Echocardiographic Right Ventricular Evaluation in Assessment of ARDS Lung Recruitment (ECHO-REVEAL) ((ECHO-REVEAL))

Study Goal The goal of this observational, multicenter study is to evaluate how positive end-expiratory pressure (PEEP) affects right ventricular (RV) function in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation. Researchers will assess the Recruitment-to-Inflation (R/I) ratio, a measurement used to determine whether increasing PEEP helps open the lungs or causes harmful effects on the heart and circulation.

Main Study Questions

This study aims to answer the following questions:

1. How does PEEP affect right heart function in ARDS patients?
2. Can the R/I ratio predict whether PEEP will have a beneficial or harmful impact on the heart?
3. Which echocardiographic parameters best detect changes in right ventricular function caused by PEEP?

Who Can Participate?

Patients will be included in the study if they meet the following criteria:

• Age: 18 to 80 years.
• Condition: Diagnosed with moderate-to-severe ARDS, with a PaO₂/FiO₂ ratio <200 mmHg (an indicator of severe breathing difficulty).
• Mechanical Ventilation: Receiving invasive ventilation with at least 5 cmH₂O of PEEP and in deep sedation (fully dependent on the ventilator).
• Cardiac Monitoring: Equipped with a MostCare Up or equivalent device for continuous heart function monitoring.
• Informed Consent: Given directly by the patient or through a legal representative.

Patients will not be included in the study if they:

• Have severe pulmonary hypertension (high pressure in the lungs, ≥70 mmHg).
• Have a tricuspid valve prosthesis or other implanted cardiac devices that interfere with echocardiographic imaging.
• Have undergone recent heart surgery (within the past month).
• Have severe tricuspid valve disease that makes it difficult to assess right heart function.
• Are hemodynamically unstable, requiring high doses of medication to maintain blood pressure.
• Have poor ultrasound imaging conditions that prevent accurate heart scans.
• Have recently had a pulmonary embolism or have known blockages in the pulmonary arteries.
• Are receiving extracorporeal membrane oxygenation (ECMO) support.

Study Procedures

Participants will undergo a series of tests to measure the impact of PEEP on lung and heart function:

1. Initial Airway Closure Test: Patients will be evaluated while on a low PEEP level of 5 cmH₂O for 10 minutes to confirm eligibility.

2. Recruitment-to-Inflation (R/I) Ratio Assessment:

   • PEEP will be adjusted between low (5 cmH₂O) and high (15 cmH₂O) levels.
   • Researchers will measure changes in lung mechanics and heart function using ultrasound.

3. Echocardiographic Heart Function Assessment:

   • Transthoracic echocardiography (TTE) will be performed at each PEEP level to assess the right ventricle (RV) and circulation in the lungs.
   • Researchers will measure RV strain, size, and blood flow to determine how the heart reacts to PEEP changes.
4. Data Collection:

oKey respiratory and hemodynamic parameters will be recorded, including heart strain, cardiac output, pulmonary artery pressure, and venous congestion.

Primary and Secondary Study Outcomes

• Primary Outcome: The study will evaluate how RV function changes in response to different PEEP levels, using 2D RV strain measurements as a key indicator.

• Secondary Outcomes: Researchers will assess:

  • How accurately echocardiographic measurements (e.g., TAPSE, FAC, VExUS score) detect changes in RV function.
  • The relationship between the VExUS score (a marker of venous congestion) and RV strain changes.
  • The sensitivity and specificity of echocardiographic findings in predicting heart function shifts under different PEEP levels.

Statistical Analysis

• Researchers will compare echocardiographic heart function results at high PEEP vs. low PEEP using statistical models.
• The relationship between the R/I ratio and RV function will be analyzed using correlation tests and logistic regression.
• Receiver Operating Characteristic (ROC) analysis will be used to determine which echocardiographic parameter best detects RV dysfunction when the R/I ratio is low.

