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Risk factor management and atrial fibrillation
<span class="paragraphSection"><div class="boxTitle">Abstract</div>The management of atrial fibrillation (AF) is multifaceted and treatment paradigms have changed significantly in the last century. The treatment of AF requires a comprehensive approach which goes beyond the treatment of the arrhythmia alone. Risk factor management has been introduced as a crucial pillar of AF management. As a result, the landscape of care delivery is changing as well, and novel models of comprehensive care delivery for AF have been introduced. This article reviews the evidence for the role of risk factor management in AF, how this can be integrated and implemented in clinical practice by applying novel models of care delivery, and finally identifies areas for ongoing research and potential healthcare reform to comprehensively manage the burgeoning AF population.</span>

The bidirectional interaction between atrial fibrillation and heart failure: consequences for the management of both diseases
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Atrial fibrillation (AF) and heart failure (HF) are both highly prevalent diseases and are accompanied by a significant disease burden and increased mortality. Although the conditions may exist independently, they often go hand in hand as each is able to provoke, sustain, and aggravate the other. In addition, the diseases share a risk profile with several coinciding cardiovascular risk factors, promoting the odds of developing both AF and HF separately from each other. When the diseases coexist, this provides additional challenges but also opportunities for the optimal treatment. The recommended management of the comorbidities has been much debated in the past decades. In this review, we describe the pathophysiological coherence of AF and HF, illustrate the current knowledge on the management of them as comorbidities of each other and look forward to future developments in this field.</span>

Innovations and paradigm shifts in atrial fibrillation ablation
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Treatment of symptomatic atrial fibrillation has seen important changes in the past decades. Advancements have especially been made in the field of non-pharmacological treatment of this disease. Patients in whom a rhythm control strategy is chosen the place of catheter ablation has become more frontline therapy in the past years. The procedure itself has also seen changes in technologies that can be used, either using point-by-point radiofrequency or one of the single-shot techniques. One of the major limitations that remain is that re-do procedures are often necessary due to incomplete pulmonary vein isolation and/or atrial fibrillation being initiated by other mechanisms than pulmonary vein triggers. Therefore, there is further need for developing ablation tools that reproducibly isolate the pulmonary vein transmurally. Furthermore, addressing the underlying conditions before and after catheter ablation has been shown to be of great importance. In this review, we will give an overview of the evolution of catheter ablation, highlight the latest technologies and their future endeavours, and lifestyle modifications are being discussed as part of the catheter ablation strategy.</span>

The RACE to the EAST. In pursuit of rhythm control therapy for atrial fibrillation—a dedication to Harry Crijns
<span class="paragraphSection"><div class="boxTitle">Abstract</div>The RACE trial was one of the first landmark trials to establish whether restoring and maintaining sinus rhythm could reduce morbidity and mortality in patients with atrial fibrillation (AF). Its neutral outcome shaped clinical decision-making for almost 20 years. However, there were two important treatment-related factors associated with mortality of rhythm control therapy at that time: One was safety of antiarrhythmic drug therapy, and the other one withdrawal of anticoagulation after restoration of sinus rhythm. Both concerns have been overcome, and, moreover, important knowledge considering the importance of time for the treatment of AF has been gained. These insights led to the concept of the EAST-AFNET 4 trial, and after more than two decades in the pursuit of ongoing therapeutic improvement, early rhythm control therapy has demonstrated to reduce a composite of cardiovascular death, stroke, and hospitalization for worsening of HF or acute coronary syndrome, by 21% (first primary outcome, absolute reduction 1.1 per 100 patient-years). For this entire period, Harry Crijns characterized the treatment of AF patients, and contributed decisively to realizing the benefit of rhythm control therapy. It is almost easier to list the clinical trials without Harry's involvement than to list those which he co-designed and led.</span>

A hybrid approach to complex arrhythmias
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Despite many years of research, the different aspects of the mechanism of atrial fibrillation (AF) are still incompletely understood. And although the latest guidelines recommend catheter ablation with pulmonary vein isolation as a rhythm control strategy, long-term results in persistent and long-standing persistent AF are suboptimal. Historically, a mechanistic-based patient-tailored approach for the treatment of AF was impossible because of the lack real-time mapping techniques and advanced ablation tools. Therefore, surgeons created lesion sets based upon the anatomy of both atria and the safety of the incisions made by the knife. These complex open-heart procedures had to be performed through a sternotomy on the arrested heart and where therefore not generally adopted. The use of controlled energy sources such as cryothermy and radiofrequency where the first step to make the creation of these lesions less complex. With the development and improvement of electrophysiology techniques and catheters, this invasive and solely anatomical approach could again be partially redesigned. Now less invasive, it prepared the way for collaboration between electrophysiologists working on the endocardial side of the heart and cardiac surgeons providing epicardial access. The introduction of video-assisted technology and hybrid procedures has further increased the possibilities of new successful therapies. Now more than 40 years since the beginning of this exciting maze of AF procedures and still working towards a less aggressive and more comprehensive approach we give an overview of the history of the different minimally invasive surgical solutions and of the hybrid approach.</span>

