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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.

Cardiogenic shock due to myocardial infarction or heart failure entails a reduction in end organ perfusion. Patients who cannot be stabilized with inotropes and who experience increasing circulatory failure are in need of an extracorporeal mechanical support system. Today, small, percutaneously implantable cardiac assist devices are available and might be a solution to reduce mortality and complications. A temporary, ventricular, continuous flow propeller pump using magnetic levitation (ImpellaJenaMACS (Jena Mechanical Assist Circulatory Support) is a monocenter, proof-of-concept study to determine whether treatment with an Impella CPThe JenaMACS study will address essential questions of extracorporeal, mechanical, cardiac support with an Impella CPThe protocol was approved by the institutional review board and ethics committee of the University Hospital of Jena. Written informed consent will be obtained from all participants of the study. The results of this study will be published in a renowned international medical journal, irrespective of the outcomes of the study. Strengths and Limitations: JenaMACS is an innovative approach to characterize the effect of additional left ventricular mechanical unloading during cardiogenic shock via a minimally invasive cardiac assist system (Impella CP

Background Albumin is a key regulator of fluid distribution within the extracellular space and has several properties beyond its oncotic activity. The accumulating evidence suggests that supplementation of albumin may provide survival advantages only when the insult is severe as in patients with septic shock. Methods/design The randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS) investigates whether the replacement with albumin and the maintenance of its serum levels of at least 30 g/l for 28 days improve survival in patients with septic shock compared to resuscitation and volume maintenance without albumin. Adult patients (≥ 18 years) with septic shock are randomly assigned within a maximum of 24 h after the onset of septic shock after obtaining informed consents to treatment or control groups. Patients assigned to the treatment group receive a 60-g loading dose of human albumin 20% over 2–3 h. Serum albumin levels are maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40–80 g human albumin 20% infusion. The control group is treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. The primary endpoint is 90 days mortality and secondary endpoints include 28-day, 60-day, ICU, and in-hospital mortality, organ dysfunction/failure, total amount of fluid administration and total fluid balance in the ICU, and lengths of ICU and hospital stay. In total, 1412 patients need to be analysed, 706 per group. For the sample size estimation, a 15% reduction in 90-day mortality is assumed, i.e. an absolute reduction of 7.5% points to 42.5% (relative risk 1.18). Assuming a dropout rate of 15%, a total of 1662 patients need to be allocated. Discussion The results of the clinical trial may influence the treatment of patients with septic shock. The expected improvement in patient survival may result in a reduction in the resources currently used in the treatment of these patients and in the socioeconomic burden of this disease. Trial registration ClinicalTrials.gov NCT03869385 . Registration on 18 July 2019. Protocol version: Final 3.0.

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.

OBJECTIVES Cardiac surgery in patients with infective endocarditis (IE) and preoperative intracranial haemorrhage (pre-ICH) is a highly debatable issue, and guidelines are still not well defined. The goal of this study was to investigate the effect of cardiac surgery and its timing on the clinical outcomes of patients with IE and pre-ICH. METHODS We did a single-centre retrospective analysis of data from patients with preoperative brain imaging who had surgery for left-sided IE between January 2007 and May 2018. RESULTS Among the 363 patients included in the study, 34 had pre-ICH. Hospital mortality was similar between the patients with and without pre-ICH (29% vs 27%, respectively; P = 0.84). Unadjusted, postoperative neurological deterioration appeared higher in patients with pre-ICH (24% vs 17%; P = 0.35). In multivariable analysis, pre-ICH did not qualify as an independent predictor for either postoperative neurological deterioration [odds ratio 1.10, 95% confidence interval (CI) 0.44–2.73; P = 0.84] or hospital mortality (odds ratio 1.02, 95% CI 0.43–2.40; P = 0.96). Postoperative partial thromboplastin time was significantly elevated in 4 patients with relevant post-ICH compared with those patients without relevant post-ICH (65.5 vs 37.6, respectively; P = 0.004). CONCLUSIONS Pre-ICH was not an independent predictor for postoperative neurological deterioration or hospital mortality in patients with IE. Postoperative coagulation management seems to be crucial in patients with IE with ICH. Although this is to date the largest monocentric study addressing surgical decision and timing, the number of patients with pre-ICH was low. Therefore, these conclusions should be regarded with caution; randomized clinical trials are needed.

Pulmonary vein isolation (PVI) in persistent atrial fibrillation (AF) has a low success rate. A newer ablation concept targets left atrial (LA) low voltage zones (LVZ) which correlate with fibrosis and predict recurrence after PVI. We aimed to determine the success of combined PVI- and LVZ-guided ablation and to identify the predictors for LVZ and for ablation success. A total of 119 consecutive patients who underwent their first ablation procedure due to persistent AF were included. After acquisition of a high-resolution LA voltage map, PVI- and LVZ-guided ablation were performed. Mean age was 69 ± 8 years, 53% were men, and 8% had longstanding persistent AF. We found LVZ in 55% of patients. Twelve-month freedom from recurrences off drugs was 69%. The only independent predictor for recurrence was the existence of LVZ (OR 4.2, 95% CI 1.54–11.41, p = 0.005). Existence of LVZ was predicted positively by age ≥ 67 years (OR 4.4, 95% CI 1.4–13.7, p = 0.011), LA volume index ≥ 68 ml/m2 (OR 3.9, 95% CI 1.4–10.5, p = 0.008), and GFR ≤ 85 ml/min/1.73 m2 (OR 12.5, 95% CI 2.0–76.6, p = 0.006). BMI ≥ 26 kg/m2 (OR 0.06, 95% CI 0.01–0.30, p = 0.001) was a negative predictor of LVZ. LVZ-guided ablation in combination with PVI results in comparably high success rates. However, the existence of LVZ remains the strongest predictor of ablation success.

Aim Aim of our study was to evaluate metabolic changes in patients with aortic stenosis (AS) before and after transcatheter aortic valve replacement (TAVR) and to assess whether this procedure reverses metabolomic alterations. Methods 188 plasma metabolites of 30 patients with severe high-gradient aortic valve stenosis (pre-TAVR and 6 weeks post-TAVR) as well as 20 healthy controls (HC) were quantified by liquid chromatography tandem mass spectrometry. Significantly altered metabolites were then correlated to an extensive patient database of clinical parameters at the time of measurement. Results Out of the determined metabolites, 26.6% (n = 50) were significantly altered in patients with AS pre-TAVR compared to HC. In detail, 5/40 acylcarnitines as well as 10/42 amino acids and biogenic amines were mainly increased in AS, whereas 29/90 glycerophospholipids and 6/15 sphingomyelins were mainly reduced. In the post-TAVR group, 10.1% (n = 19) of metabolites showed significant differences when compared to pre-TAVR. Moreover, we found nine metabolites revealing reversible concentration levels. Correlation with clinically important parameters revealed strong correlations between sphingomyelins and cholesterol (r = 0.847), acylcarnitines and brain natriuretic peptide (r = 0.664) and showed correlation of acylcarnitine with an improvement of left ventricular (LV) ejection fraction (r = − 0.513) and phosphatidylcholines with an improvement of LV mass (r = − 0.637). Conclusion Metabolic profiling identified significant and reversible changes in circulating metabolites of patients with AS. The correlation of circulating metabolites with clinical parameters supports the use of these data to identify novel diagnostic as well as prognostic markers for disease screening, pathophysiological studies as well as patient surveillance.

