Abstract Atrial Fibrillation Research Articles

Self-Organized Operational Neural Networks for The Detection of Atrial Fibrillation

Abstract Atrial fibrillation is a common cardiac arrhythmia, and its incidence increases with age. Currently, numerous deep learning methods have been proposed for AF detection. However, these methods either have complex structures or poor robustness. Given the evidence from recent studies, it is not surprising to observe the limitations in the learning performance of these approaches. This can be attributed to their strictly homogenous conguration, which solely relies on the linear neuron model. The limitations mentioned above have been addressed by operational neural networks (ONNs). These networks employ a heterogeneous network configuration, incorporating neurons equipped with diverse nonlinear operators. Therefore, in this study, to enhance the detection performance while maintaining computational efficiency, a novel model named multi-scale Self-ONNs (MSSelf-ONNs) was proposed to identify AF. The proposed model possesses a significant advantage and superiority over conventional ONNs due to their self-organization capability. Unlike conventional ONNs, MSSelf -ONNs eliminate the need for prior operator search within the operator set library to find the optimal set of operators. This unique characteristic sets MSSelf -ONNs apart and enhances their overall performance. To validate and evaluate the system, we have implemented the experiments on the well-known MIT-BIH atrial fibrillation database. The proposed model yields total accuracies and kappa coefficients of 98% and 0.95, respectively. The experiment results demonstrate that the proposed model outperform the state-of-the-art deep CNN in terms of both performance and computational complexity.

HIPSC model reveals M1 macrophages cause atrial arrhythmia correlated to electrophysiological remodelling of atrial cardiomyocytes in 2D and 3D engineered heart tissue

Abstract Atrial fibrillation (AF) is the most common sustained arrhythmia with an estimated prevalence of 1.5–2%. Current treatments lack effectiveness and do not prevent recurrence. Inflammation is reported in AF patients, however, a causal connection remains elusive. In this study, we investigated the arrhythmic effects of pro-inflammatory macrophages (M1) on human induced pluripotent stem cell (hiPSC)-derived atrial cardiomyocytes (aCM), to better understand their role in AF. Macrophages are known to play a role in cardiac electrophysiology, but their role in arrhythmia is unclear. Three healthy hiPSC lines were differentiated to aCM and M1. Multi-electrode array recordings of isogenic, 2D cocultures of M1 and aCM showed a significant increase in beat rate irregularity compared to control conditions (P<0.001). Furthermore, spike amplitude of aCM and M1 cocultures was significantly decreased (P<0.001). Arrhythmias occurred only after activation of macrophages in the coculture. Addition of anti-inflammatory glucocorticoids significantly reduced beat irregularity in aCM and M1 cocultures compared to vehicle (1.9-fold decrease for Hydrocortisone, P<0.005) further supporting macrophage mediated inflammation to be the cause of the arrhythmia. RNA sequencing of aCM and M1 cocultures revealed aberrant expression of arrhythmia associated cardiac sodium and atrial potassium ion channels (SCN5A, KCNA5). Normal expression was restored through hydrocortisone addition. In addition, inflammation-induced arrhythmia was observed in 3D engineered heart tissues containing hiPSC derived aCM, M1 and cardiac fibroblasts. Tissues showed a significant increase in beating irregularity (P<0.005) compared to controls and had a significant, median reduction (>30%) of contraction amplitude (P<0.05). Our findings suggest a causal relationship between M1 and the occurrence of atrial arrhythmia. The reduction of arrhythmia using glucocorticoids correlates to clinical observations, that show their use being linked to reduced post operative AF burden. These results strongly support the relevance of the proposed hiPSC coculture model and elucidate a new potential AF mechanism.

