Recent advances on the Role of Gut Microbiota in the Development of Heart Failure by Mediating Immune Metabolism.

The association between gut microbiota and the development of heart failure has become a research hotspot in recent years and the impact of gut microbiota on heart failure has attracted growing interest. From 2006 to 2021, the global research on gut microbiota and heart failure has gradually expanded, indicating a developed and promising research field. There were 40 countries, 196 institutions, and 257 authors involved in the publication on the relationship between gut microbiota and heart failure, respectively. In patients with heart failure, inadequate visceral perfusion leads to ischemia and intestinal edema, which compromise the gut barrier. This subsequently results in the translocation of bacteria and bacterial metabolites into the circulatory system and causes local and systemic inflammatory responses. The gastrointestinal tract contains the largest number of immune cells in the human body and gut microbiota play important roles in the immune system by promoting immune tolerance to symbiotic bacteria. Studies have shown that probiotics can act on gut microorganisms, thereby increasing choline metabolism and reducing plasma TMA and TMAO concentrations, thus inhibiting the development of heart failure. Meanwhile, probiotics induce the production of inflammatory suppressors to maintain gut immune stability and inhibit the progression of heart failure by reducing ventricular remodeling. Here, we review the current understanding of gut microbiota-driven immune dysfunction in experimental and clinical heart failure, as well as the therapeutic interventions that could be used to address these issues.

Management of anticoagulation in patients with infective endocarditis.

Infective endocarditis (IE) carries a high risk of vascular complications (e.g., cerebral embolism, intracerebral hemorrhage, and renal infarction), which are correlated with increased early and late mortality. Although anticoagulation is the cornerstone for management of thromboembolic complications, it remains controversial and challenging in patients with IE. An appropriate anticoagulation strategy is crucial to improving outcomes and requires a good understanding of the indication, timing, and regimen of anticoagulation in the setting of IE. Observational studies have shown that anticoagulant treatment failed to reduce the risk of ischemic stroke in patents with IE, supporting that IE alone is not an indication for anticoagulation. In the absence of randomized controlled trials and high-quality meta-analyses, however, current guidelines on IE were based largely on observational data and expert opinion, providing few specific recommendations on anticoagulation. A multidisciplinary approach and patient engagement are required to determine the timing and regimen of anticoagulation in patients with IE, especially in specific situations (e.g., receiving warfarin anticoagulation at the time of IE diagnosis, cerebral embolism or ischemic stroke, intracerebral hemorrhage, or urgent surgery). Collectively, individualized strategies on anticoagulation management of IE should be based on clinical evaluation, available evidence, and patient engagement, and ultimately be developed by the multidisciplinary team.

Impact of coronary artery disease on clinical outcomes after TAVR: Insights from the BRAVO-3 randomized trial.

OBJECTIVE: To determine the prognostic impact of coronary artery disease (CAD) in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: CAD is a common comorbidity among patients undergoing TAVR and studies provide conflicting data on its prognostic impact. METHODS: The Bivalirudin on Aortic Valve Intervention Outcomes-3 (BRAVO-3) randomized trial compared the use of bivalirudin versus UFH in 802 high-surgical risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence or absence of history of CAD as well as periprocedural anticoagulation. The coprimary endpoints were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding) and major Bleeding Academic Research Consortium (BARC) bleeding ≥3b at 30 days postprocedure. RESULTS: Among 801 patients, 437 (54.6%) had history of CAD of whom 223 (51.0%) received bivalirudin. There were no significant differences in NACE (adjusted odds ratio [OR]: 1.04; 95% confidence interval [CI]: 0.69-1.58) or BARC ≥ 3b bleeding (adjusted OR: 0.84; 95% CI: 0.51-1.39) in patients with vs without CAD at 30 days. Among CAD patients, periprocedural use of bivalirudin was associated with similar NACE (OR: 0.80; 95% CI: 0.47-1.35) and BARC ≥ 3b bleeding (OR: 0.64; 95% CI: 0.33-1.25) compared with UFH, irrespective of history of CAD (p-interaction = 0.959 for NACE; p-interaction = 0.479 for major bleeding). CONCLUSION: CAD was not associated with a higher short-term risk of NACE or major bleeding after TAVR. Periprocedural anticoagulation with bivalirudin did not show any advantage over UFH in patients with and without CAD.

[ECMO support during the first two waves of the corona pandemic-a survey of high case volume centers in Germany]. / ECMO-Unterstützung während der ersten 2 Wellen der Coronapandemie ­ eine Umfrage an Zentren mit hohen Fallzahlen in Deutschland.

BACKGROUND: At the onset of the coronavirus pandemic, concerns were raised about sufficiency of available intensive care resources. In many places, routine interventions were postponed and criteria for the allocation of scarce resources were formulated. In Germany, some hospitals were at times seriously burdened during the course of the pandemic. Intensive care units in particular experienced a shortage of resources, which may have led to a restriction of services and a stricter indication setting for resource-intensive measures such as extracorporeal membrane oxygenation (ECMO). The aim of this work is to provide an overview of how these pressures were managed at large ECMO centers in Germany. METHODS: One representative of each major ECMO referral center in Germany was invited to participate in an online survey in spring 2021. RESULTS: Of 34 invitations that were sent out, the survey was answered by 23 participants. In all centers, routine procedures were postponed during the pandemic. Half of the centers increased the number of beds on which ECMO procedures could be offered. Nevertheless, in one-third of the centers, the start of at least one ECMO support was delayed because of a feared resource shortage. In 17% of centers, at least one patient was denied ECMO that he or she would have most likely received under prepandemic conditions. CONCLUSION: The results of this online survey indicate that the experienced pressures and resource constraints led some centers to be cautious about ECMO indications.

[Recommendations of the S3 Guideline "Use of Extracorporeal Circulation (ECLS/ ECMO) for Cardiac and Circulatory Failure" of the Association of Scientific Medical Societies in Germany]. / Empfehlungen der S3-Leitlinie (AWMF) "Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen".

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.

[Cardiogenic shock complicating myocardial infarction]. / Infarktbedingter kardiogener Schock.

Cardiogenic shock as a complication of myocardial infarction (5-10%) increases the mortality of uncomplicated myocardial infarction from less than 10% to 40%. This is due to the development of multiple organ dysfunction syndrome triggered by the extensive shock-induced impairment of organ perfusion. Therefore, guideline-based treatment should not only be restricted to reopening of the occluded coronary artery and management of complications of the infarction: important for survival are also guideline-driven optimization of organ perfusion by inotropic and vasoactive substances and, with well-defined indications, by temporary mechanical circulatory support but not by intra-aortic counterpulsation. Equally important, however, are shock-specific intensive care measures to prevent or attenuate organ dysfunction, such as lung protective ventilation in cases where ventilation is obligatory.

Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure -A clinical practice Guideline Level 3.

Aims Worldwide applications of extracorporeal circulation for mechanical support in cardiac and circulatory failure, which are referred to as extracorporeal life support (ECLS) or veno-arterial extracorporeal membrane oxygenation (va-ECMO), have dramatically increased over the past decade. In spite of the expanding use and the immense medical as well as socio-economic impact of this therapeutic approach, there has been a lack of interdisciplinary recommendations considering the best available evidence for ECLS treatment. Methods and Results In a multiprofessional, interdisciplinary scientific effort of all scientific societies involved in the treatment of patients with acute cardiac and circulatory failure, the first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy was developed in a structured approach under regulations of the AWMF (Association of the Scientific Medical Societies in Germany) and under use of GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. This article presents all recommendations created by the expert panel, addressing a multitude of aspects for ECLS initiation, continuation, weaning and aftercare as well as structural and personnel requirements. Conclusions This first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy should be used to apply the best available care nationwide. Beyond clinical practice advice, remaining important research aspects for future scientific efforts are formulated.

Concept and Design of a Novel Pulsatile Left Heart Assist Device-The PERKAT Left Ventricle System.

