Justin M. Schaffer

Single- vs Double-Lung Transplantation in Patients With Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis Since the Implementation of Lung Allocation Based on Medical Need

IMPORTANCE Outcomes of single- and double-lung transplantation have not been rigorously assessed since the allocation of donor lungs according to medical need as quantified by the Lung Allocation Score, which began in 2005. OBJECTIVE To compare outcomes in single- and double-lung transplant recipients since the Lung Allocation Score was implemented. DESIGN, SETTING, AND PARTICIPANTS In this exploratory analysis, adults with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) who underwent lung transplantation in the United States between May 4, 2005, and December 31, 2012, were identified in the United Network for Organ Sharing thoracic registry, with follow-up to December 31, 2012. Posttransplantation graft survival was assessed with Kaplan-Meier analysis. Propensity scores were used to control for treatment selection bias. A multivariable flexible parametric prognostic model was used to characterize the time-varying hazard associated with single- vs double-lung transplantation. EXPOSURE Single- or double-lung transplantation. MAIN OUTCOMES AND MEASURES Composite of posttransplant death and graft failure (retransplantation). RESULTS Patients with IPF (n = 4134, of whom 2010 underwent single-lung and 2124 underwent double-lung transplantation) or COPD (n = 3174, of whom 1299 underwent single-lung and 1875 underwent double-lung transplantation) were identified as having undergone lung transplantation since May 2005. Median follow-up was 23.5 months. Of the patients with IPF, 1380 (33.4%) died and 115 (2.8%) underwent retransplantation; of the patients with COPD, 1138 (34.0%) died and 59 (1.9%) underwent retransplantation. After confounders were controlled for with propensity score analysis, double-lung transplants were associated with better graft survival in patients with IPF (adjusted median survival, 65.2 months [interquartile range {IQR}, 21.4-91.3 months] vs 50.4 months [IQR, 17.0-87.5 months]; P < .001) but not in patients with COPD (adjusted median survival, 67.7 months [IQR, 25.2-89.6 months] vs 64.0 months [IQR, 25.2-88.7 months]; P = .23). The interaction between diagnosis type (COPD or IPF) and graft failure was significant (P = .049). Double-lung transplants had a time-varying association with graft survival; a decreased instantaneous late hazard for death or graft failure among patients with IPF was noted at 1 year and persisted at 5 years postoperatively (instantaneous hazard at 5 years, hazard ratio, 0.67 [95% CI, 0.52-0.84] in patients with IPF and 0.89 [95% CI, 0.71-1.13] in patients with COPD). CONCLUSIONS AND RELEVANCE In an exploratory analysis of registry data since implementation of a medical need-based lung allocation system, double-lung transplantation was associated with better graft survival than single-lung transplantation in patients with IPF. In patients with COPD, there was no survival difference between single- and double-lung transplant recipients at 5 years.

Transplantation for Idiopathic Pulmonary Arterial Hypertension: Improvement in the Lung Allocation Score Era

