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Objectives: In patients with left heart disease and severe aortic stenosis (AS), pulmonary hypertension (PH) is a common comorbidity and predictor of poor prognosis. Untreated AS aggravates PH leading to an increased right ventricular afterload and, in line to right ventricular dysfunction. The surgical benefit of aortic valve replacement (AVR) in elderly patients with severe AS and PH could be limited due to the multiple comorbidities and poor outcomes. Therefore, we purposed to investigate the impact of PH on short-term outcomes in patients with moderate to severe AS who underwent surgical AVR in our heart center., Methods: In this study we retrospectively analyzed a cohort of 99 patients with severe secondary post-capillary PH who underwent surgical AVR (AVR + PH group) at our heart center between 2010 and 2021 with a regard to perioperative outcomes. In order to investigate the impact of PH on short-term outcomes, the control group of 99 patients without pulmonary hypertension who underwent surgical AVR (AVR group) at our heart center with similar risk profile was accordingly analyzed regarding pre-, intra- and postoperative data., Results: Atrial fibrillation occurred significantly more often ( p = .013) in patients who suffered from PH undergoing AVR. In addition, the risk for cardiac surgery (EUROSCORE II) was significantly higher ( p < .001) in the above-mentioned group. Likewise, cardiopulmonary bypass time ( p = .018), aortic cross-clamp time ( p = .008) and average operation time ( p = .009) were significantly longer in the AVR + PH group. Furthermore, the in-hospital survival rate was significantly higher ( p = .044) in the AVR group compared to the AVR + PH group. Moreover, the dialysis rate was significantly higher ( p < .001) postoperatively in patients who suffered PH compared to the patients without PH undergoing AVR., Conclusion: In our study, patients with severe PH and severe symptomatic AS who underwent surgical aortic valve replacement showed adverse short-term outcomes compared to patients without PH., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The prolonged use of extracorporeal membrane oxygenation (ECMO) support is associated with increased consumption of platelets and hemolysis. The prognostic impact of thrombocytopenia prior to and during ECMO support on patient's short-, mid- and long-term outcomes has been critically evaluated and discussed over the last years. However, only few data have been published on thrombocytopenia caused by mobile ECMO support. The aim of this study was to evaluate the impact of thrombocytopenia on short-term outcomes and predictors of in-hospital mortality in patients supported by mobile ECMO for transportation and subsequent weaning in a tertiary centre., Methods: This retrospective single-centre study analyzed a total of 117 patients requiring mobile veno-arterial (va) ECMO support and subsequent transportation from referral hospitals to our department from January 2015 until December 2021. A total of 15 patients had to be excluded from the analysis for missing data regarding baseline platelet count. Patients were divided into two groups: thrombocytopenia group (<130 × 109/L, n = 44) and non-thrombocytopenia group (≥130 × 109/L, n = 58). The primary outcome was in-hospital mortality. Secondary outcomes were successful ECMO-weaning, and the incidence of associated complications (bleeding, acute hepatic failure, acute renal failure, dialysis, and septic shock)., Results: The dialysis rate before ECMO initiation was significantly higher ( p = .041) in the thrombocytopenia group compared to the non-thrombocytopenia group. The rates of bleeding complications ( p = .032) and limb ischemia ( p = .003) were significantly higher in patients with low platelet count. Moreover, complication rates of acute hepatic failure ( p < .001), acute renal failure ( p < .001) and dialysis ( p = .033) were significantly higher in the thrombocytopenia group. Also, in-hospital mortality was significantly higher ( p = .002) in patients with low platelet count before initiation of ECMO support., Conclusion: Based on the results of the present study, patients with thrombocytopenia prior to mobile vaECMO support may be at significantly higher risk for associated complications and short-term mortality., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Coronary artery bypass grafting (CABG) surgery in patients with acute coronary syndrome (ACS) remains a high-risk procedure and is associated with adverse outcomes. The risk factors of acute stroke in the above-mentioned patients stay unclear and some appropriate data is lacking in the literature. Thus, we aimed to investigate the predictors of acute stroke in patients undergoing CABG surgery in ACS., Methods: The retrospective single-centre cohort analysis was conducted. All patients ( n = 1344) who suffered from acute coronary syndrome and underwent CABG procedure at the University hospital Cologne from June 2011 until October 2019 were included in our