63525. The 99th Percentile Upper Reference Limit e63626. Operationalizing Criteria for Myocardial Injury and Infarction e63627. Electrocardiographic Detection of Myocardial Infarction e63728. Application of Supplemental Electrocardiogram Leads e63829. Electrocardiographic Detection of Myocardial Injury e63930. Prior or Silent/Unrecognized Myocardial Infarction e63931. Conditions That Confound the Electrocardiographic Diagnosis of Myocardial Infarction e63932. Conduction Disturbances and Pacemakers e64033. Atrial Fibrillation e64034. Imaging Techniques e64034.1. Echocardiography e64034.2. Radionuclide Imaging e64134.3. Cardiac Magnetic Resonance Imaging e64134.4. Computed Tomographic Coronary Angiography e64135. Applying Imaging in Acute Myocardial Infarction e64136. Applying Imaging in Late Presentation of Myocardial Infarction e64237. Regulatory Perspective on Myocardial Infarction in Clinical Trials e64338. Silent/Unrecognized Myocardial Infarction in Epidemiological Studies and Quality Programs e64339. Individual and Public Implications of the Myocardial Infarction Definition e64340. Global Perspectives of the Definition of Myocardial Infarction e64441. Using the Universal Definition of Myocardial Infarction in the Healthcare System e644Appendix e645Acknowledgment e645References e6451. What is new in the Universal Definition of Myocardial Infarction?2. Universal Definitions of Myocardial Injury and Myocardial Infarction: Summary3. IntroductionIn the late 19th century, postmortem examinations demonstrated a possible relationship between thrombotic occlusion of a coronary artery and myocardial infarction (MI).1 However, it was not until the beginning of the 20th century that the first clinical descriptions appeared describing a connection between the formation of a thrombus in a coronary artery and its associated clinical features.2,3 Despite these landmark observations, considerable time elapsed before general clinical acceptance of this entity was achieved, in part due to 1 autopsy study that showed no thrombi in the coronary arteries of 31% of deceased patients with an MI.4 The clinical entity was referred to as coronary thrombosis, although use of the term “MI” ultimately prevailed. Over the years, several different definitions of MI have been used, leading to controversy and confusion. Hence, a general and worldwide definition for MI was needed. This occurred for the first time in the 1950–1970s, when working groups from the World Health Organization (WHO) established a primarily electrocardiographic (ECG)–based definition of MI intended for epidemiological use.5 The original description, with minor modifications, is still used in epidemiological surveys (Figure 1).6–8Download figureDownload PowerPointFigure 1. History of documents on the definition of myocardial infarction. ACC indicates American College of Cardiology; AHA, American Heart Association; ESC, European Society of Cardiology; ISFC, International Society and Federation of Cardiology; MONICA, MONItoring of trends and determinants in CArdiovascular disease; NHLBI, National Heart, Lung, and Blood Institute; UDMI, Universal Definition of Myocardial Infarction; WHF, World Heart Federation; WHO, World Health Organization.With the introduction of more sensitive cardiac biomarkers, the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) collaborated to redefine MI using a biochemical and clinical approach, and reported that myocardial injury detected by abnormal biomarkers in the setting of acute myocardial ischemia should be labeled as MI.9 The principle was further refined by the Global MI Task Force, leading to the Universal Definition of Myocardial Infarction Consensus Document in 2007, introducing a novel MI classification system with 5 subcategories.10 This document, endorsed by the ESC, the ACC, the American Heart Association (AHA), and the World Heart Federation (WHF), was adopted by the WHO.11 The development of even more sensitive assays for markers of myocardial injury made further revision of the document necessary, particularly for patients who undergo coronary procedures or cardiac surgery. As a result, the Joint ESC/ACC/AHA/WHF Task Force produced the Third Universal Definition of Myocardial Infarction Consensus Document in 2012.12Studies have shown that myocardial injury, defined by an elevated cardiac troponin (cTn) value, is frequently encountered clinically and is associated with an adverse prognosis.13,14 Although myocardial injury is a prerequisite for the diagnosis of MI, it is also an entity in itself. To establish a diagnosis of MI, criteria in addition to abnormal biomarkers are required. Nonischemic myocardial injury