Elsevier

Progress in Cardiovascular Diseases

Volume 68, September–October 2021, Pages 52-59
Progress in Cardiovascular Diseases

Exercising immune cells: The immunomodulatory role of exercise on atrial fibrillation

https://doi.org/10.1016/j.pcad.2021.07.008Get rights and content

Abstract

Exercise training is generally beneficial for cardiovascular health, improving stroke volume, cardiac output, and aerobic capacity. Despite these benefits, some evidence indicates that endurance training may increase the risk of atrial fibrillation (AF), particularly in highly trained individuals. Among multiple mechanisms, autonomic tone changes and atrial remodeling have been proposed as main contributors for exercise-induced AF. However, the contribution of local and systemic immunity is poorly understood in the development of atrial arrhythmogenic substrates. Here we aim to update the field of immunomodulation in the context of exercise and AF by compiling and reconciling the most recent evidence from preclinical and human studies and rationalize the applicability of “lone” AF terminology in athletes.

Introduction

The benefits of regular physical activity (PA) have been vastly documented by clinical and basic science evidence, demonstrating attenuation of cardiovascular (CV) disease (CVD) risk factors and, consequently, reducing the chance of developing CVD.1,2 Taking into consideration that multiple modifiable CVD risk factors raise the occurrence of atrial fibrillation (AF), a planned and structured exercise intervention to improve or maintain cardiorespiratory fitness (CRF) is recommended as a feasible and non-pharmacology therapy for AF patients.3, 4, 5, 6 Although the CV benefits of exercise are undeniable, there is increasing evidence suggesting an increased risk of AF in individuals participating in decades of vigorous endurance programs and in high-performance endurance athletes.7, 8, 9, 10 In this sense, studies have proposed that long-term vigorous exercise may lead to harmful arrhythmic events associated with inflammation.11,12 However, the pathophysiological and molecular mechanisms underlying the exercise-induced AF are not fully understood.

Exercise intensity has been suggested as the determining factor for the increased risk of AF in highly trained individuals.13, 14, 15 Nevertheless, other variables of exercise training and the presence of genetic or acquired CV abnormalities are also decisive to either lead to a prevention/management of AF or to trigger AF substrates. To the best of our knowledge, this is the first review to debate the implication of exercise-induced immunomodulation on AF. Additionally, here we discuss the conjecture that excessive endurance exercise over many years may induce AF by triggering atrial inflammation.

Section snippets

High-intensity exercise: too much of a good thing?

AF is the most common clinical arrhythmia with a significant impact on the healthcare system, particularly because it is associated with a 5-fold increase in the risk of stroke.16 While the therapeutic effects of exercise training have been largely reported in patients with heart failure and AF,3,17, 18, 19 opposite CVD outcomes have also been observed.20,21 Since the pioneering study by Karjalainen et al.22 reporting that endurance athletes have a higher incidence of AF than sedentary

Mechanisms of AF in athletes: a lone event?

The mechanisms by which exercise affects the development of AF are unclear. Atrial remodeling (atrial dilatation and fibrosis) is a potential factor contributing to exercise-induced proarrhythmogenic risk and a critical substrate for AF-promoting reentry and self-perpetuation.50,51 LA enlargement is commonly observed in larger cohorts of competitive athletes with AF,37,38,52, 53, 54 as well as LA function reduction.54

However, it is not clear whether atrial remodeling observed in athletes is

Exercise-induced changes in innate immunity

The concept that exercise modulates the immune system emerged from the observation of increased peripheral blood lymphocyte during vigorous exertion, which is suppressed in the following hours after exercise.63 Lymphocyte mobilization observed during acute vigorous exercise is associated with enhanced influx of natural killer and CD8+ T cells into the bloodstream.64 Upon exercise cessation, the transient lymphocyte reduction remains poorly understood, whether it represents a suppression of

What does the evidence from animal research tell Us?

Despite the compelling progress in the identification of factors related to the pathogenesis of exercise-induced AF, this area is still an emerging research topic. Multiple mechanisms, such as enhanced vagal tone, electrophysiological changes, and tissue remodeling, are viewed as critical for AF pathogenesis.50 However, genetic variants are also decisive components and facilitators of arrhythmias.79 In this context, exercise training might be deleterious or lethal in some particular cases, like

Conclusion

Given the high complexity involving interactions between stimuli generated by endurance exercise and the responses of the innate immune system, the final response might be different in healthy versus diseased individuals. Thus, linear, exponential, or J-shaped projections establishing the relationship between endurance training and the development of AF misrepresent the inherent molecular fingerprint and its interaction with the variables of exercise training. Despite the great progress both in

Disclosures

None.

Funding

None.

Declaration of Competing Interest

None.

Acknowledgement

This work was carried out with the support of the Coordination for the Improvement of Higher Education Personnel - Brazil (Capes).

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