Heart-lung Recipients Research Articles

Contemporary Immunosuppression Management and 1-Year Outcomes in Dual Organ Heart Transplantation.

There have been limited reports on immunosuppression strategies and outcomes in dual organ heart transplant populations, primarily from before the 2018 United Network for Organ Sharing (UNOS) heart allocation policy change. Recent data suggested that outcomes with heart-lung and heart-liver transplants remained comparable in the new allocation era, yet heart-kidney recipients have worse 1-year survival. This single-center retrospective study evaluated adult heart-kidney, heart-liver, and heart-lung transplant recipients from September 2019 to May 2023. Immunosuppression regimen, infectious complications, and graft outcomes were collected for 12 months. A total of 36 patients (kidney n = 20, liver n = 9, and lung n = 7) were included in this study. Basiliximab was the most commonly employed induction strategy across the organ groups (12/20 in kidney, 4/9 in liver, and 7/7 in lung). All patients were on triple immunosuppression at 12 months posttransplant with prednisone wean achieved in one heart-liver recipient. Infection complications were frequently reported (95% kidney, 75% liver, 100% lung group). One patient went back to dialysis due to focal segmental glomerulosclerosis. One chronic lung allograft dysfunction was reported, but no other severe biopsy-proven rejection or retransplant was reported. The 1-year survival was 85% (17/20) in heart-kidney, 78% (7/9) in heart-liver, and 86% (6/7) in heart-lung recipients. This study summarized real-world immunosuppression strategies and outcomes in dual organ heart transplant recipients.

Outcomes following concomitant multiorgan heart transplantation from circulatory death donors: The United States experience

BackgroundDonation after circulatory death (DCD) has reemerged as a method of expanding the donor heart pool. Given the high waitlist mortality of multiorgan heart candidates, we evaluated waitlist outcomes associated with willingness to consider DCD offers and post-transplant outcomes following DCD transplant for these candidates. MethodsUsing the United Network for Organ Sharing database, we identified adult multiorgan heart candidates and recipients between 1/1/2020 and 3/31/2023. Among candidates that met inclusion criteria, we compared the cumulative incidence of transplant, with waitlist death/deterioration as a competing risk, by willingness to consider DCD offers. Among recipients of DCD vs. brain death (DBD) transplants, we compared perioperative outcomes and post-transplant survival. ResultsOf 1,802 heart-kidney, 266 heart-liver, and 440 heart-lung candidates, 15.8%, 12.4% and 31.1%, respectively, were willing to consider DCD offers. On adjusted analysis, willingness to consider DCD offers was associated with higher likelihood of transplant for all multiorgan heart candidates and decreased likelihood of waitlist deterioration for heart-lung candidates. Of 1,100 heart-kidney, 173 heart-liver, and 159 heart-lung recipients, 5.4%, 2.3%, and 2.5%, respectively, received DCD organs. Recipients of DCD and DBD heart-kidney transplants had similar likelihood of perioperative outcomes and 1-year survival. All other DCD multiorgan heart recipients have survived to last follow-up. ConclusionsMultiorgan heart candidates who were willing to consider DCD offers had favorable waitlist outcomes, and heart-kidney recipients of DCD transplants had similar post-transplant outcomes to recipients of DBD transplants. We recommend the use of DCD organs to increase the donor pool for these high-risk candidates.

Incidence, risk factors, and outcomes of postoperative stroke in combined heart-lung transplantation: A retrospective cohort study of the UNOS registry.

Stroke is a well-characterized complication of isolated heart and lung transplantation, but has not been described in combined heart-lung transplantation (HLTx). We retrospectively reviewed national U.S. data to describe the incidence, risk factors, and impact of postoperative stroke in HLTx recipients. Of 871 heart-lung recipients between 1994-2022, 35 (4.0%) experienced stroke, and the incidence increased over time, trending toward significance (p-trend=.07). After adjustment, extracorporeal membrane oxygenation (ECMO) (Adjusted odds ratio [aOR]=2.63, 95%CI=[1.13-6.11]) and pre-transplant implantable defibrillator (aOR=2.86, 95%CI=[1.20-6.81]) were independent risk factors for stroke. Postoperative stroke is common and is increasing in an era where organ allocation is driven by mechanical circulatory support (MCS) bridging.

