Nationwide hospitalizations of patients with down syndrome and congenital heart disease over a 15-year period.

Down syndrome is one of the most common genetic diseases, generally associated with an increased probability of congenital heart diseases. This increased risk contributes to escalated levels of morbidity and mortality. In this study, we sought to analyze nationwide data of pediatric and adult patients with Down syndrome and congenital heart disease over a 15-year period. Data obtained from the hospital discharge form between 2001 and 2016 of patients diagnosed with Down syndrome in Italy and at least one congenital heart disease were included. Information on 12362 admissions of 6527 patients were included. Age at first admission was 6.2 ± 12.8 years and was a predictor of mortality (HR = 1.51, 95% CI 1.13-2.03, p = 0.006). 3923 (60.1%) patients underwent only one admission, while 2604 (39.9%) underwent multiple (> 1) admissions. There were 5846 (47.3%) admissions for cardiac related symptoms. Multiple admissions (SHR: 3.13; 95% CI: 2.99, 3.27; P < 0.01) and cardiac admissions (SHR: 2.00; 95% CI: 1.92, 2.09; P < 0.01) were associated with an increased risk of additional potential readmissions. There was an increased risk of mortality for patients who had cardiac admissions (HR = 1.45, 95% CI: 1.08-1.94, p = 0.012), and for those who underwent at least 1 cardiac surgical procedure (HR = 1.51, 95% CI 1.13-2.03, p = 0.006). CONCLUSIONS: A younger age at first admission is a predictor for mortality in patients with Down syndrome and congenital heart disease. If patients undergo more than one admission, the risk of further readmissions increases. There is a pivotal role for heart disease in influencing the hospitalization rate and subsequent mortality. WHAT IS KNOWN: • Down syndrome individuals often face an increased risk of congenital heart diseases. • Congenital heart diseases contribute significantly to morbidity and mortality in Down syndrome patients. WHAT IS NEW: • This study analyzes nationwide data covering a 15-year period of pediatric and adult patients in Italy with Down syndrome and congenital heart disease. • It identifies a younger age at first admission as a predictor for mortality in these patients, emphasizing the criticality of early intervention. • Demonstrates a correlation between multiple admissions, particularly those related to cardiac issues, and an increased risk of further readmissions, providing insights into the ongoing healthcare needs of these individuals.

Impact of age over 70 years in the new allocation system on the outcomes of heart transplantation in the US.

BACKGROUND: United Network for Organ Sharing (UNOS) allocation criteria changed in 2018 to accommodate the increased prevalence of patients on a ventricular assist device as a bridge to heart transplant and prioritize sicker people in anticipation of a heart graft. We aimed to assess the impact of patient age in the new allocation policy on mortality following heart transplantation. Secondary outcomes included the effect of age ≥70 on post-transplant events, including stroke, dialysis, pacemaker, and rejection requiring treatment. METHODS: The UNOS Registry was queried to identify patients who underwent heart transplants alone in the US between 2000 and 2021. Patients were divided into groups according to their age (over 70 and under 70 years old). RESULTS: Patients aged over 70 were more likely to require dialysis during follow-up, but less likely to experience rejection requiring treatment, compared with patients aged <70. Age ≥70 in the new allocation system was a significant predictor of 1-year mortality (adjusted HR: 1.41; 95% CI: 1.05-1.91; p = .024), but its effect on 5-year mortality was not significant after adjusting for potential confounders (adjusted HR: 1.27; 95% CI:.97-1.66; p = .077). Undergoing transplantation under the new allocation policy vs the old allocation policy was not a significant predictor of mortality in patients over 70 years old. CONCLUSIONS: Age ≥70 is a significant predictor of 1-year mortality following heart transplantation, but not at 5 and 10 years; however, the new allocation does not seem to have changed the outcomes for this group of patients.

Mitral Valve Repair of the Anterior Leaflet: Are We There Yet?

Mitral regurgitation is one of the most prevalent valvulopathies with a disease burden that incurs significant healthcare costs globally. Surgical repair of the posterior mitral valve leaflet is a standard treatment, but approaches for repairing the anterior mitral valve leaflet are not widely established. Since anterior leaflet involvement is less common and more difficult to repair, fewer studies have investigated its natural history and treatment options. In this review, we discuss surgical techniques for repairing the anterior leaflet and their outcomes, including survival, reoperation, and recurrence of regurgitation. We show that most patients with mitral regurgitation from the anterior leaflet can be repaired with good outcomes if performed at centers with expertise. Additionally, equal consideration for early repair should be given to patients with mitral regurgitation from both anterior and posterior pathology. However, more studies to better evaluate the efficacy and safety of anterior mitral valve leaflet repair are needed.

