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Definitions of acute coronary syndromes
ISCHAEMIC HEART DISEASE
Definitions of acute coronary syndromes
What’s new? C
Emily J Cantor C
Ajay K Jain Charles Knight
C
Abstract
C
The recently published third universal definition of myocardial infarction (MI) reiterates the importance of troponins as a pivotal measure in the diagnosis of MI. This importance is based on the sensitivity and specificity of the troponins and their known correlation with the outcome of acute coronary syndromes. A raised serum concentration of troponin is known to be related to a worse prognosis, including death and recurrent cardiac events. The universal definition, first published in 2007, introduces sub-types of MI, based on the differing pathological processes that can lead to myocardial necrosis. Although this definition has yet to be adopted worldwide, it has already resulted in the diagnosis of MI being made in greater numbers of patients, with important implications for work, insurance, and lifestyle. However, it is likely that this ‘new’ group of patients will receive therapy with treatments known to improve prognosis. In this paper, we describe the implications of the universal definition of MI in the context of diagnosis, investigation, treatment and prognosis.
C
C
The diagnosis of MI has major emotional, psychological and financial implications for the individual. It excludes other potentially treatable causes of chest pain that may mimic acute ST-elevation MI. The first definition of MI, produced by the World Health Organization in 1979,1 required two of three features, including symptoms consistent with myocardial ischaemia, ECG evidence of ST-segment elevation, and a rise in cardiac enzymes. This was used until the year 2000, when the American College of Cardiology (ACC) and the European Society of Cardiology (ESC) published a new version, in which the role of biomarkers had changed significantly, such that a rise in cardiac troponin became pivotal to the diagnosis of acute (evolving) MI, in concert with other ‘minor’ criteria. In conjunction with the American Heart Association and World Heart Foundation, the ACC and ESC subsequently expanded this second definition to include clinical, biochemical, electrocardiographic, imaging and pathological findings, presented in a consensus document (‘The universal definition of myocardial infarction’).2 With the evolution of more sensitive assays for markers of necrosis and revised definition of myocardial necrosis, the definition has since been modified further by a third global MI task force, consisting of the same groups, to produce ‘The third universal definition of myocardial infarction’, published in 2012 (Table 1).3 The universal definition introduced the concept that there is heterogeneity of causation in patients with acute MI, with classification into five types, the details of which have been further refined in the third definition (Table 2).3 The most common cause is a spontaneous event related to plaque rupture, fissuring, erosion or dissection of an atherosclerotic plaque, the so-called type 1 myocardial infarction. An alternative mechanism (type 2 myocardial infarction) results from an imbalance of myocardial oxygen demand and supply caused by anaemia, arrhythmia, hypertension or hypotension. Vasoconstriction or arterial spasm, causing a marked reduction in myocardial blood flow, can also lead to similar effects. In type 3 myocardial infarction, the patient
Keywords Acute coronary syndrome; cardiac troponin; myocardial infarction
Myocardial infarction (MI) is a common presentation of unstable coronary artery disease, and the cause of considerable morbidity and mortality worldwide. The clinical spectrum may include ‘silent’ events through to sudden death as a result of catastrophic cardiac dysfunction. MI may be the first presentation of coronary artery disease but, on the other hand, patients with coronary artery disease may have multiple silent MIs with progressive deterioration of cardiac function. Accurate diagnosis is important for several reasons: It fosters more accurate estimates of the prevalence and incidence of MI. The incidence of MI is a marker of the prevalence of coronary artery disease in a given population. It allows accurate research, since MI is a major clinical end-point in many studies investigating the role of therapies for the treatment of coronary artery disease.
Emily J Cantor MBChB MRCP is a Clinical Research Registrar at Barts Health, London, UK. Competing interests: none declared. Ajay K Jain BSc MRCP MD is a Consultant Cardiologist at Barts Health, London, UK. Competing interests: none declared. Charles Knight MD FRCP FESC is Director of the Cardiovascular Clinical Academic Unit at Barts Health, London, UK. Competing interests: none declared.
