Extracorporeal Life Support in Infarct-Related Cardiogenic Shock.

BACKGROUND: Extracorporeal life support (ECLS) is increasingly used in the treatment of infarct-related cardiogenic shock despite a lack of evidence regarding its effect on mortality. METHODS: In this multicenter trial, patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization was planned were randomly assigned to receive early ECLS plus usual medical treatment (ECLS group) or usual medical treatment alone (control group). The primary outcome was death from any cause at 30 days. Safety outcomes included bleeding, stroke, and peripheral vascular complications warranting interventional or surgical therapy. RESULTS: A total of 420 patients underwent randomization, and 417 patients were included in final analyses. At 30 days, death from any cause had occurred in 100 of 209 patients (47.8%) in the ECLS group and in 102 of 208 patients (49.0%) in the control group (relative risk, 0.98; 95% confidence interval [CI], 0.80 to 1.19; P = 0.81). The median duration of mechanical ventilation was 7 days (interquartile range, 4 to 12) in the ECLS group and 5 days (interquartile range, 3 to 9) in the control group (median difference, 1 day; 95% CI, 0 to 2). The safety outcome consisting of moderate or severe bleeding occurred in 23.4% of the patients in the ECLS group and in 9.6% of those in the control group (relative risk, 2.44; 95% CI, 1.50 to 3.95); peripheral vascular complications warranting intervention occurred in 11.0% and 3.8%, respectively (relative risk, 2.86; 95% CI, 1.31 to 6.25). CONCLUSIONS: In patients with acute myocardial infarction complicated by cardiogenic shock with planned early revascularization, the risk of death from any cause at the 30-day follow-up was not lower among the patients who received ECLS therapy than among those who received medical therapy alone. (Funded by the Else Kröner Fresenius Foundation and others; ECLS-SHOCK ClinicalTrials.gov number, NCT03637205.).

Ventricular septal defect complicating acute myocardial infarction: diagnosis and management. A Clinical Consensus Statement of the Association for Acute CardioVascular Care (ACVC) of the ESC, the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC and the ESC Working Group on Cardiovascular Surgery.

Ventricular septal defects are a rare complication after acute myocardial infarction with a mortality close to 100% if left untreated. However, even surgical or interventional closure is associated with a very high mortality and currently no randomized controlled trials are available addressing the optimal treatment strategy of this disease. This state-of-the-art review and clinical consensus statement will outline the diagnosis, hemodynamic consequences and treatment strategies of ventricular septal defects complicating acute myocardial infarction with a focus on current available evidence and a focus on major research questions to fill the gap in evidence.

Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation.

BACKGROUND: Myocardial infarction is a frequent cause of out-of-hospital cardiac arrest. However, the benefits of early coronary angiography and revascularization in resuscitated patients without electrocardiographic evidence of ST-segment elevation are unclear. METHODS: In this multicenter trial, we randomly assigned 554 patients with successfully resuscitated out-of-hospital cardiac arrest of possible coronary origin to undergo either immediate coronary angiography (immediate-angiography group) or initial intensive care assessment with delayed or selective angiography (delayed-angiography group). All the patients had no evidence of ST-segment elevation on postresuscitation electrocardiography. The primary end point was death from any cause at 30 days. Secondary end points included a composite of death from any cause or severe neurologic deficit at 30 days. RESULTS: A total of 530 of 554 patients (95.7%) were included in the primary analysis. At 30 days, 143 of 265 patients (54.0%) in the immediate-angiography group and 122 of 265 patients (46.0%) in the delayed-angiography group had died (hazard ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.63; P = 0.06). The composite of death or severe neurologic deficit occurred more frequently in the immediate-angiography group (in 164 of 255 patients [64.3%]) than in the delayed-angiography group (in 138 of 248 patients [55.6%]), for a relative risk of 1.16 (95% CI, 1.00 to 1.34). Values for peak troponin release and for the incidence of moderate or severe bleeding, stroke, and renal-replacement therapy were similar in the two groups. CONCLUSIONS: Among patients with resuscitated out-of-hospital cardiac arrest without ST-segment elevation, a strategy of performing immediate angiography provided no benefit over a delayed or selective strategy with respect to the 30-day risk of death from any cause. (Funded by the German Center for Cardiovascular Research; TOMAHAWK ClinicalTrials.gov number, NCT02750462.).

