What is the role of cardiac contractility modulation (CCM) in treating heart failure in patients with Duchenne muscular dystrophy (DMD)?

Cardiac Contractility Modulation in Duchenne Muscular Dystrophy

There is currently no established role for cardiac contractility modulation (CCM) in treating heart failure in patients with Duchenne muscular dystrophy (DMD), as it is not mentioned in current guidelines for DMD cardiac care. Instead, standard heart failure therapies including ACE inhibitors/ARBs, beta-blockers, and mineralocorticoid receptor antagonists remain the mainstay of treatment 1, 2.

Current Guideline-Based Approach to DMD Cardiomyopathy

First-Line Therapies

• ACE inhibitors/ARBs: Should be initiated by 10 years of age in DMD patients, even before ventricular dysfunction is detected 1, 2

  • Earlier therapy may be considered given the relatively low risk profile of these medications
  • These medications have been shown to delay the onset of LV dysfunction and improve mortality when started early 1

• Beta-blockers: Typically added after ACE inhibitor/ARB initiation 2

  • Usually initiated based on ventricular dysfunction or elevated heart rate
  • Studies have shown improvement in LV ejection fraction in <12 months of treatment 1

• Mineralocorticoid receptor antagonists (e.g., eplerenone):

  • Recent randomized studies have demonstrated attenuation in the decline of LV function, measured by circumferential strain 1
  • Timing of initiation varies widely in clinical practice 1

Monitoring and Diagnostic Approaches

• Cardiac MRI (CMR) is preferred over echocardiography when possible 1, 2

  • Provides superior information on tissue characteristics, chamber dimensions, and function
  • Can detect late gadolinium enhancement (indicator of myocardial fibrosis)
  • Limitations: May require sedation in younger children

• Regular cardiac assessment should include:

  • ECG monitoring
  • Imaging (preferably CMR)
  • Consideration of Holter monitoring in patients with decreased LVEF or symptoms 2

Advanced Therapies in DMD Cardiomyopathy

Arrhythmia Management

• ICDs: May be considered for patients with LV ejection fraction <35%, following adult heart failure guidelines 1
  • Caution: Higher risk of complications in DMD patients due to kyphoscoliosis and respiratory muscle weakness
  • Practice varies widely among centers - some providers would not place ICDs for primary prevention in DMD patients 3

Mechanical Support

• Ventricular assist devices (VADs):
  • Described in case reports and small series for DMD patients 1
  • 74% of providers in a multi-center survey would consider VAD as destination therapy 3
  • Higher risk of complications due to kyphoscoliosis and respiratory muscle weakness 1

Emerging Research and Gaps in Evidence

• Phosphodiesterase inhibition: Research in animal models suggests that cGMP-protein kinase G modulation may normalize abnormal mechanosensing in dystrophic hearts 4

  • This pathway may be a potential therapeutic target, but clinical evidence in humans is lacking

• Cardiac contractility modulation (CCM):

  • Not specifically mentioned in any of the DMD cardiac care guidelines 1, 2
  • No evidence supporting its use in DMD cardiomyopathy in the provided literature

Clinical Pitfalls and Considerations

• Symptom assessment challenges: Traditional heart failure symptoms like exercise limitation or dyspnea are often absent or difficult to assess in DMD due to skeletal muscle impairment 1

• Blood pressure considerations: DMD patients typically have lower systolic blood pressure, especially in advanced disease, complicating the use and titration of heart failure medications 1

• Cardiac monitoring in clinical trials: Even trials focused on skeletal muscle should include cardiac monitoring to detect benefits or toxicity 1

• Long-term planning: Early discussions about advanced cardiac therapies are important before urgent need arises 1

In conclusion, while research continues to evolve in DMD cardiomyopathy management, cardiac contractility modulation is not currently part of the established treatment algorithm for these patients. Standard heart failure therapies remain the foundation of care, with careful consideration of advanced therapies like ICDs and VADs in appropriate patients.