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Keywords = mechanism of atrial fibrillation

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16 pages, 738 KiB  
Review
A Rationale for the Use of Ivabradine in the Perioperative Phase of Cardiac Surgery: A Review
by Christos E. Ballas, Christos S. Katsouras, Konstantinos C. Siaravas, Ioannis Tzourtzos, Amalia I. Moula and Christos Alexiou
J. Cardiovasc. Dev. Dis. 2025, 12(8), 294; https://doi.org/10.3390/jcdd12080294 (registering DOI) - 31 Jul 2025
Abstract
This review explores the advantages of ivabradine in the management of cardiac surgery patients, particularly highlighting its heart rate (HR)-reducing properties, its role in minimizing the impact of atrial fibrillation, and its contributions to improving left ventricular diastolic function, as well as reducing [...] Read more.
This review explores the advantages of ivabradine in the management of cardiac surgery patients, particularly highlighting its heart rate (HR)-reducing properties, its role in minimizing the impact of atrial fibrillation, and its contributions to improving left ventricular diastolic function, as well as reducing pain, stress, and anxiety. In parallel, studies provide evidence that ivabradine influences endothelial inflammatory responses through mechanisms such as biomechanical modulation. Unlike traditional beta-blockers that may induce hypotension, ivabradine selectively inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, allowing for effective HR reduction without compromising blood pressure stability. This characteristic is particularly beneficial for patients at risk of atrial fibrillation post-surgery, where HR control is crucial for cardiovascular stability. This is an area in which ivabradine appears to play a role prophylactically, possibly in combination with beta-blockers. Furthermore, ivabradine has been associated with enhanced diastolic parameters in left ventricular function, reflecting its potential to improve surgical outcomes in patients with compromised heart function. In addition to its cardiovascular benefits, it appears to alleviate psychological stress and anxiety, common in postoperative settings, by moderating the neuroendocrine response to stress, thereby reducing stress-induced hormone levels. Furthermore, it has notable analgesic properties, contributing to pain management through its action on HCN channels in both the peripheral and central nervous systems. Collectively, these findings indicate that ivabradine may serve as a valuable therapeutic agent in the perioperative care of cardiac surgery patients, addressing both physiological and psychological challenges during recovery. Full article
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18 pages, 652 KiB  
Review
The Role of Advanced Glycation End-Products in the Pathophysiology and Pharmacotherapy of Cardiovascular Disease
by Karina O. Mota, Carla M. L. de Vasconcelos, Lorrie A. Kirshenbaum and Naranjan S. Dhalla
Int. J. Mol. Sci. 2025, 26(15), 7311; https://doi.org/10.3390/ijms26157311 - 29 Jul 2025
Viewed by 183
Abstract
Advanced glycation end-products (AGEs) are formed by the non-enzymatic glycation of proteins, lipids, and nucleic acids due to the consumption of high-carbohydrate diets; their production is also promoted by a sedentary lifestyle as well as cigarette smoking. Elevated levels of AGEs in the [...] Read more.
Advanced glycation end-products (AGEs) are formed by the non-enzymatic glycation of proteins, lipids, and nucleic acids due to the consumption of high-carbohydrate diets; their production is also promoted by a sedentary lifestyle as well as cigarette smoking. Elevated levels of AGEs in the circulatory system and internal organs of the body are commonly observed in a number of cardiovascular diseases such as hypertension, diabetes, atherosclerosis, coronary artery disease, aortic aneurysm, atrial fibrillation, myocardial infarction, and heart failure, which are associated with the development of oxidative stress and myocardial inflammation. The adverse effects of AGEs on the cardiovascular system are elicited by both non-receptor mechanisms involving the cross-linking of extracellular and intracellular proteins, and by receptor-mediated mechanisms involving the binding of AGEs with advanced glycation end-product receptors (RAGEs) on the cell membrane. AGE–RAGE interactions along with the cross-linking of proteins promote the generation of oxidative stress, the production of inflammation, the occurrence of intracellular Ca2+-overload, and alterations in the extracellular matrix leading to the development of cardiovascular dysfunction. AGEs also bind with two other protein receptors in the circulatory