study. In order to find the risk factors of acute stroke after bypass surgery, patients were divided into two groups (non-stroke group ( n = 1297) and stroke group ( n = 47)). In order to even above-mentioned groups propensity score matching (PSM) analysis was performed (non-stroke group ( n = 46) and stroke group ( n = 46)., Results: Duration of cardiopulmonary bypass ( p = .015) and cross clamp time ( p = .006) were significantly longer in patients who suffered stroke. Perioperative myocardial infarction was significantly higher ( p = .030) in the stroke group. Likewise, the duration of intensive care unit stay ( p < .001) and in-hospital stay ( p < .001) were significantly longer in patients with stroke. However, the mortality rate did not differ significantly ( p = .131) between above-mentioned groups. Univariate and multivariate analysis showed cardiogenic shock ( p = .003), peripheral vascular disease (PVD, p = .025) and previous stroke ( p = .045) as relevant independent predictors for acute stroke after CABG procedure in patients with ACS., Conclusion: Based on our findings, acute stroke after bypass surgery in patients with ACS is associated with increased mortality and adverse outcomes. Cardiogenic shock, peripheral vascular disease and previous stroke were independent predictors of stroke after CABG procedure. Therefore, preoperative evaluation of potential risk factors may be crucial to improve postoperative results.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a 5-year survival rate of <12%. The biggest barrier to therapy is the dense desmoplastic extracellular matrix (ECM) that surrounds the tumor and reduces vascularization, generally termed desmoplasia. A variety of drug combinations and formulations have been tested to treat the cancer, and although many of them show success pre-clinically, they fail clinically. It, therefore, becomes important to have a clinically relevant model available that can predict the response of the tumor to therapy. This model has been previously validated against resected clinical tumors. Here a simple protocol to grow desmoplastic three-dimensional (3D)-coculture spheroids is described that can naturally generating a robust ECM and do not require any external matrix sources or scaffold to support their growth. Briefly human pancreatic stellate cells (HPaSteC) and PANC-1 cells are used to prepare a suspension containing the cells in a 1:2 ratio, respectively. The cells are plated in a poly-HEMA coated, 96-well low attachment U-well plate. The plate is centrifuged to allow the cells to form an initial pellet. The plate is stored in the incubator at 37 °C with 5% CO2, and media is replaced every 3 days. Plates can be imaged at designated intervals to measure spheroid volume. Following 14 days of culture, mature desmoplastic spheroids are formed (i.e. average volume of 0.048 + 0.012 mm 3  (451 µm x 462.84 µm)) and can be utilized for experimental therapy assessment. Mature ECM components include collagen-I, hyaluronic acid, fibronectin, and laminin.

Background:  Ventricular septal defects (VSDs) remain a rare but life-threatening complication of myocardial infarction. Although the incidence has decreased due to better treatment options, the mortality rate remains high. The timing of VSD repair remains critical to outcome. The use of mechanical circulatory support is rarely described in the literature, although it may help to delay repair to allow tissue stabilization. While Impella is currently considered contraindicated due to the potential worsening of the right-to-left shunt and possible systemic embolization of necrotic debris, there is no comprehensive evidence for this. Therefore, we aimed to analyze whether the use of Impella 5.5 as a first choice for patients undergoing VSD repair should be considered for discussion., Methods:  This retrospective study analyses four consecutive patients who underwent delayed ventricular septal repair after prior implantation of Impella 5.5 (Abiomed Inc., Danvers, Massachusetts, United States)., Results:  A total of 75% of patients ( n  = 3) presented with acute right heart failure prior to implantation with a mean systolic pulmonary artery pressure of 64 ± 3.0 mmHg. Implantation was performed under local anesthesia in three cases. The mean time to surgery was 9.8 ± 3.1 days. All patients remained on the Impella 5.5 device postoperatively. Weaning from Impella 5.5 was successful in 75% ( n  = 3). The mean length of stay in the intensive care unit was 22.3 ± 7.5 days., Conclusion:  Preoperative implantation of the Impella 5.5 device is a safe and feasible option for patients undergoing VSD repair. Outcomes may be improved by performing Impella implantation under local anesthesia and continuing Impella support after VSD repair. However, it is important to note that these patients represent a high-risk cohort and the mortality rate remains high., Competing Interests: K.E. and A.C.D. received honoraria from Abiomed. No other author has any conflict of interest to declare., (Thieme. All rights reserved.)

