Left atrial remodelling in competitive adolescent soccer players

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795 Training & Testing D’Ascenzi F et al. Left Atrial Remodelling in … Int J Sports Med 2012; 33: 795–801 accepted after revision February 01, 2012 Bibliography DOI http://dx.doi.org/ 10.1055/s-0032-1304660 Published online: May 4, 2012 Int J Sports Med 2012; 33: 795–801 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0172-4622 Correspondence Dr. Flavio D’Ascenzi Department of Cardiovascular Diseases viale M. Bracci University of Siena 16 53100 Siena Italy Tel.: +39/348/7034 493 Fax: +39/057/8267 232 [email protected] Key words speckle-tracking echo- cardiography athlete’s heart left atrium training tissue Doppler imaging exercise football players Left Atrial Remodelling in Competitive Adolescent Soccer Players those of non-athletes. However, cross-sectional data are not sucient to establish whether ath- letic training is causal in the development of spe- cic cardiac morphologic and functional ndings in athletes [5]. In contrast to the number of cross- sectional comparisons, few longitudinal prospec- tive studies have been undertaken. Two-dimensional (2D) speckle-tracking echocar- diography (STE) can be considered a feasible and reproducible technique for the assessment of LA deformation dynamics and may represent a promising tool for the early detection of LA strain abnormalities [6, 21, 22, 32]. Moreover, this new echocardiographic technique may elucidate the role of LA in the context of athlete’s heart [9]. The aim of the present study was to prospectively evaluate the structural and functional changes of LA, as assessed by standard echocardiography and by 2D STE, occurring in adolescent soccer players engaged in an 8-month training program. We hypothesized a dynamic nature of LA adapta- tions to training. Introduction Physical exercise is associated with haemody- namic changes and training determines cardiac adaptations that may dier according to the sport type [12, 13]. Previous studies suggested that training leads to signicant changes in left ventricular (LV) structure and function [3, 6, 33]. The process of left atrial (LA) remodelling is a component of cardiac adaptations associated with exercise conditioning which is often neglected and encompasses not only structural changes, as demonstrated by its enlargement [7, 28], but also functional adaptation, with a dif- ferent pattern of myocardial longitudinal defor- mation dynamics in athletes in comparison with controls [9]. Moreover, some authors reported that exercise conditioning is associated with an improvement in the diastolic properties of the LV myocardium [7]. Several cross-sectional studies investigated echo- cardiographic parameters in athletes engaged in a training program, comparing these data with Authors F. D’Ascenzi 1 , M. Cameli 1 , M. Lisi 1 , V. Zacà 1 , B. Natali 1 , A. Malandrino 1 , S. Benincasa 1 , S. Catanese 2 , A. Causarano 2 , S. Mondillo 1 Aliations 1 Department of Cardiovascular Diseases, University of Siena, Siena, Italy 2 Medical Sta, Siena Football Club, Siena, Italy Abstract Left atrial (LA) enlargement and improved myo- cardial diastolic properties are a component of athlete’s heart. We performed a longitudinal study involving adolescent athletes to investi- gate the impact of training on LA remodelling and diastolic function. 21 competitive adoles- cent soccer players were enrolled and engaged in an 8-month training program. Echocardio- graphic analysis was performed at baseline, after 4 and 8 months. We assessed diastolic function by Doppler tissue imaging and we analyzed LA adaptations by 2D speckle-tracking echocardio- graphy. After 4 months, LA mean volume index signicantly increased (Δ = 5.47 ± 4.38 mL/m 2 , p 0.0001). After 8 months, a further increase occurred (Δ = 8.95 ± 4.47 mL/m 2 , p 0.0001). A higher E velocity (p = 0.001; p = 0.001), a greater E/A ratio (p = 0.002; p = 0.0009), a higher e’ peak (p = 0.005; p = 0.001), and a greater e’/a’ ratio (p = 0.01; p = 0.0006) were observed at 4 and at 8 months, respectively. E/e’ ratio signicantly decreased after 8 months (p 0.005). Global peak atrial longitudinal strain and global peak atrial contraction strain values signicantly decreased after 8 months (p = 0.0004, p = 0.01, respectively). An 8-month training program is associated with LA dimensional and functional training-specic adaptations in competitive adolescent soccer players. Myocardial diastolic properties can improve after training also in subjects already presenting with features of athlete’s heart.

Transcript of Left atrial remodelling in competitive adolescent soccer players

795Training & Testing

D’Ascenzi F et al. Left Atrial Remodelling in … Int J Sports Med 2012; 33: 795–801

accepted after revision February 01 , 2012

BibliographyDOI http://dx.doi.org/10.1055/s-0032-1304660Published online: May 4, 2012Int J Sports Med 2012; 33: 795–801© Georg Thieme Verlag KG Stuttgart · New YorkISSN 0172-4622

Correspondence Dr. Flavio D’Ascenzi Department of Cardiovascular Diseases viale M. Bracci University of Siena 16 53100 Siena Italy Tel.: +39/348/7034 493 Fax: +39/057/8267 232 fl [email protected]

