Dr. Kron describes the clinical presentation and management of patients with cardiac sarcoidosis.
I'm, I'm delighted to be here. I looked through, everyone logged on. I see a lot of familiar names there, um, and I'm so excited to be with you this morning. Um, so I'm gonna talk about, uh, sarcoidosis a little bit about our team approach, um, to patient care and research. OK. So, um, sarcoidosis is a multi-system disease characterized by the formation of non-casing granulomas in tissue. Most patients present with pulmonary disease, but the other organs can really cause a lot of damage and are very important. It tends to be a disease of middle age. It's really very rare in children, um, and mostly between ages 25 to 60. Skin involvement is common. I'll show you a few examples here. Cardiac involvement was thought to be quite rare at about 5% presenting with symptoms, but as our imaging has gotten better, we think it's about 25% of patients that have sarcoid involvement in the heart. So here are some pictures from our clinic, and you can see that sarcoidosis likes to form in tattoos or scar tissue, and you can see it on this one lining um the the tattoo lines. Good morning. How you doing Mark? So a lot of people think that sarcoidosis is a disease of African American women, and that is true in the United States. It does affect African American women more than other populations, but it really can affect anyone, and there's also higher rates in patients of Scandinavian descent. And Japanese descent as well. The lifetime risk is about 2% in African Americans and less than 1% in Caucasians, and you can see on this graph here that African American women have the most common occurrence of this disease. The etiology of sarcoidosis is really unknown. It's been postulated that there are infectious agents that lead to it, environmental exposures, there are clustering of cases among working colleagues, including nurses, firefighters, and Navy personnel, but there's also familial clustering as well. Well, very interestingly, there was a high prevalence of sarcoid or sarcoid-like pulmonary disease in firefighters and rescue workers at the 2001 World Trade Center attack in New York City. A later publication showed that it wasn't just pulmonary disease, it was extrapulmonary sarcoidosis as well. There's a genetic predisposition including HLA antigens, so we overall really think that there is an immunologic response to an unidentified antigenic trigger in genetically susceptible people, so there certainly is a genetic risk, but there's something in the environment that triggers an overactive inflammatory response. So let's talk about cardiac manifestations. It can range from asymptomatic EKG changes to sudden death. Heart failure is very common and can be both systolic and diastolic, or right heart failure related to pulmonary hypertension. Conduction abnormalities can occur in up to 60% of patients, and it can affect any part of the conduction system, but right bundle branch blocks are particularly common. Sudden death may be due to ventricular arrhythmias or heart block. And it may be the presenting symptom in up to 17% of patients. It's important to keep this diagnosis in mind because it's a tricky diagnosis to make, but it's also important to understand that it can mimic many other diseases, like myocarditis and arrhythmogenic right ventricular cardiomyopathy, and so it's, uh, you need to sort of keep a wide differential um uh for patients that have both ventricular arrhythmias and conduction abnormalities. So here's just an EKG example you can see this is a patient who presented with a right bundle branch block, and there's some of this fragmentation is what's sort of described in the literature that you have some fragmentation of the QRS complex and that's very common for sarcoidosis. So why do we care about this disease? Well, it can be very tricky. This is a story that one of our RD techs here pointed out to me many years ago, um, and this is a young woman who was 36 years old, shown here with her beautiful family, um, and she basically gasped in her sleep. Her heart stopped, um, she was resuscitated on the way to the hospital, but then ultimately died. And on autopsy she was found to have cardiac sarcoidosis, and her husband has been a champion for this and said there are really no warning signs or anything out of the ordinary. And of course in our field when we deal with sudden death it's so devastating not only to the family but to the entire community when you think about all of the school and the children and the people that knew and loved this family. So sudden death um is can be can be common in this disease, and so this is an important study looking at 351 cases of cardiac sarcoidosis in Finland. 