2016/04/28 by Stefan Agewall, John F. Beltrame, Harmony R. Reynolds +11 · 896 citations
Medicine · #Acute Myocardial Infarction Research #Cardiac Imaging and Diagnostics #Cardiac electrophysiology and arrhythmias #Medicine #Cardiology #Internal medicine #Myocardial infarction #Coronary artery disease #Chest pain #Angiography #Troponin #Coronary arteries #Coronary angiography #Acute coronary syndrome #Artery
paper · pdf · doi:10.1093/eurheartj/ehw149
published in European Heart Journal 38(3), ehw149 (Oxford University Press)
openalex publication_date 2016/04/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/08
The management of acute myocardial infarction (AMI)1 has evolved over the past century and particularly in the past 50 years. Important milestones include the development of the electrocardiogram, coronary care units, coronary angiography, reperfusion therapies, and troponin assays. These innovations are the foundation of contemporary AMI management strategies that include a diagnosis centred on elevated troponin values associated with corroborative clinical evidence,1 early use of coronary angiography, and reperfusion therapies.2–4 Pivotal in the evolution of these contemporary strategies were the early AMI coronary angiography studies undertaken by DeWood et al. These pioneering studies demonstrated that, in patients presenting with ST elevation myocardial infarction (STEMI), almost 90% had an occluded coronary artery provided that angiography was undertaken within 4 h of chest pain onset.5 In contrast, in AMI patients who did not present with ST elevation (non-ST elevation myocardial infarction or NSTEMI), only 26% had an occluded coronary artery when angiography was performed within 24 h of symptom onset.6 In both of these landmark studies,5,6 >90% of the acute MI patients had angiographic evidence of obstructive coronary artery disease (CAD), underscoring the importance of the atherosclerotic process in the pathogenesis of AMI. Although DeWood's studies underscore the importance of obstructive CAD in AMI, it is fascinating that ∼10% had no significant CAD on coronary angiography. This is confirmed in several large AMI registries7–9 where 1–13% of AMI's occurred in the absence of obstructive CAD thereby eliciting an important set of questions—what is the mechanism of the myocardial damage in these patients? Do these patients differ from those with obstructive CAD? Should they be managed with the same clinical strategies? Do patients with non-obstructive atherosclerosis differ in pathophysiology and outcomes from those with angiographically normal coronary arteries? These and other issues have prompted clinical researchers to coin the term myocardial infarction with non-obstructive coronary arteries (MINOCA). This position paper is the first authoritative international expert opinion regarding this intriguing condition. We seek to define MINOCA, describe its associated clinical features and mechanisms, detail an assessment pathway for its evaluation, as well as stimulate research into its mechanisms and treatment.10 As the name implies, the formulation of the MINOCA diagnosis requires both clinical documentation of an AMI and demonstration of non-obstructive coronary arteries (Table 1). Accordingly, the diagnosis is made following coronary angiography in the evaluation of a clinical presentation consistent with AMI. It should be noted that the Universal Definition of Myocardial Infarction specifies that the combination of symptoms and a positive cardiac biomarker in the appropriate clinical scenario is diagnostic of AMI. Therefore, if there is no clinically apparent alternative diagnosis, such as myocarditis or pulmonary embolism, the diagnosis of MINOCA is applicable. The rationale for establishing MINOCA as a clinical diagnosis includes: (i) providing a common nomenclature for this group of patients who are often overlooked in contemporary clinical practice, (ii) encouraging routine evaluation for underlying causes in these patients, and (iii) stimulating further studies into its responsible mechanisms, outcomes, and most appropriate management strategies. Myocardial infarction with non-obstructive coronary arteries should be considered as a ‘working diagnosis’, analogous to heart failure, and thus prompts further evaluation regarding its underlying mechanism(s). Diagnostic criteria for myocardial infarction with non-obstructive coronary arteries AMI criteria.1 (a) Positive cardiac biomarker (preferably cardiac troponin) defined as a rise and/or fall in serial levels, with at least one value above the 99th percentile upper reference limit. (b) Corroborative clinical evidence of infarction evidenced by at least one of the following: Symptoms of ischaemia New or presumed new significant ST-T changes or new LBBB Development of pathological Q waves Imaging evidence of new loss of viable myocardium or new RWMA Intracoronary thrombus evident on angiography or at autopsy Non-obstructive coronary arteries on angiography: Defined as the absence of obstructive CAD on angiography, (i.e. no coronary artery stenosis ≥50%), in any potential infarct-related artery. This includes both patients with: o normal coronary arteries (no stenosis >30%) o mild coronary atheromatosis (stenosis >30% but <50%). No clinically overt specific cause for the acute presentation: At the time of angiography, the cause and thus a specific diagnosis for the clinical presentation is not apparent. Accordingly, there is a necessity to further evaluate the patient for the underlying cause