ICU management of cardiogenic shock before mechanical support.

PURPOSE OF REVIEW: Treatment of cardiogenic shock remains largely driven by expert consensus due to limited evidence from randomized controlled trials. In this review, we aim to summarize the approach to the management of patients with cardiogenic shock in the ICU prior to mechanical circulatory support (MCS). RECENT FINDINGS: Main topics covered in this article include diagnosis, monitoring, initial management and key aspects of pharmacological therapy in the ICU for patients with cardiogenic shock. SUMMARY: Despite efforts to improve therapy, short-term mortality in patients with cardiogenic shock is still reaching 40-50%. Early recognition and treatment of cardiogenic shock are crucial, including early revascularization of the culprit lesion with possible staged revascularization in acute myocardial infarction (AMI)-CS. Optimal volume management and vasoactive drugs titrated to restore arterial pressure and perfusion are the cornerstone of cardiogenic shock therapy. The choice of vasoactive drugs depends on the underlying cause and phenotype of cardiogenic shock. Their use should be limited to the shortest duration and lowest possible dose. According to recent observational evidence, assessment of the complete hemodynamic profile with a pulmonary artery catheter (PAC) was associated with improved outcomes and should be considered early in patients not responding to initial therapy or with unclear shock. A multidisciplinary shock team should be involved early in order to identify potential candidates for temporary and/or durable MCS.

Advances in the Management of Cardiogenic Shock.

OBJECTIVES: To review a contemporary approach to the management of patients with cardiogenic shock (CS). DATA SOURCES: We reviewed salient medical literature regarding CS. STUDY SELECTION: We included professional society scientific statements and clinical studies examining outcomes in patients with CS, with a focus on randomized clinical trials. DATA EXTRACTION: We extracted salient study results and scientific statement recommendations regarding the management of CS. DATA SYNTHESIS: Professional society recommendations were integrated with evaluated studies. CONCLUSIONS: CS results in short-term mortality exceeding 30% despite standard therapy. While acute myocardial infarction (AMI) has been the focus of most CS research, heart failure-related CS now predominates at many centers. CS can present with a wide spectrum of shock severity, including patients who are normotensive despite ongoing hypoperfusion. The Society for Cardiovascular Angiography and Intervention Shock Classification categorizes patients with or at risk of CS according to shock severity, which predicts mortality. The CS population includes a heterogeneous mix of phenotypes defined by ventricular function, hemodynamic profile, biomarkers, and other clinical variables. Integrating the shock severity and CS phenotype with nonmodifiable risk factors for mortality can guide clinical decision-making and prognostication. Identifying and treating the cause of CS is crucial for success, including early culprit vessel revascularization for AMI. Vasopressors and inotropes titrated to restore arterial pressure and perfusion are the cornerstone of initial medical therapy for CS. Temporary mechanical circulatory support (MCS) is indicated for appropriately selected patients as a bridge to recovery, decision, durable MCS, or heart transplant. Randomized controlled trials have not demonstrated better survival with the routine use of temporary MCS in patients with CS. Accordingly, a multidisciplinary team-based approach should be used to tailor the type of hemodynamic support to each individual CS patient's needs based on shock severity, phenotype, and exit strategy.

[Prehospital resuscitation : Current status, results and strategies for improvement in Germany]. / Prähospitale Reanimationen : Aktueller Stand, Ergebnisse und Verbesserungsansätze in Deutschland.

