Behavior of Valve Leaflets Following Aortic Valve Implant (BELIEVE)

Behavior of Valve Leaflets and the Incidence of Reduced Mobility Post-surgical Aortic Valve Implant

This is a prospective, interventional, multi-center trial to report the overall incidence of reduced leaflet motion identified by CT imaging in patients receiving a commercially approved LivaNova bioprosthetic aortic heart valve up to 1 year post implant.

Study Overview

• Status: Completed
• Conditions: Aortic-valve Replacement
• Intervention / Treatment: Diagnostic test: 4D Cardiac CT Scan; Device: LivaNova Bioprothetic Aortic Valve Implant

Detailed Description

This is a prospective, interventional, multi-center trial to report the overall incidence of reduced leaflet motion identified by CT imaging in patients receiving a commercially approved LivaNova bioprosthetic aortic heart valve up to 1 year post implant, on patients that are off anticoagulation for at least 30 days. A minimum of 75 subjects with evaluable 4D CT scans will be enrolled at approximately 11 investigational sites where the devices are commercially available. For asymptomatic subjects, PIs and subjects will be blinded from the CT imaging results and from the Core Lab findings.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Montréal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
    • Québec, Quebec, Canada, G1V4G5
      • Université Laval
• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • St. Vincent Cardiovascular Research Institute
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Medical Center
  • Maryland
    • Takoma Park, Maryland, United States, 20912
      • Washington Adventist Hospital
  • Michigan
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Centennial
  • Virginia
    • Winchester, Virginia, United States, 22601
      • Valley Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subject has been successfully implanted with a commercially approved LivaNova bioprosthetic valve according to the instructions for use (IFU)
2. The subject has signed the informed consent.
3. The subject is at least 18 years of age at the time of implant and consent signature
4. The subject will be available for post-operative follow-up through one year

Exclusion Criteria:

