Immune privilege is an evolutionary adaptation that protects vital tissues with limited regenerative capacity from collateral damage by the immune response. Classical examples include the anterior chamber of the eye and the brain. More recently, the placenta, testes and articular cartilage were found to have similar immune privilege. What all of these tissues have in common is their vital function for evolutionary fitness and a limited regenerative capacity. Immune privilege is clinically relevant, because corneal transplantation and meniscal transplantation do not require immunosuppression. The heart valves also serve a vital function and have limited regenerative capacity after damage. Moreover, experimental and clinical evidence from heart valve transplantation suggests that the heart valves are spared from alloimmune injury. Here we review this evidence and propose the concept of heart valves as immune privileged sites. This concept has important clinical implications for heart valve transplantation.
Background: The treatment of neonates with unrepairable heart valve dysfunction remains an unsolved problem because there are no growing heart valve replacements. Heart valve transplantation is a potential approach to deliver growing heart valve replacements. Therefore, we retrospectively analysed the semilunar valve function of orthotopic heart transplants during rejection episodes. Methods: We included children who underwent orthotopic heart transplantation at our institution and experienced at least one episode of rejection between 1/1/2010 and 1/1/2020. Semilunar valve function was analysed using echocardiography at baseline, during rejection and approximately 3 months after rejection. Results: Included were a total of 31 episodes of rejection. All patients had either no (27) or trivial (4) aortic insufficiency prior to rejection. One patient developed mild aortic insufficiency during a rejection episode (P = 0.73), and all patients had either no (21) or trivial (7) aortic insufficiency at follow-up (P = 0.40). All patients had mild or less pulmonary insufficiency prior to rejection, which did not significantly change during (P = 0.40) or following rejection (P = 0.35). Similarly, compared to maximum pressure gradients across the valves at baseline, which were trivial, there was no appreciable change in the gradient across the aortic valve during (P = 0.50) or following rejection (P = 0.42), nor was there any meaningful change in the gradient across the pulmonary valve during (P = 0.55) or following rejection (P = 0.91). Conclusions: This study demonstrated that there was no echocardiographic evidence of change in semilunar valve function during episodes of rejection in patient with heart transplants. These findings indicate that heart valve transplants require lower levels of immune suppression than orthotopic heart transplants and provide partial foundational evidence to justify future research that will determine whether heart valve transplantation may deliver growing heart valve replacements for children.
Background Heart‐lung transplantation (HLTx) is relatively uncommon, and there is a paucity of literature to suggest an age at which older recipients may be exposed to excess risk for mortality. This analysis aimed to identify a threshold of age that predicts adverse outcomes after HLTx. Methods The United Network of Organ Sharing registry was used to identify adult patients undergoing HLTx from 2005 to 2021. The primary outcome was 1‐year mortality. Threshold regression was used to identify the threshold at which age impacts 1‐year mortality. Kaplan−Meier analysis was used to model survival, and Cox proportional hazards modeling was used for risk‐adjustment. Results We identified 453 patients undergoing HLTx. Threshold analysis identified that the risk for 1‐year mortality was significantly elevated beyond an age of 58 years, and 47 (10.38%) patients were older than this threshold. On Kaplan−Meier analysis, 1‐year survival was significantly lower in patients > 58 years compared to younger recipients (64.7% vs. 82.0%, p = .007). After risk adjustment, the hazard ratio for 1‐year mortality in recipients older than 58 years was 2.27 (95% confidence interval [1.21−4.28], p = .011). Conclusion A threshold for recipient age of 58 years of age may avoid excess 1‐year mortality after HLTx. However, patients older than this threshold demonstrate acceptable early and midterm survival, and the majority survive to 1 year. Advanced age should be considered in patient selection for HLTx, but may not be a contraindication for candidacy particularly in the absence of other risk factors.
Background: Prior studies have demonstrated deleterious outcomes for physician-patient racial discordance. We explored recipient-surgeon racial concordance and short-term postoperative survival in adults undergoing orthotopic heart transplantation (OHT). Methods:The United Network for Organ Sharing (UNOS) database was queried to identify White and Black adult (≥18 years) patients undergoing isolated OHT between 2000 and 2020. Surgeon race was obtained from publicly available images. All non-White and non-Black recipients and surgeons were excluded. Linear probability models were utilized to explore the relationship between recipient-surgeon racial concordance and 30-, 60-, and 90-day post-transplant mortality using a fixed effects approach.Results: A total of 26,133 recipients were identified (mean age 52.79 years, 74.4% male) with 77.65% (n = 20,292) being White and 22.35% (n = 5841) being Black. A total of 662 White surgeons performed 25,946 (97.56%) OHTs during the study period while 17 Black surgeons performed 437 (1.67%) OHTs. Although some evidence of differences across groups was observed in cross-tabular specifications, these differences became insignificant after the inclusion of controls (i.e., comorbidities and fixed effects). This suggests that recipient race and physician race are not correlated with post-OHT survival at 30, 60, or 90 days.Conclusions: Recipient-surgeon racial concordance and discordance among adults undergoing OHT do not appear to impact post-transplant survival. Nor do we observe significant penalties accruing for Black patients overall once controls are accounted for. Given that worse outcomes have historically been demonstrated for Black patients undergoing OHT, further work will be necessary to improve understanding of racial disparities for patients with end-stage heart failure.
Background: Infants with truncus arteriosus typically undergo repair by repurposing the truncal valve as the neo-aortic valve and using a valved conduit homograft for the neo-pulmonary valve. In cases where the native truncal valve is too insufficient for repair, it is replaced, but this is a rare occurrence with a paucity of data, especially in the infant population. Here, we conduct a meta-analysis to better understand the outcomes of infant truncal valve replacement during the primary repair of truncus arteriosus. Methods: We systematically reviewed PubMed, Scopus, and CINAHL for all studies reporting infant (<12 months) truncus arteriosus outcomes between 1974 and 2021. Exclusion criteria were studies which did not report truncal valve replacement outcomes separately. Data extracted included valve replacement type, mortality, and reintervention. Our primary outcome was early mortality, and our secondary outcomes were late mortality and reintervention rates. Results: Sixteen studies with 41 infants who underwent truncal valve replacement were included. The truncal valve replacement types were homografts (68.8%), mechanical valves (28.1%), and bioprosthetic valves (3.1%). Overall early mortality was 49.4% (95% CI: 28.4–70.5). The pooled late mortality rate was 15.3%/year (95% CI: 5.8–40.7). The overall rate of truncal valve reintervention was 21.7%/year (95% CI: 8.4–55.7). Conclusions: Infant truncal valve replacement has poor early and late mortality as well as high rates of reintervention. Truncal valve replacement therefore remains an unsolved problem in congenital cardiac surgery. Innovations in congenital cardiac surgery, such as partial heart transplantation, are required to address this.
There is a paucity of literature evaluating trends in the demographic composition of the cardiothoracic surgery workforce. Using the United Network for Organ Sharing database, we retrospectively analyzed the changes in sex, race, and ethnicity of surgeons performing heart transplantations between 2000–2020. Surgeons performing heart transplantations for adult (≥18 years) and pediatric (<18 years) patients between 2000–2020 were identified and stratified by sex (male, female) and by race/ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic of any race). Between 2000–2020, the proportion of non-White and female cardiothoracic surgeons performing adult and pediatric heart transplantations increased. Nevertheless, there remains a lack of diversity in the workforce, particularly when compared to the general United States population.
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