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Biomarkers in patients with heart failure and central sleep apnoea: findings from the SERVE‐HF trial

Joao Pedro Ferreira 1, 2, 3, 4 Kevin Duarte 1, 2, 3, 4 Holger Woehrle 5 Martin R Cowie 6 Karl Wegscheider 7 Christiane Angermann 8 Marie Pia d'Ortho 9, 10 Erland Erdmann 11 Patrick Levy 12 Anita K Simonds 13 Virend K Somers 14 Helmut Teschler 15, 16, 17 Patrick Rossignol 1, 2, 3, 4 Wolfgang Koenig 18, 19 Faiez Zannad 1, 2, 3, 4 
Abstract : Aims: 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.Methods and results: 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 ± 10 years, and > 90% were male. The groups (ASV vs. control and biomarker substudy vs. no biomarker) were well balanced. The “best” clinical prognostic model included male sex, systolic blood pressure < 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 “best” 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.Conclusions: 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).
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Submitted on : Wednesday, May 13, 2020 - 12:17:24 PM
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Joao Pedro Ferreira, Kevin Duarte, Holger Woehrle, Martin R Cowie, Karl Wegscheider, et al.. Biomarkers in patients with heart failure and central sleep apnoea: findings from the SERVE‐HF trial. ESC Heart Failure, Wiley, 2020, 7 (2), pp.503-511. ⟨10.1002/ehf2.12521⟩. ⟨hal-02571966⟩



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