Incorporating the Venous Excess Ultrasound Score (VExUS Score) Into Contemporary Haemodynamic Risk Assessment in Pulmonary Arterial Hypertension: The INVEXUS-PAH Study (INVEXUS-PAH)

This prospective observational study aims to evaluate the relationship between the Venous Excess Ultrasound Score (VEXUS) and the ESC/ERS 2022 simplified four-strata risk assessment model in adult patients with World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH). The study investigates whether VEXUS can enhance risk stratification and predict haemodynamic congestion by correlating VEXUS with functional, biochemical, and invasive haemodynamic parameters.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH); Pulmonary Arterial Hypertension (PAH)

Detailed Description

Pulmonary arterial hypertension (PAH) is a progressive disorder characterised by increased pulmonary vascular resistance, right ventricular overload, systemic venous congestion, and high mortality. The ESC/ERS 2022 simplified four-strata model (low, intermediate-low, intermediate-high, high risk) guides treatment decisions using WHO functional class, 6-minute walk distance, and BNP/NT-proBNP levels.

However, biochemical markers may be costly or insufficiently sensitive to early haemodynamic deterioration.

VEXUS (Venous Excess Ultrasound Score), a point-of-care ultrasonographic method assessing hepatic, portal, and renal venous Doppler patterns, has shown promise in representing venous congestion.

This study evaluates whether VEXUS correlates with ESC/ERS risk categories and invasive haemodynamic parameters including right atrial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance, cardiac output, and pulmonary output. The study further aims to explore whether integrating VEXUS into PAH follow-up may strengthen risk assessment.

• Study Type: Observational
• Enrollment (Actual): 86

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • FATIH
    • Istanbul, FATIH, Turkey (Türkiye), 34098
      • Istanbul University-Cerrahpasa Institute of Cardiology

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 diagnosed with World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH) who are being followed at a tertiary pulmonary hypertension centre. Participants represent a real-world cohort of clinically stable PAH patients attending routine outpatient follow-up visits. All participants undergo non-invasive assessment including VEXUS ultrasonography, 6-minute walk test (6MWT), WHO functional class evaluation, and BNP measurement at the study visit. Recent right and/or left heart catheterisation data (performed within ±2 months for standard clinical indications) are collected from medical records. Patients with other forms of pulmonary hypertension, Eisenmenger syndrome, pulmonary veno-occlusive disease, or pulmonary capillary haemangiomatosis are excluded.

Description

Inclusion Criteria

• Adults aged ≥18 years
• Established diagnosis of WHO Group 1 pulmonary arterial hypertension (PAH)
• Stable outpatient clinical status at the time of VExUS ultrasonography
• Venous Excess Ultrasound Score (VExUS) evaluation performed with adequate ultrasonographic acoustic windows
• Clinically indicated right heart catheterisation (RHC) performed within ±60 days of VExUS assessment
• Availability of ESC/ERS 2022 simplified risk assessment variables (WHO functional class, BNP/NT-proBNP, and 6-minute walk distance)
• Ability to provide written informed consent

Exclusion Criteria

• Pulmonary hypertension other than WHO Group 1, including:

  • PH due to left heart disease (WHO Group 2)
  • PH due to chronic lung disease or hypoxaemia (WHO Group 3)
  • Chronic thromboembolic pulmonary hypertension (CTEPH; WHO Group 4)
  • Multifactorial PH (WHO Group 5)
  • Eisenmenger syndrome
  • Complex or unrepaired congenital heart disease
• Suspected pulmonary veno-occlusive disease (PVOD)
• Pulmonary capillary haemangiomatosis (PCH)
• Acute decompensated right heart failure
• Severe renal dysfunction (eGFR <30 mL/min/1.73 m²)
• Severe hepatic impairment (Child-Pugh Class C)
• Congestive hepatopathy
• Active infection
• Pregnancy
• Inability or unwillingness to provide informed consent
• Poor ultrasonographic acoustic window preventing adequate VExUS scoring

