Data-Driven Phenotyping in Heart Failure With Preserved Ejection Fraction

February 20, 2026 updated by: Instituto Politécnico de Leiria

The goal of this observational study is to learn how people with Heart Failure with Preserved Ejection Fraction (HFpEF) can be grouped into different "phenotypes" based on their clinical information. The researchers want to understand whether these groups have different health profiles and different responses during a cardiopulmonary exercise test (CPET).

The main questions this study aims to answer are:

  • Can clinical data be used to identify meaningful HFpEF phenotypes?
  • Do these phenotypes match well-known HFpEF scores, such as the H2FPEF and Heart Failure Association Pre-test Assessment, Echocardiography and Natriuretic Peptide (HFA-PEFF) scores?
  • Do people in different phenotypes show different results on a CPET?

Participants will:

  • Have their past clinical records reviewed if they were diagnosed with HFpEF at the Local Health Unit of the Leiria Region (ULS RL);
  • A smaller group will attend one visit to complete a CPET, which measures how the heart, lungs and muscles respond during exercise.

This study includes adults aged 18 years or older who have HFpEF. The study does not involve any new treatments or experimental drugs.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Heart Failure with Preserved Ejection Fraction (HFpEF) is a complex condition, and people with HFpEF can have different symptoms and clinical profiles. Understanding these differences may help improve how the condition is described and studied. This study has two parts: a retrospective analysis and a cross-sectional assessment.

In the retrospective part, the researchers will collect clinical information that was previously recorded in the hospital's clinical records during past hospitalizations for HFpEF at the Local Health Unit of the Leiria Region (ULS RL). The data will be reviewed and prepared for analysis using standard data quality procedures. After the database is complete, the researchers will use data-driven methods to look for patterns among participants, in order to identify groups of people who share similar characteristics ("phenotypes") without setting predefined categories. Methods will include descriptive statistics, correlation analysis and feature selection using algorithmic approaches such as ReliefF. For phenotyping, unsupervised machine-learning techniques including K-means clustering and principal component analysis (PCA) will be applied.

The cross-sectional part will invite a sample of participants selected to represent each phenotype (planned 15 participants for each phenotype) identified in the retrospective analysis. Selected participants will complete a single on-site visit including informed consent verification, a structured clinical review and a standardized cardiopulmonary exercise test (CPET) performed according to local and international guidelines. The CPET procedures will follow the laboratory protocol, namely calibration of equipment, resting measurements, incremental workload protocol, continuous gas exchange, and electrocardiogram (ECG) monitoring. CPET data will be recorded in digital format and transferred securely to the study database.

The study will also evaluate phenotype concordance with widely used HFpEF tools (H2FPEF and HFA-PEFF) and describe differences in physiological responses during CPET across phenotypes, to help clarify how useful they are in describing different forms of HFpEF. Analyses will emphasize exploratory, data-driven evaluation and estimation of effect sizes, consistent with the phenotyping objectives of the study. Where relevant, associations between phenotype membership and CPET variables will be explored descriptively and through correlation-based analyses.

Ethical and data protection procedures are in place. Personal identifiers will be removed and replaced by study ID codes. A linkage file (study ID to personal identifiers) will be stored on an encrypted device with access restricted to the student investigator. Electronic study data will be housed on secure servers with role-based access control. Data will be retained according to institutional policy and relevant legislation. Only de-identified datasets will be used for analysis and sharing. Safety procedures for CPET include pre-test screening for absolute contraindications, continuous ECG and blood pressure monitoring during the test, availability of emergency equipment and immediate clinical oversight by qualified personnel. Adverse events during CPET will be recorded and reported per the Ethics Committee requirements.

By combining clinical record information collected during previous hospitalizations with detailed exercise testing in a selected group, this study aims to provide new insight into the variation that exists among people with HFpEF. The findings may support more personalized approaches in future research.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Portugal
      • Leiria, Portugal, 2414-016
        • ciTechCare - Center for Innovative Care and Health Technology
        • Contact:
        • Contact:
    • Leiria District

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

Adult patients (≥18 years) with a confirmed diagnosis of heart failure with preserved ejection fraction (LVEF ≥50%) admitted in the Local Health Unit of the Leiria Region since September 2018. The retrospective phase includes electronic health records from approximately 200 patients, used to obtain multimodal datasets for unsupervised clustering. A cross-sectional phase recruits volunteer participants selected for representativeness of the identified phenotypes to undergo cardiopulmonary exercise testing (CPET) for functional characterization. Collected data include sociodemographic variables, clinical history, imaging findings, laboratory biomarkers (e.g., NT-proBNP), therapeutic data and CPET-derived functional parameters.