262 patients had a clinical diagnosis, 27 were initially diagnosed with giant cell myocarditis that was later converted to CS and then 62 cases were found at autopsy by screening more than 820,000 death certificates, so that was quite a job. Um, a high degree AV block was the most common presenting symptom of cardiac sarcoidosis seen in 42%, followed by heart failure at 17%, and then aborted or fatal sudden cardiac death in 14%. So graphically, what does this look like? If you can see over here, heart block is the most common presenting sign, followed by heart failure and sudden death. When we look over here at the mechanism of death shown in this graph, you can see that sudden death is shown in green and heart failure and blue. And so this really highlights the importance of identifying who needs a defibrillator, with pacemaker capacity uh in this population, because arrhythmic death is so common, we really need to address it early on in the diagnosis to make sure that we're protecting the patients at highest risk. So to summarize this important study, sudden death is very common with AV block being the most common presenting uh sign um and sudden death being really a very important mechanism of death in these patients. I wanna take a minute here and look at the pathology because I think it's really important to keep this in mind when you're seeing these patients and when you're looking at the imaging studies. So here's a cross section of the heart with sarcoidosis, here's the left ventricle and the right ventricle up here, the dark tissue is healthy myocardium, and the white tissue is infiltration with sarcoidosis, and you can see that the whole septum in this patient is involved. This is someone with later stage disease, uh, this is flipped, so this is your left ventricle, here's your triangular shaped right ventricle with the trabeculations. This patient really had extensive fibrosis all through the myocardium. But when we look, starting at the base here, going down to the apex, it's important to keep in mind that this is a very patchy disease. So here's our septum, here's our left ventricle, this is the right ventricle over here, and the white areas are sarcoidosis involvement. This patient had extensive right ventricular involvement, um, uh, but then patchy involvement of the septum. Because the conduction system runs down the septum, and sarcoidosis has this predilection for the basal septum in particular that really explains why these patients have so much heart block, um, the other thing to keep in mind when you look at these pictures is how easy it would be in this patient who has extensive sarcoid involvement to have a normal biopsy, right? We come in from the right. Side, maybe we take a snippet over here on the septum, and even in this patient with very extensive involvement, we could easily have a normal biopsy, um, and so because of the patchy nature of this biopsies tend to have a low yield, and that's in contrast to a disease like giant cell myocarditis where it's much more diffusely involving the heart and biopsies are much higher yield. So let's look at the histology. Um, here we have the three different phases of histology early on, it's indistinguishable from lymphocytic myocarditis. The intermediate phase is the typical one we think of with active granulomas forming, you can see them here, and then late lesions are scar. We really wanna treat patients early on when we're in these inflammatory phases so that we can reverse the inflammation. At this point in time, we really don't have anything that can reverse the fibrosis, and remember fibrosis in the heart will lead to heart failure and arrhythmias, um, and so we want to treat it early on, uh, when we can. So what about screening? Uh, this is pretty simple. All patients with sarcoidosis should be screened for cardiac involvement, and it's critical to identify patients at risk for sudden death. Um, and so this is from the guidelines, the heart rhythm consensus statement that was published in 2014. We are currently updating this and so later on this year, uh. We're gonna be uh providing new updates uh for this guidelines, so stay tuned for that, but I really like this algorithm. I think it's simple, it's not that expensive, uh, and it makes a lot of sense to me. So anybody with biopsy proven extra cardiac sarcoidosis, pulmonary, ocular, or skin, they should have a cardiac history. An ECG and an echocardiogram. If any one of those is abnormal, particularly for symptoms we're looking for palpitations, pre-syncope or syncope, an abnormal ECG showing any degree of heart block, um, you know, any kind of Q waves that look abnormal, um, and an echocardiogram that shows any abnormality, those patients should go on to have advanced imaging either with an MRI or PET scan, and that might depend on what you're most comfortable with, what's available at your institution, we typically. We start with cardiac MR. Um, if all of those are negative, it's very unlikely that your patient has cardiac sarcoidosis. There's really been no studies saying, well, if we screen out negative, how often should we recheck? Um, I think it's pretty easy for these patients in our clinic, at least once a year we should ask if they're having palpitations or symptoms, and we can get an ECG and so, um, the patients, you know, we should continue to watch these patients because you certainly can get cardiac involvement down the road. Um, but on this initial screen, if they have none of those, uh, symptoms or abnormalities, it's unlikely they have cardiac involvement at that time. So I'm gonna go through a few cases that are gonna highlight some of the important challenges of managing these patients. So this is a 32 year old woman with diabetes and high blood pressure who presented with shortness of breath and dizziness. She had an echocardiogram that showed a normal ejection fraction. You can see here that she is in complete heart block, she has P waves marching through and a narrow QRS. She was uh morbidly obese and so a CMR could not be performed. We performed a PET scan. The PET scan that I'll show you next showed. Patchy extensive involvement of the heart muscle and also lymph nodes that were enlarged and inflamed um and so if you're used to looking at MR's um the anatomy is very similar um you have anterior view here and so this is the, the