The changing circumstance of atrial fibrillation - progress towards precision medicine.

The prevalence of atrial fibrillation (AF) in the general population is between 1% and 2% in the developed world and is higher in men than in women. The arrhythmia occurs much more commonly in the elderly, and the estimated lifetime risk of developing AF is one in four for men and women aged 40 years and above. Projected data from multiple population-based studies in the USA and Europe predict a two- to threefold increase in the number of AF patients by 2060. The high lifetime risk of AF and increased longevity underscore the important public health burden posed by this arrhythmia worldwide. AF has multiple aetiologies and a broad variety of presentations. The primary pathologies underlying or promoting the occurrence of AF vary more than for any other cardiac arrhythmia, ranging from autonomic imbalance to organic heart disease and metabolic disorders, such as diabetes mellitus, metabolic syndrome, hyperthyroidism and kidney disease, and lifestyle factors such as smoking, alcohol consumption and participation in endurance sports. Biomarkers are increasingly being investigated and, together with clinical and genetic factors, will eventually lead to a clinically valuable detailed classification of AF which will also incorporate pathophysiological determinants and mechanisms of the arrhythmia. In turn, this will allow the development and application of precision medicine to this troublesome arrhythmia.

A tailored treatment strategy: a modern approach for stroke prevention in patients with atrial fibrillation.

The main priority in atrial fibrillation (AF) management is stroke prevention, following which decisions about rate or rhythm control are focused on the patient, being primarily for management of symptoms. Given that AF is commonly associated with various comorbidities, risk factors such as hypertension, heart failure, diabetes mellitus and sleep apnoea should be actively looked for and managed in a holistic approach to AF management. The objective of this review is to provide an overview of modern AF stroke prevention with a focus on tailored treatment strategies. Biomarkers and genetic factors have been proposed to help identify 'high-risk' patients to be targeted for oral anticoagulation, but ultimately their use must be balanced against that of more simple and practical considerations for everyday use. Current guidelines have directed focus on initial identification of 'truly low-risk' patients with AF, that is those patients with a CHA2 DS2 -VASc [congestive heart failure, hypertension, age ≥75 years (two points), diabetes mellitus, stroke (two points), vascular disease, age 65-74 years, sex category] score of 0 (male) or 1 (female), who do not need any antithrombotic therapy. Subsequently, patients with ≥1 stroke risk factors can be offered effective stroke prevention, that is oral anticoagulation. The SAMe-TT2 R2 [sex female, age <60 years, medical history (>2 comorbidities), treatment (interacting drugs), tobacco use (two points), race non-Caucasian (two points)] score can help physicians make informed decisions on those patients likely to do well on warfarin (SAMe-TT2 R2 score 0-2) or those who are likely to have a poor time in therapeutic range (SAMe-TT2 R2 score >2). A clinically focused tailored approach to assessment and stroke prevention in AF with the use of the CHA2 DS2 VASc, HAS-BLED [hypertension, abnormal renal/liver function (one or two points), stroke, bleeding history or predisposition, labile international normalized ratio, elderly (>65 years) drugs/alcohol concomitantly (one or two points)] and SAMeTT2 R2 scores to evaluate stroke risk, bleeding risk and likelihood of successful warfarin therapy, respectively, is discussed.

An update on atrial fibrillation: focus on stroke risk reduction strategies.

Atrial fibrillation (AF) currently affects approximately 2% of the general adult population, and the number of patients suffering from AF constantly increases. Although the occurrence of AF rarely poses an immediate threat to patient's survival, the arrhythmia is associated with significant cardiovascular morbidity and mortality mostly resulting from ischemic stroke or systemic thromboembolism, or heart failure. Overall, patients with AF have a 5-fold greater risk of stroke compared to individuals in sinus rhythm, but individual stroke risk depends on the presence of various stroke risk factors, and optimal stroke prevention is essential for AF patients. Several major advances in AF-related stroke prevention have been achieved recently, including the refinements in stroke and bleeding risk assessment with an essential shift in the recognition of AF patients who should be offered oral anticoagulant (OAC) therapy, the advent of non-vitamin K antagonist oral anticoagulants (NOACs) which are increasingly used in the "real-world" setting, as well as the development of non-pharmacological means of thromboprophylaxis in AF patients (e.g., left atrial appendage [LAA] occluding devices). In this review article, we summarize these recent developments in stroke risk reduction strategies and discuss the main principles of decision-making regarding OAC therapy in AF patients.

