41 The universal definition of myocardial infarction

Myocardial infarction is defined pathologically as myocyte necrosis due to prolonged ischaemia. These conditions are met when there is a detection of a rise and/or fall of cardiac biomarkers, preferably troponins, with at least one value above the 99th percentile of the upper reference limit, together with evidence of myocardial ischaemia, as recognized by at least one of the following: symptoms of ischaemia, electrocardiographic changes of new ischaemia, the development of pathological Q waves, imaging evidence of a new loss of viable myocardium or new regional wall motion abnormality, or the identification of an intracoronary thrombus by angiography or autopsy.

MI can be defined from a number of different perspectives related to clinical, electrocardiographic, biochemical, and pathological characteristics. However, the development of sensitive assays for markers of myocardial necrosis led the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC) Committee to publish its first consensus document for the Redefinition of Myocardial Infarction in the year 2000, based on the elevations of cardiac biomarkers as a prerequisite for the diagnosis of MI [1]. The American Heart Association (AHA) and the World Heart Federation (WHF) joined the group to develop a Global Task Force for the Definition of Acute Myocardial Infarction in 2007 that also distinguished various types of MI [2]. These principles were adopted by the WHO [3]. The recent development of even more sensitive assays for cardiac troponins (cTn) has mandated a further revision of the definition, particularly when elevated cTn values occur in the setting of the critically ill, after percutaneous coronary procedures, or after cardiac surgery. The Third Global MI Task Force has therefore continued the Joint ESC/ACCF/AHA/WHF efforts by integrating these insights into the Third Universal Definition of Myocardial Infarction in 2012 [4].

MI is defined pathologically as myocardial cell death due to prolonged ischaemia. In the clinical setting, these conditions are met when the following criteria are present: the detection of a rise and/or fall of cardiac biomarkers (preferably cTn), with at least one value above the 99th percentile of the upper reference limit (URL), together with evidence of myocardial ischaemia, as recognized by at least one of the following: symptoms of ischaemia, ECG changes of new ischaemia or the development of pathological Q waves, or imaging evidence of a new loss of viable myocardium or new regional wall motion abnormality. In the most recent revision of the definition, the identification of an intracoronary thrombus by angiography or autopsy has been added as a relevant criterion [4] (see Table 41.1).

MI is defined in pathology as myocardial cell death due to prolonged ischaemia. After the onset of myocardial ischaemia, histological cell death is not immediate but takes a finite period of time to develop—as little as 20 min or less in some animal models [2, 4]. It takes several hours before myocardial necrosis can be identified by macroscopic or microscopic post-mortem examination. Complete necrosis of myocardial cells at risk requires at least 2–4 hours or longer, depending on the presence of collateral circulation to the ischaemic zone, persistent or intermittent coronary arterial occlusion, the sensitivity of the myocytes to ischaemia, preconditioning, and the individual demand for O₂ and nutrients [4]. The entire process leading to a healed infarction usually takes at least 5–6 weeks. However, reperfusion may alter the macroscopic and microscopic appearance.

Myocardial injury is detected when blood levels of sensitive and specific biomarkers, such as cTn or the myoband (MB) fraction of creatine kinase (CK), are increased. cTnI and cTnT are components of the contractile apparatus of myocardial cells and are expressed almost exclusively in the heart. Although elevations of these biomarkers in the blood reflect injury, leading to necrosis of myocardial cells, they do not indicate the underlying mechanism [4].Various possibilities have been suggested for the release of structural proteins from the myocardium, including a normal turnover of myocardial cells, apoptosis, the cellular release of troponin degradation products, an increased cellular wall permeability, the formation and release of membranous blebs, and myocyte necrosis [5]. Regardless of the pathobiology, myocardial necrosis due to myocardial ischaemia is designated as MI.

Also, histological evidence of myocardial injury with necrosis may be detectable in clinical conditions associated with a predominantly non-ischaemic myocardial injury. Small amounts of myocardial injury with necrosis may be detected which are associated with heart failure, renal failure, myocarditis, arrhythmias, PE, or otherwise uneventful percutaneous or surgical coronary procedures. These should not be labelled as MI or a complication of the procedures, but rather as myocardial injury, as illustrated in Figure 41.1. It is recognized that the complexity of clinical circumstances may sometimes render it difficult to determine where patients may lie within the ovals in Figure 41.1. In this setting, it is important to distinguish the acute causes of cTn elevation, which require a rise and/or fall of cTn values, from a chronic elevation that tends not to change acutely. A list of such clinical circumstances associated with elevated values of cTn is presented in Table 41.2. The multifactorial contributions resulting in the myocardial injury should be described in the patient record.