septum, the left ventricle, and here's your RV, uh, with your atria back here and you can see this patient has, this is a very common area to be involved, this patient has this basal septal involvement, but also extensive involvement of the LV and the RV importantly. On these PET scans, especially early on, we can often identify FDG positive lymph nodes, and you can see a few examples here. Um, we have excellent, uh, interventional pulmonologists here who will look at our scans and then can go in during an EBES, an endobronchial ultrasound guided biopsy, and go in here and target these FDG positive lymph nodes to try to help make a tissue diagnosis in these patients, and that's exactly um what we did. This, uh, patient underwent a biopsy and what it showed non-necrotizing granulomas. She received a dual chamber ICD and was discharged home on prednisone. So we're gonna come back to her in a few minutes, but I wanna talk a little bit about our sarcoidosis clinic. So this is really one of a kind in the region. We would love to see your patients. Um, we're very excited to share patients, so we, you know, we're gonna, uh, do our best to get back to you with how things are going, um, and continue to manage co-manage. The patient with you, and we were designated a WasoG FSR sarcoid Center of Excellence in 2019, um, and so this is a paper that we published as a group from our clinical team highlighting the features of a sarcoidosis center. So of course clinical care is so important, teaching, uh, training the next generation of people to treat sarcoidosis, research so that we can offer new treatments to our patients while also advancing the science. And then community engagement, this disease can be very isolating for patients, many of them who say to us, I never even heard of this disease, um, before I was diagnosed with it. And so I have a um a picture. This is actually from this Sunday. We had our 2nd annual sarcoidosis meetup. Uh, many of our team members are here. We have, uh, one of our rheumatologists, we have one of our pulmonologists, here's one of our, um, nurse practitioner pulmonologists, and this is Kelly Polly. She is. Is our sarcoid nurse and I'm gonna put up her email with my email at the end um because she's really the one who, who makes the magic happen and and and gets everybody in for all the studies and the doctors that they need to see, but the other the people on here are our patients um who came to this to sort of meet one another and and and um you know, join the community so um if we send our patients our way, this is something that we would, um, you know, love them to come to next year. So, um, this is also from that publication. I think the key point here is that the patient needs to be at the center. One of the things that's so challenging for our patients is the care is very fragmented. Their pulmonologist is, you know, points to the heart doctor for why they're short of breath. The heart doctor points at the lung doctor, um, and the patients get sort of lost in the shuffle. So we really try with all of the specialists that these patients, not, uh, each patient may only need to see. You know, a handful of these different specialists, um, but we try to keep the patient at the center and you know this can involve anything from ophthalmology. We have a neuroimmunologist now on our team, Doctor Connesario, who's just wonderful, um, and so if you have your patients seen here, we will do our best to involve any of the experts that we need, um, to really help manage the patient, um, you know, as a group. OK, so at 1 month follow-up in clinic, um, our, uh, our patient, our young patient who presented with heart block was 99% ventricularly pacing, um, but when we extended her AV delays, we found that she actually had improved, uh, conduction, and so this is what her EKG looks like at at clinic in one month, and you can see she still continues to have first degree AV block, so she's, you know, healing but not perfect. She maintained her narrow QRS but she's on the mend here. OK, so let's talk a little bit about devices in these patients. When um a patient presents with AV block, it's important to implant a device and we'll talk about which one, even if the AV block reverses. So we know that some of these patients can have intermittent heart block and heart block that gets better with steroids, but because it can be unreliable, we definitely want to implant a device early on in the course for these patients. Immunosuppression can be useful in cardiac sarcoidosis patients with high degree heart block. And then a very important recommendation that is sort of special to the sarcoidosis group is that ICD implantation can be useful in patients with cardiac sarcoid and an indication for permanent pacemaker. So if your patient needs a device, an ICD is almost always the right choice, regardless of ejection fraction. And I think this is really something that takes a little bit of time to wrap our heads around. We're very used to. Weighing ejection fraction very heavily when we're determining if a patient needs a defibrillator, but I'm gonna show you some data as to why um we don't really worry about the EF in patients with heart block, we wanna put in a defibrillator. So this is again from the finish group, 300 patients, 143 presented with high degree heart block. Either Mobic's 2, second-degree heart block, or 3rd degree heart block. They followed these patients over about 3 years. They divided the patients into 3 groups that you can see over here. Lone AV block patients was like