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

PAH Cohort; Adults with World Health Organization (WHO) Group 1 pulmonary arterial hypertension undergoing non-invasive assessment with the Venous Excess Ultrasound Score (VEXUS) and the ESC/ERS 2022 simplified four-strata risk model during routine clinical follow-up. No intervention is administered; this is an observational cohort with a single study visit in which VEXUS, 6MWT, BNP, WHO-FC and recent haemodynamic parameters are collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between the VExUS Score and Invasive Haemodynamic Parameters	Correlation between the VExUS Score (0-3 Doppler-based venous congestion score) and invasive haemodynamic measurements obtained by right heart catheterisation, including pulmonary vascular resistance (PVR; Wood units), right atrial pressure (RAP; mmHg), Fick-derived cardiac output (L/min) and pulmonary blood flow (PBF; L/min).	At the single study visit (Day 0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between the VExUS Score and Non-Invasive Clinical Markers	Correlation between the VExUS Score and serum B-type natriuretic peptide (BNP; pg/mL), WHO functional class (4-level ordinal scale) and six-minute walk distance (metres), which form key components of current ESC/ERS risk stratification models.	Day 0
Correlation Between the VExUS Score and Echocardiographic RV-PA Coupling Indices	Correlation between the VExUS Score and tricuspid annular plane systolic excursion (TAPSE; mm) and the TAPSE/systolic pulmonary artery pressure ratio (unitless).	Day 0
Predictive Value of the VExUS Score for Elevated Pulmonary Vascular Resistance (≥ 6 Wood Units)	Evaluation of the predictive performance of the VExUS Score for identifying patients with elevated pulmonary vascular resistance (≥ 6 Wood units). Predictive metrics (including odds ratios) will be reported.	Day 0
Incremental Contribution of the VExUS Score to ESC/ERS Four-Strata Risk Classification	Change in ESC/ERS simplified four-strata risk category after incorporation of the VExUS Score, including net reclassification and risk-category shifts.	Day 0

Collaborators and Investigators

• Sponsor: Istanbul University - Cerrahpasa
• Investigators: Principal Investigator: SAHRA ASENA BALCIOGLU, MD, Istanbul University-Cerrahpasa Institute of Cardiology

Publications and helpful links

General Publications

• Boucly A, Weatherald J, Savale L, Jais X, Cottin V, Prevot G, Picard F, de Groote P, Jevnikar M, Bergot E, Chaouat A, Chabanne C, Bourdin A, Parent F, Montani D, Simonneau G, Humbert M, Sitbon O. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017 Aug 3;50(2):1700889. doi: 10.1183/13993003.00889-2017. Print 2017 Aug.
• Beaubien-Souligny W, Rola P, Haycock K, Bouchard J, Lamarche Y, Spiegel R, Denault AY. Quantifying systemic congestion with Point-Of-Care ultrasound: development of the venous excess ultrasound grading system. Ultrasound J. 2020 Apr 9;12(1):16. doi: 10.1186/s13089-020-00163-w.
• Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, Ferreira DS, Ghofrani HA, Giannakoulas G, Kiely DG, Mayer E, Meszaros G, Nagavci B, Olsson KM, Pepke-Zaba J, Quint JK, Radegran G, Simonneau G, Sitbon O, Tonia T, Toshner M, Vachiery JL, Vonk Noordegraaf A, Delcroix M, Rosenkranz S; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022 Oct 11;43(38):3618-3731. doi: 10.1093/eurheartj/ehac237. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2025
• Primary Completion (Actual): November 5, 2025
• Study Completion (Actual): November 21, 2025

Study Registration Dates

• First Submitted: November 23, 2025
• First Submitted That Met QC Criteria: December 3, 2025
• First Posted (Estimated): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 6, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Pulmonary Arterial Hypertension; Risk Stratification; Right Ventricular Function; doppler ultrasound; Venous Congestion; VExUS
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Hyperemia
• Other Study ID Numbers: 2025/618IUCIC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Only de-identified individual participant data (IPD) related to primary and secondary outcome measures may be shared with qualified researchers upon reasonable request. No direct identifiers or protected health information will be released.
• IPD Sharing Time Frame: Beginning 12 months after publication of the primary manuscript and for up to 3 years thereafter.
• IPD Sharing Access Criteria: Requests must be submitted in writing to the principal investigator. Data will be provided only for methodologically sound proposals and after review by the institutional data governance committee. A data use agreement (DUA) will be required.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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