Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure (TAVR UNLOAD)

Prior treatment

• Hospitalization for acute decompensated HF within 2 weeks prior to randomization
• Cardiac resynchronization therapy (CRT) device implantation within 1 month prior to randomization
• Coronary artery revascularization (PCI or CABG) within 1 month prior to randomization
• Concomitant non-aortic valvular disease with a formal indication for valve surgery per established guidelines (ESC/ACC/AHA)
• Previous aortic valve replacement (mechanical or bioprosthetic)
• Previous stroke with permanent disability (modified Rankin score ≥ 2)
• Currently participating in an investigational drug or another device trial that has not reached its primary endpoint (excluding registries)

Other illness

• Candidates are excluded from the study if any of the following conditions are present:
• In need and suitable for revascularization per heart team consensus
• Severe lung disease as indicated by FEV1 \<30% predicted or need for chronic daytime supplemental oxygen therapy
• Gastrointestinal (GI) bleeding within the past 3 months
• Active systemic infection, including active endocarditis
• Hypersensitivity or contraindication to clopidogrel, aspirin, or to oral anticoagulation if indicated (e.g. subject in atrial fibrillation)
• Clinical signs of dementia
• Other medical, social, or psychological conditions that precludes appropriate consent and follow-up

Lab values

• LVEF \< 20% or persistent need for intravenous inotropic support
• Severe chronic kidney disease: glomerular filtration rate (GFR) \< 30 mL/min by MDRD or need for renal replacement therapy

Age

• Life expectancy \< 2 years due to cancer or other non-cardiac chronic diseases

Other

• Severe aortic and/or mitral regurgitation
• Congenital unicuspid or congenital bicuspid aortic valve
• Severe RV dysfunction
• Liver cirrhosis Child-Pugh C
• Unwilling to accept blood transfusion
• Evidence of intracardiac mass, thrombus or vegetation
• Absence of minimum amount of aortic valve calcification necessary for TAVR with the SAPIEN 3 or SAPIEN 3 Ultra THV
• Sensitivity to contrast media which cannot be adequately pre-medicated
• Women of child-bearing potential
• Unwillingness to undergo follow-up investigations

• All candidates for this study must meet all of the following inclusion criteria:
• Age ≥18 years
• Heart Failure with NYHA class ≥ 2
• Under appropriate and stable guideline-directed HF therapy for a minimum of 1 month prior to randomization.
  • Note: Patients are expected to be on appropriate pharmacologic therapy and if indicated CRT for heart failure. (12, 13) Patients with aortic stenosis may not be able to tolerate maximal doses of heart failure medications and no specific guidelines exist for the medical treatment of heart failure in the setting of aortic stenosis. It is expected that the heart failure PI will review the medical therapy and confirm that it is appropriate for the patient's condition.
• Moderate AS confirmed by the echo core lab. Moderate AS is defined as an aortic valve area (AVA) \>1.0 cm2 and ≤1.5 cm2 on rest echo or if ≤1.0 cm2 at rest and low-flow AS is suspected when the an AVA \> 1.0 cm2 with low dose dobutamine stress echo (DSE). Patients with AVA\<1.0 cm2 but with an indexed AVA of \>0.6 cm2/m2 on either rest or DSE are also eligible. Similarly, patients with AVA \>1.5 cm2 but with indexed AVA\<0.9 cm2/m2 on either rest of DSE are also eligible.
  • Note: Typically such cases will demonstrate,
  • Mean trans-aortic gradient (MG) ≥ 20 mmHg and \< 40 mmHg at rest and aortic valve area (AVA) \> 1.0 cm2 and ≤1.5 cm2 (or AVA \< 1.0 cm2 but indexed AVA \> 0.6 cm2) at rest
  • OR
  • Mean trans-aortic gradient (MG) ≥ 20 mmHg and \< 40 mmHg and aortic valve area (AVA) ≤1.0 cm2 at rest AND MG \< 40 mmHg and aortic valve area (AVA)
  • •\>1.0 cm2 (or AVA \< 1.0 cm2 but indexed AVA \> 0.6 cm2) with low dose dobutamine stress echo (DSE).
  • In atypical cases (for example mean gradient is below 20 mmHg but valve area is consistent with moderate AS, the final eligibility determination in regards to diagnosis of moderate AS will be made by the echocardiographic core lab.
• Left ventricular (LV) ejection fraction (EF) \< 50% at rest
• Anatomically suitable for transfemoral TAVR with the SAPIEN 3 or SAPIEN 3 Ultra THV
• Able to provide independent informed consent (i.e., not requiring a legally authorized representative)