Arrhythmias Research Articles

The influence of rhythm disturbances on the results of combined operations of pulmonary endarterectomy and coronary artery bypass grafting in patients with chronic thromboembolic pulmonary hypertension and coronary heart disease

Aim. To study the features of the early postoperative period in patients with chronic thromboembolic pulmonary hypertension (CTEPH) with surgically significant stenosis of the coronary arteries and to evaluate the impact of cardiac arrhythmias on the hospital period after pulmonary endarterectomy (PEA) in combination with coronary artery bypass grafting (CABG).Material and methods. The study cohort included 45 patients with CTEPH with surgically significant coronary artery stenosis at the age of 61.4 (55.3-69.5) years. All patients underwent PEA (1st stage) and CABG (2nd stage). The relationship between concomitant rhythm disturbances and various complications in the early postoperative period was assessed using logistic regression analysis.Results. Initially, in the study cohort, rhythm disturbances were recorded in 33.3% of cases, where atrial fibrillation accounted for a large proportion. Among the early postoperative complications, the leading ones were neurological disorders (28.9%). Hospital mortality was 6.7%. Concomitant rhythm disturbances in the studied patients were associated with the postoperative development of neurological disorders (OR 4.7 (2.5-7.3; p=0.02)), heart failure (OR 2.2 (1.5-6.8); p=0.03)) and acute renal failure (OR 2.4 (1.4-7.9; p=0.01)).Conclusion. In high-risk cardiac surgical patients with CTEPH and surgically significant coronary artery stenosis, various rhythm disturbances are recorded in 33.3% of cases. In the hospital period after PEA and CABG in the studied patients, neurological disorders accounted for a large proportion of complications among the complications. Hospital mortality was 6.7%. Concomitant rhythm disturbances in patients with CTEPH with surgically significant coronary artery stenosis are associated with a more severe course of the early postoperative period and increase the chances of developing neurological disorders, acute renal failure and acute heart failure.

MANAGEMENT OF ANTICOAGULATION IN ATRIAL FIBRILLATION: MINIMIZING DRUG INTERACTIONS WITH DOACS

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia that elevates the risk of thromboembolic events, necessitating effective anticoagulation strategies. Direct oral anticoagulants (DOACs) have become the preferred choice due to their safety profiles; however, drug interactions can compromise their efficacy and safety. Objective: This study aims to assess the impact of drug interactions on the efficacy and safety of DOACs in patients with AF. Method: A literature review was conducted using databases such as the Virtual Health Library, LILACS Plus, and Medline, focusing on articles published from 2019 to 2024. Inclusion criteria emphasized studies related to drug interactions involving DOACs and AF, resulting in the selection of 13 relevant articles. Results: The analysis revealed a significant prevalence of drug interactions among patients treated with DOACs. Co-prescription with CYP3A4 inhibitors and P-glycoprotein modulators was linked to increased bleeding risks. Factors such as age, renal function, and the presence of comorbidities were crucial in determining appropriate dosing and the risk of adverse events. Conclusion: Careful management of AF patients on DOACs is vital to mitigate risks associated with drug interactions. Personalized treatment approaches that consider individual clinical profiles and ongoing education for healthcare providers are essential to optimize anticoagulation therapy.

Cost Effectiveness of Catheter Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation: A Systematic Review and Meta-analysis.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is associated with substantial morbidity and mortality. Current international guidelines recommend antiarrhythmic drugs or catheter ablation (CA) as rhythm-control strategies for AF. This study aimed to comprehensively assess economic evaluations (EEs) of the treatment of AF by country income level. Seven electronic databases were systematically searched for EE literature until March 30, 2024, with no constraints on time or language. Two independent reviewers selected the studies, extracted the data, and assessed the quality of the data. Full EEs comparing CA with antiarrhythmic drugs for rhythm-control treatment were included; surgical or rate-control treatments were excluded. The quality of the included articles was assessed using the ECOBIAS checklist. Costs were converted to purchasing power parity US dollars for 2023. A random-effects meta-analysis was applied to pool incremental net benefit (INB) based on a heterogeneity test and its degree (I2 > 25% or Cochran's Q test < 0.1). We also explored heterogeneity and potential publication bias and conducted sensitivity and subgroup analyses. In total, 27 studies across nine countries were eligible, predominantly from high-income countries (n = 25), with a smaller subset from upper-middle-income countries (n = 2). Because of the heterogeneity among the studies, a random-effects model was selected over a fixed-effects model to pool INBs. Most studies (n = 21) favored CA as the cost-effective intervention, yielding an INB of $US23,796 (95% confidence interval [CI] 15,341-32,251) in high-income countries. However, heterogeneity was substantial (I2 = 99.67%). In upper-middle-income countries, the estimated INB was $US18,330 (95% CI - 11,900-48,526). The publication bias results showed no evidence of asymmetrical funnel plots. In this meta-analysis, CA emerged as a cost-effective rhythm-control treatment for AF when compared with antiarrhythmic drugs, particularly in high-income countries. However, economic evidence for upper-middle-income countries is lacking, and no primary evaluations were found for low-middle-income and low-income countries. Further EEs are necessary to expand the understanding of AF treatment globally.

