title: Rationale and design of the Transcatheter Aortic Valve Replacement to UNload the Left ventricle in patients with ADvanced heart failure (TAVR UNLOAD) trial.
abstract: BACKGROUND
  Coexistence of moderate aortic stenosis (AS) in patients with heart failure (HF) with reduced ejection fraction is not uncommon. Moderate AS increases afterload, whereas pharmacologic reduction of afterload is a pillar of contemporary HF management.
  
  
  OBJECTIVE
  Unloading the left ventricle by reducing the transaortic gradient with transfemoral transcatheter aortic valve replacement (TAVR) may improve clinical outcomes in patients with moderate AS and HF with reduced ejection fraction.
  
  
  METHODS
  The TAVR UNLOAD (NCT02661451) is an international, multicenter, randomized, open-label, clinical trial comparing the efficacy and safety of TAVR with the Edwards SAPIEN 3 Transcatheter Heart Valve in addition to optimal heart failure therapy (OHFT) vs OHFT alone in patients with moderate AS (defined by a mean transaortic gradient ≥20 mm Hg and <40 mm Hg, and an aortic valve area >1.0 cm2and ≤1.5 cm2at rest or after dobutamine stress echocardiography) and reduced ejection fraction. A total of 600 patients will be randomized in a 1:1 fashion. Clinical follow-up is scheduled at 1, 6, and 12 months, and 2 years after randomization. The primary end point is the hierarchical occurrence of all-cause death, disabling stroke, hospitalizations related to HF, symptomatic aortic valve disease or nondisabling stroke, and the change in the Kansas City Cardiomyopathy Questionnaire at 1 year. Secondary end points capture effects on clinical outcome, biomarkers, echocardiographic parameters, and quality of life.
  
  
  CONCLUSIONS
  The TAVR UNLOAD trial aims to test the hypothesis that TAVR on top of OHFT improves clinical outcomes in patients with moderate AS and HF with reduced ejection fraction.
authors.affiliation: Erasmus Medical Center, Rotterdam, The Netherlands; Cardialysis Core Laboratories and Clinical Trial Management, Rotterdam, The Netherlands.
authors.forename: Ernest
authors.initials: E
authors.lastname: Spitzer
authors.affiliation: Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address: n.vanmieghem@erasmusmc.nl.
authors.forename: Nicolas M
authors.initials: NM
authors.lastname: Van Mieghem
authors.affiliation: Québec Heart & Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pibarot
authors.affiliation: Columbia University Medical Center, NY; Cardiovascular Research Foundation, NY.
authors.forename: Rebecca T
authors.initials: RT
authors.lastname: Hahn
authors.affiliation: Columbia University Medical Center, NY; Cardiovascular Research Foundation, NY.
authors.forename: Susheel
authors.initials: S
authors.lastname: Kodali
authors.affiliation: Columbia University Medical Center, NY.
authors.forename: Mathew S
authors.initials: MS
authors.lastname: Maurer
authors.affiliation: Columbia University Medical Center, NY; Cardiovascular Research Foundation, NY.
authors.forename: Tamim M
authors.initials: TM
authors.lastname: Nazif
authors.affiliation: Québec Heart & Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Josep
authors.initials: J
authors.lastname: Rodés-Cabau
authors.affiliation: Québec Heart & Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Paradis
authors.affiliation: Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Arie-Pieter
authors.initials: AP
authors.lastname: Kappetein
authors.affiliation: Cardiovascular Research Foundation, NY.
authors.forename: Ori
authors.initials: O
authors.lastname: Ben-Yehuda
authors.affiliation: European Cardiovascular Research Institute, Rotterdam, The Netherlands.
authors.forename: Gerrit-Anne
authors.initials: GA
authors.lastname: van Es
authors.affiliation: Edwards Lifesciences, Irvine, CA.
authors.forename: Faouzi
authors.initials: F
authors.lastname: Kallel
authors.affiliation: Independent Consultant, Lake Forest, CA.
authors.forename: William N
authors.initials: WN
authors.lastname: Anderson
authors.affiliation: European Cardiovascular Research Institute, Rotterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Tijssen
authors.affiliation: Columbia University Medical Center, NY; Cardiovascular Research Foundation, NY.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Leon
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery; D006328:Cardiac Catheterization / Q000379:methods; D025401:Echocardiography, Stress / Q000379:methods; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000601:surgery; D006801:Humans; D008297:Male; D010043:Outcome and Process Assessment, Health Care; D012720:Severity of Illness Index; D013318:Stroke Volume; D065467:Transcatheter Aortic Valve Replacement / Q000009:adverse effects / Q000379:methods