Isolated Surgical Aortic Valve Replacement in Low Risk AS Patients

the Prospective, Randomized, Controlled, Multi-center Study to Establish the Safety and Effectiveness of Isolated Surgical Aortic Valve Replacement in Low Risk Patients Who Have Symptomatic Severe Aortic Stenosis

To establish the safety and effectiveness of surgical aortic valve replacement (SAVR) in patients with isolated severe, calcific aortic stenosis who are at low surgical risk.

This study is the Prospective, Randomized, Controlled, Multi-center Study of Isolated SAVR in Low Risk AS Patients (The AMETHYST trial). Patients will be randomized 1:1 to receive either SAVR or transcatheter heart valve replacement (TAVR) with a commercially available surgical and transcatheter bioprosthetic valves. The aim of this study was to assess the non-inferiority of SAVR compared with TAVR for the combined endpoints of death from any cause, stroke and rehospitalization (hospitalization related to biological valves or procedures or heart failure) at 1 year postoperatively. Patients will be seen for follow-up visits at discharge, 30 days, and annually through 10 years.

Inclusion Criteria:

1. All study participants must meet the following inclusion criteria 1. Severe, calcific aortic stenosis with the following criteria:

   • Jet velocity ≥4.0 m/s or mean gradient ≥ 40 mmHg OR
   • AVA ≤1.0 cm2 or AVA index ≤ 0.6 cm2/m2 Note: Qualifying TTE must be within 90 days prior to randomization

   AND 2. NYHA class ≥ II OR Exercisee test that demonstrates a limited exercise capacity, abnormal blood pressure response, or arrhythmia OR Asymptomatic patients with LVEF <50%

2. The Heart Team agrees that the surgical mortality risk is less than 4% according to STS-PROM. The Heart Team's assessment should include evaluation of overall clinical status and comorbidities that may not be adequately captured by risk calculators such as STS-PROM, in addition to the risk score itself.

3. The patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by certified review board.

Exclusion Criteria:

Candidates will be excluded from the study if any of the following conditions are present:

1. History of cardiovascular surgery or thoracotomy

2. Pre-existing other valvular disease, coronary artery disease or aortic disease required intervention Note: interventions for arrhythmia or root enlargement are not considered exclusionary.

3. Heart Team assessment that chest abnormalities or significant frailty would prevent safe SAVR.

4. Native aortic annulus size unsuitable for sizes the currently approved and marketed SAVR or TAVR based on preoperative 3D-CT image analysis.

5. Iliofemoral vessel characteristics that whould preclude safe insertion of the introducer sheath.

6. Evidence of an acute myocardial infarction or PCI ≤ 30 days before randomization

7. Aortic valve is unicuspid

8. Severe aortic regurgitation (>3+)

9. Severe mitral regurgitation (>3+) or ≥ moderate stenosis

10. Severe tricuspid regurgitation (>3+) or ≥ moderate stenosis

11. Pre-existing mechanical or bioprosthetic valve in any position.

12. Complex coronary artery disease:

    1. Heart Team assessment that CABG is recommended at the time of SAVR
    2. Heart Team assessment that optimal revascularization cannot be performed

13. Symptomatic carotid or vertebral artery disease or treatment of carotid stenosis within 30 days of randomization

14. Leukopenia (WBC < 3000 cell/mL), Thrombocytopenia (Plt < 50,000 cell/mL), history of bleeding diathesis or coagulopathy.

15. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of randomization

16. Hypertrophic cardiomyopathy with obstruction (HOCM)

17. Ventricular dysfunction with LVEF < 30%

18. Cardiac imaging (echo, CT, and/or MRI) evidence of intracardiac mass, thrombus or vegetation

19. Inability to tolerate or condition precluding treatment with antithrombotic/anticoagulation therapy during or after the valve implant procedure

20. Stroke or transient ischemic attack (TIA) within 90 days of randomization

21. Renal insufficiency (eGFR < 30 ml/min per the Cockcroft-Gault formula) and/or renal replacement therapy

22. Active bacterial endocarditis within 180 days of randomization

23. Severe lung disease (FEV1 < 50% predicted) or currently on home oxygen

24. Severe pulmonary hypertension (e.g., PA systolic pressure ≥ 2/3 systemic pressure)

25. History of cirrhosis or active liver disease

26. Significant abdominal or thoracic aortic disease (such as porcelain aorta, aneurysm, severe calcification, aortic coarctation, etc.) that would preclude cannulation and aortotomy for SAVR or safe passage of the delivery system for TAVR.

27. Patient refuses blood products.

28. BMI > 50 kg/m2

29. Estimated life expectancy < 24 months.

30. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication.

31. Immobility or significant cognitive impairment that would prevent completion of study procedure.

32. Currently participating in an investigational drug or another device study.

33. Unsuitable as candidates by the principal investigator or a research associate for other reasons