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.

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.

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.

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.

The First Repair of Cor Triatriatum.

This article describes the first patient treated surgically for cor triatriatum, and also describes preoperative testing, operative findings, and procedures, as well as follow-up.

Use of the donor lung after asphyxiation or drowning: effect on lung transplant recipients.

BACKGROUND: With the relative paucity of acceptable donors for lung transplantation, criteria for extended donor consideration are being explored. We sought to evaluate the suitability of donors whose cause of death was asphyxiation or drowning (A/D) as a potential option to enlarge the donor pool. METHODS: We queried the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research registry for lung transplantation from 1987 to 2010 to assess associations between cause of death and recipient survival using the Kaplan-Meier method. To adjust for potential confounders, we used a Cox proportional hazards model and a logistic regression model to evaluate incidence of rejection within the first year. RESULTS: There were 18,250 adult primary lung transplantations performed, with 309 A/D donors. There was no difference in survival between groups (log-rank, p = 0.52). There were no differences in demographics, length of stay, airway dehiscence, lung allocation score (LAS), or ischemic time in univariate analysis (all p > 0.05). The A/D lung recipients had fewer deaths from pulmonary causes (5.8% versus 9.5%; p = 0.02). Proportional hazards analysis was significant for double lung transplantation (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.8-0.9), height difference (HR, 1.002; 95% CI, 1.00-1.003), donor age greater than 50 years (HR, 0.89; 95% CI, 0.83-0.96), and recipient age greater than 55 years (HR, 0.8; 95% CI, 0.76-0.84). A/D cause of death did not impact survival in multivariate analysis. CONCLUSIONS: A/D as a donor cause of death was not associated with poor long-term survival or incidence of rejection in the first year after transplantation. Donor cause of death by A/D, when carefully evaluated and selected, should not automatically exclude the organ from transplant consideration. These results provide important justification for potentially broadening the donor pool safely.

Hemolysis, pump thrombus, and neurologic events in continuous-flow left ventricular assist device recipients.

BACKGROUND: An ongoing challenge in the management of patients with heart failure who receive left ventricular assist devices (LVADs) is achieving optimal anticoagulation. Adverse prothrombotic events include hemolysis or pump thrombus (H/T) and neurologic events (NEs), and all limit the success of LVAD therapy. Our aim was to study the incidence and clinical outcomes associated with these events in a large single-center cohort. METHODS: We retrospectively reviewed our prospectively collected database of all patients receiving a HeartMate II (Thoratec Corp, Pleasanton, CA) LVAD from 2005 to 2012. Demographic, clinical, and outcome data were analyzed using standard statistical methods. All adverse events were recorded. RESULTS: Of 193 patients receiving LVADs, we identified 39 H/T events in 26 (13.4%) patients and 22 NEs in 19 (9.8%) patients. Seventy-four percent of events occurred in the last 3 years of the series, during which time 63% of implants were placed. Of patients with H/T, 8 (31% of those having H/T, 4.1% of total) had more than 1 event and 4 (15.4% of those having H/T, 2.1% of total) underwent pump exchanges. Five (23%) patients had NEs after H/T, and 6 (32%) died as a result of the NE. Of patients with H/T, 27% had preceding episodes of infection, 31% had an international normalized ratio (INR) of less than 1.5, 31% had an INR of 1.5 to 2, 15% had a history of clotting or were hypercoagulable, and 4% had anticoagulation intentionally withheld. Lactate dehydrogenase (LDH), plasma hemoglobin, INR, and platelet determinations were significantly different at the time of H/T compared with baseline values. The survival at 6 months (alive or having undergone transplantation) for those with a prothrombotic event compared with those without was 70% versus 75.2% (p = 0.5). CONCLUSIONS: The incidence of H/T or NEs is significant and results in major morbidity after LVAD placement. Infection and suboptimal anticoagulation are associated with the majority of these events. Identification of patients at higher risk for hemolysis (ie, infection) may allow for modification of anticoagulation regimens to reduce these risks and improve clinical outcomes.

Clostridium difficile infection increases mortality risk in lung transplant recipients.

BACKGROUND: Clostridium difficile infection (CDI) and associated mortality in solid organ transplant recipients is rising, but data are scarce in lung transplant recipients. We aimed to characterize CDI and its effect on mortality in a large cohort of lung transplant recipients. METHODS: Lung transplant recipients were identified from our transplant database from 2000 to 2011. Cox proportional hazard models were used to calculate hazard ratios for CDI and death after adjusting for potential confounders identified from bivariate analysis. RESULTS: We identified 388 patients (196 female, 192 male), with a median age of 56 years (range, 8-75 years), during the study period. CDI developed after transplant in 89 (22.9%), with 27 (7.0%) developing CDI during the initial hospitalization at a mean diagnosis of 12.7 ± 11.4 days. Incidence varied widely each year (median, 24%; range, 5%-32%), with the highest rates in 2007 to 2008. Post-operative length of stay was identified as a significant predictor of CDI (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03). Early CDI was an independent significant predictor of death (HR, 1.96; 95% CI, 1.14-3.36) as well as CDI anytime after transplant (HR, 1.61; 95% CI, 1.02-2.52). CONCLUSIONS: CDI rates varied widely from 2000 through 2011, with the highest rates in 2007 to 2008. Lung transplant recipients who developed CDI had a higher risk of death, especially when CDI occurred in the first 6 months after transplant.

Left ventricular outflow tract occluding thrombus after biventricular mechanical circulatory support as a bridge to recovery.

The role of mechanical circulatory support for cardiopulmonary failure is expanding. Anticoagulation in the setting of static blood, hypercoagulable states, extracorporeal circuits, and surgery presents an intricate and delicate balance. We present a patient with large, biventricular thrombi during and succeeding biventricular mechanical support. Management of the thrombi and device selection in this patient are discussed.