Development and Validation of a Risk Score Predicting Death Without Transplant in Adult Heart Transplant Candidates

Abstract

Importance: The US heart allocation system prioritizes medically urgent candidates with a high risk of dying without transplant. The current therapy-based 6-status system is susceptible to manipulation and has limited rank ordering ability.

Objective: To develop and validate a candidate risk score that incorporates current clinical, laboratory, and hemodynamic data.

Design, setting, and participants: A registry-based observational study of adult heart transplant candidates (aged ≥18 years) from the US heart allocation system listed between January 1, 2019, and December 31, 2022, split by center into training (70%) and test (30%) datasets. Adult candidates were listed between January 1, 2019, and December 31, 2022.

Main outcomes and measures: A US candidate risk score (US-CRS) model was developed by adding a predefined set of predictors to the current French Candidate Risk Score (French-CRS) model. Sensitivity analyses were performed, which included intra-aortic balloon pumps (IABP) and percutaneous ventricular assist devices (VAD) in the definition of short-term mechanical circulatory support (MCS) for the US-CRS. Performance of the US-CRS model, French-CRS model, and 6-status model in the test dataset was evaluated by time-dependent area under the receiver operating characteristic curve (AUC) for death without transplant within 6 weeks and overall survival concordance (c-index) with integrated AUC.

Results: A total of 16 905 adult heart transplant candidates were listed (mean [SD] age, 53 [13] years; 73% male; 58% White); 796 patients (4.7%) died without a transplant. The final US-CRS contained time-varying short-term MCS (ventricular assist-extracorporeal membrane oxygenation or temporary surgical VAD), the log of bilirubin, estimated glomerular filtration rate, the log of B-type natriuretic peptide, albumin, sodium, and durable left ventricular assist device. In the test dataset, the AUC for death within 6 weeks of listing for the US-CRS model was 0.79 (95% CI, 0.75-0.83), for the French-CRS model was 0.72 (95% CI, 0.67-0.76), and 6-status model was 0.68 (95% CI, 0.62-0.73). Overall c-index for the US-CRS model was 0.76 (95% CI, 0.73-0.80), for the French-CRS model was 0.69 (95% CI, 0.65-0.73), and 6-status model was 0.67 (95% CI, 0.63-0.71). Classifying IABP and percutaneous VAD as short-term MCS reduced the effect size by 54%.

Conclusions and relevance: In this registry-based study of US heart transplant candidates, a continuous multivariable allocation score outperformed the 6-status system in rank ordering heart transplant candidates by medical urgency and may be useful for the medical urgency component of heart allocation.

Figure 1.. Study Cohort From the United Network for Organ Sharing Scientific Registry of Transplant Recipients Files

There were 16 178 unique candidates with 16 905 registrations in the final study cohort.

Figure 2.. Model Effect Estimates From the French Candidate Risk Score (French-CRS) and the US Candidate Risk Score (US-CRS)

Effect estimates on log-odds for all predictor variables in the US-CRS and current French-CRS, which represent the effect estimate of a unit change in each predictor on 6-week waiting list mortality, or medical urgency, when the other predictors are held constant. The 6-status system is not a multivariable predictor model, so it is not included. The dashed line denotes no effect, dots denote the effect size from the relevant model, and error bars denote 95% CIs. BNP indicates-type natriuretic peptide; eGFR, estimated glomerular filtration rate; LVAD, left ventricular assist device; MCS, mechanical circulatory support; NT-proBNP, N-terminal pro–B-type natriuretic peptide. ^aThe French-CRS version of short-term MCS includes extracorporeal membrane oxygenation only in the current interval. The US-CRS version includes prior or current extracorporeal membrane oxygenation, prior or current temporary surgical left ventricular assist device, and prior or current biventricular assist device without discharge. ^bMultiplied by a factor of 10, representing a 10-unit change.

Figure 3.. Performance of 6-Status, Current French Candidate Risk Score (French-CRS), and US Candidate Risk Score (US-CRS) Models for 6-Week Mortality Without a Transplant at Initial Listing

Receiver operating characteristic curves for 3 models (6-status, current French-CRS, US-CRS) evaluated in the test dataset at listing. AUC represents the area under the curve; higher AUC means the model can better differentiate between those who experience the outcome and those who do not. The dots denote the values of 1-specificity and sensitivity for each 6-status category, and the dotted line represents a model that randomly guesses, with an AUC of 0.5. The 95% CIs were calculated using 2000 stratified bootstrap replicates.

Figure 4.. US Candidate Risk Score (US-CRS) Medical Urgency Score at Listing by 6-Status

The 50-point medical urgency score based on the US-CRS, at initial listing, separated by waiting list status. The score is generated by dividing the predicted log-odds from the US-CRS on the entire 14-day interval dataset into 50 equal quantiles. Lower 6-status and higher 50-point scores represent greater medical urgency. Missing initial status (not shown): 171 (1%).