Investigation of von Willebrand factor multimer abnormalities before and after aortic valve replacement using the Hydragel-5 assay.

BACKGROUND: Severe aortic stenosis (sAS) is associated with acquired von Willebrand syndrome (AVWS) by loss of high-molecular-weight multimers (HMWM) of von Willebrand factor (VWF), potentially resulting in perioperative bleeding. Analysis of VWF multimers remains challenging. Recently, the new, rapid Hydragel 5 assay has been developed, using electrophoretic protein separation for dividing VWF-multimers into low (LMWM), intermediate (IMWM), and HMWM, the hemostatically active part of VWF. Here, we evaluated its impact on predicting blood loss in presence of AVWS after surgical aortic valve replacement (SAVR). METHODS: We prospectively examined 52 patients (age: 68 ± 7 years; 54 % male) admitted to SAVR. They were divided in two groups (A: normal VWF, n = 28; B: abnormal VWF, n = 24, defined as VWF-activity/antigen (VWF:Ac/Ag)-ratio < 0.7 and/or HMWM loss). Blood samples and echocardiographic data were collected before, seven days and three months after SAVR. Blood loss and transfusions were recorded. RESULTS: Baseline characteristics and clinical data were similar in both groups. HMWM loss was present in 38.5 % of all patients. HMWM, the VWF:Ac/Ag- and HMWM/(IMWM+LMWM)-ratios were significantly decreased preoperatively in group B but normalized after SAVR. Bleeding, re-thoracotomy and transfusion rates were comparable. HMWM loss was inversely correlated with the peak aortic gradient (Pmax) and positively with the aortic valve area (AVA), while HMWM/(IMWM+LMWM)-ratio negatively correlated with the mean aortic gradient (Pmean). CONCLUSION: HMWM and HMWM/(IMWM+LMWM)-ratio inversely correlate with severity of AS and normalize after SAVR. The Hydragel-5 assay's might be valuable for routine diagnostics to assess bleeding risk and postoperative normalization of AS and VWF abnormalities in SAVR patients.

The effect of high-dose selenium on mortality and postoperative organ dysfunction in post-cardiotomy cardiogenic shock patients supported with mechanical circulatory support - A post-hoc analysis of the SUSTAIN CSX trial.

PURPOSE: Cardiac surgery, post-cardiotomy cardiogenic shock (PCCS), and temporary mechanical circulatory support (tMCS) provoke substantial inflammation. We therefore investigated whether a selenium-based, anti-inflammatory strategy would benefit PCCS patients treated with tMCS in a post-hoc analysis of the sustain CSX trial. METHODS: Post-hoc analysis of patients receiving tMCS for PCCS in the Sustain CSX trial, which investigated the effects of high-dose selenium on postoperative organ dysfunction in cardiac surgery patients. PRIMARY OUTCOME: duration of tMCS therapy. SECONDARY OUTCOMES: postoperative organ dysfunction and 30-day mortality. RESULTS: Thirty-nine patients were treated with tMCS for PCCS. There was no difference in the median duration of tMCS between the selenium and the placebo group (3 days [IQR: 1-6] vs. 2 days [IQR: 1-7], p = 0.52). Median dialysis duration was longer in the selenium group (1.5 days [0-21.8] vs. 0 days [0-1.8], p = 0.048). There was no difference in 30-day mortality (53% vs. 41%, OR 1.44, 95% CI 0.32-6.47, p = 0.62). CONCLUSION: In this explorative study, a perioperative high-dose selenium-supplementation did not show beneficial effects on organ dysfunctions and mortality rates in patients with PCCS receiving tMCS.

Outcome of right ventricular microaxial pump support in patients undergoing cardiac surgery.