Key words ● ▶ speckle-tracking echo-

cardiography ● ▶ athlete’s heart ● ▶ left atrium ● ▶ training ● ▶ tissue Doppler imaging ● ▶ exercise ● ▶ football players

Left Atrial Remodelling in Competitive Adolescent Soccer Players

those of non-athletes. However, cross-sectional data are not suffi cient to establish whether ath-letic training is causal in the develop ment of spe-cifi c cardiac morphologic and functional fi ndings in athletes [ 5 ] . In contrast to the number of cross-sectional comparisons, few longitudinal prospec-tive studies have been undertaken. Two-dimensional (2D) speckle-tracking echocar-diography (STE) can be considered a feasible and reproducible technique for the assessment of LA deformation dynamics and may represent a promising tool for the early detection of LA strain abnormalities [ 6 , 21 , 22 , 32] . Moreover, this new echocardiographic technique may elucidate the role of LA in the context of athlete’s heart [ 9 ] . The aim of the present study was to prospectively evaluate the structural and functional changes of LA, as assessed by standard echocardiography and by 2D STE, occurring in adolescent soccer players engaged in an 8-month training program. We hypothesized a dynamic nature of LA adapta-tions to training.

Introduction ▼ Physical exercise is associated with haemody-namic changes and training determines cardiac adaptations that may diff er according to the sport type [ 12 , 13 ] . Previous studies suggested that training leads to signifi cant changes in left ventricular (LV) structure and function [ 3 , 6 , 33 ]. The process of left atrial (LA) remodelling is a component of cardiac adaptations associated with exercise conditioning which is often neglected and encompasses not only structural changes, as demonstrated by its enlargement [ 7, 28 ] , but also functional adaptation, with a dif-ferent pattern of myocardial longitudinal defor-mation dynamics in athletes in comparison with controls [ 9 ] . Moreover, some authors reported that exercise conditioning is associated with an improvement in the diastolic properties of the LV myocardium [ 7 ] . Several cross-sectional studies investigated echo-cardiographic parameters in athletes engaged in a training program, comparing these data with

Authors F. D’Ascenzi 1 , M. Cameli 1 , M. Lisi 1 , V. Zacà 1 , B. Natali 1 , A. Malandrino 1 , S. Benincasa 1 , S. Catanese 2 , A. Causarano 2 , S. Mondillo 1

Affi liations 1 Department of Cardiovascular Diseases, University of Siena, Siena, Italy 2 Medical Staff , Siena Football Club, Siena, Italy

Abstract ▼ Left atrial (LA) enlargement and improved myo-cardial diastolic properties are a component of athlete’s heart. We performed a longitudinal study involving adolescent athletes to investi-gate the impact of training on LA remodelling and diastolic function. 21 competitive adoles-cent soccer players were enrolled and engaged in an 8-month training program. Echocardio-graphic analysis was performed at baseline, after 4 and 8 months. We assessed diastolic function by Doppler tissue imaging and we analyzed LA adaptations by 2D speckle-tracking echocardio-graphy. After 4 months, LA mean volume index signifi cantly increased (Δ = 5.47 ± 4.38 mL/m 2 , p ≤ 0.0001). After 8 months, a further increase

occurred (Δ = 8.95 ± 4.47 mL/m 2 , p ≤ 0.0001). A higher E velocity (p = 0.001; p = 0.001), a greater E/A ratio (p = 0.002; p = 0.0009), a higher e’ peak (p = 0.005; p = 0.001), and a greater e’/a’ ratio (p = 0.01; p = 0.0006) were observed at 4 and at 8 months, respectively. E/e’ ratio signifi cantly decreased after 8 months (p ≤ 0.005). Global peak atrial longitudinal strain and global peak atrial contraction strain values signifi cantly decreased after 8 months (p = 0.0004, p = 0.01, respectively). An 8-month training program is associated with LA dimensional and functional training-specifi c adaptations in competitive adolescent soccer players. Myocardial diastolic properties can improve after training also in subjects already presenting with features of athlete’s heart.

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Methods ▼ Study population Male adolescent elite soccer players (Siena Football Club Acad-emy) were recruited at the beginning of the training program, after a 2-month detraining period. During the study period, ath-letes trained for 15 h/week and played 1 match a week during the regular season. The study began at the time of enrollment and lasted for 8 months. Baseline echocardiographic analysis was performed at the beginning of the training program, after 4 months and after 8 months. All players were engaged in the same training sessions, under the supervision of a dedicated coach, although there was some variability based on player’s role. Because goalkeepers were engaged in a diff erent athletic program, they were excluded from the present study. All ath-letes were evaluated at the same stage of their training program and at the same time of the day, before the training session, at least 48 h after the last strenuous training session. All partici-pants underwent complete physical examination, electrocardio-gram (ECG), standard echocardiography, and treadmill ECG test with no evidence of pathological fi ndings. Body mass index (BMI) was calculated as weight in kilograms divided by squared height (kg/m 2 ). Body surface area (BSA) was calculated using the Dubois and Dubois formula [ 10 ] . All athletes were free of mani-fested coronary artery disease, valvular and congenital heart disease, heart failure, cardiomyopathy, arterial hypertension, and diabetes mellitus. All subjects were asymptomatic and did not present family history of cardiac disease or sudden cardiac death. Participants were excluded from the study if they with-drew from the training program > 10 days. After the rationale and the study protocol were explained, the participants or the parents, if subjects were younger than 18 years-of age, gave informed consent. The study meets the ethical standards of the journal [ 15 ] .

