PERIGON Pivotal Trial

Aortic Stenosis Clinical Trial

— PERIGON  

Official title:

Medtronic PERIcardial SurGical AOrtic Valve ReplacemeNt Pivotal Trial A Multi-center, Non-randomized Trial to Determine the Safety and Effectiveness of the Model 400 Aortic Valve Bioprosthesis in Patients With Aortic Valve Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02088554
• Other study ID #: PERIGON
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 12, 2014
• Est. completion date: December 31, 2035

Study information

• Verified date: June 2024
• Source: Medtronic Cardiac Surgery
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the safety and effectiveness of the Model 400 aortic valve bioprosthesis.

Description:

This is a prospective, interventional, non-randomized, worldwide, multi-center trial. A maximum of 1300 subjects were to be implanted at a maximum of 40 sites in the US, Europe and Canada. The trial includes male and female patients of legal age to provide informed consent in the country where they enrolled in the trial, requiring replacement for a diseased, damaged, or malfunctioning native or prosthetic aortic valve. Subjects are followed out to 5 years, and select sites follow subjects out to 12 years. Enrollment closed on 14Jul2017 for all valve sizes. Enrollment was reopened in Apr2019 for the 29mm valve size at a subset of US and Canadian sites to obtain greater patient numbers required by the FDA to support US commercial approval of this valve size. Enrollment for the 29mm valve size closed on 14Feb2023.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1312
• Est. completion date: December 31, 2035
• Est. primary completion date: April 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patient has moderate or greater aortic stenosis or regurgitation, and there is clinical indication for replacement of their native or prosthetic aortic valve with a bioprosthesis, with or without concomitant procedures, which are limited to any of the following:

i. Left atrial appendage (LAA) ligation ii. CABG (coronary artery bypass grafting) iii. Patent foramen ovale (PFO) closure iv. Ascending aortic aneurysm or dissection repair not requiring circulatory arrest v. Resection of a sub-aortic membrane not requiring myectomy

2. Patient is geographically stable and willing to return to the implanting site for all follow-up visits

3. Patient is of legal age to provide informed consent in the country where they enroll in the trial

4. Patient has been adequately informed of risks and requirements of the trial and is willing and able to provide informed consent for participation in the clinical trial

Exclusion Criteria:

1. Patient has a pre-existing prosthetic valve or annuloplasty device in another position or requires replacement or repair of the mitral, pulmonary or tricuspid valve

2. Patient has had previous implant and then explant of the Model 400 aortic valve bioprosthesis

3. Patient presents with active endocarditis, active myocarditis or other systemic infection

4. Patient has an anatomical abnormality which would increase surgical risk of morbidity or mortality, including:

• Ascending aortic aneurysm or dissection repair requiring circulatory arrest

• Acute Type A aortic dissection

• Ventricular aneurysm

• Porcelain aorta

• Hostile mediastinum

• Hypertrophic obstructive cardiomyopathy (HOCM)

• Documented pulmonary hypertension (systolic >60mmHg)

5. Patient has a non-cardiac major or progressive disease, with a life expectancy of less than 2 years. These conditions include, but are not limited to:

• Child-Pugh Class C liver disease

• Terminal cancer

• End-stage lung disease

6. Patient has renal failure, defined as dialysis therapy or glomerular filtration rate(GFR)<30 mL/min/1.73 m2

7. Patient has hyperparathyroidism

8. Patient is participating in another investigational device or drug trial or observational competitive study

9. Patient is pregnant, lactating or planning to become pregnant during the trial period

10. Patient has a documented history of substance (drug or alcohol) abuse

11. Patient has greater than mild mitral valve regurgitation or greater than mild tricuspid valve regurgitation as assessed by echocardiography

12. Patient has systolic ejection fraction (EF)<20% as assessed by echocardiography

13. Patient has Grade IV Diastolic Dysfunction

14. Patient has documented bleeding diatheses

15. Patient has had an acute preoperative neurological deficit or myocardial infarction and has not returned to baseline or stabilized =30 days prior to enrollment

