In this webinar, Mayo Clinic cardiology experts
Rajiv Gulati, M.D., Ph.D., and Marysia S. Tweet, M.D., M.S., discuss how to differentiate SCAD from other causes of acute coronary syndrome on coronary angiography, identify key SCAD management strategies, and distinguish what is known and what remains unknown regarding SCAD.
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Mayo Clinic Medical Professionals — Cardiovascular Diseases. Hello everyone. Um Fantastic to be here for another one of Mayo Clinic's department of cardiovascular medicines webinar. I am rajiv Galassi. I'm an interventional cardiologist here in Rochester Minnesota. And I'm joined today with my colleague, Marissa Tweet who's also cardiologist who specializes in imaging and both of us are going to talk on a spontaneous coronary artery dissection. Top five facts that you need to know. I'll um Learning objectives are number one to differentiate scarred from other causes of acute coronary syndrome on angiography to identify key scarred management strategies and to distinguish what is known and what remains unknown regarding spontaneous coronary artery dissection. Before I hand over to dr tweet us, want to alert you to the Q. A. Button at the bottom of your screens. Please feel free to click on that. Press it type in a question. We'll try and get to as many, if not all of those. Probably mostly at the end of the webinar. But if something really important and pertinent comes up as we go along, we can interrupt each other dot tweeting myself and try and address those questions. great to have you here at the last time we had about 450 signed in from all over the world. And with that I'll hand over to my colleague, Marissa, tweet, Marissa. Thank you rajiv. Very happy to be here and talk to you about one of my favorite topics, which is spontaneous coronary artery dissection, and that is an emerging cause of non atherosclerotic acute coronary syndrome, which essentially causes what is currently classified as a Type two myocardial infarction and can also cause sudden cardiac death. And you can see the graphic to the right shows a normal coronary artery and with spontaneous coronary artery dissection, there's either hematoma or a tear within the coronary artery And occurs mostly in woman, about 80 of the time. The average age is between 42-52 years of age, with a range as young as 14 years of age to greater than 70 years of age. It is a cause of myocardial infarction commonly young, more woman. So up to a third of women less than age of 50 years of age, is also a common cause of myocardial infarction and pregnancy. And I'll start with the case and we'll have several cases throughout this presentation. This is a 40 year old female a couple of years ago with no atherosclerotic risk factors who presented to the emergency department with atypical chest pain. Her troponin was mildly elevated and the decision was made to take her to the coronary angiogram. And as you can see here on the coronary angiogram images, she has really non obstructive coronary, there's maybe a lesion and the ramos artery that was thought to perhaps not necessarily be significant, but everything else looked rather satisfactory of note. She did undergo a cardiac CT a the next day and the report said that there was a small distal left anterior descending artery. And just one thing I'll point out to you, which is easier to see in retrospect is there was kind of a haziness here and approximately lady that you could follow down when doing Ricans of this study. She was dismissed with medical therapy but then came back at one month with worsening chest pain at that time. If you look on the left hand side of the screen, you can see her coronary angiogram images. The coronary caliber actually improved quite a bit, including that Ramos area that I pointed out earlier to the right. You can see her optical coherence tomography imaging and for those who are not used to looking at these essentially where this yellow arrow is, where there's an intramural hematoma and you can see on her oh ct imaging as we call it, where she has segments of normal coronary and then segments where there's this hematoma. Um and at the end of the day, this was a dissection which presumably is in the process of healing, but even at one month was detectable with the optical coherence tomography. So the first of our five facts about scott is that scott is not always obvious. You should consider it as an ideology of myocardial infarction, especially in younger women without atherosclerotic risk factors. And especially for indeterminant findings would consider use of inter coronary imaging. If that can be safely performed. These illustrations really show to us the different types of scaD, which essentially were first introduced by doctors you've been saw and it's really helped us communicate about scaD. Because classically I think most people thought of a Type one scad as being the only scad. And with time and inter coronary imaging and awareness we're realizing that this type to scaD, which is a long extensive hematoma is likely the most common cause. Or uh subtype of scad. And then the type three scad can also be quite tricky there to the right and commonly will appear very similar to atherosclerotic coronary disease. So when trying to discern the ideology of myocardial infarction, one thing that you may recall this patient was that she actually had coronary tortuous city. So her coroners were somewhat curly for lack of a better term. And when we looked at over 200 patients with Scott and compared them to controls uh similarly aged women as best as we could on coronary angiography we found that the scab patients much more commonly had coronary tortuous city and all three major epic cardio vessels. Now what about C. T. Because this patient did have C. T. And it's tempting to want to do see tv's patients which I think can be very useful particularly if there's an initial concern about pulmonary embolism. This is a very small study of 14 studies that were done with C. T. Performed within two days of a cath among scad patients. And the one thing I want to highlight there is most of the patients did not have a dissection. So that was only 14% of the imaging but rather scattered on CT looked more like a abrupt Luminal stenosis or intramural hematoma which is not always obvious or might even look like non calcified plaque. This is another study performed by our colleagues in spain where they point out the intramural hematoma with those white arrows on C. T. Again kind of a hazy appearance which is important to be aware of. Down on the bottom panel here. You can also see that abrupt Luminal change that was described on the prior slide. So here's a patient, a 42 year old female with no risk factors who presented with non est elevation myocardial infarction and I hope that you can appreciate the only get one movie here but that there is a proximal L. A. D. Lesion here. And at that time she was told we think this is God. And uh the study was stopped and she was medically managed and was not treated with pc. You know there was some concern, however, so she was brought to the coronary catherization lab again and this is actually several months later in the setting of some persistent left ventricular dysfunction and concerns regarding symptoms. And you can you see here in approximately lady that one hasn't resolved as we often expect with scaD. But it looks actually more consistent with atherosclerosis related