Treatment Approaches for HCM

EP: 1.Overview of Hypertrophic Cardiomyopathy

EP: 2.Role of Genetic Mutations in HCM Pathophysiology

EP: 3.Symptoms of Hypertrophic Cardiomyopathy

EP: 4.The Effect of Obstructive Hypertrophic Cardiomyopathy on Health Status

EP: 5.AHA/ACC HCM Guidelines and Patient Identification and Management

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EP: 6.Treatment Approaches for HCM

EP: 7.Invasive Treatments and Challenges with HCM Treatments

EP: 8.Approaching Treatment Selection for Hypertrophic Cardiomyopathy

EP: 9.Emerging Therapies for oHCM

EP: 10.EXPLORER-HCM Trial in oHCM

EP: 11.Health Status With Different HCM Treatments

EP: 12.Long-Term Data of Mavacamten Use in oHCM

EP: 13.VALOR-HCM Study in oHCM

EP: 14.Future Directions for oHCM Treatment

EP: 15.Patient Education of HCM

James Januzzi, MD: Let’s start getting an overview of treatment approaches for hypertrophic cardiomyopathy [HCM]. Javed, why don’t we start with you? We see patients referred for dyspnea where you identify a person with HCM. What things go through your mind when you’re initiating decisions about treatment?

Javed Butler, MD, MPH, MBA: A few are basic things and some lifestyle modifications, like avoidance of heavy exercise. Heavy weightlifting is something that you might want to recommend to your patients. The first thing you might want to reach out to is cardiac-specific calcium channel blockers or beta blockers. In the long run, these are relatively younger patients when they get diagnosed, and long-term tolerability and effectiveness of those therapies is something that isn’t perfect, but at least you can start there. With patients who remain symptomatic, I’d love to see what Steve and Marty have to say.

There are other options, including disopyramide or pacemakers. What’s their role today? Eventually, if a person isn’t doing well, traditionally, your options are some type of an intervention to relieve the obstruction, and you reach out for either septal myectomy or coronary alcohol ablation. It sounds very dramatic to the patient. You’re inducing a myocardial infarction.

But as a cardiologist who’s directly responsible for the patient care, the other thing that you worry about is whether your operators have the experience. This isn’t a generic bypass surgery or generic PCI [percutaneous coronary intervention] that any interventional cardiologist or cardiac surgeon would do. Therefore, if you have regional centers or somebody to refer to the patient, even if it’s a bit of a heavy lift for the patient, have them go to another center to get the care. Some volumes, some experience may be helpful. But even then, when you talk to patients about these options, they’re looking out for an option less dramatic than what we could do.

In my experience, there have been many patients who are pretty symptomatic and have gone through the basic care. You’re avoiding nitrates and active afterload reducers. You’re giving beta blocker, calcium channel blocker, diltiazem. When it comes to patients being very symptomatic and you’re going for these procedural input, many patients would rather live with the symptoms and are afraid to go through these procedures. Then it starts going through this stuff, and that’s where you’re in a different state and you give a call to Rochester or Massachusetts and ask, “Can you see the patient?”

James Januzzi, MD: Yes, so let’s layer this, because this is so important. There are nonpharmacologic approaches, then the early pharmacologic approaches, later pharmacologic approaches, and then the procedure. Can we go through that?

Martin S. Maron, MD: Yes, maybe I’ll first expand on what Dr Butler was saying in terms of pharmacologic therapy. The first question is obstructive vs nonobstructive. For patients who have obstructive who are symptomatic—in other words, you feel they have symptoms that are due to the obstruction—the mainstay of therapy is negative inotropic therapy, decrease in contractility to lower gradience. Anything that lowers gradience makes patients in this situation feel better. It improves that symptom burden. As you were saying, the initial is beta blocker and calcium channel blocker therapies. They can be effective in some patients, but they’re relatively weak negative inotropes. As you were saying, there can be limitations to those initial therapies.

One additional drug that’s important to mention because it’s been part of that pharmacologic strategy for a long time because it’s a more potent negative inotropic, although it’s an antiarrhythmic drug, is disopyramide. The reality is that it’s really effective. It’s an old drug and there are a lot of concerns about issues. We talked about adverse effects. But the reality is that it can be a very good drug for some patients as another step in this stepwise pharmacologic management protocol for obstructive HCM.

It’s a drug you can take usually twice a day. It’s a more potent negative inotrope agent than the other…blocking agents. Generally, patients get 30% to 50% better. Two-thirds. That improvement can last years, although there’s some issue of limited long-term efficacy, which is another limitation of the drug. But it’s important to recognize that’s a part of our arsenal for treatment of symptomatic obstructive HCM. At that point, if you have tried all those or a patient doesn’t want to go on one of those, that’s when we start to have that discussion, at least today, with respect to more definitive invasive septal reduction therapy. Do you want to talk about that for a minute?

