Mayo Clinic cardiologist Steve R. Ommen, M.D., and Christopher V. DeSimone, M.D., Ph.D., discuss managing hypertrophic cardiomyopathy with new guidelines and drugs in this video first shown on
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Mayo Clinic Medical Professionals — Cardiovascular Diseases. Hello and welcome back to the male clinic Medscape video series. I'm Christopher DeSimone, cardiologist and director of marketing and today we'll be discussing hypertrophic cardiomyopathy, joined by my colleague steve Ahmann, consultant and professor of medicine and an expert in this area. Welcome dr Armand thanks chris. Well after I'm in the new guidelines are out and you played an integral role in their lead author on them, one of the takeaways is changing in sudden cardiac death screening. Can you describe to our audience how that's evolved over the years? Yeah, that's a really important question. Um you know, historically if you go back prior to the last guideline prior to 2010, we basically looked at a series of risk factors and just counted up risk factors and anyone who had two or more risk factors was eligible for NYPD. There was lots of debate and controversy about what to do with the one risk factor patient. And then patients that had zero risk factors were basically reassured. Then we tried to put some waiting around the various risk factors in that 2011 A. C. C A. J guideline document and elevated some like massive hypertrophy and family history of sudden death and and arrhythmic arrhythmic sync api as being slightly more important based on the data and that served uh us for a while. But then people pointed out that you know massive hypertrophy. Your risk doesn't just go up as a step function when you hit 30 millimeters your risk is increasing the thicker your heart is. And our colleagues in europe developed the HCM sudden cardiac death risk score that used continuous variables and generated an estimate of risk. And that really was a game changer. Because prior to that you would tell a patient you had a risk factor and they would kind of look at you and say, okay, that's great. But what is my risk and this and this tool allowed us to put it in context for the patient with the magnitude of their risk. Is there were some issues that that we felt that the way the european guidelines were written and I happen to know it was the most, one of the most arduous discussions they had in their debate was a kind of a priority set, certain risk markers as saying, well, this is high risk and therefore you get a defibrillator above a certain percentage and below this you probably don't. And we felt like that probably took the decision making out of the patient's hands and and didn't consider an individual patient's risk tolerance. So what we did in the 2020 guidelines is really blended those two methods. So we use classic risk factors to identify which patients have elevated risk. They didn't have the risk factor that their risk wouldn't be as high. And then we use the risk tool to frame that for the patient and help them make a decision for themselves. The other thing that happened with this guideline was we saw, you know, new, new risk factors have emerged in the past decade. So things like uh late Guidolin enhancement on CMR imaging. If you have a lot of that scarring. Well that's the substrate around which ventricular with me as can start. A low ejection fraction in HCM is actually a bad prognostic marker and a pickle aneurysm was another one that was really important and added to the guidelines this time. It didn't previously exist. And the final change that was important this time was we actually addressed Patients under the age of 16 for the first time in the guideline document. So we had a series of pediatric cardiologists, experts in HCM who contributed that discussion. That was new in this guideline document as well. Excellent. I think those are amazing points. You know, someone who is a cardiac electro physiologist and we were close and with lots of patients, it's very tough because it's literally a life and death situation here. And also a quality of life situation, especially with younger folks, 16 or even into their twenties and thirties and above. So, thank you for speaking on that. Now. Not only does the screening involve a complex set of testing and interpretation, but what do you believe are the rolls now, not just for sudden cardiac death screening, but for all hypertrophic cardiomyopathy is and best managements and treatment practices for our patients. What's the role of having a specialist hypertrophic cardiomyopathy center compared to just your traditional cardiac teams. Yeah, that's that's a great question as well. So we think that there's much of care of a HCM patient that that a primary cardiologist can do uh you know, initiating the screening, uh starting first line therapies, those types of things. But at some point, most patients will come to a decision point or a treatment point where they probably really should have conversations with people who see this day in and day out. Most cardiology practices see single digit HCM patients in their practice. Whereas the centers like here at Mayo, you know, I see hundreds of HCM patients every year. So I I have seen many, many different nuances and and and patient circumstances that can help me teach the patients about their disease and help them make those decisions. So if it's if it's an HCM specific therapy, like let's say we're considering septal ablation or stepped on my ectomy that really should be in the hands of an expert center where the outcomes are so good because there is a steep learning curve and there's been publications that lower volume centers have have worse outcomes than than the true expert centers do. The other thing that I think when you look at any of the guidelines documents and it's definitely true in HCM but it's probably true in the other guidelines documents any recommendation that is great at a class to be recommendation are probably the recommendations that that writing committee spent hours agonizing over the wording of it. So if the experts sitting around the table around the guidelines have a difficult time phrasing the wording. Just right. That's exactly the kind of treatment decision that needs their input with a patient. Those to be recommendations are someone who hasn't responded to frontline therapies and now you're considering doing something more and there might be risks associated with that, then that's probably when a referral or inclusion of of an HCM expert in that patient's treatment plan is really helpful. I don't I think it's important to recognize that we as an HCM center want to be part of that patients teams, they need to have a cardiologist who is taking care of them locally. If something happens on some random afternoon, a new episode of atrial fibrillation, that's highly symptomatic. They get chest pain, they haven't had before. Well, they need that local