Hearts transplanted after circulatory death in children: Analysis of the International Society for Heart and Lung Transplantation registry.

2017

2017 Sep 21

1399-3046

<p>We aimed to describe worldwide DCD HT experience in children using the International Society for Heart and Lung Transplantation Registry. The Registry was queried for primary HT performed in children (2005-2014). Kaplan-Meier analysis was used to assess survival for recipients grouped by DCD or DBD hearts. Recipient characteristics were compared between DCD and DBD and between survivors and non-survivors of DCD HT. Among 3877 pediatric HT performed, 21 (0.5%) were DCD. DCD 1-year survival was 61% vs 91% DBD, P&nbsp;&lt;&nbsp;.01. DCD recipients were more often supported by ECMO pre-HT (24% vs 6%, P&nbsp;&lt;&nbsp;.001) and more often receiving inhaled nitric oxide (10% vs 0.6%, P&nbsp;&lt;&nbsp;.001) compared to DBD. Older DCD recipients had significantly lower 1-year survival of 57% vs 93% for DBD, P&nbsp;&lt;&nbsp;.01. Survival for infant DCD recipients was not statistically different to DBD recipients (survival 62% at 1&nbsp;year and 62% at 5&nbsp;years for DCD vs 85% at 1&nbsp;year and 77% at 5&nbsp;years for DBD, P&nbsp;=&nbsp;.15). Recipients of DCD HT who died were more often supported by ECMO pre-HT (56% non-survivors vs 0% survivors, P&nbsp;=&nbsp;.004) and receiving mechanical ventilation (44% vs 0%, P&nbsp;=&nbsp;.012). DCD HT is uncommon in children. DCD-independent factors in recipients may have contributed to worse survival as DCD recipients who died were more often supported by ECMO and mechanical ventilation. More research is needed to identify donor factors and recipient factors that contribute to mortality after DCD HT.</p>

10.1111/petr.13064

Pediatr Transplant

28940999

Clinical practice patterns are relatively uniform between pediatric heart transplant centers: A survey-based assessment.

2017

2017 Jul 03

1399-3046

<p>Clinical practice variations are a barrier to the study of pediatric heart transplants and coordination of multicenter RCTs in this patient population. We surveyed centers to describe practice patterns, understand areas of variation, and willingness to modify protocol. Pediatric heart transplant centers were identified, and one survey was completed per center. Simple descriptive statistics were used. The response rate was 77% (40 responses from 52 contacted centers, 37 with complete responses). Median center volume of respondents was eight transplants/year (IQR 3-19). Most centers reported tacrolimus (36/38, 95%) and mycophenolate mofetil (36/38, 95%) as maintenance immunosuppression. Other immunosuppression agents reported were cyclosporine (7/38, 18%), everolimus or sirolimus (3/38, 8%), and azathioprine (2/38, 5%). Overall, respondents answered similarly for questions regarding clinical practices including induction therapy, maintenance immunosuppression, and rejection treatment threshold (&gt;85% agreement for all). Additionally, willingness to change clinical practices was over 70% for all practices surveyed (35 total respondents), and 97% of centers (36/37) were willing to participate in a RCT of maintenance immunosuppression. In conclusion, we found many similar clinical practice protocols. Most centers are willing to collaborate on a common protocol in order to participate in a RCT and support a trial investigating maintenance immunosuppression.</p>

10.1111/petr.13013

Pediatr Transplant

28670871

Development and validation of a major adverse transplant event (MATE) score to predict late graft loss in pediatric heart transplantation.

2018

441-450

2018 Apr

1557-3117

<p><strong>BACKGROUND: </strong>There is inadequate power to perform a valid clinical trial in pediatric heart transplantation (HT) using a conventional end-point, because the disease is rare and hard end-points, such as death or graft loss, are infrequent. We sought to develop and validate a surrogate end-point involving the cumulative burden of post-transplant complications to predict death/graft loss to power a randomized clinical trial of maintenance immunosuppression in pediatric HT.</p>

<p><strong>METHODS: </strong>Pediatric Heart Transplant Study (PHTS) data were used to identify all children who underwent an isolated orthotopic HT between 2005 and 2014 who survived to 6 months post-HT. A time-varying Cox model was used to develop and evaluate a surrogate end-point comprised of 6 major adverse transplant events (MATEs) (acute cellular rejection [ACR], antibody-mediated rejection [AMR], infection, cardiac allograft vasculopathy [CAV], post-transplant lymphoproliferative disease [PTLD] and chronic kidney disease [CKD]) occurring between 6 and 36 months, where individual events were defined according to international guidelines. Two thirds of the study cohort was used for score development, and one third of the cohort was used to test the score.</p>

<p><strong>RESULTS: </strong>Among 2,118 children, 6.4% underwent graft loss between 6 and 36 months post-HT, whereas 39% developed CKD, 34% ACR, 34% infection, 9% AMR, 4% CAV and 2% PTLD. The best predictive score involved a simple MATE score sum, yielding a concordance probability estimate (CPE) statistic of 0.74. Whereas the power to detect non-inferiority (NI), assuming the NI hazard ratio of 1.45 in graft survival was 10% (assuming 200 subjects and 6% graft loss rate), the power to detect NI assuming a 2-point non-inferiority margin was &gt;85% using the MATE score.</p>

<p><strong>CONCLUSION: </strong>The MATE score reflects the cumulative burden of MATEs and has acceptable prediction characteristics for death/graft loss post-HT. The MATE score may be useful as a surrogate end-point to power a clinical trial in pediatric HT.</p>

10.1016/j.healun.2017.03.013

28465118