No Obstruction Shouldn't Mean No Diagnosis: HARP-MINOCA in Context

Michelle L. O'Donoghue, MD, MPH; Harmony R. Reynolds, MD


January 04, 2021

This transcript has been edited for clarity.

Michelle L. O'Donoghue, MD: Hi. I'm Dr Michelle O'Donoghue, reporting for Medscape. Joining me today is Dr Harmony Reynolds. She is the director of the Soter Center for Women's Cardiovascular Research at New York University (NYU) Langone Health. Welcome, Harmony.

Harmony R. Reynolds, MD: Thank you so much, Dr O'Donoghue. I'm pleased to be here.

O'Donoghue: Thank you so much for joining me. We are just coming off the heels of the American Heart Association Scientific Sessions, and your presentation was one of the more interesting ones. It touched upon the field of myocardial infarction with nonobstructive coronary arteries (MINOCA), which has been very poorly understood. Could you lead off by walking us through the top-line findings from your study?

MINOCA and Atherosclerosis

Reynolds: Sure, thanks. We enrolled women who had myocardial infarction (MI) and were being referred for cardiac catheterization to evaluate their MI. The referring physicians expected that they were sending them for revascularization, but we knew that some of them would have MINOCA. Women who had MINOCA had multivessel optical coherence tomography (OCT) of the coronary arteries, and then cardiac MRI within a week. We found that between those two imaging tests, we were able to find an underlying cause of the MINOCA presentation in 85%, and most of those (two thirds of the women overall) had findings pointing to MI as the cause of their presentation. One in five had an alternate diagnosis like myocarditis, and in only 15% could we find no abnormal imaging to explain that presentation.

O'Donoghue: It's such a huge contribution. As I look back at the patients that I've cared for over the years, I have to admit that so many of us have been guilty of having women or men come in with chest pain symptoms and a classic presentation of an acute coronary syndrome (ACS). We sent them to the cath lab, we did not see any obstructive coronary disease, and then we essentially patted them on the back and said, "Good news — you don't have any coronary disease; there must be some alternate explanation." And we have basically tried to impart the message that that alternate explanation is probably of no consequence. This is very important for advancing the field because as you're highlighting, we are now uncovering that many of these individuals, specifically women in your study, who have no obstructive coronary disease do, in fact, have an atherosclerotic origin for their presentation.

Reynolds: It's true, and prior studies have shown that they do accrue events. It's good news in the sense that the event rate is lower than if they have obstructive coronary disease. But it's definitely higher than in people who don't have MI at all. There is a 24% major adverse cardiovascular event rate after MINOCA based on the SWEDEHEART registry and an 11% 5-year mortality. So it's not a great thing to have. But we did show that much of this is atherosclerotic. Forty-six percent of the women who had OCT had a culprit lesion, and almost all of the culprit lesions were either plaque rupture or some kind of early healed plaque rupture.

O'Donoghue: I suppose that at this point we don't have a complete understanding of why the anatomy for a woman or a man might differ, in the sense that a woman may be more likely to have plaque erosion and less classic obstructive coronary disease than a man.

Reynolds: It's really interesting. Why are these smaller plaques rupturing and then rising to the clinical level of being an MI, a MINOCA event? Whereas in men, maybe that rupture event is not really rising to clinical significance. I'd love to understand more — the next step about why that is.

Jeffrey Berger at NYU is leading a basic science project looking at thrombosis in these women to try to understand that question. Plaque erosion is a really interesting idea. We thought that plaque erosion would be a big cause of MINOCA in these women because pathologic studies have shown that that tends to be an association we see in sudden death victims and young women. But surprisingly, many of these were rupture, and if they were not rupture then they were an intraplaque cavity, or healed plaque, and all of that really is on the spectrum of plaque rupture rather than erosion. I was surprised by that one.

Role of Cardiac MRI and OCT Imaging

O'Donoghue: This would obviously have important therapeutic implications, because currently a lot of people who have MINOCA are going home without any additional therapy. Based on this, do you think that routine OCT imaging and cardiac MRI should be performed on all patients who have an ACS presentation without clear evidence of obstructive coronary disease? How do we then treat those patients?

Reynolds: These are great questions. Let me start with your question about what kind of imaging we should be doing routinely in MINOCA patients. I think that cardiac MRI is a slam dunk. We know that we may be able to find myocarditis on the MRI, and that is really important because those patients need none of the usual secondary prevention medications and it's a different diagnosis. If we have an alternative diagnosis to MI, we should be making that. I feel so strongly about it that I think it's worth getting people back within the week, as we tried to do in this study, or even getting them to an academic medical center if they don't have access to cardiac MRI. I think patients should be getting an MRI very soon. And I think that is true for pretty much everybody who qualifies for an MRI. If for some reason you have a contraindication, of course, that a different thing.

OCT is more challenging because it's not available as widely as cardiac MRI is, and the local interpretation may not be as robust in some medical centers. But I hope that we will move toward a situation where OCT is used more routinely, because we saw plenty of patients in the study who had the OCT culprit lesion and did not have anything major abnormal on their MRI. Those patients might be told that nothing is wrong if they are not getting an OCT. So I hope that in the future, we will be using OCT more. Cardiac MRI should be pretty much routine now.

Now for your question about treatment. If we don't know what we have on the OCT or even on the MRI, I'm now usually treating with antiplatelet therapy, with a statin, and then a calcium channel blocker. The calcium blocker is not based directly on our findings because we did not do spasm provocation testing. We could not; it is just too much with three-vessel OCT. But we had a number of patients who had MI or ischemic injury on their cardiac MR, and they did not have an OCT culprit lesion. We think many of those were spasms, and since calcium blockers are the treatment for spasm, I am advocating — until we have clinical trial data — for using calcium blockers in those patients.

O'Donoghue: That is incredibly helpful. I think that this is going to be an eye-opener for a lot of practitioners who, again, may have been dismissing symptoms in the absence of obstructive coronary disease. Did you see any risks with the OCT being done routinely? I know some interventionalists are worried about potentially unearthing plaques or disrupting what previously was not a problem when doing routine intracoronary imaging.

Reynolds: It was routine OCT in multiple vessels, and we had no complications. There were transient spasms, there were plenty of people who needed intracoronary nitroglycerin. But there was no MI, no dissection, no thrombosis. It was very safe in our study, which is fairly small. But still, with 145 women, we felt comfortable that there were no complications. I think the main message is that most MINOCA is MI. Most of it is ischemic in origin, and you should treat those patients accordingly.

O'Donoghue: That is just tremendously helpful. Thank you, Harmony, for joining me today. I can see that this is going to lend itself to future directions of research. Congratulations.

Reynolds: Thanks so much.

Michelle O'Donoghue is a cardiologist at Brigham and Women's Hospital and senior investigator with the TIMI Study Group. A strong believer in evidence-based medicine, she relishes discussions about the published literature. A native Canadian, Michelle loves spending time outdoors with her family but admits with shame that she's never strapped on hockey skates.

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