Mosaic Bioprosthesis 8 Year Clinical CompendiumFebruary 2004 The Mosaic® bioprosthesis is marking the 10th anniversary of its ﬁrst implant this month. We are proud to present our

MOSAIC®

Aortic and Mitral Bioprosthesis

Eight Year Clinical Compendium

February 2004

The Mosaic® bioprosthesis is marking the 10th anniversary of its first implant this month.

We are proud to present our 8-year results from the original clinical patient cohort. As part of our protocol,

all patients are followed yearly and echocardiographs are performed every other year. This comprehensive

prospective study gives us a clear picture of the outstanding performance of the Mosaic bioprosthesis in

both the aortic and mitral positions.

You will see that our hemodynamic results (gradients, EOA, regurgitation) are stable over time—a positive sign

that valve performance remains as strong as it was after implant.

Out of a total 1,029 patients, we did experience three structural valve deteriorations: two in the aortic position

and one in the mitral position. Detailed case reports on those three patients can be found in this compendium.

Both aortic valve deteriorations occurred in younger patients. The mitral valve deterioration occurred in an

older patient with a long list of co-morbidity factors. All patients underwent successful re-implantations.

The low rate of calcification reported is encouraging. We’ll continue to provide our customers with more

information regarding the effectiveness of our proprietary 3rd generation technologies: AOA®** tissue treatment

and the Physiologic Fixation™ process. A recent study by Melina and Yacoub provides some evidence of the short-

term effectiveness of these technologies in humans when compared to the homograft.*

Our combined transient and permanent thromboembolism rates are also exemplary in both aortic

(1.4%/pt. yr.) and mitral (1.6%/pt. yr.) positions. We also show excellent patient survival rates in line

with the background population.

In 2003, we introduced the Cinch® Advanced Implant System on our Mosaic aortic valve. Both it and the Mitral

Ratchet mechanism have been positively received, reinforcing our commitment to optimizing implantability,

supra-annular placement and upsizing.

We continue to follow this patient cohort closely and will report on its progress periodically.

Thank you for your continued support,

Medtronic Heart Valves

* Homograft versus Medtronic Freestyle full aortic root replacement. Five year follow-up from a prospective, randomized trial.

Melina G, Nyawo B, Amrani M, Khaghani A, Yacoub M. Academic Department of Cardiothoracic Surgery, National Heart and Lung

Institute, Imperial College, London, UK. Presented at the Society for Heart Valve Disease, Paris, 2003.

* *AOA is a registered trademark of Biomedical Design, Inc., Atlanta, GA.

M O S A I C ® B I O P R O S T H E S I S

The Mosaic® Aortic and Mitral Bioprostheses .........................................................2

The Clinical Study ............................................................................................................2

Study Design .......................................................................................................................................... 2

Patient Demographics and Methods .............................................................................................. 2

Statistical Methods ............................................................................................................................... 3

Aortic Valve Replacement .............................................................................................4

Mitral Valve Replacement ............................................................................................ 10

Case Reports .................................................................................................................... 16

Discussions and Conclusions ...................................................................................... 18

References ........................................................................................................................ 18

Clinical Centers ............................................................................................................... 18

TABLE OF CONTENTS

2 Mosaic Bioprosthesis

The Mosaic® Aortic and Mitral BioprosthesesThe Mosaic aortic and mitral bioprostheses are secured to a polyester covered, flexible acetal homo polymer stent. The inflow aspects of the aortic and mitral valves approximate the natural anatomy of the annuli. The aortic valve stent and sewing ring are scalloped to enable mounting either within the annulus or in the supra-annular (Supra-X™) position. If preferred, a larger aortic valve may be used in a supra-annular position to optimize hemodynamic performance in patients with a small aortic root and to minimize the occurrence of patient-prosthesis mismatch.

The sewing ring of the mitral valve contains polyester felt allowing for easy needle penetration and low suture drag. Both aortic and mitral stents have a lowered profile (approximately 2mm across all valve sizes) as compared to the stent of the standard Hancock® Bioprosthesis.

Studies show that calcification of bioprostheses is bi-modal—having biochemical as well as biomechanical com-ponents.1 The Mosaic bioprostheses are designed to help address the issue of tissue calcification from a bi-modal perspective. Both the Mosaic aortic and mitral bioprostheses are treated with AOA®** tissue treatment, intended to reduce the potential for mineralization of the leaflets, and Physiologic Fixation,™ a process that combines root pres-sure fixation with leaflets fixed at zero-pressure differential. The Physiologic Fixation process is intended to retain the natural leaflet structure and function and enhance hemodynamic performance by preserving aortic root geometry.

