Myocardial Infarction without Coronary Arterial Obstruction: The Mysterious MINOCA

The first time that I heard the term MINOCA, it made me think that perhaps this referred to an ancient civilization in Greece contemporaries of the Minoans on Crete. I imagined the following headline: “Archeologists unearth the remains of one of the cities of Minoca in northern Greece”. Of course, for cardiologists, MINOCA has nothing to do with ancient Greece. Rather, MINOCA refers to the 5-10% of acute myocardial infarction (MI) patients with minimal to no discernable high grade, critical, coronary arterial stenoses (Myocardial INfarction with Nonobstructed Coronary Arteries. The majority of these patients reported in the medical literature are post-menopausal females, and exactly what is appropriate therapy for these individuals remains unclear. Angioplasty is not a viable therapeutic intervention for a MINOCA patient since there is an absence of high-grade coronary arterial stenoses or occlusions. However, despite the lack of severe coronary arterial stenoses, MINOCA patients frequently do have manifestations of atherosclerotic disease in other territories, for example, peripheral vascular disease1. In addition, mortality rates are substantial for MONICA patients in the years following their MINOCA event. In the nationwide, Swedish SWEDEHEART registry (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapy), 14% of these patients died during a 4.5 year followup¹.

Although not termed MINOCA in the past, this entity has been known for many years² with a number of possible pathophysiologic mechanisms suggested, including transient coronary arterial spasm, coronary arterial embolization, endothelial dysfunction, coronary arterial dissection, and even occlusion of a small coronary arterial branch that was missed on angiography. A number of clinical observers have even suggested that some of these individuals might have had a Takatsubo event, a myocardial injury in the absence of clinically significant coronary arterial obstruction. However, patients with Takatsubo syndrome were excluded from the analysis of Nordenskjold et al¹. Recently, the 4th edition of the Universal Definition of Myocardial Infarction devoted a separate section to MINOCA³ and worked closely with the authors of the present AHA statement to make sure that the material in the two documents was consistent. Because the underlying pathophysiology and optimal therapy for these patients remains unclear, additional research in this area is needed.

The majority of MINOCA patients described in the literature are older women with atherosclerotic risk factors such as diabetes mellitus, hypertension, and hyperlipidemia. In a recently published investigation in The American Journal of Medicine, the SWEDEHEART investigators extracted information from their national registry concerning MINOCA patients who had suffered a recurrent MI. They observed that approximately 6% of MINOCA patients subsequently suffered a second MI⁴. Coronary angiography at the time of the second MI revealed that half of the MINOCA patients with a recurrent MI had developed clinically important coronary arterial stenoses since their last coronary angiogram. In other words, there had been progression of the atherosclerotic disease process in half of the patients. The second MI occurred on average approximately 2 years after the initial MINOCA event. As noted above, the prognosis for MINOCA patients was not benign and worsened further with the second MI. Twenty-two percent of the MINOCA patients in the SWEDEHEART registry who developed a re-infarction died during a 3.5 year follow-up. Half of the deaths were from cardiovascular causes.

Recently, Opolski and colleagues studied 38 patients with MINOCA with optical coherence tomography (OCT) and magnetic resonance⁵ imaging. OCT is a technique that enables visualization of the coronary arterial lumen. These investigators observed that MINOCA patients often had atherosclerotic plaque disruption and thrombosis as well as evidence for ischemic injury of the myocardium (type 1 myocardial infarction). To date, there have been no randomized, double-blind trials of therapy in patients with MINOCA. However, the SWEDEHEART investigators did observe that patients who received evidence-based therapy (EBMT) for MI, that is, beta blockers, renin-angiotensin system blockade, and statins, had better long-term outcomes compared with MINOCA patients who did not receive EBMT⁶. There are a number of large retrospective and prospective trials underway studying this enigmatic and interesting syndrome⁷. Hopefully, these studies will increase our understanding of the pathophysiology of MINOCA and thereby lead to effective therapy.