The LIVE-HCM Study

Is It Time to Ease Exercise Restrictions in Patients With Hypertrophic Cardiomyopathy?

John M. Mandrola, MD; Rachel Lampert, MD


March 10, 2023

This transcript has been edited for clarity.

John M. Mandrola, MD: Hi, everyone. This is John Mandrola from | Medscape Cardiology, and I'm here at the American College of Cardiology meeting. I'm really pleased to be with one of my friends, Rachel Lampert, who's a professor of medicine and electrophysiology at Yale University. She's here to present the LIVE-HCM study. It's a late-breaking study dealing with patients who have hypertrophic cardiomyopathy (HCM) and whether they can do vigorous exercise. It's a prospective study that has really interesting findings. Rachel, thanks for being with us.

The LIVE-HCM Study

Rachel Lampert, MD: I'm so pleased to be here presenting the findings from LIVE-HCM, or Lifestyle and Exercise in HCM study. For decades, these patients have been restricted not just from competitive sports, but even from vigorous exercise. We know that many of them then just sit on the couch and don't do anything.

What we did in this study was –that we found individuals with HCM aged 8-60 years, and we enrolled people across the spectrum of exercise. So we enrolled individuals who were vigorous exercisers, even competitive athletes; those doing moderate amounts of exercise; and those who were sedentary and had less active lifestyles.

We followed them prospectively for 3 years, and we asked them every 6 months to fill out a brief survey to let us know if they had had any of the endpoint events, which included a resuscitated cardiac arrest. If they had a defibrillator, had they had an appropriate shock for ventricular arrhythmias? If not, had they had a syncopal event or felt potentially arrhythmic? We also identified those who had died, and total mortality was another part of the composite endpoint. So we then compared the vigorous exercisers vs those exercising less vigorously — the moderate and sedentary groups combined.

Mandrola: And the findings?

Lampert: We were so pleased to find that the vigorous exercisers did not have a higher rate of the composite endpoint than the moderate and sedentary group. Overall, the event rate was low: < 5% across the board had an event over the 3 years of follow-up. This translated to 15.3 events per 1000 patient-years in the moderate-sedentary group vs 15.9 in the vigorous group. That gives us a hazard ratio of 1.01 — really pretty darn close to unity.

We looked at some subgroups, including persons who were more competitive among the vigorous exercise group. We looked at those who had only overt HCM. This study did enroll patients who had genetic variants for HCM without yet having expressed the disease. That accounted for 8% of our population. When we looked at the group without those, we basically had the same finding. The CIs were a bit wider, because it was a smaller group, but the hazard ratio was very similar.

The Exercise Paradox

Mandrola: We've both been doing this for a while, and the teaching has been that patients with HCM, these thick pro-arrhythmic ventricles, it's hazardous for them to exercise, but your data didn't bear this out.

Lampert: We and the community of physicians that care for these patients should feel reassured by these data. We're hoping that these will form the basis for more informed decision-making between physicians and their patients and families, and really all involved in their care, around levels of exercise.

One point I'd like to bring out is that the majority of our patients were followed in high-volume HCM centers. They had been risk-assessed by a knowledgeable HCM expert. Whether these data can be extrapolated to other environments is unknown. It's really important for patients with HCM to see experts in the field who can help them think about their disease overall, as well as this decision about exercise and sports.

Mandrola: You've published a lot about exercise in athletes. As a person who really loves to do endurance exercise, I'm drawn to that. And it would be very difficult if someone told me…

Lampert: You can't go on your bike, John.

Mandrola: That would be terrible. What's the genesis of this? How did you get interested in this field?

Lampert: My interest in athletes who have cardiac disease started with two patients that I had very early on in my career as an attending. They had different diseases, had gotten defibrillators. The guidelines at the time said no way, no how, you're done with vigorous exercise, which I expressed to these patients. One of them, a young adult, asked "What are the data?" And I had to tell him, "Well, we don't have any. But that's what everyone thinks." And he told me that he would keep exercising until I could show him some data one way or the other.

That was the impetus for my first study, which was called the ICD Sports Registry. That was a big series of individuals who had gotten implantable cardioverter defibrillator (ICDs) and continued to participate in competitive sports. It was just a series; it wasn't a comparative group. But there were no adverse events. Nobody died. Nobody required external resuscitation. Nobody injured themselves due to arrhythmias or shocks. And a number of those patients had HCM.

So where that left us was, if you have HCM and a defibrillator, you're safe to be more vigorous. But if you are lower-risk and don't have a need a defibrillator, then you're still restricted, which really didn't make sense to me or to patients. We knew that we needed to figure this out for HCM in general so that we can advise our patients who are lower-risk whether they can participate as well in vigorous exercise.

Mandrola: It seems logical that in someone with a thick hypertrophic ventricle, it would be hazardous. So how do you explain this, and are you surprised about these findings?