Study Size and Impact The study aims to enroll 60 patients (30 per group) to ensure that results are reliable. This sample size was calculated to detect at least a 10% change in RV strain, with a 90% probability of identifying significant effects.

Expected Benefits of the Study This study will help critical care doctors better understand how to adjust PEEP settings to balance lung recruitment and heart function in ARDS patients. By identifying the best methods to detect right heart dysfunction early, this research could lead to improved ventilation strategies and better survival outcomes for patients with severe lung injury.m

Study Overview

• Status: Active, not recruiting
• Conditions: ARDS
• Intervention / Treatment: Diagnostic test: PEEP Titration with Echocardiographic, Hemodynamic, and Ventilatory Measurements

Detailed Description

Study Summary

The purpose of this study is to assess how positive end-expiratory pressure, commonly referred to as PEEP, influences right ventricular function with particular attention to the recruitment-to-inflation ratio in patients diagnosed with acute respiratory distress syndrome who require mechanical ventilation. Conducted as a multicenter, observational, and prospective study across multiple intensive care units, the study aims to establish a correlation between PEEP-induced variations in right ventricular function and the recruitment-to-inflation ratio. By investigating this relationship, researchers intend to refine mechanical ventilation strategies and improve patient outcomes.

Background

Acute respiratory distress syndrome is a severe lung condition marked by widespread inflammation, alveolar collapse, and significant hypoxemia, often necessitating mechanical ventilation for respiratory support. While PEEP is essential in maintaining alveolar recruitment and improving oxygenation, its application can also negatively impact cardiac function. By increasing intrathoracic pressure, PEEP raises pulmonary vascular resistance and right ventricular afterload, potentially leading to right ventricular dysfunction. To address this, the recruitment-to-inflation ratio has emerged as a promising bedside tool that assesses lung recruitability versus the risk of overdistension. The ECHO-REVEAL study is designed to investigate whether this ratio can predict right ventricular dysfunction, potentially enabling a more tailored approach to ventilator settings that balances respiratory support with cardiovascular stability.

Methodology

Standard Operating Procedures (SOPs)

To ensure consistency in study implementation and data collection, the following Standard Operating Procedures (SOPs) have been developed and will be followed across all study sites:

SOP 2: Screening and Enrollment - Defines the criteria and process for selecting eligible patients.

SOP 3: Informed Consent and Privacy Form - Ensures compliance with ethical and legal guidelines.

SOP 4: Bedside Protocol - Provides step-by-step guidance for conducting PEEP titration and echocardiographic measurements.

SOP for Data Export and Transmission - Standardizes the process for securely transferring recorded echocardiographic and hemodynamic data.

SOP for VExUS Score - Establishes the methodology for assessing venous congestion using ultrasound.

Patient Recruitment and Data Collection

Patients will be recruited from three intensive care units specializing in advanced hemodynamic and respiratory monitoring. Upon ICU admission, patients will be screened based on eligibility criteria. Informed consent will be obtained before inclusion. The study involves detailed data collection at various PEEP levels to assess the correlation between lung recruitability and right ventricular function.

Recruitment Maneuver

The recruitment maneuver consists of stepwise adjustments in PEEP to evaluate lung recruitability. Initially, patients will be stabilized at a low PEEP level of 5 cmH₂O for baseline measurements. After 10 minutes, PEEP will be increased to 15 cmH₂O and maintained for 15 minutes. During these phases, extensive echocardiographic, ventilatory, and hemodynamic measurements will be recorded. Following this, PEEP will be returned to 5 cmH₂O to assess whether observed physiological changes are reversible. The maneuver allows for real-time evaluation of lung compliance, gas exchange, and hemodynamic responses, providing insight into the interplay between mechanical ventilation settings and cardiac function.

