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INTRODUCTION: Although a role for percutaneous Impella devices has been established, there is a paucity of data regarding the utility and outcomes of larger surgically implanted Impella devices. METHODS: We conducted a retrospective review of all surgical Impella implants at our institution. All Impella 5.0 and Impella 5.5 devices were included. The primary outcome was survival. Secondary outcomes included hemodynamic and end-organ perfusion as well as commonly encountered surgical complications. RESULTS: From 2012 to 2022, 90 surgical Impella devices were implanted. The median age was 63 [53–70] years, the mean creatinine was 2.07 ± 1.22 mg/dL, and the average lactate level was 3.32 ± 2.90 mmol/L. Prior to implantation, 47 patients (52%) were supported with vasoactive agents, while 43 (48%) were also supported with another device. The most common etiology of shock was acute on chronic heart failure (50, 56%), followed by acute myocardial infarction (22, 24%), and postcardiotomy (17, 19%). Overall, 69 patients (77%) survived to device removal, and 57 (65%) survived to hospital discharge. One-year survival was 54%. Neither etiology of heart failure nor device strategy was associated with 30-day or 1-year survival. On multivariable modeling, the number of vasoactive medications prior to device implantation was strongly associated with 30-day mortality (hazard ratio 1.94 [1.27–2.96], P

Although left ventricular assist device (LVAD) implantation is associated with acceptable survival, previous reports have demonstrated that advanced age is associated with increased short-term mortality. Because age is a relative contraindication to transplantation, nontransplant centers tend to implant a disproportionate number of elderly patients. We undertook this study to evaluate the impact of advanced age on LVAD outcomes at a nontransplant center. We conducted a retrospective review of all LVAD implants at our center from 2017 to 2022. Primary stratification was by age70 years. The primary outcome was survival as assessed by the Kaplan-Meier method. The risk of 1-year mortality was further evaluated using multivariable Cox proportional hazards regression modeling. From 2017 to 2022, 93 patients underwent LVAD implantation. The mean age was 65.03 ± 11.28 years, with a median age of 68 (60 to 73) years. Most patients were INTERMACS 1 or 2 (71 patients; 76.34%). When stratified by age, 41 patients (44.09%) were aged ≥70 years. Patients aged ≥70 years had similar 30-day (96.15% vs 100.00%, p = 0.213), 1-year (90.05% vs 84.00%, p = 0.444), and 2-year survival (82.03% vs 84.00%, p = 0.870). When only the INTERMACS 1 and 2 patients with higher acuity were included, there was still no difference in 30-day, 1-year, or 2-year survival. On multivariable analysis, age70 years was not associated with an increased hazard of 1-year mortality (0.90 [0.22 to 3.67], p = 0.878). In conclusion, in carefully selected patients, age70 years is not associated with increased short-term mortality. Age alone should not be a contraindication to LVAD therapy.

Severe right ventricular (RV) failure is associated with significant morbidity and mortality. Although right ventricular assist devices (RVADs) are increasingly used for refractory RV failure, there is limited data on their short- and long-term outcomes. Therefore, we undertook this study to better understand our experience with temporary RVADs.We conducted a retrospective review of all RVADS performed from 2017 to 2021. Patients supported with surgical RVADs, the Protek Duo device, and the Impella RP device were included. Patients were stratified by the type of RVAD and by etiology of RV failure. Survival was assessed by the Kaplan-Meier method and multivariable Cox proportional hazards regression models.From 2017 to 2021, 42 patients underwent RVAD implantation: 32 with a Protek Duo, 6 with an Impella RP, and 4 with a surgical RVAD. Majority of patients were already supported with an alternate form of mechanical support. Most patients had impaired renal function, decreased hepatic function, and lactic acidosis at the time of cannulation. The median duration of RVAD support was 8.5 [5-19] d. Survival to decannulation was 68.4%, to discharge was 47.4%, and to 1-y was 40.2%. Multivariable analysis identified elevated total bilirubin levels to be associated with 30-d mortality while increased hemoglobin levels were protective. After RVAD cannulation, the median number of pressors and inotropes was lower (P 0.01) and the lactic acidosis was less (P 0.01).In conclusion, RVAD support is associated with lower lactate levels, and decreased number of vasoactive medications, but is associated with significant morbidity and mortality.

