The PROTEMBO Trial

Inclusion Criteria:

1. The heart team recommends transcatheter aortic valve replacement via femoral accessconsistent with the 2020 ACC/AHA Guideline for the Management of Patients WithValvular Heart Disease.

2. The subject and the treating physician agree that the subject will undergo thescheduled pre procedural testing and return for all required post procedure followup visits.

3. The subject is able to provide informed consent, has been informed of the nature ofthe trial, agrees to its provisions and has provided written informed consent asapproved by the relevant regulatory authority of the respective clinical site.

4. Subject is a minimum of 18 years of age.

Exclusion Criteria:

General exclusion criteria:

1. Subject is a woman of child-bearing potential.

2. Arm anatomy/ vasculature precluding radial or brachial artery access.

3. Hemodialysis shunt, graft, or arterio-venous fistula involving the upper extremityvasculature.

4. Evidence of an acute myocardial infarction ≤ 1 month before the intended treatment.

5. Severe ventricular dysfunction with LVEF ≤25%.

6. Any therapeutic invasive cardiac procedure resulting in a permanent implant that isperformed within 10 days of the index procedure.

7. Blood dyscrasias as defined by clinically significant leukopenia (< 500 leukocytes / μL), acute anemia (Hgb < 8 g / dL), thrombocytopenia (< 80,000 platelets / μl),history of bleeding diathesis or coagulopathy.

8. Hemodynamic instability, or pressure dependence requiring pharmacological inotropicsupport or mechanical heart assistance.

9. Echocardiographic evidence of intracardiac or aortic mass, thrombus not adequatelytreated, or vegetation.

10. Active peptic ulcer or upper GI bleeding within the prior 6 months.

11. Contraindication for anticoagulant or antiplatelet therapy.

12. Renal insufficiency (creatinine > 3.0 mg / dL or GFR < 30) and / or renalreplacement therapy at the time of screening and dialysis patients.

13. Current or planned treatment with any investigational drug or investigational deviceduring the study follow-up period (30 days).

14. Balloon aortic valvuloplasty (BAV) within 30 days of the procedure.

15. Cardiogenic shock, hemodynamic instability, or severe hypotension (systolic bloodpressure < 90 mm Hg) at the time of the index procedure.

16. Cardiovascular surgical or interventional procedure 10 days prior or planned duringthe TAVR procedure or during the 30-day study follow-up.

17. Patients with severe chronic obstructive pulmonary disease (COPD)

NOTE: Use of general anesthesia during TAVR may affect neurocognitive function shortly after the procedure. While not an exclusion criterion, it is recommended that general anesthesia not be used if possible.

Neurological exclusion criteria:

1. Cerebrovascular event including TIA within 6 months of the procedure.

2. Subject had active major psychiatric disease.

3. Subject has severe visual, auditory, or learning impairment and is unable tocomprehend English or local language and therefore unable to be consented for thestudy.

4. Subjects with neurodegenerative or other progressive neurological disease or historyof significant head trauma followed by persistent neurologic defaults or knownstructural brain abnormalities.

Magnetic resonance imaging exclusion criteria:

1. Body Mass Index (BMI) precluding imaging in scanner.

2. Contraindications to MRI (subjects with any implantable temporary or permanentpacemaker or defibrillator, metal implants in field of view, metallic fragments,clips, or devices in the brain or eye before TAVR procedure).

3. High risk of complete AV block after TAVR, with the need of permanent pacemaker (e.g., subjects with pre-existing bifascicular block or complete right bundle branchblock plus any degree of AV block).

4. Planned implantation of a pacemaker or defibrillator implantation within the first 3days after TAVR.

5. Claustrophobia precluding MRI scanning.

Anatomical and CT exclusion criteria:

1. Excessive tortuosity in left subclavian artery (≥ 70° single kink or ≥ 50° insequential kinks).

2. Excessive tortuosity in right vascular access vessels for Sentinel introduction.

3. Significant stenosis (≥ 70%), calcification, ectasia, dissection, occlusion,aneurysm, or severe peripheral arterial disease in left or right arm access vessels

• in particular at or within 3 cm of the aortic ostia.

4. Left subclavian artery diameter is ≤ 4 mm.

5. Brachiocephalic artery at the site of Sentinel filter placement < 9 mm or > 15 mm.

6. Left common artery at the site of Sentinel filter placement < 6.5 mm or > 10 mm.

7. Symptomatic or asymptomatic severe (≥ 70%) occlusive carotid disease requiringconcomitant CEA / stenting.

8. Inner diameter of aortic arch < 25 mm as measured in any position between ascendingaorta and ostium of left subclavian artery.

9. Distance between the origin of left subclavian artery and valve plain of < 90 mm.

10. Common ostium of cerebral vessels, where all three vessels originate from one singleostium in the aortic arch.

11. Significant stenosis, ectasia, dissection, aneurysm, or atheroma (mobile or > 5 mmthick) in the ascending aorta or in the aortic arch.

12. Significant angulation of the proximal segment of the left subclavian or aortic archangulation or abnormal anatomical conditions of the aorta (a Type 3 aortic arch isnot a reason for exclusion).

13. Distance between the origin of brachiocephalic trunk and left subclavian artery of > 65 mm.