M. I. And the intravascular ultrasound imaging is consistent with atherosclerosis and as a result she was stunted with a very good final timi flow in a really good results overall. But I think this case really illustrates the importance of getting the ideology right. And this is an algorithm from the 2018 H. A scad statement. And here you can see that the management of acute scad can be conservative for many patients. We do revascularization. Certain cases is outlined here, but it is different management algorithm than you would have for atherosclerosis. So really for these patients it's critical for us to diagnose the acute cause of myocardial infarction correctly And Scott will heal in many cases. So this is a study from Canada where 86 of the patients had an geographic healing. And if the patients for over 30 days post scad there and geographic healing was occurred or apparent in 95 of patients. What about fact too? Well now I'll pass it on to my colleague dr Galotti. Thank you marisa. Um so as you say, conservative treatment has evolved really is the mainstay treatment for spontaneous Corey artery dissection, particularly when there's normal flow and no large vessel vessel occlusion. But there is a caveat and I do want to spend this number two fact talking about that caveat because I I fear there has been this linkage between scad and conservative therapy that doesn't really account for the short term after presentation of scared. So why is conservative therapy? The main stay? Well, here's just one clinical example. You see this patient who had awful looking to section of the left main underwent coronary artery bypass grafting, which I think was very reasonable. This is many years ago. Now, a year ago I had some atypical symptoms that led to another angiogram and look at the left made that has completely healed without any intervention. So, complete resolution of this ugly, scared and you know, one of the grass is open to um billy McGrath is included because of the competitive filling. The point here is that is the beauty of this native healing. One year after Corey aci bypass grafting. What this doesn't show, however, is what happens in the first few days after spontaneous coronary artery dissection. All right. So with that uh point that I want to underscore here with this case from you know, not long ago, just a few months ago, some woman who had a 47 year old severe chest pain come to the emergency department at atrial fibrillation. Which was a new finding for her. An S. T. Elevation here in a VR. An ugly looking at the depression throughout the rest of the E. C. G. Leads here concerning for I think left main or multi vessel disease. Well here's her angiogram and at the time this was taken. So I would say maybe an hour after initially presenting to the outside department, her pain had eased considerably. There is timmy three flow in the circum flex and L. A. D. But there is this focal 60 stenosis in the middle, left main. Over here. The etiology of this cannot be determined on this angiogram. There is no internal dissection flap scene could be atherosclerosis, It's not spasm because it stayed after nitrates, it could be spontaneous coronary artery dissection. This is a perfect case for where intravascular imaging will make the diagnosis. And here we did. You saw the one that marissa tweet show. This is a similar one. The catheter artifact. Here, here is the lumen that I'm going around with my arrow. This is some shadowing artifact. This luminous clean no plaque, no thrombosis. The abnormality is this dark shadowing which is bleeding in the media intramural hematoma, compressing this luminous, Upon the 60 to notice. This is classic intramural hematoma, which is synonymous with spontaneous coronary artery dissection. Now, how to treat this. Uh, there is no clear evidence based pathway. You can make a case for anything. You can make a case for coronary artery bypass grafting. And I have to say, you know, that was really kind of one of the things that we were leaning toward. You can make a case for some creative intervention, Maybe a cutting balloon or a regular balloon to deliberately tear the intimacy and decompress that bleeding into the lumen. You can make a case for conservative therapy based on the case. I just showed you with that incredible healing. At one year after do discussion, we did elect to manage medically or conservatively but keep a close eye on her in hospital and day zero, I've shown you this angiogram here of note On day four she had recurrence of chest discomfort that was relatively minor. We did elect to proceed with another angiogram and look at this incredible change over four days. Dramatic worsening near occlusion of the left main extending into the circle flex extending into the lead. So this is a cute scarred extension, acute extent of the intramural hematoma into both daughter vessels. Over here and at this stage we sent her to Korea. She backpacks crafted from which she has recovered very well. So that's the case. That illustrates the point I'm trying to make about conservative therapy is that it is not a fail safe treatment. There are risks in the first few days. Here's some data that support that anecdote from our group. This is 240 patients who have managed conservatively. We just want to look at the 1st 14 days what happened to that group of patients Or 15 or one in six deteriorated significantly within the first few days of presentation. What stage they deteriorate where most was early in the first couple of days but extending out today for by day 5678. Just an occasional patient who did worse. And when we say worse, we're talking about clinical deterioration together with the repeat angiogram showing worsening to either near occlusion or loss of flow. Just like the patient I showed you who is at risk for worsening and who is less at risk that the highest predictive. The odd ratio, the hazard ratio of three was patients who had an intramural hematoma alone. So an internal tear that was present on the and ground. That was a protective feature I. M. H. Alone. Just like the patient I showed you was a higher risk of progression. Also at higher risk are not surprisingly, but a higher grade cyanosis at baseline or multi vessel spontaneous dissection. So here's that patient again, day zero and then progression with minor pain. Underscoring the point that scatters dynamic in those first few days. Conservative therapy may well be appropriate, but it's critical to keep a close eye the deterioration given that one in six risk of something seriously changing. Here's another example of a change that I think helps us understand the early dynamics of what may be going on in scout. So here's day zero. You see an abrupt caliber change in the lady just after the origin of this large diagonal. This diffuse intramural hematoma, then plumps up again over here. But normal flow. Well, she worsened on day two. And now you see how that lady has completely occluded going down here. Another example here. So there's the axial compression is that intramural hematoma continues to push down on the lumen. We see extension to occlusion downstream. The eagle eyes amongst. You may also note that things have gone upstream. So look here a big fat plump vessel here that is now much narrower. It's a proximal extension longitudinal of the intramural hematoma. Excellent compression and occlusion. So three pathways of scat extension the first few days. So when we look at multiple early