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\begin{document}

\title{Left atrial dyssynchrony in veteran endurance athletes with and without
paroxysmal atrial fibrillation}



\author[1]{EIVIND SØRENSEN}%
\author[2]{MARIUS MYRSTAD}%
\author[2]{MAGNAR GANGÅS SOLBERG}%
\author[1]{ERIK ØIE}%
\author[3]{Pyotr G. Platonov}%
\author[3]{JONAS CARLSON}%
\author[2]{ARNLJOT TVEIT}%
\author[1]{MARIT AARØNÆS}%
\affil[1]{Diakonhjemmet Sykehus AS}%
\affil[2]{Baerum sykehus}%
\affil[3]{Lunds universitet Kardiologi}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background:~Prolonged endurance exercise is associated with an increased
risk of atrial fibrillation (AF) in men. Left atrial (LA) dilation is a
marker of pathological atrial remodeling and associated with AF in the
general population. In athletes, however, atrial dilation is part of a
physiological response to exercise, and functional parameters may help
separate physiological from pathological atrial remodeling in this
group. LA mechanical dispersion (LA MD) is a novel marker of LA
mechanical dyssynchrony associated with AF in the general population.
The associations between prolonged endurance exercise, LA MD and AF are
yet to be investigated. Purpose:~To investigate LA MD in male veteran
athletes who had regularly participated in an annual 54-kilometer
cross-country (XC) ski race in Norway with and without paroxysmal AF and
to investigate the ability of LA MD to identify veteran athletes with
paroxysmal AF. Methods:~Two hundred and ninety-three men from four
groups, veteran XC skiers with (n=57) and without (n=87) AF, and men
from a non-athletic population with (n=61) and without AF (n=88)
underwent an echocardiographic exam while in sinus rhythm. Using
speckle-tracking echocardiography, LA strain was measured in each of the
six atrial segments in an atrial-focused apical four-chamber view. We
defined LA MD as the standard deviation of time-to-peak strain (SD-TPS)
and report the average from three consecutive loops. Results:~XC-skiers
(mean age 70.9 \selectlanguage{ngerman}± 5.7 years) reported an average of 40-50 years of
regular endurance exercise and an average of 16 completed annual
Birkebeiner XC ski races. LA volumes were associated with both AF and
athletic status (p\textless{}0.001). SD-TPS was associated with AF
(p\textless{}0.001), but not with athletic status (p=0.173). We found no
significant trend between years of endurance exercise and SD-TPS in
individuals without AF (p=0.846). SD-TPS did not add incremental value
in identifying athletes with AF in addition to clinical markers, QRS
width, LA volume, and LA reservoir strain (p=0.056). Conclusion:~LA MD
was associated with paroxysmal AF regardless of athletic status.
However, it was not associated with years of performing endurance
exercise, suggesting LA MD could be a promising marker of pathological
atrial remodeling in endurance athletes, less affected by physiological
exercise-induced atrial remodeling than absolute volumetric
measurements. We found no incremental value of LA MD in identifying
veteran athletes with paroxysmal AF when LA reservoir strain was
included in the model.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Title Page}

\textbf{Title} : Left atrial dyssynchrony in veteran endurance athletes
with and without paroxysmal atrial fibrillation

\textbf{Authors} : EIVIND S\selectlanguage{ngerman}ØRENSEN \textsuperscript{1,2,3}, MARIUS
MYRSTAD \textsuperscript{2,4}, MAGNAR GANGÅS
SOLBERG\textsuperscript{2,4}, ERIK ØIE \textsuperscript{1}, PYOTR G.
PLATONOV\textsuperscript{5}, JONAS CARLSON \textsuperscript{5}, ARNLJOT
TVEIT\textsuperscript{3,4}, MARIT AARØNÆS \textsuperscript{1}

\textsuperscript{1} Department of Internal Medicine, Diakonhjemmet
Hospital, N-0370, Oslo, Norway

\textsuperscript{2} Department of Medical Research, Bærum Hospital
Vestre Viken Hospital Trust, N-1346, Gjettum, Norway

\textsuperscript{3} Institute of Clinical Medicine, University of Oslo,
N-0316, Oslo, Norway

\textsuperscript{4} Department of Internal Medicine, Bærum Hospital
Vestre Viken Hospital Trust, N-1346, Gjettum, Norway

\textsuperscript{5} Department of Cardiology, Clinical Sciences, Lund
University, Lund, Sweden