AOA treatment is the only tissue treatment evaluated in a prospective, randomized study in humans, yielding valuable information regarding calcification mitigation in both wall and leaflets.*

The Clinical StudyThe prospective, nonrandomized, multi-center clinical trial of the Mosaic bioprosthesis began on February 10, 1994. Seventeen primary centers participated in this study: five centers in Europe, nine centers in Canada, two centers in Australia, and one center in New Zealand. All centers followed a common study protocol. Following FDA approval of this bioprosthesis on July 14, 2000, a long-term clinical study of the Mosaic bioprosthesis was initiated. A cohort of six centers from the original Mosaic study are participating in this long-term follow-up study.2

This report provides an assessment of the clinical data available from February 25, 1994, through July 1, 2003 from 1029 patients who had isolated aortic valve replacement (AVR) or isolated mitral valve replacement (MVR) with the Mosaic bioprosthesis at these six centers in the long-term follow-up study.

See page 18 for the six cohort centers.

Study DesignThis prospective, nonrandomized, multi-center clinical trial used a common protocol and included only patients undergoing isolated aortic (AVR) or mitral (MVR) valve replacement. Study methods and data collection included:

• Postoperative assessments ≤30 days, 3–6 months, and annually • Collection of mortality and valve-related morbidity• Assessment of pre and post-op NYHA class• Hemodynamic data obtained by echocardiography at one year, two years, and every other year thereafter

Patient Demographics and MethodsOnly patients who were candidates for isolated aortic or isolated mitral valve replacement were considered. An isolated procedure is defined as one in which only one of the patient’s valve is replaced, with the three remaining valves being the native valves. Patients who require concomitant valve replacement or who already have a pre-existing prosthetic valve in another position were excluded from enrollment in the study. Concomitant procedures such as CABG (other than valve replacement) were permitted. Surgeons were encouraged to enroll patients

* Homograft versus Medtronic Freestyle full aortic root replacement. Five year follow-up from a prospective, randomized trial. Melina G, Nyawo B, Amrani M, Khaghani A, Yacoub M. Academic Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College, London, UK. Presented at the Society for Heart Valve Disease, Paris, 2003.

* *AOA is a registered trademark of Biomedical Design, Inc., Atlanta, GA.

No clinical data are available which evaluate the long-term impact of the AOA treatment and the Physiologic Fixation process in patients.

3Mosaic Bioprosthesis

consecutively to minimize selection bias to the extent that patient rights and welfare were not compromised. Surgical technique for implantation of the bioprosthesis was left to the discretion of the surgeon. Indications for and management of antithromboembolic therapy were prescribed by the center for each patient enrolled in the study.

A total of 797 patients had AVR: 524 men and 273 women. Age at implant ranged from 21 years to 88 years with a mean of 69 years. The implant period for the isolated aortic valve patient population was from February 25, 1994 to November 28, 1998.

A total of 232 patients had MVR: 111 men and 121 women. Age at implant ranged from 17 years to 84 years with a mean of 67 years. The implant period for the isolated mitral valve patient population was from March 22, 1994 to March 9, 1999.

This compendium includes results from 136 patients 60 years and under who have received either an aortic or mitral Mosaic bioprosthesis as part of this study since 1994.

Informed consent for the long-term study was obtained from 90% of the patients enrolled at the six centers. For the remaining 10% of patients, data available through July 14, 2000 were included in this report.

Patients were evaluated at the following postoperative intervals: early (within 30 days of implantation), late (three to six months), one year (11 to 14 months), and annually thereafter. The guidelines of the Society of Thoracic Surgeons (STS) and the American Association of Thoracic Surgeons (AATS) were followed for the reporting of mortality and valve-related morbidity.3

Statistical MethodsDescriptive statistics were used to summarize the patient population data, operative data, follow-up data, and hemodynamic data. For continuous variables, the number of patients, mean, standard deviation, minimum, and maximum were provided. For categorical variables, the number and percentage of patients were provided.

For AVR, data were summarized to eight years. However, for MVR, data were summarized to seven years because

of the small number of patients available at eight years.

Early event rates were calculated as the number of patients having the event divided by the total number of patients, expressed as a percentage. Linearized rates4 were used to summarize late events. They were calculated by dividing the number of late events by the sum of the late patient-years of experience, expressed as a percentage. Survival analyses using the Kaplan-Meier5 method were used to estimate survival and the freedom from valve-related adverse events. Peto’s formula6 was used for the calculation of the standard errors of these estimates.

