Hypertrophic obstructive CardioMyopathy (HCM), a leading cause of sudden death in young fit athletes

0:01 Hi, thanks for watching episode #143 of the Doctor Podcast show. I'm your host and creator of Doctor podcast, Doctor Robert Sichert. Please follow and subscribe to Doctor podcasts and like, repost and share this episode. It will help us get more top expert guests on the program. It's like attending medical school in a video podcast. Now today we're discussing a very important heart condition and disease that is getting more attention in recent years because it is a leading cause of death and otherwise very healthy young athletes who suddenly collapse and sometimes die during strenuous physical activity such as in a basketball game or a football game.

0:41 The disease is called hypertrophic cardiomyopathy or sometimes hypertrophic obstructive cardiomyopathy, and we'll abbreviate it as HCM or HOCM just to make it easier to say. Now today we have an excellent guest. It's Doctor Martin Marin. He's one of the world's top experts on this condition. He's the director of the Hypertrophic Cardiomyopathy Center at Leahy Hospital and Medical Center in Burlington, MA. Doctor Marron is a board certified cardiologist who is internationally recognized expert in hypertrophic cardiomyopathy or HCM, and he's got more than 250 peer reviewed publications and top journals like the New England Journal of Medicine, Lancet Circulation, and the Journal of the American College of Cardiology.

1:29 He previously built and directed the HCM program at Tufts Medical Center for about 20 years and now leads Leahy's dedicated HCM Center, which has over 75 years of combined team experience treating HCM. He serves as the principal investigator for the groundbreaking new myosin inhibitor medication called Mycorzo, which was just recently approved by the FDA in December of 2025, and it's made by the Cytokinetics pharmaceutical company. Doctor Marin has been honored as HCM Physician of the Year by the national patient advocacy group HCMA, and he's been named a Boston Magazine Top Dr. every year since 2017.

2:10 He's also an associate professor of medicine at UMass Chan Leahy and an adjunct associate professor at Tufts University School of Medicine. Today he joins us to help the general public understand HOCM or hypertrophic obstructive cardiomyopathy and the exciting new treatment options that are changing patients lives. But Doctor Marron, thanks very much for taking the time from your busy day and schedule to join us today on Doctor Podcast. Really appreciate it. Absolutely. It's a pleasure, Robert, to be with you today to talk about hypertrophic cardiomyopathy.

2:43 Pleasure. Thank you. Thanks. Now, for viewers who may be hearing about this condition for the first time, can you explain in simple terms what exactly is Hypertrophic Obstructive Cardiomyopathy or HOCM or HCM, the two abbreviations? Sure. So hypertrophicardiomyopathy and the abbreviation we use generally for the diseases, HCM, as you were just alluding to, is a genetic heart disease where patients are born with a mutation that ultimately causes the heart muscle to become thicker than it should. And that then can lead to, in some patients, adverse complications at some point in their life, such as symptoms, heart failure symptoms, increased risk of abnormal rhythms from the heart, including a risk in some patients of sudden cardiac death and also other arrhythmias like atrial fibrillation and the risk that comes with that of stroke.

3:37 Now, how many people in the USA approximately are affected by this condition? Yeah. So HCM, you know, as I was saying, is the most common genetic heart disease that we have, you know, worldwide actually. And if we look at prevalence, Yep, if we look at prevalence, we're looking at one in 500 in the general population worldwide. So that's about, you look at it for the United States view, that's about 800,000 people in the US with ATM. Not all those are diagnosed, but that's the prevalence of the disease in the US.

4:08 And, and I, and I'll just say too that again, that makes it the most common inherited heart disease. And I'll also say that there's, you know, just to talk just a second or more about the ATM in general. And you had alluded to this in terms of the terminology two types of HCM actually there is the more common form which is called obstructive HCM or OHCM where patients have an obstruction to blood flow out of the heart which increases the pressure in the heart. And then some patients have non obstructive HCM.

