Impact of Preoperative Myocardial Fibrosis Related to Mitral Valve Prolapse on Postoperative Left Ventricular Remodeling

NCT05284058 | Completed

• 2 other identifiers: 69HCL21_1210ID-RCB
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Primary mitral regurgitation (MR) is the most common valvular disease in western countries. The MR mechanism is often related to a mitral valve prolapse (MVP) defined as a single or bi-leaflet prolapse of at least 2 mm beyond the long-axis mitral annular plane. In recent years, several studies have identified a subtype of MVP patients at higher risk of ventricular arrhythmias (VA) and sudden cardiac death (SCD). The presence of regional myocardial replacement fibrosis (RMRF) has been shown as a risk marker of arrhythmic events (VA and SCD) in patients with MVP. RMRF can be identified using cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE+). In these patients, fibrosis was found in the basal inferolateral myocardium and at the level of papillary muscles (PMs). This fibrosis is developed beyond the volume overload related to the MVP. It is probably linked to the mechanical stretch acting upon the valve and the neighboring left ventricle (LV) myocardium. RMRF is associated with a high degree of MR, with specific features of mitral valve apparatus (bi-leaflet prolapse with marked leaflet redundancy, mitral annulus abnormalities (i.e. Mitral-Annular Disjunction)), and more dilated LV. It is also independently associated with the occurrence of cardiovascular events. Mitral valve repair (MVr) is the gold standard treatment for primary Mitral Regurgitation. Very little data concerning the impact of preoperative RMRF on mitral valve surgery outcomes is available, and the impact of myocardial fibrosis on the postoperative left ventricle remodeling has not been studied so far. No previous study compares preoperative and postoperative fibrosis evolution. Thus, no data exists regarding the postoperative evolution of this fibrosis and its relationship with ventricular arrhythmic risk after valve surgery. Small observational studies have suggested that mitral valve surgery did not reduce the risk of ventricular arrhythmias in patients with bileaflet MVP. Finally, the mechanisms involved in the development of regional myocardial replacement fibrosis within the left ventricle myocardium during the natural history of MVP cannot be understood with current standard medical imaging tools. Numerical simulation technologies provide an innovative and in-vivo approach to assess the physical and pathological mechanisms causing this fibrosis. They can also be used to assess the changes in mitral valve and myocardium dynamics after surgical mitral valve repair procedures. A large consortium, involving physicians and scientists, has been created to address these questions to fulfil our objectives over a 4 year period (SIMR project).

Conditions

Regurgitation, Mitral

Keywords

Mitral Regurgitation; Myocardial Fibrosis; Surgical Mitral Valve Repair; Cardiac Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• Evolution of regional myocardial replacement fibrosis after surgery

  Evolution of fibrosis mass within the left ventricle myocardium (assessed as Regional late gadolinium enhancement) on cardiac magnetic resonance (CMR) imaging at 3 months after surgery.

  at 3 months after surgery

Secondary Outcomes (48)

• Left ventricular volumes

  day 0

• Left ventricular volumes

  at 3 months after surgery

• left ventricular ejection fraction

  day 0

• left ventricular ejection fraction

  at 3 months after surgery

• Extracellular volume

  day 0

Study Arms (1)

Cardiac Magnetic Resonance Imaging

EXPERIMENTAL

All patients who are candidates for surgical mitral valve repair through minimally-invasive access according to the standard of care will be considered for inclusion in this clinical study. All patients will undergo cardiac Magnetic Resonance Imaging (MRI) exam before the surgery, as well as at 3 months follow-up.

Other: Cardiac Magnetic Resonance Imaging (MRI)

Interventions

Cardiac Magnetic Resonance Imaging (MRI) OTHER

Patients will undergo 2 MRI exams: 1 MRI before surgical intervention (maximum 21 days before) and 1 MRI three months after surgery (+/- 14 days), with intravenous administration of gadolinium.

Cardiac Magnetic Resonance Imaging

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (≥ 18 years old)
• Patients candidate for mitral valve repair after validation by the local Heart-Team
• Severe symptomatic primary Mitral Regurgitation (MR), due to:
• Posterior or bileaflet prolapse, with
• Criteria of advance disease (i.e. existence of fibrosis):
• Effective Regurgitant Orifice Area (EROA) \> 35 mm2 - Regurgitant volume \> 45 mL
• Left ventricular end-diastolic diameter \>55 mm
• Left atrium volume index \>60 mL/m2
• Pulmonary artery systolic pressure \> 30mmHg
• Patients who have provided written informed consent to participate in the study.
• Patients affiliated with a social health insurance.

You may not qualify if:

• Patients with contraindication for mitral valve repair, including:
• Patients with secondary MR; and
• Calcified leaflets segments.
• Patients with contraindication for a minimally invasive approach including:
• Previous heart surgery;
• Previous right lung surgery; or
• Vascular access contraindications.
• Patients with contraindication for CMR imaging:
• Patients without sinus rhythm
• Regular MRI contraindications (e.g. a claustrophobia, a pacemaker, defibrillator or metallic (ferromagnetic) body, a known allergy to gadolinium)
• Contraindication for Gadolinium infusion: glomerular filtration rate (GFR) \<30 ml / min
• Patients unable to understand the purpose of the study
• Patients participating in another trial that would interfere with this study
• Female patients who are pregnant, lactating or women of child-bearing potential without highly effective methods of contraception
• Patients under judicial protection

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hôpital Pneumologique et Cardiovasculaire Louis Pradel - Hospices Civils de Lyon - Groupement Hospitalier Est

Bron, 69677, France

Location

MeSH Terms

Conditions

Mitral Valve Insufficiency

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2022
• First Posted: March 17, 2022
• Study Start: June 28, 2022
• Primary Completion: July 15, 2024
• Study Completion: July 15, 2024
• Last Updated: December 2, 2024

Record last verified: 2024-11

Locations

FR (1)