may arise secondary to many cardiac conditions such as myocarditis, or may be associated with noncardiac conditions such as renal failure.15 Therefore, for patients with increased cTn values, clinicians must distinguish whether patients have suffered a nonischemic myocardial injury or one of the MI subtypes. If there is no evidence to support the presence of myocardial ischemia, a diagnosis of myocardial injury should be made. This diagnosis can be changed if subsequent evaluation indicates criteria for MI. The current Fourth Universal Definition of Myocardial Infarction Consensus Document reflects these considerations through adhering to the clinical approach of the definition of MI.Clinical Criteria for MIThe clinical definition of MI denotes the presence of acute myocardial injury detected by abnormal cardiac biomarkers in the setting of evidence of acute myocardial ischemia.4. Pathological characteristics of myocardial ISCHEMIA and infarctionMI is defined pathologically as myocardial cell death due to prolonged ischemia. Diminished cellular glycogen, and relaxed myofibrils and sarcolemmal disruption, are the first ultrastructural changes and are seen as early as 10–15 minutes after the onset of ischemia.16 Mitochondrial abnormalities are observed as early as 10 minutes after coronary occlusion by electron microscopy and are progressive.17 It can take hours before myocyte necrosis can be identified by postmortem examination in humans; this is in contrast to animal models, in which biochemical evidence of myocardial cell death due to apoptosis can be detected within 10 minutes of induced myocardial ischemia in association with myocyte death.15 Experimentally, necrosis progresses from the subendocardium to the subepicardium over several hours. The time course may be prolonged by increased collateral flow, reduced determinants of myocardial oxygen consumption, and intermittent occlusion/reperfusion, which can precondition the heart.18 Timely implementation of reperfusion therapy, when appropriate, reduces ischemic injury of the myocardium.19,205. Biomarker detection of myocardial injury and infarctionCardiac troponin I (cTnI) and T (cTnT) are components of the contractile apparatus of myocardial cells and are expressed almost exclusively in the heart.21,22 Increases in cTnI values have not been reported to occur following injury to noncardiac tissues. The situation is more complex for cTnT. Biochemical data indicate that injured skeletal muscle expresses proteins that are detected by the cTnT assay, leading to some situations where elevations of cTnT could emanate from skeletal muscle.23–27 Recent data suggest that the frequency of such elevations in the absence of ischemic heart disease may be higher than originally thought.28,29 cTnI and cTnT are the preferred biomarkers for the evaluation of myocardial injury,12,21,22,30 and high-sensitivity (hs)–cTn assays are recommended for routine clinical use.22 Other biomarkers, for example, wwm (CK-MB), are less sensitive and less specific.31 Myocardial injury is defined as being present when blood levels of cTn are increased above the 99th percentile upper reference limit (URL).12,21,22,30 The injury may be acute, as evidenced by a newly detected dynamic rising and/or falling pattern of cTn values above the 99th percentile URL, or chronic, in the setting of persistently elevated cTn levels.Criteria for Myocardial InjuryDetection of an elevated cTn value above the 99th percentile URL is defined as myocardial injury. The injury is considered acute if there is a rise and/or fall of cTn values.Although elevated cTn values reflect injury to myocardial cells, they do not indicate the underlying pathophysiological mechanisms, and can arise following preload-induced mechanical stretch or physiological stresses in otherwise normal hearts.32–34 Various causes have been suggested for the release of structural proteins from the myocardium, including normal turnover of myocardial cells, apoptosis, cellular release of cTn degradation products, increased cellular wall permeability, the formation and release of membranous blebs, and myocyte necrosis.27,35 Yet, it is not clinically possible to distinguish which increases of cTn levels are due to which mechanisms.36 However, regardless of the mechanism, acute myocardial injury, when associated with a rising and/or falling pattern of cTn values with at least 1 value above the 99th percentile URL and caused by myocardial ischemia, is designated as an acute MI.12,21,22,30 Histological evidence of myocardial injury with myocyte death can be detected in clinical conditions associated with nonischemic mechanisms of myocardial injury as