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Venoarterial extracorporeal membrane oxygenation provides cardiorespiratory support to patients in cardiogenic shock. This comes at the cost of increased left ventricle (LV) afterload that can be partly ascribed to retrograde aortic flow, causing LV distension, and leads to complications including cardiac thrombi, arrhythmias, and pulmonary edema. LV unloading can be achieved by using an additional circulatory support device to mitigate the adverse effects of mechanical overload that may increase the likelihood of myocardial recovery. Observational data suggest that these strategies may improve outcomes, but in whom, when, and how LV unloading should be employed is unclear; all techniques require balancing presumed benefits against known risks of device-related complications. This review summarizes the current evidence related to LV unloading with venoarterial extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) represents an advanced option for supporting refractory respiratory and/or cardiac failure. Systemic anticoagulation with unfractionated heparin (UFH) is routinely used. However, patients with bleeding risk and/or heparin-related side effects may necessitate alternative strategies: among these, nafamostat mesilate (NM) has been reported.We conducted a systematic literature search (PubMed and EMBASE, updated 12/08/2021), including all studies reporting NM anticoagulation for ECMO. We focused on reasons for starting NM, its dose and the anticoagulation monitoring approach, the incidence of bleeding/thrombosis complications, the NM-related side effects, ECMO weaning, and mortality.The search revealed 11 relevant findings, all with retrospective design. Of these, three large studies reported a control group receiving UFH, the other were case series (n = 3) or case reports (n = 5). The main reason reported for NM use was an ongoing or high risk of bleeding. The NM dose varied largely as did the anticoagulation monitoring approach. The average NM dose ranged from 0.46 to 0.67 mg/kg/h, but two groups of authors reported larger doses when monitoring anticoagulation with ACT. Conflicting findings were found on bleeding and thrombosis. The only NM-related side effect was hyperkalemia (n = 2 studies) with an incidence of 15%-18% in patients anticoagulated with NM. Weaning and survival varied across studies.Anticoagulation with NM in ECMO has not been prospectively studied. While several centers have experience with this approach in high-risk patients, prospective studies are warranted to establish the optimal space of this approach in ECMO.

Right ventricular failure has a high morbidity and mortality in patients suffering from advanced heart failure, pulmonary hypertension, acute myocardial infarction after cardiac surgery and in left ventricular assist device patients. The Impella RP® catheter is a mechanical circulatory device, positioned from a venous femoral percutaneous access and passing through the tricuspid and pulmonary valves, reaches the pulmonary artery. Impella RP (Abiomed Inc., MA, USA) acts as a direct right ventricle bypass and it provides a flow up to 4.4 liters per minute, unloading the right ventricle. The main contraindications are: thrombi in the vena cava, right atrium and ventricle and pulmonary artery; mechanical tricuspid or pulmonary prostheses. In this review, the principles of operations, clinical applications and results of Impella RP are summarized and evaluated.

Addition of Impella on top of venoarterial extracorporeal membrane oxygenation (VA-ECMO) has gained wide interest as it might portend improved outcomes in patients with cardiogenic shock. This has been consistently reported in retrospective propensity-matched studies, case series, and meta-analyses. The pathophysiologic background is based on the mitigation of ECMO-related side effects and the additive benefit of myocardial unloading. In this perspective, thorough knowledge of these mechanisms is required to optimize the management of mechanical circulatory support with this approach and introduce best practices, as the interplay between the two devices and the implantation-explantation strategies are key for success. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Background: Return of spontaneous circulation (ROSC) is achieved in 25% of out-of-hospital cardiac arrest (OHCA) patients. Mechanical chest compression (mechCPR) may maintain better perfusion during transport, allowing hospital treatments like extracorporeal circulation life support (ECLS). We aim to assess the effectiveness of a pre-hospital protocol introduction. Methods: Observational, retrospective study assessing all OHCA patients aged 12-75, with no-flow time 13 min, mechCPR achieved more frequently ROSC compared to manCPR. Among ECLS patients, 70% had time exceeding protocol: 8 (7.5%) had CPC

