BACKGROUND: Children and adolescents with Marfan (MFS) and Loeys-Dietz (LDS) syndromes report chronic fatigue and reduced physical endurance, which significantly impact their health-related quality of life (HRQoL). We hypothesized that a tailored physical training program could improve these parameters. To test this hypothesis, we conducted an interventional, prospective, single-center clinical trial consisting of a 3-month observation period followed by a 6-month intervention period, during which a personalized home-based training program was implemented. The primary endpoint was the change in ventilatory anaerobic threshold (VAT) assessed during a maximal exercise test. Secondary outcomes were changes in 6-minute walk test (6MWT) distance and HRQoL parameters (assessed before and after intervention using the Pediatric Quality of Life Inventory, PedsQL™) and cardiac tolerance.

RESULTS: A total of 28 children (25 with MFS and 3 with LDS) were enrolled, of whom 19 (68%) completed the study. At baseline, VAT and 6MWT distances were significantly impaired compared to the general population (p < 0.001 by one-sample t-test for both parameters), in particular in patient with a systemic score ≥ 7. During the program, there was an overall significant increase in VAT (p < 0.001 by ANOVA) and 6MWT distances (p = 0.02 by paired t-test). These improvements were accompanied by a significant enhancement in HRQoL parameters in the different dimensions assessed. No changes were observed in maximum heart rate, maximum systolic blood pressure and aortic sinus diameter.

CONCLUSIONS: This 6-month personalized home-based exercise training program significantly improved aerobic physical capacity and HRQoL in children with MFS and LDS without affecting aortic sinus diameter. Despite the small number of patients included, which is a common challenge in studies conducted on children with rare diseases, these findings provide promising perspectives for the management of these patients.

CLINICAL TRIAL REGISTRATION : URL https://clinicaltrials.gov/ ; Unique identifier NCT03236571 date of registration 28/07/2017.