Circulating T cell specific extracellular vesicle profiles in cardiac allograft acute cellular rejection.

There is a critical need for biomarkers of acute cellular rejection (ACR) in organ transplantation. We hypothesized that ACR leads to changes in donor-reactive T cell small extracellular vesicle (sEV) profiles in transplant recipient circulation that match the kinetics of alloreactive T cell activation. In rodent heart transplantation, circulating T cell sEV quantities (P < .0001) and their protein and mRNA cargoes showed time-specific expression of alloreactive and regulatory markers heralding early ACR in allogeneic transplant recipients but not in syngeneic transplant recipients. Next generation sequencing of their microRNA cargoes identified novel candidate biomarkers of ACR, which were validated by stem loop quantitative reverse transcription polymerase chain reaction (n = 10). Circulating T cell sEVs enriched from allogeneic transplant recipients mediated targeted cytotoxicity of donor cardiomyocytes by apoptosis assay (P < .0001). Translation of the concept and EV methodologies to clinical heart transplantation demonstrated similar upregulation of circulating T cell sEV profiles at time points of grade 2 ACR (n = 3 patients). Furthermore, T cell receptor sequencing of T cell sEV mRNA cargo demonstrated expression of T cell clones with intact complementarity determining region 3 signals. These data support the diagnostic potential of T cell sEVs as noninvasive biomarker of ACR and suggest their potential functional roles.

Donor extracellular vesicle trafficking via the pleural space represents a novel pathway for allorecognition after lung transplantation.

Restoration of lymphatic drainage across the bronchial anastomosis after lung transplantation requires several weeks. As donor antigen and antigen presenting cell trafficking via lymphatics into graft-draining lymph nodes is an important component of the alloresponse, alternative pathways must exist that account for rapid rejection after pulmonary transplantation. Here, we describe a novel allorecognition pathway mediated through donor extracellular vesicle (EV) trafficking to mediastinal lymph nodes via the pleural space. Pleural fluid collected early after lung transplantation in rats and humans contains donor-specific EVs. In a fully MHC mismatched rat model of lung transplantation, we demonstrate EVs carrying donor antigen preferentially accumulate in mediastinal lymph nodes and colocalize with MHC II expressing cells within 4 h of engraftment. Injection of allogeneic EVs into pleural space of syngeneic lung transplant recipients confirmed their selective trafficking to mediastinal lymph nodes and resulted in activation of T cells in mediastinal, but not peripheral lymph nodes. Thus, we have uncovered an alternative pathway of donor antigen trafficking where pulmonary EVs released into the pleural space traffic to locoregional lymph nodes via pleural lymphatics. This pathway obviates the need for restoration of lymphatics across the bronchial anastomosis for trafficking of donor antigen to draining lymph nodes.

Cytokine-Like 1 Is a Novel Proangiogenic Factor Secreted by and Mediating Functions of Endothelial Progenitor Cells.

RATIONALE: Endothelial colony forming cells (ECFCs) or late blood outgrowth endothelial cells can be isolated from human cord or peripheral blood, display properties of endothelial progenitors, home into ischemic tissues and support neovascularization in ischemic disease models. OBJECTIVE: To assess the functions of CYTL1 (cytokine-like 1), a factor we found preferentially produced by ECFCs, in regard of vessel formation. METHODS AND RESULTS: We show by transcriptomic analysis that ECFCs are distinguished from endothelial cells of the vessel wall by production of high amounts of CYTL1. Modulation of expression demonstrates that the factor confers increased angiogenic sprouting capabilities to ECFCs and can also trigger sprouting of mature endothelial cells. The data further display that CYTL1 can be induced by hypoxia and that it functions largely independent of VEGF-A (vascular endothelial growth factor-A). By recombinant production of CYTL1 we confirm that the peptide is indeed a strong proangiogenic factor and induces sprouting in cellular assays and functional vessel formation in animal models comparable to VEGF-A. Mass spectroscopy corroborates that CYTL1 is specifically O-glycosylated on 2 neighboring threonines in the C-terminal part and this modification is important for its proangiogenic bioactivity. Further analyses show that the factor does not upregulate proinflammatory genes and strongly induces several metallothionein genes encoding anti-inflammatory and antiapoptotic proteins. CONCLUSIONS: We conclude that CYTL1 can mediate proangiogenic functions ascribed to endothelial progenitors such as ECFCs in vivo and may be a candidate to support vessel formation and tissue regeneration in ischemic pathologies.

Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue.

Obesity is characterized by an accumulation of macrophages in adipose, some of which form distinct crown-like structures (CLS) around fat cells. While multiple discrete adipose tissue macrophage (ATM) subsets are thought to exist, their respective effects on adipose tissue, and the transcriptional mechanisms that underlie the functional differences between ATM subsets, are not well understood. We report that obese fat tissue of mice and humans contain multiple distinct populations of ATMs with unique tissue distributions, transcriptomes, chromatin landscapes, and functions. Mouse Ly6c ATMs reside outside of CLS and are adipogenic, while CD9 ATMs reside within CLS, are lipid-laden, and are proinflammatory. Adoptive transfer of Ly6c ATMs into lean mice activates gene programs typical of normal adipocyte physiology. By contrast, adoptive transfer of CD9 ATMs drives gene expression that is characteristic of obesity. Importantly, human adipose tissue contains similar ATM populations, including lipid-laden CD9 ATMs that increase with body mass. These results provide a higher resolution of the cellular and functional heterogeneity within ATMs and provide a framework within which to develop new immune-directed therapies for the treatment of obesity and related sequela.

Urgent transcatheter aortic valve replacement may be performed with acceptable long-term outcomes.

BACKGROUND: The wide availability of transcatheter aortic valve replacement (TAVR) and broadening of its indications to most patients with aortic stenosis may increase its utilization in the urgent setting. However, a comparison of long-term outcomes of patients undergoing urgent TAVR when compared to elective TAVR have not been well studied. METHODS: All patients that underwent TAVR from 2011 to 2018 were included. Primary outcomes included operative (30-day), 1-, and 5-year survival and readmissions. RESULTS: The total patient population undergoing TAVR was divided into urgent (n = 247) and elective (n = 946) cohorts. Thirty days mortality (6.5% vs. 2.3%; p = .001), acute kidney injury (2.8% vs. 0.6%; p = .003), and length of stay (12 vs. 3 days; p < .001) were higher for the urgent cohort. There was no significant difference between cohorts for 30-day all-cause (14.6% vs. 10.8%; p = .097) readmissions. Freedom from readmission for heart failure at 1-year (73.6% vs. 83.4%; p < .001) was lower for the urgent cohort. One- (79.0% vs. 87.1%; p < .001) and five-year (39.6% vs. 43.5%; p = .005) survival was lower for the urgent cohort. This difference was eliminated after risk adjustment (hazard ratio [HR]: 1.3; p = .158 and HR: 1.1; p = .639, respectively). CONCLUSION: Unadjusted survival was significantly worse for the urgent cohort up to 1 year. This trend continued for 5-year survival, however, after risk adjustment there was no significant difference in survival between cohorts. Although urgent TAVR is associated with increased periprocedural risk due to more comorbid disease, outcomes and long-term survival are encouraging and support the consideration of urgent TAVR as a viable alternative for this patient population.

STratification risk analysis in OPerative management (STOP score) for drug-induced endocarditis.

BACKGROUND: The opioid epidemic has seen a drastic increase in the incidence of drug-associated infective endocarditis (IE). No clinical tool exists to predict operative morbidity and mortality in patients undergoing surgery. METHODS: A multi-institutional database was reviewed between 2011 and 2018. Multivariate logistic regression was fitted in an automated stepwise fashion. The STratification risk analysis in OPerative management of drug-associated IE (STOP) score was constructed. Morbidity was defined as reintubation, prolonged ventilation, pneumonia, renal failure, dialysis, stroke, reoperation for bleeding, and a permanent pacemaker. Cross-validation provided an unbiased estimate of out-of-sample performance. RESULTS: A total of 1181 patients underwent surgery for drug-associated IE (median age, 39; interquartile range [IQR], 30-54, 386 women [32.7%], 341 reoperations for prosthetic valve endocarditis [28.9%], 316 patients with multivalve disease [26.8%]). Operative morbidity and mortality were 41.1% and 5.9%, respectively. Predictors of morbidity were dialysis (95% confidence interval [CI], 1.16-2.82), emergent intervention (1.83-4.73), multivalve procedure (1.01-1.98), causative organisms other than Streptococcus (1.09-2.02), and type of valve procedure performed [aortic valve procedure (1.07-2.15), mitral valve replacement (1.03-2.05), tricuspid valve replacement (1.21-2.60)]. Predictors of mortality were dialysis (1.29-5.74), active endocarditis (1.32-83), lung disease (1.25-5.43), emergent intervention (1.69-6.60), prosthetic valve endocarditis (1.24-3.69), aortic valve procedure (1.49-5.92) and multivalve disease (1.00-2.95). Variables maximizing explanatory power were translated into a scoring system. Each point increased odds of morbidity and mortality by 22.0% and 22.4% with an accuracy of 94.0% and 94.1%, respectively. CONCLUSION: Drug-related IE is associated with significant morbidity and mortality. An easily-applied risk stratification score may aid in clinical decision-making.

