Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

Timing of Complete Revascularization with Multivessel PCI for Myocardial Infarction.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) with multivessel coronary artery disease, the time at which complete revascularization of nonculprit lesions should be performed remains unknown. METHODS: We performed an international, open-label, randomized, noninferiority trial at 37 sites in Europe. Patients in a hemodynamically stable condition who had STEMI and multivessel coronary artery disease were randomly assigned to undergo immediate multivessel percutaneous coronary intervention (PCI; immediate group) or PCI of the culprit lesion followed by staged multivessel PCI of nonculprit lesions within 19 to 45 days after the index procedure (staged group). The primary end point was a composite of death from any cause, nonfatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year after randomization. The percentages of patients with a primary or secondary end-point event are provided as Kaplan-Meier estimates at 6 months and at 1 year. RESULTS: We assigned 418 patients to undergo immediate multivessel PCI and 422 to undergo staged multivessel PCI. A primary end-point event occurred in 35 patients (8.5%) in the immediate group as compared with 68 patients (16.3%) in the staged group (risk ratio, 0.52; 95% confidence interval, 0.38 to 0.72; P<0.001 for noninferiority and P<0.001 for superiority). Nonfatal myocardial infarction and unplanned ischemia-driven revascularization occurred in 8 patients (2.0%) and 17 patients (4.1%), respectively, in the immediate group and in 22 patients (5.3%) and 39 patients (9.3%), respectively, in the staged group. The risk of death from any cause, the risk of stroke, and the risk of hospitalization for heart failure appeared to be similar in the two groups. A total of 104 patients in the immediate group and 145 patients in the staged group had a serious adverse event. CONCLUSIONS: Among patients in hemodynamically stable condition with STEMI and multivessel coronary artery disease, immediate multivessel PCI was noninferior to staged multivessel PCI with respect to the risk of death from any cause, nonfatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year. (Supported by Boston Scientific; MULTISTARS AMI ClinicalTrials.gov number, NCT03135275.).

Cardiac Metabolism in Heart Failure and Implications for Uremic Cardiomyopathy.

Chronic kidney disease is associated with an increased risk for the development and progression of cardiovascular disorders including hypertension, dyslipidemia, and coronary artery disease. Chronic kidney disease may also affect the myocardium through complex systemic changes, resulting in structural remodeling such as hypertrophy and fibrosis, as well as impairments in both diastolic and systolic function. These cardiac changes in the setting of chronic kidney disease define a specific cardiomyopathic phenotype known as uremic cardiomyopathy. Cardiac function is tightly linked to its metabolism, and research over the past 3 decades has revealed significant metabolic remodeling in the myocardium during the development of heart failure. Because the concept of uremic cardiomyopathy has only been recognized in recent years, there are limited data on metabolism in the uremic heart. Nonetheless, recent findings suggest overlapping mechanisms with heart failure. This work reviews key features of metabolic remodeling in the failing heart in the general population and extends this to patients with chronic kidney disease. The knowledge of similarities and differences in cardiac metabolism between heart failure and uremic cardiomyopathy may help identify new targets for mechanistic and therapeutic research on uremic cardiomyopathy.

Fatal pulmonary hemorrhage, pneumothorax and skin necrosis caused by IRIS to an Aspergillus flavus infection in a young patient with metamizole associated agranulocytosis.

We report the case of a young female with steroid-dependent ulcerative colitis (UC) who developed a complex systemic infection with Aspergillus flavus. This occurred following a UC relapse while vacationing in the Middle East, leading to extended use of metamizole and subsequent agranulocytosis. On her return to Germany, she was hospitalized for neutropenic sepsis and later transferred to our hospital due to persistent cytopenia and suspected Hemophagocytic Lymphohistiocytosis (HLH). Despite initial stabilization with targeted treatment for pulmonary Aspergillus flavus infection, her condition rapidly deteriorated following the onset of an Immune Reconstitution Inflammatory Syndrome (IRIS), which manifested as skin necrosis and pneumothorax after the replenishment of neutrophil granulocytes. The patient eventually died from an unmanageable pulmonary hemorrhage. Microscopy of skin necroses showed a massive presence of Aspergillus flavus, but tissue culture remained negative, suggesting effective antifungal treatment yet delayed phagocytosis due to agranulocytosis. This case underscores the need to consider IRIS in immunosuppressed patients who worsen despite aggressive and appropriately targeted treatment, highlighting its potential beyond the commonly recognized context in HIV-positive patients.

Disparities in donor heart acceptance between the USA and Europe: clinical implications.

BACKGROUND AND AIMS: Given limited evidence and lack of consensus on donor acceptance for heart transplant (HT), selection practices vary widely across HT centres in the USA. Similar variation likely exists on a broader scale-across countries and HT systems-but remains largely unexplored. This study characterized differences in heart donor populations and selection practices between the USA and Eurotransplant-a consortium of eight European countries-and their implications for system-wide outcomes. METHODS: Characteristics of adult reported heart donors and their utilization (the percentage of reported donors accepted for HT) were compared between Eurotransplant (n = 8714) and the USA (n = 60 882) from 2010 to 2020. Predictors of donor acceptance were identified using multivariable logistic regression. Additional analyses estimated the impact of achieving Eurotransplant-level utilization in the USA amongst donors of matched quality, using probability of acceptance as a marker of quality. RESULTS: Eurotransplant reported donors were older with more cardiovascular risk factors but with higher utilization than in the USA (70% vs. 44%). Donor age, smoking history, and diabetes mellitus predicted non-acceptance in the USA and, by a lesser magnitude, in Eurotransplant; donor obesity and hypertension predicted non-acceptance in the USA only. Achieving Eurotransplant-level utilization amongst the top 30%-50% of donors (by quality) would produce an additional 506-930 US HTs annually. CONCLUSIONS: Eurotransplant countries exhibit more liberal donor heart acceptance practices than the USA. Adopting similar acceptance practices could help alleviate the scarcity of donor hearts and reduce waitlist morbidity in the USA.

The MULAN Trial - RCT on the use of MUsic in Cath-Lab to reduce ANxiety during peripheral vascular interventions.

Background: The purpose was to analyze the use of classical music to reduce procedure-related anxiety while conducting percutaneous transluminal angioplasty in patients with peripheral artery disease. Patients and methods: A total of 155 patients were analyzed in this single center randomized controlled trial. Procedure-related anxiety was assessed by a numerical rating scale (NRS, 0-10) and by recording of physiological parameters at three different points in time. A survey was conducted after the intervention. Results: This study showed that the patients listened to music overcame their procedure-related anxiety more quickly than the patients in the control group. The NRS at second timepoint was significantly reduced in intervention group compared to control group (p<0.01; r=0.2). Most participants stated that they would like to listen to music during possible future interventions. Conclusions: Classical music during endovascular interventions reduced procedure-related anxiety measured as greater reduction in NRS values in intervention group as well as in results of questionnaire performed post procedurally in PAD patients.

Analysis of interventional treatment options of the common femoral artery - a retrospective single center experience.

Background: Due to the rapid development of treatment techniques of peripheral arterial disease (PAD) treatment is nowadays predominantly interventional. An exception are lesions of the common femoral artery (CFA), which should be treated surgically according to vascular guidelines. However, recent evidence has shown that endovascular techniques, e.g. stenting, have comparable clinical outcomes while causing fewer complications. The aim of the present analysis was to evaluate the therapeutic success of endovascular therapy of CFA lesions in a single center, all - comers registry. Patients and methods: All patients who were treated for a CFA lesion at the Department of Internal Medicine I of the University Hospital Jena in the period from 01/2017 to 12/2020 were included. Treatment success was determined by evaluating the ankle-brachial-index (ABI) pre- and post-interventional as well as after follow-up (FU), measuring walking distance (WD) and by target revascularization rate (TLR) and primary patency rate (PPR). Results: The analysis included 109 patients with a mean age of 73.4 years, with 67% (73) of those being men. 72 patients received interventional treatment, whereas 33 were treated surgically and 4 conservatively. Resting ABI in the overall cohort showed an increase from 0.5 to 0.7 post intervention (p=<0.05; mean FU-time: 6.5 months). In the interventional cohort ABI increases from 0.6 to 0.8 (p=<0.05; mean FU-time: 5,8 months) at FU and from 0.3 to 0.6 (p=<0.05; mean FU-time: 8,8 month) in the surgically treated group. The WD improved in the whole collective from 116.5 meter (m) to 152.5 m (p=<0.05). The TLR showed no significant difference with 8.1% after interventional treatment and 6.1% after vascular surgery in the present analysis (p=0.72) as well as PPR with 89.8% after EVT and 90.9% after surgical approach (p=0.87). The intra-/postinterventional complication rate was 5.5% in the intervention group, compared to postoperative complication rate of 15.2% in the surgically treated group. Conclusions: The present analysis demonstrates that even in a real-world, all-comers collective, interventional therapy for CFA lesions was safe and equally effective as the surgically treated patient cohort. Continuing to generate registry data is important to eventually initiate a paradigm shift.

