Cardiac valve disorders are widely spread in the general population and represents the third most frequent cardiovascular illness after coronary disease and arterial hypertension. In this context, aortic valve stenosis (the central pathology in this project) is the most common form of valve disease. Cardiac valve replacement is in the vast majority of cases the first line therapy for degenerative heart-valve diseases. These are represented by mechanical and bioprosthetic valve (BHV). In the vast majority of cases, BHV are derived from animals and from a biological standpoint are classified as xenografts. BHV are severely penalised by a premature structural damage, with ultimate valve failure occurring around 10 years after surgery in 5 to 30% of cases, depending on the type of BHV used. Several factors [including dyslipidaemia, gender, valve position] may contribute to the ultimate failure of the BHV and there has been increasing evidence recently of a substantial immune reaction elicited by the implanted BHV. This immune response is still poorly understood. It may lead to adverse immune reactions and this will be thoroughly investigated by the TRANSLINK team. In this light, the TRANSLINK project aims to provide the necessary data to demonstrate beyond any reasonable doubt the central role of the anti-BHV immune response in the premature failure of BHV and to provide efficient strategies to enable safe implantation of BHV valves in currently unsuitable candidates

Inclusion criteria

To be enrolled, the following criteria have to be fulfilled:

*Phase A: Diagnostic Study

Inclusion criteria for SVD-patients:

• Patient age: 18 to 85 years old at the time of surgery
• Echographic signs of SVD (Mean trans-valvular gradient ≥ 30 mm Hg AND Effective Orifice Area ≤ 1 cm2 worsen over time OR Aortic Insufficiency > grade 2/4)
• Single aortic valve replacement +/- associated to CABG, Bental, Mitral or Tricuspid repair, aortic surgery, Radiofrequency.
• First cardiac surgery (no multiple cardiac surgeries)
• No immunosuppressive regimen any time within the 6 months prior surgery.
• - No use of other allo or xenogenic tissue than aortic valve prosthesis during cardiac surgery
• Patient has been informed of the nature of the study, agrees to its provisions and has signed the informed consent form prior to any study related procedure
• Patient agrees to undergo all protocol required follow-up examinations and requirements at the investigational site

Non-SVD patients (control-patients):

• Patients will be defined as patients operated on with an aortic BHV without echographic signs of SVD and matched for: Age at surgery (±2 years), type of BHV and follow-up time (± 6 months).
• Patient has been informed of the nature of the study, agrees to its provisions and has signed the informed consent form prior to any study related procedure
• Patient agrees to undergo all protocol required follow-up examinations and requirements at the investigational site

To increase the statistical power (which cannot be calculated according to the novelty of the project), two controls will be matches with each SVD-Case.

*Phase B: Prospective Study

B1: Cohort of prevalent patients

• Patient age: 18 - 85 years old at the time of surgery
• Patient scheduled for single aortic valve replacement with a BHV (surgical or percutaneous valve) +/- associated to CABG, Bental, Mitral or Tricuspid repair, aortic surgery, Radiofrequency.
• First cardiac surgery (no multiple cardiac surgeries)
• No immunosuppressive regimen any time within the 6 months prior surgery and no immunosuppressive regimen after surgery.
• No use of other allo or xenogenic tissue than aortic valve prosthesis during cardiac surgery
• Patient is affiliated to the Social Security or equivalent system
• Patient has been informed of the nature of the study, agrees to its provisions and has signed the informed consent form prior to any study related procedure
• Patient agrees to undergo all protocol required follow-up examinations and requirements at the investigational site Eight of the most frequently implanted BHV worldwide will be assessed: 1 surgical porcine valve: Mosaic (Medtronic); 4 surgical bovine pericardium valves: Perimount-Carpentier (Edwards), Magna ease (Edwards), Trifecta (St. Jude Medical) and the Mitroflow PRT valve (Sorin); 1 surgical equine valve: 3F-valve or Enable (Medtronic) and 2 percutaneous pericardium valves (TAVI): Corevalve (porcine pericardium - Medtronic) and Sapien valve (bovine pericardium - Edwards).

Fifty patients per type of BHV will be included. When 50 patients were included in one of the eight groups, we will stop the inclusions in this group.

Additionally, a control group of heart operated patients without biological valve will be included in the study (patients operated on with a mechanical valve (n=50) or for CABG without BHV (n=50).

Control group (CABG or aortic mechanical valve)

• Patient age: >65 years old for CABG and 18-85 years old for mechanical valve replacement
• Patient operated on coronary artery bypass (for CABG group)
• Patient with valve aortic replacement following aortic valve stenosis (for mechanical valve group)
• No immunosuppressive regimen any time within the 6 months prior surgery and no immunosuppressive regimen after surgery.
• No use of other allo or xenogenic tissue than aortic valve prosthesis during cardiac surgery.

B2: Cohort of incident patients

• Patient age: 18 to 85 years old (at the time of surgery) who underwent a single isolated aortic valve replacement with a BHV +/- associated to CABG, Bental, Mitral or Tricuspid repair, aortic surgery, Radiofrequency. more than 5 years ago.
• First cardiac surgery (no multiple cardiac surgeries)
• No immunosuppressive regimen any time within the 6 months before inclusion and no immunosuppressive regimen after inclusion.
• Patient is affiliated to the Social Security or equivalent system
• Patient has been informed of the nature of the study, agrees to its provisions and has signed the informed consent form prior to any study related procedure
• Patient agrees to undergo all protocol required follow-up examinations and requirements at the investigational site

As control, patients who underwent isolated CABG (n=50) or aortic mechanical valve replacement more than 5 years ago (n=50) will be enrolled.

Control group (CABG or aortic mechanical valve)

• Patient age (at the time of surgery): > 65 years old for CABG and 18-85 years old for mechanical valve replacement
• Patient operated on coronary artery bypass (for CABG group) more than 5 years ago
• Patient with valve aortic replacement following aortic valve stenosis (for mechanical valve group) more than 5 years ago
• No immunosuppressive regimen any time within the 6 months prior inclusion and no immunosuppressive regimen after inclusion.
• No use of other allo or xenogenic tissue than aortic valve prosthesis during cardiac surgery

Exclusion criteria

Any of the following is regarded as criteria for exclusion from the study:

• Female of child bearing potential
• Severe renal insufficiency: GFR <=30 ml/min/
• Severe dyslipidemia: total cholesterol >350 mg/dl, triglycerides >750 mg/dl
• Ongoing infection (patient may be evaluated for enrolment after resolution)
• HIV infection
• Active autoimmune disease
• Multiple cardiac surgeries
• Patient with immunosuppression regimen
• Presence of any condition (medical, psychological, social, or geographical), actual or anticipated, that the Investigator feels would restrict or limit the patient's successful participation for the inclusion or duration of the study
• Presence of any severe medical condition such that the patient is not expected to survive for the planned study follow-up period.
• Patient is not able to give informed consent
• Patient under trusteeship or under guardianship
• No affiliation to a social security or equivalent system
• Patient is currently participating in an investigational drug or device study that clinically interferes with the current study endpoints