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| Name | Class |
|---|---|
| Faculty of Medicine of Universidade de Lisboa (FMUL) | UNKNOWN |
| Hospital Santo André - Centro Hospitalar de Leiria | UNKNOWN |
| Fundação para a Ciência e a Tecnologia | OTHER |
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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:
Participants will:
This study includes adults aged 18 years or older who have HFpEF. The study does not involve any new treatments or experimental drugs.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| Identification and characterization of HFpEF phenotypes using multimodal 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Mean peak oxygen uptake (VO₂peak) during cardiopulmonary exercise testing | 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). |
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Inclusion Criteria
Retropective observational phase (Phase I):
Cross-sectional observational phase (Phase II - CPET):
Exclusion Criteria:
Retropective observational phase (Phase I):
Cross-sectional observational phase (Phase II - CPET):
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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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sónia C Santos, MSc | Contact | +351910724415 | sonia.c.santos@ipleiria.pt | |
| Rui M Fonseca-Pinto, PhD | Contact | +351965632378 | rui.pinto@ipleiria.pt |
| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Local Health Unit of the Leiria Region | Leiria | Leiria District | 2410-197 | Portugal |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32215700 | Background | Ferreira JP, Dewan P, Jhund PS, Lorenzo-Almoros A, Duarte K, Petrie MC, Carson PE, McKelvie R, Komajda M, Zile M, Zannad F, McMurray JJV. Covariate adjusted reanalysis of the I-Preserve trial. Clin Res Cardiol. 2020 Nov;109(11):1358-1365. doi: 10.1007/s00392-020-01632-x. Epub 2020 Mar 25. | |
| 19001508 | Background |
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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.
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D054144 | Heart Failure, Diastolic |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| Concordance between H2FPEF and HFA-PEFF scores and identified HFpEF phenotypes |
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 | Comparison of plasma NT-proBNP concentrations (pg/mL) between HFpEF phenotypes identified by clustering analysis. | Up to February 2028. |
| Vera L P Geraldes, PhD | Faculty of Medicine, University of Lisbon | Study Director |
| ciTechCare - Center for Innovative Care and Health Technology | Leiria | 2414-016 | Portugal |
|
| Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger C, Ptaszynska A; I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008 Dec 4;359(23):2456-67. doi: 10.1056/NEJMoa0805450. Epub 2008 Nov 11. |
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| 36000416 | Background | John JE, Claggett B, Skali H, Solomon SD, Cunningham JW, Matsushita K, Konety SH, Kitzman DW, Mosley TH, Clark D 3rd, Chang PP, Shah AM. Coronary Artery Disease and Heart Failure With Preserved Ejection Fraction: The ARIC Study. J Am Heart Assoc. 2022 Sep 6;11(17):e021660. doi: 10.1161/JAHA.121.021660. Epub 2022 Aug 24. |
| 35395159 | Background | Olaniyi KS, Atuma CL, Sabinari IW, Hadiza M, Saidi AO, Akintayo CO, Ajadi IO, Olatunji LA. Restoration of cardiac metabolic flexibility by acetate in high-fat diet-induced obesity is independent of ANP/BNP modulation. Can J Physiol Pharmacol. 2022 Jun 1;100(6):509-520. doi: 10.1139/cjpp-2021-0531. Epub 2022 Apr 8. |
| 35112889 | Background | Brady PF, Chua W, Nehaj F, Connolly DL, Khashaba A, Purmah YJV, Ul-Qamar MJ, Thomas MR, Varma C, Schnabel RB, Zeller T, Fabritz L, Kirchhof PF. Interactions Between Atrial Fibrillation and Natriuretic Peptide in Predicting Heart Failure Hospitalization or Cardiovascular Death. J Am Heart Assoc. 2022 Feb 15;11(4):e022833. doi: 10.1161/JAHA.121.022833. Epub 2022 Feb 3. |
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| 27206819 | Background | Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016 Jul 14;37(27):2129-2200. doi: 10.1093/eurheartj/ehw128. Epub 2016 May 20. No abstract available. |
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