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Publications

Journal Article Ahead of print

PubMed: 42490406 DOI: 10.1093/sleep/zsag202

Physiological Characteristics of Central versus Obstructive Sleep Apnea in Patients with Heart Failure.

Sleep

Authors: Raichel M Alex, Shahrokh Javaheri, Rami Khayat, James C Fang, Ruckshanda Majid, Sanjay R Patel, Sairam Parthasarathy, Bradley A Edwards, Shane Landry, Luke Thomson, Laura K Gell, Dwayne Mann, Sara Op de Beeck, Andrew Wellman, Justin Vader, Luqi Chi, Mihaela Teodorescu, Maryl Johnson, Phyllis C Zee, M Safwan Badr, Reena Mehra, Neomi Shah, Babak Mokhlesi, Eldrin F Lewis, William T Abraham, Susan Redline, Scott A Sands

Affiliations

  • Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Division of Pulmonary and Sleep Medicine, Bethesda North Hospital, Cincinnati, Ohio; Division of Medicine, The Ohio State University, Columbus, Ohio, USA.
  • Division of Pulmonary and Critical Care Medicine, Sleep Research and Treatment Center, Sleep Disorders Center, Pennsylvania State University College of Medicine, Hershey PA, USA.
  • Division of Cardiology, Department of Medicine, University of Utah, Salt Lake City, Utah, USA.
  • Divisions of Pulmonary, Critical Care and Sleep Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA.
  • Center for Sleep and Cardiovascular Outcomes Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • The University of Arizona Center for Sleep, Circadian, and Neurosciences, University of Arizona, Tucson, Arizona, USA.
  • Department of Physiology, Biomedicine Discovery Institute, Monash University, Victoria, Australia; School of Psychological Sciences, Monash University, Victoria, Australia.
  • School of Electrical Engineering and Computer Science, The University of Queensland, Brisbane, Australia.
  • Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium.
  • Department of Cardiology, Washington University School of Medicine, St Louis, Missouri, USA.
  • Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Department of Medicine and Wisconsin Institute for Sleep and Consciousness, School of Medicine and Public Health, University of Wisconsin - Madison, Wisconsin, USA.
  • Department of Medicine, Heart Failure and Transplant Cardiology, School of Medicine and Public Health, University of Wisconsin - Madison, Wisconsin, USA.
  • Center for Circadian and Sleep Medicine, Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
  • John D. Dingell VA Medical Center, Detroit, Michigan; Department of Medicine, Wayne State University, Detroit, Michigan, USA.
  • Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA.
  • Department of Medicine, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
  • Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Rush University Medical Center, Chicago, Illinois, USA.
  • Division of Cardiovascular Medicine and Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, California, USA.
  • Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA.

Abstract

STUDY OBJECTIVES

Central (CSA) and obstructive (OSA) sleep apnea are common in heart failure (HF) patients, and treatment options depend on differential classification. To better characterize CSA vs OSA, we evaluated the discriminative value of established and novel polysomnographic traits in patients with HF.

METHODS

We analyzed LOFT-HF trial participants with reduced left ventricular ejection fraction (LVEF) and apnea-hypopnea index (AHI) >15 events/hr. Central versus obstructive events were classified with expert investigator input. Multivariable logistic regression tested whether CSA (>50% of central/mixed events; otherwise OSA) was associated with increased loop gain, and other mechanistic traits (arousal threshold, collapsibility, muscle compensation). Mechanistic traits together with novel clinically-informed traits (e.g. event periodicity, flow limitation) were modeled to provide a probability score "Pr(CSA)" for objective CSA-versus-OSA discrimination.

RESULTS

Among 122 HF patients (CSA:OSA=84:38), CSA was associated with higher loop gain (OR=4.4[2.2-9.1]), lower arousal threshold (6.4[2.4-16.9]), and greater muscle compensation (2.5[1.0-6.2]). Novel traits-greater event periodicity, larger event-related drive reduction, and reduced flow limitation-further improved discrimination (likelihood ratio test P=0.013 vs. mechanistic model). The final model (AUC=0.88) identified a subgroup enriched for true CSA (OR=8.4[3.5-20.1]). Sensitivity analyses using stricter central apnea-based definitions yielded similar or stronger associations with loop gain and modestly improved discrimination, although fewer individuals met CSA criteria.

CONCLUSIONS

Patients with HF and CSA exhibit a distinct set of polysomnographic characteristics compared to OSA, which may facilitate their objective physiology-based characterization along the CSA-OSA continuum.

MeSH

Muscles, Sleep Apnea, Obstructive, Heart Failure, Heart, Sleep, Apnea, Arousal, Sleep Apnea Syndromes, Periodicity