Simultaneous Thoracic and Abdominal Transplantation
Simultaneous Thoracic and Abdominal Transplantation
Annual numbers of STA wait-list candidates and transplants have increased steadily since 1987, particularly during the last 5 years ( Table 1 ). SHK was the largest overall cohort, with a total of 1420 listed patients, and 684 received an SHK transplant. Between 2006 and 2010, 606 patients were listed for both heart and kidney and 272 received both organs, representing a 52% increase in demand and a 37% increase in transplants over the prior 5-year interval (2001–2005). More than 50 SHK transplants have been performed annually since 2007. SHLi was the second largest STA group with 212 patients listed and 92 transplants performed since 1987. Comparing the last two 5-year intervals (2006–2010 vs. 2001–2005), patients listed for both heart and liver increased from 46 to 118 (+56%) and SHLi transplants from 21 to 51 (+42%). The first SLuLi and SLuK transplants occurred in 1994 and 1995, respectively. These combinations remain relatively uncommon; however, trends were similar to those for SHK and SHLi. A total of 122 SLuLi patients have been wait-listed and 42 transplanted since 1987, with 53 wait-listed and 23 transplanted since 2006. Forty-one SLuK patients have been wait-listed since 1987 (18 since 2006) and 16 of those received transplants (10 since 2006).
Etiology of Organ Failure
Etiologies for organ dysfunction among patients wait-listed for STA are listed in Table 2 . For SHK, heart failure was most commonly due to nonischemic cardiomyopathy (N = 576), ischemic cardiomyopathy (N = 519) and retransplantation/graft failure (N = 192), whereas kidney dysfunction was due to diabetes (N = 196), tubular/interstitial disease (N = 165) and glomerulonephritis (N = 159). For those awaiting SHLi, heart failure was attributable to nonischemic (N = 129) and ischemic cardiomyopathy (N = 25), and liver dysfunction to noncholestatic (N = 76) and metabolic (N = 19) diseases. The SLuLi cohort consisted of a majority (N = 70) of patients with cystic fibrosis. The primary causes of pulmonary failure in SLuK patients included restrictive (N = 20) and pulmonary vascular diseases (N = 10).
STA Characteristics
The populations awaiting STA had distinct demographic and clinical characteristics compared to patients wait-listed for single-organ transplantation ( Table 3 ). SHLi, SLuLi and SLuK candidates were younger on average than their respective thoracic and abdominal control groups, whereas SHK candidates were older compared to heart-alone (p < 0.001). Listing status for SHK and SLuK candidates was more advanced compared to heart (p < 0.001) or lung alone (p = 0.02), but SHLi candidates were listed at lower heart status (p < 0.001). LAS scores for SLuLi were comparable to those for lung alone (p = 0.22), and MELD scores for both SLuLi and SHLi were lower compared to liver alone (p = 0.06). Compared to kidney alone, wait-list times for SHK and SLuK were significantly reduced (p < 0.001). SHK and SHLi had significantly prolonged wait-list times compared to heart-alone (p < 0.001). In all STA wait-list groups, a lower percentage of patients ultimately received transplants (either single transplant or STA) when compared to thoracic-only candidates (p < 0.001). SLuLi and SLuK candidate groups both also had lower percentages of transplantation compared to abdominal-only candidates (p < 0.001). Of note, a group of 146 patients who were initially waitlisted for SHK eventually received a heart-alone transplant. Posttransplant survival at 1 and 5 years was significantly lower in this population (56.7%, 44.1%) compared to those waitlisted for SHK who received a combined transplant (85.3%, 74.0%) (p < 0.001).
Wait-list Mortality: STA versus Single Organ
Wait-list survival at 1 and 3 years was obtained for SHK (67.4%, 40.8%), SHLi (65.7%, 43.6%), SLuLi (65.7%, 41.0%), and found to be significantly decreased compared to respective thoracic and abdominal controls (p < 0.001). Waitlist survival for SLuK at 1 and 3 years (65.0%, 51.6%) was not statistically different from lung (p = 0.34) or kidney controls (0.41) ( Table 4 ).
STA Donor and Recipient Characteristics
We next reviewed the clinical and demographic data for those candidates who proceeded to STA ( Table 5 ). As noted with the wait-list cohorts, SHK recipients were older than controls (p < 0.01), whereas SLuLi recipients were considerably younger (p < 0.001). STA recipients differed considerably from single-organ recipients with respect to level of acuity at time of transplant. Approximately half of SHK and SHLi were transplanted as hospitalized inpatients, and the majority of these occurred during an ICU admission. This was fewer than those for heart alone, but greater than kidney or liver alone (p < 0.001). SLuLi recipients were also more often hospitalized, and in the ICU, compared to lung alone at the time of transplant (p < 0.001). We also compared measures of abdominal organ dysfuction for STA and control recipients. A similar proportion of SHK and kidney alone recipients were on dialysis preoperatively. INR and total bilirubin were both lower in SHLi and SLuLi in comparison to liver alone as was transplant MELD (p < 0.001). With regard to thoracic organ failure, heart status at time of transplant was slightly more advanced compared to heart alone for SHK and less advanced for SHLi (p < 0.001). There were no significant differences between lung alone and SLuLi or SLuK in terms of LAS or FVC.