Aims Increased sympathetic activation in patients with heart failure (HF) and sleep‐disordered breathing (SDB) provokes cardiac decompensation and protein degradation and could lead to muscle wasting and muscle weakness. The aim of this study was to investigate the differences in body composition, muscle function, and the susceptibility of preclinical congestion among patients with HF and SDB compared with those without SDB. Methods and results We studied 111 outpatients with stable HF who were enrolled into the Studies Investigating Co‐morbidities Aggravating Heart Failure. Echocardiography, short physical performance battery (SPPB), cardiopulmonary exercise testing, dual‐energy X‐ray absorptiometry, bioelectrical impedance analysis (BIA), tests of muscle strength, and polygraphy were performed. SDB was defined as apnoea/hypopnoea index (AHI) >5 per hour of sleep. Central sleep apnoea (CSA) and obstructive sleep apnoea (OSA) were defined as AHI >50% of central or obstructive origin, respectively. A total of 74 patients (66.7%) had any form of SDB [CSA (24 patients, 32.4%), OSA (47 patients, 63.5%)]. Patients with SDB showed increased muscle weakness (chair stand), reduced muscle strength, and lower values of SPPB score (P 0.05) but had increased amounts of water (total body water, intracellular, and extracellular) measured using BIA (P

Aims Dendritic cells (DCs) are central mediators of adaptive immunity, and there is growing evidence of their role in myocardial inflammatory disease. We hypothesized that plasmacytoid and myeloid DCs are involved in the mechanisms of myocarditis and analysed these two main subtypes in human myocarditis subjects, as well as in a murine model of experimental autoimmune myocarditis (EAM). Methods and results Circulating DCs were analysed by flow cytometry in patients with acute myocarditis, dilated cardiomyopathy, and controls. Myocardial biopsies were immunostained for the presence of DCs and compared with non‐diseased controls. In a mouse model of acute myocarditis induced through synthetic cardiac myosine peptide injection, effects of immunomodulation including DC inhibition through MCS‐18 versus placebo treatment were tested at the peak of inflammation (Day 21), as well as 1 week later (partial recovery). Circulatory pDCs and mDCs were significantly reduced in myocarditis patients compared with controls (P

Aims Exposure to high levels of air pollution in industrialized urban areas is associated with an increased risk of heart failure (HF). On most days, the majority of European cities are only moderately affected by air pollution. The aim of this study was to evaluate the association between short‐term exposure to moderate levels of air pollution with the risk of HF in a city with good air quality. Methods and results We recruited 576 patients (median age 82 years; 58.2% men) admitted to a large university hospital in Central Germany for HF to participate in a hospital‐based, bidirectional, case‐crossover study. Diagnosis of HF and symptom onset were verified individually. The effect of short‐term exposure to nitrogen dioxide (NO2), particulate matter (PM10), and ozone (O3) on the risk of HF was estimated using linear and non‐linear (categorized) multivariate analyses for three different lag times (1, 2, and 3 days before HF onset). Air pollution variables were adjusted to the date of HF symptom onset. During the study period, the average daily concentration of air pollutants was only moderate and reflects the average European background air pollution. In particular, the concentration of air pollutants ranged from 2 to 63.39 μg/m3 (median = 17.46 μg/m3) for NO2, from 2 to 125.88 μg/m3 (median = 44.61 μg/m3) for O3, and from 2.21 to 166.79 μg/m3 (median = 18.67 μg/m3) for PM10. We did not find a linear or non‐linear association between short‐term exposure to NO2, O3, or PM10 and risk for HF at all lag times in the overall population and subgroups. Conclusions In an area with only moderate air pollution, short‐term exposure to major air pollutants does not increase the risk for HF. Future studies should focus on a potential threshold effect of air pollution on HF risk as a basis for evidence‐based development of statutory limits in highly polluted areas.

ZusammenfassungDie aktualisierte Dyslipidämie-Leitlinie von 2019 definiert noch tiefere Therapieziele in Abhängigkeit der individuellen Risikokategorie, sowohl für die Primär- als auch für die Sekundärprävention. LDL-Cholesterin bleibt das primäre Maß zur Risikoabschätzung und Haupt-Therapieziel. Daneben sollte Lp(a) einmal im Erwachsenenalter zur Identifikation von Risikopersonen bestimmt werden. Die letzten großen randomisierten Studien zu Ezetimib und PCSK9-Inhibitoren konnten eine weitere relative Risikoreduktion für kardiovaskuläre Ereignisse nachweisen. Dabei ist die Verringerung des kardiovaskulären Risikos proportional zur absoluten LDL-C-Senkung. Für Patienten mit sehr hohem Risiko ist das neue LDL-C-Ziel

Data on the prevalence of depression and anxiety in elderly cardiovascular disease patients are limited and there are only few studies focussing on treatment effects. Thus, the current study aimed to analyse elderly patients suffering from aortic stenosis (AS) and undergoing transcatheter aortic valve replacement (TAVR) with respect to both, prevalence rates before TAVR and dynamics in the clinical course.The study included 140 AS patients undergoing TAVR (77.8 ± 7.7 years, 42.9% male, mean STS-Score 4.4 ± 2.2). Detailed clinical, laboratory and functional analysis was performed. In addition, quality of life (EQ-5D, EQ VAS), clinical frailty (CFS) and anxiety/depression (HADS-D), was assessed at baseline, 6 weeks, 6 months and 12 months after TAVR.Before TAVR, HADS-D revealed ≥8 points for anxiety and/or depression in 54 patients (38.6%), depression in 33 patients (23.6%) and for anxiety in 40 patients (28.6%). In the group showing HADS-D ≥8 points for anxiety, there was an improvement already 6 weeks after TAVR for anxiety (p 0.05) but not for depression. In the group showing HADS-D ≥8 points for depression, there was a significant improvement at the 6 weeks' follow-up for both, depression (p 0.001) and anxiety (p = 0.012) remaining stable for depression but not for anxiety until 12 months after TAVR.TAVR leads to reductions of depression and anxiety in patients showing pathologic baseline values in HADS-D. There were no associations between pre-existing depression and anxiety with long-term mortality in our study.

Endpoints of large-scale trials in chronic heart failure have mostly been defined to evaluate treatments with regard to hospitalizations and mortality. However, patients with heart failure are also affected by very severe reductions in exercise capacity and quality of life. We aimed to evaluate the effects of heart failure treatments on these endpoints using available evidence from randomized trials. Interventions with evidence for improvements in exercise capacity include physical exercise, intravenous iron supplementation in patients with iron deficiency, and - with less certainty - testosterone in highly selected patients. Erythropoiesis-stimulating agents have been reported to improve exercise capacity in anaemic patients with heart failure. Sinus rhythm may have some advantage when compared with atrial fibrillation, particularly in patients undergoing pulmonary vein isolation. Studies assessing treatments for heart failure co-morbidities such as sleep-disordered breathing, diabetes mellitus, chronic kidney disease and depression have reported improvements of exercise capacity and quality of life; however, the available data are limited and not always consistent. The available evidence for positive effects of pharmacologic interventions using angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists on exercise capacity and quality of life is limited. Studies with ivabradine and with sacubitril/valsartan suggest beneficial effects at improving quality of life; however, the evidence base is limited in particular for exercise capacity. The data for heart failure with preserved ejection fraction are even less positive, only sacubitril/valsartan and spironolactone have shown some effectiveness at improving quality of life. In conclusion, the evidence for state-of-the-art heart failure treatments with regard to exercise capacity and quality of life is limited and appears not robust enough to permit recommendations for heart failure. The treatment of co-morbidities may be important for these patient-related outcomes. Additional studies on functional capacity and quality of life in heart failure are required.

In den letzten Jahren ist aufgrund technischer Fortschritte mit einer Miniaturisierung der Systeme und Reduktion der postoperativen Komplikationen, Zunahme der Pravalenz der Herzinsuffizienz, dem Spendermangel im Bereich der Transplantation sowie steigender Lebenserwartung eine deutliche Zunahme der Patientenzahl mit permanenten Herzunterstutzungssystemen zu verzeichnen. Dieses sehr spezielle Patientenkollektiv kann sowohl akute systemassoziierte Notfalle, wie z. B. Pumpenthrombose oder Device-Fehlfunktion, aber auch nichtsystemassoziierte Notfalle aufweisen. Aufgrund der Besonderheiten in der Physiologie sowie potenzieller systembezogener Komplikationen ist die Versorgung dieser Patienten in Notfallsituationen komplex. Nationale oder internationale Empfehlungen fehlen bisher. Das vorliegende Konsensuspapier bietet, basierend auf einer konsentierten Expertenmeinung, den Vorschlag fur einen Algorithmus zur strukturierten und zugigen Evaluation von Notfallen bei Patienten mit permanenten Herzunterstutzungssystemen sowie deren Management.

The treatment of patients with advanced heart failure requires interdisciplinary care in a qualified heart failure team, especially prior to and in the follow-up of mechanical circulatory support (MCS) implantation and heart transplantation (HTx). The basic prerequisite is the early specialized evaluation of symptomatic patients even under optimized heart failure treatment. Diagnostics and treatment are initially aimed at improving the prognosis. If the prerequisites for MCS or HTx treatment are present, possible contraindications and problems have to be evaluated in order to achieve an optimal risk-benefit ratio for the abovementioned complex treatments with limited resources. The optimal treatment is still HTx if the conditions are right, so this should be sought in all potential patients. At the same time, the optimal individual transplantation window should not be missed. The provision of a MCS system is a treatment performed with very good results for patients with exclusion criteria for HTx or with hemodynamic instability that prevents a longer waiting time for a donor organ. Short-term and medium-term survival is now comparable to HTx when carefully indicated. Timely implantation before the onset of manifest end-organ damage is crucial. Optimized implementation of advanced treatment requires professional structures that enable effective interdisciplinary cooperation between different sectors of health care.Die Behandlung von Patienten mit fortgeschrittener Herzinsuffizienz erfordert eine interdisziplinäre Betreuung in einem qualifizierten Herzinsuffizienzteam, insbesondere im Vorfeld und in der Nachbetreuung der Versorgung mit einem mechanischen Kreislaufunterstützungssystem (MCS) und einer Herztransplantation (HTx). Grundvoraussetzung ist die frühzeitige spezialisierte Evaluation symptomatischer Patienten auch unter optimierter Herzinsuffizienzbehandlung. Die Diagnostik und Therapie ist zunächst auf eine Prognoseverbesserung ausgerichtet. Liegen die Voraussetzungen für eine MCS- oder HTx-Therapie vor, so sind mögliche Kontraindikationen und Probleme zu evaluieren, um eine optimale Nutzen-Risiko-Relation für die genannten aufwendigen Therapien mit begrenzten Ressourcen zu erzielen. Die optimale Therapie besteht bei entsprechenden Voraussetzungen nach wie vor in der HTx, sodass diese bei allen potenziellen Patienten angestrebt werden sollte. Dabei darf das optimale, individuelle Transplantationsfenster nicht verpasst werden. Die Versorgung mit einem MCS-System ist eine mit sehr guten Ergebnissen durchgeführte Therapie für Patienten mit Ausschlusskriterien für eine HTx oder mit einer hämodynamischen Instabilität, die eine längere Wartezeit auf ein Spenderorgan verhindert. Das kurz- und mittelfristige Überleben ist bei sorgfältiger Indikationsstellung mittlerweile vergleichbar mit dem nach HTx. Entscheidend ist die rechtzeitige Implantation vor dem Auftreten von manifesten Endorganschäden. Für die optimierte Umsetzung erweiterter Therapien bedarf es professioneller Strukturen, die eine effektive interdisziplinäre Kooperation unterschiedlicher Sektoren der Gesundheitsversorgung ermöglichen.

IMPORTANCE: Machine learning algorithms enable the automatic classification of cardiovascular diseases based on raw cardiac ultrasound imaging data. However, the utility of machine learning in distinguishing between takotsubo syndrome (TTS) and acute myocardial infarction (AMI) has not been studied. OBJECTIVES: To assess the utility of machine learning systems for automatic discrimination of TTS and AMI. DESIGN, SETTINGS, AND PARTICIPANTS: This cohort study included clinical data and transthoracic echocardiogram results of patients with AMI from the Zurich Acute Coronary Syndrome Registry and patients with TTS obtained from 7 cardiovascular centers in the International Takotsubo Registry. Data from the validation cohort were obtained from April 2011 to February 2017. Data from the training cohort were obtained from March 2017 to May 2019. Data were analyzed from September 2019 to June 2021. EXPOSURE: Transthoracic echocardiograms of 224 patients with TTS and 224 patients with AMI were analyzed. MAIN OUTCOMES AND MEASURES: Area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of the machine learning system evaluated on an independent data set and 4 practicing cardiologists for comparison. Echocardiography videos of 228 patients were used in the development and training of a deep learning model. The performance of the automated echocardiogram video analysis method was evaluated on an independent data set consisting of 220 patients. Data were matched according to age, sex, and ST-segment elevation/non-ST-segment elevation (1 patient with AMI for each patient with TTS). Predictions were compared with echocardiographic-based interpretations from 4 practicing cardiologists in terms of sensitivity, specificity, and AUC calculated from confidence scores concerning their binary diagnosis. RESULTS: In this cohort study, apical 2-chamber and 4-chamber echocardiographic views of 110 patients with TTS (mean [SD] age, 68.4 [12.1] years; 103 [90.4%] were female) and 110 patients with AMI (mean [SD] age, 69.1 [12.2] years; 103 [90.4%] were female) from an independent data set were evaluated. This approach achieved a mean (SD) AUC of 0.79 (0.01) with an overall accuracy of 74.8 (0.7%). In comparison, cardiologists achieved a mean (SD) AUC of 0.71 (0.03) and accuracy of 64.4 (3.5%) on the same data set. In a subanalysis based on 61 patients with apical TTS and 56 patients with AMI due to occlusion of the left anterior descending coronary artery, the model achieved a mean (SD) AUC score of 0.84 (0.01) and an accuracy of 78.6 (1.6%), outperforming the 4 practicing cardiologists (mean [SD] AUC, 0.72 [0.02]) and accuracy of 66.9 (2.8%). CONCLUSIONS AND RELEVANCE: In this cohort study, a real-time system for fully automated interpretation of echocardiogram videos was established and trained to differentiate TTS from AMI. While this system was more accurate than cardiologists in echocardiography-based disease classification, further studies are warranted for clinical application.

