Lung Transplant Candidates Research Articles

Indications for Lung Transplantation and Patient Selection.

Globally, thousands of patients undergo lung transplantation owing to end-stage lung disease each year. As lung transplantation evolves, recommendations and indications are constantly being updated. In 2021, the International Society for Heart and Lung Transplantation published a new consensus document for selecting candidates for lung transplantation. However, it is still difficult to determine appropriate candidates for lung transplantation among patients with complex medical conditions and various diseases. Therefore, it is necessary to analyze each patient’s overall situation and medical condition from various perspectives, and ongoing efforts to optimize the analysis will be necessary. The purpose of this study is to review the extant literature and discuss recent updates.

Lung Transplantation for Patients with COVID-19 Acute Respiratory Distress Syndrome.

Patients with severe coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) may exhibit pulmonary fibrosis after the viral illness resolves. Some of these patients may experience severe functional lung impairment, and thus require transplants to prevent death or maintain a tolerable quality of life. Considering the reversibility of COVID-19 ARDS, lung transplant candidates are observed for 1–2 months and must be selected very carefully before transplantation. As the short-term outcomes of such patients are comparable to those of patients with other indications for transplantation, lung transplantation should be actively considered.

Dynamic Thiol-Disulfide Homeostasis as a Marker for Oxidative Stress in Lung Transplant Candidates.

Oxidative stress developing due to oxidant/antioxidant imbalance plays a crucial role in the etiopathogenesis of chronic progressive lung diseases.The condition is typically more severe in lung transplant candidates with end-stage lung disease. Here, we investigated dynamic thiol-disulfide homeostasis as a marker for oxidative stress in lung transplant candidates. The study included 40 patients with end-stage lung disease with indications for lung transplant (candidate group) and 40 healthy controls. Patient demographic data, laboratory results, and thiol-disulfide homeostasis values were recorded. We categorized patients according to their primary diseases and noted clinical measurements of forced expiratory volume in 1 second, forced vital capacity, 6-minute walk test, systolic pulmonary artery pressure, and lung allocation scores.Thiol-disulfide homeostasis parameters were compared before and after transplant. Demographic characteristics were similar in the candidate and control groups. In the candidate group, native thiol and total thiol levels (antioxidant parameters of thiol-disulfide homeostasis) were significantly lower, whereas disulfide-to-native thiol and disulfide-to-total thiol ratios (oxidant parameters of thiol-disulfide homeostasis) were significantly higher. We observed no significant differences between the disease subgroups in terms of thioldisulfide homeostasis parameters. Moderately significant correlations were shown between the antioxidant markers ofthiol-disulfide homeostasis and the clinical measurements, including the lung allocation scores. Our multiple regression analyses showed that native thiol and total thiol were significant predictive factors to estimate the lung allocation score. During the study period, 6 patients (15%)received lung transplant. There were significant differences in antioxidant parameters ofthiol-disulfide homeostasis in the pre- versus posttransplant periods. In patients with end-stage lung disease, the dynamic thiol-disulfide homeostasis status is altered in favor of oxidants. Thus, thiol-disulfide homeostasis parameters can be used to detect oxidative stress and estimate lung allocation scores in these patients. Lung transplant may have positive effects on oxidative stress.

Clinical assessment of scannographic markers for sarcopenia in lung transplant candidates

IntroductionThe selection of patients for lung transplantation is difficult. An aspect of the patient's general condition and frailty can be assessed by measuring the surface area of certain muscles on CT. Indeed, sarcopenia, assessed by measuring the area of psoas muscles on scannographic sections has already been shown to be associated with poor outcomes in lung transplant and other major surgeries and could thus be helpful to evaluate candidates to lung transplant. However, it is not routinely performed by radiologists. As a pilot study, we compared the reliability of computerized tomography scan assessment for sarcopenia by clinicians with that of radiologists. Materials and methodsWe conducted a retrospective single-centre study in which preoperative abdominal CT scans of lung transplant patients from 2014 to 2018 were analysed to assess sarcopenia by measuring the surface areas (mm2) of the psoas, paraspinal muscles at the L4 vertebra and diaphragm pillars at the celiac trunk bilaterally. The surfaces were blindly assessed by clinicians and radiologists and the intraclass correlation coefficients between the two measurements were estimated by a generalized linear model using SAS 9.4 software. ResultsWe performed a double reading of 200 scans. The clinicians ‘measurements were comparable to those of the radiologists for the psoas and paraspinal muscles but not for the diaphragm pillars. ConclusionCT measurement of psoas and paraspinal muscle areas by clinicians appears reliable and feasible in routine practice and could be used in the evaluation of lung transplant candidates.

