Subcortical tau is linked to hypoperfusion in connected cortical regions in 4-repeat tauopathies.

Four-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R tauopathies are progressive supranuclear palsy (PSP) and corticobasal degeneration characterized by subcortical tau accumulation and cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction, and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces remote neuronal dysfunction in functionally connected cortical regions to test a pathophysiological model that mechanistically links subcortical tau accumulation to cortical neuronal dysfunction in 4R tauopathies. We included 51 Aß-negative patients with clinically diagnosed PSP variants (n = 26) or corticobasal syndrome (n = 25) who underwent structural MRI and 18F-PI-2620 tau-PET. 18F-PI-2620 tau-PET was recorded using a dynamic one-stop-shop acquisition protocol to determine an early 0.5-2.5 min post tracer-injection perfusion window for assessing cortical neuronal dysfunction, as well as a 20-40 min post tracer-injection window to determine 4R-tau load. Perfusion-PET (i.e. early window) was assessed in 200 cortical regions, and tau-PET was assessed in 32 subcortical regions of established functional brain atlases. We determined tau epicentres as subcortical regions with the highest 18F-PI-2620 tau-PET signal and assessed the connectivity of tau epicentres to cortical regions of interest using a resting-state functional MRI-based functional connectivity template derived from 69 healthy elderly controls from the ADNI cohort. Using linear regression, we assessed whether: (i) higher subcortical tau-PET was associated with reduced cortical perfusion; and (ii) cortical perfusion reductions were observed preferentially in regions closely connected to subcortical tau epicentres. As hypothesized, higher subcortical tau-PET was associated with overall lower cortical perfusion, which remained consistent when controlling for cortical tau-PET. Using group-average and subject-level PET data, we found that the seed-based connectivity pattern of subcortical tau epicentres aligned with cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicentre showed lower perfusion. Together, subcortical tau-accumulation is associated with remote perfusion reductions indicative of neuronal dysfunction in functionally connected cortical regions in 4R-tauopathies. This suggests that subcortical tau pathology may induce cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity.

Multicenter Collaborative Study to Optimize Mass Spectrometry Workflows of Clinical Specimens.

The foundation for integrating mass spectrometry (MS)-based proteomics into systems medicine is the development of standardized start-to-finish and fit-for-purpose workflows for clinical specimens. An essential step in this pursuit is to highlight the common ground in a diverse landscape of different sample preparation techniques and liquid chromatography-mass spectrometry (LC-MS) setups. With the aim to benchmark and improve the current best practices among the proteomics MS laboratories of the CLINSPECT-M consortium, we performed two consecutive round-robin studies with full freedom to operate in terms of sample preparation and MS measurements. The six study partners were provided with two clinically relevant sample matrices: plasma and cerebrospinal fluid (CSF). In the first round, each laboratory applied their current best practice protocol for the respective matrix. Based on the achieved results and following a transparent exchange of all lab-specific protocols within the consortium, each laboratory could advance their methods before measuring the same samples in the second acquisition round. Both time points are compared with respect to identifications (IDs), data completeness, and precision, as well as reproducibility. As a result, the individual performances of participating study centers were improved in the second measurement, emphasizing the effect and importance of the expert-driven exchange of best practices for direct practical improvements.

SARS-CoV-2 Vaccination-Induced Immunogenicity in Heart Transplant Recipients.

Among heart transplant (HT) recipients, a reduced immunological response to SARS-CoV-2 vaccination has been reported. We aimed to assess the humoral and T-cell response to SARS-CoV-2 vaccination in HT recipients to understand determinants of immunogenicity. HT recipients were prospectively enrolled from January 2021 until March 2022. Anti-SARS-CoV-2-Spike IgG levels were quantified after two and three doses of a SARS-CoV-2 vaccine (BNT162b2, mRNA1273, or AZD1222). Spike-specific T-cell responses were assessed using flow cytometry. Ninety-one patients were included in the study (69% male, median age 55 years, median time from HT to first vaccination 6.1 years). Seroconversion rates were 34% after two and 63% after three doses. Older patient age (p = 0.003) and shorter time since HT (p = 0.001) were associated with lower antibody concentrations after three vaccinations. There were no associations between vaccine types or immunosuppressive regimens and humoral response, except for prednisolone, which was predictive of a reduced response after two (p = 0.001), but not after three doses (p = 0.434). A T-cell response was observed in 50% after two and in 74% after three doses. Despite three vaccine doses, a large proportion of HT recipients exhibits a reduced immune response. Additional strategies are desirable to improve vaccine immunogenicity in this vulnerable group of patients.

