Search

Background: Cardiovascular events following anti-malarial treatment are reported infrequently; only a few studies have reported adverse outcomes. This case presentation emphasizes cardiological assessment of Brugada syndrome, presenting as life-threatening arrhythmia during anti-malarial treatment. Without screening and untreated, this disease may lead to sudden cardiac death. Case presentation: This is a case of 23-year-old male who initially presented with palpitations followed by syncope and shortness of breath with a history of malaria. He had switched treatment from quinine to dihydroartemisinin-piperaquine (DHP). Further investigations revealed the ST elevation electrocardiogram pattern typical of Brugada syndrome, confirmed with flecainide challenge test. Subsequently, anti-malarial treatment was stopped and an Implantable Cardioverter Defibrillator (ICD) was inserted. Conclusions: Another possible cause of arrhythmic events happened following anti-malarial consumption. This case highlights the possibility of proarrhytmogenic mechanism of malaria infection and anti-malarial drug resulting in typical manifestations of Brugada syndrome. [ABSTRACT FROM AUTHOR]

Introduction Methods and Results Conclusion The decremental properties of the nodoventricular pathway (NVP) are uncertain.During short RP supraventricular tachycardia, a His‐refractory premature ventricular contraction (PVC) consistently terminated the tachycardia without atrial capture immediately after the PVC. Whereas a slightly earlier PVC failed to reset the subsequent His but terminated the tachycardia without atrial capture one cycle later.These observations are diagnostic of slow‐fast atrioventricular nodal reentrant tachycardia (AVNRT) with a bystander concealed‐NVP and can be explained by decremental properties in the NVP itself; greater prematurity of the PVC resulted in more decremental conduction over the NVP, causing the AVNRT termination one cycle later. [ABSTRACT FROM AUTHOR]

This document is a collection of references for articles related to the study of cardiac physiology and arrhythmias. The articles cover various topics, including calcium handling abnormalities in atrial fibrillation, the role of specific channels in atrial fibroblasts, the contribution of reactive oxygen species to the Frank-Starling mechanism, optical mapping of contracting hearts, and the role of specific channels in calcium-dependent triggered activity and cardiac arrhythmias. The articles provide valuable insights into the mechanisms and potential treatments for different cardiac conditions. The authors of the articles are funded by various organizations, including the German Cardiac Society, the Canadian Institutes of Health Research, and the Heart and Stroke Foundation of Canada. [Extracted from the article]

Background Methods Results Conclusions One of the most commonly experienced symptoms of premenstrual disorder (PMD) is anxiety, and there is a notable rise in sympathomimetic activity in this patient group. Studies have linked fluctuations in systemic autonomic tone to electrocardiography (ECG) changes. This study aims to investigate the relationship between anxiety, a common symptom of PMD, and alterations in QT dispersion (QTd) and P‐wave dispersion (Pd) in adolescent females.This cross‐sectional study included female adolescents aged 12–18 with regular menstruation for at least 3 months. Participants completed the premenstrual syndrome scale (PMSS) and were divided into two groups, PMD and control, according to the PMSS score. A standard 12‐lead body surface ECG was performed and QTd and Pd values were determined in each participant.Of the 43 participants, 27 were categorized into the PMD group, with a mean age of 15.15 ± 1.43 years. Age at menarche and menstrual cycle patterns were comparable between the PMD and control groups. Statistical analysis revealed significantly higher Pmin (p = 0.010) and Pd values (p < 0.001) in the PMD group compared to controls. A positive correlation between PMSS scores and Pd (p = 0.049) was also observed.Changes in atrial conduction and ventricular repolarization due to the pathophysiology of PMD may increase the risk of developing atrial and ventricular tachyarrhythmias over time. Screening patients with PMD using an ECG may be useful in identifying potentially at‐risk adolescents. [ABSTRACT FROM AUTHOR]

Background: Hailey-Hailey disease (HHD) is a rare autosomal dominant skin disease caused by mutations in the ATP2C1 gene, which encodes the secretory Ca2+/Mn2+-ATPase (SPCA1) pump in the Golgi apparatus. Although ATP2C1 is ubiquitously expressed in the body, possible extracutaneous manifestations of HHD are unknown. However, dysfunction of the Golgi apparatus not specifically coupled to ATP2C1 has been associated with heart disease. Objective: To investigate the association between HHD and common heart disease in a Swedish, population-based cohort. Methods: We conducted a population-based cohort study based on a linkage of Swedish nationwide registers to investigate the relationship between HHD and heart disease. We have been granted ethical approval from the Swedish Ethical Review Authority to conduct this study. The patients in this manuscript have given written informed consent to the publication of their case details. A total of 342 individuals with an ICD-10 diagnosis of HHD (Q82.8E) were identified and matched with randomly selected comparison individuals without HHD on a 1:100 ratio. Furthermore, in a separate clinical cohort we matched 23 HHD patients for age, sex, and BMI with control subjects to examine electrocardiogram parameters, electrolytes, and cardiovascular biomarkers. Results: Compared with individuals without HHD, individuals with HHD had an excess risk of arrhythmia (RR 1.4, CI 1.0–2.0), whereas no increased risks of myocardial infarction (RR 1.1, CI 0.6–1.7) or heart failure (RR 1.0, CI 0.6–1.6; Table 1) were found. We found no difference in ECG parameters, cardiovascular biomarkers, and electrolytes in the clinical subset. Conclusion: This study reveals that HHD is associated with an increased risk of arrhythmia and represents the first data of any extracutaneous comorbidity in HHD. Thus, HHD may be a systemic disease. Our findings also shed light on the importance of the Golgi apparatus' Ca2+/Mn2+ homeostasis in common heart disease. [ABSTRACT FROM AUTHOR]

The multi-lead electrocardiogram (ECG) is widely utilized in clinical diagnosis and monitoring of cardiac conditions. The advancement of deep learning has led to the emergence of automated multi-lead ECG diagnostic networks, which have become essential in the fields of biomedical engineering and clinical cardiac disease diagnosis. Intelligent ECG diagnosis techniques encompass Recurrent Neural Networks (RNN), Transformers, and Convolutional Neural Networks (CNN). While CNN is capable of extracting local spatial information from images, it lacks the ability to learn global spatial features and temporal memory features. Conversely, RNN relies on time and can retain significant sequential features. However, they are not proficient in extracting lengthy dependencies of sequence data in practical scenarios. The self-attention mechanism in the Transformer model has the capability of global feature extraction, but it does not adequately prioritize local features and cannot extract spatial and channel features. This paper proposes STFAC-ECGNet, a model that incorporates CAMV-RNN block, CBMV-CNN block, and TSEF block to enhance the performance of the model by integrating the strengths of CNN, RNN, and Transformer. The CAMV-RNN block incorporates a coordinated adaptive simplified self-attention module that adaptively carries out global sequence feature retention and enhances spatial–temporal information. The CBMV-CNN block integrates spatial and channel attentional mechanism modules in a skip connection, enabling the fusion of spatial and channel information. The TSEF block implements enhanced multi-scale fusion of image spatial and sequence temporal features. In this study, comprehensive experiments were conducted using the PTB-XL large publicly available ECG dataset and the China Physiological Signal Challenge 2018 (CPSC2018) database. The results indicate that STFAC-ECGNet surpasses other cutting-edge techniques in multiple tasks, showcasing robustness and generalization. [ABSTRACT FROM AUTHOR]

