Hospital volume does not mitigate the impact of area socioeconomic deprivation on heart transplantation outcomes.

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.

Incidence, pathophysiology, and treatment of failing Fontan after the total cavopulmonary connection.

BACKGROUND: Failing Fontan poses a significant clinical challenge. This study aims to improve patients' outcomes by comprehensively understanding the incidence, pathophysiology, risk factors, and treatment of failing Fontan after total cavopulmonary connection. METHODS: We performed a retrospective analysis of patients who underwent total cavopulmonary connection at the German Heart Center Munich between 1994 and 2022. The onset of failing Fontan was defined as: protein-losing enteropathy, plastic bronchitis, NYHA class IV, NYHA class III for > one year, unscheduled hospital admissions for heart failure symptoms, and evaluation for heart transplantation. RESULTS: Among 634 patients, 76 patients presented with failing Fontan, and the incidence was 1.48 per 100 patient-years. Manifestations included protein-losing enteropathy (n = 34), hospital readmission (n = 28), NYHA III (n = 18), plastic bronchitis (n = 16), evaluation for heart transplantation (n = 14), and NYHA IV (n = 4). Risk factors for the onset of failing Fontan were dominant right ventricle (p = 0.010) and higher pulmonary artery pressure before total cavopulmonary connection (p = 0.004). A total of 72 interventions were performed in 59 patients, including balloon dilatation/stent implantation in the total cavopulmonary connection pathway (n = 49) and embolization of collaterals (n = 24). Heart transplantation was performed in four patients. The survival after the onset of Fontan failure was 77% at 10 years. Patients with failing Fontan revealed significantly higher zlog-NT-proBNP levels after onset compared to those without (p = 0.021). CONCLUSIONS: The incidence of Fontan failure was 1.5 per 100 patient years. Dominant right ventricle and higher pulmonary artery pressure before total cavopulmonary connection were significant risks for the onset of failing Fontan. Zlog-NT-proBNP is only a late marker of Fontan failure.

Impact of waitlist weight change on outcomes in heart transplant recipients: a UNOS database analysis.

BACKGROUND: While the effect of pre-transplant weight on patient outcomes following heart transplantation (HTx) has previously been studied, data regarding the impact of dynamic weight change prior to HTx are extremely limited. OBJECTIVES: We sought to elucidate the interaction between HTx listing weight and weight change while waitlisted, and explore how that interaction impacts post-HTx survival in a continuous manner. METHODS: Adult patients listed for HTx from 1987 to 2020 were identified from UNOS database. Three-dimensional restricted cubic spline analysis explored post-HTx survival relative to both changes in BMI/weight and BMI at time of HTx listing. Continuous predictor variables were analyzed with Cox proportional hazards method. RESULTS: 9,628 included patients underwent HTx. Median recipient age was 55 [IQR 46-62] years, and 21% were females. 53% of patients lost while 47% gained weight on the waitlist. Median BMI (27.6 kg/m2 [24.3-31.3] vs. 27.4 kg/m2 [24.2-30.9], paired p < 0.001) and weight (84.8 kg [73.0-98.0] kg vs. 84.4 kg [72.6-96.6], p < 0.001) were similar at listing and transplant. One-year survival was 89.3%. Weight loss over 3 BMI points or 10 kg was associated with higher hazard of death irrespective of listing BMI. In non-obese patients, some weight gain (1-4 BMI points or 5-15 kg) was associated with improved survival. In cachectic patients (BMI < 18.5), failure to gain weight was associated with worse survival. CONCLUSIONS: Impact of weight change varies depending on listing BMI. While a survival benefit is seen in non-obese patients who gain some weight, significant weight loss is associated with poorer survival.

Pulmonary artery mass with PIK3CA mutation after orthotopic heart transplantation.

