International Journal of Cardiology 236 (2017) 270–275

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International Journal of Cardiology

journal homepage: www.elsevier.com/locate/ijcard

Training-induced right ventricular remodelling in pre-adolescent

endurance athletes: The athlete's heart in children
Flavio D'Ascenzi a,⁎, Antonio Pelliccia b, Francesca Valentini a, Angela Malandrino a, Benedetta Maria Natali a,
Riccardo Barbati c, Marta Focardi a, Marco Bonifazi d, Sergio Mondillo a
a
Department of Medical Biotechnologies, Division of Cardiology, University of Siena, Siena, Italy
b
Institute of Sports Medicine and Science, Rome, Italy
c
Division of Cardiology, Department of Cardiac, Thoracic and Vascular Sciences, Santa Maria alle Scotte Hospital, Siena, Italy
d
Department of Medicine, Surgery, and NeuroScience, University of Siena, Siena, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Aims: Little is known about the adaptation of the right ventricle (RV) to endurance exercise in children. The aim of
Received 23 November 2016 this study was to assess the effects of 5 months of intensive training on RV morphology and function in preado-
Accepted 25 January 2017 lescent endurance athletes.
Available online 27 January 2017 Methods: Ninety-four children were evaluated in this study. Fifty-seven male competitive swimmers (aged
10.8 ± 0.2 years) were evaluated before (baseline) and after 5 months of the training (peak-training), and com-
Keywords:
pared to 37 age- and sex-matched non-athlete children evaluated at baseline and after 5 months of natural
Athlete's heart
Children
growth. All subjects were asymptomatic, with negative family history for cardiomyopathies.
ARVC Results: At baseline no differences were found between athletes and controls for indexed RV outflow tract (RVOT)
Exercise-induced ARVC (18.5 ± 2.7 vs. 16.8 ± 5.0 mm/m2, p = 0.18) and RV basal end-diastolic diameter (EDD) (24.9 ± 4.1 vs. 23.6 ±
Speckle-tracking echocardiography 3.0 mm/m2, p = 0.15). After 5 months, indexed RVOT and RV basal EDD significantly increased in athletes
Strain (20.2 ± 2.9 mm/m2 and 25.4 ± 3.3 mm/m2, p b 0.0001 vs. baseline) while no differences were observed in con-
trols (p = 0.84 and p = 0.25). Despite the increase in RV size, RV function remained normal in athletes, with no
changes in RV fractional area change (p = 0.97), s′ value (p = 0.22), and RV longitudinal strain (p = 0.28).
Conclusions: Endurance training influences the growing heart of male preadolescent athletes with an addictive
increase in RV dimensions, with a preserved RV function. Therefore, in children engaged in endurance sports
the increase in RV size associated with normal RV function represents a physiological expression of the athlete's
heart and should not be misinterpreted as an expression of incipient RV cardiomyopathy.
© 2017 Elsevier B.V. All rights reserved.

1. Introduction
Cardiac remodelling induced by athletic conditioning (i.e., athlete's
heart) [1,2] has for long time been considered a physiologic adaptation
to training with no clinical consequences [3–6]. However, recently, a
special attention has been paid to right ventricular (RV) remodelling
and possible detrimental effects of intensive exercise conditioning
have been reported [7–9].
Most of the studies on ‘athlete's heart’ have been carried out in
adults [1–9] or rarely in adolescent individuals [10–12], and little is
known regarding the occurrence and extent, if any, of cardiac remodel-
ling in pre-adolescent individuals. Data derived from adults cannot be
transferable to preadolescent populations, as these young athletes are
physically less mature and exposed to a shorter intensity and duration
of training [12]. Furthermore, at the present time, data on the effects
of regular exercise training on RV morphology and function in preado-
lescent athletes are lacking [13–15].
Considering the increasing number of children involved in competi-
tive sports, the trend for more intensive training loads, and the very
young age at which pre-adolescent are being encouraged to start compet-
itive events, we believed timely and appropriate to investigate the cardiac
consequences of endurance training on pre-adolescent athletes. There-
fore, we sought to analyse: i) to what extent cardiac dimensions were al-
tered as a consequence of endurance training and body growth in athletes
and in controls during a competitive season; ii) whether changes in RV
morphology and function occurred in pre-adolescent athletes.
2. Materials and methods

