Evolut PRO China Clinical Study

All-cause mortality at 30 days

Percentage (%) of Subjects with evaluable echocardiograms with moderate or severe aortic regurgitation by transthoracic echocardiography (TTE)

Incidence of an VARC II combined composite includes the following components:

• All-cause mortality
• All stroke (disabling and non-disabling)
• Life-threatening bleeding
• Acute kidney injury: stage 2 or 3 (including renal replacement therapy)
• Coronary artery obstruction requiring intervention
• Major vascular complication
• Valve-related dysfunction requiring repeat procedure (BAV, TAVI, or SAVR)

Event rate of the individual components listed in the outcome

New permanent pacemaker rate

Device success rate:

• Percentage of participants with absence of procedural mortality, AND
• Percentage of participants with correct positioning of a single prosthetic heart valve into the proper anatomical location, AND
• Percentage of participants with intended performance of the prosthetic heart valve, defined as the absence of patient-prosthesis-mismatch and mean aortic valve gradient less than 20 mmHg (or peak velocity <3m/sec), AND absence of moderate or severe prosthetic valve regurgitation

Mean aortic gradient

Effective orifice area

Degree of aortic regurgitation (transvalvular, paravalvular, total)

Rate of the following TAVI-related complications:

• change to surgery
• need for cardiopulmonary mechanical assistance
• coronary occlusion or obstruction
• annular rupture or dissection
• ventricular perforation
• mitral valve damage
• prosthetic valve displacement, migration, or embolism
• acute kidney injury (up to 7 days post procedure)

Percentage of participants with all-cause mortality

Percentage of participants with all-cause mortality

Incidence of stroke (disabling and non-disabling)

Incidence of stroke (disabling and non-disabling)

Incidence of MI

Incidence of MI

Incidence of MI

Incidence of life-threatening bleeding:

• Fatal bleeding (BARC type 5) OR
• Bleeding in a critical organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome (BARC type 3b and 3c) OR
• Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery (BARC type 3b) OR
• Overt source of bleeding with drop in hemoglobin ≥5 g/dL or whole blood or packed red blood cells (RBCs) transfusion ≥4 units* (BARC type 3b)

Incidence of life-threatening bleeding:

• Fatal bleeding (BARC type 5) OR
• Bleeding in a critical organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome (BARC type 3b and 3c) OR
• Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery (BARC type 3b) OR
• Overt source of bleeding with drop in hemoglobin ≥5 g/dL or whole blood or packed red blood cells (RBCs) transfusion ≥4 units* (BARC type 3b)

Incidence of life-threatening bleeding:

• Fatal bleeding (BARC type 5) OR
• Bleeding in a critical organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome (BARC type 3b and 3c) OR
• Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery (BARC type 3b) OR
• Overt source of bleeding with drop in hemoglobin ≥5 g/dL or whole blood or packed red blood cells (RBCs) transfusion ≥4 units* (BARC type 3b)

Incidence of either LBBB or RBBB

Incidence of prosthetic valve endocarditis:

Any one of the following:

• Fulfillment of the following Duke criteria for definite endocarditis

• Histologic and/or microbiologic evidence of infection at surgery or autopsy, or
• 2 major criteria, or
• 1 major criteria and 3 minor criteria, or
• 5 minor criteria
• Evidence of abscess, paravalvular leak, pus, or vegetation confirmed as secondary to infection by histological or bacteriological studies during a re-operation
• Findings of abscess, pus, or vegetation involving the CoreValve™ Evolut™ PRO at autopsy

Incidence of prosthetic valve endocarditis:

Any one of the following:

• Fulfillment of the following Duke criteria for definite endocarditis

• Histologic and/or microbiologic evidence of infection at surgery or autopsy, or
• 2 major criteria, or
• 1 major criteria and 3 minor criteria, or
• 5 minor criteria
• Evidence of abscess, paravalvular leak, pus, or vegetation confirmed as secondary to infection by histological or bacteriological studies during a re-operation
• Findings of abscess, pus, or vegetation involving the CoreValve™ Evolut™ PRO at autopsy

Incidence of prosthetic valve endocarditis:

Any one of the following:

• Fulfillment of the following Duke criteria for definite endocarditis

• Histologic and/or microbiologic evidence of infection at surgery or autopsy, or
• 2 major criteria, or
• 1 major criteria and 3 minor criteria, or
• 5 minor criteria
• Evidence of abscess, paravalvular leak, pus, or vegetation confirmed as secondary to infection by histological or bacteriological studies during a re-operation
• Findings of abscess, pus, or vegetation involving the CoreValve™ Evolut™ PRO at autopsy

Incidence of Prosthetic valve thrombosis:

Any thrombus attached to or near an implanted valve that occludes part of the blood flow path, interferes with valve function, or is sufficiently large to warrant treatment.

*Valve-associated thrombus identified at autopsy in a patient whose cause of death was not valve related should not be reported as valve thrombosis.

Incidence of Prosthetic valve thrombosis:

Any thrombus attached to or near an implanted valve that occludes part of the blood flow path, interferes with valve function, or is sufficiently large to warrant treatment.

*Valve-associated thrombus identified at autopsy in a patient whose cause of death was not valve related should not be reported as valve thrombosis.

