Hi, and welcome to Conversations in Interventional Cardiology. My name is Andy Goldswog, and I'm Director of the Cardiac Cath Lab at Baystate Medical Center in Springfield, Massachusetts, and Associate Editor of J-SKY, the Journal of the Society for Cardiovascular Angiography and Interventions. I'm honored to represent J-SKY and our Editor-in-Chief, Dr. Alexander Lansky. We're here today to discuss an important study recently published in J-SKY, entitled Prevalence of Coronary Microvascular Dysfunction and Epicardial Spasm in Patients with Angena and Myocardial Bridge. I'm pleased and honored to be joined by an esteemed panel of authors and experts. First, Dr. Tess Allen, who's a cardiology fellow at Duke University, recently finished her internal medicine residency at the University of Chicago, and she is the first author of this J-SKY paper we're here to discuss. Dr. John Blair, Associate Professor of Cardiovascular Medicine at the University of Washington, previously at the University of Chicago, the senior author of this J-SKY paper. Dr. Sumit Shah, Director of the Cardiac Cath Lab at the West Haven VA Hospital, Assistant Professor of Cardiovascular Medicine at Yale University. And Dr. Odaime Quesada, who is the Medical Director of the Women's Heart Center at the Christ Hospital in Cincinnati, Ohio. So thank you all very much for joining. It's great to have you here. Thanks. Thanks. Great to be here. I'm going to start off with a question for you, Dr. Allen. First, congratulations on this important paper. In patients with angina, the significance of myocardial bridging as a possible etiology is a hot topic in our field and a very controversial one. You and your colleagues studied patients with myocardial bridging and looked for alternative causes of angina. So if you don't mind, could you briefly tell us what you did and what you found? I know you prepared some slides to share. OK, thank you. So this is our study, as mentioned, basically looking at the prevalence of coronary microvascular dysfunction and spasm in patients coming in with angina and myocardial bridge. So I wanted to start off just with a quick clinical scenario, kind of what some of the patients that inspired this work. So this was a 48-year-old gentleman, came in with exertional angina, came to the cath lab, had a coronary angiogram, and you can see one of his films here. And he's one of the people that came in and didn't have necessarily obstructive coronary disease to explain his chest pain. We can see here kind of near the loop recorder that's a little in the way there, the bridge segment that Dr. Blair saw in the lab. So just a little bit of background for our study here, bridges, as you already alluded to, are very common and do pose diagnostic dilemmas in patients coming in with chest pain. Our study was prospective. It was 30 patients who were referred for surgical evaluation for a known myocardial bridge. They all had angina that had largely been attributed to the bridge previously, and we used invasive coronary physiology testing to determine the prevalence of coronary microvascular dysfunction, microvascular spasm, and epicardial spasm in these patients. To the right here is our central figure from the article, but it just kind of goes through the flow of the workup that we did. So patients coming in with bridge had to have non-obstructive coronary arteries, and then the different testing, physiology testing that we did on these patients. So dobutamine testing for the bridge segment to see if it was hemodynamically significant, we used RFR of less than or equal to 0.76 to define significance in this study, and then we did acetylcholine testing looking at two different components, both epicardial spasm, which we defined as having greater than 90% reduction in luminal diameter or an FFR less than or equal to 0.8, and then microvascular spasm having chest pain and ischemic ECG changes along with that at low-dose acetylcholine. So we used adenosine testing to look for endothelium-independent CMD and used a cutoff of less than 2 for abnormal CFR, and then for IMR greater than or equal to 25. And then these are a couple more examples here of what we might see. So this is on the left here with dobutamine challenge, seeing that bridge segment illustrating kind of the constriction there. I think this patient actually ended up not having a hemodynamically significant bridge, but nonetheless you can appreciate the bridge a little bit better with the dobutamine. And then to the right here was a patient, same patient, with acetylcholine infusion. We can see there how much more narrow, particularly the bridge segment itself, becomes with the acetylcholine. And then going into results a little bit, so what we found here, this table is organized by hemodynamic significance of the bridge, and we found that basically all of these comorbidities and other findings in the cath lab were very common in these patients. And as you can see, it didn't really vary how prevalent they were by whether or not the bridge was significant. So you can see very high rates of endothelium-independent CMD, overt spasm, and