The Centers for Medicare and Medicaid Services recently proposed a substantial cut to reimbursement for surgical services, punctuating a steady decline in reimbursement for clinical services provided by cardiothoracic surgeons during the last several decades. Meanwhile, the costs of practicing cardiothoracic surgery continue to increase. In an effort to defect against diminishing control over patient care and further negative changes affecting reimbursement, cardiothoracic surgeons must be able to convincingly demonstrate their value to patients and the health care system. However, the overall contribution of a cardiothoracic surgeon can be difficult to measure objectively and varies widely according to a host of factors, including practice setting, experience, subspecialization, and the local market. To address these challenges, The Society of Thoracic Surgeons Workforce on Practice Management has commissioned a Writing Task Force to raise awareness, to concentrate knowledge, and to organize information related to compensation as a comprehensive resource for cardiothoracic surgeons. The purpose of this initial report is to provide an overview of the major factors having an impact on compensation for cardiothoracic surgeons.

Venoarterial extracorporeal membrane oxygenation (ECMO) in the setting of combined cardiopulmonary failure provides full support of both cardiac and respiratory systems. However, it is difficult to isolate and evaluate pulmonary recovery independent of cardiac function on venoarterial ECMO. In this case report, we demonstrate the advantage of supporting a patient in cardiopulmonary failure with venovenous ECMO and the Impella 5.5 as a method to isolate organ dysfunction, wean off ECMO as respiratory function improves, and bridge to a left ventricular assist device with Impella 5.5 monotherapy.

Although extracorporeal membrane oxygenation (ECMO) has been associated with improved outcomes in COVID patients with respiratory failure, data regarding the need for blood product utilization in this population is inadequate.We conducted a retrospective review of all COVID patients requiring ECMO support at our facility. Patient demographics, co-morbidities, measures of acuity, and blood product utilization were identified. Patients were stratified by the presence of a major bleed and the need for dialysis. The primary outcome was blood product utilization. Linear regression models were used to assess predictors of the need for blood products.From 2020 to 2021, 41 patients with COVID-19 were included in our study. Overall 1601 d of support, COVID ECMO patients received 755 units of packed red blood cells (PRBC), 51 units of fresh frozen plasma (FFP), 326 platelets, and 1702 cryoprecipitate, amounting to 18.4 units PRBC per patient or 3.30 units per week of ECMO support. Both major bleeding and the need for dialysis were associated with higher rates of transfusion of PRBC, FFP, and platelets. The average non-bleeding COVID ECMO patient who did not need dialysis required 2.17 units of PRBC, 0.12 units of FFP, 0.76 platelets, and 8.36 of cryoprecipitate per week of ECMO support. On multivariable linear regression analysis, each day on ECMO was associated with 0.30 [0.19-0.42, P 0.01] units of PRBC.In conclusion, COVID ECMO is associated with a significant need for blood and blood products. Major bleeding and dialysis are important drivers of blood product requirements.

Although the established long-term benefit of left ventricular assist device (LVAD) therapy has led to its proliferation as destination therapy (DT), few studies have evaluated LVAD outcomes at nontransplant centers. We undertook this study to better evaluate our experience in building a nontransplant, DT LVAD program.We conducted a retrospective review of all LVADs implanted from 2010 to 2021. Patient, operative, and outcome data were extracted from the electronic medical record. Secular trends were evaluated by organizing the data into eras of implant. Survival was assessed using the Kaplan-Meier method. Multivariable Cox proportional hazards regression models further evaluated outcomes.From 2010 to 2021, 100 primary LVAD implants were performed. Annual volume grew from 1 to 30 implants per year. The average age of our cohort was 65.7 years, most patients (80%) were male, 51% had an ischemic etiology, and 65 (65%) were INTERMACS profile 1 or 2. Our 1- and 2-year survival were 82% and 79%, respectively. Multivariable analysis of 1-year mortality demonstrated that decreasing renal function and increased cardiopulmonary bypass (CPB) time were associated with increased mortality while preoperative hemoglobin was protective. When stratified by era of implant, our most recent patients were more likely to be INTERMACS profile 1 or 2; had shorter CPB and aortic cross clamp times; required fewer reoperations for bleeding; and suffered less right ventricular failure requiring mechanical support.A single, nontransplant LVAD center can experience significant growth in volume in a high-acuity cohort while maintaining acceptable outcomes and quality of care.

