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

NCT ID: NCT04189029

Last Updated: 2024-03-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 175 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-12-09
• Study Completion Date: 2025-12-31

Brief Summary

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.

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.

Conditions

Heart Failure; Heart Failure With Preserved Ejection Fraction

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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

Extensive phenotyping

Intervention Type: OTHER

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)

Extensive phenotyping

Intervention Type: OTHER

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)

Extensive phenotyping

Intervention Type: OTHER

Prospective assessment of physical evaluation, biomarkers and omics, cardiac and vascular imaging and telemonitoring of cardiovascular parameters for 14 days.

Interventions

Extensive phenotyping

Prospective assessment of physical evaluation, biomarkers and omics, cardiac and vascular imaging and telemonitoring of cardiovascular parameters for 14 days.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

BPIfrance

OTHER

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: collaborator

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

BioSerenity

INDUSTRY

Sponsor Role: collaborator

Casis

UNKNOWN

Sponsor Role: collaborator

Firalis SA

INDUSTRY

Sponsor Role: collaborator

Fealinx

UNKNOWN

Sponsor Role: collaborator

Centre National de la Recherche Scientifique, France

OTHER

Sponsor Role: collaborator

ESPCI Paris

OTHER

Sponsor Role: collaborator

University of Paris 5 - Rene Descartes

OTHER

Sponsor Role: collaborator

Sorbonne University

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Sébastien HULOT, MD PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

AP - HP, Hôpital Européen Georges-Pompidou

Paris, , France

Countries

France

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Other Identifiers

2019-A01795-52

Identifier Type: OTHER

Identifier Source: secondary_id

APHP190558

Identifier Type: -

Identifier Source: org_study_id