Journal of Heart and Lung Transplantation最新文献

Despite increasing therapeutic options and evolving treatment strategies, including targeting 3 therapeutic pathways, in the management of pulmonary arterial hypertension (PAH), morbidity and mortality have remained unacceptably high. Sotatercept is a first-in-class, novel activin signaling inhibitor approved for treating PAH based on evolving efficacy and safety evidence. This state-of-the-art review summarizes the current understanding of the mechanism of action, the impact on outcomes that improve how patients feel, function, and survive, and the safety and adverse event profile to inform readers of this breakthrough novel therapy.

Background: Donor human leukocyte antigen (HLA)-specific antibodies (DSA) and non-HLA antibodies can cause allograft injury, possibly leading to chronic lung allograft dysfunction (CLAD) after lung transplantation. It remains unclear whether these antibodies are produced locally in the graft or derived solely from circulation. We hypothesized that DSA and non-HLA antibodies are produced in CLAD lungs.

Methods: Lung tissue was prospectively collected from 15 CLAD patients undergoing retransplantation or autopsy. 0.3 g of fresh lung tissue was cultured for 4 days without or with lipopolysaccharide or CD40L: lung culture supernatant (LCS) was sampled. Protein eluate was obtained from 0.3 g of frozen lung tissue. The mean fluorescence intensity (MFI) of DSA and non-HLA antibodies was measured by Luminex and antigen microarray, respectively.

Results: LCS from all 4 patients who had serum DSA at lung isolation were positive for DSA, with higher levels measured after CD40L stimulation (CD40L⁺LCS). Of these, only 2 had detectable DSA in lung eluate. MFI of non-HLA antibodies from CD40L⁺LCS correlated with those from lung eluate but not with those from sera. Flow cytometry showed higher frequencies of activated lung B cells in patients whose CD40L⁺LCS was positive for DSA (n = 4) or high non-HLA antibodies (n = 6) compared to those with low local antibodies (n = 5). Immunofluorescence staining showed CLAD lung lymphoid aggregates with local antibodies contained larger numbers of IgG⁺ plasma cells and greater IL-21 expression.

Conclusions: We show that DSA and non-HLA antibodies can be produced within activated B cell-rich lung allografts.

Background: Microvascular dysfunction after heart transplantation leads to restrictive cardiac allograft physiology (RCP), which is classified as severe coronary allograft vasculopathy (CAV); however, the prognosis of RCP remains unclear. Therefore, in this study, we aimed to elucidate the prognosis of RCP in comparison with that of severe angiographic CAV.

Methods: We assessed 116 patients with severe CAV who underwent heart transplantation between 2004 and 2023. RCP was defined as symptomatic heart failure with restrictive hemodynamic values (mean right atrial pressure >12 mm Hg, pulmonary capillary wedge pressure >25 mm Hg, and cardiac index <2.0 liter/min/m²). The primary outcome was death or retransplantation.

Results: Of the 116 patients with severe CAV, 42 had RCP (RCP-CAV group) and 74 had severe angiographic CAV without RCP (Angio-CAV group). A significantly shorter time from heart transplantation to diagnosis and lower subsequent percutaneous catheter intervention after diagnosis were seen in the RCP-CAV group than in the Angio-CAV group (both p < 0.001). Freedom from death or retransplantation at 5 years was significantly worse in the RCP-CAV group compared to the Angio-CAV group (18.4% vs 35.4%, p = 0.001). In the Cox proportional hazard model, RCP was independently associated with an increased risk of death or retransplantation (hazard ratio 2.08, 95% confidence intervals 1.26-3.44, p = 0.004).

Conclusions: The prognosis of patients with RCP was significantly worse than that of patients with severe angiographic CAV. The early detection of microvascular dysfunction and retransplantation listing may improve the prognosis of patients with RCP.

For patients with end-stage heart disease and borderline hemodynamics, high human leukocyte antigen allosensitization presents a barrier to heart transplantation in a timely manner. Conventional desensitization protocols are inadequate in this context due to time constraints and for the most highly reactive immunologically. We previously reported performing heart after liver transplant with domino liver transplant on a single patient without liver disease. We describe this patient's course to date as well as 4 subsequent patients listed for this novel therapy. This experience demonstrates that the liver effectively confers immunoprotection to the heart for patients with high-titer, preformed antibodies. This strategy may provide some measure of equity for demographic groups previously disadvantaged for heart transplantation due to allosensitization.

Background: Primary graft dysfunction (PGD) contributes substantially to both short- and long-term mortality after lung transplantation, but the mechanisms that lead to PGD are not well understood. Exposure to ambient air pollutants is associated with adverse events during waitlisting for lung transplantation and chronic lung allograft dysfunction, but its association with PGD has not been studied. We hypothesized that long-term exposure of the lung donor and recipient to high levels of ambient air pollutants would increase the risk of PGD in lung transplant recipients.

