Impact of lung transplantation on diastolic dysfunction in recipients with pretransplant pulmonary hypertension.

OBJECTIVE: Pulmonary hypertension can cause left ventricular diastolic dysfunction through ventricular interdependence. Moreover, diastolic dysfunction has been linked to adverse outcomes after lung transplant. The impact of lung transplant on diastolic dysfunction in recipients with pretransplant pulmonary hypertension is not defined. In this cohort, we aimed to assess the prevalence of diastolic dysfunction, the change in diastolic dysfunction after lung transplant, and the impact of diastolic dysfunction on lung transplant outcomes. METHODS: In a large, single-center database from January 2011 to September 2021, single or bilateral lung transplant recipients with pulmonary hypertension (mean pulmonary artery pressure > 20 mm Hg) were retrospectively identified. Those without a pre- or post-transplant echocardiogram within 1 year were excluded. Diastolic dysfunction was diagnosed and graded according to the American Society of Echocardiography 2016 guideline on assessment of diastolic dysfunction (present, absent, indeterminate). McNemar's test was used to examine association between diastolic dysfunction pre- and post-transplant. Kaplan-Meier and Cox regression analysis were used to assess associations between pre-lung transplant diastolic dysfunction and post-lung transplant 1-year outcomes, including mortality, major adverse cardiac events, and bronchiolitis obliterans syndrome grade 1 or higher-free survival. RESULTS: Of 476 primary lung transplant recipients, 205 with pulmonary hypertension formed the study cohort (mean age, 56.6 ± 11.9 years, men 61.5%, mean pulmonary artery pressure 30.5 ± 9.8 mm Hg, left ventricular ejection fraction < 55% 9 [4.3%]). Pretransplant, diastolic dysfunction was present in 93 patients (45.4%) (grade I = 8, II = 84, III = 1), absent in 16 patients (7.8%), and indeterminate in 89 patients (43.4%), and 7 patients (3.4%) had missing data. Post-transplant, diastolic dysfunction was present in 7 patients (3.4%) (grade I = 2, II = 5, III = 0), absent in 164 patients (80.0%), and indeterminate in 15 patients (7.3%), and 19 patients (9.3%) had missing data. For those with diastolic dysfunction grades in both time periods (n = 180), there was a significant decrease in diastolic dysfunction post-transplant (148/169 patients with resolved diastolic dysfunction; McNemar's test P < .001). Pretransplant diastolic dysfunction was not associated with major adverse cardiac events (hazard ratio [HR], 1.08, 95% CI, 0.72-1.62; P = .71), bronchiolitis obliterans syndrome-free survival (HR, 0.67, 95% CI, 0.39-1.56; P = .15), or mortality (HR, 0.70, 95% CI, 0.33-1.46; P = .34) at 1 year. CONCLUSIONS: Diastolic dysfunction is highly prevalent in lung transplant candidates with normal left ventricular systolic function and pulmonary hypertension, and resolves in most patients after lung transplant regardless of patient characteristics. Pre-lung transplant diastolic dysfunction was not associated with adverse lung or cardiac outcomes after lung transplant. Collectively, these findings suggest that the presence of diastolic dysfunction in lung transplant recipients with pulmonary hypertension has no prognostic significance, and as such diastolic dysfunction and the associated clinical syndrome of heart failure with preserved ejection fraction should not be considered a relative contraindication to lung transplant in such patients.

Time since primary transplant and poor functional status predict survival after redo lung transplant.