Mechanical circulatory support for adults in Japan: A 10-year perspective.

Globalization in Asia and consequent strengthening of healthcare economic factors in tandem with an increasing heart failure (HF) population have enhanced potential for development and progress in the fields of HF medicine and mechanical circulatory support (MCS). In Japan, there are unique opportunities to investigate the outcome of acute and chronic MCS and a national registry for percutaneous and implantable left ventricular assist device (LVAD) including Impella pumps has been established. A Peripheral extracorporeal membrane oxygenation (ECMO) for acute MCS has been used in more than 7000 patients annually and Impella usage in more than 4000 patients over the past 4 years was noted. Recently, a novel centrifugal pump with hydrodynamically levitated impeller was developed and approved for mid-term extracorporeal circulatory support. In terms of chronic MCS more than 1200 continuous flow LVADs have been implanted during the past decade, and 2-year survival rate after primary LVAD implantation is 91%. Because of donor organ shortage, more than 70% of heart transplant recipients required LVAD support for more than 3 years and prevention and treatment of complications during long-term LVAD support have become important. Five important topics including hemocompatibility-related complications, LVAD infections, aortic valve insufficiency, right ventricular failure and cardiac recovery during LVAD support are discussed in this review for improving clinical outcomes. Findings from Japan will continue to provide useful information regarding MCS for the Asia-Pacific region and beyond.

Differential utilization of Impella devices, extracorporeal membrane oxygenation, and combined therapies as escalation and de-escalation strategies.

Cardiogenic shock (CS) is a life-threatening condition characterized by a state of inadequate systemic tissue perfusion caused by cardiac dysfunction. When to implement, change, or remove the use of a temporary mechanical circulatory support (tMCS) in patients with CS is dependent on the aetiology and severity. Here, patient scenarios underlying the need to escalate, de-escalate, wean, or bridge from tMCS devices are taken into consideration by interdisciplinary heart failure and CS teams. This includes a comprehensive review of and focus on the rationale for specific device escalation and de-escalation strategies, device selection, and general management.

Preliminary Experience of Extracorporeal Cytokine Hemoadsorption during Left Ventricular Assist Device Implantation in Cardiogenic Shock Patients.

BACKGROUND: Systemic inflammation due to cardiogenic shock is associated with vasoplegia leading to organ hypoperfusion, right heart failure, and poor clinical outcome. Extracorporeal cytokine hemoadsorption emerged to attenuate excessive levels of inflammatory cytokines, potentially improving patient outcomes. Nevertheless, its prognostic impact during high-risk left ventricular assist device (LVAD) implantation remains unknown. METHODS: In total, 40 consecutive patients with advanced heart failure underwent continuous-flow LVAD implantation at our institution between 2018 and 2020. Out of 25 high-risk patients in cardiogenic shock (Interagency Registry for Mechanically Assisted Circulatory Support profile 1 and 2), 9 patients (CytoSorb group) underwent LVAD implantation with and 16 patients (control group) without simultaneous cytokine hemoadsorption during cardiopulmonary bypass. Besides preoperative patient characteristics, postoperative lactate clearance, vasopressor administration and mean arterial pressure, perioperative complication, and 30-day mortality rates were retrospectively analyzed. RESULTS: Apart from an increased rate of reoperations within the CytoSorb group, baseline characteristics including the severity of ventricular dysfunction and consecutive signs of end-organ failure were similar in both groups. Preoperative short-term mechanical circulatory support bridging was comparable (66.7 vs. 75%; p = 0.66) prior to LVAD implantation. Procedural characteristics including intraoperative volume management and postoperative vasopressor administration were similar in both groups. There was no difference regarding postoperative lactate clearance, although postoperative mean arterial pressure was significantly higher in the control group (71.3 vs. 57.4 mm Hg; p < 0.01). Furthermore, the 30-day mortality rate was significantly higher in the CytoSorb group (33.3 vs. 0.0%; p = 0.01). CONCLUSION: Extracorporeal cytokine hemoadsorption during high-risk LVAD implantation was not associated with a decrease of postoperative vasopressor support, improved hemodynamics, or an accelerated lactate clearance.