BACKGROUND: Patients can develop de novo malignancies following orthotopic heart transplantation. However, vascular tumors are not commonly described in this population. CASE PRESENTATION: We present a 69-year-old female with a history of orthotopic heart transplantation for chemotherapy-induced cardiomyopathy who developed an incidental pulmonary artery mass six years after her transplantation. Given concerns for malignancy, the patient underwent an operative excisional biopsy through a left anterior mini-thoracotomy with femoral artery and vein cannulation for cardiopulmonary bypass. The mass was determined to be a non-malignant vascular overgrowth with PIK3CA mutation. CONCLUSION: We present the case of an unusual pulmonary artery mass with PIK3CA mutation found in a post heart transplant patient. We were able to spare her the morbidity of a redo-sternotomy by excising the mass via a minimally invasive left anterior thoracotomy approach.

Triple-Organ Transplantation: Dual Heart-Kidney Transplantation After Lung Transplantation.

We present a patient with a history of lung transplantation who subsequently underwent dual heart-kidney transplantation for nonischemic cardiomyopathy and chronic kidney disease, becoming one of the rare cases of triple-organ transplantation. This case underscores the evolving challenges and successes in managing complex transplant recipients.

Eosinophilic Endomyocarditis After COVID-19 Infection in a Heart Transplant Recipient.

Eosinophilic myocarditis (EM) is a rare cause of heart failure, with high in-hospital mortality associated with fulminant disease. A 61-year-old female transplant recipient was diagnosed with COVID-19 after presenting with 2 days of constitutional symptoms. She developed acute heart failure from EM. After an initial response to inotropic support and corticosteroids, she had a relapse with de novo peripheral eosinophilia which responded to further eosinophilic myocarditis management and the addition of mepolizumab. Although there have been reports after COVID-19 vaccination, association with active SARS-CoV-2 infection is rare. This paper reports, for the first time, the case of a heart transplant recipient with EM after COVID-19.

Impact of left ventricular unloading on postheart transplantation outcomes in patients bridged with VA-ECMO.

INTRODUCTION AND OBJECTIVES: The impact of preoperative left ventricular (LV) unloading on postoperative outcomes in patients bridged with venoarterial extracorporeal membrane oxygenation (VA-ECMO) to heart transplantation (HT) is unknown. Our aim was to compare posttransplant outcomes in patients bridged to HT with VA-ECMO, with or without the use of different mechanical strategies for LV decompression. METHODS: We conducted a retrospective analysis of the postoperative outcomes of consecutive HT candidates bridged with VA-ECMO, with or without concomitant LV unloading. Patients were included from 16 Spanish centers from 2010 to 2020. The primary endpoint was 1-year post-HT survival, which was assessed using Cox regression. RESULTS: Overall, 245 patients underwent high-emergency HT while supported with VA-ECMO. A mechanical strategy for LV unloading was used in 133 (54.3%) patients, with the intra-aortic balloon pump being the most commonly used method (n = 112; 84.2%). One-year posttransplant survival was 74.4% in the LV unloading group and 59.8% in the control group (P = .025). In multivariate analyses, preoperative LV unloading was independently associated with lower 1-year mortality (adjusted HR, 0.50; 95%CI, 0.32-0.78; P = .003). This association was observed both in patients managed with an intra-aortic balloon pump alone (adjusted HR, 0.52; 95%CI, 0.32-0.84; P = .007) and with other strategies for mechanical LV unloading (adjusted HR, 0.43; 95%CI, 0.19-0.97; P = .042). No significant differences were found between groups regarding other postoperative complications. CONCLUSIONS: Preoperative LV unloading was independently associated with increased 1-year posttransplant survival in candidates bridged with VA-ECMO.

Comparison of waitlist and post-transplant outcomes in patients supported with total artificial heart versus continuous biventricular assist devices.

