Dr Zachary Tushak introduces the multidisciplinary group at Sentara specializing in the care of the sometimes complex, hypertrophic cardiomyopathy patient, and how the team collaborates for best outcomes.
Um, well, thank you for joining us today for our Grant Ros lecture titled The Multidisciplinary Approach to Hypertrophic Cardiomyopathy. While you may have worked with us individually, this is likely your first introduction to our multidisciplinary team. This team includes myself from advanced heart failure and Transplant cardiology, Matt Summers and Deepak Trejo from Structural Cardiology, Chris Cortino from Cariothoracic Surgery, Eric Keel from Electrophysiology, and Manic Veer from Advanced cardiac imaging. Although this list is not exhaustive, it also includes, by extension every member of our advanced heart failure, interventional electrophysiology, structural cardiology teams, CT surgery teams, internal medicine, failing medicine, the patient and their family and their loved ones. We all have a hand in their care. The reason for the development of this team is a few fold. One, patients with HCM are complex and oftentimes have multiple cardiovascular complications. 2, a multidisciplinary team approach allowed for easier collaboration amongst the main treatment fields with interest in HCM. And finally, patients with HCM deserve the highest level of standardized quality care. Today we'll take a whirlwind tour across HCM and cover the following topics. What is HCM, a differential diagnosis, pathophysiology, symptoms, a diagnostic approach, a rhythmic considerations, conservative treatment, and then lastly, disease modifying treatments. So what is HCM? Ordinarily the massites form a linear orientation I see on the left. However, in HCM, the massites are deposited in disarray as we see on the right. This abnormal orientation causes abnormal myocardial muscle thickening, commonly thought of a of a diameter of 1.5 centimeters or greater. There are several patterns in this abnormal thickening. The most commonly seen pattern is reverse curve, which is seen in approximately 60% of patients with HCM. Although not all LVH is HCM, when evaluating these patients, there are a few considerations, including other infiltrative cardiomyopathies like amyloidosis and Faber's disease, athlete's heart, hypertensive heart disease, valvular heart disease like aortic stenosis, subaoric stenosis, or supravaular aoric membrane. 60 to 70% of HCM is genetic in etiology due to an autosomal dominant missense mutation. These mutations commonly affect the myosin heavy chain, myoin binding protein, and cardio troponin as MYH7 mutation, MYBPC-3 mutation, and TNNT2 mutations respectively. HCM is usually asymmetric and disproportionately affects the intraventricular septum. Most commonly, the hypertrophied muscle is thick and heavy. It is hypercontractile due to too much activeycin binding during active phases of contraction. It takes up more space within the LV cavity, resulting in less intraventricular volume. The muscle is also stiffer and less compliant, resulting in inability to stretch, also resulting in less filling. Combined, this can result in lower stroke volumes and restrictive physiology. Hocru occurs when there is obstructive flow through the alveoflow tract. Due to the change in contour shape of the LV cavity, blood blood flow can be affected. To the left we see a smooth laminar flow through a normal LV cavity. To the right, we see the hypertroph septum of hokum. Note how the flow is disrupted with some blood flowing through the LVOT, some becoming stagnant with uh within the LV cavity itself after impeded flow, and some being regurgitated through the mitral valve into the left atrium. There are several conditions which may worsen obstruction by changing the internal geometry. A drop in pre-load such as during dehydration or aggressive diuresis. A drop in afterload usually from medications or exercise, can result in a drop in intracardiac pressures, which results in decreasing cavity size and worsening obstruction. In addition, tachy arrhythmias or increased inotropy can cause further cavity narrowing by reducing diastolic filling time and subsequently result in worsening obstruction. These factors can combine to narrow the LVOT further, causing increased velocities. These increased velocities during cystole can pull the anterior leaflet of the mitral valve due to the venturi effect causing obstruction. When examining a patient with HCM, there are a few telltale findings we should be aware of. In static stationary auscultation, a crechenodi crescendosystolic ejection murmur is heard best at the at the lower left sternal border. This murmur can sound a lot like eric stenosis, though unlike eric stenosis, the murmur of HCM is non-radiating to the carotids. In dynamic auscultation, there are a few maneuvers which may help, uh, help the clinician differentiate differentiate, uh, murmurs. The two most noteworthy are Valsava and Squatta stand. Both of these maneuvers accentuate the murmur of HCM while decreasing the murmur of er stenosis. Additional exam findings include brisk and bifed rod up stroke, a trip, a triple apical impulse, so the so-called triple ripple with an S4, a systolic thrill and recovery impulse, and we may also hear a mitral regurgitation murmur due to the systolic anterior motion of the mitral valve causing poor coaptation. Patients with HCM may be symptomatic or asymptomatic. Common symptoms include heart failure, syncope, chest pain, arrhythmias, or even sudden cardiac death. Understanding the exact ideology of the symptoms can be difficult due to the complex interplay in physiology. Heart failure symptoms include dyspnea, exercise intolerance, and edema. Diastolic dysfunction is present in all patients with HCM. Initially, there is a slowed relaxation followed by increased wall stiffness as myocardial firosis increases. This leads to an increase in left atrial pressure and dysmnea. Exercise intolerance is common in patients with HCM and approximately 25% of patients experience abnormal blood pressure responses. It is sometimes difficult to tease out the exact etiology of syncope, though the most worrisome ideologies are due to obstruction or even arrhythmia. Obstruction can be dynamic. It is present in 25 to 40% of patients with HCM. It can be caused by both thickened septal muscle and abnormal motion of the mitral valve. It can be variable and dynamic, affected by pre-load, after load, and contractility. Finally, obstruction can limit cardiac output and increase myocardial ischemia. Chest pain is a common complaint and oftentimes occurs due to microvascular ischemia from blood supply and demand mismatch, as well as abnormally small arteries with luminal obliteration worsened by thickened muscles. Beta blockers can be helpful. We should avoid nitrates and adjunctive agents such as renexa and avaidine can be useful. Lastly, patients with, uh, patients may complain of symptoms related to atrial and ventricular arrhythmias. Diagnosis of patients with HCM can be challenging, especially when evaluating for obstructive gradients. Even after diagnosis, patients with HCM require routine screening. Every year, your patients should have a repeat echo with LVOT interrogation, uh, at rest in Valsalva, as well as a cardiac