Does Preoperative Rehabilitation Influence the Quality of Life in Patients Who Are Candidates for Lung Transplant?

Lung transplant is an excellent therapeutic option for patients with advanced/end-stage pulmonary disease. The purpose of this review was to define whether preoperative rehabilitation influences quality of life in patients who are candidates for lung transplant. This was a scoping review conducted by searching 4 primary databases from inception until January 2022. Three keywords, "lung transplantation," "preoperative rehabilitation," and "quality of life," were matched using the Boolean operator AND. In each database, the following fields were searched: PubMed (all fields), Scopus (title, abstract, keywords), Cochrane Library (title, abstract, keywords), and Web of Science (topic). Filters were applied for age (adult only) and language (English only). No filters were applied for gender, publication date, and subject. The search process was completed in January 2022. We retrieved 57 citations from these databases. After removal of duplicates, 41 documents were screened for eligibility. Two articles were included in the final analysis: 1 was a systematic review, and 1 was an observational prospective study. The rehabilitative interventions were mainly focused on motor and breathing exercises and were integrated by education programs. Preoperative rehabilitation was effective atimproving quality of life and mood status and reducing dyspnea in patients waiting for lung transplant. In addition, the 6-minute walking distance increased after patients participated in preoperative rehabilitation. Preoperative rehabilitation was composed of different types of exercise with variable duration (3-20 weeks) and frequency (3-6 times per week). Patients on the active wait list for lung transplant should be encouraged to attend preoperative rehabilitation in order to preserve and improve their quality of life.

Multiresistant organisms: bacteria and beyond

Infections with multiresistant organisms are an emerging problem, cause early mortality post lung transplantation and are sometimes associated with graft dysfunction. Frequently they raise questions about the selection of lung transplant candidates and therapeutic management post lung transplantation. There are no guidelines and management must be individualized. This review summarizes the available therapeutic options in cases of multidrug-resistant (MDR) organisms and outcomes after lung transplant. Improvements in diagnosis, new and more effective drugs and the experience gained in the management of these infections in lung transplantation, lead to a more optimistic horizon than that found a decade ago. Update on the management of Burkholderia cepacia complex, Mycobacterium abscessus complex, Aspergillus spp., Scedosporium spp. and Lomentospora prolificans infections. This review clarifies current posttransplant outcomes and adds a little hope in these scenarios.

A systematic review and meta-analysis of coronary artery disease and revascularization in lung transplant patients.

Coronary artery disease (CAD) is common in candidates for lung transplantation (LTx) and has historically been considered a relative contraindication to transplantation. We look to review the outcomes of LTx in patients with CAD and determine the optimum revascularization strategy in LTx candidates. PubMed, Medline and Web of Science were systematically searched by three authors for articles comparing the outcomes of LTx in patients with CAD and receiving coronary revascularization. In total 1668 articles were screened and 12 were included in this review.Preexisting CAD in LTx recipients was not associated with significantly increased postoperative morbidity or mortality. The pooled estimates of mortality rate at 1, 3 and 5 years indicated significantly inferior survival in LTx recipients with a prior history of coronary artery bypass grafting (CABG) [odds ratio (OR), 1.84; 95% confidence interval (CI), 1.53-2.22; P < 0.00001; I2 = 0%; OR, 1.52; 95% CI, 1.21-1.91; P = 0.0003; I2 = 0%; OR, 1.62; 95% CI, 1.13-2.33; P = 0.008; I2 = 71%, respectively). However, contemporary literature suggests that survival rates in LTx recipients with CAD that received revascularization either by percutaneous coronary intervention (PCI), previous or concomitant CABG, are similar to patients who did not receive revascularization. Trends in postoperative morbidity favored CABG in the rates of myocardial infarction and repeat revascularization, whereas rates of stroke favored PCI. The composite results of this study support the consideration of patients with CAD or previous coronary revascularization for LTx. Prospective, randomized controlled trials with consistent patient populations and outcomes reporting are required to fully elucidate the optimum revascularization strategy in LTx candidates.