Out-of-hospital cardiac arrest (OHCA) is one of the most frequent causes of death in Europe and is associated with a dismal prognosis. The annual incidence in Germany is approximately 100-120 per 100,000 inhabitants (ca. 80,000-100,000 cases). With the use of cardiopulmonary resuscitation (CPR) about 40% of patients have a return of spontaneous circulation (ROSC); however, after OHCA only 15% of patients survive for 30 days and less than 10% survive with no or only minor neurological deficits. Data from the German Resuscitation Register demonstrate that there was no change in the results over the last 15 years, despite all medical innovations, higher rates of coronary interventions, higher use of mechanical support systems and improvement in intensive care treatment. A high proportion of patients with OHCA have a cardiac or coronary cause. As shown by the data from the German Cardiac Arrest Register (G-CAR) an early coronary angiography is often carried out after CPR in Germany; however, in randomized clinical studies an immediate coronary angiography in patients with non-ST segment elevation in the electrocardiogram (ECG) was not associated with an improvement in the prognosis. In large randomized studies the use of mechanical CPR systems and the implantation of mechanical circulatory support devices after OHCA also did not lead to a reduction in mortality. The most important impact factor for the success of CPR is the time interval between collapse and start of CPR, if possible also by bystander resuscitation. Therefore, the focus of efforts for improving CPR should be on increasing the rate of patients with early CPR. Experiences from Denmark and The Netherlands indicate that this can be successful by education and training of the general population, telephone resuscitation and apps for alerting lay persons.

[Management of acute coronary syndrome without ST-segment elevation]. / Management des akuten Koronarsyndroms ohne ST-Strecken-Hebung.

The collective term acute coronary syndrome (ACS) encompasses ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS). The latter comprises unstable angina pectoris and non-ST-segment elevation myocardial infarction (NSTEMI). The diagnosis of STEMI necessitates an immediate referral to cardiac catheterization. The diagnostics and management of NSTE-ACS are more challenging. The current guidelines of the European Society of Cardiology (ESC) for treatment of NSTE-ACS were published in 2020 and deal with the topics of diagnostics, risk stratification, antithrombotic treatment, invasive or non-invasive coronary diagnostics and long-term treatment. The focus of the guidelines is on the application of high-sensitivity cardiac troponin assay(hs-cTn) combined with verified diagnostic algorithms to enable a rapid triage decision (rule-in as possible NSTEMI or rule-out as NSTEMI excluded) in the emergency room or the chest pain unit.

[ERC guidelines 2021 on cardiopulmonary resuscitation]. / ERC-Leitlinien 2021 zur kardiopulmonalen Reanimation.

The current European guidelines on cardiopulmonary resuscitation were published in 2021. The guidelines, which are structured in 12 chapters, were supplemented with the chapters on epidemiology and life-saving systems. In the following article, the recommendations on basic life support, advanced measures for resuscitation in adults and postresuscitation treatment are discussed.

The novel cystatin C, lactate, interleukin-6, and N-terminal pro-B-type natriuretic peptide (CLIP)-based mortality risk score in cardiogenic shock after acute myocardial infarction.

BACKGROUND: Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) still reaches excessively high mortality rates. This analysis is aimed to develop a new easily applicable biomarker-based risk score. METHODS AND RESULTS: A biomarker-based risk score for 30-day mortality was developed from 458 patients with CS complicating AMI included in the randomized CULPRIT-SHOCK trial. The selection of relevant predictors and the coefficient estimation for the prognostic model were performed by a penalized multivariate logistic regression analysis. Validation was performed internally, internally externally as well as externally in 163 patients with CS included in the randomized IABP-SHOCK II trial. Blood samples were obtained at randomization. The two trials are registered with ClinicalTrials.gov (NCT01927549 and NCT00491036), are closed to new participants, and follow-up is completed. Out of 58 candidate variables, the four strongest predictors for 30-day mortality were included in the CLIP score (cystatin C, lactate, interleukin-6, and N-terminal pro-B-type natriuretic peptide). The score was well calibrated and yielded high c-statistics of 0.82 [95% confidence interval (CI) 0.78-0.86] in internal validation, 0.82 (95% CI 0.75-0.89) in internal-external (temporal) validation, and 0.73 (95% CI 0.65-0.81) in external validation. Notably, it outperformed the Simplified Acute Physiology Score II and IABP-SHOCK II risk score in prognostication (0.83 vs 0.62; P < 0.001 and 0.83 vs. 0.76; P = 0.03, respectively). CONCLUSIONS: A biomarker-only score for 30-day mortality risk stratification in infarct-related CS was developed, extensively validated and calibrated in a prospective cohort of contemporary patients with CS after AMI. The CLIP score outperformed other clinical scores and may be useful as an early decision tool in CS.

Extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial.

BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke. CONCLUSIONS: The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.

Impact of transcatheter mitral valve repair on ventricular arrhythmias.

AIMS: Patients with heart failure and severe mitral regurgitation (MR) have a poor prognosis and carry an increased risk for ventricular arrhythmias. The present study evaluates the impact of transcatheter mitral valve repair using the MitraClip on the potential reduction of ventricular arrhythmias. METHODS AND RESULTS: Patients undergoing MitraClip implantation were prospectively enrolled into the present study and received 24 h Holter ECG assessment prior to and 6 months after the procedure. In addition, left ventricular dimensions and function were assessed at baseline and follow-up. A total of 50 patients with mainly functional MR (82%) were included. Non-sustained or sustained ventricular tachycardia (nsVT and/or sVT) occurred in 32% of patients and was reduced to 14% at follow-up (P = 0.01). Also, premature ventricular complex (PVC) burden ≥5% decreased from 16% to 4% (P = 0.04). Patients with persistent (n = 6) or new (n = 1) nsVT and/or sVT at follow-up showed a significant decrease in left ventricular ejection fraction from 38% (interquartile range 26-45%) to 33% (interquartile range 22-44%; P = 0.03). CONCLUSIONS: In this prospective study, transcatheter mitral valve repair using MitraClip was associated with a reduced prevalence of ventricular arrhythmias. The subset of patients with persistent or new ventricular arrhythmias after MitraClip implantation showed progression of left ventricular dysfunction.

Percutaneous short-term active mechanical support devices in cardiogenic shock: a systematic review and collaborative meta-analysis of randomized trials.

AIMS: Evidence on the impact on clinical outcome of active mechanical circulatory support (MCS) devices in cardiogenic shock (CS) is scarce. This collaborative meta-analysis of randomized trials thus aims to investigate the efficacy and safety of percutanzeous active MCS vs. control in CS. METHODS AND RESULTS: Randomized trials comparing percutaneous active MCS to control in patients with CS were identified through searches of medical literature databases. Risk ratios (RR) and 95% confidence intervals (95% CI) were calculated to analyse the primary endpoint of 30-day mortality and device-related complications including bleeding and leg ischaemia. Mean differences (MD) were calculated for mean arterial pressure (MAP), cardiac index (CI), pulmonary capillary wedge pressure (PCWP), and arterial lactate. Four trials randomizing 148 patients to either TandemHeart™ or Impella® MCS (n = 77) vs. control (n = 71) were identified. In all four trials intra-aortic balloon pumping (IABP) served as control. There was no difference in 30-day mortality (RR 1.01, 95% CI 0.70 to 1.44, P = 0.98, I2 = 0%) for active MCS compared with control. Active MCS significantly increased MAP (MD 11.85 mmHg, 95% CI 3.39 to 20.31, P = 0.02, I2 = 32.7%) and decreased arterial lactate (MD - 1.36 mmol/L, 95% CI - 2.52 to - 0.19, I2 = 0%, P = 0.02) at comparable CI (MD 0.32, 95% CI - 0.24 to 0.87, P = 0.14, I2 = 44.1%) and PCWP (MD - 5.59, 95% -15.59 to 4.40, P = 0.14, I2 = 81.1%). No significant difference was observed in the incidence of leg ischaemia (RR 2.64, 95% CI 0.83 to 8.39, P = 0.10, I2 = 0%), whereas the rate of bleeding was significantly increased in MCS compared to IABP (RR 2.50, 95% CI 1.55 to 4.04, P < 0.001, I2 = 0%). CONCLUSION: Results of this collaborative meta-analysis do not support the unselected use of active MCS in patients with CS complicating AMI.

