Gender aspects of incidence of antibody-mediated rejection and allograft vasculopathy events after heart transplantation

Abstract. Despite improvements in immunosuppressive therapy, antibody-mediated rejection (AMR) remains one of the most important risk factors for poor prognosis for survival of recipients, cardiac graft dysfunction, and cardiac allograft vasculopathy (CAV) after heart transplantation.

Aim: to assess the incidence of case of antibodymediated rejection and cardiac allograft vasculopathy depending on the gender of the patients who underwent heart transplantation in our Center from January 2010 to December 2017.

Methods. The median observation was 42 months. The study comprised 606 patients (84 [14%] women) who underwent heart transplantation in 2010 to 2017. We analyzed all the episodes of antibody-mediated rejection, which were diagnosed by the results of endomyocardial biopsies.

Results. We comparing the total incidence of antibody-mediated rejection and we are found significant differences among men and women who underwent heart transplantation (p < 0.05), the survival rate during the first year after heart transplantation was 95 and 92%, respectively. The incidence of antibody-consistent rejection was significantly higher among women who had a history of pregnancy and/or use of mechanical circulatory support systems (UNOS status 1A) in the pre-transplantation history (p < 0.05), and we also found significant differences in the incidence of cardiac allograft vasculopathy in women diagnosed with AMR (p < 0.05). The survival rate among women within a year after the diagnosis of AMR is 83% compared to 96% of the recipients free from AMR.

Conclusions. Women are at higher risk for AMR after heart transplantation and it increases their risk for cardiac allograft vasculopathy. Females recipients may more frequent myocardial control biopsies and a personalized approach in prescribing immunosuppressive therapy. Women-recipients of transplanted heart should undergo These measures will help to identify in time the development of antibodymediated rejection and reduce the incidence of cardiac allograft vasculopathy after heart transplant.

1. Stehlik J, Edwards LB, Kucheryavaya AY et al. The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Heart Transplant Report – 2011. J Heart Lung Transplant. 2011; 30: 1078–1094.

2. Predergast TW, Furukawa S, Beyer AJ 3rd, Browne BJ, Eisen HJ, Jeevanandam V.The role of gender in heart transplantation. Ann Thorac Surg. 1998; 65: 88–94.

3. Banchs HL, González V, González Canmcel I, Quintana C, Calderón R, Altieri PI.Heart transplantation in females: the experience in Puerto Rico. Bol Asoc Med P R. 2005; 97: 248–256.

4. Berry GJ, Burke MM, Andersen C, Bruneval P, Fedrigo M, Fishbein MC et al. The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2013; 32: 1147–1162.

5. Taylor DO, Yowell RL, Kfoury AG et al. Allograft coronary artery disease: clinical correlations with circulating anti-HLA antibodies and the immunohistopathologic pattern of vascular rejection. J Heart Lung Transplant. 2000; 19: 518–521.

6. Soleimani B, Lechler RI, Hornick PI et al. Role of alloantibodies in the pathogenesis of graft arteriosclerosis in cardiac transplantation. Am J Transplant. 2006; 6: 1781– 1785.

7. Topilsky Y, Gandhi MJ, Hasin T et al. Donor-specific antibodies to class II antigens are associated with accelerated cardiac allograft vasculopathy: a three-dimensional volumetric intravascular ultrasound study. Transplantation. 2013; 95: 389–396.

8. Grupper A, Nestorovic EM, Daly RC, Milic NM et al. Sex Related Differences in the Risk of Antibody-Mediated Rejection and Subsequent Allograft Vasculopathy Post-Heart Transplantation: A Single-Center Experience. Transplant Direct. 2016 Oct; 2 (10): e106.

9. Almenar L.Influence of Sex on Heart Transplantation Mortality: Data From the Spanish National Heart Transplantation Registry. Rev Esp Cardiol Supl. 2008; 8: 49D–54D.

10. Wu GW, Kobashigawa JA, Fishbein MC et al. Asymptomatic antibody-mediated rejection after heart transplantation predicts poor outcomes. J Heart Lung Transplant. 2009; 28: 417–422.