Right Ventriculo-Arterial Coupling During Fluid Loading in ICU Patients (RVPA-FLICU)

Prospective Observational Study of Right Ventriculo-arterial Coupling Changes During Fluid Loading and Their Relationship With Congestion Parameters in Critically Ill Adults

Preload responsiveness and venous congestion have largely been investigated independently in recent literature. However, recent data report a similar incidence of venous congestion regardless of fluid responsiveness status, challenging the concept of a linear continuum between preload independence and fluid intolerance. These findings support the need for a more individualized hemodynamic management strategy that takes venous congestion risk into account.

The right ventricle plays a central role in this framework. Its function is to maintain an adequate venous return pressure gradient to ensure cardiac output while limiting upstream venous congestion, under strong dependence on its afterload. In physiological conditions, the right ventricle adapts to changes in afterload by increasing contractility to preserve right ventriculo-arterial coupling and optimize its performance.

In chronic cardiopulmonary diseases, right ventriculo-arterial uncoupling is a well-established prognostic factor, including the presence of occult uncoupling revealed by fluid loading. In critically ill patients, right ventricular systolic dysfunction associated with venous congestion-defining right heart failure-is strongly associated with increased mortality, as is right ventriculo-arterial uncoupling itself.

To support the concept of fluid tolerance, the investigators hypothesize that impairment of right ventriculo-arterial coupling may exist or occur during fluid loading in critically ill patients, independently of preload responsiveness, and may be associated with worsening upstream venous congestion.

Study Overview

• Status: Not yet recruiting
• Conditions: Shock; Right Ventricular Dysfunction; Venous Congestion
• Intervention / Treatment: Other: Echography

Detailed Description

This is a prospective observational study designed to evaluate right ventriculo-arterial coupling dynamics during fluid loading in critically ill patients with acute circulatory failure. The study aims to characterize alterations in coupling, their relationship with venous congestion, and the performance of different echocardiographic indices used to quantify right ventricular function and coupling.

Study Population:

Critically ill adult patient in intensive care unit who require fluid loading as part of routine clinical management, based on the attending physician's discretion. Eligible patients may present with hypotension requiring vasopressor support, low mean arterial pressure, or other signs of hemodynamic instability. Patients are prospectively and consecutively included, reflecting standard ICU practice.

Study Procedures:

Fluid loading is administered according to current clinical guidelines. Echocardiographic assessment of the right ventricle is performed immediately before and after fluid administration. The primary measure of RVPA is the TAPSE/TRV ratio. Additional echocardiographic parameters will be collected and other validated indices to define RVPA to allow comparisons across methods.

Secondary Analyses:

Secondary analyses will stratify patients based on fluid responsiveness, defined as a ≥10% increase in cardiac output after fluid loading, and on the presence of venous congestion assessed by VExUS score and portal vein pulsatility. Baseline hemodynamic and echocardiographic parameters will be analyzed to identify predictors of RVPA deterioration. The relationship between RVPA and upstream venous congestion, organ dysfunction, ICU length of stay, and mortality will also be explored. Reproducibility of right ventricule parameters measurements will be assessed by calculating intra- and inter-observer variability.

Technical Considerations:

Echocardiography will be performed by trained operators using standardized acquisition protocols.

Measurements will include TAPSE, tricuspid regurgitation velocity, tricuspid S-wave velocity, PASP, FAC, and IVC diameter.

Data will be recorded before fluid loading and immediately after completion of the fluid challenge, typically within 30 minutes.

Fluid responsiveness will be assessed according to standard dynamic parameters or maneuvers selected by the attending physician.

Patients with poor echogenicity, acute respiratory distress, ongoing myocardial infarction, acute cor pulmonale, or other exclusion criteria will not be included.

Rationale:

The right ventricle is a key determinant of venous return and cardiac output, and its function is highly dependent on afterload. RVPA reflects the efficiency of coupling between right ventricular contractility and pulmonary arterial load. Understanding RVAC dynamics during fluid loading may inform individualized fluid management strategies, potentially minimizing venous congestion and organ dysfunction. Comparing different echocardiographic indices allows evaluation of their relative performance and reliability in detecting RV uncoupling in critically ill patients.

Data Management and Analysis:

All echocardiographic and hemodynamic data will be collected prospectively and recorded in a secure database. Changes in RVAC before and after fluid loading will be analyzed descriptively and in association with fluid responsiveness and venous congestion parameters. Agreement between different RVAC indices will be assessed using correlation and Bland-Altman analyses. Predictive models may be developed to identify baseline factors associated with RVAC deterioration.

