Advances in Treatment of Obstructive Hypertrophic Cardiomyopathy - Episode 14
Drs Steve R. Ommen, Martin S. Maron, Javed Butler, and James Januzzi provide insight on the evolving treatment landscape for obstructive hypertrophic cardiomyopathy.
James Januzzi, MD: Let me ask the 2 content experts here. Once you have a drug like a direct myosin inhibitor proven to be safe and effective, how do you feel the landscape will change in terms of treatment? It strikes me that a lot of what all 4 of us are saying is very reminiscent in some ways to when we started doing alcohol septal ablation and people were like, “They’re young patients. How do you know ablating a 30-year-old won’t cause problems when they’re 50?” They’re 50 now, and we don’t see any problems. You’ve got very effective, albeit invasive treatments. You’ve got some drug therapy options that have been traditional and may or may not help. Where do you think mavacamten [Camzyos] will ultimately fit in?
Steve R. Ommen, MD: That’s a great question. I’ll go back to something you said early on when you talked about when we go from standard therapy to more advanced therapies. Mavacamten fits in the advanced therapies category of that. Assuming the long-term data stays true the way it’s going now and that it has long-term efficacy, there will be patients—those that John identified as getting that 20-point improvement in their KCCQ [Kansas City Cardiomyopathy Questionnaire]—for whom it’s going to be destination therapy and they’re going to do well on that drug for a long time. There will be other patients in whom it might end up being bridge therapy until they can get to a center that has a high enough volume invasive specialist. They can feel better, but they know in the end that they’ve chosen to have this operation because they know they can get off drug and those types of things.
We’ll also use it as a diagnostic therapeutic trial for some patients. You’ve got the person who’s short of breath who has 3 other reasons why they’re short of breath. If we try mavacamten for 2 months and they get better, but they get worse when you take them off, then I know I can offer that next step therapy potentially if that’s the right thing for them. It’s going to be there, but it’s going to be once they’ve failed beta blockers and non-dihydropyridine class calcium channel blockers. It’s going to be as part of that shared discussion with disopyramide myosin inhibitor and septal reduction therapy, and there will be nuances around anatomy and other structural heart diseases that will go through the discussion. To me, that’s where it slots. I don’t know what you think.
Martin S. Maron, MD: I’ll echo your comments completely, with 2 additional comments. One is that there are always going to be patients, because this is a mechanical form of obstruction, in which drug therapy can’t relieve symptoms. That’ll always be a principal point. Second is that 1 aspect of this discussion that we haven’t talked about in terms of answering that question but bears enormously on the answer is cost.
Steve R. Ommen, MD: Yes, cost.
Martin S. Maron, MD: We don’t know the cost because that doesn’t come until the drug is approved, but we have some idea that it could be expensive. Remember, this is a drug given to young patients for long periods of time. Cost is a real concern in this disease. They just went through a similar issue in other inherited heart diseases like [transthyretin] amyloid [cardiomyopathy] with tafamidis. We’re going to be in a similar but even more complicated situation because of that issue. Cost is going to be important in terms of how we talk about this therapy with patients.
James Januzzi, MD: That’s very helpful. Any other points?
Javed Butler, MD, MPH, MBA: I just want to ask 1 quick question. The fact that it’s advanced therapy and that based on the inclusion/exclusion criteria for these trials, we don’t have the data for what I’m about to ask, does it pathophysiologically make sense that in the future we can give it in the earlier form of the disease to prevent the progression and development of severe disease and severe gradients and start it upfront? Does that make sense?
Martin S. Maron, MD: Certainly, that makes sense in principle. Obviously, if we have a therapy that can be given earlier in an asymptomatic or mildly symptomatic obstructive patient that’s going to alter the natural history in a beneficial way with low risk, then that’s an attractive, additional potential support for this initiative. It’s going to take a long time for that to be worked out though.
James Januzzi, MD: Interesting question, though. If you think about individualizing care and trying to almost use it like a disease modifier, it’s a curious idea. We’ve talked a lot about medical therapies. We’ve talked about catheter-based or surgical myectomy. Are there any other treatments that you can think of? These are early things, device treatment, but we haven’t even talked about the old traditional RV [right ventricular] apical pacemaker that we don’t see too much anymore. Are there devices that are being examined as potential treatments for HCM [hypertrophic cardiomyopathy]?
Steve R. Ommen, MD: There are a few things. There’s always interest in different ways to do catheter-type ablation, like doing electroporation or something that’s more RV that allows the catheter team to be more precise and not just holding where the coronary arteries go. There’s work going on in those types of things. Using MitraClips to keep the mitral valve from maybe flipping up so far to the outflow tract has been tried. It can be effective in some patients, but in some patients, you get bileaflet SAM [systolic anterior motion] with it.
James Januzzi, MD: You might actually worsen things. Absolutely.
Steve R. Ommen, MD: Then there’s work being done on direct gene therapies, which is beyond my expertise.
Martin S. Maron, MD: That’s probably too far off to get too much into, but there’s also other drug therapy initiatives going forward that deal with relief of symptomatic obstructive disease that have different mechanisms of action. Some of them are myosin-based, others aren’t. There’s a lot going on.
James Januzzi, MD: What other targets are there from drug therapy?
Martin S. Maron, MD: The analogy would be how disopyramide works as a late sodium channel inhibitor, which alters intercellular calcium to decrease contractility. There are ways to decrease contractility different from addressing the sarcomere that we’ve been talking about for myosin inhibitors that are effective because disopyramide can be very effective. These are drugs being developed that have similar mechanisms of action.
James Januzzi, MD: Very interesting. We’re drawing to a close. I’ve learned a lot and I’m grateful to all of you for offering useful information.
Transcript Edited for Clarity