MEDICINE 42:9
The universal definition of myocardial infarction (MI) introduces five sub-types, categorized according to pathophysiology The use of highly sensitive cardiac troponin assays will increase the number of patients diagnosed with MI For the sake of immediate treatment strategies we should continue to use a clinical classification of acute coronary syndromes based on patient symptoms and ECG findings The universal definition will reclassify many patients as having had an MI, in whom a diagnosis of unstable angina would previously have been made Patients who have an MI according to the new definition (but acute coronary syndrome according to the old definition) have a worse prognosis, which may be improved by appropriate early investigation and therapies The new definition of MI may bias outcome in research/epidemiological studies and interpretation of results will need to take this into consideration
502
Ó 2014 Elsevier Ltd. All rights reserved.
ISCHAEMIC HEART DISEASE
Criteria for acute myocardial infarction C
C
C
C
C
Detection of a rise and/or fall of cardiac biomarkers (preferably troponin (cTn)) with at least one value above the 99th percentile of the upper reference limit (URL) together with evidence of myocardial ischaemia (at least one of the following): Symptoms of ischaemia New or presumed new significant ST-segmenteT wave (STeT) changes or new left bundle branch block (LBBB) Development of pathological Q waves in the ECG Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality Identification of an intracoronary thrombus by angiography or autopsy Cardiac death with symptoms suggestive of myocardial ischaemia and presumed new ischaemic ECG changes or new LBBB, but death occurred before blood samples could be obtained or before cardiac biomarker values would be increased Percutaneous intervention (PCI)-related MI is arbitrarily defined by elevation of cTn values (>5 99th percentile URL) in patients with normal baseline values (99th percentile URL) or a rise of cTn values >20% if the baseline values are elevated and are stable or falling. In addition, either (i) symptoms suggestive of myocardial ischaemia or (ii) new ischaemic ECG changes or (iii) angiographic changes consistent with a procedural complication or (iv) imaging demonstrating new loss of viable myocardium or new regional wall motion abnormality are required Stent thrombosis associated with MI detected by coronary angiography or autopsy in the setting of myocardial ischaemia and a rise and/or fall of cardiac biomarker values with at least one value above the 99th percentile URL Coronary artery bypass grafting (CABG)-related MI is arbitrarily defined by elevation of cardiac biomarkers (>10 99th percentile URL) in patients with normal baseline cTn values (99th percentile URL). In addition, either (i) new pathological Q waves or new LBBB, or (ii) angiographic documented new graft or native coronary artery occlusion, or (iii) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality
Adapted from Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Circulation 2012; 126: 2020e2035.
Table 1
The degree of ST-elevation is age and sex dependent.3 Acute or evolving changes in the STeT waveforms can be of great value in locating the responsible artery, the timing of the event and as an estimate of the proportion of myocardium at risk. Where biomarker values are raised but there is no ST-segment elevation at presentation, patients are said to have had a non-ST elevation MI (NSTEMI). In these patients new ST depression or T-wave changes may occur, or alternatively the ECG can be normal. It is important to interpret ECGs within the clinical context and where possible compare them to previous ECGs as ST deviation can be observed in other conditions, including left ventricular hypertrophy, Brugada syndrome, acute pericarditis and early repolarization. Patients without elevated biomarker values and symptoms at rest are labelled as having unstable angina (UA). These definitions remain helpful for guiding pharmacological and interventional management and immediate clinical care.
with a typical presentation for myocardial ischaemia/infarction dies before it is possible to detect biomarker elevation and biomarkers are of no value. Two types of type 4 myocardial infarction have been described: type 4a, where serum troponin rises following percutaneous coronary intervention (PCI); and type 4b, which relates to acute stent thrombosis. Finally, critical elevation of troponin in association with coronary artery bypass surgery is known as type 5 myocardial infarction.3
Clinical classification of myocardial ischaemia The new universal definition has stressed the ongoing use of the clinical classification of acute coronary syndromes when planning immediate treatment strategy (i.e. revascularization). In a clinical setting myocardial ischaemia can normally be identified by a patient’s history, ECG findings and highly sensitive cardiac biomarkers. Through rapid ECG interpretation we can clinically classify acute coronary syndromes (ACS) and then manage them accordingly. Patients presenting with cardiac-sounding chest pain or other ischaemic symptoms who have persistent STsegment elevation in two or more contiguous leads are designated as having a ‘ST-elevation myocardial infarction’ (STEMI).
