Prospective Evaluation of Venous Excess Ultrasound for Estimation of Venous Congestion

Abstract

Background

Venous excess ultrasound (VExUS) is a novel ultrasound technique previously reported as a noninvasive measure of venous congestion and predictor of cardiorenal acute kidney injury.

Research Question

Are there associations between VExUS grade and cardiac pressures measured by right heart catheterization (RHC) and cardiac biomarkers and clinical outcomes in patients undergoing RHC?

Study Design and Methods

We conducted a prospective cohort study at the Denver Health Medical Center from December 20, 2022, to March 25, 2023. All patients undergoing RHC underwent a blinded VExUS assessment prior to their procedure. Multivariable regressions were conducted to assess relationships between VExUS grade and cardiac pressures, biomarkers, and changes in weight among patients with heart failure, a proxy for diuretic success. Receiver operating characteristic curve and area under the curve (AUC) were derived for VExUS, inferior vena cava (IVC) diameter, and IVC collapsibility index (ICI) to predict right atrial pressure (RAP) > 10 and < 7 mm Hg.

Results

Among 81 patients, 45 of whom were inpatients, after adjusting for age, sex, and Charlson Comorbidity Index, there were significant relationships between VexUS grade of 2 (β = 4.8; 95% CI, 2.6-7.1; P < .01) and 3 (β = 11; 95% CI, 8.9-14; P < .01) and RAP, VExUS grade of 2 (β = 6.8; 95% CI, 0.16-13; P = .045) and 3 (β = 15; 95% CI, 7.3-22; P < .01) and mean pulmonary artery pressure, and VExUS grade of 2 (β = 7.0; 95% CI, 3.9-10; P < .01) and 3 (β = 13; 95% CI, 9.5-17; P < .01) and pulmonary capillary wedge pressure. AUC values for VExUS, IVC diameter, and ICI as predictors of RAP > 10 mm Hg were 0.9 (95% CI, 0.83-0.97), 0.77 (95% CI, 0.68-0.88), and 0.65 (95% CI, 0.52-0.78), respectively. AUC values for VExUS, IVC diameter, and ICI as predictors of RAP < 7 mm Hg were 0.79 (95% CI, 0.70-0.87), 0.74 (95% CI, 0.64-0.84), and 0.62 (95% CI, 0.49-0.76), respectively. In a subset of 23 patients with heart failure undergoing diuresis, there was a significant association between VExUS grade 3 and change in weight between time of RHC and discharge (P = .025).

Interpretation

Although more research is required, VExUS has the potential to increase diagnostic and therapeutic capabilities of physicians at the bedside and increase our understanding of the underappreciated problem of venous congestion.

FOR EDITORIAL COMMENT, SEE PAGE 478

Take-home Points.

Study Question: Does the novel venous excess ultrasound (VExUS) technique, designed to noninvasively measure venous congestion, correlate with cardiac filling pressures measured invasively by right heart catheterization?

Results: VExUS grade was significantly associated with invasively measured right atrial pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, and inpatient acute kidney injury. The area under the curve for detection of right atrial pressure > 10 mm Hg was 0.9 (95% CI, 0.83-0.97), significantly greater than either inferior vena cava diameter or inferior vena cava collapsibility index. The mean duration of VExUS examination was 10 min.

Interpretation: Although further study is needed, VExUS is a clinically applicable technique that may provide valuable data on venous congestion without invasive cardiac catheterization.

