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Objectives: There is an ongoing debate whether percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is the better choice for treatment of left main (LM) stenosis. We aimed to provide external validation for the recently reviewed guideline recommendations for invasive LM therapy by evaluating the impact of CABG or PCI on long-term survival from local reports of different regions in the world. We performed a systematic review and meta-analysis to address contemporary registry studies comparing PCI and CABG for patients with LM stenosis. Methods: Three databases were assessed. Our primary end point was long-term all-cause mortality. Secondary end points were major adverse cardiovascular events (MACE), myocardial infarction, repeat revascularization, stroke, and periprocedural mortality. Reconstruction of time-to-event data was performed. Results: A total of 2477 studies were retrieved. Seven studies with risk-adjusted populations were selected for the analysis. Four studies favored CABG and 3 studies showed no difference for the primary end point. Compared with PCI, patients who underwent CABG had lower risk of death (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26, P

Abstract This study aimed to conduct a systematic review and meta‐analysis comparing video‐assisted thoracoscopic surgery (VATS) and open thoracotomy (OT) in the context of pulmonary metastasectomy. Three databases were assessed. The primary outcome was overall survival. The secondary outcomes were recurrence‐free survival, ipsilateral recurrence, and hospital length of stay (LOS). Hazard ratios (HRs), odds ratios (ORs), and mean difference (MD) with 95% confidence intervals (CIs) were calculated. Reconstruction of time‐to‐event data and sensitivity analyses were performed for the primary endpoint. After screening, 11 studies were included encompassing 2159 patients undergoing lung metastasectomy (VATS: 827; OT: 1332). Compared to OT, patients who underwent VATS had higher overall survival rates (HR 0.75; 95% CI 0.67–0.85; p

Abstract Ageing is a major risk factor that contributes to increased mortality and morbidity rates during influenza A virus (IAV) infections. Macrophages are crucial players in the defense against viral infections and display impaired function during ageing. However, the impact of ageing on macrophage function in response to an IAV infection remains unclear and offers potential insight for underlying mechanisms. In this study, we investigated the immune response of young and aged human monocyte-derived macrophages to two different H1N1 IAV strains. Interestingly, macrophages of aged individuals showed a lower interferon response to IAV infection, resulting in increased viral load. Transcriptomic data revealed a reduced expression of stimulator of interferon genes (STING) in aged macrophages albeit the cGAS-STING pathway was upregulated. Our data clearly indicate the importance of STING signaling for interferon production by applying a THP-1 STING knockout model. Evaluation of mitochondrial function during IAV infection revealed the release of mitochondrial DNA to be the activator of cGAS-STING pathway. The subsequent induction of apoptosis was attenuated in aged macrophages due to decreased STING signaling. Our study provides new insights into molecular mechanisms underlying age-related immune impairment. To our best knowledge, we are the first to discover an age-dependent difference in gene expression of STING on a transcriptional level in human monocyte-derived macrophages possibly leading to a diminished interferon production.

Abstract Background Liver dysfunction is a known risk factor in the cardiovascular field. It specifically increases perioperative risk in patients undergoing coronary bypass surgery. Since percutaneous coronary intervention (PCI) is the much less invasive procedure for the treatment of coronary artery disease, we aimed to assess the relationship of liver dysfunction with outcomes in patients undergoing PCI. Methods Three libraries were searched (MEDLINE, Web of Science and The Cochrane Library). We performed a meta-analysis of all studies in patients who underwent PCI that provided information on the presence or absence of liver dysfunction. Primary outcome was short-term mortality. Secondary outcomes were major adverse cardio- and cerebrovascular events (MACCE), bleeding and acute kidney injury. Random-effects model was applied. Results Five studies were selected and the data from 10,710,317 patients were included in the final analysis. In comparison with the absence of liver dysfunction, patients with liver dysfunction were associated with higher short-term mortality (OR 2.97, 95%CI 1.23–7.18, p = 0.02), higher MACCE (OR 1.42, 95%CI 1.08–1.87, p = 0.01), and higher bleeding (OR 2.23, 95%CI 1.65-3.00, p

Background: Transcatheter Aortic Valve Implantation (TAVI) and Surgical Aortic Valve Replacement (SAVR) have different levels of invasiveness which can result in different levels of functional status after the procedure. Methods: We performed a systematic review and meta-analysis to detect studies showing direct comparison between TAVI and SAVR regarding postoperative functional status. The primary endpoint was the incidence of postoperative delirium (POD) after TAVI or SAVR, assessed using the Confusion Assessment Method (CAM). Secondary endpoints included 30-day mortality, stroke, major bleeding, and hospital length of stay (LOS). Results: We identified 1,161 manuscripts, of which 10 studies (12,015 patients) were analyzed. TAVI patients had a significantly lower incidence of POD (OR: 0.35, 95 % CI, 0.26–0.48, p

Objective: Randomized evidence suggests a high risk of pacemaker implantation for patients undergoing mitral valve (MV) surgery with concomitant tricuspid valve repair (cTVR). We investigated the impact of cTVR on outcomes in the Mini-Mitral International Registry. Methods: From 2015 to 2021, 7513 patients underwent minimally invasive MV with or without cTVR in 17 international centers (MV: n = 5609, cTVR: n = 1113). Propensity matching generated 1110 well-balanced pairs. Multivariable analysis was applied. Results: Patients with cTVR were older and had more comorbidities. Propensity matching eliminated most differences except for more TR in patients who underwent cTVR (77.2% vs 22.1% MV, P

