Characterizing the molecular landscape of venous congestion

Table 1 Characteristics of included studies, n (%)/median (interquartile range)

Variable	All studies	Critical care studies
Total manuscripts	145 (100)	5 (100)
Type of study
Prospective	88 (60.7)	2 (40.0)
Retrospective	46 (31.7)	0 (0)
Cross sectional	5 (3.4)	1 (20.0)
Case control	2 (1.4)	1 (20.0)
Other/mixed	5 (3.4)	1 (20.0)
Setting
Inpatient not specified	57 (39.3)
Outpatient	36 (24.8)
Mixed inpatient/outpatient	17 (11.7)
Cardiac unit	10 (6.9)
Emergency department	8 (5.5)
Other/not specified	8 (5.5)
Intensive care	5 (3.4)	5 (100)
Medicine unit	3 (2.1)
Operating room/surgical	1 (0.7)
Sample size
Overall	164.0 (83.5-442.0)	91.0 (70.5-255.0)
< 100 subjects	44 (30.3)	3 (60.0)
100-1000 subjects	79 (54.5)	2 (40.0)
> 1000 subjects	22 (15.2)	0 (0)
Dedicated biomarker study	43 (29.7)	2 (40.0)
Validation cohort used	10 (6.9)	1 (20.0)
Number of proteins quantified
Overall	2 (1.0-3.0)	1 (1.0-2.0)
1	68 (46.9)	4
2-10	68 (46.9)	1
11-100	7 (4.8)	0
> 100	2 (1.4)	0
Method of protein quantification
Immunoassays	74 (51.0)	3 (60.0)
O-link proximity extension	6 (4.1)	0 (0)
Not specified	65 (44.8)	2 (40.0)
Frequency of sampling
Single time point	68 (46.9)	2 (40.0)
Longitudinal	57 (39.3)	3 (60.0)
Not specified	20 (13.7)	-
Study outcome measured congestion	37 (25.5)	3

Table 2 Disease state under study and method of congestion measurement, n (%)

Variable	Number of studies
Disease state
Cardiac	116 (80.0)
Heart failure	107
Right heart failure	1
ACS	6
Cardiac surgery	2
Pulmonary	7 (4.8)
Dyspnea	4
Pulmonary hypertension	3
Gastrointestinal	10 (6.9)
Cirrhosis	3
Cardiac congestive hepatopathy	6
Cardiac induced intra-abdominal hypertension	1
Renal	8 (5.5)
Dialysis	5 (3.4)
Cardiac congestive nephropathy	3 (2.1)
Peripheral congestion	4 (2.8)
Method of identifying congestion
Physical exam	65 (44.8)
Echocardiography	56 (38.6)
Lung ultrasound	24 (16.6)
Hepatic/abdominal ultrasound	9 (6.2)
Renal ultrasound	5 (3.4)
Clinical congestion score used	40 (27.6)

ACS: Acute coronary syndrome.

Table 3 Studies in intensive care unit settings

Ref.	Objective	Disease state	Venous congestion measurement	Proteins investigated	Pathobiology findings
Benkreira et al[56], 2019 (n = 382)	To investigate if portal vein flow pulsatility identifes patients with congestion at risk for delirium	Post-cardiac surgery	US: Portal vein flow pulsatility	NTproBNP	Portal vein pulsatility was associated with cognitive dysfunction, asterixis, and delirium. ↑ NTproBNP levels were associated with cognitive dysfunction
Ishaq et al[24], 2022 (n = 77)	To compare IVC diameter and pro-BNP for IV fluid administration in critically ill patients on intermittent positive pressure ventilation	Congestive heart failure	Echo: IVC diameter	NTproBNP	↑ IVC size associated with NTproBNP in patients with heart failure, and may be beneficial in discriminating between congestion and non-congestion in heart failure
Kitai et al[57], 2017 (n = 69)	To investigate if elevated I-FABP identifies patients with advanced heart failure who have venous and intestinal congestion.	Acute decompensated heart failure	Echo: Routine parameters, TAPSE, RV FAC, E/e’, RHC: PCWP/RAP	FABP2	↑ FABP was associated with worse clinical outcomes (death, transplant or LVAD placement); No association between FABP and right sided filling pressures or with echocardiographic parameters suggesting venous congestion
Pichon et al[35], 2023 (n = 91)	To investigate arterial and venous renal doppler in acute decompensated precapillary pulmonary hypertension	Pulmonary hypertension/acute right heart failure	US: IRVF, RVSI, RRI, Echo: Routine parameters, TAPSE, tv s’, E/A, VTI, RHC: CVP, mPAP, PAWP, RAP, CI	NTproBNP	↑ RRI was associated with age, hypertension, congestion (RAP and renal pulse pressure), cardiac function (TAPSE, VTI), systemic pressure and NTproBNP. ↑ RVSI was associated with congestion (high CVP, RAP, renal pulse pressure), right cardiac function (TAPSE), severe TR and systemic pressures
Zelt et al[36], 2018 (n = 178)	To assess the utility of NTproBNP, NGAL, and hs-cTNT for prediction and detection of congestive AKI	Cardiac surgery/congestive nephropathy	Echo: RV FAC, RHC: CVP, CI, PCWP	hs-cTnT, NTproBNP, NGAL	Baseline and postoperative NTproBNP, postoperative hs-cTnT, and change in hs-cTnT predicted AKI caused by congestion. Congestive AKI was associated with duration of mechanical ventilation and hospital/ICU length of stay

US: Ultrasound; Echo: Echocardiography; IVC: Inferior vena cava; I-FABP: Intestinal fatty acid-binding protein; TAPSE: Transannular plane of systolic excursion; RV FAC: Right ventricular fractional area of change; RHC: Right heart catheterization; PAWP/PCWP: Pulmonary capillary wedge pressure; RAP: Right atrial pressure; IRVF: Intrarenal venous flow; RSVI: Renal venous stasis index; RRI: Renal resistive index; TVs’: Tricuspid valve s’; VTI: Velocity time integral; CVP: Central venous pressure; mPAP: Mean pulmonary arterial pressure; CI: Cardiac index; ICU: Intensive care unit; AKI: Acute kidney injury.