Impact of new allocation system on length of stay following heart transplantation in the United States.

BACKGROUND: United Network for Organ Sharing (UNOS) allocation criteria changed in 2018 to accommodate the increased prevalence of ventricular assist device use as a bridge to heart transplant, which consequently prioritized sicker patients. We aimed to assess the impact of this new allocation policy on the length of stay following heart transplantation. Secondary outcomes include other risk factors for prolonged hospitalization and its effect on mortality and postoperative complications. METHODS: The UNOS Registry was queried to identify patients who underwent isolated heart transplants in the United States between 2001 and 2023. Patients were divided into quartiles according to their respective length of stay. RESULTS: A total of 57 020 patients were included, 15 357 of which were allocated with the new system. The median hospital length of stay was 15 days (mean 22.7 days). Length of stay was longer in the new allocation era (25 ± 30 vs. 22 ± 27 days, p < .001). The longer length of stay was associated with increased 5-year mortality in the new allocation system (aHR: 1.18; 95% CI: 1.15, 1.20; p-value: < .001). CONCLUSION: Longer hospital stays and associated observed increased risk for mortality in the era after the allocation criteria change reflect the rationale of this shift which was to prioritize heart transplants for sicker patients. Further studies are needed to track the progress of surgical and perioperative management of these studies over time.

Staged ventricular recruitment and biventricular conversion following single-ventricle palliation in unbalanced atrioventricular canal defects.

Objective: Restoration of biventricular circulation is an alternative management strategy in unbalanced atrioventricular canal defects (uAVCDs), especially in patients with risk factors for single-ventricle palliation (SVP) failure. When ventricular volume is inadequate for biventricular circulation, recruitment procedures may accommodate its growth. In this study, we review our uAVCD experience with biventricular conversion (BIVC) after prior SVP. Methods: This is a single-institution, retrospective cohort study of uAVCD patients who underwent BIVC after SVP, with staged recruitment (staged) or primary BIVC (direct) between 2003 to 2018. Mortality, unplanned reinterventions, imaging, and catheterization data were analyzed. Results: Sixty-five patients underwent BIVC from SVP (17 stage 1, 42 bidirectional Glenn, and 6 Fontan). Decision for conversion was based on poor SVP candidacy (n = 43) or 2 adequately sized ventricles (n = 22). Of the 65 patients, 20 patients underwent recruitment before conversion. The staged group had more severe ventricular hypoplasia than the direct group, reflected in prestaging end-diastolic volume z scores (-4.0 vs -2.6; P < .01), which significantly improved after recruitment (-4.0 to -1.8; P < .01). Median follow-up time was 1.0 years. Survival and recatheterizations were similar between both groups (hazard ratio, 0.9; 95% CI, 0.2-3.7; P = .95 and hazard ratio, 1.9; 95% CI, 0.9-4.1; P = .09), but more reoperations occurred with staged approach (hazard ratio, 3.1; 95% CI, 1.3-7.1; P = .01). Conclusions: Biventricular conversion from SVP is an alternative strategy to manage uAVCD, particularly when risk factors for SVP failure are present. Severe forms of uAVCDs can be converted with staged BIVC with acceptable mortality, albeit increased reinterventions, when primary BIVC is not possible.

Pacemaker Implantation following Heart Transplantation: Analysis of a Nation-Wide Database.