Description

Inclusion Criteria

  1. Retropective observational phase (Phase I):

    • Age ≥18 years;
    • Established diagnosis of heart failure with preserved ejection fraction (LVEF ≥50%);
    • Patients receiving care (outpatient or inpatient) at the Local Health Unit of the Leiria Region (ULS RL) since September 2018.

  2. Cross-sectional observational phase (Phase II - CPET):

    • Age ≥18 years;
    • Established diagnosis of HFpEF;
    • Selection as a volunteer representative of phenotypes identified in the retrospective clustering analysis;
    • Provision of written informed consent prior to any study-specific procedures.

Exclusion Criteria:

  1. Retropective observational phase (Phase I):

    • Incomplete or inadequate medical records preventing full data extraction.

  2. Cross-sectional observational phase (Phase II - CPET):

    • Medical contraindication or physical inability to perform cardiopulmonary exercise testing (CPET);
    • Inability to provide informed consent.

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

Cohorts and Interventions

Group / Cohort
Observational HFpEF Cohort

Single observational cohort including all adults with an established diagnosis of heart failure with preserved ejection fraction (LVEF ≥50%) who received care at the Local Health Unit of the Leiria Region (ULS RL) since September 2018.

Clinical, biochemical, imaging, functional, and therapeutic information recorded during previous hospitalizations will be extracted for retrospective analysis.

A subset of participants will later be invited to complete a single cardiopulmonary exercise test (CPET) according to the study protocol.

Phenotypes (clusters) will be identified post-hoc using unsupervised machine-learning methods and are not predefined at the time of enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification and characterization of HFpEF phenotypes using multimodal clustering analysis
Time Frame: Up to December 2026 (completion of retrospective data collection and clustering analysis).
Identification of distinct phenotypic clusters in patients with heart failure with preserved ejection fraction using unsupervised machine learning applied to multimodal clinical, biochemical, imaging and functional data.
Up to December 2026 (completion of retrospective data collection and clustering analysis).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean peak oxygen uptake (VO₂peak) during cardiopulmonary exercise testing
Time Frame: December 2026 to July 2027 (single assessment per participant).
Peak oxygen uptake (VO₂peak), expressed in mL·kg-¹·min-¹, measured by breath-by-breath gas analysis during maximal cardiopulmonary exercise testing and compared across HFpEF phenotypes.
December 2026 to July 2027 (single assessment per participant).
Concordance between H2FPEF and HFA-PEFF scores and identified HFpEF phenotypes
Time Frame: Up to October 2027.
Assessment of concordance and discrimination performance of H2FPEF and HFA-PEFF scores in identifying phenotypes derived from data-driven clustering.
Up to October 2027.
Mean plasma NT-proBNP concentration (pg/mL) by HFpEF phenotypes
Time Frame: Up to February 2028.
Comparison of plasma NT-proBNP concentrations (pg/mL) between HFpEF phenotypes identified by clustering analysis.
Up to February 2028.

Collaborators and Investigators

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

Sponsor

Instituto Politécnico de Leiria

Collaborators

Faculty of Medicine of Universidade de Lisboa (FMUL)
Fundação para a Ciência e a Tecnologia (FCT)
Hospital Santo André - Centro Hospitalar de Leiria

Investigators

  • Study Director: Rui M Fonseca-Pinto, PhD, ciTechCare - Center for Innovative Care and Health Technology, Polytechnic of Leiria
  • Study Director: João C A Morais, PhD, ciTechCare - Center for Innovative Care and Health Technology, Polytechnic of Leiria
  • Study Director: Vera L P Geraldes, PhD, Faculty of Medicine, University of Lisbon

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)

December 1, 2026

Primary Completion (Estimated)

August 1, 2027

Study Completion (Estimated)

May 31, 2028

Study Registration Dates

First Submitted

January 12, 2026

First Submitted That Met QC Criteria

February 20, 2026

First Posted (Actual)

February 24, 2026

Study Record Updates

Last Update Posted (Actual)

February 24, 2026

Last Update Submitted That Met QC Criteria

February 20, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FCT 2023.05000.BDANA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data (IPD) will not be shared. The dataset contains sensitive clinical and physiological information, including cardiopulmonary exercise test (CPET) variables, with a high risk of reidentification even after de-identification procedures. Institutional policies, local ethics approval, and applicable data protection regulations do not permit external sharing of these data.

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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