Atrial fibrillation: the era of scientific breakthrough

Atrial fibrillation (AF) is a common cardiac arrhythmia, affecting an estimated 33.5 million individuals worldwide. The prevalence is increasing mainly due to the aging population, with more older patients surviving potential fatal cardiovascular events which leaves them exposed to the more insidious effects of underlying cardiovascular disease, including AF. In the recent years, a trend towards an increasing proportion of individuals who develop AF at younger age has been observed which has not been fully understood yet but is thought to be due to the changing genetic population make-up, new risk factors and associated disease, and a better awareness of the arrhythmia in lieu of effective curative and preventative therapies.1 This Focused Issue of EP-Europace is a tribute to significant advances in the medical and interventional management of AF, particularly, cutting-edge research is the field of ablation. In their review, Drs Hammond-Haley, Providência, and Lambiase2 challenge the existing temporal rhythm-based classification as well as risk stratification schemes for not accounting sufficiently for diverse clinical and therapeutical outcomes and disease progression in different types of AF or not incorporating newer risk factors and markers, such as comprehensive imaging, blood biomarkers, and genetic insights, that may provide a more pathophysiology- and individual patient-tailored approach to risk stratification and may be better suited to the changing arrhythmia landscape. The last decade has seen a growing interest in screening for AF and a galaxy of external event recorders and implanted devices has been developed and validated in the general population and specific clinical settings such as monitoring for AF recurrence after ablation and device-detected subclinical arrhythmias in patients with pacemaker and implantable cardioverter-defibrillators.3 The incidence of AF detection increases with the intensity and continuity of ECG monitoring. However, the causal relationship between subclinical AF or device-detected atrial high rate episodes and a consistently increased risk of stroke as well as their temporal relationship remains controversial. Berge et al.4 have found a relatively low diagnostic yield of 0.9% using 2-week intermittent ECG sampling and argue that the yield of screening is lower in populations with a high degree of health awareness and well-controlled risk factors. However, intuitively, identification of previously unrecognized AF should instigate appropriate treatment. The study by Engdahl et al.5 is the first report on long-term outcome of population screening for AF which demonstrated a high adherence to anticoagulant therapy and an associated reduction in the incidence of ischaemic stroke associated with running the AF screening programme. This emphasizes an additional role that AF screening programmes may play by not only identifying those at risk, but ensuring the adherence through improved awareness and education. Significant technological advancements have considerably enhanced AF detection capabilities of cardiac monitoring devices resulting in extending the duration of monitoring using external recorders and improving the reliability of AF recognition algorithm in implanted monitors.6,7 Much of AF seems to stem from cardiac disease, such as hypertension, heart failure, and ischaemic heart disease, whereby aiming at better treatment of these conditions may not only deter AF, but to modify survival in patients with AF.8 Using the UK Biobank data on over half a million middle-aged to older participants, Jani et al.9 have found risk of death to be six-fold higher in patients with AF and four or more co-morbidities. The development of pharmacological, preferably preventative strategies is vital in order to manage AF at the population level. There is accumulating evidence linking the more recently identified risk factors with the pathophysiology of AF. Obstructive sleep apnoea is associated with increased rotor burden in patients undergoing focal impulse and rotor modification (FIRM) guided AF ablation. In the study by Friedman et al.,10 FIRM mapping has demonstrated increased rotor burden in the patients with obstructive sleep apnoea and a modifying effect of continuous positive air pressure therapy on the number of right atrial rotors. A series of technological developments has been reported in the field of interventional therapies for AF, including novel electroanatomical mapping (EAM) tools which can further advance the arrhythmia substrate evaluation and define individual patient-tailored ablation strategies with a potential to improve ablation outcome and reduce complication rates. Enhancement of the signal quality has been the focus of research, leading to the introduction of high-resolution EAM catheters and systems, with a possibility of the rapid automatic acquisition of maps with high spatiotemporal resolution. The potential benefits of such systems have been demonstrated in a series of feasibility studies, two of which are presented in this issue of EP-Europace. High-resolution EAM has been shown useful in guiding the complex re-do procedures, allowing a greater precision in the identification of reconnection gaps in PVs.11 The clinical associations of left atrial low-voltage areas detected on high-resolution EAM maps in patients undergoing ablation for AF have been identified in a study by Müller et al.12 who, for the first time, reported a 13% increased risk of silent cerebral infarcts per each 1% of the detected low-voltage area, independently of clinical risk factors. Since the concept of PV ablation for treatment of AF has been introduced in late 90s, device industry has led extensive research to endeavour