1. The subject has a planned concomitant cardiac procedure other than coronary artery bypass graft (CABG) and septal myectomy, including MAZE procedures, atrial fibrillation surgery, and left atrial appendage exclusion or resection, or has a prosthetic heart valve or annuloplasty ring in any position
2. The subject has any medical condition requiring long term (> 6 months) anticoagulation or dual antiplatelet therapy
3. The subject has any clinical condition precluding the use of CT imaging with contrast
4. The subject had a stroke or myocardial infarction (STEMI and NSTEMI) within 30 days of the planned valve implant surgery
5. The subject has active endocarditis, myocarditis, or sepsis
6. The subject is in cardiogenic shock manifested by low cardiac output and needing hemodynamic support
7. The subject is already included in another clinical trial that could confound the results of this clinical investigation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Aortic Valve; LivaNova bioprosthetic aortic heart valve replacement	Diagnostic test: 4D Cardiac CT Scan; 4D CT scan obtained at minimum of 1 month after the discontinuation of the anticoagulation or dual antiplatelet therapy; Device: LivaNova Bioprothetic Aortic Valve Implant; Study includes patients that have received the commercially approved LivaNova bioprosthetic aortic heart valve Perceval, as standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in Leaflet Motion	Report the overall incidence of reduced leaflet motion identified by CT imaging in commercially approved LivaNova bioprosthetic aortic heart valves up to 1 year post implant on patients that are off anticoagulation for at least 30 days. The valve leaflets will be assessed using 4D-VR (volume-rendered) CT imaging. Leaflet motion in all leaflets will be defined as normal, mildly reduced (<50% reduction in leaflet opening), moderately reduced (50-70% reduction in leaflet motion), severely reduced (>70% reduction in leaflet motion) and immobile (no or negligible leaflet motion).	1 year post-implant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leaflet Motion in Symptomatic and Asymptomatic Subjects Outcomes	Incidence of reduced leaflet motion in symptomatic and asymptomatic subjects based on CT outcomes and anticoagulation and dual antiplatelet treatment modalities up to 1 year post-implant. The valve leaflets will be assessed using 4D-VR (volume-rendered) CT imaging. Leaflet motion in all leaflets will be defined as normal, mildly reduced (<50% reduction in leaflet opening), moderately reduced (50-70% reduction in leaflet motion), severely reduced (>70% reduction in leaflet motion) and immobile (no or negligible leaflet motion).	up to 1 year post-implant
Reduced Leaflet Motion Through 4D Volume-rendered CT Scan	Incidence of reduced leaflet motion through 4D volume-rendered CT scan with contrast up to 1 year post-implant, in subjects in which reduced leaflet motion was previously detected. The valve leaflets will be assessed using 4D-VR (volume-rendered) CT imaging. Leaflet motion in all leaflets will be defined as normal, mildly reduced (<50% reduction in leaflet opening), moderately reduced (50-70% reduction in leaflet motion), severely reduced (>70% reduction in leaflet motion) and immobile (no or negligible leaflet motion).	up to 1 year post-implant
Reduction in Leaflet Motion by Relationship to Devices or Procedure	Incidence of reduced leaflet motion considering relationship to the devices, procedure, or other causes up to 1 year post-implant The valve leaflets will be assessed using 4D-VR (volume-rendered) CT imaging. Leaflet motion in all leaflets will be defined as normal, mildly reduced (<50% reduction in leaflet opening), moderately reduced (50-70% reduction in leaflet motion), severely reduced (>70% reduction in leaflet motion) and immobile (no or negligible leaflet motion).	up to 1 year post-implant
Freedom From All-cause Mortality	Number and incidence of subjects free from all-cause mortality	up to 1 year post-implant
Freedom From Valve Re-intervention	Number and incidence of subjects free from valve reintervention	up to 1 year post-implant
Freedom From Myocardial Infarction	Number and incidence of subjects free from myocardial infarction	up to 1 year post-implant
Freedom From Structural Valve Deterioration	Number and incidence of subjects free from structural valve deterioration	up to 1 year post-implant
Freedom From Moderate or Severe Valve Regurgitation	Number and incidence of subjects free from moderate or severe valve regurgitation	up to 1 year post-implant
Freedom From Valve Endocarditis	Number and incidence of subjects free from valve endocarditis	up to 1 year post-implant
Freedom From Valve Thrombosis	Number and incidence of subjects free from valve thrombosis	up to 1 year post-implant
Freedom From Thromboembolic Events	Number and incidence of subjects free from thromboembolic events	up to 1 year post-implant
Freedom From Hemolysis	Number and incidence of subjects free from hemolysis	up to 1 year post-implant
Freedom From Major Bleeding	Number and incidence of subjects free from major bleeding	up to 1 year post-implant
New York Heart Association (NYHA) Assessment	Number and incidence of subjects in the different NYHA class at 1 year post-implant. NYHA I = Subjects with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or angina. NYHA II = Subjects with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or angina. NYHA III = Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or angina. NYHA IV = Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or angina may be present even at rest. If any physical activity is undertaken, discomfort is increased.	1 year post-implant
Aortic Peak Gradient Through Transthoracic Echocardiogram (TTE)	Summary statistics (means, Standard Deviation, median, quartiles and range values for continuous variables; count and frequency distributions for categorical variables) of Hemodynamic assessment up to 1 year post-implant through Echocardiographic Core Lab transthoracic echocardiogram (TTE)	up to 1 year post-implant
Aortic Mean Gradient Through Transthoracic Echocardiogram (TTE)	Summary statistics (means, Standard Deviation, median, quartiles and range values for continuous variables; count and frequency distributions for categorical variables) of Hemodynamic assessment up to 1 year post-implant through Echocardiographic Core Lab transthoracic echocardiogram (TTE)	up to 1 year post-implant
Effective Orifice Area Through Transthoracic Echocardiogram (TTE)	Summary statistics (means, Standard Deviation, median, quartiles and range values for continuous variables; count and frequency distributions for categorical variables) of Hemodynamic assessment up to 1 year post-implant through Echocardiographic Core Lab transthoracic echocardiogram (TTE)	up to 1 year post-implant
Global Aortic Regurgitation Through Transthoracic Echocardiogram (TTE)	Summary statistics (means, Standard Deviation, median, quartiles and range values for continuous variables; count and frequency distributions for categorical variables) of Hemodynamic assessment up to 1 year post-implant through Echocardiographic Core Lab transthoracic echocardiogram (TTE)	up to 1 year post-implant
Central Aortic Regurgitation Through Transthoracic Echocardiogram (TTE)	Summary statistics (means, Standard Deviation, median, quartiles and range values for continuous variables; count and frequency distributions for categorical variables) of Hemodynamic assessment up to 1 year post-implant through Echocardiographic Core Lab transthoracic echocardiogram (TTE)	up to 1 year post-implant
Paravalvular Aortic Regurgitation Through Transthoracic Echocardiogram (TTE)	Summary statistics (means, Standard Deviation, median, quartiles and range values for continuous variables; count and frequency distributions for categorical variables) of Hemodynamic assessment up to 1 year post-implant through Echocardiographic Core Lab transthoracic echocardiogram (TTE)	up to 1 year post-implant