Right ventricular failure (RVF) after cardiac surgery is associated with an in-hospital mortality rate of up to 75%. Microaxial flow pumps are one of the mechanical circulatory supports (MCS) options available for the treatment of RVF, however the specifics of timing and indication for MCS, as well as predictors for survival, remain unclear due to a dearth of published data. We evaluated the clinical outcome of patients treated with Impella-RP for predictors of mortality and the hemodynamic effects of the pump. This is a single-center retrospective observational study involving adult patients who underwent cardiac surgery with cardiopulmonary bypass between January 2019 and December 2020 in cardiac surgery and required therapeutic management of RVF with an Impella-RP. Overall, 18 patients were included and analyzed for factors that could be associated with mortality, or that could be predictors of patient outcomes for this population. Treatment of RVF with Impella-RP improved the patient hemodynamics significantly and had a survival rate of 61% within 30 days. Patients with isolated CABG or better liver function before implantation had a better survival rate, which may indicate that underlying disease and timing of implantation are significant for successful treatment of RVF.

Storage duration of human blood samples for fatty acid concentration analyses - How long is too long?

Polyunsaturated fatty acids such as DHA have known anti-inflammatory properties. The therapeutic implication highlights the importance of accurate serum measurements. Sample preservation is challenging when performed parallel to the clinical obligations. Impact of time between sample collection and processing regarding concentration alterations of fatty acids in human blood remains to be elucidated. Therefore, more information is required with respect to the stability and storage options in the context of potential degradation and concentration changes. This study investigates the stability of DHA in serum samples over time, given the challenges of timely sample analysis in clinical settings. Blood samples from three patients were collected and stored at +4 °C. Concentrations were analysed between 6 h and 7 days post-collection. Our data indicate that DHA concentrations remained unchanged during the observational period. Our results suggest that storage duration up to 7 days before sample processing does not affect accuracy of the results. DHA measurements is crucial for ongoing and future research in cardiovascular and inflammatory diseases. Our results reveal that DHA stability remains consistent over one week. This information is important for further clinical studies investigating PUFA concentrations, providing researches the option to postpone processing of samples if required along the clinical obligations.

Effects of aircraft noise cessation on blood pressure, cardio- and cerebrovascular endothelial function, oxidative stress, and inflammation in an experimental animal model.

Large epidemiological studies have shown that traffic noise promotes the development of cardiometabolic diseases. It remains to be established how long these adverse effects of noise may persist in response to a noise-off period. We investigated the effects of acute aircraft noise exposure (mean sound level of 72 dB(A) applied for 4d) on oxidative stress and inflammation mediating vascular dysfunction and increased blood pressure in male C57BL/6 J mice. 1, 2 or 4d of noise cessation after a 4d continuous noise exposure period completely normalized noise-induced endothelial dysfunction of the aorta (measured by acetylcholine-dependent relaxation) already after a 1d noise pause. Vascular oxidative stress and the increased blood pressure were partially corrected, while markers of inflammation (VCAM-1, IL-6 and leukocyte oxidative burst) showed a normalization within 4d of noise cessation. In contrast, endothelial dysfunction, oxidative stress, and inflammation of the cerebral microvessels of noise-exposed mice did not improve at all. These data demonstrate that the recovery from noise-induced damage is more complex than expected demonstrating a complete restoration of large conductance vessel function but persistent endothelial dysfunction of the microcirculation. These findings also imply that longer noise pauses are required to completely reverse noise-induced vascular dysfunction including the resistance vessels.

Follow-Up and Outcome after Coronary Bypass Surgery Preceded by Coronary Stent Implantation.