well37,38 (Figure 2).Myocardial ischemic or nonischemic conditions associated with increased cTn values are presented in Table 1. The complexity of clinical circumstances may sometimes make it difficult to discriminate specific individual mechanism(s) of myocardial injury. In this situation, the multifactorial contributions resulting in myocardial injury should be described in the patient record.Download figureDownload PowerPointFigure 2. Spectrum of myocardial injury, ranging from no injury to myocardial infarction. Various clinical entities may involve these myocardial categories (eg, ventricular tachyarrhythmia, heart failure, kidney disease, hypotension/shock, hypoxemia and anemia). cTn indicates cardiac troponin; and URL upper reference limit.*No myocardial injury, cTn values ≤99th percentile URL or not detectable.†Myocardial injury, cTn values >99th percentile URL.‡Myocardial infarction, clinical evidence of myocardial ischemia and a rise and/or fall of cTn values >99th percentile URL.Table 1. Reasons for the Elevation of Cardiac Troponin Values Because of Myocardial InjuryMyocardial injury related to acute myocardial ischemia Atherosclerotic plaque disruption with thrombosisMyocardial injury related to acute myocardial ischemia because of oxygen supply/demand imbalance Reduced myocardial perfusion, eg, • Coronary artery spasm, microvascular dysfunction • Coronary embolism • Coronary artery dissection • Sustained bradyarrhythmia • Hypotension or shock • Respiratory failure • Severe anemia Increased myocardial oxygen demand, eg, • Sustained tachyarrhythmia • Severe hypertension with or without left ventricular hypertrophyOther causes of myocardial injury Cardiac conditions, eg, • Heart failure • Myocarditis • Cardiomyopathy (any type) • Takotsubo syndrome • Coronary revascularization procedure • Cardiac procedure other than revascularization • Catheter ablation • Defibrillator shocks • Cardiac contusion Systemic conditions, eg, • Sepsis, infectious disease • Chronic kidney disease • Stroke, subarachnoid hemorrhage • Pulmonary embolism, pulmonary hypertension • Infiltrative diseases, eg, amyloidosis, sarcoidosis • Chemotherapeutic agents • Critically ill patients • Strenuous exerciseFor a more comprehensive listing, see references 39-41.6. Clinical presentations of myocardial infarctionOnset of myocardial ischemia is the initial step in the development of MI and results from an imbalance between oxygen supply and demand. Myocardial ischemia in a clinical setting can most often be identified from the patient’s history and from the ECG. Possible ischemic symptoms include various combinations of chest, upper extremity, mandibular, or epigastric discomfort during exertion or at rest, or an ischemic equivalent such as dyspnea or fatigue. Often, the discomfort is diffuse; not localized, nor positional, nor affected by movement of the region. However, these symptoms are not specific for myocardial ischemia and can be observed in other conditions such as gastrointestinal, neurological, pulmonary, or musculoskeletal complaints. MI may occur with atypical symptoms such as palpitations or cardiac arrest, or even without symptoms.12 Very brief episodes of ischemia too short to cause necrosis can also cause cTn release and elevations. The involved myocytes can subsequently die due to apoptosis.42If myocardial ischemia is present clinically or detected by ECG changes together with myocardial injury, manifested by a rising and/or falling pattern of cTn values, a diagnosis of acute MI is appropriate. If myocardial ischemia is not present clinically, then elevated cTn levels may be indicative of acute myocardial injury if the pattern of values is rising and/or falling, or related to more chronic ongoing injury if the pattern is unchanging.14 Similar considerations are relevant when evaluating events that are potentially related to procedures that may cause myocardial injury and/or MI. Additional evaluations may lead to a need for the initial diagnosis to be revised.Patients with suspected acute coronary syndrome (ACS) that are ruled out for MI with normal cardiac biomarker values (≤99th percentile URL) may have unstable angina or an alternative diagnosis. These patients should be evaluated and treated accordingly.11,437. Clinical classification of myocardial infarctionFor the sake of immediate treatment strategies such as reperfusion therapy, it is usual practice to designate MI in patients with chest discomfort or other ischemic symptoms, who develop new ST-segment elevations in 2 contiguous leads or new bundle branch blocks with ischemic repolarization patterns as an ST-elevation MI (STEMI) (see section 27). In