Biomarkers in Patients With Suspected HFpEF

Official title

Biomarkers in Patients With Suspected Heart Failure With Preserved Ejection Fraction

Overview

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.

Interventions

• Diagnostic test Plasma biomarker levels
  This study will investigate the diagnostic utility and performance of: 1. Alternative cut-offs for NT-proBNP to identify HF(pEF) in people with suspected HF and obesity, in whom 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). The diagnosis of heart failure will be dete

Primary outcome measures

• Optimal cut-offs for NT-proBNP to identify HFPEF in obese patients with suspected heart failure [Time frame: 3 years]

Secondary outcome measures (3)

• Prevalence of HF in patients with NT-proBNP<125ng/L [Time frame: 3 years]
• Optimal cut-offs for biomarkers to identify HFPEF in patients with suspected HF. [Time frame: 3 years]
• Utility and diagnostic performance of biomarkers (novel and adjusted stratified cut-offs) in patients with suspected HF (HFPEF, HFmREF, HFREF). [Time frame: 3 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United Kingdom · 3 centers

• Glasgow Royal Infirmary — Glasgow
• New Victoria Hospital — Glasgow
• Queen Elizabeth University Hospital — Glasgow

Publications

• McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Gro PMID 34447992
• Madamanchi C, Alhosaini H, Sumida A, Runge MS. Obesity and natriuretic peptides, BNP and NT-proBNP: mechanisms and diagnostic implications for heart failure. Int J Cardiol. 2014 Oct 20;176(3):611-7. doi: 10.1016/j.ijcard.2014.08.007. Epub 2014 Aug 9. PMID 25156856
• Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA. Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction. Circulation. 2017 Jul 4;136(1):6-19. doi: 10.1161/CIRCULATIONAHA.116.026807. Epub 2017 Apr 5. PMID 28381470
• Vaishnav J, Chasler JE, Lee YJ, Ndumele CE, Hu JR, Schulman SP, Russell SD, Sharma K. Highest Obesity Category Associated With Largest Decrease in N-Terminal Pro-B-Type Natriuretic Peptide in Patients Hospitalized With Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2020 Aug 4;9(15):e015738. doi: 10.1161/JAHA.119.015738. Epub 2020 Jul 30. PMID 32750299
• Buckley LF, Canada JM, Del Buono MG, Carbone S, Trankle CR, Billingsley H, Kadariya D, Arena R, Van Tassell BW, Abbate A. Low NT-proBNP levels in overweight and obese patients do not rule out a diagnosis of heart failure with preserved ejection fraction. ESC Heart Fail. 2018 Apr;5(2):372-378. doi: 10.1002/ehf2.12235. Epub 2018 Jan 18. PMID 29345112
• Meijers WC, Hoekstra T, Jaarsma T, van Veldhuisen DJ, de Boer RA. Patients with heart failure with preserved ejection fraction and low levels of natriuretic peptides. Neth Heart J. 2016 Apr;24(4):287-95. doi: 10.1007/s12471-016-0816-8. PMID 26940695
• Reddy YNV, Carter RE, Obokata M, Redfield MM, Borlaug BA. A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction. Circulation. 2018 Aug 28;138(9):861-870. doi: 10.1161/CIRCULATIONAHA.118.034646. PMID 29792299
• Pieske B, Tschope C, de Boer RA, Fraser AG, Anker SD, Donal E, Edelmann F, Fu M, Guazzi M, Lam CSP, Lancellotti P, Melenovsky V, Morris DA, Nagel E, Pieske-Kraigher E, Ponikowski P, Solomon SD, Vasan RS, Rutten FH, Voors AA, Ruschitzka F, Paulus WJ, Seferovic P, Filippatos G. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendati PMID 32133741

Identifiers

NCT: NCT06101693 · GN23CA025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