Thoracic Organ Transplant Registry Research Articles

Informing preconception counseling: Outcomes among female heart transplant recipients in the ISHLT registry

The numbers of women of child-bearing age undergoing heart transplantation (HT) and female pediatric HT recipients surviving to child-bearing age have increased, along with improvements in post-transplant survival. Data regarding life expectancy and comorbidities in reproductive-aged female HT recipients are needed to inform shared decision-making at the time of preconception counseling. The International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry was investigated for HT recipients between January 1, 2000 and June 30, 2017. Women of childbearing age were defined as those aged 15-45 years, either at transplant, or at the respective post-transplant follow-up. Characteristics and outcomes of female recipients of childbearing age at transplant, 5-, 10-, and 15-year follow-up were compared to females>45 years of age, males 15-45 years and males>45 years of age at the corresponding time intervals. Outcomes included survival, development of diabetes (DM), severe renal dysfunction (CKD), and cardiac allograft vasculopathy (CAV). During the study period, 71,585 HT recipients were included: 24% (n=17,194) were female and 9.2% (n=6602) were of childbearing age at HT. A pre-transplant diagnosis of peripartum cardiomyopathy was associated with significantly worse post-transplant survival, a finding that remained independent of panel reactive antibody levels. The presence of pre-transplant DM and/or severe CKD was significantly associated with lower survival as were the presence of CAV, DM, and CKD post-HT. Knowledge of the impact of pre-existing comorbidities and complications post-HT on survival are important for risk stratification for preconception counseling post-HT.

Graft survival in primary thoracic organ transplant recipients: A special report from the International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation

Graft survival in primary thoracic organ transplant recipients: A special report from the International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation

Influence of chronic kidney disease and other risk factors pre-heart transplantation on malignancy incidence post-heart transplantation.

Chronic kidney disease (CKD) pre-heart transplantation (HTx) has been proposed as a risk factor for malignancy risk post-HTx. Using multicenter registry data, our aim was to calculate the death-adjusted annual incidence of malignancies post-HTx, corroborate the association between CKD pre-HTx and malignancy risk post-HTx, and determine other risk factors for post-HTx malignancies. We used data from patients transplanted in North American HTx centers between January 2000 and June 2017 and registered in the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry. We excluded recipients with missing data on post-HTx malignancies, heterotopic heart transplant, retransplantation, multi-organ transplantation, and patients with a total artificial heart pre-HTx. Overall, 34,873 patients were included to determine the annual incidence of malignancies, 33,345 patients were included in the risk analyses. The incidence of any malignancy, solid-organ malignancy, post-transplant lymphoproliferative disease (PTLD), and skin cancer adjusted for death 15 years post-HTx, was 26.6%, 10.9%, 3.6%, and 15.8% respectively. Besides widely acknowledged risk factors, CKD stage ≥4 pre-HTx was associated with the development of all malignancies post-HTx (HR 1.17 compared to CKD stage 1, p = 0.023), as well as solid-organ malignancies (HR 1.35, p = 0.01), but not for PTLD (HR 0.73, p = 0.057), and skin cancer (HR 1.06, p = 0.59). Risk of malignancy post-HTx remains high. CKD stages ≥4 pre-HTx was associated with an increased risk for any malignancy and solid-organ malignancy post-HTx. Strategies to mitigate the impact of pre-HTx patient factors on the risk of post-HTx malignancy are needed.

Abstract 12595: De Novo Lymphoproliferative Disorders in Heart Transplant Recipients: Predictors and Clinical Outcomes

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is an important cause of morbidity and mortality in heart transplant (HTx) recipients. However, clinical characteristics and predictors of PTLD in the real world have not been well studied. Methods We retrospectively analyzed clinical characteristics, predictors, and outcomes of PTLD, in 28,136 recipients of heart alone transplants between January 2000 and June 2015 from the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry. Results Ten-year incidence of PTLD after successful discharge from HTx during 2000-2007 was 3.8%. The adjusted overall risk of mortality was significantly higher in patients diagnosed with PTLD within 3 years after HTx compared to those without PTLD (HR 2.22, 95% CI 1.86-2.65, p<0.001). Bimodal age peak of the PTLD incidence within the 3 years of HTx and mortality after the diagnosis of PTLD was noted. Both adjusted risk of PTLD incidence and mortality were lower in recent HTx; lower incidence and mortality in era of 2008-2015, compared to 2000-2007 (Incidence: HR 0.75, 95% CI 0.57-0.98, p=0.038) (Mortality: HR 0.86, 95% CI 0.81-0.91, p<0.001). Age at transplant, male recipient, high risk Epstein-Barr virus (EBV) mismatch (donor positive and recipient negative for EBV) were independent risk factors, while primary maintenance therapy with cyclosporine (vs. tacrolimus) at initial discharge was a protective factor for PTLD within 3 years. Conclusions The incidence as well as mortality of PTLD has decreased in recent years of HTx, possibly with advances in changed pattern of immunosuppression according to patient profile. Clinical characteristics such as age, male gender, EBV status and rejection history are key factors for assessing the risk of PTLD, which can be detrimental in the course of post HTx care.