Aims Despite its high incidence and mortality risk, there is no evidence-based treatment for non-ischaemic cardiogenic shock (CS). The aim of this study was to evaluate the use of mechanical circulatory support (MCS) for non-ischaemic CS treatment.Methods and results In this multicentre, international, retrospective study, data from 890 patients with non-ischaemic CS, defined as CS due to severe de-novo or acute-on-chronic heart failure with no need for urgent revascularization, treated with or without active MCS, were collected. The association between active MCS use and the primary endpoint of 30-day mortality was assessed in a 1:1 propensity-matched cohort. MCS was used in 386 (43%) patients. Patients treated with MCS presented with more severe CS (37% vs. 23% deteriorating CS, 30% vs. 25% in extremis CS) and had a lower left ventricular ejection fraction at baseline (21% vs. 25%). After matching, 267 patients treated with MCS were compared with 267 patients treated without MCS. In the matched cohort, MCS use was associated with a lower 30-day mortality (hazard ratio 0.76, 95% confidence interval 0.59-0.97). This finding was consistent through all tested subgroups except when CS severity was considered, indicating risk reduction especially in patients with deteriorating CS. However, complications occurred more frequently in patients with MCS; e.g. severe bleeding (16.5% vs. 6.4%) and access-site related ischaemia (6.7% vs. 0%).Conclusion In patients with non-ischaemic CS, MCS use was associated with lower 30-day mortality as compared to medical therapy only, but also with more complications. Randomized trials are needed to validate these findings. [GRAPHICS] Open Access funding enabled and organized by Projekt DEAL. Conflict of interest: B.S. reports speaker fees from Abiomed and AstraZeneca, outside of the submitted work. B.N.B. reports honoraria from Siemens Healthineers, outside of the submitted work. S.B. reports grants and personal fees from Abbott Diagnostics, Bayer, Siemens, Thermo Fisher, grants from Singulex, personal fees from Abbott, AstraZeneca, Amgen, Medtronic, Pfizer, Roche, Siemens Diagnostics, Novartis, outside of the submitted work. D.E. reports speaker fees from Abiomed, Bayer, Daiichi Sankyo, outside of the submitted work. P.H. reports travel compensation from Abiomed, outside of the submitted work. P.K. reports research support for basic, translational, and clinical research projects from European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK) and German Centre for Cardiovascular Research, from several drug and device companies active in atrial fibrillation, and has received honoraria from several such companies in the past, but not in the last 3 years. He is listed as inventor on two patents held by University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783; unrelated to the submitted work). S.K. reports research support from Cytosorbents and Daiichi Sankyo. He also received lecture fees from Astra, Bard, Baxter, Biotest, Cytosorbents, Daiichi Sankyo, Fresenius Medical Care, Gilead, Mitsubishi Tanabe Pharma, MSD, Pfizer, Philips and Zoll. He received consultant fees from Fresenius, Gilead, MSD and Pfizer, outside of the submitted work. P.L. reports speaker fees from AstraZeneca, Bayer, EdwardsLifesciences, Medtronic and Pfizer outside the submitted work. N.M. reports lecture fees Pfizer/Bristol-Myers Squibb and grant research from Getinge Global USA and Italfarmaco, outside of the submitted work. M.O. reports speaker honoraria from Abbott Medical, AstraZeneca, Abiomed, Bayer vital, Biotronik, Bristol-Myers Squibb, CytoSorbents, Daiichi Sankyo Deutschland, Edwards Lifesciences Services, Sedana Medical, outside of the submitted work. A.P. reports an unrestricted educational grant from Abbott Vascular, outside of the submitted work. T.R. reports speaker fees from AstraZeneca, Daiichy, Bayer, Novartis, Abiomed outside the submitted work. D.W. reports speaker fees from Abiomed, AstraZeneca, Bayer, Berlin-Chemie, Boehringer Ingelheim, Novartis and Medtronic, outside of the submitted work. All other authors have nothing to disclose.

