UK HFpEF: UK Heart Failure With Preserved Ejection Fraction
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
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 Design
Outcome Measures
Primary Outcome Measures
- Identification of distinct subgroups of HFpEF [10 years]
Identify distinct subgroups of HFpEF based on disease mechanisms, clinical factors and outcomes
- Improve understanding of the causes of HFpEF [10 years]
Improve the understanding of the cause of HFpEF to provide the basis for developing and evaluating new therapies and diagnostics
- Improve risk stratification of HFpEF [10 years]
Identify and improve risk stratification models for HFpEF patients
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Written informed consent
-
Diagnosis of HFpEF by a cardiologist with HF expertise, or a primary care physician with HF expertise, or a heart failure nurse
-
Natriuretic peptide levels measured
Exclusion Criteria:
-
LV EF < 40% (at screening or any previous measurement)
-
Known infiltrative cardiomyopathy (e.g., amyloid, sarcoid, lymphoma, endomyocardial fibrosis)
-
Known active myocarditis, constrictive pericarditis, or cardiac tamponade
-
Known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy
-
Known arrhythmogenic right ventricular cardiomyopathy
-
Known severe primary valvular heart disease
-
Known idiopathic, heritable or drug-induced pulmonary arterial hypertension
-
Heart transplantation or ventricular assist device
-
Complex congenital heart disease
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Manchester University NHS Foundation Trust
- University of Glasgow
- University of Leicester
- Sheffield Teaching Hospitals NHS Foundation Trust
- University College, London
- 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
Study Documents (Full-Text)
None provided.More Information
Publications
- 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. Review.
- 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.
- 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.
- 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, Düngen 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.
- B01434