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Sci Rep. 2025 Jul 1;15(1):21803. doi: 10.1038/s41598-025-06190-8.

ABSTRACT

A number of cardioprotective pharmacological agents are not effective in diabetic hearts. The role of AGGF1-EPCs therapy in diabetic ischaemia-reperfusion(I/R) injury and the underlying mechanism by which AGGF1 regulates EPCs under hyperglycemia (HG) + hypoxia/reoxygenation (H/R) stress are still unclear. We observed that the damaging effects of HG + H/R on EPCs were abolished by AGGF1. The EPCs implantation therapy successfully restores cardiac functions, inhibits ROS production and fibrosis in diabetic I/R mice. Mechanistically, AGGF1 activates the Nrf2 and induces the activation of downstream antioxidative proteins (HO1, NQO1, and CAT). These data suggest that AGGF1 protein reverses the damaging effects of HG + H/R on EPCs via the antioxidative Nrf2. AGGF1-EPCs therapy is a novel strategy for treating diabetic I/R injury.

PMID:40594882 | PMC:PMC12216187 | DOI:10.1038/s41598-025-06190-8

Minerva Pediatr (Torino). 2025 Jul 2. doi: 10.23736/S2724-5276.25.07753-5. Online ahead of print.

ABSTRACT

BACKGROUND: Pediatric tracheal surgery includes several complex and rare procedures. We report the surgical experience at our center.

METHODS: Our center has multidisciplinary team manages laryngotracheal malformations. We retrospectively analyzed all tracheal surgeries from January 2009 to September 2023, excluding endoscopic cases and tracheostomy insertion, revision, or closure not related to reconstructive tracheal surgery. We evaluated diagnosis, comorbidities, type of surgery, need for tracheostomy, complications, death, outcome in terms of decannulation and adequate caliber airway.

RESULTS: A total of 122 patients with a median age of 2.61 years (0-25.4 years) were operated for congenital (59.8%) or acquired (40.2%) tracheal pathology. The procedures performed were: cricothyroid resection (N.=18; 14.8%), laryngotracheal reconstruction with rib cartilage graft (N.=33; 27%), tracheal resection-anastomosis (N.=20; 16.4%), laryngotracheal cleft closure (N.=5; 4.1%), "slide tracheoplasty" (N.=15; 12.3%), posterior tracheopexy (N.=14; 11.5%); isolated tracheoesophageal fistula closure (N.=17; 13.9%). Depending on the type of operation, cardiac surgeons and otolaryngologists were involved. Preoperative tracheotomy was required in 54 patients and postoperative in 51 patients. We reported a mortality of 6.1%, or seven patients, four of whom died in the immediate postoperative period, but only one death was due to surgical causes. Other intraoperative complications were reported in two patients (1.6%) and postoperative complications in 34 patients (27.9%). Ninety-two patients (75.4%) were alive with adequate airway caliber and no need for tracheostomy.

CONCLUSIONS: There are many indications for tracheal surgery and a multidisciplinary approach has been essential. Tracheal surgery is complex and potentially associated with major complications, but outcomes are generally satisfactory.

PMID:40598991 | DOI:10.23736/S2724-5276.25.07753-5

Gen Thorac Cardiovasc Surg Cases. 2025 Jul 1;4(1):29. doi: 10.1186/s44215-025-00214-5.

ABSTRACT

A 21-year-old female patient had undergone two open heart surgeries in childhood, including Konno ventriculoplasty with mechanical aortic valve replacement. She underwent a redo mechanical aortic valve replacement and patch enlargement of stenotic ascending aorta using a triplex prosthetic graft. Unfortunately, 1 month after surgery, the patient was readmitted to the hospital with a diagnosis of midline chest wound infection. A culture sample from the wound revealed Serratia marcescens, however, subsequent all culture tests were negative. Since then, there has been a continued serous discharge from the caudal side of the midline skin incision scar and chest tube removal scar in the chest. Despite the implementation of four open chest treatments, the issue of perigraft seroma persisted, and a diagnosis was ultimately made. During her subsequent admission, negative pressure wound therapy was employed, followed by daily sterilization and film dressing post-discharge. It is understood that a gradual decrease in drainage and complete resolution of the seroma occurred 21 months after surgery, without the removal of the implanted triplex patch.

