D’Ambrosio P; The University of Melbourne, Parkville, VIC, Australia & many other centres
De Paepe J; Spencer LW; Ohanian M; Janssens K; Mitchell AM;
Flannery MD; Bekhuis Y; Pauwels R; Delpire B; Dausin C; Rowe SJ; Van
Puyvelde T; Young PE; Soka MJ; Johnson R; Yu C; Morris GM; Robyns T;
Lacaze P; Giannoulatou E; Kistler PM; Kalman JM; Heidbuchel H; Willems R;
Claessen G; Fatkin D; La Gerche A

Circulation. 153(9):616-630, 2026 Mar 03.

METHODS: We phenotyped current and former elite endurance athletes in the
Pro@Heart cohort study using multimodal cardiac imaging, cardiopulmonary
exercise testing, and Holter monitoring. Genetic susceptibility to
bradycardia was assessed using a validated HR-associated polygenic risk
score (HR-PRS), in which lower scores are associated with a lower HR, and
compared with healthy nonathletic controls. Clinical and genetic features
of bradycardic endurance athletes with minimum HR <=40 bpm on a Holter
monitor (bradycardic athletes [BAs]) were compared with non-BAs). A
healthy cohort of nonathletes from the ASPREE study (Aspirin in Reducing
Events in the Elderly) were used for genetic comparisons.

RESULTS: Among 465 endurance athletes (median age, 23 [18-49] years, 75%
men), 175 (38%) had a minimum HR on a Holter monitor <=40 bpm, of whom 7
(2% of total) had a HR <=30bpm. Pauses >=2 s were observed in 115 (25%)
athletes, of whom 12 (3% of total) had pauses >=3 s. Mobitz I
second-degree atrioventricular block was observed in 15 (3% of total)
athletes. BAs were younger and fitter and exhibited greater athletic
cardiac remodeling than non-BAs. Mean HR-PRS was significantly lower in
all athletes compared with ASPREE nonathletes (P<0.001) and in BAs
compared with non-BAs (P=0.006). When the distribution of HR-PRS within
our athletic cohort was considered, athletes with scores in the bottom
quartile had a lower minimum HR (median HR, 41 [35-45] bpm versus 45
[40-49] bpm, P<0.001) and higher bradycardia burden (14 [2-37]% versus 2
[0%-25]%, P<0.001) than those with scores in the top quartile. After
adjusting for age, sex, fitness, and indexed right atrial volume, HR-PRS
was independently associated with lower minimum HR and increased the odds
of resting bradycardia by 2-fold (odds ratio [OR], 2.2 [95% CI, 1.3-3.9];
P=0.004). Neither bradycardia nor pauses were associated with increased
risk of adverse outcomes over 5.5 years.

CONCLUSIONS: Resting bradycardia (HR <=40 bpm) and pauses of 2 to 3 s are
present in a significant proportion of endurance athletes and are well
tolerated. Our data suggest that both fitness and genetic variation
contribute to sinus node function in endurance athletes. Intriguingly,
HR-PRS differed between athletes and nonathletes, raising the possibility
that genetics may be a determinant of athleticism.