Adverse Outcomes Associated With Atrial Arrhythmias After Veno-Venous Extracorporeal Membrane Oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) is used as a treatment modality in those who fail to respond to conventional care. Hypoxia and medications used in the intensive care unit may increase risk for atrial arrhythmias (AA). This study aims to evaluate the impact of AA on post-VV ECMO outcome. A retrospective review of patients who were placed on VV ECMO between October 2016 and October 2021. One hundred forty-five patients were divided into two groups, AA and no AA. Baseline characteristic and potential risk factors were assessed. Uni- and multivariate analysis using logistic regression models were constructed to evaluate the predictors of mortality between groups. Survival between groups was estimated by the Kaplan-Meier method using the log-rank test. Advanced age with history of coronary artery disease and hypertension were associated with increased risk to develop AA post-VV ECMO placement ( p value < 0.05). Length on ECMO, time intubated, hospital length of stay, and sepsis were significantly increased in patients in the AA group ( p value < 0.05). There was no difference in the overall mortality between the two groups. AAs were associated with worse hospital course and complications but no difference in overall mortality rate. Age and cardiovascular disease seem to be predisposing risk factors for this. Further studies are needed to investigate potential strategies to prevent AAs development in this population.

Bridging strategies and cardiac replacement outcomes in patients with acute decompensated heart failure-related cardiogenic shock.

AIMS: To describe outcomes associated with bridging strategies in patients with acute decompensated heart failure-related cardiogenic shock (ADHF-CS) bridged to durable left ventricular assist device (LVAD) or heart transplantation (HTx). METHODS AND RESULTS: Durable LVAD or HTx recipients from 2014 to 2019 with pre-operative ADHF-CS were identified in the Society of Thoracic Surgeons Adult Cardiac Surgery Database and stratified by bridging strategy. The primary outcome was operative or 30-day post-operative mortality. Secondary outcomes included post-operative major bleeding. Exploratory comparisons between bridging strategies and outcomes were performed using overlap weighting with and without covariate adjustment. Among 9783 patients with pre-operative CS, 8777 (89.7%) had ADHF-CS. Medical therapy (n = 5013) was the most common bridging strategy, followed by intra-aortic balloon pump (IABP; n = 2816), catheter-based temporary mechanical circulatory support (TMCS; n = 417), and veno-arterial extracorporeal membrane oxygenation (VA-ECMO; n = 465). Mortality was highest in patients bridged with VA-ECMO (22%), followed by catheter-based TMCS (10%), IABP (9%), and medical therapy (7%). Adverse post-operative outcomes were more frequent in LVAD recipients compared with HTx recipients. CONCLUSION: Among patients with ADHF-CS bridged to HTx or durable LVAD, the highest rates of death and adverse events during index hospitalization were observed in those bridged with VA-ECMO, followed by catheter-based TMCS, IABP, and medical therapy. Patients who received durable LVAD had higher rates of post-operative complications compared with HTx recipients. Prospective trials are needed to define optimal bridging strategies in patients with ADHF-CS.

The Cost-effectiveness of Transplanting Hearts From Hepatitis C-infected Donors Into Uninfected Recipients.

BACKGROUND: The DONATE HCV trial demonstrated the safety and efficacy of transplanting hearts from hepatitis C viremic (HCV+) donors. In this report, we examine the cost-effectiveness and impact of universal HCV+ heart donor eligibility in the United States on transplant waitlist time and life expectancy. METHODS: We developed a microsimulation model to compare 2 waitlist strategies for heart transplant candidates in 2018: (1) status quo (SQ) and (2) SQ plus HCV+ donors (SQ + HCV). From the DONATE HCV trial and published national datasets, we modeled mean age (53 years), male sex (75%), probabilities of waitlist mortality (0.01-0.10/month) and transplant (0.03-0.21/month) stratified by medical urgency, and posttransplant mortality (0.003-0.052/month). We assumed a 23% increase in transplant volume with SQ + HCV compared with SQ. Costs (2018 United States dollar) included waitlist care ($2200-190 000/month), transplant ($213 400), 4-wk HCV treatment ($26 000), and posttransplant care ($2500-11 300/month). We projected waitlist time, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs [$/QALY, discounted 3%/year]; threshold ≤$100 000/QALY). RESULTS: Compared with SQ, SQ + HCV decreased waitlist time from 8.7 to 6.7 months, increased undiscounted life expectancy from 8.9 to 9.2 QALYs, and increased discounted lifetime costs from $671 400/person to $690 000/person. Four-week HCV treatment comprised 0.5% of lifetime costs. The ICER of SQ + HCV compared with SQ was $74 100/QALY and remained ≤$100 000/QALY with up to 30% increases in transplant and posttransplant costs. CONCLUSIONS: Transplanting hearts from HCV-infected donors could decrease waitlist times, increase life expectancy, and be cost-effective. These findings were robust within the context of current high HCV treatment costs.

Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm.

The immune system represents a major barrier to cancer progression, driving the evolution of immunoregulatory interactions between malignant cells and T-cells in the tumor environment. Blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare acute leukemia with plasmacytoid dendritic cell (pDC) differentiation, provides a unique opportunity to study these interactions. pDCs are key producers of interferon alpha (IFNA) that play an important role in T-cell activation at the interface between the innate and adaptive immune system. To assess how uncontrolled proliferation of malignant BPDCN cells affects the tumor environment, we catalog immune cell heterogeneity in the bone marrow (BM) of five healthy controls and five BPDCN patients by analyzing 52,803 single-cell transcriptomes, including 18,779 T-cells. We test computational techniques for robust cell type classification and find that T-cells in BPDCN patients consistently upregulate interferon alpha (IFNA) response and downregulate tumor necrosis factor alpha (TNFA) pathways. Integrating transcriptional data with T-cell receptor sequencing via shared barcodes reveals significant T-cell exhaustion in BPDCN that is positively correlated with T-cell clonotype expansion. By highlighting new mechanisms of T-cell exhaustion and immune evasion in BPDCN, our results demonstrate the value of single-cell multiomics to understand immune cell interactions in the tumor environment.

The impact of hospital size on national trends and outcomes in isolated open proximal aortic surgery.

OBJECTIVE: To determine the impact of hospital size on national trend estimates of isolated open proximal aortic surgery for benchmarking hospital performance. METHODS: Patients age >18 years who underwent isolated open proximal aortic surgery for aneurysm and dissection from 2002 to 2014 were identified using the National Inpatient Sample. Concomitant valvular, vessel revascularization, re-do procedures, endovascular, and surgery for descending and thoracoabdominal aorta were excluded. Discharges were stratified by hospital size and analyzed using trend, multivariable regression, propensity-score matching analysis. RESULTS: Over a 13-year period, 53,657 isolated open proximal aortic operations were performed nationally. Although the total number of operations/year increased (∼2.9%/year increase) and overall in-hospital mortality decreased (∼4%/year; both P < .001 for trend), these did not differ by hospital size (P > .05). Large hospitals treated more sicker and older patients but had shorter length of stay and lower hospital costs (both P < .001). Even after propensity-score matching, large hospital continued to demonstrate superior in-hospital outcomes, although only statistically for major in-hospital cardiac complications compared with non-large hospitals. In our subgroup analysis of dissection versus non-dissection cohort, in-hospital mortality trends decreased only in the non-dissection cohort (P < .01) versus dissection cohort (P = .39), driven primarily by the impact of large hospitals (P < .01). CONCLUSIONS: This study demonstrates increasing volume and improving outcomes of isolated open proximal aortic surgeries nationally over the last decade regardless of hospital bed size. Moreover, the resource allocation of sicker patients to larger hospital resulted shorter length of stay and hospital costs, while maintaining similar operative mortality to small- and medium-sized hospitals.

1-year outcomes for lung transplantation recipients with non-alcoholic fatty liver disease.

Advanced hepatic fibrosis and cirrhosis are absolute contraindications to lung transplantation. [ 1] However, whether fatty liver disease with mild-moderate fibrosis contributes to increased adverse outcomes post-lung transplantation remains unknown. We present a retrospective analysis of patients transplanted at Brigham and Women's Hospital between 2015 and 2017 to identify whether patients with mild-moderate non-alcoholic fatty liver disease (NAFLD) experience increased short-term complications compared to patients with normal liver architecture. Patients with advanced (F3-F4) fibrosis and/or cirrhosis were considered non-suitable transplant candidates, a priori. This study was powered for a difference in index hospital-free days within the first 30 days of 25% (α=0.05, ß=0.8). Secondary outcomes included index intensive care unit (ICU)-free days within the first 10 days post-transplant, perioperative blood product transfusion, incidence of index hospitalisation arrhythmias and delirium, need for insulin on discharge post-transplant, tacrolimus dose required to maintain a trough of 8-12 ng·mL-1 at index hospital discharge, and 1-year post-transplant incidence of insulin-dependent diabetes, acute kidney injury, acute cellular rejection, unplanned hospital readmissions and infection. 150 patients underwent lung transplantation between 2015 and 2017 and were included in the analysis; of these patients 40 (27%) had evidence of NAFLD. Median index hospital-free days for patients with NAFLD were non-inferior to those without (16 days, IQR 10.5-19.5 versus 12 days, IQR 0-18.0, p=0.03). Regarding secondary outcomes, both index hospitalisation and 1-year outcomes were non-inferior between patients with NAFLD and those with normal liver architecture. This study demonstrates that mild-moderate severity NAFLD may not be a contraindication to lung transplantation.

N-myc-interactor mediates microbiome induced epithelial to mesenchymal transition and is associated with chronic lung allograft dysfunction.

BACKGROUND: Recent evidence suggests a role for lung microbiome in occurrence of chronic lung allograft dysfunction (CLAD). However, the mechanisms linking the microbiome to CLAD are poorly delineated. We investigated a possible mechanism involved in microbial modulation of mucosal response leading to CLAD with the hypothesis that a Proteobacteria dominant lung microbiome would inhibit N-myc-interactor (NMI) expression and induce epithelial to mesenchymal transition (EMT). METHODS: Explant CLAD, non-CLAD, and healthy nontransplant lung tissue were collected, as well as bronchoalveolar lavage from 14 CLAD and matched non-CLAD subjects, which were followed by 16S rRNA amplicon sequencing and quantitative polymerase chain reaction (PCR) analysis. Pseudomonas aeruginosa (PsA) or PsA-lipopolysaccharide was cocultured with primary human bronchial epithelial cells (PBEC). Western blot analysis and quantitative reverse transcription (qRT) PCR was performed to evaluate NMI expression and EMT in explants and in PsA-exposed PBECs. These experiments were repeated after siRNA silencing and upregulation (plasmid vector) of EMT regulator NMI. RESULTS: 16S rRNA amplicon analyses revealed that CLAD patients have a higher abundance of phyla Proteobacteria and reduced abundance of the phyla Bacteroidetes. At the genera level, CLAD subjects had an increased abundance of genera Pseudomonas and reduced Prevotella. Human CLAD airway cells showed a downregulation of the N-myc-interactor gene and presence of EMT. Furthermore, exposure of human primary bronchial epithelial cells to PsA resulted in downregulation of NMI and induction of an EMT phenotype while NMI upregulation resulted in attenuation of this PsA-induced EMT response. CONCLUSIONS: CLAD is associated with increased bacterial biomass and a Proteobacteria enriched airway microbiome and EMT. Proteobacteria such as PsA induces EMT in human bronchial epithelial cells via NMI, demonstrating a newly uncovered mechanism by which the microbiome induces cellular metaplasia.

Advanced Surgical and Percutaneous Approaches to Pulmonary Vascular Disease.

Despite progress in modern medical therapy, pulmonary hypertension remains an unremitting disease. Once severe or refractory to medical therapy, advanced percutaneous and surgical interventions can palliate right ventricular overload, bridge to transplantation, and overall extend a patient's course. These approaches include atrial septostomy, Potts shunt, and extracorporeal life support. Bilateral lung transplantation is the ultimate treatment for eligible patients, although the need for suitable lungs continues to outpace availability. Measures such as ex vivo lung perfusion are ongoing to expand donor lung availability, increase rates of transplant, and decrease waitlist mortality.

Long-term Outcomes of Aortic Valve Replacement With Aortic Homograft: 27 Years Experience.

BACKGROUND: Aortic homografts have been used in young patients requiring aortic valve replacement. Currently, these grafts are generally reserved for aortic valve endocarditis with or without root abscess; however, longitudinal data are lacking. Our aim was to assess the long-term safety and durability of homograft implantation. METHODS: All adult patients undergoing aortic homograft implantation at a single institution from 1992 to 2019 were included. Outcomes of interest included all-cause mortality and aortic valve reoperation, studied over a median follow-up duration of 19 years. RESULTS: In all, 252 patients with a mean age of 49 years were included. Infective endocarditis was the primary indication for surgery in 95 patients (38%). The endocarditis group, compared with the no-endocarditis group, had a higher prevalence of New York Heart Association class III-IV (56% vs 26%), chronic kidney disease (22% vs 1%), prior cardiac surgery (40% vs 10%), and emergency status (7% vs 0%; all P < .001). Operative mortality was higher among endocarditis patients (16% vs 0.6%, P < .001), which persisted after risk adjustment. Among patients who survived to discharge, however, there was no difference in long-term survival between the endocarditis group and no-endocarditis group. Overall survival and freedom from reoperation were 88.3% and 80% at 15 years and 87.2% and 78% at 25 years, respectively. Indications for reoperation included structural valve deterioration (83%), endocarditis (12%), and mitral valve disease (5%). Reoperative mortality occurred in 2 patients (4.9%). CONCLUSIONS: Aortic homografts are associated with good long-term survival and admissible freedom from reoperation. Operative mortality is high among patients with endocarditis; however, for those who survive to discharge, long-term survival and durability are the same as for patients without endocarditis.

Multimodality Curative Treatment of IIIA/T4 Lung Adenocarcinoma.

We present a 41-year-old female smoker with concurrent invasive ductal carcinoma of the right breast and stage IIIA (T4N0M0) adenocarcinoma of the left lung requiring neoadjuvant chemoradiation followed by left pneumonectomy. We use this report as an educational work to show how multidisciplinary clinical decisions can be made to give way to successful treatment of a highly complex lung adenocarcinoma. Specifically, we show curative radical treatment of T4 disease and successful radical intervention of radiation-induced cardiac complications to achieve a comprehensive and curative treatment.

COVID-19 patient bridged to recovery with veno-venous extracorporeal membrane oxygenation.

BACKGROUND: In severe cases, the coronavirus disease 2019 (COVID-19) viral pathogen produces hypoxic respiratory failure unable to be adequately supported by mechanical ventilation. The role of extracorporeal membrane oxygenation (ECMO) remains unknown, with the few publications to date lacking detailed patient information or management algorithms all while reporting excessive mortality. METHODS: Case report from a prospectively maintained institutional ECMO database for COVID-19. RESULTS: We describe veno-venous (VV) ECMO in a COVID-19-positive woman with hypoxic respiratory dysfunction failing mechanical ventilation support while prone and receiving inhaled pulmonary vasodilator therapy. After 9 days of complex management secondary to her hyperdynamic circulation, ECMO support was successfully weaned to supine mechanical ventilation and the patient was ultimately discharged from the hospital. CONCLUSIONS: With proper patient selection and careful attention to hemodynamic management, ECMO remains a reasonable treatment option for patients with COVID-19.

Left ventricle unloading strategies in ECMO: A single-center experience.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a life-saving technology capable of restoring perfusion but is not without significant complications that limit its realizable therapeutic benefit. ECMO-induced hemodynamics increase cardiac afterload risking left ventricular distention and impaired cardiac recovery. To mitigate potentially harmful effects, multiple strategies to unload the left ventricle (LV) are used in clinical practice but data supporting the optimal approach is presently lacking. MATERIALS & METHODS: We reviewed outcomes of our ECMO population from September 2015 through January 2019 to determine if our LV unloading strategies were associated with patient outcomes. We compared reactive (Group 1, n = 30) versus immediate (Group 2, n = 33) LV unloading and then compared patients unloaded with an Impella CP (n = 19) versus an intra-aortic balloon pump (IABP, n = 16), analyzing survival and ECMO-related complications. RESULTS: Survival was similar between Groups 1 and 2 (33 vs 42%, P = .426) with Group 2 experiencing more clinically-significant hemorrhage (40 vs. 67%, P = .034). Survival and ECMO-related complications were similar between patients unloaded with an Impella versus an IABP. However, the Impella group exhibited a higher rate of survival (37%) than predicted by their median SAVE score (18%). DISCUSSION: Based on this analysis, reactive unloading appears to be a viable strategy while venting with the Impella CP provides better than anticipated survival. Our findings correlate with recent large cohort studies and motivate further work to design clinical guidelines and future trial design.

The impact of hepatitis C viremic donor lung allograft characteristics on post-transplantation outcomes.

BACKGROUND: There is a low utilization rate of donated donor lungs. Historically, transplantation of lungs from hepatitis C-viremic donors to hepatitis C (HCV) negative recipients was avoided due to concern for worse graft survival. In the past few years with the advent of direct acting antiviral (DAA) therapy, there are emerging data suggesting the safety and efficacy of transplanting thoracic organs from HCV-viremic donors. This study assessed the differences in donor characteristics and allograft-specific clinical features at the time of organ offer and investigated whether these variables differed in HCV-viremic versus HCV-negative donors and impacted recipient outcomes. METHODS: We conducted a single-center, retrospective cohort study of adult patients who underwent a lung transplant at Brigham and Women's Hospital between March 2017 and October 2018. Patients were stratified based on their donor HCV status (HCV-viremic versus HCV-negative). Donor and allograft-specific characteristics and clinical features including chest imaging and bronchoscopy reports, respiratory cultures, and the donor's oxygenation as measured by the arterial partial pressure of oxygen (PaO2) were collected as well as recipient baseline characteristics and transplant outcomes. RESULTS: During the study period, 42 and 57 lung transplants were performed from HCV-viremic and HCV-negative donors, respectively. Donor age was similar in both cohorts. More HCV-viremic donors died from drug intoxication (71% versus 19%, P=0.0001) and had a history of cigarette use (83% versus 5%, P=0.0001) and drug use (76% versus 49%, P=0.007). There were differences in the baseline recipient characteristics including a lower median lung allocation score in the HCV-viremic cohort. The organ-specific clinical characteristics including the terminal PaO2, chest imaging and bronchoscopy findings, and evidence of pulmonary infection were similar between the two cohorts. The recipient outcomes overall were excellent and did not differ significantly in both cohorts in terms of graft and patient survival at 6 and 12 months. CONCLUSIONS: Despite a greater proportion of HCV-viremic donors being increased risk with a history of drug and cigarette use and having died as a result of drug intoxication, the quality of the HCV-viremic donor organs did not differ from the HCV-negative donor organs or impact graft and recipient survival. Due to an increasing number of transplants from increased risk donors and in order to develop safe and effective protocols to perform lung transplants from HCV-infected donors, further characterization of the donor and allograft-specific clinical features and longer-term recipient outcomes is greatly needed.

Sternotomy versus thoracotomy lung transplantation: key tips and contemporary results.

The purpose of this report is to provide an updated description of the technique of bilateral sequential lung transplant via median sternotomy. A sternotomy provides the advantage of less morbidity than the clamshell incision, as well as exposure to perform mechanical circulatory support and concurrent cardiac procedures. Our experience shows that lung transplantation via a midline sternotomy can be done with equivalent to better short-term outcomes than a clamshell incision, including earlier extubation and fewer transfusions. Familiarity with this technique is important for all surgeons managing end-stage lung disease.

The impact of statin therapy on neurological events following left ventricular assist system implantation in advanced heart failure.

BACKGROUND: Stroke is a leading cause of disability and death in advanced heart failure patients supported with a continuous-flow left ventricular assist system (CF-LVAS). Statins (HMG-CoA reductase inhibitors) reduce the risk of major cardiovascular and neurological events such as stroke, but their impact has not been evaluated in patients implanted with a CF-LVAS. We sought to explore the association between use of statin therapy and subsequent occurrence of neurological events, particularly stroke, following CF-LVAS implantation. METHODS: We performed a single center, retrospective, observational cohort study in 200 consecutive adults implanted with a durable CF-LVAS over a 10-year period (2008-2018). We compared patients according to statin use following pump implantation, stratified by an exploratory analysis of pump type (HeartMate II, HeartWare HVAD, and HeartMate 3 [HM3] LVAS). RESULTS: Overall, 24% of CF-LVAS recipients developed at least 1 neurological event, at a rate of 0.11 events per patient-year (EPPY) among those prescribed statins and 0.22 EPPY among non-users (age-adjusted hazard ratio [HR] 0.46; 95% confidence interval [CI],0.24-0.88; p = 0.019). In the cohort without the HM3 pump, ischemic strokes were 62% lower among statin users (0.05 versus 0.12 EPPY for non-users; age-adjusted HR, 0.38; 95% CI, 0.15-0.99; p = 0.048). The risk of ischemic stroke did not differ significantly when HM3 recipients were included in the analysis (age-adjusted HR, 0.51; 95% CI, 0.22-1.21; p = 0.13). However, ischemic stroke rate in HM3 LVAS recipients was similar to the rate in statin users who received a non-HM3 LVAS (0.06 and 0.05 EPPY, respectively). Rates of hemorrhagic stroke and other safety end points were not significantly different according to statin use. CONCLUSION: Statin prescription following CF-LVAS is associated with lower rates of neurological events, driven predominantly by a reduction in ischemic strokes. These findings suggest that most patients with a pre-existing indication for statin therapy may continue using statins following CF-LVAS in an effort to decrease the incidence of ischemic stroke.

Recipient Airway Bronchoplasty for Donor "Pig Bronchus".

Dissemination of surgical techniques to manage rare donor airway anomalies may improve outcomes after lung transplantation. This report describes a case of an unsuspected donor tracheal bronchus that was successfully managed with a native right mainstem bronchoplasty.