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

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).

• Authors: João Pedro Ferreira, Kévin Duarte, Holger Woehrle, Martin R Cowie, Karl Wegscheider, Christiane Angermann, Marie-Pia d'Ortho, Erland Erdmann, Patrick Levy, Anita K Simonds, Virend K Somers, Helmut Teschler, Patrick Rossignol, Wolfgang Koenig, Faiez Zannad
• Journal: ESC heart failure (ESC Heart Fail) Vol. 7 Issue 2 Pg. 503-511 (04 2020) ISSN: 2055-5822 [Electronic] England
• PMID: 31951323 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Chemical References

• Biomarkers

Topics

• Aged
• Biomarkers
• Female
• Heart Failure (therapy)
• Humans
• Male
• Middle Aged
• Sleep Apnea Syndromes (complications, diagnosis, epidemiology)
• Sleep Apnea, Central (diagnosis, epidemiology, therapy)
• Stroke Volume