BACKGROUND: The 2018 United-Network-for-Organ-Sharing (UNOS) allocation-system changes resulted in greater recognition of mechanical circulatory support (MCS), leading to more heart transplantations (HTx) in patients with MCS. We aimed to investigate the effect of the new UNOS allocation system on the need for a permanent pacemaker and associated complications following HTx. METHODS: The UNOS Registry was questioned, to identify patients that received HTx in the US between 2000 and 2021. The primary objectives were to identify risk factors for the need for a pacemaker implantation following HTx. RESULTS: 49,529 HTx patients were identified, 1421 (2.9%) requiring a pacemaker post-HTx. Patients who required a pacemaker were older (53.9 ± 11.5 vs. 52.6 ± 12.8 years, p < 0.001), more frequently white (73% vs. 67%; p < 0.001) and less frequently black (18% vs. 20%; p < 0.001). In the pacemaker group, UNOS status 1A (46% vs. 41%; p < 0.001) and 1B (31% vs. 27%; p < 0.001) were more prevalent, and donor age was higher (34.4 ± 12.4 vs. 31.8 ± 11.5 years; p < 0.001). One-year survival was no different between the groups (HR: 1.08; 95% CI: 0.85, 1.37; p = 0.515). An era effect was observed (per year: OR: 0.97; 95% CI: 0.96, 0.98; p = 0.003), while ECMO pre-transplant was associated with lower risk of a pacemaker (OR: 0.41; 95% CI: 0.19, 0.86; p < 0.001). CONCLUSIONS: While associated with various patient and transplant characteristics, pacemaker implantation does not seem to impact one-year survival after HTx. The need for pacemaker implantation was lower in the more recent era and in patients who required ECMO pre-transplant, a finding explained by recent advances in perioperative care.

Analysis of heart retransplantation outcomes in the new donor heart allocation system.

Cardiac graft failure may require repeat heart transplantation (HTx). Outcomes of patients that undergo repeat HTx have not been well described. We compared patients that received repeat HTx with patients that received initial HTx by inquiring the United Network for Organ Sharing (UNOS) database between 2015 and 2021. The primary endpoint was all-cause mortality, while the role of baseline characteristics was also investigated. Patients were stratified according to whether they received initial HTx (n = 19,727, 97%) or repeat HTx (n = 578, 3%). Among the study population, 10,860 (53.5%) patients received a HTx using the old UNOS allocation system, whereas 9445 (46.5%) patients received a HTx after the implementation of the new UNOS donor allocation system in October 2018. In this sub-group of HTx recipients in the new allocation system era, the adjusted 1-year survival of repeat HTx patients remained lower than that of initial HTx patients (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.15, 3.18; p = 0.013). When we compared the 1-year survival of repeat HTx patients before and after the implementation of the new allocation system, the adjusted 1-year survival was similar between groups (HR: 1.14; 95% CI: 0.71, 1.84; p = 0.591). The unadjusted risk of 30-day mortality was not significantly different in the new vs old allocation system. Mortality associated with repeat HTx remained higher than initial HTx but the new donor allocation system implementation did not affect outcomes.

Machine learning-based prediction of mortality after heart transplantation in adults with congenital heart disease: A UNOS database analysis.

BACKGROUND: Machine learning (ML) is increasingly being applied in Cardiology to predict outcomes and assist in clinical decision-making. We sought to develop and validate an ML model for the prediction of mortality after heart transplantation (HT) in adults with congenital heart disease (ACHD). METHODS: The United Network for Organ Sharing (UNOS) database was queried from 2000 to 2020 for ACHD patients who underwent isolated HT. The study cohort was randomly split into derivation (70%) and validation (30%) datasets that were used to train and test a CatBoost ML model. Feature selection was performed using SHapley Additive exPlanations (SHAP). Recipient, donor, procedural, and post-transplant characteristics were tested for their ability to predict mortality. We additionally used SHAP for explainability analysis, as well as individualized mortality risk assessment. RESULTS: The study cohort included 1033 recipients (median age 34 years, 61% male). At 1 year after HT, there were 205 deaths (19.9%). Out of a total of 49 variables, 10 were selected as highly predictive of 1-year mortality and were used to train the ML model. Area under the curve (AUC) and predictive accuracy for the 1-year ML model were .80 and 75.2%, respectively, and .69 and 74.2% for the 3-year model, respectively. Based on SHAP analysis, hemodialysis of the recipient post-HT had overall the strongest relative impact on 1-year mortality after HΤ, followed by recipient-estimated glomerular filtration rate, age and ischemic time. CONCLUSIONS: ML models showed satisfactory predictive accuracy of mortality after HT in ACHD and allowed for individualized mortality risk assessment.

Prognostic implications of inactive status in highest urgency categories among heart transplantation recipients in the new donor heart allocation system.

