Possible Mechanisms of Atrial Fibrillation in Athletes: Comparison
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Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice, and it is an enormous burden worldwide because of its high morbidity, disability and mortality. It is generally acknowledged that physical activity (PA) is strongly associated with a significant reduction in the risk of cardiovascular (CV) disease and all-cause mortality. Moreover, it has been observed that moderate and regular physical activity has the potential to reduce the risk of AF, in addition to improving overall well-being.

  • atrial fibrillation
  • arrhythmia
  • physical activity

1. Introduction

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice, and it is an enormous burden worldwide because of its high morbidity, disability and mortality [1,2][1][2]. The prevalence of AF among the adult population is between 2% and 4%, with an increase in mortality between 1.5 and 3.5 times, and it has been associated with cardiovascular (CV) diseases such as heart failure, myocardial infarction, cerebral and ischemic events and all-cause mortality [3,4][3][4]. Its prevalence increases with age; indeed, more than 95% of AFs occur in those older than 60. AF is usually associated with cardiovascular and non-cardiovascular diseases [5]. However, this arrhythmia does not spare even young subjects with structurally normal hearts; this is the case of so-called lone AF [6].
It is generally recognized that physical activity (PA) is linked to a significant decrease in CV risk and all-cause mortality [7,8][7][8]. Moreover, it has been reported that moderate and regular physical activity has the potential to reduce the risk of AF [9,10][9][10].
Moderate and regular PA is considered a cornerstone in preventing AF by modifying many of its predisposing factors, which largely coincide with the classical CV disease risk factors [1,9,10,11,12,13][1][9][10][11][12][13]. Moderate, regular and aerobic physical activity improves many CV risk factors simultaneously, as opposed to drugs that are usually specific for a single factor [7]. Moderate PA can also be prescribed for subjects suffering from AF as part of their treatment because it improves muscular strength, ventricular rate control, 6 min walking test performance and quality of life [14,15][14][15]. The importance of PA in preventing AF seems to be further confirmed by the statistical correlation between a sedentary lifestyle and arrhythmia occurrence [16,17][16][17].
Nevertheless, some studies have associated intense physical activity with an increased risk of AF [18[18][19],19], reporting a higher incidence of AF in elite athletes [20,21,22][20][21][22] and suggesting a U-shaped dose–response curve [23,24][23][24]. These findings have raised doubts about the real beneficial effects of sports practice in arrhythmia prevention.

2. Electrophysiological Mechanisms of Atrial Fibrillation

Atrial fibrillation is a multifactorial arrhythmia. Its electrophysiology is complex and, even nowadays, not completely understood. Moreover, underlying arrhythmia mechanisms may differ depending on clinical scenarios and single patients [25[25][26],26], which can be crucial when considering athletes as “healthy” subjects.
Research on this topic is not new and dates back to the early twentieth century, but significant advances have been made in the last 30 years, leading to ourthe contemporary knowledge about this arrhythmia. In particular, the “Coumel triangle” marked a cornerstone in the history of arrhythmology (Figure 1) [27]. The triangle’s three corners represent the factors needed to support any type of arrhythmia: triggers, arrhythmogenic substrate and modulating factors. In this simple, although dated, model, AF still seems to fit adequately. These mechanisms have been proposed to play a crucial role in the genesis and sustainment of AF, and all factors of the triangle may occur in the same patient [28]. Generally speaking, the “trigger” is mainly identified as premature ectopic beats, often originating from inside the pulmonary veins’ ostia [29[29][30],30], but it can also be constituted by other supraventricular arrhythmias [26,31][26][31] that may degenerate into AF. The term “substrate” is a generic definition including all the structural, morphological and functional alterations that may favor arrhythmia maintenance. The “modulating factors” are mainly represented by sympathetic and vagal tone modifications, which in different clinical scenarios may favor the development of AF [17]. Understanding how these factors may be directly influenced by physical activity is intuitive.
Jcdd 10 00218 g001 550
Figure 1. To support an arrhythmia, the presence of a trigger, a substrate and modulating factors is essential.

3. Importance of the Specific Arrhythmia Triggers in Athletes

In the case of AF in a young athlete with a structurally normal heart, an underlying synchronized tachycardia inducing AF might be present. In the absence of any structural heart disease, AF is often triggered by other tachyarrhythmias. It is well known that some re-entrant tachycardias can induce atrial flutter or AF noted as “tachycardia-induced tachycardia” or “tachycardia-induced AF” [32,33][32][33].
In the general population, the occurrence of premature atrial contractions, particularly pulmonary vein ectopic beats, are the main trigger in most episodes of paroxysmal AF [29]. It has been postulated that endurance athletes present a higher burden of premature atrial beats than sedentary individuals [34,35][34][35]. Nevertheless, currently available data are insufficient to demonstrate a clear relationship between atrial premature beats and PA and whether such a little increase is enough to contribute to the AF burden in athletes significantly. In fact, Baldesberger et al. [36] and Elliot et al. [37] did not find an increased incidence of atrial ectopy in their study on former professional cyclists. Therefore, the exact role of atrial premature beats in athletes as prevalent triggers of AF remains unclear.

4. Arrhythmogenic Substrate Modification in Athletes

Intensive training leads to morphological and functional remodeling of the heart and cardiovascular system, resulting in the so-called “athlete’s heart” [38], which may play a role in the induction of AF. These CV adaptations are particularly evident when induced by endurance exercise to cope with the increase in cardiac output required during exercise and include biatrial dilatation [34], left ventricular hypertrophy [39] and enlargement of the right ventricle [40,41][40][41]. Usually, all anatomical changes disappear with detraining, but the exact amount of time required remains unclear [40]. Several factors related to exercise-related AF include atrial enlargement, an increased stretch of the atrium wall during activity and electrolyte disturbances (sodium, potassium, calcium and magnesium). It is possible to speculate that intense physical activity, combined with non- optimal electrolytic replenishment, can lead to an electrolyte imbalance that could trigger AF. However, the extent to which this aspect really contributes to the prevalence of AF in professional athletes is yet to be completely understood.

45. Possible Modulating Factor Modifications in Athletes

Autonomic tone can be significantly modified in athletes. Established cardiovascular adaptation to regular exercise is enhanced parasympathetic activity [72][42] which may generate sinus bradycardia at rest in well-trained individuals and AV conduction disturbances [73][43]. This is induced by increased sympathetic tone during exercise and a consequent downregulation at rest, which makes the vagal tone dominant [74,75,76][44][45][46]. This condition is reversible after detraining. Enhanced vagal tone and reduced sympathetic tone, characteristic of endurance athletes, have been associated with the development of AF, as well as in normal hearts [20,29,77][20][29][47]. Clinically, several features suggest that vagal tone can modulate AF, for example, when AF arises during sleep or after heavy meals. High levels of acetylcholine increase the dispersion of atrial repolarization and shorten the atrial effective refractory periods and the wavelength of atrial excitation wavefronts [20,59][20][48]. Notably, most AF relapses in athletes occur in vagally dominant situations while, conversely, adrenergic-mediated AF is less frequent in this population [22]. In a selected population of patients with paroxysmal vagal AF, vagal atrial denervation by radiofrequency ablation of right atrial ganglionated plexi was also attempted using an anatomic approach [78,79][49][50].

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