Search

Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance of immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including nonhuman primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include the appropriate selection of clinical trial participants, challenges with obtaining informed consent, animal rights and welfare considerations, and cost. Research involving recently deceased humans has also emerged as a potentially novel way to understand how xeno-organs will impact the human body. Clinical xenotransplantation and research involving decedents also raise ethical questions and will require consensus regarding regulatory oversight and protocol review. These considerations and the related opportunities for xenotransplantation research were discussed in a workshop sponsored by the National Heart, Lung, and Blood Institute, and are summarized in this meeting report., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Kiran K. Khush: recipient of NHLBI research grant on donor heart evaluation for transplantation (R01HL125303). Brendan Parent: recipient of Applebaum Foundation grant to study ethics of xenotransplantation. Karen J. Maschke and Michael Gusmano: recipients of NCATS research grant on ethical translation of xenotransplantation clinical trials (1R01TR003844-0). The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

In a workshop sponsored by the U.S. National Heart, Lung, and Blood Institute, experts identified current knowledge gaps and research opportunities in the scientific, conceptual, and ethical understanding of organ donation after the circulatory determination of death and its technologies. To minimize organ injury from warm ischemia and produce better recipient outcomes, innovative techniques to perfuse and oxygenate organs postmortem in situ, such as thoracoabdominal normothermic regional perfusion, are being implemented in several medical centers in the US and elsewhere. These technologies have improved organ outcomes but have raised ethical and legal questions. Re-establishing donor circulation postmortem can be viewed as invalidating the condition of permanent cessation of circulation on which the earlier death determination was made and clamping arch vessels to exclude brain circulation can be viewed as inducing brain death. Alternatively, TA-NRP can be viewed as localized in-situ organ perfusion, not whole-body resuscitation, that does not invalidate death determination. Further scientific, conceptual, and ethical studies, such as those identified in this workshop, can inform and help resolve controversies raised by this practice., Competing Interests: Conflict of interest statement James L. Bernat has no conflicts of interest to disclose. All authors have submitted completed JHLT conflict of interest disclosure forms., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: In an effort to optimize neurologic outcome, cerebral oxygen saturation (SCO2) is often measured intraoperatively and postoperatively. We hypothesized that SCO2 would be related to stage of palliation in children with single ventricle congenital heart disease., Methods: Cerebral oxygen saturation was continuously recorded intraoperatively in 34 infants and children undergoing palliative surgery on cardiopulmonary bypass for single ventricle congenital heart defects and in a control group of 12 neonates with ductus-dependent circulation undergoing complete repair. Saturations were correlated with the patient's stage and outcome., Results: Baseline SCO2 was 61% in single ventricle neonates (group P1, n = 10), 55% in neonates undergoing repair (group R), 42% in infants undergoing stage 2 palliation (group P2, n = 6), and 70% in children undergoing Fontan (group P3, n = 14). Baseline was lowest (41%) in infants undergoing interstage operations (group I, n = 4). After bypass, there was a significant improvement in SCO2 to 53% in group P2 infants (p = 0.04); there were no significant changes in the other groups. By the end of the operation, there was a significant decrease in SCO2 to 48% in group P1 (p = 0.001), with other groups unchanged from baseline. There were five perioperative deaths. Cerebral oxygen saturation at the conclusion of surgery was lower in children who died (38% versus 61%, p = 0.01)., Conclusions: In children with single ventricle physiology, SCO2 decreases after initial palliation, remains low before second-stage palliation, but is normal before and after the Fontan. This has implications for perioperative mortality, neurologic injury, and potentially for interim mortality. Low postoperative SCO2 predicts perioperative mortality.