Venous congestion is increasingly implicated in a range of diseases and comorbid complications, including pulmonary, hepatic, and renal injuries.^{1, 2, 3, 4, 5, 6} Accordingly, elevated right-sided heart filling pressure is associated with a variety of poor outcomes among multiple patient populations, especially the critically ill.^{1,5, 6, 7} Unfortunately, noninvasive bedside assessment of elevated venous pressure remains particularly challenging.^{8, 9, 10} As early as 1931, Winton¹¹ demonstrated the deleterious effect of increased venous pressure on the mammalian kidney, showing the clinical importance of venous hypertension to be equal to that of arterial hypotension because of its postcapillary contribution to organ perfusion pressure (OPP). OPP is precapillary arteriolar pressure minus postcapillary venular pressure, the pressure gradient that ultimately determines tissue perfusion. Both arterial hypotension and venous hypertension can lead to derangements in OPP, and subsequent tissue ischemia. This parameter has considerable clinical relevance. For example, among patients hospitalized with heart failure, guidelines recommend complete venous decongestion prior to discharge, making estimation of venous hypertension essential to appropriate management.¹² Unfortunately, accurate evaluation of venous congestion, and therefore OPP, is clinically challenging. Assessment of venous congestion by visual evaluation of the internal jugular vein has long been considered an essential component of the physical examination, but it is vulnerable to a high degree of intra-rater and interrater variability.¹³ Point of care ultrasound examinations of the internal jugular vein and inferior vena cava (IVC), commonly used point of care ultrasound proxies for venous hypertension, have important limitations, correlate imperfectly with invasive measurement, and are poorly predictive of volume responsiveness.^{14, 15, 16, 17} Two pertinent examples include dilation of the IVC in young athletes and patients undergoing mechanical ventilation. Although measurements of the IVC have been compared with invasively measured cardiac pressures previously, few of these studies were conducted in a dedicated cardiac laboratory, limiting the quality of invasive hemodynamic data.¹⁸ Despite ongoing controversy,¹⁹ the most definitive technique for measurement of venous congestion remains right heart catheterization (RHC) and direct measurement of right atrial pressure (RAP), a close proxy for venous hypertension.^10,20 However, RHC is not a feasible approach for routine clinical assessment across a spectrum of care environments. It is costly, not easily repeatable, and carries a complication rate as high as 1% in high-volume centers.²¹

These limitations highlight the need for an accurate, inexpensive, reproducible, and noninvasive means of evaluating venous hypertension. To that end, Beaubien-Souligny et al²² developed the venous excess ultrasound (VExUS) score, an ultrasonographic examination meant to assess congestion in the venous circulation including the encapsulated abdominal organs. This technique provides a readily available, low-risk method of estimating venous circulatory pressures otherwise available only by RHC.²² The VExUS is a four-point examination integrating IVC diameter with pulse-Doppler studies of the hepatic, portal, and renal veins to provide a comprehensive evaluation of the central venous return.²² This technique is a novel combination of previously documented ultrasound findings indicative of elevated RAP.^{1,8,23, 24, 25} In the author’s initial study, they reported a positive likelihood ratio of 6.37 for the development of cardiorenal acute kidney injury (AKI) in patients who were post-cardiac surgery. VExUS was also shown to correlate with AKI in patients with acute coronary syndrome,²⁶ and it has been proposed that VexUS may have applicability across a wide spectrum of patients who are critically ill, including as a marker of diuretic potential—an indicator that a patient may safely undergo further diuresis, targeting further venous decongestion.²⁷ However, VExUS has not yet been rigorously validated or compared with a true criterion standard of venous congestion. In this prospective cohort study, we assessed associations between VExUS grade and invasive RHC measurements, and cardiac biomarkers, echocardiographic parameters of diastolic dysfunction, and patient-centered outcomes including in-hospital AKI and successful diuresis. We hypothesized that VExUS grade is an accurate reflection of venous hypertension, and would be positively associated with intracardiac pressures measured by RHC, biomarkers of cardiac strain, echocardiographic markers of diastolic dysfunction, AKI, and successful diuresis.

Study Design and Methods

We conducted a prospective assessment of the diagnostic accuracy of VExUS grade for elevated intracardiac pressures, adhering to the Standards for Reporting of Diagnostic Accuracy Studies and Strengthening the Reporting of Observational Studies in Epidemiology guidelines for diagnostic accuracy and cohort studies.^28,29 The study was conducted at Denver Health Medical Center, a level I trauma and tertiary care center. The institution is a public safety net hospital in Denver, Colorado, with a socioeconomically and racially diverse patient population. Indications for RHC at Denver Health Medical Center are mixed—a plurality of RHCs are conducted for volume assessment in patients admitted with acute decompensated heart failure. The remainder include a diverse mixture of other indications including assessment of hypoxia, pulmonary hypertension, pericardial effusion assessment and drainage, chronic heart failure with declining functional status, and assessment of patients in cardiogenic shock. A consecutive cohort of patients undergoing ambulatory and inpatient RHC from December 20, 2022, to March 25, 2023, underwent VExUS examination immediately prior to RHC (e-Appendix 1). VExUS examinations were conducted and graded as previously described (e-Fig 1).²² Inclusion criteria included age > 18 years, plan to undergo RHC within 3 h, and ability and willingness to provide informed consent. Exclusion criteria included pregnancy, incarceration, and inability to consent without a proxy decision-maker.