Background: Acute kidney injury (AKI) is associated with an increased mortality in critically ill patients, especially in patients with multiorgan dysfunction syndrome (MODS). In daily clinical practice, the grading of AKI follows the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. In most cases, a relevant delay occurs frequently between the onset of AKI and detectable changes in creatinine levels as well as clinical symptoms. The aim of the present study was to examine whether a near infrared spectroscopy (NIRS)-based, non-invasive ischemia–reperfusion test (vascular occlusion test (VOT)) together with unprovoked (under resting conditions) tissue oxygen saturation (StO2) measurements, contain prognostic information in the early stage of MODS regarding the developing need for renal replacement therapy (RRT). Methods: Within a period of 18 months, patients at the medical intensive care unit of a tertiary university hospital with newly developed MODS (≤24 h after diagnosis, APACHE II score ≥20) were included in our study. The VOT occlusion slope (OS) and recovery slope (RS) were recorded in addition to unprovoked StO2. StO2 was determined non-invasively in the area of the thenar muscles using a bedside NIRS device. The VOT was carried out by inflating a blood pressure cuff on the upper arm. AKI stages were determined by the changes in creatinine levels, urinary output, and/or the need for RRT according to KDIGO. Results: 56 patients with MODS were included in the study (aged 62.5 ± 14.4 years, 40 men and 16 women, APACHE II score 34.5 ± 6.4). Incidences of the different AKI stages were: no AKI, 16.1% (n = 9); AKI stage I, 19.6% (n = 11); AKI stage II, 25% (n = 14); AKI stage III, 39.3% (n = 22). Thus, 39.3% of the patients (n = 22) developed the need for renal replacement therapy (AKI stage III). These patients had a significantly higher mortality over 28 days (RRT, 72% (n = 16/22) vs. no RRT, 44% (n = 15/34); p = 0.03). The mean unprovoked StO2 of all patients at baseline was 81.7 ± 11.1%, and did not differ between patients with or without the need for RRT. Patients with RRT showed significantly weaker negative values of the OS (−9.1 ± 3.7 vs. −11.7 ± 4.1%/min, p = 0.01) and lower values for the RS (1.7 ± 0.9 vs. 2.3 ± 1.6%/s, p = 0.02) compared to non-dialysis patients. Consistent with these results, weaker negative values of the OS were found in higher AKI stages (no AKI, −12.7 ± 4.1%/min; AKI stage I, −11.5 ± 3.0%/min; AKI stage II, −11.1 ± 3.3%/min; AKI stage III, −9.1 ± 3.7%/min; p = 0.021). Unprovoked StO2 did not contain prognostic information regarding the AKI stages. Conclusions: The weaker negative values of the VOT parameter OS are associated with an increased risk of developing AKI and RRT, and increased mortality in the early phase of MODS, while unprovoked StO2 does not contain prognostic information in that regard.

The sodium–glucose cotransporter 2 inhibitor empagliflozin reduces the risk of cardiovascular death or heart failure hospitalization in patients with chronic heart failure, but whether empagliflozin also improves clinical outcomes when initiated in patients who are hospitalized for acute heart failure is unknown. In this double-blind trial (EMPULSE; NCT04157751), 530 patients with a primary diagnosis of acute de novo or decompensated chronic heart failure regardless of left ventricular ejection fraction were randomly assigned to receive empagliflozin 10 mg once daily or placebo. Patients were randomized in-hospital when clinically stable (median time from hospital admission to randomization, 3 days) and were treated for up to 90 days. The primary outcome of the trial was clinical benefit, defined as a hierarchical composite of death from any cause, number of heart failure events and time to first heart failure event, or a 5 point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days, as assessed using a win ratio. More patients treated with empagliflozin had clinical benefit compared with placebo (stratified win ratio, 1.36; 95% confidence interval, 1.09–1.68; P = 0.0054), meeting the primary endpoint. Clinical benefit was observed for both acute de novo and decompensated chronic heart failure and was observed regardless of ejection fraction or the presence or absence of diabetes. Empagliflozin was well tolerated; serious adverse events were reported in 32.3% and 43.6% of the empagliflozin- and placebo-treated patients, respectively. These findings indicate that initiation of empagliflozin in patients hospitalized for acute heart failure is well tolerated and results in significant clinical benefit in the 90 days after starting treatment.

Background: Cardiac surgery often represents the only treatment option in patients with infective endocarditis (IE). However, IE surgery may lead to a sudden release of inflammatory mediators, which is associated with postoperative organ dysfunction. We investigated the effect of hemoadsorption during IE surgery on postoperative organ dysfunction. Methods: This multicenter, randomized, nonblinded, controlled trial assigned patients undergoing cardiac surgery for IE to hemoadsorption (integration of CytoSorb to cardiopulmonary bypass) or control. The primary outcome (change in sequential organ failure assessment score [ΔSOFA]) was defined as the difference between the mean total postoperative SOFA score, calculated maximally to the 9th postoperative day, and the basal SOFA score. The analysis was by modified intention to treat. A predefined intergroup comparison was performed using a linear mixed model for ΔSOFA including surgeon and baseline SOFA score as fixed effect covariates and with the surgical center as random effect. The SOFA score assesses dysfunction in 6 organ systems, each scored from 0 to 4. Higher scores indicate worsening dysfunction. Secondary outcomes were 30-day mortality, duration of mechanical ventilation, and vasopressor and renal replacement therapy. Cytokines were measured in the first 50 patients. Results: Between January 17, 2018, and January 31, 2020, a total of 288 patients were randomly assigned to hemoadsorption (n=142) or control (n=146). Four patients in the hemoadsorption and 2 in the control group were excluded because they did not undergo surgery. The primary outcome, ΔSOFA, did not differ between the hemoadsorption and the control group (1.79±3.75 and 1.93±3.53, respectively; 95% CI, –1.30 to 0.83; P =0.6766). Mortality at 30 days (21% hemoadsorption versus 22% control; P =0.782), duration of mechanical ventilation, and vasopressor and renal replacement therapy did not differ between groups. Levels of interleukin-1β and interleukin-18 at the end of integration of hemoadsorption to cardiopulmonary bypass were significantly lower in the hemoadsorption than in the control group. Conclusions: This randomized trial failed to demonstrate a reduction in postoperative organ dysfunction through intraoperative hemoadsorption in patients undergoing cardiac surgery for IE. Although hemoadsorption reduced plasma cytokines at the end of cardiopulmonary bypass, there was no difference in any of the clinically relevant outcome measures. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03266302.

