The plasma proteome is linked with left ventricular and left atrial function parameters in patients with chronic heart failure

S Abou Kamar; K Andrzejczyk; T B Petersen; J F Chin; Y S Aga; M de Bakker; K M Akkerhuis; M Geleijnse; J J Brugts; O Sorop; R A de Boer; D Rizopoulos; F W Asselbergs; E Boersma; H den Ruijter; B M van Dalen; I Kardys

doi:10.1093/ehjci/jeae098

The plasma proteome is linked with left ventricular and left atrial function parameters in patients with chronic heart failure

Eur Heart J Cardiovasc Imaging. 2024 Apr 10:jeae098. doi: 10.1093/ehjci/jeae098. Online ahead of print.

Authors

S Abou Kamar^{1

2

3}, K Andrzejczyk¹, T B Petersen^{1

4}, J F Chin^{1

3}, Y S Aga^{1

3}, M de Bakker¹, K M Akkerhuis¹, M Geleijnse¹, J J Brugts¹, O Sorop¹, R A de Boer¹, D Rizopoulos^{1

4}, F W Asselbergs⁵, E Boersma¹, H den Ruijter⁶, B M van Dalen^{1

3}, I Kardys¹

Affiliations

¹ Erasmus MC, Cardiovascular Institute, Thorax Center, Department of Cardiology, Rotterdam, the Netherlands.
² The Netherlands Heart Institute, Utrecht, The Netherlands.
³ Department of Cardiology, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands.
⁴ Department of Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁵ Department of Cardiology, Amsterdam Medical Center, The Netherlands.
⁶ Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, Netherlands.

PMID: 38597740
DOI: 10.1093/ehjci/jeae098

Abstract

Background: Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into HF pathophysiology.

Objective: We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters, as well as with elevated left atrial pressure (LAP), in HFrEF patients, to provide insights into underlying mechanisms.

Methods: In 173 HFrEF patients, we performed six-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7(IQR:2.5-2.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular (left ventricular ejection fraction[LVEF], global longitudinal strain[GLS]), and left atrial function (left atrial reservoir strain[LASr]) and elevated LAP(E/e' ratio >15), and used gene enrichment analyses to identify underlying pathophysiological processes.

Results: We found 723, 249, 792 and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr and E/e' ratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix (ECM). Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: Cystatin-D, Fibulin-5 and HSP40.

Conclusion: Circulating proteins show varying associations with different echocardiographic parameters in HFrEF patients. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct.

Keywords: echocardiography; heart failure; pathofysiological processes; proteomics; strain parameters.