Background— Lung transplantation and heart-lung transplantation represent surgical options for treatment of medically refractory idiopathic pulmonary arterial hypertension. The effect of the lung allocation score on wait-list and transplantation outcomes in patients with idiopathic pulmonary arterial hypertension is poorly described. Methods and Results— Adults diagnosed with idiopathic pulmonary arterial hypertension and listed for transplantation in the 80 months before and after the lung allocation score algorithm was implemented (n=1430) were identified in the United Network for Organ Sharing thoracic registry. Patients were stratified by organ listed and pre– and post–lung allocation score era. The cumulative incidences of transplantation and mortality for wait-listed patients in both eras were appraised with competing outcomes analysis. Posttransplantation survival was assessed with the Kaplan-Meier method. These analyses were repeated in propensity-matched subgroups. Cox proportional hazards analysis evaluated the effect of prelisting and pretransplantation characteristics on mortality. We found that patients in the post–lung allocation score era had significantly worse comorbidities; nevertheless, both lung transplantation and heart-lung transplantation candidates in this era enjoyed lower wait-list mortality and a higher incidence of transplantation in unmatched and propensity-matched analyses. On multivariable analysis, heart-lung transplantation and double-lung transplantation were associated with improved survival from the time of wait-listing, as was being listed at a medium- to high-volume institution. Donor/recipient sex matching predicted posttransplantation survival. Conclusions— The incidence of transplantation has increased while wait-list mortality has decreased in patients with idiopathic pulmonary arterial hypertension wait-listed for transplantation in the post–lung allocation score era. Both heart-lung transplantation and double-lung transplantation are predictive of survival in transplantation candidates with idiopathic pulmonary arterial hypertension, as is being listed at a medium- to high-volume institution. Donor/recipient sex matching is associated with better posttransplantation survival. # Clinical Perspective {#article-title-47}Background— Lung transplantation and heart-lung transplantation represent surgical options for treatment of medically refractory idiopathic pulmonary arterial hypertension. The effect of the lung allocation score on wait-list and transplantation outcomes in patients with idiopathic pulmonary arterial hypertension is poorly described. Methods and Results— Adults diagnosed with idiopathic pulmonary arterial hypertension and listed for transplantation in the 80 months before and after the lung allocation score algorithm was implemented (n=1430) were identified in the United Network for Organ Sharing thoracic registry. Patients were stratified by organ listed and pre– and post–lung allocation score era. The cumulative incidences of transplantation and mortality for wait-listed patients in both eras were appraised with competing outcomes analysis. Posttransplantation survival was assessed with the Kaplan-Meier method. These analyses were repeated in propensity-matched subgroups. Cox proportional hazards analysis evaluated the effect of prelisting and pretransplantation characteristics on mortality. We found that patients in the post–lung allocation score era had significantly worse comorbidities; nevertheless, both lung transplantation and heart-lung transplantation candidates in this era enjoyed lower wait-list mortality and a higher incidence of transplantation in unmatched and propensity-matched analyses. On multivariable analysis, heart-lung transplantation and double-lung transplantation were associated with improved survival from the time of wait-listing, as was being listed at a medium- to high-volume institution. Donor/recipient sex matching predicted posttransplantation survival. Conclusions— The incidence of transplantation has increased while wait-list mortality has decreased in patients with idiopathic pulmonary arterial hypertension wait-listed for transplantation in the post–lung allocation score era. Both heart-lung transplantation and double-lung transplantation are predictive of survival in transplantation candidates with idiopathic pulmonary arterial hypertension, as is being listed at a medium- to high-volume institution. Donor/recipient sex matching is associated with better posttransplantation survival.

Heart and Combined Heart–Kidney Transplantation in Patients With Concomitant Renal Insufficiency and End‐Stage Heart Failure

In patients with end‐stage heart failure (ESHF) who are candidates for isolated heart transplant (HRT), dialysis dependence (DD) is considered an indication for combined heart–kidney transplantation (HKT). HKT remains controversial in ESHF transplant candidates with nondialysis‐dependent renal insufficiency (NDDRI). Using United Network for Organ Sharing data, we examined the cumulative incidences of transplant and mortality in patients with DD and NDDRI waitlisted for HKT or HRT. In all groups, 3‐month waitlist mortality was dismal: 31% and 21% for HRT‐ and HKT‐listed patients with DD and 12% and 7% for HRT‐ and HKT‐listed patients with NDDRI. Five‐year posttransplant survival was improved in HKT recipients compared with HRT recipients for both patients with DD (73% vs. 51%, p < 0.001) and NDDRI (80% vs. 69%, p < 0.001). Likewise, multivariable analysis associated HKT with better outcomes than HRT in HKT‐listed patients, although both improved survival. These data argue strongly for HKT in ESHF transplant candidates with DD. However, in patients with NDDRI, HKT must be weighed against the possibility of renal recovery with isolated HRT. Whether HRT (followed by a staged kidney transplant in patients who do not recover renal function after HRT), as opposed to HKT, maximizes organ benefit for patients with NDDRI and ESHF requires assessment. Nevertheless, given their dismal waitlist outcomes and excellent posttransplant results, we suggest that patients with DD and NDDRI with ESHF be considered for early listing and transplant.