BACKGROUND: Durable biventricular support may be necessary to bridge patients with end-stage biventricular failure to heart transplantation. This study compares waitlist and post-transplant outcomes between patients supported with continuous flow, durable biventricular assist devices (BiVAD), and total artificial heart (TAH). METHODS: Using the UNOS registry, we analyzed adult (≥18 years old), first-time transplant candidates with TAH or BiVAD at the time of listing or transplantation from 10/1/2010-10/31/2020, with follow-up through 3/31/2022. Multivariable proportional subdistribution hazards models and cause-specific Cox proportional hazards models were used to compare death/deterioration or heart transplantation on the waitlist between cohorts. Kaplan-Meier and multivariable Cox proportional hazards model were used to evaluate one-year post-transplant survival and evaluate difference in outcomes based on annual transplant center volume. RESULTS: The waitlist cohort included a total of 228 patients (25% BiVAD). Waitlist outcomes between device types were similar. The transplanted cohort included a total of 352 patients (25% BiVAD). There was a trend towards worse one-year post-transplant survival in patients bridged with TAH versus BiVAD (log-rank p-value = 0.072) that persisted after adjusting for age, gender, policy, and removing dual-organ recipients (HR 1.94 (0.94, 3.98) p-value = 0.07). There was a difference in one-year post-transplant survival amongst TAH-bridged patients when stratified by annual transplant center volume (log-rank p-value = 0.013). One-year post-transplant survival between TAH-supported patients from high annual transplant volume centers and BiVAD-supported patients was similar (p-value = 0.815). CONCLUSIONS: BiVAD and TAH are reasonable support strategies with TAH implantation at high-volume transplant centers (51+ transplants/year) having similar 1-year post-transplant survival to BiVAD-supported patients.

The Rapidly Evolving Landscape of DCD Heart Transplantation.

PURPOSE OF REVIEW: To summarise current international clinical outcomes from donation after circulatory death heart transplantation (DCD-HT); discuss procurement strategies, their impact on outcomes and overall organ procurement; and identify novel approaches and future areas for research in DCD-HT. RECENT FINDINGS: Globally, DCD-HT survival outcomes (regardless of procurement strategy) are comparable to heart transplantation from brain dead donors (BDD). Experience with normothermic machine perfusion sees improvement in rates of primary graft dysfunction. Techniques have evolved to reduce cold ischaemic exposure to directly procured DCD hearts, though controlled periods of cold ischaemia can likely be tolerated. There is interest in hypothermic machine perfusion (HMP) for directly procured DCD hearts, with promising early results. Survival outcomes are firmly established to be equivalent between BDD and DCD-HT. Procurement strategy (direct procurement vs. regional perfusion) remains a source of debate. Methods to improve allograft warm ischaemic tolerance are of interest and will be key to the uptake of HMP for directly procured DCD hearts.

Evaluating the Association Between Social Vulnerability and Outcomes of Heart Transplantation in the United States.

INTRODUCTION: The Social Vulnerability Index (SVI) is a tool that was developed by the Centers for Disease Control and Prevention to help identify communities that are at risk of harm from social, economic, or environmental factors. This study evaluates the association between SVI and outcomes of adult heart transplantation (HT) in the United States. METHODS: The United Network for Organ Sharing registry was used to identify all isolated adult (≥18 y) HT recipients and their home address zip codes between 2010 and 2021. Recipients were classified into three SVI risk groups: low risk (SVI: <0.33), intermediate risk (SVI: 0.33-0.65), and high risk (SVI: ≥0.66). Kaplan-Meier analysis was used to estimate recipient survival probability based on SVI risk. Multivariable Cox proportional hazard models were built to evaluate the association of SVI with 1- and 5-y mortality. RESULTS: A total of 22,400 recipients distributed over 9753 zip codes were included. Unadjusted 1-y survival rates in the three risk groups were as follows: low risk: 90.5%, intermediate risk: 91.1%, high risk 90.9%, and Log-rank P = 0.550 and 5-y survival rates were as follows: low risk: 80.8%, intermediate risk: 78.6%, high risk: 76.1%, and Log-rank P < 0.001. Compared to low-risk recipients, risk-adjusted 1-y mortality hazard ratio was 1.02 (0.92-1.14, P = 0.657) for intermediate risk and 1.09 (0.95-1.24, P = 0.222) for high-risk recipients. Risk-adjusted 5-y mortality hazard ratio was 1.07 (0.99-1.16, P = 0.095) for intermediate-risk recipients and 1.17 (1.06-1.28, P = 0.002) for high-risk recipients. CONCLUSIONS: Social vulnerability is associated with HT outcomes. The Centers for Disease Control and Prevention SVI may be a useful tool in identifying at-risk geographic areas where targeted efforts may be prudent for reducing disparities in HT outcomes.