Collaborators and Investigators

• Sponsor: Corcym S.r.l
• Collaborators: LivaNova
• Investigators: Principal Investigator: Federico Asch, MD, Medstar Health Research Institute; Principal Investigator: Niv Ad, MD, Washington Adventist Hospital

Publications and helpful links

General Publications

• Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O'Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Jun 10;63(22):e57-185. doi: 10.1016/j.jacc.2014.02.536. Epub 2014 Mar 3. No abstract available. Erratum In: J Am Coll Cardiol. 2014 Jun 10;63(22):2489. Dosage error in article text.
• Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010 Oct 21;363(17):1597-607. doi: 10.1056/NEJMoa1008232. Epub 2010 Sep 22.
• Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Williams M, Dewey T, Kapadia S, Babaliaros V, Thourani VH, Corso P, Pichard AD, Bavaria JE, Herrmann HC, Akin JJ, Anderson WN, Wang D, Pocock SJ; PARTNER Trial Investigators. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011 Jun 9;364(23):2187-98. doi: 10.1056/NEJMoa1103510. Epub 2011 Jun 5.
• Makkar RR, Fontana G, Jilaihawi H, Chakravarty T, Kofoed KF, De Backer O, Asch FM, Ruiz CE, Olsen NT, Trento A, Friedman J, Berman D, Cheng W, Kashif M, Jelnin V, Kliger CA, Guo H, Pichard AD, Weissman NJ, Kapadia S, Manasse E, Bhatt DL, Leon MB, Sondergaard L. Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves. N Engl J Med. 2015 Nov 19;373(21):2015-24. doi: 10.1056/NEJMoa1509233. Epub 2015 Oct 5.
• Adams DH, Popma JJ, Reardon MJ. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. 2014 Sep 4;371(10):967-8. doi: 10.1056/NEJMc1408396. No abstract available.
• Mohr FW, Holzhey D, Mollmann H, Beckmann A, Veit C, Figulla HR, Cremer J, Kuck KH, Lange R, Zahn R, Sack S, Schuler G, Walther T, Beyersdorf F, Bohm M, Heusch G, Funkat AK, Meinertz T, Neumann T, Papoutsis K, Schneider S, Welz A, Hamm CW; GARY Executive Board. The German Aortic Valve Registry: 1-year results from 13,680 patients with aortic valve disease. Eur J Cardiothorac Surg. 2014 Nov;46(5):808-16. doi: 10.1093/ejcts/ezu290. Epub 2014 Jul 30.
• Laschinger JC, Wu C, Ibrahim NG, Shuren JE. Reduced Leaflet Motion in Bioprosthetic Aortic Valves--The FDA Perspective. N Engl J Med. 2015 Nov 19;373(21):1996-8. doi: 10.1056/NEJMp1512264. Epub 2015 Oct 5. No abstract available.
• Beholz S, Repossini A, Livi U, Schepens M, El Gabry M, Matschke K, Trivedi U, Eckel L, Dapunt O, Zamorano JL. The Freedom SOLO valve for aortic valve replacement: clinical and hemodynamic results from a prospective multicenter trial. J Heart Valve Dis. 2010 Jan;19(1):115-23.
• Thalmann M, Grubitzsch H, Matschke K, Glauber M, Tan E, Francois K, Amorim MJ, Hensens AG, Cesari F, Feyrer R, Diegeler A, Veit F, Repossini A; Freedom Solo Investigators. A European Multicenter Study of 616 Patients Receiving the Freedom Solo Stentless Bioprosthesis. Ann Thorac Surg. 2016 Jan;101(1):100-8. doi: 10.1016/j.athoracsur.2015.06.096. Epub 2015 Oct 9.
• Grubitzsch H, Wang S, Matschke K, Glauber M, Heimansohn D, Tan E, Francois K, Thalmann M. Clinical and haemodynamic outcomes in 804 patients receiving the Freedom SOLO stentless aortic valve: results from an international prospective multicentre study. Eur J Cardiothorac Surg. 2015 Mar;47(3):e97-104. doi: 10.1093/ejcts/ezu471. Epub 2014 Dec 13.

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2017
• Primary Completion (Actual): June 15, 2020
• Study Completion (Actual): February 25, 2021

Study Registration Dates

• First Submitted: June 9, 2017
• First Submitted That Met QC Criteria: June 26, 2017
• First Posted (Actual): June 27, 2017

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Perceval
• Other Study ID Numbers: APR002

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