Editorial Comment for: Collste et al. – Myocardial infarction with normal coronary arteries is common and associated with normal findings on Cardiovascular Magnetic Resonance – results from the Stockholm Myocardial Infarction with Normal Coronaries study.
Assessing patients with myocardial infarction and nonobstructed coronary arteries (MINOCA)
Version of Record online: 11 OCT 2012
© 2012 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 273, Issue 2, pages 182–185, February 2013
How to Cite
Beltrame, J. F. (2013), Assessing patients with myocardial infarction and nonobstructed coronary arteries (MINOCA). Journal of Internal Medicine, 273: 182–185. doi: 10.1111/j.1365-2796.2012.02591.x
- Issue online: 19 JAN 2013
- Version of Record online: 11 OCT 2012
- Accepted manuscript online: 11 SEP 2012 05:59AM EST
Over the past 20 years, the management of acute myocardial infarction (AMI) has substantially progressed due to innovations in the assessment of these patients. Firstly, development of the troponin assay has provided a more accurate diagnostic marker of myocardial injury and is now the cornerstone of contemporary AMI definitions . This assay continues to evolve with the recent development of highly sensitive troponin assays, which are likely to further impact on clinical practice. A second important innovation were the studies by DeWood et al.,  which involved undertaking coronary angiography during AMI. This group demonstrated that ST elevation myocardial infarction (STEMI) was typically associated with an occluded coronary artery, whereas this occurred less frequently in those without ST elevation myocardial infarction . These findings facilitated the development of reperfusion therapies for STEMI, initially involving intravenous thrombolytic therapy and subsequently primary percutaneous coronary interventions, when the former was shown to be less effective in restoring angiographic coronary blood flow and improving clinical outcomes. For non-ST elevation myocardial infarction (NSTEMI), revascularization of the infarct-related vessel is of benefit although not required immediately because total arterial occlusion is less frequently observed at angiography.
These innovations in AMI assessment have precipitated a conundrum because some patients with elevated troponins have no significant coronary artery disease (CAD) on angiography. This differed from the earlier findings of DeWood et al. [2, 3], where all patients had evidence of obstructive CAD, and raises the question whether these patients have experienced an AMI or have an alternate mechanism responsible for the infarct This syndrome consisting of clinical evidence of AMI  (abnormal cardiac biomarker and either ischaemic symptoms or ischaemic ECG changes) with normal or near-normal coronary arteries on angiography has been referred to as MINCA (Myocardial Infarction with Normal Coronaries) by some researchers  although it may be more appropriately termed MINOCA (myocardial infarction with nonobstructed coronary arteries) because many studies have included patients with nonobstructive lesions (< 50%) on angiography.
Although patients with MINOCA are more readily identified by contemporary AMI assessment strategies, few studies have investigated the clinical characteristics and outcomes of this condition. Data from large AMI registries [5-10] suggest a prevalence of MINOCA between 2 and 10%, depending upon the cohort studied and diagnostic criteria utilized. The largest of these studies examined NSTEMI patients from the CRUSADE registry and reported that female gender and a younger age (median age = 59 vs. 64 years for MINOCA vs. CAD, p < 0.0001) were the only independent clinical predictors of MINOCA . Further analyses of these databases confirm that MINOCA patients have better outcomes than those with obstructive CAD, both in relation to in-hospital mortality (0.65% vs. 2.36% respectively, P < 0.05)  and 12-month mortality (3.3% vs. 6.8% respectively, P < 0.05) . Furthermore, mortality rates were similar for those who had normal angiography and those with minor disease , justifying the merger of these subgroups into the clinical syndrome of MINOCA.