Prognostic significance of preoperative nutritional status for heart transplantation patients.

BACKGROUND: The association between malnutrition and outcomes of heart transplantation (HTx) has not been well studied. The purpose of this article was to evaluate the prognostic value of three different nutrition indices in HTx, including CONUT (Controlling Nutritional Status), NRI (Nutritional Risk Index) and GNRI (Geriatric Nutritional Risk Index). METHODS: A total of 438 patients who underwent THx from January 2015 to December 2020 were included in this study. The nutritional status of the patients was evaluated by CONUT, NRI and GNRI. Kaplan-Meier (KM) curves were constructed to compare the difference in overall survival (OS) between the normal and malnutrition groups in each index. Cox regression analysis was used to identify the independent risk factors of OS. The predictive power was compared by time-dependent ROC and time-dependent ccurves. Logistic regression model was used to evaluate the relationship between these three nutrition indices and postoperative clinical events. RESULTS: 336 (76.7%), 183 (43.8%), and 190 (43.4%) patients had malnutrition according to CONUT, NRI and GNRI calculations. 102 (23.3%) patients had died at the end of follow-up. After adjustment for confounding variables, multivariate Cox analysis showed that CONUT [HR 1.286 (95%CI 1.166 ~ 1.419); p < 0.001], NRI [HR 0.942 (95%CI 0.923 ~ 0.962); p < 0.001] and GNRI [HR 0.959 (95%CI 0.939 ~ 0.979); p < 0.001] were all independent predictors for OS. The predictive power of CONUT score was higher than that of NRI (p = 0.045) and GNRI (p < 0.001). Regarding the postoperative complications, multivariate logistic regression model showed that malnutrition assessed by CONUT [HR 1.156 (95%CI 1.032 ~ 1.294); p = 0.012] and NRI [HR 1.543 (95%CI 1.008 ~ 2.362); p = 0.046] was independent risk factors for posttransplant infections. CONCLUSION: Poor nutritional status, as assessed by CONUT, NRI and GNRI, was associated with an increased risk of mortality after HTx. CONUT displayed the highest predictive power compared to the other two indices. CONUT and NRI were also independently associated with posttransplant infections.

Progress in Orthotopic Pig Heart Transplantation in Nonhuman Primates.

Xenotransplantation of porcine hearts has become a promising alternative to human allotransplantation, where organ demand still greatly surpasses organ availability. Before entering the clinic, however, feasibility of cardiac xenotransplantation needs to be proven, ideally in the life supporting orthotopic pig-to-nonhuman primate xenotransplantation model. In this review, we shortly outline the last three decades of research and then discuss in detail its most recent advances. These include the genetic modifications of donor pigs to overcome hyperacute rejection and coagulation dysregulation, new organ preservation methods to prevent perioperative xenograft dysfunction, experimental immunosuppressive and immunomodulatory therapies to inhibit the adaptive immune system and systemic inflammation in the recipient, growth control concepts to avoid detrimental overgrowth of the porcine hearts in nonhuman primates, and lastly, the avoidance of porcine cytomegalovirus infections in donor pigs. With these strategies, consistent survival of 6-9 months was achieved in the orthotopic xenotransplantation model, thereby fulfilling the prerequisites for the initiation of a clinical trial.

Early Renal Outcomes Following Heart Transplantation Using Organs Procured After Circulatory Death.