2.1. Study design

⁎ Corresponding author at: Department of Medical Biotechnologies, Division of
Cardiology, University of Siena, Viale M. Bracci, 16, 53100 Siena, Italy. Sixty-two male pre-adolescent endurance athletes practicing competitive swimming
E-mail address: flavio.dascenzi@unisi.it (F. D'Ascenzi). at regional level were enrolled in this study. The mean age was 10.8 ± 0.2 (9–13 years).

http://dx.doi.org/10.1016/j.ijcard.2017.01.121
0167-5273/© 2017 Elsevier B.V. All rights reserved.
 F. D'Ascenzi et al. / International Journal of Cardiology 236 (2017) 270–275
The swimmers trained once a day, over 5 or 6 days each week. The typical training started
sessions have been previously described in details [16].
The evaluations were performed at the beginning of the season (September 2014,
named hereafter ‘baseline’) and after 5 months of intensive and closely supervised train-
ing (February 2015, named hereafter ‘peak-training’). During the 3 months preceding
the baseline evaluation athletes were active, but not engaged in any training program. In
the preceding year (winter/spring 2014), most of the participants had joined a supervised
introductory swimming program of mild intensity and duration. Young athletes were ex-
cluded from the study if they had signs of heart disease (cardiomyopathies, shunts, ven-
tricular septal defect or atrial septal defect, patent ductus arteriosus, complex ventricular
arrhythmias), family history of sudden cardiac death or cardiomyopathies, or if they with-
drew from the training program for N20 consecutive days. Accordingly, three athletes
were excluded from the initial population because of musculoskeletal injuries and two
for evidence of cardiac heart disease (1 with atrial septal defect and 1 with patent ductus
arteriosus). Thus, the final athletes' population included 57 healthy subjects.
Thirty-seven sedentary age-matched male subjects were used as controls. The mean
age was 10.2 ± 0.2 (9–13 years). Controls participated in recreational physical activities
for b2 h per week and none was engaged in a regular training program.
The participants of the study underwent complete physical examination, ECG, echo-
cardiography, and step ECG test. None of the participants showed evidence for cardiac dis-
ease, hypertension, type I diabetes mellitus, and/or endocrine disease. After the rationale
and the study protocol were explained, the parents gave written informed consent for
their offspring to participate in this study. The local Ethical Committee approved the inves-
tigational protocol.
2.2. Physical examination
Height, weight and body surface area (BSA) were obtained both at the beginning of
the study and after 5 months [17]. The biological maturation of the participants was
established using the Tanner's five stages of penile and testicular development [18], ob-
tained at the two different time-points. The presence of cardiac symptoms, fatigue, or per-
formance impairment was also investigated.
2.3. Twelve-lead ECG
A standard 12-lead ECG was performed using an ESAOTE P8000 Power Light, recorded
at 25 mm/s in a supine position during quiet respiration. ECG was interpreted by an expert
cardiologist, blinded to study time and without any knowledge of the echocardiographic
findings. The ECG examination has been previously described in details [19]. Left axis de-
viation was defined as a QRS axis exceeding −30°, and right axis deviation was defined as
a QRS axis exceeding +120°. Incomplete right bundle branch block (RBBB) was defined as
QRS duration b100 ms, with r′ or R′ wave in lead V1 and S wave of greater duration than R
wave or N40 ms in leads I and V6, while complete RBBB was defined as QRS duration
N100 ms in presence of the criteria above described [20]. The presence of negative T
waves in the peripheral leads and beyond V1 in the precordial leads was evaluated [21].
The presence of RV hypertrophy was defined by the sum of the R waves in V1 and the S
waves in V6 exceeding 1.05 mV [22].
2.4. Echocardiographic examination
The echocardiographic examination was performed by one cardiologist using a high-
quality echocardiograph (Vivid 9, GE, Milwaukee, WI, USA), equipped with a M4S
1.5–4.0 MHz transducer, and a one-lead ECG was continuously displayed. Off-line data
analysis, from three stored cycles, was performed by two experienced readers, blinded
to the study time-point, using a dedicated software (EchoPac, version 112, GE, USA).
RV chamber size was assessed as recommended [23]. Basal and mid-cavity end-
diastolic diameters were obtained. RV outflow tract (RVOT) diameter was measured at
the proximal level in the parasternal long-axis view, calculated from the anterior RV
wall to the RV septum (RVOT PLAX) [24]; at subvalvular level in the parasternal short
axis at the level of the aortic valve, calculating the maximum distance between the ante-
rior aortic wall and the RV free wall (RVOT PSAX), and at pulmonic valve from the
parasternal short-axis of pulmonary bifurcation view (RVOT distal diameter) [23]. RV
end-diastolic and end-systolic areas were calculated by tracing the RV endocardium
from a modified apical 4-chamber view, and RV fractional area change (FAC) was derived
and expressed as percentage [24]. Tricuspid annular plane systolic excursion (TAPSE) was
also calculated [23]. Left ventricular (LV) end-diastolic and end-systolic volumes and LV
ejection fraction were calculated, as recommended [24] and indexed to BSA [25].
The Z-scores were calculated both in athletes and in controls to evaluate whether
RVOT PLAX, RVOT distal diameter, and RV end-diastolic area exceeded the cut-off value re-
ported for the normal population, i.e. ≤2 [26,27].
Pulsed-wave Doppler and Tissue Doppler imaging (TDI) evaluation were recorded in
the apical four-chamber view by placing the sample volume at the tips of tricuspid valve
and at the tricuspid annulus, respectively [28]. The following measurements of RV filling
were considered: E peak and A peak velocities, E/A ratio, s′, e′, and a′ velocities, tricuspid
E/e′ ratio.
The echocardiographic examination was completed by two-dimensional speckle-
tracking echocardiographic analysis, a non-invasive imaging technique that has recently
applied to athlete's heart, enhancing our understanding of biventricular and biatrial myo-
cardial deformation in athletes [3,4,8,29–31]. Speckle-tracking echocardiography was per-
formed on narrow-sector gray-scale images of both RV and LV from an apical four-
271
chamber view with temporal resolution of 60–90 frames/s. All images were optimized
with gain, compression, and dynamic range to enhance myocardial definition with stan-
dardized depth, frequency, and insonation angle for all participants [32]. Off-line analysis
was performed by an experienced reader, blinded to the study time-point, using a com-
mercially available semi-automated 2D strain software (EchoPAC PC, version 112, GE,
USA) [32]. A region of interest was manually traced along the endocardial border of the
RV free wall from the base to the apex, and excluding the interventricular septum.
Width was set to match the wall thickness. If the automated 2D analysis appraisal of ac-
ceptable tracking quality indicated inappropriate tracking, retracing was performed until
all segments were considered acceptable [33].
2.5. Statistical analysis
Normal distribution of all continuous variables was examined using the Shapiro–Wilk
