Is there evidence for the use of phrenic nerve stimulators in patients with Cheyne-Stokes breathing?

Evidence for Phrenic Nerve Stimulation in Cheyne-Stokes Breathing

Transvenous phrenic nerve stimulation shows promise for treating Cheyne-Stokes breathing in heart failure patients but is not yet recommended as standard therapy due to limited evidence and potential adverse effects.

Background on Cheyne-Stokes Breathing

Cheyne-Stokes respiration (CSR) is a form of central sleep apnea characterized by a crescendo-decrescendo pattern of breathing alternating with central apneas. It affects approximately 40% of patients with congestive heart failure (CHF) with left ventricular ejection fraction <40% 1. CSR is associated with:

• Increased morbidity and mortality in heart failure patients
• Poor sleep quality with frequent awakenings
• Excessive daytime sleepiness
• Paroxysmal nocturnal dyspnea
• Frequent nighttime urination 2

Current Treatment Recommendations

According to the American College of Cardiology Foundation/American Heart Association guidelines, the following treatments for sleep-disordered breathing in heart failure are under active investigation:

• Nocturnal oxygen therapy
• Continuous positive airway pressure (CPAP)
• Various respiratory support techniques 3

The American Academy of Sleep Medicine currently recommends:

• CPAP and home oxygen therapy as standard treatments
• Adaptive servo-ventilation only in patients with EF >45%
• Bilevel positive airway pressure (BiPAP) only when there's inadequate response to previous treatments
• Medications like acetazolamide and theophylline only after failing other modalities 2

Evidence for Phrenic Nerve Stimulation

Transvenous phrenic nerve stimulation (PNS) is an emerging therapy for CSR in heart failure patients. The most recent evidence comes from a safety and proof-of-concept study:

• A small study (n=19) showed that unilateral transvenous PNS improved indices of CSR
• Significant decrease in apnea-hypopnea index (33.8 ± 9.3 vs 8.1 ± 2.3, p=.00)
• Increase in mean oxygen saturation (89.7% ± 1.6% vs 94.3% ± 0.9%, p=.00)
• Increase in minimal oxygen saturation (80.3% ± 3.7% vs 88.5% ± 3.3%, p=.00)
• Increase in end-tidal CO2 (38.0 ± 4.3 mm Hg vs 40.3 ± 3.1 mm Hg, p=.02)
• No significant difference in sleep efficiency (74.6% ± 4.1% vs 73.7% ± 5.4%, p=.36)
• No adverse events were reported during the overnight study 4

However, there are important limitations:

• Small sample size (19 patients)
• Short duration (overnight study)
• Failure to capture in 3 patients due to lead dislocation
• Limited long-term safety and efficacy data

Physiological Considerations

The American Thoracic Society/European Respiratory Society statement on respiratory muscle testing provides insights into phrenic nerve stimulation techniques:

• Phrenic nerve stimulation can be achieved through electrical or magnetic stimulators
• Electrical stimulation is less expensive, more precise, but more painful
• Magnetic stimulation is easier to apply and less painful but more expensive and less selective 3

Clinical Implications for Different Patient Groups

Recent research indicates that CSR severity varies by position and time of day:

• 14% of heart failure patients exhibit both supine and upright CSR
• Patients with upright CSR have worse hemodynamic profiles, exercise performance, and increased mortality risk (HR: 2.39; 95% CI: 1.08 to 5.29; p=0.032) 5

This suggests that treatment approaches may need to consider the persistence of CSR across different positions and times of day.

Potential Pitfalls and Considerations

When considering phrenic nerve stimulation for CSR:

1. Patient selection: Not all patients with CSR may benefit equally from PNS
2. Technical challenges: Lead placement and maintenance of proper stimulation
3. Long-term effects: Unknown durability of treatment effect
4. Interaction with cardiac devices: Potential interference with pacemakers or defibrillators
5. Cost-effectiveness: High cost compared to other therapies like CPAP or oxygen

Conclusion

While preliminary results for transvenous phrenic nerve stimulation in CSR are promising, current guidelines do not yet include it as a recommended therapy. The ACC/AHA guidelines classify it as an intervention "under active investigation" 3. Clinicians should prioritize optimizing heart failure management and established therapies like CPAP and oxygen while monitoring developments in this emerging treatment approach.