our patient that had normal ejection fraction. They had these middle patients here who had EF 30 to 50%. And heart block, and then the final group with heart block had either very low ejection fraction, less than 35%, or had already had ventricular tachycardia, so they put the secondary prevention patients in this group. OK, so how do these patients do? These two graphs here, the one on the left shows sudden cardiac death, and the one on the right shows sudden cardiac death or BT. I think it's not surprising that in red, the patients with VT or very low ejection fraction did the worst and had the highest incidence of sudden cardiac death, but when we look at the other groups, in blue is lone AV block, and in green is that sort of middle of the road. It's important to see that the lone AV block patients really sort of did the same as the patients who had a moderately, uh moderately reduced ejection fraction. And these patients still had a significant risk of sudden death. The same thing is sort of seen over here that the patients with BT or very low EF did the worst, but these other two groups didn't do great. And so what are the numbers for that? If we look at the patients here, these are normal ejection fraction. Patients, their 5 year risk of sudden death or VT is 24%. So when you take into mind, this is a group of middle-aged patients with normal ejection fraction, I will argue that this is a very high risk of VT or sudden death. So the take home point of this is that AV block because of cardiac sarcoidosis is not a benign condition, even if it presents as the only manifestation of cardiac involvement, and so it's interesting the consensus statement had made this recommendation before, uh, sort of based on more anecdotal data, um, but the authors here summarize that the consensus recommendation to implant an ICD whenever permanent pacing is needed seems well founded. And so the exceptions to that might be a person who really didn't want it or if there were significant comorbidities that prevented uh mortality of at least one year with good quality of life. OK, so what about screening for cardiac sarcoidosis and special presentations? This is from a Canadian study that looked at patients, uh, middle-aged patients less than 60 that presented with Mobit's 2 or 3rd degree heart block. And keep in mind these patients had no prior history of sarcoidosis in any organ system. And they screened them with PET scans and found that 34% had cardiac sarcoidosis. And so the guidelines recommend uh scanning or screening for cardiac sarcoidosis in anybody younger than 60 that presents with unexplained heart block. And so here I wanted to show some of the studies that looked at the effects of steroids on AV conduction recovery. Now, unlike some of the cardiac, uh, STEMI trials and those kind of things that have a lot of patients, our field is really challenged by small studies, anecdotal data. We're trying to advance the field, but it's a very tough population to do research in. Um, and so when you look at these numbers, you know, here we look at the bottom, these are the number of patients that were treated with steroids for heart block. We have a total of 57 of those, about half of them had AV block recovery, and then patients that did not receive steroids only. 16 patients and none of those patients had recovery. So you should implant a device even if there's reversibility because it can be unpredictable and ICD is almost always the right choice regardless of the ejection fraction. So back to our young woman, when I followed her up over time, um, she continued to have improvement. You can see here that her PR interval has actually normalized. We got her off of the steroids, and that's one thing we really work to do in our joint clinic. We have uh multiple rheumatologists on the team now who are just wonderful and as soon as we start steroids, we usually ask how can we get you off of these steroids? Often with methotrexate, but sometimes with other immunosuppressants as well, um, but we wanna try to get patients off the steroids with something, uh, longer term that's safer, um, in terms of side effects. So she was started on methotrexate, which is a great choice for her given her obesity and diabetes, um, and she's been on prednisone now for many, many years. I still see her in clinic and she's doing very well. So the next case I wanted to show is sort of a different presentation. This is a person, a woman who presented with BTSTORM. So she's a 60-year-old woman with biopsy proven sarcoidosis. She had a reduced ejection fraction of 30%, a right bundle branch block, and received a CRTD. She suffered from BT storm, underwent a BT ablation 2, failed sotalol, and now was put on amiodarone. She received another ICD shock while walking. Um, she did have improvement of her ejection fraction with therapy, standard heart failure therapy, uh, and her. Was now up to 50%. Her most recent PET scan showed no active inflammation. And so I wanna go through some of the possible treatments for VT in sarcoidosis patients because this is one of the most difficult patient populations to treat VT in. So here's the MRI from this from this patient again to orient you. It's very similar to the PET scan. We have our left ventricle here, our right ventricle here, this is the septum, and the thing what we're pointing to with this arrow is this patient has um an aneurysm right in the septum here, and this can be very arrhythmogenic. We don't see these often, but this is something that's well described. You can sometimes even