Portal Vein Flow Variability to Quantify Right-Sided Hemodynamic Congestion: A Proof-Of-Concept Study
Phase: NA
Conditions: Congestion, Heart Failure, Right Heart Catheterisation, Central Venous Pressure, Doppler Echocardiography
Sponsor: Vrije Universiteit Brussel

 
 
 
 
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Study Protocol  
 
Study Title: Portal Vein Flow Variability to Quantify Right-Sided Hemodynamic Congestion: A Proof-
Of-Concept study 
Study Acronym: PORTAL 
Phase of Development: N/A 
Protocol Number: 3 
Protocol Version and Date: Version 3.0, May 30th, 2022  
EudraCT Registry Number: N/A 
ClinicTrials.gov Registry Number:  
Investigational product: None 
 
 
 
 
 
 
 
Sponsor: UZ Brussel 
  
Coordinating/Principal Investigator: Prof. Dr. Frederik Verbrugge 
 
 
The information contained in this document is the property of the Sponsor/Coordinating Investiga-
tor and may not be reproduced, published or disclosed to others without written authorization of 
the Sponsor/Coordinating Investigator. 
PROTOCOL SIGNATURE PAGE 
 
Protocol Version and date: Version 3.0, May 30th, 2022 
 
 
Protocol Title: Portal Vein Flow Variability to Quantify Right-Sided Hemodynamic Congestion: A 
Proof-Of-Concept study 
 
 
Sponsor: UZ Brussel 
 
 
 
 
 
 
Principal Investigator: Prof. Dr. Frederik Verbrugge 
 
 
 
I agree: 
- 
to assume responsibility for the proper conduct of this study 
- 
to conduct the study in compliance with this protocol and any future amendments  
- 
not to implement any deviations from or changes to the protocol without prior review 
and written approval from the Ethics Committee, except where necessary to eliminate 
an immediate hazard to the subjects, or for administrative aspects of the study (where 
permitted by all applicable regulatory requirements) 
- 
that I am thoroughly familiar with the appropriate use of the investigational drug, as 
described in this protocol 
- 
to ensure that all persons assisting me with the study are adequately informed about 
the investigational drug and their study-related duties and functions as described in the 
protocol 
- 
that I am aware of and will comply with the current good clinical practice (GCP) guide-
lines and ethical principles outlined in the Declaration of Helsinki 
- 
to conduct the study in accordance with all applicable laws and regulations 
 
 
Printed name: Frederik Verbrugge                   Signature                                      Date: 30/05/2022 
 

 
 
 
 
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Study Protocol 
 
Portal Vein Flow Variability to Quantify Right-Sided 
Hemodynamic Congestion (PORTAL): 
 
 
A Proof-Of-Concept study 
 
 
Simon Vanhentenrijk M.D. Pharm.D. & Frederik H. Verbrugge M.D. Ph.D. 
 
1. Study design 
 
 
Prospective 
 
 
Interventional 
 
 
Single centre (UZ Brussel) 
 
 
Proof-of-concept 
 
 
2.  Purpose & rationale 
 
Right ventricular hemodynamic congestion or elevated central venous pressure (CVP) is an in-
dependent predictor of morbidity and mortality in heart failure (1). Persistent elevations of right 
atrial pressure (RAP) cause upstream venous congestion in the abdominal compartment, which 
leads to organ dysfunction in liver and kidney function, with effects on the lungs as well (2), (3). 
According to contemporary echocardiography guidelines, non-invasive assessment of RAP is 
performed by measuring inferior vena cava (IVC) size and respiratory variation (i.e., collapsibility) 
(4). However, assumptions that are not always valid (especially in critically ill patients) hamper 
the use of this technique and misinterpretation due to ‘pseudo-collapse’ could lead to erroneous 
interpretation. 

 
 
 
 
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Portal vein Doppler flow patterns may be a simple and attractive tool to aid in the evaluation of 
RAP/CVP and predicts acute kidney injury after cardiac surgery (5). The aim of this proof-of-
concept study is to assess the feasibility of portal vein Doppler flow to quantify RAP/CVP in a 
population of consecutive patients with advanced heart failure undergoing invasive right heart 
catheterization. 
 