Fibroblast growth factor 23 in acute myocardial infarction complicated by cardiogenic shock: a biomarker substudy of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial.

INTRODUCTION: Cardiogenic shock (CS) is the leading cause of death in patients hospitalized with acute myocardial infarction (AMI). Biomarkers might help in risk stratification and understanding of pathophysiology. Preliminary data suggests that patients with CS face a profound increase in the osteocyte-derived hormone fibroblast growth factor 23 (FGF-23), which acts as a negative regulator of serum phosphate levels. The present study aimed to assess the predictive role of FGF-23 for clinical outcome in a large cohort of CS patients with and without renal dysfunction. METHODS: In the randomized Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial, 600 patients with CS complicating AMI were assigned to therapy with or without IABP. Our predefined biomarker substudy included 182 patients. Blood sampling was performed in a standardized procedure at three different time points (day 1 (day of admission), day 2 and day 3). Differences in outcome of patients with FGF-23 levelsmedian were compared by log-rank testing. Stepwise logistic regression modeling was performed to identify predictors of death at 30 days and Cox regression analysis for time to death during the first year. RESULTS: At all three time points, nonsurvivors had significantly higher FGF-23 levels compared to survivors (P<0.001 for all). Patients with FGF-23 levels above the median (395 RU/mL [interquartile range 102;2,395]) were characterized by an increased 30-day mortality and 1-year mortality. In multivariable analysis FGF-23 levels remained independent predictors for 30-day (odds ratio per 10log 1.80, 95% confidence interval (CI) 1.11 to 2.92; P=0.02) and 1-year mortality (hazard ratio 1.50, 95% CI 1.11 to 2.04, P=0.009). After stratifying the patients according to their baseline serum creatinine levels, the negative prognostic association of increased FGF-23 was only significant in those with serum creatinine greater than median. CONCLUSIONS: In CS, high levels of FGF-23 are independently related to a poor clinical outcome. However, this prognostic association appears only to apply in patients with impaired renal function. TRIAL REGISTRATION: ClinicalTrials.gov NCT00491036. Registered 22 June 2007.

Circulating angiopoietins and cardiovascular mortality in cardiogenic shock.

AIMS: Vascular integrity is disturbed in shock contributing to clinical appearance and serious outcomes. While angiopoietin (Ang)-1 protects from vascular inflammation and leakage, Ang-2 disrupts endothelial barrier function. The imbalance of Ang-1 and Ang-2, their association to haemodynamic deterioration, and their prognostic relevance are not known and, thus, were prospectively evaluated in patients with cardiogenic shock (CS) in this study. METHODS AND RESULTS: Plasma Ang-1 and Ang-2 were determined by the enzyme immunoassay in patients with CS (n = 96), uncomplicated acute myocardial infarction (AMI, n = 20) and age-matched healthy controls (HC, n = 20). Angiopoietin-2 was three-fold elevated in CS compared with HC (P < 0.001), remained elevated in non-survivors, and decreased in survivors (P < 0.001). In contrast, Ang-1 decreased up to 35-fold in CS (P < 0.001). Angiopoietin-1 was correlated and Ang-2 was inversely related to a cardiac power index and mixed venous oxygen saturation, respectively (P < 0.001 for all). To assess the prognostic relevance, two outcome variables were considered: the 28-day mortality and the survival time (follow-up time 1 year). For Ang-2 at admission a cut-off point of 2500 pg/mL had a sensitivity of 61% and a specificity of 80% to determine 28-day mortality in CS (confirmed by receiver operating characteristic analysis, area under the curve = 0.71 ± 0.06, P < 0.001). Angiopoietin-2 levels >2500 pg/mL at admission were observed to be an independent predictor for 1-year mortality in CS confirmed by Cox proportional hazard analysis [hazard ratio (HR) 2.11; 95% confidence interval (CI) 1.03-4.36; P = 0.042]. CONCLUSION: Circulating Angs are closely related to outcome and severity in CS. Angiopoietin-2 emerged as an independent predictor of 28-day and 1-year mortality in CS. Larger studies are required to define the cut-off and predictive values for Ang-2. Angiopoietins may be prognostic biomarkers for survival in CS and might represent a novel therapeutic target.

