Alteration in Left Ventricular Contractile Function Develops in Puppies With Duchenne Muscular Dystrophy

Area of Science:

• Cardiology
• Genetics
• Animal Models

Background:

• Dystrophin-deficient cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD) patients.
• The developmental process of this cardiomyopathy is not well understood.
• Golden Retriever Muscular Dystrophy (GRMD) dogs serve as a valuable model for studying DMD pathologies.

Purpose of the Study:

• To investigate the progression of left ventricular (LV) dysfunction in GRMD dogs.
• To identify early echocardiographic markers of cardiomyopathy development in GRMD dogs.
• To establish a translational model for DMD-associated cardiomyopathy.

Main Methods:

• Sequential transthoracic echocardiography was performed on GRMD dogs and healthy littermates from 2 to 24 months of age.
• Conventional, tissue Doppler imaging, and speckle-tracking echocardiography parameters were analyzed.
• Receiver operator characteristic curve analysis was used to assess diagnostic ability.

Main Results:

• GRMD dogs exhibited decreased subendocardial-subepicardial radial systolic myocardial velocity gradient, altered LV twist, and longitudinal strain from 2 months of age.
• These abnormalities progressively worsened with age.
• LV ejection fraction decreased significantly from 9 months, reaching pathological levels by 24 months.

Conclusions:

• Cardiomyopathy development in GRMD dogs progresses from early subendocardial dysfunction to global LV dysfunction and heart failure in adults.
• Early detection of LV transmural myocardial velocity gradient, twist, and longitudinal strain is essential for managing DMD patients.
• GRMD dogs provide a robust model for studying DMD cardiomyopathy progression and testing interventions.