Single Versus Double Lung Transplant in Older Adults: A Propensity-Matched Analysis.

BACKGROUND: Single lung transplantation (SLT) is associated with worse long-term outcomes than bilateral lung transplantation (BLT) but is often performed for older adults at risk of not tolerating BLT. RESEARCH QUESTION: How do the outcomes of SLT and BLT compare among older adult recipients? STUDY DESIGN AND METHODS: The Scientific Registry of Transplant Recipients database (2005-2022) was queried for lung transplant recipients aged ≥65 years. Patients were stratified by whether they underwent BLT or SLT, and propensity matched. Baseline characteristics and morbidity were compared with frequentist statistics. Survival was analyzed via Kaplan-Meier estimation. Risk factors for mortality were identified with Cox regression. RESULTS: Of 9,904 included patients, 4,829 (48.8%) underwent SLT. SLT patients had lower lung allocation scores (39.6 v. 40.6, p<0.001), more interstitial lung disease (74.4% v. 64.6%, p<0.001) and lower rates of bridging (0.7% v. 2.4%, p<0.001). Groups did not differ significantly by sex, body mass index, or donor characteristics. Propensity matching resulted in 2,539 patients in each group. On matched analysis, SLT patients had shorter lengths of stay (14 v. 18 d), lower reintubation rates (14.7% v. 19.8%), and less postoperative dialysis use (4.2% v. 6.4%) (all p<0.001). SLT patients had comparable survival at 30-days (97.6% v. 97.3%, p=0.414) and 1-year (85.5% v. 86.3%, p=0.496), but lower survival at 5-years (45.4% v. 53.4%, p<0.001) on matched analysis. SLT was a risk factor for 5-year mortality (adjusted hazard ratio: 1.19, p<0.001). INTERPRETATION: In older adults, SLT is associated with less morbidity and comparable early survival relative to BLT, but lower five-year survival. SLT is reasonable to perform in older adults at high risk for BLT.

Crossing national borders for transplantation: A focused evaluation of deceased donor lung exports from the United States.

Organ transplantation is a life-saving treatment for end-stage organ failure patients, but the United States (US) faces a shortage of available organs. US policies incentivize identifying recipients for all recovered organs. Technological advancements have extended donor organ viability, creating new opportunities for long-distance transport and international sharing. We aimed to assess organ exports from deceased US donors to candidates abroad, a component of allocation policy allowed without suitable domestic candidates. Based on the national Scientific Registry of Transplant Recipients data from January 2014 to September 2023, 388 342 organs were recovered for transplantation, with 511 (0.13%) exported. Most exported organs were lungs (80%). Exported lung donors were older (41 vs 34 years, P < .001), more likely hepatitis C positive (22% vs 4%, P < .001), and more likely donors after circulatory death (20% vs 7%, P < .001). Lungs that were eventually exported were offered to more US potential transplant recipients (median = 65) than those kept in the US (median = 21 and 41 for lungs recovered by nonexporting and exporting organ procurement organizations, respectively; P < .001). Our study highlights the necessity for further research and clear policy initiatives to balance the benefits of cross-border sharing while considering potential opportunities for more aggressive organ allocation within the US.

Diaphragmatic palsy following lung transplantation.

Diaphragmatic palsy after lung transplantation has been reported infrequently. Given the role of the diaphragm in respiration, the palsy may play a significant role in the post-surgical recovery as well as morbidity and mortality. This review summarises the current literature to better understand diaphragmatic palsy in the post lung-transplant setting among adults. A thorough literature search was conducted through multiple databases and 91 publications were identified that fit the research question. The review aimed to report the burden of this problem, explore different modalities of diagnosis reported, the effect of various clinical factors and treatment modalities, as well as their effects on outcomes. Additionally, it aimed to highlight the variability, limitations of reported data, and the absence of a standardised approach. This review emphasises the crucial need for more dedicated research to better address this clinical challenge.

Real-time lung weight measurement during clinical ex vivo lung perfusion.

BACKGROUND: Real-time lung weight (LW) measurement is a simple and noninvasive technique for detecting extravascular lung water during ex vivo lung perfusion (EVLP). We investigated the feasibility of real-time LW measurement in clinical EVLP as a predictor of transplant suitability and post-transplant outcomes. METHODS: In our clinical acellular EVLP protocol, real-time LW was measured in 117 EVLP cases from June 2019 to June 2022. The estimated LW gain at each time point was calculated using a scale placed under the organ chamber. The lungs were classified into 4 categories based on LW adjusted for height and compared between suitable and unsuitable cases. The relationship between estimated LW gain and primary graft dysfunction was also investigated. RESULTS: The estimated LW gain during the EVLP significantly correlated with the LW gain (post-EVLP LW and pre-EVLP LW) measured on the back table (R2 = 0.61, p < 0.01). In the adjusted LW categories 2 to 4, the estimated LW gain at 0-1 hour after EVLP was significantly higher in unsuitable cases than in suitable cases. The area under the curve for the estimated LW gain was ≥0.80. Primary graft dysfunction grades 0 to 1 had a significantly lower estimated LW gain at 60 minutes than grades 2 to 3 (-43 vs 1 g, p < 0.01). CONCLUSIONS: Real-time lung measurements can predict transplant suitability and post-transplant outcomes by the early detection of extravascular lung water during the initial 1 hour of EVLP.

Intermittent Ex Vivo Lung Perfusion in a Porcine Model for Prolonged Lung Preservation.

BACKGROUND: Ex vivo lung perfusion expands the lung transplant donor pool and extends preservation time beyond cold static preservation. We hypothesized that repeated regular ex vivo lung perfusion would better maintain lung grafts. METHODS: Ten pig lungs were randomized into 2 groups. The control underwent 16 h of cold ischemic time and 2 h of cellular ex vivo lung perfusion. The intermittent ex vivo lung perfusion group underwent cold ischemic time for 4 h, ex vivo lung perfusion (first) for 2 h, cold ischemic time for 10 h, and 2 h of ex vivo lung perfusion (second). Lungs were assessed, and transplant suitability was determined after 2 h of ex vivo lung perfusion. RESULTS: The second ex vivo lung perfusion was significantly associated with better oxygenation, limited extravascular water, higher adenosine triphosphate, reduced intraalveolar edema, and well-preserved mitochondria compared with the control, despite proinflammatory cytokine elevation. No significant difference was observed in the first and second perfusion regarding oxygenation and adenosine triphosphate, whereas the second was associated with lower dynamic compliance and higher extravascular lung water than the first. Transplant suitability was 100% for the first and 60% for the second ex vivo lung perfusion, and 0% for the control. CONCLUSIONS: The second ex vivo lung perfusion had a slight deterioration in graft function compared to the first. Intermittent ex vivo lung perfusion created a better condition for lung grafts than cold static preservation, despite cytokine elevation. These results suggested that intermittent ex vivo lung perfusion may help prolong lung preservation.

Arterial Hyperoxemia During Cardiopulmonary Bypass Was Not Associated With Worse Postoperative Pulmonary Function: A Retrospective Cohort Study.

BACKGROUND: Arterial hyperoxemia may cause end-organ damage secondary to the increased formation of free oxygen radicals. The clinical evidence on postoperative lung toxicity from arterial hyperoxemia during cardiopulmonary bypass (CPB) is scarce, and the effect of arterial partial pressure of oxygen (Pa o2 ) during cardiac surgery on lung injury has been underinvestigated. Thus, we aimed to examine the relationship between Pa o2 during CPB and postoperative lung injury. Secondarily, we examined the relationship between Pa o2 and global (lactate), and regional tissue malperfusion (acute kidney injury). We further explored the association with regional tissue malperfusion by examining markers of cardiac (troponin) and liver injury (bilirubin). METHODS: This was a retrospective cohort study including patients who underwent elective cardiac surgeries (coronary artery bypass, valve, aortic, or combined) requiring CPB between April 2015 and December 2021 at a large quaternary medical center. The primary outcome was postoperative lung function defined as the ratio of Pa o2 to fractional inspired oxygen concentration (F io2 ); P/F ratio 6 hours following surgery or before extubation. The association between CPB in-line sample monitor Pa o2 and primary, secondary, and exploratory outcomes was evaluated using linear or logistic regression models adjusting for available baseline confounders. RESULTS: A total of 9141 patients met inclusion and exclusion criteria, and 8429 (92.2%) patients had complete baseline variables available and were included in the analysis. The mean age of the sample was 64 (SD = 13), and 68% were men (n = 6208). The time-weighted average (TWA) of in-line sample monitor Pa o2 during CPB was weakly positively associated with the postoperative P/F ratio. With a 100-unit increase in Pa o2 , the estimated increase in postoperative P/F ratio was 4.61 (95% CI, 0.71-8.50; P = .02). Our secondary analysis showed no significant association between Pa o2 with peak lactate 6 hours post CPB (geometric mean ratio [GMR], 1.01; 98.3% CI, 0.98-1.03; P = .55), average lactate 6 hours post CPB (GMR, 1.00; 98.3% CI, 0.97-1.03; P = .93), or acute kidney injury by Kidney Disease Improving Global Outcomes (KDIGO) criteria (odds ratio, 0.91; 98.3% CI, 0.75-1.10; P = .23). CONCLUSIONS: Our investigation found no clinically significant association between Pa o2 during CPB and postoperative lung function. Similarly, there was no association between Pa o2 during CPB and lactate levels, postoperative renal function, or other exploratory outcomes.

What determines outcomes in multivalve reoperations? Effect of patient and surgical complexity.

OBJECTIVE: Patient characteristics, risks, and outcomes associated with reoperative multivalve cardiac surgery are poorly characterized. Effect of patient variables and surgical components of each reoperation were evaluated with regard to operative mortality. METHODS: From January 2008 to January 2022, 2324 patients with previous cardiac surgery underwent 2352 reoperations involving repair or replacement of multiple cardiac valves at Cleveland Clinic. Mean age was 66 ± 14 years. Number of surgical components representing surgical complexity (valve procedures, aortic surgery, coronary artery bypass grafting, and atrial fibrillation procedures) ranged from 2 to 6. Random forest for imbalanced data was used to identify risk factors for operative mortality. RESULTS: Surgery was elective in 1327 (56%), urgent in 1006 (43%), and emergency in 19 (0.8%). First-time reoperations were performed in 1796 (76%) and 556 (24%) had 2 or more previous operations. Isolated multivalve operations comprised 54% (1265) of cases; 1087 incorporated additional surgical components. Two valves were operated on in 80% (1889) of cases, 3 in 20% (461), and 4 in 0.09% (2). Operative mortality was 4.2% (98 out of 2352), with 1.7% (12 out of 704) for elective, isolated multivalve reoperations. For each added surgical component, operative mortality incrementally increased, from 2.4% for 2 components (24 out of 1009) to 17% for ≥5 (5 out of 30). Predictors of operative mortality included coronary artery bypass grafting, surgical urgency, cardiac, renal dysfunction, peripheral artery disease, New York Heart Association functional class, and anemia. CONCLUSIONS: Elective, isolated reoperative multivalve surgery can be performed with low mortality. Surgical complexity coupled with key physiologic factors can be used to inform surgical risk and decision making.

Retransplantation for COVID-19-related lung graft failure: A case report of successful outcome in a critically ill lung transplant recipient.

End-stage lung disease from nonrecovered COVID-19 acute respiratory distress syndrome has become an increasingly frequent indication for lung transplant. Although reports of lung transplant recipients (LTRs) with COVID-19 suggest an increased risk for hospitalization, respiratory failure, and death, little is known about retransplant for COVID-19-related lung graft failure. In this manuscript, we present a 49-year-old man who received bilateral lung retransplantation for COVID-19-related lung graft failure, 7½ years after his initial transplant for idiopathic pulmonary fibrosis. Our case suggests that retransplantation may be a viable option for critically ill LTRs with COVID-19-related graft failure, even in the presence of other organ dysfunction, provided that they are in good condition and have an immunologically favorable donor.

Increasing surgeon experience and cumulative institutional experience drive decreasing hospital mortality after reoperative cardiac surgery.

OBJECTIVE: The study objective was to identify the effects of surgeon experience and age, in the context of cumulative institutional experience, on risk-adjusted hospital mortality after cardiac reoperations. METHODS: From 1951 to 2020, 36 surgeons performed 160,338 cardiac operations, including 32,871 reoperations. Hospital death was modeled using a novel tree-bagged, generalized varying-coefficient method with 6 variables reflecting cumulative surgeon and institutional experience up to each cardiac operation: (1) number of total and (2) reoperative cardiac operations performed by a surgeon, (3) cumulative institutional number of total and (4) reoperative cardiac operations, (5) year of surgery, and (6) surgeon age at each operation. These were adjusted for 46 patient characteristics and surgical components. RESULTS: There were 1470 hospital deaths after cardiac reoperations (4.5%). At the institutional level, hospital death decreased exponentially and became less variable, leveling at 1.2% after approximately 14,000 cardiac reoperations. For all surgeons as a group, hospital death decreased rapidly over the first 750 reoperations and then gradually decreased with increasing experience to less than 1% after approximately 4000 reoperations. Surgeon age up to 75 years was associated with ever-decreasing hospital death. CONCLUSIONS: Surgeon age and experience have been implicated in adverse surgical outcomes, particularly after complex cardiac operations, with young surgeons being novices and older surgeons having declining ability. However, at Cleveland Clinic, outcomes of cardiac reoperations improved with increasing primary surgeon experience, without any suggestion to mid-70s of an age cutoff. Patients were protected by the cumulative background of institutional experience that created a culture of safety and teamwork that mitigated adverse events after cardiac surgery.

Radiation Exposure in Extracorporeal Life Support.

Extracorporeal membrane oxygenation (ECMO) exposes patients to multiple radiologic studies. We hypothesized ECMO patients endure radiation exposure in excess of the International Commission of Radiological Protection (ICRP) recommendations of cumulative effective dose (CED, >20 mSv and 5-year cumulative limit of CED >100 mSv). We conducted a retrospective observational study in an academic medical center between January 2016 and December 2018 involving adult admissions (N = 306) on ECMO. Ionizing radiation was calculated from reference values to determine CED. Approximately 9.4% (N = 29) patients accrued CED >50 mSv and 4.5% (N = 14) accrued CED >100 mSv during ECMO. Over the entire hospitalization, 28% (N = 85) accrued >50 mSv and 14.7% (N = 45) accrued CED >100 mSv. Median CED during ECMO was 2.3 mSv (IQR, -0.82 to 8.1 mSv), and the entire hospitalization was 17.4 mSv (IQR, -4.5 to 56.6 mSv). Thirteen percent of the median CED accrued during hospitalization could be attributed to ECMO. Longer hospitalization was associated with a higher CED (50 days [IQR, -25 to 76 days] in CED >50 vs. 19 days [IQR, -10 to 32 days] in CED <50). Computer tomography (CT) scans and interventional radiology (IR) procedures contributed to 43.8% and 44.86%, respectively, of CED accrued on ECMO and 52.2% and 37.1% of CED accumulated during the whole hospitalization. Guidelines aimed at mitigating radiation exposure are urgently needed.

Lung Transplant After a Heart Transplant: A Case Report.

A heart-lung transplant is considered in patients with end-stage heart and lung disease. However, there is no report of a patient receiving a staged heart transplant followed by a lung transplant. Our case report describes a successful left single lung transplant for idiopathic pulmonary fibrosis 6 years after a heart transplant. This case illustrates that this approach can avoid significantly increased wait time until transplant, and it shows that early interstitial lung disease may not be a contraindication for the heart transplant.

Left ventricular assist device mode: Co-pulse left ventricular unloading in a working mode of ex vivo heart perfusion.