repeat angiograms, we see the natural history of scarred in those first few days typically will start as an intramural hematoma with compressive narrowing. It then may extend longitudinal E. It may cause axial compression and even occlusion. And on in in some of the cases we see the intramural hematoma evolved into an internal dissection, suggesting that an internal dissection is actually a secondary phenomenon a d compressive aspects of the haematoma hematoma first then splitting and decompressing into aluminum. Not the other way around, which is what we see with aortic dissection. And of course the majority will subsequently hell! But these first few days is when the risk occurs. So how do we manage scared conservatively. Remember, there's no randomized controlled trials that will support us, but we will typically manage here at Mayo and we recommend this single anti platelet therapy. You know, you can make a good theoretical case for dual anti platelet therapy. Um You can make a good case for no anti platelet therapy we have settled on and perhaps we can talk about this later single anti platelet therapy is the kind of a halfway house beta blockers we do use because of the Canadian study registry retrospective that suggested a lower risk of recurrence in patients on beta blockers. He kind of makes sense statins. Well, this is a controversial area. Won't spend too long on this. But there is limited data. Some registry data suggesting no benefit, no harm. Our very early study, small numbers suggesting maybe a higher risk of recurrence, but there's an awful lot of potential confounding. So we we have limited data. We don't routinely use it. If the lipids are very good. If the lipids are abnormal, we do use it. You can think about giving nitrates or calcium channel blocker. If there is persistent pain that is non s chemical and non in fact, on the assumption that some of the pain maybe spasm well that we don't really know that for sure. To be honest, it could be that the pain is just coming from the vessel wall. A tear can be uncomfortable. And standard other medication for left ventricular dysfunction, right, we can maybe talk some more about this down the line. But right now I think I'll hand over back to marissa tweet for point number three. Since you may have had a scad oh years ago, over a decade ago, they were told it was a fluke. Don't worry about it. Go live your life. Um We have learned though, however, that early um outcomes are not always favorable. And one of the primary drivers for this is recurrent scad. So what I mean by that is the patient has their acute coronary syndrome. They're diagnosed with scad they recover and then they have another separate acute coronary syndrome. So this isn't progression of the initial lesion, But rather a separate one, often in a different coronary artery at a different time, sometimes even years later. Um due to another scat. And depending on the Cohort study, you're looking at, the rates of this is between 10-29%. And in our current registry data is about 15% at five years among a little over 1000 patients. Um And we're really at this point, unable to predict who's going to go on to have more scad and some up to three or four times. Um even maybe five versus who will just have one and then never have another scat in their lifetime. I wanted to share a case to illustrate this point. So this is a dear patient of mine. He's a 59 year old gentleman. Again. No risk factors does have chronic hypertension though, presented with an honest, the elevation myocardial infarction and this is his coronary angiogram. I do want to point out on him that coronary tortuous city, but this lesion in the L. A. D. Was very suspicious and it was uncertain as to the significance of it as to whether or not it was scared. Perhaps it was afro. Um and the decision was made to conservatively manage him well. He was brought back to the catherization laboratory about five days later with worse chest pain, which is uh kind of de facto very similar to this progression or this early change of the scad during the initial process. And as you can see his L. A. D. This is a slightly different view, but you can see that it's changed in one point, it's very static and narrowed. Again. He was medically managed it well. I saw him an outpatient continued to do well tie treated some medications. Now. About one year later, a different physician decided that he didn't need his antihypertensive and and discontinued all of them. Um and so the patient followed that advice and at 60 years of age he presented with another myocardial infarction and to the left, you can actually see that prior lesion is completely healed. It looks fantastic now in regards to the LED caliber. Um But on the right you can see that there is actually a new region of scaD. And again, for those of you may be paying attention. We did query about a branch vessel scad here. So essentially multi vessel scad. So you know, recurrence. We're still trying to put our finger as to how frequent it is, who is at risk. This particular patient essentially had a recurrent scat in the setting a very high blood pressure after being taken off of his medications. Um, and when we look at our Olmstead County population based data, which is relatively recently reported, we find that at about one year the risk is four in our own state county. So patients like this 12 years risk is five and then the five year risk is 10%. This is from the Canadian Cohort, but when they included not only a recurrent heart attack, whether or not that it was progression of Scott or instant thrombosis, um death, revascularization, stroke, or tia or heart failure at 30 days. That adverse event rate was 8.8%. So not negligible. And emphasizes the importance of watching these patients and keeping tabs on them. What are the approach is currently to prevent another scad? Well obviously this is a topic of ongoing study and interest. We're still trying to determine the actual incidents, rates of this. Uh We have found in the past that per cutaneous intervention doesn't necessarily prevent another scad, partly because it tends to occur in a different vessel when it does happen. Even among those who were conservatively treated. Uh dr rajiv Galotti mentioned the beta blocker therapy um which has been associate possibly with less additional scad if tolerated blood pressure control is also uh something we achieve or try to achieve as best possible. And again from that same study, looking at the beta blockade, which was a cohort study by the Canadian group, they found that the patients with history of high blood pressure tended to have more recurrent scad work to minimize possible triggers. And I'll go into more detail about this on the next slide, but that might include extreme exercise stress and pregnancy. And then again just getting back to the beta blockers. So this is just the Kaplan meier curves from that study. It didn't give a whole lot of granular data because this is more of a retrospective study. It wasn't a randomized controlled trial. But you can see here that there was a definite difference over time. Now granted the their patients at 6, 7 years were about 20 to 30 in each arm. But over time there was a separation of the curves with a suggestion that made up those on beta blockers had less additional scad. The one thing I will point out is it's not foolproof. There were still patients who were reported as being on beta blockade who did go on to have another