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. Graphical abstract

Background Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a valuable treatment option for patients in cardiogenic shock, but complications during decannulation may worsen the overall outcome. Therefore, the aim of this study was to compare the efficacy and safety of suture-based to pure plug-based vascular closure devices for VA-ECMO decannulation. Methods In this retrospective study, the procedural outcome of 33 patients with suture-based Perclose ProGlide closure devices was compared to 38 patients with MANTA plug-based closure devices. Results Rate of technically correct placement of closure devices was 88% in the suture-based group and 97% in the plug-based group ( p = 0.27). There was a significant reduction of severe bleeding events during VA-ECMO decannulation in plug-based versus suture-based systems (3% vs. 21%, p = 0.04). Ischemic complications occurred in 6% with suture-based and 5% with plug-based device ( p = 1.00). Pseudoaneurysm formation was detected in 3% in both groups ( p = 1.00). No switch to vascular surgery due to bleeding after decannulation was necessary in both groups. Conclusion Based on our retrospective analysis, we propose that plug-based vascular closure should be the preferred option for VA-ECMO decannulation. This hypothesis should be further tested in a randomized trial.

Background The efficacy and safety of saline versus balanced crystalloid solutions in ICU-patients remains complicated by exceptionally heterogenous study population in past comparative studies. This study sought to compare saline and balanced crystalloids for fluid resuscitation in patients with cardiogenic shock with or without out-of-hospital cardiac arrest (OHCA). Methods We retrospectively analyzed 1032 propensity score matched patients with cardiogenic shock from the Munich University Hospital from 2010 to 2022. In 2018, default resuscitation fluid was changed from 0.9% saline to balanced crystalloids. The primary endpoint was defined as 30-day mortality rate. Results Patients in the saline group ( n = 516) had a similar 30-day mortality rate as patients treated with balanced crystalloids ( n = 516) (43.1% vs. 43.0%, p = 0.833), but a higher incidence of new onset renal replacement therapy (30.2% vs 22.7%, p = 0.007) and significantly higher doses of catecholamines. However, OHCA-patients with a lactate level higher than 7.4 mmol/L had a significantly lower 30-day mortality rate when treated with saline (58.6% vs. 79.3%, p = 0.013). In addition, use of balanced crystalloids was independently associated with a higher mortality in the multivariate cox regression analysis after OHCA (hazard ratio 1.43, confidence interval: 1.05–1.96, p = 0.024). Conclusions In patients with cardiogenic shock, use of balanced crystalloids was associated with a similar all-cause mortality at 30 days but a lower rate of new onset of renal replacement therapy. In the subgroup of patients after OHCA with severe shock, use of balanced crystalloids was associated with a higher mortality than saline. Trial registration : LMUshock registry (WHO International Clinical Trials Registry Platform Number DRKS00015860).

BACKGROUND It is currently unclear if active left ventricular (LV) unloading should be used as a primary treatment strategy or as a bailout in patients with cardiogenic shock (CS) treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). OBJECTIVES This study sought to evaluate the association between timing of active LV unloading and implantation of VA-ECMO with outcomes of patients with CS.METHODS Data from 421 patients with CS treated with VA-ECMO and active LV unloading at 18 tertiary care centers in 4 countries were analyzed. Patients were stratified by timing of device implantation in early vs delayed active LV unloading (defined by implantation before up to 2 hours after VA-ECMO). Adjusted Cox and logistic regression models were fitted to evaluate the association between early active LV unloading and 30-day mortality as well as successful weaning from ventilation.RESULTS Overall, 310 (73.6%) patients with CS were treated with early active LV unloading. Early active LV unloading was associated with a lower 30-day mortality risk (HR: 0.64; 95% CI: 0.46-0.88) and a higher likelihood of successful weaning from ventilation (OR: 2.17; 95% CI: 1.19-3.93) but not with more complications. Importantly, the relative mortality risk increased and the likelihood of successful weaning from ventilation decreased almost proportionally with the time interval between VA-ECMO implantation and (delayed) initiation of active LV unloading.CONCLUSIONS This exploratory study lends support to the use of early active LV unloading in CS patients on VA-ECMO, although the findings need to be validated in a randomized controlled trial.(J Am Coll Cardiol HF 2023;11:321-330) (c) 2023 by the American College of Cardiology Foundation.