The preferred biomarker overall and for each specific category of MI is cTn (I or T), which has a high myocardial tissue specificity as well as a high clinical sensitivity. The detection of a rise and/or fall of the measurements is essential to the diagnosis of acute myocardial infarction (AMI). An increased cTn concentration is defined as a value exceeding the 99th percentile of a normal reference population (URL). This discriminatory 99th percentile is designated as the decision level for the diagnosis of MI and must be determined for each specific assay, with appropriate quality control in each laboratory. The values for the 99th percentile URL defined by manufacturers, including those for many of the high-sensitivity assays in development, can be found in the package inserts for the assays or in recent publications [6–8].

Values should be presented as nanogram per litre (ng/L) or picogram per millilitre (pg/mL) to make whole numbers. Criteria for the rise of cTn values are assay-dependent but can be defined from the precision profile of each individual assay, including high-sensitivity assays [6–8]. The optimal precision, as described by the coefficient of variation (CV) at the 99th percentile URL for each assay, should be defined as ≤10%. Better precision (CV ≤10%) allows for more sensitive assays and facilitates the detection of changing values. The use of assays that do not have optimal precision (CV >10% at the 99th percentile URL) makes determination of a significant change more difficult but does not cause false positive results. Assays with a CV >20% at the 99th percentile URL should not be used [9]. It is acknowledged that pre-analytic and analytic problems can induce elevated and reduced values of cTn [6–8].

Blood samples for the measurement of cTn should be drawn on first assessment and repeated 3–6 hours later. Later samples are required if further ischaemic episodes occur or when the timing of the initial symptoms is unclear [6, 7]. To establish the diagnosis of MI, a rise and/or fall in values, with at least one value above the decision level, is required, coupled with a strong pretest likelihood. The demonstration of a rising and/or falling pattern is needed to distinguish acute from chronic elevations in cTn concentrations that are associated with structural heart disease [6, 7, 10–14]. For example, patients with renal failure or heart failure can have significant elevations in cTn chronically. These elevations can be marked, as seen in many patients with MI, but do not change acutely. However, a rising or falling pattern is not absolutely required to make a diagnosis of MI if a patient with a high pretest risk of MI presents late after symptom onset, e.g. near the peak of the cTn time–concentration curve or on the slow declining portion of that curve when detecting a changing pattern can be problematic. Values may remain elevated for 2 weeks or more, following the onset of myocyte necrosis [6].

The onset of myocardial ischaemia is the initial step in the development of MI and results from an imbalance between the O₂ supply and demand. Myocardial ischaemia in a clinical setting most often can be identified from the patient’s history and from the ECG. Possible ischaemic symptoms include various combinations of chest, upper extremity, mandibular, or epigastric discomfort on exertion or at rest, or an ischaemic equivalent such as dyspnoea or fatigue. The discomfort associated with an AMI usually lasts for >20 min. Often, the discomfort is diffuse, not localized or positional, and not affected by movement of the region, and it may be accompanied by diaphoresis, nausea, or syncope. However, these symptoms are not specific for myocardial ischaemia. Accordingly, they may be misdiagnosed and attributed to gastrointestinal (GI), neurological, pulmonary, or musculoskeletal disorders. MI may occur with atypical symptoms, such as palpitations or cardiac arrest, or even without symptoms, e.g. in women, the elderly, diabetics, or post-operative and critically ill patients. A careful evaluation of these patients is advised, especially when there is a rising and/or falling pattern of cardiac biomarkers [4].

For the sake of immediate treatment strategies, such as reperfusion therapy, it is usual practice to designate MI in patients with chest discomfort or other ischaemic symptoms that develop ST elevation in two contiguous leads (see Electrocardiographic detection of myocardial infarction section) as a ST-segment elevation myocardial infarction (STEMI). In contrast, patients without ST elevation at presentation usually are designated as having an non-ST-segment elevation myocardial infarction (NSTEMI). Many patients with MI develop Q waves (Q wave MI), but others do not (non-Q MI). Patients without elevated biomarker values can be diagnosed as unstable angina (UA). In addition to these categories, MI is classified into various types, based on pathological, clinical, and prognostic differences, along with different treatment strategies (see Table 41.3).

