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

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).

Study Overview

• Status: Completed
• Conditions: Regurgitation, Mitral
• Intervention / Treatment: Other: Cardiac Magnetic Resonance Imaging (MRI)

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Hôpital Pneumologique et Cardiovasculaire Louis Pradel - Hospices Civils de Lyon - Groupement Hospitalier Est

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cardiac Magnetic Resonance Imaging; 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); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular volumes	Left ventricular volumes assessed by Cardiac Magnetic Resonance Imaging (MRI)	day 0
Left ventricular volumes	Left ventricular volumes assessed by Cardiac Magnetic Resonance Imaging (MRI)	at 3 months after surgery
left ventricular ejection fraction	Left ventricular function quantification is assessed by left ventricular ejection fraction in %. by Cardiac Magnetic Resonance Imaging (MRI)	day 0
left ventricular ejection fraction	Left ventricular function quantification is assessed by left ventricular ejection fraction in %. by Cardiac Magnetic Resonance Imaging (MRI	at 3 months after surgery
Extracellular volume	Extracellular volume is assessed by Cardiac Magnetic Resonance Imaging (MRI)	day 0
Extracellular volume	Extracellular volume is assessed by Cardiac Magnetic Resonance Imaging (MRI)	3 months after surgery
Mitral Regurgitation (MR) residual assessment	Residual MR is assessed by Cardiac Magnetic Resonance Imaging (MRI)	day 0
Mitral Regurgitation (MR) residual assessment	Residual MR is assessed by Cardiac Magnetic Resonance Imaging (MRI)	at 3 months after surgery
Number of adverse events (AEs)	Post-operative safety is assessed by occurrence of adverse events (AEs) and serious adverse events (SAEs) at each of the follow-up times	up to 12 months
Number of serious adverse events (SAEs)	Post-operative safety is assessed by occurrence of adverse events (AEs) and serious adverse events (SAEs) at each of the follow-up times	up to 12 months
New York Heart Association (NYHA) score	Change in functional evaluation is assessed by NYHA functional classification of heart failure. It is based on symptom severity and the amount of exertion needed to provoke symptoms. NYHA heart failure classes are as follows : Class I No limitation of physical activity, Class II Slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation, or dyspnea; the person is comfortable at rest, Class III Marked limitation of physical activity, in which less-than-ordinary activity results in fatigue, palpitation, or dyspnea; the person is comfortable at rest and Class IV Inability to carry on any physical activity without discomfort but also symptoms of heart failure at rest, with increased discomfort if any physical activity is undertaken.	at day 0
New York Heart Association (NYHA) score	Change in functional evaluation is assessed by NYHA functional classification of heart failure. It is based on symptom severity and the amount of exertion needed to provoke symptoms. NYHA heart failure classes are as follows : Class I No limitation of physical activity, Class II Slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation, or dyspnea; the person is comfortable at rest, Class III Marked limitation of physical activity, in which less-than-ordinary activity results in fatigue, palpitation, or dyspnea; the person is comfortable at rest and Class IV Inability to carry on any physical activity without discomfort but also symptoms of heart failure at rest, with increased discomfort if any physical activity is undertaken.	at discharge from hospital (day 15)
New York Heart Association (NYHA) score	Change in functional evaluation is assessed by NYHA functional classification of heart failure. It is based on symptom severity and the amount of exertion needed to provoke symptoms. NYHA heart failure classes are as follows : Class I No limitation of physical activity, Class II Slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation, or dyspnea; the person is comfortable at rest, Class III Marked limitation of physical activity, in which less-than-ordinary activity results in fatigue, palpitation, or dyspnea; the person is comfortable at rest and Class IV Inability to carry on any physical activity without discomfort but also symptoms of heart failure at rest, with increased discomfort if any physical activity is undertaken.	at 1 month after surgery
New York Heart Association (NYHA) score	Change in functional evaluation is assessed by NYHA functional classification of heart failure. It is based on symptom severity and the amount of exertion needed to provoke symptoms. NYHA heart failure classes are as follows : Class I No limitation of physical activity, Class II Slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation, or dyspnea; the person is comfortable at rest, Class III Marked limitation of physical activity, in which less-than-ordinary activity results in fatigue, palpitation, or dyspnea; the person is comfortable at rest and Class IV Inability to carry on any physical activity without discomfort but also symptoms of heart failure at rest, with increased discomfort if any physical activity is undertaken.	at 3 months after surgery
