Rate of Change in Cardiac Magnetic Resonance Imaging Measures Is Associated With Death in Duchenne Muscular Dystrophy

Area of Science:

• Cardiology
• Genetics
• Neurology

Background:

• Cardiovascular disease is the primary cause of mortality in Duchenne muscular dystrophy (DMD).
• Early identification of patients at high risk for mortality is crucial for timely intervention and intensive management.
• Identifying predictive markers can establish surrogate outcomes for clinical trials in DMD.

Purpose of the Study:

• To investigate cardiac magnetic resonance imaging (CMR) parameters that predict mortality in Duchenne muscular dystrophy patients.
• To identify specific rates of change in cardiac function and structure associated with increased mortality risk.
• To evaluate the potential of these changes as surrogate endpoints in therapeutic trials.

Main Methods:

• Prospective enrollment of Duchenne muscular dystrophy subjects in observational studies.
• Utilized generalized least squares models to compare CMR measurements between deceased and surviving participants.
• Analyzed data from 63 participants with multiple CMR assessments over a median follow-up of 5 years.

Main Results:

• Twelve participants (19.1%) died during the follow-up period.
• Deceased subjects exhibited a faster rate of decline in left ventricular ejection fraction (P<0.0001).
• Increased rates of left ventricular end-diastolic (P=0.0132) and systolic (P<0.0001) volumes were observed in deceased subjects.
• Faster progression of mid-circumferential strain was noted in deceased individuals (P=0.049), but global circumferential strain showed no significant difference.
• Rates of change in late gadolinium enhancement, base T1, and mid T1 did not differ between the groups.

Conclusions:

• The rate of change in left ventricular ejection fraction, mid-circumferential strain, and ventricular volumes are significantly associated with mortality in Duchenne muscular dystrophy.
• Intensified medical therapies aimed at slowing disease progression may reduce mortality rates in DMD patients.
• A reduced rate of cardiac progression could serve as a valid surrogate outcome measure in clinical trials for Duchenne muscular dystrophy.