Acute kidney injury (AKI) is associated with an increased mortality in critically ill patients, especially in patients with multiorgan dysfunction syndrome (MODS). In daily clinical practice, the grading of AKI follows the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. In most cases, a relevant delay occurs frequently between the onset of AKI and detectable changes in creatinine levels as well as clinical symptoms. The aim of the present study was to examine whether a near infrared spectroscopy (NIRS)-based, non-invasive ischemia-reperfusion test (vascular occlusion test (VOT)) together with unprovoked (under resting conditions) tissue oxygen saturation (StOWithin a period of 18 months, patients at the medical intensive care unit of a tertiary university hospital with newly developed MODS (≤24 h after diagnosis, APACHE II score ≥20) were included in our study. The VOT occlusion slope (OS) and recovery slope (RS) were recorded in addition to unprovoked StO56 patients with MODS were included in the study (aged 62.5 ± 14.4 years, 40 men and 16 women, APACHE II score 34.5 ± 6.4). Incidences of the different AKI stages were: no AKI, 16.1% (The weaker negative values of the VOT parameter OS are associated with an increased risk of developing AKI and RRT, and increased mortality in the early phase of MODS, while unprovoked StO

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.Jüngst wurden die europäischen Leitlinien zur kardiopulmonalen Reanimation verabschiedet, die in 12 Kapitel unterteilt sind. Erstmals wurden die Themen „Epidemiologie“ und „lebensrettende Systeme“ integriert. Für jedes Kapitel wurden 5 praxisnahe Kernaussagen formuliert. In dem vorliegenden Artikel werden die aktuellen Empfehlungen zu Basismaßnahmen und erweiterten Maßnahmen der Erwachsenenreanimation sowie zur Postreanimationsbehandlung zusammengefasst und kommentiert.

(1) Background: The assessment of residual peri-device leakages (PDL) after left atrial appendage occlusion (LAAO) remains crucial for post-procedural management. Our study aimed to verify a novel echocardiographic classification for the prediction of PDL. (2) Methods: Echocardiographic data of 72 patients who underwent percutaneous LAAO were evaluated. All echo images were analyzed by two independent investigators using standard analysis software (Image-Arena IA-4.6.4.44 by TomTec

Interstitial lung disease (ILD) is a severe pulmonary complication in inflammatory rheumatic diseases (IRD) and associated with significantly increased morbidity and mortality. That is why ILD screening at a very early stage, at the onset of IRD, is essential. The objective of the present study was to evaluate the diagnostic value and utility of a stepwise approach as a potential ILD screening tool in patients with newly diagnosed IRD.Consecutively, 167 IRD patients were enrolled. To homogenize the study cohort, an age and gender matching was performed. The case-control study included 126 patients with new onset of IRD (mainly connective tissue diseases [CTD], small vessel vasculitis, and myositis). We applied a stepwise screening algorithm in which all patients underwent pulmonary function testing (PFT) and/or additional chest radiography. If there was at least one abnormal finding, pulmonary high-resolution computed tomography (HRCT) was subsequently performed.With our stepwise diagnostic approach, we identified 63 IRD patients with ILD (ILD group) and 63 IRD patients without ILD (non-ILD group). A reduced diffusing capacity for carbon monoxide (DLCO)80% showed a sensitivity of 83.6% and a specificity of 45.8% compared to chest X-ray with 64.2% and 73.6%, respectively, in detecting ILD. The combination of reduced DLCO and chest X-ray revealed a sensitivity of 95.2% and a specificity of 38.7%. The highest sensitivity (95.2%) and specificity (77.4%) were observed for the combination of reduced DLCO, chest X-ray, and pulmonary HRCT. The most common pulmonary abnormalities on HRCT were ground-glass opacities (GGO; 36.5%), followed by non-specific interstitial pneumonia (NSIP; 31.8%) and usual interstitial pneumonia (UIP; 9.5%).The combination of reduced DLCO (80%), chest X-ray, and pulmonary HRCT yielded the highest sensitivity and specificity in detecting ILD at the onset of IRD. Therefore, this stepwise approach could be a new screening algorithm to identify IRD patients with pulmonary involvement already at the time of the initial IRD diagnosis.

There is great interest to understand causal pathophysiological correlation between obesity and diabetes mellitus (DM). Vascular endothelial dysfunction is crucially involved in pathogenesis of vascular complications in DM. Recently, increased arginase expression and activity have been described as underlying mechanisms of endothelial dysfunction in DM and vascular inflammation in obesity. By limiting L-arginine bioavailability to endothelial nitric oxide synthase (NOS III), nitric oxide production is potentially impaired.We investigated the impact of plasma from diabetic and obese adolescents on arginase and NOS III expression in cultured human endothelial cells (ECs). A total of 148 male adolescents participated in this study including 18 obese, 28 type 1-, 28 type 2-DM patients, and 74 age-matched healthy volunteers.A concurrent increase in arginase-1 (1.97-fold) and decrease in NOS III expression (1.45-fold) was observed in ECs exposed to type 2 diabetic plasma compared to control subjects. ECs incubated with type 1 DM plasma had a diminished NOS III level without impact on arginase-1 expression. Urea-assay featured an increased arginase activity in treated ECs with type 1- or 2-DM plasma. Despite increased pro-inflammatory cytokines and chemokines in obese plasma, arginase-1 expression/activity did not change in treated ECs. However, NOS III expression was significantly reduced. Pearson analysis revealed positive correlation between arginase-1, but not NOS III, expression with FBS in ECs treated with type 2-DM plasma.Our data demonstrate that increased arginase-1 expression/activity in ECs, as critical pathogenic factor is correlated with development of obesity-related type 2-DM and linked vascular disease.

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.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.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,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.

Percutaneous catheter-based ultrasound-assisted thrombolysis (UACDT) is recommended for patients with intermediate-high-risk or high-risk pulmonary embolism (PE) in whom systemic thrombolysis has failed or is contraindicated.To evaluate the safety and efficiency of UACDT in patients with intermediate-high-risk or high-risk PE.Between October 2017 and January 2020, we performed UACDT using the EkoSonic™ Endovascular System (EKOS™) in 51 patients (21 males, age 63 ± 18 years) with a sPESI of 1.3 ± 0.7. The EKOS™-catheter was implanted within 24 h after admission. Over 15 hours, 11.5 mg of alteplase was administered per catheter. We evaluated right ventricular stress and cardiac biomarkers before and after UACDT.24 h post-UACDT, median RV/LV ratio decreased from 1.13 to 0.96 (The treatment with UACDT reduced right heart stress during the first 24 hours and midterm in patients with intermediate-high-risk or high-risk PE at an acceptable rate of severe complications.

MiRNA-regulated processes are pivotal in cardiovascular homeostasis and disease. These short non-coding RNAs have ideal properties that could be utilized as potential biomarkers; moreover, their functions as post-transcriptional regulators of mRNA make them interesting therapeutic targets. In this review, we summarize the current state of miRNA-based biomarkers in a variety of diseases leading to heart failure, as well as provide an outlook on developing miRNA-based therapies in the heart failure field.

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. Summary This review discusses this controversy based on findings from in vitro and in vivo studies, clinical trials, and genetic evidence.

The heart is an organ with high energy demands and metabolic flexibility, thus allowing for various energy substrates for ATP production under different physiological conditions. Zhang et al., Fernandez-Caggiano et al. and McCommis et al. converge on the mitochondrial pyruvate transporter as a key metabolic hub for the maintenance of cardiac metabolism and a critical determinant of cardiac metabolic plasticity during heart failure.