16. Patient requires emergency surgery

Related Conditions & MeSH terms

• Aortic Stenosis
• Aortic Valve Stenosis

Intervention

Device:
• Model 400 aortic valve bioprosthesis

Locations

Country	Name	City	State
Canada	London Health Sciences Centre - University Campus	London	Ontario
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)	Quebec
Canada	Toronto General Hospital	Toronto
France	Hôpital Cardiologique du Haut-Lévêque	Bordeaux
France	Hôpital Bichat - Claude Bernard	Paris
Germany	Uniklinik Köln	Cologne	Köln
Germany	Universitäts Klinikum Frankfurt - Goethe-Universität	Frankfurt
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Herzzentrum Leipzig GmbH	Leipzig
Germany	Deutsches Herzzentrum München	Munich	München
Italy	Ospedale San Raffaele - Milano	Milano
Netherlands	Leids Universitair Medisch Centrum (LUMC)	Leiden
Netherlands	Erasmus MC	Rotterdam
Switzerland	Inselspital - Universitätsspital Bern	Bern
Switzerland	UniversitätsSpital Zürich	Zürich
United Kingdom	Guy's & St Thomas' NHS Foundation Trust - St Thomas' Hospital	London
United States	University of Michigan Cardiovascular Center	Ann Arbor	Michigan
United States	Piedmont Hospital	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Cardiothoracic and Vascular Surgeons (CTVS)	Austin	Texas
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Maimonides Medical Center	Brooklyn	New York
United States	Cleveland Clinic	Cleveland	Ohio
United States	Riverside Methodist Hospital (OhioHealth)	Columbus	Ohio
United States	University of Florida Shands	Gainesville	Florida
United States	Hartford Hospital	Hartford	Connecticut
United States	Houston Methodist Hospital	Houston	Texas
United States	University of Southern California (USC) University Hospital	Los Angeles	California
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota
United States	New York-Presbyterian Hospital/Columbia University Medical Center	New York	New York
United States	The Mount Sinai Medical Center	New York	New York
United States	Oklahoma Heart Hospital	Oklahoma City	Oklahoma
United States	University of Washington Medical Center	Seattle	Washington
United States	ProMedica Toledo Hospital	Toledo	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Medtronic Cardiac Surgery	Medtronic

