Andrew Wang, MD; James Januzzi, MD; Michelle M. Kittleson, MD, PhD; and Milind Desai, MD, MBA, share a look into the future of oHCM treatment.
Anjali Owens, MD: So in the last few minutes, I'm going to ask each of you as you look into the future caring for our patients with obstructive HCM [hypertrophic cardiomyopathy] and non-obstructive HCM, what other things are you excited about? We talked a little bit about the myosin inhibitors, but clearly there are other things that Milind alluded to that are coming down the pike for us. It's an exciting time to be in HCM position. What are the things that you're most looking forward to and Jim, I'll start with you.
James Januzzi, MD: Yeah, thanks very much. I'll put my clinical trial hat on. We've fully enrolled a clinical trial looking at metabolic manipulation of myocardial function using a partial fatty acid oxidase inhibitor in patients with HCM. So approaching the question from a completely different angle that would be additive together with cardiac myosin inhibition, so thinking about newer pathways to address in patients with HCM to improve their symptoms. That's really exciting to me.
Anjali Owens, MD: Great. Michelle, how about you?
Michelle M. Kittleson, MD, PhD: So speaking as a heart failure, transplant cardiologist is what I spend most of my time doing. I think we still have so many unanswered questions in patients with non-obstructive HCM with advanced symptoms. What's the role of guideline directed medical therapy—was just traditional garden variety heart failure with preserved ejection fraction therapy like mineralocorticoid antagonists, angiotensin receptor neprilysin inhibitors, SGLT2 inhibitors. Do they work? Will they be effective in non-obstructive HCM? I think that is an unmet need in a huge space that I'm hopeful in the future we'll have more answers.
Anjali Owens, MD: I agree with you completely. That group of patients are perhaps the most difficult and challenging to treat in the clinic and hopefully will make some headway there. Milind, what are you looking forward to?
Milind Desai, MD, MBA: I will start with what Michelle alluded to the next frontier is the non-obstructive HCM. So I am not a heart failure transplant doctor, but can mavacamten or CMIs [cardiac myosin inhibitors] work in this space because it's not all about the LVOT [left ventricular outflow tract] obstruction. There are structural changes that are happening, and we are answering this question in an ongoing randomized clinical trial, RCHCM, and there is another one with aficamten, that is being planned coming down the pike. That will help us clear some of that air. Of course, we need to understand the other drugs like SGLT. Could that work? But the bigger picture I think is the genetic space, the gene therapies, the adenovirus-based therapies that can help modulate the deficient protein in the heart of MYBPC3 so that space is active and brewing the business of gene editing CRISPR, etcetera. All these things obviously, I often joke as long as it does not create mutant Ninja Turtles down the road, meaning the uncertain offshoot effects, I think the future is bright. Honestly, I just told this to one of my patients a couple of days ago is that I can excitedly look forward to having a potential cure for this disease before I hang my boots into retirement. So I'm looking forward to all and plus the PROs [patient reported outcomes] and the shared-decision making. The other thing is the HCMR trial, hypertrophic cardiomyopathy registry from NIH which I am also part of, so I have to plug it in. That is going to start reading out in the next year or so that will help understand the risk stratification space a lot more.
Anjali Owens, MD: And finally, Andrew, your thoughts?
Andrew Wang, MD: What's left? They've taken all the low hanging fruit And even the high hanging fruit from the tree. No fruit left on the tree.
Anjali Owens, MD: You're climbing all the way up the tree to the top.
Andrew Wang, MD: No fruit left on the tree. So I would echo what Jim said. I think that the potential for positive remodeling of the left ventricle not only pathologically with hypertrophy, but maybe reducing the progression of fibrosis would be a major advancement. If we can show that a therapy reduces progressive fibrosis that we can see on late gadolinium enhancement, we know its association with worsening progressive heart failure as well as ventricular arrhythmias, that would be a huge benefit. As Milind said that fibrosis is also shown with severe diastolic dysfunction as well, and many of our patients have some symptoms with outflow tract relief from diastolic dysfunction. So I think that is another unmet need. The last thing I would say is you know how normal can we make patients feel? With obstructive hypertrophic cardiomyopathy, will they be safe to be highly competitive, vigorous athletes, even with this condition? Can we really get close to normalizing what they really can do and feel like they can do and want to do?
Anjali Owens, MD: Yeah, that's what's a wonderful goal. It is a lofty goal, but one that we may meet. So with that, I'd like to thank you all for joining our panel today. This has been a very rich, informative and lively discussion and thank you audience for watching our HCPLive Peer Exchange®. You can subscribe to the enewsletter and receive other great content right in your inbox. Thanks again everyone.
Transcript is AI-generated and edited for clarity and readability.