Chapters Transcript Video Hypertrophic Cardiomyopathy Dr. Amit Badiye describes the diagnosis and clinical evaluation of the most common cardiac genetic disease known as hypertrophic cardiomyopathy. Hi, good morning everybody. Thank you for joining um US for the cardiology grand rounds. Uh Just quick announcement that next week's grand round uh will be by Doctor Summers on aortic insufficiency review and current therapies. All right. So let's start with my topic today. Hypertrophic cardio. My, but you know, very interesting and um important topic uh always baffling to see so many patients with LVH. And we're always thinking like who has hypertrophic cardio myopathy? And what does it even mean? And what's the clin uh clinical relevance of that? So, um let's see here. I don't have any financial disclosures. Uh I have gotten uh honor area or consultation free from Abbot. It's nothing relevant here. So what's the definition of hypertrophic cardio? But it's defined as the presence of increased left ventricular wall thickness that is not solely explained by abnormal loading conditions and these loading conditions as we know could be um hypertension or tic stenosis, several um conditions which can increase the loading condition, right? Even hyperthyroidism for that matter, right. And the morphological expression is confined solely to the heart. Ok. So this is a cardio centric disease. All right. Um Hypertrophy from other etiologies doesn't get into CM. So it's very important if we can cling to this definition, then everything becomes much easier to understand. And a lot of the confusion we see in clinical practice kind of goes away, right? And most of the time the septum is always involved and it's always um thickened or abnormal in these patients. And then LV chamber is not dilated, very important. Um If you just keep this slide in mind, uh 50% of the SCM is, is done. OK. And there's always a uh genetic origin. And uh you know, in Greek hypertrophy uh is, you know, excess nourishment, right? And that's the word comes from the word hypertrophy comes, right is a Greek word. And you know, you can see in these cartoons how a hypertrophic heart looks, uh how the septum is involved. This is a still image from an echo where you can see on left side, normal heart and right side uh hypertrophic card. You can see how the septum is significantly involved. And in fact, this is like a diffuse uh hypertrophy, right? Um Captain America had great nutrition. And on here on the pathology slides, you can see there is myofiber disarray as normal heart versus hypertrophic heart. And there is excessive collagen deposition and scarring, right? And that's the hallmark on uh pathology when uh these hearts are looked under autopsy, right? So, as we discuss abnormal LV, wall thickness is hall mark and you know, the definition is in adults, wall thickness, more than equal to 15 millimeter. Ok. Uh 13 to 14 millimeter is borderline. And for Children, it's two standard deviation for their age. And then there are patients who have history of um hypertrophic cardiomyopathy in uh in their family members, right? Or gene uh genes positive, those siblings or those family members. Uh you can diagnose them with SCM at a lower thickness that is 13 to 14 millimeters, uh especially females. So females with history of uh genetic history of uh or familial history of hypertrophic cardio that 1.3 centimeter or 13 millimeter. I will qualify them as HCM. So how do these uh patients present? Right, hypertrophic cardiomyopathy, patients present with m Myriads of symptoms. They could have shortness of breath on exertion. Um They may be just completely asymptomatic and someone uh looks at them and you have a murmur and then they don't know what that murmur is and they say that oh my EKG was done but couldn't find anything or many of these patients would have angina. All right. Um And then um that uh certain patient population, they may just present with syncope, unprovoked, syncope or uh sudden cardiac, that could be the first manifestation of hypertrophic card, but very important. So how do we uh evaluate this vision? So, the diagnostic testing when you're suspecting uh at CM, it's always involve EKG uh imaging, of course, uh good history, taking and good history taking, I mean, three generations of family history, you have to go back, three generations, just not stop at first or second generation, right? That's gonna give you some hint whether this is genetic or or familiar, right? And um if you on imaging, you have a positive phenotype, right? Signs of uh HCM, then you have to do a thorough risk assessment of this patient for sudden cardiac death, right, as opposed to a regular patient with hypertension, why HCM is important, right? Because sudden cardiac death, right? Um Stress testing to see if they have left ventricular outflow tract obstruction, right? And that stress could be just provocative manners like valsalva or it could be exercise, stress testing, right? Um And uh sometimes patients may need a baseline uh determination of their functional capacity, right? And then um every 1 to 2 years with change in symptoms, you have to continuously evaluate their risk. Uh I get to see a lot of HCM patients and I see that someone had an echo in 2018 or an MRI and then nothing was repeated for the next five years or six years, you know, and patients symptoms are kind of same, but probably the disease is still uh progressive and affecting them, right. Uh So every 3 to 5 years, it's class to be indication to do an cardiac MRI for S CD risk assessment. Ok. If of course, if they don't have I CD. Right. Um, and if the patient, they remain asymptomatic, you continue to evaluate them either uh with an exercise test or uh cardiopulmonary exercise testing as you know, we do in uh our heart failure office uh to assess their functional status. Right. What's their um, um, function, baseline functional capacity. If they're symptomatic, then you decide whether if their gradient is less than 50 to do provocative maneuvers or again, exercise them to see if they are candidate for any