BACKGROUND: Patients on the waiting list for heart transplantation (HT) can become inactive or made status seven because of medical reasons, such adverse events, complications, or psychosocial circumstances. If the condition that caused the inactivation is resolved, patients are re- activated. Information about the prognostic implications of Status 7 in the new donor heart allocation system has not been described. To bridge this knowledge gap, we performed an analysis of the United Network of Organ Sharing (UNOS) registry. METHODS: Data on adult patients who underwent HT between October 18th, 2018 and October 2021, were queried from the UNOS registry. The main outcomes were post- transplant all-cause mortality, 1-year all-cause mortality and treated acute rejection. Since re-transplantation is a competing event for all-cause mortality, we performed competing risk survival analysis and reported sub distribution hazard ratios (SHR) from the Fine and Gray model to examine the relationship between inactive status and all-cause mortality. RESULTS: A total of 5267 adult patients underwent HT and were previously listed as Status 1 or Status 2 in the new allocation system. We identified 946 HT recipients temporarily inactivated while on HT list (18%). The number of temporarily inactive patients remained stable since the implementation of the new donor allocation system (p = .37). Approximately, two-thirds of temporarily inactive patients (65.9%) were inactivated for being too sick, whereas other frequent justifications for inactivity included left ventricular assist device implantation (7.8%) and insurance related issues (4.8%). Temporarily inactive HT recipients were more likely to be African Americans, males, have a higher body mass index (BMI) and significantly longer waiting time (391.6 ± 600 vs. 72.3 ± 223 days, p < .001) compared with never inactivated patients. In the unadjusted analyses 30-day mortality did not differ between groups, but both 1-year and overall all-cause mortality was significantly higher in temporarily inactive patients (1-year: SHR: 1.3; 95% confidence intervals [CI]: 1.03, 1.64; p = .028, overall mortality SHR: 1.31; 95% CI: 1.06, 1.64; p = .014). After adjustment for donor and recipient characteristics, a trend towards higher 1-year and overall mortality remained (1-year: SHR 1.32; 95% CI .99, 1.76, p = .006, overall mortality SHR: 1.29; 95% CI: .98-1.68, p = .065). No differences in treated acute allograft rejection at 1 year were found between groups. CONCLUSIONS: Temporary inactive status while waiting for HT occurs in approximately one in five HT recipients listed in higher urgency categories after the implementation of the new allocation system. A signal of adverse long-term outcomes was found, and this could be explained by differences in recipient characteristics. Further research is required to elucidate pathways involved and possible implications for clinical practice.

Rejection Requiring Treatment within the First Year following Heart Transplantation: The UNOS Insight.

(1) Background: Heart failure is an extremely impactful health issue from both a social and quality-of-life point of view and the rate of patients with this condition is destined to rise in the next few years. Transplantation remains the mainstay of treatment for end-stage heart failure, but a shortage of organs represents a significant problem that prolongs time spent on the waiting list. In view of this, the selection of donor and recipient must be extremely meticulous, considering all factors that could predispose to organ failure. One of the main considerations regarding heart transplants is the risk of graft rejection and the need for immunosuppression therapy to mitigate that risk. In this study, we aimed to assess the characteristics of patients who need immunosuppression treatment for rejection within one year of heart transplantation and its impact on mid-term and long-term mortality. (2) Methods: The United Network for Organ Sharing (UNOS) Registry was queried to identify patients who solely underwent a heart transplant in the US between 2000 and 2021. Patients were divided into two groups according to the need for anti-rejection treatment within one year of heart transplantation. Patients' characteristics in the two groups were assessed, and 1 year and 10 year mortality rates were compared. (3) Results: A total of 43,763 patients underwent isolated heart transplantation in the study period, and 9946 (22.7%) needed anti-rejection treatment in the first year. Patients who required treatment for rejection within one year after transplant were more frequently younger (49 ± 14 vs. 52 ± 14 years, p < 0.001), women (31% vs. 23%, p < 0.001), and had a higher CPRA value (14 ± 26 vs. 11 ± 23, p < 0.001). Also, the rate of prior cardiac surgery was more than double in this group (27% vs. 12%, p < 0.001), while prior LVAD (12% vs. 11%, p < 0.001) and IABP (10% vs. 9%, p < 0.01) were more frequent in patients who did not receive anti-rejection treatment in the first year. Finally, pre-transplantation creatinine was significantly higher in patients who did not need treatment for rejection in the first year (1.4 vs. 1.3, p < 0.01). Most patients who did not require anti-rejection treatment underwent heart transplantation during the new allocation era, while less than half of the patients who required treatment underwent transplantation after the new allocation policy implementation (65% vs. 49%, p < 0.001). Patients who needed rejection treatment in the first year had a higher risk of unadjusted 1 year (HR: 2.25; 95% CI: 1.88-2.70; p < 0.001), 5 year (HR: 1.69; 95% CI: 1.60-1.79; p < 0.001), and 10 year (HR: 1.47; 95% CI: 1.41-1.54, p < 0.001) mortality, and this was confirmed at the adjusted analysis at all three time-points. (4) Conclusions: Medical treatment of acute rejection was associated with significantly increased 1 year mortality compared to patients who did not require anti-rejection therapy. The higher risk of mortality was confirmed at a 10 year follow-up. Further studies and newer follow-up data are required to investigate the role of anti-rejection therapy in the heart transplant population.