4:40 So together, that's one in 500. So because the heart muscle is abnormally thickened, it blocks the outflow of blood from the heart when the heart is pumping. Is is that what's happening? That's right. That's right. So patients have with HCM actually have a what we call hyper contractile heart. So the heart function is actually super normal, something we term the ejection fraction. So the ejection fraction is a little bit higher in HCM than in normal adults. And that increased in contractility with happens then is that that can actually result in pushing or dragging one of the valves of the heart, the mitral valve into the thickened muscle during that ejection phase.

5:25 And when that happens, the blood is actually impeded or obstructed by the valve touching the the muscle, the septum and it's that is the mechanism of the obstruction. And when patients have that, either under resting conditions or with exertion, they're by definition an obstructive HCM patient. OHCMI See so. This is what we see occasionally on the news where a 20 year old top basketball player or football player suddenly collapses during a game. And is that what is causing that? Yeah, that's right.

5:58 So one of the most visible consequences or risks of HCM, you know has been the risk of sudden death. And you know, as you as you were sort of alluding to there, that is, you know, taking on its greatest visibility when it has occurred in young otherwise healthy athletes. Those are the healthiest segment of our population. And so that is really touches a sort of a touches the core in the general population when that happens obviously. And so, yes, HCM, if you look at sudden deaths on the athletic field, the most common cause of that is hypertrophic cardiomyopathy.

6:33 Now you mentioned it's a genetic. Have we identified the genes that we know? Is this autosomal dominant, autosomal recessive, or some other type of inheritance pattern? Yeah, autosomal dominant, which means that it's inherited, you know, each, for example, each child of an affected parent with 50% chance of inheriting that mutation, right. And these are mutations that we've identified that encode for the protein of the structural apparatus of the heart muscle called a cardiac sarcomere. So that's what these mutations are, sarcomere mutations.

7:07 And we've identified them in about half of HCM patients. We can find the mutation and we're sort of still working on identifying the genetic cause in the other half of HCM patients, right? So if a parent has it, should the children all be tested genetically to see if they have it or not as well? That's right. So you can, you can do one of two strategies. You can test genetically, there's genetic screening that can be done. There's commercially available genetic testing that practitioners can order and can and can pursue that strategy to identify whether family members like children, have the mutation or not, and therefore whether they're at risk or not of developing HCM.

7:44 Genetic testing is not pursued or there's no mutation identified through that strategy. Then we still screen kids with imaging, echocardiography, ultrasound, and EKG at periodic intervals, usually through puberty or adolescents, and then less frequently through adulthood. I see. And these are both benign, non invasive tests, an EKG and an ultrasound. So there's a. Reason not to do it? That's right. Right now, what age do symptoms start and are they gradual or can it occur suddenly and acutely where you have a collapse of the patient?

8:17 Well, yeah, when we talk about symptoms, I mean we, we, you know, most commonly that that those include, you know, exertional shortness of breath, sometimes chest discomfort, decreased exercise tolerance, Lightheadedness, sometimes palpitations, feeling your heart racing. Those are the most common symptoms that a patient with HCM can experience. They most commonly will begin in midlife that's through the average age. So let's say late 40s, early 50s is usually the first time patients start on average start to do experience those symptoms.

8:49 Obviously we got patients that are younger that have symptoms and older, but that's that's usually most commonly when patients start to feel the effects of the disease in terms of symptoms. And then you alluded to another issue which is sudden death. Obviously the catastrophic event which obviously as we talked about before is really highly visible can occur in in athletes as well as non athletes with HCM. But that is an arrhythmic obviously issue that's an electrical risk related to HCM that most commonly can occurs in younger HCM patients.

9:20 So teenagers, young adults, the incidence of sudden death due to HCM is high as their kind of decreases in midlife and actually becomes uncommon in older HCM patients. Interesting O what are the biggest dangers or complications if HCM isn't diagnosed early enough and treated properly? Yeah. So we, the way you know that we usually start the visits out with patients is to first say, you know, right off the bat that for the vast majority of patients with ATM actually that longevity or life expectancy is normal or near normal, which is obviously a reassuring point if you're a patient, particularly one that's just been diagnosed.