Hepatitis B virus reactivation in hepatitis B core antibody positive lung transplant recipients

BackgroundSolid organ transplant recipients with resolved hepatitis B (HBV) infection are at risk for reactivation, however, most of the studies have focused on kidney transplant recipients and have short to intermediate term follow up. Risk factors for reactivation are also uncertain, with some studies suggesting surface antibody (anti-HBs) may be protective. MethodsThis retrospective single center study aimed to assess the risk of HBV reactivation (HBVr) in lung transplant recipients with prior HBV infection as well as the value of anti-HBs titers in predicting HBVr. Surface antigen (HBsAg) negative, core antibody (anti-HBc) positive adult lung and heart-lung SOTR from 2005 to 2019 were included. The primary outcome was HBVr after transplant, defined as seroreversion to HBsAg positivity. The secondary outcome compared anti-HBs titers at transplant and at posttransplant month 12. ResultsThe cohort included 38 lung and heart-lung recipients with anti-HBc positive, HBsAg negative pretransplant serology. Reactivation occurred in 3 of 38 (8%) at 49, 69 and 94 months posttransplant. Two (5% of cohort) subjects died as a consequence of HBVr. Two of the 3 HBVr patients had anti-HBs titers >10 IU/ml at transplant and one had anti-HBs >100 IU/ml at time of HBV reactivation. We did not find a statistically significant decrease in anti-HBs titers one year after transplant in subjects with baseline anti-HBs>10 IU/ml. ConclusionThe prolonged time to reactivation highlights the lifelong risk. The 8% rate of reactivation and 5% mortality support a preferred strategy of indefinite HBV antiviral prophylaxis over monitoring in anti-HBc positive lung recipients.

Cryotechnology in lung and heart-lung transplantation

Bronchial complications, along with development and progression of chronic dysfunction on the background of chronic rejection, are factors that reduce the quality and life of lung and heart-lung recipients. They also increase the frequency of hospitalizations. Application of cryotechnology is based on the contact effect of extremely low temperatures on organs and tissues using a cryoprobe. This article demonstrates the experience of using cryotechnology in the diagnosis and treatment of complications in lung and heart-lung recipients.

Graft Rejection and Survival in Patients Undergoing Multi-Organ Heart Transplantation

Purpose Graft rejection and related complications remain leading causes of death in heart transplantation. Here we compare rates of graft rejection and survival in the following transplantation groups: heart-only, heart-lung, heart-kidney, and heart-liver. Methods Using the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research Database, we retrospectively reviewed heart transplants performed from January 1988 to September 2020. Graft survival was assessed with Kaplan-Meier method and compared by log-rank test. Univariate and multivariate Cox regression analyses were performed to assess hazard ratios. Rejection rates were compared with logistic regression. Results A total of 80,058 patients were included in this study. We found increased risk of graft failure in heart-lung patients and reduced risk in heart-kidney and heart-liver transplants: HR 1.87 (95% 1.75-1.99, p <0.001), HR 0.89 (95% 0.82-0.96, p <0.01), and 0.80 (95% 0.66-0.98, p <0.05), respectively. Rejection rates were lowest in heart-liver transplants, followed by heart-kidney, and heart-lung transplants: OR 0.88 (95% 0.85-0.92, p <0.001), OR 0.91 (95% 0.9-0.93, p <0.001), and OR 0.96 (95% 0.93-1, p <0.05), respectively. These results were consistent in multivariate analysis. Adjusting for donor age, recipient age, and ethnicity found increased risk of graft failure in heart-lung recipients while heart-kidney and heart-liver recipients possessed lower risk: HR 2.01 (95% 1.88-2.14, p <0.001), HR 0.84 (95% 0.78-0.91, p<0.001), and HR 0.80 (95% 0.65-0.97, p <0.05), respectively. Conclusion Heart-lung graft survival is significantly depressed in relation to all other examined groups. Rejection rates are lowest in heart-liver transplants, though all multi-organs showed reduced risk relative to heart-only transplants. More studies are needed to account for confounding and validate these findings prospectively. Graft rejection and related complications remain leading causes of death in heart transplantation. Here we compare rates of graft rejection and survival in the following transplantation groups: heart-only, heart-lung, heart-kidney, and heart-liver. Using the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research Database, we retrospectively reviewed heart transplants performed from January 1988 to September 2020. Graft survival was assessed with Kaplan-Meier method and compared by log-rank test. Univariate and multivariate Cox regression analyses were performed to assess hazard ratios. Rejection rates were compared with logistic regression. A total of 80,058 patients were included in this study. We found increased risk of graft failure in heart-lung patients and reduced risk in heart-kidney and heart-liver transplants: HR 1.87 (95% 1.75-1.99, p <0.001), HR 0.89 (95% 0.82-0.96, p <0.01), and 0.80 (95% 0.66-0.98, p <0.05), respectively. Rejection rates were lowest in heart-liver transplants, followed by heart-kidney, and heart-lung transplants: OR 0.88 (95% 0.85-0.92, p <0.001), OR 0.91 (95% 0.9-0.93, p <0.001), and OR 0.96 (95% 0.93-1, p <0.05), respectively. These results were consistent in multivariate analysis. Adjusting for donor age, recipient age, and ethnicity found increased risk of graft failure in heart-lung recipients while heart-kidney and heart-liver recipients possessed lower risk: HR 2.01 (95% 1.88-2.14, p <0.001), HR 0.84 (95% 0.78-0.91, p<0.001), and HR 0.80 (95% 0.65-0.97, p <0.05), respectively. Heart-lung graft survival is significantly depressed in relation to all other examined groups. Rejection rates are lowest in heart-liver transplants, though all multi-organs showed reduced risk relative to heart-only transplants. More studies are needed to account for confounding and validate these findings prospectively.