This is an event related to atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection, with resulting intraluminal thrombus in one or more of the coronary arteries, leading to a decreased myocardial blood flow or distal platelet emboli, with ensuing myocyte necrosis. The patient may have underlying severe CAD, but, on occasion (5–20%), non-obstructive or no CAD may be found at angiography, particularly in women [4, 15, 16].

In instances of myocardial injury with necrosis where a condition other than CAD contributes to an imbalance between myocardial oxygen supply and/or demand, the term MI type 2 is employed (see Figure 41.2). In critically ill patients, or in patients undergoing major (non-cardiac) surgery, elevated values of cardiac biomarkers may appear, due to the direct toxic effects of endogenous or exogenous high circulating catecholamine levels [4]. Also, anaemia, tachyarrhythmias, and respiratory failure are prevalent conditions underlying MI type 2 [4a].

Patients who suffer from cardiac death, with symptoms suggestive of myocardial ischaemia, accompanied by presumed new ischaemic ECG changes or new LBBB, but without available biomarker values, represent a challenging diagnostic group. These individuals may die, before blood samples for biomarkers can be obtained or before elevated cardiac biomarkers can be identified. If patients present with clinical features of myocardial ischaemia or with presumed new ischaemic ECG changes, they should be classified as having had a fatal MI, even if cardiac biomarker evidence of MI is lacking [4].

Periprocedural myocardial injury or infarction may occur at some stages in the instrumentation of the heart that is required during mechanical revascularization procedures, either by PCI or by coronary artery bypass graft (CABG). Elevated cTn values may be detected, following these procedures, since various insults may occur that can lead to myocardial injury with necrosis. It is likely that a limitation of such injury is beneficial to the patient; however, a threshold for a worsening prognosis related to an asymptomatic increase of cardiac biomarker values, in the absence of procedural complications, is not well defined [17–19]. Subcategories of PCI-related MI are connected to stent thrombosis and restenosis that may happen after the primary procedure [4].

The ECG is an integral part of the diagnostic work-up of patients with suspected MI and should be acquired and interpreted promptly after clinical presentation. Dynamic changes in the ECG waveforms during acute myocardial ischaemic episodes often require the acquisition of multiple ECGs, particularly if the ECG at initial presentation is non-diagnostic. Acute or evolving changes in the ST–T waveforms, and Q waves when present, potentially allow the clinician to time the event, to identify the infarct-related artery, to estimate the amount of myocardium at risk as well as the prognosis, and to determine a therapeutic strategy. Other ECG signs associated with acute myocardial ischaemia include cardiac arrhythmias, intraventricular and atrioventricular (AV) conduction delays, and loss of precordial R wave amplitude. The coronary artery size and distribution of arterial segments, collateral vessels, location, extent and severity of coronary stenosis, and prior myocardial necrosis can impact ECG manifestations of myocardial ischaemia [20]. Therefore, the ECG at presentation should always be compared to prior ECG tracings when available. The ECG, by itself, is often insufficient to diagnose acute myocardial ischaemia or infarction, since an ST deviation may be observed in other conditions such as acute pericarditis, LV hypertrophy, LBBB, Brugada syndrome, stress cardiomyopathy, and early repolarization patterns [21].

The earliest manifestations of myocardial ischaemia are typically T wave and ST-segment changes. An increased hyperacute T wave amplitude with prominent symmetrical T waves in at least two contiguous leads is an early sign that may precede the elevation of the ST-segment. Transient Q waves may be observed during an episode of acute ischaemia or (rarely) during AMI with successful reperfusion. Table 41.4 lists ST–T wave criteria for the diagnosis of acute myocardial ischaemia that may or may not lead to MI. The criteria in Table 41.4 require that the ST shift be present in ≥2 contiguous leads. The J point is used to determine the magnitude of the ST-segment shift. A new, or presumed new, J point elevation of ≥0.1 mV is required in all leads, other than leads V2 and V3. In healthy men under the age of 40, the J point elevation can be as much as 0.25 mV in leads V2 or V3, but it decreases with increasing age. Sex differences require different cut-points for women, since the J point elevation in healthy women in leads V2 and V3 is less than that in men [22]. Contiguous leads refer to lead groups such as the anterior leads (V1–V6), the inferior leads (II, III, aVF), or the lateral/apical leads (I, aVL). The spplemental leads V3R and V4R reflect the free wall of the RV, and V7–V9 the inferobasal wall [4, 23].