Abstract In an era focused on value-based healthcare, the quality of healthcare and resource allocation should be underpinned by empirical evidence. Pragmatic clinical trials (pRCTs) are essential in this endeavor, providing randomized controlled trial (RCT) insights that encapsulate real-world effects of interventions. The rising popularity of pRCTs can be attributed to their ability to mirror real-world practices, accommodate larger sample sizes, and provide cost advantages over traditional RCTs. By harmonizing efficacy with effectiveness, pRCTs assist decision-makers in prioritizing interventions that have a substantial public health impact and align with the tenets of value-based health care. An international network for pRCT provides several advantages, including larger and diverse patient populations, access to a broader range of healthcare settings, sharing knowledge and expertise, and overcoming ethical and regulatory barriers. The hypothesis and study design of pRCT answers the decision-maker’s questions. pRCT compares clinically relevant alternative interventions, recruits participants from diverse practice settings, and collects data on various health outcomes. They are scarce because the medical products industry typically does not fund pRCT. Prioritizing these studies by expanding the infrastructure to conduct clinical research within the healthcare delivery system and increasing public and private funding for these studies will be necessary to facilitate pRCTs. These changes require more clinical and health policy decision-makers in clinical research priority setting, infrastructure development, and funding. This paper presents a comprehensive overview of pRCTs, emphasizing their importance in evidence-based medicine and the advantages of an international collaborative network for their execution. It details the development of PRIME-9, an international initiative across nine countries to advance pRCTs, and explores various statistical approaches for these trials. The paper underscores the need to overcome current challenges, such as funding limitations and infrastructural constraints, to leverage the full potential of pRCTs in optimizing healthcare quality and resource utilization.

Background Infective endocarditis represents a life‐threatening disease with high mortality rates. A fraction of patients receives exclusively conservative antibiotic treatment due to their comorbidities and high operative risk, despite fulfilling criteria for surgical therapy. The aim of the present study is to compare outcomes in patients with infective endocarditis and indication for surgical therapy in those who underwent or did not undergo valve surgery. Methods and Results Three databases were systematically assessed. A pooled analysis of Kaplan–Meier–derived reconstructed time‐to‐event data from studies with longer follow‐up comparing conservative and surgical treatment was performed. A landmark analysis to further elucidate the effect of surgical intervention on mortality was carried out. Four studies with 3003 patients and median follow‐up time of 7.6 months were included. Overall, patients with an indication for surgery who were surgically treated had a significantly lower risk of mortality compared with patients who received conservative treatment (hazard ratio [HR], 0.27 [95% CI, 0.24–0.31], P

Abstract Mechanisms of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) differ as CABG provides surgical collateralization and may prolong life by preventing future myocardial infarctions (MI). However, CABG benefits are unclear in octogenarians, where surgical risk is often perceived as higher and PCI is chosen more liberally. We performed a meta-analysis of studies comparing outcomes in octogenarians with left main or multivessel disease who underwent CABG or PCI. Primary outcome was late mortality (> 5 years). Secondary outcomes were perioperative mortality, MI, re-revascularization (R-R), acute renal failure (ARF), and stroke. Fourteen studies with 17,942 patients were included. CABG was associated with lower late mortality (hazard ratio, HR: 1.23, 95% confidence interval: CI 1.05–1.44, p

We present the case of a minimally invasive surgical correction for failed percutaneous atrial septal defect (ASD) closure in a 57-year-old female patient with residual ASD, tricuspid regurgitation, atrial fibrillation, and embolization of one of two occluders to the superior mesenteric artery. Our surgical approach consisted of anterolateral minithoracotomy, aortic and femoral vein cannulation, cryoablation, cardiac device removal, closure of ASD with autologous pericardium, and tricuspid repair. The procedure was uneventful and patient was discharged home on postoperative day 4.

Cardiomyocytes depend on mitochondrial oxidative phosphorylation (OXPHOS) for energy metabolism, which is facilitated by the mitochondrial electron transfer system (ETS). In a series of thermogenic redox reactions, electrons are shuttled through the ETS to oxygen as the final electron acceptor. This electron transfer is coupled to proton translocation across the inner mitochondrial membrane, which itself is the main driving force for ATP production. Oxygen availability is thus a prerequisite for ATP production and consequently contractility. Notably, cardiomyocytes are exceptionally large cells and densely packed with contractile structures, which constrains intracellular oxygen distribution. Moreover, oxygen must pass through layers of actively respiring mitochondria to reach the ones located in the innermost contractile compartment. Indeed, uneven oxygen distribution was observed in cardiomyocytes, suggesting that local ATP supply may also vary according to oxygen availability. Here, we discuss how spatial adjustment of bioenergetics to intracellular oxygen fluctuations may underlie cardiac contractile adaptation and how this adaptation may pose a risk for the development of contractile failure.

Abstract There is an ongoing debate whether coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) provide better results for the treatment of coronary artery disease (CAD). We aimed to evaluate the impact of CABG or PCI on long-term survival based on local reports from different regions in the world. We systematically searched MEDLINE selecting studies that compared outcomes for CABG or PCI as a treatment for CAD in the last 10 years. Reports without all-cause mortality, multi-national cohorts, hybrid revascularization populations were excluded. Qualifying studies were statistically compared, and their geographic location visualized on a world map. From 5126 studies, one randomized and twenty-two observational studies (19 risk-adjusted) met the inclusion criteria. The mean follow-up was 4.7 ± 7 years and 18 different countries were included. In 17 studies, CABG was associated with better survival during follow-up, six studies showed no significant difference, and no study favored PCI. Periprocedural mortality was not different in seven, lower with PCI in one, lower with CABG in three and not reported in 12 studies. In regional registry-type comparisons, CABG is associated with better long-term survival compared to PCI in most regions of the world without evidence for higher periprocedural mortality.

