Early Extubation: Who Qualifies Postoperatively in Lung Transplantation?

INTRODUCTION: Early extubation has been adopted in many settings within cardiothoracic surgery, with several advantages for patients. We sought to determine the association of timing of extubation in lung transplant recipients' short- and long-term outcomes. METHODS: Adult, primary lung transplants were identified from the United Network for Organ Sharing database. Recipients were stratified based on the duration of postoperative ventilation: 1) None (NV); 2) <5 Days (<5D); and 3) 5+ Days (5+D). Comparative statistics were performed, and both unadjusted and adjusted survival were analyzed with Kaplan-Meier Methods and a Cox proportional hazard model. A multivariable model including recipient, donor, and transplant characteristics was created to examine factors associated with NV. RESULTS: 28,575 recipients were identified (NV = 960, <5D = 21,959, 5+D = 5656). The NV group had shorter median length of stay (P < 0.01) and lower incidence of postoperative dialysis (P < 0.01). The NV and <5D groups had similar survival, while 5+D recipients had decreased survival (P < 0.01). The multivariable model demonstrated increased donor BMI, center volume, ischemic time, single lung transplant, and transplantation between 2011 and 2015 were associated with NV (P < 0.01 for all). Use of donation after cardiac death donors and transplantation between 2016 and 2021 was associated with postoperative ventilator use. CONCLUSIONS: Patients extubated early after lung transplantation have a shorter median length of stay without an associated increase in mortality. While not all patients are appropriate for earlier extubation, it is possible to extubate patients early following lung transplant. Further efforts are necessary to help expand this practice and ensure its' success for recipients.

Long-Term Survival Following Primary Graft Dysfunction Development in Lung Transplantation.

INTRODUCTION: Primary graft dysfunction (PGD) is a known risk factor for early mortality following lung transplant (LT). However, the outcomes of patients who achieve long-term survival following index hospitalization are unknown. We aimed to determine the long-term association of PGD grade 3 (PGD3) in patients without in-hospital mortality. METHODS: LT recipients were identified from the United Network for Organ Sharing Database. Patients were stratified based on the grade of PGD at 72 h (No PGD, Grade 1/2 or Grade 3). Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariable shared frailty model including recipient, donor, and transplant characteristics. RESULTS: The PGD3 group had significantly increased length of stay, dialysis, and treated rejection post-transplant (P < 0.001). Unadjusted survival analysis revealed a significant difference in long-term survival (P < 0.001) between groups; however, following adjustment, PGD3 was not independently associated with long-term survival (hazard ratio: 0.972; 95% confidence interval: 0.862-1.096). Increased mortality was significantly associated with increased recipient age and treated rejection. Decreased mortality was significantly associated with no donor diabetes, bilateral LT as compared to single LT, transplant in 2015-2016 and 2017-2018, and no post-transplant dialysis. CONCLUSIONS: While PGD3 remains a challenge post LT, PGD3 at 72 h is not independently associated with decreased long-term survival, while complications such as dialysis and rejection are, in patients who survive index hospitalization. Transplant providers should be aggressive in preventing further complications in recipients with severe PGD to minimize the negative association on long-term survival.

Single-Cell Analysis Reveals Distinct Immune and Smooth Muscle Cell Populations that Contribute to Chronic Thromboembolic Pulmonary Hypertension.

