Study population

The study population will comprise patients with severe, calcific, symptomatic aortic stenosis who are at low operative risk for SAVR.

Inclusion criteria

All study participants must meet the following inclusion criteria.

  1. Symptomatic, severe, calcific aortic stenosis with the following TTE criteria:
    1. Jet velocity ≥ 4.0 m/s or mean gradient ≥ 40 mmHg AND
    2. AVA ≤ 1.0 cm2 or AVA index ≤ 0.6 cm2/m2
      Note: Qualifying echo must be within the 90 days prior to randomization.
  2. Aortic valve annulus 273 mm2 – 683 mm2 measured by 3D imaging (CT, TEE or MRI).
  3. Adequate iliofemoral access with minimum average vessel diameter of 5.5mm (20, 23, 26mm) and 6.0mm (29mm) and acceptable level of vessel calcification and tortuosity for safe device implant.
  4. NYHA Functional Class ≥ II.
  5. Heart team agrees the patient has a risk of operative mortality < 2% (e.g., STS<4). Heart team evaluation should include risk calculators such as the STS as well as overall clinical status and comorbidities not fully addressed by the STS risk score (verified during the case review process).
  6. The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site.

Exclusion criteria

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

  1. ≥ 1/4 frailty. (Only 0/4 frail patients may be enrolled in the trial.)
  2. Evidence of an acute myocardial infarction ≤ 1 month (30 days) before randomization with evidence of myocardial necrosis in a clinical setting consistent with acute myocardial ischemia. Any one of the following criteria meets the diagnosis for MI:
    1. Detection of a rise and/or fall of cardiac biomarker values [preferably cardiac troponin (cTn)] with at least one value above the 99th percentile upper reference limit (URL) and with at least one of the following:
      1. Symptoms of ischemia.
      2. New or presumed new significant ST-segment–T wave (ST–T) changes or new left bundle branch block (LBBB).
      3. Development of pathological Q waves in the ECG.
      4. Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.
    2. Identification of an intracoronary thrombus by angiography.
  3. Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is non-calcified.
  4. Severe aortic regurgitation (>3+).
  5. Severe mitral regurgitation (>3+).
  6. Pre-existing mechanical or bioprosthetic valve in any position. (Of note, mitral ring is not an exclusion.)
  7. Any patient with a balloon valvuloplasty (BAV) within 30 days of the valve implant procedure (unless BAV is a bridge to procedure after a qualifying ECHO).
  8. Any therapeutic invasive cardiac procedure performed within 30 days of the valve implant procedure. Pre-planned PCI performed within 2 weeks prior to valve procedure or implantation of a permanent pacemaker or implantable cardioverter defibrillator (ICD) is not considered exclusionary criteria.
  9. Complex coronary artery disease:
    1. Unprotected left main coronary artery.
    2. Syntax score > 32 (in the absence of prior revascularization).
  10. Non-complex, flow limiting coronary artery disease requiring revascularization that cannot be treated at the time of or within two weeks prior to the valve procedure.
  11. Patients with a planned concomitant surgical or transcatheter ablation for atrial fibrillation.
  12. Leukopenia (WBC < 3000 cell/mL), anemia (Hgb < 9 g/dL), thrombocytopenia (Plt < 50,000 cell/mL).
  13. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of the screening visit.
  14. Emergency interventional/surgical procedures within 30 days of the valve implant procedure.
  15. Any planned surgical or peripheral procedure to be performed within the 30 day follow-up from the valve implant procedure.
  16. Hypertrophic cardiomyopathy with or without obstruction (HOCM).
  17. Ventricular dysfunction with LVEF < 45%.
  18. Cardiac imaging (echo, CT, and/or MRI) evidence of intracardiac mass, thrombus or vegetation.
  19. History of upper GI bleeding within 90 days of the valve implant procedure.
  20. Inability to tolerate anti-thrombotic/anticoagulation therapy during or after the valve implant procedure.
  21. Stroke or transient ischemic attack (TIA) within 180 days of the valve implant procedure.
  22. Renal insufficiency (eGFR < 40 ml/min per the Cockcroft-Gault formula) and/or renal replacement therapy at the time of screening.
  23. Active bacterial endocarditis within 180 days of the valve implant procedure.
  24. Severe lung disease (FEV1 < 50% predicted) or currently on home oxygen 25. Chronic liver disease (MELD Score ≥ 10 or Child-Pugh Class B or C).
  25. Significant aortic disease, including marked tortuosity (hyperacute bend), aortic arch atheroma [especially if thick (>5mm), protruding or ulcerated] or narrowing (especially with calcification and surface irregularities) of the abdominal thoracic aorta, severe “unfolding” and tortuosity of the thoracic aorta.
  26. Porcelain aorta.
  27. Complications with prior cardiac surgery (i.e., mediastinitis, prolonged intubation).
  28. Patient refuses blood products.
  29. Severe chest deformity (i.e., pectus excavaatum, mastectomy, iatrogenic radiation exposure).
  30. BMI > 50 kg/m2.
  31. Estimated life expectancy < 24 months.
  32. Known blood dyscrasia.
  33. Aortic coarctation.
  34. Absolute contraindications or allergy to iodinated contrast that cannot be pre-medicated.
  35. Immobility that would prevent completion of study procedures.
  36. Currently participating in an investigational drug or another device study. Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials. Observational studies are not considered exclusionary.
  37. Patient refuses SAVR.

Learn more about the PARTNER 3 trial at Lankenau Medical Center

To see if you are a candidate for the PARTNER 3 trial, please call 1.855.820.VALVE.