Ultrasonographers were internal and emergency medicine residents with institutional training in ultrasonography. Ultrasonographers and researchers were not part of the clinical team, and study data were not made available to clinical team members. All ultrasonographers completed a 4-h instructional video series on VExUS, developed by Beaubien-Souligny group,³⁰ before undergoing in-person training by an emergency medicine attending physician with subspeciality training in ultrasonography and familiarity with the VExUS technique. External quality assessment was provided by a co-author of the initial VExUS score manuscript who reviewed a representative subset of ultrasonographer scans to assess image quality and confirm grading accuracy.

VExUS Scanning Protocol

Patients were reclined at 45°. The ultrasonographer first measured the IVC diameter approximately 3 to 4 cm from the junction of the IVC and the right atrium, or 1 to 2 cm caudal to the confluence of the hepatic vein and the IVC. Hepatic vein pulsatility was assessed by placing the probe in either a subxiphoid or lateral view, and placing the Doppler gate across any of the hepatic veins and observing Doppler waveforms. Hepatic portal venous pulsatility was assessed similarly, by placing the Doppler gate across the portal vein and observing the pulsatility index as follows: (maximum velocity − minimum velocity)/maximum velocity. Renal vasculature was visualized with the probe in the posterior axillary line, with the Doppler gate placed to detect the flow of the interlobar or arcuate renal veins in the renal cortex, outside the hilum of the kidney. VExUS examinations were conducted using the Mindray TE7 System (Mindray Bio-Medical Electronics Co).

VExUS Scoring

As previously described, the VExUS score is composed of evaluations of the IVC, hepatic vein, portal vein, and renal vasculature.²² If a patient’s IVC diameter is < 2 cm, the examination is assigned a score of 0. In the presence of an IVC ≥ 2 cm, the examiner proceeds with the examination, categorizing each vein as either normal, mildly abnormal, or severely abnormal. For purposes of this study, all views were acquired in all patients scanned.

Hepatic Vein

Normal hepatic vein Doppler waveforms show a small, retrograde A-wave, followed by anterograde S-waves and D-waves, with the ratio of amplitudes of the S-waves to D-waves being > 1. In increasing states of congestion, the S-wave shrinks relative to the D-wave before reversing entirely, becoming retrograde. An S-wave/D-wave ratio > 1 is normal, an S-wave/D-wave ratio ≤ 1 is mildly abnormal, and a reversal of the S-wave is severely abnormal.

Portal Vein

A normal portal vein Doppler waveform shows minimal pulsatility, with a pulsatility index < 30%. A pulsatility index of 30% to 49% is mildly abnormal, and a pulsatility index > 50% is severely abnormal.

Renal Vasculature

A normal renal Doppler pattern shows arterial pulsations generating regular retrograde peaks and renal veins generating a continuous, smooth anterograde flow. As venous congestion increases, venous pulsations become visible, creating anterograde pulsations observable during systole and diastole and eventually only diastole. A smooth venous baseline is considered normal. Biphasic anterograde pulsations reflecting systole and diastole are considered mildly abnormal, and monophasic pulsation, corresponding only with diastole, is considered severely abnormal. Any combination of normal or mildly abnormal scores is given a grade of 1. If the patient has one severely abnormal score, they are given a grade of 2. Two or more severely abnormal scores results in a grade of 3, reflecting severe congestion (e-Fig 1).