contrast, patients without ST-segment elevation at presentation are usually designated non–ST-elevation MI (NSTEMI). The categories of patients with STEMI, NSTEMI, or unstable angina are customarily included in the concept of ACS. In addition to these categories, MI may be classified into various types based on pathological, clinical, and prognostic differences, along with different treatment strategies.7.1. Myocardial Infarction Type 1MI caused by atherothrombotic coronary artery disease (CAD) and usually precipitated by atherosclerotic plaque disruption (rupture or erosion) is designated as a type 1 MI. The relative burden of atherosclerosis and thrombosis in the culprit lesion varies greatly, and the dynamic thrombotic component may lead to distal coronary embolization resulting in myocyte necrosis.44,45 Plaque rupture may not only be complicated by intraluminal thrombosis but also by hemorrhage into the plaque through the disrupted surface (Figure 3).44,45Download figureDownload PowerPointFigure 3. Myocardial infarction type 1.Criteria for Type 1 MIDetection of a rise and/or fall of cTn values with at least 1 value above the 99th percentile URL and with at least 1 of the following:Symptoms of acute myocardial ischemia;New ischemic ECG changes;Development of pathological Q waves;Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology;Identification of a coronary thrombus by angiography including intracoronary imaging or by autopsy.*cTn indicates cardiac troponin; ECG, electrocardiogram; URL, upper reference limit.*Postmortem demonstration of an atherothrombus in the artery supplying the infarcted myocardium, or a macroscopically large circumscribed area of necrosis with or without intramyocardial hemorrhage, meets the type 1 MI criteria regardless of cTn values.It is essential to integrate the ECG findings with the aim of classifying type 1 MI into STEMI or NSTEMI in order to establish the appropriate treatment according to current Guidelines.46,477.2. Myocardial Infarction Type 2The pathophysiological mechanism leading to ischemic myocardial injury in the context of a mismatch between oxygen supply and demand has been classified as type 2 MI.10,12 By definition, acute atherothrombotic plaque disruption is not a feature of type 2 MI. In patients with stable known or presumed CAD, 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, may result in myocardial injury and a type 2 MI. These effects are due to insufficient blood flow to the ischemic myocardium to meet the increased myocardial oxygen demand of the stressor. Ischemic thresholds may vary substantially in individual patients depending on the magnitude of the stressor, the presence of noncardiac comorbidities, and the extent of underlying CAD and cardiac structural abnormalities.Studies have shown variable occurrences of type 2 MI depending on criteria used for diagnosis. Some reports rely on specific predetermined oxygen mismatch criteria,48,49 whereas others apply more liberal criteria. Most studies show a higher frequency of type 2 MI in women. The short- and long-term mortality rates for patients with type 2 MI are generally higher than for type 1 MI patients in most but not all studies due to an increased prevalence of comorbid conditions.49–57 Coronary atherosclerosis is a common finding in type 2 MI patients selected for coronary angiography. In general, these patients have a worse prognosis than those without CAD.54–57 Prospective evaluations of the importance of CAD with type 2 MI using consistent definitions and approaches are needed.It has been shown that the frequency of ST-segment elevation in type 2 MI varies from 3% to 24%.53 In some cases, coronary embolism caused by thrombi, calcium or vegetation from the atria or ventricles, or acute aortic dissection may result in a type 2 MI. Spontaneous coronary artery dissection with or without intramural hematoma is another non-atherosclerotic condition that may occur, especially in young women. It is defined as spontaneous dissection of the coronary artery wall with accumulation of blood within the false lumen, which can compress the true lumen to varying degrees (Figure 4).58Download figureDownload PowerPointFigure 4. Myocardial infarction type 2.All of the clinical information available should be considered in distinguishing type 1 MI from type 2 MI. The context and mechanisms of type 2 MI should be considered when establishing this diagnosis (Figure 5). The myocardial oxygen supply/demand imbalance attributable to acute myocardial ischemia may be multifactorial, related either to: reduced myocardial perfusion due to fixed coronary atherosclerosis without plaque rupture, coronary artery