(1) Herpes simplex virus (HSV) reactivation in critically ill patients can cause infection in the lower respiratory tract, prolonging mechanical ventilation. However, the association of HSV reactivation with cardiogenic shock (CS) is unclear. As CS is often accompanied by pulmonary congestion and reduced immune system activity, the aim of our study was to determine the incidence and outcome of HSV reactivation in these patients. (2) In this retrospective, single-center study, bronchial lavage (BL) was performed on 181 out of 837 CS patients with mechanical ventilation. (3) In 44 of those patients, HSV was detected with a median time interval of 11 days since intubation. The occurrence of HSV was associated with an increase in C-reactive protein and the fraction of inspired oxygen at the time of HSV detection. Arterial hypertension, bilirubin on ICU admission, the duration of mechanical ventilation and out-of-hospital cardiac arrest were associated with HSV reactivation. (4) HSV reactivation could be detected in 24.3% of patients with CS on whom BL was performed, and its occurrence should be considered in patients with prolonged mechanical ventilation. Due to the limited current evidence, the initiation of treatment for these patients remains an individual choice. Dedicated randomized studies are necessary to investigate the efficacy of antiviral therapy.

Abstract Funding Acknowledgements Type of funding sources: None. Objectives (Background): The feasibility and hemodynamic effects of isoflurane sedation in cardiogenic shock in the presence of extracorporeal membrane oxygenation (VA-ECMO) treatment is currently unknown. Design Retrospective single-center study Patients/subjects: Cardiogenic shock patients with VA-ECMO treatment under sedation with volatile isoflurane between November 2018 and October 2019 have been enrolled in this study and were matched by propensity score in a 1:1 ratio with intravenously (IV) sedated patients treated between January 2013 and November 2018 from the cardiogenic shock registry of our university hospital. Measurements and Main Results: Isoflurane sedation was used in 32 patients with cardiogenic shock and VA-ECMO treatment. The mean age of conventionally sedated patients was 58.4 ± 13.8 years and 56.3 ± 11.5 years for patients with isoflurane sedation (p = 0.51). Administration of isoflurane was associated with lower IV sedative drug use during VA-ECMO treatment (86% vs. 32%, p = 0.01). Mean systolic arterial pressure was similar (94.3 ± 12.6 mmHg versus 92.9 ± 10.5 mmHg, p = 0.65), but mean heart rate was significantly higher in the conventional sedation group, when compared to the isoflurane group (85.2 ± 20.5 /min vs. 74.7 ± 15.0 /min; p = 0.02). Catecholamine doses, VA-ECMO blood and gas flow, ventilation time (304 ± 143 h vs. 398 ± 272 h,p = 0.16), bleeding complications BARC3a or higher (59.3% vs. 65.3%, p = 0.76) and 30 day-mortality (59.2% vs. 63.4%, p = 0.80) were similar in both groups. The overall sedation costs per patient were significantly lower in the conventional group, when compared to the isoflurane group (537 ± 624 € vs. 1280 ± 837 €, p < 0.001). Conclusions Volatile sedation with isoflurane is feasible – albeit at higher costs - in patients with cardiogenic shock and VA-ECMO treatment and was not associated with higher catecholamine dosage or ECMO flow rate compared to IV sedation.

Importance:The assessment of new antithrombotic agents with a favorable safety profile is clinically relevant.Objective:To test the efficacy and safety of revacept, a novel, lesion-directed antithrombotic drug, acting as a competitive antagonist to platelet glycoprotein VI.Design, Setting, and Participants:A phase 2 randomized clinical trial; patients were enrolled from 9 centers in Germany from November 20, 2017, to February 27, 2020; follow-up ended on March 27, 2020. The study included patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous coronary intervention (PCI).Interventions:Single intravenous infusion of revacept, 160 mg, revacept, 80 mg, or placebo prior to the start of PCI on top of standard antithrombotic therapy.Main Outcomes and Measures:The primary end point was the composite of death or myocardial injury, defined as an increase in high-sensitivity cardiac troponin to at least 5 times the upper limit of normal within 48 hours from randomization. The safety end point was bleeding type 2 to 5 according to the Bleeding Academic Research Consortium criteria at 30 days.Results:Of 334 participants (median age, 67.4 years; interquartile range, 60-75.1 years; 253 men [75.7%]; and 330 White participants [98.8%]), 120 were allocated to receive the 160-mg dose of revacept, 121 were allocated to receive the 80-mg dose, and 93 received placebo. The primary end point showed no significant differences between the revacept and placebo groups: 24.4%, 25.0%, and 23.3% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .98). The high dose of revacept was associated with a small but significant reduction of high-concentration collagen-induced platelet aggregation, with a median 26.5 AU × min (interquartile range, 0.5-62.2 AU × min) in the revacept, 160 mg, group; 43.5 AU × min (interquartile range, 22.8-99.5 AU × min) in the revacept, 80 mg, group; and 41.0 AU × min (interquartile range, 31.2-101.0 AU × min) in the placebo group (P = .02), while adenosine 5'-diphosphate-induced aggregation was not affected. Revacept did not increase Bleeding Academic Research Consortium type 2 or higher bleeding at 30 days compared with placebo: 5.0%, 5.9%, and 8.6% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .36).Conclusions and Relevance:Revacept did not reduce myocardial injury in patients with stable ischemic heart disease undergoing percutaneous coronary intervention. There were few bleeding events and no significant differences between treatment arms.Trial Registration:ClinicalTrials.gov Identifier: NCT03312855.