BACKGROUND: Transplantation using hearts obtained through donation after circulatory death (DCD) is increasing, but data on recipient renal outcomes are limited. METHODS AND RESULTS: Patients at a single institution who underwent heart transplantation using organs procured through DCD or donation after brain death (DBD) from April 2016 to August 2022 were included in this retrospective cohort study. Hemodynamic measures were collected via right heart catheterization performed 1 week after transplantation. Posttransplantation renal outcomes included estimated glomerular filtration rate at 1 week, 4 weeks, and 16 weeks, and the incidence of acute kidney injury (AKI) and renal replacement therapy within 1 week. The analysis included 225 patients (55 recipients of DCD). Baseline characteristics were comparable between recipients of DCD and DBD. Renal outcomes within 1 week posttransplantation in recipients of DCD were similar to recipients of DBD, including percent change in estimated glomerular filtration rate (-37.9% [-58.6 to -6.2] versus -31.9% [-52.4 to -9.9]; P=0.91), incidence of AKI (47.3% versus 46.5%; P>0.99) and incidence of renal replacement therapy (3.6% versus 4.7%; P>0.99). Recipients of DCD with AKI within 1 week ("early AKI") did not recover to baseline estimated glomerular filtration rate (75.8 [60.2-91.3] mL/min per 1.73 m2) by week 16 (59.3 [46.9-73.6] mL/min per 1.73 m2; P=0.002), whereas recipients without early AKI exhibited comparable estimated glomerular filtration rate to baseline by week 4 (84.5 [70.8-98.5] mL/min per 1.73 m2; P=0.084). Similar trends were observed in recipients of DBD. CONCLUSIONS: Recipients of DCD demonstrated similar renal outcomes compared with recipients of DBD, supporting the ongoing use of DCD transplantation. Early AKI was associated with persistent renal dysfunction for recipients of both DCD and DBD.

Progress in Noninvasive Surveillance for Acute Rejection in Pediatric Heart Transplant Recipients: A Real-World Analysis of Donor-Derived Cell-Free DNA-Based Surveillance Protocol.

PURPOSE: Acute cellular (ACR) and antibody-mediated (AMR) rejection are risk factors for allograft loss in heart transplant (HT) recipients. Endomyocardial biopsy (EMB), although considered the gold standard for rejection surveillance, is invasive and has high interobserver variability. Noninvasive donor-derived cell-free DNA (dd-cfDNA) sampling has a high negative predictive value (NPV) for rejection in adults and is increasingly used in pediatrics. This single center study aimed to test the performance of dd-cfDNA in screening for acute rejection (AR) and donor-specific antibodies (DSAs) in pediatric HT recipients. METHODS: Blood samples for dd-cfDNA were obtained per clinical protocol for all eligible HT recipients in our center from July 1, 2022 to December 31, 2023. Primary endpoints were episodes of AR, pathology grading of EMBs temporally related to ddcfDNA sampling (0-150 days), and presence of DSAs. RESULTS: There were 471 interpretable samples, in 192 unique patients. Of those, 199 dd-cfDNA tests were paired with EMB ± DSA in 152 patients. Abnormal dd-cfDNA (> 0.2%) was found in 77 samples (median 0.48%, range 0.21%-11%) and led to EMB, where one sample was positive for ACR (grade 2R), 13 for AMR, yielding an NPV of 97% for AMR. After excluding abnormal ddcfDNA testing associated with AR, 65 abnormal dd-cfDNA tests were paired with DSA testing. The NPV of the test for detection of DSAs was 93%. CONCLUSION: Implementation of noninvasive rejection surveillance with dd-cfDNA in a pediatric cohort demonstrates high NPV for AR and high DSAs, making it an ideal screening tool for long-term monitoring of allograft health in pediatrics.

Engagement With Sports After Solid Organ Transplant.