10:01 So then, then the question is that based up, is it what can happen to me, you know, as I go through life with ATM then? And it really comes down to about two or three different issues. One is the development of symptoms like we talked about shortness of breath, decreased exercise tolerance, chest pain. So limiting symptoms that affect the patient's quality of life #2 is the risk of abnormal electrical rhythms. Those are both upper and lower chamber rhythms and most commonly atrial fibrillation. Patients with ACM are at greater risk for that.

10:29 And then as we already have alluded to already, the risk of bottom chamber rhythms that can cause sudden death in a small number of patients and then a small risk for stroke, but that's usually in the setting of a patient who has atrial fibrillation and HCM. Interesting. Now, what first sparked your your interest in HCM? You, you spent decades in this field. Tell and tell us about the HCM center that you direct at Leahy Hospital. Sure. Well, I have a, you know, my story I think is probably, you know, unique, I'd say a little bit in terms of, you know, how I found my way in this direction.

11:06 And I was fortunate to grow up with the father, who was also one of The Pioneers actually in hypertrophic cardiomyopathy, starting out his career at the National Institutes of Health in Bethesda, MD. And so I grew up in in Bethesda, MD, while he was there for over 20 years leading that division. And, you know, he, he and I, you know, are obviously very close. And kind of growing up, I, you know, sort of became, you know, in a way engaged because he was a great teacher. And I think in a lot of ways, I was inspired actually, not just toward cardiology, but toward this disease in a way that I, you know, was able to appreciate aspects of it that others would not have been able to appreciate because of that experience.

11:50 So that's the unique sort of pathway that sort of led me in this direction. And you know, we, you know, we've continued to work together actually my dad and I in this field for over 20 some years. And that's included, you know, him also being part of the development of the of the Leahy clinic. As you alluded to in the beginning, I spent most of the beginning of my career starting the, an HCM referral center at Tufts Medical Center in Boston. And over the last couple years that program moved over to the Beth Israel Leahy system and and we are continuing that clinic and center at Leahy and it's one of the largest referral Centers for Hypertuber cardiomyopathy in the US.

12:28 We see high volume of HCM patients and their family members and provide high level consultation and obviously treatments for the disease at that Leahy clinic just outside Boston. Wow, that's a great story. So you've been basically been HCM expert since high school? Probably, probably got a lot of probably even before that, if you can believe it. Yeah, actually, even as a little kid, I, I got to see echoes and Ekgs that my dad brought home and hear all the stories. And so, yes, very early exposure, which had a good effect actually.

13:00 That's great. Fantastic story. Now I mentioned earlier my corzo, which was just approved a few months ago by the FDA. Before my corzo came along, what were the main medical treatment options for people with symptomatic HCM? Yeah, beta blockers and calcium channel blockers, drugs that, you know, that have been used in a lot of different forms of heart disease to try to treat symptoms including obviously high blood pressure and hypertension. Those drugs were really the mainstay of trying to alleviate the symptom burden in patients both with obstructive and non obstructive HCM for all almost over half a century, if you can believe it.

13:40 Yeah, exactly. And so those were the drugs that we had, albeit suboptimal in terms of efficacy and also in some cases not well tolerated by patients in terms of side effects. So not really the greatest of medical therapy options, but that's what we had before Mycorza. And patients who didn't respond to those needed surgery sometimes like. That's right. That's exactly. Ectomy surgery or sometimes alcohol septal ablation. Can you tell us what percentage of patients needed that and and how that works?

14:12 Yeah. So if patients you know in the pre Mycorzoa era, you know which again expand extended I should say over decades, you know beta blockers and calciumet lockers were the first line agents. If those did not work, then generally patients were moved on to a surgical therapy which was called myectomy and that is an open heart procedure where between 3:00 and 8:00 grams of muscle out of the septum, the alpha tract area is resected out and and essentially the obstruction eliminated through that anatomical direct anatomical intervention with surgery.