Transfusion practices for pediatric oncology and hematopoietic stem cell transplantation patients: Data from the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III)

To evaluate transfusion practices in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients. This is a multicenter retrospective study of children with oncologic diagnoses treated from 2013 to 2016 at hospitals participating in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III. Transfusion practices were evaluated by diagnosis codes and pre-transfusion laboratory values. A total of 4766 inpatient encounters of oncology and HSCT patients were evaluated, with 39.3% (95% confidence interval [CI]: 37.9%-40.7%) involving a transfusion. Red blood cells (RBCs) were the most commonly transfused component (32.4%; 95% CI: 31.1%-33.8%), followed by platelets (22.7%; 95% CI: 21.5%-23.9%). Patients in the 1 to <6 years of range were most likely to be transfused and HSCT, acute myeloid leukemia, and aplastic anemia were the diagnoses most often associated with transfusion. The median hemoglobin (Hb) prior to RBC transfusion was 7.5g/dl (10-90th percentile: 6.4-8.8g/dl), with 45.7% of transfusions being given at 7 to <8g/dl. The median platelet count prior to platelet transfusion was 20 × 109 /L (10-90th percentile: 8-51 × 109 /L), and 37.9% of transfusions were given at platelet count of >20-50 × 109 /L. The median international normalized ratio (INR) prior to plasma transfusion was 1.7 (10-90th percentile: 1.3-2.7), and 36.3% of plasma transfusions were given at an INR between 1.4 and 1.7. Transfusion of blood components is common in hospitalized pediatric oncology/HSCT patients. Relatively high pre-transfusion Hb and platelet values and relatively low INR values prior to transfusion across the studied diagnoses highlight the need for additional studies in this population.

Transfusion practices in a large cohort of hospitalized children.

While previous studies have described the use of blood components in subsets of children, such as the critically ill, little is known about transfusion practices in hospitalized children across all departments and diagnostic categories. We sought to describe the utilization of red blood cell, platelet, plasma, and cryoprecipitate transfusions across hospital settings and diagnostic categories in a large cohort of hospitalized children. The public datasets from 11 US academic and community hospitals that participated in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) were accessed. All nonbirth inpatient encounters of children 0-18 years of age from 2013 to 2016 were included. 61,770 inpatient encounters from 41,943 unique patients were analyzed. Nine percent of encounters involved the transfusion of at least one blood component. RBC transfusions were most common (7.5%), followed by platelets (3.9%), plasma (2.5%), and cryoprecipitate (0.9%). Children undergoing cardiopulmonary bypass were most likely to be transfused. For the entire cohort, the median (interquartile range) pretransfusion laboratory values were as follows: hemoglobin, 7.9 g/dl (7.1-10.4 g/dl); platelet count, 27 × 109 cells/L (14-54 × 109 cells/L); and international normalized ratio was 1.6 (1.4-2.0). Recipient age differences were observed in the frequency of RBC irradiation (95% in infants, 67% in children, p < .001) and storage duration of RBC transfusions (median storage duration of 12 [8-17] days in infants and 20 [12-29] days in children, p < .001). Based on a cohort of patients from 2013 to 2016, the transfusion of blood components is relatively common in the care of hospitalized children. The frequency of transfusion across all pediatric hospital settings, especially in children undergoing cardiopulmonary bypass, highlights the opportunities for the development of institutional transfusion guidelines and patient blood management initiatives.

