How can cardiac contractility modulation be achieved in patients with heart failure?

Cardiac Contractility Modulation in Heart Failure

Cardiac contractility modulation (CCM) is a device-based therapy that delivers non-excitatory electrical signals to the heart during the absolute refractory period to improve cardiac function in patients with heart failure who have limited options with conventional therapies. This approach is particularly valuable for patients with symptomatic heart failure who are not candidates for cardiac resynchronization therapy.

Mechanism of Action

CCM works through several key mechanisms:

• Delivers biphasic high-voltage bipolar signals to the right ventricular septum during the absolute refractory period 1
• Improves calcium handling at the cellular level 1
• Reverses the fetal myocyte gene program associated with heart failure 1
• Facilitates reverse remodeling of the myocardium 2
• Does not trigger a new contraction (non-excitatory) but enhances the strength of existing contractions

Patient Selection and Indications

CCM is primarily indicated for:

• Patients with symptomatic heart failure with reduced ejection fraction (HFrEF) 1
• LVEF between 25% and 45% 3
• Normal or slightly prolonged QRS duration (<130 ms) 3
• Patients who are not candidates for cardiac resynchronization therapy (CRT) 3
• NYHA functional class II-IV symptoms despite optimal medical therapy 2

Clinical Benefits

Studies have demonstrated that CCM provides several important benefits:

• Improved quality of life and NYHA functional class 2
• Enhanced exercise tolerance and peak oxygen uptake 2
• Increased left ventricular ejection fraction 4
• Reduced rate of heart failure hospitalizations 1
• Comparable improvements in functional status and ventricular reverse remodeling to CRT-D at 12 months 4

Implementation Process

The CCM system consists of:

1. A pulse generator (implanted similar to a pacemaker)
2. Leads placed in the right ventricle (typically on the septum)
3. Programming to deliver signals during the absolute refractory period

Emerging Applications

Recent research suggests potential expanded applications:

• Beneficial effects in patients with heart failure with mildly reduced ejection fraction (HFmrEF) 5
• Potential application in heart failure with preserved ejection fraction (HFpEF) based on experimental studies 5
• May fill an important unmet need across the spectrum of heart failure with different ejection fractions 1

Comparison with Other Device Therapies

When comparing CCM to other device therapies:

• CCM is complementary to CRT, not a replacement 4
• CRT requires QRS ≥130 ms (preferably with LBBB pattern) 6
• CCM is particularly valuable for patients with narrow QRS complexes who don't qualify for CRT 3
• In a comparative study, CCM and CRT-D showed similar improvements in NYHA class and LVEF at 12 months, though CCM patients had more heart failure hospitalizations (likely due to more advanced disease at baseline) 4

Limitations and Considerations

Important considerations when implementing CCM include:

• Currently approved in Europe, China, India, Australia, and Brazil for HFrEF patients with normal or slightly prolonged QRS 1
• Limited long-term data compared to established therapies like CRT
• Higher hospitalization rates observed in some comparative studies 4
• Should be considered after optimization of guideline-directed medical therapy

Future Directions

The European Society of Cardiology and American College of Cardiology/American Heart Association guidelines identify CCM as an area for further research:

• Safety and efficacy in broader heart failure populations 6
• Potential applications in HFpEF 5
• Comparative effectiveness with other device therapies 6
• Long-term outcomes and mortality benefits

CCM represents an important therapeutic option for heart failure patients who fall into treatment gaps with conventional approaches, particularly those with symptomatic heart failure, reduced ejection fraction, and narrow QRS complexes.