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Electrocardiographic Detection of Myocardial Infarction

The ECG is an integral part of the diagnostic work-up of patients with suspected MI and should be acquired and interpreted promptly (i.e. target within 10 min) after clinical presentation.^[2] Dynamic changes in the ECG waveforms during acute myocardial ischemic episodes often require acquisition of multiple ECGs, particularly if the ECG at initial presentation is non-diagnostic. Serial recordings in symptomatic patients with an initial non-diagnostic ECG should be performed at 15–30 min intervals or, if available, continuous computer-assisted 12-lead ECG recording. Recurrence of symptoms after an asymptomatic interval are an indication for a repeat tracing and, in patients with evolving ECG abnormalities, a pre-discharge ECG should be acquired as a baseline for future comparison. 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 prognosis, and to determine therapeutic strategy. More profound ST-segment shift or T wave inversion involving multiple leads/territories is associated with a greater degree of myocardial ischemia and a worse prognosis. Other ECG signs associated with acute myocardial ischemia include cardiac arrhythmias, intraventricular and atrioventricular conduction delays, and loss of pre-cordial R wave amplitude. Coronary artery size and distribution of arterial segments, collateral vessels, location, extent and severity of coronary stenosis, and prior myocardial necrosis can all impact ECG manifestations of myocardial ischemia.^[36] 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 ischemia or infarction, since ST deviation may be observed in other conditions, such as acute pericarditis, left ventricular hypertrophy (LVH), left bundle branch block (LBBB), Brugada syndrome, stress cardiomyopathy, and early repolarization patterns.^[37] Prolonged new ST-segment elevation (e.g. >20 min), particularly when associated with reciprocal ST-segment depression, usually reflects acute coronary occlusion and results in myocardial injury with necrosis. As in cardiomyopathy, Q waves may also occur due to myocardial fibrosis in the absence of CAD.

ECG abnormalities of myocardial ischemia or infarction may be inscribed in the PR segment, the QRS complex, the ST-segment or the T wave. The earliest manifestations of myocardial ischemia are typically T wave and ST-segment changes. 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 ischemia or (rarely) during acute MI with successful reperfusion. () lists ST-T wave criteria for the diagnosis of acute myocardial ischemia that may or may not lead to MI. The J point is used to determine the magnitude of the ST-segment shift. New, or presumed new, J point elevation >0.1 mV is required in all leads other than V₂ and V₃. In healthy men under age 40, 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 J point elevation in healthy women in leads V₂ and V₃ is less than in men.^[38] ‘Contiguous leads’ refers to lead groups such as anterior leads (V₁–V₆), inferior leads (II, III, aVF) or lateral/apical leads (I, aVL). Supplemental leads such as V₃R and V₄R reflect the free wall of the right ventricle and V₇–V₉ the inferobasal wall.

Table 3.  ECG Manifestations of Acute Myocardial Ischemia (in Absence of LVH and LBBB)

The criteria in () require that the ST shift be present in two or more contiguous leads. For example, >0.2 mV of ST elevation in lead V₂, and >0.1 mV in lead V₁, would meet the criteria of two abnormal contiguous leads in a man >40 years old. However, >0.1 mV and <0.2 mV of ST elevation, seen only in leads V₂–V₃ in men (or <0.15 mV in women), may represent a normal finding. It should be noted that, occasionally, acute myocardial ischemia may create sufficient ST-segment shift to meet the criteria in one lead but have slightly less than the required ST shift in a contiguous lead. Lesser degrees of ST displacement or T wave inversion do not exclude acute myocardial ischemia or evolving MI, since a single static recording may miss the more dynamic ECG changes that might be detected with serial recordings. ST elevation or diagnostic Q waves in contiguous lead groups are more specific than ST depression in localizing the site of myocardial ischemia or necrosis.^[39,40] Supplemental leads, as well as serial ECG recordings, should always be considered in patients that present with ischemic chest pain and a non-diagnostic initial ECG.^[41,42] Electrocardiographic evidence of myocardial ischemia in the distribution of a left circumflex artery is often overlooked and is best captured using posterior leads at the fifth intercostal space (V₇ at the left posterior axillary line, V₈ at the left mid-scapular line, and V₉ at the left paraspinal border). Recording of these leads is strongly recommended in patients with high clinical suspicion for acute circumflex occlusion (for example, initial ECG non-diagnostic, or ST-segment depression in leads V₁–V₃). A cut-point of 0.05 mV ST elevation is recommended in leads V₇–V₉; specificity is increased at a cut-point >0.1 mV ST elevation and this cut-point should be used in men <40 years old. ST depression in leads V₁–V₃ may be suggestive of inferobasal myocardial ischemia (posterior infarction), especially when the terminal T wave is positive (ST elevation equivalent), however this is non-specific.^[41–43] In patients with inferior and suspected right ventricular infarction, right pre-cordial leads V₃R and V₄R should be recorded, since ST elevation >0.05 mV (>0.1 mV in men <30 years old) provides supportive criteria for the diagnosis.^[42]

