Ferreira, Joao Pedro ORCID: 0000-0002-2304-6138, Duarte, Kevin, Woehrle, Holger, Cowie, Martin R., Angermann, Christiane, d'Ortho, Marie-Pia, Erdmann, Erland, Levy, Patrick, Simonds, Anita K., Somers, Virend K., Teschler, Helmut, Wegscheider, Karl, Bresso, Emmanuel, Dominique-Devignes, Marie, Rossignol, Patrick, Koenig, Wolfgang and Zannad, Faiez (2020). Bioprofiles and mechanistic pathways associated with Cheyne-Stokes respiration: insights from the SERVE-HF trial. Clin. Res. Cardiol., 109 (7). S. 881 - 892. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1861-0692

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Abstract

Introduction The SERVE-HF trial included patients with heart failure and reduced ejection fraction (HFrEF) with sleep-disordered breathing, randomly assigned to treatment with Adaptive-Servo Ventilation (ASV) or control. The primary outcome was the first event of death from any cause, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening heart failure. A subgroup analysis of the SERVE-HF trial suggested that patients with Cheyne-Stokes respiration (CSR) < 20% (low CSR) experienced a beneficial effect from ASV, whereas in patients with CSR >= 20% ASV might have been harmful. Identifying the proteomic signatures and the underlying mechanistic pathways expressed in patients with CSR could help generating hypothesis for future research. Methods Using a large set of circulating protein-biomarkers (n = 276, available in 749 patients; 57% of the SERVE-HF population) we sought to investigate the proteins associated with CSR and to study the underlying mechanisms that these circulating proteins might represent. Results The mean age was 69 +/- 10 years and > 90% were male. Patients with CSR < 20% (n = 139) had less apnoea-hypopnea index (AHI) events per hour and less oxygen desaturation. Patients with CSR < 20% might have experienced a beneficial effect of ASV treatment (primary outcome HR [95% CI] = 0.55 [0.34-0.88]; p = 0.012), whereas those with CSR >= 20% might have experienced a detrimental effect of ASV treatment (primary outcome HR [95% CI] = 1.39 [1.09-1.76]; p = 0.008); p for interaction = 0.001. Of the 276 studied biomarkers, 8 were associated with CSR (after adjustment and with a FDR1%-corrected p value). For example, higher PAR-1 and ITGB2 levels were associated with higher odds of having CSR < 20%, whereas higher LOX-1 levels were associated with higher odds of CSR >= 20%. Signalling, metabolic, haemostatic and immunologic pathways underlie the expression of these biomarkers. Conclusion We identified proteomic signatures that may represent underlying mechanistic pathways associated with patterns of CSR in HFrEF. These hypothesis-generating findings require further investigation towards better understanding of CSR in HFrEF. Graphic abstract Summary of the findings. PAR-1 proteinase-activated receptor 1, ADM adrenomedullin, HSP-27 heat shock protein-27, ITGB2 integrin beta 2, GLO1 glyoxalase 1, ENRAGE/S100A12 S100 calcium-binding protein A12, LOX-1 lectin-like LDL receptor 1, ADAM-TS13 disintegrin and metalloproteinase with a thrombospondin type 1 motif, member13 also known as von Willebrand factor-cleaving protease. [GRAPHICS] .

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ferreira, Joao PedroUNSPECIFIEDorcid.org/0000-0002-2304-6138UNSPECIFIED
Duarte, KevinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woehrle, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cowie, Martin R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Angermann, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
d'Ortho, Marie-PiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erdmann, ErlandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levy, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simonds, Anita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Somers, Virend K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teschler, HelmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wegscheider, KarlUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bresso, EmmanuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dominique-Devignes, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rossignol, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenig, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zannad, FaiezUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-126850
DOI: 10.1007/s00392-019-01578-9
Journal or Publication Title: Clin. Res. Cardiol.
Volume: 109
Number: 7
Page Range: S. 881 - 892
Date: 2020
Publisher: SPRINGER HEIDELBERG
Place of Publication: HEIDELBERG
ISSN: 1861-0692
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CENTRAL SLEEP-APNEA; HEART-FAILURE; VENTILATION; PROTEINS; RISKMultiple languages
Cardiac & Cardiovascular SystemsMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/12685

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