Medtronic 310C27 Instructions for Use

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Mosaic™

Bioprosthesis

305, 310

Instructions for Use

Caution: Federal law (USA) restricts this device to sale by or on the order of a physician.

Trademarks may be registered and are the property of their respective owners.

Explanation of symbols on package labeling

Refer to the device labeling to see which symbols apply to this product.

Nonpyrogenic

Sterile LC: Device has been sterilized using liquid chemical sterilants according to EN/ISO 14160.

Size

Do not reuse

Do not resterilize

Use-by date

Quantity

For US audiences only

Temperature limitation

Serial number

Catalog number

Manufacturer

Date of manufacture

Authorized representative in the European Community

MR Conditional

Manufactured in

Do not use if indicator turns black

Model

Figure 1. Opening the valve container

Figure 2. Removing the retainer from the jar

Figure 3. Verifying the serial number and removing the retainer cap

Figure 4. Inserting the valve handle into the Cinch™ holder

Figure 5. Removing the valve from the retainer and rinsing

Figure 6. Ratcheting the Cinch holder (aortic)

Figure 7. Removing the Cinch holder (aortic)

Figure 8. Nondeflected Cinch holder (aortic)

1. Visible

Figure 9. Fully deflected Cinch holder (aortic)

Figure 10. Ratcheting the Cinch holder (mitral)

Figure 11. Removing the Cinch holder (mitral)

Figure 12. Nondeflected Cinch holder (mitral)

Figure 13. Fully deflected Cinch holder (mitral)

Figure 14. Right fibrous trigone (mitral)

Bioprosthesis

1. Device description

The Mosaic™ bioprostheses, Model 305 (aortic) and Model 310 (mitral) consist of porcine aortic valves that have been preserved in buffered 0.2% glutaraldehyde and fitted and secured to cloth-covered flexible stents. The fixation and preservation with buffered glutaraldehyde solutions minimize the immunogenic potential on the porcine tissue. The cross-linking process of the porcine aortic root tissue is accomplished by applying hydrostatic pressure to the root while maintaining a zero-pressure differential across the valve leaflets.

The tissue is treated with an alpha amino oleic acid antimineralization process, AOA™, which has been shown to mitigate porcine leaflet calcification in animal studies.

The Mosaic bioprostheses are designed for both the aortic position (Model 305) and the mitral position (Model 310). The sewing ring diameter on the Mosaic Ultra™ bioprosthesis has been reduced to facilitate implantation in patients with small aortic roots.

The Mosaic bioprostheses are available in the sewing ring diameters and sizes shown in Table 1, Table 2, and Table 3.

Table 1. Mosaic aortic bioprosthesis, Model 305, available sizes and sewing ring diameters

Valve size (stent O.D.a) (±0.5 mm)

Orifice diameter

(stent I.D.)

(±0.5 mm)

Suture ring

diameter

(±1 mm)

Valve height

(±0.5 mm)

Aortic protrusion

(±0.5 mm)

19 17.5 25.0 13.5 11.0 21 18.5 27.0 15.0 12.0 23 20.5 30.0 16.0 13.5 25 22.5 33.0 17.5 15.0 27 24.0 36.0 18.5 15.5

Nominal values in millimeters 29 26.0 39.0 20.0 16.0

Stent O.D. equivalent to annulus diameter

Table 2. Mosaic Ultra aortic bioprosthesis small root system, Model 305, available sizes and sewing ring diameters

Valve size (stent O.D.a) (±0.5 mm)

Orifice diameter

(stent I.D.)

(±0.5 mm)

Suture ring

diameter

(±1 mm)

Valve height

(±0.5 mm)

Aortic protrusion

(±0.5 mm)

19 17.5 24.0 13.5 11.0 21 18.5 26.0 15.0 12.0 23 20.5 28.0 16.0 13.5 25 22.5 30.0 17.5 15.0 27 24.0 32.0 18.5 15.5

Nominal values in millimeters 29 26.0 34.0 20.0 16.0

Stent O.D. equivalent to annulus diameter

Table 3. Mosaic mitral bioprosthesis, Model 310, available sizes and sewing ring diameters

Valve size (stent O.D.a) (±0.5 mm)

Orifice diameter

(stent I.D.)

(±0.5 mm)

Suture ring

diameter

(±1 mm)

Valve height

(±0.5 mm)

Mitral protrusion

(±0.5 mm)

25 22.5 33.0 18.0 13.5 27 24.0 35.0 19.0 14.0 29 26.0 38.0 20.5 15.5 31 28.0 41.0 22.0 17.0

Nominal values in millimeters 33 30.0 43.0 23.0 17.5

Stent O.D. equivalent to annulus diameter

2. Indications for use

The Mosaic bioprostheses are indicated for the replacement of malfunctioning native or prosthetic aortic and/or mitral heart valves.

3. Contraindications

No contraindications for use of this device are known.

6 Instructions for Use English

4. Warnings and precautions

4.1. Warnings

This device was designed for single patient use only. Do not reuse, reprocess, or resterilize this product. Reuse, reprocessing, or resterilization may compromise the structural integrity of the device or create a risk of contamination of the device, which could result in patient injury, illness, or death.

Check the shipping temperature indicator inside the carton. If the shipping temperature indicator window is black, the valve is not suitable for clinical use.

Do not resterilize the valve by any method. Exposure of the bioprosthesis and container to irradiation, steam, ethylene oxide, or other chemical sterilants will render the bioprosthesis unfit for use.

Do not use the bioprosthesis if:

■

The bioprosthesis has been dropped, damaged, or mishandled in any way

■

The Use-by date has elapsed

■

All tamper strips on the glass jar and lid container are damaged

■

The serial number tag does not match the container label

■

The shipping temperature indicator window has turned black

■

The glutaraldehyde storage solution does not completely cover the bioprosthesis

Do not expose the bioprosthesis to solutions other than the storage solution in which it was shipped, the sterile isotonic saline solution used during the rinsing procedure, or the sterile isotonic saline solution used to irrigate the bioprosthesis.

Do not add antibiotics to either the storage or the rinse solution. Do not apply antibiotics to the bioprosthesis. Do not allow the valve tissue to dry. Maintain tissue moisture with irrigation or immersion in normal saline solution during

surgery. Do not attempt to repair a damaged bioprosthesis. Do not use cutting needles, as they may cause structural damage to the fabric of the bioprosthesis. Do not pass a catheter, surgical instrument, or transvenous pacing lead through the bioprosthesis, as this may damage the

valve. Do not oversize. Implanting too large a valve in a patient can lead to stent distortion or valve inflow obstruction and an

increased risk for stenosis, regurgitation, or reduced valve durability. Implanting too small a valve in a patient can lead to an increased risk for stenosis.

4.2. Precautions

■

Accelerated deterioration due to calcific degeneration of bioprostheses may occur in:

■

Children, adolescents, or young adults

■

Patients with altered calcium metabolism (eg, chronic renal failure, hyperparathyroidism)

■

When selecting a bioprosthesis size, consideration of the cardiac anatomy is necessary, and care must also be taken to select a bioprosthesis which adequately provides for the hemodynamic requirements of the patient.

■

When using interrupted sutures, it is important to cut the sutures close to the knots and to ensure that exposed suture tails will not come into contact with the leaflet tissue.

■

Care must be exercised when placing sutures through the sewing ring to avoid possible laceration of the leaflet tissue.

■

Do not use other manufacturers' sizers or universal sizers to size the Mosaic bioprosthesis.

5. Adverse events

A prospective, nonrandomized, multi-center clinical study was conducted to assess the safety and effectiveness of the Mosaic bioprosthesis. Patients were evaluated preoperatively, within 30 days postoperative, 3 to 6 months postoperative, at 1 year (11 to 14 months) postoperative, and annually thereafter. Patients were monitored throughout the postoperative period for possible adverse events.

5.1. Original PMA data

One thousand two hundred fifty-two (1252) patients had isolated aortic valve replacement (AVR) and 365 patients had isolated mitral valve replacement (MVR). Mortality and valve-related morbidity rates after implantation with the Mosaic bioprosthesis are summarized in the following tables.

Observed adverse events

Isolated aortic valve replacement (AVR)

The adverse event rates were based on 1252 bioprostheses implanted in 1252 patients at 17 centers. The cumulative follow-up was 2745.3 patient-years with a mean follow-up of 2.2 years (SD=1.2 years, range=0 to 5.2 years).

Instructions for Use English 7

Table 4. Observed Adverse Event Rates for AVR All patients analyzed: N=1252 Cumulative follow-up=2745.3 patient-years

Early Events

Late Events

n % of Patients n %/Pt.-Yr.

All Deaths 41 3.3 82 3.1

Valve-Related or Unexplained 4 0.3 24 0.9

Valve-Related Adverse Events

Primary Thromboembolism

19 1.4 33 1.25 Permanent Neurological Event 7 0.6 13 0.5 Transient Neurological Event

12 0.9 20 0.8

Primary Valve Thrombosis 0 0.0 5 0.2 Structural Valve Deterioration

0 0.0 1 0.0

Nonstructural Valve Dysfunction 0 0.0 4 0.15

Leaflet Dysfunction 0 0.0 1 0.0 Patient Prosthesis Mismatch 0 0.0 3 0.1

Endocarditis 1 0.1 19 0.7 All Primary Paravalvular Leak 6 0.5 13 0.5

Major Primary Paravalvular Leak 1 0.1 2 0.1

All Antithromboembolic-Related Hemorrhage 23 1.8 28 1.1

Major Antithromboembolic-Related Hemorrhage 15 1.2 20 0.8

Primary Hemolysis 0 0.0 0 0.0 Reoperation 0 0.0 20 0.8 Explant 0 0.0 19 0.7

Early deaths occurred within 30 days of implant if the patient was discharged from the hospital, or at any time after implant if the patient was not discharged from the hospital. Early valve-related adverse events occurred within the first 30 days of implant. Early event rates were calculated as the percentage of patients.

Late deaths occurred after 30 days postoperative, if the patient was discharged from the hospital. Late valve-related adverse events occurred after 30 days postoperative. Late event rates were calculated as linearized rates (%/patient-year). Calculations for late death rates were based on 2642.5 late patient-years. Calculations for late valve-related adverse event rates were based on 2645.2 late patient-years.

Two early events occurred in 1 patient.

The adverse event occurred after 4 years postoperative.

Freedom From Event (%) [95% CI]

1 Year 2 Years

All Deaths 93.7 [92.3, 95.2] 91.9 [89.9, 93.8]

Valve-Related or Unexplained 98.7 [98.0, 99.4] 98.2 [97.2, 99.1]

Valve-Related Adverse Events

Primary Thromboembolism

96.9 [95.8, 98.0] 96.3 [94.9, 97.7] Permanent Neurological Event 98.7 [98.1, 99.4] 98.4 [97.5, 99.3] Transient Neurological Event

98.1 [97.2, 98.9] 97.8 [96.8, 98.9]

Primary Valve Thrombosis 99.7 [99.4, 100.0] 99.6 [99.2, 100.0] Structural Valve Deterioration

100.0 100.0

Nonstructural Valve Dysfunction 99.7 [99.4, 100.0] 99.7 [99.4, 100.0]

Leaflet Dysfunction 100.0 100.0 Patient Prosthesis Mismatch 99.7 [99.4, 100.0] 99.7 [99.4, 100.0]

Endocarditis 99.3 [98.8, 99.8] 98.7 [97.9, 99.5] All Primary Paravalvular Leak 99.1 [98.5, 99.7] 98.4 [97.5, 99.3]

Major Primary Paravalvular Leak 99.8 [99.4, 100.0] 99.8 [99.4, 100.0]

All Antithromboembolic-Related Hemorrhage 96.5 [95.4, 97.6] 96.3 [94.9, 97.7]

Major Antithromboembolic-Related Hemorrhage 97.6 [96.6, 98.5] 97.5 [96.3, 98.6]

Primary Hemolysis 100.0 100.0 Reoperation 99.2 [98.7, 99.8] 99.0 [98.3, 99.7] Explant 99.3 [98.8, 99.8] 99.1 [98.4, 99.8]

Freedom from event (early or late) rates were calculated using the Kaplan-Meier method. Peto’s formula was used for the calculation of the standard error of the Kaplan-Meier estimate for the confidence interval for adverse events with at least 1 occurrence.