Midterm outcomes of subcoronary stentless porcine valve versus stented aortic valve replacement.

INTRODUCTION: Stentless porcine xenografts are versatile bioprosthetic valves with the advantage of improved hemodynamics that mimic the function of the native aortic valve. However, these bioprostheses are challenging to implant in the subcoronary position. METHODS: All consecutive patients who underwent a bioprosthetic aortic valve replacement (AVR) were included from our institutional database. Cox regression analysis was preformed to determine significant predictors for mid term mortality as well as all cause, cardiac, and heart failure readmission. RESULTS: Patients in the subcoronary stentless group were older and more likely to be female and were likely to have a higher Society of Thoracic Surgery risk of mortality. Survival was superior in the stented AVR cohort at 30-days (96.4% vs 90.5%; P < .001), 1-year (90.5% vs 71.6%; P < .001), and 5-year (74.5% vs 56.9%; P < .001) follow up. Acute kidney injury (16.22% vs 5.22%; P < .001) and blood product transfusion (70.27% vs 44.0%; P < .001) were higher in the stentless group. Multivariable analysis revealed subcoronary stentless implantation as a significant independent risk factor for mortality (hazards ratio: 1.92 [1.35,2.72]; P < .001). CONCLUSION: Stentless porcine xenograft implantation with the Freestyle bioprosthetic in the subcoronary position can be successfully performed in select patients, but its use is associated with increased perioperative morbidity and mortality affecting midterm outcomes. Individual patient selection and surgeon experience are important to ensure favorable outcomes.

The role of extracorporeal life support for patients with COVID-19: Preliminary results from a statewide experience.

OBJECTIVE: There is a paucity of clinical data on critically ill patients with COVID-19 requiring extracorporeal life support. METHODS: A statewide multi-institutional collaborative for COVID-19 patients was utilized to obtain clinical data on the first 10 critically ill COVID-19 patients who required extracorporeal membrane oxygenation (ECMO). RESULTS: Of the first 10 patients that required ECMO for COVID-19, the age ranged from 31 to 62 years with the majority (70%) being men. Seven (70%) had comorbidities. The majority (80%) of patients had known sick contact and exposure to COVID-19 positive patients or traveled to pandemic areas inside the United States within the 2 weeks before symptom onset. None of the patients were healthcare workers. The most common symptoms leading to the presentation were high fever ≥103°F (90%), cough (80%) and dyspnea (70%), followed by fatigue and gastrointestinal symptoms (both 30%), myalgia, loss of taste, pleuritic chest pain, and confusion (all 10%). All patients had bilateral infiltrates on chest X-rays suggestive of interstitial viral pneumonia. All patients were cannulated in the venovenous configuration. Two (20%) patients were successfully liberated from ECMO support after 7 and 10 days, respectively, and one (10%) patient is currently on a weaning course. One patient (10%) died after 9 days on ECMO from multiorgan dysfunction. CONCLUSIONS: These preliminary multi-institutional data from a statewide collaborative offer insight into the clinical characteristics of the first 10 patients requiring ECMO for COVID-19 and their initial clinical course. Greater morbidity and mortality is likely to be seen in these critically ill patients with longer follow-up.

The long-term impact of peripheral cannulation for redo cardiac surgery.

BACKGROUND: Redo cardiac surgery carries an inherent risk for adverse short-term outcomes and worse long-term survival. Strategies to mitigate these risks have been numerous, including initiation of cardiopulmonary bypass via peripheral cannulation before resternotomy. This study evaluated the impact of central versus peripheral cannulation on long-term survival after redo cardiac surgery. METHODS: This was an observational study of open cardiac surgeries between 2010 and 2018. Patients undergoing open cardiac surgery that utilized cardiopulmonary bypass, who also had more than equal to 1 prior cardiac surgery, were identified. Kaplan-Meier survival estimation and multivariable Cox regression analysis were performed to assess the impact of peripheral cannulation on survival. To isolate long-term survival, patients with operative mortality were excluded and survival time was counted from the date of discharge until the date of death. RESULTS: Of the 1660 patients with more than equal to 1 prior cardiac surgery, 91 (5.5%) received peripheral cannulation. After excluding patients with operative mortality and after multivariable risk-adjustment, the peripheral cannulation group had significantly increased hazard of death, as compared to the central cannulation group (HR 1.53, 95% CI: 1.01, 2.30, P = .044). Yet, there were no relevant differences for other postoperative outcomes, including blood product requirement, prolonged ventilation (>24 hours), pneumonia, reoperation for bleeding, stroke, sepsis, and new dialysis requirement. CONCLUSIONS: This is the first study reporting the long-term impact of peripheral cannulation for redo cardiac surgery after excluding patients with operative mortality. These data suggest that central cannulation may to be the preferred approach to redo cardiac surgery whenever safe and possible.

Noninvasive diagnosis of recurrent autoimmune type 1 diabetes after islet cell transplantation.

Islet cell transplantation is curative therapy for patients with complicated autoimmune type 1 diabetes (T1D). We report the diagnostic potential of circulating transplant islet-specific exosomes to noninvasively distinguish pancreatic ß cell injury secondary to recurrent autoimmunity vs immunologic rejection. A T1D patient with hypoglycemic unawareness underwent islet transplantation and maintained normoglycemia until posttransplant day 1098 before requiring exogenous insulin. Plasma analysis showed decreased donor islet exosome quantities on day 1001, before hyperglycemia onset. This drop in islet exosome quantity signified islet injury, but did not distinguish injury type. However, analysis of purified transplant islet exosome cargoes showed decrease in insulin-containing exosomes, but not glucagon-containing exosomes, indicating selective destruction of transplanted ß cells secondary to recurrent T1D autoimmunity. Furthermore, donor islet exosome cargo analysis showed time-specific increase in islet autoantigen, glutamic acid decarboxylase 65 (GAD65), implicated in T1D autoimmunity. Time-matched analysis of plasma transplant islet exosomes in 3 control subjects undergoing islet cell transplantation failed to show changes in islet exosome quantities or intraexosomal cargo expression of insulin, glucagon, and GAD65. This is the first report of noninvasive diagnosis of recurrent autoimmunity after islet cell transplantation, suggesting that transplant tissue exosome platform may serve as a biomarker in islet transplant diagnostics.

Detection of lung transplant rejection in a rat model using hyperpolarized [1-13 C] pyruvate-based metabolic imaging.

The current standard for noninvasive imaging of acute rejection consists of X-ray/CT, which derive their contrast from changes in ventilation, inflammation and edema, as well as remodeling during rejection. We propose the use of hyperpolarized [1-13 C] pyruvate MRI-which provides real-time metabolic assessment of tissue-as an early biomarker for tissue rejection. In this preliminary study, we used µCT-derived parameters and HP 13 C MR-derived biomarkers to predict rejection in an orthotopic left lung transplant model in both allogeneic and syngeneic rats. On day 3, the normalized lung density-a parameter that accounts for both lung volume (mL) and density (HU)-was -0.335 (CI: -0.598, -0.073) and - 0.473 (CI: -0.726, -0.220) for the allograft and isograft, respectively (not significant, 0.40). The lactate-to-pyruvate ratios-derived from the HP 13 C MRI-for the allograft and isograft were 0.200 (CI: 0.161, 0.240) and 0.114 (CI: 0.074, 0.153), respectively (significant, 0.020). Both techniques showed tissue rejection on day 7. A separate sub-study revealed CD8+ cells as the primary source of the lactate-to-pyruvate signal. Our study suggests that hyperpolarized (HP) [1-13 C] pyruvate MRI is a promising early biomarker for tissue rejection that provides metabolic assessment in real time based on changes in cellularity and metabolism of lung tissue and the infiltrating inflammatory cells, and may be able to predict tissue rejection earlier than X-ray/CT.

Sternal wound complications in patients undergoing orthotopic heart transplantation.