Impact of the Right Atrium on Arrhythmia Vulnerability

Abstract Atrial fibrillation (AF) is one of the most common cardiac diseases. However, a complete understanding of how to treat patients suffering from AF is still not achieved. As the isolation of the pulmonary veins in the left atrium (LA) is the standard treatment for AF, the role of the right atrium (RA) in AF is rarely considered. We investigated the impact of including the RA on arrhythmia vulnerability in silico. We generated a dataset of five mono-atrial (LA) and five bi-atrial models with three different electrophysiological (EP) setups each, regarding different states of AF-induced remodelling. For every model, a pacing protocol was run to induce reentries from a set of stimulation points. The average share of inducing points across all EP setups was 0.0, 0.8 and 6.7% for the mono-atrial scenario, 0.5, 27.3 and 37.9% for the biatrial scenario. The increase in inducibility of LA stimulation points from mono- to bi-atrial scenario was 0.91 ± 2.03%, 34.55 ± 14.9% and 44.2 ± 14.9 %, respectively. In this study, the RA had a marked impact on the results of the vulnerability assessment that needs to be further investigated.

The ARTEMIS project: Mixed-Signal IC for Edge-AI-based Classification of ECG Signals

Abstract Atrial fibrillation (AF) is a common heart arrhythmia and is closely associated with causing strokes. Diagnosis is usually performed with Holter monitors over longer periods of time, causing discomfort to the patient. The proposed mixed-signal integrated circuit (IC) is designed for small patch electrocardiogram (ECG) devices and combines, an analog front-end (AFE) with tailored recording channel characteristics and 12-bit successive-approximation-register analog digital converter (SAR ADC) as well as an RISC-V based microcontroller (μC) for edge artificial intelligence (AI)-based AF-detection. The digital signal processing is supported with hardware accelerators. Including 160 kB of SRAM, the system on chip (SoC) requires 25.56 mm² in silicon area in a 180 nm technology. The recording channel shows promising simulation results with an input impedance of 230 MΩ, an input referred noise of below 1.6 μVrms and a CMMR of 95 dB. The digital part enables the integration of AI-based classification on the IC. Due to the flexibility of the software-based classification approach, this IC can also be used to detect other arrhythmias.

Kidney Function and the Use of Vitamin K Antagonists or Direct Oral Anticoagulants in Atrial Fibrillation

Abstract Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with a five-fold increase in the risk for ischemic stroke. Therefore, lifelong use of anticoagulants is crucial to reduce the morbidity and mortality burden of AF. The incidence of AF in chronic kidney disease (CKD) is two to three times greater than in the general population, and there is a mutual aggravation of the two conditions as well as the presence of both an increased thromboembolic risk in CKD and an increased bleeding risk in severe CKD. The preservation of kidney function in patients with cardiovascular diseases is important, as the latter is the leading cause of death in patients with eGFR <60 mL/min/1.73 m2. Similarly, kidney dysfunction is a serious limitation to the use of many cardiovascular drugs, including anticoagulants. Evidence is present for the faster progression of kidney disease with vitamin K antagonists, likely due to the vitamin K-related process of vascular calcification. Conversely, direct oral anticoagulants (DOACs) have been shown to reduce the progression of CKD and have a beneficial effect as far as the modulation of inflammation and oxidative stress are concerned in experimental models. Another less-discussed problem is the use of DOACs in advanced CKD.

Strategies for rate and rhythm control of atrial fibrillation in the ED.

Atrial fibrillation (AF) is one of the most common dysrhythmias managed in the ED and accounts for more than half a million visits a year in the United States. More than 6 out of 10 of these visits result in admissions. As the prevalence of AF has continued to increase in recent years, so has the presentation of patients with AF to the ED. For these reasons, clinicians in emergency settings must be knowledgeable of evidence-based rate and rhythm control strategies for stabilizing patients and preventing complications. This article discusses options, indications, contraindications, and safe implementation of rate and rhythm control strategies for ED clinicians. Recent studies have suggested that early rhythm control may benefit newly diagnosed patients, reducing stroke risk, cardiovascular deaths, and disease progression.