We conducted and scored VExUS examinations in a 3-h period prior to RHC, during which the patient was restricted from food or fluid intake to avoid ultrasonographer bias or significant changes in volume status between VExUS and RHC. VExUS results were graded and recorded before publication of RHC results. Investigators were blinded to the outcome of RAP at the time of VExUS assessment and grading, and physicians recording RAP were blinded to VExUS grade. Laboratory and clinical data available from the electronic health record were recorded in a REDCap database at the time of VExUS examination (e-Table 1) (e-Appendix 1).³¹ Fick cardiac output (CO) was calculated from directly measured oxygen content of arterial and venous blood and estimated oxygen consumption, as previously described.³² RAP, mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure (PCWP), and Fick CO and cardiac index were recorded from the final RHC report once the formal study had been recorded in the electronic health record. Baseline laboratory data including most recent N-terminal pro-brain natriuretic peptide (NT-proBNP) level and high-sensitivity troponin level in the 30 days prior to RHC were recorded from the electronic health record. For hospitalized patients, we also recorded indication for hospitalization, development of AKI as defined by KDIGO guidelines,³³ and change in creatinine level between the date of RHC and date of discharge. The average E/E' ratio from the patient’s most recent echocardiogram was recorded as a proxy for noninvasively measured cardiac filling pressures. The patient’s E/E' ratio was imported into the Nagueh formula to estimate left atrial pressure (LAP) as previously described.^{34, 35, 36} To assess the relationship between VExUS grade and diuretic potential, we evaluated a subset of patients hospitalized for heart failure exacerbation undergoing diuresis, using the difference between weights recorded on the day of RHC and the day of discharge, under the assumption that a greater decrease in weight reflected more successful diuresis. This study had the ethical approval of the local Colorado Multiple institutional review board (protocol No. 22-2024).

Statistical Methods

Continuous and categorical descriptive characteristics of the cohort were displayed using mean ± SD and frequency (%), respectively. We performed multivariable linear regression to determine relationships between VExUS grade, RAP, mPAP, and PCWP, CO, and cardiac index, controlling for possible confounders of age, sex, and Charlson Comorbidity Index (CCI).³⁷ Covariates were selected a priori to minimize overfitting. Specific conditions known to be associated with elevated RAP were avoided because of concern for colinearity, in favor of the broader variable of the CCI. We also modeled associations between VExUS grade and changes in weight between RHC and discharge, E/E', Nagueh LAP, and cardiac biomarkers NT-ProBNP and high-sensitivity troponin. Multivariable logistic regression models were developed to evaluate the relationship between the dependent variable of AKI with explanatory variables of VExUS grade, CO, cardiac index, RAP, mPAP, and PCWP. Model diagnostics were conducted using visual and statistical tests of homoscedasticity and normality of residuals. Variance inflation factors were calculated for covariates, and outliers were assessed using studentized residuals. Receiver operating characteristic curve and calculated area under the curve (AUC) were derived for VExUS grade, IVC diameter, and IVC collapsibility index¹⁷ to predict a RAP > 10 and < 7 mm Hg. VExUS grade was coded as a categorical variable in all calculations. We also determined optimal VExUS grade cutoffs for the presence of a RAP > 10 and < 7 mm Hg by Youden indexing.³⁸ Calculations were completed using R statistical software (version 4.2.1 2022-06-23; R Foundation for Statistical Computing).

