CAPTURE-HFpEF: National Study of Identification and Phenotyping of Heart Failure With Preserved Ejection Fraction

Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that will benefit from early diagnosis, extensive diagnostic work-up, and individualized therapy. HF is a global health problem and one of the leading causes of cardiovascular (CV) morbidity and mortality. While many pharmacological and interventional treatments have been developed for HF with reduced ejection fraction (HFrEF), the HFpEF syndrome is poorly characterised with very few treatment possibilities. Whilst HFrEF was previously associated with a much worse prognosis than HFpEF, the two conditions today have comparable outcomes. Besides having a high mortality, HFpEF is also associated with a low quality of life and recurrent hospitalisations. Almost all treatments that have been successful in HFrEF have failed in HFpEF, underscoring the inadequate understanding of this disease. When HFpEF is diagnosed, it is often at a very late stage (near end-stage), thus compromising the potential benefits of treatment. As HFpEF is believed to be a result of the long-term detrimental effects from various diseases such as hypertension, diabetes, obesity, chronic kidney disease and others, earlier diagnosis of HFpEF and strict disease modification of the precipitating disease(s) may alter disease course and hence prognosis.

The aim of CAPTURE-HFpEF is to identify patients with HFpEF at earlier stages of the disease at a national level and identify important subgroups (phenotypes) that may benefit from different treatments. Furthermore, the CAPTURE-HFpEF initiative will determine mechanisms important for the etiology of the different HFpEF phenotypes. This includes the use of existing and novel experimental models that mimic aspects of the syndrome for comparative phenotyping, biomarker screening, and potentially testing of experimental therapeutics. Combining insights from HFpEF experimental models with data obtained from deep phenotyping will make it possible to develop and potentially implement personalized therapeutics for each identified HFpEF phenotype.

The study leverages Danish national registries and the secure e-mail system (e-Boks) to invite potential participants. Approximately 30,000 adults with risk factors for HFpEF and self-reported dyspnea will undergo AI-driven echocardiography, ECG, blood sampling, and detailed clinical assessment. Additionally, 200-500 patients with established HFpEF diagnoses will be included for comparative analyses. Deep phenotyping includes genotyping, proteomics, metabolomics, and advanced imaging (CT, MR, echocardiography, DPD-scintigraphy), myocardial biopsies and CPET to characterize subtypes of HFpEF and explore upstream abnormalities leading to disease progression.

The operational office is the central HUB of the project. The HUB is responsible for the daily running of all parts of the initiative and will be in charge of coordinating with the spokes (Examination facilities) with regards to data gathering, administration of the database and data availability to researchers. The HUB is located at Herlev Hospital. Patient examination facilities/spokes will be present in all regions of Denmark and capable of all aspects of the initial examination. Parts of the deep phenotyping will also be performed in these clinics, whereas many advanced analyses are to be outsourced to different core laboratories. It is the intention that each spoke has a secretary, examination staff and affiliated research staff (Senior PI, PhDs and post-docs).

Inclusion criteria

• Patients >60 years with ≥1 risk factor, OR
• Patients >50 years with ≥2 risk factors
• Hypertension
• Type 1 or 2 diabetes
• Chronic kidney disease (eGFR <60 mL/min/1.73 m²)
• Previous cardiotoxic drug exposure
• atrial fibrillation
• Ischemic heart disease
• Previous heart valve surgery/intervention
• Body mass index >30 kg/m² (self-reported)
• Use of ≥40 mg furosemide
• Obstructive sleep apnea
• Non-alcoholic fatty liver disease

Exclusion criteria

• Cancer <1 year
• Dialysis
• COPD and O2
• Nursing home
• Age >90 years
• Dementia
• Known dilated cardiomyopathy
• Prior organ-transplantation
• Amyloidosis