Objectives: The Prospective Randomized On-X Mechanical Prosthesis Versus St Jude Medical Mechanical Prosthesis Evaluation (PROSE) trial purpose was to investigate whether a current-generation mechanical prosthesis (On-X; On-X Life Technologies/Artivion Inc) reduced the incidence of thromboembolic-related complications compared with a previous-generation mechanical prosthesis (St Jude Medical Mechanical Prosthesis; Abbott/St Jude Medical). This second report documents the valve-related complications by individual prostheses and by Western and Developing populations. Methods: The PROSE trial study was conducted in 28 worldwide centers and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The study protocol, and analyses of 10 demographic variables and 24 risk factors were published in detail in 2021. Results: The total patient population (N = 855) included patients receiving an On-X valve (n = 462) and a St Jude Medical valve (n = 393). The overall freedom evaluation showed no differences at 5 years between the prostheses for thromboembolism or for valve thrombosis. There were also no differences in mortality. There were several differences between Developing and Western populations. The freedom relations at 5 years for mortality favored Western over Developing populations. Valve thrombosis was differentiated by position and site: aortic

Objective: This study assesses predictors for postoperative delirium (POD) and ICU stay durations in HFrEF patients undergoing CABG, focusing on ONCAB versus OPCAB surgical methods. Summary Background Data: In cardiac surgery, especially CABG, POD significantly impacts patient recovery and healthcare resource utilization. With varying incidences based on surgical techniques, this study provides an in-depth analysis of POD in the context of HFrEF patients, a group particularly susceptible to this complication. Methods: A retrospective analysis of 572 patients who underwent isolated CABG surgery with a preoperative ejection fraction under 40% was conducted at four German university hospitals. Patients were categorized into ONCAB and OPCAB groups for comparative analysis. Results: Age and Euro Score II were significant predictors of POD. The ONCAB group showed higher incidences of re-sternotomy (OR: 3.37), ECLS requirement (OR: 2.29), and AKI (OR: 1.49), whereas OPCAB was associated with a lower incidence of delirium. Statistical analysis indicated a significant difference in ICU stay durations between the two groups, influenced by surgical complexity and postoperative complications. Conclusions: This study underscores the importance of surgical technique in determining postoperative outcomes in HFrEF patients undergoing CABG. OPCAB may offer advantages in reducing POD incidence. These findings suggest the need for tailored surgical decisions and comprehensive care strategies to enhance patient recovery and optimize healthcare resources.

Exercise capacity has been related to morbidity and mortality. It consists of an inherited and an acquired part and is dependent on mitochondrial function. We assessed skeletal muscle mitochondrial function in rats with divergent inherited exercise capacity and analyzed the effect of exercise training. Female high (HCR)- and low (LCR)-capacity runners were trained with individually adapted high-intensity intervals or kept sedentary. Interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria from gastrocnemius muscle were isolated and functionally assessed (age: 15 weeks). Sedentary HCR presented with higher exercise capacity than LCR paralleled by higher citrate synthase activity and IFM respiratory capacity in skeletal muscle of HCR. Exercise training increased exercise capacity in both HCR and LCR, but this was more pronounced in LCR. In addition, exercise increased skeletal muscle mitochondrial mass more in LCR. Instead, maximal respiratory capacity was increased following exercise in HCRs’ IFM only. The results suggest that differences in skeletal muscle mitochondrial subpopulations are mainly inherited. Exercise training resulted in different mitochondrial adaptations and in higher trainability of LCR. HCR primarily increased skeletal muscle mitochondrial quality while LCR increased mitochondrial quantity in response to exercise training, suggesting that inherited aerobic exercise capacity differentially affects the mitochondrial response to exercise training.

Background: This retrospective multicenter study investigates the impact of obesity on short-term surgical outcomes in patients with heart failure and reduced ejection fraction (HFrEF) undergoing coronary artery bypass grafting (CABG). Given the rising global prevalence of obesity and its known cardiovascular implications, understanding its specific effects in high-risk groups like HFrEF patients is crucial. Methods: The study analyzed data from 574 patients undergoing CABG across four German university hospitals from 2017 to 2023. Patients were stratified into ‘normal weight’ (n = 163) and ‘obese’ (n = 158) categories based on BMI (WHO classification). Data on demographics, clinical measurements, health status, cardiac history, intraoperative management, postoperative outcomes, and laboratory insights were collected and analyzed using Chi-square, ANOVA, Kruskal–Wallis, and binary logistic regression. Results: Key findings are a significant higher mortality rate (6.96% vs. 3.68%, p = 0.049) and younger age in obese patients (mean age 65.84 vs. 69.15 years, p = 0.003). Gender distribution showed no significant difference. Clinical assessment scores like EuroScore II and STS Score indicated no differences. Paradoxically, the preoperative left ventricular ejection fraction (LVEF) was higher in the obese group (32.04% vs. 30.34%, p = 0.026). The prevalence of hypertension, COPD, hyperlipidemia, and other comorbidities did not significantly differ. Intraoperatively, obese patients required more packed red blood cells (p = 0.026), indicating a greater need for transfusion. Postoperatively, the obese group experienced longer hospital stays (median 14 vs. 13 days, p = 0.041) and higher ventilation times (median 16 vs. 13 h, p = 0.049). The incidence of acute kidney injury (AKI) (17.72% vs. 9.20%, p = 0.048) and delirium (p = 0.016) was significantly higher, while, for diabetes prevalence, there was an indicating a trend towards significance (p = 0.051) in the obesity group, while other complications like sepsis, and the need for ECLS were similar across groups. Conclusions: The study reveals that obesity significantly worsens short-term outcomes in HFrEF patients undergoing CABG, increasing risks like mortality, kidney insufficiency, and postoperative delirium. These findings highlight the urgent need for personalized care, from surgical planning to postoperative strategies, to improve outcomes for this high-risk group, urging further tailored research.

