Feasibility Study of a Percutaneous Mitral Valve Repair System.

Mitral Regurgitation Clinical Trial

— EVEREST(I)  

Official title:

A Study of the Evalve Cardiovascular Valve Repair System Endovascular Valve Edge-to-Edge REpair STudy (EVEREST I).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00209339
• Other study ID #: Protocol #0301
• Secondary ID: Protocol #0301
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 2003
• Est. completion date: October 2011

Study information

• Verified date: November 2018
• Source: Abbott Medical Devices
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prospective, multi-center, Phase I study of the Evalve Cardiovascular Valve Repair System (CVRS) in the treatment of mitral valve regurgitation. Patients will undergo 30-day, 6 month, 12 month, and 5 year clinical follow-up.

Description:

Phase I evaluation of the safety and effectiveness of an endovascular approach to the repair of mitral valve regurgitation using the Evalve Cardiovascular Valve Repair System.

The study is a prospective, multi-center, Phase I study of the Evalve Cardiovascular Valve Repair System (CVRS) in the treatment of mitral valve regurgitation. A minimum of 20 patients will be enrolled (an additional maximum of 12 roll in-patients, a maximum of 2 per site, may be enrolled and analyzed separately). Patients will undergo 30-day, 6 month and 12 month clinical follow-up.

Up to 12 clinical sites throughout the US may participate.

The primary endpoint is acute safety at thirty days, with a secondary efficacy endpoint of reduction of MR.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: October 2011
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have moderate to severe mitral regurgitation, symptomatic or asymptomatic with evidence of left ventricular dysfunction;

• Experience regurgitation origination from the central two-thirds of the valve;

• Qualify as a candidate for mitral valve surgery including cardiopulmonary bypass.

Exclusion Criteria:

• Ejection fraction < 30%

• Endocarditis

• Rheumatic heart disease

• Renal insufficiency

Related Conditions & MeSH terms

• Mitral Insufficiency
• Mitral Regurgitation
• Mitral Valve Incompetence
• Mitral Valve Insufficiency
• Mitral Valve Regurgitation

Intervention

Device:
• Percutaneous mitral valve repair (MitraClip Implant)
Phase I evaluation of the safety and effectiveness of an endovascular approach to the repair of mitral valve regurgitation using the Evalve MitraClip Cardiovascular Valve Repair System.

Locations

Country	Name	City	State
United States	Evanston Northwestern Healthcare	Evanston	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Abbott Medical Devices

Country where clinical trial is conducted

United States, 

References & Publications (20)

Argenziano M, Skipper E, Heimansohn D, Letsou GV, Woo YJ, Kron I, Alexander J, Cleveland J, Kong B, Davidson M, Vassiliades T, Krieger K, Sako E, Tibi P, Galloway A, Foster E, Feldman T, Glower D; EVEREST Investigators. Surgical revision after percutaneous mitral repair with the MitraClip device. Ann Thorac Surg. 2010 Jan;89(1):72-80; discussion p 80. doi: 10.1016/j.athoracsur.2009.08.063. — View Citation

Borgia F, Di Mario C, Franzen O. Adenosine-induced asystole to facilitate MitraClip placement in a patient with adverse mitral valve morphology. Heart. 2011 May;97(10):864. doi: 10.1136/hrt.2010.208132. Epub 2010 Oct 29. — View Citation

Ciobanu A, Bennett S, Azam M, Clark A, Vinereanu D. Incremental value of three-dimensional transoesophageal echocardiography for guiding double percutaneous MitraClip ® implantation in a 'no option' patient. Eur J Echocardiogr. 2011 Feb;12(2):E11. doi: 10.1093/ejechocard/jeq118. Epub 2010 Sep 27. — View Citation

Fann JI, St Goar FG, Komtebedde J, Oz MC, Block PC, Foster E, Butany J, Feldman T, Burdon TA. Beating heart catheter-based edge-to-edge mitral valve procedure in a porcine model: efficacy and healing response. Circulation. 2004 Aug 24;110(8):988-93. Epub 2004 Aug 9. — View Citation