scared. So we do have our work cut out for us in this regard. So let's talk about these possible triggers. So the focus on the first um intense exercise. So about a third of patients report an intense activity at the time of the onset of their scads. So examples that I've heard in clinic have included um moving a big fan in the barn. We live kind of in an area where there's a lot of farms nearby. Another one I've heard is moving the refrigerator up a flight of stairs. Um, so really heavy veil salva kind of unusual activities. I have had some patients who are doing their usual exercise routine though when they had the onset of chest discomfort preceding their diagnosis of scattered say later that day and uh it's uncertain as to whether or not those were related or coincidental. Um emotional stress is another one that we here in about a third of patients reporting perhaps a little more than that. And it's often extreme stress. Uh single most stressful day in my life. My mom died, I was applying for a job and didn't get it. Um Other credit crisis is or a lot of things going on. Sex hormones, you know, that's a question. You know, there's some suggestion that they may play a role uh particularly since this predominantly affects women and also occurs in pregnancy. Um whether or not they're beneficial, say in regards to exogenous hormones versus harmful we don't really understand. But there is some concern about the role of sex hormones and the pathogenesis of scaD. What about medications and drugs? So, um there are some medications that have been commonly associated with scads such as Imitrex or triptans, those drugs that cause vessel constriction, or thought to perhaps contribute to the pathology. Uh In regards solicit drugs, things like cocaine would be something to think about. Um And then this kind of overlaps with the intense exercise one, but the veil Sullivan straining maneuver. Um Some patients report doing that shortly before the onset of their scat symptoms. Now, let's think about associated predisposing conditions. So, fiber muscular dysplasia is probably the most commonly associated condition with Scott and occurs in anywhere between 40-80%, depending on your cohort. And this is a non inflammatory arterial apathy that often appears as beating of the vessels. We've also found other artery apathy is that perhaps don't meet diagnosis criteria for fiber muscular dysplasia, say, like an interest, cerebral aneurysm. Um and that is also common. We have found among patients with scab Connective tissue disorders that are inherited such as Marfan disease or lost. And those have overlapped a scat as well, although the overall percentage is a little lower than the FMD group, that's probably more like 5-8 in the reported series. Uh lifetime prevalence of migraines, which is thought to perhaps have pathology related to the vasculature is 40%, which is considered relatively high. Um even compared to other young women. Um pregnancy associated heart attack is thought to be the ideology and either less than about five of cases which is more consistent with the data in Canada. And then our recent Olmstead County study versus up to 18%. Um hypertension is president about a third of patients and sometimes can be associated with fiber muscular dysplasia, specifically of the renal arteries. Um And then there's this whole catch all of other including some patients who cannot think of any associated condition or any trigger that occurred prior to the start of the myocardial infraction a topic hot for research and I'll go into this just a little bit. Are the susceptibility genes and whether or not there is a genetic predisposition we think there is but it's probably not a single scad gene mutation but rather a complex poly genetic abnormality or set of abnormalities that are affected by the environment. So fast fact number four fiber muscular dysplasia which we commonly refer to as FMD is commonly associated with scott and arterial imaging for FMD is standard of care for scab patients. So I do this at least once and it can be outpatient doesn't have to be well. The patient is in the hospital and our current practice at Mayo is actually a single protocol with C. T. A. With a single contrast injection. With radiation modulation techniques to look at that vasculature and the head, neck, abdomen and pelvis. Um camera could be a suitable substitute particularly if there's concern regarding radiation. Although in my experience I've noted um that sometimes mild fiber muscular dysplasia isn't as easily detected. Um It is also a longer study. Um While ultrasounds such as renal ultrasound or crowded ultrasound can be really helpful and can help detect if there is significant stenosis related to maybe some of the weddings of the fiber muscular dysplasia is particularly helpful and follow up. It might not detect mild fiber muscular dysplasia. And you're really unable to detect the inter cranial abnormalities which are occasionally present in some of these patients. And do require monitoring marissa. Can can I ask you a question? So the with regard to FMD screening I mean, that comes up quite a lot. You know, you get asked this question awful lot. There's two questions. One is what should you do, and I think you've really nicely suggested that C. T. Is the preferred imaging modality, but other people are so why should I do the FMD screening? What are you, what's your answer to that question? Yeah. So there's a couple of reasons. Um the first reason is because of the intracranial aneurysm or aneurysms that we find elsewhere. Sometimes we'll even see splenic artery aneurysms. And depending on the size of many cases, we like to monitor those. Um and I can think of a very clear example of a woman in her 30's who did not undergo screening, actually had a accident with injury to her head and then had a ct head, neck. Um This was after her scat diagnosis. So I had to scatter my recovered was in a motor vehicle accident. They were concerned about her heads. They did imaging with contrast, so they could see the vasculature and they didn't diagnose profound fiber muscular dysplasia with both to know season aneurysms. And um that was obviously life changing for her and she did require intervention. So the primary reason why I do it is to ensure that there's not an arterial apathy that we could be missing that might require either monitoring or some kind of intervention. The second reason is, if you've cared for a lot of these patients, you find that a lot of them were surprised they were doing everything right from the heart healthy perspective. They were a plus student, never smoker washed their cholesterol, cholesterol's normal blood pressure's normal exercise regularly and yet still have a heart attack. And I find it incredibly helpful in regards to them processing what happened in regards to why it happened. Um And also I will counsel some patients differently. For example if they have a large amount of fiber, most their dysplasia and their cervical arteries. Um And so I find it beneficial for those reasons and it's so commonly seen that the yield is high with imaging and it can be incredibly informative and for some patients who could potentially be critical. Um And it's really interesting that the overlap is high clinically because at least with some of our preliminary genetic studies including this one. Um So I mentioned that there isn't really a single scad gene mutation but there are some abnormalities were finding