Transcriptomic and proteomic pathways of diabetic and non-diabetic mitochondrial transplantation.

Reduced mitochondrial function increases myocardial susceptibility to ischemia-reperfusion injury (IRI) in diabetic hearts. Mitochondrial transplantation (MT) ameliorates IRI, however, the cardioprotective effects of MT may be limited using diabetic mitochondria. Zucker Diabetic Fatty (ZDF) rats were subjected to temporary myocardial RI and then received either vehicle alone or vehicle containing mitochondria isolated from either diabetic ZDF or non-diabetic Zucker lean (ZL) rats. The ZDF rats were allowed to recover for 2 h or 28 days. MT using either ZDF- or ZL-mitochondria provided sustained reduction in infarct size and was associated with overlapping upregulation of pathways associated with muscle contraction, development, organization, and anti-apoptosis. MT using either ZDF- or ZL-mitochondria also significantly preserved myocardial function, however, ZL- mitochondria provided a more robust long-term preservation of myocardial function through the mitochondria dependent upregulation of pathways for cardiac and muscle metabolism and development. MT using either diabetic or non-diabetic mitochondria decreased infarct size and preserved functional recovery, however, the cardioprotection afforded by MT was attenuated in hearts receiving diabetic compared to non-diabetic MT.

Impact of Pre-Operative Right Ventricular Response to Hemodynamic Optimization on Outcomes in Patients with LVADs.

Background: Right ventricular failure (RVF) continues to affect patients supported with durable left ventricular assist devices (LVAD) and results in increased morbidity and mortality. Information regarding the impact of right ventricular response to pre-operative optimization on outcomes is scarce. Methods: Single-center retrospective analysis of consecutive patients who underwent first continuous flow LVAD implantation between 2006 and 2020. Patients with bi-ventricular support before LVAD or without hemodynamic data were excluded. Invasive hemodynamics at baseline and after pre-operative medical and/or temporary circulatory support were recorded. Patients were grouped in the following categories: A: No Hemodynamic RV dysfunction (RVD) at baseline; B: RVD with achievement of RV hemodynamic optimization goals; C: RVD without achievement of RV optimization goals. The main outcomes were right ventricular failure defined as inotropes >14 days after implantation, or postoperative right ventricular mechanical support, and all-cause mortality. Results: Overall, 128 patients were included in the study. The mean age was 58 ±12.5 years, 74.2% were males and, 68.7% had non-ischemic cardiomyopathy. Hemodynamic RVD was present in 70 (54.7%) of the patients at baseline. RV hemodynamic goals were achieved in 46 (79.31%) patients with RVD and in all the patients without RVD at baseline. Failure to achieve hemodynamic optimization goals was associated with a significantly higher risk of RVF after LVAD implantation (adjusted OR 4.37, 95% CI 1.14−16.76, p = 0.031) compared with no RVD at baseline and increased 1-year mortality compared with no RVD (adjusted HR 4.1, 95% CI 1.24−13.2, p = 0.02) and optimized RVD (adjusted HR 6.4, 95% CI 1.6−25.2, p = 0.008).Conclusion: Among patients with RVD, the inability to achieve hemodynamic optimization goals was associated with higher rates of RV failure and increased 1-year all-cause mortality post LVAD implantation.

Robotic applications for intracardiac and endovascular procedures.

