Search Results (5,081)

Continuous blood pressure (BP) monitoring provides valuable insight into the body’s dynamic cardiovascular regulation across various physiological states such as physical activity, emotional stress, postural changes, and sleep. Continuous BP monitoring captures different variations in systolic and diastolic pressures, reflecting autonomic nervous system activity, vascular compliance, and circadian rhythms. This enables early identification of abnormal BP trends and allows for timely diagnosis and interventions to reduce the risk of cardiovascular diseases (CVDs) such as hypertension, stroke, heart failure, and chronic kidney disease as well as chronic stress or anxiety disorders. To facilitate continuous BP monitoring, we propose an AI-powered estimation framework. The proposed framework first uses an expert-driven feature engineering approach that systematically extracts physiological features from photoplethysmogram (PPG)-based arterial pulse waveforms (APWs). Extracted features include pulse rate, ascending/descending times, pulse width, slopes, intensity variations, and waveform areas. These features are fused with demographic data (age, gender, height, weight, BMI) to enhance model robustness and accuracy across diverse populations. The framework utilizes a Tab-Transformer to learn rich feature embeddings, which are then processed through an ensemble machine learning framework consisting of CatBoost, XGBoost, and LightGBM. Evaluated on a dataset of 1000 subjects, the model achieves Mean Absolute Errors (MAE) of 3.87 mmHg (SBP) and 2.50 mmHg (DBP), meeting British Hypertension Society (BHS) Grade A and Association for the Advancement of Medical Instrumentation (AAMI) standards. The proposed architecture advances non-invasive, AI-driven solutions for dynamic cardiovascular health monitoring. Full article

Chloride, long considered a passive extracellular anion, has emerged as a key determinant in the pathophysiology and management of heart failure (HF) and cardiorenal syndrome. In contrast to sodium, which primarily reflects water balance and vasopressin activity, chloride exerts broader effects on neurohormonal activation, acid–base regulation, renal tubular function, and diuretic responsiveness. Its interaction with With-no-Lysine (WNK) kinases and chloride-sensitive transporters underscores its pivotal role in electrolyte and volume homeostasis. Hypochloremia, frequently observed in HF patients treated with loop diuretics, is independently associated with adverse outcomes, diuretic resistance, and arrhythmic risk. Conversely, hyperchloremia—often iatrogenic—may contribute to renal vasoconstriction and hyperchloremic metabolic acidosis. Experimental data also implicate chloride dysregulation in myocardial electrical disturbances and an increased risk of sudden cardiac death. Despite mounting evidence of its clinical importance, serum chloride remains underappreciated in contemporary risk assessment models and treatment algorithms. This review synthesizes emerging evidence on chloride’s role in HF, explores its diagnostic and therapeutic implications, and advocates for its integration into individualized care strategies. Future studies should aim to prospectively validate these associations, evaluate chloride-guided therapeutic interventions, and assess whether incorporating chloride into prognostic models can improve risk stratification and outcomes in patients with heart failure and cardiorenal syndrome. Full article

Objectives: To evaluate the long-term prognostic value of left ventricular ejection fraction (LVEF) in consecutive patients undergoing invasive coronary angiography (CA). Background: LVEF is a key prognostic marker in cardiovascular disease, but its value across different clinical indications for CA remains insufficiently characterized. Methods: Consecutive patients undergoing CA between January 2016 and August 2022 were retrospectively included at one institution. Patients were stratified into four LVEF groups: ≥ 55%, 45–54%, 35–44%, and <35%. The primary endpoint was rehospitalization for heart failure (HF) at 36 months. Secondary endpoints were acute myocardial infarction (AMI) and coronary revascularization. Kaplan–Meier and multivariable Cox regression analyses were conducted within the entire study cohort and pre-defined subgroups. Results: A total of 6888 patients were included (median age: 71 years; 65.2% males). LVEF < 35% was associated with a higher comorbidity burden and more extensive coronary artery disease (e.g., three-vessel CAD: 38.6% vs. 20.7%, p < 0.001). Event rates for HF rehospitalization and AMI increased progressively with declining LVEF, while revascularization rates varied across categories. Statistically significant differences across LVEF groups were observed for all three endpoints in unadjusted analyses (log-rank p < 0.001). In multivariable models, LVEF < 35% independently predicted HF rehospitalization (HR = 3.731, p < 0.001) and AMI (HR = 4.184, p < 0.001), but not revascularization (HR = 0.867, p = 0.378). The prognostic association was demonstrated across all subgroups stratified by age, sex, subtype of acute coronary syndrome, and CAD severity. Conclusions: Reduced LVEF is an independent predictor of HF rehospitalization and AMI in patients undergoing coronary angiography, irrespective of its indication, whereas no independent association was observed with coronary revascularization. Full article

Coronary artery disease (CAD) constitutes a major contributor to morbidity, mortality and healthcare burden worldwide. Recent innovations in imaging modalities, pharmaceuticals and interventional techniques have revolutionized diagnostic and treatment options, necessitating the reevaluation of established drug protocols or the consideration of newer alternatives. The utilization of beta blockers (BBs) in the setting of acute myocardial infarction (AMI), shifting from the pre-reperfusion to the thrombolytic and finally the primary percutaneous coronary intervention (pPCI) era, has become increasingly more selective and contentious. Nonetheless, the extent of myocardial necrosis remains a key predictor of outcomes in this patient population, with large trials establishing the beneficial use of beta blockers. Computed tomography coronary angiography (CTCA) has emerged as a highly effective diagnostic tool for delineating the coronary anatomy and atheromatous plaque characteristics, with the added capability of MESH-3D model generation. Induction and preservation of a low heart rate (HR), regardless of the underlying sequence, is of critical importance for high-quality results. Landiolol is an intravenous beta blocker with an ultra-short duration of action (t1/2 = 4 min) and remarkable β1-receptor specificity (β1/β2 = 255) and pharmacokinetics that support its potential for systematic integration into clinical practice. It has been increasingly recognized for its importance in both acute (primarily studied in STEMI and, to a lesser extent, NSTEMI pPCI) and chronic (mainly studied in elective PCI) CAD settings. Given the limited literature focusing specifically on landiolol, the aim of this narrative review is to examine its pharmacological properties and evaluate its current and future role in enhancing both diagnostic imaging quality and therapeutic outcomes in patients with CAD. Full article

Background/Objectives: Haloperidol is a typical antipsychotic drug widely used for acute confusional state, psychotic disorders, agitation, delirium, and aggressive behavior. Methods: The toxicity of haloperidol was studied using zebrafish (ZF) embryos as a model organism. Dechorionated embryos were exposed to various concentrations of haloperidol (0.5–6.0 mg/L). The lethal dose concentration was estimated and was found to be 1.941 mg/L. Results: The impact of haloperidol was dose-dependent and significant from 0.25 mg/L. Haloperidol induced several deformities at sublethal doses, including abnormal somites, yolk sac edema, and skeletal deformities. Haloperidol significantly affected heart rate and blood flow and induced pericardial edema and hyperemia in a dose-dependent manner, suggesting its influence on heart development and function. Embryos exposed to haloperidol during their ontogenetic development had smaller body length and eye surface area than non-exposed ones in a dose-dependent manner. Conclusions: It was found that haloperidol significantly affects the behavior of the experimental organisms in terms of mobility, reflexes to stimuli, and adaptation to dark/light conditions. Full article

In observational causal inference studies, unmeasured confounding remains a critical threat to the validity of effect estimates. While proximal causal inference (PCI) has emerged as a powerful framework for mitigating such bias through proxy variables, existing PCI methods cannot directly handle censored data. This article develops a unified proximal causal inference framework that simultaneously addresses unmeasured confounding and right-censoring challenges, extending the proximal causal inference literature. Our key contributions are twofold: (i) We propose novel identification strategies and develop two distinct estimators for the censored-outcome bridge function and treatment confounding bridge function, resolving the fundamental challenge of unobserved outcomes; (ii) To improve robustness against model misspecification, we construct a robust proximal estimator and establish uniform consistency for all proposed estimators under mild regularity conditions. Through comprehensive simulations, we demonstrate the finite-sample performance of our methods, followed by an empirical application evaluating right heart catheterization effectiveness in critically ill ICU patients. Full article

Zebrafish are model organisms for drug screening owing to their transparent bodies, rapid embryonic development, and genetic similarities with humans. However, using standard polystyrene culture plates can limit the oxygen supply, potentially affecting embryo survival and the reliability of assays conducted in zebrafish. In this study, we evaluated the application of a novel, highly oxygen-permeable culture plate (InnoCell^TM) in zebrafish development and drug screening assays. Under both normal and oxygen-restricted conditions, zebrafish embryos cultured on InnoCell^TM plates exhibited significantly improved developmental parameters, including heart rate and body length, compared with those cultured on conventional polystyrene plates. The InnoCell^TM plate enabled a significant reduction in medium volume without compromising zebrafish embryo viability, thereby demonstrating its advantages, particularly in high-throughput 384-well formats. Drug screening tests using antiangiogenic receptor tyrosine kinase inhibitors (TKIs) revealed enhanced sensitivity and more pronounced biological effects in InnoCell^TM plates, as evidenced by the quantification of intersegmental blood vessels and gene expression analysis of the vascular endothelial growth factor receptor (vegfr, also known as kdrl). These results indicate that the InnoCell^TM highly oxygen-permeable plate markedly improves zebrafish-based drug screening efficiency and assay reliability, highlighting its potential for widespread application in biomedical research. Full article

Background/Objectives: Heart failure (HF) is a growing global health burden, yet early detection remains challenging due to the limitations of traditional diagnostic tools such as electrocardiograms (ECGs). Recent advances in deep learning offer new opportunities to identify left ventricular systolic dysfunction (LVSD), a key indicator of HF, from ECG data. This study validates AiTiALVSD, our previously developed artificial intelligence (AI)-enabled ECG Software as a Medical Device, for its accuracy, transparency, and robustness in detecting LVSD. Methods: This retrospective single-center cohort study involved patients suspected of LVSD. The AiTiALVSD model, based on a deep learning algorithm, was evaluated against echocardiographic ejection fraction values. To enhance model transparency, the study employed Testing with Concept Activation Vectors (TCAV), clustering analysis, and robustness testing against ECG noise and lead reversals. Results: The study involved 688 participants and found AiTiALVSD to have a high diagnostic performance, with an AUROC of 0.919. There was a significant correlation between AiTiALVSD scores and left ventricular ejection fraction values, confirming the model’s predictive accuracy. TCAV analysis showed the model’s alignment with medical knowledge, establishing its clinical plausibility. Despite its robustness to ECG artifacts, there was a noted decrease in specificity in the presence of ECG noise. Conclusions: AiTiALVSD’s high diagnostic accuracy, transparency, and resilience to common ECG discrepancies underscore its potential for early LVSD detection in clinical settings. This study highlights the importance of transparency and robustness in AI-ECG, setting a new benchmark in cardiac care. Full article

Purpose: The identification of cardiovascular risk factors in metastatic prostate cancer (PCa) patients prior to the initiation of androgen receptor pathway inhibitors (ARPIs) is important yet challenging. Methods and Results: A nationwide cohort study was conducted utilizing data from the National Health Insurance Research Database containing the Taiwan Cancer Registry. The study population comprised 4739 PCa patients who received abiraterone or enzalutamide between 1 January 2014, and 28 February 2022. The cohort was divided into a training set (n = 3318) and a validation set (n = 1421). Machine learning techniques with random survival forest (RSF) model incorporating 16 variables was developed to predict major adverse cardiovascular events (MACEs). Over a mean follow-up period of 2.1 years, MACEs occurred in 10.9% and 11.3% of the training and validation cohorts, respectively. The RSF model identified five key predictive indicators: age < 65 or ≥75 years, heart failure, stroke, hypertension, and myocardial infarction. The model exhibited robust performance, achieving an area under the curve (AUC) of 85.1% in the training set and demonstrating strong external validity with an AUC of 85.5% in the validation cohort. A positive correlation was observed between the number of risk factors and the incidence of MACEs. Conclusions: This machine learning approach identified five predictors of MACEs in PCa patients receiving ARPIs. These findings highlight the need for comprehensive cardiovascular risk assessment and vigilant monitoring in this patient population. Full article

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is increasingly recognized as a systemic condition with cardiovascular implications. Among these, heart failure has emerged as a significant complication. The aim of this narrative review was to explore the cellular and molecular pathways that link IBD and heart failure. Drawing upon findings from epidemiologic studies, experimental models, and clinical research, we examined the pathways through which IBD may promote cardiac dysfunction. Chronic systemic inflammation in IBD, driven by cytokines such as TNF-α and IL-1β, can impair myocardial structure and function. Furthermore, intestinal barrier dysfunction and gut dysbiosis can facilitate the translocation of proinflammatory microbial metabolites, including lipopolysaccharide and phenylacetylglutamine, and deplete cardioprotective metabolites like short-chain fatty acids, thereby exacerbating heart failure risk. Additional contributing factors include endothelial and microvascular dysfunction, autonomic dysregulation, nutritional deficiencies, shared genetic susceptibility, and adverse pharmacologic effects. IBD contributes to heart failure pathogenesis through multifactorial and interrelated mechanisms. Recognizing the role of the gut–heart axis in IBD is crucial for the early identification of cardiovascular risk, providing guidance for integrating care and developing targeted therapies to reduce the risk of heart failure in this vulnerable population. Full article

Background and Objectives: Congenital heart defects (CHD) affect around 1% of the population, making them the most common congenital disease worldwide. Thanks to advances in treatment, over 90% of affected children are able to reach adulthood, shifting focus to long-term outcomes such as disease-specific quality of life (DsQoL). To date, there has been no validated, standardized instrument for assessing DsQoL in young German CHD patients. This study introduces the Congenital Heart Disease Specific Inventory (CHDSI), the first freely available German-language instrument for measuring DsQoL in children and adolescents with CHD. Materials and Methods: The CHDSI was developed at the German Heart Center Munich in collaboration with affected children and adolescents and validated nationwide via the National Register for Congenital Heart Defects (NRCHD) with 1201 participants (46 kindergarten children, 530 children, 625 adolescents). Two age-specific versions (36/37 items) and a 31-item preschool version were created, alongside a 6-item short form (CHDSI-SF) for rapid screening. Reliability was assessed using Cronbach’s alpha and split-half methods; construct validity via confirmatory factor analysis (CFA) using DWLS; and score interpretation through standardized stanine scales. The small sample size of kindergarten children precluded a model test for this group. The standard values given for this subsample should therefore be interpreted with caution. Results: The CHDSI showed excellent internal consistency (Cronbach’s α = 0.856 to 0.900) and high split-half reliability (>0.95). CFA confirmed a robust six-factor structure with excellent model fit (CFI and TLI ≥ 0.991, RMSEA ≤ 0.05). Subscales showed strong discriminant validity, and significant differences were found by CHD severity and sex. Conclusions: The CHDSI is a psychometrically valid, age-appropriate, and freely available instrument for assessing DsQoL in children and adolescents with CHD. It provides valuable support for clinical decision-making and research. Further studies should explore international validation and cultural adaptation. Full article

Background: Atrial fibrillation (AF) recurrence following catheter ablation remains a significant clinical challenge despite technological advancements, with recurrence rates in the range of 20–40%. While left atrial parameters have been extensively studied as predictors of recurrence, the contribution of right atrial mechanical function has received limited attention. The hypothesis that the combined assessment of right and left atrial strain parameters may provide superior predictive value represents an important clinical question with potential implications for post-ablation risk stratification and follow-up strategies. Methods: This single-center, retrospective cohort study included 100 consecutive adult patients who underwent AF ablation between May 2022 and June 2024 with at least one-year follow-up. Patients were divided into two groups: those with recurrence (n = 13) and those without recurrence (n = 87). A comprehensive echocardiographic assessment, including the speckle-tracking strain analysis of both atria, was performed. Results: The median follow-up was 365 days [range: 150–912 days] in patients with recurrence. In the multivariable analysis, right ventricular diameter (OR: 0.74; 95% CI: 0.61–0.90; p = 0.001), left ventricular end-diastolic volume (OR: 1.04; 95% CI: 1.00–1.08; p = 0.022), and left ventricular global longitudinal strain rate (OR: 1.22; 95% CI: 1.05–1.40; p = 0.007) emerged as independent predictors of recurrence. Conclusions: The significant association of right atrial longitudinal reservoir strain with recurrence in univariable analysis, although not retained as an independent predictor in the multivariable model, suggests the importance of comprehensive cardiac assessment including right heart parameters in predicting AF recurrence. Full article

This paper examines a previously unknown anonymous Hebrew letter inserted into a postwar edition of Shem HaGedolim, found in the library of the Jewish University in Budapest. The letter, composed in Győr in 1947, consists almost entirely of passages copied from Tiferet Chayim, a hagiographic genealogy of the Sanz Hasidic dynasty. Although derivative in content, the letter’s form and placement suggest it was not meant for transmission but instead served as a private act of mourning and historiographical preservation. By situating the letter within the broader context of post-Holocaust Jewish and Hasidic memory practices, including yizkor books, rabbinic memoirs, and grassroots commemorative writing, this study proposes that the document constitutes a “micro-yizkor”: a bibliographic ritual that aimed to re-inscribe lost tzaddikim into sacred memory. Drawing on theories of trauma, religious coping, and bereavement psychology, particularly the Two-Track Model of Bereavement, the paper examines the letter as both a therapeutic and historiographical gesture. The author’s meticulous copying, selective omissions, and personalized touches (such as modified honorifics and emotive phrases) reflect an attempt to maintain spiritual continuity in the wake of communal devastation. Engaging scholarship by Michal Shaul, Lior Becker, Gershon Greenberg, and others, the analysis demonstrates how citation, far from being a passive act, functions here as an instrument of resistance, memory, and redemptive reconstruction. The existence of such a document can also be examined through the lens of Maurice Rickards’ insights, particularly his characterization of the “compulsive note” as a salient form of ephemera, materials often inserted between the pages of books, which pose unique challenges for interpreting the time capsule their authors sought to construct. Ultimately, the paper argues that this modest and anonymous document offers a rare window into postwar Ultra-orthodox religious subjectivity. It challenges prevailing assumptions about Hasidic silence after the Holocaust and demonstarates how even derivative texts can serve as potent sites of historical testimony, spiritual resilience, and bibliographic mourning. The letter thus sheds light on a neglected form of Hasidic historiography, one authored not by professional historians, but by the broken-hearted, writing in the margins of sacred books. Full article

Objective: This study aimed to investigate the cardioprotective effects of bosentan, an endothelin receptor antagonist, in a rat model of lung ischemia–reperfusion (I/R) injury, with a focus on myocardial tissue involvement. Methods: Twenty-four male Wistar rats were randomly assigned to four groups: sham, bosentan, I/R, and I/R + bosentan. Lung I/R injury was induced by hilar clamping for 45 min, followed by 60 min of reperfusion. Bosentan (30 mg/kg) was administered intraperitoneally 30 min prior to the procedure. Myocardial tissue was evaluated histopathologically for structural disorganization, inflammation, fibrosis, and edema. TGF-β1 protein levels in myocardial tissue were compared across the groups using β-actin as the loading control. ELISA was used to quantify ET-1, NF-κB, and p53 levels, while spectrophotometric analysis was employed to assess MDA levels and the activities of SOD and CAT enzymes in heart tissue. Results: The I/R group exhibited significant myocardial disorganization, inflammation, and interstitial edema compared to the sham and bosentan groups. Bosentan treatment markedly ameliorated these histopathological alterations. Additionally, the I/R group showed elevated levels of ET-1, NF-κB, p53, and MDA, along with reduced SOD and CAT activities; these changes were significantly attenuated by bosentan administration. Bosentan treatment significantly reduced myocardial ET-1 levels (from 136.88 ± 5.02 to 120.18 ± 2.67 nmol/g, p = 0.003), NF-κB levels (from 0.87 ± 0.04 to 0.51 ± 0.03 ng/mg, p = 0.002), and TGF-β1 expression (from 1.72 ± 0.10 to 0.91 ± 0.08 relative units, p = 0.001). Moreover, bosentan increased antioxidant enzyme activities, elevating SOD levels from 21.45 ± 1.23 to 32.67 ± 1.45 U/mg protein (p = 0.001) and CAT levels from 15.22 ± 0.98 to 25.36 ± 1.12 U/mg protein (p = 0.002). Conclusions: Bosentan exerts cardioprotective effects in rats subjected to lung I/R injury by reducing myocardial damage, inflammation, and oxidative stress. These findings suggest that bosentan may serve as a potential therapeutic agent for preventing remote organ injury associated with pulmonary I/R. Full article

This article examines the theological trajectories of Watchman Nee (1903–1972) and Witness Lee (1905–1997) on sanctification, union with Christ, and deification, situating their contributions within recent reappraisals of the doctrine of theosis in the academy. Though deification was universally affirmed by the early church and retained in various forms in medieval and early Protestant theology, post-Reformation Western Christianity marginalized this theme in favor of juridical and forensic soteriological categories. Against this backdrop, Nee and Lee offer a theologically rich, biblically grounded, and experientially oriented articulation of deification that warrants greater scholarly attention. Drawing from the Keswick Holiness tradition, patristic sources, and Christian mysticism, Nee developed a soteriology that integrates justification, sanctification, and glorification within an organic model of progressive union with God. Though he does not explicitly use the term “deification”, the language he employs regarding union and participation closely mirrors classical expressions of Christian theosis. For Nee, sanctification is not merely moral improvement but the transformative increase of the divine life, culminating in conformity to Christ’s image. Lee builds upon and expands Nee’s participatory soteriology into a comprehensive theology of deification, explicitly referring to it as “the high peak of the divine revelation” in the Holy Scriptures. For Lee, humans become God “in life and nature but not in the Godhead”. By employing the phrase “not in the Godhead”, Lee upholds the Creator–creature distinction—i.e., humans never participate in the ontological Trinity or God’s incommunicable attributes. Yet, in the first portion of his description, he affirms that human beings undergo an organic, transformative process by which they become God in deeply significant ways. His framework structures sanctification as a seven-stage process, culminating in the believer’s transformation and incorporation into the Body of Christ to become a constituent of a corporate God-man. This corporate dimension—often overlooked in Western accounts—lies at the heart of Lee’s ecclesiology, which he sees as being consummated in the eschatological New Jerusalem. Ultimately, this study argues that Nee and Lee provide a coherent, non-speculative model of deification that integrates biblical exegesis, theological tradition, and practical spirituality, and thus, present a compelling alternative to individualistic and forensic soteriologies while also highlighting the need for deeper engagement across global theological discourse on sanctification, union with Christ, and the Triune God. Full article