intervention or treatment, right. And um if these patients, there are no evidence, right? If there's no evidence uh on echo or MRI of uh uh hypertrophy and there is family history with somebody in family has known positive variant, then um the patient will undergo screening EKG and an MRI, right? If um there is no positive variant, nothing on the echo, uh you don't need to um you know, follow these patients with the imaging and it's important to know that HDM is a great masquerader, right. I mean, patient who have uh exercise, uh induced obstructive gradient or dysnea, right. They may get diagnosed as asthma, right? Um Someone who has a systolic murmur from um right, um uh anterior motion of mitral valve, someone may diagnose them with mitral valve prolapse, right? Or you may just have an innocent murmur and someone may just ignore these patients, right, panic attack, right. Patients who are getting palpitation, syncope and those who get dehydrated and now they're sweaty clammy, uh going into uh obstructive shock because of right dynamic uh lvot obstruction, someone may misdiagnose them as panic attack, right? Um, depression, the fatigue, tiredness, uh lack of energy in these patients from poor cardiac output state and get diagnosed as uh you know, depression and you know, cardiac arrest can be uh again until you investigate them further or uh sadly on autopsy, you see that, oh my God, this patient had hypertrophic cardio. So, you know, one has to be uh careful and think about HCM. In fact, uh this uh study in uh UK, uh they found that, you know, S CD can be the first manifestation of HCM, you know, and around 70% of the diagnosis was made on the autopsy. The average age of the patient was around in the forties, predominantly they were males and around 60% of them had myocardial fibrosis and around 16% had coronary artery disease. And this was unfortunately, um you know, just found on autopsy and you can see that the death occurred around quarter of this uh uh people on exercise or on emotional stress. Um So, uh can't ignore that historically. How uh did we, you know, come across this uh see this disease process? So, around 18 seventies, um the French reported the first uh few cases of, you know, at that time, it was known as idiopathic subaortic stenosis, right? And then more and more uh cases were reported until around 19 sixties. Um familial uh etiology was found, right? And then, um in 1961 Brockenborough, um you know, described the famous Brockenborough Brown W Morrow sign, which we'll discuss, right? Um In 1963 the non obstructive form of HCM was described because initially, it was only thought that, oh, this is all uh lbod obstruction and that's why we don't call the disease. Now, ho come as we used to call it before, but it's termed as hypertrophic cardiomyopathy. Because around 25 to 30% subjects may not have an obstruction but they could have hypertrophy. So the terminology uh in the guidelines has changed a little bit. And then, you know, slowly we had m mode in the 19 seventies, we started having echocardiography. Before this, the diagnosis was made either on autopsy or invasive um cardiac catheterization. And um in 19 nineties, first pathogenic mutation was implicated in HDM. And now, you know, as you know, from 2002 to 2020 there has been update in the guidelines. So historically, uh it's a very interesting story. Uh you know, uh on the right side is Eugene Brown Wall and Andrew Morrow is the surgeon who was working with him. So, um they had this 20 year old kid and uh at that time, Doctor Brown Wall was the c lab director. So he sent this kid for um septal reduction surgery to the surgeon and he said that, oh, this guy actually, he didn't even know that there is something known as hypertrophic cardio. He thought that this kid had a abnormal congenital abnormality known as, you know, sub aortic membrane. So he had a nice murmur. Took him to the cats lab, put catheter, there was no echo at that, right? And I see a lot of our echo techs wondering. Wow, that's so easy, you know, can just pulse that area. But yeah, so that time it was only right cardiac catheterization. So the surgeon is super angry. He calls Brown War like come to the or right. So it's like doctor scar, you know, calling me come to the or like, oh what did I do? I did I not select a good heart for my transplant recipient, right? So he's like, well I'm doing a case and he's like no come to the or right now he goes there. So this 20 year old kid open chest in the or and the surgeon is like, you mess it up. This guy has no sub aortic membrane, nothing. This heart is normal and Dr Burwell is sweating like how can he misdiagnose this case? I mean he had clear cut gradients in the cat lab. And the surgeon literally did a bimanual examination of this heart. He's like look it open the aorta right to clean up the subor membrane, put the finger through the aorta, the left atrium was open, puts another finger through the left atrium. He's like, look great communication. Where is your sub biotic membrane? And doctor Brown was like, super ashamed. He was like, worried what's gonna happen to my career. This is like the largest mistake of my career. This is gonna cost me my job and all that. So he goes back, you know, sadly to the cat lab, he actually calls his mom like, hey, I messed it up. I don't know what's gonna happen to me and what not. And he's just thinking, he just couldn't believe it. And then just before he leaves the or actually he told the surgeon like, well, sorry, just do me a favor. When you close this guy's chest, just put a needle in his ventricle and measure pressures. And uh and then after three hours and, you know, these patients at that time, the cardioplegia and the open heart surger are pretty complicated. It's not as straightforward as we used to do, right? This is like 70 years ago. Um So, I mean, everybody thought that this patient is gonna die, right? Because he had something going on in the heart. Nobody could figure it out. And luckily the patient survived and whatnot. And the surgeon then came and he taps on Brown's