Results

One hundred patients were screened for inclusion in the study. Of these, nine were excluded because of incarceration or inability to consent. Six patients’ RHC procedures were canceled, and four patients were excluded because of poor image quality (Fig 1). Of the 81 patients included in the study, 45 underwent RHC while hospitalized, and 36 were scheduled outpatient procedures. Demographic parameters and relevant outcomes are presented in Table 1. Ultrasonographic and hemodynamic parameters are recorded in Table 2. After adjusting for age, sex, and CCI, there were significant relationships between a VexUS grade of 2 (β = 4.8; 95% CI, 2.6-7.1; P < .01) and 3 (β = 11; 95% CI, 8.9-14; P < .01) and RAP, VExUS grade of 2 (β = 6.8; 95% CI, 0.16-13; P = .045) and 3 (β = 15; 95% CI, 7.3-22; P < .01) and mPAP, and VExUS grade of 2 (β = 7.0; 95% CI, 3.9-10; P < .01) and 3 (β = 13; 95% CI, 9.5-17; P < .01) and PCWP (Fig 2). AUC values for VExUS, IVC diameter, and IVC collapsibility index (ICI) as predictors of RAP > 10 mm Hg were 0.9 (95% CI, 0.83-0.97), 0.77 (95% CI, 0.68-0.88), and 0.65 (95% CI, 0.52-0.78), respectively (Fig 3). AUC values for VExUS, IVC diameter, and ICI as predictors of RAP < 7 mm Hg were 0.79 (95% CI, 0.70-0.87), 0.74 (95% CI, 0.64-0.84), and 0.62 (95% CI, 0.49-0.76) respectively. After adjusting for age, sex, and CCI, there were statistically significant linear relationships between VExUS grade and RAP (R² = 0.55, P < .01), mPAP (R² = 0.16, P < .01), and PCWP (R² = 0.50, P ≤ .01) (Fig 2). A statistically significant linear association between VExUS and PCWP persisted after controlling for RAP (R² = 0.66, P < .01). There were also significant linear associations between VExUS grade and inpatient AKI (P = .03) and NT-ProBNP level (P = .05) (Table 3, Table 4). There was also a positive linear associations between AKI and biomarker and RHC measurements of elevated preload (RAP and PCWP), but not with CO or cardiac index. No correlation was shown between VExUS grade and high-sensitivity troponin level or change in creatinine level between time of RHC and discharge (P > .10). The AUC values for VExUS, IVC diameter, and ICI as predictors of RAP > 10 mm Hg were 0.9 (95% CI, 0.83-0.97), 0.77 (95% CI, 0.68-0.88), and 0.65 (95% CI, 0.52-0.78), respectively. AUC values for VExUS, IVC diameter, and ICI as predictors of RAP < 7 mm Hg were 0.79 (95% CI, 0.70-0.87), 0.74 (95% CI, 0.64-0.84), and 0.62 (95% CI, 0.49-0.76), respectively (Fig 3). The optimal VExUS grade cutoff to predict a RAP < 7 mm Hg was 1 with a sensitivity of 0.95 (95% CI, 0.64-1.00) and a specificity of 0.56 (95% CI, 0.46-0.86). The optimal VExUS grade cutoff to predict a RAP > 10 mm Hg was 2, with a sensitivity of 0.87 (95% CI, 0.75-0.97) and a specificity of 0.9 (95% CI, 0.73-0.96) (e-Appendix 2). Average duration of the examination was 10 min (range, 8-13 min).

Figure 1.

Patient enrollment flow diagram. VExUS = venous excess ultrasound.

Table 1.

Clinical and Demographic Characteristics of the Study Population (N = 81)

Characteristic	Value
Respiratory rate, breaths/min	18 (16-18)
Oxygen saturation, %	96.0 (93.0-98.0)
Heart rate, beats/min	78 (65-89)
Temperature, °C	36.4 (36.3-36.7)
Mean arterial pressure, mm Hg	92 (84-103)
Age, y	61 (54-70)
Sex
Male	55 (69)
Female	25 (31)
BMI, kg/m2	27 (25-33)
History of heart failure with reduced ejection fraction	45 (56)
History of myocardial infarction	17 (22)
History of COPD	23 (28)
ESRD on HD	2 (3.1)
History of pulmonary hypertension	30 (38)
History of cirrhosis	6 (7.5)
Charlson Comorbidity Index	3.5 (2.0-5.0)
Right heart catheterization indication
Angina	8 (10)
Cardiogenic shock	1 (1)
Cardiomyopathy	3 (4)
Combined heart failure	3 (4)
Coronary artery disease	4 (5)
Diastolic heart failure	3 (4)
Dyspnea	4 (5)
NSTEMI	2 (2)
Pericardial disease	2 (2)
Pulmonary hypertension	9 (11)
Respiratory failure	2 (2)
Syncope	1 (1)
Systolic heart failure	21 (26)
Unspecified heart failure	12 (15)
Valvular disease	6 (7)

Values are No. (%) for categorical variables and value (interquartile range) for continuous variables. ESRD = end-stage renal disease; HD = hemodialysis; NSTEMI = non-ST elevation myocardial infarction.

Table 2.