as we study this and there's a risk genetic risk locus, the factor one A. D. N. One and uh the fiber muscular dysplasia as well as patients were scared are both found to be the alien carriers of the specific risk locus rs 9349379 And interestingly people who are prone to coronary heart disease as well as myocardial infarction, tend to be the opposite legal carrier. Um So there is some signal here that there is probably an overlap in mechanisms or at least genetic predisposition. This is not another signal as to what may be going on because ultimately we really want to understand the mechanism of disease so that we can try to find better ways of knowing who is at greater risk preventing future events and finding novel treatments that better than what we have now. And um the PhD actually in our lab found a rare tail in one Miss sense variant and so tail in one here is part of this integrated calm stability complex which essentially links are this acting uh complex here to this, the integrate and the extra cellular matrix. And so the thought is this contributes to the stability within the arterial infrastructure and that this is a Ryan some patients both spontaneous CAD patients but also some cases of familial scat. Um And then another really interesting finding is the GOS analysis. And so our gene loss analysis here is identified positional candidate genes associated with scared and these also have established associations with other arterial apa. These and so this is an informative and it's helping us to try to better understand mechanism as well as perhaps risk in the future. So when we talk about genetics, um I do commonly send patients to see a geneticist in clinic but it's not to discuss those novel findings and perhaps someday we'll have apologetic risk for score or something similar to that to use clinically. But I rather I offer genetics visit more so to discuss the possibility of connective tissue diseases which are also associated with scaD. So these are things like vascular hair loss, Danlos syndrome, Marfan syndrome, Louise de syndrome, possibly studios and thermal has to come and some other arterial open these that can be found in our associated with mutations in the genes for which we already have panels And approximately 5-8 of patients look scared will have one of these. Now, if you think about it, it's relatively low yield and the patients that I've cared for who have had scared in the context of one of these diseases often already knew about their disease before they had their scared um, commonly because of their family history or the other clinical manifestations. So I do discuss this with patients. I do routinely offer it to patients, but the yield over all of the genetic panel testing with the typical arterial apathy panels for some of those mutations. The overall yield is low in this group but yet sometimes worth pursuing in part because it will affect management in terms of monitoring as well as counseling of the family members when we think about scat occurring in the families. So we currently have this Mayo clinic scad registry currently with over 1300 patients who have confirmed scad on imaging. And when we look at all these patients, only about 1% of them have a family member who's also had a scad. Now a larger proportion of them will report things like, yes, my Brother died of a brain aneurysm or I have a cousin with fiber muscular dysplasia. But 99 of them do not have a family member with Scott. And we did publish this a few years ago. At that time we had a lower number of total patients, but we had five familiar cases among a little over 400 enrollees. And interestingly, you can see here that the relationships were varied. We have mother daughter, identical, twin sister sisters, aunt, niece, first cousin pairs. Um and it really this implicates complex genetic pattern. So both probably recessive and dominant modes of inheritance. We already commented about the apologetic component that may be playing a role in addition to environmental factors that might affect that. Um, and certainly this is something we're still looking at within our bio repository. This is a question I get a lot. So I put the slide in on this and this is a recent publication that we put out. It's really um focused using the Olmsted County population. So that's a limitation in regards to generalize ability. But we looked at auto immune disease among patients with scad to match controls in the population. And 11 of the scab patients had autoimmune disease with the subtypes below most of it was thyroid disease. And compared to the controls, we were matched about roughly 3-1. Um there was a similar percentage with autoimmune disease, so it was 12%. And even when we adjusted for things like race and body mass index, autoimmune disease was not associated with an increased odds of scaD and scab patients. Also, we noted, had the classic auto immune disease, but we didn't really see a strong signal for auto inflammatory autoimmune disease. So this study certainly has limitations, but it is a population based data set and really what it tells us is, yes, patients, this cat can have autoimmune disease but it doesn't seem to be of higher prevalence. So whether or not they're coexisting conditions versus um the autoimmune disease triggering the scad. I don't think we can say for certain but we do not recommend routine uh screening for autoimmune disease unless a patient has other clinical signs and symptoms to suggest that's important. Doing. And just as an additional step to this review, we looked at the key uh gos findings from our scad cohort and then we went and looked at the studies that were performed for autoimmune disease to see if there was any overlap and there was not um rather the only overlap that we could find which is we already knew about was the scat in an FMD overlap. And then the fast fact 5 # five is dedicated outpatient follow up is recommended for patients with scad for some of the reasons that I mentioned. But there are even more reasons. So, life after SCAD. So first thing first after, at the time of dismissal, it's important to refer a patient for cardiac rehabilitation. This has been both shown to be safe and beneficial to patients with SCAD, both from data here, but also Canada. And when we pull our registry patients about why they didn't go to rehab if they didn't happen to participate. The most common reason was actually failure on our part. It was because they didn't receive a referral for cardiac rehabilitation. So I do think that we can do better for our patients in that regard. I will mention that chest pain following scott is common. It could be a whole talk in of itself. It can be one of the greatest trials that we deal with. Usually the first few months are the most difficult. Many patients do start to improve of medication modification and perhaps even healing of their scad. However, there are some patients even years out who are struggling with symptoms, some of whom have normal looking at a cardio coronary arteries and follow up angiogram. And it can be quite the challenge. Of course, there are mental health concerns that arise that includes anxiety, depression, post traumatic stress disorder. There are reproductive concerns and I will go into this a little bit more. But typically in our current practice, although we really have no data to tell us this is the right thing to do is we avoid exogenous systemic hormones when possible. So if we have a postmenopausal