 I'm honored to be speaking with among all these wonderful cardiologists that I actually look up to, so this is great. So I have to give a little credit to Dr. Stainback who actually has given similar talks and discussions about Takasubo and he kind of helped me figure out what I was going to do and the approach I would take to presenting Takasubo to you guys. So here's my outline. I'm keeping this a little more clinical to keep it a little fun. So we have a patient case that I'll be talking about and then kind of bringing the etiology and the pathogenesis and all that stuff later on. So this particular case was a 71-year-old female. She was actually a retired pilot. She lived alone. She had chronic medical conditions as you can see here, COPD, hypertension, dyslipidemia, trifecta. She was a smoker. She had recently quit actually but she didn't drink alcohol. She presented initially to the ER because she was short of breath. She called 911. It was pretty sudden onset and she was transported here to St. Luke's ED. They quickly diagnosed her with pneumothorax by chest x-ray. She had a little bit of a white count. They called CV surgery. They placed a chest tube. Sounded pretty simple. They admitted her to telly. And this is, you know, the ED EKG, which was actually pretty normal, as you can see. After her chest tube was placed, she said, oh gosh, I feel so much better. They gave her some antibiotics for maybe some bronchitis and then they sent her up to the telly for her. On telly, she was actually doing quite well. She was stable. Here is just a picture of some EKG, some telly strips from her stay when she was there. Again, everything was going okay at this point. Fast forward about a week in hospital day 8 here. They could never really remove this chest tube. She had a persistent leak. It was just a complicated course. She was getting subcutaneous emphysema. This course was complicated by a UTI. So surgery at this point was probably frustrated like the patient and said, you know what, you just need to take you to surgery. And the surgery is obviously not a simple one. They were going to resect these blebs that caused her pneumothorax and then, you know, do a pleurodesis. This troubling conversation obviously caused the patient to feel terrible. And then she developed some mild moderate chest pain. So they got an EKG and the EKG had some changes that were concerning. So cardiology was called. So here this is the EKG initially they got when she was having this chest pain and shortness of breath. And right there in lead 3, you can see there are definitely some changes from her initial EKG. You see some elevation there, which is concerning. Here, this is another EKG that was obtained. When she was still having chest pain, you can see these ST changes have worsened. Most notably, you see there in AVF, the elevation is quite easy to see. I'm a first year fellow and I could pick that one up quite easily. Here we go, Hospital Day 8. She's clearly not feeling good still. And then we see this on the tele strip. And subsequent EKGs, again, very clear that we're concerned for a STEMI here or there's ST elevation that is developing. It's not going away. So here we obviously when anyone has ST elevation and has a good story with no other reasons to have it, we need to take them to the cath lab. So here this is her coronary angiography from the cath lab. And we see here, there's the image of the left system with really non-obstructive coronary arteries, but the timmy frame count is 31 and 19. Not super impressive, but on the right system you see here, again the coronary looks okay, but the timmy frame count is 41. Here is the money shot, obviously. And it's pretty impressive, again, for when we're doing the LVGram. She has a classic, beautiful picture of Takasubo cardiomyopathy. Here you can see her, let me get my little pointer, it's obvious, but in case, she has this really vigorous squeeze here near the base of the heart and then this huge ballooning at the apex, which is actually pretty awesome and impressive. Here again is just the diagram, and it was actually a pretty nice diagram they drew here of this Takasubo-like image we saw in the LVGram. And here her coronary is again really not impressive, just a mild plucking. So here Takasubo, where does it come from? That's why we call Takasubo cardiomyopathy that. It's a, if you didn't know, it's a Japanese octopus pot, and it's really perfect this imaging. It's like a replica of what these pots look like. And again Takasubo is what we say a weakening of the heart muscle, which leads to achnesis and aneurysmal dilatation or ballooning, apical ballooning, is another term we say we use often. Again the basal segments, the base of the heart is hypercontractile and can actually lead to an LVOG gradient. So here some other terms people use to describe Takasubo as a stress-induced cardiomyopathy. Again it's a transient LV apical ballooning, and transient is a really important term here because a lot of these people who develop Takasubo ultimately get better. Most of them do. It's often