The International thoracic organ transplant registry of the international society for heart and lung transplantation: Thirty-ninth adult heart transplantation report-2022; focus on transplant for restrictive heart disease.

This 39th annual international adult heart transplant report focuses on transplantation for heart disease with restrictive physiology, that is, restrictive cardiomyopathies and hypertrophic cardiomyopathy, based on data submitted to the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant (TTX) Registry between January 1992 and June 2018. Restrictive cardiomyopathy (RCM) refers to a heterogeneous group of cardiomyopathies that includes amyloid, sarcoid, radiation and/or chemotherapy-induced cardiomyopathy, and other types of heart disease that all share restrictive physiology, and reduced or normal diastolic and systolic volumes in 1 or both ventricles.

The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-ninth adult lung transplantation report-2022; focus on lung transplant recipients with chronic obstructive pulmonary disease.

The International Society for Heart and Lung Transplantation (ISHLT) International Thoracic Organ Transplant (TTX) Registry has gathered data regarding transplant procedures, donor and recipient characteristics, and outcomes from a global community of transplant centres over the last 3 decades. Close to 70,000 adult lung transplant procedures have been reported to the Registry since its initiation, each providing an opportunity for a recipient with end-stage lung disease to regain quality of life and longevity.

The International thoracic organ transplant registry of the international society for heart and lung transplantation: Twenty-fifth pediatric heart transplantation report-2022; focus on infant heart transplantation.

Traditionally, the annual pediatric heart transplant report of the International Thoracic Organ Transplant Registry has presented an updated analysis of transplant recipients after including the most recently transplanted pediatric recipients to the registry. Due to the changes in the regulatory environment, the registry is undergoing an update in data acquisition, and no new patients have been added to the registry since the 2019 report. The 2020 and 2021 registry reports focused on how the donor and the recipient characteristics, respectively, changed during the last 3 decades.

The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Twenty-fifth pediatric lung transplantation report - 2022; focus on pulmonary vascular diseases.

The annual Reports of the International Society for Heart and Lung Transplantation (ISHLT) International Thoracic Organ Transplant Registry traditionally detail analyses using a common theme across all thoracic organ transplants, using the most current data reported to the Registry. Due to a changing regulatory environment, with the Registry undergoing an update in data acquisition, the 2020 and 2021 Registry Reports were derived using the data examined in the 2019 annual Reports.1-4 The 2020 and 2021 Reports on pediatric lung transplantation presented trends in the characteristics of donors and recipients, and associated post-transplant outcomes, respectively.

The role of sensitization in post-transplant outcomes in adults with congenital heart disease sensitization in adults with congenital heart disease

IntroductionThe number of heart transplants in adults with congenital heart disease (CHD) is increasing, though outcomes remain unfavorable compared to those without CHD. The etiology of this mortality difference remains uncertain. Panel reactive antibody (PRA) is a predictor of survival post-transplantation, and adult CHD patients have been observed to have higher PRA levels. Here we assessed the relationship between PRA and outcomes in adult patients with CHD who underwent heart transplantation. MethodsThis is a retrospective cohort study using the 2004–2015 ISHLT Thoracic Organ Transplant Registry to investigate the role of sensitization in the observed excess mortality. The composite outcome of mortality or graft failure within 1-year of transplantation was compared among CHD vs. non-CHD recipients, according to sensitization as measured by pre-transplant panel reactive antibodies (PRA). ResultsAdults with CHD (n = 1188) had higher PRA level compared to non-CHD (n = 38,201) recipients (27% vs. 18% PRA>10%, respectively, p < 0.001). CHD diagnosis remained independently associated with a higher incidence of the composite outcome in multivariable analysis after adjusting for PRA and other variables. Further, even after age-matching, patients with CHD and PRA ≤10% were at higher risk of the primary outcome compared to non-CHD (OR 2.1 [1.4–3.4], p = 0.001), though both groups had comparable outcomes when PRA was >10% (OR 1.1 [0.6–2.0], p = 0.852). ConclusionsAdults with CHD are more likely to have higher sensitization and worse outcomes than non-CHD recipients. Higher sensitization rates alone do not fully explain their excess risk of adverse outcomes after heart transplantation.

