Survival in Patients Listed for Heart Transplantation
During the study period, 10,754 patients age ≥18 years were listed for HT in the United States. Of these, 273 patients were listed for multiple-organ transplantation and 322 for heart retransplantation. The remaining 10,159 patients formed the study cohort. Of these, 4,773 (47%) had dilated cardiomyopathy and 3,704 (37%) had ischemic cardiomyopathy (see Table 1 for baseline characteristics at listing). The median age of the study cohort was 55 years, 20% were listed at the highest urgency listing status (1A), and 18% were receiving mechanical support (including 2.4% with biventricular assist devices, 14% with durable left ventricular assist devices [LVADs], and 1.1% on temporary mechanical support).
Figure 1 illustrates competing outcomes during the first year after listing in the study cohort. Of 10,159 patients listed for HT, 5,970 (59%) underwent HT, 1,054 (10.4%) died without undergoing HT (695 deaths while on the waiting list, 359 deaths after removal from the list), and 2,759 (27%) were still waiting for HT at 1 year. Of 1,054 deaths without HT, 328 (31%) deaths occurred within 30 days, 596 (57%) within 90 days, and 810 (77%) within 180 days of listing. The median waiting list time to HT was 78 days for the entire cohort, 26 days in patients listed as status 1A, 69 days in patients listed as status 1B, and 155 days in patients listed as status 2. Post-transplantation outcomes were analyzed in 5,720 heart transplant recipients with 1-year follow-up (see Online Table 1 for baseline characteristics at transplantation). Of these, 576 patients (10.1%) died within 1 year of transplantation.
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Figure 1.
Competing Outcomes After Listing. Competing outcomes during the first year after listing in patients listed for heart transplantation in the United States.
A multivariate risk model for 90-day mortality without HT consisted of 7 risk factors (older age, diagnosis of restrictive cardiomyopathy, listing status 1A or 1B, ventilator support, intra-aortic balloon pump, mechanical support, and renal dysfunction) and 1 protective factor (presence of an implantable cardiac defibrillator) ( Table 2 ). The overall model was highly significant (likelihood ratio chi-square = 427.2, Akaike information criterion = 4,538.7). The model's ability to discriminate patients who died within 90 days from those who did not (C-statistic = 0.73) and to calibrate the risk for death (Hosmer-Lemeshow p = 0.23; see Online Figure 1 for predicted vs. observed 90-day mortality among the 10 risk groups) were good. On internal validation by bootstrapping, the area under the receiver-operating characteristic curve in repeated samples ranged from 0.702 to 0.761 (mean 0.732; 95% confidence interval: 0.731 to 0.734). On the basis of this model, the probability of death within 90 days of listing without HT was calculated as: p = (X/X + 1), where X = exp(intercept + coefficient for each variable in Table 2 as it applies to the patient).
Using the model, the risk for 90-day mortality without HT increased from 1.6% in the 1st risk group to 19% in the 10th risk group. Table 3 outlines the distribution of model risk factors among the 10 risk groups. Patients in the lowest 2 risk groups were younger, were more likely to have dilated or ischemic cardiomyopathy, were not supported on ventilators or balloon pumps, and had normal renal function at listing. They were either not receiving any mechanical support or were supported with continuous-flow LVADs. Patients in the 3rd and 4th risk groups tended to have only 1 risk factor, such as older age or moderate renal dysfunction. Patients in the 2 highest risk groups included those with multiple risk factors, such as certain types of mechanical support (temporary support, pulsatile LVAD, or biventricular assist device), ventilator support, intra-aortic balloon pump, and moderate or severe renal dysfunction ( Table 3 ).
Risk prediction models for post-transplantation 90-day mortality and post-transplantation 1-year mortality are shown in Table 4 . Risk factors for post-transplantation 90-day mortality included older age, a diagnosis of congenital heart disease, restrictive or ischemic cardiomyopathy, ventilator support, mechanical support, and renal dysfunction at transplantation. The overall model was highly significant (likelihood ratio chi-square = 141.3, Akaike information criterion = 2,530.9). The model's ability to discriminate survivors from nonsurvivors (C-statistic = 0.67) and the calibration between predicted and observed mortality (Hosmer-Lemeshow p value = 0.48; see Online Figure 2 for predicted vs. observed 90-day mortality among the 10 risk groups) were good. Risk factors for post-transplantation 1-year mortality were similar to those for 90-day mortality ( Table 3 ). Although the model was highly significant (likelihood ratio chi-square = 140.0, Akaike information criterion = 3,738.5), its performance was less robust compared with the 90-day model (C-statistic = 0.63, Hosmer-Lemeshow p value = 0.43) (Online Figure 3).
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Figure 2.