Midterm survival after thoracic endovascular aortic repair in more than 10,000 Medicare patients

OBJECTIVE Aneurysms and dissections of the descending thoracic aorta represent a complex substrate with a variety of therapeutic options. The introduction of thoracic endovascular aortic repair (TEVAR) has revolutionized the treatment of thoracic aortic disease. However, longitudinal analyses of post-TEVAR outcomes appropriately stratified by aortic disease remain limited. METHODS A total of 11,996 patients undergoing TEVAR from 2005-2010 were identified from the Medicare/Centers for Medicare and Medicaid Services database. Patients were stratified by underlying aortic disease and the presence of Current Procedural Terminology (CPT) codes. Survival was assessed using Kaplan-Meier analysis. Cox proportional hazards analysis determined predictors of survival from TEVAR. RESULTS After TEVAR, patients had a median survival of 57.6 months (95% confidence interval, 54.9-61.3 months). Although patients without CPT codes had significantly fewer recorded comorbidities, TEVAR survival was comparable between patients with and without CPT codes (56.3 vs 59.5 months, P = .54). The early and late incidence of death varied significantly by aortic disease. Patients with aortic rupture, acute aortic dissection, and aortic trauma had the highest early incidence of death, whereas late survival was highest in patients with acute aortic dissection, aortic trauma, and isolated thoracic aortic aneurysm. Although hospital TEVAR volume was not associated with survival, an independent hospital effect (determined by using a mixed-effect Cox model) associated certain hospitals with a hazard for death 50% of what it was at other hospitals. CONCLUSIONS TEVAR has been applied to a multitude of aortic diseases in the Medicare population; early and late post-TEVAR survival varies by aortic disease. The late incidence of death remains high in TEVAR recipients, although certain aortic diagnoses such as acute aortic dissection, aortic trauma, and isolated thoracic aortic aneurysm were associated with improved late survival. An independent hospital effect, but not hospital volume, is correlated with post-TEVAR survival. Future analyses of TEVAR outcomes using the Medicare database should adjust for underlying aortic diagnoses and the presence of CPT codes.

Heart transplant graft survival is improved after a reduction in panel reactive antibody activity.

BACKGROUND Allosensitization in potential orthotopic heart transplant recipients is evaluated with the panel reactive antibody assay. Sensitized patients have prolonged wait times and increased waitlist and post-transplant mortality. Although low panel reactive antibody activity at the time of orthotopic heart transplantation is associated with improved outcomes, literature regarding the survival benefit of a panel reactive antibody reduction in the sensitized orthotopic heart transplant recipient remains limited. METHODS Adult orthotopic heart transplant recipients listed in the United Network for Organ Sharing database (October 1, 1987, to June 29, 2004) were stratified by peak panel reactive antibody activity and whether a substantial decline from peak to most recent panel reactive antibody activity occurred before transplant. Propensity matching adjusted for differences in recipient and donor characteristics. Graft survival was assessed with Kaplan-Meier analysis. Cox proportional hazards regression determined predictors of graft survival. RESULTS Pretransplant characteristics differed between sensitized patients who had a substantial decline in panel reactive antibody activity and those who did not. Propensity matching compensated for these differences. Kaplan-Meier survival analysis of matched groups showed that the median graft survival was 120 months in patients with a significant panel reactive antibody reduction and 103 months in patients with a trivial reduction (P = .007, log-rank). In Cox proportional hazards modeling, a significant reduction in panel reactive antibody activity had an independent protective effect on graft survival (hazard ratio, 0.88; confidence interval, 0.80-0.96; P = .006). CONCLUSIONS Sensitized patients who had a substantial reduction in panel reactive antibody activity had an associated decline in the incidence of graft failure compared with those without a panel reactive antibody activity reduction. These results support efforts to reduce panel reactive antibody activity before orthotopic heart transplantation in patients with high panel reactive antibody activity.