Table 3.  ECG Manifestations of Acute Myocardial Ischemia (in Absence of LVH and LBBB)

During an episode of acute chest discomfort, pseudo-normalization of previously inverted T waves may indicate acute myocardial ischemia. Pulmonary embolism, intracranial processes, electrolyte abnormalities, hypothermia, or peri-/myocarditis may also result in ST-T abnormalities and should be considered in the differential diagnosis. The diagnosis of MI is more difficult in the presence of LBBB.^[44,45] However, concordant ST-segment elevation or a previous ECG may be helpful to determine the presence of acute MI in this setting. In patients with right bundle branch block (RBBB), ST-T abnormalities in leads V₁–V₃ are common, making it difficult to assess the presence of ischemia in these leads: however, when new ST elevation or Q waves are found, myocardial ischemia or infarction should be considered.

Prior Myocardial Infarction

As shown in (), Q waves or QS complexes in the absence of QRS confounders are pathognomonic of a prior MI in patients with ischemic heart disease, regardless of symptoms.^[46,47] 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 MI is increased; for example, minor Q waves >0.02 sec and <0.03 sec that are ≧0.1 mV deep are suggestive of prior MI if accompanied by inverted T waves in the same lead group. Other validated MI coding algorithms, such as the Minnesota Code and WHO MONICA, have been used in epidemiological studies and clinical trials.^[3]

Table 4.  ECG Changes Associated With Prior Myocardial Infarction

^a The same criteria are used for supplemental leads V₇–V₉.

Silent Myocardial Infarction

Asymptomatic patients who develop new pathologic Q wave criteria for MI detected during routine ECG follow-up, or reveal evidence of MI by cardiac imaging, that cannot be directly attributed to a coronary revascularization procedure, should be termed ‘silent MI’.^[48–51] In studies, silent Q wave MI accounted for 9–37% of all non-fatal MI events and were associated with a significantly increased mortality risk.^[48,49] Improper lead placement or QRS confounders may result in what appear to be new Q waves or QS complexes, as compared to a prior tracing. Thus, the diagnosis of a new silent Q wave MI should be confirmed by a repeat ECG with correct lead placement, or by an imaging study, and by focused questioning about potential interim ischemic symptoms.

Conditions That Confound the ECG Diagnosis of Myocardial Infarction

A QS complex in lead V₁ is normal. A Q wave <0.03 sec and <25% of the R wave amplitude in lead III is normal if the frontal QRS axis is between −30° and 0°. A Q wave may also be normal in aVL if the frontal QRS axis is between 60° and 90°. Septal Q waves are small, non-pathological Q waves <0.03 sec and <25% of the R-wave amplitude in leads I, aVL, aVF, and V₄–V₆. Pre-excitation, obstructive, dilated or stress cardiomyopathy, cardiac amyloidosis, LBBB, left anterior hemiblock, LVH, right ventricular hypertrophy, myocarditis, acute cor pulmonale, or hyperkalemia may be associated with Q waves or QS complexes in the absence of MI. ECG abnormalities that mimic myocardial ischemia or MI are presented in ().

Table 5.  Common ECG Pitfalls in Diagnosing Myocardial Infarction

Imaging Techniques

Non-invasive imaging plays many roles in patients with known or suspected MI, but this section concerns only its role in the diagnosis and characterization of MI. The underlying rationale is that regional myocardial hypoperfusion and ischemia lead to a cascade of events, including myocardial dysfunction, cell death and healing by fibrosis. Important imaging parameters are therefore perfusion, myocyte viability, myocardial thickness, thickening and motion, and the effects of fibrosis on the kinetics of paramagnetic or radio-opaque contrast agents.

