Later Loss of Ambulation Linked With Better Heart Health in DMD

Adult patients with Duchenne muscular dystrophy (DMD) who lost the ability to walk at later ages had better left ventricular ejection fraction (LVEF) in adulthood regardless of DMD genotype, a study published in Neuromuscular Disorders found.¹

The study also found that the age at respiratory thresholds did not impact the association between age and LVEF. Additionally, loss of ambulation (LOA) after age 12 reduced the risk of LVEF lower than 40%—a marker for heart failure or cardiomyopathy²—by 5-fold.¹ The results suggest that prolonging ambulation may not adversely impact cardiac function in adulthood for patients with DMD.

Past studies have explored the association between motor and cardiac function in younger patients with DMD, but there is a lack of research on this relationship as patients with DMD age. | Image credit: Nana_studio - stock.adobe.com

“An increased number of therapeutic approaches are under development in DMD specifically targeting skeletal muscles and aiming at preserving skeletal muscle strength, motor function, and ultimately prolonging ambulation,” the authors wrote. “In this context, understanding the relationship between age at LOA and cardiac function in adults with DMD can provide valuable insights into how these two outcomes relate in the long term.”

Due to a lack of dystrophin, almost all patients with DMD eventually develop a dilated form of cardiomyopathy, the authors noted. Past studies have explored the association between motor and cardiac function in younger patients with DMD, but there is a lack of research on this relationship as patients with DMD age. Therefore, their analysis assessed the association between LVEF and the age at LOA in adult patients with DMD receiving standard of care therapy had a specialized center.

A total of 84 adults with DMD receiving glucocorticoids were analyzed in the study, with a mean age of 22 years at last assessment and a mean age of 12.6 years at LOA. More than half of patients were on daily deflazacort.

At the time of their last assessment, 29 patients (34.5%) had LVEF lower than 40%, and all but 5 patients were on ACE inhibitors or angiotensin 2 receptor blockers. Regarding respiratory function, 43 patients (51.1%) were receiving ventilatory support, 39 (46.4%) showed an absolute forced vital capacity percentage of predicted (FVC) of less than 1 liter, and 46 (54.8%) had an FVCpp lower than 30%.

The study authors found that later age at LOA was linked with better LVEF preservation into adulthood (linear regression estimate, 1.49 [95% CI, 0.13-2.84; P = .03). With every additional year of ambulation, patients had higher odds of having a better LVEF percentage. The authors also conducted sensitivity analyses that excluded cardioprotective genotypes and mild motor phenotypes of DMD. These confirmed the association between age at LOA and LVEF in adulthood that was seen in the main analysis.

Patients in the cohort who experienced LOA prior to the age of 11.29 years showed LVEF lower than 40% 5.21 years earlier than patients who experienced LOA after the age of 11.92, with an adjusted restricted mean survival time of 19.08 years compared with 24.29 years (P < .001).

“The main finding of this retrospective analysis is that individuals with DMD who retain the ability to walk to an older age maintain their LV function better into adulthood compared to those who lost ambulation at a younger age,” the authors concluded. “This favorable relationship is maintained even when patients with milder genetically defined phenotypes are excluded. The results may reduce concerns that prolonged ambulation is deleterious to longer term cardiac function in DMD.”

References

1. Schiava M, Bourke JP, Díaz-Manera J, et al. Association between age at loss of ambulation and cardiac function in adults with Duchenne muscular dystrophy. Neuromuscul Disord. Published online January 6, 2025 doi:10.1016/j.nmd.2025.105276

2. Ejection Fraction Heart Failure Measurement. The American Heart Association. Updated June 14, 2023. Accessed January 8, 2024. https://www.heart.org/en/health-topics/heart-failure/diagnosing-heart-failure/ejection-fraction-heart-failure-measurement