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Phrenic Nerve Stimulation for Central Sleep Apnea

Policy Number: MP-730

Latest Review Date: May 2022

Category: Surgical

POLICY:

The use of phrenic nerve stimulation for central sleep apnea is considered investigational in all situations.

DESCRIPTION OF PROCEDURE OR SERVICE:

Central sleep apnea (CSA) is characterized by sleep-disordered breathing due to diminished or absent respiratory effort. CSA may be idiopathic or secondary (associated with Cheyne-Stokes breathing, a medical condition, drugs, or high altitude breathing). The use of positive airway pressure devices is currently the most common form of therapy for CSA. An implantable device that stimulates the phrenic nerve in the chest is a potential alternative treatment. The battery-powered device sends signals to the diaphragm in order to stimulate breathing and normalize sleep-related breathing patterns.

Central Sleep Apnea

CSA is characterized by repetitive cessation or decrease in both airflow and ventilatory effort during sleep. CSA may be idiopathic or secondary (associated with Cheyne-Stokes breathing, a medical condition, drugs, or high altitude breathing. Apneas associated with Cheyne-Stokes respiration is common among patients with heart failure (HF) or who have had strokes, and accounts for about half of the population with CSA. CSA is less common than obstructive sleep apnea. Based on analyses of a large community-based cohort of participants 40 years of age and older in the Sleep Heart Health Study, the estimated prevalence of CSA and obstructive sleep apnea are 0.9% and 47.6%, respectively. Risk factors for CSA include age (>65 years), male gender, history of HF, history of stroke, other medical conditions (acromegaly, renal failure, atrial fibrillation, low cervical tetraplegia, and primary mitochondrial diseases), and opioid use. Individuals with CSA have difficulty maintaining sleep and therefore experience excessive daytime sleepiness, poor concentration, morning headaches, and are at higher risk for accidents and injuries.

Treatment

The goal of treatment is to normalize sleep-related breathing patterns. Because most cases of CSA are secondary to an underlying condition, central nervous system pathology, or medication side effects, treatment of the underlying condition or removal of the medication, may improve CSA.

Treatment recommendations differ depending on the classification of CSA as either hyperventilation-related (most common, including primary CSA and those relating to HF or high altitude breathing) or hypoventilation-related (less common, relating to central nervous system diseases or use of nervous system suppressing drugs such as opioids).

For patients with hyperventilation-related CSA, continuous positive airway pressure (CPAP) is considered first-line therapy. Due to CPAP discomfort, patient compliance may become an issue. Supplemental oxygen during sleep may be considered for patients experiencing hypoxia during sleep or who cannot tolerate CPAP. Patients with CSA due to HF and with an ejection fraction >45% and who are not responding with CPAP and oxygen therapy, may consider bilevel positive airway pressure or adaptive servo-ventilation (ASV) as second-line therapy. Bilevel positive airway pressure devices have two pressure settings, one for inhalation and one for exhalation. ASV uses both inspiratory and expiratory pressure, and titrates the pressure to maintain adequate air movement. However, a clinical trial reported increased cardiovascular mortality with ASV in patients with CSA due to HF and with an ejection fraction <45%, and therefore, ASV is not recommended for this group.

For patients with hypoventilation-related CSA, first-line therapy is bilevel positive airway pressure.

Pharmacologic therapy with a respiratory stimulant may be recommended to patients with hyper- or hypoventilation CSA who do not benefit from positive airway pressure devices, though close monitoring is necessary due to the potential for adverse effects such as rapid heart rate, high blood pressure, and panic attacks.

Phrenic Nerve Stimulation

Several phrenic nerve stimulation systems are available for patients who are ventilator dependent. They stimulate the phrenic nerve in the chest which sends signals to the diaphragm to restore a normal breathing pattern. Currently, there is one phrenic nerve stimulation device approved by the Food and Drug Administration, the remede System (Zoll Medical). The remede System is an implantable device that stimulates the phrenic nerve in the chest which sends signals to the diaphragm to restore a normal breathing pattern. A cardiologist implants the battery powered device under the skin in the right or left pectoral region. The procedure is conducted using local anesthesia. The device has 2 leads, 1 to stimulate a phrenic nerve (either the left pericardiophrenic or right brachiocephalic vein) and 1 to sense breathing. The device runs on an algorithm that activates automatically at night when the patient is in a sleeping position, and suspends therapy when the patient sits up. Patient-specific changes in programming can be conducted externally by a programmer.

KEY POINTS:

This evidence review was created in April 2019 with searches of the MEDLINE database. The most recent literature update was performed through March 21, 2022.