BACKGROUND: Guidelines on myocardial revascularization define recommendations for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Only little information exists on long-term follow-up and quality of life (QoL) after CABG preceded by PCI. The aim of our study was to evaluate the impact of prior PCI on outcome and QoL in patients with stable coronary artery disease who underwent CABG. METHODS: In our retrospective study, CABG patients were divided in: CABG preceded by PCI: PCI-first (PCF), and CABG-only (CO) groups. The PCF group was further divided in guideline-conform (GCO) and guideline nonconform (GNC) subgroups, according to the SYNTAX score (2014 European Society of Cardiology [ESC]/European Association for Cardio-Thoracic Surgery [EACTS] guidelines). Thirty days mortality, major adverse cardiac events, and QoL using the European Quality-of-Life-5 Dimensions were evaluated. RESULTS: A total of 997 patients were analyzed, of which 784 underwent CABG without (CO), and 213 individuals with prior PCI (PCF). The latter group consisted of 67 patients being treated in accordance (GCO), and 24 in discordance (GNC) to the 2014 ESC/EACTS guidelines. Reinfarction (PCF: 3.8% vs. CO: 1.0%; p = 0.024), re-angiography (PCF: 17.6% vs. CO: 9.0%; p = 0.004), and re-PCI (PCF: 10.4% vs. CO: 3.0%; p < 0.001) were observed more frequently in PCF patients. Also, patients reported better health status in the CO compared to PCF group (CO: 72.48 ± 19.31 vs. PCF: 68.20 ± 17.86; p = 0.01). Patients from the guideline nonconform subgroup reported poorer health status compared to the guideline-conform group (GNC: 64.23 ± 14.56 vs. GCO: 73.42 ± 17.66; p = 0.041) and were more likely to require re-PCI (GNC: 18.8% vs. GCO: 2.4%; p = 0.03). Also, GNC patients were more likely to have left main stenosis (GCO: 19.7% vs. GNC: 37.5%; p < 0.001) and showed higher preinterventional SYNTAX score (GCO: 18.63 ± 9.81 vs. GNC: 26.67 ± 5.07; p < 0.001). CONCLUSION: PCI preceding CABG is associated with poorer outcomes such as reinfarction, re-angiography, and re-PCI, but also worse health status and higher rehospitalization. Nevertheless, results were better when PCI was guideline-conformant. This data should impact the Heart Team decision.

Mitigation of aircraft noise-induced vascular dysfunction and oxidative stress by exercise, fasting, and pharmacological α1AMPK activation: molecular proof of a protective key role of endothelial α1AMPK against environmental noise exposure.

AIMS: Environmental stressors such as traffic noise represent a global threat, accounting for 1.6 million healthy life years lost annually in Western Europe. Therefore, the noise-associated health side effects must be effectively prevented or mitigated. Non-pharmacological interventions such as physical activity or a balanced healthy diet are effective due to the activation of the adenosine monophosphate-activated protein kinase (α1AMPK). Here, we investigated for the first time in a murine model of aircraft noise-induced vascular dysfunction the potential protective role of α1AMPK activated via exercise, intermittent fasting, and pharmacological treatment. METHODS AND RESULTS: Wild-type (B6.Cg-Tg(Cdh5-cre)7Mlia/J) mice were exposed to aircraft noise [maximum sound pressure level of 85 dB(A), average sound pressure level of 72 dB(A)] for the last 4 days. The α1AMPK was stimulated by different protocols, including 5-aminoimidazole-4-carboxamide riboside application, voluntary exercise, and intermittent fasting. Four days of aircraft noise exposure produced significant endothelial dysfunction in wild-type mice aorta, mesenteric arteries, and retinal arterioles. This was associated with increased vascular oxidative stress and asymmetric dimethylarginine formation. The α1AMPK activation with all three approaches prevented endothelial dysfunction and vascular oxidative stress development, which was supported by RNA sequencing data. Endothelium-specific α1AMPK knockout markedly aggravated noise-induced vascular damage and caused a loss of mitigation effects by exercise or intermittent fasting. CONCLUSION: Our results demonstrate that endothelial-specific α1AMPK activation by pharmacological stimulation, exercise, and intermittent fasting effectively mitigates noise-induced cardiovascular damage. Future population-based studies need to clinically prove the concept of exercise/fasting-mediated mitigation of transportation noise-associated disease.