Identification of Serum Interleukin-22 as Novel Biomarker in Pulmonary Hypertension: A Translational Study.

Growing evidence suggests the crucial involvement of inflammation in the pathogenesis of pulmonary hypertension (PH). The current study analyzed the expression of interleukin (IL)-17a and IL-22 as potential biomarkers for PH in a preclinical rat model of PH as well as the serum levels in a PH patient collective. PH was induced by monocrotalin (60 mg/kg body weight s.c.) in 10 Sprague Dawley rats (PH) and compared to 6 sham-treated controls (CON) as well as 10 monocrotalin-induced, macitentan-treated rats (PH_MAC). Lung and cardiac tissues were subjected to histological and immunohistochemical analysis for the ILs, and their serum levels were quantified using ELISA. Serum IL levels were also measured in a PH patient cohort. IL-22 expression was significantly increased in the lungs of the PH and PH_MAC groups (p = 0.002), whereas increased IL17a expression was demonstrated only in the lungs and RV of the PH (p < 0.05) but not the PH_MAC group (p = n.s.). The PH group showed elevated serum concentrations for IL-22 (p = 0.04) and IL-17a (p = 0.008). Compared to the PH group, the PH_MAC group demonstrated a decrease in IL-22 (p = 0.021) but not IL17a (p = n.s.). In the PH patient collective (n = 92), increased serum levels of IL-22 but not IL-17a could be shown (p < 0.0001). This elevation remained significant across the different etiological groups (p < 0.05). Correlation analysis revealed multiple significant relations between IL-22 and various clinical, laboratory, functional and hemodynamic parameters. IL-22 could serve as a promising inflammatory biomarker of PH with potential value for initial diagnosis, functional classification or even prognosis estimation. Its validation in larger patients' cohorts regarding outcome and survival data, as well as the probability of promising therapeutic target structures, remains the object of further studies.

Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF).

BACKGROUND: Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear. METHODS: In this single-center, prospective, double-blind, placebo-controlled, randomized study, we randomly assigned patients with acute decompensated heart failure to empagliflozin 25 mg daily or placebo in addition to standard decongestive treatments that included loop diuretics. The primary end point was cumulative urine output over 5 days. Secondary end points included diuretic efficiency, dynamics in markers of kidney function and injury, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: Sixty patients were randomized within 12 hours of hospitalization for acute decompensated heart failure. Addition of empagliflozin daily to standard medical treatment of acute decompensated heart failure resulted in a 25% increase in cumulative urine output over 5 days (median 10.8 versus 8.7 L mL in placebo, group difference estimation 2.2 L [95% CI, 8.4 to 3.6]; P=0.003). Empagliflozin increased diuretic efficiency compared with placebo (14.1 mL urine per milligram furosemide equivalent [95% CI, 0.6-27.7]; P=0.041) without affecting markers of renal function (estimated glomerular filtration rate, 51±19 versus 54±17 mL/min per 1.73 m²; P=0.599) or injury (total urinary protein, 492±845 versus 503±847 mg/g creatinine; P=0.975; and urinary α1-microglobulin, 55.4±38.6 versus 31.3±33.6 mg/g creatinine; P=0.066) with more pronounced decrease in NT-proBNP in the empagliflozin group compared with placebo (-1861 versus -727.2 pg/mL after 5 days; quotient in slope, 0.89 [95% CI, 0.83-0.95]; P<0.001). There were no differences in the incidence of safety events between groups. CONCLUSIONS: Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04049045.