Summary of Evidence:

For individuals with CSA who receive phrenic nerve stimulation, the evidence includes 1 randomized controlled trial (RCT) and observational studies. Relevant outcomes are change in disease status, functional outcomes, and quality of life. The RCT compared the use of phrenic nerve stimulation to no treatment among patients with CSA of various etiologies. All patients received implantation of the phrenic nerve stimulation system, with activation of the system after 1 month in the intervention group and activation after 6 months in the control group. Activation is delayed 1 month after implantation to allow for lead healing. At 6 months follow-up, the patients with the activated device experienced significant improvements in several sleep metrics and quality of life measures. At 12 months follow-up, patients in the activated device arm showed sustained significant improvements from baseline in sleep metrics and quality of life. A subgroup analysis of patients with HF combined 6 and 12 month data from patients in the intervention group and 12 and 18 month data from the control group. Results from this subgroup analyses showed significant improvements in sleep metrics and quality of life at 12 months compared with baseline. Results from observational studies supported the results of the RCT. An invasive procedure would typically be considered only if non-surgical treatments had failed, but there is limited data in which phrenic nerve stimulation was evaluated in patients who had failed the current standard of care, positive airway pressure or respiratory stimulant medication. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

American Academy of Sleep Medicine

The American Academy of Sleep Medicine (2012) published a guideline on the treatment of central sleep apnea (CSA), based on results of a literature review and meta-analysis. Moderate evidence supported the use of continuous positive airway pressure or adaptive servo-ventilation to treat CSA related to congestive heart failure. Limited evidence was available for the use of positive airway pressure therapy (continuous positive airway pressure, bilevel positive airway pressure, adaptive servo-ventilation) to treat primary CSA; however, there is potential for ameliorating central respiratory events, risks are low, and the therapies are readily available. The use of phrenic nerve stimulation devices were not discussed in the guideline. An update to the guideline, published in 2016, adjusted the previous guideline, to warn that adaptive servo-ventilation is not recommended for individuals with CSA related to congestive heart failure with ejection fraction <45%. The use of phrenic nerve stimulation as a treatment option was not addressed in the guideline.

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Phrenic nerve stimulation, Remede (Respicardia), Central sleep apnea, CSA, neurostimulator for central sleep apnea

APPROVED BY GOVERNING BODIES:

In October 2017, the remedē System (Respicardia, Inc [now Zoll Medical]; Minnetonka, MN) was approved by the FDA through the premarket approval application process. The approved indication is for the treatment of moderate to severe CSA in adults. Follow-up will continue for 5 years in the post-approval study.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: FEP does not consider investigational if FDA approved and will be reviewed for medical necessity. Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING:

Code

Description

0424T

Insertion or replacement of neurostimulator system for treatment of central sleep apnea; complete system (transvenous placement of right or left stimulation lead, sensing lead, implantable pulse generator)

0425T

; sensing lead only

0426T

; stimulation lead only

0427T

; pulse generator only

0428T

Removal of neurostimulator system for treatment of central sleep apnea; pulse generator only

0429T

; sensing lead only

0430T

; stimulation lead only

0431T

Removal and replacement of neurostimulator system for treatment of central sleep apnea, pulse generator only

0432T

Repositioning of neurostimulator system for treatment of central sleep apnea; stimulation lead only

0433T

; sensing lead only

0434T

Interrogation device evaluation implanted neurostimulator pulse generator system for central sleep apnea

0435T

Programming device evaluation of implanted neurostimulator pulse generator system for central sleep apnea; single session

0436T

; during sleep study

REFERENCES:

  1. Abraham, WW, Jagielski, DD, Oldenburg, OO, Augostini, RR, Krueger, SS, Kolodziej, AA, Gutleben, KK, Khayat, RR, Merliss, AA, Harsch, MM, Holcomb, RR, Javaheri, SS, Ponikowski, PP. Phrenic nerve stimulation for the treatment of central sleep apnea. JACC Heart Fail, 2015 Mar 17;3(5).
  2. Aurora RN, Bista SR, Casey KR, et al. Updated Adaptive Servo-Ventilation Recommendations for the 2012 AASM Guideline: "The Treatment of Central Sleep Apnea Syndromes in Adults: Practice Parameters with an EvidenceBased Literature Review and Meta-Analyses". J Clin Sleep Med. May 15 2016; 12(5): 757-61.
  3. Aurora, RR, Bista, SS, Casey, KK, Chowdhuri, SS, Kristo, DD, Mallea, JJ, Ramar, KK, Rowley, JJ, Zak, RR, Heald, JJ. Updated Adaptive Servo-Ventilation Recommendations for the 2012 AASM Guideline
  4. Aurora, RR, Chowdhuri, SS, Ramar, KK, Bista, SS, Casey, KK, Lamm, CC, Kristo, DD, Mallea, JJ, Rowley, JJ, Zak, RR, Tracy, SS. The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analyses. Sleep, 2012 Jan 5;35(1).
  5. Costanzo, MM, Augostini, RR, Goldberg, LL, Ponikowski, PP, Stellbrink, CC, Javaheri, SS. Design of the remedē System Pivotal Trial: A Prospective, Randomized Study in the Use of Respiratory Rhythm Management to Treat Central Sleep Apnea. J. Card. Fail., 2015 Oct 4;21(11).
  6. Costanzo, MM, Ponikowski, PP, Javaheri, SS, Augostini, RR, Goldberg, LL, Holcomb, RR, Kao, AA, Khayat, RR, Oldenburg, OO, Stellbrink, CC, Abraham, WW. Transvenous neurostimulation for central sleep apnoea: a randomised controlled trial. Lancet, 2016 Sep 7;388(10048).
  7.  Costanzo, MM, Ponikowski, PP, Javaheri, SS, Augostini, RR, Goldberg, LL, Holcomb, RR, Kao, AA, Khayat, RR, Oldenburg, OO, Stellbrink, CC, Abraham, WW. Sustained 12 Month Benefit of Phrenic Nerve Stimulation for Central Sleep Apnea. Am. J. Cardiol., 2018 May 8;121(11).
  8. Costanzo, MM, Ponikowski, PP, Coats, AA, Javaheri, SS, Augostini, RR, Goldberg, LL, Holcomb, RR, Kao, AA, Khayat, RR, Oldenburg, OO, Stellbrink, CC, McKane, SS, Abraham, WW. Phrenic nerve stimulation to treat patients with central sleep apnoea and heart failure. Eur. J. Heart Fail., 2018 Oct 12;20(12).
  9. Cowie, MM, Woehrle, HH, Wegscheider, KK, Angermann, CC, d'Ortho, MM, Erdmann, EE, Levy, PP, Simonds, AA, Somers, VV, Zannad, FF, Teschler, HH. Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure. N. Engl. J. Med., 2015 Sep 2;373(12).
  10. Ding, N, Zhang, Xilong. Transvenous phrenic nerve stimulation, a novel therapeutic approach for central sleep apnea. J Thorac Dis. 2018 Mar; 10(3): 2005–2010.doi:  [10.21037/jtd.2018.03.59]
  11. Donovan LM, Kapur VK. Prevalence and characteristics of central compared to obstructive sleep apnea: analyses from the Sleep Heart Health Study cohort. Sleep 2016;39(7):1353-9.
  12. Fox, HH, Bitter, TT, Horstkotte, DD, Oldenburg, OO, Gutleben, KK. Long-Term Experience with First-Generation Implantable Neurostimulation Device in Central Sleep Apnea Treatment. Pacing Clin Electrophysiol, 2017 Feb 18;40(5).
  13. Hastings PC, Vazir A, Meadows GE, et al. Adaptive servo-ventilation in heart failure patients with sleep apnea: A real world study. Int J Cardiol. 2010 Feb 18;139(1):17-24. doi: 10.1016/j.ijcard.2008.08.022.
  14. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
  15. Jagielski, DD, Ponikowski, PP, Augostini, RR, Kolodziej, AA, Khayat, RR, Abraham, WW. Transvenous stimulation of the phrenic nerve for the treatment of central sleep apnoea: 12 months' experience with the remedÄ“® System. Eur. J. Heart Fail., 2016 Nov 5;18(11).

POLICY HISTORY:

Medical Policy Panel, June 2019

Medical Policy Group, June 2019 (6) New Medical Policy, Phrenic nerve stimulation transferred from MP #203 Non-invasive Positive Pressure Ventilation for Conditions Other than Obstructive Sleep Apnea.

DRAFT comment period through July 22, 2019.

Medical Policy Panel, May 2020

Medical Policy Group, May 2020 (6): Updates to Description, Key Points and Governing Bodies.

Medical Policy Panel, May 2021

Medical Policy Group, May 2021 (6): Updates to Key Points and References. Policy statement updated to remove “not medically necessary,” no change to policy intent.

Medical Policy Panel, May 2022

Medical Policy Group, May 2022 (6): Updates to Description, Key Points, Governing Bodies and References.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.