BACKGROUND:Acute cardiac tamponade is a life-threatening pathology in modern cardiology as catheter-based interventions become increasingly relevant. Pericardiocentesis is usually the primary treatment of choice. However, protocols for handling of draining pigtail catheters are very variable due to limit data and require further investigation. METHODS:We retrospectively analyzed 52 patients with acute cardiac tamponade requiring immediate pericardiocentesis from January 2017 to August 2020. Patients were treated with a classical approach of intermittent manual aspiration or continuous pericardial drainage using a redon drainage system. RESULTS:Mean age of patients was 74 years in both groups. Most common causes for cardiac tamponade were percutaneous coronary interventions in about 50% and transaortic valve implantations in 25% of all cases. 28 patients were treated with classic intermittent drainage from 2017 to 2020. 24 patients were treated with continuous drainage from December 2018-2020. Compared to classical intermittent drainage treatment, continuous drainage was associated with a lower rate of a surgical intervention or cardiac re-tamponade and a lower mortality at 5 days (HR 0.2, 95% CI 0.1-0.9, log-rank p = 0.03). Despite a longer total drainage time under continuous suction, drainage volumes were comparable in both groups. CONCLUSION:Acute cardiac tamponade can be efficiently treated by pericardiocentesis with subsequent continuous negative pressure drainage via a pigtail catheter. Our retrospective analysis shows a significantly lower mortality, a decreased rate of interventions and lower rates of cardiac re-tamponade without any relevant side effects when compared to classical intermittent manual drainage. These findings require further investigations in larger, randomized trials.

Background: Atrial Fibrillation (AF) is common pathophysiologically complex. Age is among the most important AF risk factors. However, some young patients develop early-onset AF, whereas many others do not despite an advanced age. Advanced biological aging as opposed to advanced calendar age may be an explanation. Telomere length is associated with age and may be considered a measurable marker of biological age. AF and telomere length have previously been associated, but results remained inconclusive. Hypothesis: AF is age-related and associates with telomere length in a large case-control cohort. Methods: Between 2005 and 2018, we enrolled 2475 early-onset AF patients into the prospective AFLMU cohort. 3077 AF-free individuals from the community-based KORA study (enrollment 2006-08) served as controls. Clinical characteristics, an electrocardiogram, and a blood sample was obtained in all participants. We determined telomere length by a qPCR-based method using a multiplex TaqMan assay. Telomere length was expressed as delta-CT referenced to the single copy gene 36B4 .Lower CT values indicate shorter telomere length. Telomere length in cases vs. controls was assessed using multi-variably adjusted logistic regression. Results: Mean age was 58 years in AFLMU and 56 years in KORA. Men accounted for 72.3% in AFLMU and for 51.7% in KORA. For quality control, we confirmed a reduction of telomere length with age and demonstrated shorter telomere length in men compared to women. Median telomere length was also significantly shorter in AF patients compared to controls (9.81 [5.98, 13.1] vs. 13,10 [12.60, 13.63], p<0,001). The association remained significant after adjustment for sex, body mass index, hypertension, and diabetes (odds ratio per telomere length unit 0.77 [95% confidence interval 0.74-0.77], p<0.001). Conclusion: In a large case-control cohort, AF significantly associates with telomere length. Information on telomere length may help to inform if a patient develops AF due to premature biological aging. The underlying pathomechanisms for premature aging remain to be elucidated.