Targeted Interleukin-9 delivery in pulmonary hypertension: Comparison of immunocytokine formats and effector cell study.

AIMS: Pulmonary hypertension (PH) is accompanied by pulmonary vascular remodelling. By targeted delivery of Interleukin-9 (IL9) via the immunocytokine F8IL9, beneficial effects could be demonstrated in a mouse model of PH. This study aimed to compare two immunocytokine formats (single-chain Fv and full IgG) and to identify potential target cells of IL9. METHODS: The Monocrotaline mouse model of PH (PH, n = 12) was chosen to evaluate the treatment effects of F8IL9F8 (n = 12) and F8IgGIL9 (n = 6) compared with sham-induced animals (control, n = 10), the dual endothelin receptor antagonist Macitentan (MAC, n = 12) or IL9-based immunocytokines with irrelevant antigen specificity (KSFIL9KSF, n = 12; KSFIgGIL9 n = 6). Besides comparative validation of treatment effects, the study was focused on the detection and quantification of mast cells (MCs) and regulatory T cells (Tregs). RESULTS: There was a significantly elevated systolic right ventricular pressure (104 ± 36 vs. 45 ± 17 mmHg) and an impairment of right ventricular echocardiographic parameters (RVbasal: 2.52 ± 0.25 vs. 1.94 ± 0.13 mm) in untreated PH compared with controls (p < 0.05). Only the groups treated with F8IL9, irrespective of the format, showed consistent beneficial effects (p < 0.05). Moreover, F8IL9F8 but not F8IgGIL9 treatment significantly reduced lung tissue damage compared with untreated PH mice (p < 0.05). There was a significant increase in Tregs in F8IL9-treated compared with control animals, the untreated PH and the MAC group (p < 0.05). CONCLUSIONS: Beneficial treatment effects of targeted IL9 delivery in a preclinical model of PH could be convincingly validated. IL9-mediated recruitment of Tregs into lung tissue might play a crucial role in the induction of anti-inflammatory and anti-proliferative mechanisms potentially contributing to a novel disease-modifying concept.

Prognostic Value of Galectin-3 after Left Atrial Appendage Occlusion for Predicting Peri-Device Leakage.

Echocardiographic detection of residual peri-device leakage (PDL) after percutaneous left atrial appendage occlusion (LAAO) is crucial for managing anticoagulation. Galectin-3, a protein involved in tissue-foreign body interactions, may hold significance in understanding PDL and cardiac tissue remodeling after LAAO. This study aimed to analyze galectin-3 serum levels in relation to PDL using a novel echo-morphological classification. LAAO eligible patients were included in the study. Galectin-3 serum levels were measured before LAAO, at 45 days (45D), and at 6 months (6M) after the procedure. Transesophageal echocardiography was used to assess LAAO success. A new echo-morphological classification categorized the degree of LAAO into three different types (A: homogenous echodensity, indicating completely thrombosed device; B: inhomogeneous echolucencies (<50% of device); and C: partially thrombosed device with echolucencies > 50%). Among 47 patients, complete LAAO was achieved in 60% after 45D and in 74% after 6M. We observed a significant increase and distribution of serum levels of galectin-3 [ng/mL] after 45D among the three types (baseline: 13.1 ± 5.8 ng/mL; 45D: 16.3 ± 7.2 ng/mL (Type A) vs. 19.2 ± 8.6 ng/mL (Type B) vs. 25.8 ± 9.4 ng/mL (Type C); p = 0.031), followed by a drop in galectin-3 for Types A and B after 6M toward and below the baseline levels (6M: 8.9 ± 3.1 ng/mL (Type A) vs. 12.4 ± 5.5 ng/mL (Type B)), whereas Type C persisted in showing elevated galectin-3 levels compared to all other types (6M: 17.5 ± 4.5 ng/mL (Type C); p < 0.01). Increased galectin-3 serum levels after LAAO likely reflect the transition from thrombus formation to fibrotic scar development in the LAA lumen. Successful occlusion is associated with a time-restricted decrease in galectin-3 levels after 6 months, while relevant PDL leads to persistently elevated levels, making galectin-3 a potential predictor of occlusion success.