Rationale and Initiative of the Impella in Cardiac Surgery (ImCarS) Register Platform.

OBJECTIVES: Cardiac support systems are being used increasingly more due to the growing prevalence of heart failure and cardiogenic shock. Reducing cardiac afterload, intracardiac pressure, and flow support are important factors. Extracorporeal membrane oxygenation (ECMO) and intracardiac microaxial pump systems (Impella) as non-permanent MCS (mechanical circulatory support) are being used increasingly. METHODS: We reviewed the recent literature and developed an international European registry for non-permanent MCS. RESULTS: Life-threatening conditions that are observed preoperatively often include reduced left ventricular function, systemic hypoperfusion, myocardial infarction, acute and chronic heart failure, myocarditis, and valve vitia. Postoperative complications that are commonly observed include severe systemic inflammatory response, ischemia-reperfusion injury, trauma-related disorders, which ultimately may lead to low cardiac output (CO) syndrome and organ dysfunctions, which necessitates a prolonged ICU stay. Choosing the appropriate device for support is critical. The management strategies and complications differ by system. The "heart-team" approach is inevitably needed.However despite previous efforts to elucidate these topics, it remains largely unclear which patients benefit from certain systems, when is the right time to initiate (MCS), which support system is appropriate, what is the optimal level and type of support, which therapeutic additive and supportive strategies should be considered and ultimately, what are the future prospects and therapeutic developments. CONCLUSION: The European cardiac surgical register ImCarS has been established as an IIT with the overall aim to evaluate data received from the daily clinical practice in cardiac surgery. Interested colleagues are cordially invited to join the register. CLINICAL REGISTRATION NUMBER: DRKS00024560. POSITIVE ETHICS VOTE: AZ 246/20 Faculty of Medicine, Justus-Liebig-University-Gießen.

Procedural volume and outcomes in patients undergoing VA-ECMO support.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in patients with critical cardiopulmonary failure. To investigate the association between hospital VA-ECMO procedure volume and outcomes in a large, nationwide registry. METHODS: By using administrative data from the German Federal Health Monitoring System, we analyzed all VA-ECMO procedures performed in Germany from 2013 to 2016 regarding the association of procedural volumes with outcomes and complications. RESULTS: During the study period, 10,207 VA-ECMO procedures were performed; mean age was 61 years, 43.4% had prior CPR, and 71.2% were male patients. Acute coronary syndrome was the primary diagnosis for VA-ECMO implantation (n = 6202, 60.8%). The majority of implantations (n = 5421) were performed at hospitals in the lowest volume category (≤ 50 implantations per year). There was a significant association between annualized volume of VA-ECMO procedures and 30-day in-hospital mortality for centers with lower vs. higher volume per year. Multivariable logistic regression showed an increased 30-day in-hospital mortality at hospitals with the lowest volume category (adjusted odds ratio 1.13, 95% confidence interval [CI] 1.01-1.27, p = 0.034). Similarly, higher likelihood for complications was observed at hospitals with lower vs. higher annual VA-ECMO volume (adjusted odds ratio 1.46, 95% CI 1.29-1.66, p = 0.001). CONCLUSIONS: In this analysis of more than 10,000 VA-ECMO procedures for cardiogenic shock, the majority of implantations were performed at hospitals with the lowest annual volume. Thirty-day in-hospital mortality and likelihood for complications were higher at hospitals with the lowest annual VA-ECMO volume.

Sex differences in preformed panel-reactive antibody levels and outcomes in patients undergoing heart transplantation.

BACKGROUND: Sex differences in panel-reactive antibody (PRA) levels in heart transplant recipients and their association with transplant-related outcomes are mostly unknown. METHODS: In 20 181 (24.7% women) first-time heart transplant recipients included from July 2004 to March 2015 in the prospective Organ Procurement and Transplantation Network (OPTN), we studied sex differences in most recent (mr) and peak (p)PRA and outcomes (graft failure, rejection, cardiac allograft vasculopathy [CAV], retransplantation, and mortality). Median follow-up (all-cause mortality) was 6 years. Analyses are based on OPTN data (March 6, 2017). RESULTS: MrPRA levels were associated with all-cause mortality (hazard ratio, 95% confidence interval: class I 1.03, 1.01-1.04, P < 0.001) and acute rejection (class II 1.08, 1.03-1.14, P = 0.0044). PPRA levels were associated with all-cause mortality (class I 1.02, 1.00-1.04, P = 0.015) and CAV (class II 1.03, 1.01-1.06, P = 0.020). Sex interactions were seen for the association of pPRA and graft failure with a higher risk in women, and for pPRA and CAV with a higher risk in men. CONCLUSIONS: PRA were associated with different transplant-related outcomes in both sexes. However, women with elevated pPRA were shown to be at higher risk for graft failure, whereas higher levels of pPRA were more hazardous for men in developing CAV.