woman who wants to be on replacement therapy with hormones, we try to discourage that or lean more towards the topical formulations if at all possible. For women who are trying to determine contraceptive options. For instance, um We'll treat perhaps with a marina, you d but try to avoid the systemic oral contraceptives. Um Certainly mineralogy can sometimes be a problem we see in clinic, particularly for those who are in dueling and platelet therapy or anti coagulation. Um I already mentioned for contraception, progestin I'd is something that we do use patient or partner serialization are also considered. We do discourage pregnancy, but for our women who have had scad of childbearing age, this is a big topic, especially for those who want Children. So I'll go into that a little further. Um and migraines are common, so we have to have to adjust our medications. So when the patients are placed on beta blockers many times, that does help with the migraines. But as you can imagine, nitrates make them worse. So I always ask every scared patient about their migraines to help me choose what medications to try to manage their chest pain with. Um And I won't go into this in great detail in the interest of time, but for those patients with recurrent chest pains, there is a very nice algorithm currently published in the H. A. Scat statement and then uh it was also included in the recent Jack summary um of scad with greater details about maybe how to approach some of these patients, because this is one of the most challenging aspects of caring for these patients in the outpatient setting and for the patients themselves. Um there are moments of anxiety when they're trying to decide, okay, is this my usual chest pain? Is this reflux? Is this anxiety? Is this another heart attack? I know scott can occur again, so it can be a very challenging to navigate. Um But I will talk a little more about pregnancy after scott because this is a common question have been receiving recently, and we do have a recent publication on it. Um So this publication here was from 2015 and only was eight patients with pregnancy after ScaD. And we found that most patients did well except for one who had scad recurrence that two months postpartum and it was a significant recurrence. Left main multi vessel disease. L. A. D. C. Um They tried to treat per cutaneous intervention, didn't work well, ended up going to emergency bypass surgery. She ended up getting through. That currently is doing well, hasn't had any more events, but there has been some PTSD. Um and a lot of recovery. Um Since that study, we did recently published another study again, small numbers 23 women, I believe, 32 pregnancies or so. Um but I'll show you a little more. So We looked at 990 women with completed surveys and abstracted records in the registry. 354 of them were of non childbearing status of time of scat. So they were excluded. We did a cohort time to analysis study which included 636 participants of child bearing potential. We also did a case series review of the 23 women who did have pregnancy after Scad. And then we did a nested case control analysis. So what we did is we looked at patients with confirmed recurrent scad and we matched those two controls and these were women of childbearing age without recurrent scad. And then we looked for any difference in the prevalence or history of pregnancy after scab. So focusing on the results of the Cohort analysis. So we had 636 patients. Now, we use two definitions of recurrent scad because there's some thought that maybe the early recurrent scott is actually one and the same and just a progression of the same initial process. Um So if we include the ones with the early recurrent scad, there were 122 patients if we restricted it to after a one month timeframe, Um it was 97 patients. Um and that one month was arbitrary by the way. Um and at five years the recurrence was approximately 15%. Um and pregnancy after Scott did not seem to associated with those who had recurrence when adjusting for Agent 1st Scott, you're at first cat and fiber muscular dysplasia. When we looked at the case series, there were 23 women with 32 pregnancies. Most of them were older mothers at age, 38 years at the time of their pregnancy. After scad seven of them had a history of postpartum scad, five of them had more than one postcard pregnancy and two women ended up having another scad. One of them was that woman in that very initial series. So we followed up with all those eight women called them all and then or saw them in clinic and then included them in this cohort. Another one, it's not in the original cohort, but her recurrent scout was many years after her pregnancy, so not thought to be directly related And then in regards to the nested case control. So we identified 92 cases with recurrent scad. We used that definition of a greater than one month. We looked at 158 matched controls matched as follows. And the women with recurrent scad were not more likely to have a history of pregnancy after scad when compared to those without recurrent scad, the non significant hazard ratio. And actually there were more subsequent pregnancies in the control group than the recurrent group. So what does this tell us? Um Well, one we did find that most women tolerated pregnancy and lactation after scad without evidence for increased risk of scad recurrence. And this study really suggests multiple contributors to scad recurrence. So it's not just hormones or just the pregnancy. But being an author of this paper and dealing with the data, this is small numbers and I'm going to tell you to interpret these results with extreme caution. Um selection bias may have played a role. It was a small total number of women and there are many unmeasured confounding cure's in this study. And one example of that is all women had a normal ejection fraction at the time of their uh pregnancy after scott. And we know from other data that ejection fraction is closely tied to how women do with pregnancy after any cardiac condition. Um And so for that reason, the human dynamic and hormonal changes that occur with pregnancy, the severe presentation of pregnancy associated scab that I didn't get into. But we have shown that there is a difference that women who have pregnancy associates can tend to present sicker and this has been shown in our work. But others work as well. Then those who have non pregnancy associated scab and the lack of preventative strategies and ways to identify who might have another scat are really reasons why I still discourage pregnancy after scad despite this paper overall being somewhat reassuring, but I wouldn't take it as definitive. And so again, when I talk to patients because this is a very personal decision. And if you think about it, we counsel patients with other forms of cardiac disease. Congenital heart disease, for example, who are considering pregnancy. And so for those patients with scared who are considering pregnancy, these are the things they talk about. I talk about. Scout is associated with pregnancy and postpartum. So is thought to potentially contribute to risk. Even though my data didn't show that our our data didn't show that pregnancy associated scott is often severe and life threatening. And that's data that's been shown at multiple locations and following an initial scad episode, patients might have left ventricular dysfunction. Arrhythmias may require certain medications that may or may not be uh photogenic or at least