Variation in Neonatal Transfusion Practice

To estimate the incidence of blood product transfusion, including red blood cells, platelets, and plasma, and characterize pretransfusion hematologic values for infants during their initial hospitalization after birth. Retrospective cohort study using data from 7 geographically diverse US academic and community hospitals that participated in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) from 2013 to 2016. Pretransfusion hematologic values were evaluated closest to each transfusion and no more than 24hours beforehand. Data from 60 243 infants were evaluated. The incidence of any transfusion differed by gestational age (P<.0001), with 80% (95% CI 76%-84%) transfused at <27weeks of gestation (n=329) and 0.5% (95% CI 0.5%-0.6%) transfused at ≥37weeks of gestation (n=53 919). The median pretransfusion hemoglobin was 11.2g/dL (10th-90th percentile 8.8-14.1) for the entire cohort, ranging from 10.5g/dL (8.8-12.3) for infants born extremely preterm at <27weeks of gestation to 13.0g/dL (10.5-15.5) for infants born at term. The median pretransfusion platelet count (×109/L) was 71 (10th-90th percentile 26-135) for the entire cohort, and was >45 for all gestational age groups examined. The median pretransfusion international normalized ratio for the entire cohort was 1.7 (10th-90th percentile 1.2-2.8). There is wide variability in pretransfusion hemoglobin, platelet count, and international normalized ratio values for neonatal transfusions. Our findings suggest that a large proportion of neonatal transfusions in the US are administered at thresholds greater than supported by the best-available evidence and highlight an opportunity for improved patient blood management.

Changes in multiorgan heart transplants following the 2018 allocation policy change.

This study evaluated the impact of the heart allocation policy change in 2018 on the characteristics and outcomes of multiorgan transplants involving heart allografts. Adults undergoing multiorgan heart transplantation from 2010 to 2020 were identified from the United Network for Organ Sharing (UNOS) registry. Transplants were stratified into occurring before versus after the October 2018 heart allocation change. The primary outcome was 1-year survival following transplantation. A Cox proportional hazards model was used to evaluate the risk-adjusted effect of the allocation policy change on outcomes between cohorts. A total of 1832 patients underwent multiorgan heart transplantation during the study period with 245 (13.37%) undergoing heart-lung transplantation, 244 (13.32%) undergoing heart-liver transplantation, and 1343 (73.31%) undergoing heart-kidney transplantation. There was a higher utilization of temporary MCSDs as well as longer ischemic times for all three types of transplantation following the policy change. Heart-lung and heart-liver recipients had a similar 1-year survival before and after the policy change (each p > .05). Renal failure requiring dialysis (29.5% vs. 39.4%, p = .001) as well as 1-year survival (88% vs. 82%; log-rank p = .01) were worse in the heart-kidney cohort after the organ allocation system modification. This study demonstrates similar trends in multiorgan transplants as has been observed in isolated heart transplants following the allocation change, including more frequent utilization of temporary mechanical support and longer ischemic times. Although outcomes have remained comparable in the new allocation era with heart-lung and heart-liver transplants, heart-kidney recipients have a worse 1-year survival following the change.

Red blood cell transfusion does not increase risk of venous or arterial thrombosis during hospitalization.

