Bioprosthetic valves

1. HEART VALVE SUBSTITUTES
(Bioprosthesis)

2. History
• 1955 Gordon Murray  Aortic
Homograftin DTA (saline)
• 1961 HeimbeckerAortic homograft
Orthotopic position (saline + penicillin)
• 1962 Donald Ross( Gunning + Duran)
Successful Aortic Homograft implantation

3. History
• Weldon ( Johns Hopkins) Aortic Homografts on
frames (1960)
• Angell First implanted stent mounted aortic
homografts
• Senning  Fascia Lata, Marion Ionescu Fascia Lata +
heterologous pericardium
• 1967 Donald Ross Pulmonary autograftcomplex
surgery

4. HISTORY : XENOGRAFT AORTIC VALVES
• Experimental studies of Duran and Gunning : basis for use
of xenograft in human (1962)
Jean Paul Binet ,Paris (1965)
• Direct porcine aortic valve Xenograft implantation
• sterilized and preserved in special formaldehyde solution
Carpentier,Paris (1967)
• Glutaraldehyde- preserved stent-mounted porcine valves

5. BOVINE PERICARDIAL VALVE :'IONESCU
- SHILEY PERICARDIAL XENOGRAFT.'
• Invented by Marian Ionescu-
British surgeon
• March 1971, implantation in
humans
• Glutaraldehyde treated and
mounted on Dacron-covered
titanium frame
• 1971- 1976 :implanted 212 valves 5

6. History
• Warren Hancock , Edwards Laboratories
• Porcine aortic valve fixed in formalin
• Machined stellite stent polypropylene stent
• First implated by Robert Litwack at
National Institute of Health , Washington DC

7. BIOPROSTHESIS
• Term “Bioprosthesis” was coined by Carpentier
• Prosthesis
– made from biological material
– chemically treated by means of tissue fixation to
reduce its antigenicity, to increase tissue stability, and
prevent host fibroblast infiltration and ingrowth. .
Texas Heart Institute journal.
1983;2:159-162

8. BIOLOGICAL VALVE SUBSTITUTE
• Made of biological material
• Tissue– pericardium/native
valve
• Source-
autograft/homograft/xenograf
t
• Design-Stented/stentless
• Tissue treatment - fresh or
fixed

9. Why biological valve?
• Mechanical valves
– Thromboembolism
– Hemolysis
– Life long Anticoagulation therapy
– Need for Better hemodynamics
• Biological valves:
– More natural, no anticoagulation

10. DEVELOPMENT OF BIOLOGICAL VALVE
• Tissue material: From Homograft to Xenograft
– Size Discrepancy
– Shortage of donor
– Storage
– Abundance of Xenograft
• Advancement in chemical fixation and preservation
• Modification in pressure fixation
• Use of Frame/stents
• Development of Antimineralization technique
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11. TISSUE FIXATION AND PRESERVATION
• The purpose is to
– Stabilizes tissue.
– Prevent Autolysis
– Increase their mechanical strength or stability
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12. TISSUE FIXATION AND PRESERVATION
• Chemical
– Additive – chemically link or bind to the tissue and
change it.
• Formaldehyde , Gluteraldehyde , Osmium Tetroxide ,
Potassium Dichromate , Acetic Acid
– Non-additive – acetone and alcohols
• Ex: Methyl or Ethyl Alcohols

13. Alain Frédéric Carpentier
13

14. TISSUE FIXATION-Work of Carpentier(1965-
1970)
• Carpentier initiailly used Mercurial solution (Cyalite)
• cellular ingrowth -proved harmful,most often
inflammatory
• Aim
– Chemical treatment
– Mechanical protection
14
J Thorac Cardiovasc Surg. 1969;58:467-482.; Lancet.
1965;2:1275.

15. TISSUE FIXATION-Work of Carpentier(1965-
1970)
Chemical treatment
• Cross linking inducing factors
• Glutaraldehyde
– most effective for decreasing antigenicity
– Increasing stability of tissue

16. GLUTARALDEHYDE FIXATION
• Cross-linking
• Reduces antigenicity
• Reduces enzymatic degradation
• Causes the loss of cell viability.
• Increases the risks of calcification
16

17. GLUTARALDEHYDE FIXATION
• Glutaraldehyde fixation
– at high pressure (100mm Hg)
– at low pressure (<4 mm Hg)
– zero-pressure (0 mm Hg)
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18. TISSUE FIXATION-Work of Carpentier(1965-
1970)
• Mechanical Protection:
• The Concept of Greffe Protegee(1966)
• inflammatory cellular penetration occurred at
graft-host interface
• Physical barrier-a thin cloth or a stent, was
interposed between the host and the valve
• Aortic sleeve was covered with the same
material

19. GLUTARALDEHYDE FIXATION
• Higher fixation pressures:
– tissue flattening and compression
– loss of transverse Cuspal ridges and collagen crimp
• Fixed at zero pressure
– retain the collagen architecture of relaxed aortic valve
cusp.
• Influence opening behaviour of valve and degree of
strain localisation in leaflet tissue.

