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A Pre-Clinical Study on the Use of the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor PEP 2-8 to Mitigate Ischemic Injury in a Rat Marginal Donor Model

Trasplante cardíaco - Sáb, 09/27/2025 - 10:00

Int J Mol Sci. 2025 Sep 13;26(18):8937. doi: 10.3390/ijms26188937.

ABSTRACT

Proprotein Convertase Subtilisin/Kexin type 9 PCSK9 inhibitors (PCSK9i) are a novel class of cholesterol-lowering agents that also offer protection against tissue ischemia by reducing apoptosis, pyroptosis, and myocardial infarct size. This study evaluated the effects of the PCSK9 inhibitor PEP 2-8 during hypothermic perfusion (HP) in a rat model of donation after circulatory death (DCD) kidney transplantation. DCD kidneys were perfused at 4 °C for six hours with either Perf-Gen solution alone (control) or Perf-Gen supplemented with PEP 2-8. Glucose and lactate dehydrogenase (LDH) levels were measured at baseline and after six hours (T6h). At T6h, kidneys were evaluated for ischemic injury, tubular cell proliferation, apoptosis, nitrotyrosine (N-Tyr) staining, tissue ATP and LDH levels, and gene expression of PCSK9 and NOX4. Metabolomic profiling was also performed. PEP 2-8 treatment significantly reduced PCSK9 expression, decreased tubular ischemic injury and necrosis, and lowered LDH release. Treated kidneys showed enhanced tubular cell proliferation, reduced apoptosis, and diminished oxidative stress, indicated by decreased N-Tyr staining and NOX4 expression. Energy metabolism was improved, with higher tissue ATP and glucose levels observed in the PEP 2-8 group. Metabolomic analysis further supported the antioxidant effects of PEP 2-8. This is the first study to demonstrate that PEP 2-8 administered during pre-transplant hypothermic perfusion provides renal protection by improving energy metabolism and reducing oxidative stress in the context of ischemic injury.

PMID:41009504 | PMC:PMC12469581 | DOI:10.3390/ijms26188937

Categorías: Trasplante cardíaco

Clinical and Prognostic Impact of Hemodynamic Gain Index and Heart Hemodynamic Reserve in Heart Failure with Reduced and Mildly Reduced Ejection Fraction: A Multicenter Study

Trasplante cardíaco - Sáb, 09/27/2025 - 10:00

Diagnostics (Basel). 2025 Sep 17;15(18):2366. doi: 10.3390/diagnostics15182366.

ABSTRACT

Background/Objectives: Cardiopulmonary exercise testing (CPET) is a well-established tool for risk stratification in patients with heart failure (HF); however, its utility is limited in routine clinical practice due to the associated cost and technical demands. The hemodynamic gain index (HGI), a non-metabolic parameter derived from systolic blood pressure and heart rate changes during exercise, has been demonstrated to play a promising role in HF populations. In this study, we aimed both to validate the prognostic value of the HGI and to evaluate a novel metric, heart hemodynamic reserve (HHR), in patients with HF and left ventricular ejection fraction (LVEF) below 50%. Methods: We retrospectively enrolled 479 consecutive patients with HF and reduced or mildly reduced LVEF who underwent maximal, symptom-limited CPET at three Italian university hospitals between 2012 and 2024. The HGI and HHR were computed using resting and peak exercise hemodynamic data. HHR is defined as the product of systolic blood pressure and heart rate reserve with exercise, normalized for the age-predicted maximum heart rate. The primary endpoint was a composite of cardiovascular death, urgent heart transplantation (HTx), or left ventricular assist device (LVAD) implantation. Prognostic associations were assessed using multivariable Cox regression and area under the receiver operating characteristic curves (AUCs). Results: During a median follow-up of 3.25 years, the composite outcome occurred in 56 patients (11.5%). Both the HGI and HHR were independently associated with the prespecified endpoint (HGI HR: 0.41, 95% CI: 0.20-0.83, p = 0.013; HHR HR: 0.89, 95% CI: 0.83-0.96, p = 0.004), with HHR showing a slightly higher prognostic accuracy than the HGI (AUC 0.78 vs. 0.74; p = 0.033). Conclusions: Both the HGI and HHR are independent prognostic markers in HF patients with LVEF < 50%. Their non-metabolic derivation makes them valuable tools for risk stratification in settings where CPET is unavailable.

PMID:41008738 | PMC:PMC12468042 | DOI:10.3390/diagnostics15182366

Categorías: Trasplante cardíaco

miRNA-Orchestrated Fibroinflammatory Responses in Heart Failure with Preserved Ejection Fraction: Translational Opportunities for Precision Medicine

Trasplante cardíaco - Sáb, 09/27/2025 - 10:00

Diagnostics (Basel). 2025 Sep 9;15(18):2286. doi: 10.3390/diagnostics15182286.