Cardiomyocyte Krüppel-Like Factor 5 Promotes De Novo Ceramide Biosynthesis and Contributes to Eccentric Remodeling in Ischemic Cardiomyopathy.

BACKGROUND: We previously showed that cardiomyocyte Krϋppel-like factor (KLF) 5 regulates cardiac fatty acid oxidation. As heart failure has been associated with altered fatty acid oxidation, we investigated the role of cardiomyocyte KLF5 in lipid metabolism and pathophysiology of ischemic heart failure. METHODS: Using real-time polymerase chain reaction and Western blot, we investigated the KLF5 expression changes in a myocardial infarction (MI) mouse model and heart tissue from patients with ischemic heart failure. Using 2D echocardiography, we evaluated the effect of KLF5 inhibition after MI using pharmacological KLF5 inhibitor ML264 and mice with cardiomyocyte-specific KLF5 deletion (αMHC [α-myosin heavy chain]-KLF5-/-). We identified the involvement of KLF5 in regulating lipid metabolism and ceramide accumulation after MI using liquid chromatography-tandem mass spectrometry, and Western blot and real-time polymerase chain reaction analysis of ceramide metabolism-related genes. We lastly evaluated the effect of cardiomyocyte-specific KLF5 overexpression (αMHC-rtTA [reverse tetracycline-controlled transactivator]-KLF5) on cardiac function and ceramide metabolism, and rescued the phenotype using myriocin to inhibit ceramide biosynthesis. RESULTS: KLF5 mRNA and protein levels were higher in human ischemic heart failure samples and in rodent models at 24 hours, 2 weeks, and 4 weeks post-permanent left coronary artery ligation. αMHC-KLF5-/- mice and mice treated with ML264 had higher ejection fraction and lower ventricular volume and heart weight after MI. Lipidomic analysis showed that αMHC-KLF5-/- mice with MI had lower myocardial ceramide levels compared with littermate control mice with MI, although basal ceramide content of αMHC-KLF5-/- mice was not different in control mice. KLF5 ablation suppressed the expression of SPTLC1 and SPTLC2 (serine palmitoyltransferase [SPT] long-chain base subunit ()1 2, respectively), which regulate de novo ceramide biosynthesis. We confirmed our previous findings that myocardial SPTLC1 and SPTLC2 levels are increased in heart failure patients. Consistently, αMHC-rtTA-KLF5 mice showed increased SPTLC1 and SPTLC2 expression, higher myocardial ceramide levels, and systolic dysfunction beginning 2 weeks after KLF5 induction. Treatment of αMHC-rtTA-KLF5 mice with myriocin that inhibits SPT, suppressed myocardial ceramide levels and alleviated systolic dysfunction. CONCLUSIONS: KLF5 is induced during the development of ischemic heart failure in humans and mice and stimulates ceramide biosynthesis. Genetic or pharmacological inhibition of KLF5 in mice with MI prevents ceramide accumulation, alleviates eccentric remodeling, and increases ejection fraction. Thus, KLF5 emerges as a novel therapeutic target for the treatment of ischemic heart failure.

Prediction of one- and two-year mortality after transcatheter aortic valve implantation: proposal of a fast sum-score system integrating a novel biomarker of cardiac extracellular matrix accumulation and fibrosis.

