Biomarkers in Patients With Suspected HFpEF

Recruiting

• Conditions: Obesity; Heart Failure With Preserved Ejection Fraction; Heart Failure
• Interventions: Diagnostic Test: Plasma biomarker levels

• Registration Number: NCT06101693
• Lead Sponsor: NHS Greater Glasgow and Clyde

Brief Summary

NT-proBNP does not adequately identify HF(pEF) in people with suspected HF at low levels, particularly in patients with obesity. This study will investigate:

1. alternative cut-offs for NT-proBNP to identify HF(pEF) in people with suspected HF and obesity

2. novel candidate biomarkers to identify HF(pEF) in people with suspected HF and obesity.

3. novel candidate biomarkers to identify HF(pEF) in people with suspected HF and NT-proBNP \<125 ng/L

4. the prevalence of HF in people with suspected HF and low NT-proBNP \<125 ng/L)

Detailed Description

This will be a prospective observational, non-randomised study of patients in primary care with suspected HF.

Detection of HFpEF in people without obesity is well-served by NT-proBNP. In contrast, NT-proBNP does not perform well when used to detect HFpEF in populations with obesity. There is increasing evidence that some people with low levels of NT-proBNP can have HF. As many as 50% of people with obesity and HFpEF (detected by elevated filling pressures) have NT-proBNP \<125 ng/L. Some patients with HFpEF who are not obese can also have low natriuretic peptides levels.

Delayed diagnosis can lead to adverse outcomes for patients, in particular presentation acutely to secondary care. In addition to this, some patients with HFpEF who are not obese can also have low natriuretic peptides levels.

Patients with NTproBNP levels performed in the community for stable symptoms of suspected heart failure will be invited to participate.

Assessments in this study will include clinical history and examination, patient-reported outcome measures, electrocardiography, echocardiography and biomarker (blood and urine) analysis. Heart failure diagnostic scores and clinical evaluation by heart failure experts will be used to make a clinical diagnosis of heart failure, and to correlate this with levels of plasma and urine biomarkers, both established and novel.

Patients will be followed up passively (for a minimum of 10 years) using record linkage for subsequent hospitalisations or deaths.

Study Timeline

• Study Start: 2023-02-02
• Study First Submitted: 2023-10-20
• Study First Submitted QC: 2023-10-20
• Study First Posted: 2023-10-26
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-10
• Last Update Posted: 2024-02-13
• Primary Completion: 2025-09-29
• Study Completion: 2026-09-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1028

Inclusion Criteria

• Written informed consent
• Age ≥ 18 years
• NT-proBNP sample taken by primary care physician as part of routine care for suspected heart failure

Exclusion Criteria

• Unable to consent to inclusion in study due to significant cognitive impairment
• Geographical/ social reasons preventing attending study centre
• Unable to complete study assessments
• Patients presenting with acute HF or a previous diagnosis of HF

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with NTproBNP<125ng/L and clinical suspicion of heart failure in primary care	Plasma biomarker levels	Expected recruitment of 400 patients (50-60% expected prevalence of obesity, according to population study)
Patients with NTproBNP125-399ng/L and clinical suspicion of heart failure in primary care	Plasma biomarker levels	Expected recruitment of 400 patients (50% expected prevalence of obesity, according to population study)
Patients with NTproBNP≥400ng/L and clinical suspicion of heart failure in primary care	Plasma biomarker levels	Expected recruitment of 400 patients (50% expected prevalence of obesity, according to population study)

Primary Outcome Measures

Name	Time	Method
Optimal cut-offs for NT-proBNP to identify HFPEF in obese patients with suspected heart failure	3 years	To determine the utility and diagnostic performance of alternative cut-offs for NT-proBNP or combinations of biomarkers (including novel biomarker solutions)- with clinical variables to identify HFpEF in obese patients with suspected heart failure. (New biomarkers will be used for observational purposes only.)

Secondary Outcome Measures

Name	Time	Method
Utility and diagnostic performance of biomarkers (novel and adjusted stratified cut-offs) in patients with suspected HF (HFPEF, HFmREF, HFREF).	3 years	To determine the utility and diagnostic performance of novel biomarkers, adjusted N-terminal pro-B-type natriuretic peptide (NT-proBNP) cut-offs or combinations of biomarkers with clinical variables in patients with suspected HF (HFpEF, HFmrEF, HFrEF). (New biomarkers will be used for observational purposes only.)
Optimal cut-offs for biomarkers to identify HFPEF in patients with suspected HF.	3 years	To determine the utility and diagnostic performance of alternative cut-offs for NT-proBNP or combinations of biomarkers (including novel biomarker solutions) with clinical variables to identify HFpEF in patients (with and without obesity) and suspected HF.
Prevalence of HF in patients with NT-proBNP<125ng/L	3 years	To identify the prevalence of HF in patients with NT-proBNP \<125 ng/L with and without obesity, and suspected HF.

Trial Locations

Locations (3)

Glasgow Royal Infirmary; 🇬🇧 Glasgow, United Kingdom

New Victoria Hospital; 🇬🇧 Glasgow, United Kingdom

Queen Elizabeth University Hospital; 🇬🇧 Glasgow, United Kingdom