Editorial: Atrial Fibrillation: Technology for Diagnosis, Monitoring, and Treatment

Atrial fibrillation (AF) is the most common sustained clinical arrhythmia. With a 2.4-fold risk increase, AF is the leading cause of embolic stroke. It also increases the risk for heart failure 5-fold and mortality 2-fold 1,2 . AF is reaching an epidemic proportion estimated to affect 0.51% of worldwide population and its prevalence is estimated at more than 37 million worldwide. The prevalence of AF increased by a 33% en the last 20 years and is expected to increase by more than 60% in 2050 3,4 . Its prevalence increases with age and is predicted to further surge in the future. Overall, AF is a major societal burden with immense financial costs associated with the care of patients, mostly on hospitalization and complications such as stroke 5 . It is estimated that the total annual incremental costs of AF care can reach $26 billion in the US 6 and AF costs across several European countries account for 0.28-2.60% of their total healthcare spending 3,7, 8 .The reasons for the high burden of AF may lay in its heterogenous, multi-factorial and progressive nature; despite intense research efforts, its initiation, sustenance and termination mechanisms are still poorly understood, and therapy remains suboptimal 9 . It is widely accepted that both AF research, healthcare delivery and outcomes can be improved by advancement of technology 5 . This Research Topic presents a collection of 37 original and review papers focusing on technological challenges and advances for improved understanding of AF and better diagnosis, monitoring and management of the arrhythmia. A total of 262 students and faculty of diverse background have contributed to the papers and highlight the important role of a multi-discipline research, particularly by next generation investigators, in advancing AF therapy. This is a provisional file, not the final typeset article When pharmacological cardioversion fails, atrial arrhythmias are typically treated with catheter ablation. In such case, characterizing the atrial electrical activity and structure in patients may constitute an important step towards a successful intervention. This step mostly relies on various methods for electrical activity and tissue characteristics mapping to identify the arrhythmogenic substrate. Salinet et al. review the use of non-invasive electrocardiographic imaging for AF characterization for ablation guidance and discuss the technological and validation requirements. Their method successfully identifies and quantifies the spatiotemporal repetition of high DF sites showing that recurring patterns offer a more comprehensive dynamic insight of persistent AF. The potential benefit of ablating such regions remains to be shown. An important element of catheter ablation intervention is a pacing protocol to test for non-inducibility of arrhythmia post-ablation. Azzolin et al. perform an in-silico investigation searching for a standardized protocol to induce arrhythmia after an intervention. They propose a novel method of pacing at the end of the effective refractory period for assessment of arrhythmia vulnerability. The openly available protocol can become a standard for in silico and clinical arrhythmia inducibility testing.Successful AF termination by ablation is thought to dependent on the detection of drivers and their interactions with the atrial activity at large. Among the different possible driver types, reentrant and rotor patterns have gained the most attention. Spector et al. show in a computational propagation model that the degree to which a focal reentrant driver and the surrounding chaotic activation interact depends on the relative characteristics of the anatomical and functional (rotor) reentrant substrates. Ganesan et al. developed a quantitative birth-death framework providing insight into the wavelet and rotor dynamics in AF and their spontaneous termination. In the clinic, rotor detection relies on signals recorded by multi-electrode catheters, which can be influenced by a number of structural parameters and therefore, an efficient design is key. Bartolucci et al. propose a tool for testing the ability of different catheter shapes to detect rotors in different conditions that could assist in the design of new mapping catheters.A possible factor contributing to AF recurrence after catheter ablation is atrial stretch. Lee et al.show that higher left atrium (LA) wall stress was associated with poorer rhythm outcomes after catheter ablation. Further, Eichenlaub et al. report in a fifty-patient study how LA hypertension, electrical conduction slowing, and mechanical dysfunction are all associated with relevant atrial cardiomyopathy. Their study suggests the use of these atrial cardiomyopathy markers for risk stratification of arrhythmia recurrence following catheter ablation.Heterogeneous intra-atrial conduction is known to facilitate both initiation and perpetuation of AF. In the work by Gaeta et al., a method for high resolution measurements of local activation time (LAT) differences for characterizing local changes in myocardial conduction velocity was developed. The methodology was tested with in vivo bipolar electrograms (EGMs) which showed a good agreement with standard LAT annotations and unipolar waveforms. Ye et al. developed a patient-specific signal fingerprint based on EGM features to characterize the severity and extensiveness of heterogeneity in conduction. Riccio et al. simulate impulse propagation to demonstrate a modified version of the omni-polar electrogram method for improved characterization of substrate and propagation, reduction of residual sensitivity to directionality over the standard approach and improved robustness against noise. The role of substrate heterogeneities causing conduction velocity inhomogeneitiesoften related to fibrosiswas investigated using a computational model by Pagani et al.. Their simulations show how substrate characteristics may contribute to inducing and sustaining arrhythmias and demonstrate how localized reentries tend to anchor in areas of severe slow conduction in persistent AF.The consequences of AF are not only related to heart rhythm and rate alterations but could also importantly lead to thrombus formation, most likely in left atrial appendage (LAA). Sanatkhani et al. imaged the LA appendage in a cohort of 16 AF patients and simulated the hemodynamics therein. Quantification of the appendage geometrical complexity and its characteristic time of blood residency during stasis could enhance ability to stratify stroke risk in AF patients. Similarly, Paliwal et al. investigate with personalized LA hemodynamic in silico modelling the mechanisms for increased stroke risk in patients with atrial fibrotic remodelling, indicating that patients with high LA fibrotic burden have a higher probability for clot formation and thus a higher risk of stroke.The autonomic nervous system (ANS) has an important role in the generation and maintenance of cardiac arrhythmias. Therefore, characterizing ANS activity during AF may facilitate personalized treatment. The activity of the ANS during AF can be quantified in a number of ways as for example through the magnitude of respiratory induced modulation of the f-wave frequency during AF as This is a provisional file, not the final typeset article shown by Abdollahpur et al. The ANS consists of multiple ganglionated plexi (GP) and axons, which innervate the neighbouring atrial myocardium and control their electrophysiological properties. GP ablation has been associated with a decreased risk of AF recurrence; however, accurate localization of GPs is required for ablation to be effective. Finally, pharmacological rate control during AF can be an alternative to attempting to terminate AF in rhythm control strategies. Karlsson et al. developed a network model to estimate conduction delay and refractory period of the atrio-ventricular node from ECG data from a patient at baseline and during treatment with a heart rate control drug. They demonstrate the ability of the methodology to assess the effect of rate control drugs.We are excited to present a collection of studies describing recent laboratory, computational and clinical approaches in AF. We hope that scientists, engineers, clinicians, and patients interested in the topic will find this comprehensive overview of basic and translational trends inspiring and promoting improved understanding and therapies of AF.