Lampert: There are hypothetical reasons why exercise could be dangerous and hypothetical reasons why it could be safe. In thinking about the basic physiology of HCM and exercise, there could be deleterious effects in the sense of if you have a thick enough ventricle, are you getting subendocardial ischemia when you exercise? On the other hand, we know that exercise is great for diastolic function, which is one of the problems in HCM. We know from a prior study done by Dr Sharlene Day and colleagues, called RESET, that individuals can work out and can get themselves into better shape without adverse events as well.

The other piece to think about, and this is a complicated concept, is that there's a paradox of exercise in the general population, where we know that exercise can be an immediate trigger even in fit individuals. But we also know in the general population that exercise overall lowers your mortality. How can those two things both be true? The reason is that regular exercise changes what we call sympathovagal balance: The amount of adrenaline running around in your body becomes less when you're physically fit, and the more physically fit you are, the better your sympathovagal balance.

Mandrola: Lower resting heart rate with exercise.

Lampert: Yes, a lower heart rate is one of the ways we measure sympathovagal balance. And that may be protective. So they kind of balance each other out. I'm not surprised, based on the physiology of exercise and what we know about exercise in general, that in fact, we ended up without a signal for harm.

Mandrola: Let me ask you also about the methods, because it seems to me that you couldn't really study this in a randomized controlled way. The only way to do this is with a prospective observational study. Do you agree?

Lampert: Yes. And I think that's an excellent point. You can take sedentary people and randomize them to short-term exercise or not, but to really look at vigorous exercise, competitive exercise, long term effects, it would be next to impossible to do that as a randomized trial. And in fact, even the data that we have on exercise in the general population generally come from large epidemiologic studies. So of course with any observational study, you have to be pretty careful. Are the groups equally matched? There were small differences in some of the known risk factors for sudden death between the groups, and we did control for those without seeing a change.

Vigorous Exercise Defined

Mandrola: How did you decide what's vigorous and what's not vigorous?

Lampert: Our prespecified categorization/classification used a standard definition of vigorous, which was participating in an activity greater than 6 metabolic equivalents (METs). METs, as you know, are ways of looking at the metabolic demand of exercise. So 6 METs is swimming, ice hockey, or running. We defined vigorous as exercising at greater than or equal to 6 METs at least 60 hours per year, which is a standard definition. Now, we also looked at those who self-identified as competitive. For that initial analysis, we looked at any level of competition, whether they're running marathons or they're in the tennis league at the local club, and also didn't see differences. We do have a smaller group of highest-level athletes: varsity, high school, and college. We have 56 of those, 42 of whom have overt HCM. We'll be reporting on those a little bit later. But we can say at this point, we did not see a signal for harm in that highest-level group either, although it's small.

Mandrola: How does that work? If you have documented phenotypic HCM and you're a competitive athlete, how do they get permission to participate?

Lampert: That is that is a great question, John. Basically, it used to be that decisions about sports were made in a very paternalistic manner. The initial guidelines were yes or no; you have this, you're in, you have that, you're out. What anybody thought about it or any sort of nuances of risk being unknown, what have you, were not part of that decision. Even since 2015 , when the most recent age-eligibility guidelines came out, there's been a move toward shared decision-making, where the physician is talking to the patient, and we talk about what is the risk? How much of this risk is actually known, or are we dealing with unknown risks? If there are data, how do these apply to the patient in front of you? And we really talk to patients about risk tolerance as opposed to you're in or you're out.

Even when the guidelines were so black and white, schools and leagues always have differed in their comfort level with risk tolerance. So even when it was a more historically paternalistic approach, there were always schools that did allow some of these people to participate. That's how we were able to do the ICD Sports Registry, because even though it was against the guidelines, some schools were willing to take that shared decision-making approach.

Mandrola: I want to get back to this "paradox of exercise." This is interesting in that the exercise itself can be hazardous because it can be an adrenaline rush. But in general, it's beneficial because of the all the changes that happen — sympathovagal but also larger changes to the ventricle and eccentric remodeling might be beneficial.

Lampert: Those could all be hypothesized as well.

Mandrola: Say we have a 40-year-old woman or man who has HCM. They've been evaluated by the electrophysiologists and by an expert, and they say they don't require an ICD. What can we say?

Lampert: What sport do they want to do?

Mandrola: Let's say they want to run 5Ks or 10Ks, or they want to do these group rides on their bike or something like that.

Lampert: I think what we can say is we now have data that suggest that these activities do not put them at higher risk. And in fact, if they're doing them regularly, they are probably a good thing.

Mandrola: Excellent. Rachel, thank you so much for coming on. I really appreciate it.

Lampert: Thanks so much for your interest in the study, John. It's always great to have these conversations.

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