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- Dokumenttyp:
- Article; Journal Article
- Autor(en):
- Ferreira, João Pedro; Duarte, Kévin; 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; Zannad, Faiez
- Titel:
- Bioprofiles and mechanistic pathways associated with Cheyne-Stokes respiration: insights from the SERVE-HF trial.
- 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. 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.
- Zeitschriftentitel:
- Clin Res Cardiol
- Jahr:
- 2020
- Band / Volume:
- 109
- Heft / Issue:
- 7
- Seitenangaben Beitrag:
- 881-891
- Volltext / DOI:
- doi:10.1007/s00392-019-01578-9
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/31784904
- Print-ISSN:
- 1861-0684
- TUM Einrichtung:
- 1038; Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (Prof. Schunkert)
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