Objective: This study aimed to compare postoperative outcomes and 30-day mortality in patients with reduced ejection fraction (

Abstract Non-ST-elevation acute coronary syndrome (NSTE-ACS) affects millions of patients. Although an invasive strategy can improve survival, the optimal treatment [i.e., percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] is not clear. We performed a meta-analysis of studies reporting outcomes between PCI and CABG in patients with NSTE-ACS. MEDLINE, EMBASE and Cochrane Library were assessed. The primary outcome was long-term mortality. Inverse variance method and random model were performed. We identified 13 observational studies (48,891 patients). No significant difference was found in the primary endpoint [CABG vs. PCI, incidence rate ratio (IRR) 0.93, 95% confidence interval (CI) 0.70; 1.23]. CABG was associated with lower long-term major adverse cardiovascular events (MACE) (IRR 0.64, 95% CI 0.54; 0.76) and lower long-term re-revascularization (IRR 0.37, 95% CI 0.30; 0.47). There was no significant difference in long-term myocardial infarction (CABG vs. PCI, IRR 0.96, 95% CI 0.50; 1.84) and peri-operative mortality (CABG vs. PCI, odds ratio 1.36, 95% CI 0.94; 1.95). For the treatment of NSTE-ACS, CABG and PCI are associated with similar rates of long-term mortality and myocardial infarction. CABG is associated with lower rates of long-term MACE and re-revascularization. Randomized comparisons in this setting are necessary.

Abstract Objectives The PROSE trial purpose is to investigate whether the incidence of thromboembolic—related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc.—On-X) compared with a previous generation mechanical prosthesis (St Jude Medical—SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations. Methods The PROSE study was conducted in 28 worldwide centres and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors. Results The total patient population (855) incorporated On-X population (462) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic and mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population. Conclusions The preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations.

Minimally invasive techniques in cardiac surgery have found increasing use in recent years. Both patients and physicians often associate smaller incisions with improved outcomes (i.e., less risk, shorter hospital stay, and a faster recovery). Videoscopic and robotic assistance has been introduced, but their routine use requires specialized training and is associated with potentially longer operating times and higher costs. Randomized evidence is scarce and transcatheter treatment alternatives are increasing rapidly. As a result, the concept of minimally invasive cardiac surgery may be viewed with skepticism. In this review, we examine the current status and potential future perspectives of minimally invasive and robotic cardiac surgery.

Background: Left ventricular assist devices (LVAD) and extracorporeal membrane oxygenation (ECMO) are well established therapies in heart failure (HF) management. Their use is generally associated with a sudden increase in inflammatory mediators, which are often already elevated in patients with HF prior to device implantation. An exaggerated release of proinflammatory cytokines is associated with organ dysfunction and increased mortality. Hemoadsorption has been shown to reduce inflammatory mediators during cardiopulmonary bypass. Objective: To investigate the role of hemoadsorption during the management of acute or chronic heart failure with mechanical circulatory support and its impact on survival. Methods: We systematically searched MEDLINE selecting all studies comparing the use of hemoadsorption during LVAD implantation or veno-arterial (v.a.) ECMO therapy. Records were screened by two different investigators. Reports without a control group and duplicates were excluded. Results: Our search delivered six studies. One was randomized and five were retrospective studies, of which three were risk-adjusted. During LVAD implantation, one study showed no difference in mortality but higher incidence of respiratory insufficiency in the hemoadsorption group (54% vs 30%, p = 0.024) and the other study found higher mortality in the hemoadsorption group (33% vs 0%, p = 0.01). During ECMO therapy, three of four studies including the randomized one found no difference in survival or major adverse cardiac events between the hemoadsorption and the control groups. Only one study found lower mortality in the hemoadsorption group (20% vs 60%. p = 0.02). Conclusions: The results of this literature review suggest that the use of hemoadsorption in patients undergoing LVAD implantation might be associated with higher morbidity and mortality. The majority of studies on the use of hemoadsorption during v.a. ECMO therapy showed no effect on mortality or organ dysfunction, while only one small study showed that hemoadsorption was able to reduce mortality. The results are limited by the retrospective nature and the small sample sizes of the majority of the studies included.

Despite considerable progress in treating cardiac disorders, the prevalence of heart failure (HF) keeps growing, making it a global medical and economic burden. HF is characterized by profound metabolic remodeling, which mostly occurs in the mitochondria. Although it is well established that the failing heart is energy-deficient, the role of mitochondria in the pathophysiology of HF extends beyond the energetic aspects. Changes in substrate oxidation, tricarboxylic acid cycle and the respiratory chain have emerged as key players in regulating myocardial energy homeostasis, Ca2+ handling, oxidative stress and inflammation. This work aims to highlight metabolic alterations in the mitochondria and their far-reaching effects on the pathophysiology of HF. Based on this knowledge, we will also discuss potential metabolic approaches to improve cardiac function.