BACKGROUND: Prediction of long-term mortality in patients with severe symptomatic aortic valve stenosis undergoing transcatheter aortic valve implantation (TAVI) is still challenging but of great impact with respect to the selection of treatment strategy. Whereas most of the established scores address perioperative risk and/or short-term mortality, the aim of our current study was the integrative investigation of a multitude of patients' characteristics including novel biomarkers of cardiovascular remodeling with respect to their value for the prediction of long-term mortality. METHODS: In a first subset of patients (n = 122, identification group) a wide range of baseline characteristics were assigned to three clusters with 4 to 10 items each (classical clinical parameters; risk assessment scores; novel biomarkers of cardiovascular remodeling) and tested with respect to their predictive value for one-year mortality. Thereby, a sum-score system (Jena Mortality Score, JMS) was defined and tested in a larger collective of TAVI patients (n = 295, validation group) with respect to one- and two-year mortality prediction. RESULTS: In the identification cohort, binary logistic regression analysis, with one-year mortality as dependent variable and the items per cluster as cofounders, revealed atrial fibrillation (Afib; odds ratio [OR] 7.583, 95% confidence interval [95% CI]: 2.051-28.040, p = 0.002), clinical frailty scale (CFS; OR 2.258, 95% CI: 1.262-4.039, p = 0.006) and Tissue-Inhibitor of Metalloproeinase-1 (TIMP-1; OR 1.006, 95% CI: 1.001-1.011, p = 0.019) as independent predictors of one-year mortality. These 3 parameters were integrated into a simplified sum-score as follows: presence of Afib (no = 0, yes = 1); dichotomized CFS (1 to 4 = 0; 5 to 9 = 1); TIMP-1 range (cut-off value 187.2 ng/mL; below = 0, above = 1). The resulting sum-score (JMS) ranged from 0 to 3. By binary logistic regression analysis in the validation cohort with one- and two-year mortality as dependent variable and Society of Thoracic Surgeons (STS) score (STS), staging of extra-valvular cardiac damage (stage), presence of high gradient aortic stenosis (HGAS), EQ visual analogue scale score (EQ-VAS) and JMS as cofounders, besides STS score, only JMS could be proven to serve as independent predictor of both, one-year (OR 1.684, 95% CI: 1.094-2.592, p = 0.018) and two-year (OR 1.711, 95% CI: 1.136-2.576, p = 0.010) mortality. After dichotomization of patients into a low-risk and a high-risk group according to JMS, Kaplan-Meier survival analysis displayed a significant survival benefit for the low-risk group after one and two years (p < 0.001). CONCLUSION: JMS, including TIMP-1 as a novel biomarker of cardiac extracellular matrix accumulation and fibrosis, could serve as a novel simple tool to assess long-term mortality risk after TAVI and might thereby contribute to a more precise stratification of individual risk.

[Guidelines of the European Resuscitation Council (ERC) on cardiopulmonary resuscitation 2021: update and comments]. / Leitlinien des European Resuscitation Council (ERC) zur kardiopulmonalen Reanimation 2021: Update und Kommentar.

The European guidelines on cardiopulmonary resuscitation, which are divided into 12 chapters, have recently been published. In addition to the already known chapters, the topics "epidemiology" and "life-saving systems" have been integrated for the first time. For each chapter five practical key statements were formulated. In the present article the revised recommendations on basic measures and advanced resuscitation measures in adults as well as on postresuscitation treatment are summarized and commented on.

Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: Results From an International, Multicenter Cohort Study.

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.

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.

Phytosterols and Cardiovascular Disease.

PURPOSE OF REVIEW: Coronary heart disease is the leading cause of mortality worldwide. Elevated blood cholesterol levels are not only the major but also the best modifiable cardiovascular risk factor. Lifestyle modifications which include a healthy diet are the cornerstone of lipid-lowering therapy. So-called functional foods supplemented with plant sterols lower blood cholesterol levels by about 10-15%. RECENT FINDINGS: In the recent revision of the ESC/EAS dyslipidemia guideline 2019, plant sterols are recommended for the first time as an adjunct to lifestyle modification to lower blood cholesterol levels. However, the German Cardiac Society (DGK) is more critical of food supplementation with plant sterols and calls for randomized controlled trials investigating hard cardiovascular outcomes. An increasing body of evidence suggests that plant sterols per se are atherogenic. This review discusses this controversy based on findings from in vitro and in vivo studies, clinical trials, and genetic evidence.

Access Site Complications of Peripheral Endovascular Procedures: A Large, Prospective Registry on Predictors and Consequences.

