Advances in Treatment of Obstructive Hypertrophic Cardiomyopathy - Episode 3

Symptoms of Hypertrophic Cardiomyopathy

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Drs Steve R. Ommen, Martin S. Maron, John A. Spertus, Javed Butler, and James Januzzi provide insight on the presentation of nonobstructive and obstructive hypertrophic cardiomyopathy.

James Januzzi, MD: We’re talking about hypertrophic cardiomyopathy [HCM], generally speaking. But I’d like to ask you all to distinguish between obstructive and nonobstructive and how much overlap we see between the 2 groups. I’m curious to hear.

Steve R. Ommen, MD: I’ll take it. Every patient with HCM has some degree of diastolic abnormality, with thick heart muscle stiffer than it should be. With actin and myosin not letting go of each other, the cellular mechanics don’t favor diastole, but up to two-thirds of patients have some form of obstructive physiology during systole because the left ventricle is too thick, it alters the vectors of flow through the left ventricle, and rather than flowing parallel to the mitral valve, they flow across it, push that mitral valve up against the septum, and results in obstruction.

About half of the obstructive patients have that obstruction just under resting conditions. The other half don’t have it during rest, but they have it as soon as they stand up and walk across the room. As a clinician, as an echocardiographer, your job is to look for obstruction. If you don’t find it at rest, we have to go further. You can do bedside maneuvers, or you can go on and do things like exercise echocardiography or invasive hemodynamics to try to identify patients who have obstruction. It’s particularly important if the patient has symptoms to see whether they’re obstructive.

Martin S. Maron, MD: That was great. I’ll add to that by saying that it’s so critical to identify a patient as being in the two-thirds obstructive group or the nonobstructive because that informs 2 important management issues. It gives us better sense of how we talk to the patient about natural history and treatment options. It opens up specific treatment options that may be available to an obstructive patient that aren’t available to a nonobstructive. It’s important upfront to put the patient in the right category.

James Januzzi, MD: That’s really helpful.

John A. Spertus, MD, MPH: In the nonobstructive patient, what’s the etiology of their symptoms? Is it diastolic dysfunction? Do they get the same lightheadedness and other things that an obstructive patient gets? Do they have more of a shortness of breath, fatigue profile, and not the other manifestations?

Steve R. Ommen, MD: Great question, John. There are a couple of things. It’s HFpEF [heart failure with preserved ejection fraction], which is a version of heart failure with preserved ejection fraction. It is delayed relaxation. For some patients who have extreme hypertrophy, they have almost no end-diastolic volume. They’re stroke volume limited, so they can get pure low cardiac output–type symptoms. Lastly, we also know that with all patients with HCM, the capillary network doesn’t grow commensurately with the wall thickness, so they live closer to ischemia at baseline than a heart with normal thickness does. Ischemia may play a role. Diastolic dysfunction plays a role. Low cardiac chamber size can play a role.

James Januzzi, MD: Do these facts extend to all forms of HCM? Or are there differences between those with apical HCM vs other forms, for example?

Martin S. Maron, MD: The principal point here is that in general, we’ve got the symptoms of exertional dyspnea, chest pain, decreased exercise tolerance, and sometimes lightheadedness can be present in both obstructive and nonobstructive patients. There’s overlap. There’s no question. The reality is that any patient with HCM, whether they’re obstructive or nonobstructive or have different locations of hypertrophy, can have 1 or more of those symptoms.

James Januzzi, MD: OK. That’s helpful. That brings us to the course and complications of the diagnosis, which is worth talking about. Javed?

Javed Butler, MD, MPH, MBA: Just to clarify, you’re saying that symptoms, whether it’s angina or shortness of breath, can occur in any variant, whether it’s apical or concentric or whatever, but this typical obstructive picture with systolic anterior motion of the mitral leaflet and asymmetric septal hypertrophy won’t necessarily occur with apical or the variants?

Steve R. Ommen, MD: Correct.

Martin S. Maron, MD: To be absolutely clear, there’s no question that left ventricular outflow obstruction at rest, or as Steve was saying, with provocation, is the most important driver of symptoms in this disease.

James Januzzi, MD: Yes. And a tie into treatment, as we’ll discuss. Let’s talk with Drs Butler and Spertus about the clinical picture. Javed, how does this diagnosis present? How might you define the clinical course and complications?

Javed Butler, MD, MPH, MBA: So many of the things that we lament about HFpEF are true for this condition as well, that a lot of time the diagnosis is delayed, not made, people complain of shortness of breath or other symptoms, and nobody evaluates. But the most common symptoms are dyspnea on exertion, shortness of breath, angina, and exertional angina. Many people have rest angina as well, or at least complain of that. Those will be the most common manifestations.

Then there are other issues like palpitations and syncope. In advanced cases, the symptoms continue to advance. That leads to the risk of complications that we’re talking about, whether it’s development of heart failure syndrome or sudden cardiac death. As Martin mentioned, at least some of that is directly related to how bad your gradient is and how bad your gradient gets with exertion. But the most common symptoms are shortness of breath, dyspnea, angina, difficulty of exercise, and fatigue. If a person is complaining of that, cardiac evaluation is important. While we rule out all the other common things, like hypothyroidism, COPD [chronic obstructive pulmonary disease], asthma, and anemia, keep this differential in your mind. If it’s difficult to diagnose these things in a primary care setting, at least refer to cardiology. But even our cardiology colleagues may not necessarily think about it as frequently as perhaps we should.

Steve R. Ommen, MD: One of the interesting things to build on what you’re saying is that a lot of patients with HCM with obstruction will tell you they have good days and bad days. Some days, they can do anything they want, and they have other days where they can’t walk across the house. As we’ll talk about later on, it can be due to some of the hemodynamics of why the symptoms are there. But warm, humid weather makes them worse. Being upright and hurrying makes them worse. What’s unique to HCM is a dynamic obstruction, meaning they have good days and bad days, as opposed to someone with fixed aortic stenosis or fixed coronary disease, where their angina or symptoms are predictable based on the level of effort. It changes from day to day in patients with obstructive HCM.

Martin S. Maron, MD: Yes. When patients come in, sometimes they say, “Doctor, I think I’m going crazy because I go a week where I’m fine, then I go 2 weeks where I’m terrible, and I’m back to good.” It’s a very unique pattern.

Javed Butler, MD, MPH, MBA: Is that in part related to preload and afterload variations day to day, how much exercise or weightlifting they’re doing, and all those kinds of things?

Steve R. Ommen, MD: Exactly. How much fluid you’ve had to drink, how much sodium you’ve had, whether it’s warm or cold, whether you’ve eaten recently.

James Januzzi, MD: That’s interesting. It illustrates for our viewers the point that as clinicians and as caregivers to patients, you have to keep an open mind. You won’t find something if you don’t think of it or look for it.

Transcript Edited for Clarity