The prevalence of atrial fibrillation (AF) in the developed world is currently estimated at approximately 1.5% to 2% of the general population. The average age of patients with AF rises steadily and averages now between 75 and 85 years. AF is associated with a five-fold risk of stroke and a three-fold incidence of congestive heart failure, and higher mortality. AF patients are also often hospitalized. In addition to its impact on individual patients, AF has a major socioeconomic impact. Furthermore, based on projected estimates of increased AF, incidence over the coming decades will most likely worsen both individual patient burden and impact on socioeconomics.

Worldwide approximately 20.9 million men and 12.6 million women were diagnosed with AF in 2010. In developed countries higher incidence and prevalence are reported.1,2 It is estimated that one in four middle-aged adults in Europe and the US will develop AF.3,4,5 Furthermore it is estimated that by 2030, there will be 14 to 17 million AF patients in the European Union. Important to realize is that this equals to approximately 120,000 to 215,000 newly diagnosed AF patients per year.2,6,7 AF prevalence is higher in the elderly 1 and in patients with conditions associated with AF (e.g., hypertension, heart failure, coronary artery disease (CAD), valvular heart disease, obesity, diabetes mellitus, or chronic kidney disease (CKD)).7,8,9,10,11,12,13 Better detection of silent AF,14,15,16 in combination with increasing age and increasing prevalence of conditions predisposing to AF, explains the expected increase in AF prevalence.17

AF is independently associated with a two-fold increased risk of all-cause mortality in women and a 1.5-fold increase in men.18,19,–20 Anticoagulation therapy diminishes death due to stroke in AF patients. However, even if AF patients are treated according to the latest evidence, death due to heart failure and sudden death remain common.21 AF is also related to increased morbidity of diseases such as heart failure and stroke.20,22,23 For example, approximately 25% of patients with an ischaemic stroke have AF either diagnosed before, during, or after the initial event.14,24,25 White matter lesions in the brain, cognitive impairment,26,27,28 decreased quality of life,29,30 and depressed mood 31 are common in AF patients, and between 10% and 40% of AF patients are hospitalized each year.21,32,33

Based on clinical presentation, duration, and spontaneous termination of AF episodes, five types of AF are traditionally distinguished: first diagnosed, paroxysmal, persistent, long-standing persistent, and permanent AF.34 As the most recent ESC guidelines on AF point out, it is important to realize that these AF classifications patterns do not correspond well to the AF burden measured by long-term ECG monitoring.35 Even less is known about the response to therapy in patients with long-standing persistent AF or long-standing paroxysmal AF. Despite these inaccuracies, the distinction between paroxysmal and persistent AF has been used in many trials.

Treatment of patients with AF is aimed at hemodynamic stability, reduction of cardiovascular risk, prevention of stroke, improvement of symptoms and preservation of LV function.36 Fortunately a number of valuable treatment options have been developed in recent years that help to achieve these treatment goals. However, they are not perfect and do not always solve the clinical problem.

In recent years, complete pulmonary vein ablation has arisen as an option to control rhythm in AF patients both with paroxysmal as with persistent AF. However, the rhythm outcome after catheter ablation of AF is difficult to predict in individual patients.37,38,39,40 Multiple variables have been identified as risk factors for recurrence after catheter ablation of AF, but their predictive power is weak. Therefore, the most recent ESC guideline advocates that the decision for catheter ablation should be based on a shared decision-making process.34

Apart from the risk of recurrence of AF after catheter ablation, it is important to realize that these interventions are associated with complications. Although the systematic registration of these complications is in need of improvement, the reported incidence of severe complications ranges between 5% and 7% with 2% to 3% of patients experiencing life-threatening complications.41,42,43,44

Of interest is that the addition of ganglionated plexi (GP) ablation to pulmonary vein isolation further improves AF-free survival in both patients with paroxysmal and persistent AF. Despite this improved patient outcome, the combined ablation still results in approximately 25% and 50% recurrence of AF in paroxysmal and persistent AF, respectively.45,46 These studies support the autonomic hypothesis for AF. In addition, it seems that GP activity is most important in the early stages of AF, while its importance may diminish with progression of the disease to more advance stages and the development of atrial remodeling and fibrosis. This nicely shows that a better understanding of the pathophysiology of AF leads to more targeted treatment plans (personalized medicine) and may result in better patient outcome.

One of the conclusions that can be drawn from these observations is that the success of AF ablation procedures depends on the elimination of substrate. Therefore, improved patient selection may improve outcome, i.e., only those patients with substrate most eligible to improve after a specific intervention should undergo these interventions. Therefore, an understanding of the pathophysiology related to AF initiation and progression is essential.

AF is very likely a multifactorial process (e.g., changes in the cardiac autonomic nervous system) where different factors interact resulting in either the incidence of AF or sustaining already existing AF. Amongst others, the initiation and persistence of AF is associated with inflammation. In patients with AF inflammation has been observed in cardiac tissue, epicardial adipose tissue (EAT), hematopoietic tissue, and the systemic circulation. Although the trigger for inflammation in AF is unknown (also most likely multifactorial), inflammation most likely induces electrophysiological and structural changes in the atria eventually leading to AF. On the other hand, AF by itself results in an inflammatory response, and elevated inflammatory markers have been shown in patients with long-standing AF. It is therefore not remarkable that some reports in the literature showed increased uptake of 18F-fluorodeoxyglucose (18F-FDG), as a marker of inflammation, in the atria of AF patients.

In this issue of Journal of Nuclear Cardiology, there is a study by Xie et al. reporting on factors that are associated with increased 18F-FDG uptake in the atria or atrial appendage (AA).47 In total, 48 AF patients were retrospectively identified. All patients with permanent AF showed increased atrial 18F-FDG uptake, primarily localized in the right atrium. Multivariate logistic regression analyses identified that female gender, persistent AF, and 18F-FDG uptake in EAT were independent predictors of increased atrial 18F-FDG uptake. In addition, 18F-FDG uptake in EAT was linearly correlated with the activity of the atrium and AA. The authors conclude that this finding might suggest a link between the inflammatory activity in EAT and atria in AF, pointing to the possibility that a local inflammatory burden in the EAT may lead to localized atrial inflammation.

There are some obvious limitations to this study that are adequately addressed (i.e., uniform patient preparation, low carbohydrate diet and impact on atrial 18F-FDG uptake, atrial 18F-FDG uptake in patients without AF). The main interest of this study lies in the fact that atrial 18F-FDG uptake as a surrogate marker of inflammation is related to patients with permanent AF. It is tempting to speculate on the possible role of atrial 18F-FDG uptake in the selection of patients for specific therapies. As especially patients with permanent AF tend to respond poorer to catheter ablation of the pulmonary veins, this finding may open ways to more targeted intervention studies using atrial 18F-FDG uptake as tool to guide these interventions. However, for this daydream to become reality, a lot of effort needs to be put in harmonization and standardization of the imaging protocols including patient preparation.