Patient Demographics (Patients ≤ 60 yrs)

# Patients

AVR 99

MVR 37

Total 136

Age at Implant

Mean (sd): 52 Years (10 Years)

Range: 17-60 Years

≤20 Years 2

21-30 Years 7

31-40 Years 10

41-50 Years 16

51-60 Years 101

Follow-up (Patients ≤ 60 yrs)

Years

Cumulative 706 Patient-years

Mean 5.2 Years

Maximum 8.2 Years

# of Patients

8 Years 4

7 Years 23

6 Years 32

5 Years 23

4 Years 54

Aortic Valve Replacement4 Mosaic Bioprosthesis

III III IV0

20

40

60

80

100

12.7

57.0

28.5

1.9

% o

f Pa

tien

ts

Figure 2. Distribution of Preoperative NYHA Functional Class

Operative Data

Etiology of Valvular Dysfunction

Senile degenerative calcific stenosis 58% Congenital bicuspid calcification 29%

73.3

25.7

1.0 0.1

54.3

42.8

2.6 0.3

31.6

68.4

0.0 0.00

I II III IV

20

40

60

80

100

% o

f Pa

tien

ts

1 Year (n=729)4 Year (n=589)8 Year (n=38)

Figure 3. Distribution of Postoperative NYHA Functional Class

Patient Demographics • Patients = 797

Male 524 66%

Female 273 34%

Age at Implant


Range: 21-88 Years

≤40 Years 1.5%

41-50 Years 1.6%

51-60 Years 9.3%

61-70 Years 32.4%

71-80 Years 50.9%

≥81 Years 4.3%

25 mm28%

29 mm3%

27 mm10%

19 mm1%

21 mm19%

23 mm39%

Figure 1. Distribution of Valve Sizes

Aortic Valve Replacement

Concomitant Procedures

Any concomitant procedure 57% Coronary artery bypass grafts 45% Ascending aortic replacement/repair 7%

Follow-up Cumulative 4029 Patient-Years Mean 5.1 Years Maximum 9.1 Years Follow-up Completeness 95%

Preoperative NYHA Functional Class Postoperative NYHA Functional Class

5Mosaic Bioprosthesis Aortic Valve Replacement

Table 1. Postoperative Evaluation • Antithromboembolic-Related Therapy

≤30 Days 3 to 6 Months 1 Year 2 Years 4 Years 6 Years 8 Years

# of Patients at Risk 780 753 734 710 601 353 41

Warfarin 36.4% 13.3% 8.4% 8.2% 9.2% 9.4% 9.8%

Antiplatelet 37.3% 62.8% 68.2% 68.0% 68.3% 68.2% 68.2%

Other 14.8% 0.8% 0.4% 0.4% 0.3% 0.3% 0.0%

None 11.5% 23.1% 23.0% 23.4% 22.2% 22.1% 22.0%

Table 3. Survival • Freedom from Event (%)

1 Year 4 Years 8 Years

Freedom from % SE Freedom from % SE Freedom from % SE

All Death 94.2 0.8 88.4 1.2 76.7 7.4

Cardiac 97.2 0.6 96.4 0.8 95.9 3.9

Noncardiac 98.2 0.5 94.4 0.9 84.9 6.6

Valve-Related or Unexplained 98.7 0.4 97.2 0.7 94.2 4.5

Valve-Related 99.1 0.3 98.2 0.5 97.8 2.9

Unexplained 99.6 0.2 98.9 0.4 96.4 3.7

Table 2. Mortality

Early1 Events Late2 Events

n % of Patients n %/Patient-Year3

All Death 22 2.8 98 2.47

Cardiac 15 1.9 15 0.38

Noncardiac 3 0.4 58 1.46

Valve-Related or Unexplained 4 0.5 25 0.63

Valve-Related 3 0.4 12 0.30

Unexplained 1 0.1 13 0.33

Notes:1. ≤30 days postoperative if patient was discharged from hospital, or at any time after implant if the patient was not discharged from the hospital2. Greater than 30 days postoperative, if the patient was discharged from the hospital3. Calculations were based on 3964.5 late patient-years


Table 5. Freedom from Valve-Related Adverse Events (%)