Methods: Using data from 1428 lung transplant recipients and their donors enrolled in the Lung Transplant Outcomes Group observational cohort study, we evaluated the association between the development of PGD and zip-code-based estimates of long-term exposure to 6 major air pollutants (ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, particulate matter 2.5, and particulate matter 10) in both the lung donor and the lung recipient. Exposure estimates used daily EPA air pollutant monitoring data and were based on the geographic centroid of each subject's residential zip code. Associations were tested in both univariable and multivariable models controlling for known PGD risk factors.

Results: We did not find strong associations between air pollutant exposures in either the donor or the recipient and PGD.

Conclusions: Exposure to ambient air pollutants, at the levels observed in this study, may not be sufficiently harmful to prime the donor lung or the recipient to develop PGD, particularly when considering the robust associations with other established PGD risk factors.

Background: While structural socioeconomic inequity has been linked with inferior health outcomes, some have postulated reduced access to high-quality care to be the mediator. We assessed whether treatment at high-volume centers (HVC) would mitigate the adverse impact of area deprivation on heart transplantation (HT) outcomes.

Methods: All HT recipients ≥18 years were identified in the 2005-2022 Organ Procurement and Transplantation Network. Neighborhood socioeconomic deprivation was assessed using the previously validated Area Deprivation Index. Recipients with scores in the highest quintile were considered Most Deprived (others: Less Deprived). Hospitals in the highest quartile by cumulative center volume (≥21 transplants/year) were classified as HVC. The primary outcome was post-transplant survival.

Results: Of 38,022 HT recipients, 7,579 (20%) were considered Most Deprived. Following risk adjustment, Most Deprived demonstrated inferior survival at 3 (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.06-1.21) and 5 years following transplantation (HR 1.13, CI 1.07-1.20). Similarly, Most Deprived faced greater graft failure at 3 (HR 1.14, CI 1.06-1.22) and 5 years (HR 1.13, CI 1.07-1.20). Evaluating patients transplanted at HVC, Most Deprived continued to face greater mortality at 3 (HR 1.10, CI 1.01-1.21) and 5 years (HR 1.10, CI 1.01-1.19). The interaction between Most Deprived status and care at HVC was not significant, such that transplantation at HVC did not ameliorate the survival disparity between Most and Less Deprived.

Conclusions: Area socioeconomic disadvantage is independently associated with inferior survival. Transplantation at HVC did not eliminate this inequity. Future efforts are needed to increase engagement with longitudinal follow-up care and address systemic root causes to improve outcomes.

Background: Patients of advanced age are often considered to be poor candidates for heart transplant (HT). As the U.S. population continues to age, it is important for clinicians to understand how best to select patients for advanced therapies.

Methods: This was a retrospective analysis of the U.S. Scientific Registry of Transplant Recipients data from 2006 to August 2022 in adult recipients. Patients were excluded if they were multiorgan transplant, re-do transplants, or less than 1 year post transplant.

Results: Recipients ≥70 had a 1-year survival of 87.5%, compared to 91.1% for <60%, and 88.4% for 60-69 years (p < 0.001). Survival improved numerically, but not significantly, as transplant eras progressed for those ≥70 years. Survival by Kaplan-Meier analysis was greatest at 5 years for <60 years (80.6%), compared to 60-69 years (78.2%) and ≥70 years (77.1%). When comparing 60-69 years to ≥70 years by this same metric, there was significant difference (p = 0.12). One year survival for those ≥70 years has improved from 2000-2009 (80.7%) to 88.5% since October 2018 (p < 0.001). As recipients increased in age, they were more likely to be male, and less likely to be Black or Hispanic/Latino (p < 0.001).

Conclusion: Overall, HT outcomes are excellent for carefully selected patients ≥70 years, and transplanting patients in this age cohort can be considered.

Background: Temporary mechanical circulatory support (tMCS) has become a standard treatment in cardiogenic shock but is associated with high complication rates. This study analyzes common complications associated with modern tMCS devices and their impact on mortality depending on the tMCS approach.

Methods: We conducted a retrospective single-center analysis of patients with all-cause cardiogenic shock treated with veno-arterial extracorporeal life support, microaxial flow pump, and a combination of both (ECMELLA). The primary outcome was the impact of cumulative complications on mortality, evaluated separately for nonsurgical (non-PCCS) and cardiac surgical (PCCS) patients. Secondary outcomes included the impact of complications on mortality stratified by tMCS type and rates of bleeding, the need for renal replacement therapy (RRT), hemolysis, neurological complications, bloodstream infections, and ischemic limb complications.

Results: We included 493 patients, totaling 4,881 days on tMCS support. Non-PCCS patients with 1 complication had a hazard ratio (HR) of 1.92 (95% confidence interval [CI]: 1.22, 3.00, p = 0.004) for mortality and 3.73 (95% CI: 2.48, 5.60, p < 0.001) for 2 or more complications compared to those without complications. In PCCS patients, 1 complication was associated with an HR of 2.22 (95% CI: 1.29, 3.81, p = 0.004) and 3.44 (95% CI: 2.04, 5.78, p < 0.001) for 2 or more complications. The most common complications in both non-PCCS and PCCS patients were bleeding (33% and 60%), need for RRT (31% and 43%), and severe hemolysis (26% and 35%).

Conclusion: Complications among tMCS-treated patients are common and clearly associated with an elevated mortality risk.