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Exploring HCM Diagnosis and Treatment Options: The ...
Exploring HCM Diagnosis and Treatment Options: Th ...
Exploring HCM Diagnosis and Treatment Options: The New Frontier of Cardiac Myosin Inhibitors
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All right, good evening. I think we're gonna get started. Let me just double check. Are we good to go outside? It is just about six, so I'm concerned we're gonna run out of time. Looks like there's still some people coming in. So when they come in, just try and make some room. We're gonna fill in. Thanks for coming this evening. We are excited to talk to you about exploring HCM, the diagnosis, and some new treatment options, really a new treatment option called cardiac myosin inhibitors. I'm sure you're all familiar with it, but we're gonna try and make you more familiar with it. I'm Matt Martinez. I'm a clinical cardiologist at Morristown Medical Center, which is part of Atlantic Health System. I'm the director of sports cardiology and the hypertrophic cardiomyopathy program there, and I am delighted to be on to moderate the panel with three experts in the field who are gonna educate us. I'm gonna have each of you introduce yourself, starting with Dr. Purvi Parwani. Hi, Purvi Parwani. I'm Ecolab director and imaging director at Loma Linda University Health in Loma Linda, California. Good evening, everyone. I'm Anjali Owens from the University of Pennsylvania, director of our Center for Inherited Cardiovascular Disease and the HCM program. Hello, I am Robin Bryde. I am a PGY-7, currently doing hypertrophic cardiomyopathy and sports cardiology fellowship at Morristown Medical Center under Dr. Martinez's direction. So we're gonna get started, but first things first. I'm gonna do this twice, so if you miss it the first time, but there's a QR code on the screen. I'm gonna ask you to take out your phones and scan that, and then when you do that, you're gonna put it on mute. Check your stocks later. I already lost. We have more games tonight. Take a look at that. Okay, and then we're gonna acknowledge that, our grant. So this is American College of Cardiology, of course, appreciates the educational grant support for this clinical spotlight session, and we are, of course, honored to be a part of all of that. Exploring HCM diagnosis and treatment options, the new frontier of cardiac myosin inhibitors is sponsored by Bristol-Myers Squibb. So I'm not sure if you're supposed to thank them or not, but we are thanking them for their support. And then one last time, for those who missed it, participate in the audience response system, because we have allocated, you've self-selected for which team you're going to be on. So when we get through our first two talks, then we're gonna do a quiz game, and each of you are sitting at a table, and you've been assigned to a team based on where you go, where you're sitting, and we are playing the quiz game, and we're gonna do a quiz game, where you're sitting, and we are playing for this. All right, Team Owens. So they asked how big, and I said, really big? Team Parvani, you are on the left side. You're gonna save us, right? Team Parvani. So I talked to Team Martinez, they wanted to congratulate the second, third, and fourth place teams for tonight. Thank you for participating in the quiz game. They don't know the answers, don't worry. So let's get started. Really happy everyone could be here, and the first couple talks are gonna be passive, and then the last one, of course, is the quiz game. We're gonna ask you some questions, and try and dig right in. So without further ado, I am going to go back, and start with Dr. Parvani. Thank you so much for the organizers, Dr. Martinez, for this wonderful opportunity, and thank you for being with all of us in the later hour. So my topic is Unmasking HCM, Using Imaging and AI for Diagnosis. So we're gonna start with two questions, pre-test questions. The link that you just scanned will be able to give you the options to select the answer that you think is appropriate. So let's start with this case. It's a 45-year-old African-American male that presents to cardiology clinic for evaluation of palpitations and chest pain with exertion. He's non-smoker and has normal vital signs in the office and reports no home medications. An EKG is done in the clinic, and is shown below the vignette, and based on this EKG, which do you think is the most likely finding present in this patient? Option A is hypertensive heart disease. Option B is severe coronary artery disease. Option C is hypertrophic cardiomyopathy, and option D is inferior myocardial infarction. All right, so weigh in for us. We're gonna get the answers when you get a follow-up email for this. We're not gonna tell you the answers tonight, but we're gonna sort of imply them later on anyway. But when you follow up for the survey, log in. Okay, 10 more seconds. Try and break 100. All right. Okay, I guess we have some room for improvement, but we're not gonna give you answers, sorry. We're gonna email it to you. Okay, so our second question, take a look at the chart. Okay, so our second question, take a look at this patient, 66-year-old male with multiple episodes of elevated low-level troponin, you know, called NSTEMI, chest pain, is referred to cardiology clinic. His EKG and transthoracic echocardiogram are taken and shown below. Okay, I'm gonna show you guys the options now. So based on this EKG and TTE images, what is the next best step to help clarify this diagnosis? LV strain imaging, cardiac MRI, cardiac CT, or you may say you are good and you don't need any further workup. Okay, so we're gonna show you guys the options now. Okay, so let's start the poll. All right, we're rolling now, over 100 already. All right, 10 seconds more. See if we can get everybody in. Okay. Okay, next, you're up, keep going. Okay, so these are my disclosure and I'd like to acknowledge Dr. Martinez for his help in preparation of this talk and for many other things in my professional career. The outline of my talk is we are going to speak about the HCM disease status first. We're gonna see the prevalence of hypertrophic cardiomyopathy. Then we go on and we'll discuss the diagnosis and the imaging modalities that we use for diagnosis of hypertrophic cardiomyopathy. We are gonna look at the limitation of these imaging modalities and where we fail to diagnose patients. Then we are gonna see the role of artificial intelligence, AI, in hypertrophic cardiomyopathy as it pertains to EKG and echo. And finally, I'm gonna have some take-home points for all of you guys to take home. So let's start with HCM disease status. So if we look at the prevalence of hypertrophic cardiomyopathy, it's thought to be one in 200 to one in 500 patients and actually only 10 to 15% of these patients are clinically diagnosed. So overall, if we look at this prevalence, only 15, there are almost 15 to 20 million patients that are affected worldwide with hypertrophic cardiomyopathy. So why there is such a big difference between the patients that we think are truly involved versus what we are clinically diagnosing is, in my opinion, three different factors. Of course, we utilize cardiac imaging extensively to make the diagnosis. However, there is underutilization of advanced imaging modalities, which lead to misdiagnosis. And then there is, of course, a lack of widespread expertise when it's come to hypertrophic cardiomyopathy. And hence, we fail to diagnose these patients in a timely manner. So if we look at this gap in diagnosis and the diagnostic challenge that all these patient present, it was explored in this paper that we will discuss later. And the authors are present on this stage. But 60% of the patients with obstructive hypertrophic cardiomyopathy had almost a delay of two years in definitive diagnosis. And on an average, these patients, before the clinicians, cardiologists, made the diagnosis of hypertrophic cardiomyopathy, they had four different cardiovascular misdiagnosis before the diagnosis of hypertrophic cardiomyopathy was made. And these patients had almost five average visits, and almost 78% of them saw actual cardiologists. And yet, they were not able to get the diagnosis on time. And that led to almost 32% of the patients with ER visits, which, of course, is costly. And the cost of average misdiagnosis per patient was $4,300. So if we look at how this implies, you know, on the other side, of what exactly these HCM patients go through when they are coming with the symptoms, which are, of course, heterogeneous in population, but also represent other cardiovascular disease, which makes the diagnosis tricky, and hence, there is this misdiagnosis often. So when we look at the diagnosis of hypertrophic cardiomyopathies, of course, mainstay is imaging, but every patient starts their journey in the clinic office when they are coming to see you. So once the patient comes, they can have symptoms of chest pain, shortness of breath, palpitation, and as we all know, these symptoms overlap with other cardiovascular conditions like valvular heart disease, or even ischemic heart disease with chest pain and shortness of breath. We have to explore the family history. Of course, some patients would have straightforward family history of sudden cardiac death, while others may have unexplained syncope or unexplained sudden cardiac death that no one has explored. You can see the vitals of these patients, and particularly notice if there is any atrial fibrillation, which would be irregularly irregular, or PVCs, which is, again, irregularly regular on the vitals. On physical examination, you can see if these patients have any murmur that would indicate obstructive hypertrophic cardiomyopathy. You can examine their heart sound, see if there is sustained BMI, if they have any history of hypertension, and if they have any history of hypertension, how many antihypertensive medicines they are on so that it can