Duration of corticosteroid use and long-term outcomes after adult heart transplantation: A contemporary analysis of the International Society for Heart and Lung Transplantation Registry.

BACKGROUND: Long-term corticosteroid (CS) maintenance remains an effective option for immunosuppression following heart transplantation. We used the International Society for Heart and Lung Transplantation Registry to examine characteristics and long-term survival among heart transplant recipients with different duration of CS therapy. METHODS: Primary adult heart recipients transplanted between 2000 and 2008 who survived at least 5 years were categorized into three groups according to CS use: early withdrawal (≤2 years) (EARLY D/C), late withdrawal (between 2 and 5 years) (LATE D/C), or long-term use (>5 years) (LONG-TERM). Recipient and donor characteristics, post-transplant morbidities, and mortality were compared among groups. Kaplan-Meier was used to estimate survival up to 10 years post-transplant. RESULTS: The study cohort included 8161 recipients (2043 in EARLY D/C; 2031 in LATE D/C; and 4087 in LONG-TERM). LONG-TERM use of CS decreased over time, from 60% in 2000 to 43% in 2008, while EARLY D/C increased from 19% to 33%, respectively. Survival at 10 years after transplant was lower among the LONG-TERM group (73% vs EARLY D/C 82% vs LATE D/C 80%; P < 0.0001). CONCLUSIONS: In this large multinational cohort, the practice of long-term CS maintenance was associated with lower long-term survival compared with shorter CS use.

Predicting 1-year cardiac transplantation survival using a donor-recipient risk-assessment tool.

OBJECTIVE: Many donor and recipient factors influence 1-year survival of patients after cardiac transplantation. To date, a statistical model has not been developed to assess the interplay of these factors in predicting outcomes, so we developed a risk-assessment tool to enhance decision-making. METHODS: We analyzed 29 variables that were reported in the United Network for Organ Sharing database for 24,540 cardiac transplantations performed between January 1, 2000, and June 30, 2015. For one half of the patients (the prediction population), a multivariable Cox regression model and the bootstrap resampling method were used to devise a scoring system predicting 1-year survival. The other half (the validation population) were stratified by score into 3 risk categories: high risk, medium risk, and low risk. One-year survival was compared among the 3 groups. RESULTS: Eleven variables were statistically significant in predicting 1-year survival. One-year survival for patients with risk scores of less than or equal to 8, 9 to 15, and greater than 15 were 91.2%, 81.7%, and 64.6%, respectively (P < .001). The C index of the Cox regression model was calculated at 0.62 when using risk score as a continuous predictor. CONCLUSIONS: Donor and recipient risk factors influence patient survival after cardiac transplantation. Long-term outcomes may be optimized with a statistically based risk model to improve donor-recipient matching.

Outcomes of adolescent recipients after lung transplantation: An analysis of the International Society for Heart and Lung Transplantation Registry.

BACKGROUND: Recipient adolescent age for non-lung solid-organ transplantation is associated with higher rates of rejection, graft loss and mortality. Although there have been no studies specifically examining adolescent outcomes after lung transplantation (LTx), limited data from the International Society of Heart and Lung Transplantation (ISHLT) Registry suggest that a similar association may exist. Recently, adolescence has been defined as 10 to 24 years of age, taking into account the biologic and sociologic transitions that occur during this age interval. METHODS: The ISHLT Registry was used to examine the survival outcomes of LTx recipients 10 to 24 years of age between 2005 and 2013. Given the developmental changes that occur in adolescence, survival outcomes for the tertiles of adolescence (10 to 14, 15 to 19 and 20 to 24 years old) were also examined. RESULTS: Adolescents made up 9% (n = 2,319) of the 24,730 LTxs undertaken during the study period. Kaplan-Meier survival estimates at 3 years showed lower adolescent survival (65%) when compared with younger children (73%, p = 0.006) and adults 25 to 34 (75%, p < 0.00001) and 35 to 49 (71%, p < 0.00001) years of age, without a significant survival difference compared with those 50 to 65 years old. Critically, 15- to 19-year-old recipients had the poorest outcomes, with reduced 1-year survival (82%) compared with those 10 to 14 years old (88%, p = 0.02), and reduced 3-year survival (59%) compared with those 10 to 14 (73%, p < 0.00001) and 20 to 24 (66%, p < 0.0001) years old. CONCLUSIONS: Adolescent LTx recipients have poorer overall survival when compared with younger children and adults, with those 15 to 19 years old having the highest risk of death. This survival disparity among age groups likely reflects the difficult period of adolescence and its biologic and social transitions, which may influence both immunologic function and adherence.