Patient Survival for STA and Single-Transplant Control
Kaplan–Meier estimates for 1 and 5 years patient survival were determined for SHK (85.3%, 74.0%), SHLi (85.9%, 74.3%), SLuLi (75.5%, 59.0%) and SLuK (66.7%, 55.6%) ( Table 6 ). In all groups, STA patient survival was not significantly different from thoracic single-transplant cohorts. STA patient survival was however lower than abdominal single-transplant groups for SHK (p < 0.001), SLuLi (p = 0.01) and SLuK (p < 0.001). SHLi had the greatest 1 and 5 years survival of the STA cohorts, and was unique in that survival was equivalent to the abdominal control group (p = 0.81). It was also notable that STA combinations with kidney had lower survival compared to STA combinations with liver (SHK vs. SHLi; SLuK vs. SLuLi). This may be due to baseline differences between the kidney and liver STA cohorts in terms of age (liver cohorts are younger), number of associated comorbidities or severity of organ dysfunction at time of transplant. It is also possible that this is related to differences in manifestations of systemic illness for kidney and liver failure.
Survival Benefit of STA
A multivariable Cox regression model was created to explore the potential survival benefit of a STA transplant, compared to remaining on the wait-list. Among SHK, SHLi and SLuLi a substantial increase for STA was achieved (SHK, HR 0.31, 95% CI 0.26–0.37, p < 0.001; SHLi, HR 0.34, 95% CI 0.21–0.56, p < 0.001; SLuLi HR 0.53, 95% CI 0.29–0.96, p = 0.04). (Figure 1). SLuK recipients did not incur any transplant survival benefit over wait-list patients (HR 1.05, 95% CI 0.45–2.47, p = 0.91).
(Enlarge Image)
Figure 1.
Survival benefit of transplantation for STA candidates. Survival for wait-list patients is compared to posttransplant survival for each of the STA subtypes. Hazard ratios (HR) and 95% confidence intervals (CI) were derived from multivariate Cox regression models comparing the two curves.
Results
STA Trends in Demand and Practice, 1987–2010
Annual numbers of STA wait-list candidates and transplants have increased steadily since 1987, particularly during the last 5 years ( Table 1 ). SHK was the largest overall cohort, with a total of 1420 listed patients, and 684 received an SHK transplant. Between 2006 and 2010, 606 patients were listed for both heart and kidney and 272 received both organs, representing a 52% increase in demand and a 37% increase in transplants over the prior 5-year interval (2001–2005). More than 50 SHK transplants have been performed annually since 2007. SHLi was the second largest STA group with 212 patients listed and 92 transplants performed since 1987. Comparing the last two 5-year intervals (2006–2010 vs. 2001–2005), patients listed for both heart and liver increased from 46 to 118 (+56%) and SHLi transplants from 21 to 51 (+42%). The first SLuLi and SLuK transplants occurred in 1994 and 1995, respectively. These combinations remain relatively uncommon; however, trends were similar to those for SHK and SHLi. A total of 122 SLuLi patients have been wait-listed and 42 transplanted since 1987, with 53 wait-listed and 23 transplanted since 2006. Forty-one SLuK patients have been wait-listed since 1987 (18 since 2006) and 16 of those received transplants (10 since 2006).
Medical Urgency for STA Wait-list Patients: Comparisons of Wait-list Mortality
Etiology of Organ Failure
Etiologies for organ dysfunction among patients wait-listed for STA are listed in Table 2 . For SHK, heart failure was most commonly due to nonischemic cardiomyopathy (N = 576), ischemic cardiomyopathy (N = 519) and retransplantation/graft failure (N = 192), whereas kidney dysfunction was due to diabetes (N = 196), tubular/interstitial disease (N = 165) and glomerulonephritis (N = 159). For those awaiting SHLi, heart failure was attributable to nonischemic (N = 129) and ischemic cardiomyopathy (N = 25), and liver dysfunction to noncholestatic (N = 76) and metabolic (N = 19) diseases. The SLuLi cohort consisted of a majority (N = 70) of patients with cystic fibrosis. The primary causes of pulmonary failure in SLuK patients included restrictive (N = 20) and pulmonary vascular diseases (N = 10).
