WASHINGTON – A regimen of moderately intense exercise for 16 weeks produced no adverse effects and led to a clinically meaningful improvement in exercise capacity in a multicenter, randomized trial involving 136 patients with hypertrophic cardiomyopathy.

While finding that regular exercise produced a statistically significant improvement, compared with control patients fulfilled the study’s primary endpoint, it was perhaps as important that patients with hypertrophic cardiomyopathy (HCM) randomized to the exercise arm experienced no ill effects, a finding that bucked conventional wisdom that, once diagnosed, HCM patients must adhere to a largely inactive lifestyle.

“No clinical trial previously implemented an exercise regimen in patients with HCM,” Sara Saberi, MD, said at the annual meeting of the American College of Cardiology.

“I see patients with HCM who tell me that, when they were first diagnosed, they were told by their physician not to do anything at all,” said Dr. Saberi, a cardiologist at the University of Michigan in Arbor. Although she cautioned that the findings from this modestly sized trial cannot prove that exercise is safe for HMC patients – something that would require randomizing more than 2,000 patients and following them for about 3 years – the findings provide some level of reassurance that regular, moderately intense exercise as simple as walking can benefit patients and likely not cause any problems. “We saw no signal of harm,” she stressed in an interview. “I would recommend moderate-intensity, regular exercise. Physicians can feel comfortable using the exercise prescription” used in the study, she advised.

The results “demonstrate that moderate exercise does not appear to have any adverse effects, which has never been shown before” for patients with HCM, commented Martin S. Maron, MD, director of the Hypertrophic Cardiomyopathy Center at Tufts Medical Center in Boston and a designated discussant for the report.

Concurrently with Dr. Saberi’s report at the meeting, the results also appeared in an article published online (JAMA. 2017 Mar 17. doi: 10.1001/jama.2017.2503).

The Study of Exercise Training in Hypertrophic Cardiomyopathy (RESET-HCM) ran during 2010-2015 at the University of Michigan and Stanford University, and enrolled 136 patients 18-80 years old diagnosed with HCM but without more severe manifestations such as a history of exercise-induced syncope or ventricular arrhythmia, a left ventricular ejection fraction less than 55%, recent clinical decompensation, or a history of a severe hypotensive response to exercise. Enrolled patients averaged about 50 years old, their baseline peak oxygen consumption, VO₂, was about 22 mL/kg per min, and their maximal ventricular wall thickness was about 21 mm.

Following a comprehensive baseline heart function and imaging assessment, including a cardiopulmonary exercise test, the 67 patients in the intervention arm received an individualized exercise prescription based on their heart rate reserve. At a minimum, they started with three exercise sessions per week lasting at least 20 minutes on their own, a regimen designed to bring them to 60% of their heart rate reserve. Their prescription gradually increased to four to seven exercise periods weekly lasting up to 60 minutes and designed to bring them to 70% of their heart rate reserve. Although most patients accomplished this through walking, some engaged in activities that included cycling, swimming, jogging, or elliptical training. The researchers told the 69 control patients to continue doing their usual activities. Among the patients who entered the study, 57 in the exercise group and 56 controls remained for the full 16 weeks and had a complete final assessment.

After 16 weeks, the average change in peak VO₂, was 1.35 mL/kg per min in the intervention group and 0.08 mL/kg per min in the control patients, a statistically significant difference for the primary endpoint and a 6% increase in exercise capacity, compared with baseline for the intervention group. Dr. Saberi noted that, in a prior study of patients with chronic heart failure, a 6% increase in peak VO₂ linked with an 8% decrease in cardiovascular mortality of heart failure hospitalization.

This result is “a glimmer of hope for using exercise in HCM patients,” she said. “There are no other disease-modifying treatments for HCM, so this is the first ‘treatment’ to have any impact on the disease.”

The patients who exercised had no identified major adverse effects or changes in cardiac morphology after 16 weeks. Assessment of physical function quality of life using the SF-36v2 showed an average 8-point improvement in the patients who exercised, compared with the controls. In addition, “a lot of patients in the exercise group told us that they felt better,” Dr. Saberi said.

Because patients with HCM are often advised to limit their activity, the consequence is “we increasingly see HCM patients who are obese and have complications such as sleep apnea and atrial fibrillation. Patients are even fearful of going up and down stairs.” She stressed the simplicity and ease of the intervention she and her colleagues tested, which can involve nothing more than regular, daily walks of 20 minutes or more. Dr. Saberi advised tailoring the intensity and frequency of the exercise intervention to each patient and avoiding having the patient push beyond what they find comfortable.

A multicenter U.S. registry, the Lifestyle and Exercise in Hypertrophic Cardiomyopathy Study (LIVE-HCM), is now enrolling HCM patients that should eventually follow enough patients for a long enough period of time to definitely prove whether moderate exercise is safe for HCM patients, but the results will not be available for several more years, Dr. Saberi said. A recent analysis estimated that one in every 200 adults has HCM (J Am Coll Cardiol. 2015 Mar 31;65[12]:1249-54), which means the disease likely affects more than one million Americans.

mzoler@frontlinemedcom.com

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Moderate exercise benefits hypertrophic cardiomyopathy patients