of the MINOCA presentation. AMI criteria.1 (a) Positive cardiac biomarker (preferably cardiac troponin) defined as a rise and/or fall in serial levels, with at least one value above the 99th percentile upper reference limit. (b) Corroborative clinical evidence of infarction evidenced by at least one of the following: Symptoms of ischaemia New or presumed new significant ST-T changes or new LBBB Development of pathological Q waves Imaging evidence of new loss of viable myocardium or new RWMA Intracoronary thrombus evident on angiography or at autopsy Non-obstructive coronary arteries on angiography: Defined as the absence of obstructive CAD on angiography, (i.e. no coronary artery stenosis ≥50%), in any potential infarct-related artery. This includes both patients with: o normal coronary arteries (no stenosis >30%) o mild coronary atheromatosis (stenosis >30% but <50%). No clinically overt specific cause for the acute presentation: At the time of angiography, the cause and thus a specific diagnosis for the clinical presentation is not apparent. Accordingly, there is a necessity to further evaluate the patient for the underlying cause of the MINOCA presentation. LBBB, left bundle branch block. RWMA, regional wall motion abnormality. Diagnostic criteria for myocardial infarction with non-obstructive coronary arteries AMI criteria.1 (a) Positive cardiac biomarker (preferably cardiac troponin) defined as a rise and/or fall in serial levels, with at least one value above the 99th percentile upper reference limit. (b) Corroborative clinical evidence of infarction evidenced by at least one of the following: Symptoms of ischaemia New or presumed new significant ST-T changes or new LBBB Development of pathological Q waves Imaging evidence of new loss of viable myocardium or new RWMA Intracoronary thrombus evident on angiography or at autopsy Non-obstructive coronary arteries on angiography: Defined as the absence of obstructive CAD on angiography, (i.e. no coronary artery stenosis ≥50%), in any potential infarct-related artery. This includes both patients with: o normal coronary arteries (no stenosis >30%) o mild coronary atheromatosis (stenosis >30% but <50%). No clinically overt specific cause for the acute presentation: At the time of angiography, the cause and thus a specific diagnosis for the clinical presentation is not apparent. Accordingly, there is a necessity to further evaluate the patient for the underlying cause of the MINOCA presentation. AMI criteria.1 (a) Positive cardiac biomarker (preferably cardiac troponin) defined as a rise and/or fall in serial levels, with at least one value above the 99th percentile upper reference limit. (b) Corroborative clinical evidence of infarction evidenced by at least one of the following: Symptoms of ischaemia New or presumed new significant ST-T changes or new LBBB Development of pathological Q waves Imaging evidence of new loss of viable myocardium or new RWMA Intracoronary thrombus evident on angiography or at autopsy Non-obstructive coronary arteries on angiography: Defined as the absence of obstructive CAD on angiography, (i.e. no coronary artery stenosis ≥50%), in any potential infarct-related artery. This includes both patients with: o normal coronary arteries (no stenosis >30%) o mild coronary atheromatosis (stenosis >30% but <50%). No clinically overt specific cause for the acute presentation: At the time of angiography, the cause and thus a specific diagnosis for the clinical presentation is not apparent. Accordingly, there is a necessity to further evaluate the patient for the underlying cause of the MINOCA presentation. LBBB, left bundle branch block. RWMA, regional wall motion abnormality. As summarized in Table 1, the AMI criteria for MINOCA constitute those defined by the well-established ‘Third Universal Definition of Myocardial Infarction’.1 This contemporary definition is focused upon a positive cardiac biomarker and corroborative clinical evidence of an AMI. Compared with previous AMI definitions (pre-dating the troponin assay), the criteria are more sensitive, and may be further enhanced with the introduction of ultra-high-sensitivity troponin assays, although the specificity may be compromised. Hence, the emphasis of corroborating the bioassay findings with the clinical presentation is of paramount importance in the definition. Moreover, this definition introduces the concept of types of infarcts,1 reflecting the underlying cause of the AMI. Type-1 (spontaneous) and type 2 (supply-demand mismatch, including coronary artery spasm) are most relevant to this document. A potential problem with current AMI criteria is their central focus upon troponins, since clinicians encounter elevated troponins in clinical scenarios other than AMI. A detailed discussion of troponins in the diagnosis of AMI is beyond the scope the present paper, but has been detailed in other reviews.11 There are three central concepts in interpreting troponins in the context of a coronary angiogram showing non-obstructive coronary arteries. First, it should be appreciated that cardiac troponins are ‘organ specific’ and not ‘disease specific’. An elevated cardiac troponin is not necessarily indicative of an AMI but reflects myocardial injury or necrosis. One example of a disease process causing myocardial injury and troponin elevation without an AMI is pulmonary embolism. Thus, there must be corroborative clinical evidence in addition to elevated cardiac troponins to establish the diagnosis of AMI, including MINOCA. However, there is no