ABSTRACT

Heart failure with a preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases. It continues to impose a significant global cardiovascular burden due to its rising prevalence, complex pathophysiology, and limited treatment options. The absence of effective disease-modifying therapies is primarily attributable to the complex and heterogeneous pathophysiology underlying HFpEF. The hallmark of HFpEF is systemic inflammation, mostly originating from extracardiac comorbidities, which initiates and sustains the process of myocardial fibrosis, resulting in diastolic dysfunction. Recent evidence has identified specific micro ribonucleic acids (miRNAs) as key regulatory molecules in this inflammation-fibrosis cascade. Particularly, miR-21 and miR-29 play a central role in modulating these pathological processes by regulating the post-transcriptional expression of genes involved in inflammation, cardiac fibrosis, and remodeling. The inflammation-fibrosis axis in HFpEF offers multiple therapeutic opportunities ranging from direct anti-fibrotic strategies to the modulation of inflammation and fibrosis-related miRNA signatures. Such targeted approaches, especially miRNA modulation, hold potential to disrupt fundamental molecular mechanisms driving disease progression, moving beyond conventional HFpEF management. This narrative review explores the roles of miRNAs in modulating inflammation and fibrosis in HFpEF, critically assesses their potential as diagnostic and prognostic biomarkers, and evaluates their therapeutic application. Given the urgent clinical need for efficient HFpEF treatment strategies, understanding miRNA-mediated regulation of the inflammation-fibrosis axis is essential for developing personalized, mechanism-based therapies for HFpEF that could fundamentally change the HFpEF management paradigm.

PMID:41008658 | PMC:PMC12468781 | DOI:10.3390/diagnostics15182286

Categorías: Trasplante cardíaco

N-Terminal Pro-B-Type Natriuretic Peptide and Cardiac Troponin T in Stable Renal Transplant Recipients and All-Cause Mortality, Cardiovascular, and Renal Events

Trasplante cardíaco - Sáb, 09/27/2025 - 10:00

Biomolecules. 2025 Sep 9;15(9):1298. doi: 10.3390/biom15091298.

ABSTRACT

INTRODUCTION: In renal transplant recipients (RTRs), kidney graft failure and cardiovascular (CV) disease are prevalent and associated with mortality.

OBJECTIVES: The objective of the study was to evaluate biomarkers, (cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)), to identify RTRs who are at greater risk of death, CV event, and graft renal survival.

PATIENTS AND METHODS: A total of 342 stable RTRs were enrolled in this study, with a median follow-up time of 54 months. The probability of death, CV event, and renal graft survival were calculated using Kaplan-Meier analysis for the group defined by cTnT and NT-proBNP levels above the cutoff values.

RESULTS: The probability of death for troponin T level above the cut-off was 23% and for NT-proBNP 29%. For CV events the probability for troponin T was 20% and for NT-proBNP it was 21%. Troponin T concentrations above the cutoff point suggested a 25% probability of death-censored graft survival. For NT-proBNP, it was 26%. The probability of overall graft survival was 38% for patients with higher troponin T levels, and 40% for NT proBNP.

CONCLUSIONS: These data suggest that cTnT and NT-proBNP could potentially identify patients at high risk for death, CV event, and graft survival.

PMID:41008605 | PMC:PMC12467138 | DOI:10.3390/biom15091298

Categorías: Trasplante cardíaco

Fulminant Myocarditis with VA-ECMO Support: Clinical Characteristics and Prognosis in a Cohort from a Tertiary Transplant Center

Trasplante cardíaco - Sáb, 09/27/2025 - 10:00

Biomedicines. 2025 Sep 3;13(9):2146. doi: 10.3390/biomedicines13092146.

ABSTRACT

Background/Objectives: Fulminant myocarditis (FM) is an uncommon but potentially reversible form of myocardial inflammation that can rapidly progress to cardiogenic shock (CS). In patients who are refractory to conventional treatment, venoarterial extracorporeal membrane oxygenation (VA-ECMO) represents an effective life support strategy. However, the factors that determine functional recovery remain uncertain. The primary objective of this study was to characterize patients who recover ventricular function. Secondary objectives included analyzing VA-ECMO-related complications and overall patient survival. Methods: This was a retrospective, single-center, observational study including all consecutive patients diagnosed with FM between 2008 and 2025 who were supported with VA-ECMO (n = 22). Clinical, biochemical, echocardiographic, and imaging variables were collected. Patients were classified based on their outcomes as either recovery or death/transplantation. Differential factors potentially affecting myocardial recovery, survival, and complications were analyzed. Results: The mean age was 49.7 ± 11 years, with 36% being male. Severe cardiogenic shock was the most common initial presentation (86%), and the average time from symptom onset to hospital admission was 5.7 days. Regarding mechanical support, the non-recovery group required longer ECMO support (328 ± 225 h vs. 188 ± 103 h; p = 0.03). The presence of fibrosis on cardiac magnetic resonance imaging (MRI) was associated with a lower probability of recovery (100% vs. 44.4%; p = 0.03). Renal failure and vascular complications were more frequent in the non-recovery group, with a significantly higher rate of surgical reintervention (50% vs. 10%; p = 0.04). Echocardiography performed before discharge (recovery group) vs. before death/transplant (non-recovery group) showed significant differences in left ventricular ejection fraction (51.1% vs. 29.5%; p = 0.04), along with better levels of creatinine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), leukocytes, and C-reactive protein (CRP) in the recovery group. In-hospital survival for the entire cohort was 63.6%, significantly higher in the recovery group (100% vs. 33.3%; p < 0.01). One-year survival was 59%, which was also greater among those who recovered (90% vs. 33.3%; p = 0.02). Conclusions: FM is associated with an acceptable in-hospital survival rate. The presence of myocardial fibrosis on MRI and longer ECMO support duration were observed to be associated with a lower likelihood of cardiac recovery. Patients who recovered showed better ventricular function at discharge, as well as reduced systemic inflammation and renal dysfunction. These findings highlight the importance of early identification of predictors of myocardial recovery to optimize management and therapeutic decision making in this high-risk population.

PMID:41007709 | PMC:PMC12467035 | DOI:10.3390/biomedicines13092146

Categorías: Trasplante cardíaco

In Vivo Targeted Reprogramming of Cardiac Fibroblasts for Heart Regeneration: Advances and Therapeutic Potential

Trasplante cardíaco - Sáb, 09/27/2025 - 10:00

Bioengineering (Basel). 2025 Aug 30;12(9):940. doi: 10.3390/bioengineering12090940.

ABSTRACT

Myocardial infarction-induced cardiovascular diseases remain a leading cause of mortality worldwide. Excessive post-infarct fibrosis contributes to adverse cardiac remodeling and the progression to heart failure. In vivo reprogramming strategies offer a promising avenue for heart regeneration by directly converting resident fibroblasts into cardiomyocytes through enforced expression of cardiogenic genes. This approach circumvents the need for invasive biopsies, cell expansion, induction of pluripotency, or autologous transplantation. Despite these advantages, key challenges persist, including low reprogramming efficiency and limited cellular targeting specificity. A critical factor for effective anti-fibrotic therapy is the precise and efficient delivery of reprogramming effectors specifically to fibrotic fibroblasts, while minimizing off-target effects on non-fibroblast cardiac cells and fibroblasts in non-cardiac tissues. In this review, we discuss the cellular and molecular mechanisms underlying in vivo cardiac reprogramming, with a focus on fibroblast heterogeneity, key transcriptional drivers, and relevant intercellular interactions. We also examine current advances in fibroblast-specific delivery systems employing both viral and non-viral vectors for the administration of lineage-reprogramming factors such as cDNA overexpressions or microRNAs. Finally, we underscore innovative strategies that hold promise for enhancing the precision and efficacy of cellular reprogramming, ultimately fostering translational development and paving the way for rigorous preclinical assessment.

PMID:41007184 | PMC:PMC12466987 | DOI:10.3390/bioengineering12090940

Categorías: Trasplante cardíaco

Myocardial Infarction in a Young Adult: A Rare Case of Left Coronary Artery Arising from the Pulmonary Artery

Congenital cardiac surgery - Sáb, 09/27/2025 - 10:00

Life (Basel). 2025 Sep 21;15(9):1482. doi: 10.3390/life15091482.

ABSTRACT

Anomalous origin of the Left Coronary Artery from the Pulmonary Artery (ALCAPA), also known as Bland-White-Garland syndrome, is a rare congenital coronary anomaly with an estimated incidence of 1 in 300,000 live births. While commonly diagnosed in infancy, adult presentations are exceedingly rare and pose significant diagnostic challenges. Delayed diagnosis may result in progressive myocardial ischemia, heart failure, arrhythmias, or sudden cardiac death. Surgical correction is the definitive treatment, with the goal of restoring a dual coronary artery system and preventing irreversible myocardial damage. We present the case of a 30-year-old male with a prior history of non-ST-elevation myocardial infarction who was referred for evaluation of exertional angina and symptoms of heart failure. Transthoracic echocardiography revealed a dilated left ventricle with an ejection fraction (LVEF) of 35%. Coronary angiography and cardiac MDCT identified an anomalous origin of the left circumflex artery (LCx) from the right pulmonary artery (RPA) and a coronary-pulmonary artery fistula involving the LAD. The patient underwent successful surgical correction with reimplantation of the LCx into the ascending aorta. Postoperative recovery was uneventful. At 3-month follow-up the patient was symptom-free, though echocardiography revealed persistent LV dilation and reduced LVEF, necessitating continued pharmacologic therapy and monitoring. This case highlights the importance of maintaining a high index of suspicion for ALCAPA in adult patients with unexplained cardiomyopathy or ischemic symptoms. Early diagnosis and surgical intervention remain crucial for improving long-term outcomes and preventing life-threatening complications.