New York Heart Association (NYHA) score	Change in functional evaluation is assessed by NYHA functional classification of heart failure. It is based on symptom severity and the amount of exertion needed to provoke symptoms. NYHA heart failure classes are as follows : Class I No limitation of physical activity, Class II Slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation, or dyspnea; the person is comfortable at rest, Class III Marked limitation of physical activity, in which less-than-ordinary activity results in fatigue, palpitation, or dyspnea; the person is comfortable at rest and Class IV Inability to carry on any physical activity without discomfort but also symptoms of heart failure at rest, with increased discomfort if any physical activity is undertaken.	at 12 months after surgery
The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)	The EQ-5D-3L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement.	at day 0
The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)	The EQ-5D-3L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement.	at discharge from hospital (day 15)
The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)	The EQ-5D-3L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement.	at 1 month after surgery
The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)	The EQ-5D-3L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement.	at 3 months after surgery
The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)	The EQ-5D-3L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement.	at 12 months after surgery
end-diastolic diameter in mm	Left ventricular dimension assessed by transthoracic echocardiographic exam	at day 0
end-systolic diameter in mm	Left ventricular dimension assessed by transthoracic echocardiographic exam	at day 0
Left ventricular volume	assessed by transthoracic echocardiographic exam	at day 0
end-diastolic diameter in mm	Left ventricular dimension assessed by transthoracic echocardiographic exam	at discharge from hospital (day 15)
end-systolic diameter in mm	Left ventricular dimension assessed by transthoracic echocardiographic exam	at discharge from hospital (day 15)
Left ventricular volume	assessed by transthoracic echocardiographic exam	at discharge from hospital (day 15)
Left ventricular volume	assessed by transthoracic echocardiographic exam	at 1 month after surgery
end-diastolic diameter in mm	Left ventricular dimension assessed by transthoracic echocardiographic exam	at 1 month after surgery
end-systolic diameter in mm	Left ventricular dimension assessed by transthoracic echocardiographic exam	at 1 month after surgery
Left ventricular volume	assessed by transthoracic echocardiographic exam	at 12 months after surgery
end-diastolic diameter in mm	Left ventricular dimension assessed by transthoracic echocardiographic exam	at 12 months after surgery
end-systolic diameter in mm	Left ventricular dimension assessed by transthoracic echocardiographic exam	at 12 months after surgery
Left atrium volume	Left atrium volume are assessed by transthoracic echocardiographic exam	at day 0
Left atrium volume	Left atrium volume are assessed by transthoracic echocardiographic exam	at discharge from hospital (day 15)
Left atrium volume	Left atrium volume are assessed by transthoracic echocardiographic exam	at 1 month after surgery
Left atrium volume	Left atrium volume are assessed by transthoracic echocardiographic exam	at 12 months after surgery
area	area assessed by transthoracic echocardiographic exam	at day 0
area	area assessed by transthoracic echocardiographic exam	at discharge from hospital (day 15)
area	area assessed by transthoracic echocardiographic exam	at 1 month after surgery
area	area assessed by transthoracic echocardiographic exam	at 12 months after surgery
Mitral annulus diameter	Mitral annulus diameter is assessed by transthoracic echocardiographic exam	at day 0
Mitral annulus diameter	Mitral annulus diameter is assessed by transthoracic echocardiographic exam	at discharge from hospital (day 15)
Mitral annulus diameter	Mitral annulus diameter is assessed by transthoracic echocardiographic exam	at 1 month after surgery
Mitral annulus diameter	Mitral annulus diameter is assessed by transthoracic echocardiographic exam	at 12 months after surgery
Mitral Regurgitation (MR) residual assessment	Residual MR is assessed by transthoracic echocardiographic exam	at day 0
Mitral Regurgitation (MR) residual assessment	Residual MR is assessed by transthoracic echocardiographic exam	at discharge from hospital (day 15)
Mitral Regurgitation (MR) residual assessment	Residual MR is assessed by transthoracic echocardiographic exam	at 1 month after surgery
Mitral Regurgitation (MR) residual assessment	Residual MR is assessed by transthoracic echocardiographic exam	at 12 months after surgery

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Actual): July 15, 2024
• Study Completion (Actual): July 15, 2024

Study Registration Dates

• First Submitted: February 25, 2022
• First Submitted That Met QC Criteria: March 9, 2022
• First Posted (Actual): March 17, 2022

Study Record Updates

• Last Update Posted (Estimated): December 2, 2024
• Last Update Submitted That Met QC Criteria: November 28, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Mitral Regurgitation; Myocardial Fibrosis; Cardiac Magnetic Resonance Imaging; Surgical Mitral Valve Repair
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Anatomical; Heart Diseases; Heart Valve Diseases; Heart Valve Prolapse; Fibrosis; Mitral Valve Insufficiency; Prolapse; Ventricular Remodeling; Mitral Valve Prolapse
• Other Study ID Numbers: 69HCL21_1210; ID-RCB (Other Identifier: 2026-A00289-42)

Drug and device information, study documents

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