microvascular spasm in these patients and really not being affected by whether the bridge was significant or not. This is another diagram that is a little more detailed, but just showing kind of the different endotypes and the overlap of patients. So the B is patients with hemodynamically significant myocardial bridge. C is endothelium-independent CMD, ES, epicardial spasm, and MS, microvascular spasm. You can see how much overlap there is and how many patients have multiple potential contributors to the chest pain that had been attributed previously to the bridge. Then only three patients of the 30 had, quote-unquote, no explanation for their chest pain after this invasive physiology testing. So in conclusion, this population of patients who were all referred for a surgical evaluation for myocardial bridge, 53% of them actually had a bridge that was not hemodynamically significant with dobutamine testing. And then epicardial spasm, endothelium-independent CMD, and microvascular spasm were all very common in these patients, and the rates did not vary based on the hemodynamic significance of the bridge. So I think just really raising kind of the question that we're all wondering about how often and when these bridges are causing chest pain and how often there may be another explanation or at least something else contributing to the chest pain. Wow, that's fantastic. Thank you so much for sharing those slides and sharing your data. Clearly angina is much more complicated than just atherosclerotic coronary artery disease. And clearly, as you really brilliantly demonstrated, many, even most, bridge patients have other potential causes of angina so that when these patients are being worked up, it seems like it's pretty important to figure out what the cause of angina might be prior to treatment. Let me direct a question to Dr. Blair. The standard definition for myocardial bridging is not super well established in terms of data, but the primary technique is surgical underroofing, which requires open surgery, which is pretty invasive. So you better be pretty sure that you're doing the right thing to address the patient's angina if you're undertaking that. Based on what you and Dr. Allen and your co-authors found about patients with myocardial bridging, how would you recommend that patients with angina and bridging be worked up routinely? Yes, I think the more that we recognize myocardial bridges, the more that we get into these situations where we're trying to figure out what's going on with the bridge and whether an intervention for the bridge should be undertaken. And exactly, the morbidity of a surgery, although it's a fairly straightforward surgery, it's still an open thoracotomy in most cases. So when we started seeing a lot of these patients at our institution, since we had the precedent of doing a lot of clinical microvascular studies and also we're doing a lot of research in microvascular dysfunction, our approach was to see these bridge patients as not as myocardial bridge patients, but more as patients with chest pain and taking a step back. And when we assess them in the cath lab, we looked for everything that we could look for, concomitant obstructive disease, significant myocardial bridge, microvascular dysfunction, microvascular spasm, and epicardial spasm. So we developed a protocol to evaluate these patients for those things, and we're very surprised to find that there's such a high prevalence of microvascular dysfunction and epicardial spasm. So you can have a hemodynamically significant bridge. You can also have a bridge that's hemodynamically significant with spasm. Our approach, as it evolved over time, is to treat the things that you could treat medically. So we know from Cormica study that if we take a detailed approach and endotype-specific approach towards these patients' microvascular and epicardial dysfunction, that we can get control of their chest pain in patients without bridges. So if they do have a bridge, we treat those, and if they still are symptomatic and they're willing to undergo surgery, that's when we take them to surgery. And we are now looking at our surgical data to look at outcomes from that, but at least anecdotally we've found that the patients are better cared for and get their chest pain under much better control if you understand the other factors going on other than their bridge. And if I can jump in, I just wanted to first congratulate Dr. Allen and Dr. Blair for this publication because what we have found clinically is something very similar to what you're alluding to, Dr. Blair, is clinically we're starting to have more and more of these patients sent to us from our surgeon colleagues because they were referred to them for myocardial bridge intervention. And they're now getting more and more astute about referring them for functional testing to confirm one, whether that myocardial bridge is hemodynamically significant, because as you showed, the majority are not hemodynamically significant. And it was really important in this study because it demonstrated that the prevalence of microvascular dysfunction in patients for bridges is