14:48 So very effective, but obviously invasive and and involved over years and carries with it still high efficacy with some risk of course. And the alternative option to that came along about 20 to 30 years ago, which is a catheter based procedure that we also used quite a bit called alcohol. Septal ablation catheters in the Cath lab advanced up into the heart and then usually one of the branches of the LAD, the septal perforator branch were accessed by that catheter and alcohol actually injected through the perforator into the septum where the obstruction was.

15:23 Yeah, to create a localized area of damage that then and ultimately thin that muscle to essentially mitigate the the obstruction. And so those were our two invasive options to try to alleviate symptom burden. Wow, So you were either cutting out a piece of the heart muscle to thin it out or injecting alcohol into a piece of the heart muscle to kind of kill part of the muscle. Seems like that could be extremely accurate and precise and and make sure you cut out just the right piece at the right place, right?

15:54 That's right. I mean for both of those, you know, there are limitations obviously with the alcohol ablation of about 10 to 15% of patients that injection was ultimately, you know, not in the right place or not in an optimal spot, even though we thought perhaps it was the procedure and it didn't relieve obstruction. And obviously with surgery, you know, the issue there is really having an expert surgeon, it's a very difficult operation. You're, you're, you're resecting that muscle through the aorta essentially, which is a 2cm diameter, you know, visual field.

16:22 And so you really have to have an expert surgeon who has high volume to really maintain the outcomes with that operation that you would want for your patients. And there are very few surgeons like that could be because it's not a common procedure that's. Exactly right. That's the limitation that we still have related to the operation today. It's access is limited by only a handful essentially of of of really skilled surgeons for that operation, even in the United States. Wow, amazing. So that's why we have Mycorzo now, which is great.

16:54 Now you're the principal investigator for the new medication, Mycorzo. What was it like getting FDA approval and working with the cytokinetics company to get the FDA approval and and how long did that take? Just give us an idea. From the first clinical trial to FDA approval. Yeah, Yeah, I think probably the overall process went a little bit quicker I think maybe than a lot of other drug development stories perhaps. I mean, you know, just because it, it, it performs so well throughout the clinical trial journey, which of course as people visiting may know, use the phase one and phase two studies with once the drug is available, you know, to test it for first mostly safety and safety intolerability in those phase one and two studies.

17:37 And then that with Mycorzo looked very good and then it advanced to phase three trial, which was the Sequoia pivotal phase three trial that ultimately formed the basis for approval. Once that trial was shown to demonstrate that the drug was both safe and, and, and also highly effective in this disease. That whole process probably spanned, you know, 5 plus years essentially, as you know, drug development in the in the United States is a, it's a long journey no matter what. But in this case, I think I have to say things went, you know, very well and very smoothly overall for that process.

18:12 And again, largely because the drug here, Mycorzo, you know, really performs so well in terms of both efficacy and safety. Wow, that's that's a nice journey and a good ending for that journey. That sure, that's awesome. Now tell us in plain English if you can, how does this drug actually work inside the heart? What does my corzo do to the heart muscle? Yeah, yeah, yeah, great question. So what the drug does is if we just step back for again we remember that we were talking about the obstructive HCM patients and again the my cortisone right now is approved for those patients right now who have symptoms.

18:50 OK. So the, the, the current indication is symptomatic obstructive or OHCM. And as we were talking about before, the obstruction in in HCM is due to that hyper contractile left ventricle. It's sort of is what drives the valve into the septum to then essentially obstruct the blood flow. So what my corzone does is that it, it decreases at the level of the muscle proteins. Those are called the cardiac sarcomeres. They're, they're, they're the engagement of those proteins is, is, is is increased in HCM.

19:21 So it decreases those. And essentially what that does is that translates to a slight decrease or mitigation of how contractile that heart muscle is in HCM. So if you decrease the contractility a little bit, which is what the drug is doing, then based on that mechanism, then what happens is that you decrease or eliminate that mitral valve from coming over and obstructing blood flow. And if you decrease significantly or eliminate the obstruction, that is really the primary driver to what makes patients then feel much better and function much better.