Background: An idiopathic outflow tract premature ventricular complex (OT-PVC) is a common arrhythmia, and the accuracy of site of origin prediction using the 12-lead electrocardiogram (ECG) algorithm is not high. There are no studies about a systematic strategy that can provide practical help to electrophysiologists in OT-PVC mapping and ablation. This study aims to evaluate the efficacy and safety of the proposed ablation protocol and establish an optimal catheter ablation strategy by simultaneously investigating and synthesizing various indicators observed during the mapping procedure. Methods and design: This study (ABOUT-PVC) was designed as a prospective multicenter study to enroll 210 patients from 11 tertiary university hospitals over an estimated 27 months. Patients with idiopathic OT-PVC requiring catheter ablation will receive the procedure through a proposed ablation strategy and will be followed up for at least 12 months. The primary outcome is the acute procedural success rate. The secondary outcomes are clinical success rate, procedure time, complication rate, symptom relief, and changes in echocardiographic parameters. Conclusions: The ABOUT-PVC study was designed to investigate the efficacy and safety of the proposed ablation strategy and establish an optimal catheter ablation strategy. We expect this study to overcome the limitations of the ECG prediction algorithms and provide a practical guide to electrophysiologists, increasing the procedure's success rate and reducing complications and procedure time. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation has an estimated prevalence of 1.5–2%, making it the most common cardiac arrhythmia. The processes that cause and sustain the disease are still not completely understood. An association between atrial fibrillation and systemic, as well as local, inflammatory processes has been reported. However, the exact mechanisms underlying this association have not been established. While it is understood that inflammatory macrophages can influence cardiac electrophysiology, a direct, causative relationship to atrial fibrillation has not been described. This study investigated the pro-arrhythmic effects of activated M1 macrophages on human induced pluripotent stem cell (hiPSC)-derived atrial cardiomyocytes, to propose a mechanistic link between inflammation and atrial fibrillation. Methods: Two hiPSC lines from healthy individuals were differentiated to atrial cardiomyocytes and M1 macrophages and integrated in an isogenic, pacing-free, atrial fibrillation-like coculture model. Electrophysiology characteristics of cocultures were analysed for beat rate irregularity, electrogram amplitude and conduction velocity using multi electrode arrays. Cocultures were additionally treated using glucocorticoids to suppress M1 inflammation. Bulk RNA sequencing was performed on coculture-isolated atrial cardiomyocytes and compared to meta-analyses of atrial fibrillation patient transcriptomes. Results: Multi electrode array recordings revealed M1 to cause irregular beating and reduced electrogram amplitude. Conduction analysis further showed significantly lowered conduction homogeneity in M1 cocultures. Transcriptome sequencing revealed reduced expression of key cardiac genes such as SCN5A, KCNA5, ATP1A1, and GJA5 in the atrial cardiomyocytes. Meta-analysis of atrial fibrillation patient transcriptomes showed high correlation to the in vitro model. Treatment of the coculture with glucocorticoids showed reversal of phenotypes, including reduced beat irregularity, improved conduction, and reversed RNA expression profiles. Conclusions: This study establishes a causal relationship between M1 activation and the development of subsequent atrial arrhythmia, documented as irregularity in spontaneous electrical activation in atrial cardiomyocytes cocultured with activated macrophages. Further, beat rate irregularity could be alleviated using glucocorticoids. Overall, these results point at macrophage-mediated inflammation as a potential AF induction mechanism and offer new targets for therapeutic development. The findings strongly support the relevance of the proposed hiPSC-derived coculture model and present it as a first of its kind disease model. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Myocardial ischaemia reperfusion injury (IRI) occurring from acute coronary artery disease or cardiac surgical interventions such as bypass surgery can result in myocardial dysfunction, presenting as, myocardial "stunning", arrhythmias, infarction, and adverse cardiac remodelling, and may lead to both a systemic and a localised inflammatory response. This localised cardiac inflammatory response is regulated through the nucleotide-binding oligomerisation domain (NACHT), leucine-rich repeat (LRR)-containing protein family pyrin domain (PYD)-3 (NLRP3) inflammasome, a multimeric structure whose components are present within both cardiomyocytes and in cardiac fibroblasts. The NLRP3 inflammasome is activated via numerous danger signals produced by IRI and is central to the resultant innate immune response. Inhibition of this inherent inflammatory response has been shown to protect the myocardium and stop the occurrence of the systemic inflammatory response syndrome following the re-establishment of cardiac circulation. Therapies to prevent NLRP3 inflammasome formation in the clinic are currently lacking, and therefore, new pharmacotherapies are required. This review will highlight the role of the NLRP3 inflammasome within the myocardium during IRI and will examine the therapeutic value of inflammasome inhibition with particular attention to carbon monoxide, nitric oxide, and hydrogen sulphide as potential pharmacological inhibitors of NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

Simple Summary: Cardiac fibrosis is a common manifestation of heart disease that leads to the deterioration of cardiac function and the development of cardiac arrhythmias. Atrial fibrillation (AF) is particularly influenced by cardiac fibrosis, which is considered one of the primary factors in its development. Various diagnostic techniques can be employed to assess myocardial fibrosis, including cardiac imaging and the evaluation of circulating biomarkers. Among these biomarkers, galectin-3 (Gal-3) is notable for its involvement in inflammation and tissue fibrosis associated with cardiac disease. In humans, several studies have reported that an increased serum Gal-3 concentration is a risk factor for AF. In this study, we evaluated the serum concentration of Gal-3 in 26 dogs with AF associated with acquired cardiac diseases. A total of 17 cardiac healthy dogs and 30 dogs with cardiac disease but without AF served as controls. Our findings indicated no significant difference in Gal-3 concentrations between healthy dogs and dogs with cardiac disease, regardless of the presence of AF. Gal-3 showed a significant positive correlation with age. The results of this study suggest that Gal-3 does not have an important role for the development of AF in dogs, but it is associated with advanced age. Galectin-3 (Gal-3) is a lectin associated with fibrosis and inflammation, and increased circulating concentrations are considered a risk factor for atrial fibrillation (AF) in humans. This retrospective study aimed to evaluate the serum concentration of Gal-3 in dogs with cardiac disease, both with and without AF. Dogs with AF associated with acquired heart diseases were selected, while cardiac healthy dogs and dogs with heart diseases but without AF served as controls. We statistically compared the serum concentration of Gal-3, which was assessed using a commercial canine-specific ELISA kit, among healthy dogs and dogs with heart disease with and without AF. Additionally, associations between Gal-3 and clinical and echocardiographic variables were evaluated. A total of 73 dogs were included, of which 17/73 (23.3%) were cardiac healthy and 56/73 (76.7%) had heart disease, with 26/56 (46.4%) having AF. No significant difference in Gal-3 concentration was found between cardiac healthy dogs (3.90 ± 1.65 ng/mL) and dogs with heart disease, either with or without AF (3.37 ± 1.04 ng/mL, p = 0.436 and 4.68 ± 1.80 ng/mL, p = 0.332, respectively). Gal-3 showed a significant positive correlation with age (r = 0.47, p < 0.001) and a negative correlation with body weight (r = −0.45, p < 0.001). The results of this study suggest that Gal-3 does not have an important role in the development of AF in dogs, but it is associated with advanced age. [ABSTRACT FROM AUTHOR]

Chondroitin sulfate proteoglycans (CSPGs) inhibit sympathetic reinnervation in rodent hearts post-myocardial infarction (MI), causing regional hypoinnervation that is associated with supersensitivity of β-adrenergic receptors and increased arrhythmia susceptibility. To investigate the role of CSPGs and hypoinnervation in the heart of larger mammals, we used a rabbit model of reperfused MI and tested electrophysiological responses to sympathetic nerve stimulation (SNS). Innervated hearts from MI and sham rabbits were optically mapped using voltage and Ca2+-sensitive dyes. SNS was performed with electrical stimulation of the spinal cord, and β-adrenergic responsiveness was tested using isoproterenol. Sympathetic nerve density and CSPG expression were evaluated using immunohistochemistry. CSPGs were robustly expressed in the infarct region of all MI hearts, and the presence of CSPGs was associated with reduced sympathetic nerve density in the infarct versus remote region. Action potential duration (APD) dispersion and tendency for induction of ventricular tachycardia/fibrillation (VT/VF) were increased with SNS in MI but not sham hearts. SNS decreased APD at 80% repolarization (APD80) in MI but not sham hearts, whereas isoproterenol decreased APD80 in both groups. Isoproterenol also shortened Ca2+ transient duration at 80% repolarization in both groups but to a greater extent in MI hearts. Our data suggest that sympathetic remodeling post-MI is similar between rodents and rabbits, with CSPGs associated with sympathetic hypoinnervation. Despite a reduction in sympathetic nerve density, the infarct region of MI hearts remained responsive to both physiological SNS and isoproterenol, potentially through preserved or elevated β-adrenergic responsiveness, which may underlie increased APD dispersion and tendency for VT/VF. NEW & NOTEWORTHY: Here, we show that CSPGs are present in the infarcts of rabbit hearts with reperfused MI, where they are associated with reduced sympathetic nerve density. Despite hypoinnervation, sympathetic responsiveness is maintained or enhanced in MI rabbit hearts, which also demonstrate increased APD dispersion and tendency for arrhythmias following sympathetic modulation. Together, this study indicates that the mechanisms of sympathetic remodeling post-MI are similar between rodents and rabbits, with hypoinnervation likely associated with enhanced β-adrenergic sensitivity. [ABSTRACT FROM AUTHOR]

Over the past few years non-cardiac surgery has been recognised as a serious circulatory stress test which may trigger cardiovascular events such as myocardial infarction, in particular in patients at high risk. Detection of these postoperative cardiovascular events is difficult as clinical symptoms often go unnoticed. To improve detection, guidelines advise to perform routine postoperative assessment of cardiac troponin. Troponin elevation - or postoperative myocardial injury - can be caused by myocardial infarction. However, also non-coronary causes, such as cardiac arrhythmias, sepsis and pulmonary embolism, may play a role in a considerable number of patients with postoperative myocardial injury. It is crucial to acquire more knowledge about the underlying mechanisms of postoperative myocardial injury because effective prevention and treatment options are lacking. Preoperative administration of beta-blockers, aspirin, statins, clonidine, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and preoperative revascularisation have all been investigated as preventive options. Of these, only statins should be considered as the initiation or reload of statins may reduce the risk of postoperative myocardial injury. There is also not enough evidence for intraoperative measures such blood pressure optimisation or intensified medical therapy once patients have developed postoperative myocardial injury. Given the impact, better preoperative identification of patients at risk of postoperative myocardial injury, for example using preoperatively measured biomarkers, would be helpful to improve cardiac optimisation. [ABSTRACT FROM AUTHOR]

Background: Pregnancy makes a significant demand on the cardiovascular system. Cardiac disease is the most common cause of mortality in pregnancy. Cardiac disease has the potential to remain undiagnosed; it may present with cardiovascular decompensation during pregnancy, at the time of delivery, or immediately post-partum. The main aim is early risk assessment, optimization, regular monitoring for deterioration, planning of delivery, and surveillance for deterioration in the immediate post-partum period. One of the most severe pain experienced by a woman is during child birth. Hence, relief of labour and childbirth pain, including cesarean delivery is essential. Objective of this study: To assess the impact of labour analgesia and the pregnancy outcome and cardiac events during labour. It is important to understand the pain transmission for providing labour analgesia. Hemodynamic status fluctuates greatly during labour. Therefore, pregnant women with cardiovascular disease need epidural anaesthesia during labour depending upon the type of cardiovascular disease. Methodology: This is a prospective observational study conducted at Sree Mookambika institute of medical sciences in 50 antenatal women with cardiac disease complicating pregnancy during the period of June 2022 to May 2024 (2 years). Results: A total of 50 antenatal women with cardiovascular disease admitted in the department of obstetrics and gynaecology over a period of two year out of which 30 patients had epidural analgesia during labour and 20 patients had no epidural analgesia during labour. Cardiovascular events significantly reduced in epidural group (30 patients) and there was no increase in cesarean section in epidural group. Conclusions: There was significant decrease in cardiovascular events related to arrhythmia hence decreased maternal morbidity and mortality. There was no associated increase in cesarean section rate but slight increase in instrumental vaginal delivery. [ABSTRACT FROM AUTHOR]

Pulsed-field ablation (PFA) is an emerging ablative technology that has been used successfully to eliminate cardiac arrhythmias. As a nonthermal technique, it has significant benefits over traditional radiofrequency ablation with improved target tissue specificity and reduced risk of adverse events during cardiac applications. We investigated whether PFA is safe for use in the stomach and whether it could modulate gastric slow waves. Female weaner pigs were fasted overnight before anesthesia was induced using tiletamine hydrochloride (50 mg·mL−1) and zolazepam hydrochloride (50 mg·mL−1) and maintained with propofol (Diprivan 2%, 0.2–0.4 mg·kg−1·min−1). Pulsed-field ablation was performed on their gastric serosa in vivo. Adjacent point lesions (n = 2–4) were used to create a linear injury using bipolar pulsed-field ablation consisting of 40 pulses (10 Hz frequency, 0.1 ms pulse width, 1,000 V amplitude). High-resolution electrical mapping defined baseline and postablation gastric slow-wave patterns. A validated five-point scale was used to evaluate tissue damage in hematoxylin and eosin-stained images. Results indicated that PFA successfully induced complete conduction blocks in all cases, with lesions through the entire thickness of the gastric muscle layers. Consistent postablation slow-wave patterns emerged immediately following ablation and persisted over the study period. Pulsed-field ablation induces rapid conduction blocks as a tool to modulate slow-wave patterns, indicating it may be suitable as an alternative to radiofrequency ablation. NEW & NOTEWORTHY: Results show that pulsed-field ablation can serve as a gastric slow-wave intervention by preventing slow-wave propagation across the lesion site. Stable conduction blocks were established immediately following energy delivery, faster than previous examples of radiofrequency gastric ablation. Pulsed-field ablation may be an alternative for gastric slow-wave intervention, and further functional and posthealing studies are now warranted. [ABSTRACT FROM AUTHOR]

Purpose: Pediatric Cardiac Quality of Life Inventory (PCQLI) is a disease-specific pediatric cardiac health-related quality of life (HRQOL) instrument that is reliable, valid, and generalizable. We aim to demonstrate PCQLI responsiveness in children undergoing arrhythmia ablation, heart transplantation, and valve surgery before and after cardiac intervention. Methods: Pediatric cardiac patients 8–18 years of age from 11 centers undergoing arrhythmia ablation, heart transplantation, or valve surgery were enrolled. Patient and parent-proxy PCQLI Total, Disease Impact and Psychosocial Impact subscale scores were assessed pre- and 3–12 months follow-up. Patient clinical status was assessed by a clinician post-procedure and dichotomized into markedly improved/improved and no change/worse/much worse. Paired t-tests examined change over time. Results: We included 195 patient/parent-proxies: 12.6 ± 3.0 years of age; median follow-up time 6.7 (IQR = 5.3–8.2) months; procedural groups − 79 (41%) ablation, 28 (14%) heart transplantation, 88 (45%) valve surgery; clinical status − 164 (84%) markedly improved/improved, 31 (16%) no change/worse/much worse. PCQLI patient and parent-proxies Total scores increased (p ≤ 0.013) in each intervention group. All PCQLI scores were higher (p < 0.001) in the markedly improved/improved group and there were no clinically significant differences in the PCQLI scores in the no difference/worse/much worse group. Conclusion: The PCQLI is responsive in the pediatric cardiac population. Patients with improved clinical status and their parent-proxies reported increased HRQOL after the procedure. Patients with no improvement in clinical status and their parent-proxies reported no change in HRQOL. PCQLI may be used as a patient-reported outcome measure for longitudinal follow-up and interventional trials to assess HRQOL impact from patient and parent-proxy perspectives. [ABSTRACT FROM AUTHOR]

Introduction: Ventricular arrhythmia is commonly provoked by acute cardiac ischemia through sympathetic exaggeration and is often resistant to anti-arrhythmic therapies. Thoracic epidural anesthesia has been reported to terminate fatal ventricular arrhythmia; however, its underlying mechanism is unknown. Methods: Rats were randomly divided into four groups: sham, sham plus bupivacaine, ischemia/reperfusion (IR), and IR plus bupivacaine groups. Bupivacaine (1 mg/mL, 0.05 mL/100 g body weight) was injected intrathecally into the L5–L6 intervertebral space prior to establishing a myocardial IR rat model. Thereafter, cardiac arrhythmia, cardiac function, myocardial injury, and electrical activities of the heart and spinal cord were evaluated. Results: Intrathecal bupivacaine inhibited spinal neural activity, improved heart rate variability, reduced ventricular arrhythmia score, and ameliorated cardiac dysfunction in IR rats. Furthermore, intrathecal bupivacaine attenuated cardiac injury and myocardial apoptosis and regulated cardiomyocyte autophagy and connexin-43 distribution during myocardial IR. Conclusion: Our results indicate that intrathecal bupivacaine blunts spinal neural activity to prevent cardiac arrhythmia and dysfunction induced by IR and that this anti-arrhythmic activity may be associated with regulation of autonomic balance, myocardial apoptosis and autophagy, and cardiac gap junction function. [ABSTRACT FROM AUTHOR]

Proarrhythmic cardiotoxicity remains a substantial barrier to drug development as well as a major global health challenge. In vitro human pluripotent stem cell-based new approach methodologies have been increasingly proposed and employed as alternatives to existing in vitro and in vivo models that do not accurately recapitulate human cardiac electrophysiology or cardiotoxicity risk. In this study, we expanded the capacity of our previously established 3D human cardiac microtissue model to perform quantitative risk assessment by combining it with a physiologically based pharmacokinetic model, allowing a direct comparison of potentially harmful concentrations predicted in vitro to in vivo therapeutic levels. This approach enabled the measurement of concentration responses and margins of exposure for 2 physiologically relevant metrics of proarrhythmic risk (i.e. action potential duration and triangulation assessed by optical mapping) across concentrations spanning 3 orders of magnitude. The combination of both metrics enabled accurate proarrhythmic risk assessment of 4 compounds with a range of known proarrhythmic risk profiles (i.e. quinidine, cisapride, ranolazine, and verapamil) and demonstrated close agreement with their known clinical effects. Action potential triangulation was found to be a more sensitive metric for predicting proarrhythmic risk associated with the primary mechanism of concern for pharmaceutical-induced fatal ventricular arrhythmias, delayed cardiac repolarization due to inhibition of the rapid delayed rectifier potassium channel, or hERG channel. This study advances human-induced pluripotent stem cell-based 3D cardiac tissue models as new approach methodologies that enable in vitro proarrhythmic risk assessment with high precision of quantitative metrics for understanding clinically relevant cardiotoxicity. [ABSTRACT FROM AUTHOR]

Cardiac arrhythmia treatment is a clinical challenge necessitating safer and more effective therapies. Recent studies have highlighted the role of the perinexus, an intercalated disc nanodomain enriched in voltage-gated sodium channels including both Na v 1.5 and β1 subunits, adjacent to gap junctions. These findings offer insights into action potential conduction in the heart. A 19-amino acid SCN1B (β1/β1B) mimetic peptide, βadp1, disrupts VGSC beta subunit-mediated adhesion in cardiac perinexii, inducing arrhythmogenic changes. We aimed to explore βadp1's mechanism and develop novel SCN1B mimetic peptides affecting β1-mediated adhesion. Using patch clamp assays in neonatal rat cardiomyocytes and electric cell substrate impedance sensing (ECIS) in β1-expressing cells, we observed βadp1 maintained inhibitory effects for up to 5 h. A shorter peptide (LQLEED) based on the carboxyl-terminus of βadp1 mimicked this inhibitory effect, while dimeric peptides containing repeated LQLEED sequences paradoxically promoted intercellular adhesion over longer time courses. Moreover, we found a link between these peptides and β1-regulated intramembrane proteolysis (RIP) - a signaling pathway effecting gene transcription including that of VGSC subunits. βadp1 increased RIP continuously over 48 h, while dimeric agonists acutely boosted RIP for up to 6 h. In the presence of DAPT, an RIP inhibitor, βadp1's effects on ECIS-measured intercellular adhesion was reduced, suggesting a relationship between RIP and the peptide's inhibitory action. In conclusion, novel SCN1B (β1/β1B) mimetic peptides are reported with the potential to modulate intercellular VGSC β1-mediated adhesion, potentially through β1 RIP. These findings suggest a path towards the development of anti-arrhythmic drugs targeting the perinexus. [Display omitted] • Voltage-gated sodium channel β1 subunit offers novel anti-arrhythmic target. • β1 mimetic peptides increase regulated intramembrane proteolysis (RIP) of β1. • β1 mimetic peptide monomers decrease β1-mediated adhesion. • β1 mimetic peptide dimers stabilize or increase β1-mediated adhesion. [ABSTRACT FROM AUTHOR]

Although short-term rental platforms (e.g. Airbnb) are often not considered labour platforms, their suppliers must contend with demands on labour structured by the platforms. Using Lefebvre's rhythmanalysis, this article examines the spatio-temporal dynamics of cleaning labour for STR platforms through the experiences of student-migrant-workers in Montreal between 2017 and 2020. I argue that yield-focused STR operators (i.e. owner-operators and managers) encounter spatio-temporal friction (or arrhythmia) in their efforts to outsource STR cleaning labour, but some labour intermediaries have responded with strategies to bring this conflict into harmony (eurhythmia) by incorporating the lives and labour of student-migrant-workers. At once limited in their employment options and not exclusively dependent on this work, student-migrant-workers illustrate characteristics that these intermediaries require of the workers they assemble and the flexible labour force upon which STR platforms depend. Rather than replacing labour intermediaries, online platforms have created new spatio-temporal dynamics for labour and new opportunities for those who profit from assembling the labour forces that address them. [ABSTRACT FROM AUTHOR]

This article discusses a case of neonatal flecainide toxicity resulting from a dosing error. It explores the narrow therapeutic index of flecainide and the potential for toxicity in pediatric patients. The article highlights previous cases of dosing errors and their adverse effects. It also discusses the use of activated charcoal and sodium bicarbonate as treatments for flecainide toxicity, as well as other interventions that have shown promise. The document concludes by suggesting measures to prevent dosing errors in the pediatric population. [Extracted from the article]

Oxidative phosphorylation is regulated by mitochondrial calcium (Ca2+) in health and disease. In physiological states, Ca2+ enters via the mitochondrial Ca2+ uniporter and rapidly enhances NADH and ATP production. However, maintaining Ca2+ homeostasis is critical: insufficient Ca2+ impairs stress adaptation, and Ca2+ overload can trigger cell death. In this review, we delve into recent insights further defining the relationship between mitochondrial Ca2+ dynamics and oxidative phosphorylation. Our focus is on how such regulation affects cardiac function in health and disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, mitochondrial cardiomyopathies, Barth syndrome, and Friedreich's ataxia. Several themes emerge from recent data. First, mitochondrial Ca2+ regulation is critical for fuel substrate selection, metabolite import, and matching of ATP supply to demand. Second, mitochondrial Ca2+ regulates both the production and response to reactive oxygen species (ROS), and the balance between its pro- and antioxidant effects is key to how it contributes to physiological and pathological states. Third, Ca2+ exerts localized effects on the electron transport chain (ETC), not through traditional allosteric mechanisms but rather indirectly. These effects hinge on specific transporters, such as the uniporter or the Na+/Ca2+ exchanger, and may not be noticeable acutely, contributing differently to phenotypes depending on whether Ca2+ transporters are acutely or chronically modified. Perturbations in these novel relationships during disease states may either serve as compensatory mechanisms or exacerbate impairments in oxidative phosphorylation. Consequently, targeting mitochondrial Ca2+ holds promise as a therapeutic strategy for a variety of cardiac diseases characterized by contractile failure or arrhythmias. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is a rarely reported arrhythmia in otherwise healthy newborn foals, with a single case of cardioversion using procainamide administration described in the literature. Two neonatal Thoroughbred colts were presented to an equine hospital because of an irregularly irregular tachyarrhythmia and poor latching when trying to nurse. History, physical examination, and initial diagnostic testing including ECG and echocardiography confirmed AF without structural heart disease. The 1st foal converted into normal sinus rhythm after treatment with IV metoprolol and quinidine. The 2nd foal converted to normal sinus rhythm after a single IV dose of metoprolol, intended for rate control. Demeanor and nursing behavior improved markedly after conversion. The 2 foals had normal heart rates and sinus rhythm that persisted for 6 weeks until euthanasia in the 1st foal and for 2 years in the 2nd foal. Rate control and cardioversion should be considered as a treatment for persistent lone AF in neonatal foals. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusions We aimed to investigate the long‐term impact of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D).In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP‐1 RA treatment and those who did not receive glucose‐lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event.After propensity score matching, the study included 12,123 individuals in each group. GLP‐1 RA treatment was associated with a significantly lower risk of all‐cause mortality (hazard ratio 0.23; 95% confidence interval 0.15–0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP‐1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions.In this large observational study, GLP‐1 RAs showed long‐term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP‐1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Chimeric antigen receptor T‐cell (CAR‐T) therapy has shown promise in treating hematologic malignancies, yet its potential cardiotoxic effects require thorough investigation.We aim to conduct a systematic review and meta‐analysis to examine the cardiotoxic effects of CAR‐T therapy in adults with hematologic malignancies.We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for studies reporting cardiovascular outcomes, such as arrhythmias, heart failure, and reduced left ventricle ejection fraction (LVEF).Our analysis of 20 studies involving 4789 patients revealed a 19.68% incidence rate of cardiovascular events, with arrhythmias (7.70%), heart failure (5.73%), and reduced LVEF (3.86%) being the most prevalent. Troponin elevation was observed in 23.61% of patients, while NT‐Pro‐BNP elevation was observed in 9.4. Subgroup analysis showed higher risks in patients with pre‐existing conditions, such as atrial arrhythmia (OR 3.12; p < .001), hypertension (OR 1.85; p = .002), previous heart failure (OR 3.38; p = .003), and coronary artery disease (OR 2.80; p = .003).Vigilant cardiovascular monitoring is crucial for patients undergoing CAR‐T therapy to enhance safety and treatment efficacy.Novelty Statements. [ABSTRACT FROM AUTHOR]

BACKGROUND: The clinical application of human induced pluripotent stem cell--derived cardiomyocytes (CMs) for cardiac repair commenced with the epicardial delivery of engineered cardiac tissue; however, the feasibility of the direct delivery of human induced pluripotent stem cell--derived CMs into the cardiac muscle layer, which has reportedly induced electrical integration, is unclear because of concerns about poor engraftment of CMs and posttransplant arrhythmias. Thus, in this study, we prepared purified human induced pluripotent stem cell--derived cardiac spheroids (hiPSC-CSs) and investigated whether their direct injection could regenerate infarcted nonhuman primate hearts. METHODS: We performed 2 separate experiments to explore the appropriate number of human induced pluripotent stem cell--derived CMs. In the first experiment, 10 cynomolgus monkeys were subjected to myocardial infarction 2 weeks before transplantation and were designated as recipients of hiPSC-CSs containing 2107 CMs or the vehicle. The animals were euthanized 12 weeks after transplantation for histological analysis, and cardiac function and arrhythmia were monitored during the observational period. In the second study, we repeated the equivalent transplantation study using more CMs (6107 CMs). RESULTS: Recipients of hiPSC-CSs containing 2107 CMs showed limited CM grafts and transient increases in fractional shortening compared with those of the vehicle (fractional shortening at 4 weeks after transplantation [mean ± SD]: 26.2±2.1%; 19.3±1.8%; P<0.05), with a low incidence of posttransplant arrhythmia. Transplantation of increased dose of CMs resulted in significantly greater engraftment and long-term contractile benefits (fractional shortening at 12 weeks after transplantation: 22.5±1.0%; 16.6±1.1%; P<0.01, left ventricular ejection fraction at 12 weeks after transplantation: 49.0±1.4%; 36.3±2.9%; P<0.01). The incidence of posttransplant arrhythmia slightly increased in recipients of hiPSC-CSs containing 6107 CMs. [ABSTRACT FROM AUTHOR]

Identifying and treating pediatric arrhythmias is essential for pediatric anesthesiologists. Pediatric patients can present with narrow or wide complex tachycardias, though the former is more common. Patients with inherited channelopathies or cardiomyopathies are at increased risk. Since most pediatric patients present for anesthesia without a baseline electrocardiogram, the first identification of an arrhythmia may occur under general anesthesia. Supraventricular tachycardia, the most common pediatric tachyarrhythmia, represents a broad category of predominately narrow complex tachycardias. Stimulating events including intubation, vascular guidewire manipulation, and surgical stimulation can trigger episodes. Valsalva maneuvers are unreliable as treatment, making adenosine or other intravenous antiarrhythmics the preferred acute therapy. Reentrant tachycardias are the most common supraventricular tachycardia in pediatric patients, including atrioventricular reciprocating tachycardia (due to a distinct accessory pathway) and atrioventricular nodal reentrant tachycardia (due to an accessory pathway within the atrioventricular node). Patients with ventricular preexcitation, often referred to as Wolff‐Parkinson‐White syndrome, have a wide QRS with short PR interval, indicating antegrade conduction through the accessory pathway. These patients are at risk for sudden death if atrial fibrillation degenerates into ventricular fibrillation over a high‐risk accessory pathway. Automatic tachycardias, such as atrial tachycardia and junctional ectopic tachycardia, are causes of supraventricular tachycardia in pediatric patients, the latter most typically noted after cardiac surgery. Patients with inherited arrhythmia syndromes, such as congenital long QT syndrome, are at risk of developing ventricular arrhythmias such as polymorphic ventricular tachycardia (Torsades de Pointes) which can be exacerbated by QT prolonging medications. Patients with catecholaminergic polymorphic ventricular tachycardia are at particular risk for developing bidirectional ventricular tachycardia or ventricular fibrillation during exogenous or endogenous catecholamine surges. Non‐selective beta blockers are first line for most forms of long QT syndrome as well as catecholaminergic polymorphic ventricular tachycardia. Anesthesiologists should review the impact of medications on the QT interval and transmural dispersion of repolarization, to limit increasing the risk of Torsades de Pointes in patients with long QT syndrome. This review explores the key anesthetic considerations for these arrhythmias. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most prevalent arrhythmia characterized by intermittent and asymptomatic episodes. However, traditional detection methods often fail to capture the sporadic and intricate nature of AF, resulting in an increased risk of false-positive diagnoses. To address these challenges, this study proposes an intelligent AF detection and diagnosis method that integrates Complementary Ensemble Empirical Mode Decomposition, Power-Normalized Cepstral Coefficients, Bi-directional Long Short-term Memory (CEPNCC-BiLSTM), and photoelectric volumetric pulse wave technology to enhance accuracy in detecting AF. Compared to other approaches, the proposed method demonstrates faster preprocessing efficiency and higher sensitivity in detecting AF while effectively filtering out false alarms from photoplethysmography (PPG) recordings of non-AF patients. Considering the limitations of conventional AF detection evaluation systems that lack a comprehensive assessment of efficiency and accuracy, this study proposes the ET-score evaluation system based on F-measurement, which incorporates both computational speed and accuracy to provide a holistic assessment of overall performance. Evaluated with the ET-score, the CEPNCC-BiLSTM method outperforms EEMD-based improved Power-Normalized Cepstral Coefficients and Bi-directional Long Short-term Memory (EPNCC-BiLSTM), Support Vector Machine (SVM), EPNCC-SVM, and CEPNCC-SVM methods. Notably, this approach achieves an outstanding accuracy rate of up to 99.2% while processing PPG recordings within 5 s, highlighting its potential for long-term AF monitoring. [ABSTRACT FROM AUTHOR]

Arrhythmias range from mild nuisances to potentially fatal conditions, detectable through electrocardiograms (ECGs). With advancements in wearable technology, ECGs can now be monitored on-the-go, although these devices often capture noisy data, complicating accurate arrhythmia detection. This study aims to create a new deep learning model that utilizes generative adversarial networks (GANs) for effective noise removal and ResNet for precise arrhythmia classification from wearable ECG data. We developed a deep learning model that cleans ECG measurements from wearable devices and detects arrhythmias using refined data. We pretrained our model using the MIT-BIH Arrhythmia and Noise databases. Least squares GANs were used for noise reduction, maintaining the integrity of the original ECG signal, while a residual network classified the type of arrhythmia. After initial training, we applied transfer learning with actual ECG data. Our noise removal model significantly enhanced data clarity, achieving over 30 dB in a signal-to-noise ratio. The arrhythmia detection model was highly accurate, with an F1-score of 99.10% for noise-free data. The developed model is capable of real-time, accurate arrhythmia detection using wearable ECG devices, allowing for immediate patient notification and facilitating timely medical response. [ABSTRACT FROM AUTHOR]

Over the past decade, the use of biometrics in security systems and other applications has grown in popularity. ECG signals in particular are attracting increased attention due to their characteristics, which are required for a trustworthy identification system. The majority of ECG-based person identification systems are evaluated without considering the health-state of the individuals. Few person identification systems consider person-by-person health-state annotation. This paper proposes a person identification system considering the health-state annotated ECG signals where each person's beats overlap among variant arrhythmia classes. This overlapping between the normal class and other arrhythmia classes grants the ability to isolate normal beats in the train set from the Arrhythmic beats in the test set. Therefore, this paper investigates the effect of arrhythmic heartbeats on biometric recognition. An effective lightweight CNN based on depth-wise separable convolution (DWSC) is proposed to enhance the performance of person identification for several common arrhythmia types using the MITBIH dataset. The proposed methodology has been tested on nine arrhythmia types and presents how different types of arrhythmia affect ECG-based biometric systems differently. The experimental results show excellent recognition performance (99.28%) on normal heartbeats and (93.81%) on arrhythmic heartbeats, outperforming other models in terms of mean accuracy. [ABSTRACT FROM AUTHOR]

This article discusses the importance of understanding noncoding genetic variants in cardiovascular diseases and the challenges associated with studying them. The authors highlight the use of expression quantitative trait locus (eQTL) databases to analyze the impact of noncoding variants on gene expression. They specifically focus on the variant rs13376333, which is associated with atrial fibrillation, and demonstrate how integrating human tissue and induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) eQTL datasets can provide insights into the mechanisms of noncoding variants. The authors recommend further research using diverse hiPSC-CMs and advanced QTL studies to better understand noncoding variants and develop novel therapeutic targets. [Extracted from the article]

Hypoglycemia is common in people with type 1 diabetes. Sometimes, severe hypoglycemia can be fatal. The underlying mechanisms by which severe hypoglycemia can lead to death are unclear. The sympathetic nervous system is thought to be proarrhythmic. We hypothesized that norepinephrine is the main mediator of severe hypoglycemia‐induced fatal cardiac arrhythmias. To test this hypothesis, adult, non‐diabetic Sprague–Dawley rats were subjected to hyperinsulinemic‐severe hypoglycemic clamps (3 h, 10–15 mg/dL) during two different experiments: (1) intracerebroventricular (ICV) norepinephrine (n = 26) or artificial cerebrospinal fluid (aCSF) (n = 20) infusion or (2) blockade of norepinephrine release by intraperitoneal reserpine (n = 20) or control (n = 29). In experiment 1, brain norepinephrine infusion during severe hypoglycemia led to a 2.5‐fold increase in third‐degree heart block and a 24% incidence of ST elevation compared to no ST elevation in aCSF controls. In experiment 2, reserpine successfully reduced plasma and cardiac norepinephrine levels. During severe hypoglycemia, reserpine completely prevented second and third‐degree heart block and T wave increases, a marker of myocardial infarction, compared to controls. In conclusion, norepinephrine increases while reserpine, used to reduce norepinephrine nerve terminal release, reduces heart block and markers of myocardial infarction during severe hypoglycemia. [ABSTRACT FROM AUTHOR]

Exposing cells to intense and brief electric field pulses can modulate cell permeability, a phenomenon termed electroporation. When applied in medical treatments of diseases like cancer and cardiac arrhythmias, depending on level of cellular destruction, it is also referred to as irreversible electroporation (IRE) or Pulsed Field Ablation (PFA). For ablation device testing, several pulse parameters need to be characterized in a comprehensive manner to assess lesion boundary and efficacy. Overly aggressive voltages and application numbers increase animal burden. The potato tuber is a widely used initial model for the early testing of electroporation. The aim of this study is to characterize and refine bench testing for the ablation outcomes of PFA in this simplistic vegetal model. For in vitro assays, several pulse parameters like voltage, duration, and frequency were modulated to study effects not only on 2D ablation area but also 3D depth and volume. As PFA is a relatively new technology with minimal thermal effects, we also measured temperature changes before, during, and after ablation. Data from experiments were supplemented with in silico modeling to examine E-field distribution. We have estimated the irreversible electroporation threshold in Solanum Tuberosum to be at 240 V/cm. This bench testing platform can screen several pulse recipes at early stages of PFA device development in a rapid and high-throughput manner before proceeding to laborious trials for IRE medical devices. [ABSTRACT FROM AUTHOR]

In polymicrobial sepsis, the extracellular histones, mainly released from activated neutrophils, significantly contribute to cardiac dysfunction (septic cardiomyopathy), as demonstrated in our previous studies using Echo-Doppler measurements. This study aims to elucidate the roles of extracellular histones and their interactions with Toll-like receptors (TLRs) in cardiac dysfunction. Through ex vivo assessments of ECG, left ventricle (LV) function parameters, and in vivo Echo-Doppler studies in mice perfused with extracellular histones, we aim to provide comprehensive insights into the mechanisms underlying sepsis-induced cardiac dysfunction. Langendorff-perfused hearts from both wild-type and TLR2, TLR3, or TLR4 knockout (KO) mice were examined. Paced mouse hearts were perfused with histones to assess contractility and relaxation. Echo-Doppler studies evaluated cardiac dysfunction after intravenous histone injection. Histone perfusion caused defects in contractility and relaxation, with TLR2 and TLR3 KO mice being partially protected. Specifically, TLR2 KO mice exhibited the greatest reduction in Echo-Doppler abnormalities, while TLR4 KO exacerbated cardiac dysfunction. Among individual histones, H1 induced the most pronounced abnormalities in cardiac function, apoptosis of cardiomyocytes, and LDH release. Our data highlight significant interactions between histones and TLRs, providing insights into histones especially H1 as potential therapeutic targets for septic cardiomyopathy. Further studies are needed to explore specific histone–TLR interactions and their mechanisms. [ABSTRACT FROM AUTHOR]

BACKGROUND: Alterations in the buffering of intracellular Ca2+, for which myofilament proteins play a key role, have been shown to promote cardiac arrhythmia. It is interesting that although studies report atrial myofibrillar degradation in patients with persistent atrial fibrillation (persAF), the intracellular Ca2+ buffering profile in persAF remains obscure. Therefore, we aimed to investigate the intracellular buffering of Ca2+ and its potential arrhythmogenic role in persAF. METHODS: Transmembrane Ca2+ fluxes (patch-clamp) and intracellular Ca2+ signaling (fluo-3-acetoxymethyl ester) were recorded simultaneously in myocytes from right atrial biopsies of sinus rhythm (Ctrl) and patients with persAF, alongside human atrial subtype induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs). Protein levels were quantified by immunoblotting of human atrial tissue and induced pluripotent stem cell-derived cardiac myocytes. Mouse whole heart and atrial electrophysiology were measured on a Langendorff system. RESULTS: Cytosolic Ca2+ buffering was decreased in atrial myocytes of patients with persAF because of a depleted amount of Ca2+ buffers. In agreement, protein levels of selected Ca2+ binding myofilament proteins, including cTnC (cardiac troponin C), a major cytosolic Ca2+ buffer, were significantly lower in patients with persAF. Small interfering RNA (siRNA)-mediated knockdown of cTnC (si-cTNC) in atrial iPSC-CM phenocopied the reduced cytosolic Ca2+ buffering observed in persAF. Si-cTnC treated atrial iPSC-CM exhibited a higher predisposition to spontaneous Ca2+ release events and developed action potential alternans at low stimulation frequencies. Last, indirect reduction of cytosolic Ca2+ buffering using blebbistatin in an ex vivo mouse whole heart model increased vulnerability to tachypacing-induced atrial arrhythmia, validating the direct mechanistic link between impaired cytosolic Ca2+ buffering and atrial arrhythmogenesis. CONCLUSIONS: Our findings suggest that loss of myofilament proteins, particularly reduced cTnC protein levels, causes diminished cytosolic Ca2+ buffering in persAF, thereby potentiating the occurrence of spontaneous Ca2+ release events and atrial fibrillation susceptibility. Strategies targeting intracellular buffering may represent a promising therapeutic lead in persAF management. [ABSTRACT FROM AUTHOR]

BACKGROUND: Whether vigorous exercise increases risk of ventricular arrhythmias for individuals diagnosed and treated for congenital long QT syndrome (LQTS) remains unknown. METHODS: The National Institutes of Health-funded LIVE-LQTS study (Lifestyle and Exercise in the Long QT Syndrome) prospectively enrolled individuals 8 to 60 years of age with phenotypic and/or genotypic LQTS from 37 sites in 5 countries from May 2015 to February 2019. Participants (or parents) answered physical activity and clinical events surveys every 6 months for 3 years with follow-up completed in February 2022. Vigorous exercise was defined as =6 metabolic equivalents for >60 hours per year. A blinded Clinical Events Committee adjudicated the composite end point of sudden death, sudden cardiac arrest, ventricular arrhythmia treated by an implantable cardioverter defibrillator, and likely arrhythmic syncope. A National Death Index search ascertained vital status for those with incomplete follow-up. A noninferiority hypothesis (boundary of 1.5) between vigorous exercisers and others was tested with multivariable Cox regression analysis. RESULTS: Among the 1413 participants (13% <18 years of age, 35% 18-25 years of age, 67% female, 25% with implantable cardioverter defibrillators, 90% genotype positive, 49% with LQT1, 91% were treated with beta-blockers, left cardiac sympathetic denervation, and/or implantable cardioverter defibrillator), 52% participated in vigorous exercise (55% of these competitively). Thirty-seven individuals experienced the composite end point (including one sudden cardiac arrest and one sudden death in the nonvigorous group, one sudden cardiac arrest in the vigorous group) with overall event rates at 3 years of 2.6% in the vigorous and 2.7% in the nonvigorous exercise groups. The unadjusted hazard ratio for experience of events for the vigorous group compared with the nonvigorous group was 0.97 (90% CI, 0.57-1.67), with an adjusted hazard ratio of 1.17 (90% CI, 0.67-2.04). The upper 95% one-sided confidence level extended beyond the 1.5 boundary. Neither vigorous or nonvigorous exercise was found to be superior in any group or subgroup. CONCLUSIONS: Among individuals diagnosed with phenotypic and/or genotypic LQTS who were risk assessed and treated in experienced centers, LQTS-associated cardiac event rates were low and similar between those exercising vigorously and those not exercising vigorously. Consistent with the low event rate, CIs are wide, and noninferiority was not demonstrated. [ABSTRACT FROM AUTHOR]

In this systematic review and meta-analysis, we aim to evaluate the efficacy and safety of catheter ablation as the first-line treatment of ventricular tachycardia (VT) in patients with structural heart disease (SHD) and preserved left ventricular ejection fraction (LVEF). Patients with SHD are particularly susceptible to VT, a condition that increases the risk of sudden cardiac death (SCD). Implantable cardioverter-defibrillators (ICDs) can terminate VT and prevent SCD but do not prevent VT recurrence. The efficacy and safety of CA as a first-line treatment in SHD patients with preserved LVEF remain unclear. We searched PubMed/Medline, EMBASE, Web of Science, and Cochrane CENTRAL for studies reporting the outcomes of CA therapy in patients with VT and preserved LVEF, published up to January 19, 2023. The primary outcome was the incidence of SCD following catheter ablation as the first-line treatment of VT in patients with SHD and preserved LVEF. Secondary outcomes included all-cause mortality, VT recurrence, procedural complications, CA success rate, and ICD implantation after catheter ablation. We included seven studies in the meta-analysis, encompassing a total of 920 patients. The pooled success rate of catheter ablation was 84.6% (95% CI 67.2–93.6). Complications occurred in 6.4% (95% CI 4.0–9.9) of patients, and 13.9% (95% CI 10.1–18.8) required ICD implantation after ablation. VT recurrence was observed in 23.2% (95% CI 14.8–34.6) of patients, while the rate of sudden cardiac death (SCD) was 3.1% (95% CI 1.7–5.6). The overall prevalence of all-cause mortality in this population was 5% (95% CI 1.8–13). CA appears promising as a first-line VT treatment in patients with SHD and preserved LVEF, especially for monomorphic hemodynamically tolerated VT. However, due to the lack of direct comparisons with ICDs and anti-arrhythmic drugs, further research is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions This study aims to investigate the occurrence, type and correlation of early and late atrial arrhythmias following mitral valve repair in patients with no preoperative history of atrial arrhythmias.Patients undergoing mitral valve (MV) repair for degenerative disease were included. Early and late postoperative electrocardiograms were evaluated for the incidence and type of atrial arrhythmia (atrial fibrillation [AF] or atrial tachycardia [AT]).The 192 patients were included. Early atrial arrhythmias occurred in 100/192 (52.1%) patients; AF in 61 (31.8%) patients, early AT in 15 (7.8%) and both in 24 (12.5%). In total 89% of patients were discharged in sinus rhythm. During a follow‐up time of 7.3 years, 14 patients (7.3%) died and 49 (25.5%) patients developed late atrial arrhythmias. At 10 years, the cumulative incidence of any late atrial arrhythmia, with death as competing risk, was 64% (95% confidence interval [CI] = 55%–72%). On Fine‐Gray model analysis, only early postoperative AF lasting >24 h was related to the development of late AF (hazard ratio 5.99, 95% CI = 1.78%–20.10%, p = .004). Early postoperative ATs were related to the development of late tachycardias, independent of their duration (<24 h hazard ratio 4.25, 95% CI = 1.89–9.57, p = .001 and >24 h hazard ratio 3.51, 95% CI = 1.65–7.46, p = .001).Early and late atrial arrhythmias were common after MV repair surgery. Only early postoperative AF lasting >24 h was a risk factor for the occurrence of late AF. Conversely, any postoperative AT was correlated to the development of late ATs. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with significant morbidity and mortality, posing a considerable burden on healthcare systems. In Republic of Korea, the prevalence and incidence of AF have increased in recent years. There have also been significant changes in the trends of antiarrhythmic drug (AAD) use and procedural treatments for AF. Objectives: This study aims to review the trends in AF treatment strategies in Republic of Korea, particularly focusing on the utilization of antiarrhythmic drugs and catheter ablation. Methods: The Korean National Health Insurance Service (K-NHIS) data were used to identify AF patients from 2013 to 2022. AAD usage and catheter ablation procedures were analyzed annually. AADs were classified into Class IC and III drugs. Trends in beta-blockers, calcium channel blockers, and digoxin prescriptions were also examined. The primary endpoint was the trend of AAD use and AF catheter ablation (AFCA) over 10 years. Results: In 2022, 940,063 patients had a prior diagnosis of AF. From 2013 to 2022, the use of AADs increased from 12.1 to 16.4% among prevalent AF patients. Beta-blockers were the most commonly prescribed rate control medication, while the use of calcium channel blockers and digoxin declined. The frequency of AFCA procedures also increased, from 0.5% of prevalent AF patients in 2013 to 0.7% in 2022. Younger patients, males, and those with lower CHA2DS2-VASc scores were more likely to receive AFCA. Regional variations in treatment patterns were observed, with Seoul exhibiting higher rates of procedural treatments and AAD prescriptions. Conclusions: Over the past decade, there has been a significant increase in the use of AADs and AFCA procedures in Republic of Korea. These trends reflect recent advancements in AF management advocating a refined rhythm control strategy. [ABSTRACT FROM AUTHOR]

This article explores the role of ryanodine receptors (RyR2) in calcium handling in the heart and questions the current understanding of calcium flux balance. The author suggests that the interpretation of experimental observations on calcium handling may be oversimplified, which could hinder the development of new therapeutic agents for heart failure and arrhythmias. The article also discusses the effects of caffeine on calcium transients and the potential contribution of reverse mode sodium-calcium exchange (NCX). The authors propose a hypothesis that reverse mode NCX during the early stages of the action potential allows for efficient uptake of calcium into the sarcoplasmic reticulum (SR) by sarcoplasmic reticulum calcium ATPase (SERCA). They suggest that the effects of caffeine on SR calcium content may be due to its diastolic effects rather than its effects on calcium release during action potentials. The authors call for further experiments to test their hypothesis and emphasize the importance of understanding the timing and balance of calcium fluxes in the heart for cardiac contraction and arrhythmias. [Extracted from the article]

Background Hypothesis Animals Methods Results Conclusions and Clinical Importance Improved characterization of arrhythmias is based on minimally invasive catheterizations. However, these catheterizations have been poorly explored in horses because apart from 3‐dimensional (3D) mapping systems, continuous guidance of the catheter's position with adequate detail is difficult using current imaging modalities.Position multiple electrophysiology catheters simultaneously at predetermined strategical positions in the heart using transthoracic echocardiographic guidance.Eight adult healthy horses.Observational study. Two electrophysiological studies were performed: 1 procedure with catheters positioned in the right heart in the standing sedated horse and 1 procedure under general anesthesia with catheters positioned in the left heart. Except for the coronary sinus catheter, each catheter positioning was simultaneously guided by right‐parasternal transthoracic echocardiography and 3D electro‐anatomical mapping.For each catheter position, a central imaging plane was taken as the starting point, after which the imaging probe was shifted, rotated, and angulated to visualize the catheter over its entire length, including its distal electrode. Catheter positionings in the right heart and left ventricle were successfully guided in the majority of the horses whereas catheter positionings in the left atrium, and especially the pulmonary veins, were challenging to guide echocardiographically.Ultrasound guidance of catheters to specific positions useful for electrophysiological mapping was feasible in the right heart and left ventricle but challenging for the left atrium. This approach creates a perspective for minimally invasive arrhythmia diagnosis without the need for a 3D mapping system. Left parasternal views and intracardiac echocardiography might provide better guidance for left atrial positions. [ABSTRACT FROM AUTHOR]

Background: Cardiac arrest is a critical condition with high morbidity and mortality rates, necessitating rapid and effective intervention. Thrombolysis is a therapeutic strategy used to dissolve blood clots and restore blood flow, primarily in acute myocardial infarction. This study aims to explore the hemodynamic changes associated with thrombolysis in cardiac arrest patients and assess its impact on patient outcomes. Materials and Methods: This hospital-based cross-sectional study was conducted in the Department of Emergency Medicine at a tertiary care center from May 2023 to October 2023. The study included 70 patients diagnosed with acute ST-Elevation Myocardial Infarction (STEMI) who experienced cardiac arrest. Data were collected on socio-demographic characteristics, clinical history, and hemodynamic parameters during and after thrombolysis. Hemodynamic changes, including heart rate, systolic and diastolic blood pressure, and ECG rhythm changes, were recorded at specific intervals (0, 5, 10, 15, 20, 25, 30, and 60 minutes) post-thrombolysis. Statistical analysis was performed using SPSS version 21, with a significance level set at p<0.05. Results: The mean age of participants was 58.5 years, with a predominance of males (76.6%). Comorbidities such as hypertension (29.4%) and Type 2 Diabetes Mellitus (23.2%) were prevalent. Hemodynamic monitoring revealed a slight initial decrease in systolic and diastolic blood pressure, followed by stabilization around baseline values. Heart rate decreased slightly immediately post-thrombolysis but returned to baseline within an hour. The most common ECG change observed was Ventricular Premature Contractions (43.4%). No significant differences were found in the duration of hospital stay or blood pressure outcomes between patients with and without comorbid conditions. Conclusion: Thrombolysis in cardiac arrest patients leads to manageable hemodynamic changes, with initial fluctuations in blood pressure and heart rate. The procedure is associated with a safety profile that does not significantly impact short-term outcomes or vary substantially based on the presence of comorbid conditions. Continuous hemodynamic and ECG monitoring is essential to ensure patient stability and optimize treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Arrhythmias are the most common cardiac complications occurring in pregnancy. Although atrial or ventricular premature complexes may explain the majority of palpitations in pregnancy, the full spectrum of arrhythmias can occur. Main body: This article summarizes the evaluation and management of arrhythmias in pregnancy. Hemodynamically unstable arrhythmias need urgent cardioversion. For mild cases of benign arrhythmia, treatment is usually not required. Symptomatic but hemodynamically stable arrhythmic patients should first undergo an evaluation to establish the type of arrhythmia and the presence of structural heart disease. Given the potential risks of antiarrhythmic pharmacotherapy in pregnancy, this will ultimately determine the necessity for treatment. We will discuss the main antiarrhythmic medications, which have some established evidence of safety in pregnancy. Conclusions: In hemodynamically stable pregnant patients with A.F. or AFL with rapid ventricular rates (RVR), I.V. beta-blockers are recommended as the first-line option, and digoxin or verapamil, alone or in combination are recommended as second-line options for initial rate control in the absence of preexcitation. [ABSTRACT FROM AUTHOR]

Mitral annular disjunction (MAD) is a structural abnormality of the mitral valve whereby there is a distinct separation of the mitral valve annulus-left atrial wall continuum and the basal portion of the posterolateral ventricular myocardium, a region which would normally be attached. It is usually associated with myxomatous mitral valve disease. MAD has been reported in various studies since the last four decades as constituting around 42-90% of patients with myxomatous mitral valve disease and mitral valve prolapse. It is often associated with arrhythmias ranging from benign ventricular ectopics to malignant ventricular fibrillations causing sudden cardiac deaths in the young. This condition seems to be more common in women. Last few decades have witnessed many case reports and prospective studies about this entity enhancing our understanding about its pathophysiology. We report a case of a 34 year old male with mitral valve prolapse and MAD resulting in severe mitral regurgitation who underwent mitral valve replacement. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the potential of dexmedetomidine in preventing or reducing postoperative arrhythmias in pediatric patients undergoing direct vision cardiac surgery with extracorporeal circulation (cardiopulmonary bypass (CPB)). Methods: 62 children undergoing elective CPB cardiac surgery in Northwest Women and Children's Hospital, Xian, China between May 2020 and June 2023 were randomly and equally divided into study and control groups. The study group received a loading dose of 1 μg/kg dexmedetomidine followed by continuous intravenous infusion during surgery, while control group received an equivalent volume of saline infusion during surgery. Clinical data, perioperative indices (adverse reactions and intraoperative use of vasoactive drugs), levels of lactic acid, blood urea nitrogen (BUN) glomerular filtration rate (GFR), and postoperative arrhythmias were compared between the two groups at the end of the surgery. Results: The study group showed significantly lower postoperative lactate and BUN levels compared to the control group (p < 0.05). There was no significant difference in incidence of intraoperative hypotension, bradycardia, tachycardia, and vasoactive drug use between the two groups (p > 0.05). The study group showed significantly lower incidences of postoperative nausea and vomiting as well as supraventricular and ventricular arrhythmias compared to control group (p < 0.05). Furthermore, mean arterial pressure (MAP) at T2 and T3 was significantly lower in study group compared to control group (p < 0.05). Conclusion: Dexmedetomidine reduces postoperative lactate, BUN levels, incidence of postoperative supraventricular and ventricular arrhythmias, maintains hemodynamic stability, attenuates stress responses, preserves renal function, and decreases postoperative nausea and vomiting in pediatric CPB cardiac surgery. Large-sample multicenter clinical trials are needed for validation in further studies. [ABSTRACT FROM AUTHOR]

Voltage‐gated potassium channels are expressed throughout the human body and are essential for physiological functions. These include delayed rectifiers, A‐type channels, outward rectifiers, and inward rectifiers. They impact electrical function in the heart (repolarization) and brain (repolarization and stabilization of the resting membrane potential). KCNQx and KCNHx encode Kv7.x and Kv11.x proteins, which form delayed rectifier potassium channels. KCNQx and KCNHx channelopathies are associated with both cardiac and neuronal pathologies. These include electrocardiographic abnormalities, cardiac arrhythmias, sudden cardiac death (SCD), epileptiform discharges, seizures, bipolar disorder, and sudden unexpected death in epilepsy (SUDEP). Due to the ubiquitous expression of KCNQx and KCNHx channels, abnormalities in their function can be particularly harmful, increasing the risk of sudden death. For example, KCNH2 variants have a dual role in both cardiac and neuronal pathologies, whereas KCNQ2 and KCNQ3 variants are associated with severe and refractory epilepsy. Recurrent and uncontrolled seizures lead to secondary abnormalities, which include autonomics, cardiac electrical function, respiratory drive, and neuronal electrical activity. Even with a wide array of anti‐seizure therapies available on the market, one‐third of the more than 70 million people worldwide with epilepsy have uncontrolled seizures (i.e., intractable/drug‐resistant epilepsy), which negatively impact neurodevelopment and quality of life. To capture the current state of the field, this review examines KCNQx and KCNHx expression patterns and electrical function in the brain and heart. In addition, it discusses several KCNQx and KCNHx variants that have been clinically and electrophysiologically characterized. Because these channel variants are associated with multi‐system pathologies, such as epileptogenesis, Kv7 channel modulators provide a potential anti‐seizure therapy, particularly for people with intractable epilepsy. Ultimately an increased understanding of the role of Kv channels throughout the body will fuel the development of innovative, safe, and effective therapies for people at a high risk of sudden death (SCD and SUDEP). [ABSTRACT FROM AUTHOR]

Mitral valve prolapse is a common valve disorder that usually has a benign prognosis unless there is significant regurgitation or LV impairment. However, a subset of patients are at an increased risk of ventricular arrhythmias and sudden cardiac death, which has led to the recognition of "arrhythmic mitral valve prolapse" as a clinical entity. Emerging risk factors include mitral annular disjunction and myocardial fibrosis. While echocardiography remains the primary method of evaluation, cardiac magnetic resonance has become crucial in managing this condition. Cine magnetic resonance sequences provide accurate characterization of prolapse and annular disjunction, assessment of ventricular volumes and function, identification of early dysfunction and remodeling, and quantitative assessment of mitral regurgitation when integrated with flow imaging. However, the unique strength of magnetic resonance lies in its ability to identify tissue changes. T1 mapping sequences identify diffuse fibrosis, in turn related to early ventricular dysfunction and remodeling. Late gadolinium enhancement sequences detect replacement fibrosis, an independent risk factor for ventricular arrhythmias and sudden cardiac death. There are consensus documents and reviews on the use of cardiac magnetic resonance specifically in arrhythmic mitral valve prolapse. However, in this article, we propose an algorithm for the broader use of cardiac magnetic resonance in managing this condition in various scenarios. Future advancements may involve implementing techniques for tissue characterization and flow analysis, such as 4D flow imaging, to identify patients with ventricular dysfunction and remodeling, increased arrhythmic risk, and more accurate grading of mitral regurgitation, ultimately benefiting patient selection for surgical therapy. [ABSTRACT FROM AUTHOR]

This study aimed to explore the effects of early rehabilitation nursing combined with enteral nutrition on acute myocardial infarction patients' recovery and nutritional status after percutaneous coronary intervention. A retrospective analysis was conducted on clinical data from 92 patients who underwent therapy in our hospital following percutaneous coronary intervention from February 2021 to February 2023. These patients were split into a control group and a study group. The control group received standard rehabilitation nursing and routine parenteral nutrition, while the study group was administered early rehabilitation nursing and enteral nutritional support. Post-intervention outcomes showed that the study group had higher left ventricular ejection fraction, cardiac output, 6-minute walking test results, Chinese Cardiovascular Patients' Quality of Life Assessment Questionnaire scores, and total protein and albumin levels compared to the control group (P < 0.05). Furthermore, the study group exhibited a lower incidence of complications and higher nursing satisfaction than the control group (P < 0.05). This indicates that early rehabilitation nursing combined with enteral nutrition is beneficial for enhancing postoperative recovery, improving nutritional status, and elevating the quality of life in patients with acute myocardial infarction after percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]