Previous observational studies suggest associations between red blood cell (RBC) transfusion and risk for arterial or venous thrombosis. We determined the association between thrombosis and RBC transfusion in hospitalized patients using the Recipient Database from the National Heart Lung and Blood Institute (NHLBI) Recipient Epidemiology and Donor Evaluation Study-III. A thrombotic event was a hospitalization with an arterial or venous thrombosis ICD-9 code and administration of a therapeutic anticoagulant or antiplatelet agent. Patients with history of thrombosis or a thrombosis within 24 hours of admission were excluded. A proportional hazards regression model with time-dependent covariates was calculated. Estimates were adjusted for age, sex, hospital, smoking, medical comorbidities, and surgical procedures. Of 657 412 inpatient admissions, 67 176 (10.2%) received at least one RBC transfusion. Two percent (12927) of patients experienced a thrombosis. Of these, 2587 developed thrombosis after RBC transfusion. In unadjusted analyses, RBC transfusion was associated with an increased thrombosis risk [HR = 1.3 (95% CI 1.23-1.36)]. After adjustment for surgical procedures, age, sex, hospital, and comorbidities, no association between RBC transfusion on risk of venous and arterial thrombosis was found [HR 1.0 (95% CI: 0.96-1.05)]. Thus, RBC transfusion does not appear to be an important risk factor for thrombosis in most hospitalized patients.

Heart transplant recipients with confirmed 2019 novel coronavirus infection: The Detroit experience.

A chronic immunosuppressed state as in solid organ transplant recipients is a reported risk factor for the novel 2019 coronavirus infection. Patients with a history of orthotopic heart transplant (OHT) at a tertiary care transplant center in Detroit, Michigan were retrospectively reviewed from March until May 2020. Clinical parameters and outcomes of 5 OHT recipients and one combined heart-lung recipient with confirmed SARS-CoV-2 were obtained. The cohort was predominately African American males with median age of 59years (interquartile range, 48.25-73.25). All patients were classified as having mild-moderate disease; none required intubation or ICU admission with no deaths. The most common presenting symptoms were fever and shortness of breath 83% (n=5), followed by cough and chills 67% (n=4). All admitted patients (n=5) received hydroxychloroquine and 3 received high-dose steroids. Antimetabolites were held for 2 patients (33.3%). The calcineurin inhibitor trough goal was decreased in only 1 patient; 3 other patients, without change in goal, required calcineurin inhibitor dosage reduction. Two patients requiring readmission presented 7 and 23days after initial symptoms onset. In conclusion, our experience with OHT patients infected by the SARS-CoV-2 virus did not have an elevated risk of severe infection. Impact of modifying immunosuppression remains unclear.

Characteristics and Outcomes of Patients Undergoing Combined Organ Transplantation (from the United Network for Organ Sharing)

Studies have shown that highly selected patients who underwent combined heart-kidney (HK) and heart-liver transplants (HLv) have short- and long-term outcomes comparable to those observed in primary heart transplantation (HT). Adults patients with stage D heart failure that underwent combined HK, HLv, and heart-lung (HL) were identified in the United Network for Organ Sharing registry from 1991 to 2016, with follow-up through March 2018. We conducted inverse probability of treatment weighting survival analysis of long-term survival stratified by type of combined organ transplant, accounting for donor, recipient, and operative characteristics. We identified 2,300 patients who underwent combined organ transplant (HK 1,257, HLv 212, HL 831). HL recipients were more likely white (77%), women (58%), with congenital heart disease (44.5%), and longer waiting list time (median 195 days). HK transplant increased significantly during the study period where as HL decreased significantly. Median survival was 12.2 years for HK (95% confidence intervals [CI] 10.8 to 12.8), 12 for HLv (95% CI 8.6 to 17.6) but significantly lower at 4.5 years for HL (95% CI 3.6 to 5.8). Combined HK and HLv transplantation rates are increasing and long-term survival is comparable to primary HT, unlike HL which is associated with decreasing trends and significantly lower survival.

