Journal of Heart and Lung Transplantation最新文献

Bone health after lung transplantation has not been comprehensively reviewed in over two decades. This narrative review summarizes available literature on bone health in the context of lung transplantation, including epidemiology, presentation and post-operative management. Osteoporosis is reported in approximately 30-50% of lung transplant candidates, largely due to disease-related impact on bone and lifestyle, and corticosteroid-related effects during end-stage lung disease (interstitial lung diseases, chronic obstructive pulmonary disease, and historically cystic fibrosis). After lung transplantation, many patients experience steroid-induced bone loss, followed by stabilization or recovery to baseline levels with pharmacological management. Although evidence on fracture incidence is limited, fracture risk appears to increase in the year following transplantation, with common fracture sites including the vertebrae and the ribs. Vertebral and rib fractures restrict chest expansion and affect lung function, underscoring the importance of fracture prevention in lung transplant recipients. There is limited evidence on pharmacological management of osteoporosis after lung transplantation. Existing randomized controlled trials have focused on parenteral bisphosphonates and calcitriol, but have been underpowered to evaluate their effect on fracture outcomes. Resistance training, particularly in conjunction with antiresorptive therapy, has also been shown to improve bone health when initiated two months after transplantation. No studies to date have documented effectiveness of denosumab in lung transplant recipients; more studies on pharmacotherapy are warranted to elucidate optimal medical management. Considering high osteoporosis prevalence and high fracture risk in lung transplant populations, development of formal guidance is warranted to promote improved management after transplantation.

Background: To investigate through a meta-analysis of comparative studies the impact of donor type (brain death DBD vs circulatory death DCD) on the short- and long-term outcomes of lung transplantation(LTx).

Methods: Literature search (terms "lung transplantation" AND "donation after circulatory death") was performed up to July 2022 and studies comparing outcomes of LTx from DCD versus DBD were selected. Primary endpoints were early and long-term mortality. Secondary outcomes included primary graft dysfunction (PGD),acute rejection and postoperative complications. The long-term survival was analyzed by retrieving data from each available Kaplan-Meier and restricted mean survival time difference between DBD and DCD for long-term survival was estimated.

Results: 21 studies were included comprising 60105 patients (DBD=58548 DCD=1557). Recipient and donor baseline characteristics were similar between the two groups. No significant publication bias was observed. The estimated pooled odds ratio of early mortality favored DBD (OR=0.75,CI=0.56-1.00, I²=0%). No statistically significant difference was observed in the risk of acute rejection (OR=1.33, CI=0.82-2.17), and PGD grade 2-3 (OR=0.88, CI=0.69-1.13). One- and 5-year survival were 82.1% and 51.2%, and 86.2% and 62.7% for DBD and DCD groups, respectively (Log-rank,p<0.0001). Unadjusted hazard ratio was 0.693, with DCD as reference. DCD lungs demonstrated improved survival by 4.82% over 5-years when compared to DBD lungs.

Conclusions: This meta-analysis of comparative studies between DCD and DBD demonstrates significant long-term survival advantage of DCD LTx despite an initial small but statistically significant increased mortality risk in the short-term. Data supports the continued implementation of DCD to increase the lung donor pool.

Background: Genetically engineered porcine hearts may have an application for infants in need of a bridge to cardiac allotransplantation. The current animal model that resulted in 2 human applications has been validated in adult non-human primates only. We sought to create an infant animal model of life sustaining cardiac xenotransplantation to understand limitations specific to this age group.

Methods: We performed 11 orthotopic cardiac xenotransplants from genetically modified infantile pigs into size-matched baboons (Papio spp). Porcine grafts were preserved using a modified Del Nido solution. Protocolized post-operative care and outcomes were tracked with invasive monitoring, echocardiogram, and serial chemistries (including a 7-cytokine panel).

Results: Mean ischemic time was 52.1 +/- 13.9 min. All porcine hearts separated from bypass in normal sinus rhythm with normal systolic function documented by echocardiogram at chest closure and again at 24 h. In the first 48 post-operative hours, mean vasoactive inotropic score for the recipients was 9.6 +/- 3.5. Survival >3months was achieved in 6 animals. Five animals succumbed early (<7days) either due to errors in care (n=2) or pulmonary complications (n=3) confirmed on chest radiograph and necropsy. Cytokine levels objectively increased following xenograft implant but were not significantly different between survivors and non-survivors.

