Advances in Treatment of Obstructive Hypertrophic Cardiomyopathy - Episode 5

AHA/ACC HCM Guidelines and Patient Identification and Management

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Steve R. Ommen, MD; and Martin S. Maron, MD, review the role of AHA/ACC guidelines, imaging techniques, and circulating biomarkers in approaching the diagnosis and treatment of hypertrophic cardiomyopathy.

James Januzzi, MD: We’ve had a nice discussion about the background of HCM [hypertrophic cardiomyopathy] and how we differentiate obstructive and nonobstructive. Why don’t we start with a discussion about the HCM guidelines and think a little about what the guidelines say regarding diagnosis? Then let’s transition quickly into treatment, because there’s a lot to unpack there. Steve, why don’t you give us a general overview of the AHA [American Heart Association]/ACC [American College of Cardiology] HCM guidelines?

Steve R. Ommen, MD: It’s important to understand the role of guideline documents. Guidelines aren’t law. They’re not policy. The idea is to get the playing field leveled so that we all know we’re talking about the same thing and initiating a patient’s journey in the same manner. If they have obstructive HCM, we have documents about what you need to document, specifically what Marty [Maron] and I have talked about, that if the resting echocardiogram doesn’t show the obstruction, you owe it to that patient to do more to make sure they aren’t obstructive because it’s going to have a big role on what therapies are offered.

It’s important to recognize that any time we’re asked to put a number down in a guideline—wall thickness greater than X—the job of a doctor isn’t to abdicate thinking and rely on that number and start triggering things on one side of the number and not triggering things on the other side of the number. It’s to think about the concept that’s being conveyed there.

In HCM, the risk of sudden cardiac death has been shown in a study that if the wall thickness is greater than 30, there’s a higher risk of sudden cardiac death. We have a risk marker that’s bifurcated at that level. But that doesn’t mean someone whose wall thickness is at 29 mm on an echocardiogram has lower risk than someone whose wall thickness is 31 mm. It’s the concept that the thicker the heart, the higher the risk. Guidelines are about establishing an algorithm and a baseline set of patterns, and then as a doctor, particularly as experts, recognizing deviation from the pattern to know when a patient might not fit in that guide. It’s the table stakes of how you approach a patient with HCM.

James Januzzi, MD: That’s really useful. I once heard someone say that guidelines are a suggestion.

Steve R. Ommen, MD: Yes.

James Januzzi, MD: It provides you a suggested path. You mentioned wall thickness. What role does MRI play when you’re evaluating someone?

Steve R. Ommen, MD: Most of our patients end up getting CMR [cardiac magnetic resonance imaging] as well. Every patient with HCM is going to get an echocardiogram, which is probably how they’re initially diagnosed. CMR becomes crucial in the era of poor echocardiogram images due to increasing body mass size if we can’t see the whole heart. Then also crucial in that risk stratification oven, if a patient isn’t already declared high risk by some other risk marker, if multiple family members have sudden cardiac death, the MRI offers a more comprehensive view of the global wall thickness and identifies apical aneurysms for the select few that have that, which is a risk marker.

James Januzzi, MD: What’s the mechanism of that?

Steve R. Ommen, MD: It’s probably that capillary network being less dense, causing long term ischemia and then gradual infarction of the LV left ventricle apex, particularly if there’s any obstruction to midventricle, which increases cavity pressure at the apex, so the profusion pressure is lower.

James Januzzi, MD: One would imagine by losing the apex, one accelerates the midventricular obstruction as well.

Steve R. Ommen, MD: Exactly. Then you’ve got the scar there, the border zone of which is going to be your arrhythmogenic focus. Lastly, the MRI also gives us that more diffuse look at intramyocardial fibrosis with the late gadolinium enhancement imaging. CMR is used for many of our patients with HCM to help either clarify uncertainties with echocardiogram or help give more clarity around next-level decisions we have to make with patients. Marty, what would you add to that?

Martin S. Maron, MD: That was well said. As the guidelines pointed out and as you just said, HCM has emerged as a disease in which complementary cardiovascular imaging is not only helpful but critical in a lot of ways to provide the best for our patients in terms of diagnosis and management. You get different information with different tests, so you need to use both of them.

James Januzzi, MD: That’s really helpful. I have 1 last question before we move over to treatment. We’ve talked about imaging. What about circulating biomarkers? Do they have any role?