The large incisions and long recovery periods that accompany traditional cardiac surgery procedures along with the constant patient demand for minimally invasive procedures have motivated cardiac surgeons to implement the robotic technologies in their armamentarium. The robotic systems have been utilized successfully in various cardiac procedures including atrial septal defect repair, left atrial myxoma resection, MAZE procedure and left ventricular lead placement, yet coronary artery bypass and mitral valve repair still comprise the vast majority of them. This review analyzes the development of the robot-assisted cardiac surgery in recent years, its outcomes, advantages, disadvantages, its patient selection criteria as well as its economic feasibility. Robotic endovascular surgery, albeit its limited applications, is presently considered an attractive alternative to conventional endovascular approaches. The increased flexibility and precision along with the wider range of accessible anatomy provided by the endovascular robotic systems, have increased the pool of patients that can be offered minimally invasive treatment options and have helped to overcome many limitations of the traditional endovascular procedures. With this review we aimed to summarize the applications of the commercially available endovascular robotic devices, as well as the limitations and the future perspectives in the field of endovascular robotic surgery.

Characteristics, Predictors, and Outcomes of Early mTOR Inhibitor Use After Heart Transplantation: Insights From the UNOS Database.

Background The clinical characteristics of mTOR (mammalian target of rapamycin) inhibitors use in heart transplant recipients and their outcomes have not been well described. Methods and Results We compared patients who received mTOR inhibitors within the first 2 years after heart transplantation to patients who did not by inquiring the United Network for Organ Sharing (UNOS) database between 2010 and 2018. The primary end point was all-cause mortality with retransplantation as a competing event. Rejection, malignancy, hospitalization for infection, and renal transplantation were secondary end points. There were 1619 (9%) and 15 686 (81%) mTOR inhibitors+ and mTOR inhibitors- patients, respectively. Body mass index, induction, cardiac allograft vasculopathy, calculated panel reactive antibody, and fewer days in 1A status were independently associated with mTOR inhibitors+ status. Over a follow-up of 10.4 years, there was no difference in all-cause mortality after adjusting for donor and recipient characteristics (adjusted subdistribution hazard ratio, 1.03 [0.90-1.19]; P=0.66). mTOR inhibitors+ were independently associated with increased risk for rejection (odds ratio [OR], 1.43 [1.11-1.83]; P=0.005) and basal skin cancer (OR, 1.35 [1.19-1.51]; P=0.012) but not for infection or renal transplantation. Conclusions mTOR inhibitors are used in <10% patients in the first 2 years after heart transplantation and are noninferior to contemporary immunosuppression regimens in terms of all-cause mortality, infection, malignancy, or renal transplantation. They are associated with risk for rejection.

Sex mismatch following heart transplantation in the United States: Characteristics and impact on outcomes.

BACKGROUND: Available literature indicates the possible detrimental effect of sex mismatching on mortality in patients undergoing heart transplantation. Our objective was to examine the role of sex and heart mass (predicted heart mass [PHM]) mismatch on mortality and graft rejection in patients undergoing heart transplantation in the US. METHODS: Data on adult patients who underwent heart transplantation between January 2015 and October 2021 were queried from the United Network of Organ Sharing (UNOS) registry. The main outcomes were all-cause mortality, 1-year all-cause mortality and treated acute rejection. RESULTS: A total of 19 805 adult patients underwent heart transplant during the study period. 92.2% of the patients in the female graft to male group had a PHM mismatch <25%, while only 38.5% had such a mismatch in the male graft to female group. In male to male and female to female groups, 79% and 76% of the patients had a PHM mismatch <25% (p = .122). Proportion of PHM mismatch was similar throughout the study period. Unadjusted analysis showed that male recipients of female grafts had increased risk for all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence intervals [CI]: 1.02, 1.27; p = .026) and 1-year mortality (HR: 1.26; 95% CI: 1.09, 1.45; p = .002) compared to male recipients of male grafts. Graft failure incidence was also higher (HR: 1.12; 95% CI: 1.01, 1.25; p = .041). However, all these associations were non- significant after risk factor adjustment. CONCLUSIONS: Sex mismatching is associated with post-transplant mortality with transplantation of female donor grafts to male recipients demonstrating worse outcomes, although this association disappears after risk factor adjustment. Further research is required to elucidate the need for potential changes in clinical practice.