Commonly used imaging techniques in acute and chronic infarction are echocardiography, radionuclide ventriculography, myocardial perfusion scintigraphy (MPS) using single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). Positron emission tomography (PET) and X-ray computed tomography (CT) are less common.^[52] There is considerable overlap in their capabilities and each of the techniques can, to a greater or lesser extent, assess myocardial viability, perfusion, and function. Only the radionuclide techniques provide a direct assessment of myocyte viability, because of the inherent properties of the tracers used. Other techniques provide indirect assessments of myocardial viability, such as contractile response to dobutamine by echocardiography or myocardial fibrosis by MR.

Echocardiography

The strength of echocardiography is the assessment of cardiac structure and function, in particular myocardial thickness, thickening and motion. Echocardiographic contrast agents can improve visualization of the endocardial border and can be used to assess myocardial perfusion and microvascular obstruction. Tissue Doppler and strain imaging permit quantification of global and regional function.^[53] Intravascular echocardiographic contrast agents have been developed that target specific molecular processes, but these techniques have not yet been applied in the setting of MI.^[54]

Radionuclide Imaging

Several radionuclide tracers allow viable myocytes to be imaged directly, including the SPECT tracers thallium-201, technetium-99m MIBI and tetrofosmin, and the PET tracers F-2-fluorodeoxyglucose (FDG) and rubidium-82.^[18,52] The strength of the SPECT techniques is that these are the only commonly available direct methods of assessing viability, although the relatively low resolution of the images leaves them at a disadvantage for detecting small areas of MI. The common SPECT radiopharmaceuticals are also tracers of myocardial perfusion and the techniques thereby readily detect areas of MI and inducible perfusion abnormalities. ECG-gated imaging provides a reliable assessment of myocardial motion, thickening and global function. Evolving radionuclide techniques that are relevant to the assessment of MI include imaging of sympathetic innervation using iodine-123-labelled meta-iodo-benzylguanidine (mIBG),^[55] imaging of matrix metalloproteinase activation in ventricular remodeling.^[56,57] and refined assessment of myocardial metabolism.^[58]

Magnetic Resonance Imaging

The high tissue contrast of cardiovascular MRI provides an accurate assessment of myocardial function and it has similar capability to echocardiography in suspected acute MI. Paramagnetic contrast agents can be used to assess myocardial perfusion and the increase in extracellular space that is associated with the fibrosis of prior MI. These techniques have been used in the setting of acute MI,^[59,60] and imaging of myocardial fibrosis by delayed contrast enhancement is able to detect even small areas of subendocardial MI. It is also of value in detecting myocardial disease states that can mimic MI, such as myocarditis.^[61]

Computed Tomography

Infarcted myocardium is initially visible as a focal area of decreased left ventricle (LV) enhancement, but later imaging shows hyper-enhancement, as with late gadolinium imaging by MRI.^[62] This finding is clinically relevant because contrast-enhanced CT may be performed for suspected pulmonary embolism and aortic dissection—conditions with clinical features that overlap with those of acute MI—but the technique is not used routinely. Similarly, CT assessment of myocardial perfusion is technically feasible but not yet fully validated.

Applying Imaging in Acute Myocardial Infarction

Imaging techniques can be useful in the diagnosis of acute MI because of their ability to detect wall motion abnormalities or 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, demonstration of new loss of myocardial viability in the absence of non-ischemic causes meets the criteria for MI. Normal function and viability have a very high negative predictive value and practically exclude acute MI.^[63] Thus, imaging techniques are useful for early triage and discharge of patients with suspected MI. However, if biomarkers have been measured at appropriate times and are normal, this excludes an acute MI and takes precedence over the imaging criteria.

Abnormal regional myocardial motion and thickening may be caused by acute MI or by one or more of several other conditions, including prior MI, acute ischemia, stunning or hibernation. Non-ischemic conditions, such as cardiomyopathy and inflammatory or infiltrative diseases, can also lead to regional loss of viable myocardium or functional abnormality. Therefore, the positive predictive value of imaging for acute MI 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 acute MI.

