{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T21:32:24Z","timestamp":1772659944333,"version":"3.50.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":2163,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,1,17]],"date-time":"2020-01-17T00:00:00Z","timestamp":1579219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"French National Research Agency (ANR) as part of the second \u2018Investissements d'Avenir' programme","award":["ANR-15-RHU-0004"],"award-info":[{"award-number":["ANR-15-RHU-0004"]}]},{"name":"French National Research Agency (ANR) as part of the second \u2018Investissements d\u2019Avenir\u2019 programme","award":["ANR-15-RHU-0004"],"award-info":[{"award-number":["ANR-15-RHU-0004"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients with Heart Failure trial investigated the effects of adaptive servo-ventilation (ASV) (vs. control) on outcomes of 1325 patients with heart failure and reduced ejection fraction (HFrEF) and central sleep apnoea (CSA). The primary outcome (a composite of all-cause death or unplanned HF hospitalization) did not differ between the two groups. However, all-cause and cardiovascular (CV) mortality were higher in the ASV group. Circulating biomarkers may help in better ascertain patients' risk, and this is the first study applying a large set of circulating biomarkers in patients with both HFrEF and CSA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Circulating protein-biomarkers (n = 276) ontologically involved in CV pathways, were studied in 749 (57% of the trial population) patients (biomarker substudy), to investigate their association with the study outcomes (primary outcome, CV death and all-cause death). The mean age was 69 \u00b1 10 years, and &amp;gt; 90% were male. The groups (ASV vs. control and biomarker substudy vs. no biomarker) were well balanced. The \u201cbest\u201d clinical prognostic model included male sex, systolic blood pressure &amp;lt; 120 mmHg, diabetes, loop diuretic, cardiac device, 6-min walking test distance, and N-terminal pro BNP as the strongest prognosticators. On top of the \u201cbest\u201d clinical prognostic model, the biomarkers that significantly improved both the discrimination (c-index) and the net reclassification index (NRI) of the model were soluble suppression of tumorigenicity 2 for the primary outcome; neurogenic locus notch homolog protein 3 (Notch-3) for CV-death and all-cause death; and growth differentiation factor 15 (GDF-15) for all-cause death only.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We studied 276 circulating biomarkers in patients with HFrEF and central sleep apnoea; of these biomarkers, three added significant prognostic information on top of the best clinical model: soluble suppression of tumorigenicity 2 (primary outcome), Notch-3 (CV and all-cause death), and GDF-15 (all-cause death).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12521","type":"journal-article","created":{"date-parts":[[2020,1,17]],"date-time":"2020-01-17T10:42:08Z","timestamp":1579257728000},"page":"503-511","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Biomarkers in Patients with Heart Failure and Central Sleep Apnoea: Findings From the SERVE-HF Trial"],"prefix":"10.1093","volume":"7","author":[{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[{"name":"Inserm CIC-P 1433, CHRU de Nancy, Inserm U1116, French Clinical Research Infrastructure Network Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists, Universit\u00e9 de Lorraine , Nancy ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u00e9vin","family":"Duarte","sequence":"additional","affiliation":[{"name":"Inserm CIC-P 1433, CHRU de Nancy, Inserm U1116, French Clinical Research Infrastructure Network Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists, Universit\u00e9 de Lorraine , Nancy ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Woehrle","sequence":"additional","affiliation":[{"name":"ResMed Science Center, ResMed Germany Inc. , Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin R.","family":"Cowie","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Imperial College London , London ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Wegscheider","sequence":"additional","affiliation":[{"name":"Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf , Hamburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Angermann","sequence":"additional","affiliation":[{"name":"Faculty of Medicine I and Comprehensive Heart Failure Center, University Hospital and University of W\u00fcrzburg , W\u00fcrzburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Pia","family":"d'Ortho","sequence":"additional","affiliation":[{"name":"H\u00f4pital Bichat, Explorations Fonctionnelles, DHU FIRE, AP-HP , Paris ,","place":["France"]},{"name":"UFR de M\u00e9dicine, Sorbonne Paris Cit\u00e9, Paris Diderot University , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erland","family":"Erdmann","sequence":"additional","affiliation":[{"name":"Heart Center, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Levy","sequence":"additional","affiliation":[{"name":"Inserm, HP2 lab. CHU Grenoble, Universit\u00e9 de Grenoble Alpes , Alpes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita K.","family":"Simonds","sequence":"additional","affiliation":[{"name":"Respiratory Medicine, Royal Brompton Hospital , London ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virend K.","family":"Somers","sequence":"additional","affiliation":[{"name":"Cardiovascular Facility and the Sleep Facility, Mayo Clinic and Mayo Foundation , Rochester, MN ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmut","family":"Teschler","sequence":"additional","affiliation":[{"name":"Department of Pneumology, Ruhrlandklinik , Essen ,","place":["Germany"]},{"name":"West German Lung Centre, Essen University Hospital , Essen ,","place":["Germany"]},{"name":"University Duisburg-Essen, Department of Pneumology , Essen 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