Combined Heart–Liver Transplantation in the MELD Era: Do Waitlisted Patients Require Exception Status?

Combined heart–liver transplant (HLT) is a viable therapy for patients with concomitant end‐stage heart and liver failure. Using data from the United Network for Organ Sharing database, we examined the cumulative incidences of transplant and mortality in waitlisted candidates for HLT, isolated heart transplant (HRT) and isolated liver transplant (LIV) in the Model for End‐Stage Liver Disease era. The incidence of waitlist mortality was higher in HLT candidates than in HRT candidates (p = 0.001, 26% vs. 12% at 1 year) or LIV candidates (p = 0.005, 26% vs. 14% at 1 year). These differences persisted after stratifying by disease severity. Posttransplant survival was not significantly different between HLT and HRT recipients or between HLT and LIV recipients. In a multivariable model, undergoing HLT was associated with enhanced survival for HLT candidates (hazard ratio, 0.41; confidence interval, 0.21–0.79; p = 0.008), but undergoing HRT alone was not. Interestingly, 90% of HLT recipients were allocated an organ locally, compared to 60% of HRT candidates and 73% of LIV candidates (both p < 0.001). These data suggest that the current cardiac and liver allocation systems may underestimate the risk of death for patients with concomitant end‐stage heart and liver failure on the HLT waitlist.

Midterm Outcomes of Open Descending Thoracic Aortic Repair in More Than 5,000 Medicare Patients.

BACKGROUND Diseases involving the descending thoracic aorta (DTA) represent a heterogeneous substrate with a variety of therapeutic options. Although thoracic endovascular aortic repair has been increasingly applied to DTA disease, open surgical repair is ostensibly more durable. METHODS A total of 5,578 patients who underwent open DTA repair (Current Procedural Terminology code 33875) from 1999 to 2010 were identified from the Medicare database; 5,489 patients had complete data. Survival was assessed with Kaplan-Meier analysis. Cox regression determined predictors of death. Hospital and surgeon volume and variability were modeled, and their association with survival assessed. RESULTS Median survival after open DTA repair was only 4.3 years (95% confidence interval: 4.0 to 4.6). The likelihood of death varied significantly by certain aortic diseases: aortic rupture and acute aortic dissection patients had the highest early mortality. Survival beyond 180 days was best for patients with acute aortic dissection and isolated thoracic aortic aneurysm, and lowest for patients with thoracoabdominal aneurysm and aortic rupture. Hospital and surgeon volume, as well as interhospital and intersurgeon variability, had associations with overall survival. CONCLUSIONS Open DTA repair has treated a spectrum of aortic diseases in Medicare beneficiaries. Overall mortality was high, predominately confined to the initial postoperative hazard phase. Independent hospital and surgeon effects, hospital and surgeon volume, and a more recent date of surgery correlated with improved survival, while increased operative urgency and complexity correlated with worse outcomes. These observations argue for regionalization of DTA treatment for Medicare patients in specialized centers to concentrate expertise, which should translate into better outcomes.

Influence of durable mechanical circulatory support and allosensitization on mortality after heart transplantation

