Behavior of Valve Leaflets Following 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, 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.

• 4D Cardiac CT Scan (Diagnostic test): 4D CT scan obtained at minimum of 1 month after the discontinuation of the anticoagulation or dual antiplatelet therapy
• LivaNova Bioprothetic Aortic Valve Implant (Device): Study includes patients that have received the commercially approved LivaNova bioprosthetic aortic heart valve Perceval, as standard of care.

Primary outcomes

• Reduction in Leaflet Motion [1 year post-implant]: 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).

Secondary outcomes

• Leaflet Motion in Symptomatic and Asymptomatic Subjects Outcomes [up to 1 year post-implant]: 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).
• Reduced Leaflet Motion Through 4D Volume-rendered CT Scan [up to 1 year post-implant]: 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).
• Reduction in Leaflet Motion by Relationship to Devices or Procedure [up to 1 year post-implant]: 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).
• Freedom From All-cause Mortality [up to 1 year post-implant]: Number and incidence of subjects free from all-cause mortality
• Freedom From Valve Re-intervention [up to 1 year post-implant]: Number and incidence of subjects free from valve reintervention
• Freedom From Myocardial Infarction [up to 1 year post-implant]: Number and incidence of subjects free from myocardial infarction
• Freedom From Structural Valve Deterioration [up to 1 year post-implant]: Number and incidence of subjects free from structural valve deterioration
• Freedom From Moderate or Severe Valve Regurgitation [up to 1 year post-implant]: Number and incidence of subjects free from moderate or severe valve regurgitation
• Freedom From Valve Endocarditis [up to 1 year post-implant]: Number and incidence of subjects free from valve endocarditis
• Freedom From Valve Thrombosis [up to 1 year post-implant]: Number and incidence of subjects free from valve thrombosis
• Freedom From Thromboembolic Events [up to 1 year post-implant]: Number and incidence of subjects free from thromboembolic events
• Freedom From Hemolysis [up to 1 year post-implant]: Number and incidence of subjects free from hemolysis
• Freedom From Major Bleeding [up to 1 year post-implant]: Number and incidence of subjects free from major bleeding
• New York Heart Association (NYHA) Assessment [1 year post-implant]: 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.
• Aortic Peak Gradient Through Transthoracic Echocardiogram (TTE) [up to 1 year post-implant]: 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)
• Aortic Mean Gradient Through Transthoracic Echocardiogram (TTE) [up to 1 year post-implant]: 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)
• Effective Orifice Area Through Transthoracic Echocardiogram (TTE) [up to 1 year post-implant]: 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)
• Global Aortic Regurgitation Through Transthoracic Echocardiogram (TTE) [up to 1 year post-implant]: 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)
• Central Aortic Regurgitation Through Transthoracic Echocardiogram (TTE) [up to 1 year post-implant]: 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)
• Paravalvular Aortic Regurgitation Through Transthoracic Echocardiogram (TTE) [up to 1 year post-implant]: 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)

Sex: All, ages: 18 Years to any

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

Participant flow

Outcome results

• Reduction in Leaflet Motion (Primary), Count of participants, Participants: Aortic Valve 12
• Leaflet Motion in Symptomatic and Asymptomatic Subjects Outcomes (Secondary), Count of participants, Participants: Asymptomatic Patients 11; Symtomatic Patients 1
• Reduced Leaflet Motion Through 4D Volume-rendered CT Scan (Secondary), Count of participants, Participants: Aortic Valve 2
• Reduction in Leaflet Motion by Relationship to Devices or Procedure (Secondary), Count of participants, Participants: Subjects With Reduced Leaflet Motion (RLM) Overall 12; Subjects Implanted With Perceval Size S 1; Subjects Implanted With Perceval S Size M 3; Subjects Implanted With Perceval S Size L 4; Subjects Implanted With Perceval Size XL 4; Subjects Implanted With Perceval Via Minimally Invasive Surgical Approach 5; Subjects Implanted With Perceval Via Full Sternotomy Surgical Approach 7
• Freedom From All-cause Mortality (Secondary), Count of participants, Participants: Aortic Valve 84
• Freedom From Valve Re-intervention (Secondary), Count of participants, Participants: Aortic Valve 88
• Freedom From Myocardial Infarction (Secondary), Count of participants, Participants: Aortic Valve 88
• Freedom From Structural Valve Deterioration (Secondary), Count of participants, Participants: Aortic Valve 88
• Freedom From Moderate or Severe Valve Regurgitation (Secondary), Count of participants, Participants: Aortic Valve 88
• Freedom From Valve Endocarditis (Secondary), Count of participants, Participants: Aortic Valve 88
• Freedom From Valve Thrombosis (Secondary), Count of participants, Participants: Aortic Valve 87
• Freedom From Thromboembolic Events (Secondary), Count of participants, Participants: Aortic Valve 82
• Freedom From Hemolysis (Secondary), Count of participants, Participants: Aortic Valve 88
• Freedom From Major Bleeding (Secondary), Count of participants, Participants: Aortic Valve 85
• New York Heart Association (NYHA) Assessment (Secondary), Count of participants, Participants: Aortic Valve 52
• Aortic Peak Gradient Through Transthoracic Echocardiogram (TTE) (Secondary), Mean, mmHg: Aortic Valve 22.6 +/- 9.6
• Aortic Mean Gradient Through Transthoracic Echocardiogram (TTE) (Secondary), Mean, mmHg: Aortic Valve 12.5 +/- 5.9
• Effective Orifice Area Through Transthoracic Echocardiogram (TTE) (Secondary), Mean, cm2: Aortic Valve 1.7 +/- 0.5
• Global Aortic Regurgitation Through Transthoracic Echocardiogram (TTE) (Secondary), Count of participants, Participants: Aortic Valve 51
• Central Aortic Regurgitation Through Transthoracic Echocardiogram (TTE) (Secondary), Count of participants, Participants: Aortic Valve 60
• 1 more outcome measures not shown.

Adverse events

Time frame: Overall incidences of Serious Adverse Events reported between implant (day 0) and 1 year follow up

Serious adverse events by term

• 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. PMID 25184874
• 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. PMID 20961243
• 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. PMID 25079769
• 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. PMID 26437127
• 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. PMID 26436963
• 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. PMID 20329497
• 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. PMID 26443880
• 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. PMID 25501554
• 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. PMID 24603191
• 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. PMID 21639811

• Study Protocol (PDF, 2018-12-05)
• Statistical Analysis Plan (PDF, 2019-05-14)

• Niv Ad, MD, Principal investigator, Washington Adventist Hospital
• Federico Asch, MD, Principal investigator, Medstar Health Research Institute