help you distinguish whether the reason for the LBH is hypertrophic cardiomyopathy or hypertensive heart disease, or in some cases, both, since hypertension is such a prevalent diagnosis in our patients. Finally, of course, before they leave the office, they get an EKG, and you have to examine that EKG carefully because EKG can be the first insight into that patient's diagnosis. And I have some slide on that. If we look at overall 12-lead EKG in diagnosis of hypertrophic cardiomyopathy, there can be multiple features. If we look at just the LBH findings on that EKG, the patients can, of course, have hypertensive heart disease, they can have hypertrophic cardiomyopathy, or in African-American patients, particularly if they're athletic, they can have normal EKG findings that are quite in the LBH phenotype. If you see any deep inverted T waves, apical hypertrophic cardiomyopathy becomes more likely. If there are any low QRS voltages, then amyloidosis is the more likely presentation, while a disease like febrile disease can have short PR interval or pre-excitations. So let's look at a typical case of obstructive hypertrophic cardiomyopathy on EKG. As you can see that there is not only LBH criteria but also widespread ST depressions. And on the right side, if we look at this particular EKG, that suggests apical hypertrophic cardiomyopathy, and again, you can see the LBH and deep inverted T waves. So in general, 90% of the HCM patients have abnormal EKG, and that is an important take-home point that I want all of you to take home. If we look at what are these EKG changes that these patients have, again, in this study, you can see that almost 13% of the patients can have normal EKG. And if we look at abnormal findings, it's anywhere from LBH criteria, which can be seen quite commonly, but also presence of Q waves that can be seen in 42% of the patients, and ST depressions, and T wave inversions, depending on which hypertrophic cardiomyopathy you are looking at. So of course, EKG can provide you the first insight into that patient's diagnosis, but the mainstay of the diagnosis is the imaging studies, the echocardiography and cardiac MRI. And if we look at the definition of hypertrophic cardiomyopathy, it's maximal end-diastolic wall thickness of more than 15 mm anywhere in the left ventricle, not just in the septum, anywhere in the left ventricle when you don't have any obvious another cause of hypertrophy. So on the right side, on the schematic, you can see the most common types of hypertrophic cardiomyopathy, the non-obstructive when the resting gradient is less than 30, the obstructive when the resting gradient is more than 30, and finally, when the resting gradients becomes more than 30 on exertion, on provocation, or on stress testing, that's known as the latent obstructive cardiomyopathy. So of course, this is a clinic patient of mine that I did a cardiac MRI, and this patient is very easy to diagnose because you all can see quite thickened septum, and this is a patient that has reverse curve HCM subtype, which you're gonna discuss in a minute. However, not every patient walks with this kind of phenotype. So if we look at echocardiography, there are several phenotypes that you can see in HCM patients, so that first patient is the basal septal HCM, you can see the septum that is quite thick disproportionately compared to the lateral wall or posterior wall. The second example is the concentric hypertrophic cardiomyopathy where you have hypertrophy distributed almost in equal fashion. The third example is the reverse curve hypertrophic cardiomyopathy where you have this very characteristic shape of the septum, and finally is the apical hyper, early case of apical hypertrophic cardiomyopathy where you see the physiological apical thinning is lost and there is thickness in the area of apex. So echocardiography, of course, is the first modality that we use, and echo can be quite useful, and this has to be a comprehensive echo where you evaluate this patient with 2D, of course, but also M-mode to see if there is SAM or not, color Doppler, continuous wave, as well as pulse wave Doppler, and in some cases where you're not able to see the endocardium very well, use the contrast, and on the CW Doppler, you can actually see what the resting gradient of the patient is, and when you stress this patient, they sometimes can have worsening of their obstruction, which can help you diagnose the final LVOT gradient, which in here, you have a very nice dagger-shaped LVOT signal, but you can also, if you knew the MR signal as well as the systolic blood pressure, you can actually figure out what the LVOT gradient is based on that. So exercise stress testing can be very useful in diagnosing of patients with hypertrophic cardiomyopathy. Now, of course, echo is the mainstay, but what is the limitation of echocardiography? So I told you that hypertrophy is the way, the atypical distribution of the hypertrophy is how we diagnose a hypertrophic cardiomyopathy, and this becomes a limitation because echocardiography may or may not give you the full view depending on the patient's images. So do we measure the LV wall accurately? In this study, it was tested, and there is quite intra- and inter-variable observability when it comes to measuring the septum, and it's not very reliable regardless of the modality you take. But cardiac MRI gives you this advantage because it can actually show you where the RV moderator band insertion is that can help you figure out what is actually the true septum, which can help you decide the true thickness of that septum. Cardiac MRI also, I always tell my trainees, it's a very glorified echo, it's a pretty echo, because it shows you very clearly where exactly the hypertrophy is, and you can use late carilinium enhancement to your advantage to figure out if the patient has any fibrosis or scarring or not. Now, 10 to 15% of the hypertrophic cardiomyopathy patients can have focal hypertrophy, and areas of LV that are poorly seen by echo, which is apical hypertrophy or inferior septum or any non-contiguous areas of LVH can be seen very well on the CMR. And similarly, again, there are multiple echoblind areas that can be seen very clearly on the CMR as depicted here, including the insertion of the anterior papillary muscle or crypts that can be quite diagnostic for the hypertrophic cardiomyopathy diagnosis. So if we look at the guidelines, the guidelines say that you have to do CMR in the patients that have inconclusive TTE, but you can also use CMR for risk assessment of sudden cardiac death, and also to risk stratify the patients once you have established the diagnosis of hypertrophic cardiomyopathy every three to five years. Now, finally, moving to the last segment of my talk, which is artificial intelligence in hypertrophic cardiomyopathy, I think the role artificial intelligence plays in hypertrophic cardiomyopathy is it does not only increase the efficiency of imager, but also I think it really works for the entire workflow in the healthcare system as well. So now, this is one of the first paper that came out of Mayo Clinic that tested the artificial AI in EKG space, and they showed that the sensitivity of this particular algorithm was 87%, and then with specificity of 90%. So I'd like to show you an example. So this is a patient with left bundle branch block, and you can see that the AI algorithm has identified areas in red that are thought to be diagnostic for HCM in this particular case, and why that is is because left bundle branch block, if you think about it, the depolarization happens. A later part of QRS, which comes from LV, because the depolarization is happening from RV to LV, and this leads to this algorithm diagnosing the EKG as a hypertrophic cardiomyopathy, suspicious for hypertrophic cardiomyopathy. Now, there are several deep learning echo AI software that have come out as well, and some in working progress, but in this particular paper, they were able to not only automate the wall thickness on looking at this AI algorithm, but also facilitate the identification, not only just of HCM, but also cardiac hemorrhoidosis based on the LVH. And finally, looking at the CMR space, now there are AI algorithms that are diagnosing what we call virtual native enhancement. So typically for delayed enhancement or scarring, we have to give the contrast agent, which is known as gadolinium in MRI, but in this particular paper, just by using a sequence that we call T1 mapping, they were able to see, without giving any contrast, if there was any virtual enhancement in that particular HCM patient or not. So I think the future is really exciting for this space, and we will see how AI can really help us bridge this gap in HCM care as far as our patient diagnosis is concerned. So my summary slide is patients with HCM, they present a diagnostic challenging and cardiac imaging remains the mainstay of diagnosis and patients with HCM, remember 15 mm thickness, cut off in any wall of the LV. 90% of the patients with HCM have abnormal EKG and EKG will help you, it will give you the first insight into the disease detection. And AI can really help the workflow efficiency and it really can proliferate our expertise in diagnosing these difficult phenotype in patients with HCM. Thank you very much. Thank you. All right, so now you know why we invited her. That was superb. So Dr. Owens is gonna give us our next discussion about now what's next. We've made the diagnosis, how do we treat it? Great, thank you everyone. Let's pull up the slides here. And we're going to get to our game shortly. This will be just a preview. And then we will get to the exciting part of the night. The slides are loaded here. So we're gonna talk a little bit about evolving medical treatment for obstructive HCM and best practices in those patients. So let's start with our audience response question. 