Indian Journal of Medical Research

EDITORIAL
Year
: 2012  |  Volume : 135  |  Issue : 2  |  Page : 150--151

The future of bioprosthetic heart valves


Rizwan A Manji1, Alan H Menkis1, Burcin Ekser2, David K.C. Cooper3,  
1 Department of Surgery, University of Manitoba; Cardiac Sciences Program, Winnipeg Regional Health Authority & St. Boniface Hospital, Winnipeg, Manitoba, Canada
2 Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; Department of Surgery, Transplantation & Advanced Technologies, Vascular Surgery & Organ Transplant Unit, University Hospital of Catania, Catania, Italy
3 Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

Correspondence Address:
Rizwan A Manji
I.H. Asper Clinical Research Institute, St. Boniface Hospital, CR3014 - 369 Tache Avenue, Winnipeg, Manitoba, Canada R2H 2A6




How to cite this article:
Manji RA, Menkis AH, Ekser B, Cooper DK. The future of bioprosthetic heart valves.Indian J Med Res 2012;135:150-151


How to cite this URL:
Manji RA, Menkis AH, Ekser B, Cooper DK. The future of bioprosthetic heart valves. Indian J Med Res [serial online] 2012 [cited 2019 Aug 23 ];135:150-151
Available from: http://www.ijmr.org.in/text.asp?2012/135/2/150/94201


Full Text

Two types of prosthetic valves are used for heart valve replacement surgery - mechanical or bioprosthetic. Mechanical valves have long-term durability, but require lifelong anticoagulation, with risks of thrombosis, thromboembolism, or spontaneous bleeding, and are therefore, less than ideal, particularly in young patients (injury-prone, menstruating, or pregnant) and in patients in the developing world, where close monitoring of anticoagulation may be difficult.

Bioprosthetic heart valves (BHVs) are constructed from porcine heart valves or bovine pericardium preserved with glutaraldehyde. Patients with BHVs do not require anticoagulation, but structural valve deterioration may occur, particularly in younger patients, necessitating replacement, with its associated higher risk of mortality.

The majority of the estimated 275,000 to 370,000 annual valve replacements are carried out in elderly patients in the developed world [1] . However, globally, there are an estimated 15 million patients with rheumatic heart disease, mostly young people in the developing world, with at least 280,000 new cases per year [2] . Only approximately 7-8 per cent of the Chinese and Indian populations have access to cardiac surgery [1],[3] , but demand is likely to increase markedly as the economies of these nations grow and technology continues to develop, making valve replacement more feasible. For example, percutaneous transcatheter valve replacement (in which BHVs are used) is currently performed in elderly patients too ill for standard open heart surgery [4] , but should minimize the intensity of post-operative care required, potentially making it suitable for patients worldwide. Thus, there is a huge potential 'market' for BHV replacement.

Structural valve deterioration or failure occurring in BHVs is age-dependent, with <10 per cent occurring in patients >65 yr of age, but almost uniform failure within 5 years in patients <35 yr old [5] . BHV calcification is most likely a result of a combination of chemical processes related to glutaraldehyde-fixation and an immune response to the xenograft (both humoral and cellular) [6] . The likely reason that young patients demonstrate such aggressive destruction of a BHV is heightened immune competence and calcium metabolism.

The failed valves show evidence of inflammation (macrophage and mononuclear cell infiltration) and thrombosis (platelet and fibrin deposition) [7] , histopathological features similar to those seen in experimental live tissue/organ xenotransplants. Thus, advances in the field of experimental organ xenotransplantation may be applicable to designing more durable BHVs, especially for young patients.

In the porcine-to-human xenograft combination, the galactose α1, 3 galactose (Gal) antigen (present on most pig tissues) is the major target for anti-pig human antibodies[8] . This antigen-antibody reaction has been implicated by several groups in the calcification and failure of BHVs [9],[10] . This problem may be at least partially resolved if BHVs are constructed from the genetically engineered pigs that have been developed as sources of organs for xenotransplantation.

α1, 3-galactosyltransferase gene-knockout (GTKO) pigs (that do not express Gal antigens) have been cross-bred with pigs that are transgenic for human complement-regulatory proteins, (e.g., CD46 CD55) and are known to provide resistance to human complement-mediated injury. GTKO pigs will soon be available expressing human 'anti-inflammatory' or 'anti-thrombotic' genes, both of which may provide further protection to a BHV from the human inflammatory and immune responses.

If BHVs could be fashioned to provide prolonged survival in young patients and in patients in whom long-term anticoagulation is contraindicated, there would likely be a paradigm shift to valve replacement worldwide. The raw materials required to fashion BHVs (e.g., valves or pericardial tissue from wild-type, unmodified pigs or cows) can be obtained at minimal cost from slaughterhouses. The costs of valves from genetically-modified pigs would undoubtedly be significantly greater (though would decrease significantly as breeding herds expand). Given the population of patients who might benefit most from improved BHVs, i.e., young people particularly in developing countries where the incidence of rheumatic heart disease remains high, the cost of the BHV is a major consideration. Perhaps because of this, to date, companies involved in this field have shown no enthusiasm for investigating genetically-engineered pigs as future sources of valves or pericardium. An innovative approach from entrepreneurs in countries such as China and India, coupled with increasing access to genetically-engineered pig herds, should resolve this dilemma.

References

1Zilla P, Brink J, Human P, Bezuidenhout D. Prosthetic heart valves: catering for the few. Biomaterials 2008; 29 : 385-406.
2Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. Lancet Infect Dis 2005; 5 : 685-94.
3Pezzella AT. International cardiac surgery: a global perspective. Semin Thorac Cardiovasc Surg 2002; 14 : 298-320.
4Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010; 363 : 1597-607.
5Siddiqui RF, Abraham JR, Butany J. Bioprosthetic heart valves: modes of failure. Histopathology 2009; 55 : 135-44.
6Manji RA, Zhu LF, Nijjar NK, Rayner DC, Korbutt GS, Churchill TA, et al. Glutaraldehyde-fixed bioprosthetic heart valve conduits calcify and fail from xenograft rejection. Circulation 2006; 114 : 318-27.
7Stein PD, Wang CH, Riddle JM, Magilligan DJ Jr. Leukocytes, platelets, and surface microstructure of spontaneously degenerated porcine bioprosthetic valves. J Card Surg 1988; 3 : 253-61.
8Cooper DKC, Good AH, Koren E, Oriol R, Malcolm AJ, Ippolito RM, et al. Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man. Transpl Immunol 1993; 1 : 198-205.
9McGregor CG, Carpentier A, Lila N, Logan JS, Byrne GW. Cardiac xenotransplantation technology provides materials for improved bioprosthetic heart valves. J Thorac Cardiovasc Surg 2011; 141 : 269-75.
10Cooper DKC. How important is the anti-Gal antibody response following the implantation of a porcine bioprosthesis? J Heart Valve Dis 2009; 18 : 671-2.