monitor. Every 3 to 5 years, your patients should have a repeat cardiac MR to assess for early morphologic changes and to evaluate for ICD indications. We typically recommend first starting with an echo with LVOT interrogation that rests in Valsalva, and this will hopefully elicit what the clinician is looking for. However, remember we're obtaining a two dimensional picture of a three dimensional structure with echo. So if you suspect an obstruction is present based on your patient's symptoms, clinical exam, and HPI, we would recommend to proceed with stress testing with LVOT interrogation at rest, Valsalva, and, uh, post peak exercise. In addition to human dynamic evaluation, the stress echo provides information on inducible ischemia and arrhythmias. If your stress echo is still not indicative of what you expect, sometimes invasive hemodynamic testing with and without provocation is warranted. We should consider genetic testing in all patients with HCM. HCM due to a genetic mutation can be predictive for prognosis in regards uh to prognosis, but also aid in screening family members. If the index patient is genome negative, we typically recommend screening all first degree relatives at regular intervals. And with that, I'll pass it to my colleague, Doctor Manveer to review diagnostic modalities. Hey, good morning, everybody. um, thank you for joining us early in the morning. Thank you, Zach for arranging, um, this, uh, presentation and inviting me to speak on this topic. Um, basically we're gonna cover a couple of imaging modalities and we're gonna talk about um how we get to the diagnosis and what are the common pitfalls or what are some of the things that we need to look at when we are imaging. Effectively, a diagnosis is made when we have a wall thickness of more than 15 mm or 13 mm in a person who has a family history. Now, there's 15 mm we need to be sure that it's in the absence of other um. Um, uh, clinical comorbidity such as uncontrolled hypertension, aortic stenosis, or other etiologies, and sometimes they can coexist as well. So just because you have another coexisting comorbidity doesn't imply that you may not have HCM. You could have HCM and aortic stenosis, um, uh, mild, moderate, or severe depending on the patient. So it really is paramount to determine what's causing the sickness and how we go about evaluating this. And effectively a lot of uh symptoms and a lot of issues uh associated with HCM come down to simple physiological changes that occur in the myocardium and the heart. Uh, the Laplace law uh was described very long ago, uh, physi uh physics, hemodynamics, um, it basically applies to how much pressure the left ventricle can generate and how much stress the myocardium, uh. Uh, how much stress is applied on the myocardium wall in HCM, it's asymmetric. Basically what happens is there's areas that are more thick, uh, uh, as compared to other areas and hence the stress on the wall is asymmetric, resulting in, uh, fibrosis at various regions of the myocardium, um. And uh this is basically a representative MRI and in this um uh we see a three chamber view and effectively, I want you guys to focus on this area in the LVOT during Sicily in, uh, it become oops, I'm sorry. I'm used to scrolling on the pack server with my wheel. Um, effectively, we see that uh during systole, there is an anterior uh anterior pulling of the mitral valve leaflet that results in systolic anterior uh motion resulting in contact with the uh intraventricular septum. At the same time, we see a jet or a darkness that's uh traveling posteriorly. And this is uh similar to what we would see in a person long axis color Doppler profile where we would see a Y shaped uh uh rainbow of color, uh, aliasing in the LVOT and some aliasing going into the uh mitral valve. It's evident we can uh tell uh the similar physiology on um uh echocardiogram as well as on cardiac MRI. It's just the process is a little different. Um, we have multiple different morphologies of HCM. The most typical that we very commonly see is a sigmoidal, uh, hypertrophic, uh, cardiomyopathy where the top of the septum is very thick, resulting in a very narrow LVOT. I think, um. Uh, uh, this is the morphology we see a lot of times in the echo, and um, it's very difficult to, uh, discern whether this is just some asymmetric subtle hypertrophy in a senile 80 year old, uh, aged person versus whether this is true HCM so I think we need to be very, very cautious about, uh, uh, measuring the uh thickness of the muscle at this region. The others, I think we're pretty good at picking up, uh. We have a reverse curve, we know that we will see a very, very thick septum when we have an apical HCM we know we will see a similar to a speed shaped, um, uh, a left ventricle cavity. It may be associated sometimes with, uh, uh, apical aneurysms, and we'll get into that a little bit, um, we will also see, uh, sometimes we have what we call neutral HCM, which is uh gene positive, uh, quite often, however, it's um. It's a little um challenging to pick this up, especially if you have concomitant um comorbidity such as hypertension and uh aortic stenosis because it may look like your regular run of the mill hypertrophy, however, it's not really. So we need to be very uh careful about under calling HCM. Um, on, uh, cardiac MRI, isolated basal septal hypertrophy, as we talked about is one of the more common ones. Then we have the reverse curvature, we have the apical spade shape which we can really see very nicely if we administer contrast when we do. Um, contrast enhanced echocardiogram, we have the, uh, we have concentric, uh, left ventricular hypertrophy. We have apical aneurysms associated with HCM. This is basically um asymmetric wall stress resulting from a pressure gradient in the mid ventricle that results in an aneurysmal bulging. Of the LV we need to be very cognizant of these because a lot of times the aneurysms themselves can hide uh uh thrombus in there so if we do see something like this, we definitely need to administer contrast to make sure that we are not missing a thrombus in any of the imaging um slices. So this is a representation of uh what we would find in a fixed obstruction versus a dynamic obstruction effectively uh um uh on the left hand panel is actually a syNACT. So yes, we can do a syACT uh as well. However, um, uh, we'll go more into that in a little bit. Um, it is very good for uh. Uh, uh, re, uh, for morphological evaluation of structures, there's a little bit of a dimple if you can tell. I don't know if we can tell, we can actually, uh, there's a dimple at the, um, uh, upper basal septum over here that may uh look like a membrane as well, and there's some definitely some sam in this picture where we see the mitral valve pro uh protruding forward, and that can both can result in a fixed or a dynamic obstruction. Um, on the left, uh, on the middle panel, we have some fixed obstruction, uh, profiles of continuous wave Doppler through the LVOT. Um, these are representations of, uh, uh, these, this is what a continuous wave doppler would look like in subvalvular membranes, aortic stenosis, supravalvular stenosis in obstructive HCM, as Zach talked about, uh, we have, uh, dynamic, uh, uh, uh, changes to the pressure gradients that can elevate with, uh, changes to the pre-load