Background Chronic heart valve regurgitation induces left ventricular (LV) volume overload, leading to the development of hypertrophy and progressive dilatation of the ventricle to maintain physiological cardiac output. In order to prevent potential irreversible LV structural changes, the identification of the best timing for treatment is pivotal. Objective To assess the presence and extent of fibrosis in myocardial tissue in asymptomatic patients with valvular heart disease (VHD) and preserved LV dimensions and function undergoing cardiac surgery. Methods Thirty-nine patients were enrolled. Sixteen patients were affected by aortic or mitral regurgitation: they were all asymptomatic, undergoing valve surgery according to VHD European Society of Cardiology guidelines. Twentythree patients with end-stage nonischemic dilated cardiomyopathy (DCM) and severe LV dysfunction undergoing cardiac surgery for implantation of a durable left ventricular assist device (LVAD) served as controls. During surgery, VHD patients underwent three myocardial biopsies at the level of the septum, the lateral wall and LV apex, while in LVAD patients the coring of the apex of the LV was used. For both groups, the tissue samples were analyzed on one section corresponding to the apical area. All slides were stained with hematoxylin and eosin and Masson's trichrome staining and further digitalized. The degree of fibrosis was then calculated as a percentage of the total area. Results Of 39 patients, 23 met the inclusion criteria: 12 had mitral or aortic insufficiency with a preserved ejection fraction and 11 had idiopathic dilated cardiomyopathy. Quantitative analysis of apical sections revealed a myocardial fibrosis amount of 10±6% in VHD patients, while in LVAD patients the mean apical myocardial fibrosis rate was 38±9%. In VHD patients, fibrosis was also present in the lateral wall (9±4%) and in the septum (9±6%). Conclusion Our case series study highlights the presence of tissue remodeling with fibrosis in asymptomatic patients with VHD and preserved LV function. According to our results, myocardial fibrosis is present at an early stage of the disease, well before developing detectable LV dysfunction and symptoms. Since the relationship between the progressive magnitude of myocardial fibrosis and potential prognostic implications are not yet defined, further studies on this topic are warranted.

Objectives: Six months after withdrawal of the HeartWare HVAD System (HVAD; Medtronic) from sale, approximately 4000 patients continue ongoing support with this device. In light of the diminishing experience, this global consensus document summarizes key management recommendations. Methods: International experts with experience in the management of patients with ongoing HVAD support were invited to summarize key aspects of patient and pump management and highlight differences in the current HeartMate 3 (Abbott Laboratories) ventricular assist device. Clinicians from high-implanting HVAD sites reviewed current literature and reported experience to generate a consensus statement. Results: Specific guidelines to assist in the management of ongoing HVAD patients are developed. Key management protocols and helpful techniques developed from experienced clinicians are combined into a short guideline document. As experience with HeartMate 3 increases, key differences in approach to management are highlighted, where appropriate. Conclusions: With decreasing worldwide experience in the ongoing management of HVAD-supported patients, this consensus guideline provides a summary of best practice techniques from international centers. Differences in HeartMate 3 management are highlighted.

Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality. Adjunct hemoadsorption is increasingly utilized to target underlying hyperinflammation derived from ARDS. This article aims to review available data on the use of CytoSorb© therapy in combination with V-V ECMO in severe ARDS, and to assess the effects on inflammatory, laboratory and clinical parameters, as well as on patient outcomes. A systematic literature review was conducted and reported in compliance with principles derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. When applicable, a before-and-after analysis for relevant biomarkers and clinical parameters was carried out. CytoSorb© use was associated with significant reductions in circulating levels of C-reactive protein and interleukin-6 (p = 0.039 and p = 0.049, respectively). Increases in PaO2/FiO2 reached significance as well (p = 0.028), while norepinephrine dosage reductions showed a non-significant trend (p = 0.067). Mortality rates in CytoSorb© patients tended to be lower than those of control groups of most included studies, which, however, were characterized by high heterogeneity and low power. In an exploratory analysis on 90-day mortality in COVID-19 patients supported with V-V ECMO, the therapy was associated with a significantly reduced risk of death. Based on the reviewed data, CytoSorb© therapy is able to reduce inflammation and potentially improves survival in ARDS patients treated with V-V ECMO. Early initiation of CytoSorb© in conjunction with ECMO might offer a new approach to enhance lung rest and promote recovery in patients with severe ARDS.