Background:  Surgically implanted Impella 5.5. delivers full cardiac support and left ventricular unloading for patients with heart failure. So far, the Impella device is implanted under general anesthesia (GA)., Material and Methods:  A total of n  = 3 critically ill patients presented with acute heart failure in need of cardiac support. All patients suffered cardiogenic shock of varying etiology. Due to hemodynamically unstable conditions, GA was avoided. All implantations were performed solely under local anesthesia (LAS) without any regional anesthesia., Results:  All implantations were performed successfully under LAS with 60 mL of mepivacaine of 2% solution and ropivacaine of 1% solution (50:50 ratio). All devices were placed from the right axillary artery. One patient needed hematoma evacuation several days after surgery. No other Impella-related complication was observed., Conclusion:  A surgical implantation of the Impella 5.5 device under LAS is feasible and safe. Despite the small number of cases, no disadvantage can be described at the present moment. Our series should encourage physicians to perform the procedure under LAS., Competing Interests: None declared., (Thieme. All rights reserved.)

Infective endocarditis (IE) carries a heavy burden of morbidity and mortality in chronic kidney disease (CKD) and hemodialysis (HD) patients. We investigated the risk factors, pathognomonic profile and outcomes of surgically treated IE in CKD and HD patients. We preoperatively identified patients with CKD under hemodialysis (HD group) and compared them with patients without hemodialysis (Non-HD group). Furthermore, we divided the cohort into four groups according to the underlying stage of CKD, with a subsequent outcome analysis. Between 2009 and 2018, 534 Non-HD and 58 HD patients underwent surgery for IE at our institution. The median age was 65.1 [50.6-73.6] and 63.2 [53.4-72.8] years in the Non-HD and HD groups, respectively ( p = 0.861). The median EuroSCORE II was 8.0 [5.0-10.0] vs. 9.5 [7.0-12.0] in the Non-HD vs. HD groups ( p = 0.004). Patients without CKD had a mortality rate of 5.6% at 30 days and 15.5% at 1 year. Mortality rates proportionally rose with the severity of CKD. Among HD patients, 30-day and 1-year mortality rates were 38.1% and 75.6%, respectively ( p < 0.001). Staphylococcus aureus IE was significantly more frequent in the HD group ( p = 0.006). In conclusion, outcomes after surgery for IE correlated with the severity of the underlying CKD, with HD patients exhibiting the most unfavorable results. Pre-existing CKD and staphylococcus aureus infection were independent risk factors for 1-year mortality.

