The effect of donor-recipient sex matches on lung transplant survival: An analysis of the United Network for Organ Sharing database.

Objective: To investigate the impact of donor-recipient (DR) sex matches on survival after lung transplantation while controlling for size difference in the United Network of Organ Sharing (UNOS) database. Methods: We performed a retrospective study of 27,423 lung transplant recipients who were reported in the UNOS database (January 2005-March 2020). Patients were divided into groups based on their respective DR sex match: male to male (MM), male to female (MF), female to female, (FF), and female to male (FM). Kaplan-Meier curve and Cox regression with log-rank tests were used to assess 1-, 3-, 5-, and 10-year survival. We also modeled survival for each group after controlling for size-related variables via the Cox regression. Results: Kaplan-Meier curves showed overall significance at 1-, 3-, 5-, and 10-year end points (P < .0001). Estimated median survival time based on Kaplan-Meier analysis were 6.41 ± 0.15, 6.13 ± 0.18, 5.86 ± 0.10, and 5.37 ± 0.17 years for FF, MF, MM, and FM, respectively (P < .0001). After we controlled for size differences, FF had statistically significantly longer 5- and 10-year survival than all other cohorts. MF also had statistically significantly longer 5- and 10-year survival than FM. Conclusions: When variables associated with size were controlled for, FF had improved survival than other DR groups. A female recipient may experience longer survival with a female donor's lungs versus a male donor's lungs of similar size.

A single-center analysis of lung transplantation outcomes in recipients aged 70 or older.

OBJECTIVES: As life expectancies continue to increase, a greater proportion of older patients will require lung transplants (LTs). However, there are no well-defined age cutoffs for which LT can be performed safely. At our high-volume LT center, we explored outcomes for LT recipients ≥70 years old versus <70 years old. METHODS: This is a retrospective single-center study of survival after LT among older recipients. Data were stratified by recipient age (≥70 years old versus <70 years old) and procedure type (single versus double lung transplant). Demographics and clinical variables were compared using Chi-square test and two sample t-test. Survival was assessed by Kaplan-Meier curves and compared by log-rank test with propensity score matching. RESULTS: 988 LTs were performed at our center over 10 years, including 289 LTs in patients ≥70 years old and 699 LTs in patients <70 years old. The recipient groups differed significantly by race (p < 0.0001), sex (p = 0.003), and disease etiology (p < 0.0001). Older patients were less likely to receive a double lung transplant compared to younger patients (p < 0.0001) and had lower rates of intraoperative cardiopulmonary bypass (p = 0.019) and shorter length of stay (p = 0.001). Both groups had overall high 1-year survival (85.8% versus 89.1%, respectively). Survival did not differ between groups after propensity matching (p = 0.15). CONCLUSIONS: Our data showed high survival for older and younger LT recipients. There were no statistically significant differences observed in survival between the groups after propensity matching, however, a trend in favour of younger patients was observed.

Heart Transplant Human Leukocyte Antigen Matching in the Modern Era.

BACKGROUND: Although numerous reports have studied the consequences of human leukocyte antigen (HLA) mismatching in renal transplantation, there are limited and outdated data analyzing this association in thoracic organ transplantation. Therefore, our study reviewed the impact of HLA mismatching at both the total and the loci levels in the modern-era heart-transplant procedure on survival and chronic rejection outcomes. METHODS: We performed a retrospective analysis of adult patients after heart transplant by using the United Network for Organ Sharing database from January 2005-July 2021. Total HLA and HLA-A, HLA-B and HLA-DR mismatches were analyzed. Survival and cardiac allograft vasculopathy were the outcomes of interest during a 10-year follow-up period using Kaplan-Meier curves, log-rank tests and multivariable regression models. RESULTS: A total of 33,060 patients were included in this study. Recipients with a high degree of HLA mismatching had increased incidences of acute organ rejection. There were no significant differences in mortality rates among any of the total or loci level groups. Similarly, there were no significant differences between total HLA mismatch groups in time to first cardiac allograft vasculopathy, though mismatching at the HLA-DR locus was associated with an increased risk of cardiac allograft vasculopathy. CONCLUSION: Our analysis suggests that HLA mismatch is not a significant predictor of survival in the modern era. Overall, the clinical implications of this study provide reassuring data for the continued use of non-HLA-matched donors in an effort to increase the donor pool. If HLA matching is to be considered for heart transplant donor-recipient selection, matching at the HLA-DR locus should take priority due to its association with cardiac allograft vasculopathy.

Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study-protocol for a phase 3, randomized, controlled trial.

BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

Adequacy of Size Matching With Predicted Heart Mass Ratio in Diverse Types of Cardiomyopathies.

Predicted heart mass ratio (PHMr) has been proposed as an optimal size metric in the selection of a donor heart for transplant; however, it is not known if the same size matching criteria pertains uniformly to all types of cardiomyopathies. Heart transplant recipients in the United Network for Organ Sharing registry database were categorized into 6 groups based on the type of cardiomyopathy, dilated, coronary artery disease, hypertrophic, restrictive, valvular and adult congenital heart disease. Patients in each group of etiology were stratified based on the PHMr into 5 groups: severely undersized <0.86, moderately undersized 0.86 to 0.94, matched 0.95 to 1.04, moderately oversized 1.05 to 1.24, and severely oversized >1.25. The survival and cause of death of patients in each etiology group were reviewed. The United Network for Organ Sharing registry database from January 1987 to July 2021 included 53,573 patients who received a heart transplant. Compared with patients with size matched hearts, recipients with dilated (hazard ratio 1.17, p = 0.001) and valvular (hazard ratio 1.79, p = 0.032) cardiomyopathy who had an undersized heart with PHMr <0.86 had decreased survival. In addition, the survival of patients with hypertrophic or restrictive cardiomyopathy and adult congenital heart disease was not affected by size matching based on the PHMr (0.601 and 0.079, respectively, p = 0.873). In conclusion, our analysis suggests that the size matching criteria based on PHMr may not be uniform to all patients across various etiologies of cardiomyopathy. Therefore, the data can be used to increase the acceptance rate of donor hearts, particularly, for patients with hypertrophic, restrictive cardiomyopathy and congenital heart disease in which size matching is less significant for survival outcome.

Increased-risk versus standard-risk donation in lung transplantation: A United Network of Organ Sharing analysis.

OBJECTIVES: Donors with characteristics that increase risk of hepatitis B virus, hepatitis C virus, and HIV transmission are deemed increased-risk donors (IRDs) per Public Health Service guidelines. Compared with organs from standard-risk donors (SRDs), IRD organs are more frequently declined. We sought to investigate the outcomes of IRD lung transplant recipients following the 2013 guideline change. METHODS: We retrospectively identified lung transplant recipients using the United Network of Organ Sharing registry (February 2014 to March 2020). Patients were divided into 2 cohorts, based on Centers for Disease Control and Prevention risk status of the donor: SRD or IRD. Demographics and clinical parameters were compared across groups. Survival was compared using Kaplan-Meier curves and log-rank tests. Cox proportional hazard model was performed to identify variables associated with survival outcome. RESULTS: We identified 13,205 lung transplant recipients, 9963 who received allografts from SRDs and 3242 who received allografts from IRDs. In both groups, most donors were White, male, and <30 years old. IRDs demonstrated greater rates of heavy alcohol, cigarette, and cocaine use. SRDs had greater rates of cancer, hypertension, previous myocardial infarction, and diabetes. Survival analysis demonstrated no significant difference in 90-day, 1-year, 3-year, or 5-year survival outcome between SRD and IRD recipients (P = .34, P = .67, P = .40, P = .52, respectively). Cox regression demonstrated that double-lung transplants were associated with 13% decreased mortality risk compared with single-lung (P = .0009). CONCLUSIONS: IRD and SRD recipients demonstrated equivalent survival outcomes. Our study suggests that IRDs offer a safe approach to expand the donor pool and increase availability of lungs for transplantation.

Right Coronary Artery Button Pseudoaneurysm After the Modified Bentall Procedure.

Anastomoses of the coronary buttons are the Achilles' heel of the modified Bentall procedure (MBP) for the repair of the aortic root and ascending aorta. We present a rare case of post-MBP right coronary artery button pseudoaneurysm in a 30-year-old man. The contained leak, attributed to a pseudoknot in the polypropylene suture, was visualized via computed tomography angiography and transesophageal echocardiogram and repaired under deep hypothermic circulatory arrest.

Lung transplant survival with past and concomitant cardiac revascularization.