Ultrasonographic and Physiologic Characteristics of the Study Population (N = 81)

Characteristic	Value
Maximum IVC diameter, cm	2.16 (1.79-2.46)
Hepatic vein status
Normal	41 (51)
Mildly abnormal	19 (23)
Severely abnormal	20 (25)
Unable To assess	1 (1.2)
Portal vein status
Normal	48 (59)
Mildly abnormal	21 (26)
Severely abnormal	12 (15)
Unable to assess	0 (0)
Renal vasculature status
Normal	64 (79)
Mildly abnormal	8 (9.9)
Severely abnormal	9 (11)
Unable to assess	0 (0)
VExUS grade
0	30 (37)
1	25 (31)
2	15 (19)
3	11 (14)
VExUS examination duration, min	10 (8-13)
Mean right atrial pressure, mm Hg	7 (4-11)
Right ventricular systolic pressure, mm Hg	37 (30-44)
Mean pulmonary arterial pressure, mm Hg	25 (20-30)
Pulmonary capillary wedge pressure, mm Hg	12 (8-16)
Fick cardiac index, L/min/m2	2.14 (1.90-2.43)
Pulmonary vascular resistance, dynes/s/cm−5	240 (165-329)
Tricuspid regurgitation	32 (40)
Tricuspid stenosis	0 (0)
Pulmonary valve pathology	11 (14)
Mitral regurgitation	34 (42)
Mitral stenosis	1 (1.3)
Aortic regurgitation	11 (14)
Aortic stenosis	3 (3.8)
Average E/E' ratio	13 (9-17)
Nagueh left atrial pressure, mm Hg	17 (13-23)
NT-ProBNP, pg/mL	2,477 (400-5,286)
High-sensitivity troponin, ng/L	28 (14-86)
Acute kidney injury	18 (22)
Outpatient RHC	36 (44)

Values are No. (%) for categorical variables and value (interquartile range) for continuous variables. IVC = inferior vena cava; NT-ProBNP = N-terminal pro-brain natriuretic peptide; RHC = right heart catheterization; VExUS = venous excess ultrasound.

Figure 2.

There were significant linear associations between VExUS grade and intracardiac pressures measured by right heart catheterization. Data presented as violin plots with demarcated quartiles. Width of the column represents the proportion of data located there. VExUS = venous excess ultrasound.

Figure 3.

For detection of RAP > 10 mm Hg, the AUC for VExUS was 0.9 (95% CI, 0.83-0.97) compared with 0.77 (95% CI, 0.68-0.87) for IVC diameter and 0.65 (95% CI, 0.52-0.78) for IVC collapsibility. For detection of RAP < 7 mm Hg, the AUC for VExUS was 0.8 (95% CI, 0.71-0.87) compared with 0.77 (95% CI, 0.67-0.89) for IVC diameter. VExUS examination was superior to IVC diameter alone as a means of predicting elevated RAP. AUC = area under the curve; IVC = inferior vena cava; RAP = right atrial pressure; VExUS = venous excess ultrasound.

Table 3.

Associations With Venous Excess Ultrasound Grade 3

Dependent Variable	No. of Patients	Adjusted R2 Value	P Value
Right atrial pressure, mm Hg	81	0.59	< .01a
Mean pulmonary artery pressure, mm Hg	81	0.25	< .01a
Pulmonary capillary wedge pressure, mm Hg	81	0.50	< .01a
Fick cardiac output, L/m	81	0.16	.02a
Fick cardiac index, L/min/m2	81	0.1	.07
Troponin, ng/mL	81	0.26	.07
NT-ProBNP, pmol/L	81	0.34	.03a
E/E' ratio	81	0.28	.01a
Nagueh left atrial pressure, mm Hg	81	0.23	.01a
Change in weight, kg	23	0.43	.09
LOS, d	45	0.2	< .01a

Results of linear and logistic regression models are shown using venous excess ultrasound grade as an independent variable, controlling for age, sex, and Charlson Comorbidity Index. Adjusted R² values are reported for models of continuous dependent variables, and McFadden pseudo-R² values are reported for binary dependent variables. P values are reported for venous excess ultrasound grade, modeled as a continuous variable. LOS = length of stay; NT-ProBNP = N-terminal pro-brain natriuretic peptide.

^aP < .05.

Table 4.

Hemodynamic and Ultrasonographic Predictors of Acute Kidney Injury

Independent Variable	No. of Patients	McFadden Pseudo-R2 Value	P Value
Cardiac output	81	0.1	.31
Cardiac index	81	0.08	.64
Right atrial pressure, mm Hg	81	0.192	.03a
Mean pulmonary artery pressure, mm Hg	81	0.087	.50
Pulmonary capillary wedge pressure, mm Hg	81	0.18	.031a
VExUS grade 3	81	0.26	.02a

Logistic regression results are shown using a dependent variable of acute kidney injury, modeled as a binary variable, controlling for age, sex, and Charlson Comorbidity Index. VExUS = venous excess ultrasound.