Two early events occurred in 1 patient.

The adverse event occurred after 4 years postoperative.

Freedom From Event (%) [95% CI]

3 Years 4 Years

All Deaths 88.6 [85.5, 91.7] 85.6 [79.0, 92.1]

Valve-Related or Unexplained 97.1 [95.3, 98.8] 96.5 [92.9, 100.0]

Valve-Related Adverse Events

8 Instructions for Use English

Freedom From Event (%) [95% CI]

3 Years 4 Years

Primary Thromboembolism

95.6 [93.5, 97.7] 95.6 [91.5, 99.7] Permanent Neurological Event 98.0 [96.6, 99.5] 98.0 [95.3, 100.0] Transient Neurological Event

97.5 [95.9, 99.1] 97.5 [94.3, 100.0]

Primary Valve Thrombosis 99.4 [98.7, 100.0] 99.4 [98.0, 100.0] Structural Valve Deterioration

100.0 100.0

Nonstructural Valve Dysfunction 99.7 [99.2, 100.0] 99.1 [97.3, 100.0]

Leaflet Dysfunction 100.0 99.4 [97.8, 100.0] Patient Prosthesis Mismatch 99.7 [99.2, 100.0] 99.7 [98.7, 100.0]

Endocarditis 97.7 [96.2, 99.2] 97.4 [94.3, 100.0] All Primary Paravalvular Leak 98.3 [96.9, 99.6] 98.3 [95.7, 100.0]

Major Primary Paravalvular Leak 99.8 [99.2, 100.0] 99.8 [98.8, 100.0]

All Antithromboembolic-Related Hemorrhage 95.3 [93.2, 97.5] 95.3 [91.1, 99.5]

Major Antithromboembolic-Related Hemorrhage 96.5 [94.6, 98.4] 96.5 [92.9, 100.0]

Primary Hemolysis 100.0 100.0 Reoperation 98.4 [97.2, 99.7] 95.7 [91.7, 99.6] Explant 98.5 [97.3, 99.8] 95.8 [91.8, 99.7]

Two early events occurred in 1 patient.

The adverse event occurred after 4 years postoperative.

Isolated mitral valve replacement (MVR)

The adverse event rates were based on 365 bioprostheses implanted in 365 patients at 17 centers. The cumulative follow-up was 644.2 patient-years with a mean follow-up of 1.8 years (SD=1.3 years, range=0 to 5.2 years).

Table 5. Observed Adverse Event Rates for MVR All patients analyzed: N=365 Cumulative follow-up=644.2 patient-years

Early Events

Late Events

n % of Patients n %/Pt.-Yr.

All Deaths 15 4.1 25 4.1

Valve-Related or Unexplained 2 0.5 8 1.3

Valve-Related Adverse Events

Primary Thromboembolism

13 3.0 10 1.6 Permanent Neurological Event 4 1.1 2 0.3 Transient Neurological Event

9 1.9 8 1.3 Primary Valve Thrombosis 0 0.0 1 0.2 Structural Valve Deterioration 0 0.0 0 0.0 Nonstructural Valve Dysfunction 0 0.0 0 0.0

Leaflet Dysfunction 0 0.0 0 0.0

Patient Prosthesis Mismatch 0 0.0 0 0.0 Endocarditis 2 0.5 6 1.0 All Primary Paravalvular Leak 3 0.8 9 1.5

Major Primary Paravalvular Leak 0 0.0 3 0.5 All Antithromboembolic-Related Hemorrhage 7 1.9 11 1.8

Major Antithromboembolic-Related Hemorrhage 5 1.4 7 1.1 Primary Hemolysis 0 0.0 0 0.0 Reoperation 0 0.0 5 0.8 Explant 0 0.0 5 0.8

Late deaths occurred after 30 days postoperative, if the patient was discharged from the hospital. Late valve-related adverse events occurred after 30 days postoperative. Late event rates were calculated as linearized rates (%/patient-year). Calculations for late death rates were based on 614.1 late patient-years. Calculations for late valve-related adverse event rates were based on 615.2 late patient-years.

Two early events occurred in each of 2 patients.

Freedom From Event (%) [95% CI]

1 Year 2 Years

All Deaths 92.5 [89.2, 95.7] 89.9 [85.3, 94.5]

Valve-Related or Unexplained 98.4 [96.8, 100.0] 97.3 [94.7, 99.9]

Valve-Related Adverse Events

Primary Thromboembolism

95.1 [92.3, 97.8] 93.9 [90.0, 97.8]

Instructions for Use English 9

Freedom From Event (%) [95% CI]

1 Year 2 Years

Permanent Neurological Event 98.6 [97.1, 100.0] 98.6 [96.7, 100.0] Transient Neurological Event

96.5 [94.1, 98.8] 95.3 [91.9, 98.8] Primary Valve Thrombosis 100.0 100.0 Structural Valve Deterioration 100.0 100.0 Nonstructural Valve Dysfunction 100.0 100.0

Leaflet Dysfunction 100.0 100.0

Patient Prosthesis Mismatch 100.0 100.0 Endocarditis 98.2 [96.6, 99.9] 98.2 [96.1, 100.0] All Primary Paravalvular Leak 96.9 [94.7, 99.1] 96.4 [93.4, 99.4]

Major Primary Paravalvular Leak 99.7 [99.0, 100.0] 98.6 [96.7, 100.0] All Antithromboembolic-Related Hemorrhage 95.8 [93.3, 98.4] 95.3 [91.9, 98.7]

Major Antithromboembolic-Related Hemorrhage 97.3 [95.2, 99.4] 96.7 [93.9, 99.6] Primary Hemolysis 100.0 100.0 Reoperation 99.3 [98.3, 100.0] 98.8 [97.0, 100.0] Explant 99.3 [98.3, 100.0] 98.8 [97.0, 100.0]

Two early events occurred in each of 2 patients.

Freedom From Event (%) [95% CI]

3 Years 4 Years

All Deaths 85.9 [78.7, 93.0] 80.0 [66.2, 93.7]

Valve-Related or Unexplained 96.4 [92.3, 100.0] 92.2 [82.2, 100.0]

Valve-Related Adverse Events

Primary Thromboembolism

93.9 [88.5, 99.3] 92.2 [82.0, 100.0] Permanent Neurological Event 98.6 [96.0, 100.0] 97.0 [90.5, 100.0] Transient Neurological Event

95.3 [90.5, 100.0] 95.3 [87.1, 100.0] Primary Valve Thrombosis 100.0 98.5 [93.8, 100.0] Structural Valve Deterioration 100.0 100.0 Nonstructural Valve Dysfunction 100.0 100.0

Leaflet Dysfunction 100.0 100.0

Patient Prosthesis Mismatch 100.0 100.0 Endocarditis 98.2 [95.3, 100.0] 95.9 [88.4, 100.0] All Primary Paravalvular Leak 95.3 [90.7, 100.0] 95.3 [87.1, 100.0]

Major Primary Paravalvular Leak 98.6 [96.0, 100.0] 98.6 [94.1, 100.0] All Antithromboembolic-Related Hemorrhage 93.4 [87.9, 98.9] 91.0 [80.3, 100.0]

Major Antithromboembolic-Related Hemorrhage 94.8 [89.9, 99.7] 94.8 [86.5, 100.0] Primary Hemolysis 100.0 100.0 Reoperation 98.8 [96.4, 100.0] 94.9 [86.6, 100.0] Explant 98.8 [96.4, 100.0] 94.9 [86.6, 100.0]

Two early events occurred in each of 2 patients.

5.2. Supplemental data (all aortic and mitral sizes except aortic 19 mm)

One thousand two hundred fifty-four (1254) patients had isolated aortic valve replacement (AVR) and 366 patients had isolated mitral valve replacement (MVR). Mortality and valve-related morbidity rates after implantation with the Mosaic® porcine bioprosthesis are summarized in the following tables.

Observed adverse events

Isolated aortic valve replacement (AVR)

The adverse event rates were based on 1254 bioprostheses implanted in 1254 patients at 17 centers. The cumulative follow-up was 3689.5 patient-years with a mean follow-up of 2.9 years (SD=1.4 years, range=0 to 6.2 years).

10 Instructions for Use English

Table 6. Observed Adverse Event Rates for AVR All patients analyzed: N=1254 Cumulative follow-up=3689.5 patient-years

Early Events

n % of

Late Events

n %/ Pt.-Yr. 1 Year 3 Years 5 Years

Freedom From Event (%) [95% CI]

Patients

All Deaths 41 3.3 121 3.4 93.5 [92.1,

94.9]

Valve-Related or Unexplained 4 0.3 37 1.0 98.7 [98.1,

99.3]

88.3 [85.9,

90.7]

96.8 [95.4,

98.2]

79.5 [71.9,

87.1]

95.0 [90.5,

99.5]

Valve-Related Adverse Events

Primary Thromboembolismd,

Permanent Neurological Event 8 0.6 22 0.6 98.6 [97.8,

Transient Neurological Event

Primary Valve Thrombosis 0 0.0 5 0.1 99.8 [99.6,

21 1.7 47 1.3 96.8 [95.8,

97.8]

99.4]

13 1.0 24 0.7 98.1 [97.3,

98.9]

100.0]

95.0 [93.2,

96.8]

97.5 [96.3,

98.7]

97.6 [96.4,

98.8]

99.5 [98.9,

100.0]

93.4 [88.3,

98.5]

96.6 [92.9,

100.0]

96.7 [93.0,

100.0]

99.5 [98.1,

100.0]

Structural Valve Deterioration 0 0.0 1 0.0 100.0 100.0 99.3 [97.5,

100.0]

Nonstructural Valve Dysfunction 0 0.0 5 0.1 99.8 [99.6,

100.0]

99.6 [99.2,

100.0]

99.4 [97.8,

100.0]

Leaflet Dysfunction 0 0.0 1 0.0 100.0 100.0 99.8 [98.8,

100.0]

Patient Prosthesis Mismatch 0 0.0 4 0.1 99.8 [99.6,

100.0]

Endocarditis 2 0.2 26 0.7 99.1 [98.5,

99.7]

All Primary Paravalvular Leak 6 0.5 13 0.4 99.1 [98.5,

99.7]

Major Primary Paravalvular Leak

All Antithromboembolic-Related Hemorrhage

Major Antithromboembolic-Related Hemorrhage

1 0.1 2 0.1 99.8 [99.6,

100.0]

23 1.8 42 1.2 96.5 [95.5,

97.5]

15 1.2 29 0.8 97.6 [96.6,

98.6]

99.6 [99.2,

100.0]

97.6 [96.4,

98.8]

98.4 [97.4,

99.4]

99.8 [99.4,

100.0]

95.0 [93.2,

96.8]

96.4 [95.0,

97.8]

99.6 [98.2,

100.0]

97.4 [94.1,

100.0]

98.4 [95.7,

100.0]

99.8 [98.8,

100.0]

93.8 [88.7,

98.9]

96.0 [91.9,

100.0] Primary Hemolysis 0 0.0 0 0.0 100.0 100.0 100.0 Reoperation 0 0.0 25 0.7 99.2 [98.6,

99.8]

Explant 0 0.0 24 0.7 99.2 [98.6,

99.8]

Late deaths occurred after 30 days postoperative, if the patient was discharged from the hospital. Late valve-related adverse events occurred after 30 days postoperative. Late event rates were calculated as linearized rates (%/patient-year). Calculations for late death rates were based on 3584.1 late patient-years. Calculations for late valve-related adverse event rates were based on 3588.8 late patient-years.