shoulder and he's like there's something going on here. There are some cases we can't figure out what it is. But when I put the needle in the ventricle, there was a gradient of 60 millimeters. So the radial a line and the ventricle pressure were completely discarded, right? So there was something, there was something and then after a few days of thinking what it could be, they decided that, well, there are certain things in life, we just can't reason out and they call it a day and then guess what, next week another kid shows up same story and the guy has, you know, a gradient across the tic valve. So, uh you know, they then uh kind of really methodically uh research these cases and you know, they published their paper and then uh Mauro really became the pioneer of myectomy, right? Um He did around 300 myectomy and they publish all their data about how a hypertrophic septum can cause dynamic LVOD obstruction and it can be surgically treated. And they published the first case series, ironically, Morrow who was the father of Myectomy himself had septal myectomy after 25 cases, he got diagnosed with HCM. He refused to get on treatment, he refused to uh you know, get himself evaluated. Um he actually um died from complications of stroke and uh his daughter got diagnosed with the HCM. They had the gene, they did family pedigree and then she ended up getting heart transplant. So that's the story of the, you know, father of Myectomy. So, you know, dynamic LVOT obstruction is the hallmark of HCM, right? Uh We know this um obstruction gets worse. The gradients gets worse when you reduce the preload. That's why we do the valsalva, right? You cannot tell patient to hold uh their, you know, breath or strain for at least 15 seconds or more, right, to have a good effect um by reducing after load, right. So pure vasodilators you give to this patient, the gradients go crazy. That's why Amy nitrate and all these provocative testing. And if you increase contractility, right, Isuprel uh uh you can use in cash lab to provoke these gradients. Um And you know, when you give them volume, when your fluid um resuscitate them, you increase their afterload and use negative troop agents like beta blockers or nondihydropyridine calcium channel blockers like verapamil and dilTIAZem. Uh the LVOT obstruction gets better. And uh this is a slide I stole from Doctor Dre I very nicely um shows what happens with these manures on the gradient. Um Same with the iso uh protein. All we already saw uh discuss that the baseline, there is no gradient and then as you give a low dose contact ability increases and you see the dynamic gradient. So um there's a spectrum of morphological subtypes in HCM and all the HCM uh hearts, they don't look the same. There is this reverse curve um uh septum, there's a neutral or straight septum, but you know, it's definitely thickened, right. Uh You can see corresponding echo still images. You have the sigmoid septum, which is most commonly we call it the, the, the basal knob or basal septal hypertrophy. It's really the an interoceptive wall which is hypertrophic. And, and that's why uh in the cross section on Paracet long axis view, you see the septal map and then uh there is this um apical hypertrophy or a of page cavity which you can see on contrast echo or, I mean, you do you know left Flom and the apical SCM, also known as Yamaguchi syndrome is the Japanese uh cardiologist who first uh you know, described it and you can see this predominantly apical uh hypertrophy. And then there is this Yamaguchi sign on EKG where there is this deep symmetrical TV inversion in the lateral uh leads and you can see similar morphology uh on the MRI here. So the prevalence is higher in East Asians uh than the western population for apical uh hypertrophy. They have slightly better prognosis than the patient with LVOD obstruction because there is no LVOD obstruction, right. Um And these patients, they do have risk of apical aneurysm and risk for stroke. And uh you know, arrhythmia from the scar at the apex. We have to be very careful when we are evaluating a patient with uh hypertrophic cardio myopathy. We have to think about HCM mimics. Doctor Tush had already given us great grand rounds on Amyloid, right. Um Bilateral carpal tunnel syndrome, um early satiety, um you know, low voltage EKG um you know, and positive pyp scan right. These are all things should, like, kind of work up, should come into your mind, including genetic testing. When you think about someone with, uh, you know, HCM Fabre disease. We, uh, recently had a case where, um, at least five cardiologists saw this patient. Um, and they were, I'm not sure what's going on. They knew something is wrong. Um, went to the interventional cardiologist for chest pain, coronary had slow flow. So they diagnosed her with microvascular angina because the cholesterol was abnormal and she had metabolic syndrome. Um still they were not happy, kept having symptoms uh then was sent to EP because she had some uh some arrhythmias to see if she needs like an EP study. Um finally, um you know, the patient came to advanced heart failure office and uh she had carpal tunnel syndrome and neuropathy signs. So we were like, well, uh something is missing here. Let's rule out Amyloid. So we sent her genetic testing and did a pyp scan, pyp scan. Came back positive. Ok. It's like, ok, we have the diagnosis, let's start on treatment. Well, her genetic testing was positive for Febres and now she's receiving enzyme replacement and uh she's feeling much better. So some of these hypertrophic lvs could be hiding a lot of bad stuff which, you know, we really need to think about these as differentials in your mind. And um Plaquenil related cardiom, it is very rare, but you can, it can present as hypertrophy. MRI and myocardial biopsy can diagnose that thyroid and progra related hypertrophic cardiomyopathy. Last week, I was on surveys and now we have an unfortunate patient who is transplanted nine years ago. She has developed apical hypertrophy from being on progra and this lady this time, although she was on