Background Intracranial hemorrhage (ICH) is one of the main causes for lack of surgery in patients with infective endocarditis (IE), despite the presence of surgical indications. We aimed to evaluate the impact of early surgery in patients with IE and with ICH on postoperative neurological deterioration and all‐cause mortality and to elucidate the risk of 30‐day mortality in patients who were denied surgery. Methods and Results Three libraries (MEDLINE, EMBASE, and Cochrane Library) were assessed. The primary outcome was all‐cause mortality, and the secondary outcome was neurological deterioration. Inverse variance method and random model were performed. We identified 16 studies including 355 patients. Nine studies examined the impact of surgical timing (early versus late) and were included in the meta‐analysis. Only one study examined the fate of patients with IE and with ICH who were treated conservatively despite having an indication for cardiac surgery, showing higher mortality rates than those who underwent surgery (11.8% versus 2.5%). We found no significant association between early surgery, regardless of its definition, and a higher mortality (odds ratio [OR], 1.69; 95% CI, 0.95–3.02). Early surgery was associated with higher risk for neurological deterioration (OR, 2.00; 95% CI, 1.10–3.65). Conclusions Cardiac surgery for IE within 30 days of ICH was not associated with higher mortality, but with an increased rate of neurological deterioration. The 30‐day mortality in patients with IE and with ICH who were denied surgery has not yet been sufficiently investigated. This patient group should be analyzed in future studies in more detail.

We report the rare case of a 51-year-old patient with a 15 cm mediastinal rhabdomyosarcoma with blood supply from the left anterior descending artery presenting as a large mass including the pericardium with extensive contact to the epicardium compressing heart and left lung. The tumor was successfully removed through median sternotomy, blunt dissection from the heart and the left lung, resection of the infiltrated pericardium, and ligation of the tumor-feeding vessels using off-pump stabilizers. Histopathological examination revealed a spindle cell rhabdomyosarcoma with R0 resection. The postoperative course was uneventful, and patient is feeling well at 3-month follow-up.

Abstract Two recent trials of transcatheter mitral‐valve repair in patients with functional mitral regurgitation (FMR) presented opposing results for the MitraClip® compared to medical therapy alone. The conflicting results gave rise to intensive discussions about assessment of mitral valve regurgitation (MR). A recent editorial viewpoint provided a potential explanation presenting a new pathophysiologic concept. However, the echocardiographic characterization of both trials' patients is inconsistent and the discussed concepts appear to suffer from plausibility weaknesses. It is well conceivable that limitations in the echocardiographic assessment of the trial patients introduced a bias regarding the selection of patients with severe (or less severe) MR that may be a more plausible explanation for the differences in outcome. We here illustrate our viewpoint regarding the two MitraClip trials and also illustrate the difficulties in assessing functional MR properly. It may indeed be “opening Pandora's box”, but we will also make an attempt to provide a solution.

The antitumor treatment NVP-AEW541 blocks IGF-1R. IGF-1R signaling is crucial for cardiac function, but the cardiac effects of NVP-AEW541 are ill defined. We assessed NVP-AEW541′s effects on cardiac function and insulin response in vivo and in isolated working hearts. We performed a dose–response analysis of NVP-AEW541 in male, 3-week-old rats and assessed the chronic effects of the clinically relevant dose in adult rats. We performed glucose tolerance tests and echocardiography; assessed the expression and phosphorylation of InsR/IGF-1R and Akt in vivo; and measured substrate oxidation, contractile function, and insulin response in the isolated working hearts. NVP-AEW541 caused dose-dependent growth retardation and impaired glucose tolerance in the juvenile rats. In the adults, NVP-AEW541 caused a continuously worsening depression of cardiac contractility, which recovered within 2 weeks after cessation. Cardiac Akt protein and phosphorylation were unchanged and associated with InsR upregulation. An acute application of NVP-AEW541 in the working hearts did not affect cardiac power but eliminated insulin’s effects on glucose and fatty acid oxidation. The systemic administration of NVP-AEW541 caused dose- and time-dependent impairment of glucose tolerance, growth, and cardiac function. Because cardiac insulin signaling was maintained in vivo but absent in vitro and because contractile function was not affected in vitro, a direct link between insulin resistance and contractile dysfunction appears unlikely.

Angiotensin-converting enzyme 2 (ACE2) has been identified as the cellular entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High ACE2 tissue expression and low glycine levels were suggested to increase susceptibility for SARS-CoV-2 infection and increasing circulating ACE2 has been proposed as one possible strategy to combat COVID-19. In humans, aerobic physical exercise induces an increase in plasma ACE2 in some individuals. However, it is not clear whether glycine and ACE2 levels depend on intrinsic exercise capacity or on exercise training. We used rats selectively bred for high intrinsic exercise capacity (HCR) or low exercise capacity (LCR) and tested the influence of this genetic predetermination and/or aerobic exercise on metabolites, ACE2 tissue expression and circulating ACE 2. ACE2 expression was measured in different tissues in the sedentary animals and again after 4 weeks of high-intensity aerobic exercise in both LCRs and HCRs. Sedentary HCRs exhibited significantly higher circulating ACE2 concentrations compared to LCRs, but a lower expression of ACE2 in all investigated tissues except for adipose tissue. Body weight was negatively correlated with serum ACE2 and positively correlated with ACE2 expression in the heart. Aerobic exercise caused a significant decrease in ACE2 expression in the lung, heart, muscle, and kidney both in LCRs and HCRs. Our results suggest that ACE2 expression, circulating ACE2 and glycine serum concentration are related to aerobic intrinsic exercise capacity and can be influenced with exercise. These results may support the hypothesis that physically fit individuals have a lower susceptibility for COVID-19 infection.