Conclusions: In a non-human primate model of infant orthotopic cardiac xenotransplantation, cardiac function does not hinder early peri-operative survival. Instead, pulmonary edema and pleural effusions in the setting of systemic inflammation preclude clinical progression. Targeted therapies are necessary to encourage prolonged survival.

Long-term survival after lung transplantation remains limited by chronic lung allograft dysfunction (CLAD), with 2 main phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). We aimed to assess CLAD lung allografts using imaging mass cytometry (IMC), a high dimensional tissue imaging system allowing a multiparametric in situ exploration at a single cell level. Four BOS, 4 RAS, and 4 control lung samples were stained with 35 heavy metal-tagged antibodies selected to assess structural and immune proteins of interest. We identified 50 immune and non-immune cell clusters. CLAD lungs had significantly reduced club cells. A Ki67-high basal cell population was mostly present in RAS and in proximity to memory T cells. Memory CD8⁺ T cells were more frequent in CLAD lungs, regulatory T cells more prominent in RAS. IMC is a powerful technology for detailed cellular analysis within intact organ structures that may shed further light on CLAD mechanisms.

Background: Since United Network for Organ Sharing (UNOS) revised their heart allocation policy in 2018, usage of veno-arterial extracorporeal life support (VA-ECLS) has dramatically increased as a bridge to transplant. This study investigated outcomes of VA-ECLS patients bridged to simultaneous heart-kidney transplant (SHK) in the new policy era.

Methods: This study included 774 adult patients from the UNOS database who received SHK between 10/18/18 and 12/31/21 and compared patients bridged to transplant on VA-ECLS (n = 50) with those not bridged (n = 724).

Results: At baseline, SHK recipients bridged from VA-ECLS were younger (50.5 vs 58.0 years, p = 0.007), had higher estimated glomerular filtration rate (eGFR) at time of transplant (47.6 vs 30.1, p < 0.001), and spent fewer days on the waitlist (7.0 vs 33.5 days, p < 0.001). In the perioperative period, VA-ECLS was associated with higher rates of temporary dialysis (56.0% vs 28.0%, p < 0.001) but similar 2-year cumulative incidence of chronic dialysis (7.5% vs 5.4%, p = 0.800) and renal allograft failure (12.0% vs 8.1%, p = 0.500) compared to non-ECLS cohort. However, VA-ECLS patients had decreased survival to discharge (76.0% vs 92.7%, p < 0.001) and 2-year post-transplant survival (71.7% vs 83.0%, p = 0.004), as well as greater 2-year cumulative incidence of cardiac allograft failure (10.0% vs 2.7%, p = 0.002). Multivariable analyses found VA-ECLS at time of transplant to be independently associated with 2-year post-transplant mortality (HR [95% CI]: 3.40 [1.66-6.96], p = 0.001) and cardiac allograft failure (sub-distribution hazard ratio [SHR] [95% CI]: 8.51 [2.77-26.09], p < 0.001).

Conclusion: Under the new allocation policy, patients bridged to SHK from VA-ECLS displayed greater early mortality and cardiac allograft failure but similar renal outcomes compared to non-ECLS counterparts.

Background: Extending survival after heart transplant (HT) is of paramount importance for childhood recipients of HT. Acute rejection is a significant event, and biopsy remains the most specific means for distinguishing between cellular (ACR) and antibody-mediated rejection (AMR).

Methods: All children in the Pediatric Heart Transplant Society Registry who underwent HT between January 2015 and June 2022 and had ≥1 rejection episode were included. Survival was compared between AMR and ACR-only. Secondary outcomes of infection, malignancy, and cardiac allograft vasculopathy (CAV) were assessed. Risk factors for graft loss after AMR were identified using Cox proportional hazard modeling.

Results: Among 906 children with rejection, 697 (77%) with complete biopsy information were included. AMR was present on biopsy in 261 (37%) patients; ACR-only was present in 436 (63%). Time to rejection was earlier for AMR, median time from HT to rejection 0.11 versus 0.29 years, p = 0.0006. Survival after AMR in the 1st year was lower than survival after ACR-only. Predictors of graft loss after AMR were younger age at HT, congenital heart disease, and rejection with hemodynamic compromise. There was no difference in time to CAV, infection, or malignancy after rejection between groups.

Conclusions: The largest analysis of pediatric HT rejection with biopsy data to identify AMR underscores the continued importance of AMR on survival. AMR is associated with higher graft loss versus ACR when occurring in the first-year post-HT. Predictors of graft loss after AMR identify patients who may benefit from increased surveillance or augmented maintenance immunosuppression.