Sex Disparities in Left Ventricular Assist Device Implantation: Delayed Presentation and Worse Right Heart Failure.

We explored whether women undergo continuous-flow left ventricular assist device (CF-LVAD) implantation in later stages of heart failure (HF) than men, evidenced by worse preoperative right HF (RHF). We also compared two propensity models with and without preoperative RHF to assess its effect on outcomes. INTERMACS was queried from July 2008 to December 2017. Propensity model 1 matched men and women on age ≥50 years, HF etiology, body surface area, INTERMACS class, comorbidities, device strategy, temporary mechanical circulatory support, and device type. Model 2 included these variables plus LV end-diastolic diameter, right atrial pressure/pulmonary capillary wedge pressure, pulmonary artery pulsatility index, and right ventricular ejection fraction. The primary outcome was all-cause mortality. Secondary outcomes comprise RHF, rehospitalization, renal dysfunction, stroke, and device malfunction. In model 1, characteristics were comparable between 3,195 women and 3,195 men, except women more often had preoperative RHF and postoperative right VAD support and had worse 1 year and overall survival. In model 2, after propensity matching for additional risk factors for preoperative RHF, 1,119 women and 1,119 men had comparable post-LVAD implant RVAD use and survival. These findings suggest that women present more often with biventricular failure and after implantation have higher RHF and mortality rates.

Development of a Sensor Technology to Objectively Measure Dexterity for Cardiac Surgical Proficiency.

BACKGROUND: Technical skill is essential for good outcomes in cardiac surgery. However, no objective methods exist to measure dexterity while performing surgery. The purpose of this study was to validate sensor-based hand motion analysis (HMA) of technical dexterity while performing a graft anastomosis within a validated simulator. METHODS: Surgeons at various training levels performed an anastomosis while wearing flexible sensors (BioStamp nPoint, MC10 Inc) with integrated accelerometers and gyroscopes on each hand to quantify HMA kinematics. Groups were stratified as experts (n = 8) or novices (n = 18). The quality of the completed anastomosis was scored using the 10 Point Microsurgical Anastomosis Rating Scale (MARS10). HMA parameters were compared between groups and correlated with quality. Logistic regression was used to develop a predictive model from HMA parameters to distinguish experts from novices. RESULTS: Experts were faster (11 ± 6 minutes vs 21 ± 9 minutes; P = .012) and used fewer movements in both dominant (340 ± 166 moves vs 699 ± 284 moves; P = .003) and nondominant (359 ± 188 moves vs 567 ± 201 moves; P = .02) hands compared with novices. Experts' anastomoses were of higher quality compared with novices (9.0 ± 1.2 MARS10 vs 4.9 ± 3.2 MARS10; P = .002). Higher anastomosis quality correlated with 9 of 10 HMA parameters, including fewer and shorter movements of both hands (dominant, r = -0.65, r = -0.46; nondominant, r = -0.58, r = -0.39, respectively). CONCLUSIONS: Sensor-based HMA can distinguish technical dexterity differences between experts and novices, and correlates with quality. Objective quantification of hand dexterity may be a valuable adjunct to training and education in cardiac surgery training programs.

Recovery of Lung Function After 149 Days on Extracorporeal Membrane Oxygenation for COVID-19.

This report highlights survival and the patient's perspective after prolonged venovenous extracorporeal membrane oxygenation (ECMO) for COVID-19-related respiratory failure. A 36-year-old man with COVID-19 presented with fever, anosmia, and hypoxia. After respiratory deterioration necessitating intubation and lung-protective ventilation, he was referred for ECMO. After 3 days of conventional venovenous ECMO, he required multiple creative cannulation configurations. Adequate sedation and recurrent bradycardia were persistent challenges. After 149 consecutive days of ECMO, he recovered native lung function and was weaned from mechanical ventilation. This represents the longest-duration ECMO support in a survivor of COVID-19 yet reported. Necessary strategies included unconventional cannulation and flexible anticoagulation.

Clinical Predictors and Outcomes After Left Ventricular Assist Device Implantation and Tracheostomy.

BACKGROUND: Postoperative respiratory failure is a major complication that affects up to 10% of patients who undergo cardiac surgery and has a high in-hospital mortality rate. Few studies have investigated whether patients who require tracheostomy for postoperative respiratory failure after continuous-flow left ventricular assist device (CF-LVAD) implantation have worse survival outcomes than patients who do not. OBJECTIVE: To identify risk factors for respiratory failure necessitating tracheostomy in CF-LVAD recipients and to compare survival outcomes between those who did and did not require tracheostomy. METHODS: Consecutive patients who underwent primary CF-LVAD placement at a single institution between August 1, 2002, and December 31, 2019, were retrospectively reviewed. Propensity score matching accounted for baseline differences between the tracheostomy and nontracheostomy groups. Multivariate logistic regression was used to identify tracheostomy risk factors and 90-day survival; Kaplan-Meier analysis was used to assess midterm survival. RESULTS: During the study period, 664 patients received a CF-LVAD; 106 (16.0%) underwent tracheostomy for respiratory failure. Propensity score matching produced 103 matched tracheostomy-nontracheostomy pairs. Patients who underwent tracheostomy were older (mean [SD] age, 57.9 [12.3] vs 54.6 [13.9] years; P = .02) and more likely to need preoperative mechanical circulatory support (61.3% vs 47.8%; P = .01) and preoperative intubation (27.4% vs 8.8%; P < .001); serum creatinine was higher in the tracheostomy group (mean [SD], 1.7 [1.0] vs 1.4 [0.6] mg/dL; P < .001), correlating with tracheostomy need (odds ratio, 1.76; 95% CI, 1.21-2.56; P = .003). Both before and after propensity matching, 30-day, 60-day, 90-day, and 1-year survival were worse in patients who underwent tracheostomy. Median follow-up was 0.8 years (range, 0.0-11.2 years). Three-year Kaplan-Meier survival was significantly worse for the tracheostomy group before (22.0% vs 61.0%; P < .001) and after (22.4% vs 48.3%; P < .001) matching. CONCLUSION: Given the substantially increased probability of death in patients who develop respiratory failure and need tracheostomy, those at high risk for respiratory failure should be carefully considered for CF-LVAD implantation. Comprehensive management to decrease respiratory failure before and after surgery is critical.

Twenty-year survival following lung transplantation.

Background: Lung transplantation median survival has seen improvements due to recognition of short-term survival factors but continues to trail behind other solid organs due to limited understanding of long-term survivorship. Given the creation of the United Network for Organ Sharing (UNOS) database in 1986, it was difficult to accrue data on long-term survivors until recently. This study characterizes factors impacting lung transplant survival beyond 20 years, conditional to 1-year survival. Methods: Lung transplant recipients listed in UNOS from 1987 to 2002 who survived to 1 post-transplant year were reviewed. Kaplan-Meier and adjusted Cox regression analyses were performed at 20 and 10 years to identify risk factors associated with long-term outcomes independent of their short-term effects. Results: A total of 6,172 recipients were analyzed, including 472 (7.6%) recipients who lived 20+ years. Factors associated with increased likelihood of 20-year survival were female-to-female gender match, recipient age 25-44, waitlist time >1 year, human leukocyte antigen (HLA) mismatch level 3, and donor cause of death: head trauma. Factors associated with decreased 20-year survival included recipient age ≥55, chronic obstructive pulmonary disease/emphysema (COPD/E) diagnosis, donor smoking history >20 pack-years, unilateral transplant, blood groups O&AB, recipient glomerular filtration rate (GFR) <10 mL/min, and donor GFR 20-29 mL/min. Conclusions: This is the first study identifying factors associated with multiple-decade survival following lung transplant in the United States. Despite its challenges, long-term survival is possible and more likely in younger females in good waitlist condition without COPD/E who receive a bilateral allograft from a non-smoking, gender-matched donor of minimal HLA mismatch. Further analysis of the molecular and immunologic implications of these conditions are warranted.

Intraoperative Red Blood Cell Transfusion and Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: In this international, multicenter study of patients undergoing lung transplantation (LT), we explored the association between the amount of intraoperative packed red blood cell (PRBC) transfusion and occurrence of primary graft dysfunction (PGD) and associated outcomes. METHODS: The Extracorporeal Life Support in LT Registry includes data on LT recipients from 9 high-volume (>40 transplants/y) transplant centers (2 from Europe, 7 from the United States). Adult patients who underwent bilateral orthotopic lung transplant from January 2016 to January 2020 were included. The primary outcome of interest was the occurrence of grade 3 PGD in the first 72 h after LT. RESULTS: We included 729 patients who underwent bilateral orthotopic lung transplant between January 2016 and November 2020. LT recipient population tertiles based on the amount of intraoperative PRBC transfusion (0, 1-4, and >4 units) were significantly different in terms of diagnosis, age, gender, body mass index, mean pulmonary artery pressure, lung allocation score, hemoglobin, prior chest surgery, preoperative hospitalization, and extracorporeal membrane oxygenation requirement. Inverse probability treatment weighting logistic regression showed that intraoperative PRBC transfusion of >4 units was significantly ( P < 0.001) associated with grade 3 PGD within 72 h (odds ratio [95% confidence interval], 2.2 [1.6-3.1]). Inverse probability treatment weighting analysis excluding patients with extracorporeal membrane oxygenation support produced similar findings (odds ratio [95% confidence interval], 2.4 [1.7-3.4], P < 0.001). CONCLUSIONS: In this multicenter, international registry study of LT patients, intraoperative transfusion of >4 units of PRBCs was associated with an increased risk of grade 3 PGD within 72 h. Efforts to improve post-LT outcomes should include perioperative blood conservation measures.

Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.

Primary Graft Dysfunction in Lung Transplantation: A Review of Mechanisms and Future Applications.

Lung allograft recipients have worse survival than all other solid organ transplant recipients, largely because of primary graft dysfunction (PGD), a major form of acute lung injury affecting a third of lung recipients within the first 72 h after transplant. PGD is the clinical manifestation of ischemia-reperfusion injury and represents the predominate cause of early morbidity and mortality. Despite PGD's impact on lung transplant outcomes, no targeted therapies are currently available; hence, care remains supportive and largely ineffective. This review focuses on molecular and innate immune mechanisms of ischemia-reperfusion injury leading to PGD. We also discuss novel research aimed at discovering biomarkers that could better predict PGD and potential targeted interventions that may improve outcomes in lung transplantation.

Effect of intraoperative support mode on circulating inflammatory biomarkers after lung transplantation surgery.

BACKGROUND: Processes that activate the immune system during lung transplantation can lead to primary graft dysfunction (PGD) or allograft rejection. METHODS: We analyzed cytokine expression profiles after reperfusion and allograft outcomes in a cohort of patients (n = 59) who underwent lung transplantation off-pump (n = 26), with cardiopulmonary bypass (CPB; n = 18), or with extracorporeal membrane oxygenation (ECMO; n = 15). Peripheral blood was collected from patients at baseline and at 6 and 72 h after reperfusion. To adjust for clinical differences between groups, we utilized a linear mixed model with overlap weighting. RESULTS: PGD3 was present at 48 or 72 h after reperfusion in 7.7% (2/26) of off-pump cases, 20.0% (3/15) of ECMO cases, and 38.9% (7/18) of CPB cases (p = 0.04). The ECMO and CPB groups had greater reperfusion-induced increases in MIP-1B, IL-6, IL-8, IL-9, IL1-ra, TNF-alpha, RANTES, eotaxin, IP-10, and MCP-1 levels than the off-pump group. Cytokine expression profiles after reperfusion were not significantly different between ECMO and CPB groups. CONCLUSION: Our data suggest that, compared with an off-pump approach, the intraoperative use of ECMO or CPB during lung transplantation is associated with greater reperfusion-induced cytokine release and graft injury.

Considerations for Left Atrial Appendage Occlusion During Cardiac Surgery.

Atrial fibrillation is associated with an increased risk of stroke secondary to thrombus formation in the left atrial appendage. Left atrial appendage occlusion (LAAO) is an effective method of reducing the risk of stroke in patients with atrial fibrillation. Although LAAO does not remove the requirement for anticoagulation, it reduces the risk of stroke when compared to anticoagulation alone. We critically analyze the data on LAAO in cardiac surgery. We also discuss the methods of LAAO, the risks of LAAO, and patient populations that could benefit from LAAO. We discuss high-level evidence that LAAO at the time of cardiac surgery reduces the risk of stroke in patients with a history of atrial fibrillation. In patients without a history of atrial fibrillation undergoing cardiac surgery, we suggest that LAAO should be considered in select patients at high risk of atrial fibrillation and stroke, when technically feasible.

Stroke and mortality rates after off-pump vs. pump-assisted/no-clamp coronary artery bypass grafting.

BACKGROUND: Ascending aorta manipulation during on-pump coronary artery bypass grafting (CABG) surgery can release embolic matter and may cause stroke. Strategies for lowering the stroke rate associated with coronary artery bypass grafting surgery include off-pump surgery without cardiopulmonary bypass and pump-assisted surgery with minimal aortic manipulation (i.e., without aortic cross-clamping). We examined whether one approach is superior to the other in reducing stroke and perioperative mortality rates. METHODS: We reviewed consecutive elective, urgent, and emergency off-pump/no-bypass and pump-assisted/no-clamp coronary artery bypass grafting procedures performed by a single surgeon at our institution from June 2011 through October 2017. RESULTS: Of 570 patients analyzed, 395 (69.3%) underwent off-pump/no-bypass surgery, 43 (7.5%) underwent pump-assisted/no-clamp surgery, and 132 (23.2%) transitioned mid-procedure from off-pump/no-bypass to pump-assisted/no-clamp surgery. Patients who were >70 years old, were female, or had diabetes, cardiomegaly, or a history of myocardial infarction or congestive heart failure were more likely to undergo pump-assisted/no-clamp surgery or the combined technique. None of the pump-assisted/no-clamp patients had a stroke, versus 0.3% of the off-pump/no-bypass patients and 0.8% of the combination patients. Stroke and in-hospital mortality rates did not differ by technique. CONCLUSIONS: A hybrid strategy incorporating off-pump, pump-assisted, and combined off-pump/pump-assisted techniques achieved very low stroke rates in patients undergoing coronary revascularization. Perioperative mortality was similar for all three techniques. Avoiding aortic clamping may be crucial for decreasing CABG-related stroke rates. Off-pump/no-bypass surgery had no significant advantage over the pump-assisted/no-clamp or combined techniques in reducing the stroke rate after coronary artery bypass grafting surgery.

Plasma protein biomarkers for primary graft dysfunction after lung transplantation: a single-center cohort analysis.

The clinical use of circulating biomarkers for primary graft dysfunction (PGD) after lung transplantation has been limited. In a prospective single-center cohort, we examined the use of plasma protein biomarkers as indicators of PGD severity and duration after lung transplantation. The study comprised 40 consecutive lung transplant patients who consented to blood sample collection immediately pretransplant and at 6, 24, 48, and 72 h after lung transplant. An expert grader determined the severity and duration of PGD and scored PGD at T0 (6 h after reperfusion), T24, T48, and T72 h post-reperfusion using the 2016 ISHLT consensus guidelines. A bead-based multiplex assay was used to measure 27 plasma proteins including cytokines, growth factors, and chemokines. Enzyme-linked immunoassay was used to measure cell injury markers including M30, M65, soluble receptor of advanced glycation end-products (sRAGE), and plasminogen activator inhibitor-1 (PAI-1). A pairwise comparisons analysis was used to assess differences in protein levels between PGD severity scores (1, 2, and 3) at T0, T24, T48, and T72 h. Sensitivity and temporal analyses were used to explore the association of protein expression patterns and PGD3 at T48-72 h (the most severe, persistent form of PGD). We used the Benjamini-Hochberg method to adjust for multiple testing. Of the 40 patients, 22 (55%) had PGD3 at some point post-transplant from T0 to T72 h; 12 (30%) had PGD3 at T48-72 h. In the pairwise comparison, we identified a robust plasma protein expression signature for PGD severity. In the sensitivity analysis, using a linear model for microarray data, we found that differential perioperative expression of IP-10, MIP1B, RANTES, IL-8, IL-1Ra, G-CSF, and PDGF-BB correlated with PGD3 development at T48-72 h (FDR < 0.1 and p < 0.05). In the temporal analysis, using linear mixed modeling with overlap weighting, we identified unique protein patterns in patients who did or did not develop PGD3 at T48-72 h. Our findings suggest that unique inflammatory protein expression patterns may be informative of PGD severity and duration. PGD biomarker panels may improve early detection of PGD, predict its clinical course, and help monitor treatment efficacy in the current era of lung transplantation.

Trends in marginal lung allograft survival: Advanced-age donors improve.

INTRODUCTION: Although lung demand continues to outpace supply, 75% of potential donor lungs are discarded without being transplanted in the United States. To identify the discarded cohorts best suited to alleviate the lung shortage and reduce waitlist mortality, we explored changes in survival over time for five marginal donor definitions: age >60 years, smoking history >20 pack-years, PaO2 /FiO2  < 300 mmHg, purulent bronchoscopic secretions, and chest radiograph infiltrates. METHODS: Our retrospective cohort study separated 27 803 lung recipients in the UNOS Database into three 5-year eras by transplant date: 2005-2009, 2010-2014, and 2015-2019. Multivariable Cox proportional hazards regression and Kaplan-Meier analysis with log-rank test were used to compare survival across the eras. RESULTS: Three definitions-low PaO2 /FiO2 , purulent bronchoscopic secretions, and abnormal chest radiographs-did not bear out as truly marginal, demonstrating lack of significantly elevated risk. Advanced donor age demonstrated considerable survival improvement (HR (95% CI): 1.47 (1.26-1.72) in 2005-2009 down to 1.14 (.97-1.35) for 2015-2019), with protective factors being recipients <60 years, moderate recipient BMI, and low Lung Allocation Score (LAS). Donors with smoking history failed to demonstrate any significant improvement (HR (95% CI): 1.09 (1.01-1.17) in 2005-2009 increasing to 1.22 (1.08-1.38) in 2015-2019). CONCLUSIONS: Advanced donor age, previously the most significant risk factor, has improved to near-benchmark levels, demonstrating the possibility for matching older donors to healthier non-elderly recipients in selected circumstances. Low PaO2 /FiO2 , bronchoscopic secretions, and abnormal radiographs demonstrated survival on par with standard donors. Significant donor smoking history, a moderate risk factor, has failed to improve.

Controlled DCD lung transplantation: Circumventing imagined and real barriers-time for an international taskforce?

Controlled donation after circulatory death (DCD) has the potential to substantially increase the number of lung transplants thus offsetting some of the imbalance between need and organ availability. We examine the potential benefits associated with increased DCD utilization as well as the perceived barriers to the expansion of DCD. Solutions are offered as a means to expand DCD utilization across centers and nations.

Pediatric lung transplantation for COVID-19: Unique clinical and psychosocial barriers.

BACKGROUND: SARS-CoV-2 infection in the age group of 0-17 years contributes to approximately 22% of all laboratory-confirmed SARS-CoV-2 infections. Fortunately, this age group has a lower death rate (0.5 per 100 000) that accounts for only 4% of the total deaths due to COVID-19. Despite the low mortality rate in the pediatric population, children of minority groups represented 78% of the deaths highlighting the existing disparities in access to health care. METHODS: With the emergence of the more contagious COVID-19 variants and the relatively slow pace of vaccination among the pediatric population, it is possible to see more cases of significant lung injury and potential for transplantation for the younger age group. RESULTS: To our knowledge, our patient is the youngest to have undergone lung transplantation for SARS-CoV-2. CONCLUSION: The case presented unique challenges, particularly in relation to timing for listing and psychosocial support for parents who were his decision makers.