Reduced Ejection Fraction in Elite Endurance Athletes: Clinical and Genetic Overlap With Dilated Cardiomyopathy
Authors: Claessen Guido , De Bosscher Ruben , Janssens Kristel , Young Paul , Dausin Christophe , Claeys Mathias , Claus Piet , Goetschalckx Kaatje , Bogaert Jan , Mitchell Amy M. , Flannery Michael D. , Elliott Adrian D. , Yu Chenglong , Ghekiere Olivier , Robyns Tomas , Van De Heyning Caroline M. , Sanders Prashanthan , Kalman Jonathan M. , Ohanian Monique , Soka Magdalena , Rath Emma , Giannoulatou Eleni , Johnson Renee , Lacaze Paul , Herbots Lieven , Willems Rik , Fatkin Diane , Heidbuchel Hein , La Gerche André , Van Soest Sofie , Bekhuis Youri , Pauwels Rik , De Paepe Jarne , Hespel Peter , Dymarkowski Steven , Dresselaers Tom , Miljoen Hielko , Favere Kasper , Paelinck Bernard , Vermeulen Dorien , Witvrouwen Isabel , Hansen Dominique , Op’t Eijnde Bert , Thijs Daisy , Vanvoorden Peter , Lefebvre Kristof , D’Ambrosio Paolo , Rowe Stephanie , Paratz Elizabeth , Brosnan Maria J. , Prior David L. 
Published: July 2024

BACKGROUND:
Exercise-induced cardiac remodeling can be profound, resulting in clinical overlap with dilated cardiomyopathy, yet the significance of reduced ejection fraction (EF) in athletes is unclear. The aim is to assess the prevalence, clinical consequences, and genetic predisposition of reduced EF in athletes.

METHODS:
Young endurance athletes were recruited from elite training programs and underwent comprehensive cardiac phenotyping and genetic testing. Those with reduced EF using cardiac magnetic resonance imaging (defined as left ventricular EF <50%, or right ventricular EF <45%, or both) were compared with athletes with normal EF. A validated polygenic risk score for indexed left ventricular end-systolic volume (LVESVi-PRS), previously associated with dilated cardiomyopathy, was assessed. Clinical events were recorded over a mean of 4.4 years.

RESULTS:

Of the 281 elite endurance athletes (22±8 years, 79.7% male) undergoing comprehensive assessment, 44 of 281 (15.7%) had reduced left ventricular EF (N=12; 4.3%), right ventricular EF (N=14; 5.0%), or both (N=18; 6.4%). Reduced EF was associated with a higher burden of ventricular premature beats (13.6% versus 3.8% with >100 ventricular premature beats/24 h;
P
=0.008) and lower left ventricular global longitudinal strain (–17%±2% versus –19%±2%;
P
<0.001). Athletes with reduced EF had a higher mean LVESVi-PRS (0.57±0.13 versus 0.51±0.14;
P
=0.009) with athletes in the top decile of LVESVi-PRS having an 11-fold increase in the likelihood of reduced EF compared with those in the bottom decile (
P
=0.034). Male sex and higher LVESVi-PRS were the only significant predictors of reduced EF in a multivariate analysis that included age and fitness. During follow-up, no athletes developed symptomatic heart failure or arrhythmias. Two athletes died, 1 from trauma and 1 from sudden cardiac death, the latter having a reduced right ventricular EF and a LVESVi-PRS >95%.

CONCLUSIONS:
Reduced EF occurs in approximately 1 in 6 elite endurance athletes and is related to genetic predisposition in addition to exercise training. Genetic and imaging markers may help identify endurance athletes in whom scrutiny about long-term clinical outcomes may be appropriate.

REGISTRATION:

URL:
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374976&isReview=true
; Unique identifier: ACTRN12618000716268.