Two early events occurred in 1 patient.

One late event was an acute myocardial infarction.

98.4 [97.4,

99.4]

98.5 [97.5,

99.5]

96.2 [92.3,

100.0]

96.3 [92.4,

100.0]

Isolated mitral valve replacement (MVR)

The adverse event rates were based on 366 bioprostheses implanted in 366 patients at 17 centers. The cumulative follow-up was 880.1 patient-years with a mean follow-up of 2.4 years (SD=1.4 years, range=0 to 6.1 years).

Table 7. Observed Adverse Event Rates for MVR All patients analyzed: N=366 Cumulative follow-up=880.1 patient-years

Early Events

n % of

Late Events

n %/ Pt.-Yr. 1 Year 3 Years 4 Years

Freedom From Event (%) [95% CI]

Patients

All Deaths 15 4.1 32 3.8 92.8 [90.1,

95.5]

Valve-Related or Unexplained 2 0.5 9 1.1 98.5 [97.1,

99.9]

87.5 [82.2,

92.8]

97.8 [95.3,

100.0]

82.9 [73.7,

92.1]

94.6 [88.7,

100.0]

Instructions for Use English 11

Early Events

n % of

Late Events

n %/ Pt.-Yr. 1 Year 3 Years 4 Years

Freedom From Event (%) [95% CI]

Patients

Valve-Related Adverse Events

Primary Thromboembolism

Permanent Neurological Event 4 1.1 3 0.4 98.6 [97.2,

Transient Neurological Event

13 3.0 12 1.4 95.2 [92.8,

97.6]

100.0]

9 1.9 9 1.1 96.6 [94.4,

98.8]

94.4 [90.5,

98.3]

98.6 [96.6,

100.0]

95.8 [92.3,

99.3]

92.0 [84.6,

99.4]

96.3 [91.2,

100.0]

95.8 [90.3,

100.0]

Primary Valve Thrombosis 0 0.0 1 0.1 100.0 100.0 99.2 [96.8,

100.0] Structural Valve Deterioration 0 0.0 0 0.0 100.0 100.0 100.0 Nonstructural Valve Dysfunction 0 0.0 0 0.0 100.0 100.0 100.0

Leaflet Dysfunction 0 0.0 0 0.0 100.0 100.0 100.0 Patient Prosthesis Mismatch 0 0.0 0 0.0 100.0 100.0 100.0

Endocarditis 2 0.5 7 0.8 98.3 [96.9,

99.7]

All Primary Paravalvular Leak 3 0.8 9 1.1 97.1 [95.1,

99.1]

Major Primary Paravalvular Leak

All Antithromboembolic-Related Hemorrhage

Major AntithromboembolicRelated Hemorrhage

0 0.0 3 0.4 99.7 [99.1,

100.0]

7 1.9 13 1.5 96.0 [93.8,

98.2]

5 1.4 9 1.1 97.1 [95.1,

99.1]

97.9 [95.5,

100.0]

96.0 [92.7,

99.3]

98.9 [97.1,

100.0]

94.3 [90.4,

98.2]

95.4 [91.9,

98.9]

96.8 [92.1,

100.0]

96.0 [90.7,

100.0]

98.9 [96.2,

100.0]

92.1 [84.8,

99.4]

94.3 [88.0,

100.0] Primary Hemolysis 0 0.0 0 0.0 100.0 100.0 100.0 Reoperation 0 0.0 6 0.7 99.4 [98.6,

100.0]

Explant 0 0.0 6 0.7 99.4 [98.6,

100.0]

Late deaths occurred after 30 days postoperative, if the patient was discharged from the hospital. Late valve-related adverse events occurred after 30 days postoperative. Late event rates were calculated as linearized rates (%/patient-year). Calculations for late death rates were based on 849.9 late patient-years. Calculations for late valve-related adverse events were based on 850.9 late patient-years.

Two early events occurred in each of 2 patients.

98.6 [96.6,

100.0]

98.6 [96.6,

100.0]

96.7 [92.0,

100.0]

96.7 [92.0,

100.0]

5.3. Supplemental data (aortic 19 mm only)

Twenty-three patients, implanted at 2 centers, had isolated aortic valve replacement (AVR) with the size 19 mm bioprosthesis. Three deaths were reported: a cardiac death 10 days postoperative, a noncardiac death 39 days postoperative, and a cardiac death 836 days postoperative. One minor antithromboembolic-related hemorrhage was reported 5 days postoperative. No other valve-related adverse events were reported.

5.4. Six year data (aortic and mitral 19 to 33 mm)

A clinical study was conducted to assess the long-term safety and effectiveness of the Mosaic® porcine bioprosthesis. Patients were monitored throughout the postoperative period for possible adverse events. Seven-hundred ninety-seven (797) patients had isolated aortic valve replacement (AVR) and 232 patients had isolated mitral valve replacement (MVR). Mortality and valverelated morbidity rates after implantation with the Mosaic® porcine bioprosthesis are summarized in the following tables.

Observed adverse events

Isolated aortic valve replacement (AVR)

The adverse event rates were based on 797 bioprostheses implanted in 797 patients at 6 centers. The cumulative follow-up was 4029.2 patient-years with a mean follow-up of 5.1 years (SD=2.0 years, range=0 to 9.1 years).

12 Instructions for Use English

Table 8. Observed Adverse Event Rates for AVR All patients analyzed: N=797 Cumulative follow-up=4029.2 patient-years

Early Events

n % of

Late Events

n %/ Pt.-Yr. 1 Year 4 Years 8 Years

Freedom From Event (%) [95% CI]

Patients

All Deaths 22 2.8 98 2.5 94.2 [92.6,

95.8]

Valve-Related or Unexplained 4 0.5 25 0.6 98.7 [97.9,

99.5]

88.4 [85.9,

90.8]

97.2 [95.9,

98.5]

76.7 [62.2,

91.2]

94.2 [85.4,

100.0]

Valve-Related Adverse Events

Primary Thromboembolismd,

Permanent Neurological Event 7 0.9 25 0.6 98.4 [97.6,

Transient Neurological Event

Primary Valve Thrombosis 0 0.0 4 0.1 99.7 [99.4,

17 2.0 56 1.4 96.5 [95.2,

97.8]

99.3]

10 1.1 29 0.7 97.9 [96.9,

99.0]

100.0]

93.3 [91.3,

95.3]

96.7 [95.3,

98.1]

96.4 [95.0,

97.9]

99.6 [99.1,

100.0]

88.6 [76.2,

100.0]

94.5 [85.9,

100.0]

94.2 [84.8,

100.0]

99.4 [96.3,

100.0] Structural Valve Deterioration 0 0.0 2 0.1 100.0 100.0 94.0 [84.9,

100.0] Nonstructural Valve Dysfunction 0 0.0 3 0.1 99.6 [99.2

100.0]

99.6 [99.1,

100.0]

99.6 [97.2,

100.0]

Leaflet Dysfunction 0 0.0 0 0.0 100.0 100.0 100.0 Patient Prosthesis Mismatch 0 0.0 3 0.1 99.6 [99.2,

100.0]

Endocarditis 2 0.3 25 0.6 98.8 [98.1,

99.6]

All Primary Paravalvular Leak 6 0.8 11 0.3 98.7 [97.9,

99.5]

Major Primary Paravalvular Leak

Major AntithromboembolicRelated Hemorrhage

2 0.3 2 0.1 99.6 [99.2,

100.0]

12 1.5 28 0.7 97.2 [96.0,

98.4]

99.6 [99.1,

100.0]

96.8 [95.5,

98.2]

97.8 [96.6,

98.9]

99.5 [98.9,

100.0]

95.4 [93.8,

97.1]

99.6 [97.2,

100.0]

96.2 [88.8,

100.0]

97.8 [91.9,

100.0]

99.5 [96.7,

100.0]

94.4 [85.2,

100.0] Primary Hemolysis 0 0.0 0 0.0 100.0 100.0 100.0 Reoperation 0 0.0 26 0.7 99.0 [98.2,

99.7]

Explant 0 0.0 24 0.6 99.1 [98.4,

99.8]

Late deaths occurred after 30 days postoperative, if the patient was discharged from the hospital. Late valve-related adverse events occurred after 30 days postoperative. Late event rates were calculated as linearized rates (%/patient-year). Calculations for late death rates were based on 3964.5 late patient-years. Calculations for late valve-related adverse event rates were based on 3964.8 late patient-years.

Freedom from event (early or late) was calculated using the Kaplan-Meier method. Peto’s formula was used for the calculation of the standard error of the Kaplan-Meier estimate for the confidence interval for adverse events with at least 1 occurrence.

Two early events occurred in 1 patient.

Two late events were acute myocardial infarctions.

97.1 [95.7,

98.4]

97.2 [95.9,

98.5]

90.6 [79.7,

100.0]

90.9 [80.2,

100.0]

Isolated mitral valve replacement (MVR)

The adverse event rates were based on 232 bioprostheses implanted in 232 patients at 6 centers. The cumulative follow-up was 1204.6 patient-years with a mean follow-up of 5.2 years (SD=2.3 years, range=0 to 9.0 years).

Table 9. Observed Adverse Event Rates for MVR All patients analyzed: N=232 Cumulative follow-up=1204.6 patient-years

Early Events

n % of

Late Events

n %/ Pt.-Yr. 1 Year 4 Years 8 Years

Freedom From Event (%) [95% CI]

Patients

All Deaths 7 3.0 35 3.0 93.5 [90.3,

96.7]

Valve-Related or Unexplained 0 0.0 7 0.6 98.6 [97.1,

100.0]

86.6 [81.8,

91.3]

97.6 [95.4,

99.9]

75.7 [61.1,

90.4]

95.6 [87.8,

100.0]

Valve-Related Adverse Events

Instructions for Use English 13

Early Events

n % of

Late Events

n %/ Pt.-Yr. 1 Year 4 Years 8 Years

Freedom From Event (%) [95% CI]

Patients

Primary Thromboembolismd,

Permanent Neurological Event 4 1.7 9 0.8 97.8 [95.9,

Transient Neurological Event

Primary Valve Thrombosis 0 0.0 1 0.1 100.0 99.5 [98.4,

Structural Valve Deterioration 0 0.0 1 0.1 100.0 99.5 [98.4,

8 3.0 21 1.8 95.6 [92.8,

98.3]

99.8]

4 1.3 11 0.9 97.8 [95.8,

99.8]

91.4 [87.2,

95.6]

95.2 [92.0,

98.4]

96.3 [93.4,

99.1]

83.6 [68.4,

98.8]

91.7 [81.0,

100.0]

92.6 [82.1,

100.0]

99.5 [96.6,

100.0]

99.5 [96.6,

100.0]

100.0] Nonstructural Valve Dysfunction 0 0.0 0 0.0 100.0 100.0 100.0

Leaflet Dysfunction 0 0.0 0 0.0 100.0 100.0 100.0 Patient Prosthesis Mismatch 0 0.0 0 0.0 100.0 100.0 100.0

Endocarditis 0 0.0 8 0.7 98.7 [97.1,

100.0]

All Primary Paravalvular Leak 3 1.3 8 0.7 96.9 [94.6,

99.2]

Major Primary Paravalvular Leak

Major AntithromboembolicRelated Hemorrhage

0 0.0 2 0.2 99.1 [97.8,

100.0]

3 1.3 13 1.1 96.9 [94.5,

99.2]

97.6 [95.3,

99.8]

95.8 [92.9,

98.8]

99.1 [97.7,

100.0]

95.3 [92.1,

98.5]

95.6 [87.7,

100.0]

94.9 [86.1,

100.0]

99.1 [95.4,

100.0]

90.9 [79.7,

100.0] Primary Hemolysis 0 0.0 0 0.0 100.0 100.0 100.0 Reoperation 0 0.0 7 0.6 99.1 [97.8,

100.0]

Explant 0 0.0 7 0.6 99.1 [97.8,

100.00]

Late deaths occurred after 30 days postoperative, if the patient was discharged from the hospital. Late valve-related adverse events occurred after 30 days postoperative. Late event rates were calculated as linearized rates (%/patient-year). Calculations for late death rates were based on 1185.2 late patient-years. Calculations for late valve-related adverse events were based on 1185.9 late patient-years.