Traffic noise, e.g. from aircraft, significantly contributes to an increased risk of cardiovascular or metabolic diseases in the general population by brain-dependent stress reactions leading to higher levels of circulating stress hormones and vasoconstrictors, all of which cause hypertension, oxidative stress, and inflammation. With the present experimental studies, we provide for the first time molecular mechanisms responsible for successful noise mitigation: Physical exercise, intermittent fasting, and pharmacological activation of the adenosine monophosphate-activated protein kinase (AMPK), a metabolic master regulator protein, prevent cardiovascular damage caused by noise exposure, such as hypertension, endothelial dysfunction, and reactive oxygen species formation (e.g. free radicals) and inflammation.These beneficial mitigation manoeuvers are secondary to an activation of the endothelial AMPK, thereby mimicking the antidiabetic drug metformin.

Early Detection Is the Best Prevention-Characterization of Oxidative Stress in Diabetes Mellitus and Its Consequences on the Cardiovascular System.

Previous studies demonstrated an important role of oxidative stress in the pathogenesis of cardiovascular disease (CVD) in diabetic patients due to hyperglycemia. CVD remains the leading cause of premature death in the western world. Therefore, diabetes mellitus-associated oxidative stress and subsequent inflammation should be recognized at the earliest possible stage to start with the appropriate treatment before the onset of the cardiovascular sequelae such as arterial hypertension or coronary artery disease (CAD). The pathophysiology comprises increased reactive oxygen and nitrogen species (RONS) production by enzymatic and non-enzymatic sources, e.g., mitochondria, an uncoupled nitric oxide synthase, xanthine oxidase, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). Considering that RONS originate from different cellular mechanisms in separate cellular compartments, adequate, sensitive, and compartment-specific methods for their quantification are crucial for early detection. In this review, we provide an overview of these methods with important information for early, appropriate, and effective treatment of these patients and their cardiovascular sequelae.

Fatty Acid Amide Hydrolase Deficiency Is Associated with Deleterious Cardiac Effects after Myocardial Ischemia and Reperfusion in Mice.

Ischemic cardiomyopathy leads to inflammation and left ventricular (LV) dysfunction. Animal studies provided evidence for cardioprotective effects of the endocannabinoid system, including cardiomyocyte adaptation, inflammation, and remodeling. Cannabinoid type-2 receptor (CB2) deficiency led to increased apoptosis and infarctions with worsened LV function in ischemic cardiomyopathy. The aim of our study was to investigate a possible cardioprotective effect of endocannabinoid anandamide (AEA) after ischemia and reperfusion (I/R). Therefore, fatty acid amide hydrolase deficient (FAAH)-/- mice were subjected to repetitive, daily, 15 min, left anterior descending artery (LAD) occlusion over 3 and 7 consecutive days. Interestingly, FAAH-/- mice showed stigmata such as enhanced inflammation, cardiomyocyte loss, stronger remodeling, and persistent scar with deteriorated LV function compared to wild-type (WT) littermates. As endocannabinoids also activate PPAR-α (peroxisome proliferator-activated receptor), PPAR-α mediated effects of AEA were eliminated with PPAR-α antagonist GW6471 i.v. in FAAH-/- mice. LV function was assessed using M-mode echocardiography. Immunohistochemical analysis revealed apoptosis, macrophage accumulation, collagen deposition, and remodeling. Hypertrophy was determined by cardiomyocyte area and heart weight/tibia length. Molecular analyses involved Taqman® RT-qPCR and immune cells were analyzed with fluorescence-activated cell sorting (FACS). Most importantly, collagen deposition was reduced to WT levels when FAAH-/- mice were treated with GW6471. Chemokine ligand-2 (CCL2) expression was significantly higher in FAAH-/- mice compared to WT, followed by higher macrophage infiltration in infarcted areas, both being reversed by GW6471 treatment. Besides restoring antioxidative properties and contractile elements, PPAR-α antagonism also reversed hypertrophy and remodeling in FAAH-/- mice. Finally, FAAH-/--mice showed more substantial downregulation of PPAR-α compared to WT, suggesting a compensatory mechanism as endocannabinoids are also ligands for PPAR-α, and its activation causes lipotoxicity leading to cardiomyocyte apoptosis. Our study gives novel insights into the role of endocannabinoids acting via PPAR-α. We hypothesize that the increase in endocannabinoids may have partially detrimental effects on cardiomyocyte survival due to PPAR-α activation.

