The Role of cardIac magNeTic rEsonance in surGical Decision Making in Patients With Severe pRimAry miTral rEgurgitation

NCT07366723 | Active Not Recruiting

• 1 other identifier: L2-495
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

Brief Summary

Mitral regurgitation (MR) is the second most frequent valvular heart disease and the second most frequent indication for valve surgery in Europe. The management of patients with MV prolapse (MVP) and severe MR is mainly guided by symptoms, left ventricular (LV) dimensions and ejection fraction (EF), pulmonary artery systolic pressure (PASP) and atrial fibrillation (AF) occurrence. According to the ESC/EACTS guidelines, surgical treatment of severe primary MR is indicated (recommendation Class I, Level B) in case of:

• symptomatic patients considered operable by the Heart Team;
• asymptomatic patients with LV dysfunction, intended as a LVEF ≤ 60% and/or LV end-systolic diameter (LVESD) ≥ 40 mm or LVESD indexed for body mass area (LVESDi) ≥ 20 mm/m2;
• low-risk asymptomatic patients without LV dysfunction (LVEF \> 60%, LVESD \< 40 mm, LVESDi \< 20 mm/m2) when a durable result is likely, if at least 3 of the following criteria are fulfilled:
• AF secondary to MR;
• PASP value at rest \> 50 mmHg;
• significant left atrium (LA) dilation, intended as LA volume index ≥ 60 mL/m2 or diameter ≥ 55 mm
• concomitant secondary tricuspid regurgitation ≥ moderate. Surgery should be considered (recommendation Class IIa, Level B) in asymptomatic patients with preserved LV function (LVEF \> 60%, LVESD \< 40 mm, LVESDi \< 20 mm/m2), when one of the following findings is present1:
• AF secondary to MR;
• PASP value at rest \> 50 mmHg;
• LA volume index ≥ 60 mL/m2 or diameter ≥ 55 mm, provided surgical risk is low, surgery is performed in a Heart Valve Center and a durable MV repair is likely. Preliminary data suggest that in patients with MVP, especially with Barlow's disease phenotype, left-sided chambers' enlargement and functional impairment may be disproportionate related to MR grade. Indeed, patients with BD and ≤ mild-to-moderate MR show larger LA and LV dimensions as compared to controls matched for age, gender and cardiovascular risk factors. These findings challenge the assumption that LA and LV remodeling is a direct effect of volume overload, with possible implications regarding the indication for MV intervention. On the other hand, low mortality and good durability of valve repair has led some experienced centers to perform also early surgery, namely in any asymptomatic patient with severe MR, normal LV size and function, regular sinus rhythm, normal PASP and normal LA size, as long as surgical risk is very low and likelihood of successful valve repair is high. However, some studies have demonstrated that asymptomatic patients with severe degenerative MR can be safely followed up in experienced hands and remain free of indications for surgery for extensive periods of time. A watchful waiting strategy resulted in timely referral to surgery, excellent long-term survival, and good surgical outcomes, though requiring careful and active surveillance. Several authors agree that prospective randomized trials comparing active surveillance and early elective surgery are needed. There are also data suggesting that MR quantification by CMR has better discriminative power in identifying asymptomatic patients with degenerative MR and adverse outcomes as compared to the echocardiographic-derived integrative approach. Further prospective studies are necessary to validate these preliminary findings.

Conditions

Mitral Valve Prolapse; Mitral Regurgitation

Outcome Measures

Primary Outcomes (1)

• Proportion of adverse and reverse LV remodeling

  The primary efficacy aim is to demonstrate that in patients managed based on CMR results ("unblinded CMR") the proportion of inappropriate clinical decisions is lower as compared to the proportion of inappropriate clinical decisions in patients managed on the basis of TTE results ("blinded CMR"). In group A: * clinical decision will be considered appropriate in case reverse LV remodeling, or no LV remodeling is observed by CMR at 2-year follow-up * clinical decision will be considered inappropriate in case adverse LV remodeling by CMR occurs at 2-year follow-up. In groups B and C: * clinical decision will be considered appropriate in case reverse LV remodeling by CMR occurs at 2-year follow-up * clinical decision will be considered inappropriate in case adverse LV remodeling, or no LV remodeling is observed by CMR at 2-year follow-up. Operational definitions: Adverse LV remodeling=increase in LV EDV \>/= 10% vs baseline. Reverse LV remodeling=reduction in LV EDV \>/= 30% vs. baseline.

  up to 24 months

Secondary Outcomes (4)

• Rate of composite clinical endpoints

  up to 24 months

• rate of mortality

  up to 24 months

• Measure of exercise capacity

  up to 24 moths

• SF-36 Health Survey questionnaire

  up to 24 months

Study Arms (4)

Blinded CMR - Group C1

ACTIVE COMPARATOR

Patients undergoing sugery based on TTE, showing less than severe MR by CMR

Procedure: mitral valve surgery

Unblinded CMR - Group A

OTHER

Patients with severe MR, as assessed by TTE, with less than severe MR documented by CMR (Group A), undergo clinical follow-up.

