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World J Pediatr Congenit Heart Surg. 2025 Jun 26:21501351251345805. doi: 10.1177/21501351251345805. Online ahead of print.

ABSTRACT

Cardiac surgery (CS) in sub-Saharan Africa (SSA) faces unique challenges that go beyond resource scarcity. Historical, cultural, and structural barriers continue to hinder the development of the specialty in SSA, impacting professional accreditation and the organization of healthcare systems. The colonial legacy of the subcontinent has shaped health systems in ways that often sustain external dependency, limiting local autonomy, which is particularly true for a high-resource subspecialty such as CS. Additionally, cultural resistance, the undervaluation of the specialty, and a lack of institutional recognition create a difficult environment for African cardiac surgeons. Based on the recent experience in Angola, this article explores these challenges and highlights the need for context-specific solutions, including strengthening local training, improving hospital governance, and prioritizing CS as a public health necessity. Understanding these obstacles and their potential solutions is crucial to fostering sustainable progress and ensuring equitable access to cardiovascular care in the region and in similar environments.

PMID:40567009 | DOI:10.1177/21501351251345805

World J Pediatr Congenit Heart Surg. 2025 Jun 26:21501351251345787. doi: 10.1177/21501351251345787. Online ahead of print.

ABSTRACT

We report the case of a four-month-old child with complex congenital heart disease, including tricuspid atresia, absent pulmonary valve, hypoplastic right ventricle, right ventricular coronary artery fistula, and Uhl anomaly, and to describe the challenges and management decisions involved. A Blalock-Taussig-Thomas (BTT) shunt was initially planned. However, severe ST-segment depression occurred upon oral feeding, indicating coronary insufficiency. Cardiac catheterization revealed a single coronary artery with a right ventricular coronary artery fistula, which increased the risk of myocardial ischemia with the BTT shunt. Consequently, a bidirectional Glenn (BDG) procedure with left pulmonary artery reconstruction was performed after maintaining ductal patency with prostaglandin for four months. The patient had a favorable postoperative course without ischemic events. In patients with complex congenital heart defects and coronary anomalies, the presence of a right ventricular coronary artery fistula may increase the risk of ischemia with a BTT shunt. A BDG procedure can offer a safer alternative, leading to a positive clinical outcome and avoiding ischemic complications.

PMID:40566964 | DOI:10.1177/21501351251345787

J Clin Med. 2025 Jun 18;14(12):4355. doi: 10.3390/jcm14124355.

ABSTRACT

Background/Objectives: Heart failure (HF) poses a major challenge in managing adults with congenital heart defects (ACHD). Emerging evidence suggests that HF in ACHD increases the risk of underweight due to heightened metabolic demands, gastrointestinal complications, and psychological factors such as anxiety and depression. Despite its critical implications, few studies have examined this association. This study evaluates the relationship between HF and underweight-defined as a body mass index (BMI) < 18.5-in ACHD. Methods: The Pathfinder-CHD Registry is a prospective, observational, web-based HF registry including ACHD with manifest HF, history of HF, or significant risk for HF. It documents congenital diagnoses, HF type, comorbidities, and treatments. Patients were categorized by BMI into mild (17.00-18.49), moderate (16.00-16.99), and severe (<16.00) underweight. Results: As of September 2024, the registry enrolled 1420 adults (mean age 31.8±11.3 years; 49.2% female). Underweight was present in 59 patients (4.2%): 62.7% mild, 18.6% moderate, and 18.6% severe. Among the remaining 1361 patients, 52.8% had normal weight, 32.8% were overweight, and 14.2% were obese. Women had significantly lower metabolic body weight than men (p = 0.002). Underweight correlated with younger age (p < 0.001) and CHD type (p = 0.02). Notably, 42.9% of underweight patients had cyanotic CHD. Conclusions: Underweight is an underrecognized problem in ACHD with HF. Adults with complex CHD or connective tissue disorders are disproportionately affected. Underweight should be seen as an alarm sign requiring personalized, multidisciplinary management, including nutritional support, tailored therapy, and close monitoring to improve outcomes.

PMID:40566101 | PMC:PMC12194136 | DOI:10.3390/jcm14124355

Children (Basel). 2025 Jun 16;12(6):782. doi: 10.3390/children12060782.

