UK Heart Failure With Preserved Ejection Fraction (UK HFpEF)

UK Heart Failure With Preserved Ejection Fraction Registry

Heart failure occurs when the heart is no longer able to pump blood around the body properly. It can cause breathlessness, swollen feet and ankles, and tiredness. In about half of patients with heart failure, one measure of the heart's pumping function, called the 'ejection fraction', is normal. This type of heart failure is called heart failure with preserved ejection fraction, or HFpEF.

HFpEF remains poorly understood. It is not clear why some people develop HFpEF, or what determines the severity of the condition. Treatment options may be limited.

UK HFpEF is a study that aims to gain a better understanding of why people develop HFpEF, develop better tests to diagnosis it, identify and test new treatments, and follow the health of the people taking part over many years.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF)

Detailed Description

Approximately half of patients with heart failure have a normal, or preserved, left ventricular ejection fraction (HFpEF) (Owen et al, 2006). Rather than being a single diagnosis, it has become clear that HFpEF represents a heterogeneous syndrome involving a range of pathophysiological mechanisms, clinical factors and outcomes (Lewis et al, 2017). However, to-date, HFpEF has generally been considered as a single disease entity. Several high profile phase III trials in HFpEF have shown potentially impressive efficacy in some subgroups of patients, but failed to prove significance over entire cohorts (Pitt et al, 2014) (Solomon et al, 2019). This is likely due to the 'one-size-fits-all' approach taken, with insufficient stratification of the various underlying disease mechanisms.

The large and rapidly growing burden that HFpEF places on our healthcare systems mean there is a pressing need to better understand HFpEF and improve the management of patients with it. The recurrent lack of benefit of the one-size-fits-all approach mandates a new, personalised approach.

The UK HFpEF registry will be a key platform for collaborative UK clinical and translational HFpEF research. The aim is that multiple centres will collaborate and contribute patients such that the registry will provide deep phenotyping, linked to outcomes, in, ultimately, many thousands of patients. This will enable, for example, machine learning techniques to be applied at scale in order to reclassify HFpEF more powerfully. It will provide a platform for the development of diagnostics specific to the different HFpEF subgroups, and for more effective trials that will target groups of patients in whom new, repurposed or previously discarded treatments are expected to be effective. Moreover, it will provide cohorts of patients readily available for recruitment, with linkage in place for outcomes. It could be used to leverage commercial funding and participation, facilitated by simplified, single-point access for industry. It will enable scaled investigation aimed at understanding causes of HFpEF, improving risk stratification and providing better care.

• Study Type: Observational
• Enrollment (Anticipated): 10000

Contacts and Locations

• Study Contact: Name: Fardad Soltani, MBChB MRCP; Phone Number: 0161 291 3223; Email: fardad.soltani@mft.nhs.uk

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M13 9WU
    • Recruiting
    • Manchester University NHS Foundation Trust
    • Contact: Fardad Soltani 0161 291 3223; Phone Number: 0161 291 3223; Email: fardad.soltani@mft.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All individuals will be considered for inclusion in this study regardless of age, disability, gender reassignment, marriage and civil partnership, pregnancy and maternity, race, religion and belief, sex, and sexual orientation, except where the study inclusion and exclusion criteria explicitly state otherwise.

Description

Inclusion Criteria:

1. Written informed consent
2. Diagnosis of HFpEF by a cardiologist with HF expertise, or a primary care physician with HF expertise, or a heart failure nurse
3. Natriuretic peptide levels measured

Exclusion Criteria:

1. LV EF < 40% (at screening or any previous measurement)
2. Known infiltrative cardiomyopathy (e.g., amyloid, sarcoid, lymphoma, endomyocardial fibrosis)
3. Known active myocarditis, constrictive pericarditis, or cardiac tamponade
4. Known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy
5. Known arrhythmogenic right ventricular cardiomyopathy
6. Known severe primary valvular heart disease
7. Known idiopathic, heritable or drug-induced pulmonary arterial hypertension
8. Heart transplantation or ventricular assist device
9. Complex congenital heart disease

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of distinct subgroups of HFpEF	Identify distinct subgroups of HFpEF based on disease mechanisms, clinical factors and outcomes	10 years
Improve understanding of the causes of HFpEF	Improve the understanding of the cause of HFpEF to provide the basis for developing and evaluating new therapies and diagnostics	10 years
Improve risk stratification of HFpEF	Identify and improve risk stratification models for HFpEF patients	10 years

Collaborators and Investigators

• Sponsor: Manchester University NHS Foundation Trust
• Collaborators: University College, London; Sheffield Teaching Hospitals NHS Foundation Trust; University of Leicester; University of Glasgow; Pumping Marvellous Foundation; British Society for Heart Failure; NIHR National Biosample Centre; British Heart Foundation Data Science Centre; Salisbury NHS Foundation Trust
• Investigators: Study Chair: Chris Miller, MBChB FRCP, Manchester University NHS Foundation Trust

Publications and helpful links

General Publications

• Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin-Colet J, Cleland J, Dungen HD, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP; PARAGON-HF Investigators and Committees. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019 Oct 24;381(17):1609-1620. doi: 10.1056/NEJMoa1908655. Epub 2019 Sep 1.
• Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9. doi: 10.1056/NEJMoa052256.
• Lewis GA, Schelbert EB, Williams SG, Cunnington C, Ahmed F, McDonagh TA, Miller CA. Biological Phenotypes of Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2017 Oct 24;70(17):2186-2200. doi: 10.1016/j.jacc.2017.09.006.
• Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O'Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S, McKinlay SM; TOPCAT Investigators. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014 Apr 10;370(15):1383-92. doi: 10.1056/NEJMoa1313731.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2022
• Primary Completion (Anticipated): June 1, 2037
• Study Completion (Anticipated): June 1, 2037

Study Registration Dates

• First Submitted: May 26, 2022
• First Submitted That Met QC Criteria: June 28, 2022
• First Posted (Actual): July 1, 2022

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: B01434

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Participants will be asked to provide consent for pseudonymised study data, including, for example, individual patient-level data, scans and any other study data, to be shared for research purposes with investigators or organisations, including independent commercial organisations ('industry'), in the United Kingdom or overseas, including outside of the European Economic Area and in the United States of America. Participant personal details such as name, address, date of birth, will not be shared.

Requests for access to the data will be managed by the Executive Steering Committee. Release of data to investigators or organisations requesting access, whether they reside within or outside the UK, will be covered by a Data Transfer Agreement. The Data Transfer Agreement is a legally binding document that will regulate the use of data to ensure that standards are maintained.

• IPD Sharing Time Frame: Within the life time of the study
• IPD Sharing Access Criteria: Release of data or samples to investigators or organisations requesting access, whether they reside within or outside the UK, will be covered by Data and/or Material Transfer Agreements. The Agreements are legally binding documents that will regulate the use of data and/or samples to ensure that standards are maintained.

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