55-year-old woman with worsening dyspnea on exertion presents to your office for evaluation. Her EKG shows sinus rhythm with LVH and repolarization changes. And her echo shows asymmetric septal hypertrophy with a maximal wall thickness of two centimeters, EF of 65%, a resting gradient of 15 and a valsalva gradient of 20. There's chordal systolic anterior motion of the mitral valve with trace mitral regurgitation. Which of the following is the most appropriate step in evaluation of this patient's symptoms? What is the appropriate next step? So A, coronary angiogram to exclude coronary disease. B, cardiac MRI to measure myocardial fibrosis. C, exercise stress echo to measure the peak exercise LVOT gradient. D, adobutamine stress echocardiogram to measure the LVOT gradient. Or E, a transesophageal echo to measure mitral regurgitation. And I will give you a few seconds here to put your answers into your phone. And again, if you walked in late, you can scan the QR code. It'll take you right to the section where you can answer. And you'll need it anyway when we start the quiz game to put your questions and answers in. You can also send questions for a Q&A session that we're gonna have at the end of this session. So feel free to put questions in. All right, three, two, one. And a nice smattering of selections. 57% of people are voting for stress echo and 23% voting for cardiac MRI. The next audience response question is 78-year-old woman, history of paroxysmal AFib. And a heart murmur that's been noted since her 30s presents for an outpatient follow-up at a rural outreach clinic. She reports breathlessness when climbing half a flight of stairs and some orthopnea. And a transthoracic echo reveals asymmetric septal hypertrophy. Her maximal ball thickness is 19 millimeters. She has severe SAM, severe mitral regurgitation, and a resting LVOT gradient of 120. Her medications, she's taking metoprolol succinate at 200 milligrams daily. Her resting heart rate's 62 in sinus rhythm. And her blood pressure's 110 over 70. So what is the next most appropriate step in her treatment? A, start her on a diuretic. B, stop the metoprolol succinate and instead start her on a calcium channel blocker. C, add disopiramide. Or D, refer to a hypertrophic cardiomyopathy center. And we will start the timer to answer that question. After you answer, I'll call your attention to this exciting thing next to me that you'll see more of in just a few minutes. All right, we're down to 15 seconds here. And for some questions, there are right answers. And for other questions, which is most of patient care, there are no definitive right answers. There's the gray area, there's preference, there's lots of options. So 73% of people are saying refer to a hypertrophic cardiomyopathy center for this question, interesting. So I am gonna keep my portion short and leave you with the top five things to think about when you're treating patients medically who have obstructive HCM. So here's a typical echo of a patient with obstructive HCM. You can see the asymmetric septal hypertrophy present here. You can see the presence of systolic anterior motion of the mitral valve with contact with the septum during systole. And you can see a valsalva gradient that is in the high 80s in this patient. So as you're in your day of seeing however many patients you see in a day, whether it's 15 or 50, if you're an echo reader and you're seeing all different kinds of pathology, burn this memory into your mind so that when you see it, you recognize it as obstructive HCM. So the number one point is that before we treat patients with obstructive HCM, we have to find them. And as Dr. Parwani highlighted, the prevalence of HCM is at least one in 500 individuals. And if we take into account genotype positive individuals, it's even more frequent than that. And we know that the vast majority of patients who have this condition worldwide are undiagnosed. So they're there and we haven't yet diagnosed them. And that should be our first aim. And when you see an echo like this on the left, a crappy echo is not good enough. So don't stop when you see that. You never see that at the University of Pennsylvania. We see it everywhere, right? I mean, this is the real world. We see echoes like this all the time. And if it's in someone who's getting an echo for some other random reason, like they just had gastric bypass surgery and you can't really see their heart and this is just a bunch of shadows, don't let it go. I mean, maybe not right at that moment, but if there is suspicion there on clinical history, on the ECG, then get better imaging. Don't let it go with one crappy echo. Number two, once you diagnose someone, assess a patient thoroughly and repeatedly for exercise limitation and symptoms. And this is important to do along the longitude of care for an individual. And I highly suggest, as many of us do, to talk with that patient's family member, their caregiver, whoever's with them. Because a lot of times that's where you will elicit changes in functional status that are happening gradually over time. So this is a slide that Greg Lewis from Mass General put together when we were doing a talk about VO2 in HCM. And the point is not to get a VO2 in everyone. Of course we do at the University of Pennsylvania, but you certainly don't have to have a CPET. But what you need to understand is that many patients with HCM are living with exercise limitation. And that many of them in this meta-analysis, their peak VO2 was somewhere around the 19-20 range. And this gives you a ballpark of the VO2 that's required for various activities, from getting dressed, making your bed, being independent, doing some grocery shopping, or carrying your groceries up the stairs, all the way to jogging. And some of those more high exertional activities are out of reach for our patients with HCM, but many of them may not report it to you that way. They may say, I'm fine, because they've lived with it for so long that it's gradually getting worse, and they don't realize that they're limited. And so you really need to ask thoroughly and repeatedly from that patient and their family member, what were you able to do five years ago? Are you still able to do those things? When was the last time you were able to garden, carry the laundry up the stairs? Who does the housework? And by really asking those daily living questions, you may get at someone who is limited, but they don't realize that they are, or they don't want to disappoint you. I mean, interestingly, we've seen in international studies that there is variability based on ethnic background, based on cultural differences, and what patients are willing to say to their physicians. And some interesting data, like a peak VO2 of 11, those of you who aren't VO2 aficionados, that's like way, way low, transplant low, will report sometimes a KCCQ score, patient reported outcome, of 100, I'm fine. So there can be a major discrepancy there that really you need to dig into, and I would encourage you to do that so that we can elicit symptoms when they're there. And if you find it, don't become complacent. It's easy to say, okay, so you can't do that second flight of stairs. You can do one flight of stairs, and it's okay. You go to the grocery store, and maybe you can't walk across the beach during the family reunion, but you went down and you attended the party, and maybe you can't make it to the soccer game for your grandchild when it's the third field over, but next time it'll be at the first field, and then you'll go there. Your patients don't have to live with these symptoms when there are treatment options available, and I think that's one of the things that we see is that I see patients for the last 15 years, and I see them every year, and it's easy to become a little bit just complacent about it. I'm fine, I'm the same way that I was, but is that how you want to be? And are there things that you would like to do that you're not able to do? And those are the real questions, I think, as physicians and as cardiologists, that we want to get to with our patients. And first-line therapy, we know, by the current ACC AHA guidelines for HCM, we start with AV nodal blockers, so those are beta blockers, or non-dihydropyridine calcium channel blockers. If those agents don't work, we do have an option, FDA approved, for the cardiac myosin inhibitor Mavacantin. This drug, as you know, and I'm not going to belabor all the trials, it's effective, and it requires monitoring. And the reason it requires monitoring is by its novel mechanism of action, it affects contractility, that's the way it works. So we have to monitor where you are on the continuum of contractility to make sure that you're getting benefit from the drug, but not moving to a place where it could become harmful, like any other drug that we monitor. And it does require monitoring, and this is a lot of echoes. So for those of you that are doing echoes in your daily practice, this is a lot more echoes, and that's the way that we're currently monitoring the drug. You also significantly have to monitor for drug-drug interactions, because the drug is metabolized through the cytochrome P450 system, there are drug interactions that are important with medicines that are common, including proton pump inhibitors, antibiotics, antidepressants, things that we see all the time. So you do have to be cognizant of that to avoid a significant drug-drug interaction. And if medicines don't work, or your patient prefers an invasive approach, that's okay, because those invasive therapies are also highly effective and safe as long as they're done in the right hands by someone who's experienced with doing those procedures. And so it's really about having that conversation, which is very difficult to do when you're seeing 20 patients, maybe only one of them has HCM, the rest have a variety of other cardiac conditions. And it's hard to take that time and really think about what are the options for the patients, and sitting down and going through it. I have the luxury of being in an HCM clinic, so 95% of my patients will have