imaging technology, including cardiac magnetic resonance (CMR) imaging, which can definitively exclude an ischaemic cause of troponin elevation (see ‘MINOCA with normal cardiac MR imaging’). Only a pathologic examination is definitive. Second, rarely the troponin assays may provide spurious results due to analytical issues such as heterophilic antibodies.11 Finally, there are several differential diagnoses for MINOCA, which may arise from both coronary and non-coronary mechanisms as listed in Table 2 and summarized later in this paper. Certainly, the presence of coronary atherosclerotic obstructions, does not exclude other non-cardiac causes of troponin rise. Potential causes of an elevated troponin adapted from Agewall et al.11 Coronary causes Plaque rupture or erosion Coronary artery coronary with coronary Coronary coronary Coronary causes with cardiac with Coronary causes Plaque rupture or erosion Coronary artery coronary with coronary Coronary coronary Coronary causes with cardiac with Potential causes of an elevated troponin adapted from Agewall et al.11 Coronary causes Plaque rupture or erosion Coronary artery coronary with coronary Coronary coronary Coronary causes with cardiac with Coronary causes Plaque rupture or erosion Coronary artery coronary with coronary Coronary coronary Coronary causes with cardiac with The angiographic criteria for coronary detailed in the MINOCA definition the of which is consistent with contemporary angiographic This is and there is and in of angiographic the of an acute coronary may in significant angiographic changes from coronary and the coronary a and of have to patients with angiographically normal coronary arteries with the of those patients in atherosclerosis does not a in the AMI. this is not since studies have demonstrated significant atherosclerotic in patients with coronary this is by (i) the use of and other atherosclerotic imaging in routine clinical practice, (ii) coronary and may in the of and (iii) coronary atherosclerosis may be an in non-coronary causes of an elevated troponin and Coronary angiography is more and may be considered for of atherosclerosis when imaging is not performed the diagnostic The of angiographically coronary arteries does not an of disease in MINOCA. non-obstructive atherosclerosis may development of not to be atherosclerotic in such as myocarditis and Coronary artery may be the underlying cause of MI in patients with or without Therefore, the is to define MINOCA on the of absence of a obstructive stenosis on coronary angiography than on the presence or absence of any coronary these from a research it is to patients with mild coronary atheromatosis on angiography from those with since it may have diagnostic and/or the importance of the clinical context in a diagnosis of MINOCA and the that it is a ‘working diagnosis’, it is not appropriate to use this when a specific clinical diagnosis is apparent. a with a presenting with chest ST troponin and to have normal angiography should be as clinically myocarditis with or without associated to criteria (Table than MINOCA. Definition of clinically myocarditis to the CAD stenosis disease or causes that the heart the patient is diagnostic criteria should be of and diagnosis of myocarditis requires by coronary with or without normal or regional left and/or on or with or without troponin may have a time to AMI or a and over several or New or heart heart of and left features and/or and/or any of the following: to or bundle branch or and Q and elevated cardiac troponins and on cardiac imaging and/or and abnormality. by and/or of to CAD stenosis disease or causes that the heart the patient is diagnostic criteria should be of and diagnosis of myocarditis requires by coronary with or without normal or regional left and/or on or with or without troponin may have a time to AMI or a and over several or New or heart heart of and left features and/or and/or any of the following: to or bundle branch or and Q and elevated cardiac troponins and on cardiac imaging and/or and abnormality. by and/or of to Definition of clinically myocarditis to the CAD stenosis disease or causes that the heart the patient is diagnostic criteria should be of and diagnosis of myocarditis requires by coronary with or without normal or regional left and/or on or with or without troponin may have a time to AMI or a and over several or New or heart heart of and left features and/or and/or any of the following: to or bundle branch or and Q and elevated cardiac troponins and on cardiac imaging and/or and abnormality. by and/or of to CAD stenosis disease or causes that the heart the patient is diagnostic criteria should be of and diagnosis of myocarditis requires by coronary with or without normal or regional left and/or on or with or without troponin may have a time to AMI or a and over several or New or heart heart of and left features and/or and/or any of the following: to or bundle branch or and Q and elevated cardiac troponins and on cardiac imaging and/or and abnormality. by and/or of to with MINOCA are than those with obstructive CAD and have a in patients with obstructive the of AMI is in and than in MINOCA there is only a This that the underlying MINOCA are and that and/or may a Myocardial infarction with non-obstructive coronary arteries may present with or without ST elevation on the of the underlying The of non-obstructive CAD is these for and in than As MINOCA is a diagnosis and should the to underlying analogous to heart This for diagnostic in to or exclude potential in or should