PACIFIC-PRESERVED : PhenomApping, ClassIFication, and Innovation for Cardiac Dysfunction - HF With PRESERVED LVEF Study

March 26, 2024 updated by: Assistance Publique - Hôpitaux de Paris

Redefining the Phenotypic Spectrum of Heart Failure With Preserved Ejection Fraction (HFpEF) by Deep Phenotyping and Machine Learning Methods: The PACIFIC-PRESERVED Study (PhenomApping, ClassIFication, and Innovation for Cardiac Dysfunction - HF With PRESERVED LVEF Study)

This is a prospective multicenter study to decipher phenotypic variability within patients with heart failure and preserved left ventricular ejection fraction (HFpEF). From a registry of heart failure patients (2500 anticipated) hospitalized in the participating centers in the last 3 years, up to 300 participants (with a final ratio of 3 HFpEF patients, 2 patients with heart failure and reduced ejection fraction (HFrEF) and 1 matched subjects without heart failure will be enrolled for an extensive phenotyping with physical evaluation, biomarkers and omics, cardiac and vascular imaging and telemonitoring of cardiovascular parameters. Cluster analysis with machine learning methods will be performed to define phenogroups unique to the HFpEF patient population.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Heart failure with preserved ejection fraction (HFpEF) is a complex and prevalent syndrome with currently no efficient therapy. This syndrome is likely explained by different pathophysiological inputs leading to common symptoms of heart failure. These pathophysiological abnormalities can primarily involve the heart but also other organs with secondary impact on the myocardium. There is however no clear understanding and diagnostic algorithms of the different HFpEF subpopulations. Novel mathematical methods (such as machine learning) can help identifying clusters within an heterogeneous population such as HFpEF patients.

A registry (2500 anticipated) will be constituted with patients hospitalized for congestive heart failure in the participating centers during the last 3 years. From this registry, up to 500 patients will be invited to visit in the hospital for 8-10 hours for physical examination, ECG, performance-based tests, blood draw, cMRI, echocardiography (rest and low-level exercise), Ultrafast echo (for non-invasive measurement of myocardial stiffness), low radiation cardiac CT (for calcium scoring), non-invasive measurement of arterial stiffness. They will be asked to fill out questionnaires about dyspnea, depression and about general health and quality of life. They will then be equipped with a smart connected garment (with cardiovascular & hemodynamic sensors), a connected weight balance and a blood pressure monitoring device for telemonitoring collection of cardiovascular hemodynamic parameters in real-life conditions (for 14 days).

Patients included in the registry will be followed-up for 3 years using medico-administrative databases and vital status, cardiovascular and heart failure outcomes will be collected.

Study Type

Observational

Enrollment (Estimated)

175

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

  • France
      • Paris, France
        • AP - HP, Hôpital Européen Georges-Pompidou

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

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Patients with different forms of heart failure (ie with preserved left ventricular ejection fraction vs. reduced left ventricular ejection fraction) and subjects apparently without heart failure

Description

Inclusion Criteria:

All subjects

  • Affiliation to a social security scheme, universal medical coverage (CMU) or any equivalent scheme
  • Physical state compatible with the carrying out of the investigations according to the judgment of the investigator
  • Procedure for obtaining consent

For HFpEF patients:

  • Hospitalization in one of the partner hospitals in the last 30 months
  • With a diagnosis of symptomatic congestive heart failure (NYHA II to IV)
  • With a plasma concentration of BNP ≥ 100 μg / ml or NT-proBNP ≥ 300 μg / ml or having had an administration of a dose of intravenous diuretics during hospitalization for congestive heart failure
  • Left ventricular ejection fraction ≥ 50%
  • Hospital discharge for at least 2 months

For HFrEF patients:

  • Hospitalization in one of the partner hospitals in the last 30 months
  • With a diagnosis of symptomatic congestive heart failure (NYHA II to IV)
  • Plasma concentration of BNP ≥ 100 μg / ml or NT-proBNP ≥ 300 μg / ml or administered a dose of intravenous diuretics during hospitalization for congestive heart failure
  • Hospital discharge for at least 2 months
  • Left ventricular ejection fraction ≤ 40%
  • Matched age and sex to HFpEF patients (for participants to extensive phenotyping)

For subjects apparently without heart failure :