^aP < .05.

In a subset of patients hospitalized for heart failure and undergoing diuresis with weight data available (n = 23), there was not a statistically significant association between VExUS and change in weight between time of RHC and discharge when VExUS was coded as a categorical variable. However, when VExUS was coded as a continuous variable, this relationship was significant (P = .019) (e-Fig 2). In the same subset, there was not a significant relationship between change in weight and change in creatinine, or VExUS grade and change in creatinine.

Discussion

In this preliminary study, we found strong correlations between VExUS grade and both RHC measurements, the current standard for measuring venous congestion, and clinically relevant patient outcomes in a population of adult patients undergoing RHC. Importantly, the VExUS technique had greater ability to predict elevated RAP values than measurement of IVC diameter alone or ICI, both routinely used as surrogates in standard echocardiogram protocols. These findings align with those of a recent study of 124 patients with heart failure comparing a three-component ultrasound score to IVC characteristics, which showed an AUC of 0.84 (95% CI, 0.77-0.92), slightly less accurate than VExUS results.¹⁴ That study also found IVC measurements alone to have a lower AUC (0.75; 95% CI, 0.67-0.83), comparable with findings in the current study. Although there are multiple innovative techniques for measuring venous hypertension, some form of invasive hemodynamic monitoring, and specialized skills and equipment, and considerable time and expertise is required.^9,10 In contrast, the median examination time of the 10 min we observed suggests that VExUS could feasibly be incorporated into routine clinical practice. VExUS is also relatively easy to teach, requiring only a remote video course with image evaluation to achieve adequate results. Other studies have found similar results, a finding supported by previous studies demonstrating feasibility of VExUS in clinical practice.^{39, 40, 41, 42}

The finding that VExUS grade was independently associated with PCWP after adjusting for RAP is intriguing, with multiple possible explanations. This finding may reflect a set of patients with longstanding venous or portal hypertension whose hepatic and renal vascular beds have undergone chronic remodeling. Alternatively, it has been suggested that splanchnic vasodilation may result in a larger reservoir of unstressed blood volume in the peripheral vascular beds, decompressing the right atrium by maintaining more volume in the periphery.^{43, 44, 45} Given this, it is possible that this finding represents a group of patients with splanchnic vasodilation (eg, patients with hepatic cirrhosis), who would have greater peripheral congestion while being intravascularly dry. Another consideration is that although PCWP is consistently measured at end expiration, VExUS is vulnerable to respirophasic variation that could amplify measurements of venous flow in a patient who is spontaneously breathing. In the end, the finding is hypothesis-generating but may suggest that VExUS is able to detect elevation in LAP prior to the development of venous congestion. Regardless, the number of patients in our study with isolated elevated PCWP values was small, and the observed relationship should be interpreted with caution. The greater correlation between VExUS grade and PCWP than VExUS and E/E' or Nagueh LAP may show the limitations of E/E' or Nagueh LAP as effective proxies for systemic venous congestion when compared with VExUS.

The association between elevated VExUS grade and inpatient AKI is consistent with findings by the authors of the original VExUS study, which found that among patients who were post-cardiac surgery, an elevated VExUS grade on ICU admission score had a positive likelihood ratio of 6.37 (95% CI, 2.19-18.50) for predicting cardiorenal AKI.²² This finding is also consistent with findings by Bhardwaj et al,³⁹ who found significant associations between longitudinal improvement in VExUS grade and improvement in renal function in patients diagnosed with cardiorenal syndrome. A third recent study also found a correlation between day 1 VExUS grade and AKI in patients undergoing acute coronary syndrome.²⁶ The current study further supports prior evidence that an elevated VExUS grade is representative of pathologic venous hypertension leading to cardiorenal syndrome and renal injury.⁴⁶ Interestingly, the current study supported the previous findings of Guglin et al⁴⁷ and Winton,¹¹ redemonstrating that AKI was associated with increased cardiac filling pressures, but not with cardiac index or CO, suggesting a greater contribution from venous hypertension rather than impaired CO.

