Endurance athletes and atrial fibrillation
Exercise makes the heart grow larger. This is usually a good thing, but for endurance athletes, one of the risks of extreme, long-term exercise is Atrial Fibrillation. One of the Baker Department's first seed funding projects is looking to genetics to explain why only some athletes develop this type of cardiac arrhythmia, and what this can tell us about regular patients with the same condition.
Exercise is promoted for its exceptional health benefits that extend well beyond the improvements in cardiovascular outcomes and overall survival. However, there is a small “sting in the tail” in that long-standing endurance exercise training is associated with an excess of cardiac arrhythmias.
Research Leader, Professor Andre la Gerche, says increasing participation in endurance sports means that athletes with atrial fibrillation (AF) are an important group with specific management needs. “And we suspect that the mechanical stressors that may underpin AF in athletes provides a unique model for understanding and treating the condition in the general population.”
AF is the most common sustained cardiac arrhythmia with a lifetime risk of more than 35 per cent at age 40. People with AF are predisposed to heart failure and thromboembolic stroke. AF accounts for 15 per cent of all strokes and one third of strokes in individuals over 65 years of age and it costs the Australian economy $1.25 billion a year.
Despite uniformly high levels of atrial stress during exercise, not all endurance athletes develop AF. “We suspect this is due to individual genetic susceptibility.”
Athletic cardiac remodelling represents an ideal model for studying interactions between predisposing genetic and environmental contributions to atrial fibrillation. La Gerche has created one of the world’s leading resources for the study of athletic-induced changes on cardiac structure and arrhythmogenic remodelling (read more in the Washington Post).
In an ongoing collaboration between Australia and Belgium, 279 young elite athletes, 132 ex-Olympic rowers and 71 elite athletes with AF have undergone comprehensive phenotyping with echocardiography, cardiac MRI, cardiopulmonary exercise testing and resting, ambulatory and exercise ECG monitoring.
Genetic samples have been stored in all. Initial analyses of this cohort demonstrate how ideal they are for the assessment of extreme remodelling. La Gerche’s group recently compared age and gender matched athletes and non-athletes with and without AF (four equal groups of 36 subjects) and found that traditional risk factors such as diastolic dysfunction and atrial enlargement were not associated with AF in athletes because they had universally dilated atria and excellent diastolic function. Rather, atrial contractile function was reduced in athletes suggesting an exercise-induced atrial myopathy (manuscript under second revision at EHJ CVI).
There are three potential ways in which genetic variance could cause arrhythmias such as AF in athletes. (1) Genetic causes could cause disease outright, (2) Genes and exercise could have independent but additive effects, or (3) there could be a synergistic environmental/ gene interaction. Very few studies have assessed genetic variants in athletes with cardiovascular pathology.
La Gerche led the first such study, which demonstrated that athletes with RV dysfunction and arrhythmias did not have mutations in the typical causative genes, this arguing against the first “gene only” theory. The second theory will be addressed in our study as a potential excess in genes known to be associated with AF. The third theory is the most intriguing. It posits that new genes (such as those associated with mechanoreceptors or contractile elements) may be important in causing AF when combined with exercise. This would open entirely novel insights into the pathophysiology and therapeutic targets.