1. Surgical aspects of MV replacement: New options with mechanical valves
Thierry Mesana, MD, PhD
Division of Cardiac Surgery University of Ottawa Heart Institute
Ottawa, Ontario, Canada

2. Thierry Georges Mesana, MD, PhD
I/we have no real or apparent conflicts of interest to report.

3. Gammie J. S. et al.; Ann Thorac Surg 2009;87:1431-1439
Overall mitral valve repair rates STS Database 2000 to 2007 (p < )
210,529 MV operations. Excluded 127,261 due to concomittant CABG or other valve, 15,670 redo MVR, and 1198 cardiogenic shock.
Results in 58,370 pts with primary MV procedure.
Gammie J. S. et al.; Ann Thorac Surg 2009;87:

4. What choice when we cannot repair or when repair has failed ?

5. ACC/AHA PRACTICE GUIDELINE
2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease*
Major Criteria for Aortic Valve Selection
CLASS I
1. A mechanical prosthesis is recommended for AVR in patients with a
mechanical valve in the mitral or tricuspid position.
(Level of Evidence: C)
2. A bioprosthesis is recommended for AVR in patients of any age who
will not take warfarin or who have major medical contraindications
to warfarin therapy. (Level of Evidence: C)
CLASS IIa
1. Patient preference is a reasonable consideration in the selection of
aortic valve operation and valve prosthesis. A mechanical prosthesis
is reasonable for AVR in patients under 65 years of age who do
not have a contraindication to anticoagulation. A bioprosthesis is
reasonable for AVR in patients under 65 years of age who elect to
receive this valve for lifestyle considerations after detailed discussions
of the risks of anticoagulation versus the likelihood that a second AVR may be necessary in the future. (Level of Evidence: C)
2. A bioprosthesis is reasonable for AVR in patients aged 65 years or
older without risk factors for thromboembolism. (Level of Evidence: C)
3. Aortic valve re-replacement with a homograft is reasonable for
patients with active prosthetic valve endocarditis. (Level of Evidence:
CLASS IIb
1. A bioprosthesis might be considered for AVR in a woman of childbearing age . (Level of Evidence: C)
Selection of mitral valve prostheses
CLASS I
1. A bioprosthesis is indicated for MV replacement in a patient who will not take warfarin, is incapable of taking warfarin, or has a clear contraindication to warfarin therapy.
(Level of Evidence: C)
CLASS IIa
1. A mechanical prosthesis is reasonable for MV replacement in
patients under 65 years of age with long-standing atrial fibrillation.
2. A bioprosthesis is reasonable for MV replacement in patients 65 years of age or older.
3. A bioprosthesis is reasonable for MV replacement in patients under 65 years of age in sinus rhythm who elect to receive this valve for lifestyle considerations after detailed discussions of the risks of anticoagulation versus the likelihood that a second MV replacement may be necessary in the future.
*J Am Coll Cardiol, 2008; 52:1-142

6. Prosthetic Valve Selection "Conventional Wisdom"
Mechanical Valves and Coumadin expose my patients to undue risks of stroke, valve thrombosis and higher mortality compared to bioprostheses

7. MV replacement is still frequent and Tissue Valve replacement increasing
Ratio of bioprosthetic valves/mechanical valves increasing in favor of BP.
Over2/3 MVR are tissue valves in STS database
Durability of porcine valve is less for MV than AV.
SVD starts at 8 years up to 60% at 15 years
SVD slows down after 70 y-o ? Or less reoperations due to shorter life expectancy ?

9. Reoperation after Mitral Valve Replacement
Mechanical
Bioprosthetic
Years Mech (%) Bio (%)
Patients:
Mech
Bio

10. Circulation Sept 2011

11. Duke University, 2064 pts, 1986-2006 All pathologies of MV Tissue valves showing inferior

12. Hazard Ratio for Late Death Comparing Double Biological and Double Mechanical Valve Replacement According to Age at Operation
In press in European
Journal of CT Surgery

13. MV Replacement revisited
Mechanical valves are still indicated in young patients
65 y-o may be too low when we consider current increased life expectancy in particular for MVR
Re-operation ealier for MVR and high-risk
Few MVR stay out of anticoagulants when aging and they will have both risks : reoperation + bleeding.
Double valve replacement “bar” higher for tissue (72 y-o)
Many patients with tissue valve may still need AC while new AC may improve outcomes and quality of life of patients with new generation of mechanical valve
New AC….or lower INR with Coumadin ? Which valves ?

14. New options in prosthetic valves ?
On-X valve
Proact Study

15. Low TE rates ( others >1.5%)
Overall low valve related complications
Linearized Occurrence Rate
(%/patient-year)
Major Thromboembolism
0.94 (0.36,1.52)
Hemorrhage
1.60 (0.84,2.35)
Valve-Related Reoperation
0.38 (0.01,0.74)
Valve-Related Mortality
0.19 (0.07,0.44)
J Thorac Cardiovasc Surg 2010 ;140(5): e2 Ottawa/Vancouver experience

16. PROACT STUDY
Objective : To determine whether it is safe and effective to manage On-X valve patients with less aggressive anticoagulant therapy than is currently recommend by ACC/AHA guidelines.

