Bioprostheic heart valve prosthesis

BIOPROSTHETIC HEART VALVE PROSTHESIS

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/xenograft 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 10

11. TISSUE FIXATION AND PRESERVATION The purpose is to Stabilizes tissue. Prevent Autolysis Increase their mechanical strength or stability 11

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) 17

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 20

21. Anti-mineralization strategies

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

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 24

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 26

27. 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. 29

28. Hancock II 30

29. 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 . 31

30. 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 32

31. Carpentier -Edwards Porcine Bioprosthesis CE porcine mitral CE porcine aortic CE SAV aortic porcine Duraflex 33

32. ST. JUDE MEDICAL EPIC VALVE very low stent post and base profile minimize protrusion into the aortic wall facilitate coronary clearance Composite t hree 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. 34

33. ST. JUDE MEDICAL BIOCOR Porcine stented bioprosthesis good durability low complication rates aortic and mitral valve versions 35

34. 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 36

35. 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 37

36. Perimount mitral Perimount aortic Perimount magna mitral Perimount magna aortic 38

37. 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

38. 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 40

39. 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.

40. STENTLESS BIOPROSTHESES Toronto SPV Valve Medtronic Freestyle Stentless Aortic Bioprosthesis Edwards Prima Plus Stentless Bioprosthesis ATS Medical 3f 42

41. 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

42. 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 44

43. EDWARDS PRIMA PLUS STENTLESS BIOPROSTHESIS Can be implanted either as a full root or with the subcoronary technique. low-pressure fixation 45

44. 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 46

45. 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

46. 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 48

47. 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.

48. 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

49. 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

50. 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

51. HOMOGRAFT 53

52. 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 54

53. 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 )

54. AIIMS PROTOCOL Hanks solution NaCl – 8 g ; KCl - 0.4 g MgCl 2 - 0.1 g ; MgSO 4 - 0.1 g Na 2 HPO 4 - 0.12 g KH 2 PO 4 - 0.06 g NaHCO 3 - 0.35 g water 1 lit Tissue sent for c/s: Aerobic, Anaerobic and Fungal

55. 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 -1 o C /minute down to – 40 o C placed in vapour-phase liquid nitrogen storage (about -195 o C until it is used)

56. 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 58

57. AUTOGRAFT ROSS I PROCEDURE Pulmonary autogarft in aortic position ROSS II PROCEDURE Pulmonary autograft in mitral position

58. 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 60

59. 61

60. 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 62

61. 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 63

62. 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 . 64

63. 65

64. CHOICE OF VALVE FOR REPLACEMENT

65. 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 67

66. 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 68

67. Bioprosthetic valves should be considered Women of childbearing age Contraindication to anticoagulation Anticipated lifespan under ten years 69

68. 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 70

69. Thank You