Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure (TAVR UNLOAD)
Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure (TAVR UNLOAD)
The objective of this study is to determine the safety and efficacy of transcatheter aortic
 valve replacement (TAVR) via a transfemoral approach in HF patients with moderate AS as
 compared with OHFT.
Inclusion Criteria

 All candidates for this study must meet all of the following inclusion criteria:

 1. Age ≥18 years

 2. NYHA class ≥ 2

 3. NT-proBNP > 900pg/mL (or BNP > 200 pg/mL) or hospitalization for HF within the 2
 years;

 Note: To account for the decrease in natriuretic peptide levels with
 overweight/obesity, NT-proBNP and BNP levels cutoff will be reduced by 4% for every
 increase of 1 kg/m2 in BMI above a reference BMI of 20 kg/m2).

 4. Under appropriate and stable guideline-directed HF therapy for a minimum of 1 month. o
 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.

 5. 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.

 6. Left ventricular (LV) ejection fraction (EF) < 50% at rest

 7. Anatomically suitable for transfemoral TAVR with the SAPIEN 3 or SAPIEN 3 Ultra THV

 8. Able to provide independent informed consent (i.e., not requiring a legally authorized
 representative)

 Exclusion Criteria

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

 1. LVEF < 20% or persistent need for intravenous inotropic support

 2. Hospitalization for acute decompensated HF within 2 weeks prior to randomization

 3. Cardiac resynchronization therapy (CRT) device implantation within 1 month prior to
 randomization

 4. Coronary artery revascularization (PCI or CABG) within 1 month prior to randomization

 5. In need and suitable for revascularization per heart team consensus

 6. Severe aortic and/or mitral regurgitation

 7. Congenital unicuspid or congenital bicuspid aortic valve

 8. Concomitant non-aortic valvular disease with a formal indication for valve surgery per
 established guidelines (ESC/ACC/AHA)

 9. Previous aortic valve replacement (mechanical or bioprosthetic)

 10. Severe RV dysfunction

 11. Previous stroke with permanent disability (modified Rankin score ≥ 2)

 12. Severe lung disease as indicated by FEV1 <30% predicted or need for chronic daytime
 supplemental oxygen therapy

 13. Severe chronic kidney disease: glomerular filtration rate (GFR) < 30 mL/min by MDRD or
 need for renal replacement therapy

 14. Gastrointestinal (GI) bleeding within the past 3 months

 15. Liver cirrhosis Child-Pugh C

 16. Active systemic infection, including active endocarditis

 17. Unwilling to accept blood transfusion

 18. Evidence of intracardiac mass, thrombus or vegetation

 19. Absence of minimum amount of aortic valve calcification necessary for TAVR with the
 SAPIEN 3 or SAPIEN 3 Ultra THV

 20. Hypersensitivity or contraindication to clopidogrel, aspirin, or to oral
 anticoagulation if indicated (e.g. subject in atrial fibrillation)

 21. Sensitivity to contrast media which cannot be adequately pre-medicated

 22. Women of child-bearing potential

 23. Clinical signs of dementia

 24. Other medical, social, or psychological conditions that precludes appropriate consent
 and follow-up

 25. Life expectancy < 2 years due to cancer or other non-cardiac chronic diseases

 26. Unwillingness to undergo follow-up investigations

 27. Currently participating in an investigational drug or another device trial that has
 not reached its primary endpoint (excluding registries)