Congenital dual anterior interventricular artery.

Dual anterior interventricular artery is a rare type of CHD. We reported a fifteen-year-old girl who underwent CT angiography that demonstrated one anterior interventricular artery from aorta and another from pulmonary artery.

The Molecular Role of Immune Cells in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a rare and severe condition characterized by chamber dilation and impaired contraction of the left ventricle. It constitutes a fundamental etiology for profound heart failure and abrupt cardiac demise, rendering it a prominent clinical indication for heart transplantation (HTx) among both adult and pediatric populations. DCM arises from various etiologies, including genetic variants, epigenetic disorders, infectious insults, autoimmune diseases, and cardiac conduction abnormalities. The maintenance of cardiac function involves two distinct types of immune cells: resident immune cells and recruited immune cells. Resident immune cells play a crucial role in establishing a harmonious microenvironment within the cardiac tissue. Nevertheless, in response to injury, cardiomyocytes initiate a cytokine cascade that attracts peripheral immune cells, thus perturbing this intricate equilibrium and actively participating in the initiation and pathological remodeling of dilated cardiomyopathy (DCM), particularly during the progression of myocardial fibrosis. Additionally, immune cells assume a pivotal role in orchestrating the inflammatory processes, which are intimately linked to the prognosis of DCM. Consequently, understanding the molecular role of various immune cells and their regulation mechanisms would provide an emerging era for managing DCM. In this review, we provide a summary of the most recent advancements in our understanding of the molecular mechanisms of immune cells in DCM. Additionally, we evaluate the effectiveness and limitations of immunotherapy approaches for the treatment of DCM, with the aim of optimizing future immunotherapeutic strategies for this condition.

Design, synthesis and biological evaluation of novel thiazole-derivatives as mitochondrial targeting inhibitors of cancer cells.

Mitochondria are pivotal energy production sources for cells to maintain necessary metabolism activities. Targeting dysfunctional mitochondrial features has been a hotspot for mitochondrial-related disease researches. Investigation with cancerous mitochondrial metabolism is a continuing concern within tumor therapy. Herein, we set out to assess the anti-cancer activities of a novel family of TPP-thiazole derivatives based on our earlier research on mitochondrial targeting agents. Specifically, we designed and synthesized a series of TPP-thiazole derivatives and revealed by the MTT assay that most synthesized compounds effectively inhibited three cancer cell lines (HeLa, PC3 and MCF-7). After structure modifications, we explored the SAR relationships and identified the most promising compound R13 (IC50 of 5.52 µM) for further investigation. In the meantime, we performed ATP production assay to assess the selected compounds inhibitory effect on HeLa cells energy production. The results displayed the test compounds significantly restrained ATP production of cancer cells. Overall, we have designed and synthesized a series of compounds which exhibited significant cytotoxicity against cancer cells and effectively inhibited mitochondrial energy production.

Biological evaluation of mitochondria targeting small molecules as potent anticancer drugs.

Cancer therapy targets specific metabolic pathways or a single gene. This may result in low therapeutic effects due to drug selectivity and drug resistance. Recent studies revealed that the mitochondrial membrane potential and transmembrane permeability of cancerous mitochondria are differed from normal mitochondria. Thus, chemotherapy targeting cancerous mitochondria could be an innovative and competent strategy for cancer therapy. Previously, our work with a novel group of mitochondria targeting small molecules presented promising inhibitory capability toward various cancer cell lines and suppressed adenosine triphosphate (ATP) generation. Therefore, it is critical to understand the anticancer effect and targeting mechanism of these small molecules. This study investigated the inhibitory activity of mitochondria targeting small molecules with human cervical cancer cells - HeLa to further explore their therapeutic potential. HeLa cells were exposed to 10 µM of synthesized compounds and presented elevation in intracellular reactive oxygen species (ROS) level, impaired mitochondrial membrane potential and upregulation of apoptosis as well as necrosis. In vivo, HeLa cell tumor-bearing BALB/c nude mice were treated with mitochondria targeting small molecules for 12 days consecutively. Throughout this chemotherapy study, no deleterious side effects nor the appearance of toxicity was observed. Furthermore, mitochondria targeting small molecules treated groups exhibited significant down-regulation with both tumor volume and tumor weight compared to the Doxorubicin (DOX) treated group. Thus, inhibition of mitochondrial ATP synthesis, activation of intracellular ROS production, down-regulation of mitochondrial membrane potential and upregulation of apoptosis and necrosis rates are the indications of cancer therapy. In this work, we examined the anticancer capability of four mitochondria targeting small molecules in vitro and in vivo, and demonstrated a novel therapeutic approach in cancer therapy with tremendous potential.

Design, synthesis and antitumor activities of thiazole-containing mitochondrial targeting agents.

In this study, a novel batch of thiazole-containing mitochondrial targeting agents were designed and synthesized. Four kinds of mitochondrial targeting moieties and six kinds of linkers were designed. Their structures were confirmed by NMR and HR-MS. The screening of antiproliferative activity revealed that most compounds displayed cytotoxicity on HeLa cancer cell. In particular, D1 has an IC50 value of 35.32 µmol·L-1 against HeLa cell. In addition, cellular respiratory activities were also tested on HeLa cancer cells. D1 had a basal oxygen consumption rate of 8.84 pmol·s-1·mL-1. Also, D1 inhibited the mitochondrial respiration of HeLa cell significantly at 5 µmol·L-1, as well as a complete inhibitory of oxygen consumption for cellular ATP coupling. Furthermore, the pKa, logP, and logD under different pH conditions of all the compounds were calculated by the ACD/Percepta-PhysChem Suite, and the results manifested the correlation between physicochemical properties and chemical activity of compounds. The results identify D1 as a promising mitochondria inhibitor and anticancer agent with appropriate physicochemical properties.

Mechanical Circulatory Support for Patients With Adult Congenital Heart Disease.

Advances in surgical and medical care of children born with heart defects have led to the emergence of a unique subgroup of young adults known as adults with congenital heart disease (ACHD). Heart failure (HF) is the leading cause of mortality and morbidity in this subset. Management of HF is challenging in these patients owing to inherent structural variations with their associated physiological consequences. Heart transplantation is of limited utility in this group either because of donor shortage or associated comorbidities that make these patients ineligible for transplantation. Mechanical circulatory support (MCS) devices have evolved as an alternative treatment modality in supporting the failing myocardium of this population, but are often used less frequently than in those with a structurally normal heart because of the unique anatomical and physiological variations. These variations create a need to gather adequate knowledge on how best to support the hearts of ACHD patients in order to reduce mortality and morbidity. This review presents clinical experience with MCS in ACHD patients.

Partial resection of large congenital left ventricular diverticulum in an infant: a case report.

BACKGROUND: Congenital left ventricular diverticulum is a rare cardiac malformation usually requiring total resection. CASE PRESENTATION: This report describes an infant presenting with a large apical diverticulum with a wide ventricle connection. Given the vicinity of the left anterior descending coronary artery to the diverticulum and its wide ventricular connection, partial resection was undertaken. The patient remained asymptomatic with good heart function 8 months after surgery. The last follow-up echocardiography did not demonstrate any significant left ventricular outpouching. CONCLUSIONS: We advocate early treatment of left ventricular diverticulum in children given the risk of spontaneous rupture of diverticulum, sudden death, and other serious complications if left untreated. For small patients with a wide connection of diverticulum to ventricle, partial resection is a safe option with favorable short-term outcomes.

Late deaths after Fontan procedure: the next frontier.

PURPOSE OF REVIEW: It has been more than 4 decades since the development of Fontan operation. With the contemporary surgical strategies to treat the patients with a single ventricle physiology, the medium-term survival of the patients following Fontan operation is excellent. Nonetheless, the Fontan circulation with a pumpless pulmonary circulation has fundamental physiologic limitations, which are associated with late Fontan failure and deaths. There has been an exponential growth of adolescence and adults living with a Fontan circulation, which poses significant challenges in future. RECENT FINDINGS: In this review, we discuss challenges and potential opportunities to treat the failing Fontan circulation. The specific topics include medical therapy, imaging, and therapeutic interventions for lymphatic abnormalities, transplantation, and mechanical support. The article also summarizes quality of life among the patients with the Fontan circulation. SUMMARY: Surgical techniques, developing novel diagnostic and therapeutic tools, and increasing our understanding of the failing Fontan physiology is essential to improve the overall long-term outcome of this entity.

Discovery of 2-ethoxy-4-(methoxymethyl)benzamide derivatives as potent and selective PTP1B inhibitors.

Protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of insulin signaling, is considered as a promising and validated therapeutic target for type 2 diabetes mellitus (T2DM) and obesity. Upon careful study, a series of 2-ethoxy-4-(methoxymethyl)benzamide and 2-ethoxy-5-(methoxymethyl)benzamide analogs designed by the "bioisosteric principle" were discovered, wherein their PTP1B inhibitory potency, type of PTP1B inhibition, selectivity and membrane permeability were evaluated. Among them, compound 10m exhibited high inhibitory activity (IC50 = 0.07 µM), significant selectivity (32-fold) over T-cell PTPase (TCPTP) as well as good membrane permeability (Papp = 2.41 × 10-6 cm/s). Further studies on cell viability and cellular activity revealed that compound 10m could enhance insulin-stimulated glucose uptake with no significant cytotoxicity.

The Effect of Diagnostic Blood Loss on Anemia and Transfusion Among Postoperative Patients With Congenital Heart Disease in a Pediatric Intensive Care Unit.

PURPOSE: To evaluate whether diagnostic blood loss can lead to anemia and consequent blood transfusion among postoperative patients with congenital heart disease (CHD) in the pediatric intensive care unit (PICU). DESIGN AND METHODS: This prospective observational study was conducted in a university-affiliated tertiary hospital between January and August 2016. CHD patients aged <12years, undergoing cardiac surgery, with a PICU stay >48h were included (n=205). Multivariate logistic regression analyses were used to determine the effect of diagnostic blood loss on anemia and transfusion. RESULTS: The mean daily phlebotomy volume was 5.40±1.94mL/d during the PICU stay (adjusted for body weight, 0.63±0.36mL/kg/d). Daily volume/kg was associated with cyanotic CHD, Pediatric Risk of Mortality III score, and Pediatric Logistic Organ Dysfunction (PELOD)-2 score. In total, 101 (49.3%) patients presented with new or more severe anemia after admission to PICU, which was not associated with phlebotomy volume. Forty-one (20.0%) children received one or more RBC transfusions during their PICU stay. Multivariate analysis indicated that PELOD-2 score>5, new or more severe anemia, and daily volume/kg of phlebotomy >0.63mL/kg/d were significantly associated with transfusion after 48h of admission to PICU. CONCLUSIONS: Our findings indicate that diagnostic blood loss is not related to postoperative anemia in children with CHD; however, this factor does correlate with blood transfusion, since it somewhat reflects the severity of illness. PRACTICE IMPLICATIONS: Strategies should be applied to reduce diagnostic blood loss, as appropriate.

Vasopressors induce passive pulmonary hypertension by blood redistribution from systemic to pulmonary circulation.

Vasopressors are widely used in resuscitation, ventricular failure, and sepsis, and often induce pulmonary hypertension with undefined mechanisms. We hypothesize that vasopressor-induced pulmonary hypertension is caused by increased pulmonary blood volume and tested this hypothesis in dogs under general anesthesia. In normal hearts (model 1), phenylephrine (2.5 µg/kg/min) transiently increased right but decreased left cardiac output, associated with increased pulmonary blood volume (63% ± 11.8, P = 0.007) and pressures in the left atrium, pulmonary capillary, and pulmonary artery. However, the trans-pulmonary gradient and pulmonary vascular resistance remained stable. These changes were absent after decreasing blood volume or during right cardiac dysfunction to reduce pulmonary blood volume (model 2). During double-ventricle bypass (model 3), phenylephrine (1, 2.5 and 10 µg/kg/min) only slightly induced pulmonary vasoconstriction. Vasopressin (1U and 2U) dose-dependently increased pulmonary artery pressure (52 ± 8.4 and 71 ± 10.3%), but did not cause pulmonary vasoconstriction in normally beating hearts (model 1). Pulmonary artery and left atrial pressures increased during left ventricle dysfunction (model 4), and further increased after phenylephrine injection by 31 ± 5.6 and 43 ± 7.5%, respectively. In conclusion, vasopressors increased blood volume in the lung with minimal pulmonary vasoconstriction. Thus, this pulmonary hypertension is similar to the hemodynamic pattern observed in left heart diseases and is passive, due to redistribution of blood from systemic to pulmonary circulation. Understanding the underlying mechanisms may improve clinical management of patients who are taking vasopressors, especially those with coexisting heart disease.

Systolic Function of Right Ventricular Outflow Tract is a Better Predictor to Exercise Performance After Pulmonary Valve Replacement in Tetralogy of Fallot.

Debate on the proper timing of pulmonary valve replacement (PVR) after repair of tetralogy of Fallot is still continuing. We aim to clarify how the different components of right ventricle (RV) changed with relieved volume overload in the remodeling process after pulmonary valve replacement and gain a clear idea of the relationship between different right ventricle components function and exercise capacity after PVR in these patients. The medical records and results of cardiac magnetic resonance imaging and cardiopulmonary exercise testing of 25 consecutive eligible patients were reviewed. End-diastolic, end-systolic, and ejection fraction (EF) were determined for the total RV and its components before and after PVR. There was a marked increase in EF for the outlet after PVR (39.5 ± 11.4 vs. 45.6 ± 12.7, P = 0.04); however, EF and volume change for the other components showed no significant difference. Peak oxygen consumption (VO2) correlated better with the RV outflow tract EF than with the EF of other components of the RV or the global EF (r = 0.382, P = 0.018), and the time interval between initial repair and PVR showed a significant correlation with peak VO2 (r = -0.339, P = 0.037). Multivariate analysis showed the RV outflow tract EF to be the only independent predictor of exercise capacity (ß = 0.479; P = 0.046). The systolic function of the RV outflow tract could be a reliable determinant of intrinsic RV performance in repaired TOF (rTOF) patients and a promising parameter for deciding timing of pulmonary valve replacement so as to achieve the best possible exercise capacity in repaired TOF patients.

Giant congenital left atrial appendage aneurysm.

We present a rare case of an asymptomatic giant congenital left atrial appendage aneurysm in a 19-year-old girl. We believe this is the largest congenital left atrial appendage aneurysm reported without any symptom.

A novel minimal invasive mouse model of extracorporeal circulation.

Extracorporeal circulation (ECC) is necessary for conventional cardiac surgery and life support, but it often triggers systemic inflammation that can significantly damage tissue. Studies of ECC have been limited to large animals because of the complexity of the surgical procedures involved, which has hampered detailed understanding of ECC-induced injury. Here we describe a minimally invasive mouse model of ECC that may allow more extensive mechanistic studies. The right carotid artery and external jugular vein of anesthetized adult male C57BL/6 mice were cannulated to allow blood flow through a 1/32-inch external tube. All animals (n = 20) survived 30 min ECC and subsequent 60 min observation. Blood analysis after ECC showed significant increases in levels of tumor necrosis factor α, interleukin-6, and neutrophil elastase in plasma, lung, and renal tissues, as well as increases in plasma creatinine and cystatin C and decreases in the oxygenation index. Histopathology showed that ECC induced the expected lung inflammation, which included alveolar congestion, hemorrhage, neutrophil infiltration, and alveolar wall thickening; in renal tissue, ECC induced intracytoplasmic vacuolization, acute tubular necrosis, and epithelial swelling. Our results suggest that this novel, minimally invasive mouse model can recapitulate many of the clinical features of ECC-induced systemic inflammatory response and organ injury.

Prediction of nonrecurrent laryngeal nerve before thyroid surgery--experience with 1825 cases.

BACKGROUND: Nonrecurrent laryngeal nerve (NRLN) is a rare anatomic anomaly, which often co-occurs with aberrant right subclavian artery (ARSA). With this large case series, we present our experience of predicting the presence of NRLN by the means of chest X-ray film, thoracic computed tomography (CT), and ultrasonography. MATERIALS AND METHODS: A prospective, nonrandomized study has been carried out. A total of 1825 patients with various thyroid disorders scheduled for surgery were recruited between January 2006 and July 2012. All patients underwent preoperative chest X-ray examination. Those suspected with ARSA further underwent thoracic CT scan. Unsuspected patients who had NRLN revealed by surgery were analyzed with ultrasonography postoperatively. RESULTS: A total of 41 patients (2.25%) were suspected to have ARSA by X-ray, of those 19 (46.3%) were confirmed by thoracic CT and proven to have NRLN upon subsequent surgery. No NRLN injury was inflicted. For the remaining 22 cases, CT scan suggested a normal right subclavian artery and none had NRLN upon surgery. For the 1784 unsuspected patients, 4 (0.22%) were discovered to have NRLN upon surgery, of those one was injured. For the 19 predicted NRLN, the time used for identifying the nerve was significantly shorter than the four cases with unsuspected NRLN (t = -15.978; P = 0.000). After the operation, all these unsuspected NRLN were confirmed to have ARSA by ultrasonography. CONCLUSIONS: Patients scheduled for thyroid surgery should be screened for ARSA upon routine chest X-ray and thyroid ultrasonography before surgery. Detection of ARSA can accurately predict the existence of NRLN; hence prevent NRLN injury during subsequent surgery.

Surgical restoration of left ventricular diastolic function: possible treatment for noncompaction cardiomyopathy.

Noncompaction of the left ventricle is a rare congenital cardiomyopathy characterized by prematurely arrested compaction of the endocardial and myocardial fibers resulting in impaired systolic and diastolic ventricular function. Nontransplant surgical treatment is lacking and limited to correction of accompanied valve problems or arrhythmias. We present a technique for surgical restoration of ventricular diastolic function in a patient with noncompaction of the left ventricle.

Postoperative intra-abdominal hypertension predicts worse hospital outcomes in children after cardiac surgery: a pilot study†.

OBJECTIVES: Our goal was to determine the incidence and characteristics of postoperative intra-abdominal hypertension (IAH) in paediatric patients undergoing open-heart surgery. METHODS: This single-centre study included consecutive children (aged <16 years) who underwent open-heart surgery between July 2020 and February 2021. Patients who entered the study were followed until in-hospital death or hospital discharge. The study consisted of 2 parts. Part I was a prospective observational cohort study that was designed to discover the association between exposures and IAH. Postoperative intra-abdominal pressure was measured immediately after admission to the intensive care unit and every 6 h thereafter. Part II was a cross-sectional study to compare the hospital-related adverse outcomes between the IAH and the no-IAH cohorts. RESULTS: Postoperatively, 24.7% (38/154) of the patients exhibited IAH, whereas 3.9% (6/154) developed abdominal compartment syndrome. The majority (29/38, 76.3%) of IAH cases occurred within the first 24 h in the intensive care unit. Multivariable analysis showed that the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score [odds ratio (OR) = 1.86, 95% confidence interval (CI) 1.23-2.83, P = 0.004], right-sided heart lesion (OR = 5.60, 95% CI 2.34-13.43, P < 0.001), redo sternotomy (OR = 4.35, 95% CI 1.64-11.57, P = 0.003), high baseline intra-abdominal pressure (OR = 1.43, 95% CI 1.11-1.83, P = 0.005), prolonged cardiopulmonary bypass duration (OR = 1.01, 95% CI 1.00-1.01, P = 0.005) and deep hypothermic circulatory arrest (OR = 5.14, 95% CI 1.15-22.98, P = 0.032) were independent predictors of IAH occurrence. IAH was associated with greater inotropic support (P < 0.001), more gastrointestinal complications (P = 0.001), sepsis (P = 0.003), multiple organ dysfunction syndrome (P < 0.001) and prolonged intensive care unit stay (z = -4.916, P < 0.001) and hospitalization (z = -4.710, P < 0.001). The occurrence of a composite outcome (P = 0.009) was significantly increased in patients with IAH. CONCLUSIONS: IAH is common in children undergoing cardiac surgery and is associated with worse hospital outcomes. Several factors may be associated with the development of IAH, including basic cardiac physiology and perioperative factors. TRIAL INFORMATION: This study was registered in the Chinese Clinical Trial Registry (Trial number: ChiCTR2000034322)URL site: https://www.chictr.org.cn/hvshowproject.html?id=41363&v=1.4.

Coronary artery lesions are associated with adverse cardiac events in children undergoing supravalvular aortic stenosis repair.

OBJECTIVES: The aim of this study was to identify the prevalence and anatomic characteristics of coronary artery lesions and their associated postoperative risk in patients undergoing supravalvular aortic stenosis repair. METHODS: The association between structural risk factors, postoperative ST-segment changes, and major adverse cardiac events was explored using logistic regression and the Fisher's exact test. RESULTS: In 51 consecutive patients with supravalvular aortic stenosis treated between 2000 and 2017, a total of 48 coronary lesions were identified in 27 patients (53%). Prominent ostial ridge (type I) was the most common coronary lesion, followed by small ostium with (IIIb) or without (IIIa) diffuse long-segment coronary narrowing, and adhesion of the coronary cusp (type II). There were 54 concomitant coronary procedures, including 43 primary corrections and 11 revisions. Thirty-three patients underwent supravalvular aortic stenosis repair with a bifurcated patch, of which 13 (39.4%) had right coronary artery distortion/kinking requiring patch plication (n = 8) and reimplantation (n = 5). Postoperative major adverse cardiac events (MACE) occurred in 9 patients (17.6%), including 3 deaths, 4 needing mechanical circulatory support, and 6 experiencing ventricular arrhythmias. Twenty-two patients (43.1%) had postoperative ST-segment changes, including 13 early changes that resolved within 24 h and 9 persistent changes lasting >24 h. Patients with type III lesions were associated with postoperative persistent ST-segment change (P = 0.04) and these lesions independently predicted postoperative MACE (P = 0.02). Patients with pre-existing coronary lesions were at elevated risk of right coronary artery distortion/kinking (P = 0.045). CONCLUSIONS: The prevalence of ST-segment changes and MACE is high in patients undergoing supravalvular aortic stenosis repair. The preoperative presence of complex coronary lesions is the most important predictor for postoperative major adverse cardiac events.

Identifying influence factors and thresholds of the next day's pollen concentration in different seasons using interpretable machine learning.

The prevalence of pollen allergies is a pressing global issue, with projections suggesting that half of the world's population will be affected by 2050 according to the estimation of the World Health Organization (WHO). Accurately forecasting pollen allergy risks requires identifying key factors and their thresholds for aerosol pollen. To address this, we developed a technical framework combining advanced machine learning and SHapley Additive exPlanations (SHAP) technology, focusing on Beijing. By analyzing meteorological data and vegetation phenology, we identified the factors influencing next-day's pollen concentration (NDP) in Beijing and their thresholds. Our results highlight vegetation phenology data from Synthetic Aperture Radar (SAR), temperature, wind speed, and atmospheric pressure as crucial factors in spring. In contrast, the Normalized Difference Vegetation Index (NDVI), air temperature, and wind speed are significant in autumn. Leveraging SHAP technology, we established season-specific thresholds for these factors. Our study not only confirms previous research but also unveils seasonal variations in the relationship between radar-derived vegetation phenology data and NDP. Additionally, we observe seasonal fluctuations in the influence patterns and threshold values of daily air temperatures on NDP. These insights are pivotal for improving pollen concentration prediction accuracy and managing allergic risks effectively.