Impact of anaemia and iron deficiency on outcomes in cardiogenic shock complicating acute myocardial infarction.

AIMS: Anaemia and iron deficiency (ID) are common comorbidities in cardiovascular patients and are associated with a poor clinical status, as well as a worse outcome in patients with heart failure and acute myocardial infarction (AMI). Nevertheless, data concerning the impact of anaemia and ID on clinical outcomes in patients with cardiogenic shock (CS) are scarce. This study aimed to assess the impact of anaemia and ID on clinical outcomes in patients with CS complicating AMI. METHODS AND RESULTS: The presence of anaemia (haemoglobin <13 g/dl in men and <12 g/dl in women) or ID (ferritin <100 ng/ml or transferrin saturation <20%) was determined in patients with CS due to AMI from the CULPRIT-SHOCK trial. Blood samples were collected in the catheterization laboratory during initial percutaneous coronary intervention. Clinical outcomes were compared in four groups of patients having neither anaemia nor ID, against patients with anaemia with or without ID and patients with ID only. A total of 427 CS patients were included in this analysis. Anaemia without ID was diagnosed in 93 (21.7%), anaemia with ID in 54 study participants (12.6%), ID without anaemia in 72 patients (16.8%), whereas in 208 patients neither anaemia nor ID was present (48.9%). CS patients with anaemia without ID were older (73 ± 10 years, p = 0.001), had more frequently a history of arterial hypertension (72.8%, p = 0.01), diabetes mellitus (47.8%, p = 0.001), as well as chronic kidney disease (14.1%, p = 0.004) compared to CS patients in other groups. Anaemic CS patients without ID presence were at higher risk to develop a composite from all-cause death or renal replacement therapy at 30-day follow-up (odds ratio [OR] 3.83, 95% confidence interval [CI] 2.23-6.62, p < 0.001) than CS patients without anaemia/ID. The presence of ID in CS patients, with and without concomitant anaemia, did not increase the risk for the primary outcome (OR 1.17, 95% CI 0.64-2.13, p = 0.64; and OR 1.01, 95% CI 0.59-1.73, p = 0.54; respectively) within 30 days of follow-up. In time-to-event Kaplan-Meier analysis, anaemic CS patients without ID had a significantly higher hazard ratio (HR) for the primary outcome (HR 2.11, 95% CI 1.52-2.89, p < 0.001), as well as for death from any cause (HR 1.90, 95% CI 1.36-2.65, p < 0.001) and renal replacement therapy during 30-day follow-up (HR 2.99, 95% CI 1.69-5.31, p < 0.001). CONCLUSION: Concomitant anaemia without ID presence in patients with CS at hospital presentation is associated with higher risk for death from any cause or renal replacement therapy and the individual components of this composite endpoint within 30 days after hospitalization. ID has no relevant impact on clinical outcomes in patients with CS.

German Cardiac Arrest Registry (G-CAR)-results of the pilot phase.

