Guideline-Directed Therapy in oHCM

EP: 1.The Pathophysiology of Obstructive Hypertrophic Cardiomyopathy (oHCM)

EP: 2.Signs and Symptoms of oHCM

EP: 3.Impact of Diagnosis of oHCM

EP: 4.Risk Stratification in oHCM

EP: 5.Approaches to Imaging in oHCM

EP: 6.Goals of Treatment in Symptomatic oHCM

Now Viewing

EP: 7.Guideline-Directed Therapy in oHCM

EP: 8.Septal Reduction Therapies in oHCM

EP: 9.Advances in oHCM Therapy

EP: 10.Use of Cardiac Myosin Inhibitors (CMI) in oHCM

EP: 11.Clinical Trials of Mavacamten in oHCM

EP: 12.Clinical Trials of Aficamten in oHCM

EP: 13.Implementing Novel Agents in the Treatment of oHCM

EP: 14.Unanswered Questions About CMIs in oHCM

EP: 15.The Future of oHCM Treatment

Anjali Owens, MD: So let's start with guideline directed first-line therapies for symptomatic obstructive HCM [hypertrophic cardiomyopathy]. Andrew, do you want to walk us through what our algorithm is?

Andrew Wang, MD: So I want to also build on some of the things that both Milind and Michelle said. So number 1, we're talking about the treatment options for obstructive hypertrophic cardiomyopathy. But oftentimes we'll be presented with a patient who has no obvious radiant at rest. I'm going to build on what Milind said, that the stress echocardiogram in someone who's symptomatic and is currently listed or described as non-obstructive hypertrophic cardiomyopathy is the next best test. Not only can we assess their exercise capacity, how they feel, we can look for exercise induced ECG [electrocardiogram] abnormalities, or arrhythmias. We can also evaluate the blood pressure response. But really the question is, is there a severe provokable outflow tract gradient immediately post exercise and I think one of the keys for clinicians thinking about that is that you need to. Request that you want the LV [left ventricular] outflow track gradient measured as soon as they come off that treadmill. We're not doing it to look for wall motion abnormalities or ischemia.

So for example, when I order it, I've put HCM evaluate LVOT gradient, not wall motion. So as the highest heart rate achievable, we're measuring the outflow right gradient and if there's a provokable outflow tract gradient of 50 mm or more, now you've reclassified them from non-obstructive to obstructive and to build on what Michelle said it's the presence of obstruction that opens the doors to a lot of therapies that we would not consider for non-obstructive hypertrophic cardiomyopathy, so that early differentiation of am I going to say this patient is obstructive or non-obstructive is very important for any management decisions downstream. As Michelle said, we're not treating the gradient, but the presence of the gradient or the outflow tract obstruction gives us many different options to how to help them feel better.

So the guidelines say, and this is somewhat traditional, that we should start with a beta blocker for first-line therapy for obstructive hypertrophic cardiomyopathy. It has a negative chronotropic effect, a mild negative ionotropic effect and in a moderate sized clinical trial, most recently the TEMPO trial it showed that alpha gradient was reduced, symptoms were improved, but it did not increase cardiopulmonary exercise duration or peak VO2 [peak oxygen consumption]. So it does have some hemodynamic benefit and symptom benefit, but not so much in terms of exercise capacity. Guidelines then say for patients that are not improving on beta blocker or if they have symptoms that make them intolerant to beta blocker therapy. Considering a non-dihydropyridine calcium channel blocker for rapid mill specifically, sometimes they'll tie as them as an alternative and then for patients that are still symptomatic, the sort of field widens up between adding an additional medicine such as disopyramide or considering septal reduction therapy. The interesting thing is that all of those therapies, beta blockers, non-dihydropyridine, calcium channel blockers quite how called septal ablation surgical myectomy. They're all given class one level of evidence for recommendations yet. Most of those that I've just mentioned have never been studied in a randomized trial against another therapy. I have not mentioned obviously cardiac myosin inhibitors. They were not approved. In 2020, the last version of the ACHA HCM guideline. But it'll be interesting to see in updates where that falls in the treatment algorithm for patients with obstructive hypertrophic cardiomyopathy. But all of those drugs can be effective to improve symptoms and again, as Michelle said, that's what we're aiming for. Some patients will come to me and say oh well, if I go the most invasive myectomy, will that help me live longer? I'm like no, no, no.

None of these therapies are we saying have a clear survival benefit is what do we need to do to get your quality of life to the level you want it.

Anjali Owens, MD: So Jim, you know there's a lot of options here that Andrew mentioned. We've got the beta blockers, we've got calcium channel blockers and some patients disopyramide then moving on to invasive therapies, how do you go about selecting a therapy, sequencing the therapy? What's your general approach?

James Januzzi, MD: Yeah, thanks very much. So I really appreciate the opportunity to take this question. This is very much a Dr Kittleson type answer, which is to say the best part of taking care of patients is the ability to follow them overtime and really get to know them and their individual set of symptoms and try to address them because as you've already heard from Dr Wang, our patients will come worried about prognosis and my answer to my patients is your lifespan will be fine. This is about addressing your quality of life. Patients with hypertrophic cardiomyopathy if they tell you they don't have symptoms on Monday, ask them again on Tuesday. The gradient can come and go and it can be challenging to really know if your medical therapy is effective until you follow them longitudinally so. We always start with beta blockers as the as the foundational therapy. They're simple, they're safe, we use a non-vasodilating agent, metoprolol succinate titrated to maximal effectiveness. But then you know that's when we start individualizing care. If a person remains symptomatic, as you've already heard, we may move them over to. Well the issue is, is we'll talk about with cardiac myosin inhibitors. Verapamil has an interaction with the cytochrome P450 system, so you can't use it together with a cardiac myosin inhibitor necessarily and so or safely at least. When we're starting to go to second-line agents, that's when we start thinking about whether to go to newer therapies or to septal reduction therapy. That's the big debate going on in our world these days. Now is if you really feel like you're needing to go to next line therapies, then is it time to start thinking about other approaches? We're currently doing a prospective study looking at this exact question, looking at patterns of care of individuals with hypertrophic cardiomyopathy, to really understand in, in, in real-world settings now with a wide range of different therapy options available to us how patients are being managed and what their outcomes will be.

Transcript is AI-generated and edited for clarity and readability.