Search Results (47)

While the interest and participation in general endurance training and recreational sports competitions have continuously increased in recent decades, the number of recreational master-level endurance athletes has additionally multiplied. Athletes, active men and women older than 40 years of age, who participate in competitive athletics are usually referred to by the term master athletes (MAs). Previous research revealed the significant benefits of regular moderate physical activity, i.e., its positive influence on cardiovascular risk factors and cardiovascular health; however, recent data have raised concerns that long-term endurance exercise participation is associated with cardiac remodeling and potential adverse cardiovascular outcomes. Previous research also indicated potential structural, functional, and electrical remodeling in MAs due to prolonged and repeated exposure to high-intensity endurance exercise—a condition known as athlete’s heart. In this review, we focus on the association between extreme levels of endurance exercise and potential cardiovascular controversies, such as arrhythmogenesis due to new-onset atrial fibrillation, accelerated coronary artery atherosclerosis, and exercise-induced cardiac remodeling. Additionally, the exercise-dependent modulation of immunological response, such as proteomic response and cytokine alterations, is discussed. Furthermore, we discuss the impact of nutritional supplements in MAs and their potential benefits and harmful interactions. We aim to provide sports medicine practitioners with knowledge of these contemporary longevity controversies in sports cardiology and to highlight the importance of shared decision making in situations of clinical uncertainty. Full article

Endurance training induces significant cardiac remodeling, with evidence suggesting that prolonged high-intensity exercise may increase the risk of atrial fibrillation (AF). However, physiological responses differ by event type. This review compares AF-related markers in marathon and ultramarathon runners, focusing on structural adaptations, inflammatory and endothelial biomarkers, and the incidence of arrhythmias. A systematic analysis of 29 studies revealed consistent left atrial (LA) enlargement in marathon runners linked to elevated AF risk and fibrosis markers such as Galectin-3 and PIIINP. In contrast, ultramarathon runners exhibited right atrial (RA) dilation and increased systemic inflammation, as indicated by elevated high-sensitivity C-reactive protein (hs-CRP) and soluble E-selectin levels. AF incidence in marathoners ranged from 0.43 per 100 person-years to 4.4%, while direct AF incidence data remain unavailable for ultramarathon populations, highlighting a critical evidence gap. These findings suggest distinct remodeling patterns and pathophysiological profiles between endurance disciplines, with implications for athlete screening and cardiovascular risk stratification. Full article

Background/Objectives: Among other substrates, the a disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS7) protease degrades thrombospondin-5 (the cartilage oligomeric protein, COMP), thrombospondin-1 (TSP-1) and the tissue inhibitor of metalloproteinases-1 (TIMP-1) indicating a potential role of ADAMTS7 expression on coagulation cascade, tissue remodeling and wound healing. We analyzed the potential effect of direct oral anticoagulant (DOAC) treatment on ADAMTS7 promoter methylation and followed it over time to assess whether DOACs epigenetically modulate ADAMTS7 and induce pathways associated with coagulation or endothelium repair machinery. Methods: Eighty-four DOAC-treated atrial fibrillation (AF) patients followed-up from baseline (t0) to 7 days (t1, n = 70) and 28 days of treatment (t2, n = 62) and 19 non-AF controls were included in the study. Genomic DNA was extracted from blood at all timepoints and was bisulfite-converted prior to methylation analysis. ADAMTS7 promoter DNA methylation was analyzed with MIP-qMSP-PCR. Results: A total of 16 minor bleeding events occurred. The baseline percentage of ADAMTS7 methylation did not differ between AF patients and controls (15.8% vs. 16.1%, p = 0.908). In the patient cohort, DOAC therapy marginally decreased ADAMTS7 methylation from t0 to t2 (15.2% vs. 14.0%, p = 0.044). This ADAMTS7 demethylation from t0 to t2 was statistically significant only in patients experiencing bleeding (17.1%. vs. 13.4%, p = 0.010 in bleedings, 14.5% vs. 14.2%, p = 0.561 in non-bleedings). No other differences were observed. Conclusions: ADAMTS7 is demethylated during DOAC-related bleedings, a mechanism potentially leading to COMP degradation and thus thrombin-induced platelet aggregation, as well as the induction of endothelium repair through different ADAMTS7-dependent pathways. Full article

