Characterizing the molecular landscape of venous congestion.

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.