anticoagulation, she was on doac comes in with a stroke. So, you know, there are a lot of these uh mimics we need to figure out and another thing comes up many times is the athlete's heart, you know, so what's the difference between athlete's heart and HCM? Remember the hypertrophy is concentric uh in the athlete's heart. HCM is mostly asymmetric um when they, the athletes stop exercise or their activity, the hypertrophy regresses, right? So at one instance, sometimes you may have a problem diagnosing it, right? Because you cannot say when they are gonna stop their physical activity, right? Um The left atrium is not generally enlarged and also the left ventricle is dilated to get this so much cardiac output, right? As opposed to as we saw in SCM, the it's, it's a smaller ventricle diastology is normal in athletes and it is pretty significantly abnormal because of the myofiber um disarray and fi uh scarring these patients have and of course, the strain pattern is normal in athletes, right? So something you uh need to remember. So again, what's the mechanism and how the um you know, systolic anti motion of the mitral valve, right. So use the anti mitral valve leaflet kinda gets uh into the LVOT as the LV contracts more. And as you can see, the abnormal septum doesn't help, right? Is the M mode and you can classically the dagger shaped waveform uh on uh CW on the echo, the mechanism was initially thought to be venturing that there is a high velocity jet. Uh and uh you know, and because of that about the wing, there is like a negative pressure and it lifts the, you know, the wings or lifts the anti mitral leaflet. But it's uh it's not uh that the actual mechanism is a drag force. Literally, the mitral valve leaflet gets pushed towards the septum. Why do we know that? Because the uh the Mayo Clinic group, uh they did this study in 25 patients and they notice that S AM begins even before uh the CW and PW pulse wave and continuous wave Doppler velocity start rising, right? So there is a physical mechanism and not related to uh the V although there is vary uh mechanism or phenomenon present something to um uh something to know. Again. Echo is a hallmark of measuring um the LVOT gradients. You may have patients who have, you know, uh minimum gradients like 14 or 20 in this patient at rest. And as they did valsalva, you can see the gradients uh went well above in the sixties where in this case, he had a baseline um max gradient of around um 95 or something like that. Um baseline LV ode gradient, more than 100 is an independent risk of they ge getting into pulmonary edema or not tolerating uh verapamil or sudden cardiac death. So, do not give your patient verapamil if their uh resting gradient is more than 100. And this again, um you know, emphasizing the LVR protract Doppler uh how you can see different waveforms um hiding behind each other including the Mr waveform. Um It's important to remember that, you know, consider alternate side of obstruction. It may not be always LVOT. Recently, I took care of a healthcare worker who has been diagnosed with HCM for the last eight years and um nobody thought of doing the mid cavity gradients and we saw the echo and we were like, OK, where are the mid cavity gradients? Hoping that somewhere they would show up they were not there. So we repeated the echo. Uh patient came in, got the echo done, had LVOD gradients done. Valsalva, done, sent them again again. Call back like two. You guys missed the mid cavity grade, mid cavity gradients were like 85 on valsalva. And what do the gradients really means? Gradients? What it means is the LV pressure, right is on top of your systolic pressure. So if this female had a mid gravity gradient of 85 millimeters of mercury and blood pressure of 120 or 80 that ventricular chamber is facing a systolic pressure of 225. And that's what uh you know, kinda propagates the pathology and symptoms in this patients, right? Um Cardiac MRI, it's a very important uh modality. Uh almost every one of our patients. Uh they get a cardiac MRI. It not only gives you exact localization of hypertrophy, it also rule out rules out any other infiltrative disorders, right? It also gives us like in this particular case, um scar involvement, right? You can see a nice scar in the septum with late gadolinium enhancement. Um And that's why in guidelines, you can see um to patients with HCM where echo doesn't give us a good idea of what's going on, get an MRI, right? Patients where there is your uh you know, there is something missing. This guy has skeletal muscle problems, abnormal um you know, uh bony structure and whatnot. He has congenital deformities, uh something is missing, right? You're suspecting Asteroid disorder and MRI is helpful, right? Um patients where you have to make a decision about uh I CD uh MRI is super beneficial, right? Because those who get uh LV apical aneurysm, right, extensive uh myocardial fibrosis and uh with late cardin enhancement, they're at high risk, right? And then patients where they have, we have patients where they have aortic stenosis and you know, LVOT obstruction. So how do you know that A S is predominant or LVOT? And sometimes MRI can figure it out. We have two patients like that where MRI showed no aortic stenosis when she was diagnosed with aortic stenosis and was sent to the structural heart team. You know. So think about MRI when you are, you know, uh in this situation and the importance of risk stratifying this patient every 3 to 5 years because they may get progressive scarring and may become high risk for S CD needing I CD. So just because they had an M RIA few years ago, that doesn't mean that you don't need to rescreen them. That's something um you know, was interesting to me. And again, these are the areas where you can see they could be an ius for um you know, an electrical storm or arrhythmias. And our EP docs would target this car if they know on MRI for VT ablation if this patient need one. And this is a nice study with Cmrw stratification where, you know, you can see how the obstructive versus non obstructive group in the LG