19:56 Wow. So it actually kind of weakens the heart muscle in the areas where there's too much heart muscle. Yeah, we can, Yeah. I mean, just to be clear, it usually doesn't, you know, we can has a connotation that that that's a negative issue here. I, I, I think actually maybe in fact, I would say it actually kind of helps to normalize. Normalize. Yeah, right. Exactly for the vast majority of patients. And it's that normalization that translates into the benefit by getting rid of the obstruction. Wow, that's great.

20:23 Now, how often is it given and and by what route is the medication given? Yeah, it's oral drug. So it's a pill given orally once a day. Yep. And so it's a daily drug and, and, and so it's fairly straightforward in that sense. Right. Well, that beats having major heart surgery. That's that's right. And I think there's some evidence to suggest that, you know, drug like Mycorzo can actually either delay or possibly eliminate the need for surgery. And so your thoughts there are right on the mark. Actually, because of its ability to be so effective at making patients feel better and function better, that may actually obviously translate into patients not needing or not as many patients needing something like surgery.

21:15 Right now, if a patient has this and and they're taking Mycorzo everyday, can they do vigorous strenuous exercise and activities and and not have the problem that they had before? Yeah. Well, So what the what the most dramatic, you know, aspect I think to this sort of therapy is that it really, you know, in a way kind of reverses the heart failure that these patients were experiencing before taking the drug. And so once those patients get to optimal drug dose with my Corzo, the vast majority of them feel substantially better.

21:50 It's almost like night and day. These are otherwise generally healthy patients for the most part. You know, obviously that pump function is not just normal, but it's super normal and turned to more normal. So it's not like there's a compromised heart function here at all in this situation. And so by relieving that obstruction, patients really feel and function so much better. So they can not only with their daily activity feel like they're able to engage life better, but also with recreational activities as well, I think able to engage there in a way that they weren't able to before.

22:22 And sort of together, I would say my Corzo has a substantial therefore improvement on patients health status. Their quality of life improves dramatically here. Wow, that's great. So they're not short of breath and they don't like chest pain and doing their normal activities that that's great. Now you mentioned this is just for symptomatic patients. If somebody has HCM but they have no symptoms, it's not necessary. You got to treat them. You just follow them with ultrasounds to see what's happening with the heart muscle.

22:53 Is that right? Yeah, that's right. I mean, I think that that's right for obstructive patients who are asymptomatic, there isn't, you know, an indication for Mycorzo in those patients. That actually is an area when we talk about the future of of investigation that may be undertaken, which is sort of translating these drugs to like my Corazo 2 less symptomatic or asymptomatic patients for the idea that could if we did that, could that alter the Natural History in a beneficial way, in a different way than if they didn't get the drug.

23:28 We don't know the answer to that yet, but that's yeah, that may be part of what is the next step here. But at the moment my course is not indicated for asymptomatic patients. Right now, how does it compare to the previous medical treatments? You may have mentioned the beta blocker drugs and the calcium channel blockers. Yeah, I mean it. It's, it's just not comparable in my view actually, you know, in fact Cytokinetics sponsored a, a clinical trial that came after the pivotal trial Sequoia called Maple HCM.

24:02 And that was a different clinical trial with Mycorzo that actually addressed that question. How does Mycorzo compare to a beta blocker? So monotherapy for both kind of against each other head to head in symptomatic obstructive HCM patients. And that study published in the New England Journal less than a year ago demonstrated that my Corzo was far superior to beta blocker in terms of improving how patients feel and how they function, biomarkers etcetera. And so we sort of in a way kind of got an answer that you know with that trial it's superior.

24:41 Wow, that's. Great news. Now as physicians, we know that every medication has potential risks and side effects. What are the main side effects or safety considerations with Mycorzo and how do you monitor patients who are on the drug? Yeah. So the, the main, the main issue with Mycorzo and you're right, every drug has a, you know, has a potential cost here obviously. And so here that is that it is a there is a small risk for what we call systolic dysfunction. So the drug decreasing heart function too much, okay.

