HFpEF Phenotyping With Echo, Clinical, and Biomarkers (The EPIC-HFpEF)

June 8, 2026 updated by: Erberto Carluccio, University Of Perugia

Phenotyping Heart Failure With Preserved Ejection Fraction (HFpEF) Using Echocardiographic, Clinical, and Biomarker Parameters

The EPIC-HFpEF registry is a nationwide Italian study that follows people with a specific type of heart failure called HFpEF. About 500 patients will be enrolled from several specialized hospitals and monitored for up to two years, without changing their usual treatment.

The goal is to better understand this complex condition by identifying different patient "types" based on clinical features, heart imaging, and blood markers. Researchers will also look at how these groups are treated in real life and how their disease progresses over time.

By doing this, the study aims to improve how doctors classify and manage HFpEF, moving toward more personalized and effective care for patients in the future.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Study Design: A multicenter, national, non-randomized observational study with both retrospective and prospective components, conducted at approximately 10 Italian tertiary centers specializing in the management of heart failure.The registry consecutively will enroll adult patients diagnosed with HFpEF, including both inpatients and outpatients, and includes follow-up for up to 24 months or until death or withdrawal of consent. No intervention aimed at modifying standard clinical practice is planned.

Study Purpose and Rationale: The rationale for the EPIC-HFpEF registry is to:

  • describe the true prevalence of the different HFpEF phenotypes in clinical practice;
  • characterize these phenotypes using an integrated approach that includes advanced echocardiography, clinical data, and biomarkers;
  • provide the foundation for personalized medicine, tailored to the individual patient's pathophysiological profile.

Study Objectives:

Primary Objectives

  • To identify distinct phenotypes of HFpEF based on clinical parameters, echocardiographic findings (standard and advanced), biomarkers, and comorbidities.
  • To describe the prevalence and temporal evolution of the different HFpEF phenotypes in a real-world setting.

Secondary objectives

  • Evaluate the implementation of guideline-recommended therapies (neurohormonal modulators, SGLT2 inhibitors, GLP-1 agonists) and the treatment of comorbidities across the different phenotypes.
  • Analyze the associations between circulating biomarkers and structural and functional cardiac alterations.
  • Study the impact of disease duration on clinical outcomes in relation to phenotype.
  • Assess the cumulative risk of cardiovascular events and their prognostic value in the different subgroups of HFpEF.

Inclusion Criteria

  • Age ≥ 18 years.
  • Written informed consent.
  • Diagnosis of chronic or acute heart failure with:o Left ventricular ejection fraction ≥ 50%;o Elevated natriuretic peptide levels (NT-proBNP ≥300 pg/mL in sinus rhythm or ≥600 pg/mL in atrial fibrillation); or Echocardiographic evidence of increased left ventricular filling pressures.
  • NYHA Class II-IV.

The following are also included as comparison groups:

  • Patients with recovered/improved EF (previous EF <40%);
  • Patients with mildly reduced EF (40-49%, HFmrEF).

Exclusion criteria

  • Concurrent participation in interventional clinical trials.
  • Life expectancy < 1 year due to non-cardiac causes.
  • Recent infectious, inflammatory, autoimmune, or neoplastic diseases (≤6 months).
  • Advanced chronic kidney disease (eGFR <15 ml/min/1.73 m²).
  • Recent major cardiovascular events (MI, stroke, cardiac surgery within the last 3 months).
  • Severe pulmonary diseases, congenital heart disease, primary pulmonary hypertension.
  • Moderate-to-severe degenerative valvular disease, specific or constrictive cardiomyopathies.
  • Recent implantation of an ICD or cardiac resynchronization therapy.

Study Duration

  • Enrollment period: 12 months.
  • Follow-up for each patient: up to 24 months.
  • Total study duration: approximately 3 years.

Scheduled visits include:

  • baseline (T1),
  • 6-month follow-up (T2),
  • 12-month follow-up (T3),
  • additional clinical follow-up for up to 24 months to collect event data.

Sample Size We plan to enroll approximately 500 patients with HFpEF, assuming an average of 50 patients per participating center.This sample size is considered adequate for identifying phenotypic clusters and estimating their prevalence in the real-world population of patients with HFpEF.ConclusionThe EPIC-HFpEF registry aims to improve understanding of the clinical and pathophysiological complexity of HFpEF by identifying phenotypes that are prognostically relevant and potentially responsive to targeted therapeutic strategies, with direct implications for clinical practice and the design of future interventional studies.

Study Type

Observational

Enrollment (Estimated)

500

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study population will consist of consecutive patients with HF (NYHA class II - IV), aged 18 years or older, able to give their written informed consent to participate to the registry. Each patient will be uniquely identified in the study by a combination of his/her site number and patient number. No name will be entered in the database.