or changes to the afterload resulting in, uh, worsening of the gradient. The key would be to differentiate fixed obstruction, mitral valve regurgitation, and uh dynamic obstruction, and we'll get a little bit into that as well as we go on. um, Doctor Tusha talked a little bit about the venturi effect, so I'm not gonna go too much into it effectively, it's a mechanism which results in pulling forward of the anterior mitral leaflet. There's also some talk about pushing forward of the anterior mitral leaflet, and if we do um 40 flow or other vectorial analysis, we also know that the blood as it's ejected, it uh goes around the posterior wall of the ventricle and kind of pushes forward the uh mitral valve leaflet. I don't think either one of them in isolation is the only cause. I think both of those causes result in the systolic anterior motion of the mitral valve, um. Um, and the main reason we get some LVOT obstruction with, uh, associated sam is because there can be associated mitral valve, uh, pathologies that are related with HCM. There can be leaflet elongation. There can be, um, uh, apical displacement of papillary muscle insertion. There can be cordial aparit anomalies, and there can be abnormal cord or papillary muscle connections even into the midsection of the. Um, uh, of the uh mitral valve leaflet, and all of these can result in abnormal closure or abnormal pulling forward of the muscle, um, that we see and can be associated with them, and this is just morphological, uh, evaluation or morphological specimens of abnormal pap muscles. And over here on the right we see a bied pap muscle which is a really hypertrophied. And once again, I, I got this um uh from one of the uh websites, uh, basically demonstrating the venture effect in the lift and how it results in uh forces that can uh make the mitral valve move forward. Um, so mitral regurgitation associated with ACM is usually due to distortion of the mitral valve of paratus or and uh from cys and resulting in systolic anterior motion of the mitral valve. If it's isolated due to HCM, we will usually see a posterior lateral uh regurgitation jet and a Y-shaped jet in the. Paternal long axis, um, uh, view, there'll be a lot, it'll look like a rainbow of color and the para long axis, um, uh, view. Uh, however, if we see an anterior or more of a mid, uh, atrial jet, we should be concerned about associated mitral valve pathology as well, um. All of these, uh, changes occur, uh, because of uh pre-load or after load and hemodynamic changes associated with HCM. Um, 2/3 of the patients will have structural anomalies like we said, they can be elongation of mitral valves, they can be anterior displacement of the pap muscles, abnormal corte, um, direct insertion of papillary muscle into the leaflet. Um, effectively over here we see um, uh, uh, cardiac MRI representation of an elongated mitral valve leaflet. Um, if you have a mitral valve leaflet that's 26 + minus 5, the probability is that you're dealing with HCM, um, in a normal, this was a very small study. Uh, I forget how many patients they had, but if in the control they only had, uh, 19 + minus 5. So if you, uh, if you have a very long, uh, um, uh, mitral valve anterior leaflet with uh coaptation plane that is an anomalous and uh resulting in systolic anterior motion. Uh, you're probably dealing with HCM if that, uh, if you find those things on an echo, of course we always measure the intraventricular septum, the posterior, uh, wall. I wanna challenge everyone over here. Um, perhaps we need to change the way we do a personal long axis imaging, and I've been talking to the techs about this. Perhaps, um, if we do see something that's asymmetric or hyper. perhaps it's time since we have the ability now that we actually drop an Xplane down the paraeral long axis so that we can actually screen the whole uh ventricle and measure and determine if there is asymmetry at the points that we're measuring. That's that's one of the techniques that we are able to do now because of the advancements in echocardiogram and the machines that we have. And once again, uh, over here we have uh abnormal insertion of the papillary muscle, we have associated systolic anterior motion of the mitral valve, um. And this is a TEE representation, and uh all of us who are familiar with TEEs know that the interior leaflet, this is a really bad prolapse, severe prolapse with um uh some mitral uh septal contact over here and uh on the color Doppler, like we said, we see a rainbow of color with a Y shaped jet that's going into the LVOT and another jet that's going into the posterior lateral segment of the uh. And this is a representation of uh the gradient that we would see. Unfortunately, I do not have an EKG over here, uh, otherwise I would have shown that the gradient that we see in HCM is going to be mid to, uh, will usually start in mid-systole as opposed to mitral regurgitation, which starts almost instantaneously with systole, and we'll get into that a little bit. We, we do have a tracing of that um this is another representation of myocardium thickening. Uh, and, uh, thickening of the pap muscles, uh, reduced ventricular cavity. Uh, and the same patient, basically a rainbow of colors in the LVOT and the mitral valve area. OK, great, so over here we have a continuous wave doppler that's going through the LVOT that basically shows a very uh slow peaking uh gradient and a very high 5.3 m per second gradient. Uh, going through the LVOT, when we are measuring this, we need to be cognizant of the fact that how do we discern whether this is the mitral valve or whether this is coming from the intraventricular gradient. One good way is to make sure that we inch away from the mitral valve, uh, to ensure that, um, you're not catching the mitral valve gradient. Another way is to drop two continuous wave dopplers, one into the mitral valve, one into the LVOT to see if we get two separate signals. Um, and this is a stress echo where we elicited an elevated gradient. Over here we see, we can see two curves. This is a curve that starts earlier with systole, and this is a curve that starts a little later into systole. When we have mitral regurge, we're gonna start much earlier into systole. When we have a dynamic gradient, it's gonna start a little later into the systole, and that's basically because the ventricle requires that much time to generate that pressure. Um, and on cardiac MRI, of course, we have a better resolution, um, a screening, uh, tool, uh, echocardiogram is the gold standard because everybody gets an echo. However, uh, for, uh, firm diagnosis, we use a cardiac MRI and basically this shows, uh, abnormal thickening of various segments of the left ventricle, and this is the spaces shaped appearance of the uh apex that we see. Uh, and once again in the representation of systolic anterior motion with posterior lateral regurgitation jet associated with HCM. Uh, we can have non-muscular findings or we can do an evaluation of the amount of scar that is seen, uh, using MRI. We have multiple, uh, um. Uh, assessment tools to assess the tissue and we also look at a non-left ventricular hypertrophy like right ventricular hypertrophy. We look at the mitral valve leaflet length. We can measure um the thickness of the ventricle at various segments. We also look