Abstract Background Atrial Fibrillation (AF) is common and is caused and predisposed to by a complex pathophysiology. Aging is among the most important risk factors for AF. Yet, some individuals develop AF in early years, whereas elderly individuals may remain free of AF. Aside from measurable concomitant risks, we hypothesized that a pathophysiologically relevant biological age exists, which outweighs a patient's calendar age. Telomere length is a measurable marker of age, which might reflect biological age. AF and telomere length have previously been associated, but results remained controversial. Here, we tested the relation between AF and telomere length in a well-characterized and so far largest cohort. Methods Since 2005, we enrolled 2475 patients with AF from the prospective AFLMU cohort, preferentially if they developed AF before age 65 years, and 3077 control individuals free of AF from the community-based KORA Study between 2006–08. All participants received a detailed clinical characterization, an electrocardiogram, and a blood draw for biomarker analyses. In all participants, we determined telomere length using a qPCR-based method. In a 384 well format, we employed a multiplex TaqMan assay to determine both telomere length and the single copy gene 36B4. Telomere length was expressed by the delta-CT method and was reformatted to have lower CT values indicate shorter telomere length. We compared telomere length between cases and controls using multi-variably corrected logistic regression models. Results Our cohort's mean age was 58 years in AFLMU and 56 years in KORA F4. Men were enrolled more commonly, with 72.3% in AFLMU and 51.7% in KORA F4. For consistency with available information, we confirmed that telomere length is continuously decreasing with age and that men have shorter telomere length compared to women. As a main result we found that AF patients have significantly shorter telomere length compared to controls (controls: telomere length 13,10 [12.60, 13.63] versus AF: 9.81 [5.98, 13.1], p<0,001). This relation remained significant following multi-variable adjustment for sex, body mass index, hypertension, and diabetes. The odds ratio per unit longer telomer length was 0.77 [95% confidence interval 0.74–0.77], p<0.001. We also calculated a propensity-score matched model of cases with and without AF confirming our main results (controls: telomere length 13.21 [11.65, 13.67] versus AF: 9.03 [5.35, 12.54], p<0.001). The multi-variable adjusted model revealed an odds ratio of 0,75 [95% confidence interval 0.73–0.76], p<0.001. Conclusion AF is significantly associated with telomere length in one of the largest cohorts to date. Assessment of telomere length may adjudicate patients with AF due to premature biological aging. The underlying reasons for such premature aging remain to be identified. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Commission - Horizon 2020

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.

AIMS:Prior analyses disclosed variations in antiplatelet drug response and clinical outcomes between smokers and non-smokers, thus the safety and efficacy of any dual antiplatelet therapy (DAPT) de-escalation strategy may differ in relation to smoking status. Hence, we assessed the impact of smoking on clinical outcomes and adenosine diphosphate-induced platelet aggregation following guided de-escalation of DAPT in invasively managed acute coronary syndrome (ACS) patients. METHODS AND RESULTS:The multicentre TROPICAL-ACS trial randomized 2610 biomarker-positive ACS patients 1:1 to standard treatment with prasugrel for 12 months (control group) or a platelet function testing guided de-escalation of DAPT. Current smokers (n = 1182) showed comparable event rates between study groups [6.6% vs. 6.6%; hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.64-1.56, P > 0.99]. In non-smokers (n = 1428), a guided DAPT de-escalation was associated with a lower 1-year incidence of the primary endpoint [cardiovascular death, myocardial infarction, stroke, or bleeding ≥ Grade 2 according to Bleeding Academic Research Consortium (BARC) criteria] compared with control group patients (7.9% vs. 11.0%; HR 0.71, 95% CI 0.50-0.99, P = 0.048). This reduction was mainly driven by a lower rate of BARC ≥ Grade 2 bleedings (5.2% vs. 7.7%; HR 0.68, 95% CI 0.45-1.03, P = 0.066). There was no significant interaction of smoking status with treatment effects of guided DAPT de-escalation (Pint = 0.23). Adenosine diphosphate-induced platelet aggregation values were higher in current smokers [median 28 U, interquartile range (IQR: 20-40)] vs. non-smoker [median 24 U (16-25), P < 0.0001] in the control group and in current smokers [median 42 U, IQR (27-68)] vs. non-smoker [median 37 U, IQR (25-55), P < 0.001] in the monitoring group. CONCLUSION:Guided DAPT de-escalation appears to be equally safe and effective in smokers and non-smokers. Regardless of smoking status and especially for those patients deemed unsuitable for 1 year of potent platelet inhibition this DAPT strategy might be used as an alternative antiplatelet treatment regimen.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides temporary cardiac and respiratory support and has emerged as an established salvage intervention for patients with hemodynamic compromise or shock. It is thereby used as a bridge to recovery, bridge to permanent ventricular assist devices, bridge to transplantation, or bridge to decision. However, weaning from VA-ECMO differs between centers, and information about standardized weaning protocols are rare. Given the high mortality of patients undergoing VA-ECMO treatment, it is all the more important to answer the many questions still remaining unresolved in this field Standardized algorithms are recommended to optimize the weaning process and determine whether the VA-ECMO can be safely removed. Successful weaning as a multifactorial process requires sufficient recovery of myocardial and end-organ function. The patient should be considered hemodynamically stable, although left ventricular function often remains impaired during and after weaning. Echocardiographic and invasive hemodynamic monitoring seem to be indispensable when evaluating biventricular recovery and in determining whether the VA-ECMO can be weaned successfully or not, whereas cardiac biomarkers may not be useful in stratifying those who will recover. This review summarizes the strategies of weaning of VA-ECMO and discusses predictors of successful and poor weaning outcome.