17. INCLUSION CRITERIA Isolated AVR and MVR
Concomitant cardiac surgery allowed
Adults
Risk groups for AVR defined by
Cardiac rhythm, ejection fraction, atrial and ventricular dimensions, previous thrombotic or neurologic event, spontaneous echo contrast in atrium, hypercoagulability
Full informed consent and agreement to follow-up requirements

18. 3 Low Dose Therapy Groups
Transition period 1st three months with standard therapy per AHA/ACC.
Low risk AVR
Clopidogrel 75 mg/day, plus aspirin 325 mg/day
High risk AVR
INR 1.5 to 2.0, plus 81 mg/day aspirin
All MVR
INR 2.0 to 2.5, plus 81 mg/day aspirin
Three randomized control groups, all on standard Coumadin therapy plus 81 mg/day aspirin
All patients on Coumadin receive home monitoring

19. POST-RANDOMIZATION EVENTS

20. AVR High Risk Group Completed
Event
Control (ptyr=535.7)
(2.0 – 3.0)
Test (ptyr=486.7)
(1.5 – 2.0)
Rate Ratio
95% CI
P-value N
Rate (%/ptyr)
(control/test)
Major Bleed 23
4.29 7
1.44
2.99
0.008
Minor Bleed 20
3.73 9
2.02
0.074
Total Bleed 43
8.03 16
3.29
2.44
0.002

21. AVR High Risk Group completed
Event
Control (ptyr=535.7)
(2.0 – 3.0)
Test (ptyr=486.7)
(1.5 – 2.0)
Rate Ratio
95% CI
P-value N
Rate (%/ptyr)
(control/test)
Stroke 3
0.56 5
1.03
0.55
0.545
TIA
0.93 7
1.44
0.65
0.649
Neurologic Event 8
1.49 12
2.47
0.61
0.606
Peripheral TE 1
0.19
0.62
0.30
0.273
Thrombosis 2
0.37
0.41
0.91
0.924

22. Summary
AVR High Risk
Hypothesis proven
Non-inferior treatment group
Treatment group meets FDA events criteria (OPC)
In fact, treatment group superior in bleeding event rates.
Application submitted to FDA for change in practice
Abstract to be presented at AATS plenary session #1
Follow-up still too short in low risk AVR and MVR for conclusions
Early MVR returns encouraging
Enrollment by the end of 2012 or in 2013

23. Thank you

24. COMPARISON TO OTHER MECHANICAL VALVES - %/patient-year
Valve Prosthesis
Hemorrhage
Major TE
Valve-Related Reoperation
Valve-Related Mortality
On-X
AVR 1.60
MVR 1.20
AVR 0.94
MVR 0.72
AVR 0.38
MVR 0.24
AVR 0.19
MVR 0.12
ATS
AVR 1.8
AVR 1.6
AVR 0.2 --
St. Jude
AVR 2.7
MVR
AVR 1.9
MVR
MVR 1.1
MVR 0.7
Emery RW et al. J Heart Valve Dis 2004; 13(2):231-8.
Jamieson WRE et al. Eur J Cardio-Thorac Surg 1999; 15: 786–94.
Emery RW et al. Ann Thorac Surg 2005; 79: 776–83.
Aagaard J et al. J Heart Valve Dis 2001; 10:177.
Jamieson WRE et al. J Heart Valve Dis ; 9:

25. ENROLLMENT BY GROUP Overall Patients Enrolled 1095 Test 337
Control
Pending
Removed
Low Risk AVR
Enrolled 429
Test 69
Control 74
Pending 62
Removed 224
High Risk AVR
Enrolled 425
Test 185
Control 190
Pending
Removed 50
Mitral
Enrolled 241
Test 88
Control 90
Pending 10
Removed 53
As of 6/1/2012

26. MV replacement carries a higher mortality with or without CABG
Adult Cardiac Surgery Database
STS Data Ending 12/31/2009

27. High Risk INR Status at Event
High Risk Control (2.0 – 3.0)
Bleed
66.7% of Major Bleeds occur when INR is above Target TE
33.3% of CVA’s occur when INR is below Target
High Risk Test
(1.5 – 2.0)
Bleed
62.5% of Major Bleeds occur when INR is above Target TE
50.0% of CVA’s occur when INR is below Target

28. MULTICENTER STUDY DESIGN
Randomization
Low-dose Therapy
Standard Therapy
3-months
Primary Endpoint: Composite endpoint of TE, thrombosis and bleeding events (defined per AATS/STS guidelines)
Tested against FDA objective performance criteria (OPC) –
(%/ptyr: 3.0 TE, 0.8 thrombosis, 3.5 bleeding)
Secondary endpoints : NYHA class, Valve-related adverse events