team to know what their underlying diagnosis is and what their current therapies are so they can do that. We don't want to take patients from primary Cardella is we want to help with them take care of those patients. That's extremely important. And just as you mentioned, the to be the not clear cut stuff. The class one and class three's right. Those are easy. It's the class two is that kind of even when we refer or see patients from heart rhythm clinic, heart failure clinic hypertrophic cardiomyopathy clinic that's kind of like where the nuances where you have that seasoned experience and your other colleagues in the hypertrophic center really come to play and that's where the patients really get the most benefit. That's right. Well on another aspect I want to ask you, especially in this hypertrophic world is that there's a new drug on the market have a camp town. So I just wanted to get your take on this drug and the Explorer HCM trial because I know it's riveting through all of the journals and all of the news media. Yeah, so we are super excited in the in the H HTM community that drug companies have taken up developing drugs specific for this condition and we haven't seen that ever. We've taken advantage of drugs that were designed for other purposes and we can use their their mechanisms of action is to treat our patients things like beta blockers and non di hydro purity calcium channel blockers. But this maverick Hampton is the first of several of these myostatin inhibitors that have specifically attack one of the main cellular functions in HCM and that is enhanced interaction between liasson and active. And it's again, it's great to we see this in the Explorer HCM trial which was a trial a placebo controlled trial of Maverick Hampton over usual therapy with predefined endpoints of improvement in vo two max and improvement in symptoms status. The trending data were all positive for patients with taking napa Campton Overall, about 36% of the patients taking more of a Campton achieved the primary study endpoint. And about 19% of patients in the in the non mafia arm also did so. So it wasn't 100%. But it was all the trending data was the right direction. So that's really encouraging a couple of important points to note about that trial. Most of those patients started off in new york heart association class too. Uh and they weren't necessarily the most severely impacted in patients. And and that's a trial that's ongoing right now in a different next phase trial of Maverick Hampton. Uh the other thing is is that Maverick Hampton is a very powerful negative in a trope. And in that trial, about 10% of patients had a drop in their ejection fraction to less than 50%. Now, what was temporary resumed returned to normal once Mavi captain was discontinued in those patients. But since the trial was only 30 weeks long, we don't know the implications of a potential lifelong therapy if it's going to have that potent of a negative in a tropic effect, particularly again, as we have data in HCM that an ejection fraction of less than 50% is associated with a lot of bad outcomes. So, we have a lot of safety information that we need to gain in in in the follow on trials. Excellent. How do you think that's going to influence your practice? I would say, you know, in the near future as well as later on down the road. And more data comes out but more so in the near future, how would that influence how you're going to change management? Yeah, it's a great question. I think the best guess is that Maverick Hampton will likely slot into a position of what I would term advanced therapy. So when someone is symptomatic with HCM you usually start them on a beta blocker and or delta autism and verapamil. And you might switch around and find the right cocktail for the patient in that situation depending on the side effects they may or may not be experiencing with the treatment benefits. But if patients aren't responding adequately to those presently we then consider disappear amid or separate reduction therapy. I think marva represents a 3rd 3rd arm in that. So, so some patients may consider going on Maverick Hampton rather than dissect your mind or rather than going to an invasive therapy, particularly if they would be high risk for one of those invasive therapies. But all of this really has one other wild card that we don't know yet. And that is what is the pricing information going to be on Maverick Hampton. Um You know, if we look at a drug like two families for cardiac amyloid, which is very expensive. Um well that that's going to influence how many people might choose that when we have something like sorta connect me but which might be the last therapy they need directed at their outflow tract obstruction and not have to take medications going forward. So the jury is still out. But my best guess is it will slot into their into that decision making for patients who maybe aren't ready to our high risk for invasive therapies and didn't respond to first line therapy. Excellent. I think that's that's an excellent point. One concern when I was reading the studies that I had is I was hoping people didn't say, you know, we could take this drug as opposed to other things. Especially the folks that need a lot of septal reduction, either with alcohol or surgical, especially in the younger patients. You know, having a negative in a trope from my standpoint from the standpoint, a lot of that ventricular de bulking has a lot of substrate for VT. And we started this off talking about sudden cardiac death. So I guess that would be one thing I would be worried about. But from you, I just like their does any concerns you have about this drug coming out? I don't have concerns about the drug coming out. I think it will be very beneficial for some patients. I do have concerns that perhaps uh, it will be easier to prescribe that drug than offer someone a referral to one of the major centers for a procedure which again, Most my enemies are the last procedure that patient needs and in their success rate that we've reported as 90-95% of patients have a to New York Heart Association class improvement. And many of those patients no longer have to take cardiac active medications following their surgery. So we don't want to deny patients the opportunity for that type of procedure just because it's easier to prescribe a medication that does. Again, the safety information has to come in, the cost information has to come in. And as you said in a young person, we're talking about lifelong therapy and every medication has some degree of side effect. And so we don't want to necessarily saddle patients with lifelong side effects unnecessarily. But again, I don't have concerns about the drug coming out as long as we understand that, that it's going to be safe for our patients. Excellent. Well, thank you steve for these very important insights and thank you for joining us on the heart dot org Medscape cardiology. Thank you. Mm hmm. Yeah.