called broken heart syndrome as well because as I'll talk about later a lot of these people have either experienced emotional or physical stress right before the onset of their cardiomyopathy. It's also has been described as a neurogenic myocardial stunning, and again I'll talk a little bit about why later. This is an interesting point that 90% are peri or post-menopausal women, which is quite interesting. Here are some subtypes of the Takasubos that we talk about in the literature. We most classically see the apical ballooning, but again there's reverse Takasubo, so it's the opposite, it's exactly what it says. You have a hyperdynamic apex and then you have achnesis at the bases. The mid-LV Takasubo is a little less common, of course, and it spares the base in the apex, and your mid-LV, of course, is just quite hypokinetic. And then localized affecting the anterior wall, and you could see how that would propose or would pose a diagnostic dilemma in someone who has maybe an EKG and an echo that you get with these findings, and then you go to the cath lab and you don't see anything to explain your findings. So the acute presentation in general is usually for the majority in the emergency room, and they have a sudden onset of chest pain or chest discomfort and shortness of breath. Of course, most of them end up getting troponins and they're elevated. EKGs very commonly show ischemic changes like our patients did within the ST elevation. They also, interestingly, don't often show ST depressions, so it's mostly elevations. And again, they're always admitted as an ACS acute coronary syndrome, because that's what we would all do in someone with chest pain and elevated troponins. So this disease is actually quite new, and it was first described in Japan, the way it got its name, Takasubo, in 1990. Subsequently, we all kind of agreed that this was a distinct disease and we kind of caught up with them and began diagnosing and really describing it for ourselves. In 2006, it was formally classified as a cardiomyopathy, as a primary acquired cardiomyopathy. This here just shows from 2000, 10 years after it was initially described, kind of how the literature really caught on and people began being interested in describing Takasubos and what is causing it, or really being excited about having a diagnosis for these patients that just have a cardiomyopathy and we don't know why. So it really kind of blew up in the literature and the research at about 2006, and it's still ongoing. The Mayo Clinic has their diagnostic criteria, and these are listed here. So it's a transient hypokinesis. Again, transient is that very important word or dyskinesis of the LV segments without apical involvement. Again, you're cath and you do not have obstructive CAD or reasons to be having this cardiomyopathy by cath, at least obstructive angiography. And again, ECG abnormalities, SC elevation and or two-haven versions, and it's, again, not SC depressions very often. And then they always say you have to make sure they don't have a pheo or myocarditis, which can be also diagnostically hard. Here, this just discusses how the EKG cannot reliably differentiate transient LVA apical ballooning or Takasubos from ST segment elevation like we saw in our patient. Here again, they're just describing these ST elevations that you often see in patients that come in acutely and are diagnosed with Takasubo, and you wouldn't be able to say it wasn't a STEMI or an NSTEMI. Here is an interesting discussion about the biomarkers, troponins, in Takasubos. It's similar, the peak that you have is similar to that when you have an NSTEMI, but the BNP often is more elevated and more persistent than in a STEMI. And I don't think any of us really focus on BNP when you have someone come in or the trend in BNP when someone comes in with a STEMI or an NSTEMI, but that's an interesting finding. Maybe if you have a female that you are really, you think probably has Takasubo, you could trend this. Maybe they can't get angiography, maybe they have a contraindication and you would like to know if it is Takasubo or obstructive disease. And then the catecholamines are usually higher, which goes in line with the thought that this is a stress-induced disease. So the troponins, while they're elevated, they usually do not exceed 6 for the troponin TSA or 15 for the troponin ISA. And some of the literature here says if you do have levels that are higher than this, it's probably not Takasubo. So what is the role of imaging? And as this disease is found and kind of most classically noticed by the echo images or the cath images, obviously it's important. Imaging is an important part of this. We use the cath lab of course with the ventriculography or the LV gram. With this echo, we can use cardiac MRI and then myocardial perfusion imaging as well, the less likely to be used. The cath lab, again, this is what you will see. You will see normal coronaries. Less than 50% luminal stenosis is what they often see when they have patients who present with this. But you can have some obstructive disease and