Q waves or QS complexes, in the absence of QRS confounders, are pathognomonic of a prior MI in patients with ischaemic heart disease, regardless of symptoms (see Table 41.5). The specificity of the ECG diagnosis for MI is greatest when Q waves occur in several leads or lead groupings. When the Q waves are associated with ST deviations or T wave changes in the same leads, the likelihood of an MI is increased. For example, minor Q waves of ≥0.02 s and <0.03 s that are ≥0.1 mV deep are suggestive of a prior MI, if accompanied by inverted T waves in the same lead group. Other validated MI coding algorithms, such as the Minnesota code and the WHO MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease), have been used in epidemiological studies and clinical trials [4].

Imaging techniques can be useful in the diagnosis of an AMI, because of the ability to detect wall motion abnormalities or a loss of viable myocardium in the presence of elevated cardiac biomarker values. If, for some reason, biomarkers have not been measured or may have normalized, the demonstration of a new loss of myocardial viability, in the absence of non-ischaemic causes, meets the criteria for an MI. Normal function and viability have a very high negative predictive value (NPV) and practically exclude an AMI [24]. Thus, imaging techniques are useful for an early triage and discharge of patients with suspected MI. However, if biomarkers have been measured at appropriate times and are normal, this excludes an AMI and takes precedence over the imaging criteria.

Abnormal regional myocardial motion and thickening may be caused by an AMI or by one or more of several other conditions, including prior MI, acute ischaemia, stunning, or hibernation. Non-ischaemic conditions, such as cardiomyopathy and inflammatory or infiltrative diseases, can also lead to a regional loss of viable myocardium or functional abnormality. Therefore, the positive predictive value (PPV) of imaging for an AMI is not high, unless these conditions can be excluded and unless a new abnormality is detected or can be presumed to have arisen in the setting of other features of an AMI.

Echocardiography provides an assessment of many non-ischaemic causes of acute chest pain (CP) such as perimyocarditis, valvular heart disease, cardiomyopathy, PE, or aortic dissection [25] (see Chapter 20). It is the imaging technique of choice for detecting complications of an AMI, including myocardial FWR, acute VSD, and MR secondary to papillary muscle rupture or ischaemia.

Radionuclide imaging can be used to assess the amount of myocardium that is salvaged by acute revascularization [26]. A tracer is injected at the time of presentation, with imaging deferred until after revascularization, providing a measure of myocardium at risk. Before discharge, a second resting injection provides a measure of the final infarct size, and the difference between the two corresponds to the myocardium that has been salvaged.

In cases of a late presentation after a suspected MI, the presence of a regional wall motion abnormality, thinning, or scarring, in the absence of non-ischaemic causes, provides evidence of a past MI. The high resolution and specificity of late gadolinium enhancement MRI for the detection of myocardial fibrosis has made this a very valuable technique (see Chapter 23). In particular, the ability to distinguish between subendocardial and other patterns of fibrosis provides a differentiation between ischaemic heart disease and other myocardial abnormalities. Imaging techniques are also useful for risk stratification after a definitive diagnosis of MI. The detection of residual or remote ischaemia and/or ventricular dysfunction provides powerful indicators of later outcome.

The occurrence of procedure-related myocardial cell injury with necrosis can be detected by the measurement of cardiac biomarkers before the procedure, and after this one at 3–6 hours, and optionally at 12 hours subsequently. Increasing levels can only be interpreted as procedure-related myocardial injury if the pre-procedural cTn value is normal (≤99th percentile URL) or if the values are stable or falling [4]. In patients with normal pre-procedural values, an elevation of cardiac biomarker values above the 99th percentile URL after percutaneous coronary intervention (PCI) is indicative of procedure-related myocardial injury.

In patients undergoing PCI with normal (≤99th percentile URL) baseline cTn concentrations, elevations of cTn >5 times the 99th percentile URL, occurring within 48 hours of the procedure, plus either evidence of prolonged ischaemia (>20 min), as demonstrated by prolonged CP, haemodynamic instability, ischaemic ST changes, or new pathological Q waves, or angiographic evidence of a flow-limiting complication such as the loss of patency of a side branch, persistently slow flow or no reflow, embolization, or imaging evidence of a new loss of viable myocardium, is defined as PCI-related MI (type 4a). This threshold of cTn values >5 times the 99th percentile URL is arbitrarily chosen, based on clinical judgement and societal implications of the label of periprocedural MI. When a cTn value is ≤5 times the 99th percentile URL after PCI, and the cTn value was normal before the PCI, or when the cTn value is >5 times the 99th percentile URL, in the absence of ischaemic, angiographic, or imaging findings, the term myocardial injury should be used [4]. If the baseline cTn values are elevated and are stable or falling, then a rise of >20% is required for the diagnosis of an MI type 4a, as with reinfarction. Recent data suggest that, when PCI is delayed after an MI until biomarker concentrations are falling or have normalized and an elevation of cardiac biomarker values then reoccurs, this may have some long-term significance, but additional data are needed to confirm this finding [4].