is more than 15%. That's kind of the cut off on MRI. The risk of S CD goes up, you know, they also um studied something known as diffuse dispersion or global dispersion index which more than 8.86 meaning the density of the scar combined with the scar burden gives you a higher prognostic value for uh certain cardiac, you know. So, you know, in a nutshell, um HCM is a genetic disease, right? Uh And the first genetic linkage as we saw in the history is like somewhere in the 19 nineties um uh in a large Canadian French Canadian family, they are described, right? And the HCM inheritance is autism and dominant, right? So one in 50% risk of sibling getting um the disease right, more than 10 genes and 80 mutations have been identified and of those myh seven and uh myo in binding protein, uh three have been the commonest of the mutations, right? And around 35% of the HCM that result from the cardiac um beta mio in gene mi mutations. And you know, it's important to know these mutations because it's a associated with survival depending on what mutation you have, the survival may change, right? Um And this study uh shows how this early penny transmitting early expression of um SCM phenotype in uh the white bar. That is the beta mio in heavy chain, right? Uh It's uncommon to see a child with HCM, less than 10 years old. Ok. So you have a kid who has HCM and they are less than 10 years old, you have to rule out other alternative diagnosis. OK. And as you can see with age, the prevalence kinda gets um higher and higher in both MYB BS and MYHC and MH C. And what's important is depending on the mutations, right? The uh top two mutations on the bottom two, the different mechanism but you can see the Kaplan Meer survival rates are completely different, right? So it's important to do genetic testing because it has prognostic value and they should be seen by genetic counselors cause that may change your uh you know, thought process of uh about management of these patients. You know, you may get them transplanted if they're acting up or you may get them I CD uh kinda quicker. Um Sa sarco your mutations in at CM. Uh We already talked about it. These are the different four sides you can see on the um cartoon here. And um you know why it's important also is the LV, morphology and genetics correlate. So we already had seen different morphological phenotypes which you can see on imaging uh with uh HCM, right? This reverse curve at CM where the septum itself is diffusely thickened has around 79% of gene positivity, right, as opposed to if you see um the sigmoid septum, which we commonly see if you send genetics in this patient population, it's only eight. So the genetic uh milieu drives the morphology, the morphological expression of these uh phenotypes. So very important to know. And then let's come towards the more important topics, sudden cardiac death in patients with uh HCM, you know, um patient who have a family history of sudden cardiac death. They are at high risk history of sudden cardiac death themselves. If they have an event, of course, they are super high risk, an expensing copy. We talked about that patients with ap ays non sustain VT unrest or exercise and severity of LV hypertrophy. Those who have massively hypertrophic septum like more than 30 millimeters, they are at a higher risk for um S CD and they need to be considered for um I CD, even the LVOT obstruction and scarring. We just discussed that on the MRI um increases their risk for S CD. Very important to know and why we kept talking about the LVOT gradients and whatnot because there is a linear relationship, right? Um These are the patients uh who uh had gradients, resting gradients, right? As the resting gradients, they rise, you have higher risk of sudden cardiac death, right? And if you see here, you know, even the resting gradient is still less than 30 but it's 25 to 30. That doesn't mean the risk is zero. They are still at some risk, right? So that's the message here is to risk, right? If I use different modalities, genetic testing, echo imaging, um you know, uh MRI for scarring and then re stratify your patients uh for STD because you can uh save somebody's life. Um We'll go again um over the go over again the I CD indications family history of sudden death from HCM. And this is always a board question those who are giving cardiology ep interventional boards, you are gonna see this question, massive LV, hypertrophy, unexplained, syncope, HCM. With systolic dysfunction. Once the EF drops below 50 they need an I CD. Ok. Um, as opposed to our regular patients LV, apical aneurysm, we already discussed late ga gaddo announcement. We already discussed. What's the tipping point? It's somewhere around 15% LG. Um, and nonsystemic if the VT is fast, like 200. Um, uh, and of course, those who have sustained VT they need, um, to be considered for I CD, There are different risk calculators. There is a European um calculator and um also a H A calculator. It's interesting that if you look at um the European calculator, it does not include MRI findings, which is an kind of an upgrade to the H A risk calculator. And generally, if the risk is somewhere more than 5 to 6% with the calculator, they need to be considered for I uh I CD. So it's a very handy thing one can uh you know, look at. Um and I know I'm emphasizing with every slide and this is slide directly taken from the guidelines, which patient and what are the class one and class two indications for I CD. Um I often see that some of these things are ignored when we evaluate this way. And that's why I wanted to emphasize on that. And there is just a quick slide on which antiarrhythmic drugs to use because A FB is very common in this vision in today's age. Probably Doctor Patel can um attest to this will probably go, this pain will go for an ablation and doctor gentle rather than, you know, using a lot of pharmacotherapy because each one of them can have side effects except di isobide, which is, which acts on phase zero. It's class one antiarrhythmic agent. And once you're maxed out on your beta blockers and your verapamil, you