pretty high. And so it was great to see that in a study because clinically we've been seeing similar trends. That's a great point. I have to say, Dr. Blair and Dr. Quesada, you really identify that chest pain is a syndrome, it's a symptom, but that it is very much multifactorial and there are lots of etiologies and saying that the etiology is coronary isn't enough. There's a heck of a lot that can go on in the coronary arteries. I wonder if I can direct a question to Dr. Shah. Microvascular dysfunction is clearly an underdiagnosed cause of angina and your research is focused on techniques and technologies to diagnose microvascular dysfunction. We're at a point in the history of interventional cardiology where the role and the implementation of these tests is still being defined. So I wonder if I could ask you to comment kind of broadly on indications for and modalities for testing for coronary microvascular dysfunction. Absolutely. My pleasure. And congratulations to Dr. Allen and Dr. Blair. This is a great paper and really a nice launching point for this discussion. So Andy, as you alluded to, this field has really exploded and our ability to diagnose microvascular dysfunction has caught up with that. So there's non-invasive techniques like phase contrast MRI, PET imaging, which is still mostly using rubidium, but now fluoroperidaz is a radioisotope that's much better in terms of pharmacokinetics is on the near horizon, and then invasive techniques. So a lot of this work, the foundational work was done with Doppler, which was harder to use, but as Choroflow has taken off, we now have cath labs all around the country that are actively testing for microvascular dysfunction. With that, we now have consensus statements and even working groups that have come together where we've really developed a community where we're speaking the same language and we have multicenter studies going on. So now our ability to diagnose and take care of patients with microvascular dysfunction has really expanded. Beyond that, we're now even launching into new things like continuous thermodilution, and so really we're pushing the limits of what we had previously thought possible to diagnose patients with angina and non-obstructive coronary arteries. An important point that I want to note about this paper is that of the patients who had coronary vasomotor disorders in the bridge segments, there was a good mix of endothelium-dependent and endothelium-independent physiology, and I want to turn it back to Dr. Allen and Dr. Blair to talk about what that means for testing. I think as Choroflow has really caught on in a lot of labs are using a pressure wire and adenosine, what does that say about doing endothelium-dependent testing? Yeah, that's a great question. Most interventionalists are very comfortable with using adenosine. We used that with FFR before we had IFR and RFR, but then the comfort and availability of acetylcholine varies from institution to institution, and especially we're just kind of getting over a nationwide supply shortage of acetylcholine to kind of complicate matters. So acetylcholine is the primary ingredient that we use to determine endothelium-dependent vasomotor dysfunction that you're referring to, although other medications like argonavine have also been used, but acetylcholine is probably the most available and the easiest to use. The importance of that is, as we saw in our study, 30% of these patients ended up having epicardial spasm and 29% ended up having microvascular spasm. So if you don't use the acetylcholine to make the diagnosis, then you're going to miss that big chunk of patients. Now admittedly, 60% of these patients had abnormalities with their microvascular function with adenosine. Yes, statistically and on the whole, you'll get that 60% of patients who have microvascular dysfunction, but the treatment for the fixed microvascular dysfunction and endothelium-dependent microvascular dysfunction varies a little bit. You may actually go down a treatment course that may be ineffective, potentially because they have much more dramatic and significant vasospasm. So instead of treating the vasospasm, you're treating the fixed microvascular dysfunction, so you can kind of get down the wrong pathway. The way I see it is that if you're bringing them to the cath lab anyway and you're going to do the assessment with dobutamine with a wire and you have a wire across and you're even giving the adenosine, you should also be prepared and have some wherewithal to give the acetylcholine to look for the vasospasm. Yeah, I totally agree. We see this so often, especially in bridges, but it's really in contrast to what I think all of us were taught about myocardial bridges, where the first-line therapy is a beta blocker. We're under-treating that significant portion of patients who have endothelium-dependent physiology. So I guess that raises the question, based on your work, does this set the stage for doing a randomized study, looking at calcium channel blockers versus beta blockers as the initial anti-angina therapy? I think so. I think a lot of randomized controlled trials