Characterization of Heart Failure With Preserved Ejection Fraction

The goals of this research will be to define some of the mechanisms underlying the progression and complications of heart failure (HF) with preserved left ventricular ejection fraction (HFPEF)

Aim 1: to evaluate the differences in cardiac structure, function and fibrosis markers through the spectrum of HF stages in order to deepen the understanding of the pathophysiology driving HF progression.

Aim 2: to define the mechanisms by which HF risk factors, such as hypertension, diabetes, obesity, and renal insufficiency, interact with age to increase HF risk, and to evaluate the role of precipitating factors such as myocardial ischemia, atrial fibrillation in HFPEF.

Aim 3: to determine prognostic factors in HFPEF patients, by following these patients over time. Accordingly the investigators will correlate baseline data (echocardiographic, MRI or biomarkers) with incident cardiovascular events and determine whether these measures provide incremental prognostic information beyond clinical characteristics.

Study Overview

• Status: Recruiting
• Conditions: Biomarkers; Magnetic Resonance Imaging; Heart Failure, Preserved Ejection Fraction; Cardiac Fibrosis
• Intervention / Treatment: Diagnostic test: cMR; Biological: biomarker

Detailed Description

Heart failure (HF) is a prevalent and complex clinical syndrome characterized by significant morbidity and mortality. HF patients are classified into two major groups based on their left ventricular ejection fraction (LVEF): heart failure with reduced ejection fraction (HFrEF) (LVEF < 40%) and heart failure with preserved ejection fraction (HFpEF) (LVEF ≥ 50%). These groups exhibit distinct clinical and biological characteristics, and their underlying pathophysiology have been thoroughly investigated. However, HFpEF, which represents more than 50% of HF cases, remains a poorly understood disease with limited therapeutic options

Several proposed mechanisms contribute to the development of HFpEF, including systemic inflammation, microvascular dysfunction, cardiometabolic abnormalities, and interstitial fibrosis. The aim of our research programm is to understand the differences between the pathophysiology of this syndrome compared to that of heart failure with reduced EF, with a focus on cardiac fibrosis and metabolism.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne-Catherine Pouleur; Phone Number: 003227646600; Email: anne-catherine.pouleur@uclouvain.be
• Study Contact Backup: Name: Anne Catherine Pouleur; Phone Number: 0032276600; Email: anne-catherine.pouleur@uclouvain.be

Study Locations

• Belgium
  • Brussels, Belgium
    • Recruiting
    • Cliniques Universitaires Saint Luc
    • Contact: Clotilde Roy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Controls without an history of HF and previous cardiovascular disease will be recruited

Inclusion Criteria for HF patients:

Patients need to have typical symptoms and signs of HF, New York Heart Association (NYHA) functional class II or higher, N-terminal pro-B type natriuretic peptide (NT-proBNP) >350pg/mL, or an hospitalization for HF within the previous 12 months. Left ventricular ejection fraction (LVEF) is required to be lower than 40% in patients with HFrEF and 50% or higher in HFpEF, with evident signs of diastolic dysfunction ( LA > 34 ml/m²; E/e' > 14; TR >2.8 ms, septal e' velocity < 7 cm/s or Lateral e' velocity <10 cm/s)

Exclusion Criteria for HF patients:

Patients with severe valvular disease, infiltrative or hypertrophic cardiomyopathy, acute coronary syndrome in the previous 30 days, chronic obstructive pulmonary disease GOLD 3 or 4, congenital heart disease, pericardial disease, terminal renal failure (eGFR < 15mL/min/1,73m²) or subjects requiring dialysis, atrial fibrillation with a ventricular response > 140 bpm, severe anemia (hemoglobin < 8 g/dL), liver dysfunction, and evolving cancer will be excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Controls; We plan to recruit 10 per decade of age. These subjects will allow us to evaluate the effects of age on the parameters of our study. They will have no risk factors, a normal ECG at rest and normal heart ultrasound and no abnormalities on a stress test. Intervention: cMR	Diagnostic test: cMR; cardiac MRI done to complete the diagnosis; Biological: biomarker; Biomarker correlation with cMR parameters Prognostic information
Active Comparator: HFpEF; We intend to recruit consecutive patients admitted for HFPEF in our institution during the next years. Eligible patients include those with age ≥50 years, LVEF ≥50%, symptomatic HF, and either a hospitalization for HF within the prior year or an elevated natriuretic peptide level (BNP ≥100 pg/mL or NT-proBNP ≥350 pg/mL) within the 60 days before inclusion. Intervention: cMR	Diagnostic test: cMR; cardiac MRI done to complete the diagnosis; Biological: biomarker; Biomarker correlation with cMR parameters Prognostic information
Active Comparator: HFrEF; We intend to recruit consecutive patients admitted for HFrEF in our institution during the next years. Eligible patients include those with age ≥50 years, LVEF ≤40%, symptomatic HF, and either a hospitalization for HF within the prior year or an elevated natriuretic peptide level (BNP ≥100 pg/mL or NT-proBNP ≥350 pg/mL) within the 60 days before inclusion. Intervention: cMR	Diagnostic test: cMR; cardiac MRI done to complete the diagnosis; Biological: biomarker; Biomarker correlation with cMR parameters Prognostic information

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognosis with a follow up including HF hospitalizations and/or deaths.	A follow up will be done by the investigators. After that, they will determine if fibrosis estimated by cMR or biomarkers is a significant prognostic factor.	6 months

Collaborators and Investigators

• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Investigators: Principal Investigator: Anne Catherine Pouleur, Cliniques Universitaires Saint-luc

Publications and helpful links

General Publications

• Roy C, Slimani A, de Meester C, Amzulescu M, Pasquet A, Vancraeynest D, Beauloye C, Vanoverschelde JL, Gerber BL, Pouleur AC. Associations and prognostic significance of diffuse myocardial fibrosis by cardiovascular magnetic resonance in heart failure with preserved ejection fraction. J Cardiovasc Magn Reson. 2018 Aug 8;20(1):55. doi: 10.1186/s12968-018-0477-4.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2014
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: June 20, 2017
• First Submitted That Met QC Criteria: June 22, 2017
• First Posted (Actual): June 23, 2017

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Prognosis; Imaging; heart failure with preserved ejection fraction
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Diastolic
• Other Study ID Numbers: HFpEF; 2012/23AVR/199 (Other Identifier: CEHF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No