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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Aims: 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 heart failure pathophysiology. 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 patients with HFrEF, to provide insights into underlying mechanisms. Methods and results: In 173 patients with HFrEF, we performed 6-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7 (inter-quartile range: 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/eʹratio >15) and used gene enrichment analyses to identify underlying pathophysiological processes. We found 723, 249, 792, and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr, and E/eʹratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix. 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 patients with HFrEF. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct.

Original languageEnglish
Pages (from-to)1206-1215
Number of pages10
JournalEuropean Heart Journal Cardiovascular Imaging
Volume25
Issue number9
DOIs
Publication statusPublished - 1 Sept 2024

Keywords

  • echocardiography
  • heart failure
  • pathophysiological processes
  • proteomics
  • strain parameters

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