Current Pharmaceutical Design - Volume 21, Issue 5, 2015

Patients’ beliefs about their health (and illness), medications and healthcare they receive are important determinants of whether or not they accept recommended treatments; influence their coping responses in relation to their illness; make them adhere to recommended therapy and ultimately affect health outcomes. Incorporation of patients’ preferences for therapy should now be considered an integral part of the decision-making process. This gradual shift in health-care practice from paternalistic to shared-decision making, whereby there is a two-way exchange of information between the patient and healthcare provider and both are involved in the treatment decision, requires a reasonable level of understanding and knowledge of the condition and its treatment by the patient. However, patients with atrial fibrillation (AF) often have poor knowledge about their condition and the benefits and risks of AF and AF treatments. Physicians and other healthcare providers may have doubts over a patient’s ability to adhere to certain treatment regimens, particularly oral anticoagulation, due in part to the lack of patient knowledge, and this may be an important determinant of whether such treatments are even considered as therapeutic options. Further, patients often hold misconceptions about AF and treatment options, which may act as barriers to their acceptance of the condition and adherence to therapy. This review will summarise the literature on the knowledge of patients about AF and its management, how patients’ values and preferences can impact on their treatment choices, the ideal components of patient education, the impact of educational interventions on patients’ knowledge and perceptions of AF, and where appropriate highlight specific issues facing lone AF patients.

Atrial fibrillation (AF) is the most common sustained rhythm disturbance, increasing prevalence with age, in particular in patients with cardiovascular disease. On the other hand, a subset of patients with AF being <60 years old and no evidence of underlying cardiovascular disease, and laboratory tests including thyroid function, echocardiography and exercise” test is well described. This is the called lone AF, where there is no previous cardiovascular disease, and the etiology is unknown. However, in the last years, some new factors have been related to play a role or be associated to incident AF. Conditions such as obesity, sleep apnea, alcohol intake, exercise practice, or genetic factors are associated with the development of this common arrhythmia and make the exclusion diagnosis of lone AF more complicated. The aim of the present manuscript is to provide an overview of these new risk factors for AF, which are becoming of special interest in the study of this common arrhythmia.

The term idiopathic or lone atrial fibrillation (AF) is commonly used in the young and apparently healthy individual who suffers from AF. Although there is conflicting evidence concerning prognosis, these patients are at risk to develop (vascular) comorbidities in the years following AF onset. It is conceivable that early stages of vascular disease, undetectable by the routine diagnostics, may contribute to the pathophysiology of “apparently” idiopathic AF. At present, more advanced diagnostics have become available that can be deployed at low threshold in order to detect early stage or yet subclinical cardiovascular disease. In this respect one could raise the question whether idiopathic AF exists at all or that the arrhythmia acts as a harbinger of as yet undetected underlying vascular disease in this specific population. Assuming that idiopathic AF is the final arrhythmic expression of underlying genetic mutations and/or vascular diseases, high priority should be given to trace identifiable predisposing factors or the presence of early stages of underlying disease in order to treat these, or prevent their complications. A more comprehensive quest for potential hidden causes of idiopathic AF creates new therapeutic dilemmas, but also encourages further research regarding pathophysiology and new early treatment opportunities in patients with atrial fibrillation in general. The present review provides more insight regarding diverse pathophysiological mechanisms in the fundamental basis for idiopathic AF, outlines prognostic and treatment implications, and questions the robustness of its definition.

Lone atrial fibrillation is a set of heterogeneous disorders grouped together due to our limited understanding of their pathophysiology. Rate control and rhythm control are two strategies used to treat atrial fibrillation but neither has shown improvement in mortality. Therefore, the goal of treatment in patients with lone atrial fibrillation is to improve health related quality of life. Anti-arrhythmic medications are not well studied in lone atrial fibrillation patient population in randomized controlled fashion. However, inferences can be made from trials that mainly included paroxysmal atrial fibrillation patients. Anti-arrhythmic medications are useful in maintenance of sinus rhythm and probably improve quality of life in lone atrial fibrillation.