Role of genetics in atrial fibrillation management
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Atrial fibrillation (AF) management has significantly improved during the career of professor Crijns. Research was implemented into guidelines and clinical practice. However, despite advances in AF management, large differences between individual treatment responses still exist and the mechanisms underlying initiation and perpetuation of AF are not completely understood. International collaborations have revealed the genetic contribution to AF and steps towards improving AF management are being made. In this short review, the most important paradigms shifts in the field of AF genetics are recognized and the future role of genetics in personalized management of AF is discussed.</span>

Antiarrhythmic drugs for atrial fibrillation: lessons from the past and opportunities for the future
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Atrial fibrillation (AF) remains a highly prevalent and troublesome cardiac arrhythmia, associated with substantial morbidity and mortality. Restoration and maintenance of sinus rhythm (rhythm-control therapy) is an important element of AF management in symptomatic patients. Despite significant advances and increasing importance of catheter ablation, antiarrhythmic drugs (AADs) remain a cornerstone of rhythm-control therapy. During the past 50 years, experimental and clinical research has greatly increased our understanding of AADs. As part of the special issue on paradigm shifts in AF, this review summarizes important milestones in AAD research that have shaped their current role in AF management, including (i) awareness of the proarrhythmic potential of AADs; (ii) increasing understanding of the pleiotropic effects of AADs; (iii) the development of dronedarone; and (iv) the search for AF-specific AADs. Finally, we discuss short- and long-term opportunities for better AF management through advances in AAD therapy, including personalization of AAD therapy based on individual AF mechanisms.</span>

Early atrial fibrillation detection and the transition to comprehensive management
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Current atrial fibrillation (AF) guidelines recommend screening for AF in individuals above 65 years or with other characteristics suggestive of increased stroke risk. Several mobile health (mHealth) approaches are available to identify AF. Although most wearables or ECG machines include algorithms to detect AF, an ECG confirmation of AF is necessary to establish a suspected diagnosis of AF. Early detection of AF is important to allow early initiation of AF management, and early rhythm control therapy lowered risk of adverse cardiovascular outcomes among patients with early AF aged &gt;75 or with a CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥2 and cardiovascular conditions in the EAST-AFNET 4 study. Strategies for early AF detection should be always linked to a comprehensive work-up infrastructure organized within an integrated care pathway to allow early initiation and guidance of AF treatment in newly detected AF patients. In this review article, we summarize strategies and mHealth approaches for early AF detection and the transition to early AF management including AF symptoms evaluation and assessment of AF progression as well as AF risk factors.</span>

The road goes ever on: innovations and paradigm shifts in atrial fibrillation management
<span class="paragraphSection">Symptoms suggestive of atrial fibrillation (AF) have been described for centuries, and William Harvey already noted an undulating palpitation of the right auricle in animals in 1628.<a href="#euab061-B1" class="reflinks"><sup>1</sup></a> However, it was not until 1906 that the Dutch physician and physiologist Willem Einthoven published the first electrocardiogram showing AF in a patient and it took several more years before AF was recognized as a clinical entity.<a href="#euab061-B2" class="reflinks"><sup>2</sup></a> Today, in 2021, AF remains a major clinical challenge, negatively affecting the morbidity and mortality of millions of individuals worldwide<a href="#euab061-B3" class="reflinks"><sup>3</sup></a> and consuming a significant share of the healthcare budget in the Western world.<a href="#euab061-B4" class="reflinks"><sup>4</sup></a> Since the initial reports of ‘rebellious palpitations’,<a href="#euab061-B2" class="reflinks"><sup>2</sup></a> our understanding of the underlying mechanisms, debilitating consequences and therapeutic management of AF have advanced tremendously. The progress has been particularly rapid during the last 40 years: in 1980, there were 221 papers published on AF according to PubMed, but by 2020 this number had increased to 7849 papers in 1 year. Together, this research has led to a number of important innovations and paradigm shifts in AF management.</span>

Paradigm shifts in electrophysiological mechanisms of atrial fibrillation
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Determining the sequence of activation is a major source of information for understanding the electrophysiological mechanism(s) of atrial fibrillation (AF). However, the complex morphology of the electrograms hampers their analysis, and has stimulated generations of electrophysiologists to develop a large variety of technologies for recording, pre-processing, and analysis of fibrillation electrograms. This variability of approaches is mirrored by a large variability in the interpretation of fibrillation electrograms and, thereby, opinions regarding the basic electrophysiological mechanism(s) of AF vary widely. Multiple wavelets, different types of re-entry including rotors, double layers, multiple focal activation patterns all have been advocated, and a comprehensive and commonly accepted paradigm for the fundamental mechanisms of AF is still lacking. Here, we summarize the Maastricht perspective and Cleveland perspective regarding AF mechanism(s). We also describe some of the key observations in mapping of AF reported over the past decades, and how they changed over the years, often as results of new techniques introduced in the experimental field of AF research.</span>