A subcategory of PCI-related MI is stent thrombosis, as documented by angiography and/or at autopsy, and a rise and/or fall of cTn values >99th percentile URL (labelled MI type 4b). In order to stratify the occurrence of stent thrombosis in relation to the timing of the PCI procedure, the Academic Research Consortium recommends the temporal categories of early (0 to 30 days), late (31 days to 1 year), and very late (>1 year) to distinguish likely differences in the contribution of the various pathophysiological processes during each of these intervals [27]. Occasionally, an MI occurs in the clinical setting of what appears to be a stent thrombosis; however, at angiography, restenosis is observed without evidence of thrombus (see Application of myocardial infarction in clinical trials and quality assurance programmes section).

Any increase of cardiac biomarker values after coronary artery bypass grafting (CABG), in patients with normal values before surgery, indicates myocardial necrosis, implying that an increasing magnitude of biomarker concentrations is likely to be related to an impaired outcome [28]. Unlike prognosis, scant literature exists concerning the use of biomarkers for defining an MI related to a primary vascular event in a graft or native vessel in the setting of CABG. In view of the adverse impact on survival observed in patients with a significant elevation of biomarker concentrations, it is suggested, by arbitrary convention, that cTn values >10 times the 99th percentile URL during the first 48 hours following CABG, occurring from a normal baseline cTn value (≤ 99th percentile URL), when associated with the appearance of new pathological Q waves or new LBBB, or angiography-documented new graft or new native coronary artery occlusion, or with imaging evidence of a new loss of viable myocardium, should be considered as diagnostic of a CABG-related MI (type 5) [4]. As for PCI, the existing principles from the universal definition of MI should be applied for the definition of MI >48 hours after surgery [4].

In patients who undergo cardiac surgery, new ST–T abnormalities are common. When new pathological Q waves appear in territories different to those identified before surgery, MI (types 1 or 2) should be considered, particularly if associated with elevated cardiac biomarker values, new wall motion abnormalities, or haemodynamic instability.

Novel procedures, such as transcatheter aortic valve implantation (TAVI), may cause myocardial injury with necrosis, both by direct trauma to the myocardium and by creating regional ischaemia from coronary obstruction or embolization. It is likely that, similar to CABG, the more marked the elevation of the biomarker values, the worse the prognosis, but data about that are not available. Modified criteria for the diagnosis of periprocedural MI ≤72 hours after the implantation have been proposed [29]. However, given too little evidence, it appears reasonable to apply the same criteria for procedure-related MI, as stated above for CABG.

The ablation of arrhythmias involves controlled myocardial injury with necrosis by application of radiofrequency or cooling of the tissue. The amount of injury with necrosis can be assessed by cTn measurements; however, an elevation of cTn values in this context should not be labelled as MI.

Perioperative MI is the most common major perioperative vascular complication in major non-cardiac surgery, and it is associated with a poor prognosis [30, 31]. Most patients who have a perioperative MI will not experience ischaemic symptoms. Nevertheless, asymptomatic perioperative MI is as strongly associated as symptomatic MI with 30-day mortality [31]. Studies of patients undergoing major non-cardiac surgery strongly support the concept that many of the infarctions diagnosed in this context are caused by a prolonged imbalance between myocardial O₂ supply and demand on a background of CAD [32] which, together with a rise and/or fall of cTn values, indicates MI type 2. However, one pathological study of fatal perioperative MI patients showed plaque rupture and platelet aggregation, leading to thrombus formation, in approximately half of such events [33], that is to say MI type 1. Given the differences that likely exist in the therapeutic approaches to each, close clinical scrutiny and judgement are needed [4].

Elevations of cTn values are common in patients in the ICU and are associated with adverse prognosis, regardless of the underlying disease state [34]. Some elevations may reflect MI type 2, due to an underlying CAD and an increased myocardial O₂ demand. Other patients may have elevated values of cardiac biomarkers, due to myocardial injury with necrosis induced by catecholamines or a direct toxic effect from circulating toxins. Moreover, in some patients, MI type 1 may occur. It is frequently challenging for the clinician caring for a critically ill patient with severe single-organ or multiorgan pathology to decide on a plan of action when the patient has elevated cTn values. If and when the patient recovers from the critical illness, clinical judgement should be employed to decide whether, and to what extent, a further evaluation for CAD or structural heart disease is indicated [35].