system: soluble RAGEs (sRAGEs) are released upon the proteolysis of RAGEs due to the activation of matrix metalloproteinase, and endogenous secretory RAGEs (esRAGEs) are secreted as a spliced variant of endogenous RAGEs. While the AGE–RAGE signal transduction axis serves as a pathogenic mechanism, both sRAGEs and esRAGEs serve as cytoprotective interventions. The serum levels of sRAGEs are decreased in ischemic heart disease, vascular disease, and heart failure, as well as in other cardiovascular diseases, but are increased in chronic diabetes and renal disease. Several interventions which can reduce the formation of AGEs, block the AGE–RAGE axis, or increase the levels of circulating sRAGEs have been shown to exert beneficial effects in diverse cardiovascular diseases. These observations support the view that the AGE–RAGE axis not only plays a critical role in pathogenesis, but is also an excellent target for the treatment of cardiovascular disease. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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18 pages, 605 KiB  
Review
Gut Microbiota, Microbial Metabolites, and Inflammation in Cardiac Surgery: Implications for Clinical Outcomes—A Narrative Review
by Panagiota Misokalou, Arezina N. Kasti, Konstantinos Katsas and Dimitrios C. Angouras
Microorganisms 2025, 13(8), 1748; https://doi.org/10.3390/microorganisms13081748 - 26 Jul 2025
Viewed by 345
Abstract
Cardiac surgery, particularly procedures involving cardiopulmonary bypass (CPB), is associated with a high risk of postoperative complications, including systemic inflammatory response syndrome (SIRS), postoperative atrial fibrillation (POAF), and infection. Growing evidence suggests that the gut–heart axis, through mechanisms involving intestinal barrier integrity and [...] Read more.
Cardiac surgery, particularly procedures involving cardiopulmonary bypass (CPB), is associated with a high risk of postoperative complications, including systemic inflammatory response syndrome (SIRS), postoperative atrial fibrillation (POAF), and infection. Growing evidence suggests that the gut–heart axis, through mechanisms involving intestinal barrier integrity and gut microbiota homeostasis, may influence these outcomes. This review summarizes the relationship between gut microbiota composition and the inflammatory response in patients undergoing cardiac surgery and the extent to which these alterations impact clinical outcomes. The reviewed studies consistently show that cardiac surgery induces notable alterations in microbial diversity and composition during the perioperative period. These changes, indicative of dysbiosis, are characterized by a reduction in health-associated bacteria such as Blautia, Faecalibacterium, and Bifidobacterium and an increase in opportunistic pathogens. Inflammatory biomarkers were frequently elevated postoperatively, even in patients without evident complications. Key microbial metabolites and biomarkers, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and bile acids (BAs), were implicated in modulating inflammation and clinical outcomes. Additionally, vitamin D deficiency emerged as a contributing factor, correlating with increased systemic inflammation and a higher incidence of POAF. The findings suggest that gut microbiota composition prior to surgery may influence the severity of the postoperative inflammatory response and that perioperative modulation of the gut microbiota could represent a novel approach to improving surgical outcomes. However, the relationship between dysbiosis and acute illness in surgical patients is confounded by factors such as antibiotic use and other perioperative interventions. Large-scale, standardized clinical studies are needed to better define these interactions and guide future therapeutic strategies in cardiac surgery. Full article
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15 pages, 768 KiB  
Article
Dysmagnesemia in the ICU: A Comparative Analysis of Ionized and Total Magnesium Levels and Their Clinical Associations
by Jawahar H. Al Noumani, Juhaina Salim Al-Maqbali, Mohammed Al Maktoumi, Qasim Sultan AL-Maamari, Abdul Hakeem Al-Hashim, Mujahid Al-Busaidi, Henrik Falhammar and Abdullah M. Al Alawi
Metabolites 2025, 15(8), 498; https://doi.org/10.3390/metabo15080498 - 24 Jul 2025
Viewed by 252
Abstract
Background: Magnesium (Mg) is an essential mineral that plays a vital role in various physiological processes, including enzyme regulation, neuromuscular function, and cardiovascular health. Dysmagnesemia has been associated with arrhythmias, neuromuscular dysfunction, and poor outcomes in intensive care unit (ICU) settings, representing diagnostic [...] Read more.
Background: Magnesium (Mg) is an essential mineral that plays a vital role in various physiological processes, including enzyme regulation, neuromuscular function, and cardiovascular health. Dysmagnesemia has been associated with arrhythmias, neuromuscular dysfunction, and poor outcomes in intensive care unit (ICU) settings, representing diagnostic and therapeutic challenges. However, the relationship between dysmagnesemia and health outcomes in the ICU remains inadequately defined. Aim/Objective: This study aimed to assess the prevalence of dysmagnesemia and evaluate the correlation between total (tMg) and ionized magnesium (iMg) levels in a cohort of ICU and high dependency unit (HDU) patients. It also sought to evaluate patient characteristics and relevant health outcomes by comparing both concentrations of iMg and tMg. Methods: This prospective study was conducted among adult patients admitted to the ICU and the high dependency unit (HDU). Results: Among the 134 included patients, the median age was 63.5 years (IQR: 52.0–77.0). The majority, 91.0%, required mechanical ventilation. Additionally, 50.0% were diagnosed with diabetes, 28.4% had chronic kidney disease, and proton pump inhibitors (PPIs) were administered to 67.2% of the patients. The prevalence of hypomagnesemia, as measured by iMg, was 6.7%, while hypermagnesemia was at 39.6%. When measured by tMg, hypomagnesemia and hypermagnesemia were observed at rates of 14.9% and 22.4%, respectively. The iMg measurements showed an association between the incidence of atrial fibrillation and hypomagnesemia (p = 0.015), whereas tMg measurements linked hypomagnesemia with longer hospital stays. Notably, only a few patients identified with iMg-measured hypomagnesemia received magnesium replacement during their ICU stay. Conclusions: Dysmagnesemia is prevalent among critically ill patients, with discordance between iMg and tMg measurements. iMg appears more sensitive in detecting arrhythmia risk, while tMg correlates with length of stay. These findings support the need for larger studies and suggest considering iMg in magnesium monitoring and replacement strategies. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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54 pages, 12628 KiB  
Review
Cardiac Mechano-Electrical-Fluid Interaction: A Brief Review of Recent Advances
by Jun Xu and Fei Wang
Eng 2025, 6(8), 168; https://doi.org/10.3390/eng6080168 - 22 Jul 2025
Viewed by 221
Abstract
This review investigates recent developments in cardiac mechano-electrical-fluid interaction (MEFI) modeling, with a focus on multiphysics simulation platforms and digital twin frameworks developed between 2015 and 2025. The purpose of the study is to assess how computational modeling methods—particularly finite element and immersed [...] Read more.
This review investigates recent developments in cardiac mechano-electrical-fluid interaction (MEFI) modeling, with a focus on multiphysics simulation platforms and digital twin frameworks developed between 2015 and 2025. The purpose of the study is to assess how computational modeling methods—particularly finite element and immersed boundary techniques, monolithic and partitioned coupling schemes, and artificial intelligence (AI)-enhanced surrogate modeling—capture the integrated dynamics of cardiac electrophysiology, tissue mechanics, and hemodynamics. The goal is to evaluate the translational potential of MEFI models in clinical applications such as cardiac resynchronization therapy (CRT), arrhythmia classification, atrial fibrillation ablation, and surgical planning. Quantitative results from the literature demonstrate <5% error in pressure–volume loop predictions, >0.90 F1 scores in machine-learning-based arrhythmia detection, and <10% deviation in myocardial strain relative to MRI-based ground truth. These findings highlight both the promise and limitations of current MEFI approaches. While recent advances improve physiological fidelity and predictive accuracy, key challenges remain in achieving multiscale integration, model validation across diverse populations, and real-time clinical applicability. The review concludes by identifying future milestones for clinical translation, including regulatory model certification, standardization of validation protocols, and integration of patient-specific digital twins into electronic health record (EHR) systems. Full article
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16 pages, 249 KiB  
Article
The Role of Echocardiographic Right Atrial Strain Parameters in Evaluating Atrial Fibrillation Recurrence in Patients Undergoing Atrial Fibrillation Ablation
by Hasan Can Konte, Emir Dervis, Idris Yakut and Dursun Aras
J. Clin. Med. 2025, 14(14), 5155; https://doi.org/10.3390/jcm14145155 - 21 Jul 2025
Viewed by 268
Abstract
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 [...] Read more.
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 article belongs to the Section Cardiology)
25 pages, 1308 KiB  
Review
Targeting the Substrate: Mechanism-Based Ablation Strategies for Persistent Atrial Fibrillation
by Gabriela-Elena Marascu, Alexandru Ioan Deaconu, Raluca-Elena Mitran, Laura Adina Stanciulescu and Radu Gabriel Vatasescu
J. Clin. Med. 2025, 14(14), 5147; https://doi.org/10.3390/jcm14145147 - 20 Jul 2025
Viewed by 467
Abstract
Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation, especially effective in patients with paroxysmal AF, where the pulmonary veins (PVs) are the primary triggers. More complex arrhythmogenic mechanisms are involved in persistent AF (PsAF), and PVI alone may not [...] Read more.
Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation, especially effective in patients with paroxysmal AF, where the pulmonary veins (PVs) are the primary triggers. More complex arrhythmogenic mechanisms are involved in persistent AF (PsAF), and PVI alone may not be sufficient. Personalized, substrate-based ablation strategies are increasingly used and can significantly enhance outcomes in PsAF patients. While radiofrequency ablation remains the gold standard, cryoablation provides effective PVI, and pulsed field ablation is emerging as a safer, promising alternative. Advanced mapping techniques may better target scar areas responsible for arrhythmogenesis, optimizing procedural results. While still in development, artificial intelligence and machine learning enable more personalized and precise ablation strategies and may improve long-term outcomes. Full article
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18 pages, 644 KiB  
Article
Atrial Fibrillation Risk Scores as Potential Predictors of Significant Coronary Artery Disease in Chronic Coronary Syndrome: A Novel Diagnostic Approach
by Alexandru-Florinel Oancea, Paula Cristina Morariu, Maria Godun, Stefan Dorin Dobreanu, Miron Mihnea, Diana Gabriela Iosep, Ana Maria Buburuz, Ovidiu Mitu, Alexandru Burlacu, Diana-Elena Floria, Raluca Mitea, Andrei Vâță, Daniela Maria Tanase, Antoniu Octavian Petris, Irina-Iuliana Costache-Enache and Mariana Floria
Life 2025, 15(7), 1134; https://doi.org/10.3390/life15071134 - 18 Jul 2025
Viewed by 297
Abstract
Chronic coronary syndrome (CCS) and atrial fibrillation (AF) are prevalent cardiovascular conditions that share numerous risk factors and pathophysiological mechanisms. While clinical scores commonly used in AF—such as CHA2DS2VA (which includes congestive heart failure, hypertension, age ≥ 75, diabetes, [...] Read more.
Chronic coronary syndrome (CCS) and atrial fibrillation (AF) are prevalent cardiovascular conditions that share numerous risk factors and pathophysiological mechanisms. While clinical scores commonly used in AF—such as CHA2DS2VA (which includes congestive heart failure, hypertension, age ≥ 75, diabetes, stroke/TIA, vascular disease, and age 65–74), HAS-BLED (which incorporates hypertension, abnormal renal/liver function, stroke, bleeding history, labile INR, elderly age, and drug/alcohol use), and C2HEST (incorporating coronary artery disease, COPD, hypertension, elderly age ≥ 75, systolic heart failure, and thyroid disease)—are traditionally applied to rhythm or bleeding risk prediction, their value in estimating the angiographic severity of coronary artery disease (CAD) remains underexplored. We conducted a prospective, single-center study including 131 patients with suspected stable CAD referred for coronary angiography, stratified according to coronary angiographic findings into two groups: significant coronary stenosis (S-CCS) and non-significant coronary stenosis (N-CCS). At admission, AF-related scores (CHA2DS2, CHA2DS2VA, CHA2DS2VA-HSF, CHA2DS2VA-RAF, CHA2DS2VA-LAF, HAS-BLED, C2HEST, and HATCH) were calculated. CAD severity was subsequently assessed using the SYNTAX and Gensini scores. Statistical comparisons and Pearson correlation analyses were performed to evaluate the association between clinical risk scores and angiographic findings. Patients in the S-CCS group had significantly higher scores in CHA2DS2VA (4.09 ± 1.656 vs. 3.20 ± 1.338, p = 0.002), HAS-BLED (1.98 ± 0.760 vs. 1.36 ± 0.835, p < 0.001), CHA2DS2VA-HSF (6.00 ± 1.854 vs. 5.26 ± 1.712, p = 0.021), and C2HEST (3.49 ± 1.501 vs. 2.55 ± 1.279, p < 0.001). Multivariate logistic regression identified HAS-BLED and C2HEST as independent predictors of significant coronary lesions. A threshold value of HAS-BLED ≥ 1.5 and C2HEST ≥ 3.5 demonstrated moderate discriminative ability (AUC = 0.694 and 0.682, respectively), with acceptable sensitivity and specificity. These scores also demonstrated moderate to strong correlations with both Gensini and SYNTAX scores. AF-related clinical scores, especially HAS-BLED and C2HEST, may serve as practical and accessible tools for early CAD risk stratification in patients with suspected CCS. Their application in clinical practice may serve as supplementary triage tools to help prioritize patients for further diagnostic evaluation, but they are not intended to replace standard imaging or testing. Full article
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34 pages, 1051 KiB  
Review
Atrial Fibrillation in Diabetes: Pathogenesis and Targeted Rhythm Control Strategies
by Konstantinos Grigoriou, Paschalis Karakasis, Konstantinos Pamporis, Panagiotis Theofilis, Dimitrios Patoulias, Efstratios Karagiannidis, Barbara Fyntanidou, Antonios P. Antoniadis and Nikolaos Fragakis
Curr. Issues Mol. Biol. 2025, 47(7), 559; https://doi.org/10.3390/cimb47070559 - 17 Jul 2025
Viewed by 393
Abstract
Diabetes mellitus and atrial fibrillation (AF) frequently coexist, creating a complex bidirectional relationship that exacerbates cardiovascular risk and challenges clinical management. Diabetes fosters a profibrotic, pro-inflammatory, and proarrhythmic atrial substrate through a constellation of pathophysiologic mechanisms, including metabolic remodeling, oxidative stress, mitochondrial dysfunction, [...] Read more.
Diabetes mellitus and atrial fibrillation (AF) frequently coexist, creating a complex bidirectional relationship that exacerbates cardiovascular risk and challenges clinical management. Diabetes fosters a profibrotic, pro-inflammatory, and proarrhythmic atrial substrate through a constellation of pathophysiologic mechanisms, including metabolic remodeling, oxidative stress, mitochondrial dysfunction, ion channel dysregulation, and autonomic imbalance, thereby promoting AF initiation and progression. Conventional rhythm control strategies remain less effective in diabetic individuals, underscoring the need for innovative, substrate-targeted interventions. In this context, sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as promising agents with pleiotropic antiarrhythmic properties, modulating fibrosis, inflammation, and mitochondrial integrity. Moreover, advances in anti-inflammatory, antifibrotic, and ion channel-modulating therapeutics, coupled with novel mitochondrial-targeted strategies, are reshaping the therapeutic landscape. Multi-omics approaches are further refining our understanding of diabetes-associated AF, facilitating precision medicine and biomarker-guided interventions. This review delineates the molecular nexus linking diabetes and AF, critically appraises emerging rhythm control strategies, and outlines translational avenues poised to advance individualized management in this high-risk population. Full article
(This article belongs to the Special Issue Advances in Molecular Therapies and Disease Associations in Diabetes)
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12 pages, 552 KiB  
Article
Impact of Kidney Function on the Survival of Patients with Chagas Cardiomyopathy and Implantable Cardioverter Defibrillators
by Fernanda Pinheiro Martin Tapioca, Luiz Carlos Santana Passos, Caio Cafezeiro, Willian Carvalho, Paulo Novis Rocha and Maria Gabriela Guimarães
J. Clin. Med. 2025, 14(14), 4862; https://doi.org/10.3390/jcm14144862 - 9 Jul 2025
Viewed by 329
Abstract
Background/Objectives: Impaired kidney function significantly increases mortality in recipients of implantable cardioverter defibrillators (ICDs). However, in the landmark studies evaluating ICDs and cardiac resynchronization therapy with a defibrillator (CRT-D) for the treatment of heart failure (HF) with a reduced ejection fraction (HFrEF), patients [...] Read more.
Background/Objectives: Impaired kidney function significantly increases mortality in recipients of implantable cardioverter defibrillators (ICDs). However, in the landmark studies evaluating ICDs and cardiac resynchronization therapy with a defibrillator (CRT-D) for the treatment of heart failure (HF) with a reduced ejection fraction (HFrEF), patients with Chagas cardiomyopathy (CC) have been underrepresented. This study aimed to determine whether kidney dysfunction has the same negative impacts on patients with ICDs or CRT-Ds and CC. Methods: We prospectively followed patients with CC and left ventricular ejection fractions (LVEFs) of ≤40% who underwent ICD or CRT-D implantation and had at least one prior creatinine measurement. The primary outcome was the survival rate during follow-up. Variables with a p of <0.10 from the univariate analysis were selected for inclusion in the Cox regression model. Results: A total of 343 patients were enrolled, with a median follow-up duration of 777 days. The mean age was 60.2 (±11.2) years. Fifty percent of patients were observed to have a New York Heart Association (NYHA) functional class of III, and the median left ventricular ejection fraction (LVEF) was 27% (22–32). Overall mortality events occurred in 113 (32.9%) participants during follow-up. Although the estimated glomerular filtration rate (eGFR) was significantly associated with survival in the univariate analysis [HR 0.98 (CI 95% 0.98–0.99), p = 0.007], it did not retain significance in the multivariate model [HR 0.99 (0.98–1.00), p = 0.138], which was adjusted for age, gender, atrial fibrillation (AF), body mass index (BMI), and the use of digoxin, furosemide, anticoagulants, and LVEF. Conclusions: Unlike other cardiomyopathies, impaired eGFR was not an independent predictor of mortality in this cohort of CC patients undergoing ICD or CRT-D implantation, possibly due to the distinctive pathophysiological mechanisms of the disease. These findings suggest that clinicians should not be discouraged from recommending CIEDs in patients with CC and moderately impaired kidney function, although further studies are warranted to assess outcomes in those with advanced CKD. Full article
(This article belongs to the Section Nephrology & Urology)
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17 pages, 522 KiB  
Systematic Review
Heterogeneity in Heart Failure with Preserved Ejection Fraction: A Systematic Review of Phenotypic Classifications and Clinical Implications
by Francisco Epelde
J. Clin. Med. 2025, 14(14), 4820; https://doi.org/10.3390/jcm14144820 - 8 Jul 2025
Viewed by 461
Abstract
Background/Objectives: Heart failure with preserved ejection fraction (HFpEF) has emerged as one of the most challenging syndromes in modern cardiology due to its complex pathophysiology, diagnostic ambiguity, and lack of effective targeted therapies. Unlike heart failure with reduced ejection fraction (HFrEF), HFpEF encompasses [...] Read more.
Background/Objectives: Heart failure with preserved ejection fraction (HFpEF) has emerged as one of the most challenging syndromes in modern cardiology due to its complex pathophysiology, diagnostic ambiguity, and lack of effective targeted therapies. Unlike heart failure with reduced ejection fraction (HFrEF), HFpEF encompasses a highly heterogeneous patient population unified only by a preserved left ventricular ejection fraction (LVEF) ≥ 50%. This broad definition overlooks important biological and clinical differences, leading to inconclusive results in large-scale therapeutic trials and suboptimal patient outcomes. In recent years, advances in data-driven methodologies—such as unsupervised machine learning, cluster analysis, and latent class modeling—have enabled the identification of distinct HFpEF phenotypes. These phenotypes, often defined by demographic, clinical, hemodynamic, and biomarker profiles, exhibit differential prognoses and treatment responses. Methods: This systematic review synthesizes findings from 20 studies published between 2010 and 2025, examining phenotypic classification strategies and their clinical implications. Results: Despite methodological variation, several recurring phenotypes emerge, including metabolic–obese, frail–elderly, atrial-fibrillation-dominant, cardiorenal, and pulmonary hypertension/right-heart phenotypes. Each presents a distinct pathophysiological mechanism and risk profile, highlighting the inadequacy of current one-size-fits-all treatment approaches. The review also explores the prognostic value of phenotypes, the impact of phenotypic variation on treatment efficacy, and the methodological challenges that hinder translation into clinical practice—such as inconsistent input variables, lack of external validation, and limited integration with real-world data. Conclusions: Ultimately, the findings underscore the need for a paradigm shift from ejection fraction-based classification to phenotype-guided management in HFpEF. Embracing a precision medicine framework could enable personalized treatment strategies, improve clinical trial design, and enhance outcomes for this diverse patient population. The review concludes by outlining future directions, including the development of standardized phenotyping algorithms, integration of multi-omic and digital health data, and the implementation of pragmatic, phenotype-stratified clinical trials. Full article
(This article belongs to the Section Cardiology)
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24 pages, 864 KiB  
Article
Application of Acoustic Cardiography in Assessment of Cardiac Function in Horses with Atrial Fibrillation Before and After Cardioversion
by Mélodie J. Schneider, Isabelle L. Piotrowski, Hannah K. Junge, Glenn van Steenkiste, Ingrid Vernemmen, Gunther van Loon and Colin C. Schwarzwald
Animals 2025, 15(13), 1993; https://doi.org/10.3390/ani15131993 - 7 Jul 2025
Viewed by 308
Abstract
Left atrial mechanical dysfunction is common in horses following the treatment of atrial fibrillation (AF). This study aimed to evaluate the use of an acoustic cardiography monitor (Audicor®) in quantifying cardiac mechanical and hemodynamic function in horses with AF before and [...] Read more.
Left atrial mechanical dysfunction is common in horses following the treatment of atrial fibrillation (AF). This study aimed to evaluate the use of an acoustic cardiography monitor (Audicor®) in quantifying cardiac mechanical and hemodynamic function in horses with AF before and after treatment and to correlate these findings with echocardiographic measures. Twenty-eight horses with AF and successful transvenous electrical cardioversion were included. Audicor® recordings with concomitant echocardiographic examinations were performed one day before, one day after, and two to seven days after cardioversion. Key variables measured by Audicor® included electromechanical activating time (EMAT), heart rate-corrected EMATc, left ventricular systolic time (LVST), heart rate-corrected LVSTc, systolic dysfunction index (SDI), and intensity and persistence of the third and fourth heart sound (S3, S4). A repeated-measures ANOVA with Tukey’s test was used to compare these variables over time, and linear regression and Bland–Altman analyses were applied to assess associations with echocardiographic findings. Following conversion to sinus rhythm, there was a significant decrease in EMATc and LVSTc (p < 0.0001) and a significant increase in LVST (p = 0.0001), indicating improved ventricular systolic function, with strong agreement between Audicor® snapshot and echocardiographic measures. However, S4 quantification did not show clinical value for assessing left atrial function after conversion. Full article
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53 pages, 2742 KiB  
Review
The Role of Plant-Derived Natural Products as a Regulator of the Tyrosine Kinase Pathway in the Management of Lung Cancer
by Faris Alrumaihi, Arshad Husain Rahmani, Sitrarasu Vijaya Prabhu, Vikalp Kumar and Shehwaz Anwar
Curr. Issues Mol. Biol. 2025, 47(7), 498; https://doi.org/10.3390/cimb47070498 - 30 Jun 2025
Viewed by 649
Abstract
One of the most common malignant tumors worldwide is lung cancer, and it is associated with the highest death rate among all cancers. Traditional treatment options for lung cancer include radiation, chemotherapy, targeted therapy, and surgical resection. However, the survival rate is low, [...] Read more.
One of the most common malignant tumors worldwide is lung cancer, and it is associated with the highest death rate among all cancers. Traditional treatment options for lung cancer include radiation, chemotherapy, targeted therapy, and surgical resection. However, the survival rate is low, and the outlook is still dreadfully dire. The pursuit of a paradigm change in treatment approaches is, therefore, imperative. Tyrosine kinases (TKs), a subclass of protein kinases, regulate vital cellular function by phosphorylating tyrosine residues in proteins. Mutations, overexpression, and autocrine paracrine stimulation can transform TKs into oncogenic drivers, causing cancer pathogenesis. Tyrosine kinase inhibitors (TKIs) have emerged as an attractive targeted therapy option, especially for non-small cell lung cancer (NSCLC). However, resistance to TKIs, and adverse cardiovascular effects such as heart failure, atrial fibrillation, hypertension, and sudden death, are among the most common adverse effects of TKIs. There is increasing interest in plant-derived natural products in the hunt for powerful chemosensitizer and pathway modulators for enhancing TKI activity and/or overcoming resistance mechanisms. This highlights the mechanism of TKs’ activation in cancer, the role of TKIs in NSCLC mechanisms, and the challenges posed by TKI-acquired resistance. Additionally, we explored various plant-derived natural products’ bioactive compounds with the chemosensitizer and pathway-modulating potential with TKs’ inhibitory and anticancer effects. Our review suggests that a combination of natural products with TKIs may provide a novel and promising strategy for overcoming resistance in lung cancer. In future, further preclinical and clinical studies are advised. Full article
(This article belongs to the Special Issue Natural Compounds: An Adjuvant Strategy in Cancer Management)
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21 pages, 4049 KiB  
Article
Identifying High-Risk Atrial Fibrillation in Diabetes: Evidence from Nomogram and Plasma Metabolomics Analysis
by Qiushi Luo, Xiaozhu Ma, Shuai Mei, Qidamugai Wuyun, Li Zhou, Ziyang Cai, Yi Wen, Shitao Wang, Jiangtao Yan, Huaping Li, Jiahui Fan and Meiyan Dai
Biomedicines 2025, 13(7), 1557; https://doi.org/10.3390/biomedicines13071557 - 25 Jun 2025
Viewed by 347
Abstract
Background: Diabetes significantly increases the risk of atrial fibrillation (AF), but identifying high-risk individuals remains a clinical challenge. This study aimed to improve AF risk stratification in diabetic patients through a combination of clinical modeling and untargeted metabolomic analysis. Methods: A [...] Read more.
Background: Diabetes significantly increases the risk of atrial fibrillation (AF), but identifying high-risk individuals remains a clinical challenge. This study aimed to improve AF risk stratification in diabetic patients through a combination of clinical modeling and untargeted metabolomic analysis. Methods: A clinical risk score was developed using data from the National Health and Nutrition Examination Survey (NHANES) and validated in an independent cohort from Tongji Hospital. Its association with long-term outcomes and its ability to predict AF recurrence after catheter ablation were assessed in follow-up studies. Additionally, untargeted plasma metabolomics was performed in a subset of diabetic patients with and without AF to explore underlying mechanism. Results: The risk score showed good predictive performance in both the development and validation cohorts and was significantly associated with clinical prognosis. When combined with left atrial diameter and AF type, it also improved the prediction of AF recurrence after ablation. Metabolomic profiling revealed notable disturbances in energy metabolism, heightened inflammatory activity, and elevated stress responses in AF patients, indicating a distinct metabolic risk profile. Conclusions: This study provided two approaches to identify high-risk AF in diabetic patients, discussed the underlying pathophysiological mechanisms, and compared their characteristics and applications. And integrated strategies could improve AF risk stratification and personalized management in the diabetic. Full article
(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights (2nd Edition))
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20 pages, 1609 KiB  
Review
Natural Products Acting as Senolytics and Senomorphics Alleviate Cardiovascular Diseases by Targeting Senescent Cells
by Hejing Tang, Xu Zhang, Senyang Hu, Yuhan Song, Wenhua Jin, Jianmin Zou, Yan Zhang, Jiayue Guo, Peng An, Junjie Luo, Pengjie Wang, Yongting Luo and Yinhua Zhu
Targets 2025, 3(3), 23; https://doi.org/10.3390/targets3030023 - 25 Jun 2025
Viewed by 791
Abstract
Taken together, cardiovascular diseases (CVDs) have become one of the prime causes of the global disease burden. Aging is closely related to CVDs and is considered to be one of the crucial factors in the incidence of CVDs. In the process of aging, [...] Read more.
Taken together, cardiovascular diseases (CVDs) have become one of the prime causes of the global disease burden. Aging is closely related to CVDs and is considered to be one of the crucial factors in the incidence of CVDs. In the process of aging, cellular senescence is an important cause of CVDs such as atherosclerosis and atrial fibrillation. The treatment for CVDs by targeting senescent cells has been carried out in cellular models, animal experiments, and anti-aging clinical trials. Chemical approaches to regulate the fate of senescent cells by senolytics and senomorphics, which could selectively eliminate senescent cells or inhibit their senescence-associated secretory phenotype (SASP) secretion, have been increasingly explored. Importantly, many natural products with promising biological activity extracted from food or medicine–food homology have the above-mentioned effects. Furthermore, the identification of the target cells or target proteins of these natural products is of great significance for the indication of their mechanism of action, and it also lays a scientific foundation for the realization of precision nutrition intervention in the future. This review details how senescent cells affect CVDs, how natural products target senescent cells through nutritional intervention, and research methods for natural products in cardiovascular aging. Full article
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