Introduction The previously published SYNTAX III REVOLUTION trial demonstrated that clinical decision-making between coronary artery bypass graft (CABG) and percutaneous coronary intervention based on coronary CT angiography (CCTA) had a very high agreement with the treatment decision derived from invasive coronary angiography (ICA). The study objective of the FASTTRACK CABG is to assess the feasibility of CCTA and fractional flow reserve derived from CTA (FFRCT) to replace ICA as a surgical guidance method for planning and execution of CABG in patients with three-vessel disease with or without left main disease.Methods and analysis The FASTTRACK CABG is an investigator-initiated single-arm, multicentre, prospective, proof-of-concept and first-in-man study with feasibility and safety analysis. Surgical revascularisation strategy and treatment planning will be solely based on CCTA and FFRCT without knowledge of the anatomy defined by ICA. Clinical follow-up visit including CCTA will be performed 30 days after CABG in order to assess graft patency and adequacy of the revascularisation with respect to the surgical planning based on non-invasive imaging (CCTA) with functional assessment (FFRCT) and compared with ICA. Primary feasibility endpoint is CABG planning and execution solely based on CCTA and FFRCT in 114 patients. Primary safety endpoint based on 30 day CCTA is graft assessment and topographical adequacy of the revascularisation procedure. Automatic non-invasive assessment of functional coronary anatomy complexity is also evaluated with FFRCT for functional Synergy Between percutaneous coronary intervention With Taxus and Cardiac Surgery Score assessment on CCTA. CCTA with FFRCT might provide better anatomical and functional analysis of the coronary circulation leading to appropriate anatomical and functional revascularisation, and thereby contributing to a better outcome.Ethics and dissemination Each patient has to provide written informed consent as approved by the ethical committee of the respective clinical site. Results will be submitted for publication in peer-reviewed journals and will be disseminated at scientific conferences.Trial registration number NCT04142021.

Introduction Infective endocarditis (IE) is associated with high mortality and morbidity. Multiple organ failure is the main cause of death after surgery for IE. Cardiopulmonary bypass (CPB) can cause a systemic inflammatory response. In a pilot study (REMOVE-pilot (Revealing mechanisms and investigating efficacy of hemoad-sorption for prevention of vasodilatory shock in cardiac surgery patients with infective endocarditis – a multicentric randomized controlled group sequential trial)), we found that plasma profiles of cytokines during and after CPB were higher in patients with IE compared with patients with non-infectious valvular heart disease. Sequential Organ Failure Assessment (SOFA) scores on the first and second postoperative days and in-hospital mortality were also higher in IE patients. This protocol describes the design of the REMOVE trial on cytokine-adsorbing columns, for example, CytoSorb, for non-selective removal of cytokines. The aim of the REMOVE study is to demonstrate efficacy of CytoSorb on the prevention of multiorgan dysfunction in patients with IE undergoing cardiac surgery.Methods and analysis The REMOVE study is an interventional randomised controlled multicenter trial with a group sequential (Pocock) design for assessing efficacy of CytoSorb in patients undergoing cardiac surgery for IE. The change in mean total SOFA (∆ SOFA) score between preoperative and postoperative care will be used as primary endpoint. Data on 30-day mortality, changes in cytokines levels, duration of mechanical ventilation, length of intensive care unit and hospital stay, and postoperative stroke will be collected as secondary endpoints. An interim analysis will be conducted after including 25 participating patients per study arm (with a focus on feasibility of the recruitment as well as differences in cytokines and cell-free DNA levels).Ethics and dissemination The protocol was approved by the institutional review board and ethics committee of the University of Jena as well as by the corresponding ethics committee of each participating study centre. The results will be published in a renowned international medical journal, irrespective of the outcomes of the study.Trial registration number The ClinicalTrials.gov registry (NCT03266302).

BACKGROUND:More than 50% of patients with infective endocarditis (IE) develop an indication for surgery. Despite its benefit, surgery is associated with a high incidence of multiple organ dysfunction syndrome (MODS) and mortality, which may be linked to increased release of inflammatory mediators during cardiopulmonary bypass (CPB). We therefore assessed plasma cytokine profiles in patients undergoing valve surgery with or without IE. METHODS:We performed a prospective case-control pilot study comparing patients undergoing cardiac valve surgery with or without IE. Plasma profiles of inflammatory mediators were measured at 7 defined time points and reported as median (interquartile). The degree of MODS was measured using sequential organ failure assessment (SOFA) score. RESULTS:Between May and December 2016 we included 40 patients (20 in each group). Both groups showed similar distribution of age and gender. Patients with IE had higher preoperative SOFA (6.9± 2.6 vs 3.8 ± 1.1, p

Coronary artery fistulae are an incidental finding in patients undergoing coronary angiography or computed tomography (CT) coronary angiography. A 60-year-old man with known coronary artery disease presented with dyspnea. Coronary angiography revealed a large fistula arising from the circumflex artery (CX) without a clear intrathoracic target vessel or chamber in the heart. CT angiography revealed the agenesis of the left pulmonary artery. The fistula arising from the CX ensured left lung tissue supply. Unilateral absence of a pulmonary artery is an extremely rare condition. In this case, the identification of a fistula from the heart triggered the correct diagnosis.