Increased risk of PTLD in lung transplant recipients with cystic fibrosis.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following lung transplantation. Recipients with cystic fibrosis (CF) may have an increased risk of PTLD although the literature is limited to single center cohorts. Our primary aim is to examine PTLD in an adult lung transplant population by utilizing the International Society for Heart and Lung Transplantation Registry. METHODS: We studied 30,598 adult recipients of lung transplants performed between 1999 and 2011. The primary outcome was development of and time to PTLD. In addition to indication for transplant, other predictors examined included Epstein-Barr virus (EBV) and cytomegalovirus (CMV) serostatus, gender, and age. Outcomes were assessed with univariable and multivariable Cox proportional hazard models to obtain hazard ratios (HR). RESULTS: 17% of the cohort had a diagnosis of CF. PTLD developed in 2% of CF recipients compared to 1% for non-CF recipients (p<0.001). Compared to non-CF recipients, CF recipients had higher prevalence of EBV and CMV seronegativity and higher prevalences of high risk EBV and CMV mismatch (D+/R-). There is a significant association between CF and the development of PTLD [HR 1.66 (95% CI 1.30-2.12)]. Stratified multivariable analysis controlling for age revealed EBV negative non-CF recipients have an almost 2 fold increased risk of developing PTLD, whereas EBV negative CF recipients had an almost 6.5 fold increased risk. CONCLUSIONS: CF recipients have a higher risk for PTLD compared to non-CF recipients. Further studies are needed to account for additional risk factors and management in this population post-transplant.

The complete mitochondrial genome of the horned lizard Phrynosoma blainvillii (Squamata: Phrynosomatidae) from California, USA.

Analysis of Phrynosoma blainvillii Gray from Marina, Monterey County, California, using 150 bp paired-end Illumina sequences (Illumina, San Diego, CA) resulted in the assembly of its complete mitogenome. The mitogenome is 16,946 bp in length and contains a putative origin of light strand replication (OL), control region, 22 tRNA, 2 rRNA, and 13 protein-coding genes. Its content and organization are similar to other Squamata. Phylogenetic analysis of P. blainvillii resolves it in a clade with P. sherbrookei Nieto-Montes de Oca, Arenas-Moreno, Beltrán-Sánchez & Leaché, sister in position to Uma notata Baird. Mitochondrial marker analysis of P. blainvillii from Marina shows that it belongs to a coastal Santa Lucia Mountain Range haplogroup that is distinct from other populations of P. blainvillii in California.

Association of recipient age and causes of heart transplant mortality: Implications for personalization of post-transplant management-An analysis of the International Society for Heart and Lung Transplantation Registry.

BACKGROUND: Survival beyond 1 year after heart transplantation has remained without significant improvement for the last 2 decades. A more individualized approach to post-transplant care could result in a reduction of long-term mortality. Although recipient age has been associated with an increased incidence of certain post-transplant morbidities, its effect on cause-specific mortality has not been established. METHODS: We analyzed overall and cause-specific mortality of heart transplant recipients registered in the International Society for Heart and Lung Transplantation Registry between 1995 and 2011. Patients were grouped by recipient age: 18 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥ 70 years. Multivariable regression models were used to examine the association between recipient age and leading causes of post-transplant mortality. We also compared immunosuppression (IS) use among the different recipient age groups. RESULTS: There were 52,995 recipients (78% male; median age [5th, 95th percentile]: 54 [27, 66] years). Survival through 10 years after transplant was lower in heart transplant recipients in the 2 more advanced age groups: 49% for 60 to 69 years and 36% for ≥ 70 years (p < 0.01 for pairwise comparisons with remaining groups). The risk of death caused by acute rejection (hazard ratio [HR], 4.11; p < 0.01), cardiac allograft vasculopathy (HR, 2.85; p < 0.01), and graft failure (HR, 2.29; p < 0.01) was highest in the youngest recipients (18-29 years) compared with the reference group (50-59 years). However, the risk of death caused by infection (HR, 2.10; p < 0.01) and malignancy (HR, 2.23; p < 0.01) was highest in older recipients (≥ 70 years). Similarly, the risk of death caused by renal failure was lower in younger recipients than in the reference group (HR, 0.53; p < 0.01 for 18-49 years vs 50-59 years). The use of induction IS was similar among the different recipient age groups, and differences in maintenance IS were not clinically important. CONCLUSIONS: Causes of death in this large cohort of heart transplant recipients varied significantly with recipient age at the time of transplant, with cause-specific mortality profiles suggesting a possible effect of inadequate IS in younger recipients and over-IS in older recipients. Thus, a more personalized approach, possibly including different IS strategies according to recipient age, might result in improved post-transplant survival.