PMID:40598704 | PMC:PMC12220449 | DOI:10.1186/s44215-025-00214-5

BMC Nephrol. 2025 Jul 1;26(1):334. doi: 10.1186/s12882-025-04269-y.

ABSTRACT

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) represents an important global health challenge. However, the emerging analysis of the burden of CAKUT is limited and outdated. This study aimed to evaluate the global burden and temporal trends of CAKUT across 204 countries and territories from 1990 to 2021.

METHODS: Data on the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) of CAKUT from 1990 to 2021 were obtained from the Global Burden of Disease Study 2021. Temporal trends were analyzed using Joinpoint regression. The association between CAKUT burden and the socio-demographic index (SDI) was examined via Spearman correlation analysis. Decomposition analysis was used to estimate the effects of population growth, aging, and epidemiological changes on overall change of CAKUT burdens. The Bayesian age-period-cohort model was utilized to predict the CAKUT burden through 2036.

RESULTS: From 1990 to 2021, the global prevalence of CAKUT increased by 21.50%, reaching 6.34 million (95% uncertainty interval [UI]: 5.07, 7.90), with a modest rise of 3.96% in the age-standardized prevalence rate (ASPR). In contrast, the incidence, mortality, and DALYs of CAKUT declined, with the age-standardized incidence rate (ASIR) decreasing by 2.86%, the age-standardized mortality rate (ASMR) by 20.00%, and the age-standardized DALY rate (ASDR) by 18.46%. In 2021, Southern Sub-Saharan Africa exhibited the highest ASPR and ASIR, while Central Latin America recorded the highest ASMR, and Southern Latin America had the highest ASDR. Furthermore, ASPR, ASIR, ASMR, and ASDR were all negatively correlated with SDI. Decomposition analysis revealed that population growth drove the increase in CAKUT prevalence. Projections to 2036 suggest further increases in ASPR and ASIR, whereas ASMR and ASDR are expected to decline.

CONCLUSION: Despite reductions in ASIR, ASMR, and ASDR, the increasing ASPR underscores the persistent global burden of CAKUT. Targeted interventions are urgently needed, particularly in high-burden regions such as Southern Sub-Saharan Africa.

PMID:40597805 | PMC:PMC12219625 | DOI:10.1186/s12882-025-04269-y

Sci Rep. 2025 Jul 1;15(1):20935. doi: 10.1038/s41598-025-04838-z.

ABSTRACT

The Pediatric Quality of Life Inventory™ (PedsQL™) family impact module is a widely used tool for assessing the health-related quality of life (HRQoL) of caregivers of children with chronic illnesses; however, it has not been available in Swahili. This study aimed to translate, culturally adapt, and validate the Swahili version of the PedsQL family impact module (FIM) among caregivers of children with heart disease in Tanzania. As a secondary aim, the study explored differences in caregiver HRQoL between those whose children had undergone surgery and those who had not, using the newly translated tool. A cross-sectional survey was conducted among 204 primary caregivers at a national cardiac referral centre. Standardised translation and adaptation procedures were followed. Psychometric evaluation included internal consistency reliability, construct validity through known-groups comparisons, and effect size estimation. The Swahili version demonstrated excellent internal consistency (Cronbach's α = 0.99) and good construct validity. Socioeconomic status was the only consistent predictor of HRQoL in multivariable models. Caregivers in the operated group consistently reported higher HRQoL scores, highlighting the potential benefit of surgical intervention on family well-being. These findings strongly support the Swahili PedsQL FIM as a culturally appropriate and psychometrically sound tool. It offers promise for clinical care and future outcome evaluations in similar settings.

PMID:40594323 | PMC:PMC12216588 | DOI:10.1038/s41598-025-04838-z

J Med Life. 2025 May;18(5):494-508. doi: 10.25122/jml-2025-0085.

ABSTRACT

Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery associated with adverse outcomes. Systemic inflammation is implicated in POAF pathogenesis, suggesting inflammatory biomarkers may have predictive value. This study investigated the predictive capacity of readily accessible inflammatory markers for POAF during the early postoperative period in the cardiac intensive care unit, particularly within the 48-72-hour window when POAF most commonly occurs. In this prospective, single-center study, we enrolled 70 patients undergoing elective cardiac surgery with cardiopulmonary bypass. We measured preoperative and postoperative (24h, 48h) levels of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), C-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-17A (IL-17A). POAF was systematically monitored. We assessed the predictive value of these markers using ROC curve analysis and logistic regression, adjusting for clinical risk factors. The coronary cohort showed that the NLR at both 24 hours and 48 hours were the most discriminative markers for predicting POAF, with PCR at 48 hours achieving a moderate AUC of 0.66. In multivariate regression models, PCR at 48 hours (P = 0.009) and age (P = 0.046) emerged as significant predictors, while NLR and CPB duration were moderately correlated with the occurrence of POAF. In contrast, within the valvular patient subgroup, the NLR again exhibited promising predictive value, along with increased markers of tissue injury such as CK, LDH, and creatinine. Readily accessible postoperative inflammatory markers, particularly NLR at 24 hours and CRP at 48 hours, demonstrated moderate predictive value for POAF in patients undergoing elective cardiac surgery. These markers, especially NLR and CRP, may potentially contribute to improved POAF risk stratification in clinical practice when combined with clinical risk factors. Furthermore, our analysis also indicates that preoperative IL-17A levels may influence the occurrence of POAF. Therefore, alongside CRP and NLR, preoperative IL-17A can be considered a potentially significant marker for atrial fibrillation following cardiac surgery. However, these findings are preliminary and require validation in larger, multi-center studies to confirm their clinical utility and inform preventative strategies.

PMID:40599146 | PMC:PMC12207702 | DOI:10.25122/jml-2025-0085

Sci Rep. 2025 Jul 2;15(1):22770. doi: 10.1038/s41598-025-98828-w.

ABSTRACT

Cerebral embolic protection (CEP) devices may be a tool to mitigate the perioperative stroke risk in cardiac surgery. However, studies are limited. The aim of this study was to analyze the feasibility, safety, and efficacy of CEP use in high-risk cardiac surgery. Ten high-risk surgical candidates with native valvular heart disease (mainly mitral with severe MAC) or failed bioprosthesis were consecutively enrolled between March 2023 and April 2024. All participants underwent open-heart surgery with use of Sentinel CEP. The CEP device was successfully deployed and recaptured in all cases without any Sentinel-related complications reported. Clearly visible, large deposits of calcium debris were captured. No significant neurological deficits (above mild neurological dysfunction; NIHSS > 5) were reported in any of the patients. Nine patients suffered postprocedural complications ranging from new-onset left bundle branch block to cardiogenic shock. One individual gradually deteriorated and ultimately died. Importantly, her neurological status remained intact throughout the course of the hospitalization. All other patients were discharged in good standing. The current study extends the early experience demonstrating the feasibility and safety of Sentinel CEP in high-risk cardiac surgery. Particularly in the highest-risk patient sub-sets CEP devices may offer advantages reducing the risk of periprocedural episodes and improving outcomes.

PMID:40596683 | PMC:PMC12215302 | DOI:10.1038/s41598-025-98828-w

Int J Equity Health. 2025 Jul 1;24(1):187. doi: 10.1186/s12939-025-02571-7.

ABSTRACT

BACKGROUND: We propose that all communities should have access to lifesaving technologies like pediatric extracorporeal membrane oxygenation (ECMO), and that distance is one actionable component to accessibility. We chose to examine whether geographic access by distance to pediatric ECMO differs by race/ethnicity for populations historically excluded from health services and technologies.

METHODS: Population data was obtained from the US Census Bureau's American Community Survey. Pediatric ECMO program data was obtained from the Extracorporeal Life Support Organization Registry. We compared the proportion of individuals that are American Indian/Alaska Native, Black/African American, Hispanic/Latina(o), or White that live within and outside of a 200-mile distance from pediatric ECMO programs.

RESULTS: 43% of the total US land area falls outside of the US catchment area for pediatric ECMO; and 4.91% of the US population (or 16,433,563 persons) does not have access to a Pediatric ECMO center. One of every four individuals that identify as American Indian/Native American, one of every 100 who identify as Black/African American, one of every 12 that identify as Hispanic/Latina(o), and one of every 21 that identify as White live outside of the pediatric ECMO catchment area for the United States.

CONCLUSIONS: American Indian/Native Americans and Hispanic/Latina(o)s lack access to pediatric ECMO by proximity. While Black/African Americans live close to ECMO programs, previous studies show that this population has less access to primary and specialized care. Distance is one actionable measurement that should be used to extend access to medical technologies for populations that have historically been excluded.

PMID:40597164 | DOI:10.1186/s12939-025-02571-7

Sci Rep. 2025 Jul 1;15(1):20573. doi: 10.1038/s41598-025-06607-4.

ABSTRACT

This study was aimed at developing and internally validating nomograms for predicting mortality during venoarterial-extracorporeal membrane oxygenation (VA-ECMO) and in-hospital mortality risk in patients treated with VA-ECMO. A total of 7260 patients treated with VA-ECMO from January 2017 to December 2023 were extracted from the Chinese society of extra corporeal life support registry database. The entire cohort was randomly assigned to derivation and validation cohorts at a ratio of 2:1. Multivariable Cox proportional hazards regression was conducted using bootstrapping with the likelihood ratio test and Akaike information criterion. Approximately 24% of patients died during VA-ECMO assistance, and 51% died in the hospital. The nomogram PROFIT was constructed with ten pre- and immediately post-ECMO parameters: age, body mass index (BMI), intra-aortic balloon pump before VA-ECMO, history of cardiac arrest, worst mean arterial pressure (MAP), potential of hydrogen (pH) and serum lactate levels before VA-ECMO, site of ECMO installation, peripheral cannulation and distal perfusion. Additionally, nomogram POSITIVE was also established with ten parameters: age, sex, BMI, history of cardiac arrest, MAP, pH, and serum lactate levels before VA-ECMO support, the occurrence of cardiac arrest before VA-ECMO, type of sedation and prior continuous renal replacement therapy. The area under the receiver operating characteristics (AUC) of the nomogram PROFIT (0.72 [95% CI 0.70-0.74]) and POSITIVE (0.71 [95% CI 0.68-0.73]) outperformed the SAVE score, which indicated that the nomograms were capable of effectively identifying patients with a high risk of mortality. Both nomograms demonstrated outstanding discrimination and calibration in derivation and validation cohorts. In patients treated with VA-ECMO, the nomogram PROFIT may serve as a valuable tool for predicting mortality during VA-ECMO assistance, and the nomogram POSITIVE can predict in-hospital mortality with high reliability. However, these tools still require external validation in other patient populations requiring VA-ECMO support.

PMID:40594967 | PMC:PMC12215877 | DOI:10.1038/s41598-025-06607-4

Sci Rep. 2025 Jul 1;15(1):21368. doi: 10.1038/s41598-025-06457-0.

ABSTRACT

Temporary mechanical circulatory support (MCS), including veno-arterial extracorporeal membrane oxygenation (ECMO) and micro-axial pumps (Impella), is increasingly used in clinical practice for refractory circulatory failure. Complex physiological responses to each technique or their combination (ECPELLA) remain debated and are often specific to cardiovascular pathology. A paucity of data on physiological responses to MCS in normal subjects makes comprehensive understanding of such responses in variable disease states difficult, as well as during weaning MCS in recovering hearts. This translational investigation compared three MCS techniques with variable pump flows in healthy sheep (n = 7) to establish baseline for future studies in cardiomyopathic models. All MCS techniques increased arterial elastance, but reduced LV myocardial work, coronary arterial flow and LV myocardial oxygen consumption. ECPELLA was more effective in increasing total systemic blood flow and MAP. The overall similarity between the MCS techniques suggests that the more invasive and complex combination of devices (ECPELLA) can only be justified for management of the severe failing heart as the means for decompressing LV. A study investigating the comparative impacts of different regimes and MCS techniques in a cardiomyopathic model is warranted.

PMID:40594422 | PMC:PMC12215061 | DOI:10.1038/s41598-025-06457-0

BMC Anesthesiol. 2025 Jul 1;25(1):328. doi: 10.1186/s12871-025-03206-8.

ABSTRACT

BACKGROUND: Rhomboid intercostal plane block (RIB) has been described in the last decade. In this study, we aimed to evaluate the outcomes of RIB in terms of perioperative analgesia and patient and physician satisfaction in patients undergoing CIED.

METHODS: The randomized controlled trial was structured into two arms, each comprising 25 patients and allocation was performed using a sealed-envelope randomization technique. Local anaesthesia group-LAG received only local anaesthesia (LA) (prilocaine 2%) as the standard procedure. RIB group-RIBG received RIB in addition to the standard procedure. Demographic and clinical data about the patients and the procedures performed were recorded. The first and second rescue treatments in cases of pain during the procedure and the first and second rescue treatments during the postoperative follow-up were also recorded. Pain levels during the procedure, at the end of the procedure and 3, 6, 12, and 24 h after the procedure were determined according to the NRS-11(Numeric Rating Scale-11). Patient and physician satisfaction were recorded on a five-point Likert scale. The primary outcome of the study was the efficacy of RIB in patients undergoing CIED implantation, assessed by NRS-11 pain scores during the procedure and in the postoperative period. As secondary outcome, patient and physician satisfaction levels were evaluated during the procedure.

RESULTS: There was less need for additional local anaesthetic in the RIBG than in the LAG (p < 0.001). NRS-11 scores during implantation, at the end of the implantation procedure, and at the 3-, 6-, 12-, and 24-hour follow-ups were greater in the LAG (p < 0.001). The satisfaction levels of both doctors and patients were higher in the RIBG (p < 0.001).

CONCLUSIONS: RIB application in CIED implantations showed adequate analgesic efficacy in patients during the perioperative period and up to 24 h postoperatively. At the same time, it provided high procedural satisfaction for patients and physicians. RIB should be considered in the multimodal analgesia approach in the perioperative analgesia of this patient group. There is a need for collaboration between anaesthesiologists and cardiologists to establish protocols, including RIB, for perioperative pain management in patients who undergo CIED implantation.

TRIAL REGISTRATION: This study was registered in the Clinical Trials (ID: NCT06449599, 27/05/2024).

PMID:40597579 | PMC:PMC12220544 | DOI:10.1186/s12871-025-03206-8

BMC Anesthesiol. 2025 Jul 1;25(1):309. doi: 10.1186/s12871-025-03194-9.

ABSTRACT

BACKGROUND: Increased intracranial pressure is a possible cause of postoperative delirium in open heart surgery patients. Optic nerve sheath diameter is a non-invasive measurement method used to monitor intracranial pressure changes. The authors suggested in this study that optic nerve sheath diameter monitoring could identify patients at risk of postoperative delirium.

METHOD: This prospective observational study was conducted by evaluating data from 90 patients undergoing open heart surgery. Optic nerve sheath diameter in patients was recorded before and after anesthesia induction, before and after cardiopulmonary bypass, and after intensive care transfer. Postoperative delirium was evaluated with the Confusion Assessment Method for the Intensive Care Unit scale.

RESULTS: The study was completed with 90 patients and postoperative delirium was observed in 20 of the patients (22.2%). Optic nerve sheath diameter (OR, 5.787; 95% CI, 1.489-22.496; P = 0.011), history of alcohol use (OR, 6.032; 95% CI, 1.052-34.604; P = 0.044), and EuroSCORE II (OR, 3.090; 95% CI, 1.453-6.571; P = 0.003) was associated with postoperative delirium.

CONCLUSIONS: Optic nerve sheath diameter measured by ultrasonography is associated with postoperative delirium. The increase in optic nerve sheath diameter can be used predictively for postoperative delirium in open heart surgery.

TRIAL REGISTRATION: Samsun University Samsun Training and Research Hospital, following ethics committee approval (Samsun University clinical research ethics committee (KAEK) 2023 11/7) and Clinical Trials (NCT05942183 / 05.09.2024) registration.

PMID:40596877 | DOI:10.1186/s12871-025-03194-9

Sci Rep. 2025 Jul 1;15(1):21890. doi: 10.1038/s41598-025-08181-1.

ABSTRACT

In the patients receiving coronary artery bypass grafting (CABG), arterial stiffness is an independent predictor of disease-related mortality. Higher serum levels of big endothelin-1 (BigET-1) are associated with arterial stiffness. The present study aimed to determine the association between serum BigET-1 levels and arterial stiffness in patients undergoing CABG. A total of 90 patients undergoing CABG were enrolled in the study. Serum levels of BigET-1 are examined with a commercial sandwich enzyme immunoassay. If carotid-femoral pulse wave velocity (cfPWV) > 10 m/s, arterial stiffness is diagnosed. In the study cohort, 30 (33.3%) patients with arterial stiffness were older and had lower body mass index, higher rates of diabetes mellitus and hypertension, higher systolic and diastolic blood pressures, and higher serum BigET-1 levels compared to the controls. Multivariable logistic regression analysis revealed that serum BigET-1 > 1 pg/mL was an independent predictor of arterial stiffness (odds ratio 17.492, 95% confidence interval 2.728-112.147, p = 0.003). Multivariable linear regression analysis revealed that cfPWV significantly correlated with age (β = 0.238, adjusted R2 change = 0.043, p = 0.004), systolic blood pressure (β = 0.251, adjusted R2 change = 0.102, p = 0.002), and BigET-1 level (β = 0.533, adjusted R2 change = 0.387, p < 0.001). Increased serum BigET-1 levels were associated with arterial stiffness in patients undergoing CABG.

PMID:40593258 | PMC:PMC12219143 | DOI:10.1038/s41598-025-08181-1

Cardiovasc Revasc Med. 2025 Jun 20:S1553-8389(25)00305-7. doi: 10.1016/j.carrev.2025.06.019. Online ahead of print.

ABSTRACT

BACKGROUND: Left main coronary artery disease (LMCAD) complexity is assessed using the SYNTAX score. High scores may reflect complex LM lesions or multivessel disease. Evidence on the prognosis of these distinct populations is scarce.

METHODS: Patients undergoing percutaneous coronary intervention (PCI) for unprotected LMCAD were categorized into four groups based on LM lesion location (Body/Ostial vs. Bifurcation) and non-LM SYNTAX score (≤8 vs. >8). The reference group was Body/Ostial cases with low non-LM score. The primary endpoint was Major Adverse Cardiac Events (MACE), composite of death, myocardial infarction, or target vessel revascularization (TVR) at 1 year.

RESULTS: Out of 869 patients undergoing LM PCI, 69.2 % had a LM bifurcation lesion, and 44.8 % non-LM SYNTAX score >8. Patients with high non-LM score (>8) were older, had higher rates of chronic kidney disease, and were more likely to present with congestive heart failure or low ejection fraction. After adjustment, both groups with LM bifurcation disease had higher rates of 1-year MACE, driven by TVR. In contrast, there was no difference between the Body/Ostial lesion with high non-LM score group and the reference group.

CONCLUSION: Amongst patients undergoing LM PCI, those with LM bifurcation lesions are more likely to require repeat revascularization, regardless of non-LM SYNTAX score. Lesion complexity should be considered separately from the number of lesions.

PMID:40592694 | DOI:10.1016/j.carrev.2025.06.019

Clin Cardiol. 2025 Jul;48(7):e70170. doi: 10.1002/clc.70170.

ABSTRACT

BACKGROUND: High-intensity statins are recommended for patients with chronic coronary artery disease, with reports suggesting improved clinical outcomes. However, recent findings in coronary artery bypass graft (CABG) patients question whether a treat-to-target low density lipoprotein (LDL) approach is non-inferior to high-intensity statin therapy.

METHODS: This single-center observational study analyzed all CABG only (n = 1854) procedures performed between 2013 and 2015. Patients were divided into three groups based on statin prescription: high-intensity statin therapy (atorvastatin ≥ 40 mg or rosuvastatin ≥ 20 mg), low/moderate-intensity statin therapy, and a no-statin group. The primary outcome measured was major adverse cardiovascular events (MACE), a composite of post-CABG acute coronary syndrome, cerebrovascular accident and cardiovascular mortality.

RESULTS: No-Statin group had significantly higher incidence of MACE compared to statin group (14.2% vs 8.9%; odds ratio (OR) 1.60, 95% confidence interval (CI) 1.055-2.427, p = 0.029). Low/moderate-intensity therapy (n = 1301) was associated with a numerically higher overall rate of MACE compared to high-intensity therapy (n = 397) but was not statistically significant (9.6% vs 6.6%; OR 1.45, CI 0.961-2.172, p = 0.073). Beyond 2 years post-CABG, low/moderate intensity statin use was associated with a significant higher incidence of MACE (9.1% vs 5.3%; OR 1.72, 95% CI 0.993-2.978, p = 0.047) compared to high intensity statins. Patients who received high-intensity statin therapy had the lowest LDL levels (82.21 ± 41.85 mg/dL), compared to those on low/moderate-intensity statins (90.84 ± 45.89 mg/dL) and no-statin group (104.83 ± 38.93 mg/dL, p < 0.001).

CONCLUSION: High-intensity statin therapy following CABG is associated with improved long-term clinical outcomes compared to low- or moderate-intensity statin regimens.

PMID:40590628 | PMC:PMC12210389 | DOI:10.1002/clc.70170

Eur Heart J. 2025 Jul 1:ehaf284. doi: 10.1093/eurheartj/ehaf284. Online ahead of print.

ABSTRACT

The diagnosis of refractory angina has conventionally been limited to patients with angina and ischaemia secondary to obstructive atherosclerotic epicardial coronary disease who experience persistent symptoms despite optimal pharmacological and revascularization therapies. It is now well-established that angina may also be caused by ischaemia resulting from coronary microcirculatory disorders, coronary vasospasm, and bridging in the absence of obstructive epicardial coronary disease or after "successful" revascularization. This increasingly prevalent and symptomatic group of patients, with both angina and demonstrable ischaemia, have been excluded from the conventional definition of refractory angina. In patients with obstructive epicardial coronary disease, disturbed microcirculatory and vasomotor function, amongst other ischaemic mechanisms, may account for continuing symptoms despite revascularization. Under-recognition of these mechanisms results in inadequate treatment and symptom persistence. In this review, a redefinition of refractory angina is proposed to include the full spectrum of patients experiencing persistent angina despite current maximal guideline-directed medical and revascularization therapies. Systematic approaches for comprehensive investigation are suggested to identify underlying mechanisms of ischaemia and stratify treatments accordingly. The complex needs of patients with refractory angina are likely best addressed by an inter-disciplinary Angina Heart Team with the aim of improving patient symptoms, quality of life, and clinical outcomes.

PMID:40590516 | DOI:10.1093/eurheartj/ehaf284

Results Probl Cell Differ. 2025;75:247-290. doi: 10.1007/978-3-031-91459-1_9.

ABSTRACT

This chapter highlights the hallmarks of cardiac aging, distinguishing characteristics between cardiac aging and cardiac senescence. An overview of the molecular mechanisms underlying cardiac aging, with a particular focus on the role of reversible protein acetylation, emphasizes the role of sirtuins in regulating heart function and structure. The chapter explores how alterations in energy metabolism contribute to heart dysfunction, with a focus on the impact of mitochondrial dysfunction and phenomena of protein acetylation, along with the role of acetylase and deacetylase in an aging heart. Additionally, the chapter discusses the regulation of cardiomyocyte proliferation and the potential for enhancing cardiac regeneration. Finally, therapeutic strategies, including caloric restriction and HDAC inhibitors, microRNAs, stem cells, and other pharmacological agents are examined as potential approaches to slow or reverse the effects of cardiac aging.

PMID:40593213 | DOI:10.1007/978-3-031-91459-1_9

Sci Rep. 2025 Jul 1;15(1):22207. doi: 10.1038/s41598-025-06772-6.

ABSTRACT

Homocysteine can cause damage to cardiomyocytes. However, Mitophagy is essential for preserving homeostasis in cardiomyocytes. So, we focused on investigating the impact of homocysteine on cardiomyocyte mitophagy and cardiac hypertrophy through the β-catenin/FUNDC1 pathway. Mice were administered water containing homocysteine (1.8 g/L) to induce hyperhomocysteinemia for 4 weeks. The overexpression of specific genes, including β-catenin and FUNDC1, were performed by gene delivery mediated with adeno-associated virus. In vitro, cardiomyocytes were exposed to homocysteine (1 mmol/L) and then transfected with plasmids to overexpress β-catenin and FUNDC1, respectively. The duration of cell experiments was 48 h. Western blotting was employed to assess the expression levels of β-catenin, active β-catenin, FUNDC1, LC3, p62, α-actin, and β-MHC. Immunohistochemistry and immunofluorescence techniques were applied to measure β-catenin and FUNDC1 in cardiomyocytes. Cell viability was assessed using a CCK-8 assay kit, and mitophagy was observed under transmission electron microscopy. The interaction between β-catenin protein and the promoter of the FUNDC1 gene was examined using ChIP assay and dual-luciferase reporter gene assay. Homocysteine inhibited β-catenin signaling and the FUNDC1-mediated mitophagy in the cardiomyocytes, simultaneously promoting cardiac hypertrophy in vitro and in vivo. Elevated β-catenin signaling promoted FUNDC1 expression, then restored the normal level of mitophagy, and consequently inhibited homocysteine-induced cardiac hypertrophy. Similarly, overexpression of FUNDC1 restored mitophagy and protected cardiomyocytes from hypertrophy. In addition, FUNDC1 served as a target gene of β-catenin. In summary, homocysteine induces cardiomyocyte hypertrophy by inhibiting β-catenin signaling and suppressing FUNDC1-mediated mitophagy.

PMID:40593088 | PMC:PMC12214670 | DOI:10.1038/s41598-025-06772-6

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 1. doi: 10.1007/s00210-025-04354-x. Online ahead of print.

ABSTRACT

Sepsis-induced acute myocardial injury is a major cause of morbidity and mortality, characterized by inflammation, apoptosis, and impaired cardiomyocyte survival. Lipopolysaccharide (LPS)-induced cardiac injury models are commonly used to mimic sepsis and study its pathophysiological mechanisms. In this study, we investigated the protective effects of Eupatilin, a flavonoid compound derived from Artemisia argyi, on LPS-induced cardiac injury in rats and H9c2 cardiomyocyte cells. Our results show that Eupatilin significantly attenuated LPS-induced injury, as evidenced by increased cell viability, reduced inflammatory cytokine release, and decreased apoptosis. Mechanistically, we found that Eupatilin reduced the ubiquitination of Mcl-1, thereby promoting its stability and inhibiting apoptosis. Additionally, Eupatilin activated the PI3K/Akt signaling pathway, which led to the phosphorylation of Foxo3a, resulting in the retention of Foxo3a in the cytoplasm and the inhibition of apoptosis. These findings suggest that Eupatilin exerts protective effects against sepsis-induced myocardial injury by modulating Mcl-1 ubiquitination and activating the PI3K/Akt/Foxo3a pathway. Our study provides novel insights into the potential therapeutic application of Eupatilin in the treatment of sepsis-induced acute myocardial injury.

PMID:40590921 | DOI:10.1007/s00210-025-04354-x

Front Cardiovasc Med. 2025 Jun 16;12:1581056. doi: 10.3389/fcvm.2025.1581056. eCollection 2025.

ABSTRACT

INTRODUCTION: Calcitonin gene-related peptide (CGRP), particularly its alpha isoform, might play a role in restoring physiological cardiovascular functioning. While its involvement in acute myocardial infarction (AMI) pathophysiology has been suggested, human data remain scarce. This study analyzed circulating alpha-CGRP levels during AMI, comparing them to healthy controls (HC) and post-AMI resolution levels.

METHODS: A total of 26 AMI patients and 26 age- and sex-matched HC were recruited. Blood samples were collected from patients within four hours of AMI onset and, when possible, six months post-event. Alpha-CGRP serum concentrations were measured using a validated ELISA assay.

RESULTS: Alpha-CGRP levels were significantly higher in AMI patients at admission (mean ± SD: 96.0 ± 77.4 pg/ml) compared to HC (42.0 ± 25.8 pg/ml, p < 0.0001), with an average increase of 129%. Among nine patients available for follow-up, levels normalized to the HC range (45.1 ± 26.7 pg/ml, p = 0.011). Patients with poor outcomes had numerically lower alpha-CGRP levels (72.6 ± 37.2 pg/ml) than those with a satisfactory resolution (100.3 ± 82.5 70.6 pg/ml; p = 0.241).

DISCUSSION: Alpha-CGRP is acutely elevated during AMI, likely as a compensatory vasodilator response to ischemia. Its post-AMI normalization suggests a transient protective mechanism. Further research is needed to explore its role in AMI-related pathophysiology and usefulness as a therapeutic agent.

PMID:40589453 | PMC:PMC12206774 | DOI:10.3389/fcvm.2025.1581056