Variables of importance in the Scientific Registry of Transplant Recipients database predictive of heart transplant waitlist mortality.

The prelisting variables essential for creating an accurate heart transplant allocation score based on survival are unknown. To identify these we studied mortality of adults on the active heart transplant waiting list in the Scientific Registry of Transplant Recipients database from January 1, 2004 to August 31, 2015. There were 33 069 candidates awaiting heart transplantation: 7681 UNOS Status 1A, 13 027 Status 1B, and 12 361 Status 2. During a median waitlist follow-up of 4.3 months, 5514 candidates died. Variables of importance for waitlist mortality were identified by machine learning using Random Survival Forests. Strong correlates predicting survival were estimated glomerular filtration rate (eGFR), serum albumin, extracorporeal membrane oxygenation, ventricular assist device, mechanical ventilation, peak oxygen capacity, hemodynamics, inotrope support, and type of heart disease with less predictive variables including antiarrhythmic agents, history of stroke, vascular disease, prior malignancy, and prior tobacco use. Complex interactions were identified such as an additive risk in mortality based on renal function and serum albumin, and sex-differences in mortality when eGFR >40 mL/min/1.73 m. Most predictive variables for waitlist mortality are in the current tiered allocation system except for eGFR and serum albumin which have an additive risk and complex interactions.

Hsich EM ，Thuita L ，McNamara DM ，Rogers JG ，Valapour M ，Goldberg LR ，Yancy CW ，Blackstone EH ，Ishwaran H ，Transplantation of HEarts to MaxImize Survival (THEMIS) Investigators ... -  《-》

Sex Differences in Mortality Based on United Network for Organ Sharing Status While Awaiting Heart Transplantation.

There are sex differences in mortality while awaiting heart transplantation, and the reason remains unclear. We included all adults in the Scientific Registry of Transplant Recipients placed on the heart transplant active waitlist from 2004 to 2015. The primary end point was all-cause mortality. Multivariable Cox proportional hazards models were performed to evaluate survival by United Network for Organ Sharing (UNOS) status at the time of listing. Random survival forest was used to identify sex interactions for the competing risk of death and transplantation. There were 33 069 patients (25% women) awaiting heart transplantation. This cohort included 7681 UNOS status 1A (26% women), 13 027 UNOS status 1B (25% women), and 12 361 UNOS status 2 (26% women). During a median follow-up of 4.3 months, 1351 women and 4052 men died. After adjusting for >20 risk factors, female sex was associated with a significant risk of death among UNOS status 1A (adjusted hazard ratio, 1.14; 95% confidence interval, 1.01-1.29) and UNOS status 1B (adjusted hazard ratio, 1.17; 95% confidence interval, 1.05-1.30). In contrast, female sex was significantly protective for time to death among UNOS status 2 (adjusted hazard ratio, 0.85; 95% confidence interval, 0.76-0.95). Sex differences in probability of transplantation were present for every UNOS status, and >20 sex interactions were identified for mortality and transplantation. When stratified by initial UNOS status, women had a higher mortality than men as UNOS status 1 and a lower mortality as UNOS status 2. With >20 sex interactions for mortality and transplantation, further evaluation is warranted to form a more equitable allocation system.

Hsich EM ，Blackstone EH ，Thuita L ，McNamara DM ，Rogers JG ，Ishwaran H ，Schold JD ... -  《-》

Heart Transplantation: An In-Depth Survival Analysis.

This study aims to understand the complex factors affecting heart transplant survival and to determine the importance of possible sex-specific risk factors. Heart transplant allocation is primarily focused on preventing waitlist mortality. To prevent organ wastage, future allocation must balance risk of waitlist mortality with post-transplantation mortality. However, more information regarding risk factors after heart transplantation is needed. We included all adults (30,606) in the Scientific Registry of Transplant Recipients database who underwent isolated heart transplantation from January 1, 2004, to July 1, 2018. Mortality (8,278 deaths) was verified with the complete Social Security Death Index with a median follow-up of 3.9 years. Temporal decomposition was used to identify phases of survival and phase-specific risk factors. The random survival forests method was used to determine importance of mortality risk factors and their interactions. We identified 3 phases of mortality risk: early post-transplantation, constant, and late. Sex was not a significant risk factor. There were several interactions predicting early mortality such as pretransplantation mechanical ventilation with presence of end-organ function (bilirubin, renal function) and interactions predicting later mortality such as diabetes and older age (donor and recipient). More complex interactions predicting early-, mid-, and late-mortality existed and were identified with machine learning (i.e., elevated bilirubin, mechanical ventilation, and dialysis). Post-heart transplant mortality risk is complex and dynamic, changing with time and events. Sex is not an important mortality risk factor. To prevent organ wastage, end-organ dysfunction should be resolved before transplantation as much as possible.