Long-Term Renal Outcome in Patients Bridged on ICU for Lung Transplantation

<h3>Purpose</h3> Survival in lung transplantation (LTx) patients continues to improve. The focus of post LTx care is shifting from short term survival to long term health outcome, including LTx related comorbidities like chronic kidney disease (CKD). LTx from the intensive care unit (ICU) remains controversial. However recent data showed similar long-term overall survival and allograft function in comparison with elective LTx. Long-term renal outcome for ICU bridged LTx patients is unknown. <h3>Methods</h3> Pre- and post-LTx data from all from all LTx patients bridged on ICU bridged LTx between April 2004 and 31th of December 2018 in the University Medical Center Groningen (UMCG) were used to calculate the absolute post-LTx decline of the estimated glomerular filtration rate calculated with the CKD-EPI equation (eGFR), incidence of CKD and end-stage renal disease (ESRD). <h3>Results</h3> A total of 357 patients received a LTx, of which 41 patients were bridged on ICU. Mean follow up time was 73 months. Mean age of ICU bridged LTx patients was 47 years (18-64), and 63,4% were male. 17,1% received renal replacement therapy directly post-transplantation. Of the ICU bridged patients the mean pre-LTx eGFR was 118 ml/min per 1.73 m². Mean eGFR decline at 1 and 5 years post-LTx was 61 and 69 ml/min per 1.73 m² respectively. The cumulative incidence of CKD 3a-5 for survivors post-LTx at 1 and 5 years was 54% and 69%. The cumulative incidence of CKD 4/5 at 1 and 5 years was 7.3% and 19%. In the largest international registry for LTx (International Thoracic Organ Transplant Registry, N=>10,000) the cumulative incidence of CKD 4/5 at 1 and 5 years was 5.7% and 16.3% respectively. 5 patients developed ESRD of which 3 were treated with hemodialysis an 2 received a renal transplant. <h3>Conclusion</h3> In this single center cohort, patients bridged from ICU to LTx have impaired long-term renal outcome, comparable to ISHLT registry data from patients receiving an elective LTx. However, questions remain unanswered. To complete this analysis, data from the 316 elective transplanted patients will be collected for comparison.

New-onset Diabetes Mellitus After Adult Heart Transplantation and the Risk of Renal Dysfunction or Mortality.

Diabetes mellitus (DM) may occur either pre-heart transplantation (HT) or as new-onset DM post-HT. We sought to define the contemporary incidence of post-HT DM, evaluate risk factors for post-HT DM, and assess the impact of post-HT DM on major outcomes. The cohort included International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry adult primary HT-alone recipients, transplanted January 1995-June 2017, who survived to 1 y post-HT. DM status was characterized as (1) no DM pre-HT or post-HT; (2) pre-HT DM; or (3) post-HT DM (onset within 5 y of HT). Cox proportional hazards models were constructed to identify risk factors for post-HT DM onset, as well as risk factors for post-HT severe renal dysfunction and death/retransplantation. Of 26 263 eligible subjects, 57% had no DM pre-HT or post-HT, 22% had pre-HT DM, and 21% had new-onset post-HT DM. Risk factors for the development of post-HT DM included use of tacrolimus or steroids at 1 y post-HT, as well as higher recipient age, female sex, ischemic cardiomyopathy, higher body mass index, pre-HT dialysis, and pre-HT steroid use. Post-HT DM within 5 y was associated with increased subsequent severe renal dysfunction (hazard ratio, 1.89; 95% confidence interval, 1.77-2.01) and death/retransplantation (hazard ratio, 1.38; 95% confidence interval, 1.32-1.45), compared with patients without post-HT DM. Post-HT DM is common, occurring in 21% of recipients within 5 y of HT. Post-HT DM is associated with increased risk of severe renal dysfunction and death or retransplantation.

Pulmonary Function Testing Pre-heart Transplant Predicts Posttransplant Survival.