Background: In previous studies, lower functional status measured by Karnofsky Performance Status (KPS) correlated with worse survival after redo lung transplant. We hypothesize that combining reduced functional status and time from primary lung transplant will correlate with the etiology of lung allograft failure after primary lung transplant and more accurately predict survival after redo lung transplant. Methods: This retrospective study was approved by University of Minnesota Institutional Review Board. From the Scientific Registry of Transplant Recipients (SRTR) database, 739 patients underwent redo lung transplant (01/01/2005-8/30/2019). Pre-lung transplant characteristics, KPS, time between primary and redo lung transplant, outcomes, overall survival were evaluated. Paired comparisons were used to compare pre-transplant variables. A Cox regression model was fit to examine re-transplant survival. Due to non-proportional hazards, time between transplants was split into <1-year vs. 1+ years and analyzed with time-dependent coefficients, with follow-up time considered in three segments (0-6, 6-24, 24+ months). Results: After KPS grouping (10-40%, 50-70%, 80-100%), KPS 10-40% were less likely to be discharged after primary transplant and more likely required mechanical ventilation or extracorporeal membrane oxygenation (ECMO) bridging (P<0.001). Redo lung transplant survival was worse in the KPS 10-40% group who more likely underwent lung transplant <1 year after primary lung transplant. Mortality was significantly higher for patients who underwent redo lung transplant within one year of primary transplant when KPS was 10-40% (P<0.001). These patients were more likely to require redo lung transplant due to primary graft failure or acute cellular rejection. Conclusions: Functional status and time from primary lung transplant are strong predictors of outcome after redo lung transplant. We categorized redo lung transplant recipients in two distinct groups. One group has early allograft failure and poor functional status with a very poor prognosis after redo lung transplant. The other group has chronic allograft failure and overall better functional status with relatively better survival after redo lung transplant. Salvage redo lung transplant for primary allograft failure or acute rejection is associated with low one year survival.

Lung Transplant Recipients With Prior Coronary Artery Bypass Grafting Are at Increased Risk of Death and Early Perioperative Hemorrhage.

Prior coronary artery bypass grafting (CABG) has been considered a relative contraindication to lung transplantation due to the atherosclerotic disease burden and technical challenges. We hypothesized that lung transplant recipients with prior CABG have increased mortality compared to recipients without prior CABG. Further, the causes of death are different for lung transplant recipients with prior CABG vs without CABG. The Scientific Registry of Transplant Recipients database was queried to define the survival and causes of death of lung transplant recipients with or without CABG during the Lung Allocation Score era from May 5, 2005 to December 31, 2015. The primary end-points were all-cause mortality at 1 year and 5 years, as well as mortality due to major causes of death. This retrospective study cohort included a total of 13,064 lung transplant recipients, of whom 319 patients had previously undergone CABG, representing 2.4% of all transplants. Patients without prior CABG were more likely to have undergone bilateral lung transplantation compared to those with prior CABG (61.2 % vs 15.7%, P < 0.001). Among patients with prior CABG, single right lung transplant was most common. Overall patient survival at 1 year was 76.8% for lung transplant recipients with prior CABG and 85.4% for patients without prior CABG. Freedom from death due to graft failure at 1 and 5 years in patients with a prior CABG was 93.1% and 76.2% respectively, cardiac and/or cerebrovascular disease 96.2% and 88.5% respectively, and hemorrhage 97.9% and 97.5% respectively. In a multivariate Cox regression model utilizing time-dependent coefficients for recipient age, prior CABG, among several other risk factors, was associated with increased mortality within 1 year. Prior CABG is associated with short- and long-term mortality in lung transplant recipients with history of CABG despite the majority of these patients undergoing single lung transplantation vs bilateral lung transplantation. Graft failure and/or pulmonary causes are the most common cause of death regardless of whether or not the lung transplant recipient had prior CABG, but patients with prior CABG are at increased risk of death due to graft failure, cardiac or cerebrovascular disease, and hemorrhage.

Separate Effect of Perioperative Recombinant Human Factor VIIa Administration and Packed Red Blood Cell Transfusions on Midterm Survival in Lung Transplantation Recipients.

OBJECTIVE: The purpose of this study was to determine the relationship between blood product transfusion, with or without recombinant human activated factor VIIa, and survival after lung transplantation. DESIGN: Retrospective analysis of a single center with follow-up out to 6 years post-transplantation. SETTING: Single-center academic lung transplantation program. PARTICIPANTS: The study comprised 265 adult patients who underwent single or bilateral sequential lung transplantation from March 2011 to June 2017. INTERVENTIONS: Overall survival using Kaplan-Meier curves was compared among the following 3 cohorts: those not transfused with blood products, those transfused with blood products, and those given blood products and recombinant human activated factor VIIa. Cox proportional hazards regression was used to estimate hazard ratios (HRs), confidence intervals (CIs), and p values. MEASUREMENTS AND MAIN RESULTS: Seventy-eight patients received no packed red blood cell transfusions, 149 received packed red blood cell transfusions, and 38 received both packed red blood cell transfusions and recombinant human activated factor VII. Packed red blood cell transfusion was associated with an increased risk of mortality that did not reach statistical significance (HR 2.168, CI 0.978-4.805; p = 0.057). Additional packed red blood cells beyond 15 U were associated with worsened survival (HR 1.363, CI 1.137-1.633; p = 0.001), but recombinant human activated factor VIIa did not increase the risk of mortality. CONCLUSION: Blood product transfusion during and after lung transplantation is associated with decreased survival, especially with large-volume transfusions. Survival is not worse with recombinant human activated factor VIIa administration, but additional studies are needed to determine whether recombinant human activated factor VIIa administration reduces the need for blood product transfusions.

