Is muscular dystrophy associated with cardiomyopathy?

Muscular Dystrophy and Cardiomyopathy

Yes, muscular dystrophy is strongly associated with cardiomyopathy across multiple forms of the disease, with dilated cardiomyopathy being the most common cardiac manifestation. 1 This cardiac involvement represents a significant source of morbidity and mortality in muscular dystrophy patients, particularly as respiratory support has improved survival rates.

Types of Muscular Dystrophy and Associated Cardiac Involvement

Duchenne Muscular Dystrophy (DMD)

• Most common form of muscular dystrophy (affects ~1 in 5000 live male births) 1
• Dilated cardiomyopathy is the predominant cardiac manifestation
• Cardiac features:
  • Begins with dysfunction without significant ventricular dilation 1
  • Average age for developing abnormal left ventricular ejection fraction: 14.3 years 1
  • Cardiomyopathy is now a leading cause of mortality (>20% of deaths) 1
  • Only 30% of boys with DMD have cardiac symptoms at diagnosis 1
  • Higher mortality rate compared to other forms of dilated cardiomyopathy 1

Becker Muscular Dystrophy (BMD)

• Similar to DMD but with milder course
• Dilated cardiomyopathy develops in up to 70% of patients by age 40 1
• Disease progression is less predictable than in DMD 1

Limb-Girdle Muscular Dystrophy (LGMD)

• Cardiac involvement varies by subtype:
  • LGMD2C, 2D, 2E, 2F (sarcoglycan-deficient): significant cardiac involvement 1
  • LGMD2I (FKRP mutations): cardiomyopathy can occur even without skeletal muscle involvement 1
  • LGMD1B: high risk of arrhythmias and sudden death 2
  • LGMD1D: minimal cardiac involvement 1

Other Forms

• Emery-Dreifuss muscular dystrophy: conduction defects and arrhythmias with variable cardiomyopathy 2
• Myotonic dystrophy: conduction abnormalities and arrhythmias 2
• Facioscapulohumeral muscular dystrophy: variable cardiac involvement 1
• Myofibrillar myopathy: both dilated and hypertrophic cardiomyopathies reported 1

Pathophysiology

The cardiac involvement in muscular dystrophies stems from:

1. Primary genetic defects: Mutations affecting structural proteins (e.g., dystrophin) that are expressed in both skeletal and cardiac muscle 3
2. Shared pathophysiologic mechanisms: Similar degenerative processes affecting both muscle types 4
3. Progressive nature: Fibrosis and fatty replacement of cardiac myocardium over time 2

Research has shown that dystrophin plays a critical mechanical role in cardiomyocytes similar to its role in skeletal muscle, and its absence directly contributes to cardiomyopathy 3.

Clinical Manifestations and Monitoring

• Early detection challenges: Cardiac symptoms may be masked by limited mobility due to skeletal muscle disease 1
• Imaging findings:
  • Echocardiography has limitations in DMD patients 1
  • Cardiac MRI with late gadolinium enhancement can detect early myocardial damage 1
• Arrhythmias: Risk increases with ventricular dysfunction but can occur with normal ejection fraction 1
• Conduction abnormalities: More common in myotonic dystrophy, Emery-Dreifuss, and LGMD1B 2

Management Considerations

• Early intervention: ACE inhibitors or ARBs recommended by age 10 in DMD (or earlier) 1
• Beta-blockers: Typically added after ACE inhibitors/ARBs, especially with ventricular dysfunction 1
• Mineralocorticoid receptor antagonists: Recent evidence supports their use to slow decline in left ventricular function 1
• Device therapy:
  • ICDs may be considered for patients with advanced cardiomyopathy (EF <35%) 1
  • Higher procedural risks due to skeletal deformities and respiratory muscle weakness 1
• Advanced therapies: Mechanical circulatory support and transplantation have been described in case reports 1

Important Clinical Pitfalls

1. Underdiagnosis and undertreatment: Despite increased awareness, cardiomyopathy in muscular dystrophy remains underdiagnosed and undertreated 1

2. Reliance on symptoms: Patients may not report cardiac symptoms due to limited physical activity; regular cardiac screening is essential regardless of symptoms 1

3. Echocardiography limitations: Standard echocardiography may miss early cardiac involvement; consider cardiac MRI for more sensitive detection 1

4. Variable presentation: The age of onset and severity of cardiac involvement vary significantly between different muscular dystrophies and even within the same type 1

5. Risk of sudden death: Particularly in forms with conduction abnormalities, prophylactic device therapy may be warranted before symptoms develop 2

The evidence clearly demonstrates that cardiac involvement is a common and serious complication across multiple forms of muscular dystrophy, requiring regular monitoring and proactive management to improve outcomes.