Left ventricular (LV) unloading is a crucial point in the management of patients with severe LV dysfunction supported by extracorporeal membrane oxygenation (ECMO). Indeed, ECMO increases LV afterload, which may ultimately further impair or delay cardiac recovery, worsening prognosis. The choice of the proper strategy at the right time for each patient plays a fundamental role in managing these patients in the intensive care unit. Strict and accurate monitoring of the heart and hemodynamic parameters with echocardiography and pulmonary artery catheter is crucial for decision making about timing of the LV unloading and management of MCS devices, guiding either in upgrading or weaning from mechanical support. A case discussion followed by a critical review of the current literature and multiple-choice questions gives the opportunity to obtain an implementation of new concepts in the management of cardiogenic shock patients by learning more about systematic LV venting.

Complex ascending and aortic arch surgery requires the implementation of different cerebral protection strategies to avoid or limit the probability of intraoperative brain damage during circulatory arrest. The etiology of the damage is multifactorial, involving cerebral embolism, hypoperfusion, hypoxia and inflammatory response. These protective strategies include the use of deep or moderate hypothermia to reduce the cerebral oxygen consumption, allowing the toleration of a variable period of absence of cerebral blood flow, and the use of different cerebral perfusion techniques, both anterograde and retrograde, on top of hypothermia, to avoid any period of intraoperative brain ischemia. In this narrative review, the pathophysiology of cerebral damage during aortic surgery is described. The different options for brain protection, including hypothermia, anterograde or retrograde cerebral perfusion, are also analyzed, with a critical review of the advantages and limitations under a technical point of view. Finally, the current systems of intraoperative brain monitoring are also discussed.

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation. DESIGN: Mixed method approach combining multicenter retrospective study and survey. SETTING: Sixteen ICUs worldwide. PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients. CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation.

When axillary/subclavian arteries are not suitable because of size or anatomy, alternative access for the Impella pump 5.0/5.5 via the innominate artery allows circulatory support and eventually de-escalation from VA-ECMO to isolated left-side support. Moreover, less invasive surgery without the need to open the pericardium reduces the risk of RV dysfunction and bleeding. Finally, upper body strategies allow early rehabilitation during support, which is associated with improved survival in cardiogenic shock.

Cardiogenic shock remains a deadly complication of acute on chronic decompensated heart failure (ADHF-CS). Despite its increasing prevalence, it is incompletely understood and therefore often misdiagnosed in the early phase. Precise diagnosis of the underlying cause of CS is fundamental for undertaking the correct therapeutic strategy. Temporary mechanical circulatory support (tMCS) is the mainstay of management: identifying and selecting optimal patients through understanding of the hemodynamics and a prompt profiling and timing, is key for success. A recent statement from the American Heart Association provided pragmatic suggestions on tMCS device selection, escalation, and weaning strategies. However, several areas of uncertainty still remain in clinical practice. Accordingly, we present an overview of the main pitfalls that can occur during patients’ management with tMCS through a clinical case. This case illustrates the strict interdependency between left ventricular unloading and right ventricular dysfunction in the case of low filling pressures. Moreover, it further illustrates the pivotal role of stepwise escalation of therapy in a patient with an ADHF-CS and its peculiarities as compared to other forms of acute heart failure.