Van Nynatten LR, Nabieva K, Barber G, Moroniti JJ, Iansavitchene A, Prager R, Slessarev M, Basmaji J, Leligdowicz A. Characterizing the molecular landscape of venous congestion. World J Crit Care Med 2026; 15(3): 122062 [DOI: 10.5492/wjccm.122062]
Corresponding Author of This Article
Aleksandra Leligdowicz, MD, PhD, Department of Critical Care Medicine, Western University, Robarts Research Institute, 100 Perth Dr, Room 4220, Ontario N6A5A5, Canada. aleks.leligdowicz@lhsc.on.ca
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Critical Care Medicine
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Van Nynatten LR, Nabieva K, Barber G, Moroniti JJ, Iansavitchene A, Prager R, Slessarev M, Basmaji J, Leligdowicz A. Characterizing the molecular landscape of venous congestion. World J Crit Care Med 2026; 15(3): 122062 [DOI: 10.5492/wjccm.122062]
World J Crit Care Med. Sep 9, 2026; 15(3): 122062 Published online Sep 9, 2026. doi: 10.5492/wjccm.122062
Characterizing the molecular landscape of venous congestion
Logan R Van Nynatten, Karina Nabieva, Gemma Barber, Jonathan J Moroniti, Alla Iansavitchene, Ross Prager, Marat Slessarev, John Basmaji, Aleksandra Leligdowicz
Logan R Van Nynatten, Karina Nabieva, Gemma Barber, Jonathan J Moroniti, Alla Iansavitchene, Ross Prager, Marat Slessarev, John Basmaji, Aleksandra Leligdowicz, Department of Critical Care Medicine, Western University, Ontario N6A5A5, Canada
Author contributions: Leligdowicz A, Van Nynatten LR, Basmaji J, Slessarev M, Prager R and Iansavitchene A contributed to study conception and design; Iansavitchene A, Barber G and Moroniti JJ contributed to data extraction; Van Nynatten LR and Nabieva K contributed to data extraction, data interpretation, data analysis, data presentation and manuscript preparation; Van Nynatten LR and Leligdowicz A wrote the manuscript; all authors participated in manuscript preparation and data review.
AI contribution statement: AI was not used in the extraction of data or preparation of the manuscript. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Aleksandra Leligdowicz, MD, PhD, Department of Critical Care Medicine, Western University, Robarts Research Institute, 100 Perth Dr, Room 4220, Ontario N6A5A5, Canada. aleks.leligdowicz@lhsc.on.ca
Received: April 8, 2026 Revised: June 16, 2026 Accepted: July 16, 2026 Published online: September 9, 2026 Processing time: 135 Days and 16.6 Hours
Abstract
BACKGROUND
Venous congestion is a pathologic state caused by reduced arteriovenous gradients that promote injurious tissue edema. Venous congestion can be due to etiologies such as decompensated cardiac disease, renal failure, or iatrogenic fluid administration. However, the underlying pathobiology of venous congestion is poorly investigated, particularly in critical illness. We conducted a scoping review to identify candidate circulating proteins potentially associated with venous congestion pathobiology.
AIM
To identify circulating proteins associated with the pathobiology of venous congestion.
METHODS
The MEDLINE and EMBASE databases were searched for articles relevant to venous congestion. Studies were included if they: (1) Investigated human adult subjects ≥ 18 years of age; (2) Measured plasma or serum proteins in disease states with reported measures of venous congestion; and (3) Reported clinical or ultrasound measures of assessing venous congestion. Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for scoping reviews guidelines were used.
RESULTS
A total of 3860 abstracts were eligible for screening, of which 171 manuscripts underwent full-text review, and 145 texts met inclusion criteria. The median number of circulating proteins measured was 2 (interquartile range: 1-3). Most studies (116, 80%) reported measures of venous congestion in the context of cardiac disease. Five studies (3%) were performed in a critical care setting. Significant variability was noted in the reported measures of venous congestion, with physical examination often used to presume the presence of venous congestion (45% of studies). Less than 30% of studies had the objective of investigating circulating proteins, and less than 15% of studies aimed to characterize biology of venous congestion. The candidate circulating plasma proteins measured included proteins related to myocardial function, endothelial function, and inflammation.
CONCLUSION
We present the first scoping review identifying circulating proteins with a possible role in mediating venous congestion at a molecular level. To date, no robust studies have comprehensively investigated the biology of venous congestion. These data provide a foundation for further studies of the biological mechanisms of venous congestion. Understanding these mechanisms may assist in the measurement of responses to volume resuscitation, stratification in clinical trials focusing on appropriate volume administration and removal, and the identification of novel therapies that target pathways implicated in this deleterious condition.
Core Tip: Clinicians can increasingly identify venous congestion, but they still do not understand its pathobiology. Although congestion is recognized across multiple disease states, the existing literature is largely confined to isolated protein measurements in congested cardiac populations, leaving its broader molecular biology poorly understood. This review reveals a substantial translational gap between physiologic recognition and biological understanding of venous congestion, highlighting the need for high-dimensional molecular studies to define its mechanisms and therapeutic targets.