Sex hormones and reproductive factors with cardiac arrhythmia and ECG indices: a mendelian randomization study

BackgroundSex is a determinant of the incidence and etiology of arrhythmia. Observational and basic studies suggest that sex hormones are essential in this process; however, the relationship between sex hormones and arrhythmia remains unclear. Mendelian randomization (MR) was used to investigate the causal relationships between sex hormone levels, arrhythmia, and electrocardiographic (ECG) indices.MethodsLarge genome-wide association studies (GWAS) data on sex hormones, stratified by sex, from the UK biobank consortium, were used as exposure data, and data on atrial fibrillation (AF), atrioventricular block, sick sinus syndrome, paroxysmal tachycardia, and ECG indices were obtained from the FinnGen consortium and summarized large GWAS data. Inverse variance weighting or wald odds was used as the primary analytical method, and weighted medians and MR-Egger regression were used for complementary analyses. The results of the MR of sex hormones and AF from different sources were analyzed using a meta-analysis. Summary-data-based MR analysis was utilized to explore the relationship between sex-hormone related drugs and arrhythmia.ResultsIn men, genetically predicted higher estradiol concentrations were associated with a lower risk of AF (odds ratio: 0.908 [0.852–0.967]; p = 0.0029], whereas genetically predicted higher concentrations of total testosterone were associated with lower heart rate variability. Sex hormones showed no association with atrioventricular block, sick sinus syndrome, paroxysmal tachycardia, resting heart rate, P wave duration, P wave terminal force in lead V1 [PTFV1], PR interval, QRS duration, QTc [QT interval corrected by heart rate], ST duration, spatial [spQRSTa] and frontal [fQRSTa] QRS-T angles in males. In females, there was no significant evidence that sex hormones are associated with arrhythmias or ECG indices.ConclusionIn this study, we identified a potential causal relationship between estradiol and the risk of AF in males. However, there was no significant association between sex hormones and either arrhythmias or ECG indices in females. These results suggested that sex hormones may play a limited role in cardiac arrhythmias, which requires further verification.

Role of ryanodine receptor cooperativity in Ca2+-wave-mediated triggered activity in cardiomyocytes.

Ca2+ waves are known to trigger delayed after-depolarizations that can cause malignant cardiac arrhythmias. However, modelling Ca2+ waves using physiologically realistic models has remained a major challenge. Existing models with low Ca2+ sensitivity of ryanodine receptors (RyRs) necessitate large release currents, leading to an unrealistically large Ca2+ transient amplitude incompatible with the experimental observations. Consequently, current physiologically detailed models of delayed after-depolarizations resort to unrealistic cell architectures to produce Ca2+ waves with a normal Ca2+ transient amplitude. Here, we address these challenges by incorporating RyR cooperativity into a physiologically detailed model with a realistic cell architecture. We represent RyR cooperativity phenomenologically through a Hill coefficient within the sigmoid function of RyR open probability. Simulations in permeabilized myocytes with high Ca2+ sensitivity reveal that a sufficiently large Hill coefficient is required for Ca2+ wave propagation via the fire-diffuse-fire mechanism. In intact myocytes, propagating Ca2+ waves can occur only within an intermediate Hill coefficient range. Within this range, the spark rate is neither too low, enabling Ca2+ wave propagation, nor too high, allowing for the maintenance of a high sarcoplasmic reticulum load during diastole of the action potential. Moreover, this model successfully replicates other experimentally observed manifestations of Ca2+-wave-mediated triggered activity, including phase 2 and phase 3 early after-depolarizations and high-frequency voltage-Ca2+ oscillations. These oscillations feature an elevated take-off potential with depolarization mediated by the L-type Ca2+ current. The model also sheds light on the roles of luminal gating of RyRs and the mobile buffer ATP in the genesis of these arrhythmogenic phenomena. KEY POINTS: Existing mathematical models of Ca2+ waves use an excessively large Ca2+-release current or unrealistic diffusive coupling between release units. Our physiologically realistic model, using a Hill coefficient in the ryanodine receptor (RyR) gating function to represent RyR cooperativity, addresses these limitations and generates organized Ca2+ waves at Hill coefficients ranging from ∼5 to 10, as opposed to the traditional value of 2. This range of Hill coefficients gives a spark rate neither too low, thereby enabling Ca2+ wave propagation, nor too high, allowing for the maintenance of a high sarcoplasmic reticulum load during the plateau phase of the action potential. Additionally, the model generates Ca2+-wave-mediated phase 2 and phase 3 early after-depolarizations, and coupled membrane voltage with Ca2+ oscillations mediated by the L-type Ca2+ current. This study suggests that pharmacologically targeting RyR cooperativity could be a promising strategy for treating cardiac arrhythmias linked to Ca2+-wave-mediated triggered activity.

Photon-Scanning Approach to Control Spiral Wave Dynamics in the Heart.

Self-organizing spiral electrical waves are produced in the heart during fatal cardiac arrhythmias. Controlling these waves is therefore an essential step in managing the disease. Here we present an effective method for controlling cardiac spiral waves using optogenetics. The method involves using photons to actively scan the surface of the heart for phase singularities. Once detected, these phase singularities are redirected to an inexcitable wall to be eliminated. Thus, spiral waves can be controlled in a double-blind fashion. We present two theoretical mechanisms with exvivo validation.

Single-center initial experience with a new pulsed-field ablation system:pulmonary vein isolation lesions and beyond.

Pulsed-field ablation (PFA) is a newer energy delivery method, an alternative to thermal lesion, allowing for safe and durable pulmonary vein isolation in the context of atrial fibrillation ablation. Graded tissue sensitivity allows for specifically targeting atrial cardiomyocytes, rendering collateral damage to nearby nerves and vessels unlikely. In the present rapid communication, we report on our center's initial experience with a novel PFA platform and describe the ways in which it can be used targeting sites beyond PV ostia and antra, in the context of atrial fibrillation/flutter/tachycardia ablation, alone or in conjunction with a mainstream 3-dimensional electroanatomical mapping system (3D-EAM). More specifically, the exploratory application of PFA in the vicinity of pacemaker/defibrillator leads may prove of particular significance for clinical practice, given the frequent need to isolate the superior vena cava in patients bearing a transvenous cardiac rhythm management device.

Combining Endpoint Detection with a Convolutional Neural Network Classifier for the Automatic Recognition of Cardiac Arrhythmias in Electrocardiogram Signals

Combining Endpoint Detection with a Convolutional Neural Network Classifier for the Automatic Recognition of Cardiac Arrhythmias in Electrocardiogram Signals

Design, Testing, and Validation of a Soft Robotic Sensor Array Integrated with Flexible Electronics for Mapping Cardiac Arrhythmias.

Cardiac mapping is a crucial procedure for diagnosing and treating cardiac arrhythmias. Still, current clinical techniques face limitations including insufficient electrode coverage, poor conformability to complex heart chamber geometries, and high costs. This study explores the design, testing, and validation of a 64-electrode soft robotic catheter that addresses these challenges in cardiac mapping. A dual-layer flexible printed circuit board (PCB) was designed and integrated with sensors into a soft robotic sensor array (SRSA) assembly. Design considerations included flex PCB layout, routing, integration, conformity to heart chambers, sensor placement, and catheter durability. Rigorous SRSA in vitro testing evaluated the burst/leakage pressure, block force for electrode contact, mechanical integrity, and environmental resilience. For in vivo validation, a porcine model was used to demonstrate the successful deployment, conformability, and acquisition of electrograms in both the ventricles and atria. This catheter-deployable SRSA represents a meaningful step towards translating the integration of soft robotic actuators and stretchable electronics for clinical use, showcasing the unique mechanical and electrical performance that these designs enable. The high-density electrode array enabled rapid 2 s data acquisition with detailed spatial and temporal resolution, as illustrated by the clear and consistent cardiac signals recorded across all electrodes. The future of this work will lie in enabling high-density, anatomically conformable devices for detailed cardiac mapping to guide ablation therapy and other interventions.

Prospective in silico trials identify combined SK and K2P channel block as an effective strategy for atrial fibrillation cardioversion.

Virtual evaluation of medical therapy through human-based modelling and simulation can accelerate and augment clinical investigations. Treatment of the most common cardiac arrhythmia, atrial fibrillation (AF), requires novel approaches. This study prospectively evaluates and mechanistically explains three novel pharmacological therapies for AF through in silico trials, including single and combined SK and K2P channel block. AF and pharmacological action were assessed in a large cohort of 1000 virtual patients, through 2962 multiscale simulations. Extensive calibration and validation with experimental and clinical data support their credibility. Sustained AF was observed in 654 virtual patients. In this cohort, cardioversion efficacy increased to 82% (535 of 654) through combined SK+K2P channel block, from 33% (213 of 654) and 43% (278 of 654) for single SK and K2P blocks, respectively. Drug-induced prolongation of tissue refractoriness, dependent on the virtual patient's ionic current profile, explained cardioversion efficacy (atrial refractory period increase: 133.0±48.4ms for combined vs. 45.2±43.0 and 71.0±55.3ms for single SK and K2P block, respectively). Virtual patients cardioverted by SK channel block presented lower K2P densities, while lower SK densities favoured the success of K2P channel inhibition. Both ionic currents had a crucial role on atrial repolarization, and thus a synergism resulted from the multichannel block. All three strategies, including the multichannel block, preserved atrial electrophysiological function (i.e. conduction velocity and calcium transient dynamics) and thus its contractile properties (safety). In silico trials identify key factors determining treatment success and the combined SK+K2P channel block as a promising strategy for AF management. KEY POINTS: This is a large-scale in silico trial study involving 2962 multiscale simulations. A population of 1000 virtual patients underwent three treatments for atrial fibrillation. Single and combined SK+K2P channel block were assessed prospectively. The multi-ion channel inhibition resulted in 82% cardioversion efficacy. In silico trials have broad implications for precision medicine.

Catecholamine-Induced Inflammasome Activation in the Heart Following Photothrombotic Stroke

AbstractCerebrovascular stroke patients exhibit an increased incidence of cardiac arrhythmias. The pathomechanisms underlying post-traumatic cardiac dysfunction include a surge of catecholamines and an increased systemic inflammatory response, but whether inflammasome activation contributes to cardiac dysfunction remains unexplored. Here, we used a mouse model of photothrombotic stroke (PTS) to investigate the role of inflammasome activation in post-stroke cardiac dysfunction by catecholamines and to evaluate the effectiveness of the inflammasome inhibitor IC100 on inflammasome activation. To evaluate functional electrophysiological changes in the heart by catecholamine treatment, we recorded action potential duration in excised zebrafish hearts with and without IC100 treatment. We show that PTS induced AIM2 inflammasome activation in atria and ventricles that was significantly reduced by administration of IC100. Injection of epinephrine into naïve mice induced a significant increase in AIM2, IL-1b and caspase-8 in atria. Treatment of excised zebrafish hearts with epinephrine shortened the action potential duration and this shortening that was reduced by IC100. These findings indicate that stroke initiates a catecholamine surge that induces inflammasome activation and pyroptosis in the heart that is blocked by IC100, thus providing a framework for the development of therapeutics for stroke-related cardiovascular injury.

Fatal rhabdomyolysis and fulminant myocarditis with malignant arrhythmias after one dose of ipilimumab and nivolumab.

Immune checkpoint inhibitors (ICIs) related myocarditis is a rare complication of modern immunotherapy. It can present as an asymptomatic subclinical condition or full-blown fulminant myocarditis with malignant arrythmias and cardiogenic shock. Myositis/rhabdomyolysis and/or myasthenic symptoms can be present concomitantly. We present a case of fatal fulminant myocarditis presenting with cardiac arrythmias and severe systolic dysfunction, with accompanying rhabdomyolysis after the first dose of ipilimumab and nivolumab immunotherapy. First working diagnosis of subacute late presenting acute myocardial infarction (ACS) was incorrect and the correct diagnosis was established only after additional testing and consultation. Treatment consisted of high-dose corticosteroids, intravenous immunoglobulins, sedation with mechanical ventilation, antibiotic coverage, hemodialysis, and sustained low-efficiency daily diafiltration (SLEDD) with CytoSorb or TheraNova membranes, and intra-aortic balloon pump mechanical cardiac support. No tangible improvement in the condition was observed during the whole treatment period and the patient died on the sixth day of intensive care treatment.

The Descriptive and Disproportionality Assessment of EudraVigilance Database Reports on Capecitabine Induced Cardiotoxicity.

This post-marketing research on CAP aims to assess the risk of cardiac toxicity. Five other antitumor drugs used in colorectal cancer, i.e., 5-fluorouracil (5-FU), irinotecan (IRI), oxaliplatin (OX), bevacizumab (BEV) and panitumumab (PAN), were also studied to create a relative profile of observed cardiotoxicity. A retrospective study based on reports submitted in the EudraVigilance (EV) database until 28 July 2024 was conducted. Using the aggregated data from EV, a descriptive analysis and disproportionality analysis of cardiac ADRs induced by fluoropyrimidines were performed. To evaluate the disproportionality of the signals, Reporting Odds Ratio (ROR) and 95% confidence interval (95% CI) were calculated by comparison with other drugs used in colorectal cancer: 5-FU, IRI, OX, BEV, and PAN. "Cardiac disorders" represent 3.4% of the total reports for CAP. The value is comparable to 5-FU, but higher than for other drugs. t was observed that there are no significant differences in the occurrence of cardiac ADRs in patients exposed to CAP and 5-FU treatments, and in particular MI and HF. Compared to 5-FU, which could produce cardiac arrythmias with a higher probability than all other drugs, CAP has a higher probability of reporting this ADR only in comparison with IRI (ROR: 1.2971; 95% CI: 1.0196-1.6502). CAP induces adverse cardiovascular reactions, especially MI, HF, and cardiomyopathies. Arrhythmias have been shown to be side effects more frequent associated with 5-FU than with CAP. The results emphasize the need for a rigorous cardiovascular monitoring of patients following treatment with CAP or 5-FU and especially for those with pre-existing cardiac pathology.

A clinical audit of hypomagnesaemia management at Scarborough General Hospital

BackgroundHypomagnesaemia is a common electrolyte disturbance that can lead to severe complications, including cardiac dysrhythmias and neuromuscular instability. Despite established guidelines by the York and Scarborough Teaching Hospitals NHS Foundation Trust, there is concern that these protocols are not consistently followed, potentially compromising patient outcomes. Objective: This audit aimed to evaluate the management of hypomagnesaemia at Scarborough General Hospital, focusing on adherence to trust guidelines and identifying areas for improvement in clinical practice. MethodsA retrospective analysis was conducted on 98 patients diagnosed with hypomagnesaemia between May and December 2023. Data on patient demographics, severity of hypomagnesaemia, ECG monitoring, treatment modalities and correction times were collected and analysed. The audit compared current practices against trust guidelines, specifically assessing the frequency of ECG monitoring, daily serum magnesium level checks, and the use of parenteral versus oral magnesium supplementation. ResultsThe audit revealed that 67% of patients had mild, asymptomatic hypomagnesaemia, while 33% presented with moderate to severe forms. ECGs were performed in 66% of cases, with 13.7% showing abnormalities. Despite guidelines recommending daily magnesium level monitoring, only 66% of patients received this care. Severe hypomagnesaemia was corrected within 3.5 days on average, while mild cases required 4.5 days. The frequent use of proton pump inhibitors was identified as a significant contributor to hypomagnesaemia. Notably, only half of the severe cases received the full recommended course of intravenous magnesium sulphate, with many being switched to oral supplementation prematurely. ConclusionWhile some aspects of hypomagnesaemia management at Scarborough General Hospital align with trust guidelines, significant gaps remain, particularly in monitoring practices and adherence to treatment protocols. These findings highlight the need for targeted educational initiatives and potential revisions to existing guidelines to improve patient outcomes.

The Effectiveness of a Multimedia Educational Program on the Lifestyle and Perception of Patients with Atrial Fibrillation: A Study Protocol

Background: Atrial fibrillation is a globally common cardiac dysrhythmia and preventable with education. The study protocol aimed to investigate the effectiveness of a multimedia educational program on the lifestyle and perception of patients with atrial fibrillation. Methods: The present clinical trial protocol will be conducted to investigate the effect of multimedia training on the lifestyle and perception of patients with atrial fibrillation in two phases. The multimedia training (audio, video, image, and animation) was provided in the form of two 2-hour training sessions per week for patients on the coordinated date and time on a web platform. The patients also received a weekly phone call for one month through which some educational content was covered as a type of training intervention. The second phase included the administration of pre-test and post-test interventions using standard questionnaires by an intervention (who receive training) and a control (without training) group. Conclusion: The present study provides a useful protocol regarding the design of a multimedia educational intervention program on promoting the lifestyle and perception of patients with atrial fibrillation. It can also reduce treatment costs. The strategies of this program can be cost-effective therefore the success of such a program can be effective in improving the health status of atrial fibrillation patients.Registration of this randomized control trial has been completed with the Iranian Registry of Clinical Trials.

Cardiac arrhythmias during and after thoracic irradiation for malignancies

BackgroundCardiac arrhythmia has been reported as a significant complication of thoracic radiotherapy. Both bradyarrhythmias and tachyarrhythmias have been reported, highlighting the arrhythmia-modulating potential of radiation in certain oncologic therapies. This study aimed to analyse the arrhythmic burden in patients with cardiac implantable electrical devices (CIEDs) undergoing thoracic irradiation, examining both immediate effects of radiotherapy and long-term sequelae post-therapy.Methods and resultsA retrospective cohort study was conducted involving patients with CIEDs who received thoracic radiotherapy between January 2012 and December 2022. Two distinct analyses were performed involving (1) daily CIED follow-ups during radiotherapy and (2) long-term arrhythmic outcomes post-therapy. For long-term outcomes, Patients were matched in a 1:2 ratio with non-irradiated controls based on age, sex, cardiovascular risk factors, cardiac disease, and beta-blocker use. Statistical analyses included negative binomial regression and propensity score matching. A total of 186 patients underwent daily CIED monitoring during radiotherapy, with 79 receiving thoracic irradiation. Thoracic irradiation was negatively associated with atrial arrhythmia (OR 0.11 [0.02;0.70, 95% CI], adjusted p = 0.0498) and there was a tendency towards less ventricular events (OR 0.14 [0.02;1.41, 95% CI], adjusted p = 0.3572) during radiotherapy in a univariate regression analysis. This association was not significant in the multivariate (OR 0.44 [0.10;1.80, 95%-CI], p = 0.16) model including a history of atrial fibrillation, diabetes and beta-blocker use. Coronary artery disease was associated with an increase in atrial and ventricular arrhythmia. For the long-term analysis, 122 patients were followed up after thoracic (N = 33) and non-thoracic radiation (N = 89) and compared to 244 matched controls drawn from approximately 10.000 CIED-patients. There was no significant increase in arrhythmic events compared to controls over a median follow-up of 6.6 months. A previous history of ventricular or atrial arrhythmic events was the strongest predictor for events during the follow-up.ConclusionThoracic radiotherapy can be safely administered in patients with CIEDs. However, patients with a history of arrhythmia are more prone to arrhythmic events during and after radiation. These findings highlight the need for personalized arrhythmia management strategies and further research to understand the mechanisms underlying the antiarrhythmic effects of thoracic radiation.Graphical

Prognostic Significance and Associations of Neural Network-Derived Electrocardiographic Features.

Subtle, prognostically important ECG features may not be apparent to physicians. In the course of supervised machine learning, thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology. We aimed to investigate whether neural network-derived ECG features could be used to predict future cardiovascular disease and mortality and have phenotypic and genotypic associations. We extracted 5120 neural network-derived ECG features from an artificial intelligence-enabled ECG model trained for 6 simple diagnoses and applied unsupervised machine learning to identify 3 phenogroups. Using the identified phenogroups, we externally validated our findings in 5 diverse cohorts from the United States, Brazil, and the United Kingdom. Data were collected between 2000 and 2023. In total, 1 808 584 patients were included in this study. In the derivation cohort, the 3 phenogroups had significantly different mortality profiles. After adjusting for known covariates, phenogroup B had a 20% increase in long-term mortality compared with phenogroup A (hazard ratio, 1.20 [95% CI, 1.17-1.23]; P<0.0001; phenogroup A mortality, 2.2%; phenogroup B mortality, 6.1%). In univariate analyses, we found phenogroup B had a significantly greater risk of mortality in all cohorts (log-rank P<0.01 in all 5 cohorts). Phenome-wide association study showed phenogroup B had a higher rate of future atrial fibrillation (odds ratio, 2.89; P<0.00001), ventricular tachycardia (odds ratio, 2.00; P<0.00001), ischemic heart disease (odds ratio, 1.44; P<0.00001), and cardiomyopathy (odds ratio, 2.04; P<0.00001). A single-trait genome-wide association study yielded 4 loci. SCN10A, SCN5A, and CAV1 have roles in cardiac conduction and arrhythmia. ARHGAP24 does not have a clear cardiac role and may be a novel target. Neural network-derived ECG features can be used to predict all-cause mortality and future cardiovascular diseases. We have identified biologically plausible and novel phenotypic and genotypic associations that describe mechanisms for the increased risk identified.

Effect of acupuncture on quality of life in atrial fibrillation: study protocol for a randomised controlled trial

IntroductionAtrial fibrillation (AF) is the prevalent cardiac arrhythmia and can significantly impair the quality of life (QoL). Although catheter ablation (CA) is an established treatment for AF,post-procedural complications or perceived...

Atrial septal defect (ASD), trans-catheter closure – case report

Atrial septal defect (ASD) is one of the most common types of congenital heart defects, occurring in about 25% of children. An atrial septal defect occurs when there is a failure to close the communication between the right and left atria. It encompasses defects involving both the true septal membrane and other defects that allow for communication between both atria. There are five types of atrial septal defects ranging from most frequent to least: patent foramen ovale, ostium secundum defect, ostium primum defect, sinus venosus defect, and coronary sinus defect. Small atrial septal defects usually spontaneously close in childhood. Large defects that do not close spontaneously may require percutaneous or surgical intervention to prevent further complications such as stroke, dysrhythmias, and pulmonary hypertension. This activity describes the evaluation, diagnosis, and management of atrial septal defect and highlights the role of team-based interprofessional care for affected patients. Atrial septal defects are frequently asymptomatic. The characteristic murmur is a soft, systolic ejection murmur over the pulmonic area (second intercostal space) combined with a wide, fixed splitting of S2. Many ASDs go undiagnosed until adulthood; therefore, treatment, especially of large defects, is often delayed. Untreated large defects can cause exercise intolerance, cardiac dysrhythmias, palpitations, increased incidence of pneumonia, pulmonary hypertension and increased mortality.

Quantitative Structure-Activity Relationship Models to Predict Cardiac Adverse Effects.

Drug-induced cardiotoxicity represents one of the most common causes of attrition of drug candidates in preclinical and clinical development. For this reason, the evaluation of cardiac toxicity is essential during drug development and regulatory review. In the present study, drug-induced postmarket adverse event combinations from the FDA Adverse Event Reporting System were extracted for 2002 drugs using 243 cardiac toxicity-related preferred terms (PTs). These PTs were combined into 12 groups based on their clinical relevance to serve as training sets. The optimal classification scheme was determined using a combination of data sources that included drug labeling information, published literature, clinical study data, and postmarket surveillance data. Two commercial QSAR platforms were used to construct 12 models, including general cardiac toxicity, cardiac ischemia, heart failure, cardiac valve disease, myocardial disease, pericardial disease, structural heart disease, cardiac arrhythmia, Torsades de Pointes, long QT syndrome, atrial fibrillation and ventricular arrhythmia, and cardiac arrest. The cross-validated performance for the new models reached a sensitivity of up to 80% and negative predictivity of up to 80%. These new models covering a wide range of cardiac endpoints will provide fast, reliable, and comprehensive predictions of potential cardiotoxic compounds in drug discovery and regulatory safety assessment.