25:14 And then potentially by doing that, possibly putting a patient at risk for an adverse issue like heart failure. And to be clear, there is a label for that risk, you know, with Mycorzo, to mitigate that risk, which again, if you looked at both of those clinical trials for Mycorzo, the risk of that happening in an individual patient was actually very small, very small. But to help mitigate that, you know, in terms of safety, patients have to agree to participate if they want to go on my corzone, what's called a risk evaluation mitigation strategy, it's REMS for short and that's an FDA mandated program where patients are followed.

25:54 It's different intervals using echocardiography to evaluate their heart pump function and their pressure gradients 21 and make sure that they are safe, but two to adjust dose in those patients to both, both for both efficacy and safety. So the REMS program is at the core here of of of this drug of the usage of this drug. So it's longitudinal monitoring at different intervals with ECHO to keep patients safe. Right. And that's ultrasound, which was completely benign and non invasive. That that's great.

26:28 That way you can monitor patients, make sure they're getting the correct effect. Can you adjust the dosage to lower levels if if the medication is is actually too potent? Yeah, I mean usually the introductory dose, you know, we hardly saw any low pump function issues. So what sometimes can happen is if patients titrate up and then they have they happen to have a low, a low pump function event. And by the way, in the studies when, when they had those low, you know, pump function events, they occurred very rarely.

26:56 As I said, they, they, they actually with mycorisone were not associated with heart failure or the need to interrupt the dose. All it took was to down titrate the dose in those patients. So that that is great. So that goes to sort of the, you know the I think the favorable what we call pharmacology of the drug here is that if there is a low EF event pump function event, it's a down titration of dose not usually interruption. Oh, that's, that's great news. So you can adjust it and customize it for every patient based on your follow-ups and echocardiograms and so on.

27:33 That's right. Exactly. In fact, we use that. That's exactly how we describe it. It's sort of personalized approach to sort of targeting patients with appropriate dose. That's right. That's where medicine is going correct? Now. Are there any contraindications to using Mycorzo or any serious drug? Drug interactions? Yeah, the only drug, drug interaction that is, you know, of note here in terms of, you know, contraindications would be a drug called rifampin. You can't use Rifampin if you're on Mycorzo.

28:01 Rifampin for those that you know, may not know, because it's not a drug that's commonly used. It's an infectious disease drug. It's actually was used or is used in, in some cases to treat tuberculosis or other infectious diseases. So not a common drug at all. But that would be 1 where you can't use with with with Mycorzo. And then the other thing is you can't start the drug if patients have ejection fractions that to begin with are too low, you know, which can sometimes happen at ACM. And so that's the only other scenario where, you know, people need to be aware.

28:31 Right now, as I mentioned, you're one top experts on HCM. What does the future look like? Are there even more new therapies on the horizon? Any new clinical trials you can discuss that might make things even better in the future or maybe even cure this disease? Yeah, yeah. I'll tell you what I think is really exciting, You know, when we talk about the future and really where a lot of the focus is right now in the field for sure is the, you know, anticipation for actually a trial with Mycorzo in the 1/3 of HCM patients that have the non obstructive form.

29:08 We haven't really touched on that too much because we've been focused rightfully so on the obstructive form here. But 1/3 of patients have limiting symptoms with HCM to have non obstructive HCM. So there's a lot of patients out there with that form of disease who are very frustrated by how they feel and beta blocker and calcium channel blockers don't help enough at all, you know. And so huge unmet treatment need in that in those patients. And we're hopeful that we'll see a benefit with Mycorzo for those patients as well.

29:40 That's a trial called Acacia HCM phase pivotal phase three trial that's going to read out, meaning the results will be available this year. That's great. Hopefully that'll work for them as well. Now for for our viewers who are watching this and think they or a family member might have HCM symptoms, what's your advice on the next steps they should take? Yeah. So do you think you may have symptoms that could be consistent with with HCM? Again, that would be exertional shortness of breath, chest discomfort, decreased exercise tolerance, maybe palpitations.

