Heart Transplantation: An In-Depth Survival Analysis

Abstract

Objectives: This study aims to understand the complex factors affecting heart transplant survival and to determine the importance of possible sex-specific risk factors.

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: heart transplantation; mechanical circulatory support; mortality; outcome assessment; sex.

FIGURE 1. Sex Specific Heart Transplantation Survival

Survival curves were generated parametrically in a multiphase model for patients who underwent heart transplant from January 1, 2004, to June 30, 2018.

FIGURE 2. Heart Transplantation Risk Factors With Sex Interactions

The cohort included all patients who underwent heart transplant from January 1, 2004 to June 30, 2018. Variables significant for either men or women were included in a final model and only those with sex interaction were included in the figure. The main effect and interaction are shown for early, constant, and late risk for post-transplant survival. The dashed vertical line is showing a hazard ratio of 1 (no effect). Sex interactions are identified in red. BMI = body mass index; BSA = body surface area; CNS = central nervous system.

FIGURE 3. Interactions Among Variables of Importance Predicting Heart Transplantation Survival

Heat map of interactions among variables of importance predicting survival at 90 days, 1 year, 5 years, and 10 years were identified with least significant interactions colored pink and most significant interactions colored dark blue. BMI = body mass index; DCM = dilated cardiomyopathy; ECMO = extracorporeal membrane oxygenation; GFR = glomerular filtration rate; ICM = ischemic cardiomyopathy; Ins. = insurance; Tbili = total bilirubin; other abbreviations as in Figure 2.

FIGURE 4

Predicted Heart Transplantation Survival According to Donor Age and Bilirubin the Interaction Between Donor Age and Total Bilirubin to Predict 90-Day, 1-Year, 5-Year, and 10-Year Heart Transplantation Survival Are Shown in 3-Dimensional Plots

CENTRAL ILLUSTRATION

4% mortality per year and was mainly associated with non-modifiable factors such as age, race, and socioeconomic factors difficult to change. Finally, a late phase (solid lines) was notable for sex differences in long-term survival mainly due to diabetes mellitus, obesity, age and potential transplantation complications.