A 54-year-old female with no past medical history presents to the emergency department with two hours of substernal chest pain, rated 8/10, and associated with diaphoresis and shortness of breath. She appears in mild distress and is pale. Her electrocardiogram reveals ST-segment elevation in the precordial leads. Initial cardiac troponin level was 2.25 ng/ml; otherwise, her laboratory results were unremarkable. Her past medical history is significant for hypertension and she was recently diagnosed with breast cancer 3 weeks ago. She is emergently taken to the cardiac catheterization laboratory. The expectation was that obstructive coronary artery atherosclerosis would be identified as the culprit of her acute myocardial infarction and a lifesaving percutaneous coronary intervention with stent placement would be performed. However, her coronary arteries were angiographically normal without any evidence of obstructive disease. A transthoracic echocardiogram was performed and reported apical ballooning and akinesis, with estimated ejection fraction of 35%. Her troponin levels continued to rise and peaked at 15.5 ng/ml. This patient was diagnosed with myocardial infarction with no obstructive coronary artery disease, more specifically, Takotsubo cardiomyopathy. A major life stressor, namely her recent cancer diagnosis, was identified as the provoking factor of this acute medical diagnosis. Takotsubo cardiomyopathy is a condition that falls under the category of myocardial infarction with no obstructive coronary artery disease (MINOCA).
MINOCA) is a term used to describe an enigmatic clinical condition that has been documented for more than 75 years but has been gaining attention in more recent years (Pasupathy et al., 2017). A patient with MINOCA meets diagnostic criteria for a classic myocardial infarction (MI), including rise and/or fall of troponin associated with one of the following: symptoms of myocardial ischemia, electrocardiographic changes consistent with ischemia (new ST changes or new left bundle branch block), new pathologic Q waves, loss of viable myocardium, or new wall motion abnormality, and identification of intracoronary thrombus by angiogram or autopsy (Crea & Niccoli, 2017). MINOCA is differentiated from a typical MI by angiographically proving normal or near normal coronary arteries (Crea & Niccoli, 2017).
Prevalence and Prognosis
MINOCA represents 14% of all acute MIs, and is commonly diagnosed in younger women, with a mean age of 55 years. African-American patients are the most common ethnicity diagnosed with MINOCA (Claudio et al., 2018). Risk factor profile was similar between those diagnosed with cardiovascular disease, including diabetes, smoking, hypertension, hyperlipidemia, and family history (Crea & Niccoli, 2017). Prognosis with MINOCA is more favorable than that of MI caused by obstructive coronary artery disease (CAD), however, it is far from benign. MINOCA is associated with 12-month mortality rate of 4.7% and up to 25% of MINOCA patients report persistent angina following the initial event (Claudio et al., 2018).
There are many potential pathophysiologic etiologies associated with the acute clinical presentation of MINOCA. The graphic below outlines both the coronary and non-coronary causes (Pasupathy et al., 2017).
The diagnosis of MINOCA cannot be made without a thorough history and coronary angiography (Pasupathy et al., 2017). Given that the classic clinical presentation of MINOCA mimics that of MI caused by obstructive coronary artery disease (CAD), these patients are often emergently triaged to the cardiac catheterization laboratory as standard of care. In the absence of obstructive CAD (<50% luminal obstruction), additional testing is then warranted to identify the underlying cause. While in the cardiac catheterization laboratory, intravascular ultrasound (IVUS) or optical coherence tomography (OCT) can be performed inside the epicardial arteries to identify plaque disruption, fissure, ulceration, or dissection. In addition, an ergonovine challenge is a provocative test also performed in the catherization suite and used to aid in the diagnosis of coronary vasospasm (Pasupathy et al., 2017; Crea & Niccoli, 2017).
One of the most useful non-invasive tests used to define the cause of MINOCA is transthoracic echocardiogram for assessment of the left ventricle. Regional wall motion abnormalities may indicate epicardial cause, such as vasospasm, thrombosis, or plaque rupture. Apical ballooning with apical akinesis is suggestive of Takotsubo cardiomyopathy (Pasupathy et al., 2017). Coronary artery embolism/microembolism should be considered in patients with prosthetic heart valves, atrial fibrillation, dilated cardiomyopathy with apical thrombus, infective endocarditis, and atrial myxoma. In these cases, a contrast enhanced transthoracic echocardiogram or transesophageal echocardiogram may be helpful in clarifying the etiology (Pasupathy et al., 2017).
Cardiac MRI is a useful test to identify myocardial edema, scarring or other myocardial anomalies (Pasupathy et al., 2017). Current data estimates cardiac MRI can identify the underlying cause in approximately 90% of MINOCA patients (Crea & Niccoli, 2017). Viral testing for parvovirus, human herpesvirus 6, and Coxsackie virus is indicated when suspicion for viral myocarditis is high. A hypercoagulable state can predispose a patient to coronary thrombus; Factor V Leiden, prothrombin gene mutation, Protein C and S, as well as Factor VII are most commonly tested when a hematological cause is high on the list of differential diagnoses (Pasupathy et al., 2017).
Since current acute MI guidelines to not directly address MINOCA, treatment is driven by underlying cause. Observational studies suggest long-term beneficial effects with statin and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker treatment and a trend toward positive effect with beta blockers. Dual antiplatelet therapy was noted to have a neutral effect (Crea & Niccoli, 2017). Other potential therapies include lifestyle change, management of risk factors, weight loss/diet modification, smoking cessation, and regular physical activity (Claudio et al., 2018). Since there are no randomized controlled trials or comprehensive diagnostic algorithms for MINOCA, further research studies are needed to fill the gap in knowledge and identify optimal management strategies.
Claudio, C., Quesada, O., Pepine, C., & Merz, C. (2018). Why names matter for women: MINOCA/INOCA (myocardial infarction/ischemia and no obstructive coronary artery disease. Clinical Cardiology, 41, 185-193.
Crea, F. & Niccoli, G. (2017). Myocardial infarction with no obstructive coronary atherosclerosis. In G. Saperia (Ed.), UpToDate. Retrieved September 5, 2018 from https://www.uptodate.com/contents/myocardial-infarction-with-no-obstructive-coronary-atherosclerosis
Pasupathy, S., Tavella, R., & Beltrame, J. (2017, September 14). Unraveling the enigma of MI with nonobstructive coronary arteries. Retrieved from https://www.acc.org/latest-in-cardiology/articles/2017/09/14/08/44/unravelling-the-enigma-of-mi-with-nonobstructive-coronary-arteries