spasm, coronary microvascular dysfunction (which includes endothelial dysfunction, smooth muscle cell dysfunction, and the dysregulation of sympathetic innervation), coronary embolism, coronary artery dissection with or without intramural hematoma or other mechanisms that reduce oxygen supply such as severe bradyarrhythmia, respiratory failure with severe hypoxemia severe anemia, and hypotension/shock; or to increased myocardial oxygen demand due to sustained tachyarrhythmia or severe hypertension with or without left ventricular hypertrophy. In patients who undergo timely coronary angiography, description of a ruptured plaque with thrombus in the infarct-related artery may be helpful in making the distinction between type 2 MI vs. type 1 MI, but angiography is not always definitive, clinically indicated, or required to establish the diagnosis of type 2 MI.Criteria for Type 2 MIDetection of a rise and/or fall of cTn values with at least 1 value above the 99th percentile URL, and evidence of an imbalance between myocardial oxygen supply and demand unrelated to acute coronary atherothrombosis, requiring at least 1 of the following:Symptoms of acute myocardial ischemia;New ischemic ECG changes;Development of pathological Q waves;Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiologyDownload figureDownload PowerPointFigure 5. Framework for type 2 myocardial infarction considering the clinical context and pathophysiological mechanisms attributable to acute myocardial ischemia. The illustration above is modified from Januzzi and Sandoval.59It appears advisable in the acute setting to treat the underlying ischemic imbalance of oxygen supply and demand. This treatment may include volume adjustment, blood pressure management, administration of blood products, heart-rate control, and respiratory support.47,48 Depending on the clinical situation, coronary evaluations may be indicated to assess the likelihood of CAD. If it is present, the MI Guidelines may be applied in accordance with the ECG findings of STEMI or NSTEMI.46,47 However, if CAD is absent, the benefits of cardiovascular risk reduction strategies with type 2 MI remain uncertain.7.3. Myocardial Infarction Type 2 and Myocardial InjuryType 2 MI and myocardial injury are frequently encountered in clinical practice and both are related to a poor outcome.13,14,49,51,56 A conceptual model to facilitate the clinical distinction between acute ischemic myocardial injury with or without an acute atherothrombotic event (type 1 or type 2 MI) vs. conditions without acute ischemic myocardial injury is displayed in Figure 6. Acute MI requires a rising and/or falling pattern of cTn values. Acute myocardial injury may also manifest such a pattern but if the injury is related to structural heart disease, the cTn values may be stable and unchanging. Type 2 MI and nonischemic myocardial injury may coexist. It should be recognized that some disease entities may be on both sides of the diagram (eg, acute heart failure that may occur in the context of acute myocardial ischemia). Nevertheless, abnormal cTn values in the setting of acute and/or chronic heart failure are often better categorized as a myocardial injury condition. Few studies have compared the incidence and clinical features of type 2 MI versus myocardial injury without acute myocardial ischemia.Download figureDownload PowerPointFigure 6. A model for interpreting myocardial injury. Ischemic thresholds vary substantially in relation to the magnitude of the stressor and the extent of underlying cardiac disease. MI indicates myocardial infarction; URL, upper reference limit.*Stable denotes ≤20% variation of troponin values in the appropriate clinical context.†Ischemia denotes signs and/or symptoms of clinical myocardial ischemia.7.4. Myocardial Infarction Type 3The detection of cardiac biomarkers in the blood is fundamental for establishing the diagnosis of MI.10,12 However, patients can manifest a typical presentation of myocardial ischemia/infarction, including presumed new ischemic ECG changes or ventricular fibrillation, and die before it is possible to obtain blood for cardiac biomarker determination; or the patient may succumb soon after the onset of symptoms before an elevation of biomarker values has occurred. Such patients are designated as having a type 3 MI, when suspicion for an acute myocardial ischemic event is high, even when cardiac biomarker evidence of MI is lacking.10,12 This category allows the separation of fatal MI events from the much larger group of sudden death episodes that may be cardiac (nonischemic) or noncardiac in origin. When a type 3 MI is diagnosed and a subsequent autopsy reveal