Implications of the new definition Use of the universal definition has important clinical implications for the diagnosis, investigation and treatment of patients with
Clinical classification of different types of myocardial infarction C C C
C C
Type 1 e spontaneous myocardial infarction related to ischaemia caused by a primary coronary event, such as plaque fissuring or rupture Type 2 e myocardial infarction secondary to ischaemia resulting from an imbalance between oxygen supply and demand Type 3 e sudden death from cardiac disease with symptoms of myocardial ischaemia, accompanied by new ST-elevation or left bundle branch block, or verified coronary thrombus at angiography and/or autopsy Type 4 e myocardial infarction associated with percutaneous coronary intervention Type 5 e myocardial infarction associated with coronary artery bypass grafting
Table 2
MEDICINE 42:9
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Ó 2014 Elsevier Ltd. All rights reserved.
ISCHAEMIC HEART DISEASE
and are stable or falling. The defined extent of troponin elevation for diagnosis was raised from the 2007 definition of >3 times URL after studies demonstrated that this lesser degree of elevation was of no prognostic significance.11,12 A similar revision has been necessary in type 5 MI, for which the diagnostic reference value has been doubled to >10 times URL. Clearly, the care of patients should not be simplified to categorization of the presence or absence of an MI. Other important features with important clinical implications include the size of the infarct, residual left ventricular function and the presence and severity of ‘bystander’ coronary artery disease. The cumulative impact of these and numerous other factors should be explained to the patient when discussing prognosis and lifestyle modifications, to guide decisions involving employment, family and other social circumstances. A
acute coronary syndromes and with raised cardiac troponin for other reasons. What have not been clearly defined are the implications for prognosis, particularly in the group of patients in whom the diagnosis moves from unstable angina to MI. The universal definition increases the number of patients in whom MI is diagnosed, with important resource implications for healthcare systems. Indeed, it has been shown that retrospective application of the definition to patients admitted to a coronary care unit with an acute coronary syndrome increased the incidence of MI by 58%. Extrapolated, this would equate to approximately 160,000 additional MI diagnoses per year in the United Kingdom.4 The impact has also been investigated in the setting of acute unselected patients presenting with chest pain and an abnormal (but non-diagnostic) ECG, in whom the diagnosis of MI increased from 29% to 37.5% following application of the universal definition.5 Use of the universal definition has also been shown to influence prognosis in a large cohort of patients presenting with non-ST-elevation acute coronary syndrome treated with early invasive therapy.6 Classification of 1024 consecutive patients with non-ST-segment elevation acute coronary syndrome into three groups (‘unstable angina’; myocardial infarction according to the previous WHO definition; and myocardial infarction additionally identified by the universal definition) demonstrated 3-year mortality rates of 5.6%, 9.1%, and 17.5%, respectively ( p < 0.001). Evidently, patients meeting the universal definition require further investigation and observation to determine whether changing their management will improve prognosis. Increased diagnosis of MI will increase the number of patients requiring secondary prevention and consequent increased cost associated with not only the medication itself (estimated in the UK in 2010 to be >£700 in the first year alone) but also its adverse effects, such as major bleeding (3.7% per annum or more).7 Will use of the universal definition lead to over-diagnosis of MI? Patients presenting with chest pain, a troponin rise and an abnormal ECG may have a wide variety of diagnoses, including heart muscle disease, myocarditis, pulmonary embolism, cardiac arrhythmia