BACKGROUND Allosensitization has been shown to negatively affect post-heart transplant (HTx) survival even with a negative crossmatch. Whether allosensitization related to mechanical circulatory support (MCS) is associated with worse post-HTx survival remains controversial. METHODS Adult HTx recipients listed in the United Network for Organ Sharing database (July 2006-December 2012) were identified. Multivariate Cox regression assessed the effect of allosensitization on survival. Propensity matching was performed to compare patients who were and were not allosensitized. Kaplan-Meier survival analysis compared matched and unmatched patients in the MCS and medically managed cohorts. RESULTS We identified 11,840 HTx recipients, of whom 4,167 had MCS. MCS was associated with allosensitization in multivariate logistic regression. Each different MCS device was associated with worse post-HTx survival in multivariate Cox regression. Allosensitization did not predict post-HTx mortality in MCS patients (hazard ratio, 1.07; 95% confidence interval, 0.89-1.28; p = 0.48. Among patients without MCS, allosensitization was associated with post-HTx mortality (hazard ratio, 1.19; 95% confidence interval, 1.03-1.39; p = 0.02). Kaplan-Meier analysis revealed equivalent survival in unmatched and matched cohorts when MCS patients who were allosensitized were compared with non-allosensitized MCS patients. Among non-MCS patients, allosensitization was associated with worse survival in unmatched and matched analysis. CONCLUSIONS MCS was associated with allosensitization. For MCS patients, allosensitization did not independently predict worse post-HTx outcome. Among non-MCS patients, allosensitization was associated with worse post-HTx survival. Allosensitization appears to be a heterogeneous process influenced by presence of MCS.

Elevated pretransplant pulmonary vascular resistance index does not predict mortality after isolated orthotopic heart transplantation in children: A retrospective analysis of the UNOS database

OHT is the definitive therapy in end‐stage heart failure. Elevated PVRI is considered a relative contraindication to isolated OHT; this assumption is re‐evaluated using data from the UNOS database. A retrospective review of de‐identified data from the UNOS dataset was performed. There were 1943 pediatric OHT recipients between 10/87 and 12/11 with sufficient data for analysis. Cox regression was performed to examine the effect of baseline characteristics on post‐transplant survival. Patients were propensity matched, and Kaplan–Meier survival analysis was performed comparing cohorts of patients using thresholds of 6 and 9 WU × m2. PVRI was not a significant predictor of post‐transplant outcomes in either univariate or multivariate Cox regression. Kaplan–Meier analysis revealed no difference in survival between both unmatched and propensity‐matched OHT recipients. In conclusion, elevated PVRI was not associated with post‐transplant mortality in pediatric OHT recipients. A prospective study assessing the current use of PVRI ≥6 as a threshold to contraindicate isolated OHT should be undertaken. Removing this potentially unnecessary restriction on transplant candidacy may make this life‐saving therapy available to a greater number of patients.

Impact of Discordant Views in the Management of Descending Thoracic Aortic Aneurysm

Thoracic endovascular aortic repair has a lower perceived risk than open surgical repair and has become an increasingly popular alternative. Whether general consensus exists regarding candidacy for either operation among open and endovascular specialists is unknown. A retrospective review of isolated descending thoracic aortic aneurysm at our institution between January 2005 and October 2015 was performed, excluding trauma and dissection. Two cardiac surgeons, 2 cardiovascular surgeons, 1 vascular surgeon, and 1 interventional radiologist gave their preference for open vs endovascular repair. Interobserver agreement was assessed with the kappa coefficient. k-means clustering agnostically grouped various patterns of agreement. The mean rating was predicted using least absolute shrinkage and selection operator regression. Negative binomial regression predicted the discrepancy between our panel of raters and the historical operation. Generalized estimating equation modeling was then used to evaluate the association between the extent of discrepancy and the adverse perioperative outcome. There were 77 patients with preoperative imaging studies. Pairwise interobserver agreement was only fair (median weighted kappa 0.270 [interquartile range 0.211-0.404]). Increasing age and proximal neck length predicted an increasing preference for thoracic endovascular aortic repair in our panel; larger proximal neck diameter predicted a general preference for open surgical repair. Increasing proximal neck diameter predicted a larger discrepancy between our panel and the historical operation. Greater discrepancy was associated with adverse outcome. Substantial disagreement existed among our panel, and an exploratory analysis of the effect of increasing discrepancy demonstrated an association with adverse perioperative outcome. An investigation of the effect of a thoracic aortic team with open and endovascular specialists is warranted.