SMall Annuli Randomized To Evolut™ or SAPIEN™ Trial (SMART)

The purpose of this trial is to generate clinical evidence on valve safety and performance of self-expanding (SE) versus balloon-expandable (BE) transcatheter aortic valve replacement (TAVR) in subjects with a small aortic annulus and symptomatic severe native aortic stenosis.

Additionally, a stress echocardiography sub-study will be conducted as part of the SMART Trial at select sites. The purpose of the sub-study is to evaluate performance of SE versus BE TAVR in subjects with a small aortic annulus and symptomatic severe native aortic stenosis after undergoing exercise stress echocardiographic testing.

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Valve Stenosis; Aortic Valve Replacement; Symptomatic Aortic Stenosis
• Intervention / Treatment: Device: Medtronic Evolut PRO, Evolut PRO+ or Evolut FX (where commercially available) TAV Systems; Device: Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems

Detailed Description

This is a prospective, multi-center, international, randomized controlled, post-market trial.

The primary objectives of the trial are to demonstrate clinical non-inferiority and hemodynamic superiority of the Evolut PRO/PRO+/FX System when compared to subjects treated with the SAPIEN 3/3 Ultra System at 12 months post-procedure.

Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE Transcatheter Aortic Valve (TAV) or an Edwards BE Transcatheter Heart Valve (THV). Data will be collected at pre- and post-procedure, at discharge, at 30 days, and once a year until the 5-year follow-up is completed.

Product Names:

• Medtronic Evolut PRO and Evolut PRO+ TAV Systems, Evolut FX System (Commercially available in the United States and may be used upon commercial availability in Canada.)
• Edwards SAPIEN 3 and SAPIEN 3 Ultra THV Systems

The exercise stress echocardiographic testing at select SMART Trial sites seeks to evaluate the performance of the prosthetic aortic valve during exercise. The stress echocardiogram assessment will be conducted as part of the 12-month visit for participating subjects.

• Study Type: Interventional
• Enrollment (Actual): 1103
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Providence Health-St. Paul's Hospital
    • Victoria, British Columbia, Canada
      • Victoria Heart Institute Foundation/Royal Jubilee Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
    • Toronto, Ontario, Canada
      • St. Michaels Hospital/Unity Health Toronto
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet
• Finland
  • Helsinki, Finland
    • Helsinki university hospital
• France
  • Clermont-Ferrand, France
    • Centre Hospitalier Universitaire de Clermont-Ferrand
  • Pessac, France
    • CHU Bordeaux
  • Toulouse, France
    • Clinique Pasteur
• Germany
  • Bad Oeynhausen, Germany
    • Hers-und Diabeteszentrum NRW - Ruhr -Universitati Bochum
  • Berlin, Germany
    • Deutsches Herzzentrum Berlin
  • Dortmund, Germany
    • Kath. St.-Johannes-Gesellschaft Dortmund gGmbH - St. Johannes-Hospital Dortmund
  • Düsseldorf, Germany
    • Universitätsklinikum Düsseldorf
  • Kiel, Germany
    • Universitätsklinikum Schleswig-Holstein - Campus Kiel
  • Leipzig, Germany
    • Helios Health Institute GmbH
  • Lübeck, Germany
    • Universitatsklinikum Schleswig-Holstein - Campus Lubeck
  • München, Germany
    • Deutsches Herzzentrum München
• Israel
  • Ramat Gan, Israel
    • Sheba Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
• Italy
  • Bologna, Italy
    • Policlinico Sant' Orsala - Malpighi
  • Pisa, Italy
    • Azienda Ospedaliero-Universitaria Pisana - Stabilimento di Cisanello
  • Verona, Italy
    • AOU Integrata Verona
• Netherlands
  • Eindhoven, Netherlands
    • Catharina Ziekenhuis
  • Maastricht, Netherlands
    • Maastricht Universitair Medisch Centrum (MUMC)
  • The Hague, Netherlands
    • HagaZiekenhuis - Locatie Leyweg
• Portugal
  • Carnaxide, Portugal
    • Centro Hospitalar de Lisboa Ocidental, E.P.E. Hospital de Santa Cruz
• Spain
  • Barcelona, Spain
    • Hospital Vall d'Hebron
• Switzerland
  • Bern, Switzerland
    • Inselspital - Universitätsspital Bern
• United Kingdom
  • Edinburgh, United Kingdom
    • Royal Infirmary of Edinburgh
  • Leeds, United Kingdom
    • The Leeds Teaching Hospitals NHS Trust - Leeds General Infirmary
• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Memorial Hospital
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • San Francisco, California, United States, 94109
      • Sutter Health
    • Thousand Oaks, California, United States, 91360
      • Los Robles Hospital and Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • WHC Washington MedStar
  • Florida
    • Clearwater, Florida, United States, 33756
      • Morton Plant Hospital
    • Fort Myers, Florida, United States, 33908
      • HealthPark Medical Center
    • Gainesville, Florida, United States, 32608
      • University of Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
    • Atlanta, Georgia, United States, 30308
      • Emory Structural Heart Clinic and Emory University Midtown
    • Marietta, Georgia, United States, 30060
      • Wellstar Kennestone Hospital
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore Health Systems
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
  • Indiana
    • Carmel, Indiana, United States, 46290
      • Saint Vincent Heart Center of Indiana
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Wichita, Kansas, United States, 67226
      • AscensionVia Christi St. Francis Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48236
      • Ascension St. John Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Cloud, Minnesota, United States, 56303
      • St. Cloud Hospital
  • Missouri
    • St Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
  • New York
    • Buffalo, New York, United States, 14203
      • Buffalo General Medical Center
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical Center
    • New York, New York, United States, 10029
      • The Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Memorial Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • TriHealth / Bethesda North Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Hillcrest Medical Center
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17110
      • UPMC Pinnacle Harrisburg
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Presbyterian
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
    • York, Pennsylvania, United States, 17403
      • York Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tristar Centennial Medical Center
    • Nashville, Tennessee, United States, 37205
      • St. Thomas West Hospital
  • Texas
    • Austin, Texas, United States, 78705
      • Seton Heart Institute
    • Dallas, Texas, United States, 75226
      • Baylor Jack and Jane Hamilton Heart and Vascular Hospital
    • Dallas, Texas, United States, 76231
      • Texas Health Presbyterian Hospital/Dallas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
    • Houston, Texas, United States, 77030
      • Baylor Saint Luke's Hospital
    • Houston, Texas, United States, 77030
      • University of Texas Health Sciences Center at Houston - Center for Advanced Heart Failure
    • Plano, Texas, United States, 75093
      • The Heart Hospital Baylor Plano
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • St. George, Utah, United States, 84770
      • Saint George Regional Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • J.W. Ruby Memorial Hospital/West Virginia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Heart Team agrees that the subject is deemed symptomatic and is a candidate for transcatheter aortic valve replacement (TAVR)
• Subject has a predicted risk of operative mortality < 15% as determined by the local Heart Team
• Subject has severe aortic stenosis as determined by transthoracic echocardiography (TTE) at rest
• Subject has a small aortic annulus as determined by Multi-detector computed tomography (MDCT)
• Subject's anatomy is appropriate for both Medtronic Evolut PRO/PRO+/FX TAV and Edwards SAPIEN 3/3 Ultra TAV
• Subject's anatomy is suitable for TAVR via transfemoral vessel access
• Subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits

Exclusion Criteria:

• Estimated life expectancy of fewer than 2 years
• Multivessel coronary artery disease with a Syntax score >32 and/or unprotected left main coronary artery(Syntax score calculation is not required for patients with history of previous revascularization if repeat revascularization is not planned).
• Participating in another trial that may influence the outcome of this trial
• Need for an emergent procedure for any reason
• Contraindicated for treatment with the Evolut PRO/PRO+/FX and Edwards SAPIEN 3/3 Ultra TAV in accordance with the Instructions for Use
• Other medical, social, or psychological conditions that in the opinion of the Investigator precludes the subject from appropriate consent or adherence to the protocol required follow-up exams
• Pregnant, nursing, or planning to be pregnant
• Subject is less than the legal age of consent, legally incompetent, unable to provide his/her own informed consent, or otherwise vulnerable
• Subject has an active COVID-19 infection or relevant history of COVID-19
• Previous aortic valve replacement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medtronic Self-Expanding TAV; Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE TAV or an Edwards BE THV.	Device: Medtronic Evolut PRO, Evolut PRO+ or Evolut FX (where commercially available) TAV Systems; TAVR treatment with Medtronic Evolut PRO, PRO+ System or Evolut FX System (where commercially available)
Experimental: Edwards Balloon-Expandable THV; Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE TAV or an Edwards BE THV.	Device: Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems; TAVR treatment with Edwards SAPIEN 3 or SAPIEN 3 Ultra System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality, Disabling Stroke or Heart Failure Rehospitalization	Percentage of participants with all-cause mortality, disabling stroke, or heart failure rehospitalization.	12 months
Bioprosthetic Valve Dysfunction (BVD)	Percentage of participants with BVD as determined by echocardiography (hemodynamic structural valve dysfunction (aortic valve no longer works properly as measured by hemodynamic mean gradient ≥ 20mmHg), non-structural valve dysfunction (severe prosthesis-patient mismatch (valve is too small) and/or ≥ moderate total aortic regurgitation (backward flow of blood)), thrombosis (formation of a blood clot), endocarditis (inflammation of the endocardium - the inner lining of the heart chambers and valves), or aortic valve re-intervention (a follow-up procedure to fix or replace the aortic prosthetic valve))	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Hemodynamic Structural Valve Dysfunction (HSVD)	HSVD is defined as hemodynamic mean gradient ≥ 20mmHg on any echocardiogram after implant procedure.	12 months
Hemodynamic Mean Gradient as Continuous Variable	Mean aortic gradient as measured by echocardiogram at the 12-month visit.	12 months
Effective Orifice Area (EOA) as a Continuous Variable	Effective Orifice Area (EOA) as measured by echocardiogram at the 12-month visit.	12 months
Rate of Moderate or Severe Prothesis-patient Mismatch (PPM)	Moderate or severe PPM will be defined as follows: For subjects with BMI < 30 kg/m2; Moderate PPM: EOAI = 0.85 - 0.65 cm2/m2; Severe PPM: EOAI = ≤ 0.65 cm2/m2 For subjects with BMI ≥ 30 kg/m2; Moderate PPM: EOAI = 0.70 - 0.55 cm2/m2; Severe PPM: EOAI = ≤ 0.55 cm2/m2	30 days
Percentage of Participants With BVD in Female Subjects	Percentage of participants with BVD as determined by echocardiography (hemodynamic structural valve dysfunction (aortic valve no longer works properly as measured by hemodynamic mean gradient ≥ 20mmHg), non-structural valve dysfunction (severe prosthesis-patient mismatch (valve is too small) and/or ≥ moderate total aortic regurgitation (backward flow of blood)), thrombosis (formation of a blood clot), endocarditis (inflammation of the endocardium - the inner lining of the heart chambers and valves), or aortic valve re-intervention (a follow-up procedure to fix or replace the aortic prosthetic valve)).	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Success	Device Success is defined as meeting all of the following: Freedom from mortality AND Correct positioning of a single prosthetic heart valve into the proper anatomical location AND Intended performance of the prosthetic heart valve (no prosthesis-patient mismatch (PPM) and mean aortic valve gradient <20 mmHg or peak velocity <3 m/s) AND No moderate or severe prosthetic valve regurgitation)	30 days