PURPOSE: The incidence and management of sternal wound complications in patients undergoing orthotopic heart transplantation (OHT) is not well studied. We report outcomes in heart transplant patients who developed sternal infections requiring reoperations. METHODS: From 2004 to 2013, 437 patients underwent OHT at a single institution. In a retrospective review, patients who developed sternal infections (Infection group, n = 27) were compared with those without (Control group, n = 410). RESULTS: Sternal infection rate was 6.2% (n = 27). Demographics were similar (Table 1). Infection group had higher rates of COPD 25% vs 13%, P = 0.03, and previous cardiac surgery via median sternotomy 28% vs 15%, P = 0.03. Infection group had a greater incidence of prolonged ventilation, 44% vs 31%, P = 0.2, renal failure 56% vs 24%, P = 0.001, dialysis requirement 30% vs 10%, P = 0.006, permanent stroke 11% vs 2%, P = 0.02, perioperative myocardial infarction 4% vs 0.2%, P = 0.09. The infection group had a longer ICU stay (524 + 410 vs 187 + 355 hours, P = 0.001) and hospitalization (59 + 28 vs 0.29 + 43 days, P = 0.001). In-hospital/30-day mortality was 30% vs 19%, P = 0.2. The mean time for sternal reoperation at 44 + 50 days. Deep wound infection (41%) and sternal dehiscence (22%) were common presentations. Causative organisms were Enterobacter (22%), Klebsiella (15%), and Pseudomonas (15%). Vancomycin (44%), 4th generation cephalosporin (37%), and fluoroquinolones (30%) were the most commonly used antibiotics. Surgical treatment included sternal debridement with pectoralis muscle flap (52%), primary closure (18%), and omental flap (11%). CONCLUSION: Sternal wound infections impart a significant burden on patients with OHT. Causative organisms are predominantly virulent gram-negative bacteria. Therefore, a high index of suspicion must be maintained for early detection and treatment.

Evidence That Cingulin Regulates Endothelial Barrier Function In Vitro and In Vivo.

OBJECTIVE: Cingulin is a cytoplasmic component of tight junctions. Although modulation of cingulin levels in cultured epithelial model systems has no significant effect on barrier function, evidence from cingulin knockout mice suggests that cingulin may be involved in the regulation of the behavior of epithelial or endothelial cells. Here, we investigate the role of cingulin in the barrier function of endothelial cells. APPROACH AND RESULTS: We show that cingulin is expressed in human endothelial cells of the skin, brain, and lung in vivo and in vitro. Endothelial cingulin colocalizes and coimmunoprecipitates with the tight junction proteins zonula occludens-1 and guanine nucleotide exchange factor-H1. Cingulin overexpression in human umbilical vein endothelial cell induces tight junction formation, increases transendothelial electric resistance, and strengthens barrier function for low and high molecular weight tracers. In contrast, cultured endothelial cells lacking cingulin are more permeable for low molecular weight tracers. In cingulin knockout mice, neurons of the area postrema and Purkinje cells show an increased uptake of small molecular weight tracers indicating decreased barrier function at these sites. CONCLUSIONS: We demonstrate that cingulin participates in the modulation of endothelial barrier function both in human cultured cells in vitro and in mouse brains in vivo. Understanding the role of cingulin in maintaining tight barriers in endothelia may allow developing new strategies for the treatment of vascular leak syndromes.

The role of extracorporeal membrane oxygenator therapy in the setting of Type A aortic dissection.

BACKGROUND AND AIM: Patients presenting with type A aortic dissection (TAAD) present with a wide clinical spectrum ranging from hemodynamic stability to multiorgan malperfusion with cardiovascular collapse. Extracorporeal membrane oxygenator (ECMO) therapy is increasingly being utilized as salvage therapy in patients with acute cardiopulmonary failure and for post-cardiotomy shock. We sought to determine the utility of ECMO implementation post-TAAD repair. METHODS: The Pennsylvania Health Care Cost Containment Council (PHC4) database, maintained by an independently functioning state agency, was retrospectively reviewed from 2004 to 2014. Patients with a primary diagnosis of aortic dissection requiring ECMO support during the same hospital visit were included in the analysis. RESULTS: Thirty-nine patients were identified with diagnosis/procedure codes for TAAD repair and ECMO, of which four patients did not undergo TAAD repair. Of the remaining 35, 31 patients underwent open repair, and four patients underwent TEVAR. ECMO was instituted on the same day of TAAD surgery in 27 (69.2%) patients, and on post-operative day >1 in eight (20.5%) patients. Overall mortality in patients who were on ECMO the same day was 88.9% and 87.5% when it was done after the first post-operative day. All four patients with TAAD who underwent ECMO only died. Median time from ECMO implantation to death was 1.0 day. CONCLUSIONS: Requirement for ECMO support in acute aortic dissection is associated with extremely high mortality irrespective of when the intervention is performed.