can try uh di isobide. There, there's been some nice recent review on it. A couple of comments I make is that really the sudden death, primary prevention benefit is seen in ages less than 60. So when you get greater than 60 that a lot of that sort of goes away as they've kind of timed out others in terms of family history. It's first degree family history, syncope within the last six months when you get like a distant history that kind of washes out. Um There's a little bit of graduation. You kind of mentioned that when you get 25 above, but certainly greater than 30. Uh you start to worry about it in terms of nonsustained BT, there's certain types that are higher risk, competitive, nonsustained BT, greater than 10 beats, greater than 100 and 30 beats a minute is a, is sort of a higher risk more commonly that's concerning in sort of the younger, younger cohort. And when you mix things and then in terms of delayed uh uh late uh gallo and enhancement when you get greater than 15% of the blind. So there's certain things that they, they go in there. But point of it is an 80 year old with high, you know, a thick heart. Uh, you know, if they have had sudden death, it's not really, you know, that in and of itself, unless there's something else that's typically not gonna be someone that you're looking at a primary prevention IC. Right. And very good points. And that's why, you know, and we see that reflecting in our clinical practice too right there. Now we are seeing these elderly patients, seventies eighties who have HCM. Um and I send a genetic testing and it's negative, right? So what's happening there? The heart has just remodeled in such a way that now they have obstructive physiology and it's just like a different phenotype, as you mentioned, lower risk than a classic genetic positive, right? Because these patients have normal survival, right? The their life expectancy today has become normal, ok. Um Because of the interventions we are doing on them. So if an 80 year old survives with whatever comorbidities and now develop at CM, um probably he's gonna live um normal to any other 80 year old of his age, right? And now, you know, sarcoma is the Hallmark or the target, right? It's a muscle disease, right? It's a myocardial disease at CM. And you know, beta blockers have been uh class one or first line agents, right? Acting on the beta receptors and then we have the nondihydropyridine uh calcium channel blockers, um verapamil and uh dilTIAZem. And then now um Reno Lazin has been found to be very useful for Angina uh in these patients, right? So keep something uh like that in mind. And then the new um molecule which is now recently become available is Meva Kampen and you know, just going back to the uh treatment algorithm, right? If a patient has SCM and he is symptomatic, start with beta blocker, maximize the beta blocker. OK. If there are side effects, um then you can add or change them too. Verapamil. I prefer verapamil more than uh Cardizem. Um If they have persistent LVOD gradient and persistent symptoms, there are no contraindications to di isoyama and di isopro. OK. Uh because of its negative inotropic um um action. And then if they are still refractory, then you can consider septal reduction therapy, right? Depending on the contraindication in patient's age and comorbidities, you can decide um with alcohol, septal ablation versus surgical septal a operation, right? So the landscape of disease and current therapy um you know, on these patients, which is, you know, determined by hyper conductivity of the ventricle fibrosis, diastolic abnormalities, impaired myocardial energetics, right? Um You work on genetic modifiers, lifestyle comorbidities, right? Um You have to treat their comorbidities. I have patients with HCM who are currently getting admitted and passing out because they have uncontrolled diabetes, right? Because they get dehydrated and then the lbod gradient goes through the roof, right. So beta blockers, calcium channel blockers, diarama, right, invasive septal reduction. If they have ventricular arrhythmias, I CD A FB, regardless of child vasco, they need to be anticoagulated. Ok. HCM. Patient with a FB should get a do A um and then can dehydrate and rhythm control, advanced, more advanced remodeling. There are some patients they get what we call burnt out, um left ventricle, either they get in and VT or the LV starts getting dilated, then we have to stop all these negative inotropic agents and then we just treat them as our heart failure. Patients with GD MD and some of these patients, they end up getting um a transplant, you know. Um so, you know, there are no like disease specific or disease uh modifying therapies and current treatment, you really target symptoms. If patients have no symptoms, you really don't treat them. That's what the current therapy is. And it's become so important to know how these ventricles behave. There is a very narrow um you know, kind of therapeutic line, these patients walk because of the pressure volume loop, right. It's such an if you see the corner, right, upper corner, as opposed to dilated cardiomyopathy, on the left side, the area and of the cur is so small. So if you diurese them, they become dehydrated and pass out. And if you try to uh super volume overload them, they go into pulmonary edema. So that's why the treatment algorithm is completely different than every other heart failure patient. Uh You see, so coming back to me camp right now, this is the first you know, myo in uh targeted therapy, right? Um It's a oral small molecule and it's a selective allosteric modulator of the cardiac myo in A TPS. OK. In it cm mutant mice, it prevented hypertrophy, it reduced myocyte disarray and reduce interstitial fibrosis as compared to placebo. So completely, you know, targeting you know myocyte drug, right. So what happens is uh in a normal sarcomere, you see here that there are these mice in heads attaching the acting filament and it leads to normal contractility and effective relaxation in it seems what happens is this hypercontractility. There are multiple