test, and data are presented as mean ± SD or median and interquartile range, as appropri-
ate. Categorical variables are expressed as percentages. The unpaired t-test and the Mann–
Whitney U test were used to assess the between groups significance, according to data dis-
tribution. The paired t-test and the Wilcoxon matched-pair test were used to assess the
within subjects significance of baseline and peak-training measurements, as appropriate
for data distribution. A p value b0.05 was considered significant. The potential differences
in Tanner's group assignment between athletes and controls were adjusted using sam-
pling weights so that the marginal totals on Tanner's group assignment in the athletes
group agreed with the corresponding totals of the control population, according to raking
ratio estimation [34].
Correlation analysis was performed to find association between continuous variables
using the Spearman and Pearson methods, as appropriate for data distribution. The change
of parameters between baseline and 5-month measurements were calculated and used as
dependent or independent variables.
To assess the reproducibility of RV parameters, measurements were repeated, in a
random sample of 20 subjects (10 athletes and 10 controls), by the same investigator
(intra-observer variability). Inter- and intra-observer variability was assessed by the
intraclass correlation coefficients (ICC) with 95% confidence intervals (CIs).
Statistics were performed using SPSS version 21.0 software for Windows (Statistical
Package for the Social Sciences Inc., Chicago, IL).
3. Results
The demographic characteristics of athletes and controls are report-
ed in Table 1. At baseline there were no significant differences between
athletes and controls for height, weight, and BSA. After 5 months, a sig-
nificant increase in height, weight, and BSA was found both in the ath-
letes and in the controls (p b 0.0001).
At baseline, 46% (n = 25) of athletes were at stage 1 (pre-puberty)
and the rest were at stages 2–5 (puberty). After 5 months, 9% (n = 5)
of athletes reached the sexual maturity, with 37% remaining at the
pre-pubertal stage (n = 20). At baseline the 43% (n = 16) of controls
were at stage 1 (pre-puberty) while the 16% (n = 6) reached sexual ma-
turity in the following 5 months with 27% remaining at pre-pubertal
stage (n = 10).
3.1. 12-lead resting ECG
At baseline athletes had a lower resting HR as compared with controls
and a further decrease in resting HR was observed at peak-training
(Table 1). An incomplete RBBB was found in 19% of athletes both at pre-
and peak-training time points and in 15% of controls both at baseline
and after 5-month time points (p value athletes vs. controls = 0.69). At
baseline, 6% of controls (but none of the athletes) showed negative T
waves in the precordial leads V1 to V3, which reduced to 3% after 5-
month (p = 0.16 vs. baseline). None of the athletes exhibited negative T
waves from V1 to V3 either at baseline or at peak training evaluation. At
baseline, T-wave inversion in the precordial leads from V1 to V2 were
present in 18% of athletes and 17% of controls; after 5 months a significant
decrease was observed in the former (p = 0.002). Neither athletes nor
controls showed complete RBBB. None of the participants did fulfil the
ECG criteria for RV hypertrophy.
3.2. Morphological adaptation
The baseline and peak-training measurements obtained in athletes
and the baseline and 5-month data found in controls are reported in
Table 2. At baseline, absolute and indexed RVOT PSAX did not differ
272 F. D'Ascenzi et al. / International Journal of Cardiology 236 (2017) 270–275

Table 1
Demographic characteristics of the study population.

Variable Controls Endurance athletes p value athletes p value athletes baseline- p value controls baseline
(n = 37) (n = 57) vs. controls vs. peak-training vs. 2nd evaluation
(baseline)
Baseline 2nd evaluation Baseline Peak-training

Resting HR, bpm 77 ± 12 78 ± 11 72 ± 9 67 ± 9 0.046 b0.0001 0.63

Height, cm 142.2 ± 8.3 145.9 ± 8.8 146.3 ± 10.9 149.0 ± 10.9 0.11 b0.0001 b0.0001
Weight, kg 41.5 ± 12.0 44.1 ± 12.4 41.4 ± 9.9 43.2 ± 10.0 0.94 b0.0001 b0.0001
BSA, m2 1.27 ± 0.20 1.33 ± 0.20 1.29 ± 0.20 1.34 ± 0.20 0.45 b0.0001 b0.0001

Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; BSA, body surface area.

between athletes and controls. Conversely, absolute values of RVOT
PLAX, RVOT distal diameter, RV basal and mid cavity diameters were
mildly larger in athletes (by 5%, 10%, 6%, and 19%, respectively). Howev-
er, when these measures were indexed to BSA, no significant differences
remained between athletes and controls. Also, indexed RV end-diastolic
area did not differ between athletes and controls, while indexed RV
end-systolic area was greater in the former.
After 5 months, both absolute and indexed RVOT diameters sig-
nificantly increased in athletes. Specifically, indexed values of RVOT
PLAX increased by 9% (p b 0.0001), RVOT PSAX by 14% (p b 0.0001)
and RVOT distal diameter by only 3% (p = 0.26), while no differences
were observed in controls. Indexed mid-cavity diameter did increase
both in athletes and controls (by 6%, p = 0.001 and by 6% p b 0.0001,
respectively) while neither in athletes nor in controls indexed RV
basal diameter did significantly change (2%, p = 0.24; 1%, p = 0.25,
respectively). The dimensional increase observed in athletes after
5 months of training was confirmed also by the increase in RV end-
diastolic area and RV end-systolic area (by 14% and 9% for indexed
values, p b 0.0001 and p = 0.009, respectively) while these parame-
ters did not change in controls. Fig. 1.
LV dimensions at baseline were mildly greater in athletes as com-
pared to controls (indexed LV end-diastolic volume: 47.8 ± 7.5 vs.
43.2 ± 6.2 mL/m2, respectively, p = 0.007; indexed LV end-systolic vol-
ume: 16.7 ± 3.7 vs. 14.4 ± 3.3 mL/m2, respectively, p = 0.003). After
5 months of training a further increase was found in athletes (at peak-
training indexed LV end-diastolic volume: 57.2 ± 7.3 mL/m2 and
indexed LV end-systolic diameter 20.1 ± 3.2 mL/m2, p = 0.0001 for
both), while no changes were observed in the control group.
3.3. Z scores for right ventricular size
None of the sedentary controls exceeded the normal cut-off value
when the Z-score was calculated for RVOT PLAX, RVOT distal diameter,
and RV end-diastolic area. In the athletic population the Z-score calcu-
lated for RVOT PLAX and RVOT distal diameter at baseline and peak-
training time point are showed in Fig. 2. RV end-diastolic area value
was within the normal range both at baseline and peak-training time
point in athletes. The proportion of athletes exceeding the cut-off limit
widely used for RVOT PLAX in the paediatric population did not differ
between baseline and peak-training time points (i.e., 0% vs. 2%, p =
0.32), while the proportion of athletes showing a Z score N 2 for RVOT
distal diameter significantly increased at peak training (4% to 15%,
p = 0.034).
Neither athletes nor controls exhibited significant changes in RV FAC
after 5 months of observation, although the former had a mild lower RV
FAC as compared with sedentary subjects (p = 0.007).
3.4. Right ventricular functional adaptation
Functional parameters of RV function are listed in Table 3. At base-
line TAPSE did not differ between athletes and controls (p = 0.63).
After 5 months an increase was found in athletes (p b 0.001) while
this parameter did not change in controls (p = 0.087). While E/A ratio
did not differ between athletes and controls at baseline (p = 0.37)
and did not vary in controls (p = 0.10), a significant increase was
found in athletes after training (p b 0.001). No differences were ob-
served between athletes and controls in terms of TDI-derived myocardi-
al velocities and they did not vary after 5 months with the exception of e
′ velocity (p = 0.009).
No differences were found between athletes and controls for RV
global longitudinal strain (p = 0.063). After 5 months of observation,
neither in athletes nor in controls RV global longitudinal strain did
change (p = 0.28 and p = 0.92, respectively). No RV wall motion abnor-
malities, including akinesia, dyskinesia and aneurism were found in
both groups during the period of observation.

Table 2
Right ventricular dimensional parameters observed at baseline and after 6 months of the beginning of the study in competitive athletes and in controls.

Variable Controls Endurance athletes p value athletes p value athletes baseline- p value controls baseline
(n = 37) (n = 57) vs. controls vs. peak-training vs. 2nd evaluation
(baseline)
Baseline 2nd evaluation Baseline Peak-training

RVOT PLAX, mm 22.3 ± 2.4 23.3 ± 2.9 23.4 ± 2.3 26.4 ± 3.3 0.035 b0.0001 0.032
RVOT PLAX index, mm/m2 16.8 ± 5.0 17.7 ± 2.5 18.5 ± 2.7 20.2 ± 2.9 0.18 b0.0001 0.84
RVOT PSAX, mm 24.5 ± 3.2 24.9 ± 2.7 25.5 ± 4.2 30.1 ± 4.5 0.23 b0.0001 0.31
RVOT PSAX index, mm/m2 19.0 ± 4.2 19.0 ± 2.5 20.1 ± 3.6 22.9 ± 3.5 0.95 b0.0001 0.42
RVOT distal diameter, mm 20.2 ± 2.8 20.0 ± 2.8 22.2 ± 3.1 23.3 ± 3.9 0.005 0.006 0.16
RVOT distal diameter index, mm/m2 16.4 ± 2.0 16.2 ± 1.9 17.3 ± 3.1 17.8 ± 2.9 0.15 0.26 0.42
RV basal diameter, mm 29.5 ± 2.7 29.8 ± 2.9 31.4 ± 3.2 33.5 ± 3.7 0.007 b0.0001 0.20
RV basal diameter index, mm/m2 23.6 ± 3.0 23.1 ± 3.1 24.9 ± 4.1 25.4 ± 3.3 0.15 0.24 0.25
RV mid-cavity diameter, mm 24.5 ± 2.8 25.9 ± 3.2 29.1 ± 3.3 32.4 ± 4.4 b0.0001 b0.0001 0.002
RV mid-cavity diameter index, mm/m2 19.4 ± 2.7 20.2 ± 3.1 23.1 ± 4.2 24.6 ± 3.5 0.070 0.001 b0.0001
RV end-diastolic area, cm2 13.8 ± 2.8 14.4 ± 2.5 14.7 ± 2.8 17.0 ± 3.7 0.05 b0.0001 0.077
RV end-diastolic area index, cm2/m2 10.6 ± 2.3 10.9 ± 2.5 11.5 ± 1.8 13.1 ± 1.9 0.12 b0.0001 0.62
RV end-systolic area, cm2 7.2 ± 1.9 7.5 ± 1.7 8.3 ± 1.7 9.7 ± 2.2 0.002 b0.0001 0.43
RV end-systolic area index, cm2/m2 5.5 ± 1.6 5.7 ± 1.0 6.6 ± 1.5 7.2 ± 1.2 0.003 0.009 0.70
RVFAC, % 48.6 ± 8.2 48.1 ± 7.2 42.9 ± 7.5 42.7 ± 8.5 0.007 0.97 0.86

Abbreviations: RVOT, right ventricular outflow tract; PLAX, parasternal long-axis view; PSAX, parasternal short-axis view; FAC, fractional area change.
 F. D'Ascenzi et al. / International Journal of Cardiology 236 (2017) 270–275 273

Fig. 1. Measurements of right ventricular basal end-diastolic diameter and right ventricular end-diastolic area observed at baseline and after 5 months of training and growth in athletes
and after 5 months of growth in controls, respectively.

3.5. Weighted analysis 3.7. Reproducibility analysis

The weighted analysis was performed to reassign the differences be-
tween the two groups in terms of growth and development, matching
the groups according to Tanner's scale. The comparison between base-
line and peak-training in the athletes confirmed the results of the orig-
inal analysis by demonstrating an actual increase in RV size. Indeed,
RVOT PLAX (p b 0.0001), RVOT PSAX (p b 0.0001), RVOT distal diameter
(p = 0.004), RV basal diameter (p b 0.0001), RV mid-cavity diameter
(p b 0.0001), RV end-diastolic area (p b 0.0001), and RV end-systolic
area (p b 0.0001) did change after training.
The intra-observer variability yielded an ICC of 0.97 (95% CI from
0.93 to 0.99, p b 0.001) for basal RV diameter, an ICC of 0.99 (95% CI
from 0.98 to 0.99, p b 0.001) for mid-cavity RV diameter, an ICC of
0.97 (95% CI from 0.94 to 0.99, p b 0.001) for RVOT PLAX, an ICC of
0.96 (95% CI from 0.92 to 0.99, p b 0.001) for RVOT PSAX, and an ICC
of 0.98 (95% CI from 0.97 to 0.99, p b 0.001) for RV strain.
4. Discussion

Although the number of children involved in sports activity pro-

3.6. Correlation analysis
The change of RV end-systolic area correlated with LV end-systolic
volume (R = 0.37, p = 0.009) and with LV end-diastolic volume
(R = 0.33, p = 0.012). The change of RV basal diameter correlated
with the change of LV end-diastolic volume (R = 0.38, p = 0.003).
Also RV mid-cavity diameter (R = 0.33, p = 0.010) and RV end-
diastolic area (R = 0.26, p = 0.047) did correlate with the change of
LV end-diastolic volume.
grams is increasing and there is a trend to more intensively engage
very young individuals in competitive events, a few data are currently
available on the consequences of intensive exercise conditioning on car-
diac remodelling and function. In the present study we sought to assess
whether intensive endurance training in pre-adolescent children may
affect cardiac growth and function and may induce RV remodelling
and deterioration of RV function. Our data suggest that, as combination
of natural growth, the RV did increase both in athletes and in sedentary
controls, but the extent of morphological RV remodelling was

Fig. 2. Z-score values of right ventricular outflow tract (RVOT) measured in parasternal long-axis view and Z-score values of RVOT distal diameter tract 3. Data were obtained in athletes at
peak-training time point.
274 F. D'Ascenzi et al. / International Journal of Cardiology 236 (2017) 270–275

Table 3
Right ventricular functional parameters observed at baseline and 5 months after the beginning of the study in competitive athletes and in controls.

Variable Controls Endurance athletes p value athletes p value athletes baseline- p value controls baseline
(n = 37) (n = 57) vs. controls vs. peak-training vs. 2nd evaluation
(baseline)
Baseline 2nd evaluation Baseline Peak-training

s′, cm/s 14.2 ± 2.4 14.3 ± 2.3 14.1 ± 2.1 13.7 ± 2.0 0.75 0.22 0.79
e′, cm/s 18.8 ± 3.2 18.2 ± 7.1 15.9 ± 3.1 17.2 ± 2.8 0.32 0.009 0.68
a′, cm/s 10.4 ± 2.8 11.2 ± 4.5 9.5 ± 2.3 9.5 ± 2.7 0.18 0.97 0.56
E/A ratio 1.6 ± 0.4 1.7 ± 0.8 1.6 ± 0.4 2.0 ± 0.4 0.37 b0.0001 0.10
e′/a′ ratio 1.7 ± 0.5 1.7 ± 0.4 1.8 ± 0.6 1.9 ± 0.6 0.64 0.28 0.90
E/e′ ratio 4.2 ± 0.9 4.4 ± 0.9 4.6 ± 1.4 4.6 ± 1.3 0.33 0.93 0.060
TAPSE, mm 21.8 ± 2.6 22.7 ± 2.5 22.0 ± 3.1 24.8 ± 3.2 0.63 b0.0001 0.087
Global strain, % −31.6 ± 7.0 −31.1 ± 4.8 −29.2 ± 5.8 −30.2 ± 6.0 0.063 0.28 0.92
TTP, ms 328.3 ± 32.5 326.3 ± 303 336.1 ± 30.0 327.5 ± 33.8 0.51 0.15 0.98

Abbreviations: TAPSE, tricuspid annular plane systolic excursion; TTP, time-to-peak.

significantly greater in athletes as a consequence of intensive exercise
conditioning.
At the beginning of the study, athletes demonstrated mildly
larger absolute RV dimensions than their sedentary counterparts.
However, when these measurements were indexed to BSA, no signif-
icant differences remained. Although the appropriate scaling of
cardiac structures to account for individual differences has been fre-
quently questioned, recent evidences suggest that BSA is a more im-
portant determinant of cardiac size in normal children than height
and weight [35] and that RV linear dimensions are associated in a lin-
ear fashion with two-dimensional body size scaling variable [36].
In the literature, evidence of RV adaptation in preadolescent subjects
is scant and conflicting. Indeed, while some authors demonstrated a
lack of differences between pre-adolescent athletes and controls and
hypothesized a blunted adaptation to training in children [37], others
found that 91% of preadolescent swimmers who participate extensively
in training programs have a RV cavity exceeding the 95th percentile de-
rived from the normal paediatric population [38]. However, the com-
parison among the studies is partly confounded by the predominantly
cross-sectional nature, which precludes the appropriate partitioning of
the influences of training from the concomitant influences of growth,
maturation, and training level.
In this longitudinal study we found that both trained and sedentary
groups significantly increased their height, weight, and BSA after
5 months. However, the extent of RV dimensional remodelling was
more evident in endurance-trained children, which exhibited also an in-
crease in indexed RVOT PSAX and RV end-diastolic and end-systolic
areas, suggesting that intensive training has additive effects to the
growth on RV size. In a previous longitudinal study in adult athletes
we demonstrated that, while global RV size increased after training,
RVOT diameters did not change, supporting the usefulness of RVOT di-
ameters in differentiating between arrhythmogenic right ventricular
cardiomyopathy and athlete's heart [4]. Conversely, in this study we
found that, while the percentage of changes in RV mid-cavity and
basal end-diastolic diameters and end-diastolic area was similar be-
tween preadolescent and adult athletes, RVOT diameters increased
with a greater extent in the former. Therefore, although none of the
children exhibited RV wall motion abnormalities, the present findings
demonstrate that exercise-induced RV remodelling in highly-trained
preadolescent athletes can hamper the differential diagnosis between
arrhythmogenic right ventricular cardiomyopathy and athlete's heart.
By demonstrating that both the left and the right heart rapidly adapt
in endurance-trained preadolescents, we refute the notion of a ‘matura-
tional threshold’ that must be surpassed for significant cardiac dimen-
sional influences of training to be manifested. Although the differences
in sexual maturation between athletes and in controls were normalized
by the weighted analysis, the RV dimensional remodelling occurring
with a greater extent in athletes is remarkable, considering that a
large proportion of them (i.e., 37% vs. 27% of controls) were still at the
pre-pubertal stage. These findings are in agreement with previous
observations showing that intensive physical training prolongs the
pre-pubertal stage and delays the pubertal development, particularly
in individual engaged in endurance sports [39,40].
In agreement with previous studies in adult athletes [3,4,6,41],
we confirmed in this study that also in pre-adolescent athletes the
physiological, training-induced remodelling of the heart occurs
with a balanced and symmetric adaptation, as demonstrated by the
interdependence between the RV and the LV changes found at corre-
lation analysis.
Finally, in this study we demonstrated that, after 5 months of inten-
sive endurance training, the RV dilatation was accompanied by a signif-
icant increase in functional parameters, including E/A ratio, TAPSE and e
′ velocity, with global RV strain and RV FAC remaining stable. These
findings support the hypothesis that RV function is not impaired by en-
durance training in the early phase of the sports career of an athlete.
Furthermore, repolarisation abnormalities in the right precordial leads
were found both in athletes and in controls, decreased after 5 months
and were not associated with abnormal echocardiographic findings,
suggesting that they are not an expression of RV dysfunction, are influ-
enced more by changes in sexual maturation than by training.
5. Limitations
While the present study suggests that the influence of training status
on RV size can occur also in children, this finding may be sport specific:
it is possible that the influence of age and the related hormonal and
growth factors may be more important in different (i.e., anaerobic)
sports. Furthermore, we cannot exclude that the observed response to
training may reflect genetic traits, which predispose the trained chil-
dren to a more favourable and relevant adaptation. The study was con-
ducted in a homogeneous group of male athletes in order to avoid a
misinterpretation of data, potentially influenced by differences in
terms of development and sexual hormones between males and fe-
males. Therefore, the present results should not be generalised to both
genders.
The lack of normative reference values for indexed measures of
the RV in the paediatric population represents a limitation. However,
using Z-scores for some RV dimensional parameters and the intra-
individual comparison allowed us to overcome at least in part this
limitation.
Cardiac magnetic resonance represents the gold standard technique
to non-invasively estimate cardiac size. Although difficult in longitudi-
nal studies, the assessment of RV size and function by cardiac magnetic
resonance should be performed in future investigations aimed to evalu-
ate the impact of endurance training in children.
6. Conclusions
Endurance training is able to influence the growing heart of male
preadolescent athletes with an addictive increase in cardiac dimensions,
 F. D'Ascenzi et al. / International Journal of Cardiology 236 (2017) 270–275 275

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