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

The present study is a multicenter, prospective, interventional, open randomized controlled trial. Patients will be screened for study eligibility by the clinical research staff of each investigational site. Patients meeting all inclusion criteria will be asked to sign an informed consent document prior to any trial-specific examinations and/or procedures, provided they do not have any of the exclusion criteria. After signing the informed consent, a structured interview will be performed and a clinical history obtained, assessing the presence of common cardiac risk factors, symptoms, and drug therapy (with a specific focus on anti-remodeling drugs, such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and mineralocorticoid receptor blockers). A Quality of Life (QoL) questionnaire will be administered13. Physical examination, rest ECG, CMR and a cardiopulmonary exercise test (CPET) will be also performed.

Subjects will be assigned a subject number upon enrolment. Afterwards, they will be randomized in a 1:1 ratio to a CMR-based strategy (unblinded CMR) or usual care1 (blinded CMR).

A randomization list will be generated using SAS statistical software (version 9.4, SAS Institute, Cary, NC, USA) 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 (Figure 1 and 2):

• 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 patients of group B and C have undergone 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 having severe MR (subgroup C2).

At 1-year and 2-year follow-up after enrolment (group A) and after surgery (groups B and C), all patients will undergo a complete evaluation including a clinical interview and physical examination, administration of QoL questionnaires, performance of TTE, CMR and CPET.

Inclusion criteria

• 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

Exclusion criteria

• 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.