for abnormal insertion of the papillary muscles, thickness of the papillary muscles. We can look at, uh, scar evaluation, which can be mid-ventricle, can be subendocardial, or may even be. or associated right ventricular scar, the key would be to differentiate uh the LGE patterns from various, um, uh, various, uh, other diseases and, uh, please stop me if I'm running over time. I I'm so sorry, um, in HCM we have midwall hypertrophy at various segments in sarcoidosis we can have multifocal uh enhancement we can have what we call a hook sign. In amyloidosis, we see subendocardial enhancement or diffuse enhancement. In uh Fabbrice's disease, we classically see basal posterolateral uh mid wall enhancement. Of course, we need to make sure that we differentiate HCM from other mimickers, and for Fabry's disease, we would rely on T1 mapping and the uh baseline values for T1 in Fabry's disease would be much lower as compared to HCM. Uh, although the, uh, enhancement sometimes can throw us off, so this is a summary slide, and I'm gonna run through it very quickly, very, very briefly in a minute or so, less than a minute or so. On echocardiogram, I would say we focus on the physiological aspects and we focus on the morphology to screen people on MRI we. Confirm the diagnosis as well as determine the uh enhancement and the amount of scar patients have. If your patient cannot have a cardiac MRI we can always do a retrospective gated CT a syna CT which will also give us uh accurate thickness. It will also give us aneurysms and thrombus assessment. Uh, however, for follow up of gradients and physiological function. Echo would be the key. So I'm gonna stop here. I'm sorry if I take extra time. I apologize for that, uh, but please don't, uh, hesitate to, uh, uh, ask any questions. Thank you. Thanks Zach for uh letting me chime in from an EP perspective on this. So we're just gonna kind of briefly go through in the next 5 minutes or so kind of EKG findings of hypertrophic cardiomyopathy implications for um atrial arrhythmias. Uh, ventricular arrhythmias and then indications for ICD. So in general, um, EKGs are abnormal in most patients with HCM, um. Most of them meet criteria for LVH just a typical EKG criteria, um, very many of them have signs of left atrial enlargement, which will be important when we get to the, um, wrist stratification. Q waves can be, um, pretty abnormal um in many leads, but particularly in in septal leads. And then, um, diffuse T wave inversions most prominent in V4 through V6 can be seen in apical variant hokum, which we'll show some examples of. So, um, honestly this is a more benign looking EKG for a patient with HCM, but what you can see is if you sum, uh, the, the S wave and V2 plus the R wave and uh V5, um, you'll get more than 35 millimeters and you'll see the kind of down sloping ST depressions and T wave inversions in V5 and V6 that would be consistent with the repolarization abnormalities you would expect in HCM. To be perfectly honest, a lot of times it looks a lot more prominent than this, but, uh, this would be kind of your your look for LVH. This would be a more classic example of apical variant HCM, though I would say that you could see something like this in non apical variant HCM as well. And what's most prominent here is if you look at V5 V6, those kind of terminal sharp, uh. Uh, T wave inversions where this actually becomes really relevant when we talk about ICDs, uh, is the type of ICD that's, uh, that's appropriate for a patient. So we'll go into too much detail about this because it's a very packed session, but, um, a lot of these patients with HCM are younger, right? So we have choices between subcutaneous ICDs and trans venous ICDs. In an ideal world, subcutaneous ICDs would be ideal in a younger patient because of the risk of downstream lead lead related complications. The way that, uh, SICDs sense things, they basically, well, all ICD sense things is they look at things above the baseline, so it's absolute value. So in V6 those really deep T wave inversions will be flipped. And so everything's above the bar basically and it's counting for beats and so it doesn't really discriminate between a T wave and an R wave. There are some algorithms, but basically if you have really deep T waves, it'll flip it up and that can be a risk for double counting. So there's certain patients with HCM though that they're young, you'll see that we'll end up putting in. Transvenous ICDs because we're concerned that they're gonna double count and get shocked for a heart rate of 120 when they're in sinus. So this is something when we look at EKGs as an as an EP for ICD candace, we're really looking at T waves. So from an atrial arrhythmia perspective, uh, lots of patients have atrial fibrillation with, uh, and other atrial arrhythmias with hypertrophic cardiomyopathy. They are particularly, um. Uh, at risk for developing worsening of their heart failure when they develop afib because they have such a restrictive cardiomyopathy and a stiff, uh, left ventricle that they're more reliant on their atrial kick, so more of their diastolic filling comes from the atrial kick so they in general feel really terrible with atrial fibrillation and and hemodynamically have a result it results in a decrease in their cardiac output. Um, so even in patients actually, I did a patient yesterday with HCM who has complete heart block feels extremely symptomatic when she goes into atrial fibrillation, so I did a PVI in her to try and improve her heart failure outcomes. Uh, from a, a ventricular rhythmia perspective, I think everyone knows this, um, this can result in syncope, particularly worse so if you have, um, already concomitant, uh, LV outflow tract obstruction, uh, and sudden death. You know, the risk of sudden death actually is relatively low, um, in, uh, in HCM patients I think we probably overblow this a little bit, um, but it is the number one cause of death, uh, uh, without warning in athletes and so early ICD is indicated for these patients. It's a lot of different ways you can look into this in terms of risk factors and HCM calculators. These are just from the guidelines, the, uh, class 1, 2A and 2B, and I'll just go through them personally, but personal history of sudden cardiac death or VTVF, this is a secondary prevention ICD, right? Uh, uh, 2A, so family history of sudden cardiac death, uh, severe LVH with um. A septal thickness more than 3 centimeters, unexplained syncope within 5 years, apical aneurysm, reduced EF because remember this is usually not asystolic dysfunction, uh, at in the early phases disease, um, significant scar, so LGE on CMR and then NSVT. I'll just kind of comment a little bit on we have a nice slide on um the the uh septal thickness. Some of these are are more risk factors than others regardless of which class that they're they're in. If you look at their independent odds ratios, so. Family history of sudden cardiac death, it kind of depends on the gene variant. Uh, so if you, if you tease those things out, uh, LV thickness is a huge risk factor. Unexplained syncope within 5 years can be pretty weak, to be perfectly honest, even though it's a 2A indication. LVEF can be quite prognostic. Scar is actually quite prognostic though it seems to be underrepresented in guidelines. The NSVT, I think