3. Objective 
 
To evaluate the accuracy of the portal vein pulsatility index (PVPI=Vmax-Vmin)/Vmax) to quantify 
invasively measured right-sided venous pressures. 
 
4. Study population 
 
a. Inclusion criteria 
 
 
At least 18 y/o and able to provide informed consent 
 
Consecutive patients scheduled for right heart catheterisation by a dedicated heart failure 
specialist at the Centre of Cardiovascular Diseases (University Hospital Brussels, Jette, Bel-
gium) 
 
b. Exclusion criteria 
 
 
Major anatomical variations of the portal veins (agenesis of left and right portal vein) and/or 
arterio-portal vein fistula 
 
Patients with Child-Pugh B or C liver cirrhosis or liver transplant 
 
Body Mass Index < 20 kg/m² 
 
5. Intervention 
 
All patients will undergo right heart catheterisation for clinical reasons. As part of the hemodynamic 
assessment, RAP and CVP assessed at the level of the intrathoracic and intra-abdominal IVC as 
well as the vena Hepatica is measured. In addition, the hepatic venous wedge pressure (HVWP) is 
measured. 
PVPI is simultaneously obtained using point-of-care ultrasound by placing the transducer at the right 
hypochondrium/right lateral region of the corpus. Portal vein flow velocity is obtained by using pulsed 

 
 
 
 
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wave Doppler measurements of the left portal vein. In addition, a non-invasive measuring device to 
assess the mechanical energy of the heart by registering its vibrations (i.e., Kinocardiography, 
HeartKinetics, Waterloo, Belgium) is put on the participant with sticky-gel electrodes. A 90-second 
measurement is done once the patient is in the supine position. The same measurement is per-
formed simultaneously by a smartphone application with the smartphone placed centrally on the 
participant’s chest. 
To minimize interobserver variability, the same sonographic equipment will be used by the same, 
independent researcher. Measurements are obtained in supine position at the end of the respiratory 
cycle (end-expiratory). In order to correlate the study outcome with clinical situations, demographic 
characteristics of the participants are collected.  
 
6. Safety precautions 
 
There are no known risks except for those of the clinically indicated right heart catheterisation. Echo-
cardiography can cause local discomfort and in rare occasions contusion from local pressure. The 
Kinocardiography device is completely non-invasive as well, although theoretically, there might be 
some skin irritation due to its attachment with sticky-gel electrodes. 
 
7. Statistical analysis 
 
a. Main statistical analysis 
 
The correlation between PVPI and RAP, CVP and HVWP will be assessed by classic regression 
and Bland-Altman plots. A regression formula for RAP will be constructed based on PVPI and age, 
gender, height and weight if the latter are contributory.  
 
8. References 
 
1. 
Binanay C, Califf RM, Hasselblad V, O'Connor CM, Shah MR, Sopko G, et al. Evaluation 
study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE 
trial. Jama. 2005;294(13):1625-33. 
2. 
Verbrugge FH, Guazzi M, Testani JM, Borlaug BA. Altered Hemodynamics and End-Organ 
Damage in Heart Failure: Impact on the Lung and Kidney. Circulation. 2020;142(10):998-1012. 
3. 
Verbrugge FH, Dupont M, Steels P, Grieten L, Malbrain M, Tang WH, et al. Abdominal 
contributions to cardiorenal dysfunction in congestive heart failure. J Am Coll Cardiol. 
2013;62(6):485-95. 

 
 
 
 
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4. 
Porter T, Shillcutt  S, Adams  M, Desjardins  G, Glas  K, Olson  J, Troughton R, et al. 
Guidelines for the use of echocardiography as a monitor for therapeutic intervention in adults: a 
report from the American Society of Echocardiography. J Am Soc Echocardiogr. 2015 Jan;28(1):40-
56. 
5. 
Beaubien-Souligny W, Rola P, Haycock K, Bouchard J, Lamarche Y, Spiegel R, et al. 
Quantifying systemic congestion with Point-Of-Care ultrasound: development of the venous excess 
ultrasound grading system. Ultrasound J. 2020;12(1):16.