Diaphragmatic plication among lung transplant patients: A single-center experience.

There is lack of data reporting outcomes among patients needing diaphragmatic plication (DP) during or after lung transplantation (LT). We sought to assess the association of DP with post-transplant spirometry among other outcomes. We included all patients who underwent LT between 2012 and 2016 (n=324, mean age 56.3±13.4 years; M:F 198:126). We compared early and late outcomes based on the need for DP. The frequency of diaphragmatic dysfunction (DD) on pre-transplant fluoroscopy was 52.2%. A total of 38 DP procedures were performed among 37 patients (11.4% of LT patients). DP was done for anatomic (sizing or spacing issues) or functional indications (symptomatic DD). While patients with DP had significantly lower spirometry throughout the 3-year follow-up period, their slope of decline, functional assessments at the first annual visit, the risk of CLAD, and mortality were similar to patients without DP. A sub-group analysis limited to patients with restrictive lung diseases as the transplant indication had similar findings. Pre-transplant DD is common among LT candidates although it did not predict the need for DP. DP may be performed for functional or anatomic indications especially for addressing the donor-recipient size mismatch. Despite the lack of favorable effect on post-transplant spirometry, patients undergoing DP have acceptable and comparable early and late outcomes.

Antibiotic Therapy for Difficult-to-Treat Infections in Lung Transplant Recipients: A Practical Approach.

Lung transplant recipients are at higher risk to develop infectious diseases due to multi-drug resistant pathogens, which often chronically colonize the respiratory tract before transplantation. The emergence of these difficult-to-treat infections is a therapeutic challenge, and it may represent a contraindication to lung transplantation. New antibiotic options are currently available, but data on their efficacy and safety in the transplant population are limited, and clinical evidence for choosing the most appropriate antibiotic therapy is often lacking. In this review, we provide a summary of the best evidence available in terms of choice of antibiotic and duration of therapy for MDR/XDR P. aeruginosa, Burkholderia cepacia complex, Mycobacterium abscessus complex and Nocardia spp. infections in lung transplant candidates and recipients.

Movement therapy in lung transplantation candidates assisted by a lightweight wearable robot

ABSTRACT The aim of this pilot-study was to investigate the safety, feasibility and tolerability of an assisted mobilization of patients with advanced pulmonary diseases, using a lightweight, exoskeleton-type robot (Myosuit, MyoSwiss AG, Zurich, Switzerland). Ten patients performed activities of daily life (ADL) both with and without the device. The mean age was 53.6 (±5.6) years; 70% were male. The assessment of outcome included the evaluation of vital signs, adverse events, rates of perceived exertion and dyspnea (PRE, PRD), the ability to perform ADL and the individual acceptability. Robotic-assisted mobilization was feasible in all patients. No adverse events occurred. RPE and RPD showed no significant difference with or without the Myosuit (mean difference in RPE -1.7, 95%-confidence interval (CI) -1.16, 4.49; p = 0.211; mean difference in RPD 0.00, 95%-CI -1.88, 1.88; p = 0.475). 80% of patients were interested to participate in a robotic-assisted training on a regular basis. A robotic exoskeleton-assisted mobilization is safe, feasible, well-tolerated and well-accepted. The results are highly encouraging to further pursue this highly innovative approach.

The Intersection of Aging and Lung Transplantation: its Impact on Transplant Evaluation, Outcomes, and Clinical Care.