An incident MI is defined as the individual’s first MI. When features of an MI occur in the first 28 days after an incident event, this one is not counted as a new event for epidemiological purposes. If the characteristics of an MI occur after 28 days following an incident MI, it is considered to be a recurrent MI [3].

The term reinfarction is used for an AMI that occurs within 28 days of an incident or recurrent MI [3]. The ECG diagnosis of a suspected reinfarction, following the initial MI, may be confounded by the initial evolutionary ECG changes. Reinfarction should be considered when an ST elevation of ≥0.1 mV reoccurs or new pathognomonic Q waves appear, in at least two contiguous leads, particularly when associated with ischaemic symptoms for 20 min or longer. Re-elevation of the ST-segment can, however, also be seen in threatened myocardial rupture and should lead to additional diagnostic work-up. ST depression or left bundle branch block (LBBB) alone are non-specific findings and should not be used to diagnose reinfarction [4].

In patients where reinfarction is suspected from clinical signs or symptoms, following the initial MI, an immediate measurement of cTn is recommended. A second sample should be obtained 3–6 hours later. If the cTn concentration is elevated, but stable or decreasing at the time of suspected reinfarction, the diagnosis of reinfarction requires a 20% or greater increase of the cTn value in the second sample. If the initial cTn concentration is normal, the criteria for a new AMI apply [4].

Depending on the assay used, detectable to frankly elevated cTn values, indicative of myocardial injury with necrosis, may be seen in patients with heart failure syndrome [36] (see Chapter 51). Using hscTn assays, measurable cTn concentrations may be present in nearly all patients with heart failure, with a significant percentage exceeding the 99th percentile URL, particularly in those with more severe heart failure syndrome such as in acute decompensated heart failure (ADHF) [38].

While MI type 1 is an important cause of ADHF and should always be considered in the context of an acute presentation, elevated cTn values alone in a patient with heart failure syndrome does not establish the diagnosis of MI type 1 and indeed may be seen in those with non-ischaemic heart failure. Beyond MI type 1, multiple mechanisms have been invoked to explain measurable to pathologically elevated cTn concentrations in patients with heart failure [36, 37]. For example, MI type 2 may result from an increased transmural pressure, small-vessel coronary obstruction, endothelial dysfunction, anaemia, or hypotension. Besides MI type 1 or 2, cardiomyocyte apoptosis and autophagy, due to wall stretch, have been experimentally demonstrated. Direct cellular toxicity related to inflammation, circulating neurohormones, and infiltrative processes, as well as myocarditis and stress cardiomyopathy, may present with heart failure and abnormal cTn measurements [37].

In clinical trials, MI may be an entry criterion or an endpoint. A universal definition for MI is of great benefit for clinical studies, since it will allow a standardized approach for interpretation and comparisons across different trials. The definition of MI as an entry criterion, e.g. MI type 1 and not MI type 2, will determine patient characteristics in the trial. Occasionally, an MI occurs, and, at angiography, restenosis is the only angiographic explanation [38, 39]. This PCI-related MI type might be designated as MI type 4c, defined as ≥50% of stenosis at coronary angiography, following an initially successful stent deployment or dilatation of a coronary artery stenosis with balloon angioplasty (<50%), and no other significant obstructive CAD of greater severity or complexity in the ischaemic territory, with a rise and/or fall of cTn values >99th percentile URL.

In recent investigations, different MI definitions have been employed as trial outcomes, thereby hampering comparisons and generalizations among these trials. Consistency among investigators and regulatory authorities, with regard to the definition of MI used as an endpoint, in clinical investigations is of substantial value. Adaptation of the definition to an individual clinical study may be appropriate in some circumstances and should have a well-articulated rationale. No matter what, investigators should ensure that a trial provides comprehensive data for the various types of MI and includes the 99th percentile URL decision limits of cTn or other biomarkers employed. Multiples of the 99th percentile URL may be indicated, as shown in Figure 41.3. This will facilitate the comparison of trials and meta-analyses.

The new universal definition of MI is based on troponin elevations, together with ischaemic symptoms, typical ECG changes, or imaging evidence of the loss of viable myocardium. MIs are classified into various types, whether spontaneous, secondary, or related to revascularization procedures.