title: Phrenic nerve stimulation for the treatment of central sleep apnea.
abstract: OBJECTIVE
  The aim of this study was to evaluate chronic, transvenous, unilateral phrenic nerve stimulation to treat central sleep apnea (CSA) in a prospective, multicenter, nonrandomized study.
  
  
  BACKGROUND
  CSA occurs predominantly in patients with heart failure and increases the risk for morbidity and mortality. Established therapies for CSA are lacking, and those available are limited by poor patient adherence.
  
  
  METHODS
  Fifty-seven patients with CSA underwent baseline polysomnography followed by transvenous phrenic nerve stimulation system implantation and follow-up. Feasibility was assessed by implantation success rate and therapy delivery. Safety was evaluated by monitoring of device- and procedure-related adverse events. Efficacy was evaluated by changes in the apnea-hypopnea index at 3 months. Quality of life at 6 months was evaluated using a sleepiness questionnaire, patient global assessment, and, in patients with heart failure at baseline, the Minnesota Living With Heart Failure Questionnaire.
  
  
  RESULTS
  The study met its primary end point, demonstrating a 55% reduction in apnea-hypopnea index from baseline to 3 months (49.5 ± 14.6 episodes/h vs. 22.4 ± 13.6 episodes/h of sleep; p < 0.0001; 95% confidence interval for change: -32.3 to -21.9). Central apnea index, oxygenation, and arousals significantly improved. Favorable effects on quality of life and sleepiness were noted. In patients with heart failure, the Minnesota Living With Heart Failure Questionnaire score significantly improved. Device- or procedure-related serious adverse events occurred in 26% of patients through 6 months post therapy initiation, predominantly due to lead repositioning early in the study. Therapy was well tolerated. Efficacy was maintained at 6 months.
  
  
  CONCLUSIONS
  Transvenous, unilateral phrenic nerve stimulation appears safe and effective for treating CSA. These findings should be confirmed in a prospective, randomized, controlled trial. (Chronic Evaluation of Respicardia Therapy; NCT01124370).
authors.affiliation: Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio. Electronic address: william.abraham@osumc.edu.
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.affiliation: 4th Military Hospital, Wroclaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Jagielski
authors.affiliation: Heart and Diabetes Centre NRW, Ruhr University Bochum, Bad Oeynhausen, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Oldenburg
authors.affiliation: Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Ralph
authors.initials: R
authors.lastname: Augostini
authors.affiliation: Bryan Heart, Lincoln, Nebraska.
authors.forename: Steven
authors.initials: S
authors.lastname: Krueger
authors.affiliation: 4th Military Hospital, Wroclaw, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Kolodziej
authors.affiliation: Heart and Diabetes Centre NRW, Ruhr University Bochum, Bad Oeynhausen, Germany.
authors.forename: Klaus-Jürgen
authors.initials: KJ
authors.lastname: Gutleben
authors.affiliation: Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, Ohio State University, Columbus, Ohio.
authors.forename: Rami
authors.initials: R
authors.lastname: Khayat
authors.affiliation: Bryan Heart, Lincoln, Nebraska.
authors.forename: Andrew
authors.initials: A
authors.lastname: Merliss
authors.affiliation: Technomics Research, LLC, Minneapolis, Minnesota.
authors.forename: Manya R
authors.initials: MR
authors.lastname: Harsch
authors.affiliation: Independent Biostatistician, Minneapolis, Minnesota.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Holcomb
authors.affiliation: University of Cincinnati, Cincinnati, Ohio.
authors.forename: Shahrokh
authors.initials: S
authors.lastname: Javaheri
authors.affiliation: 4th Military Hospital, Wroclaw, Poland; Medical University, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
mesh_terms: D000368:Aged; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010791:Phrenic Nerve; D017286:Polysomnography; D011446:Prospective Studies; D011788:Quality of Life; D012890:Sleep / Q000502:physiology*; D020182:Sleep Apnea, Central / Q000503:physiopathology / Q000628:therapy*; D004561:Transcutaneous Electric Nerve Stimulation / Q000379:methods*; D016896:Treatment Outcome
keywords: apnea-hypopnea index; central sleep apnea; heart failure; phrenic nerve; sleep