Freedom from % SE Freedom

from % SE Freedom from % SE

Primary Thromboembolism 96.5 0.7 93.3 1.0 88.6 6.4

Permanent Neurological Event 98.4 0.5 96.7 0.7 94.5 4.4

Transient Neurological Event 97.9 0.5 96.4 0.8 94.2 4.8

Primary Valve Thrombosis 99.7 0.2 99.6 0.3 99.4 1.6

Explant Due to Structural Valve Deterioration 100.0 0.0 100.0 0.0 94.0 4.6

Nonstructural Valve Dysfunction 99.6 0.2 99.6 0.3 99.6 1.2

Leaflet Dysfunction 100.0 0.0 100.0 0.0 100.0 0.0

Patient Prosthesis Mismatch 99.6 0.2 99.6 0.3 99.6 1.2

Endocarditis 98.8 0.4 96.8 0.7 96.2 3.8

All Primary Paravalvular Leak 98.7 0.4 97.8 0.6 97.8 3.0

Major Primary Paravalvular Leak 99.6 0.2 99.5 0.3 99.5 1.4

Major Antithromboembolic-Related Hemorrhage 97.2 0.6 95.4 0.8 94.4 4.7

Primary Hemolysis 100.0 0.0 100.0 0.0 100.0 0.0

Reoperation 99.0 0.4 97.1 0.7 90.6 5.6

Explant 99.1 0.3 97.2 0.7 90.9 5.5

Table 4. Valve-Related Adverse Events



Primary Thromboembolism 4,5 17 2.0 56 1.41

Permanent Neurological Event 7 0.9 25 0.63

Transient Neurological Event4 10 1.1 29 0.73

Primary Valve Thrombosis 0 0.0 4 0.10

Explant Due to Structural Valve Deterioration 0 0.0 2 0.05

Nonstructural Valve Dysfunction 0 0.0 3 0.08

Leaflet Dysfunction 0 0.0 0 0.00

Patient Prosthesis Mismatch 0 0.0 3 0.08

Endocarditis 2 0.3 25 0.63

All Primary Paravalvular Leak 6 0.8 11 0.28

Major Primary Paravalvular Leak 2 0.3 2 0.05

Major Antithromboembolic-Related Hemorrhage 12 1.5 28 0.71

Primary Hemolysis 0 0.0 0 0.00

Reoperation 0 0.0 26 0.66

Explant 0 0.0 24 0.61

Notes:1. ≤30 days postoperative2. Greater than 30 days postoperative3. Calculations were based on 3964.8 late patient-years4. Two early events occurred in one patient5. Two late events were acute myocardial infarctions


0 1 2 3 4 5 6 7 80

10

20

30

%

40

50

60

70

80

90

100

(n=797) (n=740) (n=722) (n=672) (n=601) (n=489) (n=303) (n=137) (n=25)

Valve-related Death

Death

Figure 4. Survival

0 1 2 3 4 5 6 7 80

10

20

30

40

50

60

70

80

90

100

(n=797) (n=739) (n=721) (n=671) (n=600) (n=487) (n=302) (n=137) (n=25)

%

Figure 5. Freedom from Reoperation

00 1 2 3 4 5 6 7 8

10

20

30

40

50

60

70

80

90

100

(n=797) (n=740) (n=722) (n=672) (n=601) (n=489) (n=303) (n=137) (n=25)

%

Figure 6. Freedom from Structural Valve Deterioration

Cumulative SurvivalThe eight-year freedom from valve-related mortality is 97.8% ± 2.9%. Patient survival at eight years is 76.7% ± 7.4%.

Freedom from ReoperationFreedom from reoperation at eight years is 90.6% ± 5.6%.

Freedom from Explant Due to Structural Valve DeteriorationFreedom from explant due to structural valve deterioration in patients ≥60 is 100%.

Overall freedom from explant due to structural valve deterioration at eight years is 94.0% ± 4.6%.

Causes of Valve-Related DeathsEarly Late

Endocarditis 1 6

Permanent neurological event 1 4

Antithromboembolic-related hemorrhage 1 1

Myocardial infarction 0 1

TOTAL 3 12

Reasons for ReoperationEarly Late

Primary valve thrombosis 0 4

Endocarditis 0 13

Primary paravalvular leak 0 6

Nonstructural valve dysfunction 0 1

Structural deterioration 0 2

TOTAL 0 26


0

5

10

15

20

25

15.2 14.8

12.911.8

9.9 10.0

mm

Hg

19mm(n=5)

21mm(n=132)

23mm(n=276)

25mm(n=192)

27mm(n=67)

29mm(n=20)

Figure 7. Average Mean Gradient (±SD) at One Year

0

5

10

15

20

25

mm

Hg

19mm*(n=0)

21mm(n=9)

23mm(n=13)

25mm(n=10)

27mm(n=4)

29mm(n=2)

15.4

13.8

10.49.5

10.5

Figure 8. Average Mean Gradient (±SD) at Eight Years

19mm(n=5)

21mm(n=132)

23mm(n=276)

25mm(n=193)

27mm(n=67)

29mm(n=20)

1.21.3

1.5

1.82.0

2.1

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

cm2

Figure 9. Average Effective Orifice Area (±SD) at One Year

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

1.3

1.6 1.6

1.9

2.2

cm2

19mm*(n=0)

21mm(n=8)

23mm(n=13)

25mm(n=10)

27mm(n=4)

29mm(n=2)

Figure 10. Average Effective Orifice Area (±SD) at Eight Years

Hemodynamic Data

* 19mm valves were introduced later in the clinical study.


