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A UNOS Analysis of Heart Transplantation in Adults with Congenital Heart Disease: Outcomes and Factors Associated with Mortality and Retransplantation
Tara Karamlou1, Jennifer Hirsch1, Richard G Ohye1, Robert Gajarski1, Edward L Bove1, Eric J Devaney1, *Karl F Welke2
1University of Michigan, Ann Arbor, MI;2Oregon Health and Science University, Portland, OR
Objectives: Prevalence of heart transplantation (HTx) in adults (18-45 years) with congenital heart disease (ACHD) is projected to increase, yet no large studies have defined how these challenging patients differ from other adult recipients (AR). We sought to determine evolution of outcomes and risk-factors for mortality and retransplantation (RTx) among ACHD patients compared to other AR.
Methods: Review of patients between 18-45 years reported to the United Network for Organ Sharing (UNOS) database undergoing HTx from 1990-2008. Trends were compared between 2 eras: Era 1 (1990-1998) and Era 2 (1999 - 2008). Multivariable semiparametric hazard models identified factors associated with time-related death and RTx.
Results: We identified 8496 patients, of whom 575 were ACHD. Prevalence of HTx among AR decreased by 40% from Era 1 to Era 2 (4033 to 2888, P<0.001), while HTx among ACHD increased by 41% (239 to 336 (P<0.001). ACHD were younger, had longer wait-list times and ischemic times, and were more likely to have preoperative ECMO support (P<0.05 for all). Overall use of induction therapy was less prevalent in ACHD (66% vs. 71%; P=0.02). In particular, ACHD patients were less likely to receive either cyclosporine (88% vs. 93%; P=0.02) or azathioprine (63% vs. 74%; P<0.001) with induction, without a corresponding increase in other agents. Maintenance therapy was similar among ACHD and AR, except that steroids were used less frequently in ACHD (92% vs. 98%; P<0.001). Post-HTx survival among AR improved over time (Era1: 1 and 5-year survival 85% and 67%; Era2: 87% and 71%, P=0.02), whereas no era effect was seen for ACHD (Era1: 1 and 5-year survival 76% and 63%; Era2: 75% and 63%, P=0.81). Overall post-HTx mortality (P=0.006), and RTx (P=0.03) were significantly higher for ACHD than AR, mainly due to an early hazard phase (Figure). Multivariable factors associated with increased mortality included ACHD (P=0.03), older age (P<0.001), longer ischemic times (P<0.001), and female gender (P=0.04). Any induction therapy was protective for all recipients against death (P=0.01) and RTx (P=0.04).
Conclusions: Patients with ACHD represent an increasing proportion of HTx recipients. Higher post-HTx mortality and RTx among ACHD compared to AR are persistent over time. Management of immunosuppression differs among ACHD and AR. Further studies should investigate whether post-HTx ACHD outcomes would be improved by more aggressive induction therapy or alternative immunosuppression regimens. 
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