uh myo heads are available, right? And the myocardial energetics is impaired. So what meva done is it attenuates hypercontractility. It reduces those myo in heads less myo in head are available with a negative action. And that's how there is reduced reduction in the number of crosslinking between mio and acting filaments. And this we we know that this crosslinking is a hallmark of HCM. So the mere uh path is what is targeted by Meakin, which is first in class and the approval came from the Explorer HCM study, you know. So in this patient, these patients were screened, it was a double bind uh trial and the inclusion criteria of a patient with LVO degraded more than 50 nyh A class two or three. OK. And uh they got it for 30 weeks. All right, with placebo and you can see the baseline characteristics. They all were pretty symptomatic. The LVOT gradients um uh were all uh somewhere in the fifties. Their peak vo two was in the 18 and they all had elevated biomarkers, right? And almost everybody had uh around 3/4 of them had genetic testing performed, These are the echo parameters I was talking about, right? The resting gradients in all these patients were above 50 and they have an LV wall thickness of around 20 millimeters, right? So with time, you can see those who got the drug, they had reduction in postexercise lbot gradient. Uh they had reduction in resting gradients, that reduction in valsalva gradients as opposed to placebo, right? And this is the dosing administration, there is uh still like a REMS program. Um You know, so risk evaluation and mitigation program, it's um the drug can be only um prescribed by certified uh uh physicians and there is a a protocol for safety, right? So once you start the drug, um you start at 5 mg dose and then if your gradients go down to less than 20 then you reduce the dose. OK. And then, and this is important for our uh echo text here because many times they are like, oh my God, last time the gradients were 80 then they're 10. Now they're back up again. What's going on? Am I doing something wrong? And I think the onus is on us, we should really write what week they are right? Because if you know that, oh, they are in eight weeks, oh, there is now in 12 weeks, something is gonna happen because they reduce the dose or they held the medicine, right? Because it's a reversible agent, right? The half life is seven days. So by the time you are at four weeks, if the drug has been stopped or the action dose has been reduced, the gradients start creeping up. And that's why you're not doing anything wrong. But we are changing the drug because of patient safety. Because if the EF goes down below 50% you have to stop the medicine, right? Twice the EF goes down below 50 you have to permanently discontinue it. So that's the whole whole thought process. So we always go through this algorithm when we are treating these patients um uh with Meva Campton and now the other agent which the new kid on the block is Afic Canton, right? Um This stabilizes the bio in um in the post power stroke uh state. So kind of similar um you know what uh Meva 10 does, but just a different mechanism of action to achieve the same goal, right? Um The Redwood HCM trial phases one and two got completed and it showed similar results, right? Reduction in Valsalva and LVO de gradient at rest, even the baseline characteristics were kinda similar. And the Secure HCM is the phase three trial which is focusing on their clinical symptoms. Um C pe uh has been done as primary end point and also quality of life questionnaire uh will be studied, right? So, moving forward surgical, um you know, treatment uh of uh um you know, HCM has grown a lot, right? As I told you, Morrow has been the pioneer of uh septal myectomy. And most of these uh patients, they, you know, it's a transaortic procedure. Uh there is a um you know, um you push the septum across so the surgeon can see it and you transect around um 3 to 5 milli five millimeter below the aortic annulus to get rid of um uh that excessive myocardium where the mitral valve is touching. Uh T is very important for these patients because if you have a jet which is not posteriorly or posterior laterally directed the multiple jets, if there is an anterior jet, that means this is not S A right. This is not gonna get better, do not leave the or if you see these kind of jets because then you will have to either repair or replace the mitral valve. And why uh myectomy is important because it improves your LVD gradient. It improves patients ny A class peak vo two functional capacity reduces I CD firing and improve survival. OK. And this is the uh Mayo clinic data on around 300 myectomy patients where you can see there is uh um a survival uh benefit from myectomy. Similarly then, right, our international cardio is also smart. So, Ulrich Sigvard, he is the one who first described um alcohol se a operation cause. Uh He knew that, you know, al can cause uh my card infection and scarring. Um and he selectively treated three patients and demonstrated that the gradients of almost equal to 200 millimeters of mercury were abolished after alcohol seal ablation. Um This is the broken bro brown wall Moro sign where you can see there is a post PV C accentuation of gradient because of the prolonged diastolic phase. Um And, and we can elicit this in the cats lab by having a um uh double human catheter. And then after alcohol septal ablation, you can see that this septal vessel was targeted. Um And uh you know, postablation, you don't see that vessel. Uh Most of the echo text which uh you know, come with doctor Summers for this procedure, you must be also seeing that we inject contrast um and during the procedure to see exactly which part of the septum lights up uh with our uh ultrasound contrast. And then you also decide which uh branch is the best branch to get the septal ablation done. And as you can see in the waveforms, post septal ablation, that gradient is gone. So, alcohol septal ablation versus myectomy if you have good patient selection and good higher volume center, the outcomes are kind of