Echocardiography provides an assessment of many non-ischemic causes of acute chest pain, such as peri-myocarditis, valvular heart disease, cardiomyopathy, pulmonary embolism or aortic dissection.^[53] It is the imaging technique of choice for detecting complications of acute MI, including myocardial free wall rupture, acute ventricular septal defect, and mitral regurgitation secondary to papillary muscle rupture or ischemia.

Radionuclide imaging can be used to assess the amount of myocardium that is salvaged by acute revascularization.^[64] 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 final infarct size, and the difference between the two corresponds to the myocardium that has been salvaged.

Applying Imaging in Late Presentation of Myocardial Infarction

In case of late presentation after suspected MI, the presence of regional wall motion abnormality, thinning or scar in the absence of non-ischemic causes, provides evidence of 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. In particular, the ability to distinguish between subendocardial and other patterns of fibrosis provides a differentiation between ischemic 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 ischemia and/or ventricular dysfunction provides powerful indicators of later outcome.

Diagnostic Criteria for Myocardial Infarction With PCI (MI Type 4)

Balloon inflation during PCI often causes transient ischemia, whether or not it is accompanied by chest pain or ST-T changes. Myocardial injury with necrosis may result from recognizable peri-procedural events—alone or in combination—such as coronary dissection, occlusion of a major coronary artery or a side-branch, disruption of collateral flow, slow flow or no-reflow, distal embolization, and microvascular plugging. Embolization of intracoronary thrombus or atherosclerotic particulate debris may not be preventable, despite current anticoagulant and antiplatelet adjunctive therapy, aspiration or protection devices. Such events induce inflammation of the myocardium surrounding islets of myocardial necrosis.^[65] New areas of myocardial necrosis have been demonstrated by MRI following PCI.^[66]

The occurrence of procedure-related myocardial cell injury with necrosis can be detected by measurement of cardiac biomarkers before the procedure, repeated 3–6 h later and, optionally, further re-measurement 12 h thereafter. Increasing levels can only be interpreted as procedure-related myocardial injury if the pre-procedural cTn value is normal (<99th percentile URL) or if levels are stable or falling.^[67,68] In patients with normal pre-procedural values, elevation of cardiac biomarker values above the 99th percentile URL following PCI are indicative of procedure-related myocardial injury. In earlier studies, increased values of post-procedural cardiac biomarkers, especially CKMB, were associated with impaired outcome.^[69,70] However, when cTn concentrations are normal before PCI and become abnormal after the procedure, the threshold above the 99th percentile URL—whereby an adverse prognosis is evident—is not well defined^[71] and it is debatable whether such a threshold even exists.^[72] If a single baseline cTn value is elevated, it is impossible to determine whether further increases are due to the procedure or to the initial process causing the elevation. In this situation, it appears that the prognosis is largely determined by the pre-procedural cTn level.^[71] These relationships will probably become even more complex for the new high-sensitivity troponin assays.^[70]

In patients undergoing PCI with normal (<99th percentile URL) baseline cTn concentrations, elevations of cTn >5 × 99th percentile URL occurring within 48 h of the procedure—plus either (i) evidence of prolonged ischemia (>20 min) as demonstrated by prolonged chest pain, or (ii) ischemic ST changes or new pathological Q waves, or (iii) angiographic evidence of a flow limiting complication, such as of loss of patency of a side branch, persistent slow-flow or no-reflow, embolization, or (iv) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality—is defined as PCI-related MI (type 4a). This threshold of cTn values >5 × 99th percentile URL is arbitrarily chosen, based on clinical judgment and societal implications of the label of peri-procedural MI. When a cTn value is <5 × 99th percentile URL after PCI and the cTn value was normal before the PCI—or when the cTn value is >5 × 99th percentile URL in the absence of ischemic, angiographic or imaging findings—the term ‘myocardial injury’ should be used.

If the baseline cTn values are elevated and are stable or falling, then a rise of >20% is required for the diagnosis of a type 4a MI, as with reinfarction. Recent data suggest that, when PCI is delayed after MI until biomarker concentrations are falling or have normalized, and elevation of cardiac biomarker values then reoccurs, this may have some long-term significance. However, additional data are needed to confirm this finding.^[73]

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 (identified as 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 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.^[74] Occasionally, 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 section on clinical trials).