and coronary artery spasm.8 It has been suggested that the sensitive assessment of cardiac troponin may lead to over-diagnosis in patients with small increases in troponin and an abnormal (but not necessarily ‘ischaemic’) ECG.9 Troponin may also be elevated in patients with a variety of chronic conditions, such as left ventricular hypertrophy, heart failure, chronic kidney disease and stable coronary artery disease.10 It has long been recognized that there may be a transient increase in cardiac biomarkers following PCI. Traditionally, an elevation of CK-MB >5 times the upper reference limit (URL) has been called ‘peri-procedural myocardial infarction’, with the importance of elevations of lesser magnitude still not fully understood. A raised troponin from a normal baseline value is a common finding following PCI. Peri-procedural MI is now clearly described in the revised universal definition as type 4 MI and characterized by a troponin rise of five times URL in patients with a normal baseline or >20% if baseline values are elevated
MEDICINE 42:9
REFERENCES 1 Nomenclature and criteria for diagnosis of ischemic heart disease. Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Circulation 1979; 59: 607e9. 2 Thygesen K, Alpert JS, White HD. Universal definition of myocardial infarction. Eur Heart J 2007; 28: 2525e38. 3 Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Circulation 2012; 126: 2020e35. 4 Pell JP, Simpson E, Rodger JC, et al. Impact of changing diagnostic criteria on incidence, management, and outcome of acute myocardial infarction: retrospective cohort study. BMJ 2003; 326: 134e5. 5 Ferguson JL, Beckett GJ, Stoddart M, et al. Myocardial infarction redefined: the new ACC/ESC definition, based on cardiac troponin, increases the apparent incidence of infarction. Heart 2002; 88: 343e7. 6 Hochholzer W, Buettner HJ, Trenk D, et al. New definition of myocardial infarction: impact on long-term mortality. Am J Med 2008; 121: 399e405. 7 Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST segment elevation. N Engl J Med 2001; 345: 494e502. 8 Jeremias A, Gibson CM. Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded. Ann Intern Med 2005; 142: 786e91. 9 Eggers KM, Lind L, Venge P, et al. Will the universal definition of myocardial infarction criteria result in an overdiagnosis of myocardial infarction? Am J Cardiol 2009; 103: 588e91. 10 Korff S, Katus HA, Giannitsis E. Differential diagnosis of elevated troponins. Heart 2006; 92: 987e93. 11 Pervaiz MH, Sood P, Sudhir K. Periprocedural myocardial infarction in a randomized trial of everolimus-eluting and paclitaxel-eluting coronary stents: frequency and impact on mortality according to historic versus universal definitions. Circ Cardiovasc Interv 2012; 5: 150e6. 12 White HD. The prequel: defining prognostically important criteria in the peri-procedural PCI troponin saga. Circ Cardiovasc Interv 2012; 5: 142e5.
504
Ó 2014 Elsevier Ltd. All rights reserved.
Definitions of acute coronary syndromes
What’s new? C
Emily J Cantor C
Ajay K Jain Charles Knight
C
Abstract
C
The recently published third universal definition of myocardial infarction (MI) reiterates the importance of troponins as a pivotal measure in the diagnosis of MI. This importance is based on the sensitivity and specificity of the troponins and their known correlation with the outcome of acute coronary syndromes. A raised serum concentration of troponin is known to be related to a worse prognosis, including death and recurrent cardiac events. The universal definition, first published in 2007, introduces sub-types of MI, based on the differing pathological processes that can lead to myocardial necrosis. Although this definition has yet to be adopted worldwide, it has already resulted in the diagnosis of MI being made in greater numbers of patients, with important implications for work, insurance, and lifestyle. However, it is likely that this ‘new’ group of patients will receive therapy with treatments known to improve prognosis. In this paper, we describe the implications of the universal definition of MI in the context of diagnosis, investigation, treatment and prognosis.
