Transvenous phrenic nerve stimulation for central sleep apnea is safe and effective in patients with concomitant cardiac devices

doi:10.1016/j.hrthm.2020.06.023

Heart Rhythm

Volume 17, Issue 12, December 2020, Pages 2029-2036

https://doi.org/10.1016/j.hrthm.2020.06.023 Get rights and content

Background

Central sleep apnea is common in heart failure patients. Transvenous phrenic nerve stimulation (TPNS) requires placing a lead to stimulate the phrenic nerve and activate the diaphragm. Data are lacking concerning the safety and efficacy of TPNS in patients with concomitant cardiovascular implantable electronic devices (CIEDs).

Objective

To report the safety and efficacy of TPNS in patients with concomitant CIEDs.

Methods

In the remedē System Pivotal Trial, 151 patients underwent TPNS device implant. This analysis compared patients with concomitant CIEDs to those without with respect to safety, implant metrics, and efficacy of TPNS. Safety was assessed using incidence of adverse events and device–device interactions. A detailed interaction protocol was followed. Implant metrics included overall TPNS implantation success. Efficacy endpoints included changes in the apnea-hypopnea index (AHI) and quality of life.

Results

Of 151 patients, 64 (42%) had a concomitant CIED. There were no significant differences between the groups with respect to safety. There were 4 CIED oversensing events in 3 patients leading to 1 inappropriate defibrillator shock and delivery of antitachycardia pacing. There was no difference in efficacy between the CIED and non-CIED subgroups receiving TPNS, with both having similar percentages of patients who achieved ≥50% reduction in AHI and quality-of-life improvement.

Conclusion

Concomitant CIED and TPNS therapy is safe. The presence of a concomitant CIED did not seem to impact implant metrics, implantation success, and TPNS efficacy. A detailed interaction protocol should be followed to minimize the incidence of device–device interaction.

Graphical abstract

Introduction

The prevalence of sleep apnea, both obstructive and central, among patients with heart failure, especially those with heart failure with reduced ejection fraction (EF), is high and approaches 50%–75% in some studies¹^,² Untreated central sleep apnea (CSA) is associated with high morbidity and mortality.³^,⁴ Transvenous phrenic nerve stimulation (TPNS) using the remedē System (Respicardia, Minnetonka, MN) is an FDA-approved therapy to treat moderate-to-severe CSA in adult patients, which requires placing a transvenous lead to stimulate the phrenic nerve and produce contraction of the diaphragm similar to normal breathing.⁵ Since many patients with advanced heart failure with reduced EF have cardiovascular implantable electronic devices (CIEDs), a clinical scenario where concomitant TPNS and CIED therapy are necessary is likely to occur. However, data are lacking concerning the safety and efficacy of TPNS in patients with CIEDs.

The remedē System Pivotal Trial was a prospective, international, multicenter, intention-to-treat, randomized controlled trial designed to evaluate the safety and effectiveness of unilateral TPNS in patients with moderate-to-severe CSA.⁶ In this trial, a total of 151 patients were enrolled, of which 42% had pre-existing CIEDs. Patients gave informed consent to participate in this trial, including consent for data collection, through each institution’s institutional review board. The objective of this paper is to report on the safety and efficacy of TPNS in patients with concomitant CIEDs.

Section snippets

Patient selection

The inclusion and exclusion criteria and trial design of the remedē System Pivotal Trial have been previously reported.⁷ Participation in and collection of data for this study was approved by the Institutional Committee on Human Research at each of the participating sites and informed consent was obtained. Briefly, 151 CSA patients underwent TPNS implantation and were randomly assigned to TPNS (treatment) or no stimulation (control) for 6 months. A history of heart failure or cardiovascular

Patient characteristics

Of the 151 patients, 64 (42%) had a pre-existing CIED. Patient characteristics are provided in Table 1. The vast majority of the population were men (89%) and there were statistically significant differences between the patients with a concomitant CIED and patients without a concomitant CIED for other baseline characteristics, as may be expected. The mean age of the patients with a concomitant CIED was 67 ± 10 years compared to 63 ± 14 years (P = .035) in patients without a concomitant CIED.