BACKGROUND: Coronary artery disease is common among lung transplant (LTx) candidates and has historically been viewed as a contraindication to the procedure. Survival outcomes of lung transplant recipients with concomitant coronary artery disease who had prior or perioperative revascularization remain a topic of conversation. METHODS: A retrospective analysis of all single and double lung transplant patients from Feb, 2012 to Aug, 2021 at a single center was performed (n = 880). Patients were split into 4 groups: (1) those who received a preoperative percutaneous coronary intervention, (2) those who received preoperative coronary artery bypass grafting, (3) those who received coronary artery bypass grafting during transplantation, and (4) those who had lung transplantation without revascularization. Groups were compared for demographics, surgical procedure, and survival outcomes using STATA Inc. A p value< 0.05 was considered significant. RESULTS: Most patients receiving LTx were male and white. Pump type (p = 0.810), total ischemic time (p = 0.994), warm ischemic time (p = 0.479), length of stay (p = 0.751), and lung allocation score (p = 0.332) were not significantly different between the four groups. The no revascularization group was younger than the other groups (p<0.01). The diagnosis of Idiopathic Pulmonary Fibrosis was predominant in all groups except the no revascularization group. The pre-coronary artery bypass grafting group had a higher portion of single LTx procedures (p = 0.014). Kaplan-Meier analysis showed no significantly different survival rates after post-LTx between the groups (p = 0.471). Cox Regression analysis showed diagnosis significantly impacted survival rates (p 0.009). CONCLUSIONS: Preoperative or intraoperative revascularization did not affect survival outcomes in lung transplant patients. Selected patients with coronary artery disease may benefit when intervened during lung transplant procedures.

A rare case of Rosai-Dorfman disease presenting as a pulmonary artery mass in a 33-year-old female with hypoxia.

Rosai-Dorfman disease (RDD) is a rare form of non-Langerhans histiocytosis. It is often idiopathic in etiology, but has been associated with viral, autoimmune, and malignant disease. Adequate diagnosis of RDD requires a combination of clinical symptoms, radiography, and histology. Most commonly, patients with RDD present with cervical lymphadenopathy. We describe a case of a young female who was initially thought to have a pulmonary embolism at the time of a COVID-19 infection but was noted to have a rare occurrence of RDD presenting as a pulmonary artery mass upon further evaluation of radiology and histology. Though RDD is frequently benign, extranodal involvement can progress to end organ damage and must be recognized appropriately.

Impact of donor ventricular function on heart transplantation outcomes.

BACKGROUND: Some heart transplant (HTx) centers have expanded their donor eligibility criteria in response to the organ shortage; one area of active interest involves utilizing hearts with ventricular dysfunction. Our study seeks to identify if a relationship exists between donor left ventricular ejection fraction (LVEF) and ischemic time or donor age on HTx outcomes. METHODS: We performed a retrospective analysis on adult patients who had a HTx between 1996 and 2021 (n = 46,936). Donor LVEF (dLVEF) values were categorized into three groups: <50%, 50%-70%, and >70%. Ischemic time and donor age were stratified into four groups: ≤2.0, 2.1-3.0, 3.1-4.0, >4.0 h, and ≤30, 31-40, 41-50, >50 years, respectively. The outcome of interest was long-term survival. RESULTS: Multivariable survival analysis found a slight increase in overall mortality risk for patients with donor ejection fractions <50% (HR = 1.16, p = .013). However, subsequent subgroup investigation discovered that this elevated hazard was only applicable when ischemic time was prolonged to >3.0 h (3.1-4.0 h: HR = 1.23, p = .024; > 4.0 h: HR = 1.52, p < .001). There was no significant difference in survival between dLVEF groups when ischemic time was limited to ≤3.0 h or when stratified by donor age. CONCLUSION: HTx patients with a low donor ejection fraction have comparable survival to recipients with a normal dLVEF when ischemic time is limited to ≤3.0 h. Reduced dLVEF does not appear to be sensitive to advanced donor age. The clinical implications of our study may encourage the recruitment of more donor hearts for transplantation.