need to be done in this space, especially as we're recognizing the various different physiology going on. I think beta blockers versus calcium channel blockers in myocardial bridges would be an interesting thing, but also maybe having a subgroup analysis for the patients who have the concomitant spasm. There is some reasonable data out there showing that certain types of beta blockers can even be used in coronary vasa spasms, so the results from that would be quite interesting. Anecdotally, what I found in the cath lab is that oftentimes when we're assessing even just with nitroglycerin, when we're given nitro and have a wire across the bridge, we do see reduction in the RFR and FFR after the nitroglycerin. So I'm not sure if nitroglycerin should be the first-line therapy in patients with bridges who have spasm concomitantly, because what you're doing is you're dilating the normal segment of vessel and leaving the constrained segment of vessel to be restricted and potentially having flow disturbances there. But that also should be looked at. It really raises the specter of all the caths we've done where we've told patients, good news, it's normal, and maybe it's just not actually that normal. How many times every day in this country do people come to the cath lab looking for a diagnosis for their chest pain, see no significant epicardial atherosclerotic stenosis, and they're told it's normal, and it seems like there's just a lot more to it. In particular, and I have a question for you, Dr. Quesada, we know nationally that women are less likely than men to receive appropriate testing, diagnosis, and treatment for cardiovascular disease in general. This paper by Dr. Allen and Dr. Blair and colleagues really speaks about important developments in testing and diagnosis of potential coronary etiologies of chest pain other than atherosclerosis. How can we ensure that this testing is used equitably? How can professional societies like SCAI, government regulatory agencies, and individual clinical practices take health equity seriously in terms of working up chest pain and making sure that everybody has access to an appropriate diagnosis and treatment? Thank you for that great question with lots of components to it. As you're pointing out, we know that angina with non-obstructive coronary artery disease or ischemia with non-obstructive coronary artery disease is historically, based on the data that we have, 70% of those patients are women. That's what we know from previous studies. As has been mentioned, we also know that if you take patients to the cath lab and do functional testing, if you take Anoka, Inoga patients, you'll find that only 10% are going to have normal functional testing, meaning that about 90% of them are going to have some kind of microvascular dysfunction, whether that's endothelial independent, endothelial dependent, microvascular spasm, or epicardial spasm. In other words, these are patients that have a reason for why they have angina, and the majority of those patients in those scenarios are women, 70%, as I said. I think what's important is that we recognize, especially I think the role of professional societies and the role of professionals like us, is to increase education. Because one of the first things that I did when I established our coronary microvascular vasomotor program as part of the Women's Heart Center, and that is in part why it lives under the umbrella of the Women's Heart Center, is because of that 70% being women, was education. So educating providers on the importance that a patient with angina, and regardless of what that angina is, traditionally we think angina means chest pain, but again, we know that women tend to have not always chest pain. They may have more, quote unquote, atypical symptoms. So we call it angina, is one, recognizing that angina doesn't have to be the classic chest pain, and that two, that these patients need to have further evaluation. So before we can tell someone, your chest pain or your angina is not cardiac and etiology, we should perform the appropriate test, and that appropriate testing should include testing per microvascular dysfunction. And what this paper has shown us is that in patients with bridges, we should go a step further, right? Before we blame it on the bridge that they likely had since they were born, if the history doesn't make sense, if this is someone that started to have angina later in life, we should really think about the concomitant microvascular dysfunction. And so in terms of what we should do on a larger scale for this, I think we need policies. We definitely need to make sure that our functional testing is covered. One of the major issues that a lot of us can allude to that do perform these kind of tests is the difficulty with getting these tests approved, whether it's non-invasive stress PET, stress MRI, or invasive fornate functional testing. And so there's a lot of work that needs to be done so that not only are we educated that these patients need further testing, but then when we are educated and we want to do it, that it actually gets covered. And not to mention all the clinical