Cardiogenic shock is associated with high mortality. Patients often require temporary mechanical circulatory support. We aimed to develop a percutaneously implantable, assist device that unloads the left ventricle (LV) in a pulsatile way. The PERkutane KATheter pump technologie (PERKAT LV) device consists of a nitinol pump chamber, which is covered by foils carrying outflow valves. A flexible tube with a pigtail-shaped tip and inflow holes represents the distal part of the pump. The system is designed for 16F percutaneous implantation. The nitinol chamber is placed in the descending aorta while the flexible tube bypasses aortic arch and ascending aorta with its tip in the LV. An intra-aortic balloon pump is placed into the chamber and connected to a console. Balloon deflation generates a blood flow from the LV into the pump chamber. During balloon inflation, blood leaves the system through the outflow foil valves in the descending aorta. Under different afterload settings using a 30 cc intra-aortic balloon pump and varying inflation/deflations rates, we recorded flow rates up to 3.0 L/min. Based on this, we believe that PERKAT LV is a promising approach for temporary LV support. The proposed design and its excellent performance give basis for in vivo tests in an animal model.

The Correlation between Gut Microbiota and Serum Metabolomic in Elderly Patients with Chronic Heart Failure.

OBJECTIVE: Chronic heart failure (CHF) refers to a state of persistent heart failure that can be stable, deteriorated, or decompensated. The mechanism and pathogenesis of myocardial remodeling remain unknown. Based on 16S rDNA sequencing and metabolomics technology, this study analyzed the gut microbiota and serum metabolome in elderly patients with CHF to provide new insights into the microbiota and metabolic phenotypes of CHF. METHODS: Blood and fecal samples were collected from 25 elderly patients with CHF and 25 healthy subjects. The expression of inflammatory factors in blood was detected by ELISA. 16S rDNA sequencing was used to analyze the changes in microorganisms in the samples. The changes of small molecular metabolites in serum samples were analyzed by LC-MS/MS. Spearman correlation coefficients were used to analyze the correlation between gut microbiota and serum metabolites. RESULTS: Our results showed that the IL-6, IL-8, and TNF-α levels were significantly increased, and the IL-10 level was significantly decreased in the elderly patients with CHF compared with the healthy subjects. The diversity of the gut microbiota was decreased in the elderly patients with CHF. Moreover, Escherichia Shigella was negatively correlated with biocytin and RIBOFLAVIN. Haemophilus was negatively correlated with alpha-lactose, cellobiose, isomaltose, lactose, melibiose, sucrose, trehalose, and turanose. Klebsiella was positively correlated with bilirubin and ethylsalicylate. Klebsiella was negatively correlated with citramalate, hexanoylcarnitine, inosine, isovalerylcarnitine, methylmalonate, and riboflavin. CONCLUSION: The gut microbiota is simplified by the disease, and serum small-molecule metabolites evidently change in elderly patients with CHF. Serum and fecal biomarkers could be used for elderly patients with CHF screening.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

Anticoagulation in cardiomyopathy: unravelling the hidden threat and challenging the threat individually.

Cardiomyopathy comprises a heterogeneous group of myocardial abnormalities, structural or functional in nature, in the absence of coronary artery disease and other abnormal loading conditions. These myocardial pathologies can result in premature death or disability from progressive heart failure, arrhythmia, stroke, or other embolic events. The European Cardiomyopathy Registry reports a high stroke risk in cardiomyopathy patients ranging from 2.1% to 4.5%, as well as high prevalence of atrial fibrillation ranging from 14.0% to 48.5%. There is a growing interest in evaluating the risk of thromboembolism depending on the type of cardiomyopathy, as well as if anticoagulation is indicated in patients with cardiomyopathy without atrial fibrillation. Data available do not unequivocally support anticoagulation therapy in all of these patients; the management of these patients remains challenging. Many published reports pertaining to the risk of thromboembolism and consecutive treatment strategies mainly focus on single cardiomyopathy subtype. We summarize essential pathophysiological knowledge and review current literature associated with thromboembolism in various cardiomyopathy subtypes, providing recommendations for the diagnostic evaluation as well as clinical management strategies in this field. Certain cardiomyopathy subtypes require anticoagulation independent of atrial fibrillation or CHA2 DS2 -VASc score. Despite the scarcity of evidence regarding the choice of anticoagulation regimen (vitamin K antagonist vs. non-vitamin K oral anticoagulants) in cardiomyopathy, it is discussed and reviewed in this article. Each patient should receive a tailored strategy based on thorough clinical evaluation, published evidence, and clinical experience, due to the current recommendations mostly developed on small-sample studies or empirical evidence. The future research priorities in this area are also addressed in this article.