still have this syndrome. And again, cardiac cath is usually necessary if not you need to do it. It's a part of the workup. Echocardiography supports the diagnosis. You will see those characteristic wall motion abnormalities that I spoke about. Again, there are different subtypes, but most classically you're going to see that apical ballooning. Some associated findings in patients with Takasubo's LV thrombus. Obviously you have this big hypochymetic apex, which is a wonderful breeding ground for thrombidiform, especially if your disease is more protracted. That LV outtrack obstruction, again, is very common because you have that hyper-dynamic base of the heart. Which, again, would make you a little weary in using some inotropic agents or some oppressors in patients that might come in in cardiogenic shock with this syndrome. You can also have some mitral regurgitation or RV involvement. Those are less common. Again, on ECHO, it's a good way to verify that your patient has recovered. Usually in a month, a month and a half, you're going to reimagine these people. If they're in a hospital and they're improving or not improving, getting another ECHO is also useful. So again, here's our 71-year-old female. And here was her ECHO. It's classic apical hypokinesis here and this hyper-dynamic base. And you can see her outflow tract is actually small. And here's some color through that outflow tract. You can see some suggestion that the speeds are elevated. The velocities are increased. Here's just another good picture. So her illness was protracted like we said. She initially came in for pneumothorax, had turned into a mess of UTI and bronchitis and persistent air leak, and her repeat image was not better. It was actually looked a little bit worse. So cardiac MRI is another imaging modality that is used and it's a good one for it. It can help you confirm or it can confirm on its own if you see the classic findings. Again, the RV involvement or the RV thrombus detection is cardiac MRI can be good for helping you see this. This is actually, the MRI is probably key reason why it can be used because in when the gadolinium is given in myocardial infarction, you have the delayed subendocardial or transviral hyper enhancement. It's different patterns of the gadolinium that help you in this case. In acute myocarditis, you have the patchy hyper enhancement, which is classic for that. And then in Takasubo, you don't have hyper enhancement. You actually have edema. So this can be helpful in these patients where it's not clear cut or they have an atypical presentation of Takasubo. And here is some MRI, some imaging that will show you what you see here. And it's very clear here in this bottom right picture that you still have this apical ballooning and then this more contractile base. Same here. And there is no hyper enhancement. I think their beautiful picture is actually. So there's no scar. And no scar. Yes, no scar. That's like, you know, there's no real damage to the muscle. Just going for a few more images here. So the myocardial perfusion imaging, again, is something you can use. I don't know how often clinically that this is used. I think there are reports, they differ in a physician's preference as to if they think this is helpful or not, but it can be used. And this just shows the initial EF here. These are serial exams. So the initial EF of 29 and then, you know, two days later. And then 96 hours, it's a very fast, a very quick recovery. And then a couple, a little more discussion about the forms. Again, the typical form is 70 to 80%. Those atypical forms, again, very uncommon, that inverted the basal ballooning very rare, 1 to 2%. So if you see this, it's obviously less likely on your radar that it would be Takasubos. And you should maybe think about other things. And then 20 to 25% for the other types. And this just kind of shows you the segments that are involved in Takasubos and they used MRI to image them. Obviously, we aren't surprised that the basal segments are often not involved and it's mostly the apex here and some involvement of the mid-LV. This is an interesting case where the right ventricle was actually involved and you see that here. You have clear hypo or, you know, achinesis here at the apex and then the contracting basal segments. And here's the reverse Takasubo. I think it's a little hard here because you can't see the apex well. And this patient, this case was here, here with us here, but had an acute cerebral bed. So what triggers these, what triggers patients to have this? And again, I think I've described lots of words that we use stress-induced cardiomyopathy that would describe this disease and it's kind of the same. There's physical stress for sure, which undoubtedly leads to emotional stress, but then there's just emotional stress in itself. The most common described events are neurogenic events or, you know, cerebral events, strokes, bleeds, seizures are actually a big one. But there's also patients where they might just be experiencing grief or stress, and that's the only thing that you can really tie