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Phytomedicine. 2025 Sep 22;148:157294. doi: 10.1016/j.phymed.2025.157294. Online ahead of print.

ABSTRACT

BACKGROUND: Acute myocardial ischemia (AMI) carries a high risk of heart failure and subsequent mortality. However, current therapies remain limited by suboptimal drug efficacy and high costs, prompting exploration of alternative strategies, such as remote therapy. Capsaicin is a natural extract from red chili peppers. Remote therapy using it as the primary component has demonstrated efficacy in AMI treatment. However, this specific mechanism requires further exploration.

PURPOSE: Here, we investigate the therapeutic effects of remote capsaicin application therapy on AMI and elucidate the underlying neuro-immune interactions responsible.

METHODS AND RESULTS: We applied capsaicin cream to the ventral forelimb of rats, finding that it enhanced the sympathetic-sensory coupling (SSC) state in the skin and dorsal root ganglia (DRGs) (C8-T6), improving cardiac function over 28 days. Localized yohimbine (YOB) injections in skin /DRGs confirmed the critical role of the SSC structure. Mechanistically, capsaicin-enhanced SSC increased neuropeptide Y-positive (NPY+) nerve fiber density in peri‑infarct myocardium, concurrently shifting cardiac NPY receptor expression toward predominant NPY2R. Inhibiting cardiac NPY2R expression eliminated the functional benefits of capsaicin. In vitro co-culture of H9C2 cardiomyocytes and RAW264.7 cells showed functional NPY2R localization in cardiomyocytes. Activation of cardiomyocyte NPY2R promoted macrophages to secrete the anti-inflammatory factor IL-10, reducing hypoxia-induced cardiomyocyte apoptosis. Adeno-associated virus (AAV)-mediated overexpression of NPY2R in cardiomyocytes mimicked the cardioprotective effects of capsaicin. RNA sequencing revealed that NPY2R overexpression inhibited the IL-1β-induced NF-κB pathway in the heart. Flow cytometry confirmed these changes were due to reduced M1 macrophages and neutrophil infiltration in the infarct area.

CONCLUSION: Capsaicin enhances the segmental SSC structure to protect cardiac function in AMI rats, primarily associated with the improvement of the immune microenvironment induced by NPY+ nerve and NPY2R activation in the heart.

PMID:41005056 | DOI:10.1016/j.phymed.2025.157294

Diabetes Res Clin Pract. 2025 Sep 24:112923. doi: 10.1016/j.diabres.2025.112923. Online ahead of print.

ABSTRACT

BACKGROUND: Bariatric surgery causes changes in the levels of metabolically active hormones that control energy expenditure. This study aims to [1] validate a Roux-en-Y gastric bypass (RYGB) rat model in comparison to RYGB operated humans and [2] investigate the correlation of amino acids with GLP-1 and PYY levels in both species.

METHODS: Fasting plasma samples were derived from the randomized controlled WAS trial (NCT01352403; RYGB = 20, Controls = 17) at baseline and after 12 months and from male Wistar rats with diet-induced obesity seven weeks after surgery (RYGB = 12, sham surgery = 12). 18 peptide hormones and 21 amino acids were measured using magnetic multiplex assays, ELISA and LC-MS/MS.

RESULTS: Levels of GLP-1 and PYY3-36 were found to be significantly lower in humans after RYGB (both p < 0.001), while in rats a trend towards an increase was observed. Fasting insulin was found to be lower in humans (p < 0.001) and rats (p < 0.01) after RYGB. Leptin was significantly lower in humans (p < 0.001) and rats (p < 0.05) after RYGB. The cytokines IL-6 and MCP-1 were significantly lower in humans (p < 0.01, p < 0.05), but unchanged in rats after RYGB. Interestingly, GLP-1 levels in humans before RYGB correlated positively with the weight change after 12 months (Pearson's r = 0.733;p < 0.05). Leucine showed a positive correlation with GLP-1 levels 12 months after RYGB in humans (Pearson's r = 0.588;p < 0.05), but not in rats.

CONCLUSION: Preoperative GLP-1 levels in humans correlate with weight loss after RYGB and could potentially be predictive. The investigated rat model shows largely comparable patterns of incretins and adipokines. Given its physiological similarity, this model is suitable for testing pharmacological agents that mimic anorexigenic hormones, potentially guiding novel treatments for severe obesity.

PMID:41005747 | DOI:10.1016/j.diabres.2025.112923

Thromb Res. 2025 Sep 22;255:109493. doi: 10.1016/j.thromres.2025.109493. Online ahead of print.

ABSTRACT

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, prompting increasing use of antiplatelet agents for primary and secondary prevention. Despite guidelines from multiple professional societies on the perioperative management of antiplatelet agents, we hypothesized that their implementation varies, leading to inconsistencies in perioperative practices across the United States (US).

METHODS: We surveyed eleven members of the Systems-Based Hematology Committee of the Venous ThromboEmbolism Network US (VENUS) to gather their institutions' guidelines on the perioperative management of antiplatelet agents for non-cardiac surgery. Institutional guidelines were compared with five professional society guidelines.

RESULTS: Of the 11 academic medical centers (AMCs), 8 (72.7 %) had institutional guidelines on perioperative management of antiplatelet agents (aspirin and three P2Y12 inhibitors) prior to non-cardiac surgery. Of the remaining three, two had guidelines on the management of antiplatelet agents prior to interventional radiology procedures (n = 1) and for neuraxial anesthesia (n = 1). Five AMCs gave differing recommendations on managing phosphodiesterase inhibitors perioperatively, while none of the five society guidelines addressed them. Five AMCs provided variable recommendations on the timing of postoperative resumption of antiplatelet agents ranging from as soon as possible to 12-24 h postoperatively depending on bleeding risk. Only two AMCs provided recommendations for those on antiplatelet agents who have life-threatening peri-operative bleeding or undergoing urgent high-bleeding risk surgery.

CONCLUSION: AMCs vary in their recommendations on the perioperative management of antiplatelet agents prior to non-cardiac surgery. Further research is needed to determine if this variability impacts patient outcomes and to identify ways to improve guideline implementation.

PMID:41005027 | DOI:10.1016/j.thromres.2025.109493

Pediatr Cardiol. 2025 Sep 26. doi: 10.1007/s00246-025-04037-7. Online ahead of print.

ABSTRACT

Infective endocarditis (IE) is uncommon in children with congenital heart disease (CHD), and limited data exist regarding in-hospital outcomes of those requiring cardiac surgery. We retrospectively reviewed hospitalizations from the pediatric health information system from January 2016 to November 2024. Among 357,031 unique pediatric patients with CHD (≤ 21 years), 2108 patients (0.5%) were hospitalized for IE. The index hospitalizations during which cardiac surgery was performed were included. We aimed to characterize in-hospital outcomes among CHD children undergoing cardiac surgery for IE, with sub-analysis of those who required surgery versus medical therapy. The incidence of IE in CHD was 5.6 cases per 1000. Microorganism coding was unavailable in 41.3%; Staphylococcus (24.1%) and Streptococcus (22.3%) were the most common. Stroke occurred in 10.7%. Prosthetic valve endocarditis was present in 9.4%. Overall, 30% of patients required cardiac surgery, most commonly pulmonary valve or conduit procedures (36.6%) and tricuspid valve surgery (16.7%). Two-valve surgery was performed in 13.3%. In-hospital mortality was comparable between surgical and medical patients (10.1% vs 9.6%, p = 0.7). Permanent pacemaker implantation was more common after surgery (6.6% vs 2.2%, p < 0.01). Length of hospital stay and hospitalization costs were higher in the surgical group. On multivariable analysis, older age, heart failure, stroke, and extracorporeal membrane oxygenation (ECMO) were associated with in-hospital mortality. IE in children with CHD remains associated with substantial morbidity and mortality. In-hospital mortality remains high despite cardiac surgery. Older age, heart failure, stroke, and ECMO requirement are independent factors of in-hospital mortality.

PMID:41006584 | DOI:10.1007/s00246-025-04037-7

JACC Case Rep. 2025 Sep 24;30(29):105142. doi: 10.1016/j.jaccas.2025.105142.

ABSTRACT

BACKGROUND: Bioprosthetic valve failure is a significant and debilitating sequela in cardiac patients caused primarily by structural changes in valve leaflets due to endocarditis, calcification, and thrombosis.

CASE SUMMARY: We describe a rare case of bioprosthetic pulmonary valve failure due to an allergic reaction to molybdenum within the valve cage. We describe the clinical presentation, clinical methods leading to the diagnosis, and treatment progression until we could resolve symptoms and a significant return of valvular competency.

DISCUSSION: After excluding infectious etiologies as a cause, we used skin allergy testing to identify molybdenum as the allergic agent. The patient's symptoms and valve function improved and stabilized with immunosuppression and antihistamines.

TAKE-HOME MESSAGES: Allergy to a valve metal component was diagnosed with skin allergy and treated with immunosuppression and antihistamines.

PMID:41005850 | DOI:10.1016/j.jaccas.2025.105142

Int J Surg Case Rep. 2025 Sep 23;136:111980. doi: 10.1016/j.ijscr.2025.111980. Online ahead of print.

ABSTRACT

BACKGROUND: Right ventricle-to-pulmonary artery (RV-PA) reconstruction often requires a valved conduit; however, no single option is ideal across ages and anatomical variations. We report early outcomes of a bovine pericardial xenograft conduit (NeoCor) as a practical solution in a resource-limited setting.

METHODS: In this single-center retrospective series, eight pediatric patients (1-14 years) underwent RV-PA reconstruction (2019-2024) using a bovine pericardial xenograft conduit sized by nomogram (10-21 mm). A single surgical team performed all procedures under standardized perioperative protocols with intraoperative echocardiography. Complications were graded using standardized criteria. The primary outcome was clean follow-up (no mortality, no reintervention on the conduit/RVOT, no ≥moderate conduit regurgitation, peak Doppler gradient ≤30 mmHg, and no echogenic calcification).