An important first step in the assessment of patients with apparent MINOCA is to exclude nonischaemic causes of an elevated troponin level such as pulmonary embolism, acute on chronic renal failure, acute on chronic heart failure, myocarditis, cardiomyopathies (infiltrative, tako-tsubo, peripartum), stroke, septic shock, acute respiratory distress syndrome, cardiac trauma (including iatrogenic), severe burns, chemotherapeutic agents and strenuous exercise . Most of these conditions are readily identifiable by the clinical scenario except for myocarditis, which may clinically mimic AMI and can be delineated on cardiac magnetic resonance imaging (CMRI).
The utility of CMRI is its ability to identify (i) infarcted/fibrotic tissue by late gadolinium enhancement imaging, (ii) inflamed/oedematous tissue by T2-weighted imaging and (iii) regional wall motion abnormalities as occur in AMI or tako-tsubo cardiomyopathy. In this issue of the Journal, Collste et al.  have provided an important advance in the assessment of MINOCA by performing CMRI on a large patient cohort with this condition. The CMRI studies revealed myocarditis in 7%, a typical myocardial infarct pattern in 19% and no significant abnormality in 67% of MINOCA patients. The myocarditis cases were detected on CMRI despite the clinically overt cases of this condition being excluded from the study; hence, the clinical utility of CMRI in delineating typical AMI from myocarditis. Of the two-thirds of MINOCA patients without any myocardial tissue abnormalities on CMRI, 30% had criteria for tako-tsubo cardiomyopathy. These findings underscore the importance of CMRI in the assessment of MINOCA and mandate this imaging modality as essential in the evaluation of these patients. Future studies are required to determine whether the subsequent clinical outcomes of patients with late gadolinium evidence of infarction differ to those without any CMRI evidence of myocardial tissue injury. Whether the later group have not sustained any myocardial damage or have minute myocardial injury that is undetectable by CMRI is open to speculation.
An additional important observation from this study  is the limited benefit of undertaking routine chest computed tomography for the detection of pulmonary embolism in patients with MINOCA. After performing chest computed tomography in 100 consecutive MINOCA cases, the investigators aborted this approach because pulmonary embolism was not observed in any of the patients. This is not only a cost-saving measure but also reduces unnecessary radiation exposure in these patients.
Once nonischaemic causes for the troponin rise have been excluded by clinical evaluation and CMRI, the underlying mechanism responsible for MINOCA needs to be considered. For AMI to occur, there must be a prolonged imbalance between myocardial oxygen demand and supply. An increase in myocardial oxygen demand is rarely responsible for AMI and usually clinically evident (e.g. rapid atrial fibrillation in the context of severe CAD); accordingly, an abrupt reduction in coronary blood flow to the myocardial tissue is the common responsible mechanism. Since there is no evidence of obstructive CAD on angiography in MINOCA patients, occlusion of the epicardial coronary artery must have been transient and/or the coronary blood flow disrupted more distally, within the coronary microvasculature. Evaluation of transient epicardial artery occlusion is particularly important because specific therapies for the underlying mechanisms are readily available, whereas there are no proven effective therapies currently available for coronary microvascular dysfunction.
Abrupt occlusion of an epicardial coronary artery typically arises from the interplay of atheroma, thrombosis and vasospasm. In MINOCA, the atheroma is not mechanically obstructive although may still functionally contribute to the process by facilitating the other processes. Thrombotic occlusion of a coronary artery may occur in thrombophilic states. Congenital thrombophilias including protein C deficiency and the factor V Leiden genotype have been documented in 12% of MINOCA patients . Acquired thrombophilias associated with connective tissue disease (lupus and sarcoidosis) and oral contraceptive pill use has been described in 3% of MINOCA patients . Although uncommon, the diagnosis of these disorders will impact on the management of MINOCA patients because they warrant consideration of anti-thrombotic therapy.