Rationale: Chronic thromboembolic pulmonary hypertension (CTEPH) is a sequela of acute pulmonary embolism (PE) in which the PE remodels into a chronic scar in the pulmonary arteries. This results in vascular obstruction, pulmonary microvasculopathy, and pulmonary hypertension. Objectives: Our current understanding of CTEPH pathobiology is primarily derived from cell-based studies limited by the use of specific cell markers or phenotypic modulation in cell culture. Therefore, our main objective was to identify the multiple cell types that constitute CTEPH thrombusy and to study their dysfunction. Methods: Here we used single-cell RNA sequencing of tissue removed at the time of pulmonary endarterectomy surgery from five patients to identify the multiple cell types. Using in vitro assays, we analyzed differences in phenotype between CTEPH thrombus and healthy pulmonary vascular cells. We studied potential therapeutic targets in cells isolated from CTEPH thrombus. Measurements and Main Results: Single-cell RNA sequencing identified multiple cell types, including macrophages, T cells, and smooth muscle cells (SMCs), that constitute CTEPH thrombus. Notably, multiple macrophage subclusters were identified but broadly split into two categories, with the larger group characterized by an upregulation of inflammatory signaling predicted to promote pulmonary vascular remodeling. CD4+ and CD8+ T cells were identified and likely contribute to chronic inflammation in CTEPH. SMCs were a heterogeneous population, with a cluster of myofibroblasts that express markers of fibrosis and are predicted to arise from other SMC clusters based on pseudotime analysis. Additionally, cultured endothelial, smooth muscle, and myofibroblast cells isolated from CTEPH fibrothrombotic material have distinct phenotypes from control cells with regard to angiogenic potential and rates of proliferation and apoptosis. Last, our analysis identified PAR1 (protease-activated receptor 1) as a potential therapeutic target that links thrombosis to chronic PE in CTEPH, with PAR1 inhibition decreasing SMC and myofibroblast proliferation and migration. Conclusions: These findings suggest a model for CTEPH similar to atherosclerosis, with chronic inflammation promoted by macrophages and T cells driving vascular remodeling through SMC modulation, and suggest new approaches for pharmacologically targeting this disease.

The Association of Persistent Poverty and Outcomes Among Patients Undergoing Cardiac Surgery.

INTRODUCTION: We sought to evaluate the association of county-level poverty duration and cardiac surgical outcomes. METHODS: Patients who underwent coronary artery bypass graft, surgical aortic valve replacement, and mitral valve repair and replacement between 2016 and 2020 were identified using the Medicare Standard Analytical Files Database. County-level poverty data were acquired from the American Community Survey and US Department of Agriculture (1980-2015). High poverty was defined as ≥19.5% of residents in poverty. Patients were stratified into never-high poverty (NHP), intermittent low poverty, intermittent high poverty, and persistent poverty (PP). A mixed-effect hierarchical generalized linear model and Cox regression models that adjusted for patient-level covariates were used to evaluate outcomes. RESULTS: Among 237,230 patients, 190,659 lived in NHP counties, while 10,273 resided in PP counties. Compared with NHP patients, PP patients were more likely to present at a younger median age (NHP: 75 y versus PP: 74 y), be non-Hispanic Black (5388, 2.9% versus PP: 1030, 10.1%), and live in the south (NHP: 66,012, 34.6% versus PP: 87,815, 76.1%) (all P < 0.001). PP patients also had more nonelective surgical operations (NHP: 58,490, 30.8% versus 3645, 35.6%, P < 0.001). Notably, PP patients had increased odds of 30-d mortality (odds ratio 1.13, 95% confidence interval [CI] 1.02-1.26), 90-d mortality (odds ratio 1.14, 95% CI 1.05-1.24), and risk of long-term mortality (hazard ratio 1.13, 95% CI 1.09-1.19) compared with patients in NHP counties (all P < 0.05). CONCLUSIONS: County-level poverty was associated with a greater risk of short- and long-term mortality among cardiac surgical patients.

XPS™ Jensen lung as a low-cost, high-fidelity training adjunct to ex-vivo lung perfusion.

BACKGROUND: Ex vivo lung perfusion (EVLP) enables lung resuscitation before transplantation, and training is key, particularly in low-volume settings. To enable technique refinement and continuing education, we sought to demonstrate the value of a low-cost, high-fidelity EVLP simulator that would allow reproducible clinical scenarios. METHODS: In partnership with our EVLP manufacturer, we utilized the XPS™ Jensen Lung with our clinical system. The Jensen Lung has two simulated lung bladders and an in-line polymethylpentene fiber oxygenator. It allows titration of ventilator support which aids in accurate clinical simulation. For simulations, blood gases (BGs) were obtained and compared with integrated in-line perfusate gas monitors (PGMs). PaO2 , PCO2 , and pH were measured and compared. RESULTS: The PGM and BG values were not significantly different throughout the range of FiO2 and sweep gas flow rates evaluated. The "delta" PaO2 was measured between LA and PA and did not show any change between approaches. The pH measurement between BG and PGM was not significantly different. CONCLUSIONS: The XPS™ Jensen Lung simulator allows for a high-fidelity simulator of clinical EVLP. The correlation of the PGM and the BG measurement of the PaO2 and pH allow for a low-cost simulation, as the PGMs are in line in the circuit, and enable real-time tracking of perfusate gas parameters with the PGM. Implementation of a standardized clinical EVLP training program allows the maintenance of technique and enables clinical simulation training without the need for costly animal perfusions and the use of multiple BG measurements.