it's important that we, we comment it's the amount of SVT NSVT because if you look at some of the guidelines, it's actually more than 3 beats, and that's not really that uh prognostic. So this is the slide I was referring to. So if you look at incidence of sudden cardiac death, uh, uh, per 1000 patient years, you can see this dramatic increase at uh greater than 3 centimeters, and then you can see the survival curves, uh, showing the same thing on the right. This is an example of the risk calculator I was referring to. There's a variety of different ones, but you put in the age, uh, the mean, uh, left ventricular wall thickness, the, uh, left atrial size that matters, right? So if you have somebody with atrial fibrillation and a more dilated left atrium that actually drives sudden cardiac death risk, the the LVOT gradient plays a huge role and actually if you play with this and you just put all the things and you play the LVOT gradient up versus down, that can drive you from recommend ICD to not. The reality is in those in those patients if that's what's driving things you probably should talk more about some sort of interventional um. Intervention whether it be surgical or or structural to try and reduce septal thickness obviously family history is is a fixed thing NSVT here it's just. Yes or no, but really the duration matters, uh, and so you can basically put this all in and then it'll give you, uh, give you an outcome. Um, and then I think we're gonna pass it along to Doctor Tao Reja who's on the line. Nice, thanks so much, Eric, Zak, Mao, thanks for the great summaries. I'll I'll have a little bit of a repeat, so I'll move quickly through those slides. We're going to talk briefly about medical therapy for this and a clinical case, and then Dr. Summers will follow me with um more discussion on alcohol subsablation and Dr. Scortina. And if you go to my next slide. All right, so we've talked about a lot of this already. We've talked about aspects of hypertrophic cardiomyopathy that ultimately affect prognosis, including sudden cardiac death, for which ICD therapy is essential, as Doctor Kee just went through. We talked about progressive heart failure from the obstruction itself and from diastolic dysfunction. An increase in the risk of advanced heart failure, as Zach alluded to, and then there's an increased risk of afib and stroke, which is particularly higher in these patients in a couple grand rounds coming up. I'll go through some of the MOC questions, but this year's focus in the general cardiology boards on EP, one of the key questions that's repeated a couple of times is in a patient with hypertrophic cardiomyopathy, that's an indication for anticoagulation regardless of Chad's vast sport because of the higher risk in these patients. Next slide please. So we're going to talk about conservative and definitive therapies focused on what we've heard about already. We've heard about the human dynamics of this, and we're going to talk about how we reduce left ventricular outflow track radient and the obstruction that causes so many of the symptoms. On this next slide, we'll look at some of those therapies, in particular, The conservative medical therapies that have been around really for a generation plus are beta blockers, non-dehydropuridine calcium channel blockers, and traditionally diopyramide, which now has fallen into increasing disfavor as we have new therapies we'll talk about at the end. So looking at the conservative medical therapies of the past for beta blockers we use selective and avoid non-selective beta blockers. We're trying to achieve negative ionotropy and to some extent chronotropy as well with attention to ultimate effects on on symptomatology. We're augmenting diastolic filling time, which increases ventricular preload. We've heard how important that is, and we're improving myocardial oxygen demand. About 50% of patients will have a significant improvement with beta blockers. They still are underutilized. On the next slide, we're going to turn to calcium channel blockers. Traditionally, verapamil has been the preferred agent. Again, we're looking for negative ionotropy and chronotropy. We're augmenting diastolic filling time. And particularly these are often used second line in patients who failed beta blockers or need additional therapy on top of beta blockers. The real danger and the reason these are second line is because they may potentially in some patients cause vasodilatation, and the patients may actually feel worse and do worse because of that change in afterload. And then finally on the next slide, Diopyramide is really a class one antiarrhythmic agent. In an era 20 years ago, this was very often used, and now it's very rarely used. It's an adjunctive agent, strong negative ionotropy in some studies it's been shown empirically to reduce outflow obstruction and in patients who are fractured to other medications, this could be a nice add-on. Again, this is largely fallen out of out of favor, but is something potentially in the background. Next slide. On top of that, we want to really think about our blood pressure management. We've heard about the importance of paying attention to preload and afterload. So diuretics, which reduce preload can potentially be counterproductive and other agents that reduce afterload, for example, um, uh. Some of the calcium channel blockers that focus in that area, for example, amlodipine can be counterproductive as well. Next slide. Um the other thing is we want to really be careful to avoid dehydration. When pre-load drops, these patients get into real trouble, and we want to think about exercise capacity. A lot of the sort of more prominent examples of sudden cardiac death in patients with hypertrophic cardiomyopathy are in the setting of exercise or other stimulants, for example, you know, cocaine use or something like that. Next slide. So again summarizing what we said, the things we want to avoid because they will increase the gradient are things that increase contractility, specifically ionotropes and heavy levels of exercise. We want to avoid decreasing preload inhaled amyl nitrate, which used to be used in diagnosis but rarely is necessary in this era because of the. Excellent diagnostics that Dr. Veer showed us. We want to avoid our carefully used diuretics and nitrates. We also want to watch for changes in afterload. If we adjust afterload and decrease it, we can often cause problems, especially with vasodilators and RAS blockade. So again, a lot of this is known to this audience, but always a good reminder to think about what things will increase the gradient and what we want to avoid in these patients. Next slide. Um, more recently, we now have, um, myocin inhibitors that specifically act to treat this, and then we have, uh, more invasive therapies, alcohol septal ablation and myectomy I alluded to earlier next slide. So the myocin inhibitor most commonly used right now is Mavacamptin. It's a specific agent targeted at the underlying genetic disorder of hypertrophic cardiomyopathy. It's the first in-class targeted allosteric inhibitor of cardiac myosin. It reduces the number of myosin actin cross bridges that are active at any point and thus really works on the excessive contractility characteristics of pokum. It's prescribed through a Res