  • Subject without a notable medical history or medical history within the last 5 years
  • Normotensive or who may have an essential hypertension of grade 1 (≤159 / 99 mmHg), treated or not
  • Can present a dyslipidemia, treated by hygieno-dietetic measures alone
  • Sinus heart rate
  • Estimated glomerular filtration rate ≥ 60 ml / min (CKD epi)
  • Matched age and sex to HFpEF patients (for participants to extensive phenotyping)

Exclusion Criteria:

All subjects

  • Pregnancy or breastfeeding
  • Participation in another interventional study
  • Person placed under the safeguard of justice
  • Subject that can not understand the procedures related to the protocol
  • Severe obesity (BMI > 40 Kg / m2)
  • For those performing the injected MRI: Patient who has already had a severe allergy to gadolinium MRI contrast agents
  • For those performing the injected MRI: MRI usual contraindications: Pace-maker, defibrillator, metallic objects
  • Administration of a vaccine dose (including anti-Sars-Cov-2) less than 3 weeks old

For both HFpEF and HFrEF patients:

  • History of right ventricular infarction
  • History of cardiac transplantation or circulatory assistance
  • Major surgery scheduled for less than 6 months, coronary revascularization of less than 3 months
  • Pacemaker or any implanted device (or foreign body) not compatible with MRI
  • Presence of very severe co-morbidity: end-stage renal failure (GFR <15ml / min), severe chronic obstructive pulmonary disease (COPD), severe valve disease (including severe aortic stenosis), organ transplantation
  • Hypertrophic cardiomyopathy of known genetic cause
  • Hereditary amyloidosis with disabling neuropathy
  • Amyloidosis under specific treatment
  • Other antecedent of known congenital heart disease type, Post-embolic chronic pulmonary heart, Restrictive Cardiopathy, Diagnosed Fabry Disease

For HFpEF patients:

- History of systolic dysfunction with proven LVEF reduction (≤ 40%)

For subjects apparently without heart failure :

  • Medication use other than pure systemic or local estrogen / progestin and progestin contraceptives and paracetamol, at the discretion of the investigator
  • Acute pathology within 8 days prior to inclusion
  • Cardiac or vascular organic impairment or apparent chronic diseases
  • Chronic treatment outside a treatment for high blood pressure
  • Having already had ≥3 MRI with injection of gadolinium contrast agents