Impact of anemia on short-term outcomes after TAVR: A subgroup analysis from the BRAVO-3 randomized trial.

OBJECTIVES: To determine the prognostic impact of anemia in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: Whether the periprocedural use of bivalirudin as compared with UFH in anemic patients undergoing TAVR has an impact on outcomes remains unknown. METHODS: The BRAVO-3 trial compared the use of bivalirudin versus UFH in 802 high risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence (defined as hemoglobin levels <13 g/dl in men and <12 g/dl in women) or absence of anemia. The primary outcomes were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or bleeding) and major bleeding (Bleeding Academic Research Consortium ≥3b) at 30 days. RESULTS: Among 798 patients with available baseline hemoglobin levels, 427 (54%) were anemic of whom 221 (52%) received bivalirudin. There were no significant differences in NACE and major bleeding at 30 days between patients with and without anemia, irrespective of the type of anticoagulant used (pinteraction  = 0.71 for NACE, pinteraction  = 1.0 for major bleeding). However, anemic patients had a higher risk of major vascular complications (adjusted OR 2.43, 95% CI 1.42-4.16, p = 0.001), and acute kidney injury (adjusted OR 1.74, 95% CI 1.16-2.59, p = 0.007) compared to non-anemic patients at 30 days. CONCLUSIONS: Anemia was not associated with a higher risk of NACE or major bleeding at 30 days after TAVR without modification of the treatment effects of periprocedural anticoagulation with bivalirudin versus UFH.

Impella versus extracorporal life support in cardiogenic shock: a propensity score adjusted analysis.

AIMS: The mortality in cardiogenic shock (CS) is high. The role of specific mechanical circulatory support (MCS) systems is unclear. We aimed to compare patients receiving Impella versus ECLS (extracorporal life support) with regard to baseline characteristics, feasibility, and outcomes in CS. METHODS AND RESULTS: This is a retrospective cohort study including CS patients over 18 years with a complete follow-up of the primary endpoint and available baseline lactate level, receiving haemodynamic support either by Impella 2.5 or ECLS from two European registries. The decision for device implementation was made at the discretion of the treating physician. The primary endpoint of this study was all-cause mortality at 30 days. A propensity score for the use of Impella was calculated, and multivariable logistic regression was used to obtain adjusted odds ratios (aOR). In total, 149 patients were included, receiving either Impella (n = 73) or ECLS (n = 76) for CS. The feasibility of device implantation was high (87%) and similar (aOR: 3.14; 95% CI: 0.18-56.50; P = 0.41) with both systems. The rates of vascular injuries (aOR: 0.95; 95% CI: 0.10-3.50; P = 0.56) and bleedings requiring transfusions (aOR: 0.44; 95% CI: 0.09-2.10; P = 0.29) were similar in ECLS patients and Impella patients. The use of Impella or ECLS was not associated with increased odds of mortality (aOR: 4.19; 95% CI: 0.53-33.25; P = 0.17), after correction for propensity score and baseline lactate level. Baseline lactate level was independently associated with increased odds of 30 day mortality (per mmol/L increase; OR: 1.29; 95% CI: 1.14-1.45; P < 0.001). CONCLUSIONS: In CS patients, the adjusted mortality rates of both ECLS and Impella were high and similar. The baseline lactate level was a potent predictor of mortality and could play a role in patient selection for therapy in future studies. In patients with profound CS, the type of device is likely to be less important compared with other parameters including non-cardiac and neurological factors.