How the cardiac myocyte epigenome is rearranged during development, postnatal maturation and disease is not well understood. Here, the authors investigate the human cardiac myocyte epigenome during development and chronic heart failure and identify distinct epigenetic programs regulating these processes.

A large (40-mm) circular structure in the right atrioventricular groove was detected by transthoracic echocardiography and was diagnosed as a giant aneurysm of the right coronary artery. Through invasive mapping by a guide extension catheter, the aneurysm could be excluded by implantation of 3 overlapping stent grafts. (Level of Difficulty: Beginner.)

Background We report the case of minimally invasive mitral valve repair in an 86-year-old female with symptomatic structural mitral regurgitation and severe pectus excavatum. Case Description The case summarizes four areas of repetitive heart team discussions. First, should an 86-year-old patient still be treated invasively? Second, if so, should treatment be interventional or surgical? Third, if surgical, should we replace or repair at that age and fourth which surgical access is best with respect to her chest deformation? Conclusion We chose to surgically repair the valve using a minimally invasive approach. The patient was extubated 3 hours after surgery and discharged after 7 days.

With a lung ultrasound (LUS) the typical findings are interstitial pneumonia. COVID-19 pneumonia is often manifested in sub-pleural areas, which is preferably detected by sonography. An RT-PCR test cannot always ensure a safe differentiation of COVID-19- and non-diseased cases. Clinically challenging is that a reliable and time efficient decision regarding COVID-19 suspects requiring isolation. Therefore, this study was aimed at evaluating the significance of LUS in symptomatic patients with COVID-19 suspicion at hospital admission. A total of 101 patients admitted to a suspect ward with COVID-19-typical symptoms were assessed. All patients received prospectively a standardized LUS at admission. Patients were classified as LUS-positive and -negative cases based on a specific LUS score. The RT-PCR test in combination with the clinical findings served as a reference. Correctly classified were 14/15 COVID-19 diseased suspects as LUS-positive (sensitivity: 93.3%). Twenty-seven out of 61 non-positive cases were classified as false positive with LUS (specificity: 55.7%). In 34/35 patients who were assessed as LUS negative, no COVID-19 disease was detected during the hospitalization. The PPV and NPV of the LUS were 34.1% and 97.1%. LUS is a valuable tool in symptomatic patients for the assessment of COVID-19-disease. The high negative predictive value of LUS is helpful to rule out the disease.

Abstract Advanced glycation end products (AGE) have been implicated in diabetes associated complications. They have been suggested as potential mediators in the progression of diabetic heart failure and as a potential target for treatment. Brunvand et al. now provided evidence in that the suggested causal relationship between AGE and diastolic myocardial dysfunction cannot be confirmed in children with type 1 diabetes. The early signs of diastolic myocardial impairment were associated with higher BMI, but not with HbA1c levels. Furthermore, higher serum levels of MG-H1 and increased arterial stiffness were not significantly associated with diastolic dysfunction. The lack of association argues against an essential role of AGEs. This sobering finding does not support the potential to treat diastolic dysfunction by reduction approaches AGE in type 1 diabetic patients. Further pathogenic mechanisms involved in diabetic cardiomyopathy, such as alterations of calcium metabolism, or remodeling of the extracellular matrix, and intramyocardial inflammation may be further promising therapeutic targets.

Background Insulin resistance in diabetes mellitus has been associated with mitochondrial dysfunction. Defects at the level of mitochondria are also characteristic of heart failure. We assessed changes in cardiac insulin response and mitochondrial function in a model of pressure overload‐induced heart failure. Methods and Results Rats underwent aortic banding to induce pressure overload. At 10 weeks, rats showed cardiac hypertrophy and pulmonary congestion, but left ventricular dilatation and systolic dysfunction were only evident after 20 weeks. This contractile impairment was accompanied by mitochondrial dysfunction as shown by markedly reduced state 3 respiration of isolated mitochondria. Aortic banding did not affect systemic insulin response. However, insulin‐stimulated cardiac glucose uptake and glucose oxidation were significantly diminished at 10 and 20 weeks, which indicates cardiac insulin resistance starting before the onset of mitochondrial and contractile dysfunction. The impaired cardiac insulin action was related to a decrease in insulin‐stimulated phosphorylation of insulin receptor β. Consistently, we found elevated activity of protein tyrosine phosphatase 1B (PTP1B) at 10 and 20 weeks, which may blunt insulin action by dephosphorylating insulin receptor β. PTP1B activity was also significantly increased in left ventricular samples of patients with systolic dysfunction undergoing aortic valve replacement because of aortic stenosis. Conclusions Pressure overload causes cardiac insulin resistance that precedes and accompanies mitochondrial and systolic dysfunction. Activation of PTP1B in the heart is associated with heart failure in both rats and humans and may account for cardiac insulin resistance. PTP1B may be a potential target to modulate insulin sensitivity and contractile function in the failing heart.

Abstract Perforation of the heart or great vessels by orthopedic wires is a rare complication that mostly results in severe or even lethal organ injury. Therefore, such conditions mostly require immediate surgical removal of the wires. However, in some individual cases, a conservative approach may be preferable. We describe a case of a 70-year-old woman whose aortic arch has been penetrated by two Kirschner wires used for fixation of a right clavicle fracture 13 years ago. Notably, the complication was an incidental finding during computed tomography angiography for clarification of transient nonspecific neurological symptoms.