Structural Analysis of Mitochondrial Dynamics-From Cardiomyocytes to Osteoblasts: A Critical Review.

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.

Mannitol Is Associated with Less Postoperative Delirium after Aortic Valve Surgery in Patients Treated with Bretschneider Cardioplegia.

BACKGROUND: Heart surgery with extracorporeal circulation (ECC) often leads to postoperative delirium (POD). This is associated with increased morbidity resulting in longer hospital stay and associated costs. The purpose of our study was to analyze the effect of intraoperative mannitol application on POD in patients undergoing elective aortic valve replacement (AVR). MATERIALS AND METHOD: s In our retrospective single-center study, 259 patients underwent elective AVR, using Bretschneider cardioplegic solution for cardiac arrest, between 2014 and 2017. Patients were divided in mannitol (n = 188) and nonmannitol (n = 71) groups. POD was assessed using the confusion assessment method for the intensive care unit (ICU). Statistical significance was assumed at p < 0.05. RESULTS: Baseline patient characteristics did not differ between the groups. Incidence of POD was significantly higher in the nonmannitol group (33.8 vs. 13.8%; p = 0.001). These patients required longer ventilation time (24.1 vs. 17.1 hours; p = 0.021), higher reintubation rate (11.3 vs. 2.7%; p = 0.009), ICU readmission (12.7 vs. 4.8%; p = 0.026), prolonged ICU (112 vs. 70 hours; p = 0.040), and hospital stay (17.8 vs. 12.6 days; p < 0.001), leading to higher expenses (19,349 € vs. 16,606 €, p < 0.001). A 30-day mortality was not affected, but nonmannitol group showed higher Simplified Acute Physiology Score II score (32.2 vs. 28.7; p < 0.001). Mannitol substitution was independently associated with lower incidence of POD (odds ratio: 0.40; 95% confidence interval: 0.18-0.89; p = 0.02). CONCLUSION: Treatment with mannitol during ECC was associated with decreased incidence of POD. This was accompanied by shorter ventilation time, ICU and hospital stay, and lower treatment expenses.

Environmental risk factors and cardiovascular diseases: a comprehensive expert review.

Non-communicable diseases (NCDs) are fatal for more than 38 million people each year and are thus the main contributors to the global burden of disease accounting for 70% of mortality. The majority of these deaths are caused by cardiovascular disease (CVD). The risk of NCDs is strongly associated with exposure to environmental stressors such as pollutants in the air, noise exposure, artificial light at night, and climate change, including heat extremes, desert storms, and wildfires. In addition to the traditional risk factors for CVD such as diabetes, arterial hypertension, smoking, hypercholesterolaemia, and genetic predisposition, there is a growing body of evidence showing that physicochemical factors in the environment contribute significantly to the high NCD numbers. Furthermore, urbanization is associated with accumulation and intensification of these stressors. This comprehensive expert review will summarize the epidemiology and pathophysiology of environmental stressors with a focus on cardiovascular NCDs. We will also discuss solutions and mitigation measures to lower the impact of environmental risk factors with focus on CVD.

Role of acquired von Willebrand syndrome in the development of bleeding complications in patients treated with Impella RP devices.