Thoracic transplantation during the COVID-19 pandemic.

The worldwide pandemic caused by COVID-19, resulting from the infection by betacoronarvirus SARS-CoV-2, has dramatically altered healthcare worldwide. Due to the highly contagious nature of SARS-CoV2, coupled with hospitals and intensive care units being overwhelmed, numerous transplant programs either slowed or shut down completely. While there have been isolated reports of COVID-19 in transplant recipients, no study to date has examined how COVID-19 affected actual transplant patterns and outcomes in the United States. Of particular importance is the impact of COVID-19 on mortality in waitlisted patients and transplant recipients. Using the Scientific Registry of Transplant Recipients (SRTR) dataset, we compared waitlist and transplant characteristics from 3/2019-8/2019 to 3/2020-8/2020, as well as COVID-19 associated mortality in patients with prior heart or lung transplant or those active on the waitlist. Overall, there was an initial decrease in transplant volume in April 2020; however, volumes have normalized since then, with comparable outcomes to similar calendar months in 2019. Additionally, there were no significant changes in post-transplant outcomes or waiting list mortality. Given the ongoing COVID-19 pandemic, it would be beneficial to maintain current practices for thoracic transplantation, to continue to provide this life-saving therapy to those in need.

Lung transplantation in the septuagenarian can be successfully performed though long-term results impacted by diseases of aging.

BACKGROUND: Advanced age is considered a risk factor for lung transplantation (LTX). We sought to evaluate the long-term outcomes of LTX in the septuagenarian. METHODS: LTX recipients in the UNOS transplant registry (May 1, 2005-June 12, 2020) were stratified into 18-59, 60-69, and > = 70 years of age. Recipient and transplant characteristics were evaluated for survival, cause of death (COD), length of stay (LOS), and complications. A Kaplan-Meier analysis examined long-term survival for all patients stratified by age, specifically looking at cause of death. RESULTS: A total of 27 632 recipients were identified. As recipients aged, we found a decrease in proportion of cystic fibrosis and an increase in restrictive disease while obstructive disease peaked in the 60-69yo cohort (P < .001). Septuagenarians had higher rates of single LTX, male gender, and white race (P < .001). Older recipients had significantly longer donor recovery distances traveled with paradoxical shorter ischemic times, shorter hospital LOS and were transplanted at higher volume centers. There was no difference with in-hospital mortality among groups (P = .5). Acute rejection during initial hospitalization, rejection within 1 year, and post-transplant dialysis incidence decreased with age. Graft failure was a common COD in younger patients while malignancy and cardio/cerebrovascular diseases were common COD in > = 70yo. CONCLUSION: Select septuagenarian LTX candidates may be safely transplanted with relatively few complications. Immunosenescence and conditions of the aged are likely contributing factors to the decreased rejection and graft failure observations. Septuagenarians should not be excluded from LTX consideration based solely on age. Transplantation in septuagenarians should only be done in very selected patients (screened for malignancies and atherosclerotic disease) and these recipients should be carefully followed after transplantation because of these risk factors.

Safety of direct oral anticoagulants in solid organ transplant recipients: A meta-analysis.