need to be strongly reviewed and predictors for recurrent scatter unknown as well as preventative therapies. Now, how do I approach a patient who is still considering pregnancy? They say, hey, you told me all this, but it's worth it. To me this is an important life decision. Or perhaps you're already pregnant and want to keep the pregnancy and continue. Um in this case, it's really important to involve the multidisciplinary pregnancy heart team that includes specialists in cardiology, anesthesiology, maternal fetal medicine, really with a comprehensive approach to in visualizing the risk assessment. Counselling in the overall care plan for the course of the pregnancy, ideally this is done pre conceptually. That's not always the case in real life. It's always important to confirm the details of scad history and treatment and if you happen to be doing a referral from another institution, very important to look at the angiogram yourself and be sure it was absolutely a scad or at least know the ideology and what it looks like. Um it's important to know the current cardiac function, symptoms and medications. It's also important to review imaging for arterial apathy such as fiber muscular dysplasia. Um and then the mode and timing of delivery. I mean there's other things we go into but I'll keep it short for the interest of time are really per standard obstetric indications with a really a preference for you being at A level for maternal care facility capable of handling any cardiac emergencies that may arise. And then we do typically plan a vaginal delivery and your axle anesthesia if at all possible. So these patients we usually scheduled for an induction with vaginal delivery unless there's a reason not to do so from abstract uh concerns or reasons. So I'll pass the sun to receive, to summarize these top five facts. Fantastic, marissa. Thanks so much for for for this wonderful series of facts here. So I'll just summarize the top five and we have a question or two. We can interact with number one scott is not always obvious and consider it as the M. I. Etiology and news inter korean imaging for indeterminate findings. Number to treat conservatively when possible but do watch for early clinically significant progression. I think we stressed that scarred can occur more than once and you saw some recent data about that. FMD is a common association and dedicated outpatient for is recommended for patients with scarred. It really is important. Probably the most important slide is the next one I'm hoping I can get to. Which is really to thank all our colleagues here listed for who. We really got. A wonderful team at mayor. We're looking at scaD in as you've seen from the genome out to cardiac rehabilitation at all levels. Active ongoing. If you have questions or patients or people who want to talk to us about mayo scattered at mail dot E D. U. Is a great first point of contact marissa question that's come in. I'm going to read it out. You is a great question from laura de Michaela. I'm going to read it out to that. I'm going to actually put it in a clinical scenario. The question is in a case of scarred, complicated by cardiac arrest. Do you follow general guidelines for secondary prevention? So here you're going to put you on the spot here. 42 year old female has a V. Fib episode outside a hospital where she's walking rapid resuscitation as an L. A. D. Scar that's managed conservatively and she does fantastically complete recovery. Her f is 52 and she turns to you now and say doc do I need a defibrillator? So I'm going to tell you exactly how I counsel my patients in this regard, um with the disclaimer that there's really limited data out there to tell us what to do. So what I'm being guided by is consensus opinion discussion with colleagues who are considered to get experts, um review of the literature, um experience the incidents of um cardiac arrest. And scott is thought to be probably about one in 10 or so, just for perspective. So, if she was in the room with me in a clinic, the first thing I wanted to know is whether or not we confirmed that this, it was approximately perhaps uh Scott had healed. So I would consider doing a cardiac ct. And the reason I say that is because of the location you told me. But also I just want to make sure at least at a minimum review the angiogram and make sure I'm absolutely certain that this was scattered and that we're not missing say uh an atherosclerotic plaque that could be revascularization. Such as that case example I showed you second my current you know if this was atherosclerosis causing V. Fib arrest we would not be putting an I. C. D. With an ejection fraction that she has. I think you said like 52%. So we currently follow the heart rhythm guidelines society guidelines regarding placement of an I. C. D. So for this patient I would not recommend ICD placement considering those factors. However I would spend a bit of time talking to her about the pros and cons what we know and don't know. And in some cases for patients who desire this I do sometimes refer to my colleagues and heart rhythm to also meet with the patient and discuss. But my current practice is for that kind of patient not to implant an I. C. D. There may be others who do differently. I can think of a patient case where she had two scads that had cardiac arrest involved. And that was when we put an IcD. And even though the ejection fraction recovered um and I don't have a slide with this data but we do have some ip strict data that we saw complications in patients who had I see placed and in those patients who presented with cardiac arrest the majority of them, even if they had another scad didn't necessarily have another cardiac arrest. So it's based on some of that data that um we didn't go into during this talk. I mean I think you said it all we agonize over these decisions right? I mean these are really tough things. And perhaps as the technology improves, you know with these leaderless uh defibrillators, maybe the calculus will shift maybe our threshold. If we know that the complication rate of the defibrillator is much lower. Perhaps psychiatrist will shift. I think it's an important area to talk about. And maybe with more data, all of these are rare events. Maybe with as we pull the data in our registry, we may have some more information. I'm going to ask you another question that I can maybe give you first personal way. And if you want from Mohammed sharaf uh colleague, I believe if it's the same Mohammed sharaf. Thank you mom for your question. Great presentation. Do you think scared is a form of FMD that presents at the level of the coronary arteries? Uh, rajiv, I'd love your input on this too. So that that is yes. Especially for some we it's not common, but once in a while you see a coronary artery that looks very suspicious. And there are some reports in the literature that clearly describes this even with inter coronary imaging and has shown, I think it's compelling that there seems to be a lot of overlap of the spectrum. But rajiv, I'd like your input on this student. No, I mean, it almost has to be right with FMD that scattered throughout the body in patients with the section. The question is, how is it manifested the Corey arteries and and it's not your typical beating, Right? We looked at this a few years ago, you were part of that look back and we were really excited when we discovered that FMD link accidentally and other groups did the same. We thought, well, gosh, we