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Netherlands,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluate the Safety of the Model 400 Avalus Valve With Regard to Valve-related Adverse Events and Death at 1 Year Post-implant (Remaining Data From 29mm Valve Participants Not Required for Meeting Primary Outcomes)	Safety of the valve is evaluated by the time-related incidence of valve-related adverse events and death. The following valve-related adverse events are evaluated in this study: Thromboembolism, Thrombosis, Hemorrhage, Paravalvular leak (PVL), Endocarditis, Hemolysis, Structural valve deterioration, Non-structural dysfunction, Reintervention, Explant, and Death. A minimum of 15 participants per valve size are evaluated. The Kaplan-Meier event rates will be used to summarize valve-related adverse events and death. The Kaplan-Meier rate and the corresponding 95% confidence interval will be presented for each visit interval.	1 year post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Change of New York Heart Association (NYHA) Classification From Baseline Through 1 Year (Remaining Data From 29mm Valve Participants Not Required for Meeting Primary Outcomes)	Participants evaluated for change in New York Heart Association (NYHA) functional classification from baseline to 1 year post-procedure.; Measure Description: Cardiac Disease with Functional Classes (lower value is more desirable than higher value) I - No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath.; II - Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain.; III - Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain.; IV - Symptoms of heart failure at rest. Any physical activity causes further discomfort.	3-6 months and 1 year post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Effective Orifice Area Through 1 Year Post-procedure (Remaining Data From 29mm Valve Participants Not Required for Meeting Primary Outcomes)	Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory. The effective orifice area (EOA) is measured as the minimal cross-sectional area of the blood flow downstream of the aortic valve.	3-6 months, 1 year post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Effective Orifice Area Index (EOAI) Through 1 Year Post-implant (Remaining Data From 29mm Valve Participants Not Required for Meeting Primary Outcomes)	Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory for effective orifice area index (EOAI = EOA/BSA) Effective orifice area index is equal to the effective orifice area (EOA) in cm^2 divided by body surface area (BSA) in m^2.; The achievement criterion for the effective orifice area index (EOAI) is defined to be =0.6 cm^2/m^2 12 months after the procedure. This criterion is in accordance with the definition of severe aortic stenosis in the American College of Cardiology (ACC) / American Heart Association (AHA) guidelines for the management of valvular heart disease.	3-6 months, and 1 year post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Peak Pressure Gradient (mmHg) From Discharge up to 1 Year (Remaining Data From 29mm Valve Participants Not Required for Meeting Primary Outcomes)	Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory.; The peak pressure gradient is the maximum value measured of flow of blood through the aortic valve as measured in millimeters of mercury.	3-6 months, and 1 year post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Mean Pressure Gradient (mmHg) Through 1 Year Post-implant (Remaining Data From 29mm Valve Participants Not Required for Meeting Primary Outcomes)	Evaluated by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The mean pressure gradient is the average flow of blood through the aortic valve measured in millimeters of mercury.	3-6 months, and 1 year post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Performance Index (L/Min) Through 1 Year Post-implant (Remaining Data From 29mm Valve Participants Not Required for Meeting Primary Outcomes)	Performance index (L/Min) measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The performance index is the measurement of the effective orifice area divided by the native orifice area.	3-6 months, and 1 year post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Cardiac Output (L/Min) Through 1 Year Post-implant (Remaining Data From 29mm Valve Participants Not Required for Meeting Primary Outcomes)	Cardiac output is the amount of blood pumped by the heart per minute. Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory.	3-6 months, and 1 year post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Cardiac Index (L/Min/m^2) Through 1 Year Post-implant (Remaining Data From 29mm Valve Participants Not Required for Meeting Primary Outcomes)	Evaluated by transthoracic echocardiography technique and will be assessed by an independent core laboratory.; The cardiac index is an assessment of the cardiac output based on a patient's size measured by dividing the cardiac output by the patient's body's surface area.	3-6 months, and 1 year post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve by Clinically Acceptable Hemodynamic Performance From Years 6 Through 12 Post-implant.	Long-term follow-up clinically acceptable hemodynamic performance defined as freedom from surgical explant and/or percutaneous valve-in-valve reintervention due to structural valve deterioration	Annually, years 6-12 post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve From Years 6 - 12 Post-implant by Freedom From Valve-related Death		Annually, years 6 though 12 post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve From Years 6 - 12 Post-implant by Freedom From All-cause Mortality	For time-to-event outcomes, Kaplan-Meier (actuarial) analysis of the event-free rate performed annually through twelve years.	