There is limited evidence comparing direct oral anticoagulants (DOACs) and warfarin in solid organ transplant (SOT) recipients. We performed a pooled analysis to study the safety and efficacy of DOACs in this patient population. We searched PubMed, Embase, and Scopus databases using the search terms "heart transplant" or "lung transplant" or "liver transplant" or "kidney transplant" or "pancreas transplant" and "direct oral anticoagulant" for literature search. Random effects model with Mantel-Haenszel method was used to pool the outcomes. Pooled analysis included 489 patients, of which 259 patients received DOACs and 230 patients received warfarin. When compared to warfarin, the use of DOACs was associated with decreased risk of composite bleed (RR .49, 95% CI .32-.76, p = .002). There were no differences in rates of major bleeding (RR .55, 95% CI .20-1.49, p = .24) or venous thromboembolism (RR .65, 95% CI .25-1.70, p = .38) between the two groups. Evidence from pooled analysis suggests that DOACs are comparable to warfarin in terms of safety in SOT recipients. Further research is warranted to conclusively determine whether DOACs are safe alternatives to warfarin for anticoagulation in SOT recipients.

Insights into early postoperative acute kidney injury following lung transplantation.

BACKGROUND: Acute kidney injury (AKI) is a common complication after lung transplantation (LT) and is associated with higher cost and mortality. We sought to evaluate the incidence of postoperative AKI, defined as AKI within 14 days of transplant, and identify associated perioperative factors. METHODS: We conducted a single-center, retrospective review of 153 lung transplant recipients. Postoperative AKI was determined using the RIFLE (Risk, Injury, Failure, Loss, End Stage) criteria. Perioperative covariates and their association with postoperative AKI were analyzed using Cox proportional hazards. Kaplan-Meier survival curves were constructed to evaluate patient survival at 1 year and data finalization. A sub-analysis was performed evaluating factors associated with early AKI (within 48 h of transplant) and late AKI. RESULTS: Postoperative AKI occurred in 36.6% of patients with 51.8% of cases occurring within 48 h of LT. Recipient race, transplant type, cardiopulmonary support, and red blood cell administration were associated with postoperative AKI. Survival was significantly lower in patients with postoperative AKI following LT. CONCLUSIONS: Postoperative AKI within 2 weeks of lung transplant is associated with lower short- and long-term survival. Perioperative factors associated with postoperative AKI may be potential points of intervention to minimize AKI development in the future.

Trends in Donation After Circulatory Death in Lung Transplantation in the United States: Impact Of Era.

Background: Use of lungs donated after circulatory death (DCD) has expanded, but changes in donor/recipient characteristics and comparison to brain dead donors (DBD) has not been studied. We examined the evolution of the use of DCD lungs for transplantation and compare outcomes to DBD lungs. Methods: The SRTR database was used to construct three 5-year intervals. Perioperative variables and survival were compared by era and for DCD vs. DBD. Geographic variation was estimated using recipient permanent address. Results: 728 DCD and 27,205 DBD lung transplants were identified. DCD volume increased from Era 1 (n = 73) to Era 3 (n = 528), representing 1.1% and 4.2% of lung transplants. Proportionally more DCD recipients were in ICU or on ECMO pre-transplant, and had shorter waitlist times. DCD donors were older, had lower PaO2/FiO2 ratios compared to DBD, more likely to be bilateral, had longer ischemic time, length of stay, post-op dialysis, and increased use of lung perfusion. There was no difference in overall survival. Geographically, use was heterogeneous. Conclusion: DCD utilization is low but increasing. Despite increasing ischemic time and transplantation into sicker patients, survival is similar, which supports further DCD use in lung transplantation. DCD lung transplantation presents an opportunity to continue to expand the donor pool.

Disparities in heart transplantation.

PURPOSE OF REVIEW: Heart transplantation remains the gold standard therapy for end stage heart failure, but barriers remain, preventing equitable access to and affecting outcomes following transplantation. The objective of this review is to summarize current and historical literature on the disparities that persist, and to highlight the gaps in evidence for further investigation. RECENT FINDINGS: Although progress has been made to increase the rates of advanced heart failure therapies to racial/ethnic minority populations and those with lower socioeconomic status, differential access and outcomes remain. The disparities that persist are categorized by patient demographics, social influences, geopolitical factors, and provider bias. SUMMARY: Disparities in heart transplantation exist, which span a wide spectrum. Healthcare professionals need to be cognizant of these disparities that patients face in terms of access to and outcomes for heart transplantation. Further research and system changes are needed to make heart transplantation a fairer option for patients of varying backgrounds with end stage heart failure.

Superior vena cava syndrome during veno-venous extracorporeal membrane oxygenation for COVID-19.

Superior vena cava (SVC) syndrome is typically associated with malignant tumors obstructing the SVC, but as many as 40% of cases have other etiologies. SVC obstruction was previously described during veno-venous extracorporeal membrane oxygenation therapy (VV ECMO) in children. In this report, we describe a woman with adult respiratory distress syndrome resulting from infection with coronavirus-19 who developed SVC syndrome during VV ECMO. A dual-lumen ECMO cannula was inserted in the right internal jugular vein, but insufficient ECMO circuit flow, upper body edema, and signs of hypovolemic shock were observed. This clinical picture resolved when the right internal jugular vein was decannulated in favor of bilateral femoral venous cannulae. Our report demonstrates that timely recognition of clinical signs and symptoms led to the appropriate diagnosis of an uncommon ECMO complication.

Early COVID-19 infection after lung transplantation.

COVID-19, the clinical syndrome caused by the novel coronavirus, SARS-CoV-2, continues to rapidly spread, leading to significant stressors on global healthcare infrastructure. The manifestations of COVID-19 in solid organ transplant recipients are only beginning to be understood with cases reported to date in transplant recipients on chronic immunosuppression. Herein, we report the first case of COVID-19 in a lung transplant recipient in the immediate posttransplant period, and we describe the epidemiologic challenges in identifying the source of infection in this unique situation.

Continuous-Flow Left Ventricular Assist Devices and the Aortic Valve: Interactions, Issues, and Surgical Therapy.

PURPOSE OF REVIEW: Concomitant valve disease is common in patients undergoing continuous-flow left ventricular assist device (CF-LVAD) implantation. In this review, we characterize the epidemiology and management of aortic valve disease following CF-LVAD. RECENT FINDINGS: Studies suggest that 20-40% of patients have mild or greater aortic insufficiency (AI) at baseline and that AI progresses following CF-LVAD implantation. AI, either pre-existing or de novo, can have deleterious effects on LVAD efficacy and clinical outcomes. Surgical methods to correct AI in patients supported with CF-LVAD include central oversewing of the aortic valve, complete closure of the aortic valve, patch closure of the ventriculo-aortic junction, or aortic valve replacement with a bioprosthesis. Transcatheter options have recently emerged as feasible modalities to address AI. CF-LVADs contribute to the progression of aortic insufficiency (AI) and its development de novo. Prompt recognition, assessment, and treatment are important. Aortic valve repairs and replacements, now including TAVR, are the primary surgical methods to correct AI.

Survival after lung transplantation in recipients with alpha-1-antitrypsin deficiency compared to other forms of chronic obstructive pulmonary disease: a national cohort study.

Alpha-1-antitrypsin deficiency (AATD) is grouped with chronic obstructive pulmonary disease (COPD); however, this may not be appropriate. This study assessed whether AATD confers a different prognosis than COPD following lung transplantation. We employed the United Network for Organ Sharing (UNOS) database, grouping patients by diagnoses of AATD or COPD. Kaplan-Meier methods and Cox modeling were performed to determine the association of diagnosis and overall survival. Of 9569 patients, 1394 (14.6%) had a diagnosis of AATD. Patients with AATD who received a single-lung transplant had reduced 1-year survival [adjusted hazard ratio (AHR): 1.68, 95% CI: 1.26, 2.23]. Among patients who received a bilateral lung transplant, there was no significant difference in survival by diagnosis (AHR for AATD as compared to COPD: 0.96, 95% CI: 0.82, 1.12). After the implementation of the lung allocation score (LAS), there was no significant difference in survival among patients who received a single (AHR: 1.15, 95% CI: 0.69, 1.95) or bilateral (AHR: 0.99, 95% CI: 0.73, 1.34) lung transplant by diagnosis. Lung transplantation is increasingly employed in the care of the patient with COPD. Although recipients undergoing LTX for AATD are at increased risk of both acute rejection and airway dehiscence post-transplant, in the post-LAS era, survival rates are similar for recipients with AATD in comparison with COPD.

Traveling to a High-volume Center is Associated With Improved Survival for Patients With Esophageal Cancer.