BACKGROUND: For normothermic ex vivo heart perfusion (EVHP), a resting mode and working mode have been proposed. We newly developed a left ventricular assist device (LVAD) mode that supports heart contraction by co-pulse synchronized LVAD. METHODS: Following resting mode during time 0 to 1 hour, pig hearts (n = 18) were perfused in either resting, working, or LVAD mode during time 1 to 5 hour, and then myocardial function was evaluated in working mode at 6 hour. The preservation ratio was defined as the myocardial mechanical function at 330 minute divided by the function at 75 minute. In LVAD mode, LVAD unloaded the pressure and the volume in the left ventricle in the systolic phase. RESULTS: The LVAD group was significantly associated with higher preservation ratios in cardiac output (resting, 33 ± 3; working, 35 ± 5; LVAD, 76% ± 5%; p < 0.001), stroke work, dP/dt maximum, and dP/dt minimum compared with the other groups. Glucose consumption was significantly reduced in the resting group. The LVAD group was significantly associated with higher myocardial oxygen consumption (resting, 2.2 ± 0.3; working; 4.6 ± 0.5; LVAD, 6.1 ± 0.5 mL O2/min/100 g, p < 0.001) and higher adenosine triphosphate (ATP) levels (resting, 1.1 ± 0.1; working, 0.7 ± 0.1; LVAD, 1.6 ± 0.2 µmol/g, p = 0.001) compared with the others. CONCLUSION: These data suggest that myocardial mechanical function was better preserved in LVAD mode than in resting and working modes. Although our data suggested similar glycolysis activity in the LVAD and working groups, the higher final ATP in the LVAD group might be explained by reduced external work in LVAD.

Effect of donor smoking and substance use on post-lung transplant outcomes.

OBJECTIVE: The study objective was to determine effects of donor smoking and substance use on primary graft dysfunction, allograft function, and survival after lung transplant. METHODS: From January 2007 to February 2020, 1366 lung transplants from 1291 donors were performed in 1352 recipients at Cleveland Clinic. Donor smoking and substance use history were extracted from the Uniform Donor Risk Assessment Interview and medical records. End points were post-transplant primary graft dysfunction, longitudinal forced expiratory volume in 1 second (% of predicted), and survival. RESULTS: Among lung transplant recipients, 670 (49%) received an organ from a donor smoker, 163 (25%) received an organ from a donor with a 20 pack-year or more history (median pack-years 8), and 702 received an organ from a donor with substance use (51%). There was no association of donor smoking, pack-years, or substance use with primary graft dysfunction (P > .2). Post-transplant forced expiratory volume in 1 second was 74% at 1 year in donor nonsmoker recipients and 70% in donor smoker recipients (P = .0002), confined to double-lung transplant, where forced expiratory volume in 1 second was 77% in donor nonsmoker recipients and 73% in donor smoker recipients. Donor substance use was not associated with allograft function. Donor smoking was associated with 54% non-risk-adjusted 5-year survival versus 59% (P = .09) and greater pack-years with slightly worse risk-adjusted long-term survival (P = .01). Donor substance use was not associated with any outcome (P ≥ 8). CONCLUSIONS: Among well-selected organs, lungs from smokers were associated with non-clinically important worse allograft outcomes without an inflection point for donor smoking pack-years. Substance use was not associated with worse allograft function. Given the paucity of organs, donor smoking or substance use alone should not preclude assessment for lung donation or transplant.

Reflux Surgery in Lung Transplantation: A Multicenter Retrospective Study.

BACKGROUND: Aspiration has been associated with graft dysfunction after lung transplantation, leading some to advocate for selective use of fundoplication despite minimal data supporting this practice. METHODS: We performed a multicenter retrospective study at 4 academic lung transplant centers to determine the association of gastroesophageal reflux disease and fundoplication with bronchiolitis obliterans syndrome and survival using Cox multivariable regression. RESULTS: Of 542 patients, 136 (25.1%) underwent fundoplication; 99 (18%) were found to have reflux disease without undergoing fundoplication. Blanking the first year after transplantation, fundoplication was not associated with a benefit regarding freedom from bronchiolitis obliterans syndrome (hazard ratio [HR], 0.93; 95% CI, 0.58-1.49) or death (HR, 0.97; 95% CI, 0.47-1.99) compared with reflux disease without fundoplication. However, a time-dependent adjusted analysis found a slight decrease in mortality (HR, 0.59; 95% CI, 0.28-1.23; P = .157), bronchiolitis obliterans syndrome (HR, 0.68; 95% CI, 0.42-1.11; P = .126), and combined bronchiolitis obliterans syndrome or death (HR, 0.66; 95% CI, 0.42-1.04; P = .073) in the fundoplication group compared with the gastroesophageal reflux disease group. CONCLUSIONS: Although a statistically significant benefit from fundoplication was not determined because of limited sample size, follow-up, and potential for selection bias, a randomized, prospective study is still warranted.