Steve R. Ommen, MD: Yes, I will. I also want to go back to nonpharmacologic things, which you mentioned. That’s important to add that in there. One of them is to make sure the patients are hydrated, that they’re drinking plenty of water. There are some patients who get better simply with that or anticipating when they’re going to go out and be active and having some water beforehand. Another thing is getting them off the wrong medications and on the right medications.

James Januzzi, MD: What medications would you avoid? This is so important.

Steve R. Ommen, MD: Pure vasodilators, so the amlodipines, nifedipines, the dihydropyridine class. Calcium channel blockers are pure vasodilators. They’re not going to be helpful. Verapamil and diltiazem are the 2 effective calcium channel blockers in HCM. Things like ACEs [angiotensin converting enzyme inhibitors] and ARBs [angiotensin-receptor blockers] are pure vasodilators. We also like to avoid high-dose diuretics. Sometimes you can get by with low-dose thiazide to help treat that concomitant hypertension and that isn’t going to drop their volume too much. But trying to get them off of high-dose diuretics and vasodilators and onto these first-line medications can be very effective for many patients.

James Januzzi, MD: What about noncardiovascular drugs to avoid? I’ll give you my recent example of a person with significant outflow obstruction who was started on tamsulosin for an enlarged prostate and within a day fainted.

Steve R. Ommen, MD: Fainted, yes.

James Januzzi, MD: Of course, cardiology was called urgently because this must be related to their HCM, and in a sense it was.

Steve R. Ommen, MD: It was.

James Januzzi, MD: But are there other things that clinicians should consider?

Steve R. Ommen, MD: Yes, I used to have a slide in my talks that I showed of a guy going into a hot tub with a bottle of wine and a bottle of Viagra. He has something in mind, and that’s not what’s going to happen. He’s probably going to end up passed out next to the hot tub. Anything that causes you to vasodilate, such as alcohol, makes some of our patients very symptomatic. The flushing we get obviously is vasodilation and dropping preload and afterload.

Martin S. Maron, MD: Before I forget, this is important, too. Not infrequently, Steve and I have patients who come to us on huge doses of a beta-blocker because it’s been titrated up and they feel awful. All it takes is coming down off the beta-blocker because there are so many adverse effects. They’ve been terrible. Once you go down, it does them really well. Sometimes overmedication of beta-blockers is an issue too.

Steve R. Ommen, MD: Overmedication is a problem.

James Januzzi, MD: Deprescription, avoidance of meds. That’s really useful. That’s the practical information that really helps.

Javed Butler, MD, MPH, MBA: Before we move to the more definitive therapies, can you also comment on physical activity?

Steve R. Ommen, MD: It’s important that patients with HCM are active, like most of society is supposed to be. The low-to-moderate intensity exercise seems to be able to show benefits and can improve VO2 [maximal oxygen consumption]. Someone who goes from sedentary to low-to-moderate intensity, similar to what some of the recent drug trials have shown for active agents, can make a difference.

The concerns are extremes of efforts and extremes of exposures. We know from long-standing observational data that competitive athletes with HCM have higher event rates than athletes who don’t have HCM. What we don’t know is, for an individual patient with HCM, how much the risk is for them to choose to be highly competitive vs not competitive at all. It’s a long counseling session, but we usually talk to patients about the healthy lifestyle that we’re trying to get all of society to participate in. That said, there were data presented at ESC [European Society of Cardiology Congress] last year looking at higher levels of intensities of forms of recreational exercise and seemed to indicate that there was safety there, but we haven’t seen the peer review yet, so we don’t have all the details on that.

Javed Butler, MD, MPH, MBA: Is there any difference in physical activity vs weightlifting exercise?

Steve R. Ommen, MD: I usually tell patients that you should be able to breathe with whatever form of exercise you’re doing. If you’re walking or exercising, you should be able to speak a full sentence without having to gasp for breath. If you’re lifting weights, resistance training is good for lots of reasons, but you shouldn’t be doing the Valsalva maneuver to lift that weight. You should be able to do lower weights in higher repetitions.

Martin S. Maron, MD: And avoiding burst exertion.

James Januzzi, MD: I’ve heard the analogy that a person can run a 1-mile race, but it’s during the last sprint at the finish when they’re racing with someone that a catastrophe occurs. It’s important that we touch on the nuances of treatment.

Transcript Edited for Clarity