Incidence of Prosthetic valve thrombosis:

Any thrombus attached to or near an implanted valve that occludes part of the blood flow path, interferes with valve function, or is sufficiently large to warrant treatment.

*Valve-associated thrombus identified at autopsy in a patient whose cause of death was not valve related should not be reported as valve thrombosis.

Incidence of valve-related dysfunction defined as moderate or severe prosthetic valve stenosis, or moderate or severe prosthetic regurgitation (per VARC II)

Incidence of Valve-related dysfunction requiring repeat procedure

Incidence of Valve-related dysfunction requiring repeat procedure

Incidence of Valve-related dysfunction requiring repeat procedure

Mean aortic gradient

Effective orifice area

Degree of aortic regurgitation (transvalvular, paravalvular, total)

New York Heart Association (NYHA) functional classification system is a tool that classifies patients with heart failure into one of four classes according to their degree of systems at rest and with activity. Below are the four classes and the associated patient symptoms (i.e., Class I has no limitations of physical activity vs. Class IV is most symptomatic and patient has symptoms of heart failure at rest).

Class I: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath.

Class II: Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain.

Class III: Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain.

Class IV: Symptoms of heart failure at rest. Any physical activity causes further discomfort.

New York Heart Association (NYHA) functional classification system is a tool that classifies patients with heart failure into one of four classes according to their degree of systems at rest and with activity. Below are the four classes and the associated patient symptoms (i.e., Class I has no limitations of physical activity vs. Class IV is most symptomatic and patient has symptoms of heart failure at rest).

Class I: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath.

Class II: Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain.

Class III: Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain.

Class IV: Symptoms of heart failure at rest. Any physical activity causes further discomfort.

New York Heart Association (NYHA) functional classification system is a tool that classifies patients with heart failure into one of four classes according to their degree of systems at rest and with activity. Below are the four classes and the associated patient symptoms (i.e., Class I has no limitations of physical activity vs. Class IV is most symptomatic and patient has symptoms of heart failure at rest).

Class I: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath.

Class II: Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain.

Class III: Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain.

Class IV: Symptoms of heart failure at rest. Any physical activity causes further discomfort.

EuroQol Group developed this Quality of Life (QOL) questionnaire referred to as EQ-5D that includes a descriptive system comprising five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions.

The answers given to ED-5D can be converted into EQ-5D index and utility scores anchored at 0 for death and 1 for perfect health.

The EQ-5D Index Score is calculated for each study participant and the descriptive statistical summary of the EQ-5D score for the study population is provided.

The EQ-5D Visual Analog Scale (VAS) Score is a scale numbered 0 to 100 (0 is the worse health the patient can imagine and 100 is the best health the patient can imagine).

EuroQol Group developed this Quality of Life (QOL) questionnaire referred to as EQ-5D that includes a descriptive system comprising five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions.

The answers given to ED-5D can be converted into EQ-5D index and utility scores anchored at 0 for death and 1 for perfect health.

The EQ-5D Index Score is calculated for each study participant and the descriptive statistical summary of the EQ-5D score for the study population is provided.

The EQ-5D Visual Analog Scale (VAS) Score is a scale numbered 0 to 100 (0 is the worse health the patient can imagine and 100 is the best health the patient can imagine).

Percentage of participants with all-cause mortality

Incidence of stroke (disabling and non-disabling)

Incidence of MI

Incidence of life-threatening bleeding:

• Fatal bleeding (BARC type 5) OR
• Bleeding in a critical organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome (BARC type 3b and 3c) OR
• Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery (BARC type 3b) OR
• Overt source of bleeding with drop in hemoglobin ≥5 g/dL or whole blood or packed red blood cells (RBCs) transfusion ≥4 units* (BARC type 3b)

Incidence of prosthetic valve endocarditis:

Any one of the following:

• Fulfillment of the following Duke criteria for definite endocarditis

• Histologic and/or microbiologic evidence of infection at surgery or autopsy, or
• 2 major criteria, or
• 1 major criteria and 3 minor criteria, or
• 5 minor criteria
• Evidence of abscess, paravalvular leak, pus, or vegetation confirmed as secondary to infection by histological or bacteriological studies during a re-operation
• Findings of abscess, pus, or vegetation involving the CoreValve™ Evolut™ PRO at autopsy

Incidence of Prosthetic valve thrombosis:

Any thrombus attached to or near an implanted valve that occludes part of the blood flow path, interferes with valve function, or is sufficiently large to warrant treatment.

*Valve-associated thrombus identified at autopsy in a patient whose cause of death was not valve related should not be reported as valve thrombosis.

Incidence of valve-related dysfunction defined as moderate or severe prosthetic valve stenosis, or moderate or severe prosthetic regurgitation (per VARC II)

Incidence of Valve-related dysfunction requiring repeat procedure

Mean aortic gradient

Effective orifice area

Degree of aortic regurgitation (transvalvular, paravalvular, total)

New York Heart Association (NYHA) functional classification system is a tool that classifies patients with heart failure into one of four classes according to their degree of systems at rest and with activity. Below are the four classes and the associated patient symptoms (i.e., Class I has no limitations of physical activity vs. Class IV is most symptomatic and patient has symptoms of heart failure at rest).

Class I: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath.

Class II: Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain.

Class III: Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain.

Class IV: Symptoms of heart failure at rest. Any physical activity causes further discomfort.