Older adults (age ≥ 65 years) are the fastest growing age group undergoing lung transplantation. Further, international consensus document for the selection of lung transplant candidates no longer suggest a fixed upper age limit. Although carefully selected older adults can derive great benefit, understanding which older adults will do well after transplant with improved survival and health-related qualiy of life is key to informed decision-making. Herein, we review the epidemiology of aging in lung transplantation and its impact on outcomes, highlight selected physiological measures that may be informative when evaluating and managing older lung transplant patients, and identify directions for future research. In general, listing and transplanting older, sicker patients has contributed to worse clinical outcomes and greater healthcare use. Emerging evidence suggest that measures of physiological age, such as frailty, body composition, and neurocognitive and psychosocial function, may better identify risk for poor transplant outcomes than chronlogical age. The evidence base to inform transplant decision-making and improvements in care for older adults is small but growing. Multipronged efforts at the intersection of aging and lung transplantation are needed to improve the clinical and patient centered outcomes for this large and growing cohort of patients. Future research should focus on identifying novel and ideally modifiable risk factors for poor outcomes specific to older adults, better approaches to measuring physiological aging (e.g., frailty, body composition, neurocognitive and psychosocial function), and the underlying mechanisms of physiological aging. Finally, interventions that can improve clinical and patient centered outcomes for older adults are needed.

Routine Coronary Angiography is Still the Key Test for Patients Eligible for Lung Transplantation Also for Those With No Symptoms and With High Risk of Coronary Artery Disease

Coronary artery disease (CAD) has a considerable morbidity and mortality effect on the outcomes of a lung transplant. Currently, coronary angiography is performed as part of the pretransplant evaluation process. Unfortunately, there are no clear guidelines about performing cardiac angiography in lung transplant candidates. The aim of our work is to find a correlation between cardiovascular risk and coronary arterial status to optimize the selection of patients for coronary angiography prior transplantation. We retrospectively analyzed 48 patients in whom coronary angiography and cardiac catheterization was performed during assessment for bilateral lung transplantation at the Medical University of Gdańsk from 2018 to 2021. The coronary artery disease status was classified into 2 categories: without any stenosis and with stenosis. For each patient, the 10-year cardiovascular risk was estimated by using a Systematic COronary Risk Evaluation calculator modified for the Polish population. Coronary stenosis was detected in 15 patients during angiography (31%). The group with coronary stenosis had a median SCORE risk of 8%, which is considered as high risk, and in patients without stenosis it was 5%, which is also considered a high risk. Median mean pulmonary artery pressure in patients with stenosis was the same as that in patients without stenosis (23 mm Hg). CAD among lung transplant candidates cannot be predicted by risk factors, so coronary angiography is very important as a part of the evaluation process. Because pulmonary hypertension has a big impact on surveillance after transplantation, performing heart catheterization during the qualification process is crucial.

Symptom-Illness Severity Profiles and Healthcare Use Among Lung Transplant Candidates

<h3>Purpose</h3> Symptoms experienced by lung transplant candidates are heterogenous and may not reflect objective measures of illness severity. Both may contribute to healthcare use. We aimed to identify distinct profiles using integrated data on symptoms and illness severity and examine differences in healthcare use among observed profiles. <h3>Methods</h3> This was a single-center prospective study of adult lung transplant candidates. Symptoms were assessed within 3 months of transplant with the Memorial Symptom Assessment Scale (MSAS). Two subscales, the MSAS physical and psychological, were calculated by averaging the severity, frequency, and distress scores for 12 physical and 6 psychological symptoms (score range 0-4, higher=more severe). The LAS, a score (0-100) that represents illness severity and survival benefit, was our measure of illness severity and obtained from the health record at time of MSAS completion. Latent class analysis was used to identify distinct symptom-illness severity profiles based on two MSAS subscales and LAS. Differences in pretransplant hospitalization rates and posttransplant length of stay (LOS) among profiles were determined by comparative statistics. <h3>Results</h3> Among 93 candidates, three distinct symptom-illness severity profiles were identified: 71% had congruent symptom-illness severity; mild symptoms (MSAS phys 0.49; MSAS psych 0.57) matched mild illness severity (LAS 39.75) and 29% had symptom-illness severity mismatch; 9% had moderate symptoms (MSAS phys 0.88; MSAS psych 1.47) but severe illness severity (LAS 83.59) and 20% had severe symptoms (MSAS phys 1.30; MSAS psych 1.94) but mild illness severity (LAS 42.64). Compared to the congruent profile, mismatch profiles were younger (65 vs 53 and 52 years, p=0.007), more racially diverse (% white: 88 vs 62 and 63, p=0.002), with higher psychosocial risk scores (7.5 vs 10.5 and 13, p=0.03). Hospitalization at time of transplant was more common among the mismatch profiles compared to the congruent profile (11% vs 50% and 26%, p=0.02). Post-transplant hospital LOS did not significantly differ (p= 0.5). <h3>Conclusion</h3> We found incongruence between symptom and illness severity in a subset of patients. Higher rates of pretransplant hospitalization were observed among the mismatch profiles suggesting that both severity of symptoms and illness may be clinically relevant drivers of pretransplant healthcare use.