Female sex is considered a significant risk in cardiac surgery and is included in the majority of scores for risk assessment. However, the evidence is controversial and older women undergoing cardiac surgery have not specifically been investigated. We assessed the influence of female sex on surgical risk (30-day mortality) in a secondary analysis of the GOPCABE trial (German Off-Pump Coronary Artery Bypass grafting in the Elderly (GOPCABE) trial, comparing on- to off-pump) and also evaluated its impact on risk prediction from commonly used risk scores.We performed logistic regression analyses on the GOPCABE trial population, where patients were randomized to either on- or off-pump CABG. The study was performed in 12 cardiac surgery centers in Germany and analyzed 2394 patients having undergone CABG at age ≥75 years (1187 on-pump, 1207 off-pump). Of the 2394 patients, 755 (32%) were women. The logistic EuroSCORE and the German KCH score were calculated as expected (E) mortality and values were compared to observed (O) 30-day mortality (O/E ratio).There was no difference in mortality or major cardiovascular adverse events after 30 days between men and women for both on- and off-pump CABG (men: on- vs. off-pump OR = 0.90, 95%-CI: [0.63;1.27]; women: on- vs. off-pump OR = 1.07, 95%-CI: [0.62;1.87]). Therefore, groups were combined for further analyses. Both men and women had considerable and similar comorbidities. Expected mortality was significantly higher for women than for men (logistic EuroSCORE: 8.88±6.71% vs. 7.99±6.69%, p = 0.003; KCH score: 4.42±3.97% vs. 3.57±3.65%, p = 0.001). However, observed mortality rates (O) tended to be even lower in women (2.1% vs. 3.0%). The O/E ratio was closer to 1 in men than in women (0.84 vs. 0.47). Excluding female sex from the risk models increased O/E ratio to 0.69.Female sex is not a risk factor in coronary bypass surgery in the GOPCABE population. The result is the same for on- and off-pump surgery. Since female sex is a component of most risk scores, the findings may identify a potential inaccuracy in current surgical risk assessment, specifically for elderly women.Clinicaltrials.gov GOPCABE trial No. NCT00719667.

A 52-year-old heart–lung transplant patient presented to the emergency department with acute onset of neurologic symptoms. MRI showed ballooning of the left ventricle, midline shift and contrast enhancement in the anterior horn of the left ventricle. Ventricle neuroendoscopy revealed whitish, floccose aerial structures within the left ventricle. Brain biopsy cultures grew Rhizopus arrhizus. Therapy with liposomale amphotericin B and posaconazole was performed. Except for hemianopsia and deficits in minute motor activity, the patient completely recovered.

Adiponectin deficiency leads to increased myocardial infarct size following ischemia reperfusion and to exaggerated cardiac hypertrophy following pressure overload, entities that are causally linked to mitochondrial dysfunction. In skeletal muscle, lack of adiponectin results in impaired mitochondrial function. Thus, it was our objective to investigate whether adiponectin deficiency impairs mitochondrial energetics in the heart. At 8 weeks of age, heart weight-to-body weight ratios were not different between adiponectin knockout (ADQ-/-) mice and wildtypes (WT). In isolated working hearts, cardiac output, aortic developed pressure and cardiac power were preserved in ADQ-/- mice. Rates of fatty acid oxidation, glucose oxidation and glycolysis were unchanged between groups. While myocardial oxygen consumption was slightly reduced (-24%) in ADQ-/- mice in isolated working hearts, rates of maximal ADP-stimulated mitochondrial oxygen consumption and ATP synthesis in saponin-permeabilized cardiac fibers were preserved in ADQ-/- mice with glutamate, pyruvate or palmitoyl-carnitine as a substrate. In addition, enzymatic activity of respiratory complexes I and II was unchanged between groups. Phosphorylation of AMP-activated protein kinase and SIRT1 activity were not decreased, expression and acetylation of PGC-1α were unchanged, and mitochondrial content of OXPHOS subunits was not decreased in ADQ-/- mice. Finally, increasing energy demands due to prolonged subcutaneous infusion of isoproterenol did not differentially affect cardiac contractility or mitochondrial function in ADQ-/- mice compared to WT. Thus, mitochondrial and contractile function are preserved in hearts of mice lacking adiponectin, suggesting that adiponectin may be expendable in the regulation of mitochondrial energetics and contractile function in the heart under non-pathological conditions.

BACKGROUND: Diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF) may result in pulmonary congestion and lung remodeling. We evaluated the usefulness of major diastolic echocardiographic parameters and of the deceleration rate of early transmitral diastolic velocity (E/DT) in predicting lung remodeling in a rat model of HFpEF. METHODS AND RESULTS: Rats underwent aortic banding (AoB) to induce pressure overload (PO). Left ventricular hypertrophy fully developed 2 weeks after AoB. At 4 and 6 weeks, the lung weight-to-body weight ratio (LW/BW), a sensitive marker for pulmonary congestion and remodeling, dramatically increased despite preserved fractional shortening, indicating the presence of HFpEF. The time course of LW/BW was well reflected by E/DT, by the ratio of early to late transmitral diastolic velocity (E/A) and the deceleration time of E (DT), but not by the ratio of transmitral to mitral annular early diastolic velocity (E/e'). In agreement, the best correlation with LW/BW was found for E/DT (r = 0.76; p