Proteomic Biomarkers Are Linked to QTc Interval in Patients With Chronic Heart Failure
This study is the first to investigate the association between QTc interval and a broad panel of over 1000 plasma proteins in patients with heart failure with reduced ejection fraction (HFrEF). We identified 11 proteins significantly linked to QTc interval, five of which also demonstrated prognostic relevance for adverse cardiovascular outcomes. The associated biomarkers are linked to inflammation, fibrosis, and angiogenesis-related pathways. These findings provide novel insights into the multifactorial mechanisms associated with QTc prolongation, potentially due to direct or indirect effects. The results emphasize the potential of circulating biomarkers as tools for understanding the pathophysiological processes associated with QTc prolongation and arrhythmogenesis in heart failure. Moreover, the identification of interleukin-1 receptor-like 1 (ST2), angiopoietin-2, atrial natriuretic factor, IGFBP7, and carbonic anhydrase 4 (CA4) as shared markers of QTc interval prolongation and adverse outcomes underscores their clinical utility as both diagnostic and prognostic biomarkers.
Authors
- Jasper J. Brugts (ORCID: https://orcid.org/0000-0002-5522-9318)
- Sabrina Abou Kamar
- Teun B. Petersen (ORCID: https://orcid.org/0000-0002-2338-9931)
- Peter D. Katsikis (ORCID: https://orcid.org/0000-0001-7690-5218)
- Victor A. Umans (ORCID: https://orcid.org/0000-0002-5587-9097)
- Rudolf A. de Boer (ORCID: https://orcid.org/0000-0002-4775-9140)
- K. Martijn Akkerhuis (ORCID: https://orcid.org/0000-0003-4833-3130)
- Sing‐Chien Yap (ORCID: https://orcid.org/0000-0003-4520-2725)
- Folkert Wouter Asselbergs (ORCID: https://orcid.org/0000-0002-1692-8669)
- Navin Suthahar (ORCID: https://orcid.org/0000-0002-7781-2897)
- Isabella Kardys (ORCID: https://orcid.org/0000-0002-2115-9745)
- Peter J. van der Spek (ORCID: https://orcid.org/0000-0002-2203-0652)
- Nick van Boven (ORCID: https://orcid.org/0000-0003-3749-9303)
- Eric H. Boersma (ORCID: https://orcid.org/0000-0002-2559-7128)
- Mylène Barry‐Loncq de Jong
Institutions
- Erasmus MC (NL)
- Northwest Hospital (US)
- Health Data Research UK (GB)
- Erasmus MC Cancer Institute (NL)
- Amsterdam University Medical Centers (NL)
- University College London (GB)
- University of Amsterdam (NL)
- Erasmus University Rotterdam (NL)
Publication Details
- Journal
- PROTEOMICS - CLINICAL APPLICATIONS
- Published
- 2025-09-03
- DOI
- https://doi.org/10.1002/prca.70020
- Primary Topic
- Heart Failure Treatment and Management
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Federation of Pharmaceutical Industries and Associations
- Jaap Schouten Foundation