Heart Transplantation Outcomes in Multiorgan Transplants

We sought to elucidate the differences in outcomes between patients undergoing Heart-Lung (HL) Heart-Lung-Kidney (HLK) and Heart-Lung-Liver (HLL) multiorgan transplantation. Using the UNOS registry, we compared outcomes in HL, HLK, and HLL recipients. Analysis was performed using multivariate Cox proportional hazard regression model that adjusted for age, sex, race, diagnosis of diabetes, ischemic time, recipient wait-time, HLA mismatch, need for dialysis, and need for life support. We excluded patients who were age less than 18 years old or who were lost-to-follow-up. Kaplan-Meier survival analysis was performed. 1177 HL patients, 8 HLK, and 12 HLL patients were identified. HL recipients were more likely to have undergone prior non-transplant cardiac surgery (HL 91.6% vs HLK 75.0% vs HLL 75.0% p=0.033). HLK patients were more likely to require VAD support (HL 1.2% vs HLK 12.5% vs HLT 0.0% p=0.015), have higher serum creatinine (HL 1.0 mg/dL ± 0.6 vs HLK 2.4 ± 1.3 vs HLL 0.9 ± 0.5 p<0.001), require dialysis (HL 1.5% HLK 37.5% and HLL 0.0% p<0.001), and have higher pulmonary capillary wedge pressures (HL 15.5mmHg ± 9.4 vs HLK 26.2 ± 11.0 vs HLL 13.0 ± 10.1 p=0.038). There was no significant difference in mortality between the groups (p=0.2866). Despite increasing risk factors, HL concomitant with either kidney or liver transplant did not affect survival compared to HL alone. Carefully selected patients may benefit from triple organ transplantation, however, ethical issues of organ utilization may arise.

Increased Use of Multiorgan Transplantation in Heart Transplantation: Only Time Will Tell

The utilization of multiorgan transplantation in cardiac transplantation has steadily increased over the past several years. We sought to characterize the trends and outcomes in simultaneous heart and other organ transplantation compared with heart transplantation alone. The United Network for Organ Sharing database was queried for all adult patients (age ≥ 18 y) who underwent isolated heart transplantation or simultaneous heart-lung or heart-kidney transplantation from 1987-2016. Patients were stratified into 3 equal time intervals. Demographics and postoperative outcomes were compared. A total of 58,060 patients were identified with a distribution based on era. Dual organ recipients had more factors associated with increased operative risk including higher rates of diabetes, pulmonary hypertension, intensive care unit admissions, and dialysis prior to transplantation. Heart-lung and heart-kidney recipients had decreased 1-year survival compared with isolated heart recipients from 2007-2016. However, heart-kidney recipients had significantly increased 5-year post-transplantation survival compared with isolated heart recipients with impaired renal function. For isolated heart transplants and heart-lung transplants, 5-year survival rates improved over time, whereas 5-year survival for heart-kidney recipients did not improve with time. We found a significantly increased 5-year survival rate for heart-kidney transplant recipients compared with isolated heart transplant recipients with renal impairment. Lack of improvement in 5-year postoperative outcomes for heart-kidney recipients in the setting of higher-risk pretransplant clinical characteristics suggests decreased selectivity regarding heart-kidney recipients. Continued scrutiny and evaluation of postoperative outcomes are required to ensure just and appropriate utilization of organs.

Use of dd-cfDNA in Multiorgan Transplantation

Purpose Gene expression profiling testing (GEP; AlloMap) and donor-derived cell free DNA (dd-cfDNA; AlloSure) each provide non-invasive means to detect possible heart allograft rejection, including acute cellular rejection (ACR). Use of dd-cfDNA in multiorgan transplantation has not previously been reported. This report describes the largest single center use of dd-cfDNA to date in this population. Methods Post heart transplant (HT) management is standardized at our center such that endomyocardial biopsy is used for rejection surveillance in the early period with crossover to GEP testing at day 56. Elevated GEP (≥34) prompts biopsy. dd-cfDNA was utilized in conjunction with biopsy or in lieu of biopsy (barrier to biopsy). A cohort of 26 HT patients underwent dd-cfDNA testing, including 3 multiorgan (same donor) and 5 retransplant patients. The dd-cfDNA (%, AlloSure) and GEP (AlloMap, score 0-40) results were correlated patient survival. Results Among 26 HT patients, there were 3 multiorgan transplant recipients (2 heart-kidney & 1 heart-lung). Mean dd-cfDNA was 0.9 ± 0.5%. Mean GEP score was 32.8 ± 4.0. dd-cfDNA usage was due to inability to biopsy (33.3%), anticoagulation (33.3%) & elevated Allomap (33.3%). Mean LVEF was 55 ± 1%. Mean day post transplant for first dd-cfDNA was 153 (IQR 119-347). There were no deaths. Of the heart-kidney recipients, mean ACR & AMR biopsy grade was 0.67 & 0, respectively. The heart-lung recipient underwent 2 lung biopsies with mean grade of 0. Conclusion In surveillance of heart allograft recipients for rejection, consideration of dd-cfDNA levels may improve patient management decisions particularly when endomyocardial biopsy may not be feasible. This is the first report of use of dd-cfDNA in multiorgan transplantation. Baseline levels of dd-cfDNA appear to be higher than that of heart-only recipients. Further study is warranted to assess the utilization of dd-cfDNA in multiorgan transplantation.