see it on echo um and so we were concerned that this might be uh the source of her VT. So in terms of arrhythmia mechanism, re-entran arrhythmias are the most common uh that occurs around granulomatous scar, but there are case reports of triggered activity and abnormal automaticity in these patients as well. Active inflammation may play a role in promoting VT and that's something that really we'd like to try to treat before we take these patients to the lab for ablation. We try to treat the inflammation first, uh, and then go ahead for um for the ablation because we feel that the lesions will heal in better, um, and then we've sort of taken the active inflammation that may be triggering arrhythmias out of the picture. Some studies suggest that there's a benefit of immunosuppression, and there's clearly cases well described that most of the ventricular arrhythmias get better with immunosuppression, but it's important to realize that in some cases, the steroids can actually worsen ventricular arrhythmias or lead to aneurysm formation. So when we talk about anti-arrhythmic drugs, we typically start with sotalol and amiodarone. Sotalol is usually my first line agent for these patients, I, you know, because it's a little bit better tolerated than amiodarone. Amiodarone is challenging because it affects, uh, some of the organs that we worry about most. With our patients, so you can have liver, pulmonary and ocular side effects, and these patients may already have disease in those areas. That said, if you have intractable arrhythmias that are not responding to other agents, uh, this is certainly something that we will use in these patients when weighing the risk, uh, benefit ratio. Quinidine can certainly be considered in these patients. Um, the class one agents we, uh, previously were very cautious about. I'm still very careful with them, um, but I think that flecainide and propafenone can be used with caution, um, in these patients, there's not a lot of data, and I really only use them if the patient has a defibrillator. But I've had some patients with PVCs that have responded very nicely to flecainide. OK, so let's look at some of the ICD trials. I'll tell you some of the data that was this is one of the first things I um did, how I got involved, um, in sarcoidosis research, but there's some other important data here from the Penn Group and the University of Colorado. Um, in our study, we had 235 cardiac sarcoidosis patients with defibrillators followed over about 4 years, and the annualized appropriate shock, uh, shock or ATP therapy rate was about 9%, and that's similar for these other studies, so probably between 8 and 14%. Adverse events were quite high in this group, but you need to remember that this involved some earlier patients who had um some leads that were recalled. Um, so I do think that this patient population has a high rate of adverse events, but some of this is just, um, uh, sort of a sign of the times that there were some recalls, um, leads at that time. It was the time of Fidelis, uh, lead recalls. That said, I do think we need to be careful with these patients. They're high risk for infection because they are immunosuppressed. They're also high risk for inappropriate shocks because they're young, many times they're sick, um, and are often on many other medications as well. OK, so one of the best predictors of ventricular arrhythmias in this patient population is. Late gadolinium enhancement on MRI and so MRI has really proved critical in these patients to help us figure out first of all, who needs a defibrillator and who's highest risk for having uh ventricular arrhythmias. But one of the challenges is that it's not really been quite defined how much scar is too much scar, and I'm not really sure that we quite have the answer for this yet. In the 2017, ventricular arrhythmias got. Guidelines, they recommend that patients with an EF greater than 35% should still get a defibrillator if there's evidence of extensive myocardial scar on MRI or PET scan, but they really do not define how much is extensive myocardial scar, and many centers do not really even report the the burden of scar, and apparently it's also very dependent on how the scans are. Red as well. There have been studies that looked at a scar cutoff, a late gadolinium enhancement or scar cutoff of 20%, 21%, 1 that looked at about 8%, and so I think the jury is still out. There was a recent publication that uh ended up with a scar tissue of about 10%. I think the number's still out, but one thing I wanna show you is that it's not only the amount of scar, it's also where the scar is located. Um, and so this is a really important recent study that looked at 504 patients with histologically proven sarcoidosis who underwent CMR and they sort of put them into different categories of, uh, up top here normal EF and no scar tissue. Abnormal EF but no scar tissue shown here um on this uh little diagram um and what they focused on here was this pathology frequent LGE. The LGE um uh pathology frequent uh or pathology rare was based on the frequency of cardiac damage features on growth, on gross pathology assessment of the heart and the patients who had sudden death or cardiac transplant. And so what this pathology frequent definition included. Was LV subepicardial, LV multifocal involvement, septum, or RV free wall involvement, and when we look at the outcomes of these patients, you can see the pathology frequent is shown here on top, this is cumulative incidence um uh it was like a cumulative incidence I believe of um