Coronary artery spasm is another important cause of transient occlusion of an epicardial artery and the hallmark of variant or vasospastic angina. The presence of transient ST changes during chest pain that is responsive to nitrate therapy is consistent with a diagnosis of vasospastic angina but often not observed because the pain may have subsided prior to hospital arrival. Thus, the diagnosis of vasospastic angina frequently requires undertaking provocative spasm testing during coronary angiography, with vasospastic agents such as ergonovine and acetylcholine. De Costa et al.  performed provocative spasm testing in 71 MINOCA patients with intravenous ergonovine and reported inducible spasm in 16% of patients. In contrast, Wang et al.  reported ergonovine-induced spasm in 74% of MINOCA patients. Similarly, Ong et al.  reported acetylcholine-inducible spasm in 50% of patients with an acute coronary syndrome and no culprit lesion, although only some of the patients had a positive troponin. Clearly, further studies are required in this area especially as vasospastic angina is associated with an increased risk of AMI/death , and the use of calcium channel blockers in this condition has been shown to improve survival .
Comprehensive evaluation of the coronary microvasculature involves specialize techniques such as coronary Doppler and pressure wire procedures (to evaluate coronary flow reserve and index of microvascular resistance) that are often performed in clinical research facilities. However, simpler techniques, such as the delayed passage of contrast flow through the coronary arteries, have been used as a marker of microvascular dysfunction . This later approach defines the coronary slow flow phenomenon, which has been associated with an acute coronary syndrome presentation, including AMI . Moreover, patients with MINOCA have been shown to have delayed contrast flow . Although documentation of microvascular dysfunction in MINOCA patients is useful in providing a pathophysiologic mechanism for the AMI, it is unlikely to impact on the management of these patients considering the lack of effective therapies for the microvasculature.
As summarized in the Table 1, patients with MINOCA are not uncommon in contemporary clinical practice and have a lower mortality than patients with obstructive CAD, although still at alarming rates. In evaluating these patients, it is important to firstly exclude nonischaemic causes for the apparent AMI (i.e. nonischaemic causes of a troponin rise) and secondly determine the underlying cause of the AMI, especially for potentially life-threatening conditions (thrombophilias and vasospastic angina) that have effective therapies. Adopting this systematic approach in the assessment of MINOCA patients will improve our understanding of this condition and may result in improved outcomes, similar to that achieved with obstructive CAD over the past 20 years.
|AMI diagnosis|| |
(i) Elevated cardiac marker, and
(ii) Ischaemic symptoms or ECG changes
|Angiography||Nonobstructive CAD (i.e. normal or lesions < 50%)|
|Prevalence||5–10% of AMI patients undergoing angiography|
|Demographics||Higher prevalence in women and young|
|Prognosis||Mortality: in-hospital = 0.65%, 12 month = 3.3%|
|Exclude nonischaemic cause||Pulmonary embolism, heart failure, cardiomyopathy, myocarditis, renal failure, stroke, trauma, exercise|
|Cardiac MRI|| |
Often normal. May identify myocardial necrosis
Excludes myocarditis or tako-tsubo cardiomyopathy
|Thrombophilia screen|| |
Protein C, protein S, anti-thrombin-III, factor V Leiden
Connective tissue disorders
|Coronary spasm testing|| |
Nitrate-responsive transient ST segment changes
Provocative spasm testing
|Consider microvasculature|| |
Coronary slow flow phenomenon
Specialized coronary haemodynamic studies
Conflict of interest statement
No conflicts of interest to declare.
- 4Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance - results from the stockholm myocardial infarction with normal coronaries study. J Intern Med 2012 doi:10.1111/j.1365-2796.2012.02567.x, , et al.
- 6Characterization and outcomes of women and men with non-st-segment elevation myocardial infarction and nonobstructive coronary artery disease: results from the can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the acc/aha guidelines (crusade) quality improvement initiative. Am Heart J 2009; 158: 688–94., , et al.
- 10Prevalence, predictors, and outcomes of patients with non-st-segment elevation myocardial infarction and insignificant coronary artery disease: results from the can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the acc/aha guidelines (crusade) initiative. Am Heart J 2006; 152: 641–7., , et al.