C
C
The diagnosis of MI has major emotional, psychological and financial implications for the individual. It excludes other potentially treatable causes of chest pain that may mimic acute ST-elevation MI. The first definition of MI, produced by the World Health Organization in 1979,1 required two of three features, including symptoms consistent with myocardial ischaemia, ECG evidence of ST-segment elevation, and a rise in cardiac enzymes. This was used until the year 2000, when the American College of Cardiology (ACC) and the European Society of Cardiology (ESC) published a new version, in which the role of biomarkers had changed significantly, such that a rise in cardiac troponin became pivotal to the diagnosis of acute (evolving) MI, in concert with other ‘minor’ criteria. In conjunction with the American Heart Association and World Heart Foundation, the ACC and ESC subsequently expanded this second definition to include clinical, biochemical, electrocardiographic, imaging and pathological findings, presented in a consensus document (‘The universal definition of myocardial infarction’).2 With the evolution of more sensitive assays for markers of necrosis and revised definition of myocardial necrosis, the definition has since been modified further by a third global MI task force, consisting of the same groups, to produce ‘The third universal definition of myocardial infarction’, published in 2012 (Table 1).3 The universal definition introduced the concept that there is heterogeneity of causation in patients with acute MI, with classification into five types, the details of which have been further refined in the third definition (Table 2).3 The most common cause is a spontaneous event related to plaque rupture, fissuring, erosion or dissection of an atherosclerotic plaque, the so-called type 1 myocardial infarction. An alternative mechanism (type 2 myocardial infarction) results from an imbalance of myocardial oxygen demand and supply caused by anaemia, arrhythmia, hypertension or hypotension. Vasoconstriction or arterial spasm, causing a marked reduction in myocardial blood flow, can also lead to similar effects. In type 3 myocardial infarction, the patient
Keywords Acute coronary syndrome; cardiac troponin; myocardial infarction
Myocardial infarction (MI) is a common presentation of unstable coronary artery disease, and the cause of considerable morbidity and mortality worldwide. The clinical spectrum may include ‘silent’ events through to sudden death as a result of catastrophic cardiac dysfunction. MI may be the first presentation of coronary artery disease but, on the other hand, patients with coronary artery disease may have multiple silent MIs with progressive deterioration of cardiac function. Accurate diagnosis is important for several reasons: It fosters more accurate estimates of the prevalence and incidence of MI. The incidence of MI is a marker of the prevalence of coronary artery disease in a given population. It allows accurate research, since MI is a major clinical end-point in many studies investigating the role of therapies for the treatment of coronary artery disease.
Emily J Cantor MBChB MRCP is a Clinical Research Registrar at Barts Health, London, UK. Competing interests: none declared. Ajay K Jain BSc MRCP MD is a Consultant Cardiologist at Barts Health, London, UK. Competing interests: none declared. Charles Knight MD FRCP FESC is Director of the Cardiovascular Clinical Academic Unit at Barts Health, London, UK. Competing interests: none declared.
MEDICINE 42:9
The universal definition of myocardial infarction (MI) introduces five sub-types, categorized according to pathophysiology The use of highly sensitive cardiac troponin assays will increase the number of patients diagnosed with MI For the sake of immediate treatment strategies we should continue to use a clinical classification of acute coronary syndromes based on patient symptoms and ECG findings The universal definition will reclassify many patients as having had an MI, in whom a diagnosis of unstable angina would previously have been made Patients who have an MI according to the new definition (but acute coronary syndrome according to the old definition) have a worse prognosis, which may be improved by appropriate early investigation and therapies The new definition of MI may bias outcome in research/epidemiological studies and interpretation of results will need to take this into consideration
502
Ó 2014 Elsevier Ltd. All rights reserved.
ISCHAEMIC HEART DISEASE
Criteria for acute myocardial infarction C
C
C
C
C
Detection of a rise and/or fall of cardiac biomarkers (preferably troponin (cTn)) with at least one value above the 99th percentile of the upper reference limit (URL) together with evidence of myocardial ischaemia (at least one of the following): Symptoms of ischaemia New or presumed new significant ST-segmenteT wave (STeT) changes or new left bundle branch block (LBBB) Development of pathological Q waves in the ECG Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality Identification of an intracoronary thrombus by angiography or autopsy Cardiac death with symptoms suggestive of myocardial ischaemia and presumed new ischaemic ECG changes or new LBBB, but death occurred before blood samples could be obtained or before cardiac biomarker values would be increased Percutaneous intervention (PCI)-related MI is arbitrarily defined by elevation of cTn values (>5 99th percentile URL) in patients with normal baseline values (99th percentile URL) or a rise of cTn values >20% if the baseline values are elevated and are stable or falling. In addition, either (i) symptoms suggestive of myocardial ischaemia or (ii) new ischaemic ECG changes or (iii) angiographic changes consistent with a procedural complication or (iv) imaging demonstrating new loss of viable myocardium or new regional wall motion abnormality are required Stent thrombosis associated with MI detected by coronary angiography or autopsy in the setting of myocardial ischaemia and a rise and/or fall of cardiac biomarker values with at least one value above the 99th percentile URL Coronary artery bypass grafting (CABG)-related MI is arbitrarily defined by elevation of cardiac biomarkers (>10 99th percentile URL) in patients with normal baseline cTn values (99th percentile URL). In addition, either (i) new pathological Q waves or new LBBB, or (ii) angiographic documented new graft or native coronary artery occlusion, or (iii) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality
Adapted from Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Circulation 2012; 126: 2020e2035.