Hsich EM ，Blackstone EH ，Thuita LW ，McNamara DM ，Rogers JG ，Yancy CW ，Goldberg LR ，Valapour M ，Xu G ，Ishwaran H ... -  《-》

Regional differences in recipient waitlist time and pre- and post-transplant mortality after the 2006 United Network for Organ Sharing policy changes in the donor heart allocation algorithm.

This study examined the impact of the United Network for Organ Sharing (UNOS) policy changes for regional differences in waitlist time and mortality before and after heart transplantation. The 2006 UNOS thoracic organ allocation policy change was implemented to allow for greater regional sharing of organs for heart transplantation. We analyzed 36,789 patients who were listed for heart transplantation from January 1999 through April 2012. These patients were separated into 2 eras centered on the July 12, 2006 UNOS policy change. Pre- and post-transplantation characteristics were compared by UNOS regions. Waitlist mortality decreased nationally (up to 180 days: 13.3% vs. 7.9% after the UNOS policy change, p < 0.001) and within each region. Similarly, 2-year post-transplant mortality decreased nationally (2-year mortality: 17.3% vs. 14.6%; p < 0.001) as well as regionally. Waitlist time for UNOS status 1A and 1B candidates increased nationally 17.8 days on average (p < 0.001) with variability between the regions. The greatest increases were in Region 9 (59.2-day increase, p < 0.001) and Region 4 (41.2-day increase, p < 0.001). Although the use of mechanical circulatory support increased nearly 2.3-fold nationally in Era 2, significant differences were present on a regional basis. In Regions 6, 7, and 10, nearly 40% of those transplanted required left ventricular assist device bridging, whereas only 19.6%, 22.3%, and 15.5% required a left ventricular assist device in regions 3, 4, and 5, respectively. The 2006 UNOS policy change has resulted in significant regional heterogeneity with respect to waitlist time and reliance on mechanical circulatory support as a bridge to transplantation, although overall both waitlist mortality and post-transplant survival are improved.

Schulze PC ，Kitada S ，Clerkin K ，Jin Z ，Mancini DM ... -  《-》

Trends in the Use of Inotropes to List Adult Heart Transplant Candidates at Status 1A.

The number of adult heart transplant candidates waiting at the most urgent status 1A has increased over time despite the expansion of geographic sharing of hearts in 2006. We aimed to determine whether candidates listed with inotropes contribute to the excess status 1A candidates. The initial registrations of all adult heart-only candidates listed from 2000 to 2015 were analyzed using the Scientific Registry of Transplant Recipients data set. Trends in listing status, justifications, and candidate factors were measured. Adjusted trends in listing status pre- and post-geographic sharing were estimated using multilevel logistic regression. Competing risks models provided trends in transplant-free waitlist survival. There were 46 853 adult heart-alone listings during 2000 to 2015. Pre-sharing, status 1A listing was unchanged over time (adjusted odds ratio, 0.98; 95% confidence interval, 0.78-1.23). Post-sharing, the adjusted odds of status 1A listing increased 117% over 9 years (adjusted odds ratio 2.17, 95% confidence interval, 1.82-2.58). The number of candidates listed as status 1A with inotropes increased by 193 a year, whereas the dobutamine, dopamine, and milrinone doses used decreased 49%, 55%, and 29% (P<0.001). The risk of waitlist death or deterioration of status 1A inotrope candidates relative to status 2 candidates decreased 62% for 2006 to 2010 and 70% for 2011 to 2015 compared with that for 2003 to 2006. After the wider geographic sharing of hearts in 2006, transplant programs used multiple inotropes to list candidates at status 1A more frequently with progressively lower doses. Concurrently, the status 1A inotrope candidate waitlist outcomes improved substantially. These trends suggest that overtreatment with multiple inotropes contributes to the current critical excess of status 1A candidates.

Parker WF ，Garrity ER Jr ，Fedson S ，Churpek MM ... -  《-》