Ethical Considerations:

Fluid loading is part of routine clinical care. No experimental interventions are applied. All patients or their legally authorized representatives will provide informed consent in accordance with institutional and national regulations.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Morgan CAPLAN; Phone Number: 0033 03 10 73 60 22; Email: mcaplan@chu-reims.fr
• Study Contact Backup: Name: Guillaume THERY; Email: gthery@chu-reims.fr

Study Locations

• France
  • Reims, France
    • Marie Muller
    • Contact: Morgan CAPLAN; Phone Number: 0033 03 10 73 60 22; Email: mcaplan@chu-reims.fr
    • Contact: Guillaume THERY; Email: gthery@chu-reims.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult critically ill patients with acute circulatory failure. Eligible patients are those for whom the attending physician independently decides to perform fluid loading as part of standard care, in accordance with current European recommendations. Patients may present with hypotension requiring vasopressor support, low mean arterial pressure, or other signs of hemodynamic instability.

Participants are prospectively and consecutively included at the time of fluid loading decision, and undergo standardized echocardiographic assessment of right ventricular function and venous congestion before and after fluid administration. The population reflects routine clinical practice in the intensive care unit.

Description

Inclusion criteria:

• Critically ill hospitalized patients
• Age ≥ 18 years
• Patients undergoing fluid loading at the discretion of the attending physician, following prediction of fluid responsiveness using any recommended maneuver or dynamic parameter, in the setting of acute circulatory failure requiring vasopressor support and/or mean arterial pressure < 65 mmHg (or a decrease of ≥ 30 mmHg from baseline in patients with chronic hypertension), and/or other signs of hemodynamic instability (tachycardia, mottling, oliguria, hyperlactatemia)
• Affiliated with a national health insurance system

Exclusion criteria :

• Formal refusal from the patient or legally representative after information
• Patients transferred from another intensive care unit
• Pregnant or postpartum patients
• Acute respiratory distress (defined as respiratory rate ≥ 35 breaths/min and/or signs of increased work of breathing)
• Ongoing acute coronary syndrome
• Acute or pulmonale (defined by right ventricular dilation associated with paradoxical septal motion related to an abrupt increase in right ventricular afterload)
• Primary pulmonary arterial hypertension
• Intra-abdominal hypertension (intravesical pressure > 15 mmHg)
• Poor echogenicity precluding adequate echocardiographic assessment of the right ventricle
• Severe valvular heart disease or early postoperative period following valvular surgery

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Critically Ill Patients Receiving Fluid Loading; The study group consists of adult critically ill patients admitted to the intensive care unit who undergo fluid loading as part of routine clinical care, at the discretion of the attending physician. All patients are prospectively and consecutively included in a single observational cohort. Echocardiographic assessment of right ventricular function, right ventriculo-arterial coupling, and venous congestion parameters is performed before and after fluid administration. The group will be analyzed as a whole, with secondary analyses stratifying patients according to fluid responsiveness or presence of venous congestion. This cohort reflects standard clinical practice in critically ill patients with acute circulatory failure.