Table 1
The degree of ST-elevation is age and sex dependent.3 Acute or evolving changes in the STeT waveforms can be of great value in locating the responsible artery, the timing of the event and as an estimate of the proportion of myocardium at risk. Where biomarker values are raised but there is no ST-segment elevation at presentation, patients are said to have had a non-ST elevation MI (NSTEMI). In these patients new ST depression or T-wave changes may occur, or alternatively the ECG can be normal. It is important to interpret ECGs within the clinical context and where possible compare them to previous ECGs as ST deviation can be observed in other conditions, including left ventricular hypertrophy, Brugada syndrome, acute pericarditis and early repolarization. Patients without elevated biomarker values and symptoms at rest are labelled as having unstable angina (UA). These definitions remain helpful for guiding pharmacological and interventional management and immediate clinical care.
with a typical presentation for myocardial ischaemia/infarction dies before it is possible to detect biomarker elevation and biomarkers are of no value. Two types of type 4 myocardial infarction have been described: type 4a, where serum troponin rises following percutaneous coronary intervention (PCI); and type 4b, which relates to acute stent thrombosis. Finally, critical elevation of troponin in association with coronary artery bypass surgery is known as type 5 myocardial infarction.3
Clinical classification of myocardial ischaemia The new universal definition has stressed the ongoing use of the clinical classification of acute coronary syndromes when planning immediate treatment strategy (i.e. revascularization). In a clinical setting myocardial ischaemia can normally be identified by a patient’s history, ECG findings and highly sensitive cardiac biomarkers. Through rapid ECG interpretation we can clinically classify acute coronary syndromes (ACS) and then manage them accordingly. Patients presenting with cardiac-sounding chest pain or other ischaemic symptoms who have persistent STsegment elevation in two or more contiguous leads are designated as having a ‘ST-elevation myocardial infarction’ (STEMI).
Implications of the new definition Use of the universal definition has important clinical implications for the diagnosis, investigation and treatment of patients with
Clinical classification of different types of myocardial infarction C C C
C C
Type 1 e spontaneous myocardial infarction related to ischaemia caused by a primary coronary event, such as plaque fissuring or rupture Type 2 e myocardial infarction secondary to ischaemia resulting from an imbalance between oxygen supply and demand Type 3 e sudden death from cardiac disease with symptoms of myocardial ischaemia, accompanied by new ST-elevation or left bundle branch block, or verified coronary thrombus at angiography and/or autopsy Type 4 e myocardial infarction associated with percutaneous coronary intervention Type 5 e myocardial infarction associated with coronary artery bypass grafting
Table 2
MEDICINE 42:9
503
Ó 2014 Elsevier Ltd. All rights reserved.