The Effect of Augmenting OPTN Data With External Death Data on Calculating Patient Survival Rates After Organ Transplantation.

BACKGROUND: Although the Organ Procurement and Transplantation Network (OPTN) database contains a rich set of data on United States transplant recipients, follow-up data may be incomplete. It was of interest to determine if augmenting OPTN data with external death data altered patient survival estimates. METHODS: Solitary kidney, liver, heart, and lung transplants performed between January 1, 2011, and January 31, 2013, were queried from the OPTN database. Unadjusted Kaplan-Meier 3-year patient survival rates were computed using 4 nonmutually exclusive augmented datasets: OPTN only, OPTN + verified external deaths, OPTN + verified + unverified external deaths (OPTN + all), and an additional source extending recipient survival time if no death was found in OPTN + all (OPTN + all [Assumed Alive]). Pairwise comparisons were made using unadjusted Cox Proportional Hazards analyses applying Bonferroni adjustments. RESULTS: Although differences in patient survival rates across data sources were small (≤1 percentage point), OPTN only data often yielded slightly higher patient survival rates than sources including external death data. No significant differences were found, including comparing OPTN + verified (hazard ratio [HR], 1.05; 95% confidence interval [95% CI], 1.00-1.10); P = 0.0356), OPTN + all (HR, 1.06; 95% CI, 1.01-1.11; P = 0.0243), and OPTN + all (Assumed Alive) (HR, 1.00; 95% CI, 0.96-1.05; P = 0.8587) versus OPTN only, or OPTN + verified (HR, 1.05; 95% CI, 1.00-1.10; P = 0.0511), and OPTN + all (HR, 1.05; 95% CI, 1.00-1.10; P = 0.0353) versus OPTN + all (Assumed Alive). CONCLUSIONS: Patient survival rates varied minimally with augmented data sources, although using external death data without extending the survival time of recipients not identified in these sources results in a biased estimate. It remains important for transplant centers to maintain contact with transplant recipients and obtain necessary follow-up information, because this information can improve the transplantation process for future recipients.

Amiodarone use in patients listed for heart transplant is associated with increased 1-year post-transplant mortality.

BACKGROUND: Pre-transplant amiodarone use has been postulated as a risk factor for morbidity and mortality after orthotopic heart transplantation (OHT). We assessed pre-OHT amiodarone use and tested the hypothesis that it is associated with impaired post-OHT outcomes. METHODS: We performed a retrospective cohort analysis of adult OHT recipients from the registry of the International Society for Heart and Lung Transplantation (ISHLT). All patients had been transplanted between 2005 and 2013 and were stratified by pre-OHT amiodarone use. We derived propensity scores using logistic regression with amiodarone use as the dependent variable, and assessed the associations between amiodarone use and outcomes with Kaplan-Meier analysis after matching patients 1:1 based on propensity score, and with Cox regression with adjustment for propensity score. RESULTS: Of the 14,944 OHT patients in the study cohort, 32% (N = 4,752) received pre-OHT amiodarone. Amiodarone use was higher in recent years (29% in 2005 to 2007, 32% in 2008 to 2010, 35% in 2011 to 2013). Amiodarone-treated patients were older and more frequently had a history of sudden cardiac death (27% vs 13%) and pre-OHT mechanical circulatory support. Key donor characteristics and allograft ischemia times were similar between groups. In propensity-matched analyses, amiodarone-treated patients had higher rates of cardiac reoperation (15% vs 13%) and permanent pacemaker (5% vs 3%) after OHT and before discharge. Amiodarone-treated patients also had higher 1-year mortality (hazard ratio 1.15, 95% confidence interval 1.02 to 1.30), but the risks of early graft failure, retransplantation and rehospitalization were similar between groups. CONCLUSIONS: Amiodarone use before OHT was independently associated with increased 1-year mortality. The need for amiodarone therapy should be carefully and continuously assessed in patients awaiting OHT.