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, associated with significant morbidity, mortality, and healthcare burdens. Despite therapeutic advances, recurrence rates remain high, particularly in persistent AF, underscoring the need for deeper mechanistic insight. Epigenetic regulation—comprising DNA methylation, histone modifications, chromatin remodeling, RNA methylation, and non-coding RNAs—has emerged as a key contributor to the structural, electrical, and inflammatory remodeling underlying AF. These mechanisms operate at the interface of genetic susceptibility and environmental exposure, offering a dynamic framework for understanding disease progression. Systemic stressors such as aging, obesity, diabetes, hypertension, hypoxia, and alcohol have been shown to induce epigenetic reprogramming in atrial tissue, further promoting atrial cardiomyopathy and arrhythmogenesis. Additionally, circulating epigenetic markers, particularly microRNAs, are being investigated for their potential in AF diagnosis, risk stratification, and therapeutic monitoring. Therapeutic strategies targeting epigenetic pathways—ranging from histone deacetylase inhibitors and miRNA-based therapeutics to CRISPR/dCas9-mediated epigenome editing—are under investigation. Additionally, sodium-glucose cotransporter 2 inhibitors may indirectly influence epigenetic programs and miRNA expression relevant to atrial remodeling. While promising, these approaches require further validation in terms of safety, delivery specificity, and long-term efficacy. High-resolution epigenomic mapping and integrative multi-omic approaches may enhance understanding of AF heterogeneity and enable personalized treatment strategies. This review provides an integrated appraisal of epigenetic mechanisms in AF and outlines their emerging diagnostic and therapeutic relevance. Full article

Atrial fibrillation (AF), the most prevalent tachyarrhythmia worldwide, is a complex condition influenced by genetic, structural, and environmental factors. While AF in the elderly is often associated with underlying cardiac disease, early-onset or “lone” AF (LAF) exhibits a stronger genetic predisposition. Studies have identified both monogenic and polygenic contributors to AF risk. Monogenic mutations, inherited in Mendelian patterns, often affect ion channels and regulatory proteins, while polygenic variants modulate susceptibility and interact with environmental factors. Genome-wide association studies (GWAS) and exosome-wide association studies (ExWAS) have expanded our understanding of AF genetics, identifying numerous susceptibility loci, though challenges remain in linking these variants to specific molecular mechanisms. Pathophysiologically, AF results from a balance of triggers, drivers, and substrates. Triggers, such as ectopic foci in the pulmonary veins, initiate AF episodes, while structural and electrical remodeling perpetuates the arrhythmia. Fibrosis, atrial dilation, and tachycardia-induced remodeling promote reentry circuits and irregular conduction, increasing AF vulnerability. The interplay between genetic predisposition and remodeling processes underscores the complexity of AF maintenance, particularly in persistent AF forms. Emerging insights into AF genetics and pathophysiology highlight the need for personalized approaches to its prevention and management. Understanding genetic risk, combined with targeted therapies addressing structural and electrical remodeling, holds promise for improved patient outcomes. Future research into AF’s molecular and genetic mechanisms will be key to advancing precision medicine in this field. Full article

Postoperative atrial fibrillation (POAF) is the most common arrhythmia following cardiac surgery. This review critically explores the interplay between cardiopulmonary bypass (CPB) and aortic cross-clamping (ACC) times in POAF development. CPB disrupts systemic homeostasis by inducing inflammatory cascades, oxidative stress, and ischemia–reperfusion injury. Prolonged ACC times further exacerbate myocardial ischemia and structural remodeling, with durations exceeding 60–75 min consistently linked to an increased POAF risk. However, variability in outcomes across studies reveals the complex, multifactorial nature of POAF pathogenesis. Patient-specific variables, such as baseline comorbidities and myocardial protection strategies, modulate these risks, emphasizing the need for personalized surgical approaches. Despite advancements in myocardial protection techniques and anti-inflammatory strategies, the incidence of POAF remains persistently high, indicating a gap in translating mechanistic insights into effective interventions. Emerging biomarkers, including microRNAs (e.g., miR-21, miR-483-5p, etc.) and markers of myocardial injury like troponin I, offer potential for enhanced risk stratification and targeted prevention. However, their clinical applicability requires further validation in diverse patient populations. This review underscores the critical need for integrative research that combines clinical, molecular, and procedural variables to elucidate the nuanced interplay of factors driving POAF. Future directions include leveraging advanced intraoperative monitoring tools, refining thresholds for CPB and ACC times, and developing individualized perioperative protocols. Full article

Atrial fibrillation (AF) is associated with energetic deficiency and oxidative stress due to mitochondrial dysfunction, resulting in electric remodeling. Long-term treatment was found to ameliorate mitochondrial function and decrease inducibility in animal models. No studies examine the short-term effect of SGLT-2 inhibitors administration in AF. In the present study, the samples of the right atrial appendage collected from 10 patients subjected to elective cardiac surgery were sliced and incubated in a control buffer (EMPA 0), 0.2 µmol/L empagliflozin (EMPA 0.2), or 1.0 µmol/L (EMPA 1). The expression of mitochondrial biogenesis, fission, and fusion proteins was measured by Western blot after 30 min of electrical stimulation (control—1 Hz or tachypacing—5 Hz). The PGC-1α protein expression was increased after 30 min of stimulation with 1 Hz when incubated under a higher concentration of empagliflozin. After tachypacing, EMPA 0.2 increased PGC-1α, while EMPA 1.0 upregulated NRF-1. Both concentrations increased NRF-2 during control stimulation. The oxygen consumption was higher in AF, and was decreased by SGLT-2i. Empagliflozin exerts dynamic effects on the expression of PGC-1α and other proteins involved in mitochondrial function and oxidative stress in cardiomyocytes and may modulate cellular response to tachycardia. Full article

Atrial fibrillation (AF) is the most common sustained arrhythmia, contributing to significant morbidity and healthcare burden worldwide. This review evaluates the role of early risk factor modification and timely catheter ablation in preventing AF progression and improving patient outcomes. A comprehensive literature search was conducted using PubMed, MEDLINE, and Google Scholar, focusing on studies published after the ESC 2020 guidelines for the diagnosis and management of AF up to the release of the updated ESC 2024 guidelines for the management of AF. Keywords included “atrial fibrillation”, “catheter ablation”, “risk factor management”, and “psychological stress”. Relevant clinical trials, randomized controlled trials, systematic reviews, and meta-analyses were included, with particular emphasis on novel studies contributing to the ESC 2024 updated recommendations. Traditional risk factors such as obesity, hypertension, diabetes, sleep apnea, alcohol consumption, and physical exertion are well established in AF progression. Early evidence also suggests a role for psychological stress and mood disorders, including depression and post-traumatic stress disorder (PTSD), in increasing AF susceptibility. Psychological stress and mood disorders are linked to AF primarily through behavioral changes such as poor medication adherence, unhealthy lifestyle choices, and increased substance use. Recent guidelines recommend early catheter ablation in selected patients to reduce AF burden, prevent atrial remodeling, and improve quality of life, particularly in those resistant to antiarrhythmic drugs or individuals with AF-induced cardiomyopathy. Furthermore, we highlight the importance of a patient-centered, multidisciplinary approach, integrating electrophysiologists, cardiologists, and primary care providers with structured risk factor interventions and shared decision-making. Despite these advances, gaps remain in defining optimal timing, patient selection, and long-term benefits of catheter ablation in persistent AF, necessitating the need for further research. By integrating early intervention, personalized treatment strategies, and collaborative care models, we may usher in a paradigm shift in AF management, improving long-term cardiovascular outcomes and patient quality of life. Full article

Atrial fibrillation is a prevalent cardiac arrhythmia influenced by multifactorial mechanisms, including the emerging role of epicardial adipose tissue. Left atrial epicardial adipose tissue, through its endocrine and paracrine activities, contributes to atrial remodeling by fostering inflammation, fibrosis, and electrical remodeling. Objectives: This review aims to explore the interaction between left atrial epicardial adipose tissue and atrial dysfunction, highlighting the utility of strain imaging as a diagnostic and prognostic tool in atrial fibrillation management. Additionally, it examines emerging therapeutic strategies targeting epicardial adipose tissue to improve outcomes. Methods: We analyzed recent advances in imaging techniques, with a specific focus on speckle-tracking echocardiography for non-invasive strain assessment. Strain imaging parameters, including atrial reservoir, conduit, and contractile strain, were evaluated alongside volumetric measures of epicardial adipose tissue. Emerging therapies, such as weight management and GLP-1 receptor agonists, were reviewed for their impact on left atrial epicardial adipose tissue and atrial remodeling. Results: Strain imaging demonstrates a significant association between reduced strain parameters and atrial remodeling induced by left atrial epicardial adipose tissue. Combining strain assessment with volumetric measures enhances diagnostic accuracy and stratification of patients at risk for recurrent or progressive atrial fibrillation. Emerging therapies, particularly GLP-1 receptor agonists, show promise in reducing epicardial adipose tissue volume and mitigating atrial remodeling, thereby improving catheter ablation outcomes. Conclusions: Strain imaging is a valuable tool for the early detection of atrial dysfunction and personalized treatment planning in atrial fibrillation. Integrating these imaging approaches into routine clinical practice can optimize atrial fibrillation management and improve patient outcomes. Full article

Background: Atrial fibrillation (AF) is a major cause of stroke. An individual risk estimation remains challenging, as AF patients with and without cerebrovascular event (CVE) may differ in yet unknown factors beyond those covered by the CHA₂DS₂-VASc score. We aimed to identify differences between AF patients with and without CVE with regard to AF characteristics and treatment, vascular risk factors and comorbidities, prognosis and outcome. Methods: We analyzed patients included in the Atrial Fibrillation Rhine-Neckar Region (ARENA) Project, an observational cohort study of patients with AF. Patients were recruited by their general practitioner or during a hospital stay and were divided into two groups for the present analysis: patients with acute CVE at baseline and/or history of CVE versus patients without CVE. Follow-up at 1 year was conducted via phone call. Results: Of 2061 included patients (60.6% male), 292 (14.2%) belonged to the CVE group. Patients in the CVE group were older (mean age 74.6 versus 71.7 years; p < 0.001) and had a higher CHA₂DS₂-VASc score at baseline (5.3 versus 3.3 points; p < 0.001) based on the preceding CVE. Moreover, patients with either acute or chronic CVE had a larger left atrium (median diameter 47/46 mm versus 44 mm; p = 0.001). Patients with acute CVE had structural heart diseases (p < 0.001) less frequently than patients with previous or without CVE. Mortality at 1 year (HR 1.95; 95%-CI 1.37–2.78) was more frequent in the CVE group (p < 0.001). During 1-year of follow-up, stroke occurred more frequently in survivors with CVE (2.9% versus 0%; p < 0.001). Conclusions: AF patients with CVE have a significantly worse prognosis than AF patients without CVE. Atrial structural remodeling, underlying cardiovascular disease, stroke-induced heart injury and further unidentified factors may account for this finding. Characterization of AF patients including echocardiography to detect atrial structural remodeling may be helpful in risk stratification beyond classical scores. Full article

Atrial fibrillation (AF) in the setting of heart failure (HF) with preserved ejection fraction (HFpEF) is a prevalent comorbidity and is enabled by adverse left atrial (LA) remodeling, dilation, and scar tissue formation. These changes are facilitated by poor left ventricular compliance. A growing body of clinical evidence and medical guidelines suggest that managing atrial tachyrhythms with catheter ablation (CA) is paramount to treating concomitant HF. This recommendation is complicated in that thermal CA modalities, namely radiofrequency ablation and cryoablation, are both therapeutic via inducing additional scar tissue. AF treatment with thermal CA may compound the atrial scar burden for patients who already have extensive scars secondary to HFpEF. Therefore, thermal CA could act as “gasoline” to the slowly burning “fire” within the LA, increasing the rate of AF recurrence. Pulsed-field ablation (PFA), which utilizes high-voltage irreversible electroporation, is a non-thermal CA technique that is capable of disrupting reentrant microcircuits and arrhythmogenic foci without inducing significant scar burden. PFA has the potential to mitigate the strong fibrosis response to thermal CA that predisposes to AF by serving as “water” rather than “gasoline”. Thus, PFA may increase the efficacy and durability of CA for AF in HFpEF, and subsequently, may decrease the risk of procedural complications from repeat CAs. In this article, we provide a summary of the clinical concepts underlying HFpEF and AF and then summarize the data to date on the potential of PFA being a superior CA technique for AF in the setting of comorbid HFpEF. Full article

Recent epidemiological studies have shown that patients with right-sided breast cancer (RBC) treated with X-ray irradiation (IR) are more susceptible to developing cardiovascular diseases, such as arrhythmias, atrial fibrillation, and conduction disturbances after radiotherapy (RT). Our aim was to investigate the mechanisms induced by low to moderate doses of IR and to evaluate changes in the cardiac sympathetic nervous system (CSNS), atrial remodeling, and calcium homeostasis involved in cardiac rhythm. To mimic the RT of the RBC, female C57Bl/6J mice were exposed to X-ray doses ranging from 0.25 to 2 Gy targeting 40% of the top of the heart. At 60 weeks after RI, Doppler ultrasound showed a significant reduction in myocardial strain, ejection fraction, and atrial function, with a significant accumulation of fibrosis in the epicardial layer and apoptosis at 0.5 mGy. Calcium transient protein expression levels, such as RYR2, NAK, Kir2.1, and SERCA2a, increased in the atrium only at 0.5 Gy and 2 Gy at 24 h, and persisted over time. Interestingly, 3D imaging of the cleaned hearts showed an early reduction of CSNS spines and dendrites in the ventricles and a late reorientation of nerve fibers, combined with a decrease in SEMA3a expression levels. Our results showed that local heart IR from 0.25 Gy induced late cardiac and atrial dysfunction and fibrosis development. After IR, ventricular CSNS and calcium transient protein expression levels were rearranged, which affected cardiac contractility. The results are very promising in terms of identifying pro-arrhythmic mechanisms and preventing arrhythmias during RT treatment in patients with RBC. Full article

Aims: Atrial fibrillation (AF) is the most common chronic/recurrent arrhythmia, which significantly impairs quality of life and increases cardiovascular morbidity and mortality. Therefore, the aim of the present study was to investigate the properties of three repolarizing potassium currents which were shown to contribute to AF-induced electrical remodeling, i.e., the transient outward (I_to), inward rectifier (I_K1) and acetylcholine-sensitive (I_K,ACh) potassium currents in isolated atrial myocytes obtained from dogs either with sinus rhythm (SR) or following chronic atrial tachypacing (400/min)-induced AF. Methods: Atrial remodeling and AF were induced by chronic (4–6 weeks of) right atrial tachypacing (400/min) in dogs. Transmembrane ionic currents were measured by applying the whole-cell patch-clamp technique at 37 °C. Results: The I_to current was slightly downregulated in AF cells when compared with that recorded in SR cells. This downregulation was also associated with slowed inactivation kinetics. The I_K1 current was found to be larger in AF cells; however, this upregulation was not statistically significant in the voltage range corresponding with atrial action potential (−80 mV to 0 mV). I_K,ACh was activated by the cholinergic agonist carbachol (CCh; 2 µM). In SR, CCh activated a large current either in inward or outward directions. The selective I_K,ACh inhibitor tertiapin (10 nM) blocked the outward CCh-induced current by 61%. In atrial cardiomyocytes isolated from dogs with AF, the presence of a constitutively active I_K,ACh was observed, blocked by 59% with 10 nM tertiapin. However, in “AF atrial myocytes”, CCh activated an additional, significant ligand-dependent and tertiapin-sensitive I_K,ACh current. Conclusions: In our dog AF model, I_to unlike in humans was downregulated only in a slight manner. Due to its slow inactivation kinetics, it seems that I_to may play a more significant role in atrial repolarization than in ventricular working muscle myocytes. The presence of the constitutively active I_K,ACh in atrial myocytes from AF dogs shows that electrical remodeling truly developed in this model. The I_K,ACh current (both ligand-dependent and constitutively active) seems to play a significant role in canine atrial electrical remodeling and may be a promising atrial selective drug target for suppressing AF. Full article

Atrial fibrillation (AF) is the most common sustained arrhythmia to affect 1% of the global population and increases with age. Atrial fibrosis is a crucial substrate for promoting structural remodeling to cause atrial arrhythmogenesis. Bone morphogenic protein 2 (BMP2) has been reported to be involved in cardiac fibrogenesis. However, its role in modulating atrial fibrosis to affect AF development remains unknown. Our study aimed to investigate the expression of BMP2 under different AF conditions and the effect of BMP2 on the progression of atrial fibrosis using an angiotensin II (Ang II) rat model and an ex vivo cardiac fibroblast model. The qRT-PCR and Western blot assay showed increased BMP2 mRNA and protein levels in the atria of chronic AF patients and the right atria of a tachypacing rabbit model. In contrast, the levels of BMP2 receptor mRNA were comparable. The AF incidence of the Ang II rat was higher than that of a control rat, which was reduced by BMP2 treatment. Masson staining demonstrated an anti-fibrogenic impact on BMP2-subjected rat atria compared to only Ang II-treated rat atria. RNA-sequencing indicated the potential function of blocking NLRP3-associted inflammasome activation in BMP2-treated rat atrial tissues. In vitro, transfecting BMP2 shRNA into neonatal rat atrial fibroblasts upregulated the mRNA levels of NLRP3/Caspase-1/p20/ASC and the secretion of IL-1β and IL-6. In contrast, recombinant BMP2 protein attenuated the increased levels of the NLRP3 inflammasome pathway induced by Ang II. In summary, BMP2 opposes atrial fibrosis to alleviate AF susceptibility by inhibiting the activation of the inflammasome in atrial fibroblasts. Full article

Variants (pathogenic) of the LMNA gene are a common cause of familial dilated cardiomyopathy (DCM), which is characterised by early-onset atrioventricular (AV) block, atrial fibrillation and ventricular tachyarrhythmias (VTs), and progressive heart failure. The unstable internal nuclear lamina observed in LMNA-related DCM is a consequence of the disassembly of lamins A and C. This suggests that LMNA variants produce truncated or alternative forms of protein that alter the nuclear structure and the signalling pathway related to cardiac muscle diseases. To date, the pathogenic mechanisms and phenotypes of LMNA-related DCM have been studied using different platforms, such as patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) and transgenic mice. In this review, point variants in the LMNA gene that cause autosomal dominantly inherited forms of LMNA-related DCM are summarised. In addition, potential therapeutic targets based on preclinical studies of LMNA variants using transgenic mice and human iPSC-CMs are discussed. They include mitochondria deficiency, variants in nuclear deformation, chromatin remodelling, altered platelet-derived growth factor and ERK1/2-related pathways, and abnormal calcium handling. Full article