ISCHAEMIC HEART DISEASE
and are stable or falling. The defined extent of troponin elevation for diagnosis was raised from the 2007 definition of >3 times URL after studies demonstrated that this lesser degree of elevation was of no prognostic significance.11,12 A similar revision has been necessary in type 5 MI, for which the diagnostic reference value has been doubled to >10 times URL. Clearly, the care of patients should not be simplified to categorization of the presence or absence of an MI. Other important features with important clinical implications include the size of the infarct, residual left ventricular function and the presence and severity of ‘bystander’ coronary artery disease. The cumulative impact of these and numerous other factors should be explained to the patient when discussing prognosis and lifestyle modifications, to guide decisions involving employment, family and other social circumstances. A
acute coronary syndromes and with raised cardiac troponin for other reasons. What have not been clearly defined are the implications for prognosis, particularly in the group of patients in whom the diagnosis moves from unstable angina to MI. The universal definition increases the number of patients in whom MI is diagnosed, with important resource implications for healthcare systems. Indeed, it has been shown that retrospective application of the definition to patients admitted to a coronary care unit with an acute coronary syndrome increased the incidence of MI by 58%. Extrapolated, this would equate to approximately 160,000 additional MI diagnoses per year in the United Kingdom.4 The impact has also been investigated in the setting of acute unselected patients presenting with chest pain and an abnormal (but non-diagnostic) ECG, in whom the diagnosis of MI increased from 29% to 37.5% following application of the universal definition.5 Use of the universal definition has also been shown to influence prognosis in a large cohort of patients presenting with non-ST-elevation acute coronary syndrome treated with early invasive therapy.6 Classification of 1024 consecutive patients with non-ST-segment elevation acute coronary syndrome into three groups (‘unstable angina’; myocardial infarction according to the previous WHO definition; and myocardial infarction additionally identified by the universal definition) demonstrated 3-year mortality rates of 5.6%, 9.1%, and 17.5%, respectively ( p < 0.001). Evidently, patients meeting the universal definition require further investigation and observation to determine whether changing their management will improve prognosis. Increased diagnosis of MI will increase the number of patients requiring secondary prevention and consequent increased cost associated with not only the medication itself (estimated in the UK in 2010 to be >£700 in the first year alone) but also its adverse effects, such as major bleeding (3.7% per annum or more).7 Will use of the universal definition lead to over-diagnosis of MI? Patients presenting with chest pain, a troponin rise and an abnormal ECG may have a wide variety of diagnoses, including heart muscle disease, myocarditis, pulmonary embolism, cardiac arrhythmia and coronary artery spasm.8 It has been suggested that the sensitive assessment of cardiac troponin may lead to over-diagnosis in patients with small increases in troponin and an abnormal (but not necessarily ‘ischaemic’) ECG.9 Troponin may also be elevated in patients with a variety of chronic conditions, such as left ventricular hypertrophy, heart failure, chronic kidney disease and stable coronary artery disease.10 It has long been recognized that there may be a transient increase in cardiac biomarkers following PCI. Traditionally, an elevation of CK-MB >5 times the upper reference limit (URL) has been called ‘peri-procedural myocardial infarction’, with the importance of elevations of lesser magnitude still not fully understood. A raised troponin from a normal baseline value is a common finding following PCI. Peri-procedural MI is now clearly described in the revised universal definition as type 4 MI and characterized by a troponin rise of five times URL in patients with a normal baseline or >20% if baseline values are elevated
MEDICINE 42:9
REFERENCES 1 Nomenclature and criteria for diagnosis of ischemic heart disease. Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Circulation 1979; 59: 607e9. 2 Thygesen K, Alpert JS, White HD. Universal definition of myocardial infarction. Eur Heart J 2007; 28: 2525e38. 3 Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Circulation 2012; 126: 2020e35. 4 Pell JP, Simpson E, Rodger JC, et al. Impact of changing diagnostic criteria on incidence, management, and outcome of acute myocardial infarction: retrospective cohort study. BMJ 2003; 326: 134e5. 5 Ferguson JL, Beckett GJ, Stoddart M, et al. Myocardial infarction redefined: the new ACC/ESC definition, based on cardiac troponin, increases the apparent incidence of infarction. Heart 2002; 88: 343e7. 6 Hochholzer W, Buettner HJ, Trenk D, et al. New definition of myocardial infarction: impact on long-term mortality. Am J Med 2008; 121: 399e405. 7 Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST segment elevation. N Engl J Med 2001; 345: 494e502. 8 Jeremias A, Gibson CM. Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded. Ann Intern Med 2005; 142: 786e91. 9 Eggers KM, Lind L, Venge P, et al. Will the universal definition of myocardial infarction criteria result in an overdiagnosis of myocardial infarction? Am J Cardiol 2009; 103: 588e91. 10 Korff S, Katus HA, Giannitsis E. Differential diagnosis of elevated troponins. Heart 2006; 92: 987e93. 11 Pervaiz MH, Sood P, Sudhir K. Periprocedural myocardial infarction in a randomized trial of everolimus-eluting and paclitaxel-eluting coronary stents: frequency and impact on mortality according to historic versus universal definitions. Circ Cardiovasc Interv 2012; 5: 150e6. 12 White HD. The prequel: defining prognostically important criteria in the peri-procedural PCI troponin saga. Circ Cardiovasc Interv 2012; 5: 142e5.
504
Ó 2014 Elsevier Ltd. All rights reserved.