Impact of the COVID-19 pandemic on cardiovascular mortality and catherization activity during the lockdown in central Germany: an observational study.

AIMS: During the COVID-19 pandemic, hospital admissions for cardiac care have declined. However, effects on mortality are unclear. Thus, we sought to evaluate the impact of the lockdown period in central Germany on overall and cardiovascular deaths. Simultaneously we looked at catheterization activities in the same region. METHODS AND RESULTS: Data from 22 of 24 public health-authorities in central Germany were aggregated during the pandemic related lockdown period and compared to the same time period in 2019. Information on the total number of deaths and causes of death, including cardiovascular mortality, were collected. Additionally, we compared rates of hospitalization (n = 5178) for chronic coronary syndrome (CCS), acute coronary syndrome (ACS), and out of hospital cardiac arrest (OHCA) in 26 hospitals in this area. Data on 5,984 deaths occurring between March 23, 2020 and April 26, 2020 were evaluated. In comparison to the reference non-pandemic period in 2019 (deaths: n = 5832), there was a non-significant increase in all-cause mortality of 2.6% [incidence rate ratio (IRR) 1.03, 95% confidence interval (CI) 0.99-1.06; p = 0.16]. Cardiovascular and cardiac mortality increased significantly by 7.6% (IRR 1.08, 95%-CI 1.01-1.14; p = 0.02) and by 11.8% (IRR 1.12, 95%-CI 1.05-1.19; p < 0.001), respectively. During the same period, our data revealed a drop in cardiac catherization procedures. CONCLUSION: During the COVID-19-related lockdown a significant increase in cardiovascular mortality was observed in central Germany, whereas catherization activities were reduced. The mechanisms underlying both of these observations should be investigated further in order to better understand the effects of a pandemic-related lockdown and social-distancing restrictions on cardiovascular care and mortality.

[Out-of-hospital cardiac arrest: current diagnostic and therapeutical concepts]. / Diagnostik und Therapie nach präklinischem Kreislaufstillstand.

Out-of-hospital circulatory arrest represents a challenging situation in emergency medicine even until today. Despite optimal emergency care and clinical treatment pathways, we are faced with a mortality rate above 90 %. It is possible to improve the survival rate to more than 40 % under ideal clinical and preclinical conditions. Thus, more people's life could be saved by standardized SOPs and networks in emergency medicine. About 14.000 preclinical resuscitation cases are reported in Germany per year. The prognosis out-of-hospital circulatory arrest patients is determined by best preclinical treatment including early resuscitation by bystanders. However, ethical considerations for not performing cardiopulmonary resuscitation include comorbidities, advanced age, and prognostic markers of intensive care medicine like lactate level or neuron-specific enolase. Since myocardial infarction is the underlying disease in about 3 quarters of acute circulatory arrest cases, early angiography and coronary revascularization is of upmost importance. In addition, it is essential to provide hemodynamic stabilization for prevention of multiorgan dysfunction syndrome. Neuroprotection by therapeutic hypothermia may further help to improve survival and quality of life. Mechanical circulatory support devices may be considered adjunct to pharmacological measures for hemodynamic stabilization. Due to lack of evidence, these devices are currently under evaluation and prospectively randomized trials. We expect new treatment algorithms for optimal care of these high-risk patients in the near future.

Acute right heart failure: future perspective with the PERKAT RV pulsatile right ventricular support device.

Acute right heart failure is associated with impaired prognosis in cardiogenic shock. Since most pharmacological therapies are not evaluated for the failing right ventricle, or even contraindicated, there is a need for rapid minimal invasive circulatory right heart support. The PERKAT RV is such a device for acute therapy in congestive heart failure. It reduces the central venous pooling by pumping blood from the inferior vena cava into the pulmonary artery with flow rates of up to 4 litres/min. The device was evaluated in an animal model of acute pulmonary embolism after careful in vitro tests. PERKAT RV increased cardiac output by 59% in sheep suffering from acute right heart failure. We await the first human implantation in the near future. Based on the PERKAT concept, future devolvement will also focus on left heart support.