program currently because the FDA approved it very early in the game and our experience has increased. There are now a little over a dozen providers in our system, physicians and APPs scattered across structural heart, across general cardiology, and across AHF teams that will be happy to get patients on this therapy. The patients have to get it from a specific pharmacy. On the next slide you'll see there's an algorithm for utilizing it. That there's pretty significant data from two large studies and long-term extensions which are really exciting. They show a very significant compared to placebo decrease in Valsalva gradients of about 47 millimeters of mercury, significant improvement in symptoms monitored by New York Heart Association class and other measures, and there can be a slight decrease in LVEF, and that's the main thing we're looking. For when we initiate this therapy, tolerance is quite good, and in two large studies we've seen really effective results. This is typically used as monotherapy or as add-on to one of the other therapies, typically a beta blocker or a calcium channel blocker, but we tend not to use it as a third drug. This will be increasingly utilized, and there are other myocin inhibitors on board. And on this slide you see the difference if you look at. The first half of the curve, that's the Mevacampin versus placebo, and then in the second half, the placebo group was offered to initiate therapy and mirror the results that the treatment group had shown with a dramatic decrease in LVOT gradients. And on the last slide of this Mevacamptin discussion, we'll see that there's a pretty close monitoring algorithm if we go to the next one. That after initiation, and actually I think I left it out to cut slides, but after initiation, typically there's monthly echocardiography follow up for the 1st 3 months and then every 3 months thereafter to make sure there's not a drop in EF. These patients with hokum really have pretty impressive gradients that can be induced by Valsalva as shown in this slide that when I was in training at Mayo, we, we ended up publishing and on the next two we'll see some of the therapies. So we talked about how you can have an increase in the gradient with certain maneuvers. This is the classic Brockenro maneuver. are typically tested on boards where you have a post PVC significant increase in the gradient. The murmur gets louder, and that's one of the things that distinguishes on auscultation HCM from, for example, aortic valve stenosis. So a useful diagnostic and board testable concept. Next slide. And then in patients who don't have much of a baseline gradient, this is a baseline, and then on the next slide we'll see what happens when we add isoproturinol. So you really want to be careful with pressure selections. Pressure selection should be made to increase afterload once every 5 or 10 years. Most large organizations will have a patient who is. Given pressors in the setting of hypotension with HCM typically in a surgical scenario and rapidly decompensates many, many of these patients actually even expire in that setting. But here you see from baseline to isoproturinol that this can induce a gradient and that's why we want to be careful with press selection. Next slide. Uh, this is with high dose, you see a dramatic increase in the gradient and also in the MR in that LA curve that's on the very bottom. So again, careful use suppressors in these patients. Um, I'll share this was an area of interest for me when I first came here in 2004, training at Mayo. We actually put out one paper on the next slide. I'll show you the the image that came into Jack was thoughtfulness about when we have different therapies for, for example, septal reduction, we have alcohol septal ablation, which we'll hear about and surgical septal reduction. There are differential impacts on the conduction system, and we looked about the impact on right and left bundle branch blocks based on anatomic location. The last thing I'd like to show in my last couple of slides here, if we go forward one more, is our first example of an alcohol septal ablation. We did this in 2004, so we've been involved in this therapy for really over two decades. It was a 47-year-old gentleman who had severe non-nichemic cardiomyopathy. The next slide we'll go to, you see that he actually got a transplant which ended up being a hypertroph heart and in the setting of that with the hypertroph heart transplanted in, he had significant decompensation. The teams here did a great job. It was actually an error at another location, but on the next slide you'll see that. If you can play those for me, Amy, we see exactly what we saw beautifully on manic slides earlier. There's LVLT obstruction with significant MR, which is that posteriorly directed jet, and LV acceleration out the aortic valve. This is in this patient who's sick on the vent, not doing well in the setting of this hypertroph heart. Next slide just to go through for historical interest as much as anything else. We see what Moni showed earlier on the next slide, which is we see those gradients, and he had a wall thickness of 24, a resting gradient of 120, with 3 plus Sam. Next slide. So there was significant mitral regurgitation. We did a lot with pressers to try to improve and ultimately elected to take him to the cath lab for an alcohol septal ablation. Dr. Carl Hartman, Dr. Emin Almar, doctors Old and Hurry were a number of the clinicians involved that helped take care of this patient, and this is his cath lab gradients at baseline 120 with an echo gradient of around 100 just prior to sedation and again very much in line with what we saw from Dr. Veer earlier. Next slide. And so the next slide again, we ended up because he was turned down for surgical intervention doing the alcohol septal ablation, so you'll hear more about from Matt. And this is the very first one you see on the left that large septal perforator branch and on the right you see the image of a balloon in place and us injecting contrast, and you see the contrast now filling that large septal perforator, and then we put in alcohol in there as well. Next slide. You can see the ancient synagrams here and what we can see with diffinity administration is we can see the left ventricle on the left side of the screen headed up with the apex at the top of the screen, and you see that white speckling right at the basal septum, and that's where we're targeting our alcohol septal ablation. And so we can actually see that we're targeting exactly the spot where the san contact is next slide. And pre-ablation we saw the gradients where you see a peak velocity of almost 5 m per second and post ablation it's now down to a gradient of 13, and that's so often the case, and that's what we saw with this patient who still was quite sick afterwards but had a significant improvement in his hope. Next slide. And next slide I'll turn it over to Dr. Summers next to talk about more of this in the modern era. Thanks, uh, Deepak and, and Zach for, for having me here. I'll, I'll be quick with this, um, so that Doctor Scortino can talk, but basically, uh, I thought that when we talked about septal reduction therapies when Mava Hampton came out that we would be doing far less alcohol septal ablations. It turns out that the types of alcohol septal