Three Surprising Studies on Exercise Restriction and an Exercise Sweet Spot 

John M. Mandrola, MD


March 09, 2023

Evidence from three studies in Sports Cardiology presented at ACC piqued my interest. Not only because I love endurance sport but because the studies reported data that upset prevailing ideas.

LIVE HCM: Surprising Result Number 1

Rachel Lampert, MD, from Yale University presented results of the LIVE-HCM observational study of vigorous exercise in more than 1600 patients with hypertrophic cardiomyopathy (40% female). The investigators aimed to determine whether engagement in vigorous exercise, including competitive sports, is associated with increased risk for life-threatening ventricular arrhythmia and/or mortality in patients with HCM.

Due to the myocardial disease, HCM comes with a risk for ventricular arrhythmia. Prevailing wisdom held that vigorous exercise in these patients would be hazardous. It was all expert opinion; there were no data. Now there are.

Lampert and colleagues recruited patients from 42 international HCM centers. Patients self-enrolled and the researchers created three groups based on self-reported levels of exercise — vigorous, moderate, and sedentary. The main comparison was between vigorous vs non-vigorous exercisers (including moderate and sedentary). The two groups were mostly matched on baseline characteristics and typical of patients with HCM.

The primary endpoint was a composite of death, resuscitated cardiac arrest, syncope likely due to an arrhythmia, or an appropriate shock from an ICD.

The event rates were low in all groups and almost identical in vigorous vs non-vigorous exercisers. Sub-group analyses found no increased risk in HCM patients who identified as competitive athletes.

Lampert said these data "do not support universal restriction of vigorous exercise in patients with HCM."

Return to Play: Surprising Result Number 2

Undergraduate student Katherine Martinez from Loyola University in Chicago presented an observational analysis of 76 elite athletes with genetic heart disease who gained a return-to-play approval from four expert centers in the US.

The three-step, return-to-play protocol from these specialized centers deserves emphasis. First was the initial evaluation, including 2 ECGs, 24-hour ECG monitor, echocardiography, and treadmill exercise testing. Second was a discussion between clinicians and patients regarding the athlete's situation. The third step was to inform coaches and staff of the team and instruct athletes to obtain a personal AED, stay replenished with electrolytes, avoid QT-prolonging drugs, and continue with annual follow-up.

Slightly more than half of these patients had HCM and almost a third had long QT syndrome. Nearly one third had an ICD implant and 22 were women.

Of the 76 athletes, 73 chose to return to play; however, 4 of these remained disqualified because of their team's decision. Of the remaining 69, only 3 had 1 or more breakthrough cardiac events during 200 patient-years of follow-up.

These comprised one male Division I basketball player with HCM who had an ICD shock while moving furniture; another male Division 1 hockey player with long QT syndrome who was taking beta-blockers experienced syncope while coming off the bench and while cooking; and a third male professional hockey player with HCM, on beta-blockers, had syncope without exertion.

The authors concluded that when there was careful evaluation by experts and shared decision-making, a specific plan to return to sport can be put into place for the highest-level athletes.

Masters@Heart: Surprising Result 3

Ruben De Bosscher MD, PhD, from KU Leuven in Belgium, presented the Masters@Heart study on behalf of a Belgian team of researchers. The question they asked was whether lifelong endurance exercise is associated with more coronary atherosclerosis than standard "normal" exercise levels.

That question brings up the paradox of exercise, which is that numerous observational studies find that exercise strongly associates with lower rates of cardiovascular events, but imaging studies also report high rates of coronary artery calcium in endurance athletes, especially in those who have run multiple marathons.

Masters@Heart investigators sought to explore this paradox by performing detailed coronary imaging in three groups — lifelong athletes, late-onset athletes (after age 30 years), and super-healthy controls. Through advertisements they obtained about 1100 middle-aged male volunteers (mean age, 55 years). Of these, 605 men were selected at random to participate to reduce the chance of enrolling people who responded to the ads because of health concerns.

Investigators assigned those selected based on self-report of exercise. The control group was notable for their good health: they were free of any risk factors, took (almost) no meds, exercised regularly but not excessively (about 3 hours per week) and had a VO2 max of 122% of predicted.

The groups were well matched on baseline characteristics. Cycling predominated as the exercise of choice (this is a Belgian study after all). All patients had an extensive evaluation including coronary CT imaging.

European Heart Journal published the provocative results:

  • Lifelong exercisers had a significantly higher CAC burden than controls, which confirms previous work.

  • Lifelong exercisers had a higher percentage of multiple coronary plaques, plaques ≥ 50%, and proximal plaques.

  • There were no significant differences in the mixture of plaque types in the three groups. About two thirds of the plaques in each group were calcified and the remainder were deemed noncalcified or mixed.

  • When looking only at noncalcified plaques, lifelong exercisers tended to have a higher prevalence of multiple plaques, plaques ≥ 50%, and proximal plaques.

  • So named "vulnerable" plaques were extremely infrequent in all three groups.

The authors concluded that lifelong endurance sport relative to a generic healthy lifestyle was not associated with more favorable coronary plaque composition.


Each of these three studies provided data where there was none. That is always a good thing.

The major theme from the first two studies is that expert opinion was too cautious. Doctors have long held the idea that patients with genetic heart disease, especially hypertrophic cardiomyopathy, are vulnerable, fragile even, when it comes to vigorous sport.

This new evidence upends this belief, as long as return to sport occurs in the setting of robust patient education and expert evaluation and surveillance.

Paternalism in prohibiting participation in sport because of genetic heart disease has joined the long list of medical reversals.

Masters@Heart provides a slightly different message. It finds that lifelong high-level exercise does not prevent coronary atherosclerosis in men. And, more provocatively, if replicated, might even show that long-term exposure to the biochemical, inflammatory, or hormonal effects of endurance training may actually be atherogenic. Like all good science, these findings raise more questions to explore in the realm of atherogenesis.

Two of the main limitations of the Belgian study was that the control arm was quite healthy; had the comparison arm been typical of sedentary controls in say, the Southeastern US, the coronary lesions found in longtime exercisers may have looked more favorable. The more significant limitation is the lack of outcomes. Images of coronary arteries remain a surrogate marker. It's possible that, like statins, higher levels of exercise may stabilize plaque and actually lower the risk for events.

The Belgian authors suggest — as many have — a j-curve of exercise benefits, wherein too little exercise is clearly bad, but too much exercise may also increase risk. In other words, for maximizing health, there may be a Goldilocks amount of exercise.

The problem with this idea comes in its pragmatic translation. The number of lifelong high-level, middle-aged endurance athletes that cite heart health reasons for their affliction is…almost zero. Nearly everyone I have met in the endurance sport fraternity harbors no notion that racing a bike or running multiple marathons per year is a healthy endeavor.

Paternalism, therefore, would also fall in the realm of limiting lifelong exercise in addicted middle-aged athletes.

Via email, sports cardiologist Michael Emery, MD, reiterated the main immediate message from Masters@Heart: "Exercise does not make you immune from heart disease (which is a message a lot of athletes need to hear honestly)."

I for one cannot give up on endurance exercise. I won't likely race anymore but I am like the lab rat who needs to run on the wheel. Whether this affects my coronary plaque burden matters not to me.

John Mandrola practices cardiac electrophysiology in Louisville, Kentucky and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. 

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