20. Ann Thorac Surg 2005;79:1072-
1080
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21. Anti-mineralization strategies

22. ANTIMINERALISATION
• AoA (Medtronic)
• Linx AC (St. JudeMedical)
• XenoLogiX (Edwards)
• ThermaFix (Edwards)
• T6 (Hancock)
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23. 23

24. BIOPROSTHETIC VALVES
First-Generation bioprostheses
• Higher fixation pressure and placed in annular
position
• Medtronic Hancock Standard and Modified Orifice
• Carpentier-Edwards Standard porcine prostheses
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25. BIOPROSTHETIC VALVES
Second-Generation Prostheses
• Low or zero fixation pressure
• Suprannular implantation
• Porcine second generation prostheses
• Medtronic Hancock II valve
• Medtronic Intact porcine valve
• Carpentier-Edwards Supraannular valve (SAV)
• Pericardial Second generation prostheses
• Carpentier-Edwards Perimount
• Pericarbon(Sorin Biomedica, Italy)

26. BIOPROSTHETIC VALVES
Third-Generation Prostheses
• zero- or low pressure fixation
• antimineralization process
• thinner, lower profile, more flexible
• sewing rings -scalloped for supra-annular
placement
– Medtronic Mosaic porcine valve
– St. Jude Medical Epic valve
– Carpentier-Edwards Magna valve
– Mitroflow Pericardial aortic prosthesis
– St jude Trifecta
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29. HANCOCK PORCINE BIOPROSTHESIS
• The Hancock Standard, Hancock II, and
Hancock Modified Orifice II (Medtronic)
• Hancock II aortic and mitral prostheses : lower
profile flexible stent with reduced sewing cuff
to increase orifice area.
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30. Hancock II
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31. MEDTRONIC MOSAIC PORCINE
BIOPROSTHESIS
• zero-pressure Glutaraldehyde fixation
• antimineralization treatment: α-amino oleic acid(AOA)
• low-profile semiflexible stent; porcine aortic root is predilated
to 40 mm Hg in an attempt to maximize valve orifice area.
• Mosaic Ultra
– has a reduced sewing cuff
– can be placed completely supra-anularly.
– the valve stent is very flexible, facilitates implantation through small
incisions.
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32. CARPENTIER-EDWARDS PORCINE
BIOPROSTHESIS
• Carpentier-Edwards standard valve (Edwards Lifesciences,
Inc.) 1975
– first generation(fixed with glutaraldehyde at 60 mm Hg) ,intra annular
• Carpentier-Edwards supra-anular valve (CE-SAV) 1982
– second-generation valve (low-pressure glutaraldehyde fixation at 2 mm Hg )
– improving the durability and hemodynamics
– Flexible stent; Surfactant polysorbate-80 as antimineralization agent
• Carpentier-Edwards Duraflex mitral bioprosthesis : low-
pressure fixation
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33. Carpentier-Edwards Porcine
Bioprosthesis
CE porcine
mitral CE porcine aortic
CE SAV aortic
porcine
Duraflex
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34. ST. JUDE MEDICAL EPIC VALVE
• very low stent post and base profile
– minimize protrusion into the aortic wall
– facilitate coronary clearance
• Compositethree separate porcine leaflets
• low-pressure glutaraldehyde fixation
• Proprietary Anticalcification treatment –Linx AC(ethanol)
• Outflow edge of stent is covered with pericardium
– prevent leaflet contact with fabric of sewing cuff.
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35. ST. JUDE MEDICAL BIOCOR
• Porcine stented bioprosthesis
• good durability
• low complication rates
• aortic and mitral valve versions
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36. PERICARDIAL BIOPROSTHESES :
CARPENTIER-EDWARDS PERIMOUNT
• Stented bovine pericardial aortic bioprosthesis
• flexible cobalt-chromium alloy (Elgiloy) stent
• Leaflets (biomechanically engineered) produced
by computer aided design
• Neutralogic stress free zero-pressure fixation
• Xenologix :polysorbate-80 and ethanol
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37. PERICARDIAL BIOPROSTHESES :
CARPENTIER-EDWARDS PERIMOUNT
MAGNA
• Suprannular design
• stent modified and reduced -> increase EOA
• Thermafix :extended heating process of
pericardium
• Mitral Magna
– low-profile stent
– keep posterior prosthetic strut away from left
ventricular free wall.
• Magna Ease
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38. Perimount mitral
Perimount aortic
Perimount magna
mitral
Perimount magna
aortic
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39. TRANSCATHETER STENTED
BIOPROSTHESES
• Dr Aalain Cribier (Rouen, France)
• percutaneous implantable prosthesis , 3 bovine leaflets
mounted on a balloon–expandable stent
• First successful human implantation, Apr. 2002
• Valve comprised of Equine pericardium mounted on stents
•
• delivered by three different techniques
– antegrade approach
– retrograde femoral approach
– Trans apical trans catheter valve delivery
Portico