ABSTRACT

Background: Severe neonatal Ebstein's anomaly (EA) is associated with a high risk of mortality. A new therapeutic approach aims to combine the advantages of Starnes' procedure in stabilizing critically ill neonates with the long-term superiority of biventricular physiology after cone reconstruction. Case report: The echocardiography of a male preterm (36 weeks' gestation; birth weight 2400 g) demonstrated EA Carpentier type C, membranous pulmonary atresia, and hypoplastic pulmonary arteries (PAs). After undergoing the Starnes procedure postnatally, multiple dilatations of the AP shunt and the Starnes fenestration followed. Cone reconstruction was performed at 15 months of age. Surgical revision addressed tricuspid and pulmonary valve insufficiency and PA bifurcation stenosis. Subsequently, PA branch stenosis with severe impairment of right ventricular function and dilatation required stent implantation. At the last follow-up, at 3 years of age, the patient was asymptomatic with sufficient exercise tolerance. Discussion: The American Association for Thoracic Surgery recently recommended evaluating all Starnes patients for potential conversion to cone. Consequently, the Starnes procedure should be modified to facilitate subsequent biventricular correction. Both the optimal timing of conversion and the appropriate assessment to reliably evaluate feasibility and the prospects for success require further investigation. Conclusions: Conversion from Starnes to cone is technically feasible, even in cases of severe EA, prematurity, low birth weight, and additional cardiac comorbidities, and provides promising initial results. Further research is needed to define candidacy and the optimal timing of conversion, and to assess long-term outcomes. The high therapeutic effort and complexity make this treatment approach suitable only for quaternary centers.

PMID:40564740 | PMC:PMC12191472 | DOI:10.3390/children12060782

Children (Basel). 2025 Jun 13;12(6):767. doi: 10.3390/children12060767.

ABSTRACT

Objectives: In the neonatal period, 25% of cases with critical congenital heart disease (CCHD) require surgical or interventional palliative and corrective procedures. Prenatal diagnosis and timely intervention can positively impact neonatal mortality and morbidity. This study evaluated the effects of perinatal follow-up on the management of CCHD. Methods: The study was conducted on term neonates diagnosed with CCHD, who were monitored in the neonatology and pediatric cardiac intensive care unit between 1 January 2023 and 1 January 2024. The cases were categorized into CCHD with prenatal follow-up (Group I), CCHD born without follow-up at our hospital (Group II), and CCHD accepted from external centers (Group III). Neonatal mortality and morbidity outcomes of these cases that underwent surgical or interventional procedures were statistically evaluated. Results: During the study period, there were 280 neonatal cases (50% male). Among these cases, 30% were in Group I (n = 84), 20% in Group II (n = 56), and 50% in Group III (n = 140). The cesarean section rate was higher in Group I compared to the other groups (80% vs. 52% vs. 45%), and the preoperative lactate levels were lower (0.9 vs. 1.7 vs. 2.1). The anatomical diagnoses, ventricular physiology, operation time, and interventional procedure time were similar. After interventional or surgical procedures, morbidity (22% vs. 25% vs. 36%) and mortality rates (6% vs. 9% vs. 18%) were lower in Group I and Group II compared to Group III. Conclusions: All infants diagnosed with CCHD before birth should be delivered in a tertiary heart center, which positively contributes to neonatal mortality and morbidity. More effort is needed to improve prenatal screening programs.

PMID:40564725 | PMC:PMC12191443 | DOI:10.3390/children12060767

Children (Basel). 2025 May 29;12(6):705. doi: 10.3390/children12060705.

ABSTRACT

OBJECTIVES: This study aimed to describe the prevalence of malnutrition and its impact on postoperative outcomes in infants and children with congenital heart diseases (CHDs) undergoing cardiac surgeries.

METHODS: We conducted a single-center, retrospective review of medical records of children aged 1 month to 5 years with CHDs who underwent cardiac surgery at the American University of Beirut Medical Center (AUBMC) between January 2015 and January 2017. Anthropometric data were collected and z-scores for weight-for-age (WAZ), height-for-age (HAZ), weight-for-height (WHZ), and BMI-for-age were calculated. Malnutrition was classified based on the World Health Organization (WHO) definitions and the American Society for Parenteral and Enteral Nutrition (ASPEN) criteria. The postoperative outcomes were analyzed using bivariate and multivariable models.

RESULTS: The prevalence of malnutrition was 33.8%, with children younger than 24 months having significantly higher odds of malnutrition. The most common CHDs were ventricular septal defect (VSD) and tetralogy of Fallot (TOF), with malnutrition being significantly more prevalent in the children with VSD. Malnutrition was significantly associated with a prolonged pediatric intensive care unit (PICU) stay, with underweight being the strongest predictor. Malnourished children also had a significantly longer mechanical ventilation time (median 9.0 vs. 5.0 h, p = 0.017). Lower weight-for-age (WAZ) and BMI-for-age z-scores were associated with longer hospital stay, PICU stay, and mechanical ventilation durations.

CONCLUSIONS: Malnutrition is prevalent among children with CHDs and is independently associated with longer hospital and PICU stays, as well as extended mechanical ventilation. Early nutritional assessment and intervention may improve postoperative outcomes in this vulnerable population.

PMID:40564663 | PMC:PMC12191067 | DOI:10.3390/children12060705

Children (Basel). 2025 May 23;12(6):669. doi: 10.3390/children12060669.

ABSTRACT

Congenital heart disease (CHD), the most common congenital anomaly, remains a significant lifelong burden despite advancements in medical and surgical interventions. Induced pluripotent stem cells (iPSCs) have emerged as a groundbreaking platform in CHD research, offering patient-specific models to investigate the genetic, epigenetic, and molecular mechanisms driving the disease. Utilizing technologies such as CRISPR/Cas9 gene editing, cardiac organoids, and high-throughput screening, iPSCs enable innovative strategies in disease modeling, precision drug discovery, and regenerative therapies. However, clinical translation faces challenges related to immaturity, differentiation variability, large-scale feasibility, and tumorigenicity. Addressing these barriers will require standardized protocols, bioengineering solutions, and interdisciplinary collaboration. This review examines the critical role of iPSCs in advancing CHD research and care, demonstrating their potential to revolutionize treatment through patient-specific, regenerative approaches. By addressing current limitations and advancing iPSC technology, the field is positioned to pave the way for precision-based CHD therapies for this lifelong condition.

PMID:40564627 | PMC:PMC12190934 | DOI:10.3390/children12060669

Children (Basel). 2025 May 22;12(6):661. doi: 10.3390/children12060661.

ABSTRACT

Objective: To evaluate early and midterm outcomes of cryopreserved aortic homograft implantation in pediatric patients undergoing aortic valve and root replacement. Methods: A retrospective analysis was conducted on 36 pediatric patients aged 2 to 7 years who underwent cryopreserved aortic homograft implantation between January 2016 and December 2024. Indications included complex congenital aortic valve disease, annular hypoplasia, failed Ross procedure, and infective endocarditis. The standard root replacement technique was used under moderate hypothermic cardiopulmonary bypass. Postoperative outcomes were analyzed, including early complications, mortality, echocardiographic parameters, and long-term graft performance. Statistical analyses included the use of chi-square test, the Mann-Whitney U test, and Spearman correlation. Results: There was no 30-day mortality. One patient (2.8%) experienced late mortality at year 3, and two patients (5.6%) underwent reoperation at years 4 and 7 due to root aneurysm and severe regurgitation, respectively. Early postoperative echocardiography showed satisfactory hemodynamic performance with a mean gradient of 8.4 ± 3.2 mmHg. At 5-year follow-up, 92.9% of grafts maintained normal function. Conclusions: Cryopreserved homografts provide a safe and effective option for pediatric aortic valve replacement in the early and midterm period. However, potential late complications such as structural degeneration or root dilation necessitate long-term surveillance. Advances in decellularized grafts may improve future durability and integration.

PMID:40564621 | PMC:PMC12191320 | DOI:10.3390/children12060661

J Clin Med. 2025 Jun 9;14(12):4083. doi: 10.3390/jcm14124083.

ABSTRACT

This review provides an in-depth analysis of argatroban as an alternative anticoagulant in cardiac surgery, with a focus on its use in patients with heparin-induced thrombocytopenia (HIT). We examine argatroban's pharmacokinetics and dosing regimens and the challenges associated with cosnventional monitoring methods-such as activated clotting time (ACT) and activated partial thromboplastin time (aPTT)-to evaluate its safety and effectiveness in high-risk surgical settings. Drawing on data from multiple case reports and series, our review highlights both the potential benefits and limitations of argatroban, including complications such as clot formation in extracorporeal circulation systems and prolonged postoperative coagulopathy. In addition to the literature review, we present a detailed clinical case of urgent HeartMate 3 left ventricular assist device implantation in a patient with advanced heart failure and active HIT. In this case, despite targeting an ACT above 400 s, intraoperative complications such as clot formation in the heart-lung machine and difficulty achieving hemostasis highlight the need for improved monitoring and dosing protocols. Our findings call for refined anticoagulation strategies and advanced monitoring techniques to optimize argatroban use in cardiac surgery, offering valuable insights for clinicians managing complex scenarios where conventional heparin therapy is contraindicated.

PMID:40565829 | PMC:PMC12194504 | DOI:10.3390/jcm14124083

Life (Basel). 2025 Jun 9;15(6):928. doi: 10.3390/life15060928.

ABSTRACT

Sepsis is a life-threatening condition driven by a dysregulated host immune response to infection, with cytokine overproduction contributing to organ dysfunction and high mortality. Levosimendan, a calcium sensitizer used in acute heart failure, has been proposed to exert anti-inflammatory effects, but information on its immunomodulatory effects in early sepsis remains scarce. This study aimed to investigate the dose- and time-dependent effects of levosimendan on cytokine profiles in a rat model of lipopolysaccharide (LPS)-induced sepsis. Thirty-two male Wistar albino rats were randomly assigned to four groups: sham, sepsis control, low-dose levosimendan (1 mg/kg), and high-dose levosimendan (2 mg/kg). Cytokine levels (TNF-α, IL-1β, IL-6, IL-8, IL-17, MCP-1) were measured at 5 and 10 h post-LPS administration. High-dose levosimendan significantly reduced TNF-α, IL-1β, IL-6, and MCP-1 levels by the 10th hour, accompanied by improved Murine Sepsis Scores. IL-17 and IL-6 showed biphasic responses, increasing initially and decreasing significantly later, particularly with high-dose treatment. IL-8 reduction was observed only in the high-dose group. These findings support levosimendan's dose and time-dependent anti-inflammatory effects and suggest it may modulate both early and late-phase cytokines in sepsis. Further studies are warranted to clarify its potential role in clinical sepsis management.

PMID:40566580 | PMC:PMC12193883 | DOI:10.3390/life15060928

Children (Basel). 2025 May 22;12(6):661. doi: 10.3390/children12060661.

ABSTRACT

Objective: To evaluate early and midterm outcomes of cryopreserved aortic homograft implantation in pediatric patients undergoing aortic valve and root replacement. Methods: A retrospective analysis was conducted on 36 pediatric patients aged 2 to 7 years who underwent cryopreserved aortic homograft implantation between January 2016 and December 2024. Indications included complex congenital aortic valve disease, annular hypoplasia, failed Ross procedure, and infective endocarditis. The standard root replacement technique was used under moderate hypothermic cardiopulmonary bypass. Postoperative outcomes were analyzed, including early complications, mortality, echocardiographic parameters, and long-term graft performance. Statistical analyses included the use of chi-square test, the Mann-Whitney U test, and Spearman correlation. Results: There was no 30-day mortality. One patient (2.8%) experienced late mortality at year 3, and two patients (5.6%) underwent reoperation at years 4 and 7 due to root aneurysm and severe regurgitation, respectively. Early postoperative echocardiography showed satisfactory hemodynamic performance with a mean gradient of 8.4 ± 3.2 mmHg. At 5-year follow-up, 92.9% of grafts maintained normal function. Conclusions: Cryopreserved homografts provide a safe and effective option for pediatric aortic valve replacement in the early and midterm period. However, potential late complications such as structural degeneration or root dilation necessitate long-term surveillance. Advances in decellularized grafts may improve future durability and integration.

PMID:40564621 | PMC:PMC12191320 | DOI:10.3390/children12060661

Cardiovasc Revasc Med. 2025 Jun 21:S1553-8389(25)00312-4. doi: 10.1016/j.carrev.2025.06.027. Online ahead of print.

ABSTRACT

BACKGROUND: Intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) of complex coronary lesions is currently recommended by international guidelines. Complex coronary anatomy is observed in up to one third of the patients undergoing coronary interventions and is associated with worse clinical outcomes. Data on lesion characteristics and outcomes are scarce in census-defined minority groups.

METHODS/DESIGN: The Intravascular Ultrasound Guidance for Complex High-Risk Indicated Procedures in Underrepresented Patient Populations (UPP) Registry is a prospective, observational, multicenter, single-arm study describing the safety and efficacy of IVUS-guided PCI in approximately 1010 subjects who self-identify within a demographic minority and undergo complex high-risk procedures. Criteria for optimal stenting include final minimal stent area (MSA) >5 mm2 or MSA >90 % of the distal reference lumen, plaque burden <50 % within 5 mm proximal or distal to stent edges, and absence of edge dissections involving the media and > 3 mm in length. The primary endpoint of target-vessel failure is a composite of cardiac death, target vessel myocardial infarction, or clinically indicated target-vessel revascularization at 1 year. Secondary endpoints include the individual components of the primary end point as well as procedural and imaging endpoints.

SUMMARY: The IVUS CHIP UPP Registry is the first prospective investigation of procedural and clinical outcomes related to an IVUS-guided PCI for management of complex coronary lesions among minority patient populations in the United States.

PMID:40562607 | DOI:10.1016/j.carrev.2025.06.027

West J Emerg Med. 2025 May 20;26(3):729-736. doi: 10.5811/westjem.35271.

ABSTRACT

INTRODUCTION: The use of coronary artery bypass grafting (CABG) for primary revascularization during the acute care of ST-elevation myocardial infarction (STEMI) patients has declined significantly in the past decade; but there is little data to determine whether there has been a change in the use of CABG for STEMI patients treated by emergency medical services (EMS). In this study we described the incidence of urgent or emergent CABG for STEMI patients treated in a large, regionalized cardiac care system.

METHODS: We obtained data obtained for patients transported by EMS between January 2011-December 2022 who were diagnosed with acute STEMI on prehospital or emergency department (ED) electrocardiogram and taken for primary diagnostic catheterization. All STEMI patients were transported by EMS to one of 34 STEMI receiving centers (SRC) in a regionalized cardiac care system, all of which are required to maintain onsite cardiac surgery as a condition of their SRC designation. Patients were considered to have undergone urgent or emergent CABG if it was performed within 72 hours of the primary diagnostic cardiac catheterization. We excluded patients if no diagnostic catheterization was performed or if CABG was performed >72 hours after diagnostic catheterization. The primary outcome was the incidence of urgent or emergent CABG. Patients were further stratified by time between diagnostic catheterization and CABG (<24 hours, 24-48 hours, 48-72 hours).

RESULTS: A total of 28,349 patients were transported by EMS and diagnosed with an acute STEMI during the study period. Only 384 (1.35%) patients underwent CABG within 72 hours of diagnostic catheterization: 268 (0.95%) underwent CABG in <24 hours; 71 (0.25%) in 24-48 hours, and 45 (0.16%) in 48-72 hours. The median age of patients undergoing CABG was 64 years (interquartile range 58-72). Twenty-eight (7.3%) experienced prehospital cardiac arrest, and eight (2.1%) required vasopressors. Prior to undergoing CABG, 137 patients (36%) underwent primary percutaneous coronary intervention. The proportion of patients undergoing CABG within 72 hours remained relatively stable between 2011-2022 at 1.19% and 1.96%, respectively.

CONCLUSION: Urgent or emergent CABG remained infrequently performed for acute STEMI patients after primary diagnostic catheterization. There was little change in the percentage of STEMI patients who received CABG within 72 hours of diagnostic catheterization over the past decade. These findings suggest that regional or local policies requiring on-site cardiac surgery at SRCs may be reconsidered.

PMID:40562005 | PMC:PMC12208032 | DOI:10.5811/westjem.35271

J Integr Med. 2025 Jun 13:S2095-4964(25)00081-0. doi: 10.1016/j.joim.2025.06.002. Online ahead of print.

ABSTRACT

OBJECTIVE: The occurrence and development of atrial fibrillation (AF) are influenced by the autonomic nervous system and inflammation. Acupuncture is an effective treatment for AF. This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.