HCM. We have this conversation every single day, 30 times a day, as Dr. Martinez says. But for those of you that aren't in that setting, it's still important to recognize that patient, do the evaluation, assess for those symptoms, and then if needed, send them on to somewhere else. So the ESC guidelines that came out last fall did now incorporate this new class of medications, the cardiac myosin inhibitors. And you can see they're listed down there in parallel with disoperamide. Disoperamide, we have issues with in terms of supply, so it can be hard to get. And as those of you who've used it know, there are some side effects that come with it that are anticholinergic, that can be quite uncomfortable, and sometimes dose limiting. So it's a medication that is effective for gradient, but can come with its own side effects. And of course, septal reduction therapy has a class one indication in the appropriate patient. We've moved in HCM from a realm of single center, observational studies, to yes, randomized controlled trials, although they don't include the 10,000 patients that are in some of the other cardiovascular trials. It's a step in the right direction, and it's randomized data that's placebo controlled with patients who are already on background therapy. So very important data to incorporate. So finally, I'll leave you with number five, which is next in class cardiac myosin inhibitors, and drugs with even newer mechanism of action are coming. So this is Sequoia HCM trial design. This is Afecamton, the next in class cardiac myosin inhibitor for obstructive HCM. The top line results have been released and are positive, and we're looking forward for the full results to be released, hopefully within the next month. So exciting times to have another choice for patients in this class. And finally, I would recommend to you to consider having your patients participate in clinical trials. That is how we're going to advance this field. And there are a number of trials I have listed here. One is a study of a brand new agent with a different mechanism of action. That's the Cirrus HCM, that's an early phase trial. There's Mercutio HCM, which is another next in class cardiac myosin inhibitor, phase two trial. And then a phase three trial that's really going to help us with evidence generation. This is the MAPLE HCM trial, beta blocker metoprolol versus Afecamton. So again, trying to understand what should really be first line therapy in this group of patients. So I will leave you with those top five, and team Owens, I'm expecting a win. Excellent. Okay, so now you know why Dr. Owens is here, superb. As expected, what we're doing, what's coming, and then even beyond that, she is about an hour and a half or so from where I practice, and we go back and forth about who of us is seeing more patients. So we have some, I'm going to encourage the audience to ask questions if they want to go to the mic. We're going to get right to the quiz in a little bit. But there are some online questions that I'm going to try and throw out there for you. So Anjali, I'm going to start with you. The first question is an interesting one. It says, in the HCM patients who end up getting transplant, what are the odds of requiring medical therapy again? Is Mavacampton tested in this population? So post cardiac transplant, what do you think? So we do not generally have HCM patients who end up requiring medical therapy for HCM after transplant, because once we give you a brand new heart, it does not redevelop hypertrophic cardiomyopathy. So that is not an issue. But what we do see is post heart transplant, some patients who develop a hypertrophic phenotype that can involve outflow tract obstruction or mid-cavitary obstruction. So in that situation, one could consider Mavacampton. The other situation that we sometimes see is a patient who receives a heart and the donor has unrecognized or early hypertrophic cardiomyopathy that then progresses after the time of transplantation. And then they get a de novo diagnosis of HCM in their donor heart. And in those patients, we have had success with doing septal myectomy if needed, with using standard therapies. And you could consider a cardiac myosin inhibitor. What I would say to you as a caution, if you have a patient who you think is going to undergo cardiac transplant, do not leave them on a cardiac myosin inhibitor as they await transplant. Because what you don't want with a drug that has a fairly long half-life like Mavacampton is to have that patient called for transplant and the Mavacampton is still in their system. Because the donor heart may not do well with Mavacampton. So if you have someone who you think is sick enough to be listed for transplant, we're not usually transplanting severely obstructed patients. These are usually non-obstructive HCM that's reached the end stage. That's not somebody you should have on Mavacampton. If someone gets a second heart with HCM, I usually refer them to you to enjoy that conversation. That's right. What we have done, which is sort of of academic interest, but in some of those patients, we routinely do endomyocardial biopsy to look for rejection. We will take those biopsy samples and we can genotype them. And we can see if the donor had sarcomeric HCM. So we've had to do that in at least one case, notable case. Okay, so there's a question about the diagnosis and how we do it. I'm gonna send this one to you, Dr. Parwani. Talk to us about septal to posterior wall ratio and if that's still playing a role or not. Yeah, that's a great question. I think septal to posterior ratio, all the images or even anyone that reads echo, it can really indicate if there is any disproportionate septal thickness and can help you make the diagnosis. But I would caution because the diagnostic criteria still remains 15 millimeters for any diagnosis of HCM. So by just taking the ratio as a diagnostic criteria, I don't think, we used to use that back in the day, but right now the guidelines and data suggest that we use the absolute wall thickness of 15 mm in patients that do not have any genotype positive history or any family history. For those patients, we use the cutoff of 13 mm. I'm gonna push my imagers on this issue a little. Thinking about a 100 pound female versus a six foot five, 350 pound male, are we right in having a one size fits all wall thickness for the diagnosis of HCM? And might we be more sophisticated in time to move past that to make a more personalized diagnosis based on the things that we know affect LV mass, wall thickness, et cetera. And does that account for why sometimes females are diagnosed late, they're already in bad heart failure, because by the time they reach 18 mm, they're way far gone in the course of their disease. I see some nodding in the audience. So I'm interested in your thoughts on that. It's really an important question and I think the one that we're gonna answer. I hope, I've been married 26 years, I'm still trying to figure out women. So I'm a little, I'm still cautionary about it. But the answer is, I think we have to do a better job indexing. And there was a paper from Hughes in 2023 talking about specifically apical HCM. And I think that all made us pause. And it should have made each of us pause to start to say, we're over diagnosed. So for instance, if you've got a 13 or a 14 mm apex, is that apical HCM or not? And I think those of us who see these folks say, it is. This is probably apical HCM. It's not always, but most of the time it is. That's not a physiologic adaptation, including in the athletic population. But if you index that, there's a lack of taper. And we've always talked about how a lack of taper from the base to the tip of the heart is representative of apical HCM. And then we now need to extend this into indexing for body size. And certainly men versus women have a role in this. And we've seen this in hearts, like in the NBA athletes. We know that the size of the ventricle matches the size of the individual. It actually correlates linearly. The aorta does not, but the size of the ventricular, the LV chamber does. So I think we have to start to now take a half step back and look at the, this is the way we've done it, right? 15 mm is the way we've done it. And start to wonder if we should now do a better job of applying some academic rigor to that to improve our diagnostic capabilities. And we're doing that in the disease in total, right? We're doing that for exercise, we're doing that for, do they need AV nodal blocking agents all the way to 200 milligrams of Toprol, or should we be now adjusting differently? We're going to learn a lot in the next year or two and change the way the disease is managed. It's really an important question. Questions from the audience? All right. Someone's got to break the ice. Thanks for doing it. All right. I have a question sort of out of naivety. How do you differentiate upper septal hypertrophy sigmoid symptom from asymmetric HCM? Say it again? How do you differentiate upper septal hypertrophy sigmoid symptom in these older hypertensive patients compared to asymmetric HCM? I think that's a difficult one, right? I think you have to, this is why we had the entire discussion on diagnosis. You have to look at your patient, what medicines they are, whether they're hypertensive or not, what age they are coming from, and do they have that characteristic that we see in older women particularly, if they have that shape. I think thickness criteria still matters. In my opinion, you would see that that criteria may not be met all the way. You would not get, you may get that asymmetric thickness, but it may not go all the way to 15. So I think you can use that to your advantage, and also look at the patient overall, and that may help the diagnosis. So I'm just going to add to it that it is unusual, based on the data, to drive a wall thickness to 16, 17 millimeters with just hypertension alone. And if you're getting into the 18 and above, it's impossible, so virtually