to their onset of their cardiomyopathy. This is an interesting comparison of the triggers in different countries. So here's California, so the U.S., versus Hiroshima, Japan. And it's quite interesting if you look at just the difference here. So singing in a public area or singing in a public space or playing a guitar in public, these are real examples that they attributed to the onset of the cardiomyopathy. Versus here, there's so much more, there's so much more like tactile, you know, like burns, seizures, death of two sons, a little more harsh. And I don't know if that speaks to the cultural differences, but it's very interesting to see the differences in geography and what people are attributing this cardiomyopathy to. And that gets us to the pathophysiological mechanisms. What really does cause this at the base of it all, at the cellular level or, you know, the muscle level? What is causing it? Today, we don't exactly know, which is frustrating but also makes for an interesting thing to study. So a couple of the proposed mechanisms is the stress hypothesis, the adrenergic stress hypothesis. You have excess catecholamines, which you find in patients with this, which can directly lead to the beta receptor changes and the cardiomyopathy itself. People suggest it's epicardial coronary dysfunction and vasospasm that could cause this. And this is quite interesting. Most of these patients are peri or postmenopausal. Some think it's an estrogen depletion or the lack of estrogen that your body was used to. And then, of course, the brain-heart interaction, which is undoubtedly a part of this, we just don't know exactly how, but they think that this catecholamine response has some involvement in it. But the brain-heart interaction is definitely there. Most of these patients have something going on. This is taken from actually the Takasubo Registry, which I don't know if you haven't just Googled Takasubo Registry, you should do it. It's multi-, many countries, many medical centers or hospitals or physicians. You can go on this Takasubo Registry and you can report your patients that have Takasubo. You have to tell your patients, of course. But it's this large registry, thousands of patients with patient data, and they are all working for the same cause to try to figure out more about this disease and what they can do to maybe prevent or help diagnose or help treat the disease. They also have their publications on this website that they the data that they got was from this registry. One of the interesting papers that they published was about microRNAs. They found, to get to the meat of it, they described the first time that a signature of for circulating microRNAs were biomarkers to distinguish Takasubos from STEMI. Now how clinically relevant is that now we don't check microRNAs in the ER, right? It would be kind of fun if we could, but we don't. But this is just showing you that there are cellular mechanisms and biomarkers maybe that in the future we might be able to use to make the diagnosis of this easier or to at least follow these patients and make the follow-up of these patients better. So, gender and triggering events. I talked a lot about this but again, for females there's a little bit of a difference between females and males. For females it's usually mostly an emotional event or they can't figure out what caused it. For men it's more of a physical event or a physical illness, a little more tactile event that causes them or that we attribute to them having this. 90% of current of these patients or Takasubo cases occur in women and again that mean ages is post-menopausal or perimenopausal of the patients that do meet that criteria for ACS that diagnostic dilemma you have when they first come in for women, 69% will have Takasubo's and then compare that to men where only 0.5% or less than 0.5% will actually have Takasubo's. Men when they have it they will more likely than women have an out-of-hospital arrest which I found quite interesting. Alright so treatment again why the registry exists we don't really know what the best treatment is for Takasubo's at this point it's extrapolated how do we treat normal patients who have decreased scallic function so in any patient with heart failure we give them an ACE inhibitor or beta blocker. If they have cardiogenic shock we're going to probably if they need it put some sort of advanced mechanical circulatory support. It's not common that these people come in cardiogenic shock but if they do that's something you can do again because of that LVM outflow tract obstruction inotropic agents are very difficult because you might worsen that obstruction and actually make them worse. Patients who come in with an LV thrombus of course are going to anticoagulate them you're going to make sure that they don't have any arrhythmias from their underlying prolonged QT which is common not common but can happen in these patients and then post-recovery of course if your repeat echo shows that their LV is back to normal most people stop that ACE inhibitor and say we'll keep following you. The