Predicted Risks for 90-Day Mortality and Survival Benefit Among the 10 Risk Groups. (A) Predicted risks for 90-day waiting list and 90-day post-transplantation mortality at listing for heart transplantation (HT) in patients with increasing risk for waiting list mortality. (B) Survival benefit associated with transplantation in these groups.
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Figure 3.
1-Year Mortality Without and With HT and Survival Benefit Among the 10 Risk Groups. (A) Observed 1-year waiting list mortality and predicted 1-year post-transplantation mortality at listing for heart transplantation (HT) in patient-groups with increasing risk for waiting list mortality. (B) Survival benefit associated with transplantation in these groups.
Figure 2A illustrates the risks for 90-day mortality without HT and 90-day mortality after transplantation estimated at the time of listing among the 10 risk groups. The survival benefit from HT at 90 days (percent reduction in risk for 90-day mortality) (Figure 2B) was negative or neutral in the lowest 6 risk groups (risk for post-transplantation mortality higher or similar to risk for waiting list mortality). Survival benefit increased from 1.2% in the 7th risk group to 8.5% in the 10th risk group (risk for waiting list mortality 19.5%, risk for post-transplantation mortality 11%). Overall, the increase in survival benefit across the 10 risk groups was significant (p <0.001 for trend).
Observed 1-year mortality without HT was 5.2% in the lowest risk group and increased progressively to 26.7% in the 10th risk group (Figure 3A). The risk for 1-year post-transplantation mortality at the time of listing was higher or similar to the observed 1-year mortality (in percent) without HT in the first 6 risk groups (Figure 3A). Thus, there was no 1-year survival benefit from HT in the first 6 risk groups. Survival benefit increased progressively between the 7th and 10th risk groups (Figure 3B). For the entire cohort, there was a significant association of survival benefit from HT with increasing risk for death without HT (p < 0.001 for trend).
The observed 90-day mortality without HT was 3.2%, 6%, and 11% in patients listed as UNOS listing statuses 2, 1B, and 1A, respectively. The observed 1-year mortality without HT was 8.1%, 10.1%, and 14% in these groups, whereas the predicted 1-year post-HT mortality on undergoing HT close to listing was 9.2%, 9.2%, and 10.8%, respectively. Thus, there was no 1-year survival benefit from HT in patients listed as status 2 (−1.1%), whereas status 1A patients derived higher 1-year survival benefit (3.2%) than those listed as status 1B (0.9%).
Results
Study Population
During the study period, 10,754 patients age ≥18 years were listed for HT in the United States. Of these, 273 patients were listed for multiple-organ transplantation and 322 for heart retransplantation. The remaining 10,159 patients formed the study cohort. Of these, 4,773 (47%) had dilated cardiomyopathy and 3,704 (37%) had ischemic cardiomyopathy (see Table 1 for baseline characteristics at listing). The median age of the study cohort was 55 years, 20% were listed at the highest urgency listing status (1A), and 18% were receiving mechanical support (including 2.4% with biventricular assist devices, 14% with durable left ventricular assist devices [LVADs], and 1.1% on temporary mechanical support).
Figure 1 illustrates competing outcomes during the first year after listing in the study cohort. Of 10,159 patients listed for HT, 5,970 (59%) underwent HT, 1,054 (10.4%) died without undergoing HT (695 deaths while on the waiting list, 359 deaths after removal from the list), and 2,759 (27%) were still waiting for HT at 1 year. Of 1,054 deaths without HT, 328 (31%) deaths occurred within 30 days, 596 (57%) within 90 days, and 810 (77%) within 180 days of listing. The median waiting list time to HT was 78 days for the entire cohort, 26 days in patients listed as status 1A, 69 days in patients listed as status 1B, and 155 days in patients listed as status 2. Post-transplantation outcomes were analyzed in 5,720 heart transplant recipients with 1-year follow-up (see Online Table 1 for baseline characteristics at transplantation). Of these, 576 patients (10.1%) died within 1 year of transplantation.
(Enlarge Image)
Figure 1.
Competing Outcomes After Listing. Competing outcomes during the first year after listing in patients listed for heart transplantation in the United States.
Model for 90-day Waiting List Mortality
A multivariate risk model for 90-day mortality without HT consisted of 7 risk factors (older age, diagnosis of restrictive cardiomyopathy, listing status 1A or 1B, ventilator support, intra-aortic balloon pump, mechanical support, and renal dysfunction) and 1 protective factor (presence of an implantable cardiac defibrillator) ( Table 2 ). The overall model was highly significant (likelihood ratio chi-square = 427.2, Akaike information criterion = 4,538.7). The model's ability to discriminate patients who died within 90 days from those who did not (C-statistic = 0.73) and to calibrate the risk for death (Hosmer-Lemeshow p = 0.23; see Online Figure 1 for predicted vs. observed 90-day mortality among the 10 risk groups) were good. On internal validation by bootstrapping, the area under the receiver-operating characteristic curve in repeated samples ranged from 0.702 to 0.761 (mean 0.732; 95% confidence interval: 0.731 to 0.734). On the basis of this model, the probability of death within 90 days of listing without HT was calculated as: p = (X/X + 1), where X = exp(intercept + coefficient for each variable in Table 2 as it applies to the patient).