heart failure and and arrhythmic endpoints. Actually, I'm sorry, this, this graph is just for arrhythmic endpoints. These patients really were the ones who, excuse me, had a significant. Arrhythmias. The other groups that had no significant LGE or pathology rare variants really had very, very low risk of ventricular arrhythmias. Um, this is an earlier study that we did with University of Michigan, um, that looked at right ventricular involvement and in this case, these patients had sort of moderate, moderately reduced ejection fractions and we looked at adverse events and you can see here that patients had that had no right ventricular involvement here did much better than. Patients that had RV involvement and so that RV involvement is felt to be very arrhythmogenic and in multiple studies has been correlated with poor outcomes, and so it's really important that not only the amount of scar tissue, but the location is really very critical for these patients in terms of defining arrhythmic risk. Hi, um, and so here's an example of what an MRI might look like. We'll show, take a look over here. We have again your LV, your RV over here, and in this case, the white areas are showing the late gadolinium enhancement. This patient has patchy involvement of the septum, which is very commonly seen, but also over here we have some lateral wall involvement and some right ventricular involvement as well. OK, so, uh, management with, uh, these ventricular arrhythmias can be very challenging. Um, these were, these are some early studies that showed, you know, these are very small numbers of patients, 8 or 9 patients in these, but I wanted to point out, these are some very, really big centers that did a lot of VT ablation, can see that the recurrence rates are really quite high, 75% in one study, 44% in another in another study. Um, had recurrence rates and so, um, you know, some of the findings from the, this, uh, these studies were that most VTs are reentrant, um, and that many will require an epicardial approach as well. So I wanna bring you back to our 60 year old patient who had recurrent shocks from their defibrillator, and remember the EF had improved and the PET scan showed no active inflammation, and so they were taken to the lab where there were two ventricular tachycardias, uh, one. Um, was right bundle, one was left bundle morphology, so sort of two separate BTs. The end of the epicardium was mapped and really showed normal voltage, and then the endocardium was mapped and showed low voltage areas, uh, in the mid septum, and a large septal aneurysm in this area that correlated to that aneurysm we saw on the MRI and so ablation was given in the LB septum and also in the RV basal septum. Um, at the end of the case, no BT was inducible with triple extra stimuli, and so let me show you this electroanatomic map, and so this is looking at the LV septum with the RV peeled away. And so for those of you not an EP not used to looking at these maps, the, the. Purple area shows healthy myocardium. The gray area, um, is sort of dense scar tissue, and this is all the, the colored areas sort of scar tissue here and so we're looking at this area of the aneurysm and you can see a lot of ablation was delivered in this aneurysm. OK, so, um, let's talk a little bit about some of the research infrastructure and then I think we, if we keep going here, we're gonna certainly have some time for questions, um, so the Cardiac Sarcotosis Consortium is something, um, that has been going on now for over a decade, probably almost 15 years, um, it is an international multi-center partnership that was founded in 2011, we had our first meeting at. Heart rhythm, it is a web-based, uh, registry, uh, with many centers involved. I think we have more than 25 centers from around the world that are contributing annual data. It is housed, um, uh, with secured data at the University of Michigan, and Thomas Crawford at the University of Michigan manages this, and we have wonderful statistician, um, and team there that helps manage the data. Um, and so these are some of the goals, um, of the consortium, one of the most important of which, um, is to establish this global community of researchers, uh, and so if this is a map of the consortium, you can see here that many of the centers are located in the United States. But we also have collaborate collaborators in Europe, uh, and India, and then a couple of centers in Japan as well. So let me show you some of our BT ablation data from the consortium, and this is published by Doctor Bogan, um, and I, I think it was published in Heart Rhythm, um, and it looked at 158 patients with CS, um, the mean age was 52, again, supporting our idea that this is sort of a disease of middle age. Uh, from 16 centers nested within the, the cardiac sarcoidosis consortium, and the primary outcome was a composite of VT recurrence, heart transplant, or death. VTSTORM was eliminated in 82% of patients, and ICD shocks, I'll show you this on the next graph, was significantly reduced post ablation. The word of caution though is that 1 year and 2 year survival free from this primary composite endpoint was only 60 and then 52%. So VT ablation certainly can reduce shocks and it's a very important piece of man. Managing particularly ventricular storm, so pre-ablation, um, this is a little bit fuzzy here, but pre-ablation, these are the number of ICD shocks compared with postablation. Not every single person did better, but overall the number of shocks was significantly reduced. And so this is a really an important, uh, ablation