Concomitant antegrade stent grafting of the descending thoracic aorta during transverse hemiarch reconstruction for acute DeBakey I aortic dissection repair improves aortic remodeling.

BACKGROUND AND AIM: Concomitant endovascular stent grafting of the descending thoracic aorta during open repair for acute DeBakey I aortic dissection can be performed in patients with extensive dissection and malperfusion. We analyzed the effects of this strategy on distal aortic remodeling. METHODS: From 2006-2014, acute DeBakey I dissection patients without primary aortic arch tear undergoing open distal hemiarch reconstruction (Standard group) versus those undergoing hemiarch with descending thoracic aorta (DTA) thoracic endovascular aortic repair (TEVAR group) were retrospectively reviewed. We studied aortic remodeling only in patients with three-dimensional computed tomography scans available at 1 and 12 months following surgery (Standard group n = 26; Stent group n = 21). RESULTS: At 1 month, abdominal aortic diameters were similar, but true lumen (TL) and true lumen to total diameter ratios (TL index [TLI]) in the DTA were significantly improved in the TEVAR group (P < 0.05). Mean number of fenestrations were similar (1.8 ± 1.5 vs. 2.4 ± 1.9, P = 0.32). At 12 months, DTA true lumen and TLI remained significantly improved in the TEVAR group at all locations (P < 0.01). This translated to increased complete false lumen thrombosis rates in the thoracic aorta (83% vs. 32%, P = 0.01) in the TEVAR group. In the Standard group, DTA true lumen diameter and TL index were significantly decreased at 12 months compared to 1 month time period (P < 0.05). In the TEVAR group, DTA true lumen diameters and TLI were significantly improved at 12 months (P < 0.05). CONCLUSIONS: Antegrade TEVAR during open repair for DeBakey I dissection improves DTA remodeling by increasing true lumen diameter without enlargement of the total aortic diameter and by promoting false lumen thrombosis.

Innovative, simplified orthotopic lung transplantation in rats.

BACKGROUND: Various techniques of orthotopic single lung transplantation in rats have been reported; however, their widespread use has been limited owing to the complexity of the procedure. We report a novel microsurgical lung transplantation model in rats with a high survival rate that can be performed by one surgeon alone. METHODS: A total of 90 left lung allografts were transplanted from Fischer to Wistar Kyoto rats. We developed a triple axis precision system to place and stabilize the vascular clips intrathoracically to clamp the bronchovascular structures, thereby avoiding interference with the heart and contralateral lung movement. A single-suture bronchial anastomosis technique and proximal cuffing approach for vascular anastomosis was used, rendering surgical assistance unnecessary. RESULTS: In our recent series, both short-term (12 h) and long-term (21 d) survival was 100%. The lungs showed excellent perfusion and ventilation immediately on transplantation. Blood gas samples drawn from the left pulmonary vein and the histologic sections revealed excellent graft function. The donor operation lasted 20 ± 2 min, donor left lung dissection required 20 ± 2 min, and implantation required 90 ± 5 min. CONCLUSIONS: The present innovative method of left orthotopic single lung transplantation can be performed by one experienced surgeon alone, with excellent results and a high degree of reproducibility.

Clinical use and outcome of extracorporeal membrane oxygenation in patients with pulmonary embolism.

AIM OF THE STUDY: Extracorporeal membrane oxygenation (ECMO) is considered a life-saving treatment option for patients in cardiogenic shock or cardiac arrest undergoing cardiopulmonary resuscitation (CPR) due to acute pulmonary embolism (PE). We sought to analyze use and outcome of ECMO with or without adjunctive treatment strategies in patients with acute PE. METHODS: We retrospectively analyzed data on patient characteristics, treatments, and in-hospital outcomes for all PE patients (ICD-code I26) undergoing ECMO in Germany between 2005 and 2018. RESULTS: At total of 1,172,354 patients were hospitalized with PE; of those, 2,197 (0.2%) were treated with ECMO support. Cardiac arrest requiring cardiopulmonary resuscitation was present in 77,196 (6.5%) patients. While more than one fourth of those patients were treated with systemic thrombolysis alone (n = 20,839 patients; 27.0%), a minority of patients received thrombolysis and VA-ECMO (n = 165; 0.2%), embolectomy and VA-ECMO (n = 385; 0.5%) or VA-ECMOalone (n = 588; 0.8%). A multivariable logistic regression analysis indicated the lowest risk for in-hospital death in patients who received embolectomy in combination with VA-ECMO (OR, 0.50 [95% CI, 0.41-0.61], p < 0.001), thrombolysis and VA-ECMO (0.60 [0.43-0.85], p = 0.003) or VA-ECMO alone (0.68 [0.57-0.82], p < 0.001) compared to thrombolysis alone (1.04 [0.99-1.01], p = 0.116). CONCLUSION: Our findings suggest that the use of VA-ECMO alone or as part of a multi-pronged reperfusion approach including embolectomy or thrombolysis might offer survival advantages compared to thrombolysis alone in patients with PE deteriorating to cardiac arrest.