impossible. Multiple drugs, 25 years, probably kidney transplant before you can get to that level. So I would still tell you that 15 millimeters or thicker is HCM until proven otherwise, but it's an opportunity to be comprehensive. That's when you're going to do the MRI, you're going to try and figure out their family history. The genetic yield in that group is actually on the lower side, but if you find it, it can really help you with their family and screening for them and making the diagnosis. So I would still submit to you that 15 or thicker, they've got to have multiple drugs for a long time before you're going to call that hypertensive heart disease. And what I'm hoping we can do, and we're trying to do, is recognize that we always go to hypertensive heart disease, and I want us to now go to hypertrophic cardiomyopathy first. This is really common, and you can probably have both, right? We know that for sure, because HCM is common, hypertension is common. You often can have both, and I do wonder if they contribute to each other. So anything over 15, I would say you have hypertrophic cardiomyopathy, and you probably have hypertension too. I completely agree. I think as cardiologists, I think we have a bit of inertia. We almost feel like, oh God, I don't want to call hypertrophic cardiomyopathy because that's going to give a patient a special diagnosis. And so many patients, even when you see SAM, even when you see obstruction, it's just attributed to hypertensive heart disease with HCM physiology. Why not call that patient HCM and then downgrade them if you think that you're truly, that patient was in the dehydrated status, which made SAM worse? But I do think it's a difficult diagnosis. Even for images, it's a difficult diagnosis. So I would say have really low threshold for using cardiac MRI. It's a diagnostic tool that is available. There is a misconception that I've discovered in this conference that cardiac MRI is very expensive. It is not, if you look at the Medicare rates. So I think use cardiac MRI to your advantage, and it may help clarify a lot of diagnosis for your patients. Next question. Thank you for a great talk so far. Really exciting to see all the drugs coming out with cardiac myocyte inhibitors. What do you guys think the role would be as far as surgical myomectomy or alcohol septal ablation? Do you anticipate head-to-head trials with something like maveramectin? Because we know there's a chance of, that you can depress the EF with that. Should we reach for something like alcohol septal ablation or myomectomy? That's a great question. Are you a cardiac surgeon? No, I'm going to be a cardiology fellow starting in July. Okay, I just want to make sure before we answer this, I wasn't sure if you were making a macaroni payment or something. Dr. Martinez joking with you. Yeah, I did a general surgery. Dr. Owens, this is a good one for you. You and I have had this discussion. You're in. Yeah. So since we started using cardiac myosin inhibitors after FDA approval of maveramectin, it was a big question at our center, what would happen? And we have a lot of patients over 120, 30 that are on maveramectin. Our surgical volume has gone up. And that's because we're getting referred complex patients with concomitant valve disease, intrinsic mitral or aortic stenosis, and they require surgery. So our volumes have gone up overall. And there are a good number of patients that are candidates for CMI, but there are some are not. And there are some patients who don't want a CMI. They want surgery or alcohol ablation. And that's what we should do. We should have that option for them, that toolkit. We have a heart team approach where we have our surgeon, our interventional cardiologist, our cardiologist, our genetic counselors, our NPs. We look at the entire case. We look at all the imaging. We take into account the patient's preference. And that's the way that we go. And I would say that we should continue to do that. I completely agree. I think it's one of the reasons why all of us should consider, should we be sending into a center of excellence at least to start things and then have them come back to you? And I think that's the future of this, where you talk about all the potential options and let the patient decide with their full menu and then go back to one. And it's rarely one size, it's almost never one size fits all. And then by the way, it could be MAVA for a few years and then surgery after that. Or the reverse. We've had surgeries that don't go as well as they're supposed to. And then I add MAVA on top. Cardiologists are always looking to compare, my echo's better than your cath and better than your nuke. I don't think this is an or, I really think it's going to probably be an and. I'm an imaging cardiologist from North Dakota. And what is your, I mean, practice pattern on genetic testing in your clinical practice? Like, do you do it on certain patients or do you do it on most of them? I can start first. In our practice, we have a tandem visit with our genetic counselor for all of our new patients, who does a pedigree analysis, and we offer genetic testing to anyone in whom we've made the clinical diagnosis of HCM. So that's 100% all comers, we offer it. The yield on the testing is going to be lower in those patients with an older age of diagnosis, concomitant hypertension, upper septal thickening, you know, that phenotype, the yield's going to be lower. And in the apicals, and we tell them that. The yield is going to be low, but not zero. If you think your family members might use this information, if we find a pathogenic variant, we offer it to everyone. I think probably you see some cases that may be borderline for HCM. You're trying to figure out if it is truly HCM, and I'm not sure if that was the context you are asking in. But most of the times, once the diagnosis is made, we also have started an HCM clinic at Loma Linda, and, you know, all those patients get genotype testing, and we also have counselor. But I think if you are trying to decide whether this is truly HCM, and you want to use genetics to your benefit, that may not always work in your favor, depending on what you find, as just mentioned by Dr. Owens, that the yield may not be, you know, 100% in those cases. So I think in those cases, I just say that, you know, you need to see the evolution of that LVH if it looks very asymmetric in a young patient, but you're just meeting, you know, 13 mm for so, and you'd still do the genotype testing. But if it is negative, it does not exclude the diagnosis. I'm just going to bring that patient back further and follow up the guidelines, say, two to five years. I personally do it one year if they are very young, just to see where the thickness is going. I don't know if you have anything. Terrific. No, that was perfect. We're going to go. So one last question. Okay. Do you do SCAR quantification routinely in your practice on cardiac MRI? Did you go to the LZ debate? There is debate. No, I do. Because my HCM heart failure colleague, she always asks for it. And I will tell you that I'm very, you know, as an imager, we know that imaging modalities have certain amount of variability depending on when you do it versus I do it. I will tell you that I use five standard deviation or anything more, you know, when I'm deciding. And I do it, you know, mostly I do it blindly at least twice to see the minimum and the maximum number that I'm getting. Because, you know, it's quite variable. We know that HCM patients can have LGE, 50% of them have LGE, and it's more than 15% that met us. But it can be very tricky. So you have to be very careful where you draw. And I think AI can really come to our benefit. So next, I think, five, 10 years in this space can be really exciting. And I'm really looking forward, but yeah, we do it. Last question, and I'll tell you that there's an SCMR paper coming out that we're writing on this very topic. It's timely visual estimation separating between replacement fibrosis, the bright white stuff, and the interstitial fibrosis is really important. They are different. Replacement fibrosis, the bright white, is the part that causes risk. The interstitial fibrosis is not. But it all gets added together, and really, we see people with scar burden of 40%, and we know that that's wrong. Last question. Last question. So for patients that you have to start on cardiac myosin inhibitor, do you have to stop the CCB and beta blocker before initiating, or do you have to stop it later on? Yeah, that's a great question. So in the trials that were done, they were done on background therapy. So in EXPLORE, the pivotal phase three for Mavicamten, patients were either on beta blocker or calcium channel blocker. Mavicamten was added in addition to those agents. So it is perfectly fine to start Mavicamten on top of beta blocker, calcium blocker. In the VALOR study, second phase three, smaller study, sicker patients, all of whom were eligible for SRT, their patients were on maximally tolerated therapy, beta blocker plus calcium channel blocker, 20% on disopyramide plus a navy nodal blocker. In that study, Mavicamten started on top of background therapy, so it's perfectly fine to do. What you'll find is people come back with no gradient, and they say, take me off my beta blocker. For sure. Now. Yes. For sure. Slowly. Taper it down. All right, we're going to start the quiz. All right. Remember what we're playing for. We're playing for bragging rights and the largest trophy in the history of the ACC. Dr. Bride, take us away. All righty. If you have not joined team battle yet, pull up your phone and you'll see a little link right there that you can click to join team battle. It's closer to me. Oh, you're taking it. Okay, never mind. I'm taking it. I'm taking it. I thought that's Dean Parvani. I want to know how I'm going to get home on the plane. All righty. Here's our trophy. So everyone join. If you need to re-scan the QR code, take a second to do that. I