40. STENTLESS BIOPROSTHESES
• First introduced by Tirone David (1986)
• Xenografts- neither have rigid stent nor sewing cuff
• Larger EOA and better hemodynamics(no inherent gradient
)
• Less chance for patient-prosthesis mismatch
• Supported by aortic root of patient
• Can be implanted as stand-alone aortic root replacement
prostheses-similar to technique used with homograft
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41. STENTLESS BIOPROSTHESES
• Preservation of dynamic nature of aortic annulus
• Retain critical function of sinuses of valsalva in dissipating stress
associated with valve closure
• More favourable ventricular remodeling after implantation compared
with stented prostheses
• Implantation techniques -are more complex and are associated with
longer cross-clamp times.

42. STENTLESS BIOPROSTHESES
• Toronto SPV Valve
• Medtronic Freestyle Stentless Aortic
Bioprosthesis
• Edwards Prima Plus Stentless Bioprosthesis
• ATS Medical 3f
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43. TORONTO SPV VALVE
43
• Offered by St. Jude Medical
Inc.
• Glutaraldehyde-preserved
porcine valve
• Covered with polyester for
ease of handling
• Designed for subcoronary
implantation

44. MEDTRONIC FREESTYLE STENTLESS AORTIC
BIOPROSTHESIS
• Used as freestanding aortic root
prosthesis
• it can be trimmed and implanted
with a subcoronary technique.
•
• Lower transvalvular gradients and
less aortic insufficiency
• Excellent durability and freedom
from aortic insufficiency
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45. EDWARDS PRIMA PLUS STENTLESS
BIOPROSTHESIS
• Can be implanted either
as a full root or with the
subcoronary technique.
• low-pressure fixation
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46. ATS MEDICAL 3f
• Equine pericardium fixed with zero pressure.
• Implantation facilitated by valve’s flexibility.
• Affixed both to annulus and with sutures at
commissural posts
• Unique design
– point of maximal stress on valve moved from
commissure to midpoint of the leaflet.
– Excellent Hemodynamics and orifice properties
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47. HOMOGRAFT
ADVANTAGES :
• superior flow dynamics,
• avoidance of anticoagulation
• resistance to infection.
DISADVANTAGES
• limited availability and durability.
• durability depends on method of sterilization and preservation,
• availability depends on the maintenance of a valve bank

48. HOMOGRAFT-HISTORICAL PERSPECTIVE
First orthotopic insertions of an allograft valve
(1962)
• Donald Ross of Guy’s Hospital in London,
• Barratt-Boyes of Green Lane Hospital in
Auckland,New zealand
• Paneth and O’Brien of The Brompton Hospital
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49. DONOR SELECTION :
• Fresh cadaver donors less than 24 hours old
• From heart-beating organ donors whose
hearts are not suitable for transplantation
• Heart transplant recipients.

50. GENERAL GUIDELINES FOR SELECTION OF
CADAVER DONORS
• no sepsis, infectious, or communicable disease
• no neoplasm other than carcinoma of skin, in-situ carcinoma of uterus, or an
intracranial neoplasm
• no evidence of serious illness of unknown etiology
• no drug abuse, poisoning, prolonged steroid treatment
• NO Chest trauma or resuscitation

51. PROCUREMENT AND PRESERVATION
• Collected aseptically and implanted as fresh
valves
• Unsterile collection and sterilization by β-
propiolactone, ethylene oxide, or irradiation
• Placed in Hanks balanced salt solution at 4°C
for up to 4 weeks, followed by freeze-drying

52. PROCUREMENT AND PRESERVATION
• Antibiotic sterilization : Barratt-Boyes (1968)
– Hanks balanced salt solution with
– 50 U penicillin,1 mg streptomycin,1 mg
kanamycin,25 U Amp B
• Cryopreservation : O’Brien and colleagues (1975)
– increase the cell viability
– prolongs shelf life