Other: Echography; Fluid loading administered according to standard clinical practice at the discretion of the treating physician. Echocardiographic assessment of right ventricular function and venous congestion is performed before and after fluid administration. No experimental treatment is applied.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right Ventriculo-Arterial Coupling Changes During Fluid Loading	Echocardiographic assessment of right ventriculo-arterial coupling will be performed using the TAPSE/TRV ratio before and after fluid loading. The primary outcome is the change in TAPSE/TRV, reflecting alterations in right ventricular contractility and coupling with the pulmonary circulation in response to fluid administration. This outcome will be used to evaluate the prevalence and dynamics of RV uncoupling in critically ill patients.	Before a fluid loading procedure (approximately 30 min)
Right Ventriculo-Arterial Coupling Changes During Fluid Loading	Echocardiographic assessment of right ventriculo-arterial coupling will be performed using the TAPSE/TRV ratio before and after fluid loading. The primary outcome is the change in TAPSE/TRV, reflecting alterations in right ventricular contractility and coupling with the pulmonary circulation in response to fluid administration. This outcome will be used to evaluate the prevalence and dynamics of RV uncoupling in critically ill patients.	after a fluid loading procedure (approximately 30 min)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variation of Right Ventriculo-Arterial Coupling According to Fluid Responsiveness	Changes in right ventriculo-arterial coupling (TAPSE/TRV ratio) will be compared between fluid responders (RV+) and non-responders (RV-) to assess the influence of fluid responsiveness on coupling dynamics.	Before a single fluid loading episode
Variation of Right Ventriculo-Arterial Coupling According to Fluid Responsiveness	Changes in right ventriculo-arterial coupling (TAPSE/TRV ratio) will be compared between fluid responders (RV+) and non-responders (RV-) to assess the influence of fluid responsiveness on coupling dynamics.	after a single fluid loading episode
Association Between Right Ventriculo-Arterial Coupling and Venous Congestion	The relationship between TAPSE/TRV ratio and upstream venous congestion parameters, including VExUS score and portal vein pulsatility, will be evaluated to determine the impact of right ventricular uncoupling on venous congestion.	Before fluid loading
Association Between Right Ventriculo-Arterial Coupling and Venous Congestion	The relationship between TAPSE/TRV ratio and upstream venous congestion parameters, including VExUS score and portal vein pulsatility, will be evaluated to determine the impact of right ventricular uncoupling on venous congestion.	after fluid loading
Predictors of Right Ventriculo-Arterial Coupling Deterioration	Baseline hemodynamic and echocardiographic parameters will be analyzed to identify predictors of subsequent deterioration in right ventriculo-arterial coupling during fluid loading.	before fluid loading
Comparison of Echocardiographic Parameters Across Groups	Echocardiographic indices characterizing right ventricular function and coupling will be compared between fluid responders, non-responders, and patients with or without venous congestion to assess differences in right ventricular performance.	before fluid loading
Comparison of Echocardiographic Parameters Across Groups	Echocardiographic indices characterizing right ventricular function and coupling will be compared between fluid responders, non-responders, and patients with or without venous congestion to assess differences in right ventricular performance.	after fluid loading
Comparison of Echocardiographic Parameters Characterizing Right Ventriculo-Arterial Coupling	Different echocardiographic indices of right ventriculo-arterial coupling, including TAPSE/PASP ratio, tricuspid S-wave velocity/PASP ratio, and other validated measures, will be compared to assess their agreement and performance in detecting right ventricular uncoupling. Analyses will consider fluid responsiveness and presence of venous congestion.	before fluid loading
TAPSE/PASP Ratio as a Marker of Right Ventriculo-Arterial Coupling Coupling	The TAPSE/PASP ratio will be measured by echocardiography to assess right ventriculo-arterial coupling. Its diagnostic performance in detecting right ventricular uncoupling will be evaluated, considering fluid responsiveness and the presence of venous congestion./PASP ratio, tricuspid S-wave velocity/PASP ratio, and other validated measures, will be compared to assess their agreement and performance in detecting right ventricular uncoupling. Analyses will consider fluid responsiveness and presence of venous congestion.	after fluid loading
Tricuspid S-wave Velocity/PASP Ratio as a Marker of Right Ventriculo-Arterial Coupling	The tricuspid annular S-wave velocity/PASP ratio will be measured by echocardiography to assess right ventriculo-arterial coupling. Its diagnostic performance in detecting right ventricular uncoupling will be evaluated, considering fluid responsiveness and the presence of venous congestion.	After fluid loading
Agreement Between Echocardiographic Indices of Right Ventriculo-Arterial Coupling	The level of agreement between the different validated echocardiographic indices of right ventriculo-arterial coupling (TAPSE/PASP ratio, tricuspid S-wave velocity/PASP ratio) will be assessed using Bland-Altman analysis and intraclass correlation coefficients. Analyses will account for fluid responsiveness and the presence of venous congestion.	After fluid loading

Collaborators and Investigators

• Sponsor: CHU de Reims

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: April 16, 2026
• First Posted (Actual): April 17, 2026

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Fluid loading; Venous congestion; VEXUS score; Right ventriculo-arterial coupling; Critical care echocardiography
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Ventricular Dysfunction; Pathological Conditions, Signs and Symptoms; Shock; Ventricular Dysfunction, Right; Hyperemia; Physical Phenomena; Radiation; Radiation, Nonionizing; Ultrasonic Waves; Sound; High-Energy Shock Waves
• Other Study ID Numbers: PL26041

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No