Cardiogenic shock is still a major driver of mortality on intensive care units and complicates ∼10% of acute coronary syndromes with contemporary mortality rates up to 50%. In the meantime, percutaneous circulatory support devices, in particular venoarterial extracorporeal membrane oxygenation (VA-ECMO), have emerged as an established salvage intervention for patients in cardiogenic shock. Venoarterial extracorporeal membrane oxygenation provides temporary circulatory support until other treatments are effective and enables recovery or serves as a bridge to ventricular assist devices, heart transplantation, or decision-making. In this critical care perspective, we provide a concise overview of VA-ECMO utilization in cardiogenic shock, considering rationale, critical care management, as well as weaning aspects. We supplement previous literature by focusing on therapeutic issues related to the vicious circle of retrograde aortic VA-ECMO flow, increased left ventricular (LV) afterload, insufficient LV unloading, and severe pulmonary congestion limiting prognosis in a relevant proportion of patients receiving VA-ECMO treatment. We will outline different modifications in percutaneous mechanical circulatory support to meet this challenge. Besides a strategy of running ECMO at lowest possible flow rates, novel therapeutic options including the combination of VA-ECMO with percutaneous microaxial pumps or implementation of a venoarteriovenous-ECMO configuration based on an additional venous cannula supplying towards pulmonary circulation are most promising among LV unloading and venting strategies. The latter may even combine the advantages of venovenous and venoarterial ECMO therapy, providing potent respiratory and circulatory support at the same time. However, whether VA-ECMO can reduce mortality has to be evaluated in the urgently needed, ongoing prospective randomized studies EURO-SHOCK (NCT03813134), ANCHOR (NCT04184635), and ECLS-SHOCK (NCT03637205). These studies will provide the opportunity to investigate indication, mode, and effect of LV unloading in dedicated sub-analyses. In future, the Heart Teams should aim at conducting a dedicated randomized trial comparing VA-ECMO support with vs. without LV unloading strategies in patients with cardiogenic shock.

