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Completed

NCT Number: NCT05284058

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

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).

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Key information

Conditions

Regurgitation, Mitral Cardiovascular Diseases Heart Diseases Heart Valve Diseases Mitral Valve Insufficiency

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

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

Bron, 69677, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Primary outcomes

  1. Evolution of regional myocardial replacement fibrosis after surgery

    Time frame: at 3 months 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.

Secondary outcomes

  1. Left ventricular volumes

    Time frame: day 0

    Left ventricular volumes assessed by Cardiac Magnetic Resonance Imaging (MRI)

  2. Left ventricular volumes

    Time frame: at 3 months after surgery

    Left ventricular volumes assessed by Cardiac Magnetic Resonance Imaging (MRI)

  3. left ventricular ejection fraction

    Time frame: day 0

    Left ventricular function quantification is assessed by left ventricular ejection fraction in %. by Cardiac Magnetic Resonance Imaging (MRI)

  4. left ventricular ejection fraction

    Time frame: at 3 months after surgery

    Left ventricular function quantification is assessed by left ventricular ejection fraction in %. by Cardiac Magnetic Resonance Imaging (MRI

  5. Extracellular volume

    Time frame: day 0

    Extracellular volume is assessed by Cardiac Magnetic Resonance Imaging (MRI)

  6. Extracellular volume

    Time frame: 3 months after surgery

    Extracellular volume is assessed by Cardiac Magnetic Resonance Imaging (MRI)

  7. Mitral Regurgitation (MR) residual assessment

    Time frame: day 0

    Residual MR is assessed by Cardiac Magnetic Resonance Imaging (MRI)

  8. Mitral Regurgitation (MR) residual assessment

    Time frame: at 3 months after surgery

    Residual MR is assessed by Cardiac Magnetic Resonance Imaging (MRI)

  9. Number of adverse events (AEs)

    Time frame: up to 12 months

    Post-operative safety is assessed by occurrence of adverse events (AEs) and serious adverse events (SAEs) at each of the follow-up times

  10. Number of serious adverse events (SAEs)

    Time frame: up to 12 months

    Post-operative safety is assessed by occurrence of adverse events (AEs) and serious adverse events (SAEs) at each of the follow-up times

  11. New York Heart Association (NYHA) score

    Time frame: at day 0

    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.

  12. New York Heart Association (NYHA) score

    Time frame: at discharge from hospital (day 15)

    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.

  13. New York Heart Association (NYHA) score

    Time frame: at 1 month after surgery

    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.

  14. New York Heart Association (NYHA) score

    Time frame: at 3 months after surgery

    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.

  15. New York Heart Association (NYHA) score

    Time frame: at 12 months after surgery

    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.

  16. The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)

    Time frame: at day 0

    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.

  17. The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)

    Time frame: at discharge from hospital (day 15)

    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.

  18. The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)

    Time frame: at 1 month after surgery

    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.

  19. The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)

    Time frame: at 3 months after surgery

    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.

  20. The 3-level version of EQ-5D (EQ-5D-3L) health status score (quality of life score)

    Time frame: at 12 months after surgery

    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.

  21. end-diastolic diameter in mm

    Time frame: at day 0

    Left ventricular dimension assessed by transthoracic echocardiographic exam

  22. end-systolic diameter in mm

    Time frame: at day 0

    Left ventricular dimension assessed by transthoracic echocardiographic exam

  23. Left ventricular volume

    Time frame: at day 0

    assessed by transthoracic echocardiographic exam

  24. end-diastolic diameter in mm

    Time frame: at discharge from hospital (day 15)

    Left ventricular dimension assessed by transthoracic echocardiographic exam

  25. end-systolic diameter in mm

    Time frame: at discharge from hospital (day 15)

    Left ventricular dimension assessed by transthoracic echocardiographic exam

  26. Left ventricular volume

    Time frame: at discharge from hospital (day 15)

    assessed by transthoracic echocardiographic exam

  27. Left ventricular volume

    Time frame: at 1 month after surgery

    assessed by transthoracic echocardiographic exam

  28. end-diastolic diameter in mm

    Time frame: at 1 month after surgery

    Left ventricular dimension assessed by transthoracic echocardiographic exam

  29. end-systolic diameter in mm

    Time frame: at 1 month after surgery

    Left ventricular dimension assessed by transthoracic echocardiographic exam

  30. Left ventricular volume

    Time frame: at 12 months after surgery

    assessed by transthoracic echocardiographic exam

  31. end-diastolic diameter in mm

    Time frame: at 12 months after surgery

    Left ventricular dimension assessed by transthoracic echocardiographic exam

  32. end-systolic diameter in mm

    Time frame: at 12 months after surgery

    Left ventricular dimension assessed by transthoracic echocardiographic exam

  33. Left atrium volume

    Time frame: at day 0

    Left atrium volume are assessed by transthoracic echocardiographic exam

  34. Left atrium volume

    Time frame: at discharge from hospital (day 15)

    Left atrium volume are assessed by transthoracic echocardiographic exam

  35. Left atrium volume

    Time frame: at 1 month after surgery

    Left atrium volume are assessed by transthoracic echocardiographic exam

  36. Left atrium volume

    Time frame: at 12 months after surgery

    Left atrium volume are assessed by transthoracic echocardiographic exam

  37. area

    Time frame: at day 0

    area assessed by transthoracic echocardiographic exam

  38. area

    Time frame: at discharge from hospital (day 15)

    area assessed by transthoracic echocardiographic exam

  39. area

    Time frame: at 1 month after surgery

    area assessed by transthoracic echocardiographic exam

  40. area

    Time frame: at 12 months after surgery

    area assessed by transthoracic echocardiographic exam

  41. Mitral annulus diameter

    Time frame: at day 0

    Mitral annulus diameter is assessed by transthoracic echocardiographic exam

  42. Mitral annulus diameter

    Time frame: at discharge from hospital (day 15)

    Mitral annulus diameter is assessed by transthoracic echocardiographic exam

  43. Mitral annulus diameter

    Time frame: at 1 month after surgery

    Mitral annulus diameter is assessed by transthoracic echocardiographic exam

  44. Mitral annulus diameter

    Time frame: at 12 months after surgery

    Mitral annulus diameter is assessed by transthoracic echocardiographic exam

  45. Mitral Regurgitation (MR) residual assessment

    Time frame: at day 0

    Residual MR is assessed by transthoracic echocardiographic exam

  46. Mitral Regurgitation (MR) residual assessment

    Time frame: at discharge from hospital (day 15)

    Residual MR is assessed by transthoracic echocardiographic exam

  47. Mitral Regurgitation (MR) residual assessment

    Time frame: at 1 month after surgery

    Residual MR is assessed by transthoracic echocardiographic exam

  48. Mitral Regurgitation (MR) residual assessment

    Time frame: at 12 months after surgery

    Residual MR is assessed by transthoracic echocardiographic exam

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Acronym: IMPARED

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Mar 17, 2022
Registry last updated
Dec 2, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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