BACKGROUND: In Europe, more than 300,000 persons per year experience out-of-hospital cardiac arrest (OHCA). Despite medical progress, only few patients survive with good neurological outcome. For many issues, evidence from randomized trials is scarce. OHCA often occurs for cardiac causes. Therefore, we established the national, prospective, multicentre German Cardiac Arrest Registry (G-CAR). Herein, we describe the first results of the pilot phase. RESULTS: Over a period of 16 months, 15 centres included 559 consecutive OHCA patients aged ≥ 18 years. The median age of the patients was 66 years (interquartile range 57;75). Layperson resuscitation was performed in 60.5% of all OHCA cases which were not observed by emergency medical services. The initial rhythm was shockable in 46.4%, and 29.1% of patients had ongoing CPR on hospital admission. Main presumed causes of OHCA were acute coronary syndromes (ACS) and/or cardiogenic shock in 54.8%, with ST-elevation myocardial infarction being the most common aetiology (34.6%). In total, 62.9% of the patients underwent coronary angiography; percutaneous coronary intervention (PCI) was performed in 61.4%. Targeted temperature management was performed in 44.5%. Overall in-hospital mortality was 70.5%, with anoxic brain damage being the main presumed cause of death (38.8%). Extracorporeal cardiopulmonary resuscitation (eCPR) was performed in 11.0%. In these patients, the in-hospital mortality rate was 85.2%. CONCLUSIONS: G-CAR is a multicentre German registry for adult OHCA patients with a focus on cardiac and interventional treatment aspects. The results of the 16-month pilot phase are shown herein. In parallel with further analyses, scaling up of G-CAR to a national level is envisaged. Trial registration ClinicalTrials.gov identifier: NCT05142124.

Ischaemia-induced up-regulation of Toll-like receptor 2 in circulating monocytes in cardiogenic shock.

AIMS: To investigate the role of Toll-like receptor 2 (TLR2) in uncomplicated acute myocardial infarction (AMI) and in cardiogenic shock (CS). METHODS AND RESULTS: In patients with uncomplicated AMI (n = 20), CS (n = 30) and in age-matched healthy controls (HC; n = 20), TLR2 expression on monocytes was assessed by flow cytometry. Tumour necrosis factor alpha (TNFα) and interleukin-6 (IL6) expression in monocytes was analysed by intracellular cytokine staining. TLR2 expression was increased in patients with AMI compared with HC [mean fluorescence intensity (MFI) 111.1 ± 8.2 vs. 66.9 ± 1.5, P < 0.001]. In patients with CS, TLR2 expression was further increased (132.8 ± 5.6 MFI, P = 0.009 vs. AMI). This was accompanied by an increased expression of the proinflammatory cytokines TNFα (4.3 ± 1.6% in AMI vs. 20.5 ± 5.9% in CS, P = 0.004) and IL6 (6.3 ± 1.6% in AMI vs. 20.6 ± 6.2% in CS, P = 0.032). Furthermore, in all patients with myocardial infarction (AMI + CS; n = 50), a strong correlation between the monocytic TLR2 expression and the symptom to reperfusion time (r(2)= 0.706, P < 0.001) was found, implying tissue hypoxia dependency. Symptom to reperfusion time is a main factor to influence TLR2 expression but not the presence of CS. TLR2 expression of mononuclear cells exposed in vitro to hypoxia was assessed by flow cytometry and western blot. In vitro measurements showed a hypoxia-mediated monocytic TLR2 expression up-regulation. CONCLUSION: We demonstrate TLR2 up-regulation and increased proinflammatory cytokine expression in circulating monocytes in AMI/CS depending on disease severity, implying an important role of TLR2 expression in ischaemic injury.

Percutaneous Left Atrial Appendage Occlusion-Current Evidence and Future Directions.

Over the past two decades, percutaneous left atrial appendage occlusion (LAAO) has proven to be a viable alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF), in particular in those patients who are at increased risk for stroke and bleeding complications. This systematic review provides a comprehensive evaluation of anatomical features, patient selection, procedural planning and execution, complications, medical treatment following the procedure, and contemporary outcome data.