Trends in the use of mechanical circulatory support as a bridge to heart transplantation across different age groups.

INTRODUCTION: Numerous cohort analyses suggest rapidly increasing use of mechanical circulatory support (MCS) as a bridge to heart transplantation (HTx), but the role of age in selection for MCS remains unknown. METHODS: We assessed adult HTx in the International Society for Heart And Lung Transplantation Registry between 2005 and 2013 and we determined MCS use by recipient age group and transplant year. Multivariable logistic regression models were constructed to identify variables associated with continuous flow (CF) left ventricular assist device (LVAD) use within each age group. RESULTS: Among 16,480 HTx recipients the percentage of overall MCS use increased from 23% to 38%, 21% to 41%, and 17% to 42% in age groups 18-39 years, 40-59 years and over 60 years, respectively. This effect was mainly due to an increase in CF LVAD use and primarily in HTx recipients aged over 60. In multivariable analyses, male gender and blood group O were significantly associated with CF LVAD use in all age groups. CONCLUSIONS: Bridge to transplant MCS use increased dramatically between 2005 and 2013 primarily due to increased use of CF LVAD and primarily in higher ages. Pre-HTx CF LVAD use was more frequent in men and blood group O.

Proceedings of the AST heart allocation meeting at the American Transplant Congress, Philadelphia, Pennsylvania, May 4, 2015.

Ensuring fair and equitable allocation of donor hearts in the US is the charge of the Organ Procurement and Transplantation Network (OPTN). However, the recent increase of candidates waiting without a corresponding increase in available donors, higher waitlist mortality rates in higher status patients, the presence of disadvantaged subgroups, and the changing management of heart failure patients with increased VAD usage, has necessitated review of allocation policy. Therefore, the Heart Subcommittee of the OPTN/UNOS Thoracic Committee is exploring a further-tiered allocation system, devising a "straw man" model as a starting point for modeling analyses and public discussion. On May 4, 2015, an American Society of Transplantation (AST)-endorsed forum to discuss these potential proposed changes took place. Attendees included 41 people, mostly highly experienced transplant cardiologists and cardiothoracic surgeons, representing 19 heart transplant centers across the US, UNOS, and the Scientific Registry of Transplant Recipients (SRTR). There was unanimous agreement that the potential proposed policy will require careful wording to avoid ambiguity and "gaming" of the system, and strong support for abolishment of local organ sharing in favor of geographic sharing. However, contention existed concerning the appropriate prioritization levels of ECMO, temporary VAD/TAH patients as well as the 30-day LVAD listing.

Effect of the lung allocation score on lung transplantation in the United States.

BACKGROUND: On May 4, 2005, the system for allocation of deceased donor lungs for transplant in the United States changed from allocation based on waiting time to allocation based on the lung allocation score (LAS). We sought to determine the effect of the LAS on lung transplantation in the United States. METHODS: Organ Procurement and Transplantation Network data on listed and transplanted patients were analyzed for 5 calendar years before implementation of the LAS (2000-2004), and compared with data from 6 calendar years after implementation (2006-2011). Counts were compared between eras using the Wilcoxon rank sum test. The rates of transplant increase within each era were compared using an F-test. Survival rates computed using the Kaplan-Meier method were compared using the log-rank test. RESULTS: After introduction of the LAS, waitlist deaths decreased significantly, from 500/year to 300/year; the number of lung transplants increased, with double the annual increase in rate of lung transplants, despite no increase in donors; the distribution of recipient diagnoses changed dramatically, with significantly more patients with fibrotic lung disease receiving transplants; age of recipients increased significantly; and 1-year survival had a small but significant increase. CONCLUSIONS: Allocating lungs for transplant based on urgency and benefit instead of waiting time was associated with fewer waitlist deaths, more transplants performed, and a change in distribution of recipient diagnoses to patients more likely to die on the waiting list.