METHODS: Male Sprague-Dawley rats (n = 130) were randomly divided into blank control (Con), sham operation (Sham), AF, and acupuncture treatment (Acu) groups. A paroxysmal AF model was established by rapid atrial pacing through the jugular vein. Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint (PC6) for 20 min daily for seven days. The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture. The AF induction rate, AF duration, cardiac electrophysiological parameters, and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals. After the intervention, the rats were euthanized, and atrial morphology was assessed using haematoxylin and eosin staining. The expression of macrophage F4/80 antigen (F4/80) and cluster of differentiation (CD) 86 in atrial myocardial tissue was detected using immunohistochemistry, immunofluorescence and flow cytometry. The expression levels or contents of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), α7 nicotinic acetylcholine receptor (α7nAChR), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in atrial myocardial tissue were detected using Western blotting, reverse transcription-quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. The role of α7nAChR in acupuncture treatment was verified by intraperitoneal injection of the α7nAChR antagonist methyllycaconitine (MLA).

RESULTS: Compared with the AF group, acupuncture significantly reduced AF duration and induction rate, improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance. It also decreased the pro-inflammatory M1 macrophage proportion, alleviating myocardial injury and infiltration. MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect. Results suggest that acupuncture triggers the α7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.

CONCLUSION: Acupuncture significantly reduced the AF induction rate, shortened AF duration, improved cardiac electrophysiological parameters, enhanced vagus nerve activity, and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF. Its positive effects are related to the activation of the α7nAChR-mediated JAK2/STAT3 signalling pathway, indicating that the interaction between cardiac vagus nerve and macrophages may be a potential target for acupuncture in the prevention and treatment of AF. Please cite this article as: Li ZH, Yang WM, Huang Q, Shi GX, Liu CZ, Zhang YQ. Acupuncture activates vagus nerve-macrophage axis and improves cardiac electrophysiology and inflammatory response in rats with atrial fibrillation via α7nAChR-JAK2/STAT3 pathway. J Integr Med. 2025; Epub ahead of print.

PMID:40562587 | DOI:10.1016/j.joim.2025.06.002

Phytomedicine. 2025 Jun 17;145:156990. doi: 10.1016/j.phymed.2025.156990. Online ahead of print.

ABSTRACT

BACKGROUND: Yangxinshi tablet (YXST), as the traditional Chinese medicine, could significantly improve cardiac function and exercise tolerance in patients with coronary heart disease. However, molecular mechanisms of YXST protecting against myocardial injury and promoting skeletal muscle exercise capacity is still unclear.

PURPOSE: This study aimed to clarify the efficacy and potential mechanisms of YXST in myocardial injury and skeletal muscle exercise capacity.

METHODS: Mice were randomly divided into 6 groups (n = 10-20 every group) and administrated for 6 weeks: control group, myocardial ischemia‒reperfusion group (I/R group), YXST group (I/R mice treated with YXST, respectively 250,500 and 1000 mg/kg/day) and I/R treated with trimetazidine (TMZ) group (20 mg/kg/day). Meanwhile, the mice were divided into 4 groups (n = 8-9 every group), which were control group, YXST group (250, 500 and 1000 mg/kg/day for 6 weeks). Cardiac function, exercise tolerance, grip strength, skeletal muscle structure and myoblasts proliferation were detected. RNA-sequence assays and mass spectrometry analysis of C2C12 myotubes were performed and analyzed. UHPLC was employed to detect YXST's characterize and its principal components. The target protein of YXST were assessed by molecular docking methods. Mitochondria oxygen consumption rate was detected by Seahorse.

RESULTS: YXST improved cardiac function and exercise tolerance, enhanced the slow type I fibers expression, ameliorated mitochondrial biogenesis, and attenuated inflammation level under I/R condition in vivo. YSXT could directly promote exercise capacity and satellite cells proliferation of skeletal muscle under normal condition in vivo. We also found that YXST promoted C2C12 myoblasts differentiation and myotubes formation by regulating mitochondrial biogenesis, mitophagy, and oxidative phosphorylation in vitro. Molecular docking analysis demonstrated that the top 9 compounds identified in blood may bind with BTB and CNC homology 1 protein (BACH1). CETSA assay revealed that YXST had a significantly effect on increasing the thermal stability of BACH1 protein. Interestingly, YXST stimulated the secretion of cardioprotective myokines.

CONCLUSION: This study revealed that YXST improved cardiac function and exercise tolerance in I/R mice, particularly we found that YXST could directly enhance the exercise capacity of mice under normal condition. Mechanismly, YXST significantly regulated mitochondrial biogenesis, oxidative phosphorylation and myokine production in vivo and in vitro. Our findings provide novel mechanistic insights and pharmacological basis for the application of YXST against coronary heart disease and skeletal muscle injury.

PMID:40561862 | DOI:10.1016/j.phymed.2025.156990

Biochem Biophys Res Commun. 2025 Jun 21;776:152242. doi: 10.1016/j.bbrc.2025.152242. Online ahead of print.

ABSTRACT

Despite its potent chemotherapeutic efficacy, cyclophosphamide (CP) is associated with severe cardiac complications, limiting its clinical utility. Recent evidence suggests that the mucolytic agent ambroxol (ABX) exhibits antioxidant and anti-inflammatory properties, making it a candidate for mitigating CP cardiotoxicity. This study explored the protective effects of ABX against CP-mediated cardiotoxicity, with emphasis on oxidative stress, NF-κB/NLRP3 inflamamsome axis and Nrf2/HO-1 signaling. Rats were administered ABX (20 mg/kg) for 7 days and received a single injection of CP (100 mg/kg) on day 5, and blood and heart samples were collected for analyses. CP administration induced significant cardiac dysfunction, marked by elevated LDH, CK-MB, and troponin-I, alongside histopathological evidence of myocardial injury. ABX alleviated cardiac biomarkers, prevented histopathological alterations, reduced lipid peroxidation, and restored antioxidant defenses. CP upregulated NF-κB p65, NLRP3, ASC1, caspase-1, gasdermin D, and IL-1β, and suppressed Nrf2 and HO-1 in the heart of rats. ABX suppressed the NF-κB/NLRP3 inflamamsome axis mediators and upregulated Nrf2 and HO-1. In silico data revealed the binding affinity of ABX towards NF-κB p65 and NLRP3 and ASC1 PYD domains. In conclusion, ABX confers significant protection against CP-induced cardiotoxicity through multifaceted mechanisms, including attenuation of oxidative stress, inhibition of NF-κB/NLRP3 inflamamsome axis, and upregulation of Nrf2/HO-1 signaling. These findings suggest that ABX could serve as an effective adjunct therapy to improve the safety profile of CP in clinical oncology.

PMID:40561755 | DOI:10.1016/j.bbrc.2025.152242

PLoS One. 2025 Jun 25;20(6):e0326249. doi: 10.1371/journal.pone.0326249. eCollection 2025.

ABSTRACT

Low cardiorespiratory fitness (CRF) is a well-established risk factor for cardiovascular disease (CVD) and all-cause mortality. Since CRF is largely genetically determined, understanding the genetic influences on CRF might reveal the protective mechanisms of high CRF. One gene found to be associated with CRF is COX7A2L. COX7A2L is a mitochondrial supercomplex assembly factor, but its role in cellular metabolism remains a topic of discussion. We hypothesized that COX7A2L could play a role in cellular respiration in cardiomyocytes, affecting cardiac function and CRF. To determine the effect of COX7A2L on cardiomyocyte function, we overexpressed and knocked down COX7A2L in human AC16 cardiomyocytes and performed MTT assays and Seahorse XF Cell Mito Stress Tests to assess cell viability and mitochondrial function. For the mitochondrial function measurements, we stimulated the cells with isoproterenol to investigate if the effect of altering COX7A2L levels would be larger under simulated increased energy demand. Overexpression and knockdown were validated using sandwich ELISA. Our findings showed that altering COX7A2L expression in human AC16 cardiomyocytes did not significantly affect cell viability or mitochondrial function. Further research is necessary to determine whether COX7A2L influences cardiomyocyte function and CRF.

PMID:40560843 | PMC:PMC12194157 | DOI:10.1371/journal.pone.0326249

Am J Physiol Cell Physiol. 2025 Jun 25. doi: 10.1152/ajpcell.01006.2024. Online ahead of print.

ABSTRACT

Aberrant autophagy mediated by AMPK/mTOR/ULK1 pathway (a canonical autophagy pathway) plays important roles in diabetic cardiomyopathy (DCM). Asprosin (ASP) secreted by white adipose tissue involves in systemic metabolism disorders. However, its role in DCM remains poorly understood. Therefore, the purpose of this study was to investigate its roles and underlying mechanism in the DCM from the perspective of autophagy and apoptosis. In the in vivo experiments, we observed the effects of ASP-deficiency (ASP-/-) or ASP intervention on cardiac function, fibrosis, autophagy and apoptosis in a diabetes mellitus (DM) mouse model induced by high-fat feeding and streptozotocin (STZ) injection; in the in vitro experiments, we evaluated the effects of ASP intervention with or without 3-MA (autophagy inhibitor) or siAMPK in a H9c2 model injured by high glucose (HG). Our results show that ASP intervention attenuates the myocardial injury induced by DM (P<0.05) and HG (P<0.05). Additionally, the autophagy level markedly increases (P<0.05) in diabetic mice and ASP-deficiency worsens the increase induced by DM (P<0.05). In contrast, ASP intervention alleviates over-autophagy induced by DM (P<0.05) or HG (P<0.05). Mechanistically, the protective effect of ASP against myocardial injury is through inhibiting the over-autophagy mediated by AMPK/mTOR/ULK1 pathway (P<0.05). Taken together, the findings suggest that ASP would be a potential therapeutic target and the recombinant ASP might be a promising candidate to treat metabolism-associated CVD. Although the findings would present a promise for the treatment of DCM, it is worth noting that the mouse model used fails to fully mimic the human DCM pathophysiology.

PMID:40560772 | DOI:10.1152/ajpcell.01006.2024

BMJ Open. 2025 Jun 25;15(6):e100553. doi: 10.1136/bmjopen-2025-100553.

ABSTRACT

INTRODUCTION: Ischaemia-reperfusion (I/R) injury remains a major challenge in heart transplantation, with mortality risk increasing significantly when allograft ischaemic time exceeds 4 hours. Non-ischaemic heart preservation (NIHP), using continuous hypothermic perfusion, has shown promise in preliminary studies for reducing I/R injury and improving outcomes. This randomised controlled trial aims to compare NIHP with standard static cold storage (SCS) in adult heart transplantation.

METHODS AND ANALYSIS: The trial is a prospective, open-label, multicentre, single-blinded, randomised controlled trial including 66 adult heart transplant recipients across four Swedish hospitals. Participants will be randomised into 1:1 ratio to NIHP or SCS preservation groups and undergo a 12-month follow-up period. The primary outcome is 1-year survival free from acute cellular rejection or retransplantation. Secondary outcomes include quality of life, I/R injury markers, graft function and adverse events. Substudies will evaluate renal function using MRI and continuously monitor physical activity and heart rhythm via wearable devices. Analysis will follow intention-to-treat principles, with time-to-event analysis using Cox proportional hazard models and Kaplan-Meier estimates.

ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority. It will be conducted according to the Declaration of Helsinki and relevant local and international regulations. Results will be published in peer-reviewed journals following Consolidated Standards of Reporting Trials guidelines.

TRIAL REGISTRATION NUMBER: NCT04066127.

PMID:40562558 | PMC:PMC12198846 | DOI:10.1136/bmjopen-2025-100553

Rev Esp Cardiol (Engl Ed). 2025 Jun 23:S1885-5857(25)00190-2. doi: 10.1016/j.rec.2025.04.011. Online ahead of print.

ABSTRACT

Introduction and objectives This report presents updated data on heart transplants in Spain, including procedures carried out in 2024. It reviews trends over the past decade (2015-2024) in donor and recipient characteristics, surgical techniques, immunosuppression strategies, and survival rates. Methods Data were drawn from the Spanish heart transplant registry, which is updated annually. The analysis includes 347 transplants performed in 2024, as well as procedures from 2015 to 2023 (n = 2721). Results In 2024, the number of heart transplants increased by 6.8% compared with 2023. There were no significant changes in recipient age or sex, but the proportion of urgent transplants rose to 47.0%. Use of circulatory support devices increased, particularly extracorporeal membrane oxygenation. The average donor age showed a slight increase in 2024, although the long-term trend remained downward. Donation after circulatory death accounted for 29.1% of transplants in 2024. One-year survival rates improved, reaching 85.2% for transplants performed between 2021 and 2023. Conclusions The number of heart transplants continued to grow, nearing historic highs, largely due to the expansion of donation after circulatory death. Improved 1-year survival reflects the maturity of transplant programs, advances in surgical and medical management, and better pretransplant conditions in recipients. Full English text available from: www.revespcardiol.org/en.

PMID:40562161 | DOI:10.1016/j.rec.2025.04.011