A potential clinical use for VExUS was suggested by the subgroup analysis of hospitalized patients with heart failure undergoing diuresis, in whom an elevated VExUS grade was associated with greater weight loss over the course of their hospitalization, representing more successful diuresis. This suggests a potential role for VExUS in predicting diuretic potential during heart failure admissions. The fact that no relationship was observed between change in creatinine level and change in weight, or between VExUS grade and change in creatinine level, supports previous studies in suggesting that serum creatinine level is an unreliable marker of renal function or diuretic success during AKI.^48,49 Indeed, there is evidence to suggest that increases in serum creatinine level when associated with evidence of venous congestion are associated with better patient outcomes.⁵⁰

The persistence of the relationship between VExUS and RHC measurements in a more diverse patient population than has been previously reported is an important strength of this study and increases the generalizability of the VExUS examination, suggesting the potential of VExUS in the evaluation of noncardiac pathologies (eg, as a measurement of fluid tolerance during initial resuscitation of patients with septic shock). Additionally, all RHCs were conducted in a dedicated cardiac laboratory at a high-volume center, where standardization of practice and quality of measurements are likely to be higher than in patients undergoing continuous central pressure monitoring in the ICU. However, like all diagnostic tests, VExUS has inherent diagnostic limitations, and must be interpreted in the potentially confounding clinical context of each patient. This is especially true because of the sensitive nature of VExUS grading, in which a patient need have only one severe finding to be judged as having moderate congestion. For example, a patient with hepatic cirrhosis with concomitant GI bleeding may demonstrate portal vein pulsatility despite intravascular hypotension. Similarly, a patient with severe tricuspid regurgitation may show retrograde flow during systole in their hepatic vein Doppler tracing despite low cardiac filling pressures. Based on current VExUS guidelines, each of these patients could be graded as having moderate venous congestion, but would be unlikely to benefit from diuresis, highlighting the importance of patient-specific physiology.

A notable weakness of this study is the inclusion to a single center and the small sample size that, although inclusive of a diverse set of pathologies, is insufficient to fully evaluate the validity of VExUS in a full spectrum of patient subpopulations. For example, VExUS scoring may be confounded in patients with cirrhosis and tense ascites, severe tricuspid regurgitation, or chronic kidney disease—all populations in which local vascular flow could be altered for reasons other than increased venous pressures, and future studies should be dedicated to evaluation of VExUS in these populations. Furthermore, we did not include patients who were critically ill and unable to provide their own informed consent, or judged too unstable to undergo RHC, leading to a selection bias toward patients who were less severely ill. This is particularly relevant for patients undergoing mechanical ventilation because the effects of positive pressure ventilation on VExUS remain unknown and warrant further investigation. Finally, as in all ultrasound measurements, data acquisition and interpretation are significantly dependent on user experience and technique. Further assessment of the human factor aspects regarding VExUS performance, including duration of examinations, interobserver reliability of image interpretation, and interuser reproducibility of diagnostic images, remains scarce, and further study of implementation is required before VExUS should be recommended broadly.

Interpretation

This study suggests that VExUS assessment may provide an accurate reflection of venous congestion as measured by RHC in a select population of patients undergoing elective RHC across a variety of common cardiac pathologies. Elevated VExUS grade showed high sensitivity and specificity for detecting elevated RAP when compared with other common bedside assessment techniques. An elevated VExUS grade was also associated with AKI in hospitalized patients, building on prior studies suggesting that VExUS can detect pathologic renal venous hypertension as a component of AKI. The association between VExUS and decrease in weight among patients with heart failure undergoing diuresis suggests that VExUS may be predictive of diuretic responsiveness and diuretic resistance in this patient population. Although further study of the technique is required, our results suggest that VExUS has the potential to increase the diagnostic and therapeutic capabilities of physicians at the bedside and increase our understanding of the underappreciated problem of venous congestion.

Future studies should focus on understanding VExUS performance among more diverse patient populations in which the technique might be confounded. Test performance using interobserver reliability and interuser reproducibility of users at different stages of training would be important as a prerequisite for prospective evaluation of VExUS to guide therapy (eg, diuresis in patients with heart failure, fluid resuscitation in patients with septic shock).

Funding/Support

The authors have reported to CHEST that no funding was received for this study.

Financial/Nonfinancial Disclosures

None declared.