Outcomes of multidisciplinary inpatient rehabilitation following heart and/or lung transplantation

Heart and lung transplantation is becoming a more common treatment option for patients with end-stage cardiopulmonary disease. Both the incidence and survival of transplant operations are increasing, resulting in heightened interest in optimising long-term patient outcomes, functional ability and quality-of-life following transplant. Specialist rehabilitation can help to promote recovery and enhance functional ability following transplant surgery, particularly for frail and debilitated patients. A retrospective file audit was conducted to review all admissions for multidisciplinary inpatient rehabilitation following heart and/or lung transplant between 2009–2016, at St-Vincent's Hospital Sydney, Australia. This is the largest and oldest heart and lung transplant centre in Australia. Between 2009–2016, 603 heart/lung transplant surgeries were performed at St-Vincent's Hospital Sydney. Of these patients, 116 (19.2%) were admitted for inpatient rehabilitation: 49 heart, 65 lung and 2 combined heart-lung recipients. The rehabilitation cohort was comprised of 63 men and 53 women, mean age 53.4 ± 12.2 years. Average rehabilitation length-of-stay was 26.9 ± 2.0 days. Functional Independence Measure (FIM) scores improved significantly with rehabilitation, from 79.8 ± 1.9 on admission to 101.8 ± 2.8 at discharge ( P < 0.001), resulting in a mean FIM efficiency of 0.9 ± 0.1. Physical measures of mobility and balance also showed significant improvements, including the 6 Minute Walk Test ( P < 0.001), Timed Up and Go ( P < 0.001) and Berg Balance Scale ( P < 0.001); 33.6% of admissions were interrupted by an acute medical complication, however this did not prevent completion of rehabilitation or attainment of functional gains for the majority of cases. One hundred and nine patients (94%) were discharged to a private residence following rehabilitation, 2 were transferred to a regional hospital and 5 died in hospital. Multidisciplinary inpatient rehabilitation resulted in significant functional improvements for debilitated patients following heart and/or lung transplantation. These results support a role for specialist inpatient rehabilitation in optimising functional capacity and independence post-transplant.

272 - Single-Center Outcomes of Biopsy-Negative Rejection in Heart Transplantation

Allograft rejection, defined as acute cellular rejection (ACR) or antibody-mediated rejection (AMR), carries significant morbidity and mortality after heart transplantation. Allograft dysfunction, characterized by left ventricular ejection fraction (EF) ≤ 45%, in the absence of ACR or AMR is termed biopsy-negative rejection (BNR). To date, little data exist regarding the outcomes of such patients, as BNR in the era of better-defined AMR criteria is rare. Treatment consensus is also lacking. We sought to describe our experience with BNR in a single center. Between 1992 and 2016 at the University of Maryland Medical Center, 6 patients were identified as having BNR. Mean time interval between transplant and date of BNR diagnosis was 76 ± 95 days. One was a heart-lung recipient, and 1 was a re-transplant patient. Standard immunosuppressant drugs included mycophenolate mofetil, prednisone and a calcineurin inhibitor. No one was treated for rejection before BNR, or had severe coronary allograft vasculopathy by coronary angiography with intravascular ultrasound. All had normal hemodynamics by right heart catheterization at the time of BNR diagnosis. One patient developed de novo donor-specific antibodies (DSA) prior to BNR onset. This patient received a prednisone burst with subsequent EF recovery. The heart-lung recipient did not receive BNR treatment out of concern for increased infection. His EF remained depressed (20–30%) after 6 months. One patient was also not treated at the time of BNR, only to develop grade 2R ACR 2 months later. He was then treated with a methylprednisolone burst with EF recovery. Two patients received a prednisone burst; one recovered and maintained EF > 45% (the re-transplant patient), the other's EF stayed low at 30–40%. The 6th patient had recurrent BNR in the span of 3 months, both episodes treated with methylprednisolone burst. After the 2nd episode, he had de novo DSA which prompted treatment with plasmapheresis and thymoglobulin. His EF normalized after each episode of treatment. Increased glucose uptake by PET and cardiac MRI are emerging as tools to detect rejection, so they were done for these patients but were unrevealing and did not contribute towards determining treatment. In conclusion, BNR was diagnosed within one year post transplant in all six patients. Four out of 5 patients treated for BNR recovered their heart functions. The most common treatment was steroid burst. Given the paucity of data concerning BNR, there needs to be a multi-centered study focused on non-invasive diagnostic modalities, treatments and outcomes to better serve this special heart transplant population.