\textbf{Corresponding author:}

Eivind Sørensen

Department of Internal Medicine, Diakonhjemmet Hospital

P.O. Box 23 Vinderen, 0319 Oslo, Norway e-mail: eivindso@alumni.ntnu.no
phone: 0047 99737439

ORCID: 0000-0002-4801-6146

\textbf{Conflict of interest} : Authors declare no conflict of interest
regarding the submitted article

\textbf{Data availability statement:} The data underlying this article
will be shared on reasonable request to the corresponding author

\textbf{Funding information:} This work was supported by Diakonhjemmet
Hospital, Department of Medical Research Bærum Hospital Vestre Viken
Hospital Trust, the Norwegian Institute of Public Health, the Raagholt
foundation, and the Dam foundation through a Ph.D. grant.

\textbf{Ethics approval statement:} The study complies with the
Declaration of Helsinki and is approved by the Regional Committee for
Medical and Health Research Ethics (ref.nr: 2016/565).

\textbf{Patient consent statement:} All participants gave written
consent.

\textbf{Clinical trial registration} : The study is registered at
ClinicalTrials.gov (NCT 03741491)

\textbf{Abstract:}\emph{Background:} ~Prolonged endurance exercise is
associated with an increased risk of atrial fibrillation (AF) in men.
Left atrial (LA) dilation is a marker of pathological atrial remodeling
and associated with AF in the general population. In athletes, however,
atrial dilation is part of a physiological response to exercise, and
functional parameters may help separate physiological from pathological
atrial remodeling in this group. LA mechanical dispersion (LA MD) is a
novel marker of LA mechanical dyssynchrony associated with AF in the
general population. The associations between prolonged endurance
exercise, LA MD and AF are yet to be investigated.

\emph{Purpose:} ~To investigate LA MD in male veteran athletes who had
regularly participated in an annual 54-kilometer cross-country (XC) ski
race in Norway with and without paroxysmal AF and to investigate the
ability of LA MD to identify veteran athletes with paroxysmal
AF.\emph{Methods:} ~Two hundred and ninety-three men from four groups,
veteran XC skiers with (n=57) and without (n=87) AF, and men from a
non-athletic population with (n=61) and without AF (n=88) underwent an
echocardiographic exam while in sinus rhythm. Using speckle-tracking
echocardiography, LA strain was measured in each of the six atrial
segments in an atrial-focused apical four-chamber view. We defined LA MD
as the standard deviation of time-to-peak strain (SD-TPS) and report the
average from three consecutive loops.\emph{Results:} ~XC-skiers (mean
age 70.9 ± 5.7 years) reported an average of 40-50 years of regular
endurance exercise and an average of 16 completed annual Birkebeiner XC
ski races. LA volumes were associated with both AF and athletic status
(p\textless{}0.001). SD-TPS was associated with AF (p\textless{}0.001),
but not with athletic status (p=0.173). We found no significant trend
between years of endurance exercise and SD-TPS in individuals without AF
(p=0.846). SD-TPS did not add incremental value in identifying athletes
with AF in addition to clinical markers, QRS width, LA volume, and LA
reservoir strain (p=0.056).

\emph{Conclusion:} ~LA MD was associated with paroxysmal AF regardless
of athletic status. However, it was not associated with years of
performing endurance exercise, suggesting LA MD could be a promising
marker of pathological atrial remodeling in endurance athletes, less
affected by physiological exercise-induced atrial remodeling than
absolute volumetric measurements. We found no incremental value of LA MD
in identifying veteran athletes with paroxysmal AF when LA reservoir
strain was included in the model.

\textbf{Keywords:} Atrial fibrillation, dyssynchrony, left atrium,
exercise, echocardiography

\textbf{Abbreviations:} AF, atrial fibrillation; LA, left atrium;
LAVI\textsubscript{max,} maximal left atrial volume indexed; LA MD, left
atrial mechanical dispersion; SD-TPS, standard deviation of time-to-peak
strain; LASr, left atrial reservoir strain; LV, left ventricle/left
ventricular; GLS, global longitudinal strain; XC, cross-country;

