Transcatheter Aortic Valve Replacement to UNload the Left Ventricle in Patients With ADvanced Heart Failure (TAVR UNLOAD)
Aortic Valve Stenosis
About this trial
This is an interventional treatment trial for Aortic Valve Stenosis focused on measuring Valve
Eligibility Criteria
Inclusion Criteria
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)
Exclusion Criteria
Candidates are excluded from the study if any of the following conditions are present:
- LVEF < 20% or persistent need for intravenous inotropic support
- 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
- In need and suitable for revascularization per heart team consensus
- Severe aortic and/or mitral regurgitation
- Congenital unicuspid or congenital bicuspid aortic valve
- 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)
- Severe RV dysfunction
- Previous stroke with permanent disability (modified Rankin score ≥ 2)
- Severe lung disease as indicated by FEV1 <30% predicted or need for chronic daytime supplemental oxygen therapy
- Severe chronic kidney disease: glomerular filtration rate (GFR) < 30 mL/min by MDRD or need for renal replacement therapy
- Gastrointestinal (GI) bleeding within the past 3 months
- Liver cirrhosis Child-Pugh C
- Active systemic infection, including active endocarditis
- 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
- Hypersensitivity or contraindication to clopidogrel, aspirin, or to oral anticoagulation if indicated (e.g. subject in atrial fibrillation)
- Sensitivity to contrast media which cannot be adequately pre-medicated
- Women of child-bearing potential
- Clinical signs of dementia
- Other medical, social, or psychological conditions that precludes appropriate consent and follow-up
- Life expectancy < 2 years due to cancer or other non-cardiac chronic diseases
- Unwillingness to undergo follow-up investigations
- Currently participating in an investigational drug or another device trial that has not reached its primary endpoint (excluding registries)
Sites / Locations
- Chandler Regional Medical Center
- UCSD/Sulpizio Cardiovascular Center
- University of Southern California - Los Angeles
- UCLA Medical Center
- St. Joseph Hospital
- UCSF
- Medical Center of the Rockies
- Yale University
- Medstar Washington Hospital Center
- University of Miami
- Cleveland Clinic Florida
- Advocate Christ Hospital
- Northwestern University
- Alexian Brothers Medical Center
- Evanston Hospital/NorthShore Univ. Health System
- Advocate Lutheran General Hospital
- Carle Foundation Hospital
- Maine Medical Center
- Tufts Medical Center
- Massachusetts General Hospital
- Beaumont Hospital
- Ascension St. Mary's Hospital
- Minneapolis Heart Institute
- Mayo Clinic - Rochester
- HealthEast Medical Research Institute
- Washington University in St. Louis
- University of Nebraska Medical Center
- Morristown Memorial
- NYU Langone Medical Center
- Columbia University Medical Center/New York Presbyterian Hospital
- St. Francis Hospital
- Oregon Health Science University (OHSU)
- University of Pennsylvania
- UPMC Presbyterian
- PinnacleHealth Cardiovascular Institute
- WellSpan York Hospital
- Rhode Island Hospital
- Vanderbilt Heart and Vascular
- Seton Medical Center Austin
- IHC Health Services, Inc. dba Intermountain Medical Center
- University of Vermont Medical Center
- Virginia Commonwealth University (VCU)
- Swedish Medical Center
- Oklahoma Heart Hospital
- Advocate Aurora- St. Lukes
- Medical College of Wisconsin
- St. Michael's Hospital
- University Medical Center Utrecht
- Leiden University Medical Center
- Erasmus Medical Center
- Isala Clinics
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
TAVR (with SAPIEN 3 THV) and OHFT
OHFT
Transcatheter heart valve and Optimal Heart Failure Therapy
Optimal Heart Failure Therapy