BACKGROUND: An association between volume and outcomes has been observed for esophagectomy, though little is known about why or how patients choose low- or high-volume centers. The purpose of this study was to evaluate how travel burden and hospital volume influence treatment and outcomes of patients with locally advanced esophageal cancer. METHODS: Predictors of receiving esophagectomy for patients with T1-3N1M0 mid or distal esophageal cancer in the National Cancer Data Base from 2006 to 2011 were identified using multivariable logistic regression. Survival was compared using propensity score-matched groups: patients in the bottom quartile of travel distance who underwent treatment at low-volume facilities (Local) and patients in the top quartile of travel distance who underwent treatment at high-volume facilities (Travel). RESULTS: Of 4979 patients who met inclusion criteria, we identified 867 Local patients who traveled 2.7 [interquartile range (IQR): 1.6-4 miles] miles to centers that treated 2.6 (IQR: 1.9-3.3) esophageal cancers per year, and 317 Travel patients who traveled 107.1 (IQR: 65-247) miles to centers treating 31.9 (IQR: 30.9-38.5) cases. Travel patients were more likely to undergo esophagectomy (67.8% vs 42.9%, P < 0.001) and had significantly better 5-year survival (39.8% vs 20.6%, P < 0.001) than Local patients. CONCLUSIONS: Patients who travel longer distances to high-volume centers have significantly different treatment and better outcomes than patients who stay close to home at low-volume centers. Strategies that support patient travel for treatment at high-volume centers may improve esophageal cancer outcomes.

The association of donor age and survival is independent of ischemic time following deceased donor lung transplantation.

PURPOSE: Early research suggests prolonged ischemic time in older donor lungs is associated with decreased survival following lung transplantation. The purpose of this study was to determine whether this association holds in the post-lung allocation score era. METHODS: We analyzed the United Network for Organ Sharing database 2005-2013 for adult recipients of cadaveric lung transplants. Cox proportional hazards modeling was utilized to determine the association of donor age, ischemic time, and the interaction of donor age and ischemic time with transplant-free survival. RESULTS: Eleven thousand eight hundred thirty-five patients met criteria. Median donor age was 32 years, and median ischemic time was 4.9 hours. Cox modeling demonstrated that donor age 50-60 (adjusted hazard ratio (HR): 1.11) and ≥60 (adjusted HR: 1.42) were associated with reduced overall survival. Neither ischemic time nor interaction of ischemic time and donor age were significantly associated with overall survival. Subanalysis demonstrated that this finding held true for patients undergoing either single or bilateral lung transplantation. CONCLUSIONS: Prolonged ischemic time is not associated with decreased overall survival in patients undergoing lung transplantation regardless of the donor's age. However, donor age >50 is independently associated with decreased survival. The lack of an association between ischemic time and survival should encourage broader geographic allocation of pulmonary allografts.

Lung transplantation delays gastric motility in patients without prior gastrointestinal surgery-A single-center experience of 412 consecutive patients.

PURPOSE: To examine the impact of lung transplantation on gastric motility. METHODS: Adult recipients at a large, single center, who were retrospectively evaluated with solid gastric emptying (SGE) study post-lung transplantation, but had no history of gastrointestinal intervention (ie, pyloroplasty or fundoplication), were selected between June 2005 and August 2013. Multivariable logistic regression was performed to determine risk factors associated with delayed gastric emptying (DGE) after transplantation. RESULTS: Delayed gastric emptying (DGE) was noted in 236 patients (57%) after transplantation. On multivariable logistic regression, an underlining diagnosis of cystic fibrosis (CF)/bronchiectasis (adjusted odds ratio [AOR] 3.26, P < .01) was a significant risk factor in predicting DGE after lung transplantation. There was no survival difference between patients with postoperative DGE vs those without (log-rank test P = .53). CONCLUSIONS: Delayed gastric emptying is very common following lung transplantation, occurring in over half of all lung transplant recipients with increased prevalence in patients with CF. The association with cystic fibrosis could be secondary to extra-pulmonary manifestations of the underlying disease or indicative of increased intraoperative vagal nerve injury. We speculate that DGE may play a substantial role in the increased reflux-induced allograft injury seen after lung transplantation. Further prospective studies are needed to validate this hypothesis.