RESULTS: Indications included TGA/VSD/PS (n = 4), tetralogy of Fallot with absent pulmonary valve (n = 2), VSD-PA with confluent PAs/PDA (n = 1), and truncus arteriosus redo (n = 1). Follow-up ranged 6 months-5 years (mean 2 years). All patients met the clean follow-up definition. Conduit Doppler gradients were 5-8 mmHg perioperatively and 8-12 mmHg at follow-up; no calcification or ≥ moderate regurgitation was observed.

CONCLUSIONS: A bovine pericardial xenograft conduit is a feasible, accessible option for RV-PA reconstruction with promising short-term hemodynamics in this context. Larger prospective studies and/or registry participation are warranted to evaluate durability, reintervention rates, and cost-effectiveness.

PMID:41005129 | DOI:10.1016/j.ijscr.2025.111980

Heart Lung Circ. 2025 Sep 25:S1443-9506(25)00493-7. doi: 10.1016/j.hlc.2025.06.005. Online ahead of print.

ABSTRACT

BACKGROUND: The Perceval bioprosthesis is a contemporary sutureless technology utilised for surgical aortic valve replacement (AVR). Perceval valves allow for AVR with reduced cross-clamp and cardiopulmonary bypass times, which correlates with improved postoperative patient morbidity and mortality. However, there is a paucity of literature reporting the medium-term outcomes from Perceval AVR in New Zealand. We aimed to investigate the mid-term outcomes from Perceval AVR at our single centre.

METHOD: All consecutive patients undergoing Perceval AVR (during isolated or combined procedures) at our unit from March 2011 to August 2021 were retrospectively analysed from a prospectively-collected database.

RESULTS: Across the 10-year study period, 145 patients (mean age: 73.2 years; males: 71.7%; mean EuroSCORE II: 3.78%) underwent Perceval AVR. The most common indication for surgery was aortic stenosis (82.5%). The operative caseload was complex, with only 27.6% of patients undergoing first-time isolated AVR. The mean crossclamp and cardiopulmonary bypass times were 74.7±40.6 and 111.3±63.6 minutes respectively. Latest follow-up transthoracic echocardiography (performed at a mean of 2.2±1.7 years postoperatively) revealed that 96% of patients had either none or only trivial paravalvular/transvalvular leaks. The 30-day mortality and stroke rates were 6.2% and 2.1% respectively. Medium-term survival rates across 5-year and 9.5-year follow-up were 70% and 55% respectively. There was only one reoperation on the aortic valve.

CONCLUSIONS: Across an older patient population undergoing complex cardiac surgery, Perceval AVR facilitates acceptable short-term and medium-term outcomes in terms of both prosthetic valvular function and survival.

PMID:41006104 | DOI:10.1016/j.hlc.2025.06.005

JACC Case Rep. 2025 Sep 24;30(29):105142. doi: 10.1016/j.jaccas.2025.105142.

ABSTRACT

BACKGROUND: Bioprosthetic valve failure is a significant and debilitating sequela in cardiac patients caused primarily by structural changes in valve leaflets due to endocarditis, calcification, and thrombosis.

CASE SUMMARY: We describe a rare case of bioprosthetic pulmonary valve failure due to an allergic reaction to molybdenum within the valve cage. We describe the clinical presentation, clinical methods leading to the diagnosis, and treatment progression until we could resolve symptoms and a significant return of valvular competency.

DISCUSSION: After excluding infectious etiologies as a cause, we used skin allergy testing to identify molybdenum as the allergic agent. The patient's symptoms and valve function improved and stabilized with immunosuppression and antihistamines.

TAKE-HOME MESSAGES: Allergy to a valve metal component was diagnosed with skin allergy and treated with immunosuppression and antihistamines.

PMID:41005850 | DOI:10.1016/j.jaccas.2025.105142

J Thorac Cardiovasc Surg. 2025 Sep 24:S0022-5223(25)00793-7. doi: 10.1016/j.jtcvs.2025.09.027. Online ahead of print.

ABSTRACT

OBJECTIVE: This study examined the feasibility of creating Cox-Maze IV lesions, including the ablation of the left posterior wall (box) and the isthmus lines, using nanosecond pulsed field ablation (nsPFA) in a beating heart porcine model.

METHODS: Nine pigs underwent surgical nsPFA. Lesions included right atrial appendage, left atrial appendage, left atrial posterior wall (the box), and isthmus lines, as replicated by ablating across the mitral and tricuspid annuli. Each ablation lasted 2.5 - 5 s. At 30 days, the cardiac tissue was examined histologically. Ablation lines were sectioned at 5-mm intervals and stained with 10% triphenyl tetrazolium chloride and Gomori trichrome. Exit block testing and echocardiography were performed before, after, and 30-days post-ablation. Valvular and coronary tissues were assessed by a blinded pathologist.