Axial flow pumps are standard treatment in cases of cardiogenic shock and high-risk interventions in cardiology and cardiac surgery, although the optimal anticoagulation strategy remains unclear. We evaluated whether laboratory findings could predict bleeding complications and acquired von Willebrand syndrome (avWS) among patients who were treated using axial flow pumps. We retrospectively evaluated 60 consecutive patients who received Impella devices (Impella RP: n = 20, Impella CP/5.0: n = 40; Abiomed Inc., Danvers, USA) between January 2019 and December 2020. Thirty-two patients (53.3%) experienced major or fatal bleeding complications (Bleeding Academic Research Consortium score of > 3) despite intravenous heparin being used to maintain normal activated partial thromboplastin times (40-50 s). Extensive testing was performed for 28 patients with bleeding complications (87.5%). Relative to patients with left ventricular support, patients with right ventricular support were less likely to develop avWS (87.5% vs. 58.8%, p = 0.035). Bleeding was significantly associated with avWS (odds ratio [OR]: 20.8, 95% confidence interval [CI]: 3.3-128.5; p = 0.001) and treatment duration (OR: 1.3, 95% CI 1.09-1.55; p = 0.003). Patients with avWS had longer Impella treatment than patients without avWS (2 days [1-4.7 days] vs. 7.3 days [3.2-13.0 days]). Bleeding complications during Impella support were associated with avWS in our cohort, while aPTT monitoring was not sufficient to prevent bleeding complications. A more targeted anticoagulation monitoring might be needed for patients who receive Impella devices.

Disturbed Lipid Metabolism in Diabetic Patients with Manifest Coronary Artery Disease Is Associated with Enhanced Inflammation.

BACKGROUND: Diabetic vasculopathy plays an important role in the pathophysiology of coronary artery disease (CAD) with oxidative stress as a strong mediator. This study aims to elucidate the underlying pathomechanisms of diabetic cardiac vasculopathy leading to coronary disease with an emphasis on the role of oxidative stress. Therefore, novel insights into antioxidant pathways might contribute to new strategies in the treatment and prevention of diabetic CAD. METHODS: In 20 patients with insulin-dependent or non-insulin dependent diabetes mellitus (IDDM/NIDDM) and 39 non-diabetic (CTR) patients, myocardial markers of oxidative stress, vasoactive proteins, endothelial nitric oxide synthase (eNOS), activated phosphorylated eNOS (p-eNOS), and antioxidant enzymes, e.g., tetrahydrobiopterin generating dihydrofolate reductase (DHFR), heme oxygenase (HO-1), as well as serum markers of inflammation, e.g., E-selectin, interleukin-6 (IL-6), and lipid metabolism, e.g., high- and low-density lipoptrotein (HDL- and LDL-cholesterol) were determined in specimens of right atrial tissue and in blood samples from type 2 diabetic and non-diabetic patients undergoing coronary artery bypass graft (CABG) surgery. RESULTS: IDDM/NIDDM increased markers of inflammation (e.g., E-selectin, p = 0.005 and IL-6, p = 0.051), decreased the phosphorylated myocardial p-eNOS (p = 0.032), upregulated the myocardial stress response protein HO-1 (p = 0.018), and enhanced the serum LDL-/HDL-cholesterol ratio (p = 0.019). However, the oxidative stress markers in the myocardium and the expression of vasoactive proteins (eNOS, DHFR) showed only marginal adverse changes in patients with IDDM/NIDDM. CONCLUSION: Dyslipidemia and myocardial inflammation seem to be the major determinants of diabetic CAD complications. Dysregulation in pro-oxidative enzymes might be attributable to the severity of CAD and oxidative stress levels in all included patients undergoing CABG.