Need for tracheostomy after lung transplant predicts decreased mid- and long-term survival.

BACKGROUND: Tracheostomy is an important adjunct for lung transplant patients requiring prolonged ventilation. We explored the effects of post-transplant tracheostomy on survival and bronchiolitis obliterans syndrome after lung transplant. METHODS: A retrospective, single center analysis was performed on all lung transplant recipients during the Lung Allocation Score (LAS) era. Risk factors for post-transplant tracheostomy or death within 30 days were assessed. Kaplan-Meier estimates and Cox proportional hazards models were used to examine the association between tracheostomy within 30 days after transplant and survival at 1 and 3 years. A total of 403 patients underwent single or bilateral lung transplant between May 2005 and February 2016 with complete data for 352 cases, and 35 patients (9.9%) underwent tracheostomy or died (N = 10, 2.8%) within 30 days. RESULTS: In adjusted analyses, primary graft dysfunction grade 3 (PGD3) was associated with a composite end point of tracheostomy or death within 30 days (HR 3.11 (1.69, 5.71), P-value < .001). Tracheostomy within 30 days was associated with decreased survival at 1(HR 4.25 [1.75, 10.35] P-value = .001) and 3 years (HR 2.74 [1.30, 5.76], P-value = .008), as well as decreased bronchiolitis obliterans (BOS)-free survival at 1 (HR 1.87 [1.02, 3.41] P-value = .042) and 3 years (HR 2.15 [1.33, 3.5], P-value = .002). CONCLUSION: Post-transplant tracheostomy is a marker for advanced lung allograft dysfunction with significant reduction in long-term overall and BOS-free survival.

Greater survival despite increased complication rates following lung transplant for alpha-1-antitrypsin deficiency compared to chronic obstructive pulmonary disease.

BACKGROUND: Alpha-1-antitrypsin (A1AT) deficiency (A1ATD) is characterized by accelerated degradation of lung function. We examined our experience with lung transplantation for chronic obstructive pulmonary disease (COPD) with and without A1ATD to compare survival and rates of postoperative surgical complications. METHODS: Patients with A1ATD and non-A1ATD COPD undergoing lung transplantation from 1988-2015 at our institution were analyzed. Complications were categorized into non-gastroenteritis gastrointestinal (GI), wound, airway, and reoperation for bleeding. Overall and complication-free survival were evaluated using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Three hundred and eighty-five patients underwent lung transplant for COPD (98 A1ATD). For A1ATD, 56.1% underwent single lung transplantation (80.6% for COPD). Early overall and complication-free survival was worse for A1ATD, but this trend reversed at longer follow up. Unadjusted estimated survival showed advantage for COPD at 90 days and 1 year, which attenuated by 5 years and reversed at 10 years (P<0.001). On adjusted analysis, A1ATD was associated with a trend toward lower complication-free survival at 90 days and 1 year, due partly to increased rates of post-transplant GI pathology, particularly in the era of the lung allocation score (LAS). CONCLUSIONS: A1ATD lung recipients had worse short-term complication-free survival but improved long-term survival compared to COPD patients. A1ATD was associated with greater risk of new GI pathology after transplant. Close monitoring of A1ATD patients with timely evaluation of GI complaints after transplant is warranted.