Once obtained approval from each Ethics Committee center, consecutive patients will be included, up to the achievement of the study size. Patients may also be enrolled retrospectively, provided they give their written informed consent during a follow-up visit. Enrollment will be performed during outpatient visits or at-discharge in patients hospitalized for HF. Outpatient's visits will be further classified as planned or unplanned visits for worsening HF symptoms.

Patient data collected during the study will include demographics, medical history, vital signs, LVEF and main cardiac structure and function parameters, and laboratory assessments.

Description

Inclusion Criteria:

  • Patients ≥ 18 years old
  • Signed patient informed consent form (ICF)
  • Diagnosis of chronic (documented HF hospitalization in the last year) or acute decompensated HF shown by signs and symptoms of HF and LVEF >50% and, according to guidelines and the universal definition of HF, elevated levels of natriuretic peptides (NT-proBNP ≥300 pg/ml in sinus rhythm or NTproBNP ≥600 pg/ml in atrial fibrillation), at the time of enrolment (10)
  • Echocardiographic evidence of increased estimated LV filling pressures according to current guidelines

Exclusion Criteria:

  • Planned participation or participation in a clinical trial;
  • Life expectancy < 1 year because of non-cardiac causes;
  • History of recent (6 months) infective, or inflammatory, autoimmune or neoplastic diseases.
  • Stage >4 CKD (estimated glomerular filtration rate [eGFR] < 15 ml/min/1.73m2),
  • Myocardial infarction (increase in cardiac enzymes in combination with symptoms of ischemia or newly developed ischemic ECG changes), coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA in past 3 months;
  • Chronic pulmonary disease requiring home oxygen, oral steroid therapy or hospitalization for exacerbation within 12 months;
  • Congenital heart disease.
  • Primary pulmonary hypertension
  • Moderate-to-severe degenerative (primary) valve disease
  • Cardiomyopathy based on muscular dystrophies, cardiomyopathy with reversible causes (e.g. stress cardiomyopathy), or known pericardial constriction;
  • Implantation of cardioverter defibrillator (ICD) within 3 months
  • Implanted cardiac resynchronization therapy (CRT) and/or stable RV pacing.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of HFpEF phenotypes
Time Frame: At Baseline
to evaluate the prevalence of distinct phenotypic subgroups of HFpEF agnostically classified (unsupervised) using detailed standard and advanced echocardiography (at rest and/or during exercise), clinical evaluation, biomarker characteristics, and comorbidities assessment
At Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of treatment patterns according to different phenotypes
Time Frame: 1 year, year 1
Implementation of Guidelines-indicated drugs, including neurohormonal modulators, SGLT2-inhibitors, GLP1 agonists, and comorbidities-related treatment (including atrial fibrillation, iron deficiency, kidney dysfunction), according to the different phenotypes
1 year, year 1
Correlations between biomarkers and structural and functional alterations of the heart
Time Frame: At baseline
Assessing biomarker correlations with specific morphological and structural alterations of the heart, according to the different phenotypes
At baseline
Rate of major cardiovascular events
Time Frame: 3 years, year 3

To assess cumulative rate of CV events (- death from cardiovascular cause;

  • all-cause death;
  • Heart Failure re-hospitalization;
  • the composite of death from cardiovascular cause and HF-rehospitalization;
  • Incident Atrial Fibrillation;
  • Non-fatal Myocardial infarction;
  • Non-fatal stroke;
  • Hospitalization for acute kidney injury or other kidney disease event including dialysis or end-stage renal disease defined as eGFR < 15 mL/min/1.73 m2 or the need for renal replacement therapy) according to different HFpEF phenotypes
3 years, year 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Of Perugia

Collaborators

Azienda Ospedaliera di Perugia
University of Foggia
Ospedale Le Scotte

Investigators

  • Study Chair: Erberto Carluccio, MD, Cardiology and Cardiovascular Pathophysiology Unit, University of Perugia and Azienda Ospedaliera di Perugia, Italy
  • Study Chair: Alberto Palazzuoli, MD, Cardio Thoracic and Vascular Department, Cardiovascular Diseases Unit, Le Scotte Hospital, Siena, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 2, 2026

Primary Completion (Estimated)

June 30, 2027

Study Completion (Estimated)

July 31, 2029

Study Registration Dates

First Submitted

March 23, 2026

First Submitted That Met QC Criteria

June 8, 2026

First Posted (Actual)

June 11, 2026

Study Record Updates

Last Update Posted (Actual)

June 11, 2026

Last Update Submitted That Met QC Criteria

June 8, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CET N° 5131/26

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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