Background: Recent work has focused attention on interim mortality (death after hospital discharge and before second-stage surgery) in hypoplastic left heart syndrome. This study investigates interim mortality in infants undergoing systemic-to-pulmonary artery shunts for pulmonary atresia with intact ventricular septum., Methods: At two centers in 11 years (January 1991 through December 2001), 35 infants underwent placement of shunts for palliation of pulmonary atresia with intact septum. Patients were identified from the cardiology database at each institution, and data were collected retrospectively. The infants were classified into two groups, with and without severe right ventricular hypoplasia, based on the initial surgical plan (Fontan or two-ventricle repair)., Results: The mean age and weight of the infants were 9 days and 3.1 kg. The right ventricle was severely hypoplastic in 22 of 35 infants. Hospital death occurred in 2 patients (9.1%), 1 with severe right ventricular hypoplasia. The remaining 33 patients form the study population. There were a total of 5 deaths (15%) after discharge and before second-stage operation, all in patients with severe right ventricular hypoplasia. Two patients, 1 with hypoplastic right ventricle, died after second-stage operation., Conclusions: These data confirm a significant incidence of interim death in infants with pulmonary atresia and hypoplastic right ventricle. The interim mortality rate in the current two-institution study of infants with pulmonary atresia with intact ventricular septum is similar to that in hypoplastic left heart syndrome if all patients are considered (15%), and is somewhat higher (24%) than that for hypoplastic left heart syndrome if only patients with severe right ventricular hypoplasia are considered. This rate of interim death must be considered when different treatment options (such as shunt or transplant) are contemplated.

Background: Graft failure after cardiac transplantation in children can be managed acutely with mechanical support, most commonly extracorporeal membrane oxygenation (ECMO). The purpose of this study was to evaluation the long-term outcome of ECMO support early and late after pediatric cardiac transplantation., Methods: From February 1982 through October 2002, 168 patients underwent isolated cardiac transplantation. Twenty patients (11.9%) required mechanical support early or late after transplantation. Inpatient and outpatient records of these were reviewed., Results: Indication for transplantation was complex congenital heart disease in 12, cardiomyopathy in 7, and graft failure (retransplant) in 1. One patient was also on ECMO preoperatively. Fifteen patients required circulatory support immediately or shortly (less than 6 weeks) after transplantation. The remaining 5 patients were placed on ECMO for ventricular dysfunction late (3 months to 7 years) after transplantation. In the perioperative ECMO group, 8 (53%) were successfully decannulated and subsequently discharged. Three of 5 (60%) patients placed on ECMO late were successfully decannulated, 1 of whom died in hospital 10 days later and 2 of whom are still alive., Conclusions: Mechanical circulatory support using ECMO can be a useful strategy is the management of graft dysfunction after pediatric cardiac transplantation both early and late postoperatively. The mortality rate is acceptable in this very high risk group of patients and long-term outcome is good.

Background: This retrospective review examines the risks and causes of death in infants with aortopulmonary shunts between the time of hospital discharge and planned reintervention., Methods: From January 1991 through December 2000, a total of 146 infants aged 60 days or less underwent placement of systemic-to-pulmonary artery shunts and were discharged from the hospital alive. Inpatient, outpatient, and autopsy records were reviewed., Results: Indications for surgery were single-ventricle anatomy in 90 cases and complex double-ventricle anatomy in 56. Of the patients, 21 (14%) died after discharge and before further planned surgery. Of these 21 infants, 17 (81%) were clinically doing well before sudden death. Autopsies were obtained in 15 cases and attributed the cause of death to shunt thrombosis in 5 infants (33%), myocardial infarction in 2 (13%), and pneumonia or lung disease in 3. Five autopsies were nondiagnostic. The mortality of patients discharged on aspirin (11.1%) was almost identical to that of patients discharged on no anticoagulation (12.3%). Four infants with sudden death had been notably irritable for 24 to 48 hours before death., Conclusions: There is a significant incidence of sudden death among infants who have undergone shunting. Death may be preceded by unexplained irritability, and such symptoms should therefore be carefully evaluated. Autopsy-proven shunt thrombosis is one of the leading causes of interim sudden death, and aspirin therapy may not be helpful. Options to reduce interim mortality include alternative regimens of anticoagulation (such as low-molecular weight heparin), alternative conduit material, and earlier reoperation.