studies that we still need, that I know a lot of us are working on to advance the field and actually come up with treatments that are based on these mechanisms, because we are lacking treatments specifically based on mechanisms. There's a lot of work that needs to be done in that field too. Dr. Gonsalves, you made me think about this, both in terms of coverage, but also reimbursement. The work that Drs. Allen and Blair did for this paper, even those 30 patients, all of this testing takes time, and increasingly in the cath lab, we're asked to show productivity. And so I guess, Dr. Blair, what do you think about reimbursement for functional testing in the cath lab? Yeah, so I don't think too much about the reimbursement. Fortunately, the bean counters at my hospital never get after me for doing this stuff, so I just keep doing it, and it helps take care of patients, and I can always justify it. So it's not so much of an issue. I think that if you get into the space, I think every group should have somebody who champions this, because it comes up so often. And if you have one person or two people who champion this, then those people can get proficient at it, train the cath lab staff, and do this in high throughput. So oftentimes, recently we've been stacking patients because of the nationwide shortage of acetylcholine that I alluded to, and once we did that, we can get a lot of these patients done in a single day. The most I've done in a day has been six, I think six or seven, and we're done before early afternoon, and it's totally fine. And that's after repetition. It's training your staff, knowing the equipment, knowing how to use the equipment and interpret the results, and doing it in a reproducible fashion. So once you do that, then your time that you spend in the cath lab is much less, and I'm sure the reimbursement works out. But I haven't run the numbers, but I know that it does reimburse for a pressure wire or an IVAS procedure, which I believe is slightly double than a regular diagnostic coronary angiogram, which is pretty good. I mean, we're not doing PCI, we're not leaving anything in the patient, we're not expending a stent. It's just one wire and a system to read and interpret your results, a guide, and the medications that you're giving. And what you're avoiding on the backside is repeat angiograms, repeat testing, repeat stress testing, hospital visits, patient loss of wages from work, and all this stuff that can be very costly to both the hospital system and to the patient. So I don't think about it, and it's worked out so far in two different hospital systems that I've worked under, and I don't think that should be a major deterrent for people to not do this. But I will say, if I could interject, I will say there are issues with getting functional testing approved by insurance companies. I'm not sure if this is dependent on the state, but that is why we do need that push, because even if a provider wants to do the test and are not concerned about RVUs, et cetera, there is that issue of not being able to do the test because it's just not covered. We've had multiple tests that actually get canceled on the day of procedure or the day before for that reason. So still have work to do there. Absolutely. I think there needs to be, it seems like for insurance, there needs to be some objective evidence of angina involved. I've been able to get patients in by demonstrating that they have angina on the treadmill and really try to push these treadmill studies to demonstrate that even though in a lot of cases their regular nuclear stress test can be fairly bland and normal. And they've done other studies that have shown that it's almost worse than a flip of a coin to diagnose microvascular dysfunction and spasm when you do a traditional system, maybe a SPECT scan. But if they're having angina on the treadmill or angina when they're doing their stress test and you try an anti-angina and they're still having angina, they're still going to the hospital ER with the recurrent angina, that makes it a little bit more palatable for the insurance companies to reimburse that and that's how personally we've been able to do that. I think it also helps that the recent guidelines for chest pain have also advocated for this type of testing for patients with ischemia and angina and non-obstructive coronary disease. So that's a great step in the right direction. And if we can get societies and other societies on board and then Medicare and other insurers to follow suit, that would make my life and the number of phone calls that I have to make a lot easier. And I'm sure you guys can attest to that as well. Wonderful. Well, thank you so much, Dr. Allen, Dr. Blair, Dr. Shah and Dr. Quesada. We are absolutely thrilled to share this discussion with this incredible panel of experts. Please follow J-Sky, submit your own work to J-Sky. J-Sky is the official journal of Sky and you can find us online at jsky.org and on X at MyJSky. Thank you all very much.

coronary microvascular dysfunction

myocardial bridges

angina

diagnostic protocols

equitable healthcare access

cardiovascular care