Coronavirus disease of 2019 pneumonia with respiratory failure refractory to maximum medical therapy has been successfully managed with venovenous extracorporeal membrane oxygenation. We describe a novel process of utilizing directed hypercapnia in five patients to wean prolonged extracorporeal support secondary to refractory hypercarbic respiratory failure.

Despite the recent increase in the use of minimally invasive approaches to mitral valve surgery in patients with a prior sternotomy, the outcomes of the robotic approach to mitral valve surgery in this patient population have not been examined.We retrospectively reviewed 342 consecutive patients who underwent mitral valve surgery after a prior sternotomy between 2013 and 2020, in which the robotic approach was used in 21 patients (6.1%). We reviewed the clinical details of these 21 patients.The median age was 71 years [interquartile range 64.00, 74.00 years], and mean Society of Thoracic Surgeons Predicted Risk of Mortality was 4.2% ± 3.8%. The indication for mitral valve surgery was degenerative mitral valve disease in 33.3% (7/21), functional disease in 28.6% (6/21), mixed disease in 4.8% (1/21), rheumatic disease in 9.5% (2/21), and failed repair for degenerative disease in 23.8% (5/21). No cases required conversion from robotic assistance to alternative approaches, there were no intraoperative deaths, and intraoperative transesophageal echocardiogram confirmed complete elimination of mitral regurgitation in 90.5% (19/21) of cases. Thirty-day mortality was 0.0% (0/21), and 1-year mortality was 4.8% (1/21). There were no strokes or wound infections at 30 days, and 14.3% (3/21) of patients received intraoperative blood product transfusions.The results of this retrospective review suggest that the robotic approach to mitral valve surgery in patients with a prior sternotomy is safe in experienced hands. Although some centers have considered prior sternotomy a relative contraindication to robotic mitral valve surgery, this approach is feasible and can be considered an option for experienced surgeons.

Background Extracorporeal membrane oxygenation (ECMO) can be effective for refractory acute respiratory distress syndrome (ARDS) in patients with influenza, but its utility in patients with coronavirus disease 2019 (COVID-19) is uncertain. We compared outcomes of patients with refractory ARDS from COVID-19 and influenza placed on ECMO. Methods We conducted a retrospective analysis of 120 patients with refractory ARDS due to COVID-19 or influenza placed on ECMO at 2 referral centers from January 2013 to October 2020. Patient characteristics and clinical outcomes were compared. The primary endpoint was survival to discharge. Results Baseline characteristics and comorbidities were similar. During the study period, 53 patients with COVID-19 and 67 patients with influenza were supported. Venovenous ECMO was the predominant initial cannulation strategy in both groups (COVID 92.5% vs influenza 95.5%; P = .5). Survival to hospital discharge was 62.3% (33 of 53 patients) in the COVID-19 group and 64.2% (43 of 67 patients) in the influenza group (P = .8). In patients successfully decannulated, median length of time on ECMO was longer in COVID-19 patients (14 [interquartile range (IQR), 9-30] days vs influenza 10.5 [IQR, 6.8-14.3] days; P = .004). Among patients discharged alive, COVID-19 patients had longer overall length of stay (COVID-19 37 [IQR, 27-62] days vs influenza 13.5 [IQR, 9.3-24] days; P = .007). Conclusions In patients with refractory ARDS from COVID-19 or influenza placed on ECMO, there was no significant difference in survival to hospital discharge. In patients surviving to decannulation, the duration of ECMO support and total length of stay were longer in COVID-19 patients.