Midterm outcomes and durability of sinus segment preservation compared with root replacement for acute type A aortic dissection.

OBJECTIVE: The durability of root repair for acute type A aortic dissection is not well studied in the context of aortic insufficiency and stability of the sinuses of Valsalva. We compared clinical and functional outcomes in patients undergoing root repair and replacement for acute type A aortic dissection. METHODS: Of 716 patients undergoing surgery for acute type A aortic dissection, 585 (81.7%) underwent root repair and 131 (18.3%) underwent root replacement. Survival, cumulative incidence of reoperation, aortic insufficiency, and sinuses of Valsalva dilation were compared between the 2 groups. RESULTS: Survival at 1, 5, and 10 years was 84.1% versus 77.3%, 70.8% versus 69.2%, 57.6% versus 58.0% in the root repair and replacement groups, respectively (P = .69). Cumulative incidence of reoperation at 1, 5, and 10 years was 0.0% versus 0.8%, 1.4% versus 3.8%, and 3.4% versus 8.6% in the root repair and root replacement groups, respectively (P = .011). Multivariable Cox regression identified sinuses of Valsalva diameter 45 mm or more as a risk factor for proximal aortic reoperation (hazard ratio, 9.06; 95% confidence interval, 1.26-65.24). In a repeated-measures, linear, mixed-effects model, root replacement was associated with smaller follow-up of sinuses of Valsalva dimensions (ß = -0.66, P < .001). In an ordinal longitudinal mixed model, root replacement was associated with lower severity of postoperative aortic insufficiency (ß = -3.10, P < .001). CONCLUSIONS: Survival is similar, but the incidence of aortic insufficiency and root dilation may be greater after root repair compared with root replacement for acute type A aortic dissection.

Midterm outcomes of emergency surgery for acute type A aortic dissection in octogenarians.

OBJECTIVE: The incidence of elderly patients with acute type A aortic dissection is increasing. A recent analysis of the International Registry of Acute Aortic Dissection failed to show a mortality benefit with surgery compared with medical management in octogenarians. Therefore, we compared our institutional outcomes of emergency surgery for acute type A aortic dissection in octogenarians versus septuagenarians to understand the outcomes of surgical intervention in elderly patients. METHODS: From 2002 to 2017, 70 octogenarians (aged ≥80 years) and 165 septuagenarians (70-79 years) underwent surgery for acute type A aortic dissection (N = 235, total). Quality of life was assessed by the RAND Short Form-36 quality of life survey. Midterm clinical and functional data were obtained retrospectively. RESULTS: At baseline, septuagenarians had a higher prevalence of diabetes (20.6% vs 5.7%, P = .01). The prevalence of cardiopulmonary resuscitation was 4.8% versus 10.0% (P = .24) in septuagenarians and octogenarians. The prevalence of cardiogenic shock was 18.2% versus 27.1% (P = .17). Thirty-day/in-hospital mortality was 21.2% versus 28.6% (P = .29). Multivariable logistic regression identified cardiogenic shock as an independent risk factor for in-hospital mortality (odds ratio, 10.07; 95% confidence interval, 2.30-44.03) in octogenarians. Survival at 5 years was 49.7% (42.1%-58.6%) versus 34.2% (23.9%-48.8%) in septuagenarians and octogenarians, respectively. Responses to the quality of life survey were no different between septuagenarians and octogenarians across all 8 quality of life categories. CONCLUSIONS: Clinical outcomes after surgery for acute type A aortic dissection are similar in octogenarians and septuagenarians. For discharged survivors, quality of life remains favorable and does not differ between the 2 groups.