Two early events occurred in 1 patient.

One late event was a peripheral arterial event.

96.5 [93.8,

99.2]

96.5 [93.8,

99.2]

96.5 [89.4,

100.0]

96.5 [89.4,

100.0]

5.5. Potential adverse events

Adverse events potentially associated with the use of bioprosthetic heart valves include:

■

Angina

■

Cardiac dysrhythmias

■

Death

■

Endocarditis

■

Heart failure

■

Hemolysis

■

Hemolytic anemia

■

Hemorrhage, anticoagulant/antiplatelet-related

■

Infection, other than endocarditis

■

Leak, transvalvular or paravalvular

■

Myocardial infarction

■

Nonstructural dysfunction (obstructive pannus ingrowth, suture dehiscence, inappropriate sizing, other)

■

Stroke

■

Structural deterioration (calcification, leaflet tear, other)

■

Thromboembolism

■

Valve thrombosis

It is possible that these complications could lead to:

■

Reoperation

■

Explantation

14 Instructions for Use English

■

Permanent disability

■

Death

6. Instructions for use

6.1. Physician training

No specific training is required to implant the Mosaic bioprostheses. The techniques for implanting these bioprostheses are similar to those used for any stented bioprosthesis.

6.2. Device features

The stents are constructed from a polymeric material. To allow radiographic visualization, both the aortic and mitral stents are fitted with stent post markers. The stent post markers

are placed close to the apex of each stent post to allow visualization of the relationship of the stent posts to one another and to the aortic or ventricular wall.

The stents of both the aortic and mitral models are covered with polyester fabric. The inflow edge of the stent of the aortic bioprosthesis is scalloped, as is the sewing ring. The sewing ring is mounted flush with

the inflow edge of the stent. This facilitates implantation in either the supra-annular or intra-annular position. If the supraannular position is preferred, the entire bioprosthesis can be seated superior to the annulus, allowing the use of a larger Mosaic aortic bioprosthesis. The inflow edge of the mitral bioprosthesis stent and sewing ring are flat. The mitral bioprosthesis sewing ring contains polyester felt allowing for easy needle penetration and low suture drag.

Disposable Cinch holders are sutured to both aortic and mitral bioprostheses. These holders incorporate a ratchet mechanism, which, after screwing the bioprosthesis holder onto the handle, is actuated by further handle rotation. This then causes the stent posts to be drawn inward, easing bioprosthesis implantation. In the case of the mitral bioprosthesis, the suture attaching the bioprosthesis holder prevents looping of the surgeon’s sutures during implantation.

The disposable holders are designed to fit the reusable Medtronic valve handle, Model 7639. Each handle is also used with Mosaic™ mitral obturators for measuring the annulus.

6.3. Handling and preparation instructions

Proper bioprosthesis size selection is an important part of heart valve replacement. The internal diameter of the patient’s aortic root at the annulus and supracommissural areas and at the mitral annulus may be measured preoperatively, during diastole, using angiographic or echocardiographic techniques. The size selection of a Mosaic bioprosthesis is aided by the use of the appropriate aortic sizer or mitral obturator. Refer to the Accessories section in this Instructions for Use for sizer and obturator product names and models.

Because of the complexity and variation in surgical procedures for cardiac valve replacement, the choice of surgical and suturing techniques is left to the discretion of the individual surgeon. In general, interrupted and mattress suturing are the most commonly reported techniques used for stented valve implantation. Spacing of sutures when using the mattress technique must be carefully matched in length between the annulus and sewing ring to prevent sewing ring distortion. When using the interrupted suturing technique, it is important to trim all suture tail remnants close to the knots to prevent contact of suture tails with the leaflets.

Within the sterile operative field, prepare 2 rinse basins, each containing 500 mL of sterile normal saline solution. The exterior of the device container and lid are nonsterile. Examine the tamper strips to verify that the container has not been

damaged or previously opened. Do not use if all the tamper strips are damaged. Turn the lid counterclockwise and open the container (Figure 1).

The bioprosthesis and all packaging components inside the container are sterile and must be handled accordingly. With the thumb and index finger, grasp the retainer and slowly lift it out of the container allowing for drainage of the glutaraldehyde storage solution (Figure 2).

Verify that the serial number on the retainer matches that of the container lid, shelf carton, and Patient Registration Form. Record the serial number of the bioprosthesis in the patient's record using the stickers provided on the Patient Registration Form.

Hold the retainer upright. Remove the retainer cap by turning it counterclockwise using the thumb and index finger (Figure 3). The Cinch holder will be visible.

While grasping the retainer, insert a sterile Medtronic valve handle into the Cinch holder. To secure the handle, rotate the handle clockwise into the threaded opening of the holder until resistance is felt. Stop rotation if a first click is heard (Figure 4).

Caution: Do not overtighten the handle, as this will actuate the ratcheting mechanism. Remove the bioprosthesis from the retainer by pulling upward on the handle (Figure 5).

Instructions for Use English 15

6.4. Rinse procedure

Using the Medtronic valve handle, continually agitate the entire bioprosthesis and holder for a minimum of 15 seconds in each of the 2 previously prepared rinse basins (Figure 5). In each basin, gently squeeze the sewing ring to remove any residual glutaraldehyde. Do not touch the tissue portion of the bioprosthesis. The bioprosthesis should remain in the second rinse basin until needed for implantation.

6.5. Device implantation Caution: Do not use if the bioprosthesis has been damaged. Caution: Extreme care must be taken to prevent damage to the delicate bioprosthesis tissue. Do not handle the tissue portion

of the bioprosthesis with instruments. Even a minor perforation may enlarge in time to produce significant impairment of bioprosthesis function. Should a bioprosthesis be damaged during insertion, do not attempt repair.

Caution: Do not use cutting needles, as they may cause structural damage to the fabric of the bioprosthesis. Caution: Passage of a catheter, surgical instrument or transvenous pacing lead through any bioprosthesis may damage the

delicate bioprosthesis tissue and is, therefore, not recommended.

Aortic bioprosthesis Caution: Orient the bioprosthesis to avoid obstruction of the coronary ostia.

Stent deflection is accomplished by lightly grasping the sewing ring of the bioprosthesis and rotating the handle clockwise (Figure 6). The aortic holder, shown in a nondeflected state, is considered fully deflected when 2 of the 3 stent post tips are no longer visible beneath the blue holder body when viewed from the outflow aspect (Figure 8 and Figure 9). Further deflection does not provide increased ease of implant benefit. Do not deflect the stent posts past their fully deflected position. It is recommended that valve stent deflection (cinching) be performed prior to lowering the valve into the aorta. Do not cinch the valve stent posts for more than 30 minutes.

Caution: Suture used to deflect the stent posts may break if the handle is overtightened. If the holder suture breaks while cinching the valve stent posts, inspect the valve stent for remnants of suture after removal of the holder. If suture remnants are present, remove them prior to completion of the valve implantation.

During implantation, the bioprosthesis should be periodically irrigated with sterile, normal saline to prevent drying of bioprosthesis tissue. Following placement of the sutures in the sewing ring, positioning of the bioprosthesis in the annulus, and tying all knots, release the holder by cutting the holder sutures (Figure 7).

Hold the bioprosthesis in place and gently remove the holder and holder sutures. Examine the valve sewing ring, the valve stent posts, and the valve holder to ensure that there are no holder suture remnants with the bioprosthesis. If suture remnants are present, remove them prior to completion of valve implantation. The holder should be detached from the handle and discarded.

Mitral bioprosthesis

Actuate the ratchet mechanism of the holder by lightly grasping the sewing ring of the bioprosthesis and rotating the handle clockwise (Figure 10). The stent posts are thus deflected inward to facilitate insertion of the bioprosthesis into the patient's annulus. The mitral holder, shown in a nondeflected state, is considered fully deflected when a gap of 1 to 2 mm exists between any 2 of the 3 stent posts when viewed from the outflow aspect (Figure 12 and Figure 13). Further deflection does not provide increased ease of implant benefit. Do not deflect the stent posts past their fully deflected position.

Caution: If the bioprosthesis is implanted with broken holder suture(s), looping of the surgeon’s suture(s) around the stent posts may occur, causing damage and significant impairment to bioprosthetic function.

Caution: Special care should be exercised when implanting a bioprosthesis in the mitral position in a patient with a small left ventricle. Adequate clearance must be available to avoid contact between the prosthesis stent post and the ventricular wall. Repeated contact between these structures could result in perforation of the ventricular wall.

Caution: To avoid potential stent post obstruction in the left ventricular outflow tract, the bioprosthesis should be oriented in the mitral annulus so that the widest intercommissural space coincides with the patient's left ventricular outflow tract.

Viewed from the inflow aspect of the valve sewing flange, the widest intercommissural space of the bioprosthesis lies between the green suture marker and the first commissure post in the counterclockwise direction.

Orienting the bioprosthesis in the annulus such that the green suture marker is directed approximately towards the right fibrous trigone should position the widest intercommissural space appropriately (Figure 14). Verify proper positioning by examining stent post orientation in the ventricle before tying off implantation sutures.

During implantation, periodically irrigate the bioprosthesis with sterile normal saline to prevent drying of the bioprosthesis tissue. Do not use cutting needles as they could cause structural damage to the bioprosthesis. Following placement of the

16 Instructions for Use English

sutures, the bioprosthesis should be lowered into the annulus, taking care to prevent suture entanglement. Maintaining tension on the sutures at this point is helpful. Suture ends must be trimmed close to the knot to prevent abrasion of leaflet tissue.

Following placement of the bioprosthesis in the annulus, the holder should be removed by cutting the 3 retaining sutures with scissors or scalpel (Figure 11).

After cutting the 3 sutures, hold the bioprosthesis in place while gently pulling away the handle with the holder attached. Examine the valve sewing ring, the valve stent posts, and the valve holder to ensure that there are no holder suture remnants with the bioprosthesis. If suture remnants are present, remove them prior to completion of the valve implantation. The holder should be detached from the handle, inspected, and discarded.

7. Clinical studies

7.1. Original PMA data

One thousand two hundred fifty-two (1252) patients had isolated aortic valve replacement (AVR) and 365 patients had isolated mitral valve replacement (MVR).

The safety endpoints captured in this study were mortality and valve-related morbidity. The effectiveness endpoints in this study were New York Heart Association (NYHA) functional classification and hemodynamic assessments obtained by echocardiography. Patient demographic data and effectiveness data are summarized in the following tables.