Intraoperative Red Blood Cell Transfusion and Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: In this international, multicenter study of patients undergoing lung transplantation (LT), we explored the association between the amount of intraoperative packed red blood cell (PRBC) transfusion and occurrence of primary graft dysfunction (PGD) and associated outcomes. METHODS: The Extracorporeal Life Support in LT Registry includes data on LT recipients from 9 high-volume (>40 transplants/y) transplant centers (2 from Europe, 7 from the United States). Adult patients who underwent bilateral orthotopic lung transplant from January 2016 to January 2020 were included. The primary outcome of interest was the occurrence of grade 3 PGD in the first 72 h after LT. RESULTS: We included 729 patients who underwent bilateral orthotopic lung transplant between January 2016 and November 2020. LT recipient population tertiles based on the amount of intraoperative PRBC transfusion (0, 1-4, and >4 units) were significantly different in terms of diagnosis, age, gender, body mass index, mean pulmonary artery pressure, lung allocation score, hemoglobin, prior chest surgery, preoperative hospitalization, and extracorporeal membrane oxygenation requirement. Inverse probability treatment weighting logistic regression showed that intraoperative PRBC transfusion of >4 units was significantly ( P < 0.001) associated with grade 3 PGD within 72 h (odds ratio [95% confidence interval], 2.2 [1.6-3.1]). Inverse probability treatment weighting analysis excluding patients with extracorporeal membrane oxygenation support produced similar findings (odds ratio [95% confidence interval], 2.4 [1.7-3.4], P < 0.001). CONCLUSIONS: In this multicenter, international registry study of LT patients, intraoperative transfusion of >4 units of PRBCs was associated with an increased risk of grade 3 PGD within 72 h. Efforts to improve post-LT outcomes should include perioperative blood conservation measures.

Red Blood Cell Transfusion Prior to Lung Transplantation: Impact on Patient Outcomes.

There is an established association between red blood cell (RBC) transfusion and increased mortality and morbidity in cardiac surgery; however, there is little data demonstrating the influence of blood transfusion while awaiting lung transplantation. Therefore, our study compared the impact of pretransplant RBC transfusion on patient survival and post-transplantation adverse events. Adult lung transplant patient data were extracted retrospectively using the United Network for Organ Sharing thoracic database. Patients were stratified into two groups based on pretransplant transfusion status. In total, 28,217 patients were analyzed in our study (transfused: n = 1,415 and not transfused: n = 26,802). There was an increasing trend in pretransplant transfusion rates from 2006 to 2020. Transfused patients had a higher incidence of adverse events post-transplantation, including dialysis, stroke, and acute organ rejection before discharge. Multivariable survival analysis found an increased mortality risk in patients who required pretransplant transfusion(s) compared to those who did not have a transfusion (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.17-1.41; p < 0.001). There was no significant difference in bronchiolitis obliterans syndrome development between groups (HR: 0.92; 95% CI: 0.82-1.04; p = 0.185). To conclude, our study provides data to suggest that RBC transfusion(s) before lung transplantation are associated with increased patient morbidity and mortality, but have no association with chronic graft rejection development.

Lung Transplantation for COVID-19 Pulmonary Sequelae.

BACKGROUND: The role of lung transplantation for coronavirus disease 2019 (COVID-19)-related lung failure is evolving as the pandemic persists. METHODS: From January 2021 to April 2022, 20 patients (median age 62 y; range 31-77) underwent lung transplantation for COVID-related lung failure at our institution. We reviewed their clinical and intraoperative characteristics and early outcomes including postoperative complications. RESULTS: Eleven patients (55%) had chronic lung disease when they contracted COVID-19. All 20 patients required hospitalization for antivirus treatment. Median lung allocation score was 74.7 (33.1-94.0). Thirteen patients (65%) underwent single-lung transplants, and 7 patients (35%) underwent double-lung transplants. Concomitant coronary artery bypass graft surgery was performed in 2 (10%) patients because of severe coronary artery disease. Postoperatively, venovenous extracorporeal membrane oxygenation was needed in 3 patients (15%) because of severe primary graft dysfunction; all were eventually weaned. Ten patients (50%) experienced deep venous thrombosis, and 1 eventually developed a major pulmonary embolus. The median intensive care unit stay and hospital stays were 6.5 d (3-44) and 18 d (7-77), respectively. During a median follow-up of 201 d (47-418), we experienced 1 late mortality due to COVID-19-related myocarditis. Among the 13 patients with single-lung transplant, 5 demonstrated improvement in their native lungs. CONCLUSIONS: Lung transplantation yielded favorable early outcomes in a heterogeneous patient cohort that included older patients, obese patients, and patients with coronary artery disease or preexisting chronic lung disease. Our data also shed light on the transforming role of lung transplantation for the pulmonary sequelae of a complex multisystem COVID-19 disorder.

