Association Between Coronary and Peripheral Vascular Injury in Heart Failure Patients With Preserved Ejection Fraction. (COROVASC)

Heart failure with preserved ejection fraction (HPEF, defined as LVEF ≥50%) represents 50% of hospital admissions for heart failure. Although its morbi-mortality is similar to that of heart failure with reduced ejection fraction (HFPEF), it remains an unknown disease with limited data especially from an etiological point of view. The underlying causes are imperfectly understood, and more than half of the patients have HPEF labeled "idiopathic."

A non-hierarchical clustering study of HPEF patients led to the identification of a subgroup of patients (25%) with a predominant coronary vascular phenotype (i.e., a history of coronary stenosis with or without the need for revascularization). In these patients, vascular endothelial dysfunction would play a central role in the development and progression of heart failure.One of the mechanisms leading to HPEF could be a decrease in the bioavailability of nitric oxide (NO) involved in the relaxation of the cardiac muscle. As the mechanism of action of NO is pleiotropic, a decrease in NO bioavailability could also be observed at the peripheral level, favoring in the long term the development of unfavorable vascular remodeling, for example in the small digital or retinal arteries.Some HPEF patients could thus be distinguished from others by their predominant "vascular" profile. The link between HPEF and endothelial dysfunction has been suspected but never clearly demonstrated.

Ultra-high frequency ultrasound is an innovative technology to estimate the remodeling of small distal arteries in a non-invasive way. The investigators propose to use this imaging on digital arteries in HPEF patients and to study the association with known coronary macrovascular damage.The remodeling parameters will be measured and compared in patients with HPEF with or without identified macrovascular coronary disease.This characterization of arterial remodeling on the digital arteries could be a powerful tool for non-invasive screening in the identification of a subgroup of HPEF that is still considered idiopathic.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Other: Ultrahigh-frequency ultrasound

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Natacha Nohilé; Email: natacha.nohile@aphp.fr
• Study Contact Backup: Name: Annie BERGERA; Phone Number: 33 (0)1 44 84 17 24; Email: gestion-locale.drc@aphp.fr

Study Locations

• France
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou - AP-HP
    • Contact: Roxane GAÏSSET, MD; Phone Number: 33 156095398; Email: roxane.gaisset@aphp.fr
    • Contact: Jean-Sébastien HULOT, MD-PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria :

Group 1 :

• Patients who are ≥ 18 years old
• Heart failure with preserved ejection fraction (LVEF ≥ 50%)
• B-type natriuretic peptide (BNP) > 35 pg/mL at inclusion
• Coronary macrovascular disease (significant coronary stenosis, which may have required revascularization by stenting or coronary bypass surgery).

Group 2 :

• Patients who are ≥ 18 years old
• Heart failure with preserved ejection fraction (LVEF ≥ 50%)
• B-type natriuretic peptide (BNP) > 35 pg/mL at screening
• Absence of coronary macrovascular disease (no significant coronary atheroma (< 30%) or history of stenting or coronary bypass surgery).

Non-inclusion Criteria :

Group 1 and group 2 :

• Patients under legal protection
• Patients not affiliated to a Social Security system
• Patient under State Medical Help (France - AME)
• Pregnancy or breastfeeding
• Refusal or inability to sign consent
• Known and treated retinal vasculopathy
• Severe or non-stabilized hypertension (BP > 180/100 mmHg at screening)
• History of LVEF < 40%.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Heart Failure Preserved Ejection Fraction with coronary disease	Other: Ultrahigh-frequency ultrasound; Arterial remodeling of the digital arteries will be measured by ultrahigh-frequency ultrasound and will be compared in heart failure patients with preserved ejection fraction with and without identified macroscopic coronary disease
Other: Heart Failure Preserved Ejection Fraction without coronary disease	Other: Ultrahigh-frequency ultrasound; Arterial remodeling of the digital arteries will be measured by ultrahigh-frequency ultrasound and will be compared in heart failure patients with preserved ejection fraction with and without identified macroscopic coronary disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Digital vascular remodeling by ultrahigh-frequency ultrasound	The wall-to-lumen ratio of digital arteries recorded with ultrahigh-frequency ultrasound.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radial vascular remodeling by echo-tracking	Measurement of peripheral vascular remodeling on radial arteries by arterial distension parameters.	Day 1
Carotid vascular remodeling by echo-tracking	Measurement of peripheral vascular remodeling on carotid arteries by arterial distension parameters.	Day 1
Endothelial dysfunction	Level of endothelial function measured by arterial flow-mediated vasodilation (FMD, expressed in %).	Day 1
Pulse wave velocity	Pulse wave velocity (PWV, velocity expressed in m/s) carotid-femoral (aortic elasticity).	Day 1
Retinal microvascularization	To study the retinal microvascularization by Optical Coherence Tomography Angiography (OCT-A) : density measurement per sector (% per studied area).	Day 1
Calcium score	Compare the calcium score (expressed by the Agatston score) in patients with heart failure with preserved ejection fraction with or without a priori coronary artery disease.	Day 1

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Roxane GAÏSSET, MD, Assistance Publique - Hopitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2023
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: May 10, 2023
• First Submitted That Met QC Criteria: May 22, 2023
• First Posted (Actual): June 1, 2023

Study Record Updates

• Last Update Posted (Estimated): June 2, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Ischemia; Microcirculation; Heart Failure with Preserved Ejection Fraction; Ultrahigh-frequency ultrasound; Arterial remodeling; Small arteries
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Wounds and Injuries; Heart Failure; Vascular System Injuries
• Other Study ID Numbers: APHP230214; 2022-A02455-38 (Other Identifier: Agence Nationale de Sécurité du Médicament et des produits de santé); 23.00664.000175 (Other Identifier: Commission Nationale des Recherche Impliquant la Personne Humaine)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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