Navigation of the aorta and its branch vessels using standard of care 2D X-ray fluoroscopy in thoracic, fenestrated, and infrarenal endovascular aortic aneurysm repair (TEVAR/FEVAR/EVAR) has multiple disadvantages including exposure to ionizing radiation, contrast agent administration, and limited visualization of complex anatomy. The objective of this study is to demonstrate the safety and efficacy of the electromagnetic-based intraoperative positioning system (IOPS) in providing accurate 3D vessel mapping and guidance for wire and catheter navigation as an adjunct to fluoroscopy during TEVAR/FEVAR/EVAR. Thirty patients with aortic aneurysms suitable for TEVAR/FEVAR/EVAR were enrolled across 2 sites in the United States from 2020 to 2022. Prior to repair, patients underwent computed tomography angiography to generate a 3D anatomical model that was fused with intraoperative cone beam computed tomography. The intervention was performed utilizing IOPS as a 3D guidance system for sensorized wire and catheter manipulation as an adjunct to 2D fluoroscopy. Technical success was defined as the ability to navigate the infrarenal, visceral, and descending thoracic aorta as well as cannulate any necessary aortic branch vessels. Successful cannulation was confirmed using fluoroscopy. Patients were monitored for serious adverse events (SAEs) and nonserious adverse events (non-SAEs) attributable to IOPS intraoperatively and postoperatively. Demographic and patient history data were collected. Patients were predominantly White (83%) males (80%) with a history of coronary artery disease (66.7%) and hypertension (90%). The mean age was 75 years (standard deviation [SD] = 8.2). Interventions included EVAR, FEVAR, and TEVAR procedures. Physicians selected the most suitable graft for treatment, with grafts manufactured by Gore, Endologix, Terumo, Medtronic, and Cook. The fenestrated grafts utilized consisted of commercially available devices, custom made devices, and physician-modified endografts. Technical success was achieved in 100% of patients with IOPS providing adjunctive 3D guidance for wire and catheter manipulation during aortic navigation and branch vessel cannulation. There were zero SAEs and non-SAEs attributable to the IOPS system at the 10-day follow-up. A single sensorized guidewire was used in 80% of cases, and a single sensorized catheter was used in 90% of cases. The electromagnetic-based (IOPS is safe and effective in providing adjunctive 3D guidance for wire and catheter manipulation in infrarenal and fenestrated endovascular abdominal aortic aneurysm repair in humans. The 3D anatomical maps generated allowed for accurate aortic navigation in all targets during TEVAR/FEVAR/EVAR. Future research is needed to investigate the potential for IOPS to reduce radiation exposure to patients and operators, reduce contrast usage, and overall reduce operative time.
Myocardial fibrosis is defined by excessive collagen buildup and is a common feature of cardiomyopathy. The present study was undertaken to detect and measure interstitial and perivascular fibrosis in the left anterior descending (LAD) artery territory of adult hearts and to explore differences based on age and sex using Masson's trichrome (MT) stain. Fifteen formalin-fixed cadaver hearts donated for teaching and research were studied. For each heart, we took a myocardial tissue block near the LAD, embedded it in paraffin, sectioned it into 4-5 μm slices, and stained it with MT. We captured digital images and analyzed them using ImageJ software. We quantified fibrosis as the percentage of collagen-positive area relative to the total myocardial tissue area. Interstitial and perivascular fibrosis were measured separately. We analyzed the data by age group (< 60 vs ≥ 60 years) and sex. Interstitial fibrosis was found in all hearts, with an average area fraction of 18.2% (range: 11.2-25.7%). Perivascular fibrosis was less extensive, typically affecting two to three intramural vessels per section. This type of fibrosis was more noticeable in older cadavers (≥ 60 years) than in younger ones (< 60 years) (p = 0.01). Male hearts exhibited a higher, though not statistically significant, level of fibrosis compared to females. Masson's trichrome staining of cadaver hearts is a valuable tool for demonstrating the extent of myocardial fibrosis. Both interstitial and perivascular fibrosis were demonstrated, and these were more extensive in the older age groups and more pronounced around intramural vessels, highlighting the role of microvascular changes in heart disease. This work shows that using cadaveric tissue models to quantify myocardial fibrosis is practical and can aid anatomical and pathological research.
The effect of adjunctive glucocorticoids in the primary treatment of Kawasaki disease in unselected patients remains unknown. In this multicenter, open-label, randomized, controlled trial in China, we assigned participants with newly diagnosed Kawasaki disease in a 1:1 ratio to receive prednisolone plus standard treatment or standard treatment alone. The primary outcome was the occurrence of coronary-artery lesions at 1 month after illness onset. Prespecified key secondary outcomes, for which analyses were not controlled for multiplicity, included receipt of rescue therapy, duration of fever, change in the C-reactive protein (CRP) level, and changes in coronary-artery z scores. A total of 3208 participants underwent randomization, with coronary-artery lesions detected at baseline in 870 of 3184 participants (27.3%). At 1 month, coronary-artery lesions were detected in 16.0% of the participants receiving prednisolone plus standard treatment and in 13.8% of those receiving standard treatment alone (adjusted risk difference, 1.1 percentage points; 95% confidence interval, -1.0 to 3.4; P = 0.31). Rescue therapy was used in 4.6% of the participants receiving prednisolone plus standard therapy and in 10.1% of those receiving standard treatment alone; the median duration of fever was 8.4 hours and 13.2 hours, respectively, and the reductions in the C-reactive protein level at 72 hours were 67.5 mg per liter and 59.8 mg per liter. Decreases in coronary-artery z scores were similar in the two groups. At 3 months, the incidence of coronary-artery lesions was 12.6% with prednisolone plus standard therapy and 10.5% with standard treatment alone; the percentage of participants with progression of coronary-artery lesions was 28.6% and 28.9%, respectively, and the incidence of medium-to-giant coronary-artery aneurysms was 1.9% and 1.1%. The overall incidence of adverse events did not differ significantly between the two groups. The addition of prednisolone to standard primary treatment for Kawasaki disease did not reduce the incidence of coronary-artery lesions at 1 month after illness onset. (Funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences and the National Natural Science Foundation of China; ClinicalTrials.gov number, NCT04078568.).
A novel telemonitoring system utilizing contactless sensor technologies combined with automated overnight respiratory stability time (RST) analysis has emerged as a sensitive and specific indicator of early deteriorating heart failure (HF). However, the association between RST and clinical parameters, including hemodynamics, remains unclear. Patients admitted to our institute due to worsening HF between February and December 2025 and underwent RST monitoring and simultaneous right heart catheterization were enrolled in this study. The relationship between RST and patient characteristics, hemodynamic parameters, and clinical outcomes was retrospectively investigated. A total of 30 patients (median age, 75 years; 70% male) were included. RST was negatively correlated with the number of HF hospitalizations, serum creatinine, plasma B-type natriuretic peptide, pulmonary artery pressure and dose of loop diuretics. During a median follow-up of 178 days, a lower RST (≤ 25 s) group showed a numerically higher cumulative incidence of the composite outcomes of HF readmission and all-cause death compared with the higher RST group (50.6% versus 0%, p = 0.019). Lower RST may reflect heart failure severity, including pulmonary congestion. Further research is warranted to establish the clinical efficacy of RST-guided HF management.
The study of associations between an individual's age and imaging and non-imaging data is an active research area that attempts to aid understanding of the effects and patterns of aging. In this work, we have conducted a supervoxel-wise association study between both volumetric and tissue attenuation features in coronary computed tomography angiograms (CCTA) and the chronological age of a subject, to understand the localized changes in morphology and CT attenuation (as a measure of tissue density) with age. To enable a supervoxel-wise correlation study, we developed a novel method based on image segmentation, inter-subject image registration, and robust supervoxel-based correlation analysis to achieve a statistical association study between the images and age. We evaluated the registration methodology in terms of the Dice coefficient for the heart chambers and myocardium, and the inverse consistency of the transformations, showing that the method works well in most cases with high overlap and inverse consistency. In a sex-stratified study conducted on a subset of [Formula: see text] images from the SCAPIS study, the supervoxel-wise analysis was able to find localized associations with age outside of the commonly segmented and analyzed sub-regions, and several substantial differences between the sexes in the association of age and volume.
In this video tutorial, we describe the step-by-step procedure of a totally beating heart transplant in a setting of controlled donation after circulatory death. The donor and recipient of the cardiac allograft were present in the same hospital, the same operating block and different operating rooms. After a mandatory no-touch time of asystolic electrocardiographic registering, which per Italian law is 20 minutes, the sternum is opened and supra-aortic vessels are occluded. Thoraco-abdominal normothermic regional perfusion is promptly initiated, interrupting the warm ischaemia time. After the multiparametric evaluation of the cardiac allograft, its procurement from the donor, its transportation from the donor to the recipient and its subsequent implantation are performed completely on a beating heart. Cardiac perfusion in the aortic root was guaranteed continuously with the donor blood during procurement and transportation, and with the recipient blood from the cardiopulmonary bypass during the implantation. By avoiding the two periods of cold ischaemic cardiac arrest typically used in a donation after circulatory death setting, this procedure may reduce ischaemic cardiac injury and potentially improve the allograft performance after the transplant procedure.
This study aimed to describe the normal radiographic anatomy of relevant thoracic structures in clinically healthy pet rabbits and provide morphometric data for some of these structures in lateral and ventrodorsal radiographs. Radiographs of 100 pet rabbits without clinical or radiographic signs of respiratory, cardiovascular, or mediastinal diseases were included in the study. The radiographic appearance of the aorta, the caudal vena cava, pulmonary vessels, the trachea, the delineation (visibility) of the cranial heart contour, and the extension of the diaphragm were evaluated using lateral radiographs. Additionally, the height of the trachea at 2 locations and the angle between the trachea and the thoracic spine were measured. On radiographs in ventrodorsal projection, the visibility of the cranial cardiac contour, the shape of the thorax, and the extension of the diaphragm were evaluated. Thoracic radiographs of 100 pet rabbits, including 54 males (14 intact and 40 neutered) and 46 females (29 intact and 17 neutered) were included. The animals were aged between 6 months and 11 years (median 4.75 years) and had a median body weight of 1.8 kg (range: 0.8-2.7 kg). On the lateral projection, the aorta and vena cava were visible on all radiographs, whereas small pulmonary vessels were recognizable in only 61 animals. The cranial contour of the heart was well defined in 45 rabbits and moderately defined in 55 rabbits. The trachea was exclusively ventrally mineralized in all rabbits. Median tracheal height was 3.2 mm at the level of the first thoracic vertebra and 3.2 mm at the level of the fourth thoracic vertebra. The median angle between the trachea and thoracic spine was 11.6°. On the ventrodorsal projection, the cranial contour of the heart was well defined in 74 rabbits and moderately in 26 rabbits. The median diaphragmatic extension was at the level of the 7th thoracic vertebra. Our study provides an overview of the thoracic structures visible on radiographs in pet rabbits weighing up to 3 kg. The results of our study contribute to the detection of pathological changes in the thorax. Ziel der Studie ist es, die röntgenologische Anatomie verschiedener thorakaler Strukturen bei klinisch thoraxgesunden Heimtierkaninchen zu beschreiben und morphometrische Daten für einige dieser Strukturen in laterolateraler und ventrodorsaler Projektion zu ermitteln.In die Studie wurden Röntgenaufnahmen von 100 Heimtierkaninchen ohne klinische oder radiologische Anzeichen einer Erkrankung der Atemwege, des Herz-Kreislaufsystems oder des Mediastinums einbezogen. Das radiologische Erscheinungsbild der Aorta, der Vena cava caudalis, der Lungengefäße, der Trachea, die Abgrenzbarkeit der kranialen Herzkontur und die Ausdehnung des Zwerchfells wurden anhand der lateralen Röntgenaufnahmen bewertet. Zusätzlich wurden die Höhe der Trachea an 2 Punkten sowie der Winkel zwischen Trachea und Brustwirbelsäule gemessen. Auf den Röntgenaufnahmen in ventrodorsaler Projektion wurden die Abgrenzbarkeit der kranialen Herzkontur, die Form des Thorax und die Ausdehnung des Zwerchfells bewertet.Es wurden Röntgenaufnahmen des Thorax von 100 Heimtierkaninchen, 54 Männchen (14 intakt, 40 kastriert) und 46 Weibchen (29 intakt, 17 kastriert) ausgewertet. Die Tiere waren 6 Monate bis 11 Jahre alt (Median: 4,75 Jahre) und hatten ein medianes Körpergewicht von 1,8 kg (Messbereich: 0,8–2,7 kg). In der lateralen Projektion waren Aorta und Vena cava bei allen Kaninchen sichtbar, während kleine Lungengefäße nur bei 61 Tieren erkennbar waren. Die kraniale Herzkontur war bei 45 Tieren gut und bei 55 Tieren mäßig gut abgrenzbar. Die Trachea war bei allen Kaninchen ausschließlich ventral mineralisiert. Die mediane Höhe der Trachea betrug 3,2 mm auf Höhe des ersten Brustwirbels und 3,2 mm auf Höhe des vierten Brustwirbels. Der Winkel zwischen Luftröhre und Brustwirbelsäule betrug im Median 11,6°. In der ventrodorsalen Projektion war die kraniale Herzkontur bei 74 Kaninchen gut und bei 26 Kaninchen mäßig gut abgrenzbar. Zwerchfellausdehnung lag im Median auf Höhe des 7. Brustwirbels.Die Studie gibt einen Überblick über röntgenologisch sichtbare thorakale Strukturen bei Heimtierkaninchen mit einem Körpergewicht von bis zu 3 kg.Die Ergebnisse tragen dazu bei, pathologische Thoraxveränderungen zu erkennen.
The optimal surgical strategy for congenitally corrected transposition of the great arteries (ccTGA) remains debated. This study aimed to compare the long-term outcomes of each surgical approach and to explore the optimal management strategy. We retrospectively reviewed 107 consecutive patients with ccTGA who underwent biventricular repair at our institution between 1978 and 2023. Patients were categorized into 4 groups: atrial switch with arterial switch (AR-A, n = 17), atrial switch with Rastelli (AR-R, n = 59), physiological repair with Rastelli (PR-R, n = 17), and physiological repair with a native pulmonary valve (PR-N, n = 14). The primary end-point was all-cause mortality. Secondary end-points included reoperation, heart failure, arrhythmia, and pacemaker implantation. Median follow-up was 16 years (IQR, 5.2-25). Twenty-year survival did not differ between anatomical and physiological repair (79% vs 82%, P = .97). Among the 4 groups, survival was 94% (AR-A), 75% (AR-R), 86% (PR-R), and 77% (PR-N). Reoperation-free survival was lowest in PR-R (29%) and significantly lower in Rastelli-type repairs (P = .009). Heart failure occurred more often in Rastelli groups. AR-A achieved the most favourable functional outcomes, with preserved systemic ventricular function, the highest maximum oxygen uptake (37 mL/kg/minute), and the lowest brain natriuretic peptide (13 pg/mL). In this 40-year experience, survival after physiological repair was comparable to anatomical repair. However, AR-A yielded the most favourable long-term functional outcomes and should be considered the preferred strategy when anatomically feasible. Rastelli-type repairs were associated with increased reoperation and heart failure, underscoring the need for refinement of systemic ventricle outflow tract reconstruction techniques.
Eleutherococcus senticosus fruit (ESF) originates from the mature fruit of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim, which is effective in treating essential hypertension (EH). However, the incomplete comprehension of how ESF antihypertensives impedes its further development. This study aims to elucidate the potential molecular mechanism of ESF in treating EH through network pharmacology, Chinmedomics, molecular docking, and experimental verification. In this study, blood pressure, body weight, organ indices, histopathology, and related kits were employed to systematically evaluate the therapeutic efficacy of ESF on EH. Metabolomics analyzed the core metabolites in serum and urine and delineated the metabolic pathways. Subsequently, an integrated approach combining network pharmacology, Chinmedomics, molecular docking, molecular dynamics simulations, and experimental verification was adopted to elucidate the molecular mechanism underlying the antihypertensive effect of ESF. ESF significantly reduced blood pressure, dilated blood vessels, ameliorated oxidative stress, alleviated pathological injuries of the heart and kidney, and reversed the disruption of tryptophan metabolism, taurine and hypotaurine metabolism, vitamin B6 metabolism and other pathways. Chinmedomics combined with network pharmacology identified 5 active constituents targeting 3-hydroxyanthranilic acid oxygenase (3HAO), kynureninase (KYNU), thromboxane synthase (ThrS), sphingosine kinase (SphK), cystathionine γ-lyase (CGL) and pyridoxal 4-dehydrogenase (PLDH). Molecular docking and molecular dynamics simulations verified their stable binding. Furthermore, these components exhibit a synergistic effect. This study sheds light on the molecular mechanisms insights underlying ESF treatment of EH, providing a new translational strategy for developing precision therapeutic drugs for EH.
In turtles, most internal organs lie deep within the coelomic cavity and are covered by the rigid shell, which makes clinical assessment difficult. MRI can provide valuable information, but detailed descriptions of normal MRI anatomy in the European pond turtle (Emys orbicularis) are limited. To document how the non-respiratory coelomic organs of adult female Emys orbicularis appear on MRI and where they are located within the coelomic cavity. Ten adult females were examined using a 3-Tesla MRI scanner with T1- and T2-weighted transverse, sagittal, and dorsal sequences. Organs were identified based on their signal characteristics and anatomic position, and findings were compared with published anatomical studies in chelonians. MRI provided clear visualisation of the heart, major vessels, liver, gallbladder, gastrointestinal tract, spleen, kidneys, urinary bladder and reproductive tissues. All ventricular components including the cavum pulmonale, cavum venosum, cavum arteriosum, muscular ridge, and interventricular canal were consistently identified. Two separate hepatic veins (right and left) drained into the sinus venosus, which differs from patterns reported in several other turtle species. The right and left lateral abdominal veins joined near the midline to form a common vessel before entering the left hepatic lobe. The spleen was positioned on the right side of the coelomic cavity, ventral to the lung. The pancreas could not be distinguished due to similar signal intensity to the liver. The arrangement of the jejunum and ileum showed notable differences compared with other freshwater and marine turtles. This study provides the first clear MRI guide to the non-respiratory coelomic organs in female Emys orbicularis. These observations can help veterinarians interpret routine MRI exams and better identify disorders involving the gut, reproductive tract, vessels and urinary system. Studies that include contrast media or anatomical dissection are still needed to fully define the vascular pattern and the pancreas.
Early detection of cancer and advances in treatment have significantly improved the survival rate of patients with cancer. Both cancer and its treatment can accelerate the onset of cardiovascular disease, adversely affecting prognosis of patients with cancer and survivors. Coronary (CAD) and peripheral arterial disease (PAD) are common complications in patients with cancer. Cardiovascular imaging plays a central role in baseline risk assessment, detection and treatment planning. The indications for the use of various imaging modalities are similar as in the general population. However, due to unique pathophysiological characteristics and clinical presentations of this population, the use of cardiac imaging in these vulnerable patients often needs to be adapted to the clinical circumstances and individual patient characteristics. In this clinical consensus statement, the European Society of Cardiology (ESC) Council of Cardio-Oncology (CCO) and the European Association of Cardiovascular Imaging (EACVI) of the ESC have reviewed and summarized the current evidence in this field to aid clinicians in the selection of appropriate imaging modalities for the diagnosis, monitoring and treatment of CAD and PAD in patients with cancer.
The transition from childhood to puberty involves profound physiological transformations that significantly impact the cardiovascular system. As biological maturation progresses, mainly driven by hormonal changes, both structural and functional adaptations occur in the heart and blood vessels. The heart increases in size and mass, particularly the left ventricle, allowing for a greater pumping capacity to meet the growing body's metabolic demands. Simultaneously, the vasculature adapts through changes in diameter and elasticity, improving the regulation of blood flow and arterial pressure.Functionally, this stage is marked by a gradual enhancement of cardiovascular efficiency: resting heart rate tends to decrease, stroke volume increases, and autonomic nervous system control becomes more balanced. These changes support improved physical performance. Additionally, sex-specific differences begin to emerge during puberty, reflecting the distinct influence of sex hormones on cardiovascular physiology. Understanding the cardiovascular changes that occur during puberty is essential not only for accurately characterizing normal physiological development but also for identifying early deviations that may be associated with an increased risk of cardiovascular disease later in life.In this context, physical exercise plays a pivotal role. Regular physical activity during childhood and adolescence not only accompanies the biological maturation process but also acts as a key modulator of the hemodynamic, metabolic, and autonomic mechanisms underlying cardiovascular remodeling. Through its influence on variables such as cardiac output, blood pressure, baroreflex sensitivity, endothelial function, and autonomic tone, exercise helps shape a more efficient cardiovascular profile that is better equipped to withstand future physiological and pathological challenges.
Heart failure and atherosclerotic comorbidities are common among patients receiving maintenance hemodialysis, yet therapeutic options remain limited. We aimed to clarify the long-term prognostic impact of reduced left ventricular ejection fraction (LVEF) and coronary heart disease (CHD) and explore potential determinants of cardiac recovery in this population. We retrospectively analyzed 310 hemodialysis patients who underwent coronary angiography for suspected CHD. Patients were stratified by baseline LVEF (< 40% vs. ≥ 40%) and the presence of CHD. Five-year mortality was compared between the groups, and associations with coronary intervention were examined. In a subset with follow-up echocardiography, changes in LVEF were analyzed in relation to medication use, coronary intervention, and relative post-dialysis body weight reduction. Patients with reduced LVEF had worse survival than those with normal LVEF (log-rank p = 0.001). Moreover, patients with reduced LVEF and concomitant CHD exhibited the poorest prognosis (log‑rank p = 0.001). Neither PCI nor medical therapy was associated with improvement in LVEF. In contrast, greater post-dialysis body weight reduction independently predicted attenuated recovery of cardiac function (HR 0.89; 95% CI 0.81-0.98; p = 0.018), with continuous analyses confirming an inverse relationship between ultrafiltration intensity and ΔLVEF. In hemodialysis patients with reduced LVEF, the coexistence of CHD requiring intervention identifies a high-risk phenotype, while cardiac recovery appears more strongly influenced by dialysis-related physiology than by conventional therapies. These findings highlight the need for personalized care strategies that integrate ischemic risk assessment with individualized dialysis management.
Myocardial ischemia-reperfusion (I/R) injury exacerbates cardiac dysfunction and heart failure following clinical revascularization. The main mechanisms involve aberrant accumulation of reactive oxygen species (ROS) that induce mitochondrial dysfunction, trigger pyroptosis, and amplify immune-inflammatory responses. Herein, we developed exosome-mitochondrial hybrid membrane vessels to encapsulate carbon monoxide (EM@CO) for targeted delivery of CO to attenuate myocardial I/R injury. Due to the adhesive properties of exosomes and the homologous mitochondrial targeting capacity of the mitochondrial membrane (MM), EM@CO exhibits sequential targeting from infarcted myocardium to myocardial cell mitochondria. The released CO in mitochondria reduces abnormal mitochondrial ROS generation to maintain mitochondrial function, thereby decreasing mtDNA release and inhibiting pyroptosis in vitro and in vivo. Moreover, a single intravenous injection of EM@CO attenuates inflammatory amplification in cardiac tissue by promoting M1 to M2 macrophage polarization. It can effectively decrease the pro-inflammatory cytokine release and inhibit inflammation, thereby attenuating myocardial infarction and improving cardiac function. In summary, the findings of this study reveal the potential for restoring mitochondrial function through targeted gas therapy to eliminate reactive oxygen species (ROS) and inhibit cellular pyroptosis, which holds promise for ameliorating myocardial ischemia-reperfusion injury.
Postoperative delirium (POD) is a serious complication after cardiovascular surgery, and preoperative cognitive impairment is a well-established risk factor. However, the specific cognitive domains relevant to POD prediction remain unclear. This study investigated whether preoperative frontal lobe function, assessed by the Frontal Assessment Battery (FAB), predicts POD in patients undergoing cardiovascular surgery and explored the potential mediating role of frontal executive function in the relationship between global cognitive function and POD. We retrospectively studied 105 patients (mean age 69 ± 12 years) undergoing cardiovascular surgery. Preoperative global cognitive and frontal lobe functions were assessed using the Mini-Mental State Examination (MMSE) and the FAB, respectively. POD was diagnosed using the Confusion Assessment Method for the Intensive Care Unit. POD occurred in 16 patients (15.2%). In univariate analysis, both lower FAB (odds ratio [OR], 0.75; 95% confidence interval [CI] 0.60-0.92) and MMSE (OR, 0.78; 95% CI 0.63-0.97) predicted POD with similar effect sizes. After adjusting for age (≥ 65 years) and sex, FAB remained a significant predictor (adjusted OR, 0.79; 95% CI 0.62-0.99), whereas MMSE showed a similar magnitude of association that did not reach statistical significance (adjusted OR, 0.82; 95% CI 0.65-1.02). Exploratory mediation analysis suggested that FAB may partially mediate the MMSE-POD association (indirect effect: p = 0.029; proportion mediated, 55%), although these findings require cautious interpretation given the limited sample size. Both FAB and MMSE predict POD with comparable effect sizes. Frontal executive function may contribute to the cognitive pathway underlying POD risk, and prospective studies with larger samples are needed to validate these findings.
Insulin resistance in type 2 diabetes is associated with cardiovascular disease. Nutritional overload, hyperinsulinemia, and physical inactivity are the major etiological factors driving the development of insulin resistance. In an obesogenic environment, insulin resistance has been proposed to protect the body against toxic fuel overload, hyperinsulinemia-induced injury, and metabolic stress. Insulin resistance has been further hypothesized to defend the heart and blood vessels against fuel overload when an individual is chronically overeating. Recent landmark cardiovascular outcome trials in type 2 diabetes show major improvements in cardiovascular disease outcomes after treatment with GLP-1 receptor agonists or SGLT2 inhibitors. Bariatric surgery achieves even greater improvements in cardiovascular disease outcomes than treatments with these newer pharmacological agents. It had been previously predicted that glucose-lowering approaches that normalize whole-body energy balance have the greatest potential to improve cardiovascular outcomes in type 2 diabetes. This review hypothesizes that treatment with bariatric surgery, GLP-1 receptor agonists, or SGLT2 inhibitors lowers glucose and nutritional off-loading, normalizes whole-body energy balance, and reduces ectopic fat depositions. This plays a central role in the dramatic reduction in cardiovascular disease and the reversal of insulin resistance in type 2 diabetes, which are observed after these three treatments.
Pulmonary arterial hypertension (PAH) has a poor prognosis despite available treatments. TPN171H, structurally modified from traditional Chinese medicine (Epimedium), was reported to have a high affinity for phosphodiesterase type 5 and exhibited anti-inflammatory and vasodilatory effects in preclinical studies. This phase 2a randomized trial (NCT04483115) evaluated the hemodynamic effects and safety of TPN171H in PAH. Sixty patients with PAH were randomly assigned to receive placebo, TPN171H (2.5, 5, or 10 mg) or tadalafil (20 or 40 mg) and evaluated for hemodynamic changes for 24 h. The primary endpoint was the maximum change (%) in pulmonary vascular resistance (PVR) from baseline. The key secondary endpoint was the change (%) in PVR to systemic vascular resistance (SVR) ratio at each observation point from baseline. Compared to the placebo group, the least square mean differences in the maximum change in PVR were -16.8% (95% CI, -29.1 to -4.5, p = 0.008) in TPN171H 5 mg, -15.4% (95% CI, -28.2 to -2.7, p = 0.019) in tadalafil 20 mg, and -13.3% (95% CI, -25.6 to -0.9, p = 0.036) in the tadalafil 40 mg group. Moreover, TPN171H 5 mg, but none of the tadalafil doses, showed a significant reduction in PVR/SVR ratio at 2 h (p = 0.026), 3 h (p = 0.030), and 5 h (p = 0.046) compared to the placebo group. No serious adverse events occurred. TPN171H 5 mg demonstrated favorable acute hemodynamic effects and an acceptable short-term safety profile in this exploratory trial, supporting further evaluation in adequately powered trials.
In thoracic tissues, the lymphatic vasculature not only contributes to fluid and solute homeostasis but also plays a critical role in shaping overall tissue physiology. Although the general morphology of lymphatic vessels and their organization within the vascular circuit are largely conserved inter-organs, thoracic lymphatics exhibit highly specialized structural features, such as the presence of stomata and large lacunae, which are exclusively found in pleural and peritoneal mesothelia. These distinct anatomical specializations characterize thoracic lymphatics, which extensively supply organs such as the lung and the heart, as well as serosal compartments including the pleural space and the suprahepatic subdiaphragmatic peritoneal regions, and are associated with equally specialized mechanisms that sustain lymph formation and propulsion. While lymph flow in all tissues may rely on spontaneous contraction of the lymphatic muscles located within the vessel wall and/or on extrinsic tissue motion, the thoracic lymphatic vasculature displays an exceptional diversity of morphological and functional solutions that allow these mechanisms to be exploited with high efficiency, in close adaptation to local anatomical and mechanical environments. Accordingly, this Review focuses on the inter-organ strategies developed by thoracic lymphatics to match local drainage requirements, highlighting how structural specialization and mechanical integration with surrounding tissues optimize lymphatic function and, ultimately, overall tissue performance.
Patients with congenitally corrected transposition of the great arteries (ccTGA) may undergo physiologic repair, leaving the right ventricle systemic, or anatomic repair, correcting the double discordance. We compared both strategies in an international study using propensity-score matching. Patients from 12 European centres, aged <18 years, who underwent either physiologic or anatomic repair between 1990 and 2010 were included (n = 266). Patients were matched by optimal pair matching on ventricular septal defect, subpulmonary left ventricular outflow tract obstruction, ≥mild systemic tricuspid valve regurgitation, age, and gender, resulting in a 1:1 matched cohort of 162 patients. The resulting groups were compared for long-term survival, reoperations, and function of the systemic ventricle and atrioventricular valve. Transplant-free survival at 10 and 15 years was 87 ± 4%, 95% confidence interval (CI) [79%-95%] and 80 ± 6% [68%-93%] for the physiologic group and 85 ± 5% [78%-96%] and 85 ± 5% [78%-96%] for the anatomic group (P = .568). Freedom from cardiac reoperation at 10 and 15 years was 73 ± 6% [62%-85%] and 56 ± 8% [41%-75%] for the physiologic group and 61 ± 8% [47%-76%] and 36 ± 9% [26%-62%] for the anatomic group (P = .279). Tricuspid valve regurgitation at final follow-up was present in 57% (27/47) vs 17% (12/72), respectively (P < .001). Long-term survival and reoperation rates are similar in comparable patients following physiologic and anatomic repair of ccTGA in childhood. Tricuspid valve function may deteriorate when left in the systemic position following physiologic repair. In contrast, patients with tricuspid regurgitation may benefit from anatomic repair, with improved function in the subpulmonary position.
Acute myocarditis is an immune-mediated inflammatory disease characterized by myocardial inflammation and oedema. Although cardiac lymphatic vessels are essential for fluid clearance and immune regulation, their role in modulating autoimmune cardiac inflammation remains largely undefined. We aimed to determine whether promoting lymphangiogenesis could mitigate inflammation and preserve cardiac function in autoimmune myocarditis. We used a murine model of experimental autoimmune myocarditis (EAM) induced by cardiac myosin peptide immunization and examined human autopsy hearts for lymphatic expansion. Mice received VEGF-C C156S, a VEGFR3-selective agonist, starting one week after immunization. We assessed lymphangiogenesis, oedema, immune infiltration, fibrosis, and cardiac function using immunohistochemistry, echocardiography, qPCR, and RNA sequencing. VEGF-C treatment enhanced lymphatic sprouting and function, reduced myocardial water content, and attenuated immune cell infiltration and interstitial fibrosis. Cardiac function was preserved, as measured by echocardiography. Notably, VEGF-C selectively decreased the accumulation of iNOS+ inflammatory macrophages without broadly suppressing T cells or reparative macrophage subsets. Transcriptomic profiling confirmed down-regulation of inflammatory gene programmes associated with macrophage activation. Early stimulation of cardiac lymphangiogenesis by VEGF-C promotes inflammation resolution, limits myocardial injury, and preserves cardiac function in autoimmune myocarditis. Targeting the cardiac lymphatic system may represent a novel therapeutic strategy for inflammatory heart disease.