Growing evidence suggests that inflammation is crucially involved in the pathogenesis of pulmonary hypertension (PH) and consecutive right heart failure. The present study analyzed the inflammatory response in lung and right ventricle in a rat model of PH and evaluated the effects of the dual endothelin receptor antagonist (ERA) Macitentan. PH was induced by monocrotalin (60 mg/kg body weight s.c.) in Sprague-Dawley rats (PH, n = 10) and compared to healthy controls (CON, n = 10) as well as monocrotalin-induced, macitentan-treated rats (THER, n = 10). Detection of Dendritic cells (DCs), regulatory T cells (Tregs) and others as well as RT-PCR based inflammatory gene expression analysis were performed. Circulating DCs and Tregs were quantified by flow cytometry in the rat model and in PH patients (n = 70) compared to controls (n = 52). Inflammatory cells were increased in lung and right ventricular tissue, whereas DCs and Tregs were decreased in blood. Expression of 17 genes in the lung and 20 genes in the right ventricle were relevantly (>2.0 fold) regulated in the PH group. These effects were, at least in part, attenuated in response to Macitentan treatment. In humans as well as rats, immune cells showed significant correlations to clinical, echocardiographic, and haemodynamic parameters. PH is accompanied by a distinct inflammatory response in lung and right but not left ventricular tissue attenuated by Macitentan. Correlations of circulating DCs as well as tissue resident immune cells with parameters reflecting right ventricular function raise the idea of both, promising biomarkers and novel treatment strategies.

Background Both falls and fractures are increased in older persons living with HIV (PLWH). Low serum total 25-hydroxyvitamin D (25-OHD) levels have been associated with falls, fractures and poor muscle strength. We hypothesized that vitamin D (VitD) supplementation would improve muscle strength in postmenopausal PLWH. Methods In a 12-month prospective, randomized, double-blind, study of 69 African American and Hispanic post-menopausal PLWH on antiretroviral therapy with 25-OHD ≥10 ng/ml and ≤32 ng/ml, we investigated the effects of daily low (1,000 IU; n=31) and moderate (3,000 IU; n=38) cholecalciferol doses on lean mass and strength. Change in lean body mass was assessed by dual-energy X-ray absorptiometry (DXA), and isometric and isokinetic muscle strength in the dominant lower extremity was assessed using the Biodex System 4 Pro. Results Mean age was 56 ±5 years, median CD4+ T-cell count 722 cells/mm3 and 74% had HIV RNA≤50 copies/ ml. Serum 25-OHD did not differ at baseline, but was higher in the moderate than low VitD group at 6 and 12 months. In both groups, there were significant increases in lower extremity isokinetic torque, work and power at 12 months, with no change in lean mass. Conclusions VitD supplementation was associated with a modest increase in lower extremity strength in postmenopausal PLWH, without a concomitant increase in muscle mass. Magnitude of increase in strength were similar with 3,000 IU and 1,000 IU daily. Future larger studies will be required to determine the optimal dose of VitD to improve muscle strength and to determine whether supplementation reduces the risk of falls and fractures in PLWH.

© 2019 The Authors European Journal of Heart Failure © 2019 European Society of Cardiology, Recent evidence suggests comparable in‐hospital and long‐term outcomes between takotsubo syndrome (TTS) and acute coronary syndrome. Medical scoring systems are practical tools for decision making and prognostic assessment. However, TTS‐specific scoring systems for risk stratification have not yet been established. Recently, classification based on triggering conditions proved useful in predicting adverse outcomes in TTS (InterTAK Classification).1 Since clinical parameters other than triggering conditions can be associated with adverse outcomes in TTS, such as systolic blood pressure and heart rate, the present study aimed to establish a scoring system combining triggering factors with other important but easily‐ obtainable clinical parameters of daily clinical practice., C.T. has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation. L.S.M. was supported by EU HORIZON 2020 (SILICOFCM ID777204). The InterTAK Registry is supported by the Biss Davies Charitable Trust.

Background: Metabolic remodeling in heart failure contributes to dysfunctional lipid trafficking and lipotoxicity. Acyl coenzyme A synthetase-1 (ACSL1) facilitates long-chain fatty acid (LCFA) uptake and activation with coenzyme A (CoA), mediating the fate of LCFA. The authors tested whether cardiac ACSL1 overexpression aids LCFA oxidation and reduces lipotoxicity under pathological stress of transverse aortic constriction (TAC). Methods: Mice with cardiac restricted ACSL1 overexpression (MHC-ACSL1) underwent TAC or sham surgery followed by serial in vivo echocardiography for 14 weeks. At the decompensated stage of hypertrophy, isolated hearts were perfused with 13 C LCFA during dynamic-mode 13 C nuclear magnetic resonance followed by in vitro nuclear magnetic resonance and mass spectrometry analysis to assess intramyocardial lipid trafficking. In parallel, acyl CoA was measured in tissue obtained from heart failure patients pre- and postleft ventricular device implantation plus matched controls. Results: TAC-induced cardiac hypertrophy and dysfunction was mitigated in MHC-ACSL1 hearts compared with nontransgenic hearts. At 14 weeks, TAC increased heart weight to tibia length by 46% in nontransgenic mice, but only 26% in MHC-ACSL1 mice, whereas ACSL1 mice retained greater ejection fraction (ACSL1 TAC: 65.8±7.5%; nontransgenic TAC: 45.9±7.3) and improvement in diastolic E/E’. Functional improvements were mediated by ACSL1 changes to cardiac LCFA trafficking. ACSL1 accelerated LCFA uptake, preventing C16 acyl CoA loss post-TAC. Long-chain acyl CoA was similarly reduced in human failing myocardium and restored to control levels by mechanical unloading. ACSL1 trafficked LCFA into ceramides without normalizing the reduced triglyceride storage in TAC. ACSL1 prevented de novo synthesis of cardiotoxic C16- and C24-, and C24:1 ceramides and increased potentially cardioprotective C20- and C22-ceramides post-TAC. ACLS1 overexpression activated AMP activated protein kinase at baseline, but during TAC, prevented the reduced LCFA oxidation in hypertrophic hearts and normalized energy state (phosphocreatine:ATP) and consequently, AMP activated protein kinase activation. Conclusions: This is the first demonstration of reduced acyl CoA in failing hearts of humans and mice, and suggests possible mechanisms for maintaining mitochondrial oxidative energy metabolism by restoring long-chain acyl CoA through ASCL1 activation and mechanical unloading. By mitigating cardiac lipotoxicity, via redirected LCFA trafficking to ceramides, and restoring acyl CoA, ACSL1 delayed progressive cardiac remodeling and failure.

Dietary guidance for patients with heart failure (HF) has traditionally focused on sodium and fluid intake restriction, but dietary quality is frequently poor in patients with HF and may contribute to morbidity and mortality. Restrictive diets can lead to inadequate intake of macronutrients and micronutrients by patients with HF, with the potential for deficiencies of calcium, magnesium, zinc, iron, thiamine, vitamins D, E, and K, and folate. Although inadequate intake and low plasma levels of micronutrients have been associated with adverse clinical outcomes, evidence supporting therapeutic repletion is limited. Intravenous iron, thiamine, and coenzyme Q10 have the most clinical trial data for supplementation. There is also limited evidence supporting protein intake goals. Obesity is a risk factor for incident HF, and weight loss is an established approach for preventing HF, with a role for bariatric surgery in patients with severe obesity. However weight loss for patients with existing HF and obesity is a more controversial topic owing to an obesity survival paradox. Dietary interventions and pharmacologic weight loss therapies are understudied in HF populations. There are also limited data for optimal strategies to identify and address cachexia and sarcopenia in patients with HF, with at least 10%-20% of patients with ambulatory systolic HF developing clinically significant wasting. Gaps in our knowledge about nutrition status in patients with HF are outlined in this Statement, and strategies to address the most clinically relevant questions are proposed.