(1) Background: Fluid resuscitation is a necessary part of therapeutic measures to maintain sufficient hemodynamics in extracorporeal membrane oxygenation (ECMO) circulation. In a post-hoc analysis, we aimed to investigate the impact of increased volume therapy in veno-arterial ECMO circulation on renal function and organ edema in a large animal model. (2) Methods: ECMO therapy was performed in 12 female pigs (Deutsche Landrasse × Pietrain) for 10 h with subsequent euthanasia. Applicable volume, in regard to the necessary maintenance of hemodynamics, was divided into moderate and extensive volume therapy (MVT/EVT) due to the double quantity of calculated physiologic urine output for the planned study period. Respiratory and hemodynamic data were measured continuously. Additionally, renal function and organ edema were assessed by blood and tissue samples. (3) Results: Four pigs received MVT, and eight pigs received EVT. After 10 h of ECMO circulation, no major differences were seen between the groups in regard to hemodynamic and respiratory data. The relative change in creatinine after 10 h of ECMO support was significantly higher in EVT (1.3 ± 0.3 MVT vs. 1.8 ± 0.5 EVT; p = 0.033). No major differences were evident for lung, heart, liver, and kidney samples in regard to organ edema in comparison of EVT and MVT. Bowel tissue showed a higher percentage of edema in EVT compared to MVT (77 ± 2% MVT vs. 80 ± 3% EVT; p = 0.049). (4) Conclusions: The presented data suggest potential deterioration of renal function and intestinal mucosa function by an increase in tissue edema due to volume overload in ECMO therapy.

Objectives: Extracorporeal cardiopulmonary resuscitation (eCPR) is increasingly used due to its beneficial outcomes and results compared to conventional CPR. After cardiac arrest, the overall ejection fraction is severely impaired; thus, weaning from ECMO is often prolonged or impossible. We hypothesized that early application of levosimendan in these patients facilitates ECMO weaning and survival., Methods: From 2016 until 2020, patients who underwent eCPR after cardiac arrest at our institution were analyzed retrospectively and divided into two groups: patients who received levosimendan during ICU stay (n = 24) and those who did not receive levosimendan (n = 84) and analyzed for outcome parameters. Furthermore, we used propensity-score matching and multinomial regression analysis to show the effect of levosimendan on outcome parameters., Results: Overall, in-hospital mortality was significantly lower in the group which received levosimendan (28% vs. 88%, p ≤ 0.01), and ECMO weaning was more feasible in patients who received levosimendan (88% vs. 20%, p ≤ 0.01). CPR duration until ECMO cannulation was significantly shorter in the levosimendan group (44 + 26 vs. 65 + 28, p = 0.002); interestingly, the rate of mechanical chest compressions before ECMO cannulation was lower in the levosimendan group (50% vs. 69%, p = 0.005)., Conclusion: In patients after cardiac arrest treated with eCPR, levosimendan seems to contribute to higher success rates of ECMO weaning, potentially due to a short to mid-term increase in inotropy. Also, the survival after levosimendan application was higher than patients who did not receive levosimendan., (© 2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: The use of simultaneous veno-arterial extracorporeal membrane oxygenation (ECMO) with or without an Intra-Aortic Balloon Pump (IABP) is a widely used tool for mechanical hemodynamic support. Endothelial function, especially in relation to different cannulation techniques, is rarely investigated in the setting of extracorporeal life support (ECLS). In this study, we analyzed endothelial function in relation to hemodynamic and laboratory parameters for central and peripheral ECMO, with or without concomitant IABP support in a large animal model to gain a better understanding of the underlying basic mechanisms., Methods: In this large animal model, healthy female pigs with preserved ejection fraction were divided into the following groups related to cannulation strategy for ECMO and simultaneous IBAP support: control (no ECMO, no IABP), peripheral ECMO (pECMO), central ECMO (cECMO), pECMO and IABP or cECMO and IABP. During the experimental setting, the blood flow in the ascending aorta, left coronary artery and arteria carotis was measured. Afterwards, endothelial function was investigated after harvesting the right coronary artery, arteria carotis and renal artery. In addition, laboratory markers, such as creatine kinase (CK), creatine kinase muscle-brain (CK-MB), troponin, creatinine and endothelin were analyzed., Results: The blood flow in the ascending aorta and the left coronary artery was significantly lower in all discussed experimental settings compared to the control group. Of note, the cECMO cannulation strategy generated favorable hemodynamic circumstances with higher blood flow in the coronary arteries than pECMO regardless of flow circumstances in the ascending aorta. The concomitant usage of IABP did not result in an improvement of the coronary blood flow, but partially showed a negative impact on the endothelial function of coronary arteries in comparison to the control. These findings correlate to higher CK/CK-MB levels in the setting of cECMO + IABP and pECMO + IABP., Conclusions: The usage of mechanical circulatory support with concomitant ECMO and IABP in a large animal model might have an influence on the endothelial function of coronary arteries while not improving the coronary artery perfusion in healthy hearts with preserved ejection.