0

20

40

60

None

% o

f Pa

tien

ts

Trivial Mild Moderate ModeratelySevere

Severe

100

8072.8

17.7

7.61.6 0.3 0.0

Figure 11. Valvular Regurgitation at One Year (n=734)

None Trivial Mild Moderate ModeratelySevere

Severe0

20

40

6059.0

30.8

10.2

0.0 0.0 0.0

% o

f Pa

tien

ts

100

80

Figure 12. Valvular Regurgitation at Eight Years (n=39)


Severe0

20

40

64.159.0

23.1

30.8

7.7 10.25.1

0.0 0.0 0.0 0.0 0.0

60

% o

f Pa

tien

ts

100

801 Year (n=39)8 Year (n=39)

Figure 13. Patient Matched Valvular Regurgitation at One and Eight Years

Hemodynamic Data

Valvular RegurgitationWhen patients are matched at one and eight years, valvular regurgitation is comparable.

Mitral Valve Replacement10 Mosaic Bioprosthesis

27 mm37%

25 mm19%

31 mm10%

33 mm2 %

29 mm32%

0

20

40

60

% o

f Pa

tien

ts

100

80

I

0.0

26.3

63.4

10.3

II III IV

Figure 15. Distribution of Preoperative NYHA Functional Class

Operative Data

Etiology of Valvular Dysfunction

Myxomatous degeneration 39% Ruptured chordae tendineae 25%

I II III IV0

20

40

60

% o

f Pa

tien

ts

100

801 Year (n=207)4 Year (n=170)7 Year (n=40)

68.1

42.9

50.0

30.9

54.1

42.5

1.0 2.97.5

0.0 0.0 0.0

Figure 16. Distribution of Postoperative NYHA Functional Class

Patient Demographics • Patients = 232

Male 111 48%

Female 121 52%

Age at Implant


Range: 17-84 Years

≤40 Years 3.0%

41-50 Years 1.3%

51-60 Years 11.6%

61-70 Years 32.8%

71-80 Years 48.7%

≥81 Years 2.6%

Figure 14. Distribution of Valve Sizes

Mitral Valve Replacement

Concomitant Procedures

Any concomitant procedure 54% Coronary artery bypass grafts 44% Intra-aortic balloon pump insertion 4%

Follow-up Cumulative 1055 Patient-Years Mean 4.5 Years Maximum 8.3 Years Follow-up Completeness 98%

Preoperative NYHA Functional Class Postoperative NYHA Functional Class

11Mosaic Bioprosthesis Mitral Valve Replacement

Table 8. Survival • Freedom from Event (%)


Freedom from % SE Freedom from % SE Freedom from % SE

All Death 93.5 1.6 87.0 2.5 81.5 7.0

Cardiac 97.4 1.1 95.3 1.7 92.9 5.0

Noncardiac 97.4 1.1 93.6 1.9 92.7 5.0

Valve-Related or Unexplained 98.6 0.8 97.6 1.2 94.7 4.4

Valve-Related 99.1 0.6 98.6 0.9 96.4 3.7

Unexplained 99.5 0.5 99.0 0.8 98.2 2.6

Table 6. Postoperative Evaluation • Antithromboembolic-Related Therapy

≤30 Days 3 to 6 Months 1 Year 2 Years 4 Years 6 Years 7 Years

# of Patients at Risk 226 214 210 199 171 73 42

Warfarin 58.4% 41.1% 35.2% 33.2% 35.1% 39.7% 38.1%

Antiplatelet 18.1% 45.4% 52.0% 52.7% 49.1% 39.8% 47.6%

Other 18.1% 1.4% 2.8% 2.5% 2.3% 4.1% 0.0%

None 5.3% 12.1% 10.0% 11.6% 13.5% 16.4% 14.3%

Table 7. Mortality



All Death 7 3.0 27 2.61

Cardiac 4 1.7 8 0.77

Noncardiac 3 1.3 12 1.16

Valve-Related or Unexplained 0 0.0 7 0.68

Valve-Related 0 0.0 4 0.39

Unexplained 0 0.0 3 0.29

Notes:1. ≤30 days postoperative if patient was discharged from hospital, or at any time after implant if the patient was not discharged from the hospital2. Greater than 30 days postoperative, if the patient was discharged from the hospital3. Calculations were based on 1036.0 late patient-years