To report long-term safety and efficacy of combined percutaneous LAA and PFO/ASD closure.A retrospective study of 370 consecutive patients undergoing LAAC procedures using the Watchman (WM) device. Data were compared between 330 cases only with LAAC procedure (Group I) and 25/5 (PFO/ASD) cases with sequential procedures of LAAC and PFO/ASD closure (Group II).Compared to Group I, Group II had more males (86.7% vs. 65.8%, p0.05) and a higher rate of stroke (33.3% vs. 10.6%, p0.01), but there were no statistical differences in the remaining patient characteristics. During the follow-up period, there were no significant differences between the two groups in embolism events (6.1% vs. 0%, p = 0.39), device related thrombus (5.8% vs 3.3%, p = 1.0), major bleeding (9.4% vs. 6.7%, p = 1.0) and cardiac death (3.6% vs. 0%, p = 0.61). The observed rate of all thromboembolic events by Kaplan-Meier analysis was decreased by 39.9% and 100% and the observed annual rate of bleeding was reduced by 32.9% and 57.6% in Group I and Group II, respectively.LAAC combined with PFO/ASD closure might be an ideal choice to prevent stroke and other thrombotic complications in patients with both NVAF and PFO/ASD.

Accurate assessment of the aortic annulus is crucial for successful transcatheter aortic valve replacement (TAVR), in particular to prevent paravalvular regurgitation (PVR). We compared aortic annular sizing using multidetector computed tomography (MDCT) and three-dimensional transoesophageal echocardiography (3-D TEE) to determine the predictive value of MDCT. All patients admitted for transfemoral TAVR [n = 227; 48.9% balloon expandable (Edwards Sapien 3); 51.1% self-expandable (Core Valve, Evolut R)] at our institution from January 2015 until December 2016 were analysed retrospectively. Aortic annular parameters were obtained either by MDCT or 3-D TEE. Additionally, we included a cohort of patients (n = 27) assessed by both MDCT and 3D TEE between October 2017 and April 2018 to enable intra-individual comparison of the two methods. Indications for TAVR were severe degenerative aortic stenosis (AS; 94.7%) or re-stenosis after surgical AVR (5.3%). 74.4% were classified as high-gradient AS. The mean age was 80 (37–94) years and 75.8% presented with NYHA III/IV. STS risk of mortality was intermediate (3.5 ± 2.3). MDCT and 3-D TEE were performed in 116 and 111 patients for aortic annulus sizing, respectively. Significantly larger implants were chosen in the CT group irrespective of prosthesis type or post-dilatation. Follow-up (median at 79 days) revealed significantly less PVR in the MDCT compared to 3-D TEE group (absence of PVR in 59.3% and 40.7%, p = 0.016), without differences in mortality. Patients without PVR or mild PVR had a better clinical performance according to NYHA class (p = 0.016). MDCT is superior to 3-D TEE in terms of sizing accuracy and clinical outcomes. Reduction of PVR after TAVR with MDCT is likely due to valve annulus undersizing by TEE.

Applications of virtual reality (VR) and augmented reality (AR) assist both health care providers and patients in cardiovascular education, complementing traditional learning methods. Interventionalists have successfully used VR to plan difficult procedures and AR to facilitate complex interventions. VR/AR has already been used to treat patients, during interventions in rehabilitation programs and in immobilized intensive care patients. There are numerous additional potential applications in the catheterization laboratory. By using AR, interventionalists could combine visual fluoroscopy information projected and registered on the patient body with data derived from preprocedural imaging and live fusion of different imaging modalities such as fluoroscopy with echocardiography. Persistent technical challenges to overcome include the integration of different imaging modalities into VR/AR and the harmonization of data flow and interfaces. Cybersickness might exclude some patients and users from the potential benefits of VR/AR. Critical ethical considerations arise in the application of VR/AR in vulnerable patients. In addition, digital applications must not distract physicians from the patient. It is our duty as physicians to participate in the development of these innovations to ensure a virtual health reality benefit for our patients in a real-world setting. The purpose of this review is to summarize the current and future role of VR and AR in different fields within cardiology, its challenges, and perspectives.

Since the beginning of 2020 the coronavirus disease 2019 (COVID-19) pandemic has extensively impacted medical care in Germany and worldwide. Germany is currently facing the so-called third wave of the COVID-19 pandemic. This is exacerbated by emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants with increased virus transmission and severe courses of disease. Rising numbers of SARS-CoV‑2 infections translate into an increasing number of severe COVID-19 cases requiring intensive care, which interacts with limited structural and personnel resources for COVID-19 and non-COVID-19 critically ill patients. Therefore, prioritization and triage for critically ill patients with allocation of intensive care capacities becomes necessary, as with all situations with higher strain on capacities. Both strategies are meaningful forms of organization and are not to be equated with a collapse of medical care. Cardiovascular comorbidities and cardiac involvement in COVID-19 are of particular importance for disease severity and the clinical course. In addition to the medical care of patients with SARS-CoV‑2 infections due to the pandemic, other patients with acute sometimes life-threatening diseases must also continue to receive high-quality treatment. This article provides a current overview of proposed restructuring measures in German hospitals as well as the accompanying triage and prioritization algorithms. Moreover, it is necessary to adapt existing treatment algorithms to the pandemic situation. Due their special importance this is sketched using cardiovascular diseases as an example.Seit Anfang des Jahres 2020 hat die durch die „coronavirus disease 2019“ (COVID-19) verursachte Pandemie weitreichende Folgen für die medizinische Versorgung in Deutschland und weltweit. Aktuell befindet sich Deutschland in der sog. 3. Pandemiewelle. Dazu kommen Mutanten des „severe acute respiratory syndrome coronavirus 2“ (SARS-CoV-2) mit erhöhter Virustransmission und schwerem Erkrankungsverlauf. Steigende SARS-CoV-2-Infektionszahlen münden in einer erhöhten Zahl schwerer COVID-19-Verläufe und einem erhöhten Bedarf intensivmedizinischer Behandlungen, die auf begrenzte strukturelle und personelle Ressourcen für COVID-19- und Non-COVID19-Patienten treffen. Dies – wie alle Situationen mit hoher Kapazitätsbelastung – macht eine Triagierung und Priorisierung von Erkrankten mit Zuteilung intensivmedizinischer Kapazitäten notwendig. Beide Strategien sind sinnvolle Organisationsformen und dürfen nicht mit einem Zusammenbruch der medizinischen Versorgung gleichgesetzt werden. Kardiovaskuläre Komorbiditäten und eine kardiale Mitbeteiligung bei COVID-19 sind für die Krankheitsschwere und den Krankheitsverlauf von besonderer Bedeutung. Neben der medizinischen Versorgung der Patienten mit pandemiebedingten akuten SARS-CoV-2-Infektionen müssen auch andere Patienten mit akuten, u. U. lebensbedrohlichen Erkrankungen unverändert mit hoher Qualität versorgt werden. Dieser Beitrag gibt eine aktuelle Übersicht über die vorgeschlagenen Restrukturierungsmaßnahmen in deutschen Krankenhäusern sowie damit einhergehenden Triagierungs- und Priorisierungsalgorithmen. Daneben ist es erforderlich, bestehende Behandlungsalgorithmen an die pandemische Lage zu adaptieren; dies wird aufgrund ihres besonderen Stellenwerts exemplarisch an kardiovaskulären Erkrankungen skizziert.