Steve R. Ommen, MD: Yes. Most of our patients will have NT-proBNP [N-terminal pro-brain natriuretic peptide] measured. We’ll measure troponins. Almost all of the patients have elevations of those markers. Some data suggest that they identify patients who have more compositive outcomes. It doesn’t give you interventions. They don’t trigger therapies other than maybe knowing when to watch a patient more closely.

Usually with a patient, they’re going to come into your office, you’re going to see in their patient portal that their NT-proBNP is 500 p/mL, and they’re freaking out because they don’t know what that means. We usually say, “That’s a normal range established in people who have normal thickness hearts. That normal range doesn’t necessarily apply to you. This is your first value. We’ll use that in the future. If you come back next time and there’s more shortness of breath and that number is higher, I’m going to feel like that’s internally consistent and we’re looking at your heart. If the patient has more shortness of breath and that number is lower, I’m going to look for other causes for your shortness of breath.” We have to put it in context for patients because the normal ranges weren’t established in patients with HCM.

James Januzzi, MD: No, certainly not. When we think mechanistically, the triggers for release in these patients is going to be variable. Wall stress alone in patients with HCM would explain things, transmural ischemia and tissue remodeling, especially with troponin. It’s an interesting issue. But what about outflow tract obstruction? What about gradient?

Martin S. Maron, MD: As we were talking about before, it’s such an important aspect of the evaluation of patients with HCM. You can’t treat patients with this disease in the right ways or effectively enough unless you put those patients in the right group, obstructive vs nonobstructive. As Steve was talking about before, there are a lot of different ways to go about demonstrating whether a patient with HCM who comes to you for an evaluation who doesn’t have obstruction should get evaluated for that. There are a number of different provocative maneuvers and tests that can be done.

There has been general preference over the more recent years that exercise echocardiogram may be the one we give the greatest weight to, although it’s not the only. There’s the Valsalva maneuver and other ways to do it. But there’s a bit of preference for exercise echocardiogram because that’s a physiologic test. That’s when patients normally are getting symptomatic with normal daily activities. We’re trying to mimic that in the echocardiography laboratory by doing exercise echocardiogram to see after the symptom-limited Bruce protocol whether there’s the development of obstruction. You don’t necessarily need to exercise a patient if they’ve got resting gradients of more than 50 mm of mercury, because you’re not going to gain any additional information. You know that gradient is only going to go up.

James Januzzi, MD: That’s really helpful.

Steve R. Ommen, MD: Jim, I have another comment I want to jump in with. You asked about the gradient. It’s also important for our audience to point out that you can’t follow the gradient to determine treatment effect. Because that gradient is so influenced by loading conditions, if you get them in a cold echocardiography laboratory vs a hot echocardiography laboratory, the gradient is going to be different. We need measures like asking patients how they’re doing. For all of our medical therapy, the goal is symptom relief. If the patient feels better and their KCCQ [Kansas City Cardiomyopathy Questionnaire] is better, then treatment is being effective, even if this week’s echo gradient might be higher. Don’t get stuck following echocardiogram numbers rather than treating the patient who’s telling you how they’re doing.

Martin S. Maron, MD: Don’t treat numbers. We treat the patients. That’s the message.

James Januzzi, MD: Absolutely. That’s a great clinical message and establishes the goals of HCM treatment, which is focusing on symptom relief and mitigation of cardiac remodeling. Javed?

Javed Butler, MD, MPH, MBA: Out of curiosity, do the biomarkers troponin and natriuretic peptides give an idea about the general prognosis? Or can they also guide us to high risk for certain cardiac death in this patient population?

Martin S. Maron, MD: The biomarkers in general are all over the map in this disease. That’s the reality. We don’t rely on them for that reason in terms of prediction.

John A. Spertus, MD, MPH: Within a patient, is the biomarker a reasonable way to follow response to therapy or is it still driven primarily by symptom response?

Martin S. Maron, MD: That’s something that we don’t do. Because it’s so variable, as Steve was just saying, the greatest weight is on clinical response. That’s why history-taking is so important.

Steve R. Ommen, MD: Anecdotally, the peptides seem to follow the way the patient is doing, but it’s a noisy signal.

Martin S. Maron, MD: It’s very noisy.

Transcript Edited for Clarity