a PRagmatic Observational Study of Congestion proFILes in patiEnts With Acute Heart Failure (PROFILE-AHF)

a PRagmatic Observational Study of Congestion proFILes in patiEnts With Acute Heart

The goal of this observational is to study the prevalence of distinct congestion phenotypes and study their association with response to therapy and outcomes in acute heart failure patients. The main question[s] it aims to answer [is/are]:

• Primary objective: to study the prevalence of distinct congestion phenotypes

• Other objectives (including):

  • Response to therapy as assessed by

    • Natriuresis after 24 hours
    • Rehospitalization and/or deats after 6 months
  • Length of hospital stay
  • Congestion at discharge
  • Changes in filling pressures over time
  • Relationship between liver stiffness, as assessed with Fibroscan and congestion
  • Substudy: glycosaminoglycan netword and endothial glycocalyx

Participants will undergo several extra study related measurements:

• Assessment of filling pressures with ultrasound
• Ultrasound investigation of the lungs and kidneys
• Fibroscan of the liver
• Sidestream darkfield imaging sublingual
• As part of substudy GLYCO-AHF: skin biopsy to determine glycocalyx, as well as salt and water content.
• As part of substudy PREACH-AHF: the effects of peripheral venous congestion and endothelial dysfunction on a large screen of plasma proteins

Study Overview

• Status: Recruiting
• Conditions: Acute Heart Failure

Detailed Description

Objective: to study the prevalence of distinct congestion phenotypes and investigate their association with response to therapy and outcomes in acute heart failure patients.

Study design: Observational, prospective study

Study population: 270 patients admitted with the primary diagnosis of acute heart failure requiring intravenous loop diuretics.

Main study parameters/endpoints:

To identify distinct congestion phenotypes and study their association with response to therapy and outcomes

Secondary outcomes: total natriuresis after 24 hours, and first occurrence of all-cause mortality or heart failure rehospitalisation at 6 months Exploratory outcomes include: length of hospital stay, congestion at discharge and changes in filling pressures over time. Furthermore, as part of the GLYCO-AHF substudy: the expression of glycosaminoglycans and, as part of the PREACH-AHF substudy: the effects of peripheral venous congestion and endothelial dysfunction on a large screen of plasma proteins.

• Study Type: Observational
• Enrollment (Estimated): 270

Contacts and Locations

• Study Contact: Name: Jozine M. ter Maaten, MD, PhD; Phone Number: +31503616161; Email: j.m.ter.maaten@umcg.nl
• Study Contact Backup: Name: Lara E.E.C. Zonneveld, MD; Phone Number: +31503616161

Study Locations

• Netherlands
  • Groningen, Netherlands
    • Recruiting
    • UMCG
    • Contact: Lara E.E.C. Zonneveld, MD; Phone Number: +31503616161; Email: l.e.e.c.zonneveld@umcg.nl

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Adult patients admitted to the hospital with a primary diagnosis of acute heart failure

Description

Inclusion Criteria:

• Able and willing to give written informed consent
• Age ≥ 18 years
• Male or female
• Primary diagnosis of acute heart failure at presentation, with signs and symptoms of tissue decongestion. Diagnosis is based on the criteria in the ESC HF guidelines (1)
• Requirement of intravenous loop diuretics

Exclusion Criteria:

• Patients with severe kidney dysfunction (in need for ultrafiltration or dialysis)
• Previous participation in this study
• Inability to follow instructions
• Dyspnoea or oedema primarily due to non-cardiac causes

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To study the prevalence of distinct congestion phenotypes	Based on the degree of congestion and edema in combination with intravascular pressures, patients will be classified into different phenotypes (high/low intravascular pressures and extensive/minimal edema.	From date of hospital admission untill the date of discharge (from this admission), with an expected discharge after 5 to 10 days after admission.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total natriuresis after 24 hours	To assess this, urine is collected for 24 hours after the first administration of diuretics according to the hospital protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L).with natriuresis as the primary outcome measure.	24 hours
Rehospitalization and/or death after 6 months		180 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Congestion at discharge	Congestion at discharge will be assessed by several measures; clinical symptoms (e.g. orthopnoea, dyspnoea), physical examination (e.g. oedema, rales, jugular venous pressure), ultrasound examination (lungs, heart, inferior vena cava,.	Date of discharge, or maximum two days before. Expected to be between 5-10 days after admission.
Changes in filling pressures over time	Using either a Swan Ganz catheter (if present as part of standard of care) or echocardiography, intravasculair filling pressures will be measured daily.	From date of hospital admission untill the date of discharge, or maximum two days before. Expected to be between 5-10 days after admission.
Length of stay	Number of days of the index hospitalization	Variable, from date of admission untill date of discharge. Expected to be between 5-10 days after admission.
Liver stiffness, as assessed with Fibroscan	Congestion of the liver reflected by liver stifness will be determined after admission and at discharge (with maximum two days before).	From date of hospital admission untill the date of discharge, or maximum two days before. Expected to be between 5-10 days after admission.
Differences in microvasculature	Subligual sidestream darkfield imaging will be performed at day 1 or 2 and will be repeated at discharge (or maximum two days before). This technique allows for a detailed observation of capillary blood flow, capillary density and glycocalyx integrity. Comparing the microvasculature between the different congestion phenotype groups, as well as studying changes in the microvasculature from admission to discharge will provide novel information with regards to the microvasculature in AHF patients.	From date of hospital admission untill the date of discharge, or maximum two days before. Expected to be between 5-10 days after admission.
(Substudy GLYCO-AHF): Differences in glycosaminoglycan network	A skin biopsy will be performed at day 1 or 2. At discharge, or maximum two days before, patients will receive a second skin biopsy. With the biopsy the glycosaminoglycan network and glygocalyx can be determined. Cryosections will be stained using available antibodies for glycosaminoclycans, whereafter their immunochemical expression will be quantified. The expression will be compared between both the different patient groups (based on phenotype) as well as between the two biopsies (at admission and at discharge).	From date of hospital admission untill the date of discharge, or maximum two days before. Expected to be between 5-10 days after admission.
(Substudy PREACH-AHF): Effects of peripheral venous congestion on plasma proteins	To study the effect of peripheral venous congestion and endothelial dysfunction on plasma proteins, blood samples will be taken via an intravenous line before and after inflating a pressure cuff, while a pressure transducer measures the peripheral venous pressure. Patients will also undergo a reactive hyperaemia index measurement to investigate the link between plasma proteins and endothelial dysfunction. These measurements will be performed at discharge or a maximum of 2 days before.	Date of discharge, or maximum two days before.

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: August 25, 2024
• First Submitted That Met QC Criteria: September 4, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: 20486

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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