Other: Clinical Follow up

Unblinded CMR - Group B

ACTIVE COMPARATOR

Patients with severe MR, as quantified by both TTE and CMR, undergo surgery.

Procedure: mitral valve surgery

Blinded CMR - Group C2

ACTIVE COMPARATOR

Patients undergoing surgery based on TTE, showing severe MR by CMR

Procedure: mitral valve surgery

Interventions

mitral valve surgery PROCEDURE

mitral valve repair or replacement

Blinded CMR - Group C1; Blinded CMR - Group C2; Unblinded CMR - Group B

Clinical Follow up OTHER

Patients undergo clinical active surveillance.

Unblinded CMR - Group A

Eligibility Criteria

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

You may qualify if:

• age ≥ 18 years;
• patients agree to all provisions of the protocol;
• patient can give informed consent;
• TTE diagnosis of MVP (defined as a systolic displacement of one or both mitral leaflets ≥ 2 mm above the plane of the MV annulus in long-axis views), and chronic severe MR;
• no symptoms;
• LVEF \> 60%, LVESD \< 40 mm and LVESDi \< 20 mm/m2;
• sinus rhythm;
• PASP value at rest \< 50 mmHg;
• LA volume index ≥ 60 mL/m2 or diameter ≥ 55 mm or normal LA size if likelihood of a successful and durable repair without residual MR is \>95% and expected mortality rate is \<1%
• ongoing adequate treatment per applicable standards;
• patient referred for isolated MV repair or replacement;
• willingness to undergo TTE, CMR and CPET at different timepoints

You may not qualify if:

• inability to provide informed consent;
• pregnancy or planned pregnancy within next 2 years;
• poor TTE image quality;
• usual contraindications to CMR and/or to gadolinium administration;
• inability to sustain a breath hold;
• known intracardiac shunts;
• coexistence of other cardiomyopathies or other \> mild valve diseases;
• untreated clinically significant coronary artery disease requiring revascularization;
• planned concomitant cardiac surgical procedures (e.g. other valve procedures, or coronary artery bypass);
• need for an emergent/urgent surgery for any reason or any planned cardiac surgery within the next months;
• hemodynamic instability requiring inotropic support or mechanical heart assistance;
• sustained cardiac arrhythmias;
• active endocarditis;
• like expectancy \< 12 months due to non-cardiac conditions.

Sponsors & Collaborators

• Centro Cardiologico Monzino: lead
• Azienda Ospedaliero-Universitaria di Parma: collaborator
• Policlinico SS Annunziata di Chieti: collaborator

Study Sites (1)

Centro Cardiologico Monzino, IRCCS

Milan, MI, 20131, Italy

Location

MeSH Terms

Conditions

Mitral Valve Prolapse; Mitral Valve Insufficiency

Condition Hierarchy (Ancestors)

Heart Valve Prolapse; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases

Study Officials

• Gianluca Pontone, MD

  Centro Cardiologico Monzino, IRCCS Milan 20131

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized in a 1:1 ratio to a CMR-based strategy (unblinded CMR) or usual care (blinded CMR). A randomization list will be generated using SAS statistical software and will be created by the Biostatistics Unit of Centro Cardiologico Monzino IRCCS, without direct contact with trial participants or involvement in the assessment of study eligibility. After randomization, patients will be classified as follows: * group A: patients with severe MR, as assessed by TTE, with less than severe MR documented by CMR, undergoing clinical follow-up; * group B: patients with severe MR, as quantified by both TTE and CMR, undergoing surgery; * group C: patients with severe MR, as assessed by TTE, undergoing surgery as per clinical practice. After surgery, baseline CMR of Group C will be unblinded. Then, patients of group C will be furtherly divided into two subgroups: those having less than severe MR as assessed by CMR (subgroup C1) and those with severe MR (subgroup C2).

Study Record Dates

• First Submitted: December 3, 2025
• First Posted: January 26, 2026
• Study Start: December 1, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: April 15, 2026

Record last verified: 2025-12

Locations

IT (1)