Background While it is the most common thoracic venous anomaly, a persistent left vena cava superior may present in atypical variations, which are important to consider during clinical management. Case presentation Here we report a 35-year-old Caucasian female patient with drainage into the left atrial appendage who presented with shortness of breath accompanied by mild hypoxemia. Venous contrast filling in the context of pulmonary scintigraphy suspected an additional superior caval vein connected to the left atrial appendage. Diagnosis was confirmed by transesophageal echocardiography. Cardiac catheterization revealed a minor right-to-left shunt. The symptoms could be allocated to a bronchial asthma and treated according to guidelines. Cerebral lesions detected in the patient were due to a coincident multiple sclerosis rather than cerebral embolisms. Thus, the venous anomaly was classified as an incidental finding currently requiring no treatment. Conclusions To the best of our knowledge, this is the first report of a persistent left vena cava superior draining into the left atrial appendage. Supplementary Information The online version contains supplementary material available at 10.1186/s13256-021-03210-9.

Background: Depression and anxiety are frequently occurring and likely to be linked to the severity of cardiac diseases like aortic stenosis (AS). This seems to be of interest since a staging classification of extra-valvular cardiac damage in AS has been introduced and shown to be of prognostic relevance. Objective: The current study aimed to investigate the frequency of depression and anxiety in association to staging and their dynamics after transcatheter aortic valve implantation (TAVI). Methods: A total number of 224 AS patients undergoing TAVI were classified according to the 2017 staging classification into stage 0 to 4 and further dichotomized into group A (stage 0 to 2) and B (stage 3 and 4). Using the Hospital Anxiety and Depression Scale (HADS-D), patients were assigned to depressive versus non-depressive or anxious versus non-anxious per staging group respectively, and analyzed at baseline, 6 weeks, 6 months and 12 months after TAVI. Results: After dichotomization, 158 patients (70.5%) were assigned to group A and 66 patients (29.5%) to group B. The part showing pathologic values for depression was 25.4% (57/224 patients) in the entire collective, 26.6% (42/158 patients) in group A and 22.7% (15/66 patients) in group B (p = n.s.). The proportion showing pathologic values for anxiety was 26.8% (60/224 patients) in the entire collective and did not differ between group A (24.7%, 39/158 patients) and B (31.8%, 21/66 patients) (p = n.s.). In patients revealing pathologic values for depression or anxiety prior to TAVI, there were significant and stable improvements over time observable already in short-term (6 weeks) follow-up in group A, and likewise, but later, in long-term (6/12 months) follow-up in group B. Conclusions: Although of proven prognostic relevance, higher stages of extra-valvular cardiac damage are not associated with higher rates of pre-existing depression or anxiety. The TAVI procedure resulted in a persisting reduction of depression and anxiety in patients showing pathologic values at baseline. Notably, these improvements are timely delayed in higher stages.

More than twenty years ago, knowledge about the importance of cholesterol absorption and the potential therapeutic effect of its inhibition led to the discovery and clinical application of the first and only cholesterol absorption inhibitor to date - ezetimibe. Since then, ezetimibe has become a well-recognized player in lipid-lowering therapy. Recent findings of IMPROVE-IT and EWTOPIA 75 imply that elderly patients over the age of 75 years in particular benefit from ezetimibe. This review summarizes the evidence, discusses the possible underlying pathophysiological mechanisms and calls for a change in future dyslipidemia guidelines.

Background and Aims: Pulmonary hypertension (PH) is a heterogeneous disorder associated with poor prognosis. For the majority of patients, only limited therapeutic options are available. Thus, there is great interest to develop novel treatment strategies focusing on pulmonary vascular and right ventricular remodeling. Interleukin 9 (IL9) is a pleiotropic cytokine with pro- and anti-inflammatory functions. The aim of this study was to evaluate the therapeutic activity of F8IL9F8 consisting of IL9 fused to the F8 antibody, specific to the alternatively-spliced EDA domain of fibronectin, which is abundantly expressed in pulmonary vasculature and right ventricular myocardium in PH. Methods: The efficacy of F8IL9F8 in attenuating PH progression in the monocrotaline mouse model was evaluated in comparison to an endothelin receptor antagonist (ERA) or an IL9 based immunocytokine with irrelevant antibody specificity (KSFIL9KSF). Treatment effects were assessed by right heart catheterization, echocardiography as well as histological and immunohistochemical tissue analyses. Results: Compared to controls, systolic right ventricular pressure (RVPsys) was significantly elevated and a variety of right ventricular echocardiographic parameters were significantly impaired in all MCT-induced PH groups except for the F8IL9F8 group. Both, F8IL9F8 and ERA treatments lead to a significant reduction in RVPsys and an improvement of echocardiographic parameters when compared to the MCT group not observable for the KSFIL9KSF group. Only F8IL9F8 significantly reduced lung tissue damage and displayed a significant decrease of leukocyte and macrophage accumulation in the lungs and right ventricles. Conclusions: Our study provides first pre-clinical evidence for the use of F8IL9F8 as a new therapeutic agent for PH in terms of a disease-modifying concept addressing cardiovascular remodeling.

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.

Heart failure remains the most common cause of death in the industrialized world. In spite of new therapeutic interventions that are constantly being developed, it is still not possible to completely protect against heart failure development and progression. This shows how much more research is necessary to understand the underlying mechanisms of this process. In this review, we give a detailed overview of the contribution of impaired mitochondrial dynamics and energy homeostasis during heart failure progression. In particular, we focus on the regulation of fatty acid metabolism and the effects of fatty acid accumulation on mitochondrial structural and functional homeostasis.

Objectives and Background: Atrial fibrillation (AF) is still associated with higher recurrence rate. This is prospective study of Redo pulmonary vein isolation (PVI) combined with remote magnet navigation. We have done high density mapping and in retrospective Analysis we tried to find criteria for better Ablation success. Materials and Methods: 50 patients (male 36, female 14) with indication for Redo-PVI ware included. A 20 polig multielectrode catheter was used for mapping. Mapping data were collected bevor and after ablation and processed in terms of low-voltage areas bipolar (3 groups: 0.05-0.15 mV, 0.15-0.25 mV, 0.25-0.5 mV) and change in unipolar amplitude at the ablation lesions. The primary endpoint (symptom freedom at 12 months) was evidenced by follow-up examinations at 3, 6,9,12 months. Non-parametric statistical methods were used for variables with non-normal distributions. Trends in success rates were evaluated using the Kaplan-Meier methodology and compared using a log-ranking test. Results: In all analysed low-voltage bipolar groups occurs a change in the distribution after ablation in patients with AF. There are 3 parameters which related with endpoint: area of bipolar signals 0.05-0.15 mV (Me +32%, [95% CI: -10% to +167%], p