Diagnostic Criteria for Myocardial Infarction With CABG (MI Type 5)

During CABG, numerous factors can lead to periprocedural myocardial injury with necrosis. These include direct myocardial trauma from (i) suture placement or manipulation of the heart, (ii) coronary dissection, (iii) global or regional ischemia related to inadequate intra-operative cardiac protection, (iv) microvascular events related to reperfusion, (v) myocardial injury induced by oxygen free radical generation, or (vi) failure to reperfuse areas of the myocardium that are not subtended by graftable vessels.^[75–77] MRI studies suggest that most necrosis in this setting is not focal but diffuse and localized in the subendocardium.^[78]

In patients with normal values before surgery, any increase of cardiac biomarker values after CABG indicates myocardial necrosis, implying that an increasing magnitude of biomarker concentrations is likely to be related to an impaired outcome. This has been demonstrated in clinical studies employing CKMB, where elevations 5, 10 and 20 times the URL after CABG were associated with worsened prognosis; similarly, impaired outcome has been reported when cTn values were elevated to the highest quartile or quintile of the measurements.^[79–83] 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 addition, when the baseline cTn value is elevated (>99th percentile URL), higher levels of biomarker values are seen post-CABG. Therefore, biomarkers cannot stand alone in diagnosing MI in this setting. In view of the adverse impact on survival observed in patients with significant elevation of biomarker concentrations, this Task Force suggests, by arbitrary convention, that cTn values >10 x 99th percentile URL during the first 48 h following CABG, occurring from a normal baseline cTn value (<99th percentile URL). In addition, either (i) new pathological Q waves or new LBBB, or (ii) angiographically documented new graft or new native coronary artery occlusion, or (iii) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality, should be considered as diagnostic of a CABG-related MI (type 5). Cardiac biomarker release is considerably higher after valve replacement with CABG than with bypass surgery alone, and with on-pump CABG compared to off-pump CABG.^[84] The threshold described above is more robust for isolated on-pump CABG. As for PCI, the existing principles from the universal definition of MI should be applied for the definition of MI >48 h after surgery.

Assessment of MI in Patients Undergoing Other Cardiac Procedures

New ST-T abnormalities are common in patients who undergo cardiac surgery. When new pathological Q waves appear in different territories than 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 hemodynamic instability.

Novel procedures such as transcatheter aortic valve implantation (TAVI) or mitral clip may cause myocardial injury with necrosis, both by direct trauma to the myocardium and by creating regional ischemia from coronary obstruction or embolization. It is likely that, similarly to CABG, the more marked the elevation of the biomarker values, the worse the prognosis—but data on that are not available.

Modified criteria have been proposed for the diagnosis of periprocedural MI <72 h after aortic valve implantation.^[85] However, given that there is too little evidence, it appears reasonable to apply the same criteria for procedure-related MI as stated above for CABG.

Ablation of arrhythmias involves controlled myocardial injury with necrosis, by application of warming or cooling of the tissue. The extent of the injury with necrosis can be assessed by cTn measurement: however, an elevation of cTn values in this context should not be labeled as MI.

Myocardial Infarction Associated With Non-cardiac Procedures

Perioperative MI is the most common major perioperative vascular complication in major non-cardiac surgery, and is associated with a poor prognosis.^[86,87] Most patients who have a perioperative MI will not experience ischemic symptoms. Nevertheless, asymptomatic perioperative MI is as strongly associated with 30-day mortality, as is symptomatic MI.^[86] Routine monitoring of cardiac biomarkers in high-risk patients, both prior to and 48–72 h after major surgery, is therefore recommended. Measurement of high-sensitivity cTn in post-operative samples reveals that 45% of patients have levels above the 99th percentile URL and 22% have an elevation and a rising pattern of values indicative of evolving myocardial necrosis.^[88] Studies of patients undergoing major non-cardiac surgery strongly support the idea that many of the infarctions diagnosed in this context are caused by a prolonged imbalance between myocardial oxygen supply and demand, against a background of CAD.^[89,90] Together with a rise and/or fall of cTn values, this 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,^[91] that is to say, MI type 1. Given the differences that probably exist in the therapeutic approaches to each, close clinical scrutiny and judgment is needed.