Table 10. Patient Demographics

Mosaic Bioprosthesis Clinical Study AVR (N = 1252)

Age at implant in years (mean ± SD, N [min., max.]) 70 ± 8, 1252 [21, 89] Gender (% male / % female) 64% / 36% Etiology

Stenosis- % of pts. with stenosis alone (% (number in subgroup/N))

Insufficiency- % of pts. with insufficiency alone (% (number in subgroup/N))

Mixed-% of pts. with stenosis and insufficiency (% (number in subgroup/N))

67% (842/1252)

11% (141/1252)

21.5% (269/1252)

Mosaic Bioprosthesis Clinical Study MVR (N = 365)

Age at implant in years (mean ± SD, N [min., max.]) 68 ± 11, 365 [17, 84] Gender (% male / % female) 47% / 53% Etiology

Stenosis- % of pts. with stenosis alone (% (number in subgroup/N))

Insufficiency- % of pts. with insufficiency alone (% (number in subgroup/N))

Mixed-% of pts. with stenosis and insufficiency (% (number in subgroup/N))

Table 11. Effectiveness Outcomes, Functional NYHA

NYHA Class Preoperative 3–6 Months 1 Year 3 Years

n/N % n/N % n/N % n/N %

Mosaic Bioprosthesis Clinical Study AVR (N = 1252)

I 30/1252 2% 865/1150 75% 812/1090 74.5% 287/498 58%

II 311/1252 25% 266/1150 23% 261/1090 24% 202/498 41% III 732/1252 58.5% 17/1150 1% 16/1090 1.5% 9/498 2% IV 179/1252 14% 2/1150 0% 1/1090 0% 0/498 0%

NYHA Class Preoperative 3–6 Months 1 Year 3 Years

n/N % n/N % n/N % n/N %

Mosaic Bioprosthesis Clinical Study MVR (N = 365)

I 2/363 1% 190/322 59% 161/260 62% 56/101 55%

II 74/363 20% 119/322 37% 88/260 34% 39/101 39%

10% (38/365)

76% (279/365)

13% (48/365)

Instructions for Use English 17

NYHA Class Preoperative 3–6 Months 1 Year 3 Years

n/N % n/N % n/N % n/N %

Mosaic Bioprosthesis Clinical Study MVR (N = 365)

III 213/363 59% 11/322 3% 9/260 3.5% 5/101 5% IV 74/363 20% 2/322 1% 2/260 1% 1/101 1%

Table 12. Effectiveness Outcomes, Hemodynamics, Valvular Regurgitation: AVR All patients analyzed: N=1252, percent

(numerator/N)

Endpoint ≤ 30 Days 3–6 Months 1 Year 3 Years Valvular Regurgitation

% of pts. with no regurgitation 79% (958/1207) 76% (882/1153) 75% (824/1094) 77% (378/490) % of pts. with trivial regurgitation 13% (155/1207) 15% (172/1153) 16% (175/1094) 15% (73/490) % of pts. with mild regurgitation 7% (85/1207) 7% (85/1153) 7% (79/1094) 6% (30/490) % of pts. with mod regurgitation 1% (9/1207) 1% (12/1153) 1% (14/1094) 2% (9/490) % of pts. with mod severe regurgitation 0% (0/1207) 0% (2/1153) 0% (2/1094) 0% (0/490) % of pts. with severe regurgitation 0% (0/1207) 0% (0/1153) 0% (0/1094) 0% (0/490)

Note: Data reflect transvalvular, paravalvular and indeterminate regurgitation noted at all locations combined.

Table 13. Effectiveness Outcomes, Hemodynamics, Mean Pressure Gradient: AVR All patients analyzed: N=1252, number in

subgroup/N, mean ± SD [min., max.]

Endpoint ≤ 30 Days 3–6 Months Mean Pressure Gradient (mm Hg)

21 mm 217/240, 14.6 ± 6.5 [2.7, 54.7] 199/240, 13.3 ± 5.3 [3.0, 34.4] 23 mm 456/495, 13.0 ± 5.3 [0.9, 37.0] 446/495, 11.8 ± 4.9 [2.0, 43.1] 25 mm 334/362, 11.6 ± 4.9 [2.0, 32.0] 331/362, 10.6 ± 4.4 [1.1, 35.7] 27 mm 119/130, 11.1 ± 4.1 [2.0, 21.5] 114/130, 9.1 ± 4.0 [2.0, 23.1] 29 mm 24/25, 12.6 ± 5.8 [7.0, 28.8] 21/25, 8.6 ± 2.9 [3.5, 16.8]

Endpoint 1 Year 3 Years Mean Pressure Gradient (mm Hg)

21 mm 189/240, 14.5 ± 5.3 [2.0, 40.5] 87/240, 15.5 ± 5.6 [4.5, 32.5] 23 mm 425/495, 12.8 ± 5.0 [3.0, 32.7] 198/495, 14.0 ± 5.5 [3.1, 35.5] 25 mm 310/362, 11.8 ± 5.2 [2.0, 38.9] 127/362, 12.1 ± 5.8 [1.4, 43.1] 27 mm 105/130, 10.0 ± 4.0 [3.4, 22.7] 45/130, 10.5 ± 4.1 [3.3, 24.6] 29 mm 21/25, 10.3 ± 2.6 [4.6, 16.0] 16/25, 9.9 ± 2.5 [5.9, 15.1]

Table 14. Effectiveness Outcomes, Hemodynamics, Effective Orifice Area: AVR All patients analyzed: N=1252, number in

subgroup/N, mean ± SD [min., max.]

Endpoint ≤ 30 Days 3–6 Months Effective Orifice Area (cm2)

21 mm 217/240, 1.4 ± 0.4 [0.6, 3.7] 199/240, 1.4 ± 0.4 [0.7, 3.8] 23 mm 458/495, 1.6 ± 0.5 [0.7, 3.9] 447/495, 1.6 ± 0.5 [0.8, 5.4] 25 mm 336/362, 1.8 ± 0.5 [0.8, 4.2] 331/362, 1.8 ± 0.5 [0.7, 4.0] 27 mm 119/130, 1.9 ± 0.6 [1.0, 4.3] 114/130, 2.0 ± 0.5 [1.0, 3.4] 29 mm 24/25, 2.0 ± 0.5 [1.0, 2.9] 21/25, 2.3 ± 0.6 [1.4, 3.6]

Endpoint 1 Year 3 Years Effective Orifice Area (cm2)

21 mm 189/240, 1.3 ± 0.4 [0.6, 3.1] 86/240, 1.3 ± 0.3 [0.7, 2.5] 23 mm 426/495, 1.5 ± 0.4 [0.7, 3.4] 199/495, 1.5 ± 0.4 [0.7, 3.2] 25 mm 311/362, 1.8 ± 0.5 [0.7, 4.2] 127/362, 1.7 ± 0.4 [0.6, 3.0] 27 mm 105/130, 1.9 ± 0.6 [1.1, 3.7] 45/130, 1.9 ± 0.7 [1.0, 4.2] 29 mm 21/25, 2.2 ± 0.7 [1.3, 4.1] 16/25, 2.2 ± 0.6 [1.2, 3.4]

18 Instructions for Use English

Table 15. Effectiveness Outcomes, Hemodynamics, Valvular Regurgitation: MVR All patients analyzed: N=365, percent

(numerator/N)

Endpoint ≤ 30 Days 3–6 Months 1 Year 3 Years Valvular Regurgitation

% of pts. with no regurgitation 80% (280/348) 77% (255/331) 77% (206/267) 77% (75/97) % of pts. with trivial regurgitation 15% (51/348) 15% (51/331) 16% (42/267) 18% (17/97) % of pts. with mild regurgitation 3% (12/348) 5% (18/331) 5% (13/267) 2% (2/97) % of pts. with mod regurgitation 1% (5/348) 2% (6/331) 2% 5/267) 1% (1/97) % of pts. with mod severe regurgitation 0% 0/348) 0% (1/331) 0% (0/267) 2% (2/97) % of pts. with severe regurgitation 0% (0/348) 0% (0/331) 0% (1/267) 0% (0/97)

Note: Data reflect transvalvular, paravalvular and indeterminate regurgitation noted at all locations combined.

Table 16. Effectiveness Outcomes, Hemodynamics, Mean Pressure Gradient: MVR All patients analyzed: N=365, number in

subgroup/N, mean ± SD [min., max.]

Endpoint ≤ 30 Days 3–6 Months Mean Pressure Gradient (mm Hg)

25 mm 42/48, 5.9 ± 2.2 [3.0, 13.0] 40/48, 5.5 ± 2.1 [1.0, 12.0] 27 mm 107/115, 5.3 ± 2.2 [2.0, 12.0] 104/115, 4.8 ± 2.1 [1.0, 13.1] 29 mm 133/136, 5.0 ± 2.1 [1.0, 15.0] 125/136, 4.4 ± 2.0 [1.0, 12.5] 31 mm 56/57, 4.7 ± 1.9 [2.0, 10.3] 52/57, 4.1 ± 1.6 [1.0, 7.6]

Endpoint 1 Year 3 Years Mean Pressure Gradient (mm Hg)

25 mm 32/48, 5.6 ± 1.6 [3.0, 9.3] 10/48, 5.1 ± 1.8 [1.9, 8.0] 27 mm 83/115, 4.5 ± 2.2 [1.0, 13.0] 33/115, 4.9 ± 3.0 [1.0, 16.2] 29 mm 101/136, 4.3 ± 1.7 [1.0, 8.6] 36/136, 3.9 ± 1.5 [1.0, 8.3] 31 mm 43/57, 3.7 ± 1.4 [1.0, 6.5] 15/57, 4.0 ± 2.1 [2.0, 9.1]

Table 17. Effectiveness Outcomes, Hemodynamics, Effective Orifice Area: MVR All patients analyzed: N=365, number in

subgroup/N, mean ± SD [min., max.]

Endpoint ≤ 30 Days 3–6 Months Effective Orifice Area (cm2)

25 mm 39/48, 1.6 ± 0.4 [0.9, 2.9] 36/48, 1.7 ± 0.8 [0.7, 5.6] 27 mm 95/115, 1.7 ± 0.6 [0.8, 4.6] 93/115, 1.7 ± 0.4 [0.9, 2.9] 29 mm 118/136, 1.7 ± 0.5 [0.7, 3.1] 111/136, 1.8 ± 0.5 [0.7, 3.4] 31 mm 53/57, 1.6 ± 0.5 [0.5, 3.0] 47/57, 1.8 ± 0.6 [1.0, 3.1]

Endpoint 1 Year 3 Years Effective Orifice Area (cm2)

25 mm 27/48, 1.6 ± 0.5 [0.8, 2.3] 7/48, 1.8 ± 0.6 [1.2, 2.8] 27 mm 76/115, 1.7 ± 0.5 [0.7, 3.7] 28/115, 1.6 ± 0.5 [0.3, 3.3] 29 mm 92/136, 1.8 ± 0.5 [0.8, 3.0] 32/136, 1.7 ± 0.5 [1.2, 3.1] 31 mm 37/57, 1.7 ± 0.6 [1.0, 3.2] 14/57, 1.9 ± 0.7 [1.1, 3.8]

7.2. Supplemental data (all aortic and mitral sizes except aortic 19 mm)

One thousand two hundred fifty-four (1254) patients had isolated aortic valve replacement (AVR) and 366 patients had isolated mitral valve replacement (MVR).

Table 18. Patient Demographics: AVR All patients analyzed: N=1254

Age at implant in years (mean ± SD, N [min., max.]) 70 ± 8, 1254 [21, 89] Gender (% male / % female) 64% / 36% Etiology

Stenosis- % of pts. with stenosis alone (% (number in subgroup/N))

67% (842/1254)

Instructions for Use English 19

Insufficiency- % of pts. with insufficiency alone (% (number in subgroup/N))

Mixed-% of pts. with stenosis and insufficiency (% (number in subgroup/N))

Table 19. Patient Demographics: MVR All patients analyzed: N=366

Age at implant in years (mean ± SD, N [min., max.]) 68 ± 11, 366 [17, 84] Gender (% male / % female) 47% / 53% Etiology

Stenosis- % of pts. with stenosis alone (% (number in subgroup/N))

Insufficiency- % of pts. with insufficiency alone (% (number in subgroup/N))

Mixed-% of pts. with stenosis and insufficiency (% (number in subgroup/N))

Table 20. Effectiveness Outcomes, Functional NYHA: AVR All patients analyzed: N=1254

11% (141/1254)

22% (271/1254)

10% (38/366)

77% (280/366)

13% (48/366)

NYHA Class

I 30/1254 2% 867/1157 75% 825/1128 73% 420/744 57% 55/121 45%

II 311/1254 25% 271/1157 23% 285/1128 25% 303/744 41% 57/121 47%

III 733/1254 59% 17/1157 1% 17/1128 2% 19/744 3% 8/121 7%

IV 180/1254 14% 2/1157 0% 1/1128 0% 2/744 0% 1/121 1%

NYHA Class

I 2/365 1% 193/326 59% 198/317 63% 83/147 57% 49/83 59%

II 74/365 20% 120/326 37% 108/317 34% 54/147 37% 30/83 36%

III 214/365 59% 11/326 3% 9/317 3% 8/147 5% 4/83 5%

IV 75/365 21% 2/326 1% 2/317 1% 2/147 1% 0/83 0%

Table 22. Effectiveness Outcomes, Hemodynamics, Valvular Regurgitation: AVR All patients analyzed: N=1254, percent

Endpoint ≤ 30 Days 3–6 Months 1 Year 3 Years 5 Years Valvular Regurgitation

% of pts. with no regurgitation

% of pts. with trivial regurgitation

% of pts. with mild regurgitation

% of pts. with mod regurgitation

% of pts. with mod severe regurgitation

% of pts. with severe regurgitation

Note: Data reflect transvalvular, paravalvular, and indeterminate regurgitation noted at all locations combined.