Objectives: The feasibility and hemodynamic effects of isoflurane sedation in cardiogenic shock in the presence of venoarterial extracorporeal membrane oxygenation treatment are currently unknown. Design: Retrospective single-center study. Setting: Cardiac ICU of Munich university hospital. Patients/Subjects: Cardiogenic shock patients with venoarterial extracorporeal membrane oxygenation treatment under sedation with volatile isoflurane between November 2018 and October 2019 have been enrolled in this study and were matched by propensity score in a 1:1 ratio with IV sedated patients treated between January 2013 and November 2018 from the cardiogenic shock registry of the university hospital of Munich. Measurements and Main Results: Isoflurane sedation was used in 32 patients with cardiogenic shock and venoarterial extracorporeal membrane oxygenation treatment. The mean age of conventionally sedated patients was 58.4 ± 13.8 years and 56.3 ± 11.5 years for patients with isoflurane sedation (p = 0.51). Administration of isoflurane was associated with lower IV sedative drug use during venoarterial extracorporeal membrane oxygenation treatment (86% vs 32%; p = 0.01). Mean systolic arterial pressure was similar (94.3 ± 12.6 vs 92.9 ± 10.5 mm Hg; p = 0.65), but mean heart rate was significantly higher in the conventional sedation group, when compared with the isoflurane group (85.2 ± 20.5 vs 74.7 ± 15.0 beats/min; p = 0.02). Catecholamine doses, venoarterial extracorporeal membrane oxygenation blood and gas flow, ventilation time (304 ± 143 vs 398 ± 272 hr; p = 0.16), bleeding complications bleeding academic research consortium 3a or higher (59.3% vs 65.3%; p = 0.76), and 30-day mortality (59.2% vs 63.4%, p = 0.80) were similar in both groups. The overall sedation costs per patient were significantly lower in the conventional group, when compared with the isoflurane group (537 ± 624 vs 1280 ± 837 €; p < 0.001). Conclusions: Volatile sedation with isoflurane is feasible—albeit at higher costs—in patients with cardiogenic shock and venoarterial extracorporeal membrane oxygenation treatment and was not associated with higher catecholamine dosage or extracorporeal membrane oxygenation flow rate compared with IV sedation.

Abstract Background Transcatheter edge-to-edge tricuspid valve repair (TTVR) is a novel treatment approach in heart failure patients with moderate-to-severe tricuspid regurgitation (TR) at prohibitive surgical risk. Aim The aim of this study was to investigate the mean tricuspid valve gradient (TVG) over time and compare patient characteristics and outcome of patients with a post-procedure TVG of >3 mmHg vs. ≤3 mmHg. Methods All patients who were treated between between March 2016 and October 2018 with TTVR were included in this analysis. Trans-thoracic echocardiographic assessment of TVG was performed pre-procedurally, pre-discharge, after 1, 6, and 12 month. Results We treated 145 consecutive patients with moderate-to-severe secondary TR with TTVR. Patients were treated with TTVR for severe TR alone (70 patients) or in combination with mitral valve repair for concomitant severe mitral regurgitation and severe or moderate-severe TR with significant annulus dilatation (75 patients). One clip was implanted in 17 (11.7%), 2 clips in 83 (57.2%), 3 clips in 40 (27.6%) and 4 clips in 4 patients (2.8%). Reduction of at least 1 degree of TR was achieved in 136 Patients (93.8%). The median baseline TVG of all patients was 1 mmHg [Inter Quarter Range, IQR 1.0–1.4 mmHg]. The median TVG – measured at post-procedural trans-thoracic echocardiogram pre-discharge – increased to 2 mmHg [IQR, 1.6–3.0 mmHg] and remained constant up to 12 month (2.0 mmHg [IQR 1.0–2.0 mmHg). Of these, twenty-five patients showed an elevated TVG >3 mmHg post-procedurally. Patients with TVG >3 mmHg were younger (73.1±11.0 vs. 77.5±9.2 years, p=0.038) and presented with lower levels of pro-BNP at baseline (median 2276 ng/l [IQR, 906–5150] vs. 4182 ng/l [2310–8629], p=0.008) compared to patients with TVG ≤3mmHg. All other baseline characteristics were balanced. There were no differences in procedural success (TR reduction of ≥1 grade in 96% vs. 93.3%, p=0.946) and number of clips implanted (p=0.697). At one month follow-up there were no differences in NYHA class (NYHA class ≥3 in 24% vs. 30.8%, p=0.559), quality of life measured with the Minnesota Living With Heart Failure questionnaire (32.0±22.9 vs. 31.1±16.3, p=0.833), 6 minute walking distance (255.5±140.6 vs. 250.5±111.7 metre, p=0.872). The clinical endpoints 1-year mortality (HR 1.07; 95% CI [0.43–2.65], p=0.88) and the combined endpoint mortality and hospitalization for heart failure at one year (HR 1.07; 95% CI [0.46 to 2.48], p=0.88, see Figure) did not differ between patients with a TVG >3 mmHg vs. patients with a TVG ≤3mmHg. Figure 1 Conclusion TTVR results in a small increase in the tricuspid valve gradient, which remains constant up to one year. A small cohort of patients shows an elevated TVG higher than 3 mmHg after the procedure. This elevation has no impact on NYHA class at 1 month and the clinical endpoints mortality and hospitalization for heart failure at 1 year.