Comparison of Outcomes of Tricuspid Valve Surgery in Patients with Reduced and Normal Right Ventricular Function.

Background: To study the effect of tricuspid valve repair/replacement on outcomes of patients with reduced systolic right ventricular function. Methods: Between January 2012 and July 2016, 191 patients with isolated tricuspid valve regurgitation and/or in combination with other valve diseases were enrolled into this retrospective study. We compared early postoperative outcomes (i.e., 30 days after surgery) between patients' cohort with a preoperative reduced (i.e., at least moderately) versus normal (or mildly reduced) right ventricular function as defined by means of preoperative echocardiography. Results: A total of 82 (43%) patients had preoperatively reduced right ventricle function with tricuspid annular plane systolic excursion (TAPSE) of 13.3 ± 3.3 versus 20.2 ± 4.9 mm (p < 0.001). Ring annuloplasty was the most common surgical technique (i.e., 91% in both groups). Time of procedure (317 ± 123 vs. 262 ± 88 minutes, p < 0.01) and time on cardiopulmonary bypass (163 ± 77 vs. 143 ± 57 minutes, p = 0.036) were significantly longer in patients with impaired right ventricular function. Postoperative lactate (3.5 ± 3 vs. 2 ± 1 mmol/L, p = 0.001) and dose of catecholamines (epinephrine, 0.07 ± 0.15 vs. 0.013 ± 0.02 µg/kg/min, p = 0.001; norepinephrine, 0.18 ± 0.23 vs. 0.07 ± 0.09 µg/kg/min, p = 0.007) were also higher in this group. Postoperative rate of low cardiac output syndrome (10 vs. 27%, p = 0.005) and early mortality (n = 2 vs. n = 9, p = 0.018) were significantly increased in patients with reduced right ventricular function. Previous cardiac operation (p = 0.045), preoperative higher number of acute decompensations of heart failure (p < 0.001), reduced right ventricular function (p = 0.018), postoperative low cardiac output syndrome (p < 0.001), and renal replacement therapy (p < 0.001) were identified as risk factors for early mortality. Echocardiography at discharge revealed tricuspid valve regurgitation grade of 0.9 ± 0.7 versus 0.7 ± 0.6 (p = 0.052) and TAPSE of 12 ± 3 versus 15 ± 5 mm (p = 0.026) in patients with reduced right ventricular function. The New York Heart Association (NYHA) class improved to 1.7 ± 0.7 versus 1.3 ± 1 (p < 0.001) in this group of patients. Conclusion: Tricuspid valve repair/replacement effectively eliminated severe tricuspid regurgitation and improved clinical signs of heart failure. Although mortality and morbidity were increased in the group with reduced right ventricular function, even these patients benefitted from improved functional status and right ventricular systolic function early postoperatively.

High-risk donors: extending our criteria in times of organ shortage.

PURPOSE OF REVIEW: Increasing waiting lists and declining transplant numbers due to organ shortage are a global problem that needs a multimodal approach to overcome this situation. Extending the criteria for transplantation may be one part of the solution. RECENT FINDINGS: There are political efforts to increase the donor rate and change the listing criteria and the allocation process. Recently, the cardiac allocation score was introduced enhancing the factor urgency to the allocation process. Marginal donor organs can be accepted using ex-vivo perfusion strategies. Experimental approaches, such as donation after circulatory death and xenotransplantation, need to be further developed to be applied to humans and increase the pool of available transplant organs. SUMMARY: Organ shortage needs new approaches to overcome the discrepancy between the number of patients on the wait list and performed heart transplantations, reduce wait list mortality and improve long-term outcomes after transplantation.

Association of early changes in arterial carbon dioxide with acute brain injury in adult patients with extracorporeal membrane oxygenation: A ten-year retrospective study in a German tertiary care hospital.

