A randomized controlled multicenter study comparing the acute hemodynamic performance of the Edwards Sapien XT and the Medtronic CoreValve transcatheter heart valves in high risk patients with severe symptomatic aortic stenosis.

Study design: randomized open-label multicenter

Primary endpoint:

'Device success' as recently defined by VARC which is a 'technical' composite endpoint including:

1. Successful vascular access, delivery and deployment of the device and successful retrieval of the delivery system,
2. Correct position of the device in the proper anatomical location,
3. Intended performance of the prosthetic heart valve (aortic valve area > 1.2 cm2 and mean aortic valve gradient < 20 mmHg or peak velocity < 3 m/s, without moderate or severe prosthetic valve AR) and
4. Only one valve implanted in the proper anatomical location.

Secondary endpoints:

• 30-day-combined safety endpoint which is a combined endpoint defined by VARC as:

  1. All cause mortality,
  2. Major stroke,
  3. Life threatening (or disabling) bleeding,
  4. Acute kidney injury-Stage 3 (including renal replacement therapy),
  5. Periprocedural myocardial infarction,
  6. Major vascular complications and
  7. Repeat procedure for valve-related dysfunction (surgical or interventional therapy). *

• Combined efficacy endpoint at 1 year which is a composite endpoint defined by VARC as:

  1. All cause mortality between 30 days and one year,
  2. Failure of current therapy for aortic stenosis, requiring hospitalization for symptoms of valve-related or cardiac decompensation and
  3. Prosthetic heart valve dysfunction (aortic valve area < 1.2 cm2 and mean aortic valve gradient > 20 mmHg or peak velocity > 3 m/s or moderate or severe prosthetic valve AR). *

• Cardiovascular mortality as defined by VARC at 1 month, 6 and 12 months. *

• Major adverse cardiovascular and cerebrovascular events (MACCE): myocardial infarction, cardiac or vascular surgery and stroke at 30 days, 6 & 12 months.

• Rehospitalization for heart failure at 12 months

• Quality of life (assessed with the Euro5Qual-questionnaire) at 12 months

• NYHA-class improvement at 30 days, 6 and 12 months

• Vascular complication as defined by VARC at 30 days.

• Post-procedural pacemaker implantation at 1 month

• Major or minor Bleeding at 30 days as defined be VARC.

Inclusion Criteria:

1. Severe aortic valve stenosis defined as aortic valve area (AVA) ≤ 1cm2 or 0.6 cm2/m2
2. Presence of clinical symptoms defined as New York Heart Association (NYHA) functional class ≥ 2
3. Age > 75 years and/or Logistic EuroSCORE ≥ 20% and/or STS risk score ≥ 10% and/or contraindication to conventional surgical aortic valve replacement (porcelain aorta, previous chest radiation, chest deformation)
4. Native aortic valve annulus measuring 20-25 mm
5. Patients must be suitable for a transfemoral vascular access
6. The patient signing a written informed consent prior to intervention

Exclusion Criteria:

1. Life expectancy < 12 months due to co-morbid conditions
2. Native aortic valve annulus < 20 mm and > 25 mm (this could be amended if further valve sizes for the transfemoral approach become available for both prostheses during the study period)
3. Pre-existing aortic bioprosthesis
4. Cardiogenic shock or hemodynamic instability
5. History of, or active endocarditis
6. Contraindications for a transfemoral access
7. Active peptic ulcer or upper gastro-intestinal bleeding within the prior 3 months.
8. Hypersensitivity or contraindication to aspirin, heparin or clopidogrel
9. Active infection requiring antibiotic treatment
10. An elective surgical procedure is planned that would necessitate interruption of thienopyridines during the first 3 months post-enrolment
11. Patients actively participating in another drug or device investigational study and have not yet completed the primary endpoint follow-up period