Elective Surgery but not Transjugular Intrahepatic Portosystemic Shunt Precipitates Acute-On-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a syndrome associated with organ failure and high short-term mortality. Presence of ACLF at interventions, such as surgery or transjugular intrahepatic portosystemic shunt (TIPS), has been shown to determine outcome, but those interventions have also been attributed to precipitate ACLF in different studies. However, dedicated investigation for the risk of ACLF development in these interventions, especially in elective settings, has not been conducted. Patients with cirrhosis undergoing elective surgery were propensity score matched and compared to patients receiving TIPS. The primary endpoint was ACLF development within 28 days after the respective procedure. The secondary endpoint was 3-month and 1-year mortality. In total, 190 patients were included. Within 28 days, ACLF developed in 24% of the surgery and 3% of the TIPS cohorts, with the highest ACLF incidence between 3 and 8 days. By day 28 after the procedure, ACLF improved in the TIPS cohort. In both cohorts, patients developing ACLF within 28 days after surgery or TIPS placement showed significantly worse survival than patients without ACLF development at follow-up. After 12 months, mortality was significantly higher in the surgery cohort compared to the TIPS cohort (40% vs. 23%, respectively; P = 0.031). Regression analysis showed a European Foundation Chronic Liver Failure Consortium acute decompensation (CLIF-C AD) score ≥50 and surgical procedure as independent predictors of ACLF development. CLIF-C AD score ≥50, C-reactive protein, and ACLF development within 28 days independently predicted 1-year mortality. Conclusion: Elective surgical interventions in patients with cirrhosis precipitate ACLF development and ultimately death, but TIPS plays a negligible role in the development of ACLF. Elective surgery in patients with CLIF-C AD ≥50 should be avoided, while the window of opportunity would be CLIF-C AD <50.

CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in mice upon transverse aortic constriction.

The CX3CL1/CX3CR1 axis mediates recruitment and extravasation of CX3CR1-expressing subsets of leukocytes and plays a pivotal role in the inflammation-driven pathology of cardiovascular disease. The cardiac immune response differs depending on the underlying causes. This suggests that for the development of successful immunomodulatory therapy in heart failure due to chronic pressure overload induced left ventricular (LV) hypertrophy, the underlying immune patterns must be examined. Here, the authors demonstrate that Fraktalkine-receptor CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in a mouse model of transverse aortic constriction (TAC). The comparison of C57BL/6 mice with CX3CR1 deficient mice displayed reduced LV hypertrophy and preserved cardiac function in response to pressure overload in mice lacking CX3CR1. Moreover, the normal immune response following TAC induced pressure overload which is dominated by Ly6Clow macrophages changed to an early pro-inflammatory immune response driven by neutrophils, Ly6Chigh macrophages and altered cytokine expression pattern in CX3CR1 deficient mice. In this early inflammatory phase of LV hypertrophy Ly6Chigh monocytes infiltrated the heart in response to a C-C chemokine ligand 2 burst. CX3CR1 expression impacts the immune response in the development of LV hypertrophy and its absence has clear cardioprotective effects. Hence, suppression of CX3CR1 may be an important immunomodulatory therapeutic target to ameliorate pressure-overload induced heart failure.

Objective method to evaluate the competency of residents in cardiac surgery.

OBJECTIVES: Cardiac surgery training has become more challenging as patients and their diagnoses become more complex. Our goal was to develop a multicategorical assessment model for evaluating residents in cardiac surgery. This model is intended to ensure goal-directed progress in their training as well as to recognize and support their surgical talents. METHODS: We developed a new questionnaire in a multistage, 3-round process based on the Delphi method 'estimate-talk-estimate', using 55 competencies, including 38 general and 17 domain-specific competencies. Each competency is evaluated with 1 or more questions, to which 1 (not competent) to 6 (very competent) points can be chosen as an answer. RESULTS: The resulting model achieved 2 main goals: first, presenting a well-defined competency list for cardiac surgical training and second, providing an objective and realistic evaluation of trainees' abilities. Residents were assessed by all trainers to achieve a high level of objectivity. CONCLUSIONS: This evaluation model is highly objective, because residents are evaluated by multiple trainers. It allows individual support and enables better transparency in residency training. Talents and skills are evaluated, recognized and adopted as a base for individual feedback and personalized training programmes.

CpG postconditioning after reperfused myocardial infarction is associated with modulated inflammation, less apoptosis, and better left ventricular function.