ablations we're doing are more to head off, uh, issues with another procedure TMVR trans catheter mitral valve replacement, preventing outflow tract obstruction. Than fur hokum themselves, but because of the cost of Mavacaton, we still do about half dozen of these for hokum a year, um, but I wanna compare and contrast, uh, what we know from the guidelines about septal reduction therapies, particularly with the invasive or interventional approaches to these, and then show a quick case. So our guidelines, uh, pretty much dictate that these SRT septal reduction therapies are reserved for drug refractory symptoms. So class 3 symptoms refracture the medical therapy that Deepak outlined. We have 3 different variations of course Mavaantin is the newest one, so it's a way to medically reduce the septum. Uh, surgical is extended septal myectomy which has a lot of data to support it, particularly in young patients. And then what I provide and what DPA provides is percutaneous septal reduction therapy, which is alcohol septal ablation which is effectively causing a controlled, uh, myocardial infarction in the area of septum, uh, that is thick and so generally when I talk to patients about the two, historically we've reserved septal myectomy for younger patients that aren't, uh, that are better surgical candidates versus alcohol septal ablation. There's some caveats to that. There's a lot of selection bias in the data, but. Uh, what we do know about, uh, myectomy is that we get a better reduction in the LV outflow tract, uh, gradient reduction. Um, it's better therefore in people that have really high, uh, provocable gradients, uh, bigger septums. There's significantly less pacemaker, uh, than an alcohol septal ablation, and it allows for the treatment of concomitant mitral abnormalities which, uh, um, uh, Doctor Fer outlined. Uh, there's potentially better 10 year mortality although there's pretty significant, uh, selection bias in that because most, uh, patients that are committed to alcohol septal ablation are, are older and not good surgical candidates. Uh, the big takeaway from alcohol septal ablation is that, um, sure we don't have sternotomy and we have lower length of stay, but, um. The the pacemaker rate can be up to 20%, so 1 in 5. The key considerations here that they're uh reserved again for a drug refractory uh symptoms and um the pacemaker rate is is a significant differentiator um. We, we use it, uh, pretty, uh, commonly, um, in preparation for a trans catheter mitral valve replacement we're trying to reduce pretty normal septums to avoid LV outflow tract obstruction, but as Deepak outlined, effectively what we're doing is, is we're going into a septal perforator we have to have concordance between the, the, uh, uh, epicardial and then the septal anatomy in the area of the myocardium that is thickest and causing the outflow obstruction and so you have to have good septal perforators, otherwise you can't do this. Uh, but effectively what we're doing is we're wiring that with the coronary, uh, wire and, uh, inflating a balloon to prevent reflux. We can see a reduction in those Brock and brow, uh, Brunwald moro, uh, effects and the peak to peak gradients, the provocable gradients just with balloon dilation, so causing local ischemia before we inject alcohol, and that's actually the biggest prognostic factor for success for alcohol septal ablation, the reduction in the gradients when we just have the balloon up. We then take uh definity contrast as Deepak showed and inject that through uh the end of the inflated balloon, the over the wire balloon, and we can see on echo uh exactly which part of the septum lights up and so it's a very gratifying procedure in that you see real time the gradient reductions you have a pigtail catheter in the LV and you can see these reductions. You can see the anatomy on on fluoro uh and on uh coronary angiography, and then you can also see with definity and echo exactly the area that you're targeting. This is a 65 year old gentleman that had a prior stent procedure and had a long standing murmur and progressive dysp beyond exertion. You can see with Valsalva he had a uh peak gradient, uh, that went up substantially. You can see the uh uh Sam and the severe MR as well. This is his MRI. It's a 2.2 centimeter upper upper septum, coal sam and moderate MR 89% scar and fibrosis. And this is his, his gradient. So there's different types as we outlined, but the resting gradient was about 45 millimeters. It's peak to peak. You can see that late predominance, so we see that on our spectral waveforms as well on echo, um, but post PVC you get augmentation, you get a drop in your systemic pressure and an increase in your LV pressure and so that's the classic, uh, Brunwald, uh, rock and brown moro effect. This is this patient's um. So over a 200 millimeter provocable gradient post PVC. You can see the septal anatomy there. There's a good septal perforator that that feeds. This large area of septum. He had class 3 refractory symptoms and this is our intervention. So we put a pacemaker in first. That's the key here. 20% of people again get a pacemaker. We watched him in the ICU for 48 hours. Um, we have a pigtail catheter in the LV to measure these, these gradients in real time. We wire the septal perforator. It's with an over the wire balloon. We then inflate that balloon, inject dye to show exactly what that we're not refluxing contrast into the LED. One of the biggest risks of this procedure is that you reflux alcohol down the LAD cause a massive LED infarct. Um, you can see after the ablation, uh, with 2 CCs of of ethanol usually give 1 CC per centimeter thickness of the LV in a uh peristeral lung, and you can see the area of, uh, hypokinesis on the LV gram. This is echo, so this is why this is such a gratifying procedure from an interventional standpoint is you can correlate all three of these echo, cath, and gradients. And at the end of the procedure, um, you can see the significant reduction in in resting gradients. This is definity showing the exact area that we're we're lighting up. You wanna make sure it doesn't go into the RV too much because you can cause uh ventricular septal rupture. This is the final. You can see there's no significant MR left. There's no uh flow acceleration or very, very little flow acceleration across the upper septum. In 2 years post ASA, he's uh asymptomatic. His last echo last summer showed a resting gradient of 20 and a provoked gradient of 35. We have other septal uh uh reduction therapies. You can coil these. There's less significant reduction in the less significant infarction of the septal, and then, uh, bipolar endocardial ablation, which we've done once to facilitate someone who did not have septal perforators. D Pattel did this in a valve and Mac case, um. But basically endocardial ablation of that area. And then uh Doctor Scortino. OK, Matt, your sedation for these procedures, what do you use? Fenel said usually about twice what you normally use during a stent procedures. They don't scream. It's not a real pleasant. They're having an infarct. There's no question, yeah. Speaking of screaming, And indeed. I wish I, no, I was talking about the surgeons, not the, uh, not the patients. Um, well, thank you for the opportunity to briefly speak about the surgical