Discussion

The main findings in the present study are as follows: (1) concomitant CIED and TPNS therapy is safe; (2) the presence of a pre-existing CIED does not adversely affect the success or procedural metrics of TPNS implantation; and (3) the efficacy of TPNS therapy is not impacted by the presence of a concomitant CIED.

Historically, device–device interactions primarily included concomitant pacemaker and defibrillator therapy and concerned 3 important potential interactions: (1) oversensing of the

Conclusion

Concomitant CIED and TPNS therapy is safe. The presence of a concomitant CIED did not seem to impact implant metrics, success of implantation, and overall efficacy of TPNS. A step-by-step detailed interaction protocol should be followed to minimize the incidence of device–device interaction. More data are needed, particularly in patients with CIEDs from various manufacturers and those who are pacemaker dependent.

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Cited by (2)

Transvenous Phrenic Nerve Stimulation for Central Sleep Apnea
2022, American Journal of Cardiology
Citation Excerpt :
The effectiveness was further supported with QOL evaluations, either the Epstein Sleepiness scale, Minnesota Living with HF questionnaire, or patient global assessments. Many patients reported statistically significant mild to marked improvement in their QOL postoperatively.7,8,14,16,18 AHI is an unbiased end point, and reduction in AHI has been shown to improve outcomes for patients with obstructive sleep apnea.
RespiCardia remedē System (Minnetonka, MN 2017), a transvenous phrenic nerve stimulator, is indicated to treat central sleep apnea (CSA) by stimulating the phrenic nerve to cause diaphragmatic contraction to restore normal breathing during sleep. CSA is associated with decreased patient quality of life and worsens cardiovascular outcomes. Systematic review was conducted according to the Preferred Reporting of Systematic Reviews and Meta-Analysis guidelines. PubMed/MEDLINE, Cochrane, EBSCO CINAHL, and Ovid databases were queried by 2 independent reviewers for English-language studies published between 2000 and 2021. The initial search screened for all occurrences of “remedē” then was further refined to include studies evaluating use of the RespiCardia remedē System as a treatment for CSA in multiple patients. A total of 124 articles were identified from the initial search results. A total of 37 articles were identified through screening of title and abstracts from initial results. Full-text review of all the articles was then completed. Of the 13 articles included, a total of 232 patients underwent device implantation. We sought to summarize the available evidence regarding patient selection for implantation, immediate and delayed complications, adherence to therapy, and polysomnographic evidence of efficacy. All 13 articles detailed significant decreases in central apnea index and many patients reported significant mild to marked improvement in quality of life. In conclusion, the remedē System has been demonstrated to improve sleep and respiratory parameters, with few complications. This device demonstrates safe and effective treatment of moderate to severe CSA in adult patients, including those with heart failure.
Research progress of children's diaphragm rehabilitation
2022, Chinese Journal of Rehabilitation Medicine

: Funding sources: Respicardia funded the pivotal study from which these data were generated and subsequently analyzed for this paper.

: Disclosures: Scott McKane, Kristofer J. James, Timothy E. Meyer, and Robin E. Germany are employees of Respicardia. The other authors do not have any relevant conflicts of interest.

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ClinicalTransvenous phrenic nerve stimulation for central sleep apnea is safe and effective in patients with concomitant cardiac devices

Background

Objective

Methods

Results

Conclusion

Graphical abstract

Introduction

Section snippets

Patient selection

Patient characteristics

Discussion

Conclusion

Sleep Med Clin

Lancet

J Card Fail

Am J Cardiol

HeartRhythm Case Rep

Clinical
Transvenous phrenic nerve stimulation for central sleep apnea is safe and effective in patients with concomitant cardiac devices