see a few phones out, so we'll let you guys join, and then you can pick your team. I see Dr. Parvani has some fans that switch tables. All righty. I think we should be good to go now. Okay. It's the one under Martinez. Yeah. I have a little ... Yeah, I should be good. Okay, here we are. We're good to go. We're good. We're good. Okay. So just a fun little quiz. You guys are going to have 10 seconds to answer questions with this quiz. Last one, you had 30, so we got to be a little quicker on our toes to keep you from falling asleep. So question number one. This is 10 points. Gina presented after her primary doctor evaluated her before a marathon. An ECG was performed, and she has no prior ECGs. She's asymptomatic. Which one of the following is true regarding this EKG? Take a second to take a look at this. For the sake of time, I don't want to give you too much time so we can get through all of our questions. So which of the following is true regarding this EKG? Would you say that these are athletic ECG changes from her performing in marathons and you would do nothing further? Would you say that this ECG suggests a cardiomyopathy and cardiac imaging is needed? This ECG is diagnostic of hypertrophic cardiomyopathy. This ECG requires a stress echocardiogram, or transthoracic echo is recommended every five years in this patient? So what are the answers? Press them quickly. We showed you some slides on this, so remember that. Three, two, one. Answers in. Oh, we only got 50, 60. You guys are putting them in fast. OK. OK, Team Parvani, go. All right. So we're saying this ECG suggests a cardiomyopathy. All right. What happened? Team Brian. Team Brian. Here we go. The cardiology fellow taking the lead. OK. So we answered that. So yes, this ECG suggests a cardiomyopathy and cardiac imaging is needed. So as Dr. Parvani stated in her presentation, 90% of our HCM patients are going to have some ECG abnormalities. In the top left corner, you can see the abnormal Q waves. I'll have another slide where it will be a little more apparent. Again, top right corner, some more Q waves suggesting fibrosis. And then in the bottom, we have the T wave inversions throughout the inferior and lateral leads. So this is, again, the arrows pointing out these T wave inversions, these repolarization abnormalities, which are never normal in the athlete. Even though this patient was an athlete, ran marathons, this is not normal. This is highly suggestive of HCM. We can also have our pathologic Q waves, if you were paying attention to the earlier discussions. Pathologic Q waves, the duration is greater than or equal to 40 milliseconds and or the depth has to be greater than 25% of the preceding R wave. That's an and or. Dr. Martinez and I had this discussion the other day in clinic. So certainly, these arrows are pointing out the pathologic Q waves. All right. Moving on to question number two. She gets her TTE for further evaluation. Now, what would be your diagnosis based on the TTE results? And I'm just going to let you digest the pictures. We're going to go over them at the end. So what would be your diagnosis based off of this TTE? Would you say that she has obstructive hypertrophic cardiomyopathy? Do you think these findings are suggestive of an apical aneurysm? Would you say this is amyloidosis or ischemic heart disease? Vote quickly. Speed and numbers get to the leaderboard. She's dying, you guys. All right. Apical aneurysm. Spot on. And? Yes, let's go. But your fellow is still being Parwani. I can't believe it, everybody. Easy grasshopper. Oh, my God. Where is Team Parwani? Don't leave. This is... Come on, Team Parwani. So clearly, we can see... You see the turbulent flow at the apex here in this color doppler imaging. And this should spike your interest that something is not right here. We have our continuous wave doppler signal... Oh, I'm sorry. I accidentally hit that. Our continuous wave doppler signal through the LV cavity. We have these two signals. We notice two forward flows and then a signal void. Maybe look at the first and the last signal. There is some continuation through there because this is a CW doppler. So you're going to have some forward flow there. But let's dissect the pulse wave doppler. I'm sorry. We'll dissect the apical images first. So you have to get multiple views. You can miss this if you're just getting one view of the apex. So we have your two-chamber view. Not as apparent there, but you do see hypokinesis. Then you move to your four-chamber view. You can certainly appreciate the outpouching there in the... I must be clicking. This is very sensitive. Sorry, guys. So in your apical four-chamber view, you can see the apical outpouching. And then in this next, this is that little pouch highlighted in red or outlined in red. So the echocontrast agent you can clearly see here is very helpful in pointing that out to you. And when we're talking about apical aneurysm, there's two differences that we need to distinguish here. Apical LVH or apical hypertrophy versus apical aneurysm. So they're both part of the HCM spectrum. They both are caused by the same sarcomeric mutations. Not quite sure why some present with a certain phenotype versus... You can have the same genetic mutation in different phenotypic expressions. But it's important to know that the apical hypertrophy is generally lower sudden cardiac death risk compared to your apical aneurysm. And you do have an increased risk of stroke with your apical aneurysm compared to just your apical hypertrophy. With your apical aneurysm, you do have increased adverse events by the study by Dr. Rowan showing that increased adverse events with apical HCM include higher HCM mortality, sudden death events, heart failure, and thromboembolic events. And that CW Doppler is really important because you may not be able to get contrast depending on how you do your echoes. But if you see that CW Doppler, that's your opportunity to say, maybe we go back for an ultrasound enhancing agent or, better yet, let's do a cardiac MRI that'll give us all of that. So the apex is one of those areas that echo can't shine. So that's really important to know that if you see that CW Doppler, the quote lobster claw, that's an apical aneurysm until proven otherwise. Yeah, I'm sorry. I thought we had a pulse wave in here. But the CW should help you see exactly that lobster claw, my most favorite signal in echo imaging or favorite name for something abnormal. Okay, question three. Team Bride, you guys are doing great. Which signal corresponds to left ventricular outflow tract obstruction? If you came by our learning booth today, you will know the answer to this. So you guys, you're going to go ahead and show the slide. I advance. Don't advance. Go ahead and start the polling. Team Bride is coming in strong. I gave them the answer ahead of time. Nice work. Nice work, Team Bride. So let's go through these signals because these are very important. The first signal, Team Bride, we all know this, I was going to say let's say it but it's up there, mitral regurgitation. So I'm going to have another slide to really show you where in the QRS complex you can determine if it's mitral regurgitation versus LVOT obstruction. So I'm not going to harper too much on this image, we'll have a better one in a minute. Image B, the arrow is pointing to a late systolic signal. This is indicative of your LVOT, mid-cavitary obstruction. So it's a little more narrow, a little more dagger-like, and late systolic signal. C is mild aortic valve stenosis. And most importantly here, definitely take home point with AS versus HCM is late peaking or early peaking. Your AS signal is going to be your early peaking signal. Your HCM signal is going to be your late peaking dagger signal. So looking at the LVOT versus the MR signal, because sometimes we'll have patients come in the clinic and we read a note and the gradient is reported to be 200 millimeters of mercury and we're going, how is that possible? What's happening is the MR signal is being confused for the LVOT obstruction. So looking at the true LVOT signal, the dagger is starting after the QRS complex. Looking at your MR signal, your AV valve closure starts right at the QRS complex and that's when you can get your regurgitation, or I'm sorry, right a little bit before your QRS complex. So that's a big tip right here. And in addition to the velocity, they both look a little late peaking. That's probably just a little bit later MR, maybe a little mitral valve prolapse. But again, that late peaking signal and then look at your QRS complex as to is this MR or is this LVOT obstruction. Perfect. So this is really important for Dr. Owens, right, for her talk, talking about the obstruction, right. When you're managing patients using Mavicamptan, you're going to dial it up based on the LVOT obstruction. So if you're measuring the MR signal, you're going to cause harm. That's really important. And then of course, you want to be able to also make the diagnosis, part of Dr. Parwani's talk, as whether or not they are obstructive or not obstructive. It changes the way we manage them. They're not obstructive. They don't need any of the outflow tract obstruction medicines. They don't need high doses of beta blockers or even Mavikampton yet, maybe. But they're gonna use goal-directed medical therapy, right, ACE, ARB, things like that, which are actually gonna make the obstruction worse. So it's really important that we're able to distinguish this. So the MR signal starts early. It's a little more rounded, and it's always higher than the true LVOT signal. Those are the pearls for that. Good job. Next one. And this is great. When you start seeing this in clinical practice and you do your physical exam, I love going into the rooms, and I just tell Martinez's patients to just stand up where they are, and I hear it. So really start correlating your physical exam findings to what you're seeing on your echo and what your patients are telling you. Okay, question