Table 9. Valve-Related Adverse Events



Primary Thromboembolism 4,5 8 3.0 17 1.64

Permanent Neurological Event 4 1.7 7 0.68

Transient Neurological Event4 4 1.3 9 0.87

Primary Valve Thrombosis 0 0.0 1 0.10

Explant Due to Structural Valve Deterioration 0 0.0 1 0.10

Nonstructural Valve Dysfunction 0 0.0 0 0.00

Leaflet Dysfunction 0 0.0 0 0.00

Patient Prosthesis Mismatch 0 0.0 0 0.00

Endocarditis 0 0.0 7 0.68

All Primary Paravalvular Leak 3 1.3 6 0.58

Major Primary Paravalvular Leak 0 0.0 2 0.19

Major Antithromboembolic-Related Hemorrhage 3 1.3 11 1.06

Primary Hemolysis 0 0.0 0 0.00

Reoperation 0 0.0 7 0.68

Explant 0 0.0 7 0.68

Table 10. Freedom from Valve-Related Adverse Events (%)


Freedom from % SE Freedom

from % SE Freedom from % SE

Primary Thromboembolism 95.6 1.4 91.9 2.2 88.0 6.5

Permanent Neurological Event 97.8 1.0 95.7 1.6 94.2 4.5

Transient Neurological Event 97.8 1.0 96.2 1.6 94.9 4.5

Primary Valve Thrombosis 100.0 0.0 99.5 0.6 99.5 1.5

Explant Due to Structural Valve Deterioration 100.0 0.0 99.5 0.6 99.5 1.4

Nonstructural Valve Dysfunction 100.0 0.0 100.0 0.0 100.0 0.0

Leaflet Dysfunction 100.0 0.0 100.0 0.0 100.0 0.0

Patient Prosthesis Mismatch 100.0 0.0 100.0 0.0 100.0 0.0

Endocarditis 98.7 0.8 97.6 1.2 95.3 4.1

All Primary Paravalvular Leak 96.9 1.2 95.8 1.6 95.8 4.1

Major Primary Paravalvular Leak 99.1 0.6 99.1 0.8 99.1 1.9

Major Antithromboembolic-Related Hemorrhage 96.9 1.2 95.8 1.6 90.1 5.9

Primary Hemolysis 100.0 0.0 100.0 0.0 100.0 0.0

Reoperation 99.1 0.6 96.5 1.5 96.5 3.6

Explant 99.1 0.6 96.5 1.5 96.5 3.6

Notes:1. ≤30 days postoperative2. Greater than 30 days postoperative3. Calculations were based on 1036.7 late patient-years4. Two early events occurred in one patient5. One late event was a peripheral arterial event


0 1 2 3 4 5 6 7 8(n=232) (n=215) (n=201) (n=188) (n=152) (n=100) (n=60) (n=25) (n=6)

0

10

20

30

40

50

60

70

80

90

100

Valve-related Death

Death

%

Figure 17. Survival

0 1 2 3 4 5 6 7 8(n=232) (n=215) (n=201) (n=188) (n=152) (n=100) (n=60) (n=25) (n=6)

0

10

20

30

40

50

60

70

80

90

100

%

Figure 19. Freedom from Structural Valve Deterioration

Cumulative SurvivalThe seven-year freedom from valve-related mortality is 96.4% ± 3.7%. Patient survival at seven years is 81.5% ± 7.0%.

Freedom from ReoperationFreedom from reoperation at seven years is 96.5% ± 3.6%.

Freedom from Explant Due to Structural Valve DeteriorationFreedom from explant due to structural valve deterioration at seven years is 99.5% ± 1.4%.

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8(n=232) (n=215) (n=201) (n=188) (n=152) (n=100) (n=60) (n=25) (n=6)

%

Figure 18. Freedom from Reoperation

Causes of Valve-Related DeathsEarly Late

Endocarditis 0 3

Congestive heart failure due toparavalvular leak 0 1

TOTAL 0 4

Reasons for ReoperationEarly Late

Primary valve thrombosis 0 1

Endocarditis 0 3

Primary paravalvular leak 0 2

Structural deterioration 0 1

TOTAL 0 7


5.8

4.9 4.8

4.0 4.0

mm

Hg

0

2

4

6

8

10

25mm(n=39)

27mm(n=74)

29mm(n=69)

31mm(n=23)

33mm(n=4)

0

2

4

6

8

10

mm

Hg

25mm(n=7)

27mm(n=22)

29mm(n=23)

31mm(n=11)

33mm(n=2)

4.85.1 4.9

4.0

3.2

cm2

3.0

2.5

2.0

1.5

1.0

0.5

0

1.61.7

1.8

2.01.9

25mm(n=33)

27mm(n=71)

29mm(n=67)

31mm(n=20)

33mm(n=4)

cm2

3.0

2.5

2.0

1.5

1.0

0.5

025mm(n=7)

27mm(n=18)

29mm(n=21)

31mm(n=11)

33mm(n=2)

1.7 1.7 1.71.8

2.1

Hemodynamic Data

Figure 20. Average Mean Gradient (±SD) at One Year Figure 21. Average Mean Gradient (±SD) at Six Years