to perfect the existing and develop new technologies such as precise mapping and novel catheter systems and energy sources as well as the introduction of enhanced, modified protocols that have significantly improved the effectiveness and safety of ablation procedures. Contact force (CF)-sensing ablation catheters were designed with the aim of enabling the creation of more durable lesions. Philips et al.13 have employed the ‘CLOSE’ strategy which is a novel CF-guided approach to enclose PVs with contiguous and optimized radiofrequency lesions. Compared with a historical control group of conventional CF-guided PV isolation, this approach is associated with higher rates of acute durable isolation of PVs and increased single-procedure arrhythmia-free survival at 1 year. The prospective, multicentre observational registry reported by De Potter et al.14 has shown that ablation with a CF-sensing catheter had high acute success rates of 98.8% and 12-month freedom from symptomatic AF of 75.7% and constitute an important addition to the literature. The group led by Andrea Natale, carried out a prospective, open-label, non-randomized study exploring the feasibility and safety of ablation with a new CF-sensing catheter with 56-hole porous tip designed for uniform cooling and reduction of fluid delivery.15 At this early stage, the primary adverse event rate was 2.5% which is comparable to that reported for traditional irrigated catheters. The study by Wolf et al.16 was the first study to evaluate and validate point-by-point radiofrequency (RF) ablation combining criteria of contiguous and optimized lesions for left atrial linear lesions. A single linear set of RF lesions was delivered at the roof and posterior mitral isthmus according to the ALINE criteria, i.e. point-by-point RF delivery (up to 35W) using the strict criteria of contiguity and indirect lesion depth assessment (ablation index ≥550) and was feasible and effective at the roof, with a very high rate of first-pass roof line block. Technological advances and growing operators’ experience and confidence have led to the extension of indications from strictly paroxysmal AF to much more challenging cases of persistent and long-standing persistent AF.17 Albeit these patients now represent a significant proportion of those treated with ablation, success rates remain disappointing at a 43% probability of sinus rhythm maintenance after a single procedure without the use of antiarrhythmic drugs as assessed in a meta-analysis of 113 studies in over 18 000 patients, whilst repeat procedures and/or the use of drugs increased success to 69%.18 Of note, the addition of extra-PV substrate ablation was associated with a declining efficacy compared with PV ablation alone, suggesting that the ablation strategy should be tailored to the individual patient needs, after the extensive evaluation of the substrate characteristics by more precise EAM. Several recent studies have investigated a number of non-invasive scoring systems such as the ALARMEc, BASE-AF, APPLE, CAAP-AF, and DR-FLASH, which include clinical variables and biomarkers to predict ablation outcomes and/or atrial arrhythmogenic substrate.19 In the quest to achieve optimal ablation outcomes, these tools have the potential to inform patient risk assessment and help guide selection for catheter ablation on an individual patient basis. Two new scores have been reported: the ATLAS score [age >60 years (1 point), female sex (4 points), non-paroxysmal AF (2 points), current smoking (7 points), and indexed left atrial volume (1 point for each 10 mL/m2)] to predict AF recurrence after the first ablation procedure demonstrating a good discriminative power, with c-statistic of 0.75,20 and the PLAAF score (persistent AF, left atrial area, abnormal PV anatomy, AF history, and female gender) to be used to predict AF recurrence in patients undergoing ablation with cryoballoon.21 These attempts represent an important step towards identifying those persistent AF patients least likely to benefit from catheter ablation. Many of new developments in mapping and ablation field are at the preclinical level, with promising efficacy results when implemented in the clinical arena, and many are aimed at a reduction of potential complications by better understanding the physiology of PV ablation. Ghosh and McGuire22 carried out second-generation cryoballoon ablation simulations in vitro using a PV phantom constructed from bovine muscle in order to assess the effect of incomplete PV occlusion. In this experiment, incomplete venous occlusion resulted in warmer balloon and tissue temperatures and shorter balloon warming times, which in the clinical setting may lead to late electrical reconnection of the pulmonary vein, and recurrent AF. Mansour et al.23 reports the feasibility of safe and effective delivery of high-power short-duration radiofrequency ablation lesions. The safe implementation of this ablation technique was made possible due to the utilization of an advanced ablation catheter system equipped with novel thermocouple technology that allows accurate measurement of catheter–tissue interface temperature. In summary, there is high-volume basic science and clinical research in the field of AF diagnosis and management empowering the physicians and their patients with a new knowledge and better, safer therapies. We sincerely hope that you enjoy reading this Focused Issue, and that these insights will be helpful to you for the management of patients with AF. Conflict of interest: G.H. is Editor-in-Chief of EP-Europace. He reports research grants from Abbott, Biotronik, Boston Scientific, and Medtronic to the Heart Center Leipzig (no personal fees). I.S. is Deputy Editor of EP-Europace and has nothing to disclose in respect of this work.