PURPOSE: To assess the association between fluctuations of arterial carbon dioxide early after start of extracorporeal membrane oxygenation (ECMO) with intracranial hemorrhage (ICH) or ischemic stroke (IS). MATERIALS AND METHODS: This single-center retrospective study included patients who required ECMO for circulatory or respiratory failure between January 2011 and April 2021 and for whom a cerebral computed tomography (cCT) scan was available. Multivariable logistic regression models were fitted to evaluate the association between the relative change of arterial carbon dioxide (RelΔPaCO2) and ICH, IS or a composite of ICH, IS, and mortality. RESULTS: In 618 patients (venovenous ECMO: n = 295; venoarterial ECMO: n = 323) ICH occurred more frequently in patients with respiratory failure (19.0%) compared with patients with circulatory failure (6.8%). Conversely, the incidence of IS was higher in patients with circulatory failure (19.2%) compared with patients with respiratory failure (4.7%). While patients with ECMO for respiratory failure were more likely to have ICH (OR 3.683 [95% CI: 1.855;7.309], p < 0.001), they had a lower odds for IS (OR 0.360 [95%CI: 0.158;0.820], p = 0.015) compared with patients with circulatory failure. There was no significant association between RelΔPaCO2 and ICH or IS. CONCLUSIONS: Irrespective of the indication for ECMO, we did not find a significant association between the relative change in PaCO2 early after ECMO initiation and acute brain injury. Aside from early PaCO2 decline at cannulation, future studies should address fluctuations of PaCO2 throughout the course of ECMO support and their effect on acute brain injury.

Pragmatic approach to temporary mechanical circulatory support in acute right ventricular failure.

Acute right ventricular failure (RVF) is prevalent in multiple disease states and is associated with poor clinical outcomes. Right-sided temporary mechanical circulatory support (tMCS) devices are used to unload RV congestion and increase cardiac output in cardiogenic shock (CS) with hemodynamically significant RVF. Several RV-tMCS device platforms are available; however consensus is lacking on patient selection, timing of escalation to RV-tMCS, device management, and device weaning. The purposes of this review are to 1) describe the current state of tMCS device therapies for acute RVF with CS, 2) discuss principles of escalation to RV-tMCS device therapy, 3) examine important aspects of clinical management for patients supported by RV-tMCS devices including volume management, anticoagulation, and positive pressure ventilation, and 4) provide a framework for RV-tMCS weaning.

GFAP and NfL as fluid biomarkers for clinical disease severity and disease progression in multiple system atrophy (MSA).

BACKGROUND: Multiple system atrophy (MSA), an atypical parkinsonian syndrome, is a rapidly progressive neurodegenerative disease with currently no established fluid biomarkers available. MSA is characterized by an oligodendroglial α-synucleinopathy, progressive neuronal cell loss and concomitant astrocytosis. Here, we investigate glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as fluid biomarkers for differential diagnosis, assessment of clinical disease severity and prediction of disease progression in MSA. METHODS: GFAP and NfL levels were analyzed in plasma and CSF samples of 47 MSA patients as well as 24 Parkinson's disease (PD) and 25 healthy controls (HC) as reference cohorts. In MSA, biomarker levels were correlated to baseline and longitudinal clinical disease severity (UMSARS scores). RESULTS: In MSA, GFAP levels in CSF and plasma predicted baseline clinical disease severity as indicated by UMSARS scores, while NfL levels predicted clinical disease progression as indicated by longitudinal changes in UMSARS scores. Cross-sectionally, NfL levels in CSF and plasma were significantly elevated in MSA compared to both PD and HC. Receiver operating curves (ROC) indicated high diagnostic accuracy of NfL for distinguishing MSA from PD (CSF: AUC = 0.97, 95% CI 0.90-1.00; plasma: AUC = 0.90, 95% CI 0.81-1.00). DISCUSSION: In MSA, GFAP shows promise as novel biomarker for assessing current clinical disease severity, while NfL might serve as biomarker for prediction of disease progression and differential diagnosis of MSA against PD.

Association of Neurofilament Light Chain, [18F]PI-2620 Tau-PET, TSPO-PET, and Clinical Progression in Patients With ß-Amyloid-Negative CBS.