Single Versus Bilateral Lung Transplantation for Idiopathic Pulmonary Fibrosis in the Lung Allocation Score Era.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease. Lung transplantation is the only therapy associated with prolonged survival. The ideal transplant procedure for IPF is unclear. Outcomes after single transplantation (SLTx) versus bilateral lung transplantation (BLTx) in IPF patients after introduction of the Lung Allocation Score were examined. METHODS: Records of patients undergoing lung transplantation for IPF at our institution between May 2005 and March 2017 were reviewed to examine the effect of transplant laterality. Primary outcomes were overall, rejection-free, and bronchiolitis obliterans (BOS)-free survival at 1 and 5 years post-transplant. RESULTS: Lung transplantation was performed in 151 IPF patients post-Lung Allocation Score. Most recipients were male with average age 59 ± 8 years. SLTx was performed in 94 patients (62%). In the overall cohort, comparative survival between SLTx and BLTx was similar at 1 and 5 years before and after adjusting for age and pulmonary hypertension (PH). SLTx was associated with shorter ventilator time and intensive care unit stay and trended toward improved survival over BLTx in patients without PH. CONCLUSIONS: The use of SLTx versus BLTx in IPF did not correspond to significantly different survival adjusting for age and PH. BLTx was associated with prolonged postoperative ventilation and length of stay compared with SLTx. Patients without PH, all older patients, and patients with PH and advanced disease should be considered for SLTx for IPF.

Tailored Approach to Surgical Exposure Reduces Surgical Site Complications after Bilateral Lung Transplantation.

BACKGROUND: We evaluated the effects of tailoring the operative approach on major surgical site complications and outcomes in lung transplant recipients. PATIENTS AND METHODS: Beginning in July 2013, bilateral lung transplants at a single institution were performed either through sternotomy or clamshell depending on proximity of hilar structures by computed tomography (CT), anticipated complexity, past surgical history, and surgeon experience. Patient demographics and outcomes were collected in the institution's Transplant Information Services (TIS). A major surgical site complication was defined as a sterile or infected incision requiring operative intervention. RESULTS: One hundred six bilateral lung transplants (68 via clamshell and 38 via median sternotomy) were performed between July 2013 and June 2016. Median sternotomy patients were older (mean age 55 vs. 50 y, p = 0.04), and less likely to have cystic fibrosis (5 [13%] vs. 19 [28%], p = 0.21) or diabetes (5 [13%] vs. 26 [38%], p = 0.01). There was no statistically significant difference in mean lung allocation score (LAS) (45 vs. 48, p = 0.39) and body mass index (BMI; kg/m2; 25.3 vs. 24.4, p = 0.29) between the sternotomy and clamshell group. Fifteen (14.2%) patients experienced a total of 25 surgical site complications (19 major and 6 minor). No sternotomy patient had a major surgical site complication and 11 (16.2%) clamshell patients had a major surgical site complication (p = 0.01). Of these 11 patients, 5 (45%) required multiple operative revisions related to the surgical site. Freedom from major surgical site complications at three years was 100% for sternotomy patients and 80% for clamshell patients (p = 0.017). CONCLUSIONS: Tailoring the operative approach can reduce surgical site complications in lung transplant patients by avoiding a clamshell whenever feasible.

Clinical implications of donor age: A single-institution analysis spanning 3 decades.

BACKGROUND: We sought to clarify the effect of donor age as a continuous variable on morbidity and mortality in a single-institution experience. METHODS: From 1986 to 2016, 882 adult lung transplants were performed, including 396 in the lung allocation score era. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate the association of donor age with overall survival and bronchiolitis obliterans syndrome (BOS) score ≥1-free survival. Logistic regression was used to evaluate the association with primary graft dysfunction grade 3. Natural cubic splines were used to explore donor age in a continuous fashion to allow for nonlinear relationships. RESULTS: In the lung allocation score era, unadjusted 5-year survival was not significantly different between 3 a priori-defined donor age groups: age <40, 40 to 54, and age ≥55 years (64%, 61%, and 69%, P = .8). Unadjusted 5-year freedom from BOS ≥1 was not significantly different (34%, 20%, and 33%, respectively, P = .1). After we adjusted for comorbidities, cubic spline analysis demonstrated no effect between donor age as a continuous variable and hazard for mortality at 5 years. Similarly, no interaction was seen between donor age and risk of BOS or primary graft dysfunction 3. Adjusted analysis of all 882 transplants pre- and postinception of the lung allocation score also showed no effect of age on 10-year survival. CONCLUSIONS: Long-term survival of lung transplant recipients was not affected by the age of the donor. These findings support the notion that donor age could be relaxed.

Gender differences in long-term survival post-transplant: A single-institution analysis in the lung allocation score era.