Figure 22. Average Effective Orifice Area (±SD) at One Year Figure 23. Average Effective Orifice Area (±SD) at Six Years



Severe

0.00.00.00.00.0 1.51.5

20.0

1.5

12.3

76.9

86.2

0

20

40

60

% o

f Pa

tien

ts

100

801 Year (n=65)6 Year (n=65)

Figure 26. Patient Matched Valvular Regurgitation at One and Six Years

1.40

20

40

60

% o

f Pa

tien

ts

100

80

None

78.5

15.8

3.80.0 0.5

Trivial Mild Moderate ModeratelySevere

Severe

77.3

1.5

19.7

1.5 0.0 0.00

20

40

60

% o

f Pa

tien

ts

100

80


Severe

Figure 24. Valvular Regurgitation at One Year (n=209) Figure 25. Valvular Regurgitation at Six Years (n=66)

Hemodynamic Data

Case Reports16 Mosaic Bioprosthesis

C A S E R E P O R T

Patient #1 Age: 38 Sex: Male

Medical History:Tissue valve was originally selected over a mechanical valve due to patient occupation. History of atrial fibrillation and left ventricular dilation. Pre-operative echo showed severe aortic regurgitation due to bicuspid valve.

Surgery: Received 29mm aortic valve. Atrial septal defect closed.

Follow-up:

Normal bi-yearly echos.

Occasional episodes of atrial fibrillation.

Patient reported satisfaction with improved quality of life and return to full activity.

Reoperation:Patient presented to the Emergency Room 2920 days (8 years) post implant with shortness of breath.

Pathology:Sections of the leaflets showed moderate to focally marked dystrophic calcification. There were degenerative changes with leaflet tears and pannus overgrowth along with calcified vegetation.

Outcome: Valve successfully replaced.

Case Reports

Out of 1029 patients, 3 have experienced structural valve deterioration at 8 years. The following case reports describe those 2 aortic and 1 mitral patients. All three had successful interventions.

17Mosaic Bioprosthesis Case Reports

C A S E R E P O R T

Patient #3 Age: 70 Sex: Female

Medical History:

Hypothyroidism, atrial fibrillation, thrombocytopenia, hepatic dysfunction, transient renal failure, left atrial enlargement, LV hypertrophy, hypertension, CHF.

Pre-op echo showed severe mitral regurgitation. Barlow’s valve. Large myxomatous with calcification and significant annular dilatation.

Surgery:Received 27mm mitral valve. Complicated 14 days hospital recovery including acute renal failure.

Follow-up: Second year echo showed moderate transvalvular regurgitation.

Reoperation:Patient presented to cardiologist 944 days (2.5 years) post implant.

Referred to surgery for severe regurgitation.

Pathology: Valve showed tear along the base of the mitral leaflet near the intertrigonal region.

No evidence of endocarditis or calcification.


C A S E R E P O R T

Patient #2 Age: 57 Sex: Male

Medical History:Smoker with hypertension, CAD, left atrial enlargement, left ventricular hypertrophy, renal failure and bicuspid aortic valve. Obese with a BSA of 2.28. Pre-op echo showed severe aortic stenosis with moderate regurgitation.

Surgery: Received 23mm aortic valve.

Follow-up:Early exam revealed higher than average gradients due to Patient-Prosthesis Mismatch. Patient remained active with slightly elevated gradients but no regurgitation. Patient con-tinued to smoke and remained hypertensive.

Reoperation:Patient presented to the Emergency Room 2756 days (7.5 years) post implant.

Flail prosthetic leaflet and one calcified leaflet.

Pathology:Marked structural degeneration of porcine valve with marked mineralization. Focal stripped mineralization on non-coronary cusps suggestive of remote vegetation. No evidence of active infection, gram stain negative.


18 Mosaic Bioprosthesis

Discussions and Conclusions

The primary objectives of this study were to evaluate the long-term efficacy, safety, and clinical performance of the Mosaic bioprosthesis. Specifically, improvement in postoperative NYHA classification was used to assess the efficacy of this bioprosthesis. Postoperative mortality and valve-related morbidity were evaluated to address the safety of the Mosaic bioprosthesis. To address the clinical performance of this bioprosthesis, hemodynamic data obtained by echocardiography were evaluated.

Due to high patient and investigator compliance, only 43 patients (5%) who had AVR were lost to follow-up, whereas, only four patients (2%) who had MVR were lost to follow-up.

The data from this clinical compendium study provides information which an experienced physician may use to make his or her own judgment about the durability and performance of the Mosaic bioprosthesis in aortic and mitral valve replacements.