PMID:41010424 | PMC:PMC12471381 | DOI:10.3390/life15091482

Categorías: Cirugía congénitos

Elbow Contracture Secondary to Congenital Shoulder Luxation in a Dog: Surgical Management with Elbow Muscle Release and Circular Osteotomy-Based Shoulder Arthrodesis

Congenital cardiac surgery - Sáb, 09/27/2025 - 10:00

Animals (Basel). 2025 Sep 16;15(18):2717. doi: 10.3390/ani15182717.

ABSTRACT

A 10-month-old Poodle was presented with intermittent non-weight-bearing lameness of the left thoracic limb. Orthopedic and radiographic examinations revealed medial shoulder luxation and markedly reduced elbow extension. A two-stage surgical approach was performed. In the first stage, selective myotomy of periarticular structures, including the biceps brachii-brachialis complex and the extensor carpi radialis muscle, was conducted via medial and lateral approaches. A trans-articular external skeletal fixator was applied to maintain elbow extension. Elbow extension improved from 105° preoperatively to 142°. After confirming functional recovery of the elbow joint, the second stage involved shoulder arthrodesis using a circular osteotomy technique with a radial saw, which enabled fine-tuned intraoperative adjustment of limb alignment based on the contralateral limb posture. At nine months postoperatively, the patient exhibited a symmetrical gait, full weight-bearing, and no evidence of discomfort on range of motion assessment. This case highlights the clinical relevance of secondary elbow contracture associated with congenital shoulder instability and suggests that a combination of targeted muscle release and adjustable arthrodesis may offer favorable outcomes in managing complex joint dysfunction.

PMID:41007962 | PMC:PMC12466446 | DOI:10.3390/ani15182717

Categorías: Cirugía congénitos

Esophageal Atresia and Intrathoracic Stomach in a Complex Case of Congenital Anomalies

Congenital cardiac surgery - Sáb, 09/27/2025 - 10:00

Children (Basel). 2025 Sep 16;12(9):1244. doi: 10.3390/children12091244.

ABSTRACT

Background/Objectives: Complex cases in pediatric surgery involving multiple congenital anomalies pose significant diagnostic and therapeutic challenges. These conditions require coordinated interdisciplinary care tailored to the individual patient. We present a case of syndromic congenital anomalies in a neonate, later diagnosed with CHARGE syndrome, to illustrate the importance of staged, multidisciplinary management. Methods: A 34-year-old woman in her third pregnancy developed significant polyhydramnios at 31 weeks of gestation, followed by preterm labor. The neonate presented with esophageal atresia with tracheoesophageal fistula (EA/TEF), intrathoracic stomach, aortic coarctation, patent ductus arteriosus, atrial septal defect, and bilateral choanal atresia. A structured treatment protocol was developed and implemented at Klinikum Stuttgart by an interdisciplinary team comprising gynecology, pediatric surgery, cardiology, ENT, neonatology, and genetics. Results: Initial pediatric surgical procedures included ligation of the tracheoesophageal fistula, repositioning of the intrathoracic stomach, and primary esophageal anastomosis. Cardiovascular anomalies were managed through staged interventions. Bilateral choanal atresia was surgically corrected. Genetic testing confirmed CHARGE syndrome. Postoperative care included respiratory support, enteral nutrition, and regular esophageal dilations. Due to persistent reflux esophagitis, antireflux surgery is planned. Conclusions: This case underscores the importance of a highly individualized and interdisciplinary approach in the management of syndromic congenital anomalies. The presence of CHARGE syndrome with multiple system involvement required careful staging of surgical interventions and long-term coordination of follow-up care. Early genetic diagnosis and integrated team planning were critical in optimizing outcomes in this complex neonatal case.

PMID:41007109 | PMC:PMC12468033 | DOI:10.3390/children12091244

Categorías: Cirugía congénitos

Clinical Impact of Patient-Specific 3D Models in Neonatal Surgery: A Case-Based Review of Applications and Future Directions

Congenital cardiac surgery - Sáb, 09/27/2025 - 10:00

Children (Basel). 2025 Sep 9;12(9):1202. doi: 10.3390/children12091202.

ABSTRACT

Three-dimensional (3D) modeling and printing technologies are increasingly used in pediatric surgery, offering improved anatomical visualization, surgical planning, and personalized approaches to complex conditions. Compared to standard imaging, patient-specific 3D models-virtual or printed-provide a more intuitive spatial understanding of congenital anomalies, tumors, and vascular anomalies. This review compiles evidence from pediatric surgical fields including oncology, abdominal, and thoracic surgery, highlighting the clinical relevance of 3D applications. The technological workflow-from image segmentation to computer-aided design (CAD) modeling and multimaterial printing-is described, emphasizing accuracy, reproducibility, and integration into hospital systems. Several clinical cases are presented: neuroblastoma, cloacal malformation, conjoined twins, and two cases of congenital diaphragmatic hernia (one with congenital pulmonary airway malformation, CPAM). In each, 3D modeling enhanced anatomical clarity, increased surgeon confidence, and supported safer intraoperative decision-making. Models also improved communication with families and enabled effective multidisciplinary planning. Despite these advantages, challenges remain, such as production time, cost variability, and lack of standardization. Future directions include artificial intelligence-based automation, expanded use of virtual and mixed reality, and prospective validation studies in pediatric cohorts. Overall, 3D modeling represents a significant advance in pediatric precision surgery, with growing evidence supporting its safety, clinical utility, and educational value.

PMID:41007067 | PMC:PMC12469229 | DOI:10.3390/children12091202

Categorías: Cirugía congénitos

Revisiting Hepatic Fibrosis Risk in Congenital Heart Disease: Insights from Non-Invasive Markers and Echocardiography

Congenital cardiac surgery - Sáb, 09/27/2025 - 10:00

Children (Basel). 2025 Aug 27;12(9):1131. doi: 10.3390/children12091131.

ABSTRACT

BACKGROUND/OBJECTIVES: This study aimed to investigate the prevalence of liver damage and its associated non-invasive markers and echocardiographic risk factors in patients who underwent surgery for congenital heart disease.

METHODS: This retrospective observational study was conducted at a single tertiary-care university hospital in Niigata, Japan. Of 142 patients (ventricular septal defect [VSD] n = 47, tetralogy of Fallot [TOF] n = 67, Fontan n = 28), 52.8% were male [median age: 22.7 years; VSD (24.3 years), TOF (24.0 years), and Fontan (12.5 years)]. Pediatric patients with liver diseases unrelated to congestive liver disease, such as viral hepatitis and alcoholic liver disease, were excluded. We compared non-invasive liver fibrosis age-invariant biomarkers, such as the aspartate aminotransferase-to-platelet ratio index (APRI), and various serum markers and echocardiographic parameters to assess the prevalence and predictors of hepatic fibrosis.

RESULTS: The Fontan circulation group had the highest APRI, followed by the TOF group, while the VSD group had a low risk of APRI elevation. Postoperative TOF patients required monitoring for cirrhosis progression. Inferior vena cava mobility was associated with echocardiographic parameters and fibrosis severity, along with a loss of respiratory variability. The limitations of other cardiac assessments were highlighted by poor anatomical measurements. Gamma-glutamyl transpeptidase (γ-GTP) demonstrated strong discriminatory ability. The optimal cutoff value was 53.0 U/L, suggesting its use as a clinical marker.

CONCLUSIONS: Assessing fibrosis is crucial in CHD patients, especially those with late post-TOF repair findings. Non-invasive markers (APRI, γ-GTP, and B-type natriuretic peptide), along with echocardiographic findings, may help detect fibrosis early, enabling timely intervention and improving long-term outcomes.

CLINICAL TRIAL REGISTRATION: 2020-0199.

PMID:41006995 | PMC:PMC12468072 | DOI:10.3390/children12091131

Categorías: Cirugía congénitos

CT-Derived Aortic Valve Anatomy and Acute Complications After Self-Expanding and Balloon-Expandable TAVI

Valvular cardiac surgery - Sáb, 09/27/2025 - 10:00

Medicina (Kaunas). 2025 Sep 11;61(9):1650. doi: 10.3390/medicina61091650.

ABSTRACT

Background and Objectives: This study aimed to assess the clinical and anatomical predictors of acute cardiac complications after transcatheter aortic valve implantation (TAVI). Materials and Methods: All patients who underwent a TAVI procedure for severe aortic stenosis between November 2016 and May 2025 at a tertiary center in Romania were screened for inclusion. Of those, patients who had available computer tomography valvular sizing reports were included in the present study. Results: A total of 485 patients were included in this study. Balloon-expandable valves were implanted in 381 patients (78.5%), while self-expanding valves were used in 104 patients (21.4%). A total of sixty-nine (14.2%) patients suffered at least one acute cardiac complication following TAVI, and in-hospital death occurred in nine (1.8%) patients. In the multivariable analysis, clinical parameters-such as diabetes mellitus, left bundle branch block, or left ventricular diameter-and anatomic parameters, such as left coronary artery height and sinotubular junction height, were predictors of acute complications. Similarly, periprocedural characteristics, such as maximum transprosthetic gradient and the use of the Portico/Navitor valve platform was also associated with the occurrence of acute complications. Conclusions: A high acute complications rate is typical for TAVI, although most complications can be successfully treated and the in-hospital death rate is low. Left coronary artery height and sinotubular junction height were predictors of acute complications, among other clinical and procedural characteristics.

PMID:41011039 | PMC:PMC12472114 | DOI:10.3390/medicina61091650

Categorías: Cirugía valvular

Preoperative Activation of c-Src Kinase in Atrial Tissue in Patients Developing Postoperative Atrial Fibrillation

Extracorporeal circulation - Sáb, 09/27/2025 - 10:00

Medicina (Kaunas). 2025 Sep 15;61(9):1669. doi: 10.3390/medicina61091669.

ABSTRACT

Background and Objectives: Atrial fibrillation (AF) is a common complication of cardiac surgery. c-Src has been implicated in atrial remodeling in chronic AF, but its role in the early postoperative setting remains unclear. We, therefore, investigated whether baseline c-Src expression in atrial tissue is associated with the subsequent development of postoperative AF (PoAF). The aim of the present work was the evaluation of atrial c-Src expression and activity in patients subjected to open heart surgery who were previously free from AF and to check if changes to the initial level of this protein predispose to the development of postoperative AF (PoAF). Materials and Methods: Forty-two patients without previous AF history we enrolled. Patients with an AF episode during postoperative in-hospital follow-up were assigned to the PoAF group, while the rest (in sinus rhythm-SR) constituted the control group. Samples of the right atrial appendage were harvested before the introduction of the extracorporeal circulation. The expression of c-Src and phospho-c-Src(Tyr416), as well as upstream regulators of c-Src kinase, STAT3, ERK1/2, PDGFRα, and PDGFRβ, was assessed using Western blot. Results: AF occurred in 14 subjects. Expression of c-Src and phospho-c-Src was significantly higher in the PoAF group than in the SR group (c-Src: 1.65×, p = 0.037, and phospho-c-Src: 2.75×, p = 0.003). In addition, in the right atrium of PoAF patients, there was significantly elevated expression of STAT3, ERK1/2, and PDGF receptors, which may facilitate activation of c-Src kinase in patients with PoAF. Conclusions: Our preliminary findings suggest that c-Src expression and activity may contribute to atrial vulnerability and could represent a molecular target for future therapeutic interventions to prevent PoAF.

PMID:41011060 | PMC:PMC12471775 | DOI:10.3390/medicina61091669

Sex-Specific Longitudinal Changes in Metabolic, Endocrine, Renal, Cardiovascular, and Inflammatory Biomarkers of Vaccinated COVID-19 Survivors: 30-Month Follow-Up Study

Anestesia y reanimación cardiovascular - Sáb, 09/27/2025 - 10:00

Medicina (Kaunas). 2025 Aug 22;61(9):1510. doi: 10.3390/medicina61091510.

ABSTRACT

Objectives: Sex-based disparities in COVID-19 outcomes are well-documented, with men experiencing greater acute severity and women showing increased vulnerability to post-viral syndromes. However, longitudinal immunometabolic trajectories in vaccinated individuals remain underexplored. In this study, sex-based differences in long-term metabolic, endocrine, renal, cardiovascular, and inflammatory responses were investigated among vaccinated individuals recovering from SARS-CoV-2 infection. Methods: This retrospective single-center cohort study included 426 adults (199 females, 227 males) with PCR-confirmed symptomatic COVID-19 and at least two vaccine doses. Serial assessments were conducted at baseline, 18-, 24-, and 30-month post-infection. Parameters included fasting glucose, HbA1c, lipid profile, thyroid function, renal markers, CRP, D-dimer, fibrinogen, troponin, and hematologic indices. Statistical analyses assessed longitudinal changes and sex-stratified correlations. Results: Fasting glucose and HbA1c levels significantly declined over time, more prominently in males. Glucose correlated with age and BMI only in females. Lipid levels remained largely unchanged, although males had higher baseline triglycerides. Females showed rising TSH levels and persistently lower free T3; males exhibited higher creatinine, urea, and troponin levels throughout. Inflammatory markers declined significantly in both sexes, with males displaying higher CRP and troponin, and females showing sustained fibrinogen elevation and a temporary lymphocyte surge. D-dimer was elevated in females at the 30-month point. Conclusions: Sex-specific physiological recovery patterns were evident among vaccinated COVID-19 survivors. Males exhibited earlier metabolic and cardiac alterations, while females had more persistent endocrine and inflammatory shifts. These findings underscore the need for sex-tailored long-term monitoring strategies prioritizing early metabolic and cardiac screening in men and prolonged immunoendocrine surveillance in women.

PMID:41010901 | PMC:PMC12471504 | DOI:10.3390/medicina61091510

Acute Normovolemic Hemodilution Changes the Aquaporin Expression Profile in Specific Tissues and Induces Apoptotic and Inflammatory Processes in a Rat Model

Anestesia y reanimación cardiovascular - Sáb, 09/27/2025 - 10:00

Medicina (Kaunas). 2025 Aug 22;61(9):1506. doi: 10.3390/medicina61091506.

ABSTRACT

Background and Objectives: Acute normovolemic hemodilution (ANH) is commonly used to minimize perioperative blood loss and transfusion requirements. While it is considered safe, the molecular effects of ANH on vital organs remain unclear. Aquaporins (AQPs), the principal cellular water transporters, may play a role in tissue adaptation or injury under hemodilution stress. This study aimed to evaluate the impact of ANH on AQP1, AQP3, and AQP4 expression profiles and their association with apoptotic and inflammatory markers in the aorta, heart, kidney, and liver. Materials and Methods: Male Hannover-Sprague Dawley rats (6 months old) were assigned to control (no procedure), sham (anesthesia only), and hemodilution (anesthesia and ANH) groups. ANH was induced using balanced crystalloid infusion. Physiological parameters, blood gases, electrolytes, and metabolic profiles were monitored. At 24 h post-ANH, tissues were harvested for immunoblot analysis of AQPs, as well as apoptotic and inflammatory markers. Results: At 24 h post-ANH, changes in potassium, calcium, and glucose levels, decreased hematocrit, increased lactate, decreased pH, base excess, and PaCO2 were detected, indicating mild metabolic acidosis due to tissue hypoxia and impaired oxygen delivery. Apoptotic and inflammatory responses were observed across all tissues, but AQP alterations were organ-specific. In the heart, AQP1 downregulation correlated inversely with NF-κB and TNF-α levels, while AQP3 upregulation positively correlated with apoptosis. The aorta showed the opposite pattern. In the kidney, AQP4 downregulation was strongly associated with apoptosis and inflammation. Furthermore, ANH selectively increased the AQP3 expression without affecting AQP1 or AQP4 in the liver. Conclusion: ANH induces differential aquaporin expression patterns in major organs, with tissue-specific associations with apoptosis and inflammation. These findings highlight a potential mechanistic role for AQPs, particularly AQP1 and AQP3, in modulating tissue response to hemodilution. These molecular adaptations may serve as early indicators of tissue stress, suggesting clinical relevance for perioperative fluid strategies.

PMID:41010898 | PMC:PMC12471857 | DOI:10.3390/medicina61091506

Left Main Vasospasm Masquerading as Critical Stenosis Leading to Unnecessary Surgery

http:www.cardiocirugia.sld.cu - Vie, 09/26/2025 - 10:00

JACC Case Rep. 2025 Sep 24;30(29):105231. doi: 10.1016/j.jaccas.2025.105231.

ABSTRACT

BACKGROUND: Vasospastic angina is a condition determined by epicardial coronary artery spasm, which is usually diagnosed from resting angina.

CASE SUMMARY: A 62-year-old man was admitted for recurrent rest angina despite previous coronary artery bypass grafting and plain-old balloon angioplasty for multivessel disease. Coronary computed tomography angiography revealed occluded bypass grafts but nonsignificant coronary atherosclerosis, along with diffuse coronary ectasia and myocardial bridging. During invasive re-evaluation, intravascular ultrasound confirmed positive remodeling and intimal thickening, suggestive of vasospastic pathology. Critical, focal epicardial vasospasm during angiography triggered ventricular fibrillation, reversed by defibrillation. A transient right coronary artery occlusion with ST-elevation resolved with nitrates, highlighting the dynamic nature of the vasospasm.

DISCUSSION: The case emphasizes the importance of considering coronary vasospasm in patients with ambiguous angiographic findings, the diagnostic and therapeutic role of intracoronary nitroglycerin, and the value of imaging in avoiding unnecessary revascularization. Careful pharmacologic testing and physiologic assessment are essential to distinguish functional vasospasm from fixed coronary disease, especially in left main involvement.

PMID:41005853 | DOI:10.1016/j.jaccas.2025.105231

Categorías:

Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Left Main Coronary Artery Disease: The OPTIVUS-Complex PCI Study LMCA Cohort

http:www.cardiocirugia.sld.cu - Vie, 09/26/2025 - 10:00

Am J Cardiol. 2025 Sep 24:S0002-9149(25)00574-0. doi: 10.1016/j.amjcard.2025.09.018. Online ahead of print.

ABSTRACT

The impact of optimal intravascular ultrasound (IVUS)-guided left main coronary artery (LMCA) percutaneous coronary intervention (PCI) on clinical outcomes has not been adequately evaluated yet. The OPTIVUS-Complex PCI study LMCA cohort was a prospective multicenter single-arm trial enrolling 902 patients undergoing LMCA PCI targeting the prespecified IVUS criteria (minimal stent area ≥5.0 mm2 for left circumflex artery ostium, ≥6 mm2 for left anterior descending coronary artery ostium, ≥7 mm2 for polygon of confluence, and ≥8.0 mm2 for proximal LMCA). The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization. The predefined performance goals were based on the CREDO-Kyoto PCI/coronary artery bypass grafting (CABG) registry cohort-2 (PCI: 32.0%, and CABG: 13.9%). The OPTIVUS criteria were met in 73.7% of patients. The prevalence of true bifurcation LMCA lesion was 18.4%. The cumulative 1-year incidence of the primary endpoint was 13.2% (95%CI: 11.0-15.4%), which was significantly lower than the PCI performance goal (32.0%, P<0.0001), and numerically lower than the CABG performance goal (13.9%). The cumulative 1-year incidences of target-lesion revascularization and target-lesion revascularization for LMCA lesions were 4.2% and 3.0%. The cumulative 1-year incidence of the primary endpoint was not different regardless of meeting or not meeting the OPTIVUS criteria (13.4% versus 14.2%, log-rank P=0.79), while those of target-lesion revascularization and target-lesion revascularization for LMCA lesions were significantly lower in patients meeting the OPTIVUS criteria than in patients not meeting the OPTIVUS criteria (3.3% versus 7.7%, log-rank P=0.01, and 2.3% versus 5.5%, log-rank P=0.02). In conclusion, IVUS-guided LMCA PCI targeting the OPTIVUS criteria in the contemporary clinical practice was associated with a significantly lower rate of cardiovascular event than the predefined PCI performance goal, and with a numerically lower rate of cardiovascular event than the predefined CABG performance goal at 1 year.

PMID:41005598 | DOI:10.1016/j.amjcard.2025.09.018

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Chronic inhibition of cGMP-specific phosphodiesterase 5 attenuates myocardial hypertrophy by promoting mitophagy in cardiomyocytes

Protección miocárdica - Vie, 09/26/2025 - 10:00

Biochem Pharmacol. 2025 Sep 24;242(Pt 3):117366. doi: 10.1016/j.bcp.2025.117366. Online ahead of print.

ABSTRACT

Cardiac hypertrophy is a pathological adaptive response to chronic hemodynamic stress or injury, which may progress irreversibly to heart failure if left untreated. The objective of the study was to investigate whether inhibition of phosphodiesterase 5 can induce mitophagy to alleviate pathological cardiac hypertrophy. Sildenafil (Sif) effectively alleviates isoproterenol-induced cardiac hypertrophy in vivo by decreasing left ventricular wall thickness, reducing cardiac interstitial fibrosis, and improving cardiac functional parameters. Additionally, Sif protects against cardiomyocyte hypertrophy in vitro by lowering atrial natriuretic peptide levels and cardiomyocyte cross-sectional area. It also enhances mitochondrial function through the activation of PTEN-induced putative kinase-1 (PINK1)/Parkin-mediated mitophagy. Importantly, the autophagy inhibitor chloroquine abolished Sif-induced mitophagy and cardioprotection, thereby confirming the essential role of autophagic flux. Furthermore, the protective effects of Sif were reversed by the protein kinase G (PKG) inhibitor KT5823, indicating a dependence on the cyclic GMP (cGMP)-PKG signaling pathway. Altogether, Sif enhances mitophagy and maintain mitochondrial integrity by activating the PINK1/Parkin pathway through the cGMP-PKG signaling cascade, highlighting its potential to protect the myocardium perioperatively.

PMID:41005622 | DOI:10.1016/j.bcp.2025.117366

Sirtuin-mediated modulation of cardiac fibrosis: Emerging molecular insights and therapeutic perspectives

Protección miocárdica - Vie, 09/26/2025 - 10:00

Pharmacol Res. 2025 Sep 24;221:107970. doi: 10.1016/j.phrs.2025.107970. Online ahead of print.

ABSTRACT

Fibrosis is a fundamental pathological process driving heart failure progression by promoting extracellular matrix deposition and impairing myocardial compliance. In recent years, the sirtuin family of NAD⁺-dependent deacetylases, traditionally linked to aging and metabolism, has emerged as a key regulator of cardiac fibrotic remodeling. This review investigates the roles of sirtuins in mitigating cardiac fibrosis, with emphasis on mechanisms such as mitochondrial preservation and the therapeutic potential of their modulation. Sirtuin signaling attenuates fibrosis by regulating intracellular pathways that control fibroblast activation. In particular, sirtuin-mediated deacetylation modulates pro-fibrotic mediators, including the TGF-β/Smad pathway, thereby reducing collagen synthesis and fibrotic gene expression. However, their effects are isoform- and context-dependent: SIRT1, SIRT3, SIRT6, and SIRT7 generally exert protective roles, whereas SIRT2 and SIRT5 may display neutral or even pro-fibrotic actions depending on the cell type, disease stage, and experimental context. Recognizing this complexity is essential to evaluate their therapeutic relevance. Building on these mechanistic insights, the review explores the preclinical development of sirtuin-targeted therapies. Strategies include NAD⁺ precursors, natural compounds, novel small-molecule activators with enhanced specificity, and agents that indirectly stimulate sirtuins through metabolic modulation. Such approaches highlight the potential of pharmacologically enhancing sirtuin activity to counteract maladaptive cardiac remodeling and improve outcomes in heart failure. By integrating molecular insights with advances in pharmacology, this review synthesizes the most recent mechanistic findings from the past three years with a dedicated focus on the translational challenges and opportunities of pharmacologically targeting sirtuins for anti-fibrotic therapy.

PMID:41005588 | DOI:10.1016/j.phrs.2025.107970

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