• Age ≥ 18 years

• NYHA functional II, III or ambulatory IV

• Severe mitral regurgitation (MR grade 3-4+)

• Subject is on optimal guideline-directed medical therapy for heart failure for at least 30 days or CRT if indicated.

• Elevated risk for conventional open mitral valve repair or replacement surgery in the consideration of the site Heart Team (including a cardiac surgeon, a cardiologist and imaging specialist as a minimum) based on STS/Euro Score II (per MVARC Part 1), frailty and co-morbidities.

• Able to undergo Transesophageal Echocardiography (TEE).

• Subject understands the study requirements and the treatment procedures and provides written Informed Consent before any study-specific tests or procedures are performed.

• The subject commits to return for the scheduled post-operative follow-up visits at the hospital.

• Anatomical Inclusion Criteria

• Suitable for femoral access procedure and trans septal catheterization

⁃ Native mitral valve geometry and size and LV outflow tract characteristics compatible with the Cardiovalve (as assessed by the independent Screening Committee)

‣ Cardiovascular Exclusion Criteria

• Prior stroke or TIA within 3 months or Modified Rankin Scale ≥4 disability

• Acute myocardial infarction within the previous 30 days

• Any prior heart valve surgery or transcatheter mitral intervention

• Any percutaneous cardiovascular intervention, cardiovascular surgery, or carotid surgery within 30 days

• Rheumatic heart disease or endocarditis within the previous 3 months

• Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, or any other structural heart disease causing heart failure other than dilated cardiomyopathy of either ischemic or non-ischemic etiology

• Existence of inferior vena cava filter or atrial septal device (contraindicating femoral access and transseptal catheterization)

• Untreated clinically significant coronary artery disease requiring revascularization

• Tricuspid valve disease requiring surgery or severe tricuspid regurgitation

⁃ Aortic or pulmonic valve disease requiring surgery

⁃ CRT/ICD implant within 30 days

⁃ Anatomical Exclusion Criteria (assessed by pre-procedural imaging)

⁃ Left Ventricular Ejection Fraction (LVEF) \<30%

⁃ LV end diastolic diameter \> 70mm

⁃ Significant abnormalities of the mitral valve and sub-valvular apparatus.

⁃ Severe mitral annular or leaflets calcification

⁃ Left atrial or LV thrombus or vegetation

⁃ Severe right ventricular dysfunction

⁃ Severe tricuspid or aortic valve disease