Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. Methods: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score–matched cohort. Results: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63–0.98]; P =0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site–related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%). Conclusions: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.

A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19. Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively. Most post-COVID-19 syndrome patients are moderately to severely impaired in daily live. 19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients. Hand grip strength is diminished in most patients compared to normal values in healthy. Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms.

Catheter-based closure of the left atrial appendage is an alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation. The effectiveness of this strategy, as compared with physician-directed best medical care, in patients at high risk for stroke and bleeding is unknown. In this multicenter randomized trial conducted in Germany, we assigned patients with atrial fibrillation and a high risk of stroke and bleeding to undergo left atrial appendage closure or to receive physician-directed best medical care (including direct oral anticoagulants, if eligible). The primary end point, tested for noninferiority, was a composite of stroke (ischemic or hemorrhagic), systemic embolism, major bleeding, or cardiovascular or unexplained death, assessed in a time-to-event analysis. The noninferiority margin was a hazard ratio of 1.3. A total of 912 adult patients underwent randomization. The primary end-point analysis included 446 patients who were assigned to undergo left atrial appendage closure (device group) and 442 who were assigned to physician-directed best medical care (medical-therapy group). The mean (±SD) age was 77.9±7.1 years; 38.6% of the patients were women, the mean CHA₂DS₂-VASc score was 5.2±1.5 (range, 0 to 9, with higher scores indicating a greater risk of stroke), and the mean HAS-BLED score was 3.0±0.9 (range, 0 to 9, with higher scores indicating higher risk of bleeding). After a median follow-up of 3 years (interquartile range, 1.7 to 4.7), a first primary end-point event had occurred in 155 patients (incidence per 100 patient-years, 16.8) in the device group and in 127 patients (incidence per 100 patient-years, 13.3) in the medical-therapy group (difference in restricted mean survival time, -0.36 years; 95% confidence interval, -0.70 to -0.01; P = 0.44 for noninferiority). Serious adverse events occurred in 368 patients (82.5%) in the device group and 342 (77.4%) in the medical-therapy group. Among patients with atrial fibrillation at high risk for stroke and bleeding, left atrial appendage closure was not noninferior to physician-directed best medical care with regard to a composite end point of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death. (Funded by the German Center for Cardiovascular Research; CLOSURE-AF ClinicalTrials.gov number, NCT03463317.).

Objective: We investigated the benefit of Impella, a modern percutaneous mechanical support (pMCS) device, versus former standard intra-aortic balloon pump (IABP) in acute myocardial infarction complicated by cardiogenic shock (AMICS). Methods: This single-centre, retrospective study included patients with AMICS receiving pMCS with either Impella or IABP. Disease severity at baseline was assessed with the IABP-SHOCK II score. The primary outcome was all-cause mortality at 30 days. Secondary outcomes were parameters of shock severity at the early postimplantation phase. Adjusted Cox proportional hazards models identified independent predictors of the primary outcome. Results: Of 116 included patients, 62 (53%) received Impella and 54 (47%) IABP. Despite similar baseline mortality risk (IABP-SHOCK II high-risk score of 18 % vs 20 %; p = 0.76), Impella significantly reduced the inotropic score (p < 0.001), lactate levels (p < 0.001) and SAPS II (p = 0.02) and improved left ventricular ejection fraction (p = 0.01). All-cause mortality at 30 days was similar with Impella and IABP (52 % and 67 %, respectively; p = 0.13), but bleeding complications were more frequent in the Impella group (3 vs 4 units of transfused erythrocytes concentrates due to bleeding complications, p = 0.03). Previous cardiopulmonary resuscitation (HR 3.22, 95% CI 1.76 to 5.89; p < 0.01) and an estimated intermediate (HR 2.77, 95% CI 1.42 to 5.40; p < 0.01) and high (HR 4.32 95% CI 2.03 to 9.24; p = 0.01) IABP-SHOCK II score were independent predictors of all-cause mortality. Conclusions: In patients with AMICS, haemodynamic support with the Impella device had no significant effect on 30-day mortality as compared with IABP. In these patients, large randomised trials are warranted to ascertain the effect of Impella on the outcome.

Atrial fibrillation (AF) is associated with an increased risk of stroke and systemic embolism, and the left atrial appendage (LAA) has been identified as a principal source of thromboembolism in these patients. While oral anticoagulation is the current standard of care, LAA closure (LAAC) emerges as an alternative or complementary treatment approach to reduce the risk of stroke or systemic embolism in patients with AF. Moderate-sized randomized clinical studies have provided data for the efficacy and safety of catheter-based LAAC, largely compared with vitamin K antagonists. LAA device iterations, advances in pre- and peri-procedural imaging, and implantation techniques continue to increase the efficacy and safety of LAAC. More data about efficacy and safety of LAAC have been collected, and several randomized clinical trials are currently underway to compare LAAC with best medical care (including non-vitamin K antagonist oral anticoagulants) in different clinical settings. Surgical LAAC in patients with AF undergoing cardiac surgery reduced the risk of stroke on background of anticoagulation therapy in the LAAOS III study. In this review, we describe the rapidly evolving field of LAAC and discuss recent clinical data, ongoing studies, open questions, and current limitations of LAAC.

Aim: The expression of leptin and resistin is known to be positively correlated with the incidence of chronic heart failure (CHF). Both adipokines have been implicated in immunomodulation and cardiac remodelling. Therefore, we performed for the first time a clinical study to elucidate the effects of leptin and resistin on progression of CHF in patients with non-ischaemic dilated (DCM) and inflammatory (DCMi) cardiomyopathy. Methods and results: For the clinical study 120 patients were divided into a control (n = 16), DCM (n = 52), and DCMi (n = 52) group to determine the effect of leptin and resistin on CHF progression. Nuclear factor-κB (NF-κB) activation, reactive oxygen species generation, and tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression following adipokine exposition were determined in vitro in cardiomyocytes. Leptin and resistin systemic plasma levels and not cardiac expression were significantly elevated in patients with DCM (leptin, 13.12 ± 17.2 ng/mL, P < 0.05; resistin, 6.87 ± 2.25 ng/mL, P < 0.05) and DCMi (leptin, 13.63 ± 16 ng/mL, P < 0.05; resistin, 7.27 ± 2.2 ng/mL, P < 0.05) compared with the control group (leptin, 7.34 ± 5.7 ng/mL; resistin, 4.4 ± 1.18 ng/mL). A multivariate linear regression model revealed low leptin and resistin plasma levels as contributors for favourable cardiac functional parameters at 6-month follow-up independent of inflammatory conditions. Cell culture experiments in vitro showed leptin and resistin to be potent regulators of TNF-α and IL-6 expression in cardiomyocytes, leading to significantly increased redox stress in cardiac cells. Conclusions: High leptin and resistin expression in patients with DCM and DCMi is associated with CHF progression, i.e. severe cardiac dysfunction, independent of immune responses.