The purpose of this study was to clarify the significance of recipient gender status on lung transplant outcomes in a large single-institution experience spanning three decades, we analyzed data from all lung transplants performed in our institution since 1986. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate the effect of recipient characteristics on survival and BOS score ≥1-free survival. Logistic regression analysis was used to explore the association of gender with short-term graft function. About 876 lung transplants were performed between 1986 and 2016. Kaplan-Meier survival estimates at 5 years post-transplant for females vs males in the LAS era were 71% vs 58%. In the LAS era, females showed greater unadjusted BOS≥1-free survival than males (35% vs 25%, P=.02) over 5 years. Female gender was the only factor in the LAS era significantly associated with improved adjusted 5-year survival [HR 0.56 (95% CI 0.33, 0.95) P=.03]. Conversely, in the pre-LAS era female gender was not associated with improved survival. Female recipients showed significantly improved survival over 5 years compared to males in the LAS era. A prospective analysis of biologic and immunologic differences is warranted.

Paravertebral Catheter Use for Postoperative Pain Control in Patients After Lung Transplant Surgery: A Prospective Observational Study.

OBJECTIVE: Effective postoperative pain management has been shown to be a positive predictive factor for postoperative recovery following a thoracotomy. The primary objective of this study was to examine the efficacy and safety of continuous paravertebral blockade in managing acute postsurgical pain following unilateral and bilateral single-lung transplantation. DESIGN: The authors conducted a prospective observational trial of patients. SETTING: The study was conducted in an academic university hospital. PARTICIPANTS: Patients (≥18 years of age) who underwent either unilateral or bilateral single-lung transplantation and received a postoperative paravertebral catheter. INTERVENTIONS: Paravertebral catheters were placed via an ultrasound-guided technique on either postoperative day 1 or 2. After placement, a continuous infusion of 0.2% ropivacaine was run at 0.2 to 0.25 mL/kg/h with maximum dose of 7 mL/h per side in bilateral lung transplant patients, and 14 mL/h in unilateral lung transplant patients. MEASUREMENTS AND MAIN RESULTS: Patients were followed up to 120 hours after placement of catheters, and pain scores, opioid use, and adverse events were recorded. There were 35 patients who completed the study from October 2013 to December 2014 (21 bilateral transplants and 14 unilateral transplants). The mean time to paravertebral catheter placement was 1.14 days in the overall group, with median time to extubation occurring 543 minutes after placement (range, 23-2,985 minutes). Catheters remained in place for a mean of 7.18 days. The mean maximal pain scores for both groups was 5.94 (day 1), 6.26 (day 2), 6.20 (day 3), 5.12 (day 4), and 5.60 (day 5). There were no adverse events related to the paravertebral catheters in either group. CONCLUSIONS: Paravertebral catheters provide a feasible option for postoperative pain control following unilateral or bilateral single-lung transplant in adult patients. Future research should focus on randomized trials of thoracic epidurals compared to paravertebral catheters.

Process Improvement in Thoracic Donor Organ Procurement: Implementation of a Donor Assessment Checklist.

BACKGROUND: Donor organs are often procured by junior staff in stressful, unfamiliar environments where a single adverse event can be catastrophic. A formalized checklist focused on preprocedural processes related to thoracic donor organ procurement could improve detection and prevention of near miss events. METHODS: A checklist was developed centered on patient identifiers, organ compatibility and quality, and team readiness. It went through five cycles of feedback and revision using a panel of expert procurement surgeons. Educational in-service sessions were held on the use of the checklist as well as best organ assessment practices. Near miss events before the survey were tallied by retrospective review of 20 procurements, and near misses after checklist implementation were prospectively recorded. We implemented the checklist for 40 donor lung and heart procurements: 20 from Cleveland Clinic and 20 from the University of Minnesota. A final survey assessment was used to determine ease of use. RESULTS: Nine near miss events were reported in 20 procurements before use of the checklist. Thirty-one near miss events of 40 organ procurements were identified and potentially prevented by the checklist. Eighty-seven percent of fellows found the checklist to be unobtrusive to work flow, and 100% believed its use should be mandatory. Mortality was the same before and after implementation of the checklist despite increased patient volumes. CONCLUSIONS: Implementation of a simple checklist for use during thoracic organ procurement uncovered a substantial number of near miss events. A preprocedural checklist for all thoracic organ transplants in the United States and abroad is feasible and would likely reduce adverse events.