Table 23. Effectiveness Outcomes, Hemodynamics, Mean Pressure Gradient: AVR All patients analyzed: N=1254, number in

Preoperative 3–6 Months 1 Year 3 Years 5 Years

n/N % n/N % n/N % n/N % n/N %

Table 21. Effectiveness Outcomes, Functional NYHA: MVR All patients analyzed: N=366

Preoperative 3–6 Months 1 Year 3 Years 4 Years

n/N % n/N % n/N % n/N % n/N %

(numerator/N)

79% (960/1210) 77% (889/1160) 75% (851/1132) 76% (480/634) 69% (42/61)

13% (156/1210) 15% (172/1160) 16% (181/1132) 16% (98/634) 16% (10/61)

7% (85/1210) 7% (85/1160) 7% (84/1132) 7% (44/634) 10% (6/61)

1% (9/1210) 1% (12/1160) 1% (14/1132) 2% (12/634) 5% (3/61)

0% (0/1210) 0% (2/1160) 0% (2/1132) 0% (0/634) 0% (0/61)

0% (0/1210) 0% (0/1160) 0% (0/1132) 0% (0/634) 0% (0/61)

subgroup/N, mean ± SD [min., max.]

Endpoint ≤ 30 Days 3–6 Months 1 Year 3 Years 5 Years Mean Pressure Gradient (mm Hg)

21 mm 217/240 14.6 ± 6.5

[2.7, 54.7]

23 mm 458/497 13.0 ± 5.3

[0.9, 37.0]

20 Instructions for Use English

203/240 13.4 ± 5.4

[3.0, 34.4]

449/497 11.8 ± 4.8

[2.0, 43.1]

198/240 14.7 ± 5.5

[2.0, 40.5]

439/497 12.9 ± 5.1

[3.0, 32.7]

114/240 16.1 ± 6.1

[4.5, 39.1]

258/497 14.0 ± 5.4

[3.1, 35.5]

19/240 15.0 ± 4.7

[7.3, 24.0]

25/497 12.6 ± 5.4

[4.4, 31.9]

Endpoint ≤ 30 Days 3–6 Months 1 Year 3 Years 5 Years

25 mm 335/362 11.6 ± 4.9

[2.0, 32.0]

27 mm 119/130 11.1 ± 4.1

[2.0, 21.5]

29 mm 24/25 12.6 ± 5.8

[7.0, 28.8]

Table 24. Effectiveness Outcomes, Hemodynamics, Effective Orifice Area: AVR All patients analyzed: N=1254, number in

Endpoint ≤ 30 Days 3–6 Months 1 Year 3 Years 5 Years Effective Orifice Area (cm2)

21 mm 217/240 1.4 ± 0.4

[0.6, 3.7]

23 mm 460/497 1.6 ± 0.5

[0.7, 3.9]

25 mm 337/362 1.8 ± 0.5

[0.8, 4.2]

27 mm 119/130 1.9 ± 0.6

[1.0, 4.3]

29 mm 24/25 2.0 ± 0.5 [1.0,

2.9]

Table 25. Effectiveness Outcomes, Hemodynamics, Valvular Regurgitation: MVR All patients analyzed: N=366, percent

331/362 10.6 ± 4.4

[1.1, 35.7]

114/130 9.1 ± 4.0

[2.0, 23.1]

21/25 8.6 ± 2.9 [3.5,

16.8]

subgroup/N, mean ± SD [min., max.]

203/240 1.4 ± 0.4

[0.7, 3.8]

450/497 1.6 ± 0.5

[0.8, 5.4]

331/362 1.8 ± 0.5

[0.7, 4.0]

114/130 2.0 ± 0.5

[1.0, 3.4]

21/25 2.3 ± 0.6 [1.4,

3.6]

(numerator/N)

316/362 11.7 ± 5.2

[2.0, 38.9]

110/130 10.0 ± 4.0

[3.4, 22.7]

22/25 10.1 ± 2.6

[4.6, 16.0]

198/240 1.3 ± 0.4

[0.6, 3.1]

440/497 1.5 ± 0.4

[0.7, 3.4]

317/362 1.8 ± 0.5

[0.7, 4.2]

110/130 2.0 ± 0.6

[1.1, 3.7]

22/25 2.1 ± 0.7 [1.3,

4.1]

169/362 12.1 ± 5.5

[3.3, 43.1]

51/130 10.6 ± 4.1

[3.3, 24.6]

16/25 9.9 ± 2.5 [5.9,

15.1]

114/240 1.3 ± 0.3

[0.7, 2.5]

259/497 1.5 ± 0.4

[0.7, 3.2]

170/362 1.7 ± 0.5

[0.6, 4.0]

51/130 1.9 ± 0.6

[1.0, 4.2]

16/25 2.2 ± 0.6 [1.2,

3.4]

11/362 9.3 ± 2.4

[6.3, 13.4]

2/130 10.4 ± 0.3

[10.2, 10.6]

1/25 7.5 [7.5, 7.5]

19/240 1.5 ± 0.3

[1.1, 2.1]

25/497 1.8 ± 0.3

[1.3, 2.4]

11/362 2.2 ± 0.5

[1.6, 3.0]

2/130 2.6 ± 0.6 [2.2,

3.0]

1/25 3.1 [3.1, 3.1]

Endpoint ≤ 30 Days 3–6 Months 1 Year 3 Years 4 Years Valvular Regurgitation

% of pts. with no regurgitation

% of pts. with trivial regurgitation

% of pts. with mild regurgitation

% of pts. with mod regurgitation

% of pts. with mod severe regurgitation

% of pts. with severe regurgitation

Note: Data reflect transvalvular, paravalvular, and indeterminate regurgitation noted at all locations combined.

Table 26. Effectiveness Outcomes, Hemodynamics, Mean Pressure Gradient: MVR All patients analyzed: N=366, number in

Endpoint ≤ 30 Days 3–6 Months 1 Year 3 Years 4 Years Mean Pressure Gradient (mm Hg)

25 mm 42/48 5.9 ± 2.2 [3.0,

27 mm 107/115 5.3 ± 2.2

29 mm 134/137 5.0 ± 2.1

31 mm 56/57 4.7 ± 1.9 [2.0,

33 mm 9/9 4.1 ± 2.0 [2.0,

81% (281/349) 77% (258/336) 77% (248/321) 77% (96/124) 75% (54/72)

15% (51/349) 16% (52/336) 15% (49/321) 17% (21/124) 17% (12/72)

3% (12/349) 6% (19/336) 5% (15/321) 3% (4/124) 7% (5/72)

1% (5/349) 2% (6/336) 2% (7/321) 1% (1/124) 0% (0/72)

0% (0/349) 0% (1/336) 0% (1/321) 2% (2/124) 1% (1/72)

0% (0/349) 0% (0/336) 0% (1/321) 0% (0/124) 0% (0/72)

subgroup/N, mean ± SD [min., max.]

13.0]

[2.0, 12.0]

[1.0, 15.0]

10.3]

7.1]

40/48 5.5 ± 2.1 [1.0,

12.0]

105/115 4.8 ± 2.1

[1.0, 13.1]

128/137 4.4 ± 2.0

[1.0, 12.5]

53/57 4.1 ± 1.6 [1.0,

7.6]

8/9 3.3 ± 2.6 [1.0,

9.0]

41/48 5.7 ± 1.7 [3.0,

10.6]

98/115 4.6 ± 2.1

[1.0, 13.0]

123/137 4.4 ± 1.8

[1.0, 9.0]

50/57 3.7 ± 1.4 [1.0,

6.5]

8/9 3.4 ± 1.8 [1.0,

5.3]

11/48 5.0 ± 1.7 [1.9,

8.0]

42/115 4.8 ± 2.8

[1.0, 16.2]

48/137 3.9 ± 1.7

[1.0, 8.7]

18/57 3.9 ± 2.0 [2.0,

9.1]

4/9 4.1 ± 1.8 [2.0,

6.0]

8/48 5.1 ± 1.2 [3.2,

7.0]

21/115 4.3 ± 2.1

[1.0, 9.7]

27/137 4.7 ± 2.1

[1.8, 12.0]

15/57 3.5 ± 2.2 [1.0,

9.6]

1/9 6.0 [6.0, 6.0]

Instructions for Use English 21

Table 27. Effectiveness Outcomes, Hemodynamics, Effective Orifice Area: MVR All patients analyzed: N=366, number in

subgroup/N, mean ± SD [min., max.]

Endpoint ≤ 30 Days 3–6 Months 1 Year 3 Years 4 Years Effective Orifice Area (cm2)

25 mm 39/48 1.6 ± 0.4 [0.9,

2.9]

27 mm 95/115 1.7 ± 0.6

[0.8, 4.6]

29 mm 119/137 1.7 ± 0.5

[0.7, 3.1]

31 mm 53/57 1.6 ± 0.5 [0.5,

3.0]

33 mm 8/9 1.6 ± 0.6 [0.9,

2.5]

7.3. Supplemental data (aortic 19 mm only)

Twenty-three patients, implanted at 2 centers, had isolated aortic valve replacement (AVR) with the size 19 mm bioprosthesis. The safety endpoints were mortality and valve-related morbidity. The effectiveness endpoints were New York Heart Association

(NYHA) functional classification and hemodynamic assessments obtained by echocardiography. Patient demographic data and effectiveness data are summarized in the following tables.

Age at implant in years (mean ± SD, N [min., max.]) 77 ± 5, 23 [67, 89] Gender (% male / % female) 9% / 91% Etiology

Stenosis-% of pts with stenosis alone (% (number in subgroup/N))

Insufficiency-% of pts with insufficiency alone (% (number in subgroup/N))

Mixed-% of pts. with stenosis and insufficiency (% (number in subgroup/N))

Table 29. Effectiveness Outcomes, Functional NYHA: AVR All patients analyzed: N=23, (numerator/N), percent

36/48 1.7 ± 0.8 [0.7,

5.6]

94/115 1.7 ± 0.4

[0.9, 2.9]

114/137 1.8 ± 0.5

[0.7, 3.4]

48/57 1.8 ± 0.6 [1.0,

3.1]

6/9 1.8 ± 0.4 [1.3,

2.6]

Table 28. Patient Demographics: AVR

35/48 1.6 ± 0.4 [0.8,

2.3]

90/115 1.7 ± 0.5

[0.7, 3.7]

114/137 1.8 ± 0.5

[0.8, 3.0]

43/57 1.7 ± 0.5 [1.0,

3.2]

6/9 1.9 ± 0.5 [1.3,

2.6]

8/48 1.8 ± 0.6 [1.2,

2.8]

37/115 1.7 ± 0.5

[0.3, 3.3]

44/137 1.8 ± 0.5

[1.1, 3.1]

16/57 1.9 ± 0.7 [1.1,

3.8]

4/9 1.9 ± 0.3 [1.6,

2.2]

65% (15/23)

0% (0/23)

35% (8/23)

8/48 1.9 ± 0.5 [1.2,

3.0]

18/115 1.6 ± 0.3

[1.2, 2.4]

24/137 1.7 ± 0.4

[1.1, 2.8]

14/57 1.9 ± 0.6 [0.7,

3.0]

1/9 1.8 [1.8, 1.8]

NYHA Class Preoperative 3–6 Months 1 Year

n/N % n/N % n/N %

I 0/23 0% 4/16 25% 3/15 20%

II 7/23 30% 12/16 75% 12/15 80% III 12/23 52% 0/16 0% 0/15 0% IV 4/23 17% 0/16 0% 0/15 0%

Table 30. Effectiveness Outcomes, Hemodynamics, Valvular Regurgitation: AVR All patients analyzed: N=23, percent

(numerator/N)

Endpoint ≤ 30 Days 3–6 Months 1 Year Valvular Regurgitation

% of pts. with no regurgitation 71% (15/21) 63% (10/16) 60% (9/15) % of pts. with trivial regurgitation 14% (3/21) 31% (5/16) 27% (4/15) % of pts. with mild regurgitation 14% (3/21) 6% (1/16) 13% (2/15) % of pts. with mod regurgitation 0% (0/21) 0% (0/16) 0% (0/15) % of pts. with mod severe regurgitation 0% (0/21) 0% (0/16) 0% (0/15) % of pts. with severe regurgitation 0% (0/21) 0% (0/16) 0% (0/15)

Note: Data reflect transvalvular, paravalvular and indeterminate regurgitation noted at all locations combined.