Clinical observations implicate a role of eosinophils in cardiovascular diseases because markers of eosinophil activation are elevated in atherosclerosis and thrombosis. However, their contribution to atherosclerotic plaque formation and arterial thrombosis remains unclear. In these settings, we investigated how eosinophils are recruited and activated through an interplay with platelets. Here, we provide evidence for a central importance of eosinophil-platelet interactions in atherosclerosis and thrombosis. We show that eosinophils support atherosclerotic plaque formation involving enhanced von Willebrand factor exposure on endothelial cells and augmented platelet adhesion. During arterial thrombosis, eosinophils are quickly recruited in an integrin-dependent manner and engage in interactions with platelets leading to eosinophil activation as we show by intravital calcium imaging. These direct interactions induce the formation of eosinophil extracellular traps (EETs), which are present in human thrombi and constitute a substantial part of extracellular traps in murine thrombi. EETs are decorated with the granule protein major basic protein, which causes platelet activation by eosinophils. Consequently, targeting of EETs diminished thrombus formation in vivo, which identifies this approach as a novel antithrombotic concept. Finally, in our clinical analysis of coronary artery thrombi, we identified female patients with stent thrombosis as the population that might derive the greatest benefit from an eosinophil-inhibiting strategy. In summary, eosinophils contribute to atherosclerotic plaque formation and thrombosis through an interplay with platelets, resulting in mutual activation. Therefore, eosinophils are a promising new target in the prevention and therapy of atherosclerosis and thrombosis.

Despite dual antiplatelet therapy patients undergoing percutaneous coronary intervention (PCI) continue to experience periprocedural ischemic events. In addition, all currently used antithrombotic drugs increase the bleeding risk. Thus, there is an unmet clinical need for antithrombotic strategies with improved efficacy and no increase in bleeding. Revacept is a novel, lesion-directed antithrombotic drug that does not interfere with the function of circulating platelets. This dimeric fusion protein of the extracellular domain of glycoprotein VI (the major platelet collagen receptor) and the human Fc-fragment inhibits collagen-mediated platelet adhesion and subsequent aggregation at the site of vascular injury. The randomized, double-blinded, phase II ISAR-PLASTER trial is based on extensive preclinical evaluation of Revacept and a favorable first-in-man trial. A total of 332 patients with stable coronary artery disease undergoing elective PCI will be randomized to either Revacept 160 mg, Revacept 80 mg, or placebo administered as single intravenous infusion directly before the intervention, on top of standard dual antiplatelet therapy and either heparin or bivalirudin, based on local practice and current guidelines. The primary endpoint is the composite of death or myocardial injury (defined as increase in high sensitivity troponin T >= 5 times the upper limit of normal) at 48 hours. The safety endpoint is bleeding of class 2 or higher according to the Bleeding Academic Research Consortium at 30 days. This phase II randomized, double blind trial will assess for the first time the efficacy and safety of Revacept-a lesion-directed inhibitor of platelet adhesion-in patients undergoing elective PCI.

AIMS:The aim of this study was to compare the outcome of patients with a post-procedural tricuspid valve gradient (TVG) of >3 mmHg vs ≤3 mmHg after transcatheter edge-to-edge tricuspid valve repair (TTVR). METHODS AND RESULTS:Between March 2016 and October 2018 we treated 145 patients with severe tricuspid regurgitation (TR) with TTVR by placing 2.2±0.7 clips per patient. Device success (TR reduction ≥1° to at least moderate) was achieved in 125 patients (86.2%). TTVR resulted in an elevated TVG >3 mmHg in 25 (17.2%) patients. Device success (84% vs 86.7%, p=0.9), number of clips implanted (2.3±0.7 vs 2.2±0.7, p=0.33), clinical improvement including NYHA class (III/IV 24% vs 28%, p=0.92) and increase in six-minute walking test at one month (67 m [IQR 5-103 m] vs 56 m [IQR 8-97 m], p=0.93), mortality (HR 1.07, 95% CI: 0.43-2.65, plogrank=0.88) and the combined endpoint mortality and hospitalisation for heart failure at one year (HR 1.07, 95% CI: 0.46-2.48, plogrank=0.88) were similar between patients with a TVG >3 mmHg versus patients with a TVG ≤3 mmHg. CONCLUSIONS:A small cohort of patients demonstrated an elevated TVG higher than 3 mmHg at discharge. This elevation had no impact on clinical improvement, mortality or hospitalisation for heart failure.