Treatment approaches for HCM

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James Januzzi, MD: Let’s start to get an overview of treatment approaches for hypertrophic cardiomyopathy [HCM]. Javed, why not start with you? We see patients referred for dyspnea where you identify a person with HCM. What things come to mind when making treatment decisions?

Javed Butler, MD, MPH, MBA: A few are basic things and some lifestyle modifications like avoiding strenuous exercise. Heavy lifting is something you may want to recommend to your patients. The first thing you may want to contact is heart specific calcium channel blockers or beta blockers. In the long term, these are relatively younger patients when diagnosed, and the long-term tolerability and effectiveness of these therapies isn’t perfect, but at least you can start there. With patients who remain symptomatic, I’d like to see what Steve and Marty have to say.

There are other options, including disopyramide or pacemakers. What is their role today? Eventually, if a person is unwell, traditionally your options are some type of intervention to relieve the obstruction, and you reach for a septal myectomy or coronary alcohol ablation. This seems very dramatic for the patient. You cause a myocardial infarction.

But as a cardiologist directly responsible for patient care, the other thing you’re concerned about is whether your operators have the experience. This is not a generic bridging or generic ICP [percutaneous coronary intervention] that any interventional cardiologist or heart surgeon would do. Therefore, if you have regional centers or someone to refer the patient to, even if it is a bit burdensome for the patient, ask him to go to another center to get the care. A few volumes, some experience can be useful. But even then, when you talk to patients about these options, they’re looking for a less dramatic option than what we could do.

In my experience, many patients are quite symptomatic and have followed basic care. You avoid nitrates and active afterload reducers. You give a beta blocker, a calcium channel blocker, diltiazem. When dealing with highly symptomatic patients and opting for these procedural interventions, many patients prefer to live with the symptoms and are afraid to go through these procedures. Then it starts going through this stuff, and that’s when you’re in a different state and you call Rochester or Massachusetts and say, “Can you see the patient?”

James Januzzi, MD: Yeah, so let’s layer that on, because it’s so important. There are the non-pharmacological approaches, then the first pharmacological approaches, the later pharmacological approaches, then the procedure. Can we get through this?

Martin S. Maron, MD: Yeah, maybe I’ll expand on what Dr. Butler was saying first in terms of pharmacological therapy. The first question is obstructive vs. non-obstructive. For patients who have an obstruction who are symptomatic – in other words, you feel they have symptoms due to the obstruction – the mainstay of treatment is negative inotropic therapy, a decrease in contractility at a lower gradient . Anything that decreases gradient makes patients in this situation feel better. It improves this symptom burden. As you said, the initial is beta blockers and calcium channel blockers. They may be effective in some patients, but they are relatively weak negative inotropes. As you said, there may be limitations to these initial therapies.

An additional drug that is important to mention because it has been part of this pharmacological strategy for a long time because it is a more potent negative inotrope, although it is an antiarrhythmic drug, is disopyramide. The reality is that it really does work. It’s an old drug and there’s a lot of concern about the problems. We talked about side effects. But the reality is that it can be a very good drug for some patients as another step in this stepwise pharmacological management protocol for obstructive HCM.

It is a medicine that you can usually take twice a day. It is a more powerful negative inotropic agent than the other… blocking agents. Typically, patients achieve a 30-50% improvement. Two-thirds. This improvement can last for years, although there is a problem of limited long-term effectiveness, which is another limitation of the drug. But it’s important to recognize that it’s part of our arsenal for the treatment of symptomatic obstructive HCM. At that point, if you’ve tried all of those or if a patient doesn’t want to follow any of them, that’s when we start having that discussion, at least today’ today, regarding a more definitive invasive septal reduction therapy. Do you want to talk about that for a minute?

Steve R. Ommen, MD: Yes. I also want to come back to the non-pharmacological things, which you talked about. It is important to add it here. One of them is making sure patients are hydrated, drinking plenty of water. There are patients who just get better with this or by anticipating when they are going to go out and be active and drink water beforehand. Another thing is to get them off the wrong drugs and on the right drugs.

James Januzzi, MD: What drugs would you avoid? It’s so important.

Steve R. Ommen, MD: Pure vasodilators, therefore amlodipines, nifedipines, the class of dihydropyridines. Calcium channel blockers are pure vasodilators. They will not be useful. Verapamil and diltiazem are the 2 effective calcium channel blockers in HCM. Things like ACEs [angiotensin converting enzyme inhibitors] and ARB [angiotensin-receptor blockers] are pure vasodilators. We also like to avoid high dose diuretics. Sometimes you can get by with low dose thiazides to help with this co-occurring hypertension and it’s not going to decrease their volume too much. But trying to get them off high-dose diuretics and vasodilators and on those first-line drugs can be very effective for many patients.

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

Steve R. Ommen, MD: Passed out, yes.

James Januzzi, MD: Of course, cardiology was rushed because it had to be related to their HCM, and in a way it was.

Steve R. Ommen, MD: It was.

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

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

Martin S. Maron, MD: Before I forget, that’s important too. It’s not uncommon for Steve and I to have patients come to us with huge doses of beta-blockers because they’ve been titrated and feel bad. All it takes is to stop the beta blocker because there are so many side effects. They were terrible. Once you get down it does them just fine. Sometimes overmedication of beta-blockers is also a problem.

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

James Januzzi, MD: Deprescribing, drug avoidance. It’s really helpful. It’s the practical information that really helps.

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

Steve R. Ommen, MD: It is important for HCM patients to be active, as most members of society are expected to be. Low to moderate intensity exercise appears to be able to show benefits and may 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.

Concerns are extreme exertion and extreme exposure. We know from long-standing observational data that competitive athletes with HCM have higher event rates than athletes without HCM. What we don’t know is, for an individual patient with HCM, what is the risk of choosing to be very competitive or not at all competitive. It’s a long counseling session, but we usually talk to patients about healthy living, which we try to involve the whole society. That said, data was presented to the ESC [European Society of Cardiology Congress] last year looking at higher levels of intensities of forms of recreational exercise and seemed to indicate there was safety there but we haven’t seen the peer review yet so we we don’t have all the details about it.

Javed Butler, MD, MPH, MBA: Is there a difference between physical activity and weightlifting exercise?

Steve R. Ommen, MD: I usually tell patients that you should be able to breathe no matter what form of exercise you do. If you’re walking or exercising, you should be able to say a full sentence without having to catch your breath. If you lift weights, resistance training is good for many reasons, but you shouldn’t do the Valsalva maneuver to lift that weight. You should be able to do lower weights in higher reps.

Martin S. Maron, MD: And avoiding intense efforts.

James Januzzi, MD: I’ve heard the analogy that a person can run a 1 mile race, but it’s in the last sprint to the finish when they’re running with someone that disaster strikes. It is important that we touch on the nuances of the treatment.

Transcript edited for clarity

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