Clinical trial NCT05284058: Impact of Preoperative Myocardial Fibrosis Related to Mitral Valve Prolapse on Postoperative Left Ventricular Remodeling
Official title: Impact of Preoperative Myocardial Fibrosis Related to Mitral Valve Prolapse on Postoperative Left Ventricular Remodeling
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Regurgitation, Mitral
Keywords: Mitral Regurgitation
Myocardial Fibrosis
Surgical Mitral Valve Repair
Cardiac Magnetic Resonance Imaging
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2022-03-17
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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).


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Evolution of regional myocardial replacement fibrosis after surgery
timeFrame: at 3 months after surgery
Secondary outcomes:
measure: Left ventricular volumes
timeFrame: day 0
measure: Left ventricular volumes
timeFrame: at 3 months after surgery
measure: left ventricular ejection fraction
timeFrame: day 0
measure: left ventricular ejection fraction
timeFrame: at 3 months after surgery
measure: Extracellular volume
timeFrame: day 0
measure: Extracellular volume
timeFrame: 3 months after surgery
measure: Mitral Regurgitation (MR) residual assessment
timeFrame: day 0
measure: Mitral Regurgitation (MR) residual assessment
timeFrame: at 3 months after surgery
measure: Number of adverse events (AEs)
timeFrame: up to 12 months
measure: Number of serious adverse events (SAEs)
timeFrame: up to 12 months
measure: New York Heart Association (NYHA) score
timeFrame: at day 0
measure: New York Heart Association (NYHA) score
timeFrame: at discharge from hospital (day 15)
measure: New York Heart Association (NYHA) score
timeFrame: at 1 month after surgery
measure: New York Heart Association (NYHA) score
timeFrame: at 3 months after surgery
measure: New York Heart Association (NYHA) score
timeFrame: at 12 months after surgery
measure: The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)
timeFrame: at day 0
measure: The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)
timeFrame: at discharge from hospital (day 15)
measure: The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)
timeFrame: at 1 month after surgery
measure: The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)
timeFrame: at 3 months after surgery
measure: The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)
timeFrame: at 12 months after surgery
measure: end-diastolic diameter in mm
timeFrame: at day 0
measure: end-systolic diameter in mm
timeFrame: at day 0
measure: Left ventricular volume
timeFrame: at day 0
measure: end-diastolic diameter in mm
timeFrame: at discharge from hospital (day 15)
measure: end-systolic diameter in mm
timeFrame: at discharge from hospital (day 15)
measure: Left ventricular volume
timeFrame: at discharge from hospital (day 15)
measure: Left ventricular volume
timeFrame: at 1 month after surgery
measure: end-diastolic diameter in mm
timeFrame: at 1 month after surgery
measure: end-systolic diameter in mm
timeFrame: at 1 month after surgery
measure: Left ventricular volume
timeFrame: at 12 months after surgery
measure: end-diastolic diameter in mm
timeFrame: at 12 months after surgery
measure: end-systolic diameter in mm
timeFrame: at 12 months after surgery
measure: Left atrium volume
timeFrame: at day 0
measure: Left atrium volume
timeFrame: at discharge from hospital (day 15)
measure: Left atrium volume
timeFrame: at 1 month after surgery
measure: Left atrium volume
timeFrame: at 12 months after surgery
measure: area
timeFrame: at day 0
measure: area
timeFrame: at discharge from hospital (day 15)
measure: area
timeFrame: at 1 month after surgery
measure: area
timeFrame: at 12 months after surgery
measure: Mitral annulus diameter
timeFrame: at day 0
measure: Mitral annulus diameter
timeFrame: at discharge from hospital (day 15)
measure: Mitral annulus diameter
timeFrame: at 1 month after surgery
measure: Mitral annulus diameter
timeFrame: at 12 months after surgery
measure: Mitral Regurgitation (MR) residual assessment
timeFrame: at day 0
measure: Mitral Regurgitation (MR) residual assessment
timeFrame: at discharge from hospital (day 15)
measure: Mitral Regurgitation (MR) residual assessment
timeFrame: at 1 month after surgery
measure: Mitral Regurgitation (MR) residual assessment
timeFrame: at 12 months after surgery
Other outcomes:
Locations:
city: Bron
country: France
facility: Hôpital Pneumologique et Cardiovasculaire Louis Pradel - Hospices Civils de Lyon - Groupement Hospitalier Est
Study officials:
References: