BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection.

Cardiac injury and dysfunction occur in COVID-19 patients and increase the risk of mortality. Causes are ill defined but could be through direct cardiac infection and/or inflammation-induced dysfunction. To identify mechanisms and cardio-protective drugs, we use a state-of-the-art pipeline combining human cardiac organoids with phosphoproteomics and single nuclei RNA sequencing. We identify an inflammatory "cytokine-storm", a cocktail of interferon gamma, interleukin 1ß, and poly(I:C), induced diastolic dysfunction. Bromodomain-containing protein 4 is activated along with a viral response that is consistent in both human cardiac organoids (hCOs) and hearts of SARS-CoV-2-infected K18-hACE2 mice. Bromodomain and extraterminal family inhibitors (BETi) recover dysfunction in hCOs and completely prevent cardiac dysfunction and death in a mouse cytokine-storm model. Additionally, BETi decreases transcription of genes in the viral response, decreases ACE2 expression, and reduces SARS-CoV-2 infection of cardiomyocytes. Together, BETi, including the Food and Drug Administration (FDA) breakthrough designated drug, apabetalone, are promising candidates to prevent COVID-19 mediated cardiac damage.

Lysozyme 1 Inflamed CCR2+ Macrophages Promote Obesity-Induced Cardiac Dysfunction.

BACKGROUND: Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage's role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response. METHODS: In this study, we used single-cell RNA-sequencing analysis of Cd45+CD11b+F4/80+ cardiac macrophages to explore the heterogeneity of cardiac macrophages. The CCR2+ (C-C chemokine receptor 2) macrophages were specifically removed by a dual recombinase approach, and the macrophage CCR2 was deleted to investigate their functions. We also performed cleavage under target and tagmentation analysis, chromatin immunoprecipitation-polymerase chain reaction, luciferase assay, and macrophage-specific lentivirus transfection to define the impact of lysozyme C in macrophages on obesity-induced inflammation. RESULTS: We find that the Ccr2 cluster undergoes a functional transition from homeostatic maintenance to proinflammation. Our data highlight specific changes in macrophage behavior during cardiac dysfunction under metabolic challenge. Consistently, inducible ablation of CCR2+CX3CR1+ macrophages or selective deletion of macrophage CCR2 prevents obesity-induced cardiac dysfunction. At the mechanistic level, we demonstrate that the obesity-induced functional shift of CCR2-expressing macrophages is mediated by the CCR2/activating transcription factor 3/lysozyme 1/NF-κB (nuclear factor kappa B) signaling. Finally, we uncover a noncanonical role for lysozyme 1 as a transcription activator, binding to the RelA promoter, driving NF-κB signaling, and strongly promoting inflammation and cardiac dysfunction in obesity. CONCLUSIONS: Our findings suggest that lysozyme 1 may represent a potential target for the diagnosis of obesity-induced inflammation and the treatment of obesity-induced heart disease.

Cardiovascular Management of Patients Undergoing Hematopoietic Stem Cell Transplantation: From Pretransplantation to Survivorship: A Scientific Statement From the American Heart Association.

Hematopoietic stem cell transplantation can cure various disorders but poses cardiovascular risks, especially for elderly patients and those with cardiovascular diseases. Cardiovascular evaluations are crucial in pretransplantation assessments, but guidelines are lacking. This American Heart Association scientific statement summarizes the data on transplantation-related complications and provides guidance for the cardiovascular management throughout transplantation. Hematopoietic stem cell transplantation consists of 4 phases: pretransplantation workup, conditioning therapy and infusion, immediate posttransplantation period, and long-term survivorship. Complications can occur during each phase, with long-term survivors facing increased risks for late effects such as cardiovascular disease, secondary malignancies, and endocrinopathies. In adults, arrhythmias such as atrial fibrillation and flutter are the most frequent acute cardiovascular complication. Acute heart failure has an incidence ranging from 0.4% to 2.2%. In pediatric patients, left ventricular systolic dysfunction and pericardial effusion are the most common cardiovascular complications. Factors influencing the incidence and risk of complications include pretransplantation therapies, transplantation type (autologous versus allogeneic), conditioning regimen, comorbid conditions, and patient age. The pretransplantation cardiovascular evaluation consists of 4 steps: (1) initial risk stratification, (2) exclusion of high-risk cardiovascular disease, (3) assessment of cardiac reserve, and (4) optimization of cardiovascular reserve. Clinical risk scores could be useful tools for the risk stratification of adult patients. Long-term cardiovascular management of hematopoietic stem cell transplantation survivors includes optimizing risk factors, monitoring, and maintaining a low threshold for evaluating cardiovascular causes of symptoms. Future research should prioritize refining risk stratification and creating evidence-based guidelines and strategies to optimize outcomes in this growing patient population.

Gestational Hypoxia and Developmental Plasticity.

Hypoxia is one of the most common and severe challenges to the maintenance of homeostasis. Oxygen sensing is a property of all tissues, and the response to hypoxia is multidimensional involving complicated intracellular networks concerned with the transduction of hypoxia-induced responses. Of all the stresses to which the fetus and newborn infant are subjected, perhaps the most important and clinically relevant is that of hypoxia. Hypoxia during gestation impacts both the mother and fetal development through interactions with an individual's genetic traits acquired over multiple generations by natural selection and changes in gene expression patterns by altering the epigenetic code. Changes in the epigenome determine "genomic plasticity," i.e., the ability of genes to be differentially expressed according to environmental cues. The genomic plasticity defined by epigenomic mechanisms including DNA methylation, histone modifications, and noncoding RNAs during development is the mechanistic substrate for phenotypic programming that determines physiological response and risk for healthy or deleterious outcomes. This review explores the impact of gestational hypoxia on maternal health and fetal development, and epigenetic mechanisms of developmental plasticity with emphasis on the uteroplacental circulation, heart development, cerebral circulation, pulmonary development, and the hypothalamic-pituitary-adrenal axis and adipose tissue. The complex molecular and epigenetic interactions that may impact an individual's physiology and developmental programming of health and disease later in life are discussed.

Multimodality Cardiac Imaging in COVID.

Infection with SARS-CoV-2, the virus that causes COVID, is associated with numerous potential secondary complications. Global efforts have been dedicated to understanding the myriad potential cardiovascular sequelae which may occur during acute infection, convalescence, or recovery. Because patients often present with nonspecific symptoms and laboratory findings, cardiac imaging has emerged as an important tool for the discrimination of pulmonary and cardiovascular complications of this disease. The clinician investigating a potential COVID-related complication must account not only for the relative utility of various cardiac imaging modalities but also for the risk of infectious exposure to staff and other patients. Extraordinary clinical and scholarly efforts have brought the international medical community closer to a consensus on the appropriate indications for diagnostic cardiac imaging during this protracted pandemic. In this review, we summarize the existing literature and reference major societal guidelines to provide an overview of the indications and utility of echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging for the diagnosis of cardiovascular complications of COVID.

Adverse cardiac remodeling augments adipose tissue ß-adrenergic signaling and lipolysis counteracting diet-induced obesity.

Cardiac triacylglycerol accumulation is a common characteristic of obesity and type 2 diabetes and strongly correlates with heart morbidity and mortality. We have previously shown that cardiomyocyte-specific perilipin 5 overexpression (Plin5-Tg) provokes significant cardiac steatosis via lowering cardiac lipolysis and fatty acid (FA) oxidation. In strong contrast to cardiac steatosis and lethal heart dysfunction in adipose triglyceride lipase deficiency, Plin5-Tg mice do not develop heart dysfunction and show a normal life span on chow diet. This finding prompted us to study heart function and energy metabolism in Plin5-Tg mice fed high-fat diet (HFD). Plin5-Tg mice showed adverse cardiac remodeling on HFD with heart function only being compromised in one-year-old mice, likely due to reduced cardiac FA uptake, thereby delaying deleterious cardiac lipotoxicity. Notably, Plin5-Tg mice were less obese and protected from glucose intolerance on HFD. Changes in cardiac energy catabolism in Plin5-Tg mice increased ß-adrenergic signaling, lipolytic, and thermogenic protein expression in adipose tissue ultimately counteracting HFD-induced obesity. Acute cold exposure further augmented ß-adrenergic signaling in Plin5-Tg mice, whereas housing at thermoneutrality did not protect Plin5-Tg mice from HFD-induced obesity albeit blood glucose and insulin levels remained low in transgenic mice. Overall, our data suggest that the limited capacity for myocardial FA oxidation on HFD increases cardiac stress in Plin5-Tg mice, thereby stimulating adipose tissue ß-adrenergic signaling, triacylglycerol catabolism, and thermogenesis. However, long-term HFD-mediated metabolic stress causes contractile dysfunction in Plin5-Tg mice, which emphasizes the importance of a carefully controlled dietary regime in patients with cardiac steatosis and hypertrophy.

Sex-based differences in short- and longer-term diet-induced metabolic heart disease.

Sex-based differences in the development of obesity-induced cardiometabolic dysfunction are well documented, however, the specific mechanisms are not completely understood. Obesity has been linked to dysregulation of the epitranscriptome, but the role of N6-methyladenosine (m6A) RNA methylation has not been investigated in relation to the sex differences during obesity-induced cardiac dysfunction. In the current study, male and female C57BL/6J mice were subjected to short- and long-term high-fat/high-sucrose (HFHS) diet to induce obesogenic stress. Cardiac echocardiography showed males developed systolic and diastolic dysfunction after 4 mo of diet, but females maintained normal cardiac function despite both sexes being metabolically dysfunctional. Cardiac m6A machinery gene expression was differentially regulated by duration of HFHS diet in male, but not female mice, and left ventricular ejection fraction correlated with RNA machinery gene levels in a sex- and age-dependent manner. RNA-sequencing of cardiac transcriptome revealed that females, but not males may undergo protective cardiac remodeling early in the course of obesogenic stress. Taken together, our study demonstrates for the first time that cardiac RNA methylation machinery genes are regulated early during obesogenic stress in a sex-dependent manner and may play a role in the sex differences observed in cardiometabolic dysfunction.NEW & NOTEWORTHY Sex differences in obesity-associated cardiomyopathy are well documented but incompletely understood. We show for the first time that RNA methylation machinery genes may be regulated in response to obesogenic diet in a sex- and age-dependent manner and levels may correspond to cardiac systolic function. Our cardiac RNA-seq analysis suggests female, but not male mice may be protected from cardiac dysfunction by a protective cardiac remodeling response early during obesogenic stress.

Dietary Selenium Insufficiency Induces Cardiac Inflammatory Injury in Chicks.

BACKGROUND: Laying hens undergo intensive metabolism and are vulnerable to cardiac insults. Previous research demonstrated overt heart disorders of broiler chickens induced by dietary Se deficiency. OBJECTIVES: This study aimed to reveal effects and mechanism of dietary Se insufficiency on cardiac injuries of egg-type chicks in their early life. METHODS: White Leghorn chicks (0-d-old, female) were fed a corn-soy, Se-insufficient basal diet (BD, 0.05 mg Se/kg; n = 11) or the BD supplemented with 0.3 mg Se/kg (as sodium selenite; n = 8) for 35 d. Cardiac tissues were collected at the end of study for histology and to determine its relationship with heart Se contents, selenoprotein expression profiles, antioxidant and inflammatory status, and the Toll-like receptor 4/extracellular signal-regulated kinases/p38 map kinase/c-Jun N-terminal kinase (TLR4/ERK/P38/JNK) pathway. RESULTS: Compared with those fed 0.35 mg Se/kg, chicks fed BD had significantly lower body weights and average daily gain, and 28% lower heart Se, and developed cardiac mononuclear inflammatory cell infiltration, along with elevated (P < 0.05) serum concentrations of creatine kinase, aldolase, and interleukin-1 (IL-1). The BD decreased (P < 0.05) body weight and heart glutathione contents and expression of selenoproteins but increased (P < 0.05) heart concentrations of malondialdehyde and reactive oxygen species. These changes were associated with increased (P < 0.05) mRNA and/or protein concentrations of cyclooxygenases, lipoxygenase-12, cytokines (IL-1ß), nuclear factor (NF) κB subunit, chemokines, and receptors (CCL20, CXCR1, and CXCLI2) and increased (P < 0.1) TLR4/ERK /P38/JNK in the heart of Se-insufficient chicks. CONCLUSIONS: Dietary Se insufficiency induces infiltration of mononuclear inflammatory cells in the heart of egg-type chicks. This cardiac injury was mediated by decreased functional expressions of selenoproteins, which resulted in apparent elevated oxidative stress and subsequent activations of the TLR4 pathway and NF κB.

Cardiomyocyte-specific Peli1 contributes to the pressure overload-induced cardiac fibrosis through miR-494-3p-dependent exosomal communication.

Cardiac fibrosis is an essential pathological process in pressure overload (PO)-induced heart failure. Recently, myocyte-fibroblast communication is proven to be critical in heart failure, in which, pathological growth of cardiomyocytes (CMs) may promote fibrosis via miRNAs-containing exosomes (Exos). Peli1 regulates the activation of NF-κB and AP-1, which has been demonstrated to engage in miRNA transcription in cardiomyocytes. Therefore, we hypothesized that Peli1 in CMs regulates the activation of cardiac fibroblasts (CFs) through an exosomal miRNA-mediated paracrine mechanism, thereby promoting cardiac fibrosis. We found that CM-conditional deletion of Peli1 improved PO-induced cardiac fibrosis. Moreover, Exos from mechanical stretch (MS)-induced WT CMs (WT MS-Exos) promote activation of CFs, Peli1-/- MS-Exos reversed it. Furthermore, miRNA microarray and qPCR analysis showed that miR-494-3p was increased in WT MS-Exos while being down regulated in Peli1-/- MS-Exos. Mechanistically, Peli1 promoted miR-494-3p expression via NF-κB/AP-1 in CMs, and then miR-494-3p induced CFs activation by inhibiting PTEN and amplifying the phosphorylation of AKT, SMAD2/3, and ERK. Collectively, our study suggests that CMs Peli1 contributes to myocardial fibrosis via CMs-derived miR-494-3p-enriched exosomes under PO, and provides a potential exosomal miRNA-based therapy for cardiac fibrosis.

Risk factors and survival outcomes in children with early cardiotoxicity after allogeneic hematopoietic stem cell transplantation.

Cardiotoxicity in children is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); therefore, early identification of risk factors can improve patient prognosis. However, there are few data on the clinical characteristics of early-stage cardiotoxicity in children after allo-HSCT. We conducted a retrospective single-center study of pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2016 and December 2022 at the Children's Hospital Affiliated with Chongqing Medical University to evaluate the clinical characteristics of early cardiac events (ECEs) after allo-HSCT and their impact on survival outcomes. We enrolled 444 patients who underwent allo-HSCT-304 males (68%) and 140 females (32%)-with a median age of 3.3 years (1.8-6.5 years) at transplantation. We found that 73 patients (16.4%) had ECEs after allo-HSCT. The ECEs included valvular disease (n = 46), pericardial effusion (n = 38), arrhythmia (n = 9), heart failure (n = 16), and dilated cardiomyopathy (n = 1). Female sex, age ≥ 6 years, body mass index (BMI) < 16 kg/m2 and HLA-type mismatches were risk factors for ECEs. We designed a stratified cardiac risk score that included these risk factors, and the higher the score was, the greater the cumulative incidence of ECEs. The occurrence of an ECE was closely associated with a lower overall survival (OS) rate and greater nonrelapse mortality (NRM). In addition, stratified analysis based on the number of combined ECEs showed that the greater the number of combined ECEs was, the more significant the negative impact on OS rates.

Long-term post-transplantation outcomes in patients with hypertrophic cardiomyopathy: Single-center 35-year experience.

BACKGROUND: Heart transplantation (HT) is the only option for most patients with end-stage heart failure and hypertrophic cardiomyopathy (HCM) who fail medical therapy. Data on the long-term outcomes post-transplant in HCM individuals remain scarce. METHODS: We analyzed data of 319 adult patients who underwent HT between 1984 and 2019. Patients were followed for cardiac allograft rejection, cardiac allograft vasculopathy (CAV), death, or re-transplantation. RESULTS: Outcomes of 24 patients with HCM, 160 with ischemic, and 135 with dilated cardiomyopathy were compared. During a mean follow-up of 11.6 ± 7.2 (max 27.8), 16.7 ± 8.2 (max 32.7), and 16.1 ± 9.7 (max 34.6) years after HT in hypertrophic, ischemic, and dilated cardiomyopathy groups, respectively: 10-year survival rate was 67%, 62%, 69%, respectively (p = .04). Post-transplantation, HCM individuals more often than the other two studied groups required prolonged inotropic support (37%, 12%, 17%, respectively, p = .02), temporary mechanical circulatory support (45%, 13%, 14%, respectively, p < .01), and renal replacement therapy immediately post-HT (55%, 19%, 24%, respectively, p < .01). No significant inter-group differences were noted in the 10-year freedom from acute allograft rejection (38%, 46%, 43%, respectively, p = .38) or 10-year freedom from CAV (88%, 78%, 81%, respectively, p = .57). CONCLUSIONS: The long-term post-transplant prognosis of adult patients with hypertrophic cardiomyopathy is favorable despite more challenging immediate post-HT course.

New advances in management and treatment of cardiac implantable electronic devices infections.

Cardiac implantable electronic devices (CIED) are increasingly used worldwide, and infection of these devices remains one of the most feared complications.CIED infections (CDIs) represent a challenge for physicians and the healthcare system in general as they require prolonged hospitalization and antibiotic treatment and are burdened by high mortality and high costs, so management of CDIs must be multidisciplinary.The exact incidence of CDIs is difficult to define, considering that it is influenced by various factors mainly represented by the implanted device and the type of procedure. Risk factors for CDIs could be divided into three categories: device related, patient related, and procedural related and the etiology is mainly sustained by Gram-positive bacteria; however, other etiologies cannot be underestimated. As a matter of fact, the two cornerstones in the treatment of these infections are device removal and antimicrobial treatment. Finally, therapeutic drug monitoring and PK/PD correlations should be encouraged in all patients with CDIs receiving antibiotic therapy and may result in a better clinical outcome and a reduction in antibiotic resistance and economic costs.In this narrative review, we look at what is new in the management of these difficult-to-treat infections.

Brain-Heart Axis and the Inflammatory Response: Connecting Stroke and Cardiac Dysfunction.

BACKGROUND: In recent years, the mechanistic interaction between the brain and heart has been explored in detail, which explains the effects of brain injuries on the heart and those of cardiac dysfunction on the brain. Brain injuries are the predominant cause of post-stroke deaths, and cardiac dysfunction is the second leading cause of mortality after stroke onset. SUMMARY: Several studies have reported the association between brain injuries and cardiac dysfunction. Therefore, it is necessary to study the influence on the heart post-stroke to understand the underlying mechanisms of stroke and cardiac dysfunction. This review focuses on the mechanisms and the effects of cardiac dysfunction after the onset of stroke (ischemic or hemorrhagic stroke). KEY MESSAGES: The role of the site of stroke and the underlying mechanisms of the brain-heart axis after stroke onset, including the hypothalamic-pituitary-adrenal axis, inflammatory and immune responses, brain-multi-organ axis, are discussed.

Factors predicting resolution of left ventricular thrombus in different time windows after myocardial infarction.

BACKGROUND: Left ventricular thrombus (LVT) is a serious complication after myocardial infarction. However, due to its asymptomatic nature, early detection is challenging. We aimed to explore the differences in clinical correlates of LVT found in acute to subacute and chronic phases of myocardial infarction. METHODS: We collected data from 153 patients who were diagnosed with LVT after myocardial infarction at the Affiliated Hospital of Qingdao University from January 2013 to December 2022. Baseline information, inflammatory markers, transthoracic echocardiograph (TTE) data and other clinical correlates were collected. Patients were categorized into acute to subacute phase group (< 30 days) and chronic phase group (30 days and after) according to the time at which echocardiograph was performed. The resolution of thrombus within 90 days is regarded as the primary endpoint event. We fitted logistic regression models to relating clinical correlates with phase-specific thrombus resolution. RESULTS: For acute to subacute phase thrombus patients: C-reactive protein levels (OR: 0.95, 95% CI: 0.918-0.983, p = 0.003) were significantly associated with thrombus resolution. For chronic phase thrombus patients: anticoagulant treatment was associated with 5.717-fold odds of thrombus resolution (OR: 5.717, 95% CI: 1.543-21.18, p = 0.009). CONCLUSIONS: Higher levels of CRP were associated with lower likelihood of LVT resolution in acute phase myocardial infarction; Anticoagulant therapy is still needed for thrombus in the chronic stage of myocardial infarction.

Cardiac involvement and its clinical significance in patients with anorexia nervosa.

Cardiac complications are a major concern in patients with anorexia nervosa (AN) which contribute to morbidity and mortality. However, limited information exists regarding risk factors for the development of these complications. Our objective was to investigate the prevalence and associated risk factors of cardiac involvement among children and adolescents with AN admitted to a tertiary pediatric hospital. We collected demographic, clinical, and laboratory data from individuals with AN hospitalized between 2011 and 2020 in Schneider Children's Medical Center in Israel. Diagnosis was based on established criteria (DSM-5). Patients with other co-morbidities were excluded. Cardiac investigations included electrocardiograms (ECG) and echocardiograms. We conducted correlation tests between cardiac findings and clinical and laboratory indicators. A total of 403 AN patients (81.4% were females) with a median age of 15 ± 2 years were included in the study. Sinus bradycardia was the most common abnormality, observed in 155 (38%) participants. Echocardiogram was performed in 170 (42.2%) patients, of whom 37 (22%) demonstrated mild cardiac aberrations. Among those aberrations, 94.6% could be attributed to the current metabolic state, including pericardial effusion (15.3%) and valve dysfunction (8.8%). Systolic or diastolic cardiac dysfunction, tachyarrhythmias, or conduction disorders were not observed. Patients with new echocardiographic aberration had significantly lower body mass index (BMI) at admission, and the prevalence of amenorrhea and hypotension was higher in this group. CONCLUSIONS: The prevalence of cardiac involvement, except for sinus bradycardia, was notably low in our cohort. The presence of cardiac aberrations is correlated with several clinical variables: lower body mass index (BMI) and the presence of amenorrhea and hypotension at admission. Patients presenting with these variables may be at high risk for cardiac findings per echocardiography. Dividing the patients into high and low risk groups may enable targeted evaluation, while avoiding unnecessary cardiac investigations in low-risk patients. WHAT IS KNOWN: • Cardiac involvement in anorexia nervosa (AN) patients is a major concern, which contributes to morbidity and mortality. • It is unknown which patients are prone to develop this complication. WHAT IS NEW: • Cardiac complications in our cohort are less frequent compared to previous studies, and it is correlated with lower body mass index (BMI) at admission, and the prevalence of amenorrhea and hypotension.

Blood group AB is associated with reduced blood loss but also elevated cardiovascular mortality in aortocoronary bypass surgery.

Patient blood group (BG) is predictive for von-Willebrand-factor (VWF) and Factor VIII variation. The clinical impact of this ABO-effect on blood loss, cardiovascular complications and outcome has been described for several patient cohorts. The aim of this study was to investigate the impact of patient BG on blood loss and outcome after coronary artery bypass surgery (CABG). Patient records, intraoperative data and perioperative transfusion records of 5713 patients receiving an on-pump CABG procedure between 05/2004 and 12/2018 were analyzed. A logistic regression model for death due to perioperative myocardial ischaemia (PMI) was developed from initially 24 variables by using an univariate and multivariate selection process. BG AB patients required less blood transfusions as compared to the other blood groups, especially in case of emergency operations. However, BG AB patients also had a higher mortality which was due to secondary cardiovascular complications. The impact of blood type on the rate of cardiovascular mortality was confirmed in the logistic regression model. BG AB patients have a worse outcome after CABG surgery due to an increased incidence of fatal cardiovascular complications. As perioperative myocardial ischemia due to graft occlusion appears to be the most likely explanation, stricter anticoagulation for BG AB patients should be discussed.

Locoregional Anesthesia Has Lower Risks of Cardiac Complications Than General Anesthesia After Prolonged Endovascular Repair of Abdominal Aortic Aneurysms.

OBJECTIVES: Although general anesthesia is the primary anesthesia in endovascular aneurysm repair (EVAR), some studies suggest locoregional anesthesia could be a feasible alternative for eligible patients. However, most evidence was from retrospective studies and was subjected to an inherent selection bias that general anesthesia is often chosen for more complex and prolonged cases. To mitigate this selection bias, this study aimed to compare 30-day outcomes of prolonged, nonemergent, intact, infrarenal EVAR in patients undergoing locoregional or general anesthesia. In addition, risk factors associated with prolonged operative time in EVAR were identified. DESIGN: Retrospective large-scale national registry study. SETTING: American College of Surgeons National Surgical Quality Improvement Program targeted database from 2012 to 2022. PARTICIPANTS: A total of 4,075 out of 16,438 patients (24.79%) had prolonged EVAR. Among patients with prolonged EVAR, 324 patients (7.95%) were under locoregional anesthesia. There were 3,751 patients (92.05%) under general anesthesia, and 955 of them were matched to the locoregional anesthesia cohort. INTERVENTIONS: Patients undergoing infrarenal EVAR were included. Exclusion criteria included age <18 years, emergency cases, ruptured abdominal aortic aneurysm, and acute intraoperative conversion to open. Only cases with prolonged operative times (>157 minutes) were selected. A 1:3 propensity-score matching was used to address demographics, baseline characteristics, aneurysm diameter, distant aneurysm extent, and concomitant procedures between patients under locoregional and general anesthesia. Thirty-day postoperative outcomes were assessed. Moreover, factors associated with prolonged EVAR were identified by multivariate logistic regression. MEASUREMENTS AND MAIN RESULTS: Except for general anesthesia contraindications, patients undergoing locoregional or general anesthesia exhibited largely similar preoperative characteristics. After propensity-score matching, patients under locoregional and general anesthesia had a lower risk of myocardial infarction (0.93% v 2.83%, p = 0.04), but comparable 30-day mortality (3.72% v 2.72%, p = 0.35) and other complications. Specific concomitant procedures, aneurysm anatomy, and comorbidities associated with prolonged EVAR were identified. CONCLUSIONS: Locoregional anesthesia can be a safe and effective alternative to general anesthesia, particularly in EVAR cases with anticipated complexity and prolonged operative times, as it offers the potential benefit of reduced cardiac complications. Risk factors associated with prolonged EVAR can aid in preoperative risk stratification and inform the decision-making process regarding anesthesia choice.

Cardiac disease-induced trauma and stress-related disorders.

OBJECTIVE: This review aims to present an updated overview of cardiac disease-induced trauma and stress-related disorders such as acute stress disorder (ASD), adjustment disorder (AjD), and posttraumatic stress disorder (PTSD). First, the prevalence of these disorders, their diagnostic criteria, and their differences from other trauma-related disorders are described. Special challenges in diagnosis and treatment are identified, with various screening tools being evaluated for symptom assessment. Additionally, the risk factors studied so far for the development of symptoms of cardiac-induced posttraumatic stress disorder and the bidirectional relationship between posttraumatic stress disorder and cardiovascular diseases are summarized. Various therapeutic interventions, including pharmacological approaches, are also discussed. Finally, various areas for future research are outlined. BACKGROUND: Experiencing a cardiovascular disease, particularly a life-threatening cardiac event, can potentially lead to stress-related disorders such as ASD, AjD, and cardiac disease-induced PTSD (CDI-PTSD). If left untreated, these disorders are associated with a worsening cardiac prognosis and higher mortality rates. Approaching treatment through a trauma-focused lens may be beneficial for managing CDI-PTSD and stress-related disorders. CONCLUSION: Future research should explore treatment options for both the patients and the caregivers as well as investigate the long-term effects of trauma-focused interventions on physical and mental health outcomes.

Children With Cardiac Disease and Heat Exposure: Catastrophic Converging Consequences?

The detrimental impact of extreme heat exposure on the health and well-being of children is widely acknowledged. The direct and indirect effects of climate change have led to an increased risk of certain cardiovascular events which may be particularly harmful to children who are born with, or develop, heart disease. PURPOSE: To highlight the worrying paucity of investigative research aimed at differentiating how higher ambient temperatures further tax an already compromised cardiovascular system in children. METHODS: This commentary describes basic thermoregulatory concepts relevant to the healthy pediatric population and summarizes common heart diseases observed in this population. RESULTS: We describe how heat stress and exercise are important factors clinicians should more readily consider when treating children with heart disease. Countermeasures to physical inactivity are suggested for children, parents, clinicians, and policymakers to consider. CONCLUSIONS: As sudden, excessive heat exposures continue to impact our rapidly warming world, vulnerable populations like children with underlying heart conditions are at greater heat health risk, especially when coupled with the negative physical activity and fitness trends observed worldwide.

Association between Immune Checkpoint Inhibitors and Atherosclerotic Cardiovascular Disease Risk: Another Brick in the Wall.

In recent years, immune checkpoint inhibitors have significantly changed the field of oncology, emerging as first-line treatment, either alone or in combination with other regimens, for numerous malignancies, improving overall survival and progression-free survival in these patients. However, immune checkpoint inhibitors might also cause severe or fatal immune-related adverse events, including adverse cardiovascular events. Initially, myocarditis was recognized as the main immune checkpoint inhibitor-related cardiac event, but our knowledge of other potential immune-related cardiovascular adverse events continues to broaden. Recently, preclinical and clinical data seem to support an association between immune checkpoint inhibitors and accelerated atherosclerosis as well as atherosclerotic cardiovascular events such as cardiac ischemic disease, stroke, and peripheral artery disease. In this review, by offering a comprehensive overview of the pivotal role of inflammation in atherosclerosis, we focus on the potential molecular pathways underlying the effects of immune checkpoint inhibitors on cardiovascular diseases. Moreover, we provide an overview of therapeutic strategies for cancer patients undergoing immunotherapy to prevent the development of cardiovascular diseases.