Table 31. Effectiveness Outcomes, Hemodynamics, Mean Pressure Gradient And Effective Orifice Area: AVR All patients

analyzed: N=23, number in subgroup/N, mean ± SD [min., max.]

Endpoint ≤ 30 Days 3–6 Months 1 Year Mean Pressure Gradient (mm Hg) 18/23, 18.0 ± 6.4 [9.0, 32.5] 16/23, 15.6 ± 6.0 [7.0, 31.0] 14/23, 15.3 ± 5.3 [8.0, 26.0] Effective Orifice Area (cm2)

18/23, 1.2 ± 0.4 [0.8, 2.8] 16/23, 1.1 ± 0.2 [0.8, 1.4] 14/23, 1.1 ± 0.1 [0.9, 1.3]

22 Instructions for Use English

7.4. Six year data (aortic and mitral 19 to 33 mm)

Seven hundred ninety-seven (797) patients had isolated aortic valve replacement (AVR) and 232 patients had isolated mitral valve replacement (MVR). The safety endpoints captured in this study were mortality and valve-related morbidity. The effectiveness endpoints in this study were New York Heart Association (NYHA) functional classification and hemodynamic assessments obtained by echocardiography. Patient demographic data and effectiveness data are summarized in the following tables.

Table 32. Patient Demographics

Mosaic Bioprosthesis Clinical Study AVR (N = 797)

Age at implant in years (mean ± SD, N [min., max.]) 69 ± 8, 797 [21, 88] Gender (% male / % female) 66% / 34% Etiology

Stenosis- % of pts. with stenosis alone (% (number in subgroup/N))

Insufficiency- % of pts. with insufficiency alone (% (number in subgroup/N))

Mixed-% of pts. with stenosis and insufficiency (% (number in subgroup/N))

Mosaic Bioprosthesis Clinical Study MVR (N = 232)

Age at implant in years (mean ± SD, N [min., max.]) 67 ± 10, 232 [17, 84] Gender (% male / % female) 48% / 52% Etiology

Stenosis- % of pts. with stenosis alone (% (number in subgroup/N))

Insufficiency- % of pts. with insufficiency alone (% (number in subgroup/N))

Mixed-% of pts. with stenosis and insufficiency (% (number in subgroup/N))

Table 33. Effectiveness Outcomes, Functional NYHA

64% (513/797)

13% (106/797)

22% (178/797)

9% (20/232)

78% (181/232)

13% (31/232)

NYHA Class Preoperative 1 Year 4 Years 8 Years

n/N % n/N % n/N % n/N %

Mosaic Bioprosthesis Clinical Study AVR (N = 797)

I 15/797 1.9% 534/729 73.3% 320/589 54.3% 12/38 31.6%

II 227/797 28.5% 187/729 25.6% 252/589 42.8% 26/38 68.4% III 454/797 57.0% 7/729 1.0% 15/589 2.6% 0/38 0.0% IV 101/797 12.7% 1/729 0.1% 2/589 0.3% 0/38 0.0%

NYHA Class Preoperative 1 Year 4 Years 8 Years

n/N % n/N % n/N % n/N %

Mosaic Bioprosthesis Clinical Study MVR (N = 232)

I 0/232 0.0% 141/207 68.1% 74/172 43.0% 16/36 44.4%

II 61/232 26.3% 64/207 30.9% 93/172 54.1% 20/36 55.6%

III 147/232 63.4% 2/207 1.0% 5/172 2.9% 0/36 0.0% IV 24/232 10.3% 0/207 0.0% 0/172 0.0% 0/36 0.0%

Table 34. Effectiveness Outcomes, Hemodynamics, Valvular Regurgitation: AVR All patients analyzed: N=797, percent

(numerator/N)

Endpoint 1 Year 4 Years 8 Years Valvular Regurgitation

% of pts. with no regurgitation 72.8% (534/734) 71.8% (417/581) 59.0% (23/39) % of pts. with trivial regurgitation 17.7% (130/734) 19.6% (114/581) 30.8% (12/39) % of pts. with mild regurgitation 7.6% (56/734) 7.1% (41/581) 10.3% (4/39) % of pts. with mod regurgitation 1.6% (12/734) 1.4% (8/581) 0.0% (0/39) % of pts. with mod severe regurgitation 0.3% (2/734) 0.0% (0/581) 0.0% (0/39) % of pts. with severe regurgitation 0.0% (0/734) 0.2% (1/581) 0.0% (0/39)

Note: Data reflect transvalvular, paravalvular and indeterminate regurgitation noted at all locations combined.

Instructions for Use English 23

Table 35. Effectiveness Outcomes, Hemodynamics, Mean Pressure Gradient: AVR All patients analyzed: N=797, number in

subgroup/N, mean ± SD [min., max.]

Endpoint 1 Year 4 Years 8 Years Mean Pressure Gradient (mm Hg)

19 mm 5/7 15.2 ± 4.5 [10.6, 22.3] 0/7 0/7 21 mm 132/154 14.8 ± 5.3 [2.0, 40.5] 104/154 16.6 ± 6.5 [7.0, 48.6] 9/154 15.4 ± 7.3 [8.7, 30.8] 23 mm 276/316 12.9 ± 5.1 [3.0, 32.7] 226/316 13.7 ± 5.6 [3.9, 48.8] 13/316 13.8 ± 7.5 [7.7, 28.8] 25 mm 192/221 11.8 ± 5.3 [2.9, 38.9] 154/221 12.2 ± 5.4 [3.4, 36.3] 10/221 10.4 ± 4.5 [4.4, 19.4] 27 mm 67/77 9.9 ± 4.1 [3.4, 22.7] 53/77 10.3 ± 4.1 [2.2, 22.0] 4/77 9.5 ± 2.8 [6.9, 12.6] 29 mm 20/22 10.0 ± 2.8 [4.6, 16.0] 15/22 10.3 ± 4.1 [6.5, 20.5] 2/22 10.5 ± 1.7 [9.3, 11.7]

Table 36. Effectiveness Outcomes, Hemodynamics, Effective Orifice Area: AVR All patients analyzed: N=797, number in

subgroup/N, mean ± SD [min., max.]

Endpoint 1 Year 4 Years 8 Years Effective Orifice Area (cm2)

19 mm 5/7 1.2 ± 0.1 [1.1, 1.3] 0/7 0/7 21 mm 132/154 1.3 ± 0.3 [0.6, 3.1] 105/154 1.3 ± 0.3 [0.7, 2.1] 8/154 1.3 ± 0.3 [0.8, 1.7] 23 mm 276/316 1.5 ± 0.4 [0.8, 3.4] 225/316 1.5 ± 0.4 [0.7, 3.3] 13/316 1.6 ± 0.3 [1.0, 2.1] 25 mm 193/221 1.8 ± 0.5 [0.7, 4.2] 153/221 1.7 ± 0.5 [0.4, 3.4] 10/221 1.6 ± 0.3 [1.2, 2.2] 27 mm 67/77 2.0 ± 0.6 [1.1, 3.5] 51/77 1.9 ± 0.6 [1.2, 3.3] 4/77 1.9 ± 0.7 [1.4, 3.0] 29 mm 20/22 2.1 ± 0.7 [1.3, 4.1] 15/22 2.3 ± 0.7 [1.3, 3.8] 2/22 2.2 ± 1.2 [1.4, 3.1]

Table 37. Effectiveness Outcomes, Hemodynamics, Valvular Regurgitation: MVR All patients analyzed: N=232, percent

(numerator/N)

Endpoint 1 Year 4 Years 8 Years Valvular Regurgitation

% of pts. with no regurgitation 78.5% (164/209) 69.4% (118/170) 70.6% (24/34) % of pts. with trivial regurgitation 15.8% (33/209) 7.6% (13/170) 2.9% (1/34) % of pts. with mild regurgitation 3.8% (8/209) 20.0% (34/170) 20.6% (7/34) % of pts. with mod regurgitation 1.4% (3/209) 1.8% (31/170) 2.9% (1/34) % of pts. with mod severe regurgitation 0.0% (0/209) 0.0% (0/170) 0.0% (0/34) % of pts. with severe regurgitation 0.5% (1/209) 1.2% (2/170) 2.9% (1/34)

Note: Data reflect transvalvular, paravalvular and indeterminate regurgitation noted at all locations combined.

Table 38. Effectiveness Outcomes, Hemodynamics, Mean Pressure Gradient: MVR All patients analyzed: N=232, number in

subgroup/N, mean ± SD [min., max.]

Endpoint 1 Year 4 Years 8 Years Mean Pressure Gradient (mm Hg)

25 mm 39/44 5.8 ± 1.7 [3.0, 10.6] 30/44 5.7 ± 2.0 [2.6, 12.4] 5/44 5.4 ± 1.3 [3.3, 6.4] 27 mm 74/86 4.9 ± 2.0 [2.0, 13.0] 58/86 4.7 ± 2.0 [1.0, 10.0] 9/86 5.1 ± 1.3 [3.7, 8.3] 29 mm 69/74 4.8 ± 1.7 [2.0, 9.0] 58/74 5.1 ± 2.3 [1.9, 14.1] 12/74 5.7 ± 2.5 [2.8, 10.3] 31 mm 23/24 4.0 ± 1.2 [1.9, 6.5] 21/24 3.9 ± 1.8 [1.6, 9.6] 8/24 4.6 ± 3.1 [2.3, 12.0] 33 mm 4/4 4.0 ± 1.5 [2.0, 5.3] 3/4 4.6 ± 2.5 [3.0, 7.5] 0/4

Table 39. Effectiveness Outcomes, Hemodynamics, Effective Orifice Area: MVR All patients analyzed: N=232, number in

subgroup/N, mean ± SD [min., max.]

Endpoint 1 Year 4 Years 8 Years Effective Orifice Area (cm2)

25 mm 33/44 1.6 ± 0.4 [0.8, 2.3] 28/44 1.5 ± 0.4 [0.7, 2.2] 5/44 1.4 ± 0.7 [0.9, 2.5] 27 mm 71/86 1.7 ± 0.5 [0.8, 3.5] 52/86 1.7 ± 0.6 [0.7, 3.9] 6/86 1.4 ± 0.3 [1.2, 2.0] 29 mm 67/74 1.8 ± 0.5 [0.8, 3.0] 53/74 1.8 ± 0.5 [0.8, 2.9] 10/74 1.8 ± 0.5 [0.8, 2.5] 31 mm 20/24 2.0 ± 0.6 [1.3, 3.2] 20/24 1.9 ± 0.6 [0.7, 3.1] 8/24 1.6 ± 0.5 [1.0, 2.4] 33 mm 4/4 1.9 ± 0.6 [1.3, 2.6] 3/4 2.6 ± 1.4 [1.2, 4.0] 0/4

8. Individualization of treatment

Long-term anticoagulant and/or antiplatelet therapy should be considered for patients with a dilated left atrium, a history of thromboembolic events, or a cardiac rhythm of atrial fibrillation or atrial flutter.