Feldman T, Kar S, Rinaldi M, Fail P, Hermiller J, Smalling R, Whitlow PL, Gray W, Low R, Herrmann HC, Lim S, Foster E, Glower D; EVEREST Investigators. Percutaneous mitral repair with the MitraClip system: safety and midterm durability in the initial EVER — View Citation

Franzen O, Baldus S, Rudolph V, Meyer S, Knap M, Koschyk D, Treede H, Barmeyer A, Schofer J, Costard-Jäckle A, Schlüter M, Reichenspurner H, Meinertz T. Acute outcomes of MitraClip therapy for mitral regurgitation in high-surgical-risk patients: emphasis on adverse valve morphology and severe left ventricular dysfunction. Eur Heart J. 2010 Jun;31(11):1373-81. doi: 10.1093/eurheartj/ehq050. Epub 2010 Mar 10. — View Citation

Geidel S, Ostermeyer J, Lass M, Schmoeckel M. Complex surgical valve repair after failed percutaneous mitral intervention using the MitraClip device. Ann Thorac Surg. 2010 Jul;90(1):277-9. doi: 10.1016/j.athoracsur.2009.12.048. — View Citation

Herrmann HC, Kar S, Siegel R, Fail P, Loghin C, Lim S, Hahn R, Rogers JH, Bommer WJ, Wang A, Berke A, Lerakis S, Kramer P, Wong SC, Foster E, Glower D, Feldman T; EVEREST Investigators. Effect of percutaneous mitral repair with the MitraClip device on mitral valve area and gradient. EuroIntervention. 2009 Jan;4(4):437-42. — View Citation

Herrmann HC, Rohatgi S, Wasserman HS, Block P, Gray W, Hamilton A, Zunamon A, Homma S, Di Tullio MR, Kraybill K, Merlino J, Martin R, Rodriguez L, Stewart WJ, Whitlow P, Wiegers SE, Silvestry FE, Foster E, Feldman T. Mitral valve hemodynamic effects of percutaneous edge-to-edge repair with the MitraClip device for mitral regurgitation. Catheter Cardiovasc Interv. 2006 Dec;68(6):821-8. — View Citation

Jönsson A, Settergren M. MitraClip catheter-based mitral valve repair system. Expert Rev Med Devices. 2010 Jul;7(4):439-47. doi: 10.1586/erd.10.23. — View Citation

Kalarus Z, Kukulski T, Lekston A, Streb W, Sikora J, Nadziakiewicz P, Gasior M, Polonski L, Zembala M. [Methodology and safety of transvascular reduction of severe ischaemic mitral insufficiency with MitraClip in high-surgical-risk patients - first three cases in Poland]. Kardiol Pol. 2010 Jun;68(6):729-35. Polish. — View Citation

Lim DS, Kunjummen BJ, Smalling R. Mitral valve repair with the MitraClip device after prior surgical mitral annuloplasty. Catheter Cardiovasc Interv. 2010 Sep 1;76(3):455-9. doi: 10.1002/ccd.22547. — View Citation

Luk A, Butany J, Ahn E, Fann JI, St Goar F, Thornton T, McDermott L, Madayag C, Komtebedde J. Mitral repair with the Evalve MitraClip device: histopathologic findings in the porcine model. Cardiovasc Pathol. 2009 Sep-Oct;18(5):279-85. doi: 10.1016/j.carpath.2008.07.001. Epub 2008 Aug 13. — View Citation

Mauri L, Garg P, Massaro JM, Foster E, Glower D, Mehoudar P, Powell F, Komtebedde J, McDermott E, Feldman T. The EVEREST II Trial: design and rationale for a randomized study of the evalve mitraclip system compared with mitral valve surgery for mitral regurgitation. Am Heart J. 2010 Jul;160(1):23-9. doi: 10.1016/j.ahj.2010.04.009. — View Citation

Rogers JH, Yeo KK, Carroll JD, Cleveland J, Reece TB, Gillinov AM, Rodriguez L, Whitlow P, Woo YJ, Herrmann HC, Young JN. Late surgical mitral valve repair after percutaneous repair with the MitraClip system. J Card Surg. 2009 Nov-Dec;24(6):677-81. doi: 10.1111/j.1540-8191.2009.00901.x. Epub 2009 Jul 24. — View Citation

Silvestry FE, Rodriguez LL, Herrmann HC, Rohatgi S, Weiss SJ, Stewart WJ, Homma S, Goyal N, Pulerwitz T, Zunamon A, Hamilton A, Merlino J, Martin R, Krabill K, Block PC, Whitlow P, Tuzcu EM, Kapadia S, Gray WA, Reisman M, Wasserman H, Schwartz A, Foster E, Feldman T, Wiegers SE. Echocardiographic guidance and assessment of percutaneous repair for mitral regurgitation with the Evalve MitraClip: lessons learned from EVEREST I. J Am Soc Echocardiogr. 2007 Oct;20(10):1131-40. Epub 2007 Jun 13. — View Citation

St Goar FG, Fann JI, Komtebedde J, Foster E, Oz MC, Fogarty TJ, Feldman T, Block PC. Endovascular edge-to-edge mitral valve repair: short-term results in a porcine model. Circulation. 2003 Oct 21;108(16):1990-3. Epub 2003 Oct 6. — View Citation

Tamburino C, Immè S, Barbanti M, Mulè M, Pistritto AM, Aruta P, Cammalleri V, Scarabelli M, Mangiafico S, Scandura S, Ussia GP. Reduction of mitral valve regurgitation with Mitraclip® percutaneous system. Minerva Cardioangiol. 2010 Oct;58(5):589-98. — View Citation

Tamburino C, Ussia GP, Maisano F, Capodanno D, La Canna G, Scandura S, Colombo A, Giacomini A, Michev I, Mangiafico S, Cammalleri V, Barbanti M, Alfieri O. Percutaneous mitral valve repair with the MitraClip system: acute results from a real world setting. Eur Heart J. 2010 Jun;31(11):1382-9. doi: 10.1093/eurheartj/ehq051. Epub 2010 Mar 18. — View Citation

Ussia GP, Barbanti M, Tamburino C. Feasibility of percutaneous transcatheter mitral valve repair with the MitraClip system using conscious sedation. Catheter Cardiovasc Interv. 2010 Jun 1;75(7):1137-40. doi: 10.1002/ccd.22415. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mitral Regurgitation Severity	All patients were screened and determined eligible by Investigators who utilized transthoracic echocardiograms (TTE) to determine MR severity grades based on the American Society of Echocardiology recommendations for the determination of native valvular regurgitation. MR severity was assessed by an independent Echocardiography Core Laboratory (ECL).	At baseline
Primary	Mitral Regurgitation Severity	All patients were screened and determined eligible by Investigators who utilized transthoracic echocardiograms (TTE) to determine MR severity grades based on the American Society of Echocardiology recommendations for the determination of native valvular regurgitation. MR severity was assessed by an independent Echocardiography Core Laboratory (ECL).	At discharge or within 30 days of the procedure
Primary	Mitral Regurgitation Severity	All patients were screened and determined eligible by Investigators who utilized transthoracic echocardiograms (TTE) to determine MR severity grades based on the American Society of Echocardiology recommendations for the determination of native valvular regurgitation. MR severity was assessed by an independent Echocardiography Core Laboratory (ECL).	At 12 months
Primary	Mitral Regurgitation Severity	All patients were screened and determined eligible by Investigators who utilized transthoracic echocardiograms (TTE) to determine MR severity grades based on the American Society of Echocardiology recommendations for the determination of native valvular regurgitation. MR severity was assessed by an independent Echocardiography Core Laboratory (ECL).	At 24 months
Primary	Mitral Regurgitation Severity	All patients were screened and determined eligible by Investigators who utilized transthoracic echocardiograms (TTE) to determine MR severity grades based on the American Society of Echocardiology recommendations for the determination of native valvular regurgitation. MR severity was assessed by an independent Echocardiography Core Laboratory (ECL).	At 3 years
Primary	Mitral Regurgitation Severity	All patients were screened and determined eligible by Investigators who utilized transthoracic echocardiograms (TTE) to determine MR severity grades based on the American Society of Echocardiology recommendations for the determination of native valvular regurgitation. MR severity was assessed by an independent Echocardiography Core Laboratory (ECL).	At 4 years
Primary	Mitral Regurgitation Severity	All patients were screened and determined eligible by Investigators who utilized transthoracic echocardiograms (TTE) to determine MR severity grades based on the American Society of Echocardiology recommendations for the determination of native valvular regurgitation. MR severity was assessed by an independent Echocardiography Core Laboratory (ECL).	At 5 years
Primary	Major Adverse Events (MAE)	Defined in the Protocol as a combined clinical endpoint of death, myocardial infarction, cardiac tamponade, cardiac surgery for failed MitraClip device, single leaflet device attachment, stroke and septicemia.	Through 30 days
Primary	Major Adverse Events (MAE)	Defined in the Protocol as a combined clinical endpoint of death, myocardial infarction, cardiac tamponade, cardiac surgery for failed MitraClip device, single leaflet device attachment, stroke and septicemia.	Through 6 Months
Secondary	Procedure Time	Procedure Time, defined as the time of start of the transseptal procedure to the time the Steerable Guide Catheter (SOC) is removed, averaged 255 minutes, or just over 4 hours.; The reported Procedure Time includes the time required to collect Protocol required hemodynamic data pre- and post-implantation of the MitraClip device.	At day 0 (on the day of index procedure)
Secondary	Device Time	Device Time, defined as the time of insertion of the Steerable Guide Catheter (SGC) to the time the MitraClip Delivery Catheter is retracted into the SGC.	At day 0 (on the day of index procedure)
Secondary	Contrast Volume	Mean contrast volume utilized during the MitraClip procedure.	At day 0 (on the day of index procedure)
Secondary	Fluoroscopy Duration	Mean fluoroscopy duration during the MitraClip procedure.	At day 0 (on the day of index procedure)
Secondary	Number of Mitraclip Devices Implanted		At day 0 (on the day of index procedure)
Secondary	Intra-procedural Major Adverse Events	Significant intra-procedural Major adverse events are defined as Major Adverse Events that occurred on the day of the procedure	At day 0 (on the day of index procedure)
Secondary	Post-procedure Intensive Care Unit (ICU)/Critical Care Unit (CCU)/Post-anesthesia Care Unit (PACU) Duration		Post index procedure within 30 days
Secondary	Post-procedure Hospital Stay		Post-index procedure until hospital discharge (1 to 19 days)
Secondary	Second Intervention to Place a Second MitraClip Device		Post index procedure through 5 years
Secondary	MitraClip Device Embolizations and Single Leaflet Device Attachment	MitraClip device embolizations means the detachment from both mitral leaflets. Single Leaflet Device Attachment (SLDA) is defined as the attachment of a single leaflet to the MitraClip device.	Post index procedure through 5 years
Secondary	Mitral Valve Surgery Post-MitraClip Device Implant Procedure (Kaplan-Meier Freedom From Mitral Valve Surgery)	Freedom from mitral valve surgery required to treat mitral regurgitation and/or mitral stenosis and/or for Cardiac Surgery for Failed Clip following the MitraClip device procedure.	At baseline
Secondary	Mitral Valve Surgery Post-MitraClip Device Implant Procedure (Kaplan-Meier Freedom From Mitral Valve Surgery)	Freedom from mitral valve surgery required to treat mitral regurgitation and/or mitral stenosis and/or for Cardiac Surgery for Failed Clip following the MitraClip device procedure.	At 12 months
Secondary	Mitral Valve Surgery Post-MitraClip Device Implant Procedure (Kaplan-Meier Freedom From Mitral Valve Surgery)	Freedom from mitral valve surgery required to treat mitral regurgitation and/or mitral stenosis and/or for Cardiac Surgery for Failed Clip following the MitraClip device procedure.	At 24 months
Secondary	Mitral Valve Surgery Post-MitraClip Device Implant Procedure (Kaplan-Meier Freedom From Mitral Valve Surgery)	Freedom from mitral valve surgery required to treat mitral regurgitation and/or mitral stenosis and/or for Cardiac Surgery for Failed Clip following the MitraClip device procedure.	At 3 Years
Secondary	Mitral Valve Surgery Post-MitraClip Device Implant Procedure (Kaplan-Meier Freedom From Mitral Valve Surgery)	Freedom from mitral valve surgery required to treat mitral regurgitation and/or mitral stenosis and/or for Cardiac Surgery for Failed Clip following the MitraClip device procedure.	At 4 Years
Secondary	Mitral Valve Surgery Post-MitraClip Device Implant Procedure (Kaplan-Meier Freedom From Mitral Valve Surgery)	Freedom from mitral valve surgery required to treat mitral regurgitation and/or mitral stenosis and/or for Cardiac Surgery for Failed Clip following the MitraClip device procedure.	At 5 Years
Secondary	Death (Kaplan-Meier Freedom From Death)		Within 30 days of the procedure
Secondary	Death (Kaplan-Meier Freedom From Death)		At 12 months
Secondary	Death (Kaplan-Meier Freedom From Death)		At 24 months
Secondary	Death (Kaplan-Meier Freedom From Death)		At 3 years
Secondary	Death (Kaplan-Meier Freedom From Death)		At 4 years
Secondary	Death (Kaplan-Meier Freedom From Death)		At 5 years
Secondary	Major Vascular and Bleeding Complications	Major bleeding complications is defined as transfusion of >=2 units of blood due to bleeding related to the index procedure	Through 30 days
Secondary	Major Vascular and Bleeding Complications	Major bleeding complications is defined as transfusion of >=2 units of blood due to bleeding related to the index procedure	Through 6 Months
Secondary	Other Secondary Safety Events	Other safety event includes Endocarditis, MitraClip DeviceThrombosis, Hemolysis, Mitral Valve Injury (major).	Through 30 days
Secondary	Other Secondary Safety Events	Other safety event includes Endocarditis, MitraClip DeviceThrombosis, Hemolysis, Mitral Valve Injury (major).	Through 6 months
Secondary	Left Ventricular End Diastolic Volume	Left Ventricular end-diastolic volume (LVEDV) as determined by the core echo laboratory. Left Ventricular end-diastolic volume (LVEDV) measured using 2-dimensional echocardiography. The endocardium is traced at end-diastole (frame before mitral valve closure or maximum cavity dimension) in the 2- and 4-chamber views to calculate volumes.	Baseline
Secondary	Left Ventricular End Diastolic Volume	Left Ventricular end-diastolic volume (LVEDV) as determined by the core echo laboratory. Left Ventricular end-diastolic volume (LVEDV) measured using 2-dimensional echocardiography. The endocardium is traced at end-diastole (frame before mitral valve closure or maximum cavity dimension) in the 2- and 4-chamber views to calculate volumes.	During the hospital stay with a maximum of 3 days post index procedure (Discharge)
Secondary	Left Ventricular End Diastolic Volume	Left Ventricular end-diastolic volume (LVEDV) as determined by the core echo laboratory. Left Ventricular end-diastolic volume (LVEDV) measured using 2-dimensional echocardiography. The endocardium is traced at end-diastole (frame before mitral valve closure or maximum cavity dimension) in the 2- and 4-chamber views to calculate volumes.	12 months
Secondary	Left Ventricular End Diastolic Volume	Left Ventricular end-diastolic volume (LVEDV) as determined by the core echo laboratory. Left Ventricular end-diastolic volume (LVEDV) measured using 2-dimensional echocardiography. The endocardium is traced at end-diastole (frame before mitral valve closure or maximum cavity dimension) in the 2- and 4-chamber views to calculate volumes.	24 months
Secondary	Left Ventricular End Diastolic Volume	Left Ventricular end-diastolic volume (LVEDV) as determined by the core echo laboratory. Left Ventricular end-diastolic volume (LVEDV) measured using 2-dimensional echocardiography. The endocardium is traced at end-diastole (frame before mitral valve closure or maximum cavity dimension) in the 2- and 4-chamber views to calculate volumes.	60 months
Secondary	Left Ventricular End Systolic Volume	Left Ventricular end-systolic volume (LVESV) as determined by the core echo laboratory. Left Ventricular end-systolic volume (LVESV) measured using 2-dimensional echocardiography. The endocardium is traced at end-systole (frame prior to mitral valve opening or the minimum cavity area) in the 2- and 4-chamber views to calculate volumes.	Baseline
Secondary	Left Ventricular End Systolic Volume	Left Ventricular end-systolic volume (LVESV) as determined by the core echo laboratory. Left Ventricular end-systolic volume (LVESV) measured using 2-dimensional echocardiography. The endocardium is traced at end-systole (frame prior to mitral valve opening or the minimum cavity area) in the 2- and 4-chamber views to calculate volumes.	During the hospital stay with a maximum of 3 days post index procedure (Discharge)
Secondary	Left Ventricular End Systolic Volume	Left Ventricular end-systolic volume (LVESV) as determined by the core echo laboratory. Left Ventricular end-systolic volume (LVESV) as determined by the core echo laboratory. Left Ventricular end-systolic volume (LVESV) measured using 2-dimensional echocardiography. The endocardium is traced at end-systole (frame prior to mitral valve opening or the minimum cavity area) in the 2- and 4-chamber views to calculate volumes.	12 months
Secondary	Left Ventricular End Systolic Volume	Left Ventricular end-systolic volume (LVESV) as determined by the core echo laboratory. Left Ventricular end-systolic volume (LVESV) as determined by the core echo laboratory. Left Ventricular end-systolic volume (LVESV) measured using 2-dimensional echocardiography. The endocardium is traced at end-systole (frame prior to mitral valve opening or the minimum cavity area) in the 2- and 4-chamber views to calculate volumes.	24 months
Secondary	Left Ventricular End Systolic Volume	Left Ventricular end-systolic volume (LVESV) as determined by the core echo laboratory. Left Ventricular end-systolic volume (LVESV) as determined by the core echo laboratory. Left Ventricular end-systolic volume (LVESV) measured using 2-dimensional echocardiography. The endocardium is traced at end-systole (frame prior to mitral valve opening or the minimum cavity area) in the 2- and 4-chamber views to calculate volumes.	60 months
Secondary	Mitral Valve Area - Single Orifice	Mitral valve area measured by planimetry. Using a cineloop acquired at the mitral valve leaflet tips, the point in diastole corresponding to the maximal opening is identified. The area pre-device as well as post-device are planimetered. Post-device, the mitral valve orifice area is the sum of the area of each of the two orifices.	Baseline
Secondary	Mitral Valve Area - Single Orifice	Mitral valve area measured by planimetry. Using a cineloop acquired at the mitral valve leaflet tips, the point in diastole corresponding to the maximal opening is identified. The area pre-device as well as post-device are planimetered. Post-device, the mitral valve orifice area is the sum of the area of each of the two orifices.	During the hospital stay with a maximum of 3 days post index procedure (Discharge)
Secondary	Mitral Valve Area - Single Orifice	Mitral valve area measured by planimetry. Using a cineloop acquired at the mitral valve leaflet tips, the point in diastole corresponding to the maximal opening is identified. The area pre-device as well as post-device are planimetered. Post-device, the mitral valve orifice area is the sum of the area of each of the two orifices.	12 months
Secondary	Mitral Valve Area - Single Orifice	Mitral valve area measured by planimetry. Using a cineloop acquired at the mitral valve leaflet tips, the point in diastole corresponding to the maximal opening is identified. The area pre-device as well as post-device are planimetered. Post-device, the mitral valve orifice area is the sum of the area of each of the two orifices.	24 months
Secondary	Mitral Valve Area - Single Orifice	Mitral valve area measured by planimetry. Using a cineloop acquired at the mitral valve leaflet tips, the point in diastole corresponding to the maximal opening is identified. The area pre-device as well as post-device are planimetered. Post-device, the mitral valve orifice area is the sum of the area of each of the two orifices.	60 months
Secondary	Mitral Valve Area (MVA) by Pressure Half-Time	The pressure half time (PHT) measurement for assessing the severity of mitral stenosis is a widely accepted echocardiographic method.; The decline of the velocity of diastolic transmitral blood flow is inversely proportional to mitral valve area (MVA), and MVA is derived using the empirical formula: MVA (cm^2) = 220/PHT PHT is calculated automatically by tracing the deceleration slope of the E-wave of transmitral flow, obtained with continuous wave Doppler echocardiography.	Baseline
Secondary	Mitral Valve Area (MVA) by Pressure Half-Time	The pressure half time (PHT) measurement for assessing the severity of mitral stenosis is a widely accepted echocardiographic method.; The decline of the velocity of diastolic transmitral blood flow is inversely proportional to mitral valve area (MVA), and MVA is derived using the empirical formula: MVA (cm^2) = 220/PHT; PHT is calculated automatically by tracing the deceleration slope of the E-wave of transmitral flow, obtained with continuous wave Doppler echocardiography.	During the hospital stay with a maximum of 3 days post index procedure (Discharge)
Secondary	Mitral Valve Area (MVA) by Pressure Half-Time	The pressure half time (PHT) measurement for assessing the severity of mitral stenosis is a widely accepted echocardiographic method.; The decline of the velocity of diastolic transmitral blood flow is inversely proportional to mitral valve area (MVA), and MVA is derived using the empirical formula: MVA (cm^2) = 220/PHT PHT is calculated automatically by tracing the deceleration slope of the E-wave of transmitral flow, obtained with continuous wave Doppler echocardiography.	12 months
Secondary	Mitral Valve Area (MVA) by Pressure Half-Time	The pressure half time (PHT) measurement for assessing the severity of mitral stenosis is a widely accepted echocardiographic method.; The decline of the velocity of diastolic transmitral blood flow is inversely proportional to mitral valve area (MVA), and MVA is derived using the empirical formula: MVA (cm^2) = 220/PHT PHT is calculated automatically by tracing the deceleration slope of the E-wave of transmitral flow, obtained with continuous wave Doppler echocardiography.	24 months
Secondary	Mitral Valve Area (MVA) by Pressure Half-Time	The pressure half time (PHT) measurement for assessing the severity of mitral stenosis is a widely accepted echocardiographic method.; The decline of the velocity of diastolic transmitral blood flow is inversely proportional to mitral valve area (MVA), and MVA is derived using the empirical formula: MVA (cm^2) = 220/PHT PHT is calculated automatically by tracing the deceleration slope of the E-wave of transmitral flow, obtained with continuous wave Doppler echocardiography.	60 months
Secondary	Mitral Valve Gradient	Defined as the mean and peak pressure gradients across the mitral valve as measured by echocardiography.	Baseline
Secondary	Mitral Valve Gradient	Defined as the mean and peak pressure gradients across the mitral valve as measured by echocardiography.	During the hospital stay with a maximum of 3 days post index procedure (Discharge)
Secondary	Mitral Valve Gradient	Defined as the mean and peak pressure gradients across the mitral valve as measured by echocardiography.	12 months
Secondary	Mitral Valve Gradient	Defined as the mean and peak pressure gradients across the mitral valve as measured by echocardiography.	24 months
Secondary	Mitral Valve Gradient	Defined as the mean and peak pressure gradients across the mitral valve as measured by echocardiography.	60 months
Secondary	Cardiac Output	Cardiac output as measured by core lab echocardiography. Cardiac output is the product of forward stroke volume and heart rate.	Baseline
Secondary	Cardiac Output	Cardiac output as measured by core lab echocardiography. Cardiac output is the product of forward stroke volume and heart rate.	During the hospital stay with a maximum of 3 days post index procedure (Discharge)
Secondary	Cardiac Output	Cardiac output as measured by core lab echocardiography. Cardiac output is the product of forward stroke volume and heart rate.	12 months
Secondary	Cardiac Output	Cardiac output as measured by core lab echocardiography. Cardiac output is the product of forward stroke volume and heart rate.	24 months
Secondary	Cardiac Output	Cardiac output as measured by core lab echocardiography. Cardiac output is the product of forward stroke volume and heart rate.	60 months
Secondary	Cardiac Index	Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index is measured by core lab echocardiography.	Baseline
Secondary	Cardiac Index	Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index is measured by core lab echocardiography.	During the hospital stay with a maximum of 3 days post index procedure (Discharge)
Secondary	Cardiac Index	Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index is measured by core lab echocardiography.	12 months
Secondary	Cardiac Index	Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index is measured by core lab echocardiography.	24 months
Secondary	Cardiac Index	Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index is measured by core lab echocardiography.	60 months
Secondary	New York Heart Association (NYHA) Functional Class	Defined as assessment of NYHA functional class status at follow-up compared to baseline NYHA functional class status.; Class I: Patients with cardiac disease but without resulting limitations of physical activity.; Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.; Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain.; Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.	Baseline
Secondary	New York Heart Association (NYHA) Functional Class	Defined as assessment of NYHA functional class status at follow-up compared to baseline NYHA functional class status.; Class I: Patients with cardiac disease but without resulting limitations of physical activity.; Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.; Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain.; Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.	6 months
Secondary	New York Heart Association (NYHA) Functional Class	Defined as assessment of NYHA functional class status at follow-up compared to baseline NYHA functional class status.; Class I: Patients with cardiac disease but without resulting limitations of physical activity.; Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.; Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain.; Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.	30 days
Secondary	New York Heart Association (NYHA) Functional Class	Defined as assessment of NYHA functional class status at follow-up compared to baseline NYHA functional class status.; Class I: Patients with cardiac disease but without resulting limitations of physical activity.; Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.; Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain.; Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.	12 months
Secondary	New York Heart Association (NYHA) Functional Class	Defined as assessment of NYHA functional class status at follow-up compared to baseline NYHA functional class status.; Class I: Patients with cardiac disease but without resulting limitations of physical activity.; Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.; Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain.; Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.	18 months
Secondary	New York Heart Association (NYHA) Functional Class	Defined as assessment of NYHA functional class status at follow-up compared to baseline NYHA functional class status.; Class I: Patients with cardiac disease but without resulting limitations of physical activity.; Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.; Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain.; Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.	24 months
Secondary	New York Heart Association (NYHA) Functional Class	Defined as assessment of NYHA functional class status at follow-up compared to baseline NYHA functional class status.; Class I: Patients with cardiac disease but without resulting limitations of physical activity.; Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.; Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain.; Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.	36 months
Secondary	New York Heart Association (NYHA) Functional Class	Defined as assessment of NYHA functional class status at follow-up compared to baseline NYHA functional class status.; Class I: Patients with cardiac disease but without resulting limitations of physical activity.; Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.; Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain.; Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.	48 months
Secondary	New York Heart Association (NYHA) Functional Class	Defined as assessment of NYHA functional class status at follow-up compared to baseline NYHA functional class status.; Class I: Patients with cardiac disease but without resulting limitations of physical activity.; Class II: Patients with cardiac disease resulting in slight limitation of physical activity. Patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.; Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation dyspnea, or anginal pain.; Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.	60 months