Myocardial Infarction in the Intensive Care Unit

Elevations of cTn values are common in patients in the intensive care unit and are associated with adverse prognosis, regardless of the underlying disease state.^[92,93] Some elevations may reflect MI type 2 due to underlying CAD and increased myocardial oxygen demand.^[94] Other patients may have elevated values of cardiac biomarkers, due to myocardial injury with necrosis induced by catecholamine or direct toxic effect from circulating toxins. Moreover, in some patients, MI type 1 may occur. It is often a challenge for the clinician, caring for a critically ill patient with severe single organ or multi-organ 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 judgment should be employed to decide whether—and to what extent—further evaluation for CAD or structural heart disease is indicated.^[95]

Recurrent Myocardial Infarction

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

Reinfarction

The term ‘reinfarction’ is used for an acute MI that occurs within 28 days of an incident or recurrent MI.^[3] The ECG diagnosis of suspected reinfarction following the initial MI may be confounded by the initial evolutionary ECG changes. Reinfarction should be considered when ST elevation >0.1 mV recurs, or new pathognomonic Q waves appear, in at least two contiguous leads, particularly when associated with ischemic 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 workup. ST depression or LBBB alone are non-specific findings and should not be used to diagnose reinfarction.

In patients in whom 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 h 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 new acute MI apply.

Myocardial Injury or Infarction Associated With Heart Failure

Depending on the assay used, detectable-to-clearly elevated cTn values, indicative of myocardial injury with necrosis, may be seen in patients with HF syndrome.^[96] Using high-sensitivity cTn assays, measurable cTn concentrations may be present in nearly all patients with HF, with a significant percentage exceeding the 99th percentile URL, particularly in those with more severe HF syndrome, such as in acutely decompensated HF.^[97]

Whilst MI type 1 is an important cause of acutely decompensated HF—and should always be considered in the context of an acute presentation—elevated cTn values alone, in a patient with HF syndrome, do not establish the diagnosis of MI type 1 and may, indeed, be seen in those with non-ischemic HF. Beyond MI type 1, multiple mechanisms have been invoked to explain measurable-to-pathologically elevated cTn concentrations in patients with HF.^[96,97] For example, MI type 2 may result from increased transmural pressure, small-vessel coronary obstruction, endothelial dysfunction, anemia or hypotension. Besides MI type 1 or 2, cardiomyocyte apoptosis and autophagy due to wall stretch has been experimentally demonstrated. Direct cellular toxicity related to inflammation, circulating neurohormones, infiltrative processes, as well as myocarditis and stress cardiomyopathy, may present with HF and abnormal cTn measurement.^[97]

Whilst prevalent and complicating the diagnosis of MI, the presence, magnitude and persistence of cTn elevation in HF is increasingly accepted to be an independent predictor of adverse outcomes in both acute and chronic HF syndrome, irrespective of mechanism, and should not be discarded as ‘false positive’.^[97,98]

In the context of an acutely decompensated HF presentation, cTn I or T should always be promptly measured and ECG recorded, with the goal of identifying or excluding MI type 1 as the precipitant. In this setting, elevated cTn values should be interpreted with a high level of suspicion for MI type 1 if a significant rise and/or fall of the marker are seen, or if it is accompanied by ischemic symptoms, new ischemic ECG changes or loss of myocardial function on non-invasive testing. Coronary artery anatomy may often be well-known; such knowledge may be used to interpret abnormal troponin results. If normal coronary arteries are present, either a type 2 MI or a non-coronary mechanism for troponin release may be invoked.^[97]

On the other hand, when coronary anatomy is not established, the recognition of a cTn value in excess of the 99th percentile URL alone is not sufficient to make a diagnosis of acute MI due to CAD, nor is it able to identify the mechanism for the abnormal cTn value. In this setting, further information, such as myocardial perfusion studies, coronary angiography, or MRI is often required to better understand the cause of the abnormal cTn measurement. However, it may be difficult to establish the reason for cTn abnormalities, even after such investigations.^[96,97]