four. We're going up in points a little bit. So Martinez, Parwani, Owens, your teams can maybe make up for a little bit of lost time here. Which measurement is correct for LV wall thickness? Again, if you were paying attention. Oh boy, this is a tough one. So a few different measurements up there. It might be a little hard to see. Not so much the actual number that you need to pay attention to, but just where the line is measuring. So let's go ahead and start the polling. Okay. Oh, yeah. All right, should be 70 responses in. We can show who the winner is. Oh, no! One point. We're coming for you, Bride. We're coming for you. That's all it takes, Bride. That's all it takes. We're coming for you, Bride. That's one point. Two more. It's getting close. Yeah, team Parwani wants everyone else to win. Go, Owens. That's okay. Two more points, guys. We got Martinez. All right, so we have a little bit of time. So I want to focus on the illustrations here. Very important to show you the cartoon images at the top. The solid lines, of course, are the correct measurements. The dotted lines are the incorrect measurements. So the first image, the basal dimension. Oftentimes, people will come in over-measuring the crista superventricularis. It's very easy to do. The cine image below that, if you look at it closely, you can see the echolucent area that is demarcating the perimeter of the actual left ventricle. And of course, you have additional muscle structures that are part of the right ventricle, not the left, but they frequently get confused as part of the left ventricle, and a patient will come in with a wall thickness of 30 millimeters with recommendations to get an ICD. And then you can get an MRI and clearly see that what was over-measured was the crista. Or if you look at the other dotted line in that basal measurement is the papillary muscle. Same thing can happen there. Definitely can overestimate the LV wall thickness with this. And again, this is why MRI is so important to obtain in these patients, so you're getting accurate dimensions. In the mid-ventricular view, we see, again, a moderator band included in that mid-ventricular level, and the actual dimension is highlighted by that solid line. And as you can see, too, in the image below, oh, you have a, thank you. Martinez has a pointer. He is now pointing out the moderator band on the bottom right corner. So incorrect measurement is, again, with the solid line measuring all the way over to the moderator band. Here's the correct dimension, and that's significant. You can see that. Did you point that out over there for them? Yeah, so this has both diagnostic and therapeutic. So this is an over-measurement. This is the RV. These are LV cords. You want to stay right in that smaller line there. Sorry, I've had a lot of coffee today. A little shake there, jeez. Martinez is getting jumpy. It's 7.15. I have to start the Parkinson therapy here soon. So this is important because not only is it diagnostic, but it's also therapeutic. If you're measuring 26 and it's actually 30, if you're measuring 32 and it's actually 26, you're gonna lead to inappropriate diagnoses for ICD therapy. So both important, not in this case, but in the other case for sure. Next one, next slide. I think we go back to the, can we go to the, so could you go back to the original answer? I think it's important to point out some of the, this is a hard question. And for those who are wondering, this comes from the website learnhcm.org. It's free online through the ACC. And it's again sponsored by BMS. But here you see we're over-measuring. RV structure there, RV structure there. There's just too much here. You're into the LV as well as into the RV. And here you're just into the cord. So we're hoping is that you're gonna go right in this separation line. Again, it's a still image, so it's hard. You wanna go back and forth. And here you wanna avoid those LV cords. This is one of those ones that no matter what you end up measuring on, you're probably gonna recommend doing a cardiac MRI. And it's just a better use of that tool. It does a better job. Echo over-estimates and under-estimates. So the key is to not overdo it here. RV crista superventricularis is there. You wanna avoid that structure there. Okay, next question. Questions about that before she goes on? We're okay with that? Get an MRI. Okay. Okay, question five. A 53-year-old male comes in with reports of increased dypsia on exertion. Physical exam is notable for a provocable crescendo-decrescendo murmur with squat-to-stand maneuver. And TTE shows no gradient at rest, but a 93-millimeter mercury gradient with a valsalva maneuver. His heart rate is 80 beats per minute, blood pressure's 128 over 68, and he's currently on no medications. So what is your next step in management with this patient? Would you refer him to septal myectomy or an alcohol ablation? Start beta blocker or calcium channel blocker therapy? Are you gonna perform an exercise echo to see if he has an exercise-induced gradient? Or will you begin Mavicamton at 10 milligrams? All right. Initiate beta blocker or calcium channel blocker therapy. I think someone over here was thinking we were pushing Mavicampton. First. Oh boy. Team Owens is making a comeback. Team Martinez, he actually has a fellowship to where you can learn a little bit more of this. So if one of you on that. My daughter's back there actually gave her the wrong answer. She's on your team. Martinez is sabotaging pride. And wait, so Owens took the lead on you. I'm coming for you, Martinez. We're coming for you. Sorry. Sorry. Moving on. We did. We said beta blocker, calcium channel blocker was the answer. So this is the next question. Can you go back to the question before that? Yes. I just want to make sure we know. So obviously not on medical therapy. So we can't go on to myectomy or alcohol ablation. This is not an appropriate next step. Initiate beta blocker, of course, is correct. We don't need an exercise stress test because we already have a gradient that's over 50 and we already have symptoms. We already have enough gradient to explain what's going on. It's therapy that's next. And Mavicampted is not the first-line therapy unless we're on baseline drug, at least for now, right? There's also another issue which we're going to talk about next. Okay, I'll save that one. Save lowering points. So we initiate him on the beta blocker therapy. We put him at 50 milligrams, which is a good starting dose for someone with a gradient like this. His resting heart rate is now 58 and his gradient remains at 80 millimeters of mercury. And this patient is still symptomatic. So he's coming to you. What are you going to do next? Are you going to refer him for surgery now? You've tried your beta blocker therapy and he's still symptomatic and still has a gradient. So let's send him to surgery. Increase the beta blocker to 100 milligrams. Add Barapimil 180 or begin Mavicampted 5 milligrams. Martina, stay away from Team Owens. I don't mind. Should I help out his team a little bit? Yeah, I think so. Yeah? Do you guys need some help? All right. All right, begin Mava. Love it. 5 milligrams. So we can go to the next slide. Oh, yeah. We're coming for you. Owens has been whipping me for years. We like to be in a comfortable place. So we're going to stay where we are. Go back to the answers. Okay. So there are some... I think it's a learning moment, right? So there's no reason to increase the beta blocker to 100. It's already 58, right? So we're on maximum therapy. You're going to give them chronotropic incompetence. They're going to be breathless from that. So we don't want to do that. Adding in Barapimil, same story. It's not going to really get us any bang for our buck. There's no reason to do that. Septal myectomy is not unreasonable. And I put both of them in here intentionally because based on the current guidelines, maximum tolerated medical therapy on a beta blocker, still symptomatic. So it's not unreasonable. There's no reason. In fact, based on the current guidelines, that would be appropriate. But with all of the data, the guidelines are guidelines, right? But we know that the data's there. And we're already using Mavicamptin clinically. It's FDA approved. Mavicamptin, 5 milligrams is the starting dose. The last question actually had 10 milligrams. That's why that was not a good answer in the last one. That's not the starting dose for Mavicamptin. 5 milligrams is. With me? But septal myectomy is the correct answer. Mavicamptin is not an unreasonable answer. We good? Okay, next. Keep moving on. Tell us how we do it. We're coming in for the kill. So maybe this is easier to be done at a high volume center where you do have the expertise of starting patients on Mavicamptin. We have an incredible nurse coordinator who is incredibly competent in doing this. But it can be a little bit of a heavy weight to lift in the beginning if your staff isn't used to it. So referring to a high volume center may help. But before, just like Dr. Martinez said, before we initiate therapy, we're going to give patients all the options. And one option that I love giving patients if they're not quite sure that they want to proceed with surgery is sometimes we actually offer to start patients on Mavicamptin so they can see if they feel the benefit. And then if they do and they say I don't want to take a medication every day for the rest of my life and go through then they go to have surgery. So sometimes it is a bit of a litmus test to see how much better they really will feel when you relieve the obstruction. Because as we said earlier, and as somebody in the crowd mentioned too, some patients just don't know how symptomatic they are until you make them feel better. So if the patient does want to proceed with Mavicamptin, at week four and eight we're going to get an echo to assess the ejection fraction and gradient. And at week eight, that's generally where we're going to start titrating medications. We may start