P56 ROLE OF CARDIAC TROPONINS IN THE EMERGENCY DEPARTMENT IN PATIENTS WITH ATRIAL FIBRILLATION

Abstract Atrial fibrillation (AF) is the most frequent arrhythmia among those encountered in the emergency department. It’s well known that elevated values ​​of cardiac troponin in "stable” conditions is generally indicative of myocardial cytonecrosis and is associated with a worse prognosis in various clinical conditions. The role of cardiac biomarkers in the context of an AF episode has not yet been fully understood and is a source of debate in the cardiology community. Recent studies suggest the association of elevated troponin values in the context of an AF episode with an increased incidence of major cardiovascular events. Consequently, its measurement could be extensively taken into consideration also in the Emergency Department and implemented for risk stratification. There is currently insufficient evidence to support the dosing of cardiac troponins in all AF patients for risk stratification. The aim of this study is to investigate the significance of elevated troponin values ​​during AF and whether these are related to an increased cardiovascular risk. Methods and Results This is a retrospective and observational study and focuses on a population of patients who arrived in the Emergency Department of San Raffaele Hospital in Milan between the 1st of January 2018 and 22nd May 2021 with atrial fibrillation. Data were collected for 625 patients of whom 232 were enrolled for statistical analysis. The population was stratified based on cardiovascular risk factors and prior AF ablation. At 12–month follow–up we found that elevated troponin values ​​during atrial fibrillation in the Emergency Department do not correlate with an increase of deaths from any cause, major cardiovascular events or hospitalizations for heart failure. The presence of elevated cardiac troponin was not associated with an increased rate of CAD at coronary CT nor coronaru angiography. A weak association was seen between non–elevated cTnT–hs and higher rate of AF ablation. Conclusions Our data reject the hypothesis according to which elevated levels of highly sensitive cardiac troponin measured during an atrial fibrillation episode could be correlated with an higher incidence of major adverse cardiovascular events at 1–year follow up.

Atrial fibrillation fundamentals: from physiopathology to transcatheter ablation.

Atrial fibrillation (AF) is a common and harmful arrhythmia. Its complex pathogenesis can be outlined using Coumel's Triangle, that considers at the base of AF three different factors: substrate, trigger, and catalyst factor. The triangle can serve as a guide to understand the mechanism of action of the different possible treatments. Anti-arrhythmic drug therapies have a modest efficacy and no proven benefit on prognosis. Interventional therapy is more effective, especially if employed in the first stages of the disease, and can reduce mortality in selected populations. Ablative schemes must be different depending on the type of AF (paroxysmal, persistent) and the presence or absence of atrial dilation.

How much does the presentation pattern of atrial fibrillation affect thrombo-embolic risk and mortality?

Atrial fibrillation (AF) is associated with a substantial increase in mortality and morbidity. Systemic thrombo-embolism is the most serious complication associated with this arrhythmia. The use of anticoagulant drugs is the cornerstone of therapy for the prophylaxis of stroke and peripheral ischaemia in these patients. The current guidelines recommend the use of anticoagulant drugs based on the thrombo-embolic risk profile of each individual patient calculated by SCORE based on the presence or absence of clinical risk factors and regardless of the presentation pattern of AF. A review of literature data investigating the effect of AF presentation pattern on thrombo-embolic risk and mortality showed an increased risk of both thrombo-embolic events and death in patients with non-paroxysmal AF compared to patients with paroxysmal AF. Most of these studies, however, consist of post-hoc analyses of large trials or observational studies and meta-analyses derived from these, resulting in an important limitation in the interpretation of data derived from such studies. At the same time, these data suggest the need for both new therapies to prevent AF progression and for further studies to explore the integration of AF presentation pattern into models of thrombo-embolic risk.

Atrial fibrillation in heart failure: drugs or ablation?

Atrial fibrillation (AF) and heart failure (HF) frequently coexist and mutually exert negative influences with important clinical implications. Although there is evidence that restoring and maintaining sinus rhythm may have favourable clinical effects in patients with HF, there is no evidence of a survival benefit with pharmacological antiarrhythmic intervention compared with a heart rate control strategy. In these patients, transcatheter ablation (CA) of AF represents a procedure with an excellent safety profile in centres with expertise and a high volume of interventions. However, in the absence of definite evidence of benefit on major clinical end-points that can be generalized to the heterogeneous population with AF and HF, the option of CA should be discussed and shared with the patient, and mainly considered in patients with conditions that are associated with a greater prospect of clinical benefit, such as 'young' age (65-70 years), good health conditions and few or no comorbidities, recent onset of HF and AF (especially if with high heart rate), left atrial volume not excessively compromised (<55 mm in diameter), and without evidence of substantial fibrotic remodelling, left ventricular ejection fraction (LVEF) >25%, including HF with preserved EF (HFpEF).

Beta-blockers in atrial fibrillation-trying to make sense of unsettling results.

Atrial fibrillation is closely associated with heart failure and adversely affects outcomes. Beta-blockers are strongly recommended to avoid rapid ventricular conduction and tachycardia-induced cardiomyopathy. In this Viewpoint article, we discuss an emerging body of evidence that questions beta-blockers as a preferred rate-control therapy in patients with atrial fibrillation.

THE ROLE OF MEDITERRANEAN DIET IN THE PRIMARY AND SECONDARY PREVENTION OF ATRIAL FIBRILLATION: A SCOPING REVIEW

Abstract Atrial fibrillation (AF) is the most common cardiac arrhythmia, especially in patients older than 65. The prevalence of AF increased 3-fold over the last 50 years. All treatments, such as cardioversion, ablation, and anticoagulation, are associated with risks and relapses. Besides, these strategies may not apply to all patients with AF. Adherence to the Mediterranean dietary pattern is assumed as an ideal nutritional model for AF. Yet, there is a gap on 1) how adherence to the Mediterranean diet prevents AF and 2) how the Mediterranean diet affects complications in patients with AF. A scoping review was performed in June 2022 to identify studies focusing on the Mediterranean diet and AF. A total of 334 articles were retrieved and 12 met inclusion criteria. Six studies were interventions (n=6) and six were observational studies (n=6). In the six intervention studies, five were nested within the PREDIMED (Prevención con Dieta Mediterránea) study. In AF occurrence (n=6), the results were inconsistent. The Mediterranean diet plus extra virgin olive oil was significantly and favorably related to AF, however, Mediterranean diet plus nuts was not, when compared with the low-fat diet; Mediterranean diet modified how long chain acylcarnitine affected development of AF but not how tryptophan or arginine metabolites affected AF. In patients diagnosed with AF (n=6), Mediterranean diet favorably related to adverse cardiovascular events, oxidative stress, and Mediterranean diet adherence, and did not affect anticoagulation for those taking anticoagulants. Further research is needed to examine how the Mediterranean diet affects the development of AF.

Therapeutic uncertainties: first finding of atrial fibrillation in acute coronary syndrome.

Atrial fibrillation (AF) and coronary artery disease share several risk factors and their simultaneous presentation in the same patient, sometimes in the course of acute coronary syndrome (ACS), is not a rare occurrence. Patients with AF and ACS represent an important clinical challenge in terms of diagnosis, prognosis and therapy. From a diagnostic point of view, AF may be new onset as a complication of ACS, or a pre-existing asymptomatic AF that is occasionally diagnosed during ACS. Regarding the prognosis, AF, whether new onset or already known, has been shown to exert a negative prognostic impact during ACS. Finally, the main therapeutic dilemma concerns the selection of the optimal antithrombotic therapy, which, at least in the first period following ACS, would require the combination of anticoagulant and antiplatelet drugs, with a consequent increase in the risk of bleeding complications. Several randomized studies have evaluated the therapeutic options in patients with AF and coronary artery disease, overall showing the advantage of a dual therapy with an antiplatelet and an anticoagulant compared with a long-term triple therapy with dual antiplatelet and anticoagulant therapy; the analyses of the ACS subgroups of these randomized studies confirmed such results also in the acute setting.

Some good reasons to proceed with the occlusion of the auricle.

Atrial fibrillation (AF) is the most common arrhythmia. The most fearful complication of AF is represented by cardio-embolic stroke and 30% of ischaemic strokes are attributable to AF. The prevention of cardio-embolic risk is therefore based on oral anticoagulant therapy (OAT). Some categories of patients do not benefit from OAT. These are patients at increased bleeding risk and with varying degrees of contraindication to long-term anticoagulant therapy. On the opposite are those patients who develop an embolic event related to AF despite a well-conducted OAT. These types of patients benefit from an interventional approach, percutaneous closure of the left auricle (LAAO), aimed at eliminating what is the primary source of AF-related thrombo-embolism, precisely the left auricle. Percutaneous closure of the left auricle has proven to be an effective and safe procedure, significantly reducing the bleeding risks of patients who, after the procedure, will no longer have to take OAT. Furthermore, it has been shown to be effective in reducing cardio-embolic risk. Uncertainty still remains as to what is the optimal antithrombotic therapy after LAAO. In any case, LAAO represents a valid alternative to OAT for those patients in whom it is contraindicated or ineffective.

Association between heart and dementia… keep an eye on the left atrium.

Atrial fibrillation is associated with an increased risk of cognitive impairment and dementia. The mechanisms are not well known, but they are probably multifactorial and involve atrial myopathy, cardio-embolism, cerebral hypoperfusion, and comorbidities (systemic vascular sclerosis, disease of the small cerebral vessels, inflammation, etc.). Atrial fibrillation therapy could have a protective effect on dementia through diversified actions: (i) prevention of left atrial remodelling; (ii) prevention of cardio-embolism and silent (and not) cerebral infarcts; (iii) improvement of cardiac output and cerebral perfusion. Randomized trials will be needed to clarify the links between left atrium and dementia and to identify the most appropriate therapeutic strategies.

Refining the Eikonal Model to Reproduce the Influence of Atrial Tissue Geometry on Conduction Velocity

Abstract Atrial fibrillation is responsible for a significant and steadily rising burden. Simultaneously, the treatment options for atrial fibrillation are far from optimal. Personalized simulations of cardiac electrophysiology could assist clinicians in the risk stratification and therapy planning for atrial fibrillation. However, the use of personalized simulations in clinics is currently not possible due to either too high computational costs or non-sufficient accuracy. Eikonal simulations come with low computational costs but cannot replicate the influence of cardiac tissue geometry on the conduction velocity of the wave propagation. Consequently, they currently lack the required accuracy to be applied in clinics. Biophysically detailed simulations on the other hand are accurate but associated with too high computational costs. To tackle this issue, a regression model is created based on biophysically detailed bidomain simulation data. This regression formula calculates the conduction velocity dependent on the thickness and curvature of the heart wall. Afterwards the formula was implemented into the eikonal model with the goal to increase the accuracy of the eikonal model without losing its advantage of computational efficiency. The results of the modified eikonal simulations demonstrate that (i) the local activation times become significantly closer to those of the biophysically detailed bidomain simulations, (ii) the advantage of the eikonal model of a low sensitivity to the resolution of the mesh was reduced further, and (iii) the unrealistic occurrence of endo-epicardial dissociation in simulations was remedied. The results suggest that the accuracy of the eikonal model was significantly increased. At the same time, the additional computational costs caused by the implementation of the regression formula are neglectable. In conclusion, a successful step towards a more accurate and fast computational model of cardiac electrophysiology was achieved.

Atrial fibrillation ablation: the position of computed tomography in pre-procedural imaging

Abstract Atrial fibrillation (AF) is the most common supraventricular arrhythmia. Despite significant advances in its treatment, it still remains one of the leading causes of cardiovascular morbidity and mortality. In the last two decades, pulmonary vein isolation (PVI) was developed as the most effective treatment option. The reported effectiveness of a single ablation procedure ranges from 40% to 69% with single, and up to 88% with repeated procedures, with acceptable safety profile. The PubMed database was searched, using terms including ‘atrial fibrillation ablation’, ‘pulmonary vein isolation’, ‘computed tomography’, ‘pulmonary vein anatomy’ and ‘ovality index’. Papers were reviewed for relevance and scientific merit. Different imaging techniques are used for pre-procedural assessment of left atrial (LA) anatomy, of which computed tomography (CT) is the most common. It allows assessing pulmonary vein (PV) anatomy, the LA wall thickness in different regions and the left atrial appendage (LAA) anatomy, together with excluding the presence of intracardiac thrombi. Pre-procedural PVs imaging is important regardless of the selected ablation technique, however, cryoballoon (CB) ablation seems to be particularly anatomy-dependent. Additionally, CT also permits assessment of several PVs characteristics (geometry, dimensions, angulations, the ostium area, orientation and ovality index (OI), which are essential for the patients’ qualification and designing the strategy of AF ablation. In this paper, we have reviewed the role of CT imaging in patients undergoing ablation procedure due to recurrent/symptomatic atrial fibrillation. Moreover, we discussed the relevant literature.

Decoding the PITX2-controlled genetic network in atrial fibrillation.

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia and a major risk factor for stroke, often arises through ectopic electrical impulses derived from the pulmonary veins (PVs). Sequence variants in enhancers controlling expression of the transcription factor PITX2, which is expressed in the cardiomyocytes (CMs) of the PV and left atrium (LA), have been implicated in AF predisposition. Single nuclei multiomic profiling of RNA and analysis of chromatin accessibility combined with spectral clustering uncovered distinct PV- and LA-enriched CM cell states. Pitx2-mutant PV and LA CMs exhibited gene expression changes consistent with cardiac dysfunction through cell type–distinct, PITX2-directed, cis-regulatory grammars controlling target gene expression. The perturbed network targets in each CM were enriched in distinct human AF predisposition genes, suggesting combinatorial risk for AF genesis. Our data further reveal that PV and LA Pitx2-mutant CMs signal to endothelial and endocardial cells through BMP10 signaling with pathogenic potential. This work provides a multiomic framework for interrogating the basis of AF predisposition in the PVs of humans.

New evidence: Cryoballoon ablation vs. antiarrhythmic drugs for first-line therapy of atrial fibrillation.

Atrial fibrillation (AF) is a commonly encountered chronic and progressive heart rhythm disorder, characterized by exacerbations and remissions. Contemporary clinical practice guidelines recommend a trial of antiarrhythmic drugs (AADs) as the initial therapy for sinus rhythm maintenance; however, these medications have modest efficacy and are associated with significant adverse effects. Recently, several trials have demonstrated that an initial treatment strategy of cryoballoon catheter ablation significantly improves arrhythmia outcomes (e.g. freedom atrial tachyarrhythmia and reduction in arrhythmia burden), produces clinically meaningful improvements in patient-reported outcomes (e.g. symptoms and quality of life), and significantly reduces subsequent healthcare resource utilization (e.g. hospitalization), without increasing the risk of serious or any adverse events. These findings are relevant to patients, providers, and healthcare systems, helping inform the decision regarding the initial choice of rhythm-control therapy in patients with treatment-naïve AF.

Expert Opinion on the Use of Novel Oral Anticoagulants for Stroke Prevention in Non-valvular Atrial Fibrillation for the Primary Care Setting in India: A Literature Review.

Atrial fibrillation (AF), the most prevalent cardiac arrhythmia encountered in clinical practice, is linked with substantial morbidity and mortality due to accompanying risk of stroke and thromboembolism. Patients with AF are at a five-fold higher risk of suffering from a stroke. Anticoagulation therapy, with either vitamin K antagonists or novel oral anticoagulants (NOACs), is a standard approach to reduce the risk. Consultant physicians (CPs) in India are the primary point of contact for the majority of patients before they approach a specialist. The CPs may face challenges in screening and diagnosing AF patients. The apprehensions associated with managing AF patients with anticoagulants, further add to the challenges of a CP. This review aimed to identify the key decision points for the CPs to diagnose AF and initiate anticoagulation in patients with non-valvular AF (NVAF) and bring to the table a simplified recommendation supported by expert opinion and guidelines for stroke prevention in NVAF patients.