Atrial fibrillation occurring in the absence of cardiovascular disease in individuals younger than 60 years is known as lone atrial fibrillation. Nearly 1-12% of atrial fibrillation is considered to be lone atrial fibrillation. As our understanding of atrial fibrillation grows, we wonder as to whether there is such as thing as “lone” atrial fibrillation? We know that male sex, obesity, obstructive sleep apnea, alcohol consumption and endurance sports increase the risk of developing lone atrial fibrillation. Family history of atrial fibrillation increases the risk strongly and there are several recognized mutations that are causative of lone atrial fibrillation. Common triggers for origin of atrial fibrillation are the pulmonary veins. The atrial substrate provides the reentry circuits for perpetuating the arrhythmia. The autonomic nervous system is a key modulator and allows the continuation of the atrial fibrillation. Catheter ablation has been very effective in the treatment of this condition. The ablation procedure involves isolation of the pulmonary veins, antrum, complex fractionated electrograms and other sites. Alternatively surgical techniques can be used to isolate the pulmonary veins and surgical techniques have evolved to minimally invasive procedures and these are as effective as catheter ablation. Early intervention improves the left atrial remodeling and may lead to fewer recurrences.

Atrial fibrillation is the most common sustained arrhythmia in clinical practice, associated with increased mortality, risk of stroke and heart failure, as well as the reduction of the quality of life. Atrial fibrillation may be encountered in young otherwise healthy individuals, due to the isolated electrophysiological disorder limited mostly to the pulmonary veins and posterior left atrial wall, or associated with the presence of advanced underlying heart disease and numerous cardiac and non-cardiac comorbidities with significant structural remodeling of the atrial myocardium. Due to limited efficacy and serious side effects of antiarrhythmic drugs, catheter ablation of atrial fibrillation, based on the pulmonary vein isolation for paroxysmal atrial fibrillation and adjunctive substrate modification for persistent atrial fibrillation, has emerged as an attractive and promissing alternative therapeutic option for selected patients with atrial fibrillation. In this review article, we discuss the electrophysiological left atrial abnormalities underlying lone atrial fibrillation and the role of pulmonary veins in pathophysiology of arrhythmia, and we summarize results of the studies on the long term outcome of catheter ablation of atrial fibrillation, as well as the studies on comparison of antiarrhythmic drugs with catheter ablation for treatment of atrial fibrillation. In addition, we present available data that provide better understanding of mechanisms, diagnosis, prevention and treatment of specific procedure-related complications and discuss current periprocedural anticoagulation strategies and their impact on the thromboembolic risk reduction.

“Lone” atrial fibrillation (AF) is generally used to refer to patients with AF in the absence of structural heart disease. When the decision for oral anticoagulation is discussed, “lone” AF refers to patients who do not have established stroke risk factors. Imaging is often used to rule out structural heart disease, e.g. coronary artery disease, peripheral vascular disease, mitral stenosis or left ventricular (LV) dysfunction. Imaging of the heart has a central role in establishing the “lone” aspect in patients with “lone”AF, similar to the measurement of blood glucose and blood pressure: Patients with structural heart disease, defined as e.g. reduced LV ejection fraction, clinical evidence for heart failure, or evidence for coronary artery disease, will not be considered as patients with “lone” AF. The search for these conditions requires some cardiac imaging, often done by echocardiography and non-invasive tests for coronary artery disease or ischemia. Increasingly, brain imaging is used to define the clinical diagnosis of a stroke, thus also contributing to the detection of stroke risk factors. Cerebral imaging in AF patients without competing causes for silent strokes or microbleeds (“lone” AF, rather used in the context of anticoagulation, i.e. clinical absence of structural heart disease) would allow to better understand the contribution of AF to these brain lesions. The assumption that silent strokes are likely drivers of cognitive dysfunction, and the fact that microbleeds put patients at risk for intracerebral hemorrhage, illustrates the need to collect information on brain imaging. In this review article, we summarize current data on heart and brain imaging in patients with “lone” AF and discuss their clinical implications for risk assessment and management of patients with “lone” AF.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in adult population and confers significant thromboembolic risk. Endothelial dysfunction has been recognized as a possible contributor to thrombogenesis in AF. The arrhythmia has been associated with thrombogenic atrial endocardial lesions and evidence of increased circulating biomarkers of endothelial dysfunction (e.g. von Willebrand factor, soluble thrombomodulin, E-selectin, asymmetric dimethylarginine, circulating endothelial cells and microparticles), and impairment of endothelium-dependent vasodilatation in the peripheral and coronary circulation has been reported in AF patients. Increased levels of biomarkers of endothelial origin (e.g. von Willebrand factor, soluble thrombomodulin, E-selectin, asymmetric dimethylarginine) have been associated with adverse outcomes in AF patients. Importantly, endothelial dysfunction has been documented in AF patients without cardio-pulmonary comorbidities or risk factors (so-called ‘lone AF’), as well. In this review, we provide an overview of contemporary evidence for the alterations in endothelial function and endothelial injury in AF, with a focus on endothelial (dys)function in lone AF.

Lone atrial fibrillation (LAF) is generally regarded as a benign disorder that does not significantly increase the risk of thromboembolism and mortality. However, there is growing evidence that “lone” atrial fibrillation (AF) is a “heterogeneous” disorder with varying risk for thromboembolism based on the patient’s underlying cardiovascular risk factors. Blood biomarkers, including markers of myocardial strain, inflammation, endothelial injury, platelet activation, and hypercoagulability, have potential to improve our risk stratification and management of LAF. Currently, there is a paucity of data on biomarkers in strictly defined LAF. The majority of studies that aimed to study lone atrial fibrillation excluded patients with structural heart disease, but did not exclude patients with co-existing cardiovascular risk factors such as hypertension or diabetes mellitus. Moreover, many of the studies did not exclude patients based on age, thereby increasing the likelihood of including patients with cardiovascular co-morbidities. There are currently a limited number of studies aimed to investigate the role of biomarkers in true LAF. The results are conflicting as to whether these biomarkers are associated with LAF or stroke risk. Future studies enrolling patients with true LAF using strict definition are needed. Herein, we review our current knowledge of biomarkers in association with atrial fibrillation and LAF and discuss their potential clinical utility.

Atrial fibrillation (AF) may occur in the absence of identifiable causes, co-morbidities or structural cardiac disease (lone AF). Silent AF is common and patients may have a completely asymptomatic arrhythmia or may experience both symptomatic and asymptomatic AF episodes. It has been estimated that among patients with recognized AF, one third has no appreciable symptoms. In contemporary clinical practice, AF remains largely underdiagnosed and 25% of patients with AF-associated cardioembolic stroke have not been previously diagnosed with AF. The strategies for AF screening include opportunistic and systematic screening. Several methods for AF detection are nowadays available: from very simple (pulse palpation) to more advanced technologies proposed for ambulatory external monitoring of variable time duration. In patients previously implanted with cardiac electrical devices with an atrial lead, according to current clinical indications, the ability to continuously detect AF and to monitor its evolution is magnified, and AF burden can be precisely measured and monitored along with time. Similar information on AF burden can be also obtained by implantation of subcutaneous cardiac monitors that rely on the analysis of consecutive RR intervals for the diagnosis of AF. The prognosis is generally favorable for patients presenting with lone AF, but adverse outcomes, including stroke and thromboembolic events may occur at long term, in association with aging, or the development of underlying heart disease, or progression from paroxysmal to permanent AF. In this respect, the role of new technologies and diagnostic tools for AF detection and monitoring should be fully defined.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. A subgroup of patients presents with AF without traditional risk factors and is diagnosed before the age of 60 years. Such patients are commonly referred as having “lone AF” and comprise 10-20% of all cases. A number of studies have demonstrated that AF, and in particular lone AF, have a substantial genetic component. Genome-wide association studies (GWAS) have indicated that common single-nucleotide polymorphisms (SNPs) have a role in the development of AF. Furthermore, rare variants in genes encoding cardiac gap junction proteins, signalling molecules, ion channels, and accessory subunits have been associated with lone AF in several recent genetic reports. Most of these reports show gain-of-function or loss-of-function mutations, leading to increased risk of lone AF. To date, the pathophysiological mechanisms responsible for AF are not fully understood, and it is likely that this arrhythmia represents a final common phenotype of multiple. This review focuses on the genetic basis of lone AF and the role of both common and rare variants in the susceptibility of developing lone AF. Furthermore, three conceptual pathogenetic models of lone AF are discussed.

Ever since the original description of a ‘peculiar pulse irregularity’, atrial fibrillation (AF) has been studied extensively and has come a long journey from the recognition of its cardiac origins, to the modern concept of AF as a serious public health challenge with profound social and economic implications. This arrhythmia affects around 2% of adult population, and the most common underlying heart diseases accompanying AF in the modern era are hypertension, heart failure and coronary artery disease, as well as valvular heart diseases and numerous other cardiac as well as non-cardiac disorders which have been shown to predispose to AF. On occasions, AF occurs in young otherwise apparently healthy individuals (so called ‘lone AF’). For a long time, ‘lone’ AF has been believed to bear a favourable prognosis as compared to AF with underlying structural heart disease, but increasing evidence suggests that ‘lone’ AF patients represent a rather heterogeneous cohort, with highly variable individual risk profiles due to the presence of various subclinical cardiovascular risk factors or genetically determined subtle alterations at the cellular or molecular level. For these reasons, the existence of truly ‘lone’ AF has recently been questioned. In this review article, we present a brief history of the recognition of the public health burden of AF. We discuss some of the misconceptions and breakthroughs on modern knowledge on AF, including the rise (and fall) of the ‘lone’ AF concept.