STA Characteristics
The populations awaiting STA had distinct demographic and clinical characteristics compared to patients wait-listed for single-organ transplantation ( Table 3 ). SHLi, SLuLi and SLuK candidates were younger on average than their respective thoracic and abdominal control groups, whereas SHK candidates were older compared to heart-alone (p < 0.001). Listing status for SHK and SLuK candidates was more advanced compared to heart (p < 0.001) or lung alone (p = 0.02), but SHLi candidates were listed at lower heart status (p < 0.001). LAS scores for SLuLi were comparable to those for lung alone (p = 0.22), and MELD scores for both SLuLi and SHLi were lower compared to liver alone (p = 0.06). Compared to kidney alone, wait-list times for SHK and SLuK were significantly reduced (p < 0.001). SHK and SHLi had significantly prolonged wait-list times compared to heart-alone (p < 0.001). In all STA wait-list groups, a lower percentage of patients ultimately received transplants (either single transplant or STA) when compared to thoracic-only candidates (p < 0.001). SLuLi and SLuK candidate groups both also had lower percentages of transplantation compared to abdominal-only candidates (p < 0.001). Of note, a group of 146 patients who were initially waitlisted for SHK eventually received a heart-alone transplant. Posttransplant survival at 1 and 5 years was significantly lower in this population (56.7%, 44.1%) compared to those waitlisted for SHK who received a combined transplant (85.3%, 74.0%) (p < 0.001).
Wait-list Mortality: STA versus Single Organ
Wait-list survival at 1 and 3 years was obtained for SHK (67.4%, 40.8%), SHLi (65.7%, 43.6%), SLuLi (65.7%, 41.0%), and found to be significantly decreased compared to respective thoracic and abdominal controls (p < 0.001). Waitlist survival for SLuK at 1 and 3 years (65.0%, 51.6%) was not statistically different from lung (p = 0.34) or kidney controls (0.41) ( Table 4 ).
Transplant Efficacy: STA versus Single-Organ Controls
STA Donor and Recipient Characteristics
We next reviewed the clinical and demographic data for those candidates who proceeded to STA ( Table 5 ). As noted with the wait-list cohorts, SHK recipients were older than controls (p < 0.01), whereas SLuLi recipients were considerably younger (p < 0.001). STA recipients differed considerably from single-organ recipients with respect to level of acuity at time of transplant. Approximately half of SHK and SHLi were transplanted as hospitalized inpatients, and the majority of these occurred during an ICU admission. This was fewer than those for heart alone, but greater than kidney or liver alone (p < 0.001). SLuLi recipients were also more often hospitalized, and in the ICU, compared to lung alone at the time of transplant (p < 0.001). We also compared measures of abdominal organ dysfuction for STA and control recipients. A similar proportion of SHK and kidney alone recipients were on dialysis preoperatively. INR and total bilirubin were both lower in SHLi and SLuLi in comparison to liver alone as was transplant MELD (p < 0.001). With regard to thoracic organ failure, heart status at time of transplant was slightly more advanced compared to heart alone for SHK and less advanced for SHLi (p < 0.001). There were no significant differences between lung alone and SLuLi or SLuK in terms of LAS or FVC.
Patient Survival for STA and Single-Transplant Control
Kaplan–Meier estimates for 1 and 5 years patient survival were determined for SHK (85.3%, 74.0%), SHLi (85.9%, 74.3%), SLuLi (75.5%, 59.0%) and SLuK (66.7%, 55.6%) ( Table 6 ). In all groups, STA patient survival was not significantly different from thoracic single-transplant cohorts. STA patient survival was however lower than abdominal single-transplant groups for SHK (p < 0.001), SLuLi (p = 0.01) and SLuK (p < 0.001). SHLi had the greatest 1 and 5 years survival of the STA cohorts, and was unique in that survival was equivalent to the abdominal control group (p = 0.81). It was also notable that STA combinations with kidney had lower survival compared to STA combinations with liver (SHK vs. SHLi; SLuK vs. SLuLi). This may be due to baseline differences between the kidney and liver STA cohorts in terms of age (liver cohorts are younger), number of associated comorbidities or severity of organ dysfunction at time of transplant. It is also possible that this is related to differences in manifestations of systemic illness for kidney and liver failure.
Survival Benefit of STA
A multivariable Cox regression model was created to explore the potential survival benefit of a STA transplant, compared to remaining on the wait-list. Among SHK, SHLi and SLuLi a substantial increase for STA was achieved (SHK, HR 0.31, 95% CI 0.26–0.37, p < 0.001; SHLi, HR 0.34, 95% CI 0.21–0.56, p < 0.001; SLuLi HR 0.53, 95% CI 0.29–0.96, p = 0.04). (Figure 1). SLuK recipients did not incur any transplant survival benefit over wait-list patients (HR 1.05, 95% CI 0.45–2.47, p = 0.91).
(Enlarge Image)
Figure 1.
Survival benefit of transplantation for STA candidates. Survival for wait-list patients is compared to posttransplant survival for each of the STA subtypes. Hazard ratios (HR) and 95% confidence intervals (CI) were derived from multivariate Cox regression models comparing the two curves.
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