Human Leukocyte Antigen Mismatch and Other Factors Affecting Cryopreserved Allograft Valve Function


  • Cheng-Hon Yap
  • Peter D. Skillington
  • George Matalanis
  • Bruce B. Davis
  • Brian D. Tait
  • Fiona Hudson
  • Lyn Ireland
  • Ian Nixon
  • Michael Yii



The causes of cryopreserved allograft heart valve degeneration are poorly understood. We investigated HLA mismatch and other factors implicated in allograft valve degeneration. For this study we recruited 110 adult recipients of allograft heart valves who underwent surgery between June 1998 and March 2003 in the state of Victoria, Australia. Recipients and donors were HLA typed using serological and molecular methods. Valve function at most recent echocardiographic follow-up was examined for an association with the following variables using univariate and multivariate methods: HLA-A,-B, and -DR donor-recipient mismatch; HLA class I mismatch; total HLA mismatch; valve ischemic time; recipient age; donor age; ABO blood group donor-recipient match; and allograft size. Mean recipient age was 45 years (18-75 years), 75% were men. Seventy-four pulmonary (62 Ross procedure) and 36 aortic allografts were examined. Median valve ischemic time was 31 hours, range 20-48 hours. Echocardiographic follow-up was complete at a mean of 41 (±18) months, range 6-85 months. At univariate analysis longer ischemic time and younger recipient age were associated with valve dysfunction. HLA-A, -B, or DR mismatch, HLA class I mismatch, total HLA mismatch, donor age, ABO mismatch, and allograft size were not associated with valve dysfunction. Only younger recipient age remained significant at multivariate analysis. In conclusion, longer ischemic times and younger patient age predicted valve dysfunction at a mean of 3 years follow-up. Recipient age remained the strongest predictor of valve dysfunction. These results indicate that allograft ischemic times should be minimized.


Albert JD, Bishop DA, Fullerton DA, et al. 1993. Conduit reconstruction of the right ventricular outflow tract. Lessons learned in a twelve-year experience. J Thorac Cardiovasc Surg 106:228-35.nBaskett RJ, Nanton MA, Warren AE, Ross D. 2003. Human leukocyte antigen-DR and ABO mismatch are associated with accelerated homograft valve failure in children: implications for therapeutic interventions. J Thorac Cardiovasc Surg 126:232-9.nBechtel JF, Bartels C, Schmidtke C, et al. 2001. Does histocompatibility affect homograft valve function after the Ross procedure? Circulation 104(suppl 1):125-8.nDaenen W, Gewillig M. 1997. Factors influencing medium-term performance of right-sided cryopreserved homografts. J Heart Valve Dis 6:347-54.nDignan R, O'Brien M, Hogan P, et al. 2000. Influence of HLA matching and associated factors on aortic valve homograft function. J Heart Valve Dis 9:504-11.nDignan R, O'Brien M, Hogan P, et al. 2003. Aortic valve allograft structural deterioration is associated with a subset of antibodies to human leukocyte antigens. J Heart Valve Dis 12:382-90.nForbess JM, Shah AS, St Louis JD, Jaggers JJ, Ungerleider RM. 2001. Cryopreserved homografts in the pulmonary position: determinants of durability. Ann Thorac Surg 71:54-9.nFrater RW, Furlong P, Cosgrove DM, et al. Long-term durability and patient functional status of the Carpentier-Edwards Perimount pericardial bioprosthesis in the aortic position. J Heart Valve Dis 7:48-53.nGall KL, Smith SE, Willmette CA, O'Brien MF. 1998. Allograft heart valve viability and valve-processing variables. Ann Thorac Surg 65:1032-8.nGerestein CG, Takkenberg JJ, Oei FB, et al. 2001. Right ventricular outflow tract reconstruction with an allograft conduit. Ann Thorac Surg 71:911-8.nHawkins JA, Breinholt JP, Lambert LM, McGough CC, Shaddy RE. 2000. Class I and class II anti-HLA antibodies after implantation of cryopreserved allograft material in pediatric patients. J Thorac Cardiovasc Surg 119:324-30.nHoekstra F, Knoop C, Vaessen L, et al. 1996. Donor-specific cellular immune response against human cardiac valve allografts. J Thorac Cardiovasc Surg 112:281-6.nKurz B, Steiert I, Heuchert G, Müller CA. 1999. New high resolution typing strategy for HLA-A locus alleles based on dye terminator sequencing of haplotypic group-specific PCR-amplicons of exon 2 and exon 3. Tissue Antigens 53:81-96.nLund O, Chandrasekaran V, Grocott-Mason R, et al. 1999. Primary aortic valve replacement with allografts over twenty-five years: valve-related and procedure-related determinants of outcome. J Thorac Cardiovasc Surg 117:77-90.nMiller SA, Dykes DD, Polesky HF. 1988. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215.nMittal KK, Mickey MR, Singal DP, et al. 1968. Serotyping for homo-transplantation. 18. Refinement of microdroplet lymphocyte cytotoxicity test. Transplantation 6:913-27.nNiwaya K, Knott-Craig CJ, Lane MM, Chandrasekaren K, Overhold ED, Elkins RC. 1999. Cryopreserved homograft valves in the pulmonary position: risk analysis for intermediate-term failure. J Thorac Cardiovasc Surg 117:141-6.nO'Brien MF, Finney RS, Stafford EG, et al. 1995. Root replacement for all allograft aortic valves: preferred technique or too radical? Ann Thorac Surg 60(suppl 2):S87-91.nO'Brien MF, Harrocks S, Stafford EG, et al. 2001. The homograft aortic valve: a 29-year, 99.3% follow up of 1,022 valve replacements. J Heart Valve Dis 10:334-44.nPalka P, Harrocks S, Lange A, et al. 2002. Primary aortic valve replacement with cryopreserved aortic allograft: an echocardiographic follow-up study of 570 patients. Circulation 105:61-6.nSchorn K, Yankah AC, Alexi-Meskhishvili V, et al. 1997. Risk factors for early degeneration of allografts in pulmonary circulation. Eur J Cardiothorac Surg 11:62-9.nSmith JD, Horninck PI, Rasmi N, et al. 1998. Effect of HLA mismatching and antibody status on "homovital" aortic valve homograft performance. Ann Thorac Surg 66:212-5.nTweddell JS, Pelech AN, Frommelt PC, et al. 2000. Factors affecting longevity of homograft valves used in right ventricular outflow tract reconstruction for congenital heart disease. Circulation 102(suppl 3):III130-5.nYacoub M, Rasmi NR, Sundt TM, et al. 1995. Fourteen-year experience with homovital homografts for aortic valve replacement. J Thorac Cardiovasc Surg 110:186-93.nYankah AC, Alexi-Meskhishvili V, Weng Y, et al. 1995. Accelerated degeneration of allografts in the first two years of life. Ann Thorac Surg 60(suppl 2):S71-6.n



How to Cite

Yap, C.-H., Skillington, P. D., Matalanis, G., Davis, B. B., Tait, B. D., Hudson, F., Ireland, L., Nixon, I., & Yii, M. (2008). Human Leukocyte Antigen Mismatch and Other Factors Affecting Cryopreserved Allograft Valve Function. The Heart Surgery Forum, 11(1), E42-E45.