considerations of Houm. Um, I'd like to start by thanking Doctor Tushak for Bert and his team together. Um, this is a very important program for Centerra and for the region which is here to for not been a thing. And I think the impact moving forward is going to be um very important. This is what this region needs and has needed for a long time and thank you for your leadership on this. I only have a couple of minutes. I'm gonna kinda get right to the um right to the sexy pictures of what we do, um, at least they are to us. Um You've heard about all of um the the background and such uh operative myectomy is um a challenging operation it's simple in concept, cut out the extra meat um but in practice, um. It is very challenging, um, because, uh, especially for, um. For surgeons who don't do this often, it is very anxiety provoking because too little and you do no good for the patient, yet they've had a stomy too much and you're in the other side of the heart, which thankfully doesn't happen all that often, so it really does take a lot of concentration and a lot of thought. Uh, a lot of, uh, geometric perspective to do this correctly and not a lot of surgeons do this because of, because of the, um, the technical challenges of operative myectomy. Um, this is the original moral procedure I put it up because we should always thank our ancestors for having the courage of, uh, just trying these operations and making it, making it work. So this is an operative view, um, of, uh, of a myectomy. And what what you see here is that um the aorta is opened at the root and the aortic valve has been retracted back and we're looking straight into the LVOT and and what you see is the the excess muscle and actually what what's commonly uh this fibrous scar that tells you you're in the right place and what you can't see is you can't see the LV chamber. OK, and, and this is, this is the best view you're ever gonna get with us surgically, um, so, uh, what is important is understanding all of the the preoperative imaging, what you need to remove and, and the three dimensional anatomy, not just with what you see but what you with what you can't see, um, so. That when we do cut this out we're taking angles um that are aggressive enough to remove the uh excess muscle but not so aggressive um that uh like I said you're in the wrong side of the heart. Um, this is just an image of the fibrous band that we often see. Um, this is a path image, so it's not one of my patients. And I will see if this will play for us. So What this is is just a surgical image or a little video of cutting out the the excess muscle looks very, very simple, right? There's extra meat here you put a knife in and you cut it out. um what you can't see is the sweat dripping off the surgeon's brow as he's making these cuts to clear out. The uh the obstruction at the end what you can see kind of with the blood is you can see um the actual uh LV chamber, uh, straight down the barrel OK and so angle is important trajectory is important, um, and, uh, experience is very important with this, uh, in training this is the this is the operation that the attendings always did. Um, um, because it was so high, high anxiety and it was only late in the game that they would, they would let a trainee even approach, uh, this operation and for those of us to take this on, um, it takes years to get comfortable with this, um. It's not frequent, but a second cut, sometimes a 3rd cut with this gets gets infinitely harder because um once you take your initial cut with this, um, trying to trim excess muscle, it's just fibrous or or it's just granular tissue and so you're sort of you're sort of picking at it. And it's hard to get, it's hard to, um, uh, really clear more so you know the courage of the initial cut and the initial um trajectory is of utmost importance. Uh, let's see if we can go with this, um, yeah, same gradient stuff you see it works, uh, let's see if I have any other pictures. Uh, unlike, um, uh, other techniques, um, we don't have the advantage of, uh, adjunctive imaging during this and so it's all in the preoperative planning and it's all unknown where where you're going. Um, and this is, this is ripe for innovation for this, uh, operation for new tools and techniques. Uh, people like me who try to be a little inventive, have a couple of tricks up our sleeve. Um, I make a measuring needle to know exactly how. I don't even know what that noise means. um, um, I'm just kidding. I kind of know what that noise means. I'm not as dumb as you look. Um, uh, to try to, to get, to get this to be a well contoured LVOT and the same thing goes for extended myectomies where you have to go all the way down or even apical myectomies, um, which are more rare, uh, at least, at least in around here, um, when, when you're when you're trimming out the, um, the, the muscle from the apex. Um, and, and again, just another picture of a before and after, um, what you, what you can't see here you can see here, which is the LVOT. I don't really have time to go into the extended myectomy uh the apical myectomy, but sim similar things, um, uh. Really cleaning out the muscle uh while staying out of the right side of the heart uh while while you're doing this and and trying to do this on the first pass so that um that you get enough of of myectomy uh to ensure that you have the result that you want um and um and yet not being so aggressive that. Um, you, you make a mistake. Oops, I don't know what that is. Surprisingly, maybe even disappointingly at the end of the case, um, uh, what we're taking out is not a hell of a lot of tissue, uh, but it's enough tissue, uh, to, to do the job um it's, it's a, it's a lot of work, um, uh, and, and kind of slow, slow going uh compared to other operations, uh, where it's more procedural, uh, but at the end of the day we get the entire scar out and we get, we get the obstruction out. OK, I think that um. I think we'll skip over this and get to uh just two other things uh one is we, we do attend to the mitral valve. Some patients uh who have MR pre, um, that's solely related to Sam others, it's a combination of the hocu plus some other, um, mitral valve disorder. So typically at least the way that I do it is we deal with the myectomy first. If we have to deal with the mitral unless we know that there's a flail or something like that, we deal with that second, um, and, and deal, um. Uh, deal with that in, in, um, the inner part of of the case. Also, uh, since we're in there, if there is an afib, we can do a common Afib procedure so we can take care of the whole thing surgically, um, both the, the obstruction, the valve, and any dysrhythmias. And I'll leave the conclusion to Zach. OK, take my pager. So in conclusion, uh, LV outflow tract obstructions can be dynamic. Testing with provocation and progression of testing may be warranted. Patients with HCM are at high risk of atrial and ventricular arrhythmias. Early ICD considerations should be warranted. The cornerstone of treatment is conservative management for refractory patients. Disease modifying treatments such as Mavocamptin, a septal ablation, and septomectomy, uh, may be needed. Uh, thank you so much for attending, and if you have any questions, uh, we'll open it at this point.
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