Collected Variables

The study will systematically collect a range of variables at both low and high PEEP levels to evaluate the interaction between lung recruitment and right ventricular function. These include:

Echocardiographic Parameters:

Right ventricular longitudinal strain (2D speckle-tracking echocardiography)

Tricuspid annular plane systolic excursion (TAPSE)

Right ventricular fractional area change (RVFAC)

Pulmonary artery systolic pressure (sPAP)

Right ventricular end-diastolic area/left ventricular end-diastolic area ratio (RVEDA/LVEDA)

Right ventricular myocardial performance index (RIMP)

Venous excess ultrasound (VExUS) score to assess systemic venous congestion

Inferior vena cava (IVC) diameter and collapsibility index

Ventilatory Parameters:

Respiratory system compliance (Crs)

Plateau pressure (Pplat) and driving pressure (ΔP)

Airway resistance (Raw)

Tidal volume (Vt) and minute ventilation

End-expiratory lung volume (EELV)

Recruitment-to-Inflation (R/I) ratio calculated at different PEEP levels

Hemodynamic Parameters:

Cardiac output (continuous monitoring using MostCare Up)

Systemic vascular resistance (SVR)

Central venous pressure (CVP)

Right atrial pressure (RAP)

Mean arterial pressure (MAP)

Pulmonary vascular resistance index (PVRI)

Stroke volume variation (SVV) as an indicator of preload dependency

These variables will be measured at both low and high PEEP settings, allowing for a comprehensive evaluation of the cardiopulmonary interactions involved in ARDS management.

Outcome Evaluation and Quality Control

To ensure the reliability and accuracy of the primary outcome, all echocardiographic measurements, particularly right ventricular strain analysis, will be evaluated by a blinded expert operator in echocardiography. This independent evaluation will minimize bias and improve the robustness of the data. Additionally, periodic quality control assessments will be conducted to verify adherence to the study protocol.

Conclusion

The ECHO-REVEAL study aims to improve acute respiratory distress syndrome management by integrating echocardiographic right ventricular function assessment with lung recruitability metrics. By determining the optimal PEEP settings that enhance alveolar recruitment without negatively impacting right ventricular function, this study has the potential to significantly influence ventilatory management strategies in intensive care units. Ultimately, the findings may contribute to the development of more personalized approaches to mechanical ventilation that optimize both pulmonary function and cardiovascular stability in critically ill patients.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • Hôpital Erasme - Cliniques universitaires de Bruxelles
  • Brussels, Belgium, 1000
    • Hôpital universitaire - CHU Saint-Pierre
• Italy
  • Bari, Italy, 70100
    • Azienda Ospedaliero Universitaria Consorziale Policlinico

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 patients (aged 18-80 years) diagnosed with moderate-to-severe acute respiratory distress syndrome (ARDS) who are undergoing mechanical ventilation in intensive care units (ICUs) at participating medical centers. Participants will be recruited from tertiary care hospitals specializing in critical care and echocardiography, specifically from the Intensive Care Units (ICU) of the following institutions:

1. Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Italy - Department of Intensive Care
2. Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium - Department of Intensive Care
3. Centre Hospitalier Universitaire (CHU) Saint-Pierre, Brussels, Belgium - Department of Intensive Care The study focuses on critically ill patients requiring invasive mechanical ventilation, where PEEP titration and recruitment maneuvers are part of standard clinical practice.

Description

Inclusion Criteria:

• Patients within 1 week from the diagnosis of acute respiratory distress syndrome (ARDS), defined according to the Berlin criteria.
• Non-pregnant.
• Age greater than or equal to 18 years.
• Monitored through MostCare Up or any other system for cardiac output (CO) monitoring and with invasive CVP catheter.
• Able to provide written informed consent to participate in the study directly or by a delegate.