Lone atrial fibrillation - an overview.

Atrial fibrillation (AF) sometimes develops in younger individuals without any evident cardiac or other disease. To refer to these patients who were considered to have a very favourable prognosis compared with other AF patients, the term 'lone' AF was introduced in 1953. However, there are numerous uncertainties associated with 'lone' AF, including inconsistent entity definitions, considerable variations in the reported prevalence and outcomes, etc. Indeed, increasing evidence suggests a number of often subtle cardiac alterations associated with apparently 'lone' AF, which may have relevant prognostic implications. Hence, 'lone' AF patients comprise a rather heterogeneous cohort, and may have largely variable risk profiles based on the presence (or absence) of overlooked subclinical cardiovascular risk factors or genetically determined subtle alterations at the cellular or molecular level. Whether the implementation of various cardiac imaging techniques, biomarkers and genetic information could improve the prediction of risk for incident AF and risk assessment of 'lone' AF patients, and influence the treatment decisions needs further research. In this review, we summarise the current knowledge on 'lone' AF, highlight the existing inconsistencies in the field and discuss the prognostic and treatment implications of recent insights in 'lone' AF pathophysiology.

Practical use of dabigatran etexilate for stroke prevention in atrial fibrillation.

Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists (VKAs) have been the standard of care for stroke prevention in patients with AF since the early 1990s. They are very effective for the prevention of cardioembolic stroke, but are limited by factors such as drug-drug interactions, food interactions, slow onset and offset of action, haemorrhage and need for routine anticoagulation monitoring to maintain a therapeutic international normalised ratio (INR). Multiple new oral anticoagulants have been developed as potential replacements for VKAs for stroke prevention in AF. Most are small synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). These drugs have predictable pharmacokinetics that allow fixed dosing without routine laboratory monitoring. Dabigatran etexilate, the first of these new oral anticoagulants to be approved by the United States Food and Drug Administration and the European Medicines Agency for stroke prevention in patients with non-valvular AF, represents an effective and safe alternative to VKAs. Under the auspices of the Regional Anticoagulation Working Group, a multidisciplinary group of experts in thrombosis and haemostasis from Central and Eastern Europe, an expert panel with expertise in AF convened to discuss practical, clinically important issues related to the long-term use of dabigatran for stroke prevention in non-valvular AF. The practical information reviewed in this article will help clinicians make appropriate use of this new therapeutic option in daily clinical practice.

New anticoagulation drugs for atrial fibrillation.

Atrial fibrillation (AF) confers an increased risk of ischemic stroke or thromboembolism that is reduced by long-term oral anticoagulant therapy. Until recently, the latter has typically been one from the vitamin K antagonist (VKA) class of drugs. Although highly effective, VKAs have limitations, and their use is challenging for both patients and clinicians. A new generation of oral anticoagulant drugs is emerging, including several drugs that appear to be viable alternatives to VKAs in AF patients.

Lone atrial fibrillation: what is known and what is to come.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in adults, affecting >1% of general population. Atrial fibrillation is commonly associated with structural heart disease and is a major cause of significant cardiovascular morbidity and mortality. AF sometimes develops in a subset of young patients (e.g. aged ≤60 years), with no evidence of associated cardiopulmonary or other comorbid disease (including hypertension), and has been referred to as 'lone AF'. The latter generally has a favourable prognosis; the prognostic and therapeutic implications of an accurate identification of patients with truly lone AF (that is, truly at low risk of complications), if any, would be of the utmost importance. The true prevalence of lone AF is unknown, varying between 1.6% and 30%, depending on the particular study population. Nonetheless, novel risk factors for AF, including obesity, metabolic syndrome, sleep apnea, alcohol consumption, endurance sports, anger, hostility, subclinical atherosclerosis and others, have been increasingly recognised. Also, various underlying pathophysiological mechanisms predisposing to AF, including increased atrial stretch, structural and electrophysiological alterations, autonomic imbalance, systemic inflammation, oxidative stress and genetic predisposition, have been proposed. The growing evidence of these diverse (and numerous) pathogenic mechanisms and factors related to AF inevitably raises the question of whether 'lone AF' does exist at all. In this review article, we summarise the current knowledge of the epidemiology, pathophysiology, clinical course and treatment of patients with so-called 'lone AF' and outline emerging insights into its pathogenesis and the potential therapeutic implications of a diagnosis of lone AF.