Introduction Transplant Games lend a unique opportunity not only by providing a platform for donors and recipients to engage in sports but also to counter the negativity surrounding organ donation and showcase to the world that transplant recipients can lead active lives. When the Transplant Games were held in Kochi, Kerala, India, for the first time, it provided a venue to engage with transplant recipients, donors, and the families of deceased donors. We aimed to understand the impact that engagement in sports brings on the lives of donors and recipients. Methods After obtaining permission from the organizers, we explained the objectives of the survey to the participants and encouraged them to participate. A survey, covering basic demographic information, transplantation details, and questions related to sports engagement was formulated. Participants could complete the survey electronically via a quick response code or in hard copy. They were fully informed about the objectives of the survey and had the right to withdraw at any stage without consequences. The survey was available for five hours during the games. The study received institutional ethics committee approval (ECASM-AIMS-2024-059). Results Among the approximate 150 participants, we received 78 respondents (52%). After the nine who withdrew consent were removed, we had a full response from 69 participants. Of these, 59 were males (85.5%), and 10 (14.5%) were females. The average age of the participants was 45 ± 13 years. Self-motivation was the most common factor in taking up sports for 30.4% of the responders, followed by family and friends in 23.2% and transplant doctors in 5.8%. Liver Foundation of Kerala (LIFOK), a self-help group of transplant recipients, played a major role in 4.3% of the responders. Bowling was the most popular sport with 23 mentions, followed by carroms and badminton with 27 and 20 mentions, respectively. Donors started to take an active role in sports earlier than recipients, 3.1 ± 1.89 vs. 5.7 ± 5.5 months. The most common reason cited for taking up sports was to become part of the transplant community, followed by a desire to embrace a healthier lifestyle and improve fitness levels. Although none had a personalized coach, most intensified their training and improved nutrition as part of their preparation for the games. Conclusion Our survey is limited by its small and self-selected sample size. Our study highlights the significant role of self-motivation, family support, and self-help groups in encouraging solid organ transplant recipients and donors to engage in sports after surgery. It also highlights the need for more proactive encouragement from doctors and better availability of sports facilities and support staff to help transplant recipients and donors engage in physical activities, which are crucial for their physical and emotional well-being.

Heart Transplantation and Left Ventricular Assist Devices: Long-Term Prognosis and Effects on Mental Health.

Heart transplantation and left ventricular assist devices (LVADs) have emerged as crucial interventions for end-stage heart failure, dramatically improving patient outcomes. This narrative review examines their historical context, indications, procedures, and outcomes, as well as their impact on long-term survival, quality of life, functional status, and mental health. While heart transplantation remains the optimal treatment, donor scarcity limits its application. LVADs have become a viable alternative, either as a bridge to transplantation or as destination therapy. Both interventions demonstrate similar long-term survival rates and significant improvements in health-related quality of life and functional status. However, they present distinct long-term management challenges, including immunosuppression needs for transplant recipients and device-related issues for LVAD patients. Mental health effects are considerable, necessitating psychological support and adaptive coping strategies. Complications such as infection, bleeding, and thrombosis remain concerns for both interventions. Patient selection criteria, technological advancements, and long-term management strategies are critical factors in optimizing outcomes. Future research should focus on device miniaturization, enhanced biocompatibility, and less invasive insertion techniques to further advance these therapies and improve patient care in end-stage heart failure.

The Outcome of Restrictive Cardiac Allograft Physiology in Severe Coronary Allograft Vasculopathy.

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 mmHg, pulmonary capillary wedge pressure >25 mmHg, and cardiac index <2.0 L/min/m2). The primary outcome was death or re-transplantation. 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 re-transplantation 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 re-transplantation (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 re-transplantation listing may improve the prognosis of patients with RCP.

Walter Brendel and the dawn of transplantation research in Germany.

Walter Brendel was a physiologist who headed the Institut of Experimental Surgery at the University of Munich (LMU) from 1961 until 1989. His legendary career began with the development of an anti-human lymphocyte globulin (ALG) at his Institute during the late 1960s. The initial successful treatment of a small number of patients culminated in the co-treatment of the first successfully heart-transplanted patient in Capetown, South Africa (successful reversal with ALG of an acute allograft rejection). Walter Brendel was a pioneering personality whose work has laid a wide platform for the promotion of interdisciplinarily conducted innovative research programs in various domains of translational science and medicine. Among the many innovative achievements, the most notable are: discovery of involvement of the alternative pathway of complement activation in hyperacute xenograft rejection; induction of immunological tolerance to horse IgG as a means to prevent anaphylactic reactions during ALG therapy; development and clinical implementation of the extracorporeal shock wave lithotripsy for extracorporeal destruction of renal and ureteral calculi. The legacy of Brendel continues with the foundation of the Walter-Brendel Kolleg für Transplantationsmedizin (i.e., the German Transplant School for Transplantation Medicine), which has been held annually since 1994.