International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry data were utilized. Survival was assessed using Kaplan-Meier method and compared via log-rank test. Cox proportional hazard modeling was used to evaluate univariate and multivariate predictors of survival. Eight hundred two patients pretransplant PFT data were available for evaluation. Forced expiratory volume in 1 s (FEV1) < 50% predicted (P < 0.0001), and forced vital capacity (FVC) < 50% predicted each had significantly higher mortality (P = 0.001) compared with patients with FEV1 or FVC 50%-80% or >80%. FEV1/FVC < 0.7 was not associated with increased mortality. FEV1 and FVC below 50% both predicted longer lengths of stay (P = 0.028 for FEV1 and P = 0.0075 for FVC). After adjusting for male gender, age, body mass index, smoking history, chronic obstructive pulmonary disease, creatinine, albumin, and total bilirubin, FEV1 < 50% (hazard ratio, 4.91; P < 0.0001; 95% confidence interval, 2.69-8.94) and FVC < 50% (hazard ratio, 2.75; P = 0.003; 95% confidence interval, 1.4-5.4) both remained independent predictors of mortality. Abnormal pulmonary function (FEV1 or FVC below 50% of predicted) pre-heart transplantation is associated with increased mortality and longer lengths of stay posttransplant.

The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-eighth adult lung transplantation report — 2021; Focus on recipient characteristics

For over 30 years, the International Society for Heart and Lung Transplantation (ISHLT) International Thoracic Organ Transplant (TTX) Registry has gathered data regarding transplant procedures, donor and recipient characteristics, and outcomes from a global community of transplant centers. Almost 70,000 adult lung transplant procedures have been reported to the Registry since its inception, each one providing an opportunity for a recipient with end-stage lung disease to regain quality of life and longevity. With each year's report, we provide more detailed analyses on a particular focus theme important to recipient outcomes. Since 2013, these have been donor and recipient age; retransplantation; early graft failure; indication for transplant; allograft ischemic time; multiorgan transplantation; and donor and recipient size matching.1-7 In response to a changing regulatory environment, the ISHLT TTX Registry is undergoing an update in data acquisition, and the patient cohort examined in this report is therefore derived from the same data source or datasets as that examined in the 2019 annual reports.2,8-10 We refer the reader to the 2019 and prior reports for a detailed description of the baseline characteristics of the cohort, and additional core analyses not directly related to the focus explored in this year's report. To complement the 2020 report which focussed on donor characteristics, the goal of this year's report was to focus entirely on changes in recipient factors over the past 3 decades and to identify important recipient characteristics and transplant processes that may influence post-transplant outcomes. Due to small numbers, heart-lung transplant recipient characteristics and transplant outcomes have not been included. This 38th annual adult lung transplant report is hence based on data submitted to the ISHLT TTX Registry on 67,493 adult recipients of deceased recipient transplants between January 1, 1992 and June 30, 2018.

The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Twenty-fourth pediatric heart transplantation report — 2021; focus on recipient characteristics

Despite a progressive increase in the complexity of pediatric heart transplant recipients, post-transplant survival has continued to improve over the last 3 decades.1 This improvement may be attributed to advances in the pre-transplant, peri-transplant, and long-term management of transplant recipients. Although the fundamental role of heart transplantation as the only accepted therapy for end-stage heart failure remains the same, there have been significant changes in the recipient profile over time with advances in congenital heart disease surgery, in particular for children with single ventricle disease, and the development and widespread use of ventricular assist devices for children awaiting heart transplantation.

The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Twenty-fourth pediatric lung transplantation report — 2021; Focus on recipient characteristics

In recent years, we have seen innovations in organ procurement and organ preservation, post-transplant management, and the use of non-transplant treatments for advanced heart and lung diseases. These developments continue to influence our decisions on recipient selection and transplantation. This focused report aims to document the changes that took place in the pediatric lung transplant recipient profile over the years and to identify important trends in recipient characteristics and their impact on post-transplant outcomes.

The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-eighth adult heart transplantation report — 2021; Focus on recipient characteristics

Heart transplantation continues to be the final therapeutic option for patients with end-stage heart disease of varying etiologies, with more than 6,000 heart transplants performed annually worldwide. As survival of patients with heart disease has improved over time due to the availability of better medical, surgical, and device-based therapies, the heart transplant recipient population has changed. Similarly, candidate acceptance criteria for heart transplantation have expanded over the years. This focused report aims to document the changes that have taken place in the adult heart transplant recipient pool over the years and to identify important recipient characteristics and transplant processes that influence post-transplant outcomes.