Annually, years 6 though 12 post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve From Years 6 - 12 Post-implant by Change in NYHA Functional Classification Status From Baseline		Annually, years 6 though 12 post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Effective Orifice Area Through 12 Years Post-procedure	Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory. The effective orifice area (EOA) is measured as the minimal cross-sectional area of the blood flow downstream of the aortic valve.	Annually, years 6 though 12 post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Effective Orifice Area Index (EOAI) Through 12 Years Post-implant	Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory for effective orifice area index (EOAI = EOA/BSA) Effective orifice area index is equal to the effective orifice area (EOA) in cm^2 divided by body surface area (BSA) in m^2.; The achievement criterion for the effective orifice area index (EOAI) is defined to be =0.6 cm^2/m^2 12 months after the procedure. This criterion is in accordance with the definition of severe aortic stenosis in the American College of Cardiology (ACC) / American Heart Association (AHA) guidelines for the management of valvular heart disease.	Annually, years 6 though 12 post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Peak Pressure Gradient (mmHg) up to 12 Years Post-implant	Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory.; The peak pressure gradient is the maximum value measured of flow of blood through the aortic valve as measured in millimeters of mercury.	Annually, years 6 though 12 post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Mean Pressure Gradient (mmHg) Through 12 Years Post-implant	Evaluated by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The mean pressure gradient is the average flow of blood through the aortic valve measured in millimeters of mercury.	Annually, years 6 though 12 post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Performance Index (L/Min) Through 12 Years Post-implant	Performance index (L/Min) measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The performance index is the measurement of the effective orifice area divided by the native orifice area.	Annually, years 6 though 12 post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Cardiac Output (L/Min) Through 12 Years Post-implant	Cardiac output is the amount of blood pumped by the heart per minute. Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory.	Annually, years 6 though 12 post-implant
Other	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Cardiac Index (L/Min/m^2) Through 12 Years Post-implant	Evaluated by transthoracic echocardiography technique and will be assessed by an independent core laboratory.; The cardiac index is an assessment of the cardiac output based on a patient's size measured by dividing the cardiac output by the patient's body's surface area.	Annually, years 6 though 12 post-implant
Primary	Evaluate the Safety of the Model 400 Avalus Valve With Regard to Valve-related Adverse Events and Death at 1 Year Post-implant	Safety of the valve is evaluated by the time-related incidence of valve-related adverse events and death. The following valve-related adverse events are evaluated in this study: Thromboembolism, Thrombosis, Hemorrhage, Paravalvular leak (PVL), Endocarditis, Hemolysis, Structural valve deterioration, Non-structural dysfunction, Reintervention, Explant, and Death. A minimum of 15 participants per valve size are evaluated. The incidence rates will be used to summarize valve-related adverse events and death.	1 year post-implant
Primary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Change of New York Heart Association (NYHA) Classification From Baseline Through 1 Year	At each timepoint, a minimum of 15 participants per valve size evaluated for change in New York Heart Association (NYHA) functional classification from baseline to 1 year post-procedure.; Measure Description: Cardiac Disease with Functional Classes (lower value is more desirable than higher value) I - No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath.; II - Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain.; III - Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain.; IV - Symptoms of heart failure at rest. Any physical activity causes further discomfort.	Discharge (up to 30 days), 3-6 months, and 1 year post-implant
Primary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Effective Orifice Area Through 1 Year Post-procedure	A minimum of 15 participants per valve size evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory. The effective orifice area (EOA) is measured as the minimal cross-sectional area of the blood flow downstream of the aortic valve.	Discharge (up to 30 days), 3-6 months, 1 year post-implant
Primary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Effective Orifice Area Index (EOAI) Through 1 Year Post-implant	A minimum of 15 participants per valve size evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory for effective orifice area index (EOAI = EOA/BSA) Effective orifice area index is equal to the effective orifice area (EOA) in cm^2 divided by body surface area (BSA) in m^2.; The achievement criterion for the effective orifice area index (EOAI) is defined to be =0.6 cm^2/m^2 12 months after the procedure. This criterion is in accordance with the definition of severe aortic stenosis in the American College of Cardiology (ACC) / American Heart Association (AHA) guidelines for the management of valvular heart disease.	Discharge (up to 30 days), 3-6 months, and 1 year post-implant
Primary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Peak Pressure Gradient (mmHg) From Discharge up to 1 Year	A minimum of 15 participants per valve size evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory.; The peak pressure gradient is the maximum value measured of flow of blood through the aortic valve as measured in millimeters of mercury.	Measured at discharge (up to 30 days), 3-6 months, and 1 year post-implant
Primary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Mean Pressure Gradient (mmHg) Through 1 Year Post-implant	A minimum of 15 participants per valve size evaluated by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The mean pressure gradient is the average flow of blood through the aortic valve measured in millimeters of mercury.	Discharge (up to 30 days), 3-6 months, and 1 year post-implant