Two Staged Single Lung Transplants in the Current Era: A United Network for Organ Sharing Study.

BACKGROUND: We hypothesized that outcomes after 2 staged, contralateral single lung transplantation procedures (SSLTs) may be equivalent to those of double lung transplantation (DLT) by capitalizing on the known long-term survival advantages of DLT. METHODS: Using the United Network for Organ Sharing data set (1987-2018), the largest national data set available, the outcomes of 278 SSLTs were retrospectively analyzed and compared with the outcomes of 21,121 standard DLTs. RESULTS: During SSLT, the median interval between the 2 transplants was 960 days, and the indication for the second transplant was most often chronic lung allograft dysfunction (n = 148; 53.2%) or the same disease that necessitated the first transplant (n = 81; 29.1%). The patients who underwent SSLT were significantly older and had a higher baseline creatinine level than the patients who underwent DLT. Most posttransplantation short-term outcomes were equivalent between the second stage of SSLT and DLT, but renal insufficiency requiring hemodialysis was notably higher after SSLT. There were no differences in long-term survival. In multivariate analysis, baseline creatinine, O2 support at rest, ventilator support at the time of the second transplantation, and posttransplantation renal insufficiency requiring dialysis were independent predictors of 1-year mortality after SSLT. CONCLUSIONS: Over a study period of 30 years, long-term survival after SSLT was comparable with survival after DLT. With further analysis of individual risk profiles, including the contributions of preoperative renal function and functional status, SSLT can be a valuable option for patients who would have undergone single lung transplantation to reap the long-term benefits of a second transplant.

COMPETENCE Trial: The EVAHEART 2 continuous flow left ventricular assist device.

BACKGROUND: Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices. METHODS: A prospective, multi-center randomized non-inferiority study, COMPETENCE Trial, is underway to assess non-inferiority of the EVA2 to the HeartMate 3 LVAS when used for the treatment of refractory advanced heart failure. The primary end-point is a composite of the individual primary outcomes: Survival to cardiac transplant or device explant for recovery; Free from disabling stroke; Free from severe Right Heart Failure after implantation of original device. Randomization is in a 2:1 (EVA2:HM3) ratio. RESULTS: The first patient was enrolled into the COMPETENCE Trial in December of 2020, and 25 subjects (16 EVA2 and 9 HM3) are currently enrolled. Enrollment of a safety cohort is projected to be completed by third quarter of 2022 at which time an interim analysis will be performed. Short-term cohort (92 EVA2 subjects) and long-term cohort is expected to be completed by the end of 2023 and 2024, respectively. CONCLUSIONS: The design features of the EVA2 such as a novel inflow cannula and large blood gaps may improve clinical outcomes but require further study. The ongoing COMPETENCE trial is designed to determine if the EVA2 is non-inferior to the HM3.

Surgical management of primary aortic thrombus in thoracic aorta.

Background: Primary aortic thrombus (PAT) in the absence of underlying aortic pathology such as atherosclerosis or aneurysm is quite rare and presents with various symptoms related to distal embolization. Treatment options include anticoagulation alone, open surgical thrombectomy, endovascular repair, and a combination of these approaches. The optimal management strategy remains controversial. Methods: Between 2016 and 2020, 10 patients (6 females; mean age, 49.1 years) presented to our institution with PAT in the thoracic aorta. All 10 patients were active tobacco users, and 6 patients were found to have an underlying hypercoagulable state. Locations of the PAT included the ascending aorta in 4 patients, the descending thoracic aorta in 3 patients, and the aortic root, aortic arch, and thoracoabdominal aorta in 1 patient each. At presentation, 2 patients had developed myocardial infarction, and 2 others had cerebral infarction. All patients but 1, who was managed medically for PAT, underwent open surgical thrombectomy via either sternotomy or left thoracotomy. Concomitant procedures included coronary artery bypass grafting in 2 patients and pulmonary thromboembolectomy in 1 patient. There were no operative deaths. During a median follow-up of 18 months, 2 patients developed recurrent PAT, owing primarily to poor compliance with anticoagulation. One patient required redo open thrombectomy. Two patients had mesenteric ischemia necessitating small bowel resection. Conclusions: Open surgical thrombectomy of the thoracic aorta can be performed with low mortality and morbidity; however, PAT can recur, especially in patients who have difficulty managing anticoagulation.