Vasculitis on Heart Transplant as an Emerging Prognostic Factor

Purpose Vasculitis had been considered a histopathological marker in severe form of both cellular and humoral rejection. However, in mild forms of rejections, it has not been considered a diagnostic and prognostic histopathologic criterion. Aim of this study is to assess clinical relevance of vasculitis, in terms of mortality and cardiac allograft vasculopathy development, in the mild forms of rejection in heart transplanted patients. Methods We reviewed 2794 monitoring endomyocardial biopsies from 170 adult heart transplanted pts at our center. On endomyocardial biopsies, we evaluated the presence of vasculitis in the different types of rejection . Clinical data were collected during follow up. A Multi-State Markov model was applied to describe the rejection dynamic profile and hazard for mortality, persistence of rejection and CAV development.. We used as reference population the registry data of patients who underwent HTX from 2004 to 2018 provided by the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry Results Vasculitis was detected in 442 endomyocardial biopsies ( 442/2794, 15,8%) with an incremental percent distribution according to the severity of rejection. In ACR, vasculitis significantly increased the risk of mortality by 9% (HR [95% CI]: 1.09; [1.00-1.18]) the hazard of mortality if the patient was negative for ACR and by 14% (HR [95% CI]: 1.14; [1.02-1.37], if the patients was negative for ACR, and by 14% in a mild form of rejection (1R). Similar results were obtained for pAMR and mixed rejection. In ACR, pAMR and mixed rejection patients with vasculitis have a shorter life expectancy than patients without with a loss of four months at ten year follow up for ACR, and of 9 months for pAMR and mixed rejection. Conclusion Vasculitis when present, independently from the grade and type of rejection, carries a negative prognostic value. The worse histopathological feature was represented by the association of pAMR+ACR and vasculitis.

Frailty and aging-associated syndromes in lung transplant candidates and recipients.

Many lung transplant candidates and recipients are older and frailer compared to previous eras. Older patients are at increased risk for pre- and posttransplant mortality, but this risk is not explained by numerical age alone. This manuscript represents the product of the American Society of Transplantation (AST) conference on frailty. Experts in the field reviewed the latest published research on assessment of elderly and frail lung transplant candidates. Physical frailty, often defined as slowness, weakness, low physical activity, shrinking, and exhaustion, and frailty evaluation is an important tool for evaluation of age-associated dysfunction. Another approach is assessment by cumulative deficits, and both types of frailty are common in lung transplant candidates. Frailty is associated with death or delisting before transplant, and may be associated with posttransplant mortality. Sarcopenia, cognitive dysfunction, depression, and nutrition are other important components for patient evaluation. Aging-associated inflammation, telomere dysfunction, and adaptive immune system senescence may also contribute to frailty. Developing tools for frailty assessment and interventions holds promise for improving patient outcomes before and after lung transplantation.

Cocaine use in organ donors and long-term outcome after heart transplantation: An International Society for Heart and Lung Transplantation registry analysis

Cardiac allografts from donors with a history of cocaine use (DHCU) are often discarded owing to concerns regarding organ quality. We investigated long-term outcomes of de novo adult heart transplantation (HTx) using DHCU. Using the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry, we identified 24,430 adult recipients of primary, deceased donor, heart-alone transplants between January 1, 2000, and June 30, 2013. Transplants were categorized on the basis of DHCU. Survival rates were compared using Kaplan-Meier curves and log-rank tests. A total of 3,246 (13.3%) HTx were performed using DHCU during the study period. Of these, 1,477 (45.5%) were classified as current users. Organs from DHCU were transplanted at a later sequence number (data from a sub-group of patients transplanted in the United States) than those from the non-cocaine use group (mean sequence number 16.1 ± 55.6 vs 11.5 ± 38.2; p < 0.001), suggesting higher decline rates by centers. Kaplan-Meier estimates of survival were not different between groups (p = 0.16), with post-transplant survival rates at 1, 5, and 10 years of 88.1%, 75.8%, and 58.5%, respectively, in the non-cocaine use group and 90.0%, 76.7%, and 59.7%, respectively, in the DHCU group. On multivariate analysis, DHCU were not associated with mortality (hazard ratio [HR]: 0.94; 95% CI: 0.88-1.00; p = 0.050), cardiac allograft vasculopathy (HR: 1.02; 95% CI: 0.94-1.11; p = 0.56), or allograft rejection (HR: 0.98; 95% CI: 0.92-1.05; p = 0.61). Our findings demonstrate that adult HTx performed using DHCU is not associated with an adverse impact on long-term clinical outcomes. These findings should spur efforts to reduce discard rates of organs from DHCU.

The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: 37th adult lung transplantation report — 2020; focus on deceased donor characteristics

The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: 37th adult lung transplantation report — 2020; focus on deceased donor characteristics