Incidence of an Early Safety Composite	Incidence of an early safety composite at 30 days defined as: All-cause mortality; All stroke (disabling and non-disabling); Life-threatening bleeding; Acute kidney injury-Stage 2 or 3 (including renal replacement therapy); Coronary artery obstruction requiring intervention; Major vascular complication; Valve-related dysfunction requiring repeat procedure (BAV, TAVR, or SAVR)	30 days
Hospital Readmission Rate for Any Cause		30 days
Incidence of Clinical Efficacy	Incidence of clinical efficacy (after 30 days) at 12 months defined as a composite of: All-cause mortality; All stroke (disabling and non-disabling); Requiring hospitalizations for valve-related symptoms or worsening congestive heart failure; NYHA class III or IV; Valve-related dysfunction (mean aortic valve gradient ≥20 mmHg, EOA ≤0.9-1.1 cm2 and/or Doppler velocity index (DVI) <0. 35m/s, AND/OR moderate or severe prosthetic valve regurgitation)	12 months
Mean Gradient ≥ 20 mmHg Based on Stress Echocardiogram	Mean gradient ≥ 20 mmHg based on stress echocardiogram at select sites.	12 months
Percentage of Participants With Individual Clinical Endpoint Components Including Mortality, Disabling Stroke and Heart Failure Rehospitalization		12 months and 2 Years
New Pacemaker Implantation Rate	Note: This section is excluding subjects with pacemaker or ICD at baseline.	30 days, 12 Months, 2 Years
Aortic Valve Re-intervention Rate	Aortic valve re-intervention rate as measured as the percentage of patients that had a procedure to fix or replace their prosthetic valve at the 30 days, 12 months and 2 Year visit.	30 days, 12 months, 2 Years
6-minute Walk Test (6MWT) Change From Baseline		30 days, 12 Months and 2 Years
Quality of Life (QoL) Change From Baseline (EuroQol- 5 Dimension [EQ-5D])	EuroQol Group developed this Quality of Life (QOL) questionnaire referred to as EQ-5D that includes a descriptive system comprising five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The answers given to ED-5D can be converted into EQ-5D index and utility scores anchored at 0 for death and 1 for perfect health. The EQ-5D Index Score is calculated for each study participant and the descriptive statistical summary of the EQ-5D score for the study population is provided. The EQ-5D Visual Analog Scale (VAS) Score is a scale numbered 0 to 100 (0 is the worse health the patient can imagine and 100 is the best health the patient can imagine).	30 days, 12 Months and 2 Years
Quality of Life (QoL) Change From Baseline (Kansas City Cardiomyopathy Questionnaire [KCCQ]	Kansas City Cardiomyopathy Questionnaire (KCCQ): Quantifies physical function, symptoms, social function, selfefficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. Note: This is the overall summary score for KCCQ.	30 days, 12 Months and 2 Years
Bioprosthetic Valve Dysfunction (BVD)	Percentage of participants with BVD as determined by echocardiography (hemodynamic structural valve dysfunction (aortic valve no longer works properly as measured by hemodynamic mean gradient ≥ 20mmHg), non-structural valve dysfunction (severe prosthesis-patient mismatch (valve is too small) and/or ≥ moderate total aortic regurgitation (backward flow of blood)), thrombosis (formation of a blood clot), endocarditis (inflammation of the endocardium - the inner lining of the heart chambers and valves), or aortic valve re-intervention (a follow-up procedure to fix or replace the aortic prosthetic valve))	2 Years
Effective Orifice Area (EOA) as a Continuous Variable	Effective Orifice Area (EOA) as measured by echocardiogram at the following intervals: Discharge, 30 Days, 12 Months and 2 Years	Discharge, 30 Days, 12 Months and 2 Years
Hemodynamic Mean Gradient as a Continuous Variable	Mean aortic gradient as measured by echocardiogram at the following intervals: Discharge, 30 Days, 12 Months and 2 Years	Discharge, 30 Days, 12 Months and 2 Years
Rate of Paravalvular Leak (PVL) by Degree of Severity	Paravalvular Leak as measured by the percentage of participants that had none, trace, mild, moderate and severe, at Discharge, 30 Days, 12 Months and 2 Years	Discharge, 30 Days, 12 Months and 2 Years