(1) Introduction: Simultaneous ECMO and IABP therapy is frequently used. Haemodynamic changes responsible for the success of the concomitant mechanical circulatory support system approach are rarely investigated. In a large-animal model, we analysed haemodynamic parameters before and during ECMO therapy, comparing central and peripheral ECMO circulation with and without simultaneous IABP support. (2) Methods: Thirty-three female pigs were divided into five groups: (1) SHAM, (2) (peripheral)ECMO(-)IABP, (3) (p)ECMO(+)IABP, (4) (central)ECMO(-)IABP, and (5) (c)ECMO(+)IABP. Pigs were cannulated in accordance with the group and supported with ECMO (±IABP) for 10 h. Systemic haemodynamics, cardiac index (CI), and coronary and carotid artery blood flow were determined before, directly after, and at five and ten hours on extracorporeal support. Systemic inflammation (IL-6; IL-10; TNFα; IFNγ), immune response (NETs; cf-DNA), and endothelial injury (ET-1) were also measured. (3) Results: IABP support during antegrade ECMO circulation led to a significant reduction of left ventricular pressure in comparison to retrograde flow in (p)ECMO(-)IABP and (p)ECMO(+)IABP. Blood flow in the left anterior coronary and carotid artery was not affected by extracorporeal circulation. (4) Conclusions: Concomitant central ECMO and IABP therapy leads to significant reduction of intracavitary cardiac pressure, reduces cardiac work, and might therefore contribute to improved recovery in ECMO patients.

Objectives: Out-of-hospital cardiac arrest (OHCA) is associated with excessively high mortality rates. Recent studies suggest benefits from extracorporeal cardiopulmonary resuscitation (ECPR) performed in selected patients. We sought to present the first results from our interdisciplinary ECPR program with a particular focus on early outcomes and potential risk factors associated with in-hospital mortality., Methods: Between January 2016 and December 2019, 44 patients who underwent ECPR selected according to our institutional ECPR protocol were retrospectively analyzed regarding pre-hospital, in-hospital, and early outcome parameters. Patients were divided into survivors (S) and non-survivors (NS). Statistical analysis of risk factors regarding in-hospital mortality of the patient cohort analyzed was performed., Results: The mean age of the population was 53 ± 12 years, with most patients being male ( n  = 40). The leading cause of cardiac arrest (CA) was myocardial infarction ( n  = 24, 55%). The median hospital stay was 1 (1;13) day. Twenty-three percent of patients ( n  = 10) were discharged from hospital including eight patients (18%) with CPC 1-2. Survivors showed a trend toward shorter pre-hospital CPR duration (60 (59;60) min (S) vs 60 (55;90) min (NS), p = 0.07)., Conclusion: Establishing ECPR programs in large population areas offers the option to improve survival rates for OHCA patients. Stringent compliance of institutional criteria (mainly age, witnessed arrest, and time of pre-hospital resuscitation) and providing ECPR to strictly selected patients seems to be a vital factor for such programs' success. Pre-clinical settings and therapeutic measures must be adjusted in this regard to improve outcomes for this highly demanding patient cohort.

