Health Status With Different HCM Treatments

Martin S. Maron, MD: I had a question for you about the health status impact that you were just talking about in terms of EXPLORER-HCM. Do we know how that compares with what we were just talking about for the invasive septal reduction therapy options? Do we know how the magnitude of improvement seen in EXPLORER-HCM compares with surgery or alcohol ablation?

John A. Spertus, MD, MPH: It’s a great question. As you both articulated, these mechanical interventions have been around a long time, long before the KCCQ [Kansas City Cardiomyopathy Questionnaire] was repeatedly used to monitor outcomes. There’s a study. I forget the magnitude of benefit that was seen. It was a small, I think 38-patient study. There was just a single arm. We gave the KCCQ after doing septal ablation, and it seemed to be about this magnitude. There’s a call for more work to understand this, so we’ll see.

This isn’t an either-or thing. There were people in EXPLORER-HCM who didn’t get better. For those patients, having mechanical interventions to offer them can be exceedingly helpful. But for those who do get better, perhaps you could delay these interventions. The VALOR-HCM study was just released at the ACC [American College of Cardiology Scientific Session & Expo], which is where we are. It showed that there was delay in meeting the guidelines for it. It was a small study, but it was important work, slowly getting data to understand how to integrate a range of different therapeutic options.

Martin S. Maron, MD: We welcome the idea that there are going to be more options. We’re all enthusiastic about that. That’s huge. It isn’t 1 vs another. It’s going to be incorporating all of this in the toolbox to individualize care in a way that will hopefully have more options for patients than we have today, which is great. I totally agree with that. That’s a hugely important point with these new therapies coming along.

John A. Spertus, MD, MPH: The other thing, which we talked briefly about before, holds for the management of ischemic heart disease as the guidelines are recommending. The guidelines for HCM [hypertrophic cardiomyopathy] recommend shared decision-making, but we haven’t built the toolkit to give empirical data to inform how much better I’ll do if I try a beta blocker, 1 of the new direct myosin inhibitors, or if I go to surgical or percutaneous septal ablation, and what the risks of these procedures are.

This is something that has to happen in specialized centers. There needs to be a certain experience. When you’re going to offer these interventions, I’m nervous about people who as a rare hobby will do a quick alcohol septal ablation. It makes me a little nervous. But it’s important to think about the infrastructure required to give good HCM care and create the tools to take the expertise that the 2 of you have to Kansas City, Dallas, and other areas of the country. It’s a professional challenge that we have to start to think about meeting.

Martin S. Maron, MD: That’s well said.

James Januzzi, MD: Dr Butler?

Javed Butler, MD, MPH, MBA: I’d like to make a qualitative comment and then I have a question as well. Having thought a lot about health status and quality of life in both drug- and device-based interventions and heart failure in general—not necessarily in this space—although I don’t know of any data with KCCQ with septal ablation or myomectomy, if you have an average population-based difference between with the use of this therapy for 9 or 10 points and an NNT [number needed to treat] of 5 for a 20-point improvement, I can imagine that those other interventions will be a whole lot better than that. I wouldn’t be surprised if they aren’t comparably equal.

In other words, this is impressive health status improvement with this therapy. There are likely no data to that, but do the different genetic variants related to HCM portray a different response to therapy because some are just affecting calcium handling and the other have structural change in your proteins and stuff like that? Do we know anything about that?

Steve R. Ommen, MD: We don’t know much about that. We know a little about that. There was another trial where they used valsartan for nonobstructive patients with minimal hypertrophy and it showed less disease progression in the patients treated with valsartan vs placebo. Those were all gene-positive individuals, and there might have been a stronger signal in 1 of the gene families and 1 of the other gene families. The issue with HCM is there are over 500 different gene variants that have been described as resulting in HCM. Your N [number] for any 1 genetic abnormality becomes so small that you can’t draw conclusions about macrophenomenon. It’s a problem of too much variation.

James Januzzi, MD: That’s useful to know.

Transcript Edited for Clarity