24 Instructions for Use English

8.1. Specific patient populations

The safety and effectiveness of the Mosaic bioprosthesis has not been established for the following specific populations because it has not been studied in these populations:

■

Patients who are pregnant

■

Nursing mothers

■

Patients with abnormal calcium metabolism (eg, chronic renal failure, hyperparathyroidism)

■

Patients with aneurysmal aortic degenerative conditions (eg, cystic medial necrosis, Marfan’s Syndrome)

■

Children, adolescents, or young adults

9. Patient counseling information

Patients may require anticoagulation and/or antiplatelet therapy for an indefinite period based on each patient’s condition. Patients with bioprostheses are at risk for bacteremia (eg, undergoing dental procedures) and should be advised about

prophylactic antibiotic therapy. Patients should be encouraged to carry the Implanted Device Identification Card, provided by Medtronic, with them at all times.

10. How supplied

10.1. Packaging

The Mosaic bioprosthesis is chemically sterilized and is supplied sterile in a buffered 0.2% glutaraldehyde storage solution. Sterility is compromised if the glass jar and lid container is opened and/ or damaged. The outside of the container is not sterile and should not be placed in the sterile field.

10.2. Storage

The Mosaic bioprosthesis must be stored between 5°C and 25°C (41°F and 77°F). Refrigeration is not required, and freezing may damage the bioprosthesis. Room temperature storage up to 25°C (77°F) is satisfactory provided the bioprosthesis is not exposed to sunlight or other ultraviolet light sources or placed where significant temperature fluctuations may occur.

Appropriate inventory control should be maintained so that bioprostheses with earlier Use-by dates are preferentially implanted and expiration is avoided.

10.3. Return of explanted bioprostheses

Medtronic is interested in obtaining recovered Mosaic bioprostheses. When determined to be appropriate, explants will be studied by a consulting pathologist. A written report summarizing the findings will be returned to the physician. Product return kits, including an explant information form, are available by contacting Medtronic distribution centers or a Medtronic sales representative. It is important that the explant form be completely filled out. If a kit is not available, place the explanted bioprosthesis in a container of glutaraldehyde or 10% buffered formalin immediately after excision. For further instructions on the return of an explanted device, contact a Medtronic sales representative.

11. Patient information

11.1. Registration information Note: Patient registration does not apply in countries where patient privacy laws conflict with providing patient information,

including countries from the European Union. A Patient Registration Form is included in each device package. After implantation, please complete all requested information.

The serial number may be found on the package and on the identification tag attached to the retainer. Return the original form to the Medtronic address indicated on the form and provide the temporary identification card to the patient prior to discharge.

An Implanted Device Identification Card is provided to the patient. The card contains the name and telephone number of the patient’s physician, as well as information that medical personnel would require in the event of an emergency.

11.2. Patient manual

Medtronic has prepared a Patient Information Pamphlet that the physician should provide to the patient prior to discharge. Copies of these pamphlets may be obtained from a Medtronic sales representative.

12. Postoperative information

12.1. MRI safety information

Nonclinical testing has demonstrated the Mosaic bioprosthesis is MR Conditional. A patient with this device can be safely scanned immediately after implantation in an MR system meeting the following conditions:

■

Static magnetic field of 1.5 T or 3 T

■

Maximum spatial field gradient of 2500 gauss/cm or less

■

Maximum MR system reported, whole-body-averaged specific absorption rate (SAR) of 4 W/kg (First Level Controlled Operating Mode)

Instructions for Use English 25

Under the scan conditions defined above, the Mosaic bioprosthesis is expected to produce a maximum temperature rise of less than 2.2°C after 15 minutes of continuous scanning.

In nonclinical testing, the image artifact caused by the device extends approximately 20 mm from the Mosaic bioprosthesis when imaged with a gradient echo pulse sequence and 3T MRI system.

13. Accessories

Use the sizers or obturators specified below to determine the appropriate size Mosaic bioprostheses.

■

Mosaic™ aortic sizers, Model 7308C

■

Mosaic Ultra™ aortic sizers, Model 7308U

■

Mosaic mitral obturators, Model 7310

■

Medtronic valve handle, Model 7639

■

Medtronic lock nut, Model 7642

Caution: Do not use other manufacturers’ valve sizers/obturators, or sizers/obturators for another Medtronic prosthesis, to size the Mosaic bioprosthesis.

Caution: Do not use the accessories until they have been thoroughly cleaned and sterilized. Refer to the appropriate Instructions for Use for further instructions.

14. Indexed EOA chart—aortic valve

The Indexed Effective Orifice Area (iEOA) chart may be utilized to identify the aortic valve size to avoid patient-prosthesis mismatch1. The iEOA chart information is intended for reference purposes only. Base the final valve size selection on the sizer criteria and each patient’s individual clinical situation. To assist in avoiding patient-prosthesis mismatch, select a valve size that achieves an indexed effective orifice area of ≥ 0.75 cm2/m2. If the indexed effective orifice area is < 0.75 cm2/m2 (shaded in gray), consideration should be given to a root enlargement procedure. The hemodynamic data is at 1 year follow-up2.

1. Determine the patient’s Body Surface Area (BSA).

2. Using the chart, select valve size with iEOA ≥ 0.75 to maximize patient-prosthesis matching.

Valve size (mm)

19 21 23 25 27 29

EOA (cm2)

1.20 1.30 1.50 1.80 2.00 2.10

Patient’s BSA

(m2)

1.0 1.20 1.30 1.50 1.80 2.00 2.10

1.1 1.09 1.18 1.36 1.64 1.82 1.91

1.2 1.00 1.08 1.25 1.50 1.67 1.75

1.3 0.92 1.00 1.15 1.38 1.54 1.62

1.4 0.86 0.93 1.07 1.29 1.43 1.50

1.5 0.80 0.87 1.00 1.20 1.33 1.40

1.6 0.75 0.81 0.94 1.13 1.25 1.31

1.7 0.71 0.76 0.88 1.06 1.18 1.24

1.8 0.67 0.72 0.83 1.00 1.11 1.17

1.9 0.63 0.68 0.79 0.95 1.05 1.11

2.0 0.60 0.65 0.75 0.90 1.00 1.05

2.1 0.57 0.62 0.71 0.86 0.95 1.00

2.2 0.55 0.59 0.68 0.82 0.91 0.95

2.3 0.52 0.57 0.65 0.78 0.87 0.91

2.4 0.50 0.54 0.63 0.75 0.83 0.88

2.5 0.48 0.52 0.60 0.72 0.80 0.84

2.6 0.46 0.50 0.58 0.69 0.77 0.81

2.7 0.44 0.48 0.56 0.67 0.74 0.78

Note: Hemodynamic data at 1 year follow-up, PMA data

Warning: Do not oversize. Implanting too large a valve in a patient can lead to stent distortion and/or valve inflow obstruction

and an increased risk for stenosis, regurgitation, or reduced valve durability. Warning: Implanting too small a valve in a patient can lead to an increased risk for stenosis.

Daneshvar S, Rahimtoola SH.Valve Prosthesis-patient mismatch (VP-PM): A long-term perspective. Journal American College of Cardiology. 2012;60:1123-35.

Fradet GJ, Bleese N, Burgess J, and Cartier PC. Mosaic valve international clinical trial: Early performance results. Ann Thorac Surg. 2001;71:S273-277.

26 Instructions for Use English

15. Disclaimer of warranty

THE FOLLOWING DISCLAIMER OF WARRANTY APPLIES TO UNITED STATES CUSTOMERS ONLY:

ALTHOUGH THE MOSAIC BIOPROSTHESES, MODELS 305 AND 310, HEREAFTER REFERRED TO AS “PRODUCT,” HAVE BEEN MANUFACTURED UNDER CAREFULLY CONTROLLED CONDITIONS, MEDTRONIC HAS NO CONTROL OVER THE CONDITIONS UNDER WHICH THIS PRODUCT IS USED. MEDTRONIC THEREFORE DISCLAIMS ALL WARRANTIES, BOTH EXPRESS AND IMPLIED, WITH RESPECT TO THE PRODUCT, INCLUDING, BUT NOT LIMITED TO, ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. MEDTRONIC SHALL NOT BE LIABLE TO ANY PERSON OR ENTITY FOR ANY MEDICAL EXPENSES OR ANY DIRECT, INCIDENTAL, OR CONSEQUENTIAL DAMAGES CAUSED BY ANY USE, DEFECT, FAILURE, OR MALFUNCTION OF THE PRODUCT, WHETHER A CLAIM FOR SUCH DAMAGES IS BASED UPON WARRANTY, CONTRACT, TORT, OR OTHERWISE. NO PERSON HAS ANY AUTHORITY TO BIND MEDTRONIC TO ANY REPRESENTATION OR WARRANTY WITH RESPECT TO THE PRODUCT.

The exclusions and limitations set out above are not intended to, and should not be construed so as to, contravene mandatory provisions of applicable law. If any part or term of this DISCLAIMER OF WARRANTY is held by any court of competent jurisdiction to be illegal, unenforceable, or in conflict with applicable law, the validity of the remaining portion of the DISCLAIMER OF WARRANTY shall not be affected, and all rights and obligations shall be construed and enforced as if this DISCLAIMER OF WARRANTY did not contain the particular part or term held to be invalid.

Instructions for Use English 27

Medtronic, Inc.

*1220016001*

710 Medtronic Parkway Minneapolis, MN 55432 USA www.medtronic.com +1 763 514 4000 LifeLine Technical Support, 24-hour consultation service: 1 877 526 7890

Medtronic Heart Valves Division 1851 E. Deere Avenue Santa Ana, CA 92705 USA

Medtronic B.V. Earl Bakkenstraat 10 6422 PJ Heerlen The Netherlands +31 45 566 8000

Canada

Medtronic of Canada Ltd 99 Hereford Street Brampton, Ontario L6Y 0R3 Canada 1 800 268 5346

Medtronic 310C27 Instructions for Use

Specifications and Main Features

Frequently Asked Questions

User Manual

1. Device description

2. Indications for use

3. Contraindications

4. Warnings and precautions

4.1. Warnings

4.2. Precautions

5. Adverse events

5.1. Original PMA data

5.2. Supplemental data (all aortic and mitral sizes except aortic 19 mm)

5.3. Supplemental data (aortic 19 mm only)

5.4. Six year data (aortic and mitral 19 to 33 mm)

5.5. Potential adverse events

6. Instructions for use

6.1. Physician training

6.2. Device features

6.3. Handling and preparation instructions

6.4. Rinse procedure

6.5. Device implantation Caution: Do not use if the bioprosthesis has been damaged. Caution: Extreme care must be taken to prevent damage to the delicate bioprosthesis tissue. Do not handle the tissue portion

7. Clinical studies

7.1. Original PMA data

7.2. Supplemental data (all aortic and mitral sizes except aortic 19 mm)

7.3. Supplemental data (aortic 19 mm only)

7.4. Six year data (aortic and mitral 19 to 33 mm)

8. Individualization of treatment

8.1. Specific patient populations

9. Patient counseling information

10. How supplied

10.1. Packaging

10.2. Storage

10.3. Return of explanted bioprostheses

11. Patient information

11.1. Registration information Note: Patient registration does not apply in countries where patient privacy laws conflict with providing patient information,

11.2. Patient manual

12. Postoperative information

12.1. MRI safety information

13. Accessories

15. Disclaimer of warranty