beta blocker it's again controversial but they most suggest you can consider continuing that beta blocker so the prognosis again it's good most people most recover and they recover well. Mortality however it still is one to three percent for these people recurrent episodes and this is important actually we just had a patient in the hospital with this four years ago had Takasubo recovered beautifully EF went back to normal came in again in acute heart failure and had a recurrence of her Takasubo took her to the cath lab again because she presented like a stemmy and she was Takasubo so the recurrence is about ten percent they say and that's a four year recurrence rate here is a New England journal article I forget exactly oh here we go September of last year quite recent and it came from this registry that I was talking to you guys about they looked at all the clinical features and the outcomes of all the patients that they had in this registry which was huge so up here you see 1700 about patients and they took them down and they got their clinical profile they got their in hospital complications and they figured they tried to decipher what characteristics made some patients do better or some patients do worse so I'll spare you from trying to read this but the most interesting points of this article was more than half of the patients with Takasubo's had an acute former or chronic neurologic illness and that's that brain heart interaction that we know exists we just don't know exactly why consistently and this speaks to that point consistently histopathological findings in the cardiac tissue resemble in patients that died of an unexpected epilepsy or seizures or subarachnoid or some large event in their brain resembled those of patients who died during an episode of Takasubo cardiomyopathy so those patients that died from just a neurogenic event had very similar histopath histology that resembled these Takasubo patients and here are from that same article the data from the registry the death from any cause per patient year in patients with Takasubo's was 5.6% the rate of major versus cardiac events was 9.9% per patient year and the rate of stroke or TA was 1.7% per patient year the recurrence rate again per patient year was 1.8% with a span of 25 days up to 9.5 years to the first event so that the increased risk sticks with you even if it doesn't happen in 4 years down the line or 4 years down the line like the patient we just had and then interestingly men had an increased rate of death from any cause compared to women if they had prior Takasubo and this this point helped me in dealing with a patient that we just had in the hospital the use of Acer ARBs pretended a mortality benefit but a beta blocker didn't in patients that had Takasubo so if you put them both on both Acer and beta blocker the beta blocker patients or the patients who were kept on a beta blocker didn't do better the ACE inhibitor was the only thing that pretended any mortality benefit down the line so maybe keeping them on a beta blocker is not helpful and then with all of this are we under diagnosing Takasubo it's such a new disease a lot of these patients just get admitted with the thought they had a STEMI or an NSTEMI or maybe they had an NSTEMI and then they recanelized we do need perspective studies this is just going to show you that in patients who came in post-menopausal patients with an ACS at a community hospital non-ACS in 75% and Takasubo in .3% of those ACS with troponin and EKG with troponin and a clinical story but Takasubo in .6% about .6% of those it's pretty impressive actually so how you know how concerned should we be and what could we do to prevent Takasubo in patients who you might identify as high risk who is at high risk we don't know about that and then who really gets it like that comparison of the patient or the patients in Japan or the patients in California what amount of stress actually causes this heart-brain interaction or this emotional stress to become physical and this is just another example should this patient have Takasubo or should this patient have Takasubo again we don't know so here are some key points Takasubo is relatively relatively new it's I guess now 26 years later since its first was described 90% of the patients are women greater than 50 years old you have to have a clinical suspicion and if you look at that Takasubo registry website they have a little risk score so if you have a patient that you're taking care of who comes in with a troponin and ST elevation you can put their clinical features in and it'll say the probability that they have Takasubo and the data that they use from the patients they have the complications while they're not quite not that frequent they are real and you have to monitor the patients for them especially that alvephorombus and the hallmark if you have a patient with them as you can tell them they're probably going to get better and there are plenty of review articles and you can go online and look and read more about Takasubo and thank you very much for listening thank you