Relaxin-2, pathophysiological insights and outcomes in heart failure with preserved ejection fraction: Findings from the NETDiamond cohort

Autores da FMUP

• Mariana Marques Santos Pintalhão

  Autor

• Francisco Aguiar Vasques Novoa Faria

  Autor

• João Sérgio De Lima Soares Neves

  Autor

• Luís Carlos Ferreira Mendonça

  Autor

• Francisca Almeida Saraiva

  Autor

• André Pedro Leite Martins Lourenço

  Autor

• Luís Filipe Vilela Pereira De Macedo

  Autor

• José Paulo Araújo De Figueiredo

  Autor

• João Pedro Melo Marques Pinho Ferreira

  Autor

• Paulo Manuel Barreiros De Castro Chaves

  Autor

• Joaquim Adelino Correia Ferreira Leite Moreira

  Autor

Participantes de fora da FMUP

• Couto Viana, B
• Pimentel, MJ
• Ferreira, G
• von Hafe, P.
• Almeida, J.

Unidades de investigação

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Medicina

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Aims: The role of relaxin-2 as a circulating marker in heart failure (HF) with preserved ejection fraction (HFpEF) is poorly understood. We aimed to characterize relaxin-2 circulating levels in a population of chronic HFpEF patients and their association with long-term prognosis. Methods: Relaxin-2 serum levels were measured in 85 chronic HFpEF patients from a prospective cohort study (NETDiamond). Clinical, imaging, and analytical data were compared across relaxin-2 tertiles. The primary outcome was a composite of cardiovascular death, HF hospitalisation, acute HF episode or diuretic intensification and the secondary outcome a composite of cardiovascular death and total HF hospitalisations. Cox regression and negative binomial models were used to assess the relation between relaxin-2 and the outcomes. Results: Relaxin-2 levels were positively associated with left atrial volume, left ventricular mass and peripheral oedema, and negatively associated with ischemic heart disease and statin use. Higher relaxin-2 levels were associated with an increased risk of primary outcome, even after adjustment for age, B-type natriuretic peptide (BNP) and glomerular filtration rate (eGFR) (adjusted HR = 2.80, 95%CI 1.4-7.3, p = 0.034 for tertile 3). They were also associated with the occurrence of the secondary outcome (Incidence Rate Ratio = 5.28, 95%CI 1.2-23.2, p = 0.027), but this significance was lost when simultaneously adjusted for BNP and eGFR. Conclusion: In chronic HFpEF patients, higher relaxin-2 circulating levels were associated with left chambers remodelling, congestion, and adverse prognosis. These findings support a potential role for relaxin-2 as a pathophysiological agent and as a circulating biomarker in HFpEF.

Copyright © 2022 Elsevier B.V. All rights reserved.

Keywords

• Heart failure with preserved ejection fraction; Relaxin-2; Prognosis; Biomarker