53. HOMOGRAFT
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54. AIIMS PROTOCOL
• Heart harvested with Aseptic precaution
• Gentle rinsing of heart
• Heart packed in 500 ml of cold saline solution at 4 deg -
placed in double plastic bag
• Blood from donor heart: tested for HIV,HCV,HBsAg,
Treponema pallidum and Blood group
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55. AIIMS PROTOCOL
• Dissection of allograft with aseptic technique
under Laminar flow cabinet
• After dissection -placed in sterile Hanks solution
containing antibiotic Solution for 72 hrs
(cefotaxime,lincomycin,vancomycin,amphotericin
, polymixinB)

56. AIIMS PROTOCOL
• Hanks solution
– NaCl – 8 g ; KCl - 0.4 g
– MgCl2- 0.1 g ; MgSO4 - 0.1 g
– Na2HPO4 - 0.12 g
– KH2PO4- 0.06 g
– NaHCO3 - 0.35 g
– water 1 lit
• Tissue sent for c/s: Aerobic, Anaerobic and Fungal

57. AIIMS PROTOCOL-
CRYOPRESERVATION
• Homograft : used within 40 days or prepared for cryopreservation
• 50 ml RPMI (Rose Park Memorial Institute tissue culture medium )+ 5
ml DMSO (DiMethyl SulphOxide)+5 ml Fetal calf serum sealed in plastic
bag and again in aluminium pouch
• Within 2 hours of exposure to DMSO
– allograft is frozen at -1oC /minute down to – 40oC
– placed in vapour-phase liquid nitrogen storage (about -195oC until it is
used)

58. HOMOGRAFT - INDICATION
• primary indication : full root replacement for complicated aortic
valve endocarditis.
• For cure - All infected tissue has to be radically débrided.
• Mitral valve curtain and attached septal muscle of homograft
– reconstructing mitral annulus and left ventricular outflow tract.
• Infected composite root grafts : amenable for reconstruction
• Absence of prosthetic material
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59. AUTOGRAFT
ROSS I PROCEDURE
• Pulmonary autogarft in aortic position
ROSS II PROCEDURE
• Pulmonary autograft in mitral position

60. ROSS PROCEDURE
ADVANTAGES:
• Freedom from thromboembolism
• no need of anticoagulation
• Improved hemodynamics through valve orifice
without obstruction or turbulence
• Growth of autograft with time
• Beneficial for young patients
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62. ROSS PROCEDURE
• ABSOLUTE CONTRAINDICATIONS
– Significant pulmonary valve disease,
– Congenitally abnormal pulmonary valves (e.g., bicuspid or
quadricuspid),
– Marfan syndrome
– unusual coronary artery anatomy
– Severe coexisting autoimmune disease, particularly if it is the
cause of the aortic valve disease
– Bacterial Endocarditis is not a contraindication
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63. RECENT ADVANCES: Tissue Engineered
Heart Valves(TEHV)
• fabricate a viable and functional heart valve from autologus
cells.
• Idea to transplant autologous cells onto a biocompatible and
biodegradable scaffold shaped like a heart valve.
• Potential advantages
– Eliminate need for anticoagulation
– Would not calcify
– Life long durability
– Growth
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64. Tissue Engineered Heart Valves
• Biologic or synthetic scaffold : populated with patients cell
• Synthetic Biodegradable scaffold
– Polyglycolic acid (PGA)
– Polylactic acid (PLA)
• Xenogenic valve tissue- after decellularization
– gentle enzymatic washing -the cellular protein components of
the graft are removed ; the collagen matrix remains intact.
– No fixation or cross-linking of the collagen matrix
– Sterilized with gamma-irradiation and cryopreserved.
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66. CHOICE OF VALVE FOR
REPLACEMENT

67. Selection of a Valve Prosthesis
• Size and Quality of the Annulus
– Heavily calcified, rigid, and rough annulus
– Damaged by endocarditis/abscess
– Small annulus
• Risk of Thromboembolism
– Atrial fibrillation,
– Large left atrium (>55 mm)
– History of thromboembolism
– Presence of thrombi in the left atrium
– Postinfarction
– Left ventricular dyskinesis with thrombus
• Pregnancy
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68. Mechanical valves are recommended
for any patient with
• No contraindication to anticoagulation
• Anticipated life span over 10 years
• No plans for childbearing
• Mitral valve replacement when there is a small,
hypercontractile, or hypertrophic left ventricle to avoid
the risk of LV rupture
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69. Bioprosthetic valves should be
considered
• Women of childbearing age
• Contraindication to anticoagulation
• Anticipated lifespan under ten years
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70. Homograft valves should be
considered
• Endocarditis
• Small aortic root
• Any young patient who requires a tissue valve in the
aortic position
• Women of childbearing age
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71. Thank You