Using the model, the risk for 90-day mortality without HT increased from 1.6% in the 1st risk group to 19% in the 10th risk group. Table 3 outlines the distribution of model risk factors among the 10 risk groups. Patients in the lowest 2 risk groups were younger, were more likely to have dilated or ischemic cardiomyopathy, were not supported on ventilators or balloon pumps, and had normal renal function at listing. They were either not receiving any mechanical support or were supported with continuous-flow LVADs. Patients in the 3rd and 4th risk groups tended to have only 1 risk factor, such as older age or moderate renal dysfunction. Patients in the 2 highest risk groups included those with multiple risk factors, such as certain types of mechanical support (temporary support, pulsatile LVAD, or biventricular assist device), ventilator support, intra-aortic balloon pump, and moderate or severe renal dysfunction ( Table 3 ).
Models for Post-transplantation Mortality
Risk prediction models for post-transplantation 90-day mortality and post-transplantation 1-year mortality are shown in Table 4 . Risk factors for post-transplantation 90-day mortality included older age, a diagnosis of congenital heart disease, restrictive or ischemic cardiomyopathy, ventilator support, mechanical support, and renal dysfunction at transplantation. The overall model was highly significant (likelihood ratio chi-square = 141.3, Akaike information criterion = 2,530.9). The model's ability to discriminate survivors from nonsurvivors (C-statistic = 0.67) and the calibration between predicted and observed mortality (Hosmer-Lemeshow p value = 0.48; see Online Figure 2 for predicted vs. observed 90-day mortality among the 10 risk groups) were good. Risk factors for post-transplantation 1-year mortality were similar to those for 90-day mortality ( Table 3 ). Although the model was highly significant (likelihood ratio chi-square = 140.0, Akaike information criterion = 3,738.5), its performance was less robust compared with the 90-day model (C-statistic = 0.63, Hosmer-Lemeshow p value = 0.43) (Online Figure 3).
(Enlarge Image)
Figure 2.
Predicted Risks for 90-Day Mortality and Survival Benefit Among the 10 Risk Groups. (A) Predicted risks for 90-day waiting list and 90-day post-transplantation mortality at listing for heart transplantation (HT) in patients with increasing risk for waiting list mortality. (B) Survival benefit associated with transplantation in these groups.
(Enlarge Image)
Figure 3.
1-Year Mortality Without and With HT and Survival Benefit Among the 10 Risk Groups. (A) Observed 1-year waiting list mortality and predicted 1-year post-transplantation mortality at listing for heart transplantation (HT) in patient-groups with increasing risk for waiting list mortality. (B) Survival benefit associated with transplantation in these groups.
Survival Benefit From HT at Listing
Figure 2A illustrates the risks for 90-day mortality without HT and 90-day mortality after transplantation estimated at the time of listing among the 10 risk groups. The survival benefit from HT at 90 days (percent reduction in risk for 90-day mortality) (Figure 2B) was negative or neutral in the lowest 6 risk groups (risk for post-transplantation mortality higher or similar to risk for waiting list mortality). Survival benefit increased from 1.2% in the 7th risk group to 8.5% in the 10th risk group (risk for waiting list mortality 19.5%, risk for post-transplantation mortality 11%). Overall, the increase in survival benefit across the 10 risk groups was significant (p <0.001 for trend).
Observed 1-year mortality without HT was 5.2% in the lowest risk group and increased progressively to 26.7% in the 10th risk group (Figure 3A). The risk for 1-year post-transplantation mortality at the time of listing was higher or similar to the observed 1-year mortality (in percent) without HT in the first 6 risk groups (Figure 3A). Thus, there was no 1-year survival benefit from HT in the first 6 risk groups. Survival benefit increased progressively between the 7th and 10th risk groups (Figure 3B). For the entire cohort, there was a significant association of survival benefit from HT with increasing risk for death without HT (p < 0.001 for trend).
Survival Benefit by Listing Status
The observed 90-day mortality without HT was 3.2%, 6%, and 11% in patients listed as UNOS listing statuses 2, 1B, and 1A, respectively. The observed 1-year mortality without HT was 8.1%, 10.1%, and 14% in these groups, whereas the predicted 1-year post-HT mortality on undergoing HT close to listing was 9.2%, 9.2%, and 10.8%, respectively. Thus, there was no 1-year survival benefit from HT in patients listed as status 2 (−1.1%), whereas status 1A patients derived higher 1-year survival benefit (3.2%) than those listed as status 1B (0.9%).
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