is a really important part of managing these patients, but this I think was a really interesting study of 780 non-ischemic cardiomyopathy patients, and the centers that contributed to this were very big ablation centers, so they looked at VT recurrence after ablation adjusted by etiology. So you can see here they have myocarditis. This is shown in purple, they have hypertrophic cardiomyopathy shown here in gray, and the disease process that had the highest rates of recurrence is shown here on top in red is sarcoidosis. So it's just a word of caution, these patients are very complicated to manage, um, and they tend to have multiple ventricular arrhythmia circuits, um, and they're just, they're just challenging patients to manage. So I'll spend just a few minutes talking about a couple ongoing and completed studies. As I've alluded to, it's very tricky to do um research in this area. The patients are complicated with with multi-organ system disease uh and it's a rare disease which makes it hard to recruit patients. The CASM study is being led by David Burney up in Ottawa, um, and this is really the, the largest randomized controlled trial in this field, uh, and it's underway right now. um, the hypothesis is that low dose prednisone and methotrexate will be non-inferior to standard dose prednisone for treating people. With newly diagnosed cardiac sarcoidosis, and so this is a 6-month trial. Patients are randomized to either prednisone, typically 30 mg a day for 6 months, or they go on a prednisone taper for 3 months and then methotrexate for 6 months. The rationale for that design is that methotrexate takes a few months to kick in. In about 3 months to really reach its stride and so it's important to have prednisone coverage for those first few months, but again it's a non-inferiority study, um, this study is currently underway, um, we're actually only have about 7 more patients to enroll, um, before we're gonna start finalizing the data and so this is gonna be a really exciting study that um is gonna hopefully be, you know, coming out with data in the next couple of years. And then I wanna talk to you about one study um that we have completed here um which is the magic art study and this is um um a much smaller study um here is some very early data looking at the NLRP3 inflammosome in patients that had active cardiac sarcoidosis. So these we had a few patients that we had pathology from that either underwent a heart transplant or LVAD, and we took that the core from the LVAD or the or the transplant, looked at. Under a microscope and stained it for um the inflammosome. Now the inflammosome is a macromolecular structure that sort of um produces interleukin one. Interleukin one is this uh is a protein that really plays a key role in almost every inflammatory process. It plays a role in sepsis. It plays a role in heart failure, um, and we show here that this inflammosome that produces interleukin one is active here in patients with cardiac sarcoidosis and you can. See here is a granuloma, and the granuloma here staining in pink is showing that there's inflammosome activation and so this is some of the baseline data that we use for um for studying interleukin 1 blocker in cardiac sarcoidosis patients, and that is this magic art study um this is some uh interim data that we published, uh, we had 16 patients from VCU and University of Michigan and what this study shows is that at 1 month time, this is a very early study, it showed. Significant decrease in inflammatory biomarker which was C-reactive protein, while the patients who were standard of care, they were on other medications for sarcoid, really did not have a significant change um in the inflammatory biomarkers, so this is uh not ready for prime time uh in terms of treating with IL-1 blockers, but certainly some exciting preliminary data that is encouraging us to do more and we're currently designing a longer term study for uh an interleukin 1 blocker. So before we open up for questions, I wanna sort of leave you with these take home points. All patients with sarcoidosis should be screened for cardiac involvement. It's very important to identify these patients who may be at risk for sudden death uh and need treatment for heart involvement. All patients with unexplained heart block under age 60 should undergo a workup for cardiac sarcoidosis with either PET scan or MRI. And then finally, patients with cardiac sarcoid are at increased risk for death from bradyarrhythmias and tachyarrhythmias. And so I sort of show this up here, proceed with caution. I, these are challenging patients and we would love to co-manage them with you, um, and so please. you know, send them our way or call me, um, I'll, I'll pop up my number here but I think it's on the last slide, um, but we want to manage these patients with you and we're really excited to, you know, to treat them with our team approach and then also involve them in some of the research studies that we have going on. Um, I have so many people to thank so many people I've been so lucky to work with my, my sarcodos. This team here is just amazing. I love working and learning from these doctors, uh, every day, and we have a lot of research, uh, collaborators as well, um, and so here is my email and my phone number, and this is Kelly Polly, she's our sarcoid nurse, you can message us about patients, you can call me, um, and we're happy to, to see these patients with you, um, thank you so much and I'm delighted to take some questions.
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