must be seeing, seeing in the corn reality. We looked at tons of these and that typical beating was extremely rare. In fact only remember seeing in two out of a few 100 patients. So you don't have that classic FMD appearance at what was apparent when macaulay did that analysis of ours was the tortuous city does appear to be very strongly associated with FMD in the rest of the body. So my suspicion is that that's the form fruits. That is the manifestation of countries. A severe tortuous. It's all part of the same artery apathy. But in the Koreans it's something to do with the tortuous city which must reflect the architecture of the vessel somehow. And that I think could be a form Proust of FND. But a super interesting question. An area of a future study. Another question here you want to add. It's just going to add and you hear about the S curve. You know the looping and the crowd arteries and patients FMD too. And you know when we talk about these arterial open these, I can tell you when we look at some of these ct scans. Even the abdominal aorta sometimes is a nice big S. And so definitely it's really interesting actually on that note, your paper on that when when you mega prasad looked at that you call them Eva is extra vascular anomalies, abnormalities, extra coronary vascular of your mouth. That's what it was. Right. You just distress the point that it's not just kind of beat at FMD. We're talking about there's something funky going on, right? Yeah. Fantastic. The third question here is how about the cardiac rehabilitation guidelines? I think you touched on that It said guidelines. So, maybe you can maybe just underscore your thoughts on that. All right. And that's also an excellent question. Because what comes up a lot that I didn't touch upon is what can patients do afterwards, especially those who had exertion related scott. And we currently, I think maybe on this list of um participants in people contributing, we do have exercise physiologists involved, but we actually have a subgroup of team trying to decide how to navigate the cardiac rehabilitation. And we have a small series from here. But then the Canadian group also showed that cardiac rehabilitation after status safe. We often use as a protocol very similar to what we use with our other patients, but we're not afraid to continue to advance the patient as they go along. In regards to understanding that some of these patients at baseline, we're actually quite healthy and somewhere athletic or even elite athletes, although I feel like the elite athlete thing is not as common as I think we originally proposed or thought um I can get more into the activities. I have kind of a spiel that I give patients about what they should and shouldn't do, but it's really challenging. So I tell people they absolutely should continue to exercise because I've seen patients get so debilitated that they have exertion and Disney and I think it's from their heart, but it's just really from de conditioning and it's not only a problem for their mental health, but for their physical health too. And they will sometimes gain weigh in on beta blockers and so forth. So tell patients that came to, you know, have cardiac rehab, guide them into what they can do safely. And that also helps with their comfort level. Uh after that, you know, try to abide by the recommendations for regular exercise as we commonly give, but really aim for moderate exercise to stay within that board received exertion scale between 12 to 14 and try not to get into the red zone, so to speak. And when it comes to lifting, you know, if you look at our HS 2018 statement, which is essentially a collaboration of the minds from people from multiple academic centers. Um, there's a comment about restricting the weight for men is 50 and for women it was forgive was 20 or 30, but for some people that can be extremely restrictive. So I'm perhaps a little more um, or less restrictive and that I tell patients that you're able to breathe through uh weight lifting and comfortably even talk through it without doing a lot of el Salvador bearing down that is likely okay, you're finding that you're really bearing down hard or you can't talk through it. You're like, you know, straining. We don't want you to continue to do that repeatedly and I try to emphasis low amounts of weights but high repetitions. And so those are some examples ridge, if I'd be interested in what you counsel patients about, I do have some activities I discourage or at least discuss, especially for those with firearms through dysplasia, but like your thoughts. Yeah, I mean, I will just tell you my one liner is that I I feel so blessed to work here to have colleagues like you and and people in sports medicine, sports rehab, like Todd Miller, our cardiology colleague. So these high level athletes who have these really questions that I struggle with. I asked one of you guys with Todd militancy and and and we're blessed to have that Jeff, I'm going to ask if we can go back a slide to the summary slide. Somebody has asked for that, if that's possible, and I'm going to go the final question. I think we're in the last minute or so. Maybe I can take this one. The questions from an anonymous attendee is visa reactivity or constrictors? Divisor delays is different in scarred patients. Is the scene in the Cath lab in the corners of scattered patients. Uh Thanks Jeff. You can see the summary slide up there. I'm happy to take this one on because we did look at this actually interestingly, there's a published in the european Heart Journal acute cardiovascular care a couple of years ago and 10 patients who had a full on spasm study, invasive study in the Cath lab. 10 patients were scared from between months and years after their event. And interestingly it was a negative study. So there was no difference in microvascular function and no difference in provoke a ble spasm compared to match controls. So, of course this is a small number of patients selected group who had atypical or typical pain after scared. But there was no clear signal for there being in the field dysfunction or micro vascular disease in scad. That's my, anything you want to add on to that marissa. No, but I find that a lot of that, you know, I was commenting on how so many of these patients have chest pain symptoms afterwards and it's likely multifactorial and sometimes non cardiac. But so many of these patients do respond to your usual anti angel therapy. Um I often start in very low doses, especially for those who have migraines, for instance, like I'll do as low as in your 15, for example. Um and then the other thing I will comment on again when we're trying to figure out how the hormones play into this is, I do have a subgroup of women who can predict their men sees based on their angina and their chest pain will get worse about 12 days prior to onset of their menstrual periods. So interesting for hypothesis generation and I even have some patients where we up titrate their anti originals right beforehand and then we come back down on the dose afterwards. Super interesting. I think, set up for a future webinar on newer facts in scarred. Well, thanks marisa for joining me today. It's been a wonderful our with you and wonderful to get some questions and I want to thank everyone who has attended to really appreciate that. And they will be of course other webinars coming up in different topics from Department of cardiovascular Medicine. Thank you everyone for your time.