Survival Outcomes of Lung Recipients with Body Mass Index ≥35 kg/m2

<h3>Purpose</h3> Transplant consensus statements identify advanced lung disease patients with a body mass index (BMI) ≥35 kg/m² as unlikely candidates for lung transplantation (LT); however, such patients with an otherwise acceptable risk profile tend to cluster in large volume centers. We reviewed our experience with long-term survival of overweight and obese lung transplant recipients (LTRs). <h3>Methods</h3> Of 1004 LTRs from 2007-2021, patients were excluded for BMI <25 kg/m² (n=410), retransplant (n=30), or missing data (n=3); remaining LTRs were divided by listing BMI: overweight (OWT, 25-29.9 kg/m²), obesity class-I (C-I, 30-34.9 kg/m²), and obesity class-II (C-II, ≥35 kg/m²). The primary endpoint was survival. <h3>Results</h3> In total, 561 LTRs were divided into OWT (n=337), C-I (n=208), and C-II (n=16). Subjects in C-II were younger than those in OWT (p<0.01), tended to be the sickest (median LAS 40 [37, 56]), and underwent LT fairly quickly after listing (median 19 [9, 45] days). Of note, the median BMI of C-II patients (35.9 [35, 36] kg/m²) was at the low end of the class. Length of stay for LT was comparable between groups. Compared to OWT, the risk of death at 60 days after LT was 6-fold higher in C-I and 11-fold higher in C-II [p=0.03 and p<0.01, respectively]. At 60 days after LT, OWT had the highest probability of survival followed by C-I and C-II [99.4% vs 96.6% vs 93.8%, respectively, p=0.02]; however, there was no difference between C-I and C-II. Furthermore, survival at 1 and 5 years was similar between groups (Figure 1). <h3>Conclusion</h3> Carefully selected candidates with a BMI slightly higher than 35 kg/m², no other contraindications to LT, and rapidly decompensating lung disease were a small proportion of the overall cohort with an unrealistic amount of time to lose weight. Despite higher perioperative mortality, LTRs with a listing BMI ≥35 kg/m² may have near-equivalent long-term survival as those with BMI 30-34.9 kg/m². In otherwise strong candidates, severe obesity should not be a significant predictor of long-term mortality. Further validation is needed.

Preliminary Development of the Lung Transplant Frailty Index

<h3>Purpose</h3> Existing measures of frailty developed in community dwelling older adults may misclassify frailty in lung transplant candidates. We aimed to develop a novel frailty index for lung transplantation with improved performance characteristics compared to existing measures. <h3>Methods</h3> In a three-center cohort study of lung transplant candidates, we measured the Short Physical Performance Battery (SPPB) and Fried Frailty Phenotype (FFP) measures; body composition by bioelectrical impedance; and serum biomarkers associated with frailty (hemoglobin, albumin, and C-reactive protein). We evaluated individual variable domains to identify those associated with the criterion of candidate delisting for becoming too ill or death. Next, we built composite multidimensional models by testing the addition of domain variables in clusters: (1) performance measures (gait speed, balance, grip strength, low physical activity level); (2) body composition (low skeletal muscle, high % body fat), and (3) biomarkers. Domain cut-points were determined using receiver operating curve analyses. Three threshold selection methods for variable retention were evaluated; where methods differed, we prioritized specificity for delisting/death. Logistic regression analyses then estimated the odds of death/delisting across candidate Lung Transplant Frailty Index models. <h3>Results</h3> In 533 participants, we identified two candidate Lung Transplant Frailty Index (LT-FI) measures that maximized specificity, area under the curve, and had stronger associations with delisting and death compared to either the SPPB or FFP (Table). <h3>Conclusion</h3> Candidate LT-FI measures that include measures of physical performance, body composition, and serum biomarkers have improved discrimination for candidate delisting or death compared to the SPPB and FFP. Validating these candidate LT-FI measures' capacity to identify people at risk for peri- and post-operative complications and at other centers will help to define the optimal measure of frailty in lung transplantation.

Effects of Blood Group and ABO Compatibility on Lung Transplant Waitlist and Post-Transplant Outcomes

PurposeBlood group O individuals are universal donors, but O recipients are limited to O donors. This constraint combined with the current lung allocation system places O recipients at a hypothetical disadvantage. This study evaluates waitlist outcomes, post-transplant outcomes, and overall survival from time of listing by blood group.MethodsLung transplant candidates from 2/2015 - 2/2019 were identified from the Scientific Registry of Transplant Recipients. A Fine and Gray model adjusted for OPO region, height, sex, and LAS was used to determine the competing risk for waitlist mortality or transplant by blood group and a model adjusted for LAS at transplant used to determine the competing risk for post-transplant mortality. A Cox proportional hazards regression model utilizing a time-varying covariate of transplant and adjusted for the above was used to determine the adjusted risk from listing to death by blood group. Unadjusted outcomes were visualized using Kaplan-Meir curves.ResultsA total of 9,846 candidates were identified, with 8,181 (83%) receiving a lung transplant and 964 (10%) experiencing waitlist death. Blood group A candidates had higher adjusted access to transplant (sHR 1.23, 1.17-1.29) and lower waitlist mortality (sHR 0.77, CI 0.66-0.89) (Fig 1a). AB candidates had a higher adjusted access to transplant (sHR 1.24, CI 1.1-1.4). There was no difference in the adjusted risk for post-transplant death by blood type (Fig 1b). There was no significant difference in mortality from time of listing across blood groups (Fig 1c) and in graft failure or post-transplant mortality by ABO compatibility.ConclusionTransplant equity varies across blood groups with significant differences in adjusted access to transplant and waitlist mortality by blood group. Despite this, post-transplant survival and survival from the time of listing are similar across blood groups. These results support the need to reconsider allocation schemas to mitigate blood group waitlist inequalities. Blood group O individuals are universal donors, but O recipients are limited to O donors. This constraint combined with the current lung allocation system places O recipients at a hypothetical disadvantage. This study evaluates waitlist outcomes, post-transplant outcomes, and overall survival from time of listing by blood group. Lung transplant candidates from 2/2015 - 2/2019 were identified from the Scientific Registry of Transplant Recipients. A Fine and Gray model adjusted for OPO region, height, sex, and LAS was used to determine the competing risk for waitlist mortality or transplant by blood group and a model adjusted for LAS at transplant used to determine the competing risk for post-transplant mortality. A Cox proportional hazards regression model utilizing a time-varying covariate of transplant and adjusted for the above was used to determine the adjusted risk from listing to death by blood group. Unadjusted outcomes were visualized using Kaplan-Meir curves. A total of 9,846 candidates were identified, with 8,181 (83%) receiving a lung transplant and 964 (10%) experiencing waitlist death. Blood group A candidates had higher adjusted access to transplant (sHR 1.23, 1.17-1.29) and lower waitlist mortality (sHR 0.77, CI 0.66-0.89) (Fig 1a). AB candidates had a higher adjusted access to transplant (sHR 1.24, CI 1.1-1.4). There was no difference in the adjusted risk for post-transplant death by blood type (Fig 1b). There was no significant difference in mortality from time of listing across blood groups (Fig 1c) and in graft failure or post-transplant mortality by ABO compatibility. Transplant equity varies across blood groups with significant differences in adjusted access to transplant and waitlist mortality by blood group. Despite this, post-transplant survival and survival from the time of listing are similar across blood groups. These results support the need to reconsider allocation schemas to mitigate blood group waitlist inequalities.

A Simple Scoring System for Lung Transplant Waitlist Mortality Risk Factors

<h3>Purpose</h3> Current lung allocation score (LAS) waitlist mortality prediction models are complex and incorporate correlated predictors. This study identified and evaluated three multidimensional indices of correlated risk factors. This approach could enable more efficient use of risk factor information and improve dynamic models of end-stage lung disease and transplant outcomes. <h3>Methods</h3> We analyzed 2015-2020 data on U.S. lung transplant candidates on the waiting list, obtained from the Scientific Registry for Transplant Recipients (N=13990). We used hierarchical clustering to identify distinct respiratory support groups based on supplemental oxygen device, rate and frequency of use; steroid use and extracorporeal membrane oxygenation. We used confirmatory factor analysis (CFA) to derive indices of i) airway function (forced expiratory volume, forced vital capacity, and partial pressure of carbon dioxide [PCO₂]) and ii) oxygen function (partial pressures of oxygen (PO₂), PO₂/FiO₂ ratio, and mean pulmonary artery pressure). Cox proportional hazards regression was used to characterize relationships between the developed constructs and waitlist mortality (or removal) after adjusting for disease group, age and sex. <h3>Results</h3> Four respiratory support clusters were identified (see the panel labels in the <b>Figure</b>). Contours of predicted 6-month waitlist mortality risk are displayed for a sample 63-year-old patient with idiopathic pulmonary fibrosis in the Figure. The area under the receiver-operating characteristic curve [95% confidence interval] for 1-year predictions from the fitted Cox model was 0.75 [0.71, 0.79], which was marginally lower than that of the full LAS waitlist mortality model (AUC = 0.79 [0.75, 0.83]). <h3>Conclusion</h3> The three developed constructs of respiratory support, oxygen function and airway function distilled information in 11 correlated risk factors for waitlist mortality, facilitating interpretation of risk profiles without adversely impacting model accuracy. <h3>Funding</h3> NIH R01HL15375

Outcomes of cardiopulmonary resuscitation in patients with pulmonary arterial hypertension.

Over the past 20 years, despite significant advancements in pulmonary arterial hypertension (PAH) medical therapy, many patients require admission to the hospital and are at risk for in‐hospital cardiac arrest (IHCA). Prior data found poor survival in PAH patients after cardiac arrest. The purpose of this study was to explore post‐IHCA outcomes in PAH patients receiving advanced medical therapies. This is a single‐center retrospective study of PAH patients who underwent cardiopulmonary resuscitation for IHCA between July 2005 and May 2021. Patients were identified through an internal cardiac arrest database. Twenty six patients were included. Half of the cohort had idiopathic PAH, with 54% of patients on combination therapy, 27% on monotherapy, and 19% of patients on no therapy. Mean right atrial pressure, mean pulmonary artery pressure, cardiac index, and pulmonary vascular resistance were 13 ± 6 mmHg, 57 ± 13 mmHg, 2.0 ± 0.7 L/min/m2, and 14.5 ± 7.6 Wood units, respectively. Most common etiology of cardiac arrest was circulatory collapse. Initial arrest rhythm in all but one patient was pulseless electrical activity. Six patients (23%) achieved return of spontaneous circulation (ROSC) and one patient (4%) survived to hospital discharge. Rates of ROSC and survival to discharge after IHCA are poor in patients with PAH. Even patients with mild hemodynamics had low likelihood of survival. In patients who are lung transplant candidates, there should be early consideration of extracorporeal support before cardiac arrest.

Molecular Phenotypes of Frailty in Lung Transplant Candidates

<h3>Purpose</h3> The potential for heterogenous pathobiology underlying physical frailty might explain the inconsistent associations observed between frailty and poor outcomes in lung transplantation. We hypothesize that molecular phenotyping could refine frailty measurement and ultimately tailor interventions. <h3>Methods</h3> In a three-center cohort of lung transplant candidates, we measured frailty by the Short Physical Performance Battery (SPPB); demographic and clinical variables; body composition by bioelectrical impedance, and 17 serum biomarkers reflecting commonly cited causes of frailty including inflammation, sarcopenia, adiposity, mitochondrial and neurohormonal dysfunction. Among those pre-frail or frail (SPPB <12), we first applied latent class modelling to the baseline data and then followed participants forward in time. The best-fitting model was determined by the Bayesian Information Criteria and the Vuong-Lo-Mendell-Rubin test. We tested predictive validity of these classes with disability by the Lung Transplant Valued Life Activities scale and by candidate delisting for becoming too ill or death. <h3>Results</h3> In 442 participants, a 3 latent class model best fit (p = 0.046; Figure 1A). Type A was characterized by higher serum biomarkers of inflammation and sarcopenia (lower muscle mass [ASMI] and grip strength); Type B by sarcopenia, high adiposity (VFA), and lack of inflammation, and Type C was relatively fit (higher ASMI and grip strength) and without inflammation (Figure 1B). Amongst the Type A endotype, 13% of participants died or were delisted compared to 6% in both Type B and C (p = 0.15). Participants comprising Type A reported worse disability (LT-VLA 1.7) than Types B and C (1.4 and 1.3, respectively) (p < 0.001) and had shorter time to delisting or death (1.4 vs 8.0 and 4.0 months, respectively) (p < 0.001). <h3>Conclusion</h3> We identified distinct biological phenotypes of frailty. A frailty phenotype characterized by systemic inflammation and sarcopenia appears to be associated with worse clinical outcomes.

Never Say Never: A 3D Anatomic Model Creates a Surgical Roadmap for Ultra-Complex Lung Transplant Recipient

<h3>Introduction</h3> Prior cardiac surgery, particularly coronary artery bypass graft (CABG) with a left internal mammary artery (LIMA), poses a technical challenge to lung transplant (LT). LT candidates with a history of CABG most often undergo a single LTx, limiting candidacy for those who require bilateral LTx (BLTx). Three-dimensional (3D) modeling may afford an opportunity for improved surgical planning when performing BLTx in recipients with multiple operative challenges. <h3>Case Report</h3> A 61-year-old man with a history of idiopathic pulmonary fibrosis, single vessel CABG (LIMA to left anterior descending artery), aortic valve replacement, and septal myomectomy was transferred to our center with hypoxemic respiratory failure requiring mechanical ventilation and veno-venous extracorporeal membrane oxygenation (VV-ECMO). Evaluation revealed a dilated right ventricle with reduced systolic function due to severe pulmonary hypertension (PH). The presence of PH and right ventricular dysfunction suggested a need for BLTx; however, we had concerns regarding the steric relationship of his patent LIMA to LAD graft. Traditionally, he would not be a candidate for BLTx based on these anatomic concerns and ongoing physiology. A 3D printed model of the patient's chest was developed as a novel means to plan the surgical approach. The donor's lungs were procured and placed on Organ Care System^TM to decrease ischemic time. The patient underwent bilateral anterolateral thoracotomies with sternal preservation. A left-sided dissection plane was created and, using the cues of the 3D model, the area where the anterior aspect of the left lung adhered to the mediastinum was identified and the lung was divided distal to and on both sides of the predicted location of the LIMA. In a planned fashion, the patient was transitioned from VV-ECMO to central CPB with cannulation of the ascending aorta through the right chest and conversion of ECMO cannulas into bicaval venous drainage. At the conclusion of the BLTx, the patient was decannulated and transferred to the ICU for ongoing care. He left the hospital a month after transplant and is doing well without supplementary oxygen as an outpatient. <h3>Summary</h3> Patient-specific 3D modeling may be used to help guide a safe and individualized surgical approach in complex patients with a prior history of CABG requiring a BLTx.