be performed in the acute to wall This the in is a diagnostic magnetic resonance imaging is the diagnostic to be in MINOCA when of the of myocardial damage and into an of in the an ischaemic cause of although it does not the cause of ischaemia or a in of In other patients, a of may a diagnosis of myocarditis or an Imaging for myocardial and may the of with Intracoronary imaging at the time of cardiac with or may be to atherosclerotic and erosion as well as coronary or which may not have been appreciated angiography. research is to the potential of routine of imaging at the time of coronary in patients with MINOCA. Coronary angiography is to further regarding underlying atherosclerosis the acute angiogram but does not rupture or We that clinicians pulmonary as a cause of myocardial damage and exclude this diagnosis with elevated in the of and/or pulmonary angiography as However, no pulmonary was patients with MINOCA who pulmonary angiography in one it is important to in which a other than coronary to an myocardial and and cause myocardial such as and as potential causes of MINOCA. clinically apparent the most common causes of MINOCA that the must are rupture or coronary artery coronary and other of myocardial is a cause of MINOCA. Plaque is within AMI in the Universal Definition of Myocardial when no thrombus can be the Universal definition MINOCA of AMI The term imaging and pathologic findings of or may a studies rupture or in of patients with imaging an of but this has not been in studies within the MINOCA Plaque erosion has been in MINOCA and is by thrombus on with an or without a with thrombus has been as a cause of AMI on on angiography, the in MINOCA patients and is this does not for of the Plaque may in of the which normal on However, of if is on coronary angiography in patients with in MINOCA with is by or a combination of these One that has been as an for MINOCA in the presence of myocardial infarction is or of a coronary is to be an mechanism thrombus in the presence of a coronary imaging may large of myocardial with or without of patients with MINOCA and that was in a The that coronary than to this can be and both may a In other of MINOCA with imaging a of by a that of from the is the most mechanism of and/or almost a in pathogenesis of MINOCA with Therefore, is for by for patients with or confirmed and on a of non-obstructive is if only a of atherosclerosis is The of patients with as the cause of MINOCA has not been in with other of MINOCA. However, the of rupture on was associated with cardiac in a of patients for acute coronary the of myocardial infarction or in MINOCA patients is to Coronary artery may to the pathogenesis of AMI in patients with obstructive CAD and particularly in those with MINOCA. It reflects a to in but may in the context of or has demonstrated in of patients with MINOCA that it is a common and an important mechanism in that and are for coronary artery with the to cardiac in this diagnosis and to be Myocardial infarction with non-obstructive coronary arteries may be the presentation for patients with or an in those with the of the features of that may to the diagnosis in patients with MINOCA include of that to if associated with ischaemic changes and a as Thus, a diagnosis of can be made if of are associated with changes that to However, are to be undertaken if the diagnosis is to be This has been performed by clinical researchers in patients with a the should be in the acute of AMI. is a potential cause of MINOCA since elevated troponins have been assays following the absence of large research is into the and value of in MINOCA. may be a mechanism to AMI in the of or coronary artery or may be the cause of MI in the absence of these Coronary may arise from or and coronary may from coronary or include and studies in patients with MINOCA have a of these should be considered such as the and although these have not been in MINOCA. Coronary may in the context of the above or other such as and heart may arise from including cardiac and and The clinical assessment of coronary including embolism, as a potential cause of MINOCA is summarized in Table Although the of coronary in MINOCA is to be this in may be due to coronary with or may be on angiography. disease or may not be noted and may not be The importance of these potential causes is the of therapies, although their use in the context of MINOCA is Diagnostic cardiac Diagnostic cardiac coronary causes an AMI although this may not be apparent on coronary angiography, a diagnosis of of the coronary arteries without Intracoronary imaging is in this The is more common The for the of coronary are but is present in other in the of when is in the due to and have been in the absence of atherosclerotic disease and in these is not A management is coronary and to cause of the and outcomes are with often as an acute coronary with ST The of left has presentation is by heart associated with myocardial in the absence of The is although several studies have demonstrated significant in the acute and more studies with are The diagnostic criteria or of the left with or without the regional wall motion beyond a a is but not The absence of obstructive CAD or angiographic evidence of acute rupture it is that obstructive CAD may the in New elevation and/or or elevation in cardiac The absence of and from acute myocarditis and AMI due to CAD may be are in with AMI. but not patients present and may no have the left magnetic resonance imaging performed early to in to establish the diagnosis on a of the