PURPOSE: The purpose of this study was to investigate predictors and consequences of acute vascular access site complications (ASCs) related to peripheral endovascular diagnostic or interventional procedures. Despite improvement of puncture techniques, access site-related morbidity and mortality is still considerable. MATERIALS AND METHODS: A total of 5263 participants who underwent 5385 endovascular procedures at a single center were consecutively included in this prospective, observational study. Primary outcomes were ASCs defined as composite of puncture site hematoma, pseudoaneurysm, arteriovenous fistula, and overt puncture site bleeding on the first day after procedure. RESULTS: ASCs occurred in 16.6% of peripheral endovascular procedures (78.6% hematomas, 18.9% pseudoaneurysms, 1.4% arteriovenous fistulas, 1.1% overt bleedings). Independent predictors were advanced age [odds ratio (OR) per 10 years: 1.12, p=0.004], female sex (OR men, 0.77; p=0.001), lysis (OR 3.56; p<0.001), periprocedural heparin (OR 5000 IU, 1.96; p=0.001; OR >5000 IU, 3.56; p=0.02), time to access (OR per 10 seconds, 1.01; p<0.001), sheath size (OR per French, 1.59; p<0.001), brachial artery access (OR vs retrograde transfemoral, 4.58; p<0.001), and compression only (OR Angio-Seal, 0.57, p=0.02; ProGlide, 0.36, p<0.001; FemoSeal, 0.57, p<0.001). Treatment was required in 20.2% and prolonged hospitalization in 17.7% of ASC. Three participants died from access site-related bleeding. CONCLUSION: ASCs after peripheral endovascular procedures are associated with advanced age, female sex, periprocedural antithrombotic medication, brachial artery access, postinterventional bleeding, and nonuse of vascular closure devices.

Patent foramen ovale-When to close and how?

Closure of a patent foramen ovale (PFO) in patients after cryptogenic/cardioembolic stroke is recommended by current guidelines for patients who are 16-60 years of age with a high-risk PFO (class of recommendation A, level of evidence I). The use of double-disk occlusion devices followed by antiplatelet therapy is recommended. The procedure of interventional PFO closure compared with other interventions in cardiology is rather easy to learn. However, it should be performed carefully to avoid postinterventional complications. The number needed to treat (NNT) to avoid one stroke in 5 years in the RESPECT trial was 42, in the CLOSE trial even lower with 20. In the REDUCE trial, the NNT was 28 at 2 years. This can be reduced by longer follow-up, e.g., at 10 years the NNT is 18. While other conditions such as migraine are currently under investigation with respect to the impact of PFO closure, sufficiently powered trials are lacking so that closure in diseases other than stroke should always be individualized.

Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced left ventricular failure.

Adipose tissue lipolysis occurs during the development of heart failure as a consequence of chronic adrenergic stimulation. However, the impact of enhanced adipose triacylglycerol hydrolysis mediated by adipose triglyceride lipase (ATGL) on cardiac function is unclear. To investigate the role of adipose tissue lipolysis during heart failure, we generated mice with tissue-specific deletion of ATGL (atATGL-KO). atATGL-KO mice were subjected to transverse aortic constriction (TAC) to induce pressure-mediated cardiac failure. The cardiac mouse lipidome and the human plasma lipidome from healthy controls (n = 10) and patients with systolic heart failure (HFrEF, n = 13) were analyzed by MS-based shotgun lipidomics. TAC-induced increases in left ventricular mass (LVM) and diastolic LV inner diameter were significantly attenuated in atATGL-KO mice compared to wild type (wt) -mice. More importantly, atATGL-KO mice were protected against TAC-induced systolic LV failure. Perturbation of lipolysis in the adipose tissue of atATGL-KO mice resulted in the prevention of the major cardiac lipidome changes observed after TAC in wt-mice. Profound changes occurred in the lipid class of phosphatidylethanolamines (PE) in which multiple PE-species were markedly induced in failing wt-hearts, which was attenuated in atATGL-KO hearts. Moreover, selected heart failure-induced PE species in mouse hearts were also induced in plasma samples from patients with chronic heart failure. TAC-induced cardiac PE induction resulted in decreased PC/ PE-species ratios associated with increased apoptotic marker expression in failing wt-hearts, a process absent in atATGL-KO hearts. Perturbation of adipose tissue lipolysis by ATGL-deficiency ameliorated pressure-induced heart failure and the potentially deleterious cardiac lipidome changes that accompany this pathological process, namely the induction of specific PE species. Non-cardiac ATGL-mediated modulation of the cardiac lipidome may play an important role in the pathogenesis of chronic heart failure.