Postconditioning attenuates inflammation and fibrosis in myocardial infarction (MI). The aim of this study was to investigate whether postconditioning with the cytosine-phosphate-guanine (CpG)-containing Toll-like receptor-9 (TLR9) ligand 1668-thioate (CpG) can modulate inflammation and remodeling in reperfused murine MI. Thirty minutes of left descending coronary artery (LAD) occlusion was conducted in 12-wk-old C57BL/6 mice. Mice were treated with CpG intraperitoneally 5 min before reperfusion. The control group received PBS; the sham group did not undergo ischemia. M-mode echocardiography (3, 7, and 28 days) and Millar left ventricular (LV) catheterization were performed (7 and 28 days) before the hearts were excised and harvested for immunohistochemical (6 h, 24 h, 3 days, 7 days, and 28 days), gene expression (6 h, 24 h, and 3 days; Taqman RT-qPCR), protein, and FACS analysis (24 h and 3 days). Mice treated with CpG showed significantly better LV function after 7 and 28 days of reperfusion. Protein and mRNA expressions of proinflammatory and anti-inflammatory cytokines were significantly induced after CpG treatment. Histology revealed fewer macrophages in CpG mice after 24 h, confirmed by FACS analysis with a decrease in both classically M1- and alternative M2a-monocytes. CpG treatment reduced apoptosis and cardiomyocyte loss and was associated with induction of adaptive mechanisms, e.g., of heme-oxigenase-1 and ß-/α-myosin heavy chain (MHC) ratio. Profibrotic markers collagen type Iα (Col-Ια) and Col-III induction was abrogated in CpG mice, accompanied by fewer myofibroblasts. This led to the formation of a smaller scar. Differential matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) expression contributed to attenuated remodeling in CpG, resulting in preserved cardiac function in a Toll-like receptor 1- and TLR9-dependent manner. Our study suggests a cardioprotective mechanism of CpG postconditioning, involving Toll-like receptor-driven modulation of inflammation. This is followed by attenuated remodeling and preserved LV function.NEW & NOTEWORTHY Cytosine-phosphate-guanine (CpG) postconditioning seems to mediate inflammation via Toll-like receptor-1 and Toll-like receptor-9 signaling. Enhanced cytokine and chemokine expressions are partly attenuated by IL-10 and matrix metalloproteinase-8 (MMP8) induction, being associated with lower macrophage infiltration and M1-monocyte differentiation. Furthermore, switch from α- to ß-MHC and balanced MMP/TIMP expression led to lesser cardiomyocyte apoptosis, smaller scar size, and preserved cardiac function. Data of pharmacological postconditioning have been widely disappointing to date. Our study suggests a new pathway promoting myocardial postconditioning via Toll-like receptor activation.

A National Survey: Current Clinical Practice in Pediatric Anesthesia for Congenital Heart Surgery.

BACKGROUND: Providing anesthesia for pediatric patients undergoing congenital cardiac surgery is complex and requires profound knowledge and clinical experience. Prospective studies on best anesthetic management are missing, partially due to different standards. The aim of the present study was to survey the current standard practice in anesthetic management in pediatric cardiac surgical centers in Germany. METHODS: All 78 cardiac surgical centers in Germany were reviewed for a congenital cardiac surgery program. Centers with an active program for congenital cardiac surgery were interviewed to participate in the present online questionnaire to assess their current anesthetic practice. RESULTS: Twenty-seven German centers running an active program for congenital heart surgery were identified, covering more than 3,000 pediatric cardiac surgeries annually. Of these centers, 96.3% (26/27) participated in our survey. Standard induction agents were etomidate in 26.9% (7/26), propofol in 19.2% (5/26), a combination of benzodiazepines and ketamine in 19.2% (5/26), and barbiturates in 11.5% (3/26). General anesthesia was preferentially maintained using volatile agents, 61.5% (16/26), with sevoflurane being the most common volatile agent within this group, 81.2% (13/16). Intraoperative first-choice/first-line inotropic drug was epinephrine, 53.8% (14/26), followed by milrinone, 23.1% (6/26), and dobutamine 15.4% (4/26). Fast-track programs performing on-table extubation depending on the type of surgical procedure were established at 61.5% (16/26) of the centers. CONCLUSION: This study highlights the diversity of clinical standards in pediatric cardiac anesthesia for congenital cardiac surgery in Germany.