Respiratory Advances Extend DMD Patient Life, Pose Cardiac Challenges

Duchenne muscular dystrophy (DMD) is a devastating muscle-wasting disease primarily affecting males, with an incidence rate of approximately 1 in 5000 live male births. It results from the absence of the protein dystrophin, leading to increased fragility of skeletal muscle membranes and the dysregulation of signaling processes, ultimately causing muscle necrosis and fibrosis. DMD typically leads to premature death in young adulthood, often due to respiratory or heart failure. Recent advancements in respiratory therapies have increased the lifespan of DMD patients, raising the prevalence of advanced heart disease among them, according to a recent study published in Neuromuscular Disorders.

Cardiomyopathy associated with DMD is a progressive disorder, with early signs manifesting before age 10 and severe myocardial fibrosis and contractile deficits occurring in later stages. Chronic treatment with ACE inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) has been shown to slow the progression of established heart disease in DMD patients. As a result, treatment guidelines recommend initiating one of these drugs by age 10 to mitigate fibrosis and adverse cardiac remodeling. ACE-I has historically been the preferred choice despite ARBs being better tolerated.

In 2015, new guidelines for treating DMD cardiomyopathy marked a significant shift in disease management. These guidelines favored early initiation of prophylactic therapy based on advanced cardiac imaging, which could detect cardiac dysfunction even before traditional evaluations. These changes prompted an evaluation of clinical management practices in light of the guidelines.

Data from the MOVR Data Hub, representing DMD patients from multiple US clinics, revealed insights into the management of dystrophic cardiomyopathy. Heart failure, defined as an ejection fraction of <40%, increased in prevalence after age 15, irrespective of steroid treatment.

Four main therapeutic classes were identified:

• ACE-I
• ARBs
• Aldosterone antagonists (Aldo Ant); and
• β-adrenergic receptor blockers (β-Blockers)

ACE-I and ARBs were the most prescribed, often in combination with other medications. However, most DMD patients did not receive recommended cardiac-directed therapy, and those who did received it at an earlier age post-guideline implementation.

Despite the importance of cardiac care in DMD patients, echocardiographic data was reported for only 70% of patients, likely due to the younger age of this cohort. Cardiomyopathy in DMD patients is a major concern, with early signs appearing in childhood. The guidelines now recommend initiating ACE-I or ARBs by age 10, but these drugs are still underutilized.

This study highlights the need for wider distribution of known therapies to the DMD patient population and the importance of understanding the factors contributing to the treatment gap. Discrepancies in treatment were observed even within the same centers, suggesting that access to resources may not be the sole determinant. Addressing these issues is crucial in improving the care and outcomes of DMD patients with cardiomyopathy.

"It is important to note that most of the facilities contributing data to this data set are in the United States, which is not known for its equitable distribution of health care resources. It would be very interesting to determine if similar treatment gaps exist in countries will lower barriers to health care access," said researchers.

Reference

Karachunski P, Townsend D. Systemic under treatment of heart disease in patients with Duchenne muscular dystrophy. Neuromuscular Disorders. Published online September 19, 2023. Accessed October 2, 2023. doi:10.1016/j.nmd.2023.09.004