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.

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.

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

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

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.

Will become available from the time when summary data are published

Sharing access criteria will be discussed between the sponsor and collaborate