Background: Cardiac surgery often represents the only treatment option in patients with infective endocarditis (IE). However, IE surgery may lead to a sudden release of inflammatory mediators, which is associated with postoperative organ dysfunction. We investigated the effect of hemoadsorption during IE surgery on postoperative organ dysfunction., Methods: This multicenter, randomized, nonblinded, controlled trial assigned patients undergoing cardiac surgery for IE to hemoadsorption (integration of CytoSorb to cardiopulmonary bypass) or control. The primary outcome (change in sequential organ failure assessment score [ΔSOFA]) was defined as the difference between the mean total postoperative SOFA score, calculated maximally to the 9th postoperative day, and the basal SOFA score. The analysis was by modified intention to treat. A predefined intergroup comparison was performed using a linear mixed model for ΔSOFA including surgeon and baseline SOFA score as fixed effect covariates and with the surgical center as random effect. The SOFA score assesses dysfunction in 6 organ systems, each scored from 0 to 4. Higher scores indicate worsening dysfunction. Secondary outcomes were 30-day mortality, duration of mechanical ventilation, and vasopressor and renal replacement therapy. Cytokines were measured in the first 50 patients., Results: Between January 17, 2018, and January 31, 2020, a total of 288 patients were randomly assigned to hemoadsorption (n=142) or control (n=146). Four patients in the hemoadsorption and 2 in the control group were excluded because they did not undergo surgery. The primary outcome, ΔSOFA, did not differ between the hemoadsorption and the control group (1.79±3.75 and 1.93±3.53, respectively; 95% CI, -1.30 to 0.83; P =0.6766). Mortality at 30 days (21% hemoadsorption versus 22% control; P =0.782), duration of mechanical ventilation, and vasopressor and renal replacement therapy did not differ between groups. Levels of interleukin-1β and interleukin-18 at the end of integration of hemoadsorption to cardiopulmonary bypass were significantly lower in the hemoadsorption than in the control group., Conclusions: This randomized trial failed to demonstrate a reduction in postoperative organ dysfunction through intraoperative hemoadsorption in patients undergoing cardiac surgery for IE. Although hemoadsorption reduced plasma cytokines at the end of cardiopulmonary bypass, there was no difference in any of the clinically relevant outcome measures., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03266302.

Background: Extracorporeal cardiopulmonary resuscitation (eCPR) is a rapidly growing treatment strategy due to increasing survival rates in selected patients. Additional left ventricular mechanical unloading, using a transfemoral micro-axial blood pump (Impella® Denver, Massachusetts, USA), might improve patients' outcomes. In this regard, we sought to investigate patients who suffered OHCA (out-of hospital cardiac arrest) or IHCA (in-hospital cardiac arrest) with subsequent eCPR via VA-ECMO (veno-arterial extracorporeal membrane oxygenation) and concomitant Impella® implantation based on survival and feasibility of ECMO weaning., Methods: From January 2016 until December 2020, 108 patients underwent eCPR at our institution. Data prior to eCPR and early outcome parameters were analyzed comparing patients who were supported with an additional Impella® (2.5 or CP) (ECMO+Impella®, n = 18) and patients without additional (ECMO, n = 90) support during V-A ECMO therapy. The primary endpoint was in-hospital mortality; secondary endpoints were, among others: ECMO explantation, need for hemodialysis, stroke, and need for blood transfusions., Results: Low-flow time was significantly lower in the ECMO+Impella group (60 min vs. 55 min, p = .01). All-cause mortality was significantly lower in the ECMO+Impella® group (82% vs. 56%, p = .01). The time of circulatory support was shorter in the ECMO cohort (2.0 ± 1.73 vs. 4.76 ± 2.88 p = .05). ECMO decannulation was significantly more feasible in patients with ECMO+Impella® (72% vs. 32%, p = .01). Patients treated with additional Impella® showed significantly more acute kidney injury with the need for dialysis (72% vs. 18%, p ≤ .01)., Conclusion: Concomitant Impella® support might positively influence survival and ECMO weaning in eCPR patients. Treatment-associated complications such as the need for dialysis were more common in this highly selected patient group. Further studies with larger numbers are necessary to evaluate the clinical relevance of concomitant LV-unloading in eCPR patients using an Impella® device., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)