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. 2022 Sep;10(9):623-632.
doi: 10.1016/j.jchf.2022.05.013.

Pathophysiologic Processes and Novel Biomarkers Associated With Congestion in Heart Failure

Paloma Pandhi  1 , Jozine M Ter Maaten  1 , Stefan D Anker  2 , Leong L Ng  3 , Marco Metra  4 , Nilesh J Samani  3 , Chim C Lang  5 , Kenneth Dickstein  6 , Rudolf A de Boer  1 , Dirk J van Veldhuisen  1 , Adriaan A Voors  7 , Iziah E Sama  1
Affiliations
Free article

Pathophysiologic Processes and Novel Biomarkers Associated With Congestion in Heart Failure

Paloma Pandhi et al. JACC Heart Fail. 2022 Sep.
Free article

Abstract

Background: Congestion is the main driver behind symptoms of heart failure (HF), but pathophysiology related to congestion remains poorly understood.

Objectives: Using pathway and differential expression analyses, the authors aim to identify biological processes and biomarkers associated with congestion in HF.

Methods: A congestion score (sum of jugular venous pressure, orthopnea, and peripheral edema) was calculated in 1,245 BIOSTAT-CHF patients with acute or worsening HF. Patients with a score ranking in the bottom or top categories of congestion were deemed noncongested (n = 408) and severely congested (n = 142), respectively. Plasma concentrations of 363 unique proteins (Olink Proteomics Multiplex CVD-II, CVD-III, Immune Response and Oncology II panels) were compared between noncongested and severely congested patients. Results were validated in an independent validation cohort of 1,342 HF patients (436 noncongested and 232 severely congested).

Results: Differential protein expression analysis showed 107/363 up-regulated and 6/363 down-regulated proteins in patients with congestion compared with those without. FGF-23, FGF-21, CA-125, soluble ST2, GDF-15, FABP4, IL-6, and BNP were the strongest up-regulated proteins (fold change [FC] >1.30, false discovery rate [FDR], P < 0.05). KITLG, EGF, and PON3 were the strongest down-regulated proteins (FC <-1.30, FDR P < 0.05). Pathways most prominently involved in congestion were related to inflammation, endothelial activation, and response to mechanical stimulus. The validation cohort yielded similar findings.

Conclusions: Severe congestion in HF is mainly associated with inflammation, endothelial activation, and mechanical stress. Whether these pathways play a causal role in the onset or progression of congestion remains to be established. The identified biomarkers may become useful for diagnosing and monitoring congestion status.

Keywords: biomarkers; congestion; heart failure; pathway analysis.

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Conflict of interest statement

Funding Support and Author Disclosures The University Medical Center Groningen, which employs some of the authors, has received research grants and/or fees from Abbott, AstraZeneca, Boehringer Ingelheim, Cardior Pharmaceuticals, Ionis Pharmaceuticals, Novo Nordisk, and Roche (outside the submitted work). Dr de Boer is supported by a grant from the European Research Council (ERC CoG 818715, SECRETE-HF). Dr Anker has been a consultant and/or received speaker fees from Abbott, Astra, Bayer, Boehringer Ingelheim, Brahms, Cardiac Dimension, Impulse Dynamics, Janssen, Novartis, Respicardia, Servier, Stealth Peptides, St. Jude Medical, and Vifor Pharma; and has received grant support from Abbott Vascular and Vifor Pharma. Dr Metra has received personal fees from Actelion, Amgen, AstraZeneca, Abbott Vascular, Bayer, Servier, Edwards Therapeutics, Livanova, Vifor Pharma, and WindTree Therapeutics as member of trial committees or for speeches at sponsored meetings in the past 3 years. Dr Lang has received consultancy fees and/or research grants from Amgen, Applied Therapeutics, AstraZeneca, Boehringher Ingelheim, Merck Sharp & Dohme, Novartis, and Novo Nordisk. Dr de Boer has received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche (outside the submitted work). Dr Voors has received fees and/or grants from Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, GlaxoSmithKline, Merck, Myokardia, Novacardia, Novartis, Roche Diagnostics, Servier, and Vifor International. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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