Effects of Lung Cotransplantation on Cardiac Allograft Tolerance Across a Full Major Histocompatibility Complex Barrier in Miniature Swine.

A 12-day course of high-dose tacrolimus induces tolerance of major histocompatibility complex-mismatched lung allografts in miniature swine but does not induce tolerance of heart allografts unless a kidney is cotransplanted. To determine whether lungs share with kidneys the ability to induce cardiac allograft tolerance, we investigated heart-lung cotransplantation using the same induction protocol. Hearts (n = 3), heart-kidneys (n = 3), lungs (n = 6), and hearts-lungs (n = 3) were transplanted into fully major histocompatibility complex-mismatched recipients treated with high-dose tacrolimus for 12 days. Serial biopsy samples were used to evaluate rejection, and in vitro assays were used to detect donor responsiveness. All heart-kidney recipients and five of six lung recipients demonstrated long-term graft survival for longer than 272 days, while all heart recipients rejected their allografts within 35 days. Tolerant recipients remained free of alloantibody and showed persistent donor-specific unresponsiveness by cell-mediated lympholysis/mixed-lymphocyte reaction. In contrast, heart-lung recipients demonstrated rejection of both allografts (days 47, 55, and 202) and antidonor responsiveness in vitro. In contrast to kidneys, lung cotransplantation leads to rejection of both heart and lung allografts, indicating that lungs do not have the same tolerogenic capacity as kidneys. We conclude that cells or cell products present in kidney, but not heart or lung allografts, have a unique capacity to confer unresponsiveness on cotransplanted organs, most likely by amplifying host regulatory mechanisms.

Post-transplant lymphoproliferative disease in heart and lung transplantation: Defining risk and prognostic factors

Heart and lung transplant recipients have among of the highest incidence rates of post-transplant lymphoproliferative disease (PTLD). Despite this, there is a paucity of data specific to this group. We collated data on heart, lung and heart-lung transplant recipients with PTLD to identify disease features and prognostic factors unique to this group of patients. Seventy cases of PTLD were identified from a single institution (41 heart, 22 lung, 6 heart-lung and 1 heart-kidney transplant) from 1984 to 2013. Demographics, immunosuppression, treatment, response, complications and survival data were analyzed. Uni- and multivariate Cox regression analyses were performed to identify prognostic factors. The incidence of PTLD was 7.59% in heart-lung, 5.37% in heart and 3.1% in lung transplant recipients. Extranodal disease (82%) with diffuse large B-cell lymphoma (72%) was the most common presentation. Bone marrow involvement (13%) and central nervous system disease (3%) were uncommon. Heart transplant recipients had later onset of PTLD (>1 year post-transplant), with less allograft involvement, compared with lung and heart-lung recipients. Poor prognostic markers were bone marrow involvement (HR 6.75, p < 0.001) and serum albumin <30 g/liter (HR 3.18, p = 0.006). Improved survival was seen with a complete response within 3 months of treatment (HR 0.08, p < 0.001). Five-year overall survival was 29%. This analysis is the largest to date on PTLD in heart and lung transplant recipients. It provides a detailed analysis of the disease in this group of patients and identifies unique prognostic features to aid risk stratification and guide treatment allocation.