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
HFpEF patients
Heart failure patients (NYHA II-IV) with left ventricular ejection fraction ≥ 50%, 1000 patients anticipated among which up to 300 with extensive phenotyping
Other: Extensive phenotyping
Prospective assessment of physical evaluation, biomarkers and omics, cardiac and vascular imaging and telemonitoring of cardiovascular parameters for 14 days.
HFrEF patients
Heart failure patients (NYHA II-IV) with left ventricular ejection fraction ≤ 40%, 1000 patients anticipated among which up to 100 with extensive phenotyping (age- and gender-matched on participating HFpEF patients)
Other: Extensive phenotyping
Prospective assessment of physical evaluation, biomarkers and omics, cardiac and vascular imaging and telemonitoring of cardiovascular parameters for 14 days.
Subjects apparently without heart failure
Subjects without history or signs of heart failure, up to 100 subjects anticipated with extensive phenotyping (age- and gender-matched on participating HFpEF patients)
Other: Extensive phenotyping
Prospective assessment of physical evaluation, biomarkers and omics, cardiac and vascular imaging and telemonitoring of cardiovascular parameters for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Machine learning algorithm to identify distinct phenotypic subgroups among HFpEF patients
Time Frame: 14 days
Machine learning-based cluster analysis using extensive phenotyping data from HFpEF, HFrEF and subjects without apparent HF
14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prognosis
Time Frame: 3 years
Identify phenotypic subgroup(s) with higher risk of cardiovascular and HF outcomes
3 years
Myocardial stiffness
Time Frame: 3 years
Assess the diagnostic and prognostic value of myocardial stiffness measured with ultrafast cardiac echography
3 years
Sarcopenia and muscular capacity
Time Frame: 3 years
Prevalence and importance of muscle loss, weakness measured with hand grip strength test (Kg) and with the short physical performance battery (SPPB, combining the results of gait speed, chair stand and balance tests) in HFpEF patients
3 years
Exercise tolerance
Time Frame: 3 years
Measure exercise tolerance with 6-minute walk test
3 years
Cardiac fibrosis
Time Frame: 3 years
Prevalence, diagnostic and prognostic importance of cardiac fibrosis (as estimated by cMRI and specific biological markers) in HFpEF patients
3 years
Arterial Stiffness
Time Frame: 3 years
Assess the diagnostic and prognostic value of arterial stiffness measured by pulse wave velocity
3 years
Right heart and pulmonary circulation
Time Frame: 3 years
Assess the diagnostic and prognostic value of novel markers to quantify right heart function and pulmonary circulation measured with cMRI
3 years
Ventricular-arterial coupling
Time Frame: 3 years
Machine learning-based analysis on 4D MRI recordings to estimate ventricular-arterial coupling
3 years
Omics signature
Time Frame: 3 years
Apply multi-omics techniques (including measurements of miRNA, lNcRNA, inflammation markers, and DNA methylation level) to define specific biological signatures to HF and HFpEF patients
3 years
Quality of life evaluation
Time Frame: 3 years
General and HF QOL questionnaires: Kansas city cardiomyopathy questionnaire - the sum of responses from all 12 items, Range for subscale is 0-100 and the range for the summary score is 0-100 with lower scores indicating more significant disease impact; Global quality of life score with SF36 (Short form 36 health survey): The norm data is 0-100, the health related quality of life is increased as the scores are increased.
3 years
Telemonitoring of weight
Time Frame: 3 years
Remote measurement of body weight
3 years
Telemonitoring of cardiac rythm
Time Frame: 3 years
Remote measurement of cardiac arrhythmias
3 years
Telemonitoring of ECG
Time Frame: 3 years
Remote measurement of heart rate variability
3 years
Telemonitoring of physical activity
Time Frame: 3 years
Remote measurement of physical activity with an actimeter
3 years
Telemonitoring of blood pressure
Time Frame: 3 years
Remote measurements of blood pressure in mmHg
3 years
Telemonitoring of pulmonary function
Time Frame: 3 years
Remote measurement of respiratory rate
3 years
Telemonitoring of oxygen saturation
Time Frame: 3 years
Remote measurement of oxygen saturation (%)
3 years
Telemonitoring of pulmonary congestion
Time Frame: 3 years
Remote evaluation of pulmonary congestion with measurement of thoracic impedance
3 years
Digitalized ECG
Time Frame: 3 years
Develop novel machine learning based markers of HF, of HFpEF and HFrEF
3 years
Cardiac echography
Time Frame: 3 years
Rest and low-effort evaluation of cardiac parameters
3 years
Cardiac calcium scoring
Time Frame: 3 years
Evaluation of calcium scoring among participants
3 years
Cardiac MRI
Time Frame: 3 years
Novel biomarkers of cardiac fibrosis, extra-cellular volume, matrix remodeling
3 years
Left atria
Time Frame: 3 years
Evaluation of LA remodeling (volumes) and function (strain)
3 years

Collaborators and Investigators

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

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Sanofi
Institut National de la Santé Et de la Recherche Médicale, France
Institut de Recherches Internationales Servier
University of Paris 5 - Rene Descartes
Sorbonne University
BioSerenity
ESPCI Paris
BPIfrance
Centre National de la Recherche Scientifique, France
Firalis SA
Casis
Fealinx

Investigators

  • Principal Investigator: Jean-Sébastien HULOT, MD PhD, AP - HP, Hôpital Européen Georges-Pompidou, Paris, France

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 (Actual)

December 9, 2019

Primary Completion (Actual)

December 9, 2023

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

November 28, 2019

First Submitted That Met QC Criteria

December 4, 2019

First Posted (Actual)

December 6, 2019

Study Record Updates

Last Update Posted (Actual)

March 28, 2024

Last Update Submitted That Met QC Criteria

March 26, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP190558
  • 2019-A01795-52 (Other Identifier: N° IDRCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data used for publication could be shared through scientific collaboration with the sponsor or any collaborations implied.The sharing will respect the unital consortium agreement.

IPD Sharing Time Frame

Will become available from the time when summary data are published

IPD Sharing Access Criteria

Sharing access criteria will be discussed between the sponsor and collaborate

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

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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