bumping down the beta blocker at week four, and then when they come back in at week eight if they still have a gradient we may bump it down again and bump up the Mavicamptin. But certainly you'll get used to titrating this medication. And then after week 12 with no changes in the Mavicamptin dose then you can enter your maintenance phase where they'll just come back every three months for an echocardiogram. I'll reiterate what Dr. Owen said. A lot of the patients at that point stay on a smidge, 25, 12.5. They like that, I think, from a diastolic filling pressure phenomenon. But I usually cut the beta blocker in half when I start the Mava and then we dial them up that way. That's usually the best way to manage the gradient. The first four weeks, if the gradient goes under 20 then you have to reduce the dose of Mavicamptin and it really starts this whole snowball of extra echoes. So that's typically how I do it at week... When I start it, if you're on 100 I typically start the Mava and then re-evaluate it four weeks. Is that how you do it? I think this is more of an art than a science at this point. We need more data on really what we should be doing with background therapy and what we need in the long run. Do keep in mind that there's a drug-drug interaction between calcium channel blockers and Mava. So those are the two that I'd be cautious with. And we often half the dose of calcium blocker before starting, particularly high dose for Rapamil. But we tend to leave the Toprol on. And again, this is a drug that has a longer half-life. It takes a while to get to steady state. And that's why you're seeing this somewhat slower initiation phase. Because you want to give your patient a chance to get to steady state so that the drug doesn't accumulate. Because if it accumulates later, that's when you're at risk to potentially drop your ejection fraction if you get too much effect. So you go slow, wait for steady state, and the first option for up titration is really at week 12. In those first 12 weeks, it's just an option to stay or to down titrate for people that may be poor metabolizers. So keep that in mind. You don't want too many moving parts at once. So a comment back here? Yeah. Dr. Adujo, a clinical pharmacist with Atrium Health. I just wanted to point out another reason why Rapamil was not a good idea because of the heart rate, obviously. But one thing as a clinical pharmacist that you have to be aware of for approval for Mavacamtin, you have to make sure you're documenting that in your clinical notes in order for approval. So that a patient, sometimes they failed a beta blocker or a costume channel blocker before they can be approved for Mavacamtin. When are you titrating up your Mavac? Week 12. Come in. Thank you. I'm just wondering clinically how quickly or how long does it take for patients to start to appreciate the benefits of Mavacamtin? Generally, I find in clinic when they come back the first four weeks they're not feeling a whole lot of benefit. Come eight weeks and actually, I'm sorry, that's a really good segue into our next slide. Coming eight weeks or more they're starting to feel some of the benefit and then they're starting to feel some of the benefit when we peel back the beta blockers. So let me go to that because that's a really good question. Perfect. I think I paid you to do this, right? So looking at the LVOT gradients when you start Mavacamtin, and then when you do a Valsalva gradient at around two months we see reduction of the gradient with Valsalva. Again, ejection fraction is staying largely unchanged. And like you asked, this is generally when we see that they're starting to feel better. You should expect like five to eight, five to ten percentage points drop in ejection fraction when you start the drug. Five to ten percent, sometimes more. Yeah, I would say on average in the trial data it's five percent, four or five percent, somewhere there. And there's individual variability for sure. Usually holds on from there and the symptom benefit varies six to eight weeks I seem to get a benefit and then usually we're titrating after that at 12 and then you're getting some benefit certainly clinically after that. So this is real world data. That's what we're seeing for sure. Next slide. So again, looking at an actual patient pre- and post-MAVA. So this is our pre-MAVA. You see a very turbulent flow through the LVOT and great appreciation for the systolic interior motion and the obstruction at the LVOT. And our gradient highlighted 69 millimeters of mercury. Remember, that's our late peaking gradient. So post-MAVA, where did the SAM go? It's gone. And now nine millimeters of mercury. This was at about 12 weeks. This was actually patient number two at our institution. Next slide. Importantly too is pre-MAVA. Looking at the EKG, again we're seeing our T-wave inversions and actually a patient on MAVA-Camden can have some normalization of their ECG abnormalities. And we did look at some AI data and with AI actually post-myectomy the AI algorithm on EKGs will still show LVH. Post-MAVA-Camden some of the AI ECG algorithms show normalization and do not see LVH. So interesting finding more work to come on that. When you start to hear about disease modifying drug, that's what we're talking about. We don't see this in everybody, right? It's probably 30-40% or so that we see a change and I don't know how to predict that. Probably younger patients, hypertrophy, hard to say. But we are definitely seeing this more often than not and what this means clinically is unclear. But I was impressed that the AI algorithm could not see that that was an HCM patient any longer and called it normal. Dr. Martinez, have you seen any change in T1 mapping or ECV when the EKG normalizes like this with MAVA-Camden? I don't have anybody that we've repeated the MRs on that I can think of. And the strain imaging we haven't seen a whole lot of change in diastology. The data suggests that there's changes in feeling pressure but I'm not sure we've seen it in total. That long-term MRI data I think will come from our long-term extension open-label trials of both MAVA-Camden and AFI-Camden both have long-term MRIs and I think we'll hopefully get the data there. Speaking of MRIs, in patients with HCM, cardiac imaging is required for diagnosis. What is the advantage of obtaining a cardiac MRI over echo? Is it that CMR provides additional information on mean LVOT gradient? Does a CMR provide additional information on the need for a surgical intervention? Does it provide additional information on the mitral valve anatomy? Or is it that it provides additional information on sudden cardiac death risk stratification? This is the second to last question. Keep the lead, Team Owens. Come in strong. Don't give up now. I also realize we need some indexing on my team. You have to index the votes because there are less people on my team. Excuses, excuses, Dr. Parwani. We need some index data on this voting. Alright. Coming in strong, Team Owens. Nice work. Okay, next slide. We don't need to look at that too long. Go back. It's stuck. It's so happy. Alright, final question. This one's worth the big dollars. 100 points, guys. Everyone get your math caps on, okay? You're unable to obtain a clear LVOT signal, but you have a good MR signal. You have a good MR signal. And you know that your systolic blood pressure is 100 milliliters of mercury, your LA pressure is 15. What is the LVOT gradient? I'm going to stay here for a few more seconds because you might need some time to get Calculating. Calculating. Calculating. Are we ready? Ten seconds. Ten seconds. Calculating. Is anybody subtracting yet? Six, five, four, three, two, one. Put in your answer. Come on team Owens. Come on team Owens. Here we go. We know four V squared is gonna give you that gradient through the mitral valve, that gradient going backwards. You have to add to that your LA pressure of 15. So when you do four V squared by 7.2, you get 207 plus 15, 122, and then take away your systolic blood pressure. So 122 millimeters of mercury is your LVOT gradient. And this will be an echo boards question for all of the cardiology fellows out there. And I had given them a slide. Nice work, teams. Thank you. Please thank folks on the way out. This was, again, sponsored by BMS and an ACC product. We really appreciate y'all staying to the end. We really enjoyed this. I hope you did too. You learned something, got some good food, and had some fun along the way. Thanks for coming. Good night, everyone. Good night. So team Martina has come up here for the victory photo. The victory photo.
Video Summary
The video transcript discusses the management of patients with hypertrophic cardiomyopathy (HCM), focusing on the use of medications like Mavacampten and the decision-making process regarding surgical interventions like septal myectomy or alcohol ablation. It emphasizes the importance of using cardiac imaging, specifically cardiac MRI, for accurate diagnosis and treatment planning. The transcript highlights the benefits of Mavacampten, including reducing LVOT gradients and improving ECG abnormalities. It also underscores the role of cardiac MRI in providing additional information for risk stratification and assessment of mitral valve anatomy in HCM patients. The quiz towards the end tests knowledge on calculating LVOT gradients, showcasing the practical application of the information discussed in the video. Overall, the transcript provides insights into the comprehensive management of HCM patients, from medication initiation to potential surgical interventions, stressing the importance of individualized patient care based on clinical findings and imaging results.
Keywords
Hypertrophic cardiomyopathy
Mavacampten
Surgical interventions
Septal myectomy
Alcohol ablation
Cardiac imaging
Cardiac MRI
LVOT gradients
ECG abnormalities
Risk stratification
Mitral valve anatomy
Individualized patient care
Clinical findings
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