30:15 And you know, you, you maybe you've seen your doctor and you really aren't getting the right answer or it's continuing despite, you know, somebody telling you or trading you for something that's another cardiac or or non cardiac disease. You've got to keep going and you've got to, you know, try to, you know, ensure that you get the appropriate test for diagnosis of HCM, which is the echocardiogram, the ultrasound, OK. And that could be ordered by, for example, an internist or you could see a cardiologist.

30:40 But that would be the, the, the gold standard test to determine if you have HCM. And then I'll say in terms of advice as well, if you have a diagnosis of HCM, you know, my advice there as well is to at least at least one time to seek input or counsel or consultation from one of the many now expert HCM centers that exist in the United States today. I think the the level of education that patients get and also you know, certainly treatment recommendations is very high in those areas in centers of excellence, what we call ACM centers of excellence in the US.

31:14 And so I think patients will benefit from a a visit there if they have HCM. Right, you read my mind. I was going to ask you what if somebody doesn't live in Massachusetts or nearby state where they can't see you? There are centers all over the country that they can look up online. That's right. So there's a patient advocacy group called the Hypertrophic Cardiomyopathy Association, which can be easily searched and found. And in that within that organization online and etcetera, you can access a list of centers of excellence that, you know, incorporate, you know, experts in the disease coast to coast.

31:52 I think there's almost 50 of them now at this point in the United States. So you're nobody's more than I think a couple hour drive from an HCM center of excellence. So it's accessible today. That's great, now can any cardiologist prescribe Mycorzo or? OR it should only be done by HCM experts like you? Yeah. Well, I think physicians have to be enrolled in a, in the REMS program. There's a, you know, brief educational online, you know, and then they can become certified. So that's how patients, I mean that's how physicians can be, you know, certified to write for it.

32:23 I think it's probably the kind of drug and disease that probably should be, you know, dealt with mostly by cardiologists, you know, in general of course and then of and then, you know, experts in ATM obviously as well would be would be I think preferable if I was giving advice on that. Right, great idea. Now, do you find that this condition is under diagnosed or sometimes a diagnosis completely missed and patients keep going or doctors and they just don't get better? Have you seen many patients who have gone to several doctors and cardiologists and the diagnosis wasn't made?

32:59 Oh, yeah, It's a huge problem here. Huge problem. The delay in diagnosis is perhaps the biggest challenge, you know, we have today. We have many patients who delay in diagnosis because they're either misdiagnosed or they don't get the appropriate test. Part of the reason, you know, for that is that HCM symptoms overlap of course, with other heart diseases and actually non heart diseases, lung disease, you know, lung, lung disease as well. And so, you know, and it's not a disease that's on the top of the list, you know, so to speak, among obviously many general practitioners and even some cardiologists sometimes.

33:35 And so for that reason, there is still a significant delay in inappropriate diagnosis, which impacts obviously the the care of that patient and the quality of life of that patient, particularly since we have, as we've just been talking about great treatments that exist for this disease. We this is a treatable disease today. And so those patients have unfortunately gone a certain period of time where they weren't able to access their appropriate treatments because of that delay. Wow, so avoiding lay is critically important there.

34:04 Anything else you wish more people understood about living with HCM today? Well, I think you know, I think you know, what I would say is this is just sort of expanding on what I, you know, just sort of under score which I think is a really important concept here. This is a treatable disease in 2026. No better example than than than what the story that we just talked about with my Corzo therapy that can provide patients enormous benefit. So we've got great treatments like Mycorzo for patients with this disease that can ultimately achieve the goals that we want, which is to make patients feel better, give them back a great quality of life and hopefully in other ways, other examples to extend life needing normal longevity as well.

34:49 Those are our two most important goals. Those can be achieved today in almost all patients with HCM. That's the really important message. All right, that's, that's important to know, but I want to thank you very much for taking the time to educate us about HCM and and my Corzo. We appreciate your knowledge, experience and expertise. So I appreciate you having me, Robert. I mean, you know, there's a great opportunity to talk about HCM and educate people that wouldn't have happened if you hadn't reached out.

35:18 So I appreciate this very much. So thank you. Thank you. My pleasure.