Cardiovascular Prevention In Myocardial Infarction With Nonobstructive Coronary Arteries: Is It Needed And Why?

A myocardial infarction (MI) is in most cases caused by the sudden rupture of an unstable atherosclerotic plaque/stenosis in the coronary arteries. This leads to thrombus formation with total or subtotal occlusion of the artery, distal myocardial ischemia, and necrosis of cardiomyocytes.

However, 5-10% of all patients diagnosed with MI do not have significant coronary stenosis. The term MI with nonobstructive coronary arteries (MINOCA) has been coined for this entity. MINOCA may be the result of various causes, e.g. coronary spasm, thromboembolism or dissection, microvascular dysfunction, or myocardial injury due to a mismatch between oxygen supply and demand. Even the rupture of small atherosclerotic plaques with no angiographically evident stenosis may be a possible cause of MINOCA.

It has previously been thought that MINOCA would be a benign condition since significant stenoses are absent. New data, however, suggests that MINOCA patients are at considerable risk for adverse events in the near future. Their one-year mortality is 4.7%, being threefold higher compared to healthy people of the same age and sex. MINOCA patients also more often suffer new MI and frequently develop congestive heart failure. This has been recognized in international guidelines from 2018 (Fourth Definition of MI, European guidelines on the management of ST-segment elevation MI) that emphasize the importance of MINOCA.

Although first position papers on the management of MINOCA have recently been published as well, evidence on how these patients should be followed after the acute event still is lacking. A central question is whether they need to be targeted to secondary preventive measures (e.g. lowering of cholesterol levels and of blood pressure, smoking cessation, physical exercise), similar to MI patients with significant coronary artery stenoses.

In order to elucidate this important issue, we conducted a retrospective analysis assessing 5830 MINOCA patients who had been identified through the Swedish SWEDEHEART registry. These patients had been admitted to hospitals between 2005 and 2013, were followed for a median of 3.6 years regarding the occurrence of major adverse events (MAE) and compared with 54,631 MI patients having significant coronary artery disease (MI-CAD).

As a first finding, we noted that MINOCA patients less often than those with MI-CAD participated in follow-up controls which according to Swedish routines are scheduled 6-10 weeks after hospital discharge. MINOCA patients also less often achieved secondary preventive targets which likely reflects the uncertainty of caregivers on appropriate treatment standards.

Nonetheless, achieving a low LDL-cholesterol level was associated with a 24-32% reduction in the risk of MAE, similar as for patients with MI-CAD. This finding extends previous data from our group demonstrating prognostic benefit from statin treatment in MINOCA. Why is that if coronary stenoses are absent? In fact, some MINOCA patients may have angiographically non-evident but ruptured coronary plaques that tend to get stabilized by statin treatment, thereby reducing the risk of new MI and cardiac death. A smaller invasive ultrasound study demonstrating such plaques in 38% of MINOCA patients seems to support this assumption, and 20-25% of MINOCA patients have MI-CAD-specific findings when assessed with magnetic resonance imaging.

We also noted moderate prognostic benefit from participation in physical exercise training with a 10-23% reduction in the risk of MAE. Physical exercise exerts positive effects on many cardiovascular risk factors, improves cardiac function and attenuates myocardial remodeling. The degree of risk reduction in our MINOCA cohort was similar to that seen in patients with MI-CAD. That physical exercise and an active lifestyle improve cardiac health is common knowledge, and our findings extend this notion to MINOCA.

Smoking cessation did not improve outcome in MINOCA. The relatively small number of active smokers in our MINOCA cohort may represent a possible explanation for this, on first sight, surprising finding. Even the achievement of target range blood pressure levels did not reduce the risk of MAE. This appears to contradict previous data from our group demonstrating a significant risk reduction by angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment. One might speculate that this benefit rather is mediated by the cardioprotective effects of these drugs, e.g. the prevention of adverse myocardial remodeling, than lowering of blood pressure levels.

For many clinicians, MINOCA represents a conundrum given the heterogeneity of potentially underlying etiologies and disease mechanisms. This often causes frustration, and the terms false-positive MI or troponinemia have sometimes been used to describe MINOCA. This, however, may tempt clinicians to trivialize this condition. MINOCA should instead be regarded as a preliminary diagnosis requiring careful diagnostic work-up.

Considering the results of our study, MINOCA patients should be scheduled for close follow-up, liberally treated with statins, and encouraged to exercise regularly. As to whether other pharmacological treatments would be necessary for MINOCA is subject of debate. The ongoing MINOCA-BAT trial randomizing patients to beta blockers vs. placebo and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers vs. placebo will help us to fill this knowledge gap.

These findings are described in the article entitled Myocardial Infarction with Nonobstructive Coronary Arteries: The Importance of Achieving Secondary Prevention Targets, recently published in the American Journal of MedicineThis work was conducted by Kai M. Eggers, Nermin Hadziosmanovic, Tomasz Baron, and Bertil Lindahl from Uppsala University, Kristina Hambraeus from Falun Hospital, Tomas Jernberg and Per Tornvall from the Karolinska Institutet, and Anna Nordenskjöld from Örebro University.

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