Exclusion Criteria:

• Patients with severe pulmonary hypertension for any causes, defined by am echocardiographic PAPs ≥ 70 mmHg.
• Patients with tricuspid valve prostheses or percutaneous implanted devices (Triclip).
• Patients recently (within 1 month) undergoing cardiac surgery involving pericardiotomy.
• Patients with pre-existing severe tricuspid regurgitation.
• Patients with haemodynamic instability requiring high-dose vasopressors and/or inotropic agents in which recruitment manoeuvre are not considered to be safe according to clinical judgement.
• Patients whose acoustic window does not allow for the acquisition of the measurements under examination with transthoracic echocardiography.
• Patients with documented moderate-to-severe pulmonary embolism or known pulmonary artery stenosis.
• Patients undergoing Extracorporeal Membrane Oxygenation (ECMO).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
High Recruitment-to-Inflation (R/I) Ratio Group; This cohort includes ARDS patients with a Recruitment-to-Inflation (R/I) ratio > 0.5, indicating high lung recruitability in response to increased PEEP. These participants undergo a structured PEEP titration protocol, where ventilatory and hemodynamic parameters are assessed at low PEEP (5 cmH₂O) and high PEEP (15 cmH₂O). The primary focus is on evaluating right ventricular function, pulmonary pressures, and systemic hemodynamics to determine if high recruitability is associated with better tolerance to PEEP without inducing RV dysfunction.	Diagnostic test: PEEP Titration with Echocardiographic, Hemodynamic, and Ventilatory Measurements; This intervention consists of clinical recruitment maneuvers performed in mechanically ventilated patients by adjusting positive end-expiratory pressure (PEEP) at two levels: low PEEP (5 cmH₂O) and high PEEP (15 cmH₂O). Throughout these maneuvers, echocardiographic imaging, hemodynamic assessments, and ventilatory measurements are performed to evaluate the cardiorespiratory effects of PEEP adjustments. Transthoracic echocardiography (TTE) is used to assess right ventricular function, pulmonary pressures, and venous congestion, while mechanical ventilator parameters are recorded to monitor lung mechanics and compliance.; Other Names: Recruitment Maneuvers with Cardiorespiratory Monitoring
Low Recruitment-to-Inflation (R/I) Ratio Group; This cohort consists of ARDS patients with a Recruitment-to-Inflation (R/I) ratio < 0.5, signifying limited lung recruitability and an increased risk of lung overdistension when PEEP is raised. These participants undergo the same PEEP titration protocol, with echocardiographic and ventilatory assessments at 5 cmH₂O and 15 cmH₂O PEEP levels. The objective is to evaluate the hemodynamic impact of higher PEEP in patients with poor lung recruitability, particularly in terms of right ventricular strain, pulmonary vascular resistance, and systemic venous congestion.	Diagnostic test: PEEP Titration with Echocardiographic, Hemodynamic, and Ventilatory Measurements; This intervention consists of clinical recruitment maneuvers performed in mechanically ventilated patients by adjusting positive end-expiratory pressure (PEEP) at two levels: low PEEP (5 cmH₂O) and high PEEP (15 cmH₂O). Throughout these maneuvers, echocardiographic imaging, hemodynamic assessments, and ventilatory measurements are performed to evaluate the cardiorespiratory effects of PEEP adjustments. Transthoracic echocardiography (TTE) is used to assess right ventricular function, pulmonary pressures, and venous congestion, while mechanical ventilator parameters are recorded to monitor lung mechanics and compliance.; Other Names: Recruitment Maneuvers with Cardiorespiratory Monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association Between the Recruitment-to-Inflation (R/I) Ratio and Right Ventricular Dysfunction in Mechanically Ventilated ARDS Patients	The primary outcome of this study is to determine whether an unfavorable Recruitment-to-Inflation (R/I) ratio (<0.5) is associated with right ventricular (RV) dysfunction in ARDS patients undergoing PEEP titration during mechanical ventilation. RV function will be assessed through 2D speckle-tracking echocardiography (STE) of the RV free wall longitudinal strain (RVFWS) at low PEEP (5 cmH₂O) and high PEEP (15 cmH₂O). The study hypothesizes that patients with an R/I ratio <0.5 will show a significant increase (less negative values) in RV strain at high PEEP, indicating impaired RV function due to excessive lung overdistension and increased pulmonary vascular resistance.	Within 30 minutes of PEEP titration at both high and low PEEP levels.