Adaptive mutations of the severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) virus have emerged throughout the coronavirus disease 2019 (COVID-19) pandemic. The characterization of outcomes in patients requiring extracorporeal membrane oxygenation (ECMO) for severe respiratory distress from COVID-19 during the peak prevalence of different variants is not well known.There were 131 patients with laboratory-confirmed SARS-CoV-2 infection supported by ECMO at two referral centers within a large healthcare system. Three predominant variant phase time windows (Pre-Alpha, Alpha, and Delta) were determined by a change-point analyzer based on random population sampling and viral genome sequencing. Patient demographics and outcomes were compared.The average age of patients was 46.9 ± 10.5 years and 70.2% (92/131) were male. Patients cannulated for ECMO during the Delta variant wave were younger compared to earlier Pre-Alpha (39.3 ± 7.8 vs. 48.0 ± 11.1 years) and Alpha phases (39.3 ± 7.8 vs. 47.2 ± 7.7 years) (p .01). The predominantly affected race in the Pre-Alpha phase was Hispanic (52.2%; 47/90), while in Alpha (61.5%; 16/26) and Delta (40%; 6/15) variant waves, most patients were White (p .01). Most patients received a tracheostomy (82.4%; 108/131) with a trend toward early intervention in later phases compared to Pre-Alpha (p .01). There was no significant difference between the duration of ECMO, mechanical support, intensive care unit (ICU) length of stay (LOS), or hospital LOS over the three variant phases. The in-hospital mortality was overall 41.5% (54/131) and was also similar. Six-month survival of patients who survived to discharge was 92.2% (71/77).There was no significant difference in survival or time on ECMO support in patients during the peak prevalence of the three variants.

Supplementary Figure 7 from Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling

Supplementary Figure 6 from Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling

Supplementary Figure 1 from Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling

Supplementary Figure 3 from Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling

Supplementary Table 4 from Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling

Supplementary Table 3 from Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling

Supplementary Figure and Table Legends from Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling

By expressing two genes (hTERT and Cdk4), we have developed a method to reproducibly generate continuously replicating human bronchial epithelial cell (HBEC) lines that provide a novel resource to study the molecular pathogenesis of lung cancer and the differentiation of bronchial epithelial cells. Twelve human bronchial epithelial biopsy specimens obtained from persons with and without lung cancer were placed into short-term culture and serially transfected with retroviral constructs containing cyclin-dependent kinase (Cdk) 4 and human telomerase reverse transcriptase (hTERT), resulting in continuously growing cultures. The order of introduction of Cdk4 and hTERT did not appear to be important; however, transfection of either gene alone did not result in immortalization. Although they could be cloned, the immortalized bronchial cells did not form colonies in soft agar or tumors in nude mice. The immortalized HBECs have epithelial morphology; express epithelial markers cytokeratins 7, 14, 17, and 19, the stem cell marker p63, and high levels of p16INK4a; and have an intact p53 checkpoint pathway. Cytogenetic analysis and array comparative genomic hybridization profiling show immortalized HBECs to have duplication of parts of chromosomes 5 and 20. Microarray gene expression profiling demonstrates that the Cdk4/hTERT-immortalized bronchial cell lines clustered together and with nonimmortalized bronchial cells, distinct from lung cancer cell lines. We also immortalized several parental cultures with viral oncoproteins human papilloma virus type 16 E6/E7 with and without hTERT, and these cells exhibited loss of the p53 checkpoint and significantly different gene expression profiles compared with Cdk4/hTERT-immortalized HBECs. These HBEC lines are a valuable new tool for studying of the pathogenesis of lung cancer.

Supplementary Figure 9 from Immortalization of Human Bronchial Epithelial Cells in the Absence of Viral Oncoproteins

Supplementary Figures 1-8 from Immortalization of Human Bronchial Epithelial Cells in the Absence of Viral Oncoproteins

Supplementary Figure 5 from Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling

Supplementary Figure 4 from Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling

Aldehyde dehydrogenase (ALDH) is a candidate marker for lung cancer cells with stem cell-like properties. Immunohistochemical staining of a large panel of primary non–small cell lung cancer (NSCLC) samples for ALDH1A1, ALDH3A1, and CD133 revealed a significant correlation between ALDH1A1 (but not ALDH3A1 or CD133) expression and poor prognosis in patients including those with stage I and N0 disease. Flow cytometric analysis of a panel of lung cancer cell lines and patient tumors revealed that most NSCLCs contain a subpopulation of cells with elevated ALDH activity, and that this activity is associated with ALDH1A1 expression. Isolated ALDH+ lung cancer cells were observed to be highly tumorigenic and clonogenic as well as capable of self-renewal compared with their ALDH− counterparts. Expression analysis of sorted cells revealed elevated Notch pathway transcript expression in ALDH+ cells. Suppression of the Notch pathway by treatment with either a γ-secretase inhibitor or stable expression of shRNA against NOTCH3 resulted in a significant decrease in ALDH+ lung cancer cells, commensurate with a reduction in tumor cell proliferation and clonogenicity. Taken together, these findings indicate that ALDH selects for a subpopulation of self-renewing NSCLC stem-like cells with increased tumorigenic potential, that NSCLCs harboring tumor cells with ALDH1A1 expression have inferior prognosis, and that ALDH1A1 and CD133 identify different tumor subpopulations. Therapeutic targeting of the Notch pathway reduces this ALDH+ component, implicating Notch signaling in lung cancer stem cell maintenance. Cancer Res; 70(23); 9937–48. ©2010 AACR.

Supplementary Figure 2 from Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling

Supplementary Table 2 from Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling

Supplementary Table 1 from Aldehyde Dehydrogenase Activity Selects for Lung Adenocarcinoma Stem Cells Dependent on Notch Signaling

Massive and submassive pulmonary emboli (PE) are increasingly being treated with percutaneous lytic and embolectomy procedures. While these procedures are overwhelmingly safe, patients with significant right ventricular strain are at risk for hemodynamic compromise requiring extracorporeal membrane oxygenation (ECMO). We conducted a retrospective study of all patients requiring ECMO support for PE from 2014 through 2022. The primary outcome was survival. Secondary outcomes included commonly encountered ECMO complications. From 2014 to 2022, 10 patients with submassive or massive PE required ECMO support. All 10 patients (100%) had right ventricular strain on echocardiography, 7 (70%) had a saddle PE, and 3 (30%) had extensive bilateral PE. Six (60%) patients required cardiopulmonary resuscitation prior to ECMO cannulation, and 4 (40%) were undergoing cardiopulmonary resuscitation while being cannulated. Nine (90%) patients were placed on venoarterial ECMO through the femoral vessels, while 1 (10%) was cannulated with right atrial to pulmonary artery ECMO. The median duration of support was 4 [3–8] days. During their course, 5 patients underwent percutaneous embolectomy, 1 underwent surgical embolectomy, and 4 underwent percutaneous lytic therapy. All patients (100%) survived to ECMO decannulation, and 6 (60%) survived to discharge. With a mean follow-up of 496 days, there were no postdischarge mortalities. In conclusion, although therapy for large PE is well tolerated, a small number of patients will experience periprocedural hemodynamic collapse requiring ECMO support. ECMO for PE patients is associated with acceptable morbidity and mortality. Further investigation is warranted to better characterize which patients are likely to require ECMO support.

Patients with massive pulmonary embolism undergoing catheter-directed therapy are at high risk for cardiopulmonary arrest in the periprocedural period due to severe right ventricular dysfunction. We report the outcomes of three patients with massive pulmonary embolism treated successfully with catheter-directed thrombolytic therapy and veno-arterial extracorporeal membrane oxygenation.