O1023: Pilot Study of the Effects of Moderate Intensity Exercise on Children and Young Adults with Marfan Syndrome

Background: Given anecdotal reports of aortic dissection with exercise, limited evidence from in-vitro studies, and theoretical concerns, the majority of patients with MFS are restricted from certain physical activities. While clinicians may intend to restrict patients only from specific activities like competitive sports or those with risk of collision, often families interpret this as applying to almost all exercise, resulting in a large number of sedentary patients. This is likely to have detrimental effects on endurance, strength, and mental health. Recent animal studies have demonstrated cardioprotective effects of a moderate intensity exercise program in mice with Marfan Syndrome. We hypothesized that a moderate intensity exercise intervention in children and young adults would improve fitness without accelerating aortic root growth.

Methods: Patients with Marfan syndrome (+FBN1 variant and meeting Ghent 2010 clinical criteria) age 12-21 years were prospectively recruited. Those status post aortic surgery or unable to undergo magnetic resonance imaging (MRI) or exercise stress testing were not eligible for recruitment. The pilot study was designed to enroll 20 subjects. All subjects were initially screened, given a wearable activity tracker, and educated on moderate intensity exercise goals. Each then underwent a supervised, moderate-intensity exercise protocol. Participants underwent baseline and post-intervention testing (exercise stress Test, cardiac MRI, endothelial function, and carotid-femoral applanation tonometry) and mental health screening (DASS-21). The primary outcome was max VO2. Shortly into the study, the intervention was modified due to poor compliance to 1) add virtual partnered exercise sessions and 2) shorten the intervention from 16 weeks to 8 weeks. Given the protocol change, the decision was made to perform a mid-study assessment. This report is for the first 10 subjects.

Results: In the first group (n=5), one enrolled patient was lost to follow-up, and two did not participate in the exercise intervention, for a failure rate of 60%. After the intervention modification, all subjects actively participated and completed the study. For the 7 subjects completing the study, median age of subjects was 20.3 years (range 12.0-21.0 years), and 5 were female. For the primary outcome, Max VO2 significantly increased and systolic blood pressure at rest decreased, while aortic root dimension and z-score did not change (Figures 1). Stress scores also decreased (Figure 1). Left ventricular ejection fraction decreased although maintained in the normal range, and this appeared to be driven by a decrease in left-ventricular end-diastolic volume without a decrease in end-systolic volume (Figure 2).

Conclusion: These pilot data suggests that there is potential for a moderate intensity exercise intervention to improve cardiovascular fitness without accelerating aortic root growth, although a larger sample size is needed. We also noted that the addition of virtual partnered exercise sessions improved compliance in this cohort.