Collaborators and Investigators

• Sponsor: University of Bari
• Collaborators: Erasme University Hospital; Centre Hospitalier Universitaire Saint Pierre
• Investigators: Study Chair: Francesco Grasso, Medicine and Surgery, University of Bari Aldo Moro

Publications and helpful links

General Publications

• WHITTENBERGER JL, McGREGOR M, BERGLUND E, BORST HG. Influence of state of inflation of the lung on pulmonary vascular resistance. J Appl Physiol. 1960 Sep;15:878-82. doi: 10.1152/jappl.1960.15.5.878. No abstract available.
• Zapol WM, Snider MT. Pulmonary hypertension in severe acute respiratory failure. N Engl J Med. 1977 Mar 3;296(9):476-80. doi: 10.1056/NEJM197703032960903.
• Mahmood SS, Pinsky MR. Heart-lung interactions during mechanical ventilation: the basics. Ann Transl Med. 2018 Sep;6(18):349. doi: 10.21037/atm.2018.04.29.
• Vieillard-Baron A, Schmitt JM, Augarde R, Fellahi JL, Prin S, Page B, Beauchet A, Jardin F. Acute cor pulmonale in acute respiratory distress syndrome submitted to protective ventilation: incidence, clinical implications, and prognosis. Crit Care Med. 2001 Aug;29(8):1551-5. doi: 10.1097/00003246-200108000-00009. Erratum In: Crit Care Med 2002 Mar;30(3):726.
• Vieillard-Baron A, Prin S, Chergui K, Dubourg O, Jardin F. Echo-Doppler demonstration of acute cor pulmonale at the bedside in the medical intensive care unit. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1310-9. doi: 10.1164/rccm.200202-146CC. No abstract available.
• Banavasi H, Nguyen P, Osman H, Soubani AO. Management of ARDS - What Works and What Does Not. Am J Med Sci. 2021 Jul;362(1):13-23. doi: 10.1016/j.amjms.2020.12.019. Epub 2020 Dec 26.
• Price LC, McAuley DF, Marino PS, Finney SJ, Griffiths MJ, Wort SJ. Pathophysiology of pulmonary hypertension in acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2012 May 1;302(9):L803-15. doi: 10.1152/ajplung.00355.2011. Epub 2012 Jan 13.
• Evrard B, Goudelin M, Giraudeau B, Francois B, Vignon P. Right ventricular failure is strongly associated with mortality in patients with moderate-to-severe COVID-19-related ARDS and appears related to respiratory worsening. Intensive Care Med. 2022 Jun;48(6):765-767. doi: 10.1007/s00134-022-06730-0. Epub 2022 May 12. No abstract available.
• Repesse X, Charron C, Vieillard-Baron A. Acute cor pulmonale in ARDS: rationale for protecting the right ventricle. Chest. 2015 Jan;147(1):259-265. doi: 10.1378/chest.14-0877.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2025
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: February 2, 2025
• First Submitted That Met QC Criteria: February 2, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 11, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: ARDS; Mechanical Ventilation; PEEP; Right ventricle; Acute Respiratory Syndrome; Heart-lung interaction; Right Ventricular Strain; Recruitment manouvres; critical care ultrasounds
• Other Study ID Numbers: Prot.2026/CEL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared due to ethical considerations, patient confidentiality, and data protection regulations. The study involves sensitive clinical and echocardiographic data collected from critically ill patients in intensive care units, which are subject to strict privacy and institutional policies. Additionally, the study protocol does not include provisions for external data sharing. However, aggregated and anonymized results will be made available through scientific publications and conference presentations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No