Real-time Lung Weight Measurement During Cellular Ex Vivo Lung Perfusion: An Early Predictor of Transplant Suitability.

BACKGROUND: Increased extravascular lung water during ex vivo lung perfusion (EVLP) is associated with ischemia reperfusion injury and poor pulmonary function. A non-invasive technique for evaluating extravascular lung water during EVLP is desired to assess the transplant suitability of lungs. We investigated real-time lung weight measurements as a reliable method for assessing pulmonary functions in cellular EVLP using a porcine lung model. METHODS: Fifteen pigs were randomly divided into 3 groups: control (no warm ischemia) or donation after circulatory death groups with 60 or 90 min of warm ischemia (n = 5, each). Real-time lung weight gain was measured by load cells positioned at the bottom of the organ chamber. RESULTS: Real-time lung weight gain at 2 h was significantly correlated with lung weight gain as measured on a back table ( R = 0.979, P < 0.01). Lung weight gain in non-suitable cases (n = 6) was significantly higher than in suitable cases (n = 9) at 40 min (51.6 ± 46.0 versus -8.8 ± 25.7 g; P < 0.01, cutoff = +12 g, area under the curve = 0.907). Lung weight gain at 40 min was significantly correlated with PaO 2 /FiO 2 , peak inspiratory pressure, shunt ratio, wet/dry ratio, and transplant suitability at 2 h ( P < 0.05, each). In non-suitable cases, lung weight gain at 66% and 100% of cardiac output was significantly higher than at 33% ( P < 0.05). CONCLUSIONS: Real-time lung weight measurement could potentially be an early predictor of pulmonary function in cellular EVLP.

The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: The use of mechanical circulatory support in lung transplantation.

OBJECTIVE: The use of mechanical circulatory support (MCS) in lung transplantation has been steadily increasing over the prior decade, with evolving strategies for incorporating support in the preoperative, intraoperative, and postoperative settings. There is significant practice variability in the use of these techniques, however, and relatively limited data to help establish institutional protocols. The objective of the AATS Clinical Practice Standards Committee (CPSC) expert panel was to review the existing literature and establish recommendations about the use of MCS before, during, and after lung transplantation. METHODS: The AATS CPSC assembled an expert panel of 16 lung transplantation physicians who developed a consensus document of recommendations. The panel was broken into subgroups focused on preoperative, intraoperative, and postoperative support, and each subgroup performed a focused literature review. These subgroups formulated recommendation statements for each subtopic, which were evaluated by the entire group. The statements were then developed via discussion among the panel and refined until consensus was achieved on each statement. RESULTS: The expert panel achieved consensus on 36 recommendations for how and when to use MCS in lung transplantation. These recommendations included the use of veno-venous extracorporeal membrane oxygenation (ECMO) as a bridging strategy in the preoperative setting, a preference for central veno-arterial ECMO over traditional cardiopulmonary bypass during the transplantation procedure, and the benefit of supporting selected patients with MCS postoperatively. CONCLUSIONS: Achieving optimal results in lung transplantation requires the use of a wide range of strategies. MCS provides an important mechanism for helping these critically ill patients through the peritransplantation period. Despite the complex nature of the decision making process in the treatment of these patients, the expert panel was able to achieve consensus on 36 recommendations. These recommendations should provide guidance for professionals involved in the care of end-stage lung disease patients considered for transplantation.