What neuromuscular diseases can cause heart failure in young patients?

Neuromuscular Diseases Causing Heart Failure in Young Patients

Duchenne muscular dystrophy (DMD) is the most important neuromuscular disease causing heart failure in young patients, with cardiomyopathy and heart failure now representing the leading cause of death in this population. 1

Primary Neuromuscular Diseases with Cardiac Involvement

Dystrophinopathies (Most Common)

Duchenne Muscular Dystrophy (DMD)

• DMD is an X-linked genetic disorder affecting approximately 1 in 5,000 live male births, making it the most prevalent neuromuscular disease with cardiac involvement in young patients. 1
• Cardiomyopathy has become the most common cause of death, surpassing respiratory failure due to improved respiratory therapies. 1
• Risk of left ventricular dysfunction increases dramatically with age: 5% in boys <10 years to >75% in men >20 years, with average age for abnormal ejection fraction being 14.3 years. 1
• The cardiomyopathy is characterized by progressive myocyte loss leading to regional then global dysfunction, with chamber dilation occurring only in late stages. 1
• Some patients develop reduced ejection fraction as early as 8 years of age, though myocardial damage on cellular level starts much earlier. 1

Becker Muscular Dystrophy (BMD)

• BMD is a milder dystrophinopathy with more variable phenotype and cardiac involvement. 1
• Only a small proportion of subjects <16 years have symptomatic cardiac involvement, but up to 70% develop symptomatic heart failure by age 40. 1
• Disease progression is much less predictable than DMD. 1

X-linked Dilated Cardiomyopathy

• Part of the dystrophinopathy spectrum, can present with predominantly cardiac manifestations. 1

Limb-Girdle Muscular Dystrophies (LGMD)

LGMD2 Subtypes with Cardiac Phenotype

• LGMD2 presents during childhood or adolescence as progressive skeletal myopathy with phenotypic overlap with DMD/BMD. 1
• Specific subtypes with cardiac involvement include LGMD2C, 2D, 2E, 2F (sarcoglycan-deficient muscular dystrophies) and LGMD2I (FKRP mutations). 1
• Age of onset ranges from 2 to 15 years, with variable progression and loss of ambulation from 10 years to young adulthood. 1
• Prevalence is estimated at 1 in 14,500 to 1 in 123,000. 1

Other Neuromuscular Disorders

Emery-Dreifuss Muscular Dystrophy

• Has important cardiac involvement with conduction defects and cardiomyopathy. 2

Friedreich Ataxia

• Associated with significant cardiac involvement, typically hypertrophic cardiomyopathy. 2

Myotonic Dystrophy

• Has important cardiac manifestations including conduction abnormalities and cardiomyopathy. 2

Key Clinical Considerations

Diagnostic Challenges

• Early signs of cardiac failure may not appear clinically in DMD patients due to limitations of movement from skeletal muscle disease. 1
• Decreased cardiac function or LV dilation might only be detected by echocardiogram or cardiac imaging, not by symptoms. 1
• Functional measurements and quality-of-life assessment are confounded by already impaired skeletal muscle function, with typical heart failure symptoms like exercise limitation or dyspnea often absent. 1

Cardiac Phenotype Specificity

• DMD/BMD cardiomyopathy has less ventricular dilation early in disease course compared to other causes of dilated cardiomyopathy, simply beginning with dysfunction without dilation. 1
• Conduction system involvement is NOT a feature of DMD/BMD (unlike many other neuromuscular diseases), though tachyarrhythmias can occur. 1

Female Carriers

• Female carriers of DMD typically do not manifest disease but when symptomatic, present with mild to moderate dilated cardiomyopathy in the fifth decade of life with slowly progressive disease. 3
• Female carriers require cardiac surveillance given their risk of late-onset cardiomyopathy. 3

Surveillance Recommendations

• Cardiac care should begin shortly after initial diagnosis of DMD/BMD, with yearly echocardiograms recommended until the child is old enough to undergo CMR without sedation. 1
• CMR is preferred over echocardiography for assessing cardiac status due to superior information on tissue characteristics, chamber dimensions, and function. 1