References

1. Schoen FJ, Hirsch D, Bianco RW, Levy RJ. Onset and progression of calcification in porcine aortic bioprosthetic valves implanted as orthotopic mitral valve replacements in juvenile sheep. J Thorac Cardiovasc Surg. 1994;108:880-887.

2. Clinical Investigational Plan for the Mosaic Bioprosthesis: Aortic Model 305, Mitral Model 310 (US version dated October 10, 1994; European version dated April 25, 1994). Medtronic Cardiac Surgery, Inc./Medtronic Heart Valves, Inc.

3. Edmunds LH Jr, Clark RE, Cohn LH, Miller DC, Weisel RD: Guidelines for reporting morbidity and mortality after cardiac valvular operations. J Thorac Cardiovasc Surg. 1988;96:351-353.

4. Grunkemeier GL. Statistical Analysis of Prosthetic Valve Series. Heart Valve Replacement: Current Status and Future Trends. Rábago G and Cooley DA. eds. Futura Publishing Company, Inc. Mount Kisco, NY 1987; pp. 11-26.

5. Kaplan EL and Meier P. Nonparametric Estimation from Incomplete Observations. Journal of the American Statistical Association. 1958; 53: 457-481.

6. Peto R, Pike MC, Armitage P, et. al. Design and Analysis of Randomized Clinical Trials Requiring Prolonged Observation of Each Patient. British Journal of Cancer. 1977; 35(1): 1-39.

Mosaic® Bioprosthesis Clinical Centers

Center Country Date of First Implant # of Implants

Monash Medical Centre Australia August 10, 1995 108

Hôpital Laval Canada June 05, 1995 152

Vancouver Hospital and HSC/St. Paul’s Hospital Canada September 14, 1994 184

Regina General Hospital Canada March 20, 1995 171

Albertinen Krankenhaus Germany February 25, 1994 302

Greenlane Hospital New Zealand May 30, 1995 112

World HeadquartersMedtronic, Inc.710 Medtronic Parkway Minneapolis, MN 55432-5604USAInternet: www.medtronic.comTelephone: (763) 514-4000FAX: (763) 514-4879

Medtronic USA, Inc.Toll-free: 1-800-328-2518(24-hour consultation for physicians and medical professionals)

Europe/Africa/Middle East HeadquartersMedtronic Europe SàrlCase PostaleRoute du Molliau 31 CH-1131 Tolochenaz-SwitzerlandTelephone: (41 21) 802 7000FAX: (41 21) 802 7900

CanadaMedtronic of Canada Ltd.6733 Kitimat RoadMississauga, Ontario L5N 1W3CanadaTelephone: (905) 826-6020FAX: (905) 826-6620Toll-free: 1-800-268-5346

Asia-PacificMedtronic International, Ltd.Suite 1602 16/F.Manulife PlazaThe Lee Gardens, 33 Hysan AvenueCauseway BayHong KongTelephone: (852) 2891 4456FAX: (852) 2891 6830

Latin AmericaMedtronic, Inc.2700 S. Commerce Parkway Ste. 105 Weston, FL 33331USAInternet: www.medtronic.comTelephone: (954) 384-4500FAX: (954) 306-0176

Medtronic Heart Valves24 hr. Technical Support 1-800-328-2518 ext. 46779Direct: (763) 514-6779Fax: (763) 514-2877

For more informationon heart valves visit:www.heartvalves.com

UC200202659c EN© Medtronic, Inc. 2004All Rights ReservedPrinted in USA

No clinical data are available which evaluate the long-term impact of the AOA treatment and the Physiologic Fixation process in patients. For more detailed information describing intended use, contraindications, warnings, precautions and adverse events; refer to the instructions for use provided with the product.

Mosaic and Cinch are a registered trademarks and Physiologic Fixation is a trademark of Medtronic, Inc.

AOA is a registered trademark of Biomedical Design Inc., Atlanta, Georgia.

Mosaic® Porcine Bioprosthesis

Indications: Replacement of impaired native or prosthetic aortic and mitral heart valves

Contraindications: None known

Warnings/Precautions/Adverse Events: Accelerated deterioration due to calcific degeneration of bioprosthesis may occur in: children, adolescents, young adults, and patients with altered calcium metabolism (e.g., chronic renal failure, hyperparathyroidism). Adverse events can include: angina, cardiac arrhythmia, death, endocarditis, heart failure, hemolysis, hemolytic anemia, hemorrhage, transvalvular or paravalvular leak, myocardial infarction, nonstructural dysfunction, stroke, structural deterioration, thromboembolism, or valve thrombosis.

For additional information, please refer to the Instructions For Use provided with the product.

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

Documents

Mosaic Bioprosthesis 8 Year Clinical CompendiumFebruary 2004 The Mosaic® bioprosthesis is marking the 10th anniversary of its ﬁrst implant this month. We are proud to present our