BACKGROUND AND OBJECTIVES: Corticobasal syndrome (CBS) with underlying 4-repeat tauopathy is a progressive neurodegenerative disease characterized by declining cognitive and motor functions. Biomarkers for assessing pathologic brain changes in CBS including tau-PET, 18 kDa translocator protein (TSPO)-PET, structural MRI, neurofilament light chain (NfL), or glial fibrillary acidic protein (GFAP) have recently been evaluated for differential diagnosis and disease staging, yet their association with disease trajectories remains unclear. Therefore, we performed a head-to-head comparison of neuroimaging (tau-PET, TSPO-PET, structural MRI) and plasma biomarkers (NfL, GFAP) as prognostic tools for longitudinal clinical trajectories in ß-amyloid (Aß)-negative CBS. METHODS: We included patients with clinically diagnosed Aß-negative CBS with clinical follow-up data who underwent baseline structural MRI and plasma-NfL analysis for assessing neurodegeneration, [18F]PI-2620-PET for assessing tau pathology, [18F]GE-180-PET for assessing microglia activation, and plasma-GFAP analysis for assessing astrocytosis. To quantify tau and microglia load, we assessed summary scores of whole-brain, cortical, and subcortical PET signal. For structural MRI analysis, we quantified subcortical and cortical gray matter volume. Plasma NfL and GFAP values were assessed using Simoa-based immunoassays. Symptom progression was determined using a battery of cognitive and motor tests (i.e., Progressive Supranuclear Palsy Rating Scale [PSPRS]). Using linear mixed models, we tested whether the assessed biomarkers at baseline were associated with faster symptom progression over time (i.e., time × biomarker interaction). RESULTS: Overall, 21 patients with Aß-negative CBS with ∼2-year clinical follow-up data were included. Patients with CBS with more widespread global tau-PET signal showed faster clinical progression (PSPRS: B/SE = 0.001/0.0005, p = 0.025), driven by cortical rather than subcortical tau-PET. By contrast, patients with higher global [18F]GE-180-PET readouts showed slower clinical progression (PSPRS: B/SE = -0.056/0.023, p = 0.019). No association was found between gray matter volume and clinical progression. Concerning fluid biomarkers, only higher plasma-NfL (PSPRS: B/SE = 0.176/0.046, p < 0.001) but not GFAP was associated with faster clinical deterioration. In a subsequent sensitivity analysis, we found that tau-PET, TSPO-PET, and plasma-NfL showed significant interaction effects with time on clinical trajectories when tested in the same model. DISCUSSION: [18F]PI-2620 tau-PET, [18F]GE-180 TSPO-PET, and plasma-NfL show prognostic potential for clinical progression in patients with Aß-negative CBS with probable 4-repeat tauopathy, which can be useful for clinical decision-making and stratifying patients in clinical trials.

Complications in patients with cardiogenic shock on veno-arterial extracorporeal membrane oxygenation therapy: distribution and relevance. Results from an international, multicentre cohort study.

AIMS: Veno-arterial extracorporeal membrane oxygenation therapy (VA-ECMO) restores circulation and tissue oxygenation in cardiogenic shock (CS) patients, but can also lead to complications. This study aimed to quantify VA-ECMO complications and analyse their association with overall survival as well as favourable neurological outcome (cerebral performance categories 1 + 2). METHODS AND RESULTS: All-comer patients with CS treated with VA-ECMO were retrospectively enrolled from 16 centres in four countries (2005-2019). Neurological, bleeding, and ischaemic adverse events (AEs) were considered. From these, typical VA-ECMO complications were identified and analysed separately as device-related complications. n = 501. Overall, 118 were women (24%), median age was 56.0 years, median lactate was 8.1 mmol/L. Acute myocardial infarction caused CS in 289 patients (58%). Thirty-days mortality was 40% (198/501 patients). At least one device-related complication occurred in 252/486 (52%) patients, neurological AEs in 108/469 (23%), bleeding in 192/480 (40%), ischaemic AEs in 123/478 (26%). The 22% of patients with the most AEs accounted for 50% of all AEs. All types of AEs were associated with a worse prognosis. Aside from neurological ones, all AEs and device-related complications were more likely to occur in women; although prediction of AEs outside of neurological AEs was generally poor. CONCLUSION: Therapy and device-related complications occur in half of all patients treated with VA-ECMO and are associated with a worse prognosis. They accumulate in some patients, especially in women. Aside from neurological events, identification of patients at risk is difficult, highlighting the need to establish additional quantitative markers of complication risk to guide VA-ECMO treatment in CS.