Biomarkers in Patients With Suspected HFpEF

Study Overview
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Brief Summary
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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: alternative cut-offs for NT-proBNP to identify HF(pEF) in people with suspected HF and obesity novel candidate biomarkers to identify HF(pEF) in people with suspected HF and obesity. novel candidate biomarkers to identify HF(pEF) in people with suspected HF and NT-proBNP <125 ng/L the prevalence of HF in people with suspected HF and low NT-proBNP <125 ng/L)

Detailed Description
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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.

Official Title
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Biomarkers in Patients With Suspected Heart Failure With Preserved Ejection Fraction

Conditions
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Heart Failure, Obesity, Heart Failure With Preserved Ejection Fraction

Intervention / Treatment
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* Diagnostic Test: Plasma biomarker levels


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with NTproBNP<125ng/L and clinical suspicion of heart failure in primary care<br>Expected recruitment of 400 patients (50-60% expected prevalence of obesity, according to population study) | Diagnostic Test: Plasma biomarker levels<br>* This study will investigate the diagnostic utility and performance of: Alternative cut-offs for NT-proBNP to identify HF(pEF) in people with suspected HF and obesity, in whom Novel candidate biomarkers to identify HF(pEF) in people with suspected HF and obesity. Novel candidate biomarkers to identify HF(pEF) in people with suspected HF and NT-proBNP <125 ng/L The prevalence of HF in people with suspected HF and low NT-proBNP <125 ng/L). The diagnosis of heart failure will be determined according to international guidelines, when there are symptoms and/or signs of HF in association with objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/raised LV filling pressures. Non-invasive testing with rest and diastolic stress echocardiography will be used to evaluate for evidence of raised filling pressures, in order to make the study procedures applicable to usual clinical practice.<br>* Other names: Diastolic stress echocardiography;|
| Patients with NTproBNP125-399ng/L and clinical suspicion of heart failure in primary care<br>Expected recruitment of 400 patients (50% expected prevalence of obesity, according to population study) | Diagnostic Test: Plasma biomarker levels<br>* This study will investigate the diagnostic utility and performance of: Alternative cut-offs for NT-proBNP to identify HF(pEF) in people with suspected HF and obesity, in whom Novel candidate biomarkers to identify HF(pEF) in people with suspected HF and obesity. Novel candidate biomarkers to identify HF(pEF) in people with suspected HF and NT-proBNP <125 ng/L The prevalence of HF in people with suspected HF and low NT-proBNP <125 ng/L). The diagnosis of heart failure will be determined according to international guidelines, when there are symptoms and/or signs of HF in association with objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/raised LV filling pressures. Non-invasive testing with rest and diastolic stress echocardiography will be used to evaluate for evidence of raised filling pressures, in order to make the study procedures applicable to usual clinical practice.<br>* Other names: Diastolic stress echocardiography;|
| Patients with NTproBNP≥400ng/L and clinical suspicion of heart failure in primary care<br>Expected recruitment of 400 patients (50% expected prevalence of obesity, according to population study) | Diagnostic Test: Plasma biomarker levels<br>* This study will investigate the diagnostic utility and performance of: Alternative cut-offs for NT-proBNP to identify HF(pEF) in people with suspected HF and obesity, in whom Novel candidate biomarkers to identify HF(pEF) in people with suspected HF and obesity. Novel candidate biomarkers to identify HF(pEF) in people with suspected HF and NT-proBNP <125 ng/L The prevalence of HF in people with suspected HF and low NT-proBNP <125 ng/L). The diagnosis of heart failure will be determined according to international guidelines, when there are symptoms and/or signs of HF in association with objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/raised LV filling pressures. Non-invasive testing with rest and diastolic stress echocardiography will be used to evaluate for evidence of raised filling pressures, in order to make the study procedures applicable to usual clinical practice.<br>* Other names: Diastolic stress echocardiography;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal cut-offs for NT-proBNP to identify HFPEF in obese patients with suspected heart failure | 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.) | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of HF in patients with NT-proBNP<125ng/L | To identify the prevalence of HF in patients with NT-proBNP <125 ng/L with and without obesity, and suspected HF. | 3 years | 
| Optimal cut-offs for biomarkers to identify HFPEF in patients with suspected HF. | 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. | 3 years | 
| Utility and diagnostic performance of biomarkers (novel and adjusted stratified cut-offs) in patients with suspected HF (HFPEF, HFmREF, HFREF). | 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.) | 3 years |