Primary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Performance Index (L/Min) Through 1 Year Post-implant	A minimum of 15 participants per valve size will have performance index (L/Min) measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The performance index is the measurement of the effective orifice area divided by the native orifice area.	Discharge (up to 30 days), 3-6 months, and 1 year post-implant
Primary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Cardiac Output (L/Min) Through 1 Year Post-implant	Cardiac output is the amount of blood pumped by the heart per minute. A minimum of 15 participants per valve size were evaluated for this outcome measure by transthoracic echocardiography technique and assessed by an independent core laboratory.	Discharge (up to 30 days), 3-6 months, and 1 year post-implant
Primary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Cardiac Index (L/Min/m^2) Through 1 Year Post-implant	A minimum of 15 participants per valve size evaluated by transthoracic echocardiography technique and will be assessed by an independent core laboratory.; The cardiac index is an assessment of the cardiac output based on a patient's size measured by dividing the cardiac output by the patient's body's surface area.	Discharge (up to 30 days), 3-6 months, and 1 year post-implant
Secondary	Evaluate the Safety of the Model 400 Avalus Valve With Regard to Valve-related Adverse Events and Death Annually Through 5 Years Post-implant	Safety of the valve is evaluated by the time-related incidence of valve-related adverse events and death. The following valve-related adverse events are evaluated in this study: Thromboembolism, Thrombosis, Hemorrhage, Paravalvular leak (PVL), Endocarditis, Hemolysis, Structural valve deterioration, Non-structural dysfunction, Reintervention, Explant, and Death. The Kaplan-Meier event rates will be used to summarize valve-related adverse events and death. The Kaplan-Meier rate and the corresponding 95% confidence interval will be presented for each visit interval.	Annually, at years 2, 3, 4, and 5 post-implant
Secondary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Change of New York Heart Association (NYHA) Classification From Baseline Through 5 Years Post-implant	At each timepoint, participants were evaluated for change in New York Heart Association (NYHA) functional classification from baseline through 5 years post-procedure.; Measure Description: Cardiac Disease with Functional Classes (lower value is more desirable than higher value) I - No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath.; II - Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain.; III - Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain.; IV - Symptoms of heart failure at rest. Any physical activity causes further discomfort.	Annually, at years 2, 3, 4, and 5 post-implant
Secondary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Effective Orifice Area Through 5 Years Post-procedure	Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory. The effective orifice area (EOA) is measured as the minimal cross-sectional area of the blood flow downstream of the aortic valve.	Annually, at years 2, 3, 4, and 5 post-implant
Secondary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Effective Orifice Area Index (EOAI) Through 5 Years Post-implant	Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory for effective orifice area index (EOAI = EOA/BSA) Effective orifice area index is equal to the effective orifice area (EOA) in cm^2 divided by body surface area (BSA) in m^2.; The achievement criterion for the effective orifice area index (EOAI) is defined to be =0.6 cm^2/m^2 12 months after the procedure. This criterion is in accordance with the definition of severe aortic stenosis in the American College of Cardiology (ACC) / American Heart Association (AHA) guidelines for the management of valvular heart disease.	Annually, at years 2, 3, 4, and 5 post-implant
Secondary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to the Peak Pressure Gradient (mmHg) From Discharge up to 5 Years Post-implant	Evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory.; The peak pressure gradient is the maximum value measured of flow of blood through the aortic valve as measured in millimeters of mercury.	Annually, at years 2, 3, 4, and 5 post-implant
Secondary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Mean Pressure Gradient (mmHg) Through 5 Years Post-implant	Evaluated by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The mean pressure gradient is the average flow of blood through the aortic valve measured in millimeters of mercury.	Annually, at years 2, 3, 4, and 5 post-implant
Secondary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Performance Index (L/Min) Through 5 Years Post-implant	Performance index (L/Min) measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory. The performance index is the measurement of the effective orifice area divided by the native orifice area.	Annually, at years 2, 3, 4, and 5 post-implant
Secondary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Cardiac Output (L/Min) Through 5 Years Post-implant	Cardiac output is the amount of blood pumped by the heart per minute, evaluated by transthoracic echocardiography technique and assessed by an independent core laboratory.	Annually, at years 2, 3, 4, and 5 post-implant
Secondary	Confirm the Effectiveness of the Model 400 Avalus Valve With Regard to Cardiac Index (L/Min/m^2) Through 5 Years Post-implant	Evaluated by transthoracic echocardiography technique and will be assessed by an independent core laboratory.; The cardiac index is an assessment of the cardiac output based on a patient's size measured by dividing the cardiac output by the patient's body's surface area.	Annually, at years 2, 3, 4, and 5 post-implant