\textbf{Introduction:}

Exercise is beneficial for a wide range of diseases and associated with
lower cardiovascular morbidity and mortality.\textsuperscript{1, 2} When
it comes to atrial fibrillation (AF), however, the effect of exercise is
ambiguous. While exercise of low and moderate intensity and duration
lowers the risk of AF, prolonged endurance exercise is associated with
an increased risk of AF in men.\textsuperscript{3-6} To accommodate the
increased demands of exercise, endurance athletes experience structural,
functional, and electrical cardiac remodeling referred to as the
``athlete's heart''.\textsuperscript{7} While cardiac remodeling is a
physiological response to exercise, the athlete's heart shares several
common features with pathologically remodeled hearts, and to separate
physiological from pathological atrial remodeling in athletes is a
challenging task.\textsuperscript{8, 9} Current knowledge indicates that
functional measures obtained by speckle-tracking echocardiography could
be more helpful than mere size when trying to differentiate
physiological from pathological atrial remodeling in veteran endurance
athletes. However, data is sparse and somewhat
conflicting.\textsuperscript{9-12} Studies assessing atrial function in
athletes with AF have focused on left atrial (LA) strain
values.\textsuperscript{10-13} Speckle-tracking echocardiography can
also be used to measure the timing of atrial contraction. LA mechanical
dispersion (LA MD), defined by the standard deviation of time-to-peak
strain (SD-TPS), is a marker of electromechanical atrial function. It is
reported to be a novel predictor of AF in the general population, linked
to the recurrence of AF after catheter ablation, and associated with
stroke among AF patients.\textsuperscript{14-17} Watanabe et al. found
an association between increased LA MD and low voltage zones recognized
by voltage mapping in paroxysmal AF patients indicating regional
fibrosis in the LA wall.\textsuperscript{18} There has also been a
report of increased atrial fibrosis assessed by magnetic resonance
imaging (MRI) in a group of healthy veteran endurance athletes, linking
long-term endurance exercise to increased atrial
fibrosis.\textsuperscript{19} Still, the impact of long-term endurance
exercise on LA MD, the interplay between AF, endurance exercise, aging,
and LA MD, and the ability of LA MD to identify athletes with paroxysmal
AF in sinus rhythm have yet to be investigated.

The main aim of this study was to investigate LA MD in veteran endurance
athletes with and without AF and to evaluate the ability of LA MD to
identify veteran athletes with paroxysmal AF when in sinus rhythm.

\textbf{Material and methods:}

\emph{Study population:}

Cross-country (XC) skiing ranks among the sports with the highest
cardiovascular demands and profound cardiac
remodeling.\textsuperscript{20} The Norwegian Birkebeiner XC ski race is
one of the world's most demanding XC ski races, with a course length of
54 km, covering approximately 1000 altitude meters. Previous studies
have demonstrated how participation in the Birkebeiner XC ski race is
associated with athletic cardiac remodeling and an increased risk of
AF.\textsuperscript{4, 13, 21} To cover the whole range of physical
activity in the population, the Birkebeiner Atrial Fibrillation study
(2012) comprised two independent cohorts; one cohort consisting of
persons who had completed the Birkebeiner XC ski race, and another
cohort of individuals that had participated in a population-based health
survey (The Oslo Health study).\textsuperscript{4} With the aim to
investigate athletic cardiac remodeling in relation to AF, we invited
520 former participants in the Birkebeiner Atrial Fibrillation study to
participate in a cross-sectional clinical study performed between
January 2019 and October 2020. All veteran skiers with AF living within
a 2-hour perimeter from the study site were invited. Participants with
supraventricular tachycardia other than AF, prior open-heart surgery,
heart failure (EF \textless{}35\%), or clinically significant valvular
disease were excluded. Veteran skiers without AF, age-matched to the
included skiers with AF, were invited until reaching the same number of
included skiers with and without a history of AF. Age-matched
participants from the non-athletic cohort with and without a history of
AF were consecutively invited until reaching the same number of included
individuals in all four groups. Because the original study cohort lacked
age-matched non-athletic controls, the group of non-athletes with AF was
supplemented by male patients visiting the AF outpatient clinic at
Diakonhjemmet Hospital between May and September 2020. All patients were
screened, and men of the proper age were consecutively invited to
participate. Participants with AF during the examination, paced rhythm,
or left bundle branch block were excluded from the current analysis
(Figure 1). The methods of the study have been described in detail
earlier.\textsuperscript{10}

All participants answered a questionnaire and underwent physical
examination by the main investigator (ES). Data from the questionnaire
(age, sex, history of heart failure, hypertension, stroke, coronary
heart disease, and diabetes mellitus) were used to estimate the
CHA\textsubscript{2}DS\textsubscript{2}-VASc score as a marker of
cardiovascular risk.\textsuperscript{22} Regular endurance exercise was
self-reported in the questionnaire on an eight-level ordinal scale. To
evaluate the dose-response relationship between years of endurance
exercise and LA MD, we condensed this scale into four categories in the
same matter used previously.\textsuperscript{13}

A 12-lead electrocardiogram (ECG) was obtained and exported in digital
format for offline processing using standard Glasgow algorithm with
automatic identification of fiducial points, intervals and amplitudes of
the components of the PQRST-complex.\textsuperscript{23} We affirmed the
history of AF by review of medical journals, adjudicating AF according
to guidelines.\textsuperscript{24} In 13 participants (5 athletes and 8
non-athletes), it was challenging to differentiate paroxysmal AF from
persistent AF, these were included as having paroxysmal AF.

The study complies with the Declaration of Helsinki and was approved by
the Regional Committee for Medical and Health Research Ethics (ref.nr:
2016/565). All participants gave written consent.

\emph{Transthoracic echocardiography:}

Resting echocardiograms were recorded in the left lateral decubitus
position by the main investigator (ES) using the same digital ultrasound
scanner in all participants (Vivid E9, GE Vingmed Ultrasound, Horten,
Norway). We obtained 2D-greyscale, tissue Doppler, and color Doppler
images in parasternal and apical views according to
recommendations.\textsuperscript{25} Three to five consecutive loops
were obtained and saved in cine loop format, including 200 milliseconds
(ms) before and after all beats.

The main investigator (ES) performed all analysis offline (Echo PAC
version 203, GE Vingmed Ultrasound, Horten, Norway), blinded to the
patients' other data.

Conventional parameters of left ventricular (LV) size were obtained,
calculated, and indexed to body surface area according to
recommendations.\textsuperscript{25} We obtained LA 2D acquisitions from
atria-focused apical views. LA volumes were calculated by the summation
of discs in apical four- and two-chamber
views.\textsuperscript{25}Atrial volumes were indexed to body surface
areas, and an average from three consecutive loops was computed.

\emph{Strain analysis:}

We assessed strain parameters by speckle-tracking echocardiography. LV
global longitudinal strain (GLS) was computed from apical four-chamber,
two-chamber, and long-axis views using the 18-segment
model.\textsuperscript{26} GLS was defined as the peak negative strain
during systole.

LA strain was obtained from LA-focused apical four-chamber 2D views at
frame rates \textgreater{}60 frames per second. The LA border was traced
along the endocardium from one side of the mitral annulus to the other,
and a region of interest was automatically defined, then adjusted
manually as recommended to fit the thickness of the LA
wall.\textsuperscript{27} The software divided the LA into six segments,
scoring tracking quality with the possibility of manual correction. Zero
strain reference was set at LV end-diastole, defined by the frame prior
to mitral valve closure. LA strain values were computed as the average
of accepted atrial segments averaged over three heart cycles and stated
as LA reservoir strain (LASr), LA conduit strain (LAScd), and LA
contractile strain (LASct).\textsuperscript{27} SD-TPS was calculated as
the mean value of the time-to-peak strain in the six atrial segments.
SD-TPS was calculated separately in three consecutive loops, and an
average of these values is reported. In addition to crude SD-TPS in ms,
SD-TPS was also corrected by the cycle length and expressed as a
percentage of the cardiac cycle SD-TPS (\%) = (\(\frac{SD-TPS(ms)}{Cycle\ length(ms)}\ X\ 100\)). A
higher value of SD-TPS reflects a higher degree of LA MD (Figure 2).

\emph{Statistical analysis:}

Normally distributed continuous variables are reported as mean ±
standard deviation, other continuous variables are reported as median
(25\textsuperscript{th}-75\textsuperscript{th} percentile). Categorical
variables are reported using frequencies and percentages.

Reproducibility analyses were conducted offline on 15 randomly selected
anonymized recordings using a two-way mixed model with absolute
agreement between measures. The main investigator (ES) performed
intra-observer analysis with a two-week interval between measurements.
Rater two (MGS) conducted inter-rater analysis, separated in time and
place from rater one, on the same set of recordings from each
participant. The raters could select different pictures and loops
randomly for analysis and re-analysis.

To explore the interplay between AF, athletic status, and
echocardiographic values, we conducted a two-way between-groups analysis
of variance with athletic status and AF status as independent variables.
In addition, a one-way analysis of variance with polynomial contrasts
investigating for a linear trend between SD-TPS and years of regular
exercise was performed in all participants without a history of AF to
explore the associations between prolonged endurance exercise and LA MD.

To assess the association between AF and SD-TPS, we performed a logistic
regression analysis with AF as the dependent variable, adjusting for
weight, height, CHA\textsubscript{2}DS\textsubscript{2}-VASc score, GLS,
QRS width, and indexed maximal LA volume (LAVI\textsubscript{max}) in
all participants and in athletes. We also performed a hierarchical
logistic regression adding LASr to the model to evaluate the independent
incremental value of SD-TPS in identifying athletes with AF.

Tests with \emph{P} -values \textless{}0.05 were considered
statistically significant. All analyses were performed using SPSS
Statistics version 26 (IBM, Armonk, NY).

\textbf{Results:}

Of 520 invited individuals, 394 (76\%) met for examination. After
exclusions, 57 athletes with paroxysmal AF, 87 athletes without AF, 88
non-athletes without AF, and 61 non-athletes with paroxysmal AF were
included (Figure 1).

\emph{Baseline characteristics:} All participants were men, with a mean
age of 70.7 ± 6.7 years. Athletes with and without AF reported a median
of 40-50 years of performing regular endurance exercise and a median of
16 completed annual Birkebeiner XC-races. Eighty-six participants had
never practiced regular endurance exercise, whereas 49 participants had
practiced regular endurance exercise for 1 to 20 years, 43 participants
for 20 to 40 years, and 115 participants for \textgreater{}40 years.
Almost 80\% of the athletes still participated in regular endurance
exercise at the time of examination. Athletes had a very low comorbidity
burden, a lower BMI and a lower resting heart rate than non-athletes.
Blood pressure was similar between all four groups. Individuals with AF
were taller than those without AF. The AF burden was low in both AF
groups, with more than three out of four individuals experiencing
paroxysms of AF less than once a month. While a higher proportion of
athletes had performed AF ablation, the use of antiarrhythmic drugs was
higher among non-athletes (Table 1).

\emph{Echocardiographic parameters:} LA echocardiographic parameters are
presented in Table 2, and LV echocardiographic values are presented as
supplemental material (Table S1). There was no significant interaction
between athletic status and AF status regarding atrial parameters. LA
size was associated both with athletic status and AF status. SD-TPS
stated in ms was associated with AF status but not athletic status. When
correcting SD-TPS by the R-R interval, we found SD-TPS (\%) to be
associated with both athletic and AF status. LASr, LAScd, and LASct were
lower in the AF groups regardless of athletic status. As opposed to
LAVI\textsubscript{max,} we could not identify any significant trend
between years of performing endurance exercise and SD-TPS in individuals
without a history of AF (p=0.893) (Figure 3).

SD-TPS remained significantly associated with AF after adjusting for
height, weight, CHA\textsubscript{2}DS\textsubscript{2}-VASc score,
LAVI\textsubscript{max}, GLS, and QRS width in all participants and the
athletic group alone (Table S2 and S3). However, SD-TPS did not remain
significantly associated with AF in athletes when LASr was included in
the model (p=0.06) (Table S4). Hence, in a hierarchical logistic
regression model, SD-TPS did not add independent incremental value in
identifying individuals with AF on top of clinical characteristics,
CHA\textsubscript{2}DS\textsubscript{2}-VASc score, QRS width, standard
echocardiographic values, and LASr (Figure 4).

Athletes had larger left ventricles and slightly lower GLS and E/e` than
non-athletes. There were no significant interactions between AF and
athletic status regarding LV values except for LV mass index. GLS was
not significantly affected by AF status.

\emph{Reproducibility:}

For SD-TPS intra-observer intraclass correlation coefficient (ICC) was
0.935 (0.812-0.978), and the inter-observer ICC was 0.932 (0.803-0.977).
LAVI\textsubscript{max} intra-observer ICC was 0.985 (0.957-0.995) and
inter-observer ICC 0.984 (0.954-0.995). For LAVI\textsubscript{min,} the
corresponding numbers were 0.980 (0.922-0.994) and 0.959 (0.881-0.986).
For LASr, intra-observer ICC was 0.846 (0.543-0.948) and inter-observer
ICC 0.893 (0.676-0.964). LAScd intra-observer ICC was 0.872
(0.614-0.956), inter-observer ICC 0.854 (0.557-0.951), and for LASct the
intra-observer ICC was 0.869(0.614-0.956) and the inter-observer ICC
0.820 (0.452-0.940).

\textbf{Discussion:} The main finding of this study is that LA MD was
associated with paroxysmal AF regardless of athletic status and not
associated with years of performing endurance exercise, despite
extensive cardiac remodeling among those reporting the longest history
of endurance exercise. However, LA MD had no independent incremental
value in identifying veteran athletes with a history of AF on top of
clinical markers, other relevant echocardiographic variables, and LASr.

Due to promising results in its ability to identify patients with
paroxysmal AF when in sinus rhythm, association with atrial fibrosis on
MRI, and ability to identify electrical remodeling regardless of LA
size, LA MD has emerged as an interesting marker when evaluating LA
remodeling in athletes.\textsuperscript{18, 28, 29} The present study is
the first to investigate the associations between LA MD, prolonged
endurance and AF in a large group of veteran endurance athletes.

Most studies of LA MD have defined the parameter as SD-TPS corrected by
the R-R interval (\%) instead of the crude SD-TPS value in
ms.\textsuperscript{14, 17, 28, 30} Endurance athletes experience
exercise-induced bradycardia and as expected, the athletes in the
present study had a lower resting heart rate than the non-athletic
group.\textsuperscript{31} Hence, we introduced an association between
athletic status and LA MD when correcting SD-TPS by the R-R interval.
Consequently, we chose to focus on SD-TPS in ms in this study and
suggest stating the crude SD-TPS values in ms as well as SD-TPS (\%)
when investigating LA MD in endurance athletes.

An MRI study by Peritz et al. suggested an association between long-term
endurance exercise and atrial fibrosis among a small group of healthy
athletes, and LA MD has been demonstrated to associate with LA fibrosis
on MRI.\textsuperscript{19, 29} We found no association between years of
reported endurance exercise and LA MD in this study, despite increasing
atrial volumes by years of exercise, indicating that athletic remodeling
per se has little effect on LA MD measured by echocardiography.

We found a highly significant association between paroxysmal AF and LA
MD irrespective of athletic status, suggesting LA MD assessed by SD-TPS
could be a promising marker of pathological atrial remodeling in
endurance athletes, less affected by physiological exercise-induced
cardiac remodeling than absolute volumetric measurements. However,
SD-TPS did not add an independent incremental value in identifying
veteran athletes with AF when including LASr in the model. This
questions the clinical utility of LA MD in veteran athletes, especially
considering novel software with automated function imaging of the LA,
making LA strain measurements more feasible without including LA MD
measurements as an option. Several studies in non-athletic cohorts have
demonstrated LA MD to have an independent incremental value at
identifying individuals with AF on top of LASr and to predict the
recurrence of AF post ablation.\textsuperscript{14, 16} Current
knowledge indicates that LA MD increases with increasing age in healthy
individuals.\textsuperscript{32} As the mean age in this study is 70
years, we must assume age-induced alterations in electromechanical
function are present and affect LA MD. As LA MD is perceived to increase
as associated with the pathophysiology of healthy aging, prospective
studies and studies in younger endurance athletes will have to answer
whether LA MD is an independent predictor of AF in endurance athletes
and if it adds incremental value to LASr when trying to identify younger
athletes with AF.

\emph{Strengths and limitations:} This is the first study to explore the
relationship between endurance exercise, AF, and LA MD, and it comprises
a unique cohort of veteran XC skiers with an average of 40-50 years of
performing endurance exercise.

The study may have seemed more appealing to individuals interested in
endurance exercise, attracting the fittest members of the non-athletic
control cohort, and possibly diluting the effect of training in the
athletic group. Finally, this is a single-center study, and due to the
low number of female participants in the Birkebeiner study with
exercise-related AF, men only were included.

\emph{Conclusion:} LA MD was associated with paroxysmal AF regardless of
athletic status but not associated with years of performing endurance
exercise despite considerable atrial remodeling in those reporting the
longest history of endurance exercise. These results suggest LA MD could
be a relevant marker of pathological atrial remodeling in endurance
athletes. However, LA MD did not add incremental value to LASr
identifying veteran athletes with AF, questioning its clinical utility
in this group.

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2. Warburton DER, Bredin SSD. Health benefits of physical activity: a
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3. Morseth B, Løchen ML, Ariansen I, Myrstad M, Thelle DS. The ambiguity
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gender. Echocardiography 2021;\textbf{38} (3):417-426.\selectlanguage{english}
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