similar. Ok. Um There's always debate versus who gets more complications and which one is more durable. Um uh There's some data that if you do alcohol seal ablation, you have to come back for another procedure and there is a risk of permanent pacemaker, right? So now what and the researchers did was rather than alcohol se ablation. Now, we have a myo inhibitor. Can we compare alcohol septal ablation with myo inhibitors? And that's the valor HCM trial. So those patients who are eligible for alcohol septal ablation, they gave them my Meva Camp. OK. And then they followed the same protocol and you know, uh evaluated these patients and these were actually sicker patients with gradients in the seventies at baseline. And as you can see that patients who were eligible for Meva Campton versus those who were just given placebo, there are significant reduction uh in the NYH A class um and gradients. So, and also there was a reduction in the BNP levels and troponin levels uh when they were on Meva Campton. So, um the thought process is you can give uh Myosin inhibitors before even considering septal ablation and they are still persistently symptomatic, then move on to uh you know, septal ablation. So we have really come a long way in the treatment of these patients, right? Um If you see the general us population and their overall mortality, the mortality of HCM population is well below that. Right. It's because of the treatment we are giving them uh icds they're getting right and again, outside hospital, cardiac arrest resuscitation protocols and whatnot. Right. Um And HCM really needs uh care from diverse care teams, you know, imaging research, gene genetic structural team, advanced heart failure team. Um HCM centers, primary cardiologist, everybody has to work together. Right. And you know, it's challenging just like I described so many cases, 80% of the cases are undiagnosed, right? It's insane, right? Um Four are misdiagnosed, right? Uh There's poor coordinations during visits and they are not diagnosed for almost five years, just like the nurse I was talking about who was not treated with anything uh despite having gradients. So um the goal is to find cases in the community and try to, you know, direct them to specialist. So, Viz A I is a company which now recently their algorithm got FDA approved. So basically what they do is latch on to your EKG reading um you know, software and this their protocol, their algorithm screens for patients who are high risk for HCM. So an EKG they just quickly diagnosed at CM by their uh algorithm and then the EKG or patient's name goes to the Navigator and then you can initiate work up, right? You can do imaging further EKG S Holter, uh MRI whatever you want to do and genetic testing to get to the diagnosis in this patient. So um we are trying to the these people uh also work with our uh you know, neuro team. So whenever there is a stroke alert and the neurologist is remotely available, uh this, this is the company which uses or provides the neurology, the algorithm whether to thrombose or not. So it will be interesting to see whether our system is interested in getting this um patient so that it will go through this algorithm, right? The EKG gets analyzed and uh uh A I gets uh uh that and a suspected patient is notified uh and the list is generated and comes to us and then we go through the chart and then we decide which patient needs to be screened and whatnot, you know. So I think it will be a cool thing to do uh to diagnose more patients with HCM who are at risk for so many badness, which we see one quick slide on exercise in HCM because there's always a controversy like what shall we do? And a truck driver shows up or um you know, a firefighter shows up with HCM, what shall you advise them? So, um you know, mild to moderate physical activity is always good. It improves quality of life, lowers other cardiac risk factors. So the risk of mild to moderate level activity is lower, right than HCM, high intensity uh activity. You really have to work as a group, right? There, um, exercise, physiologist, MRI, you have to risk, ratify them, tell them that, hey, you may have a higher risk of S CD. Um, and just because they are going into a high risk sport, um, putting them, uh, implanting an I CD is kind of controversial, right. So there has to be a team decision. Um, there has to be an emergency response plan available, uh, with the team when these kind of athletes are playing on the field, right? Uh like football and hockey and they have to be hydrated on hot weather. It looks pretty basic, but these things are how many times you see kids passing out on the feet, right on the soccer game. So, uh especially uh electrolytes and um you know, hydration is very important because we know dehydration increases alde gradient, right? And they should know when to worry, right, worsening, dysnea, dizziness or fainting, chest pain, heart palpitation, something is wrong. These people uh should seek help. Um So overall to conclude, you know, HC MA is most common genetic disease. Uh it's diagnosed by, you know, an atomic assessment, by imaging echo MRI. We confirm diagnosis by genetic testing. 30% of them may not have positive genes. Um And we have to assess the risk for sudden cardiac death and also if they have a FB, then risk for C VA as we know that Chad Vasco doesn't apply if an HCM patient has a F put them on um uh doac as a first line Coumadin as second line. And uh you know, now we have newer agents like cardiac myo inhibitors as treatment available. And in refractory patient consider septal addiction therapy, whether it's alcohol septal ablation or myectomy. And then really the emphasis guidelines is on shared decision making. You know, you have to talk with all the caregivers of the patient and figure out what is the best treatment and therapy for this patient so that um you reduce the risk of death and I will stop here. Published May 10, 2024 Created by Related Presenters Amit Badiye, M.D. Sentara Advanced Heart Failure Center View full profile
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