RESULTS: Seven pigs were survived for an average of 26 ± 8 days. Two pigs died acutely from refractory ventricular fibrillation immediately after transvalvular ablations. Transmurality was confirmed for 99.6% (251/252) of histological cross-sections and 97% (32/33) of lesions. The mean ablated tissue thickness was 6.7 ± 3.3 mm. At 30 days, exit block was confirmed at 94% of available testing sites (16/17). There was no evidence of progression of baseline valvular regurgitation. Histological assessment did not find significant differences between ablated and non-ablated valves or coronary arteries.

CONCLUSION: An nsPFA clamp device effectively created transmural lesions, including the box and isthmus lesions. This non-thermal energy source may shorten procedural time and enable surgical ablation in the beating heart. However, the relationship between nsPFA and ventricular arrhythmias warrants additional study.

PMID:41005435 | DOI:10.1016/j.jtcvs.2025.09.027

Herz. 2025 Sep 26. doi: 10.1007/s00059-025-05340-y. Online ahead of print.

ABSTRACT

BACKGROUND: Acute chest pain is a common emergency department (ED) presentation requiring rapid risk stratification for major adverse cardiovascular events (MACE; including death, myocardial infarction, and urgent revascularization). While the HEART (History, ECG, Age, Risk factors, Troponin) and GRACE scores are widely used, their comparative predictive accuracy for short-term MACE remains unclear. This study aimed to directly compare the diagnostic performance of HEART and GRACE (Global Registry of Acute Coronary Events) in predicting 30-day MACE among ED patients with acute chest pain.

METHODS: We systematically searched PubMed, Embase, Cochrane Library, Scopus, and Web of Science from inception to May 2025 for prospective cohort studies directly comparing HEART and GRACE scores. Included studies applied both scores at ED presentation, reported 30-day MACE (death, myocardial infarction, urgent revascularization), and provided data for 2 × 2 contingency tables. Pooled sensitivity, specificity, likelihood ratios (PLR/NLR), diagnostic odds ratio, and area under the curve (AUC) were calculated using a bivariate random-effects model. Heterogeneity was assessed via I2 statistics, and subgroup analyses explored sources of variation.

RESULTS: In total, 19 studies (14,862 patients) were included. The HEART score demonstrated significantly higher sensitivity (0.96, 95% CI: 0.94-0.98 vs. 0.88, 95% CI: 0.85-0.91; ratio: 1.09 [1.05-1.14]) and lower negative likelihood ratio (NLR: 0.08, 95% CI: 0.03-0.17 vs. 0.42, 95% CI: 0.39-0.46) than the GRACE score. Specificity was lower for HEART (0.50, 95% CI: 0.41-0.60) versus GRACE (0.61, 95% CI: 0.58-0.64), while GRACE showed higher specificity. HEART also had superior discriminative power (AUC: 0.80, 95% CI: 0.77-0.84 vs. 0.72, 95% CI: 0.69-0.75; ratio: 1.11 [1.07-1.15]). Subgroup analyses confirmed HEART's advantage in sensitivity across geographic regions and age groups, particularly in Eastern populations (sensitivity ratio: 1.57 [1.27-1.93]).

CONCLUSION: The HEART score outperforms GRACE in sensitivity and rule-out capability (lower NLR) for 30-day MACE in ED patients with acute chest pain, supporting its utility for safe discharge of low-risk individuals. GRACE's higher specificity may aid in identifying high-risk cases requiring intervention. Standardization of troponin assays and MACE definitions is critical for future implementation.

PMID:41003766 | DOI:10.1007/s00059-025-05340-y

J Cardiovasc Dev Dis. 2025 Sep 3;12(9):338. doi: 10.3390/jcdd12090338.

ABSTRACT

Imaging techniques such as positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MR) have emerged as powerful and versatile tools for the comprehensive assessment of coronary artery disease (CAD). By combining anatomical and functional information in a single examination, these modalities offer complementary insights that significantly enhance diagnostic accuracy and support clinical decision-making. This is particularly relevant in complex clinical scenarios, such as multivessel disease, balanced ischemia, or suspected microvascular dysfunction, where conventional imaging may be inconclusive. This review aims to provide clinicians with an up-to-date summary of the principles, technical considerations, and clinical applications of hybrid PET/CT and PET/MR in CAD. Here, we describe how these techniques can improve the evaluation of myocardial perfusion, coronary plaque characteristics, and ischemic burden. Advantages such as improved sensitivity, spatial resolution, and quantification capabilities are discussed alongside limitations including cost, radiation exposure, availability, and workflow challenges. A dedicated focus is given to the emerging role of artificial intelligence (AI), which is increasingly being integrated to optimize image acquisition, fusion processes, and interpretation. AI has the potential to streamline hybrid imaging and promote a more personalized and efficient management of CAD. Finally, we outline future directions in the field, including novel radiotracers, automated quantitative tools, and the expanding use of hybrid imaging to guide patient selection and therapeutic decisions, particularly in revascularization strategies.

PMID:41002617 | PMC:PMC12471169 | DOI:10.3390/jcdd12090338

Cureus. 2025 Aug 25;17(8):e90952. doi: 10.7759/cureus.90952. eCollection 2025 Aug.

ABSTRACT

INTRODUCTION: Non-ST elevation myocardial infarction (NSTEMI) carries a substantial risk of early major adverse cardiovascular events (MACE) despite advances in therapy. Easily obtainable biochemical and echocardiographic markers may improve early risk stratification, particularly in patients managed without revascularization. This prospective study assessed the prognostic significance of inferior vena cava (IVC) diameter, serum uric acid, homocysteine, and selected hematological indices in predicting 90-day MACE in NSTEMI patients treated with conservative medical therapy. Unlike prior studies that examined these biomarkers individually, our study integrates biochemical (uric acid, homocysteine), echocardiographic (IVC diameter), and hemogram-derived indices into a combined model for early risk stratification in conservatively treated NSTEMI patients.

METHODS: A total of 170 consecutive NSTEMI patients admitted to the University Clinical Center Tuzla between February 2022 and January 2023 were included. All patients received guideline-directed medical therapy. Clinical, echocardiographic, and laboratory data were obtained within 24 hours of admission. The primary endpoint was MACE (cardiac death, reinfarction, or urgent coronary revascularization) within 90 days. Logistic regression identified independent predictors; discriminatory ability was assessed using receiver operating characteristic (ROC) analysis, and Kaplan-Meier curves evaluated event-free survival.

RESULTS: MACE occurred in 87 patients (51.2%). Compared to event-free patients, those with MACE had larger IVC diameters (20.25 ± 2.52 mm vs. 18.36 ± 2.16 mm; p < 0.001), higher uric acid (432.8 ± 47.3 μmol/L vs. 358.9 ± 44.6 μmol/L; p < 0.001), and elevated homocysteine levels (18.42 ± 4.13 μmol/L vs. 13.39 ± 2.88 μmol/L; p < 0.001). In multivariate analysis, uric acid (OR per 10 μmol/L = 1.32; 95% CI: 1.05-1.65; p = 0.015) and homocysteine (OR per 1 μmol/L = 1.23; 95% CI: 1.06-1.42; p = 0.005) remained independent predictors. ROC analysis showed excellent discrimination for homocysteine (AUC: 0.844) and uric acid (AUC: 0.830). IVC diameter was associated with lower MACE-free survival (log-rank p = 0.036) but lost significance after adjustment.

CONCLUSION: Elevated homocysteine and uric acid independently predicted 90-day MACE in NSTEMI patients managed without revascularization. While IVC diameter was not independently predictive, its combination with biochemical markers may enhance risk stratification and guide early post-discharge management. These findings warrant validation in larger multicenter studies.

PMID:41001293 | PMC:PMC12459640 | DOI:10.7759/cureus.90952

Front Cardiovasc Med. 2025 Sep 10;12:1574829. doi: 10.3389/fcvm.2025.1574829. eCollection 2025.

ABSTRACT

BACKGROUND: Rapid diagnosis of patients with acute coronary syndrome (ACS) is crucial for saving their lives. The de Winter electrocardiogram (ECG) pattern is rare and is treated similarly to ST-segment elevation myocardial infarction (STEMI) and acute thrombotic occlusion of the coronary artery. The de Winter ECG pattern has been previously reported, but its dynamic evolution and characteristics have not been summarized.

METHODS: We reported two male patients who presented with de Winter ECG pattern at rest, and neither patient had a family history of hypertension, diabetes, or coronary heart disease. An urgent examination in our hospital showed elevated levels of cardiac troponin T. Both patients underwent emergency coronary angiography, which revealed subtotal proximal left anterior descending (LAD) stenosis. There was an improvement in chest tightness and pain after stent implantation. Serial ECGs before and after percutaneous coronary intervention showed dynamic evolution of ECG. A literature review was conducted to examine reported coronary angiography findings in patients with the de Winter pattern. The review focused on the dynamic evolution of the ECG and the accuracy of this pattern in diagnosing acute coronary artery occlusion (culprit vessel). It also highlighted the danger of the de Winter ECG pattern and the importance of emergency treatment.

RESULTS: Eighteen patients, including two of our patients, presented with the de Winter ECG pattern. Our two cases demonstrated two different forms of ST-segment dynamic evolution, with Case 2 being the only one among 18 cases that dynamically evolved into a life-threatening non-STEMI (NSTEMI). All cases were male patients with sudden chest pain. ECG examination showed an upward-sloping ST-segment depression with tall symmetrical T waves in the chest leads, and multiple follow-up ECGs revealed dynamic ST-segment evolution. Emergency coronary angiography showed occlusion of the LAD, left main artery (LMA), right coronary artery (RCA), first diagonal branch (D1), and left circumflex (LCX) artery as well as multiple vascular lesions. Most cases support subtotal stenosis or complete occlusion of the anterior descending artery. Timely identification of the de Winter ECG pattern and prompt transfer to the catheterization laboratory for emergency revascularization can be lifesaving and improve prognosis.

CONCLUSION: These two cases and the literature review indicated that the de Winter ECG pattern is dynamically evolving. Its ECG pattern evolution is variable, progressing to STEMI, NSTEMI, Wellens, or even a normal. In patients presenting with chest pain, a de Winter ECG pattern, regardless of the subsequent dynamic evolution of the ECG, indicates the presence of severe coronary artery stenosis. The de Winter ECG pattern may be an early manifestation of ACS and requires urgent coronary angiography to save the patient's life and improve prognosis.

PMID:41000532 | PMC:PMC12457363 | DOI:10.3389/fcvm.2025.1574829

Kidney Blood Press Res. 2025 Sep 18:1-25. doi: 10.1159/000548172. Online ahead of print.

ABSTRACT

Introduction Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease and mortality. However, data on the prediction of long-term adverse outcomes in advanced predialysis CKD patients is lacking. Methods We studied the factors associated with mortality and major adverse cardiovascular and cerebrovascular events (MACCE, including cardiovascular death, myocardial infarction, stroke and coronary revascularization) in a cohort of 210 patients with non-dialysis CKD stage 4-5 during a five-year follow-up. The participants underwent stress ergometry testing to study maximal exercise capacity (Wmax%), a plain lateral abdominal radiograph to study abdominal aortic calcification score (AAC) and laboratory tests including cardiac troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (ProBNP). Furthermore, a dichotomous composite covariate was created and explored by combining ProBNP and Wmax% using the cut-offs determined with the Youden index. The associations between covariates of interest and study outcomes were explored using multivariable Cox proportional hazards models adjusted with age, sex, coronary artery disease (CAD) and incident kidney transplantation (KTx). Results Median age at baseline was 65 (52-73) years and eGFR 12 (10-15) ml/min/1.73 m2, 34.8 % were female and 44.8 % had diabetes. Altogether 67 (31.9 %) patients died during follow-up and 65 (31.0%) were observed with a MACCE. In separate multivariable Cox proportional hazards models adjusted for age, gender, CAD and KTx, Wmax% (HR 0.983 [95 % CI: 0.968-0.999], p=0.019), TnT (HR 1.004 [95 % CI: 1.002-1.005], p<0.001 and) and ProBNP (HR 1.036 per 1000 ng/l [95 % CI: 1.014-1.059], p=0.002 were independently associated with mortality. In similarly adjusted multivariable Cox models Wmax% (HR 0.977 [95 % CI: 0.962-0.992], p=0.003), TnT (HR 1.004 [95 % CI: 1.002-1.005], p<0.001) and ProBNP (HR 1.034 per 1000 ng/l [95 % CI: 1.010-1.058], p=0.006) were independently associated with the occurrence of MACCE during follow-up. AAC was associated with the risk of an incident MACCE (HR 1.080 [95% CI 1.028-1.135], p=0.002) but, surprisingly, not with mortality (HR 1.046 [95% CI 0.994-1.101], p=0.083). Finally, in participants with Wmax ≤50 % and ProBNP ≥1270 ng/l the risk of mortality (HR 8.760 [95 % CI: 4.730-16.222], p<0.001) and MACCE (HR 3.293 [95 % CI: 1.850-5.862], p<0.001) was significantly greater than those with Wmax>50% and/or ProBNP <1270 ng/L. Conclusion Wmax% and ProBNP separately and together as a composite risk factor may serve as important predictors of long-term all-cause mortality and MACCE in patients with CKD stage 4-5 not undergoing dialysis at baseline.

PMID:40999822 | DOI:10.1159/000548172

Front Pharmacol. 2025 Sep 10;16:1667140. doi: 10.3389/fphar.2025.1667140. eCollection 2025.

ABSTRACT

Myocardial infarction (MI) remains a leading cause of cardiovascular mortality despite advances in reperfusion strategies, necessitating innovative therapeutic approaches. Human umbilical cord mesenchymal stem cell-derived exosomes (HUCMSCs-Exos) have emerged as promising next-generation therapeutics, offering superior advantages including enhanced stability, reduced immunogenicity, and ability to cross biological barriers compared to cellular therapies. These naturally occurring nanovesicles exert comprehensive cardioprotective effects through multifaceted mechanisms encompassing anti-apoptotic signaling, angiogenesis promotion, immunomodulation, anti-fibrotic activity, oxidative stress reduction, and cardiac regeneration enhancement. The therapeutic arsenal includes diverse molecular cargo such as microRNAs (miR-29b, miR-133a-3p, miR-24-3p), long non-coding RNAs, circular RNAs, and bioactive proteins that synergistically target key pathophysiological processes in MI. Advanced engineering approaches, including genetic modification, surface functionalization, and biomaterial integration, have further enhanced therapeutic efficacy through targeted delivery and sustained release systems. While preclinical studies demonstrate significant cardioprotective effects, clinical translation faces challenges in standardization, manufacturing scalability, and regulatory approval. The convergence of innovative engineering strategies, personalized medicine approaches, and emerging technologies positions HUCMSCs-Exos as promising therapeutic approach that could fundamentally alter MI treatment paradigms and improve global cardiovascular health outcomes.

PMID:41001344 | PMC:PMC12457780 | DOI:10.3389/fphar.2025.1667140

PLoS One. 2025 Sep 26;20(9):e0332862. doi: 10.1371/journal.pone.0332862. eCollection 2025.

ABSTRACT

This study aimed to investigate the potential compensatory role of plasma exosomal microRNAs (miRNAs), particularly miR-320b, in mitigating early myocardial damage in severe obstructive sleep apnea (OSA) patients without comorbidities. AC16 human cardiomyocytes were co-incubated with plasma exosomes isolated from healthy volunteers (Ctrl-exo) and patients with uncomplicated severe OSA (OSA-exo). Functional assays revealed that OSA-exo significantly enhanced AC16 cell viability, promoted proliferation, and reduced apoptosis. RNA sequencing (RNA-seq) identified 14 myocardial function-related mRNAs in AC16 cardiomyocytes differentially influenced by OSA-exo. Out of the 14 mRNAs, FOXM1, a critical regulator of cardiomyocyte stress response, survival, and regeneration, was verified to be upregulated by OSA-exo by RT-qPCR. Bioinformatic analysis predicted a regulatory relationship between miR-320b and FOXM1, which was confirmed by a dual-luciferase reporter assay. MiR-320b was found to be downregulated in OSA-exo by RT-qPCR. MiR-320b overexpression downregulated FOXM1, induced G0/G1 cell cycle arrest, reduced cell viability, and increased apoptosis. In a mouse model of chronic intermittent hypoxia (CIH), myocardial FOXM1 exhibited a biphasic expression pattern during disease progression. After 4 weeks of CIH exposure, the mouse myocardium exhibited significantly increased FOXM1 expression and reduced levels of apoptosis compared to control, suggesting an early compensatory response. However, after 12 weeks of CIH exposure, decreased myocardial FOXM1 expression and increased apoptosis were detected, suggesting that the early compensatory protective mechanism was overwhelmed by myocardial injury caused by chronic hypoxia, leading to enhanced cardiomyocyte apoptosis and consequent FOXM1 downregulation. These results suggested that miR-320b downregulation in OSA-exo may serve as a compensatory mechanism to protect against early myocardial injury through the upregulation of FOXM1, highlighting miR-320b and FOXM1 as potential therapeutic targets for OSA-associated cardiomyopathy.

PMID:41004495 | PMC:PMC12469182 | DOI:10.1371/journal.pone.0332862

Biosci Rep. 2025 Sep 23:BSR20253737. doi: 10.1042/BSR20253737. Online ahead of print.

ABSTRACT

FGR proto-oncogene (Fgr), a member of the Src family kinases, has garnered attention for its potential involvement in apoptotic signaling, yet its role in cardiovascular diseases, particularly acute myocardial infarction (AMI), remains unexplored. This study sought to investigate whether elevated left ventricular Fgr expression alleviates myocardial injury in the infarcted area and whether this protective mechanism is mediated by modulating phosphoinositide 3-kinase (PI3K)/Akt phosphorylation. The transcriptome-wide association study was initially utilized to screen for susceptibility genes in the left ventricle, with findings validated using bulk-RNA sequencing data from a rat model of left anterior descending coronary artery (LAD) ligation; subsequently, human spatial transcriptomics combined with single-nucleus RNA sequencing data confirmed differential expression of Fgr and PI3K/Akt in the infarcted region. Fgr knockdown via siRNA in H9C2 cells and pharmacological inhibition with TL02-59 in rats were conducted to assess cellular survival and cardiac function, respectively. Fgr emerged as a common candidate gene identified through multi-omics data analysis, with its up-regulation confirmed both in vivo and in vitro. Fgr silencing in an in vitro oxygen-glucose deprivation model significantly reduced cell survival and suppressed PI3K/Akt phosphorylation, whereas TL02-59 administration in rats subjected to LAD ligation impaired post-infarction cardiac function while concurrently inhibiting PI3K/Akt phosphorylation levels. This study demonstrates that Fgr is markedly up-regulated in AMI and exerts cardioprotective effects, possibly through modulation of PI3K/Akt signaling phosphorylation, thereby underscoring its potential as a therapeutic target.

PMID:41004172 | DOI:10.1042/BSR20253737

J Cardiovasc Dev Dis. 2025 Aug 28;12(9):329. doi: 10.3390/jcdd12090329.

ABSTRACT

The possible protective effect of obesity in the outcomes of chronic kidney disease (CKD) patients is an understudied field. We aimed to evaluate the prognostic value of vascular calcification (VC) on long-term outcomes in obese and non-obese CKD patients. We conducted a single-centre, prospective observational study of 150 CKD patients. Patients were divided into two groups using body mass index (BMI) scores (BMI ≥ 30 kg/m2 and BMI < 30 kg/m2). Lateral lumbar X-rays (Kauppila score), the ankle-brachial index (ABI), and echocardiography were used for assessing VC. By the 11.2-year follow-up, 70 patients had died (47%). Twenty-four patients had had CV complications: stroke, myocardial infarction, decompensated heart failure, amputation caused by atherosclerosis, and aortic rupture. Among obese patients (BMI ≥ 30 kg/m2), only LVH was a significant predictor of CV complications (p = 0.01) and mortality (p = 0.004). In patients with BMI < 30 kg/m2, predictors of CV complications and mortality were ABI (p = 0.03; p = 0.009), LVH (p = 0.02 for CV complications) and heart valve lesions (p = 0.009; p = 0.004). There were no differences in the measured parameters of VC between the obese and non-obese groups. Moreover, no significant differences were found comparing patients with and without obesity according to the studied parameters; we found no significant differences in complications and mortality. VC in patients with CKD is a significant complication that negatively impacts outcomes. Obesity does not have a protective effect in long-term outcomes in CKD patients.

PMID:41002608 | PMC:PMC12470804 | DOI:10.3390/jcdd12090329

Cells. 2025 Sep 16;14(18):1452. doi: 10.3390/cells14181452.

ABSTRACT

Sepsis-induced cardiomyopathy is a life-threatening complication lacking targeted therapies. While empagliflozin (Empa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, confers robust cardioprotection, its specific efficacy in treating sepsis-induced cardiomyopathy and the Empa mechanisms remain poorly defined, limiting its targeted therapeutic use. In this study, we investigated Empa's effects and its novel mechanisms in a murine lipopolysaccharide (LPS)-induced model of septic cardiomyopathy. Empa pre-treatment effectively prevented LPS-induced cardiac dysfunction, preserving ejection fraction and mitigating myocardial injury (assessed by histology and ELISA) and fibrosis. Transcriptomic analysis revealed that Empa's protective effects were profoundly linked to the preservation of cardiomyocyte cytoskeletal pathways, alongside its anti-inflammatory actions. The results indicate that LPS induced a pathological dissociation of the matrix protein Integrin α5 (ITGA5) from the cell-cell adhesion protein Desmocollin-2 (DSC2), a structural disruption completely abrogated by Empa in vivo. This ITGA5-DSC2 stabilization was further confirmed to be a cardiomyocyte-intrinsic effect, recapitulated in vitro in both neonatal mouse cardiomyocytes and human AC16 cells. Building on this mechanistic insight, a computational design was successfully employed to develop 13 novel helical protein binders specifically targeting the ITGA5, yielding candidates with favorable structural properties as potential therapeutic leads. These findings establish the cardiomyocyte structural homeostasis via the ITGA5-DSC2 adhesion axis as a novel, key SGLT2-independent mechanism for empagliflozin's cardioprotection, revealing promising new therapeutic approaches for sepsis-induced cardiomyopathy.

PMID:41002417 | PMC:PMC12468141 | DOI:10.3390/cells14181452

Drug Dev Res. 2025 Nov;86(7):e70171. doi: 10.1002/ddr.70171.

ABSTRACT

‌Oleuropein (OLEU), a natural polyphenol, exhibits cardioprotective potential through mitochondrial modulation, yet its precise mechanisms remain elusive. This study elucidates OLEU's role in alleviating oxidative stress and regulating mitochondrial quality control via the PINK1/Parkin pathway. In vitro, H9C2 cardiomyocytes exposed to H₂O₂-induced oxidative stress were treated with OLEU (0-200 μM), and analyses included cell viability, ROS, SOD, MDA, ΔΨm, ATP, PINK1/Parkin expression and detection of Mitophagic Flux. In vivo, myocardial infarction (MI) was induced in SD rats via coronary ligation, followed by OLEU administration, with assessments of cardiac function, histopathology, and mitophagy using echocardiography, electron microscopy, immunohistochemistry and immunofluorescence. Results showed that OLEU (≤200 μM) dose-dependently restored cell viability, reduced ROS, and normalized SOD/MDA (p < 0.05), while mitigating ΔΨm collapse and ATP depletion, indicating enhanced mitochondrial bioenergetics. OLEU upregulated PINK1/Parkin, promoting mitophagic clearance of damaged mitochondria, and metabolomic analysis revealed modulation of arginine/proline and lipid pathways. In MI rats, OLEU attenuated ROS, preserved myocardial structure, and improved cardiac function, supported by elevated mitophagy in electron microscopy. These findings demonstrate that OLEU protects cardiomyocytes by suppressing oxidative stress, stabilizing mitochondrial integrity, and activating PINK1/Parkin-mediated mitophagy, highlighting its therapeutic potential for myocardial injury and mitochondrial dysfunction.

PMID:41001689 | DOI:10.1002/ddr.70171