importance of in MINOCA. The mechanisms responsible for are and may These mechanisms have been in that a detailed of these is beyond the scope of this position paper. the of the in this over the past no to define the management of these strategies may include the of the use of in those with left in those with left in those with and of potential However, it must be that the and other of MINOCA may be in clinical presentation is the has criteria for clinically that are in Table diagnosis of myocarditis and of its specific can only be by This has a presentation including an acute coronary presentation in the of and without obstructive CAD (Table In patients with a myocarditis the specific diagnosis of myocarditis should be made or at coronary angiography, but in the diagnosis not be clinically apparent and the diagnosis of MINOCA should be made specific is The of myocarditis patients with a clinical diagnosis of MINOCA on the with a of in a The most common cause of myocarditis is confirmed with of the on causes of myocarditis are and myocarditis may with cardiac or in the context of and is by on The of myocarditis should include Although this with the of only the of the underlying cause for the et that imaging of in the new on disease is for the of myocardial as a The importance of myocarditis in patients with MINOCA to its and Although myocarditis over a in of patients, may and to heart or heart myocarditis is particularly associated with a patients with myocarditis may and/or as a to or and not in other causes of MINOCA. The diagnosis of myocarditis is the for that is in specific such as in which is associated with a cardiac as well as in to differential diagnosis with other causes of MINOCA, including 2 AMI is defined as myocardial due to mismatch, by significant and/or in troponins with at least one value above the 99th percentile of a normal reference in the absence of evidence for coronary rupture in addition to at least one of the other criteria for of myocardial include wall and heart myocardial is by coronary and underlying AMI include failure, with or without left heart failure, and of and these may underlying obstructive patients with non-obstructive a should be present to AMI. the underlying the is to be if and may be There are at present no clinical the of AMI and the patient is findings in AMI have been to be with in of the of specific must be considered in the context of the specific of AMI not be when the cause of is and a has not been magnetic resonance imaging is a in MINOCA patients it not only into potential causes but may provide of the diagnosis of AMI. In the presence and of any may a or However, of patients with MINOCA have no evidence of myocardial or wall motion on The MINOCA with normal the the troponin was a of myocardial injury or to an on imaging is to as as of myocardium with current patients with normal may have to be the normal may be the of a of may be over a with no of of to be by with normal imaging to have troponin troponin the upper of normal may be in the absence of Myocardial imaging evidence of myocardial injury but is in patients with MINOCA and normal In the this may have occurred the imaging was undertaken in the clinical or the were the evolution of for imaging of myocardial and its routine in patients with MINOCA, further may be in the is normal and diagnostic evaluation as does not the mechanism of AMI, there is a diagnostic and for there are no this first coronary or may cause MINOCA with normal In a of patients with MINOCA who both and imaging, a of those with had a normal imaging had not been performed cardiac this diagnosis have been MINOCA studies or have not performed However, coronary artery may myocardial ischaemia that is associated with a troponin An alternative is that the troponin rise is not indicative of AMI and is due to other causes such as pulmonary or These causes should be when is In the absence of evaluation of underlying mechanisms and clinical any We in of as routine since these be of for the potential underlying mechanisms of coronary coronary and diagnostic and for myocardial infarction with non-obstructive coronary arteries. be with in the acute as the definition requires imaging to of left In the patients with apparent have ischaemic injury or We when is Plaque or should be and imaging considered an of the clinical presentation such as myocarditis or has not been particularly those patients with evidence of atherosclerosis on the coronary and more atherosclerotic than may be appreciated on angiography. for imaging is to be it is appropriate to this imaging at the time of the acute cardiac diagnostic angiography. should be made of the the can provide and the in associated with for coronary artery has been performed by clinical researchers in patients with a acute myocardial However, have been and this should not be a the patients, particularly in the acute myocarditis (no angiographic stenosis on cardiac magnetic resonance by of and diagnosis of myocarditis requires by AMI, acute myocardial left magnetic resonance Myocardial infarction with non-obstructive coronary arteries is a with a of 1–13% of patients with a clinical diagnosis of AMI. There are several potential that should be by a diagnostic from an diagnosis, since that may be appropriate for one cause for or for not be appropriate for MINOCA In MINOCA patients without an evaluation including a routine examination with clinical of diagnostic and strategies are These results have on both and of these and the and the the and made of the for of