Collaborators and Investigators

• Sponsor: Medtronic Cardiovascular
• Investigators: Principal Investigator: Howard Herrmann, MD, University of Pennsylvania, United States; Principal Investigator: Roxana Mehran, MD, Mount Sinai School of Medicine, United States; Principal Investigator: Didier Tchétché, MD, Clinique Pasteur Toulouse, France

Publications and helpful links

General Publications

• Herrmann HC, Abdel-Wahab M, Attizzani GF, Batchelor W, Bleiziffer S, Verdoliva S, Chang Y, Gada H, Gillam L, Guerrero M, Mahoney PD, Petronio AS, Rogers T, Rovin J, Szerlip M, Whisenant B, Mehran R, Tchetche D. Rationale and design of the SMall Annuli Randomized To Evolut or SAPIEN Trial (SMART Trial). Am Heart J. 2022 Jan;243:92-102. doi: 10.1016/j.ahj.2021.09.011. Epub 2021 Sep 26.
• Tchetche D, Mehran R, Blackman DJ, Khalil RF, Mollmann H, Abdel-Wahab M, Ben Ali W, Mahoney PD, Ruge H, Bleiziffer S, Lin L, Szerlip M, Grubb KJ, Byku I, Guerrero M, Gillam LD, Petronio AS, Attizzani GF, Batchelor WB, Gada H, Rogers T, Rovin JD, Whisenant B, Benton S, Gardner B, Padang R, Althouse AD, Herrmann HC. Transcatheter Aortic Valve Implantation by Valve Type in Women With Small Annuli: Results From the SMART Randomized Clinical Trial. JAMA Cardiol. 2024 Dec 1;9(12):1106-1114. doi: 10.1001/jamacardio.2024.3241.
• Herrmann HC, Mehran R, Blackman DJ, Bailey S, Mollmann H, Abdel-Wahab M, Ben Ali W, Mahoney PD, Ruge H, Wood DA, Bleiziffer S, Ramlawi B, Gada H, Petronio AS, Resor CD, Merhi W, Garcia Del Blanco B, Attizzani GF, Batchelor WB, Gillam LD, Guerrero M, Rogers T, Rovin JD, Szerlip M, Whisenant B, Deeb GM, Grubb KJ, Padang R, Fan MT, Althouse AD, Tchetche D; SMART Trial Investigators. Self-Expanding or Balloon-Expandable TAVR in Patients with a Small Aortic Annulus. N Engl J Med. 2024 Jun 6;390(21):1959-1971. doi: 10.1056/NEJMoa2312573. Epub 2024 Apr 7.

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2021
• Primary Completion (Actual): November 10, 2023
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 20, 2021
• First Submitted That Met QC Criteria: January 22, 2021
• First Posted (Actual): January 25, 2021

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: MDT20023EVR012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes