AVJ-514 Japan Trial

MAE is a composite of death, stroke, myocardial infarction (MI), renal failure, and non-elective cardiovascular surgery for device or procedure related adverse events occurring after the femoral vein puncture for transseptal access. This outcome measure calculates the percentage of participants with MAE at 30 days (= total subjects with MAE/total subjects enrolled).

MAE is a composite of death, stroke, myocardial infarction (MI), renal failure, and non-elective cardiovascular surgery for device or procedure related adverse events occurring after the femoral vein puncture for transseptal access. This outcome measure calculates the percentage of participants with MAE at 30 days (= total subjects with MAE/total subjects enrolled).

MAE listed below will be adjudicated by the Clinical Events Committee at 30 days:

• Death
• Stroke
• Myocardial infarction
• Renal failure
• Non-elective cardiovascular surgery for device or procedure related adverse events

Defined as a mitral valve orifice of less than 1.5 cm^2 as measured by the Echocardiography Core Laboratory.

Defined as a mitral valve orifice of less than 1.5 cm^2 as measured by the Echocardiography Core Laboratory.

SLDA is defined as attachment of one mitral valve leaflet to the AVJ-514 device.

SLDA is defined as attachment of one mitral valve leaflet to the AVJ-514 device.

Defined as defect ('hole') in the septum between the left and right atria; considered clinically significant if it requires percutaneous or surgical intervention.

Defined as the rate of successful delivery and deployment of one or more AVJ-514 device with echocardiographic evidence of leaflet approximation and retrieval of the delivery catheter.

Defined as the time elapsed from the start of the transseptal procedure to the time the Steerable Guide Catheter is removed.

Defined as the time elapsed from the first of any of the following: intravascular catheter placement, anesthesia or sedation, or transesophageal echocardiogram (TEE), to the removal of the last catheter and TEE.

Defined as the time the Steerable Guide Catheter is placed in the intra-atrial septum until the time the AVJ-514 Delivery System (CDS) is retracted into the Steerable Guide Catheter.

Defined as the duration of exposure to fluoroscopy during the AVJ-514 procedure.

Length of stay in ICU/CCU/PACU is cumulative hours of Hospital stay in (PACU/CCU/ICU)

Length of hospital stay excluding rehabilitation stay = Length of hospital stay (Date of Discharge - Date of Admission)

Cumulative days of rehabilitation stay during hospitalization.

Location to which subject was discharged (home or another facility).

If subject discharged to another facility (different from baseline facility), length of stay at facility to which subject was discharged. Length of Stay (not at baseline facility) = Sum for all eligible log lines which had been entered in Electronic Data Capture (EDC) for ICU/CCU/PACU and rehabilitation.

Mitral regurgitation severity is determined based on the American Society of Echocardiography (ASE) Recommendations for Evaluation of The Severity of Native Valvular Regurgitation with Two-Dimensional and Doppler Echocardiography. MR severity grade was assessed by the core lab using the transthoracic echocardiogram (TTE) at baseline, discharge and subsequent follow-up visits. The severity of MR is determined by the amount of blood being pushed back into the left atrium when it should be circulating through the left ventricle with each heart beat. MR severity is typically classified as mild (grade 1+), moderate (grade 2+), moderate to severe (grade 3+) or severe (grade 4+).

Mitral regurgitation severity is determined based on the American Society of Echocardiography (ASE) Recommendations for Evaluation of The Severity of Native Valvular Regurgitation with Two-Dimensional and Doppler Echocardiography. MR severity grade was assessed by the core lab using the transthoracic echocardiogram (TTE) at baseline, discharge and subsequent follow-up visits. The severity of MR is determined by the amount of blood being pushed back into the left atrium when it should be circulating through the left ventricle with each heart beat. MR severity is typically classified as mild (grade 1+), moderate (grade 2+), moderate to severe (grade 3+) or severe (grade 4+).

Mitral regurgitation severity is determined based on the American Society of Echocardiography (ASE) Recommendations for Evaluation of The Severity of Native Valvular Regurgitation with Two-Dimensional and Doppler Echocardiography. MR severity grade was assessed by the core lab using the transthoracic echocardiogram (TTE) at baseline, discharge and subsequent follow-up visits. The severity of MR is determined by the amount of blood being pushed back into the left atrium when it should be circulating through the left ventricle with each heart beat. MR severity is typically classified as mild (grade 1+), moderate (grade 2+), moderate to severe (grade 3+) or severe (grade 4+).

Mitral regurgitation severity is determined based on the American Society of Echocardiography (ASE) Recommendations for Evaluation of The Severity of Native Valvular Regurgitation with Two-Dimensional and Doppler Echocardiography. MR severity grade was assessed by the core lab using the transthoracic echocardiogram (TTE) at baseline, discharge and subsequent follow-up visits. The severity of MR is determined by the amount of blood being pushed back into the left atrium when it should be circulating through the left ventricle with each heart beat. MR severity is typically classified as mild (grade 1+), moderate (grade 2+), moderate to severe (grade 3+) or severe (grade 4+).

Mitral regurgitation severity is determined based on the American Society of Echocardiography (ASE) Recommendations for Evaluation of The Severity of Native Valvular Regurgitation with Two-Dimensional and Doppler Echocardiography. MR severity grade was assessed by the core lab using the transthoracic echocardiogram (TTE) at baseline, discharge and subsequent follow-up visits. The severity of MR is determined by the amount of blood being pushed back into the left atrium when it should be circulating through the left ventricle with each heart beat. MR severity is typically classified as mild (grade 1+), moderate (grade 2+), moderate to severe (grade 3+) or severe (grade 4+).

Mitral regurgitation severity is determined based on the American Society of Echocardiography (ASE) Recommendations for Evaluation of The Severity of Native Valvular Regurgitation with Two-Dimensional and Doppler Echocardiography. MR severity grade was assessed by the core lab using the transthoracic echocardiogram (TTE) at baseline, discharge and subsequent follow-up visits. The severity of MR is determined by the amount of blood being pushed back into the left atrium when it should be circulating through the left ventricle with each heart beat. MR severity is typically classified as mild (grade 1+), moderate (grade 2+), moderate to severe (grade 3+) or severe (grade 4+).

Mitral regurgitation severity is determined based on the American Society of Echocardiography (ASE) Recommendations for Evaluation of The Severity of Native Valvular Regurgitation with Two-Dimensional and Doppler Echocardiography. MR severity grade was assessed by the core lab using the transthoracic echocardiogram (TTE) at baseline, discharge and subsequent follow-up visits. The severity of MR is determined by the amount of blood being pushed back into the left atrium when it should be circulating through the left ventricle with each heart beat. MR severity is typically classified as mild (grade 1+), moderate (grade 2+), moderate to severe (grade 3+) or severe (grade 4+).

Mitral regurgitation severity is determined based on the American Society of Echocardiography (ASE) Recommendations for Evaluation of The Severity of Native Valvular Regurgitation with Two-Dimensional and Doppler Echocardiography. MR severity grade was assessed by the core lab using the transthoracic echocardiogram (TTE) at baseline, discharge and subsequent follow-up visits. The severity of MR is determined by the amount of blood being pushed back into the left atrium when it should be circulating through the left ventricle with each heart beat. MR severity is typically classified as mild (grade 1+), moderate (grade 2+), moderate to severe (grade 3+) or severe (grade 4+).

Regurgitant volume as determined by the Echocardiographic Core Laboratory (ECL). In the presence of regurgitation of one valve, without any intracardiac shunt, the flow through the affected valve is larger than through other competent valves. The difference between the two represents the regurgitant volume.

Regurgitant volume as determined by the Echocardiographic Core Laboratory (ECL). In the presence of regurgitation of one valve, without any intracardiac shunt, the flow through the affected valve is larger than through other competent valves. The difference between the two represents the regurgitant volume.

Regurgitant volume as determined by the Echocardiographic Core Laboratory (ECL). In the presence of regurgitation of one valve, without any intracardiac shunt, the flow through the affected valve is larger than through other competent valves. The difference between the two represents the regurgitant volume.

Regurgitant volume as determined by the Echocardiographic Core Laboratory (ECL). In the presence of regurgitation of one valve, without any intracardiac shunt, the flow through the affected valve is larger than through other competent valves. The difference between the two represents the regurgitant volume.

Regurgitant volume as determined by the Echocardiographic Core Laboratory (ECL). In the presence of regurgitation of one valve, without any intracardiac shunt, the flow through the affected valve is larger than through other competent valves. The difference between the two represents the regurgitant volume.

Regurgitant volume as determined by the site. In the presence of regurgitation of one valve, without any intracardiac shunt, the flow through the affected valve is larger than through other competent valves. The difference between the two represents the regurgitant volume.

Regurgitant volume as determined by the site. In the presence of regurgitation of one valve, without any intracardiac shunt, the flow through the affected valve is larger than through other competent valves. The difference between the two represents the regurgitant volume.

Regurgitant volume as determined by the site. In the presence of regurgitation of one valve, without any intracardiac shunt, the flow through the affected valve is larger than through other competent valves. The difference between the two represents the regurgitant volume.

Regurgitant fraction as determined by the Echocardiographic Core Laboratory (ECL). Regurgitant fraction is defined as the regurgitant volume divided by the forward stroke volume through the regurgitant valve.

Regurgitant fraction as determined by the Echocardiographic Core Laboratory (ECL). Regurgitant fraction is defined as the regurgitant volume divided by the forward stroke volume through the regurgitant valve.

Regurgitant fraction as determined by the Echocardiographic Core Laboratory (ECL). Regurgitant fraction is defined as the regurgitant volume divided by the forward stroke volume through the regurgitant valve.

Regurgitant fraction as determined by the Echocardiographic Core Laboratory (ECL). Regurgitant fraction is defined as the regurgitant volume divided by the forward stroke volume through the regurgitant valve.

Regurgitant fraction as determined by the Echocardiographic Core Laboratory (ECL). Regurgitant fraction is defined as the regurgitant volume divided by the forward stroke volume through the regurgitant valve.

Left Ventricular End Diastolic Volume (LVEDV) as measured by the Echocardiography Core Laboratory (ECL). 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.

Left Ventricular End Diastolic Volume (LVEDV) as measured by the Echocardiography Core Laboratory (ECL). 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.

Left Ventricular End Diastolic Volume (LVEDV) as measured by the Echocardiography Core Laboratory (ECL). 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.

Left Ventricular End Diastolic Volume (LVEDV) as measured by the Echocardiography Core Laboratory (ECL). Left Ventricular enddiastolic 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.

Left Ventricular End Diastolic Volume (LVEDV) as measured by the Echocardiography Core Laboratory (ECL). 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.

Left Ventricular End Diastolic Volume (LVEDV) as measured by the site. Left Ventricular enddiastolic 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.

Left Ventricular End Diastolic Volume (LVEDV) as measured by the site. Left Ventricular enddiastolic 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.

Left Ventricular End Diastolic Volume (LVEDV) as measured by the site. Left Ventricular enddiastolic 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.

Left Ventricular End Systolic Volume (LVESV) as measured by the Echocardiography Core Laboratory (ECL). 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.

Left Ventricular End Systolic Volume (LVESV) as measured by the Echocardiography Core Laboratory (ECL). 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.

Left Ventricular End Systolic Volume (LVESV) as measured by the Echocardiography Core Laboratory (ECL). 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.

Left Ventricular End Systolic Volume (LVESV) as measured by the Echocardiography Core Laboratory (ECL). 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.

Left Ventricular End Systolic Volume (LVESV) as measured by the Echocardiography Core Laboratory (ECL). 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.

Left Ventricular End Systolic Volume (LVESV) as measured by the site. 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.

Left Ventricular End Systolic Volume (LVESV) as measured by the site. 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.

Left Ventricular End Systolic Volume (LVESV) as measured by the site. 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.

Left Ventricular End Diastolic Dimension (LVEDD) as measured by the Echocardiography Core Laboratory (ECL).

Left Ventricular End Diastolic Dimension (LVEDD) as measured by the Echocardiography Core Laboratory (ECL).

Left Ventricular End Diastolic Dimension (LVEDD) as measured by the Echocardiography Core Laboratory (ECL).

Left Ventricular End Diastolic Dimension (LVEDD) as measured by the Echocardiography Core Laboratory (ECL).

Left Ventricular End Diastolic Dimension (LVEDD) as measured by the Echocardiography Core Laboratory (ECL).

Left Ventricular End Diastolic Dimension (LVEDD) as measured by the site.

Left Ventricular End Diastolic Dimension (LVEDD) as measured by the site.

Left Ventricular End Diastolic Dimension (LVEDD) as measured by the site

Left Ventricular End Systolic Dimension (LVESD) as measured by the ECL.

Left Ventricular End Systolic Dimension (LVESD) as measured by the ECL.

Left Ventricular End Systolic Dimension (LVESD) as measured by the ECL.

Left Ventricular End Systolic Dimension (LVESD) as measured by the ECL.

Left Ventricular End Systolic Dimension (LVESD) as measured by the ECL.

Left Ventricular End Systolic Dimension (LVESD) as measured by the site.

Left Ventricular End Systolic Dimension (LVESD) as measured by the site.

Left Ventricular End Systolic Dimension (LVESD) as measured by the site.

Left Ventricular Ejection Fraction (LVEF) as measured by the ECL.

Left Ventricular Ejection Fraction (LVEF) as measured by the ECL.

Left Ventricular Ejection Fraction (LVEF) as measured by the ECL.

Left Ventricular Ejection Fraction (LVEF) as measured by the ECL.

Left Ventricular Ejection Fraction (LVEF) as measured by the ECL.

Left Ventricular Ejection Fraction (LVEF) as measured by the site.

Left Ventricular Ejection Fraction (LVEF) as measured by the site.

Pulmonary Artery Systolic Pressure (PASP) is presented in place of Right Ventricular Systolic Pressure (RVSP). PASP is equal to RVSP in the absence of pulmonic stenosis.

Pulmonary Artery Systolic Pressure (PASP) is presented in place of Right Ventricular Systolic Pressure (RVSP). PASP is equal to RVSP in the absence of pulmonic stenosis.

Pulmonary Artery Systolic Pressure (PASP) is presented in place of Right Ventricular Systolic Pressure (RVSP). PASP is equal to RVSP in the absence of pulmonic stenosis.

Pulmonary Artery Systolic Pressure (PASP) is presented in place of Right Ventricular Systolic Pressure (RVSP). PASP is equal to RVSP in the absence of pulmonic stenosis.

Pulmonary Artery Systolic Pressure (PASP) is presented in place of Right Ventricular Systolic Pressure (RVSP). PASP is equal to RVSP in the absence of pulmonic stenosis.

Pulmonary Artery Systolic Pressure (PASP) is presented in place of Right Ventricular Systolic Pressure (RVSP). PASP is equal to RVSP in the absence of pulmonic stenosis.

Pulmonary Artery Systolic Pressure (PASP) is presented in place of Right Ventricular Systolic Pressure (RVSP). PASP is equal to RVSP in the absence of pulmonic stenosis.

Pulmonary Artery Systolic Pressure (PASP) is presented in place of Right Ventricular Systolic Pressure (RVSP). PASP is equal to RVSP in the absence of pulmonic stenosis.

Pulmonary Artery Systolic Pressure (PASP) is presented in place of Right Ventricular Systolic Pressure (RVSP). PASP is equal to RVSP in the absence of pulmonic stenosis.

It is the orifice area of the mitral valve.

It is the orifice area of the mitral valve.

It is the orifice area of the mitral valve.

It is the orifice area of the mitral valve.

It is the orifice area of the mitral valve.

It is the orifice area of the Mitral Valve

It is the orifice area of the Mitral Valve.

It is the orifice area of the Mitral Valve.

Defined as the mean and peak pressure gradients across the mitral valve as measured by the Echocardiography Core Laboratory (ECL).

Defined as the mean and peak pressure gradients across the mitral valve as measured by the Echocardiography Core Laboratory (ECL).

Defined as the mean and peak pressure gradients across the mitral valve as measured by the Echocardiography Core Laboratory (ECL).

Defined as the mean and peak pressure gradients across the mitral valve as measured by the Echocardiography Core Laboratory (ECL).

Defined as the mean and peak pressure gradients across the mitral valve as measured by the Echocardiography Core Laboratory (ECL).

Defined as the mean and peak pressure gradients across the mitral valve as measured by the site.

Defined as the mean and peak pressure gradients across the mitral valve as measured by the site.

Defined as the mean and peak pressure gradients across the mitral valve as measured by the site.

Systolic Anterior Motion (SAM) of the mitral valve is measured by the ECL.

Systolic Anterior Motion (SAM) of the mitral valve is measured by the ECL

Systolic Anterior Motion (SAM) of the mitral valve is measured by the ECL

Systolic Anterior Motion (SAM) of the mitral valve is measured by the ECL

Systolic Anterior Motion (SAM) of the mitral valve is measured by the ECL

Systolic Anterior Motion (SAM) of the mitral valve is measured by the site.

Systolic Anterior Motion (SAM) of the mitral valve is measured by the site.

Systolic Anterior Motion (SAM) of the mitral valve is measured by the site.

Defined as the volume of blood pumped from the left ventricle per heartbeat.

Defined as the volume of blood pumped from the left ventricle per heartbeat.

Defined as the volume of blood pumped from the left ventricle per heartbeat.

Defined as the volume of blood pumped from the left ventricle per heartbeat.

Defined as the volume of blood pumped from the left ventricle per heartbeat.

Cardiac output as measured by the Echocardiographic Core Laboratory (ECL). Cardiac output is the product of forward stroke volume and heart rate.

Cardiac output as measured by the Echocardiographic Core Laboratory (ECL). Cardiac output is the product of forward stroke volume and heart rate.

Cardiac output as measured by the Echocardiographic Core Laboratory (ECL). Cardiac output is the product of forward stroke volume and heart rate.

Cardiac output as measured by the Echocardiographic Core Laboratory (ECL). Cardiac output is the product of forward stroke volume and heart rate.

Cardiac output as measured by the Echocardiographic Core Laboratory (ECL). Cardiac output is the product of forward stroke volume and heart rate.

Cardiac output as measured by the site. Cardiac output is the product of forward stroke volume and heart rate.

Cardiac output as measured by the site. Cardiac output is the product of forward stroke volume and heart rate.

Cardiac output as measured by the site. Cardiac output is the product of forward stroke volume and heart rate.

Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index was measured by the Echocardiographic Core Laboratory (ECL).

Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index was measured by the Echocardiographic Core Laboratory (ECL).

Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index was measured by the Echocardiographic Core Laboratory (ECL).

Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index was measured by the Echocardiographic Core Laboratory (ECL).

Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index was measured by the Echocardiographic Core Laboratory (ECL).

Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index was measured by the site.

Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index was measured by the site.

Cardiac index is defined as cardiac output divided by body surface area. Cardiac Index was measured by the site.

MAE is a composite of death, stroke, MI, renal failure, and non-elective cardiovascular surgery for device or procedure related adverse events occurring after the femoral vein puncture for transseptal access. No of Participants with the MAEs at 12 months. One death and One Renal Failure was reported in two subjects.

MAE is a composite of death, stroke, MI, renal failure, and non-elective cardiovascular surgery for device or procedure related adverse events occurring after the femoral vein puncture for transseptal access.

MAE is a composite of death, stroke, MI, renal failure, and non-elective cardiovascular surgery for device or procedure related adverse events occurring after the femoral vein puncture for transseptal access.

MAE is a composite of death, stroke, MI, renal failure, and non-elective cardiovascular surgery for device or procedure related adverse events occurring after the femoral vein puncture for transseptal access.

MAE is a composite of death, stroke, MI, renal failure, and non-elective cardiovascular surgery for device or procedure related adverse events occurring after the femoral vein puncture for transseptal access.

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. Patients 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.

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. Patients 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.

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. Patients 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.

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. Patients 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.

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. Patients 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.

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. Patients 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.

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. Patients 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.

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. Patients 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.

KCCQ is a self-administered questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. This questionnaire is a reliable and responsive health status measure used in various cardiovascular research studies. A minimum mean group difference in KCCQ score of ≥5 is considered to be clinically significant. Each question responses are coded sequentially (1, 2, 3, 4, 5 and 6) from worst to best status. Scores are generated by adding points for all questions and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status.

KCCQ is a self-administered questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. This questionnaire is a reliable and responsive health status measure used in various cardiovascular research studies. A minimum mean group difference in KCCQ score of ≥5 is considered to be clinically significant. Each question responses are coded sequentially (1, 2, 3, 4, 5 and 6) from worst to best status. Scores are generated by adding points for all questions and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status.

KCCQ is a self-administered questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. This questionnaire is a reliable and responsive health status measure used in various cardiovascular research studies. A minimum mean group difference in KCCQ score of ≥5 is considered to be clinically significant. Each question responses are coded sequentially (1, 2, 3, 4, 5 and 6) from worst to best status. Scores are generated by adding points for all questions and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status.

KCCQ is a self-administered questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. This questionnaire is a reliable and responsive health status measure used in various cardiovascular research studies. A minimum mean group difference in KCCQ score of ≥5 is considered to be clinically significant. Each question responses are coded sequentially (1, 2, 3, 4, 5 and 6) from worst to best status. Scores are generated by adding points for all questions and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status.

KCCQ is a self-administered questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. This questionnaire is a reliable and responsive health status measure used in various cardiovascular research studies. A minimum mean group difference in KCCQ score of ≥5 is considered to be clinically significant. Each question responses are coded sequentially (1, 2, 3, 4, 5 and 6) from worst to best status. Scores are generated by adding points for all questions and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status.

KCCQ is a self-administered questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. This questionnaire is a reliable and responsive health status measure used in various cardiovascular research studies. A minimum mean group difference in KCCQ score of ≥5 is considered to be clinically significant. Each question responses are coded sequentially (1, 2, 3, 4, 5 and 6) from worst to best status. Scores are generated by adding points for all questions and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status.

The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.

The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.

The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.

The Short Form(SF) (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

The physical \& mental functions were assessed by the Physical Component Summary (PCS) score \& Mental Component Summary (MCS) score. Normal PCS and MCS scores vary depending on the demographics of the population studied. The PCS\&MCS norms for 65-75 year old are 44 \& 52, respectively while the norms for congestive heart failure (CHF) population are 31 \& 46, respectively.

The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

The physical \& mental functions were assessed by the Physical Component Summary (PCS) score \& Mental Component Summary (MCS) score. Normal PCS and MCS scores vary depending on the demographics of the population studied. The PCS\&MCS norms for 65-75 year old are 44 \& 52, respectively while the norms for CHF population are 31 \& 46, respectively.

The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

The 6MWT is a practical simple test that requires a 100-ft hallway but no exercise equipment or advanced training for technicians. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. It does not provide specific information on the function of each of the different organs and systems involved in exercise or the mechanism of exercise limitation, as is possible with maximal cardiopulmonary exercise testing. The self-paced 6MWT assesses the submaximal level of functional capacity.

The 6MWT is a practical simple test that requires a 100-ft hallway but no exercise equipment or advanced training for technicians. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. It does not provide specific information on the function of each of the different organs and systems involved in exercise or the mechanism of exercise limitation, as is possible with maximal cardiopulmonary exercise testing. The self-paced 6MWT assesses the submaximal level of functional capacity.

The 6MWT is a practical simple test that requires a 100-ft hallway but no exercise equipment or advanced training for technicians. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. It does not provide specific information on the function of each of the different organs and systems involved in exercise or the mechanism of exercise limitation, as is possible with maximal cardiopulmonary exercise testing. The self-paced 6MWT assesses the submaximal level of functional capacity.

The 6MWT is a practical simple test that requires a 100-ft hallway but no exercise equipment or advanced training for technicians. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. It does not provide specific information on the function of each of the different organs and systems involved in exercise or the mechanism of exercise limitation, as is possible with maximal cardiopulmonary exercise testing. The self-paced 6MWT assesses the submaximal level of functional capacity.

The 6MWT is a practical simple test that requires a 100-ft hallway but no exercise equipment or advanced training for technicians. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. It does not provide specific information on the function of each of the different organs and systems involved in exercise or the mechanism of exercise limitation, as is possible with maximal cardiopulmonary exercise testing. The self-paced 6MWT assesses the submaximal level of functional capacity.

The 6MWT is a practical simple test that requires a 100-ft hallway but no exercise equipment or advanced training for technicians. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. It does not provide specific information on the function of each of the different organs and systems involved in exercise or the mechanism of exercise limitation, as is possible with maximal cardiopulmonary exercise testing. The self-paced 6MWT assesses the submaximal level of functional capacity.

The 6MWT is a practical simple test that requires a 100-ft hallway but no exercise equipment or advanced training for technicians. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. It does not provide specific information on the function of each of the different organs and systems involved in exercise or the mechanism of exercise limitation, as is possible with maximal cardiopulmonary exercise testing. The self-paced 6MWT assesses the submaximal level of functional capacity.

Surgical access to repair or replace the mitral valve. Measured per occurrence.

Surgical access to repair or replace the mitral valve. Measured per occurrence.

Number of participants with any additional AVJ-514 procedure after the index procedure. Measured per occurrence.

Number of participants with any additional AVJ-514 procedure after the index procedure. Measured per occurrence.

Defined as a mitral valve orifice of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory.

Defined as a mitral valve orifice of less than 1.5 cm2 as measured by the site.

Defined as a mitral valve orifice of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory.

Defined as a mitral valve orifice of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory.

Defined as a mitral valve orifice of less than 1.5 cm2 as measured by the Echocardiography Core Laboratory.

Defect ('hole') in the septum between the left and right atria; considered clinically significant if it requires percutaneous or surgical intervention (repair of ASD completed at the time of surgery for other reasons, but not as the primary reason for surgery, is not counted as ASD.)

Defect ('hole') in the septum between the left and right atria; considered clinically significant if it requires percutaneous or surgical intervention (repair of ASD completed at the time of surgery for other reasons, but not as the primary reason for surgery, is not counted as ASD.)

Defect ('hole') in the septum between the left and right atria; considered clinically significant if it requires percutaneous or surgical intervention (repair of ASD completed at the time of surgery for other reasons, but not as the primary reason for surgery, is not counted as ASD.)

Defect ('hole') in the septum between the left and right atria; considered clinically significant if it requires percutaneous or surgical intervention (repair of ASD completed at the time of surgery for other reasons, but not as the primary reason for surgery, is not counted as ASD.)

Defect ('hole') in the septum between the left and right atria; considered clinically significant if it requires percutaneous or surgical intervention (repair of ASD completed at the time of surgery for other reasons, but not as the primary reason for surgery, is not counted as ASD.)

Major bleeding is defined as bleeding ≥ Type 3 based on a modified Bleeding Academic Research Consortium (BARC) definition.

Type 3:

• Type 3a (i) Overt bleeding plus hemoglobin drop of 3 to <5 g/dL* (provided hemoglobin drop is related to bleed) (ii) Any transfusion with overt bleeding
• Type 3b (i) Overt bleeding plus hemoglobin drop ≥5 g/dL* (provided hemoglobin drop is related to bleed) (ii) Cardiac tamponade (iii) Bleeding requiring surgical intervention for control (excluding dental/nasal/skin/hemorrhoid) (iv) Bleeding requiring intravenous vasoactive agents
• Type 3c (i) Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation, does include intraspinal) (ii) Subcategories confirmed by autopsy or imaging or lumbar puncture (iii) Intraocular bleed compromising vision

Major bleeding is defined as bleeding ≥ Type 3 based on a modified Bleeding Academic Research Consortium (BARC) definition.

Type 3:

• Type 3a (i) Overt bleeding plus hemoglobin drop of 3 to <5 g/dL* (provided hemoglobin drop is related to bleed) (ii) Any transfusion with overt bleeding
• Type 3b (i) Overt bleeding plus hemoglobin drop ≥5 g/dL* (provided hemoglobin drop is related to bleed) (ii) Cardiac tamponade (iii) Bleeding requiring surgical intervention for control (excluding dental/nasal/skin/hemorrhoid) (iv) Bleeding requiring intravenous vasoactive agents
• Type 3c (i) Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation, does include intraspinal) (ii) Subcategories confirmed by autopsy or imaging or lumbar puncture (iii) Intraocular bleed compromising vision

Number of participants with any change in type of medication from baseline to follow-up. Measured in overall counts.

Number of participants with any change in type of medication from baseline to follow-up. Measured in overall counts.

Number of participants with any change in type of medication from baseline to follow-up. Measured in overall counts.

Number of participants with any change in type of medication from baseline to follow-up. Measured in overall counts.

Device embolization is defined as detachment of the deployed AVJ-514 device from both mitral leaflets.

Device embolization is defined as detachment of the deployed AVJ-514 device from both mitral leaflets.

Regurgitant fraction as determined by the site. Regurgitant fraction is defined as the regurgitant volume divided by the forward stroke volume through the regurgitant valve.

Regurgitant fraction as determined by the site. Regurgitant fraction is defined as the regurgitant volume divided by the forward stroke volume through the regurgitant valve.

Regurgitant fraction as determined by the site. Regurgitant fraction is defined as the regurgitant volume divided by the forward stroke volume through the regurgitant valve.