Echocardiographic analysis Echocardiographic examination was performed by one cardiolo-gist using a high-quality echocardiograph (Vivid 7, GE, USA) equipped with a 2.5 MHz probe. Subjects were studied in the steep left-lateral decubitus position. For all measurements, three beats were stored and analyzed off -line (EchoPac, GE, USA). Off -line data analysis was performed by one experienced reader, blinded to the study time point. All echocardiographic data were analyzed at the end of the data collection. Heart rate (HR) was measured from the electrocardiographic tracing taken during the echocardiographic examination. LA size was measured at the end-LV systole, when the LA cham-ber is at its greatest dimension, as recommended [ 18 ] . LA size was assessed by volume determinations. LA area and volume were calculated by biplane method of disks (modifi ed Simpson’s rule) in the apical 4- and 2-chamber views: an average value was obtained. In order to correct the infl uence of body composition, this value was indexed to BSA. Care was taken to exclude the pulmonary veins and LA appendage from the LA tracing. The plane of the mitral annulus was used as inferior border [ 18 ] . As recommended, LA mild enlargement was defi ned as a LA vol-ume/BSA ≥ 29 mL/m 2 and ≤ 33 mL/m 2 , a moderate enlargement as a LA volume/BSA ≥ 34 mL/m 2 and ≤ 39 mL/m 2 , while a severe abnormal LA dilatation as a LA volume/BSA ≥ 40 mL/m 2 [ 18 ] . In order to identify independent determinants of LA mean vol-umes, LV mass (LVM), LV end-diastolic diameter (EDD), LV end-diastolic volume (EDV), LV end-systolic volume (ESV), and LV stroke

volume (SV) were calculated. All echocardiographic measure-ments were indexed to BSA. LVM was obtained by the formula: LVM = 0.8 × {1.04 [(LVEDD + PWTd + SWTd) 3 − (LVEDD) 3 ]} + 0.6 g, where PWTd and SWTd are posterior wall thickness at end dias-tole and septal wall thickness at end diastole, as recommended [ 18 ] .

Standard and tissue Doppler imaging Pulsed-wave (PW) Doppler was performed in the apical 4-cham-ber view to obtain mitral infl ow velocities to assess LV fi lling. A 1-mm to 3-mm sample volume was placed between mitral leaf-let tips during diastole, as recommended [ 24 ] . Measurements of mitral infl ow included the peak of early fi lling (E-wave) and late diastolic fi lling (A wave), and the E/A ratio. The timings of mitral and aortic valve opening and closure were defi ned by pulsed wave Doppler tracings of mitral infl ow and the left ventricular outfl ow. LV longitudinal function was explored by pulsed tissue Doppler imaging, placing the sample volume at the level of mitral lateral annulus from the apical 4-chamber view [ 35 ] . Peak systolic (s’), early diastolic (e’), and late diastolic (a’) annular velocities were obtained. s’ was considered as a relatively load-independent index of LV longitudinal systolic function. e’ and the derived e’/a’ ratio were used as load-independent markers of ventricular diastolic relaxation [ 16 ] . The E/e’ ratio was also obtained and used as a reliable index of LV fi lling pressures [ 27 ] .

Two-dimensional speckle-tracking echocardiography Image acquisition The same basic principles for image acquisition, as mentioned for standard echocardiography recordings, were applied for 2D STE. Speckle-tracking imaging: apical 4- and 2-chamber views images were obtained using conventional 2D gray scale echocar-diography, during breath hold with a stable ECG recording. Care was taken to obtain true apical images using standard anatomic landmarks in each view and not foreshorten the left atrium, allowing a more reliable delineation of the atrial endocardial border. 3 consecutive heart cycles were recorded and an average value was obtained. The frame rate was set between 60 and 80 frames per second.

2D STE measurements The analysis of fi les recorded was performed off -line by a single experienced and independent reader, who was not directly involved in the image acquisition and had no knowledge of other echocardiographic parameters representing LV and LA structure and function, using commercially available semi-automated 2D strain software (EchoPac, GE, USA). As previously described [ 6 ] and as stated in the current ASE/EAE consensus statement [ 23 ] , LA endocardial border was manually traced in both 4- and 2-cham-ber views, thus delineating a region of interest (ROI), composed by 6 segments. Then, after the segmental tracking quality analy-sis and the eventual manual adjustment of the ROI, the longitu-dinal strain curves were generated by the software for each atrial segment. Peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) were calculated by averaging val-ues observed in all LA segments (global PALS and global PACS, respectively), and by separately averaging values observed in 4- and 2-chamber views (4- and 2-chamber average PALS and PACS, respectively). When some segments were excluded because of the impossibility of achieving adequate tracking, PALS and PACS were calculated by averaging values measured in the remaining

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segments. The E/e’ ratio was used in conjunction with global PALS to derive a noninvasive dimensionless parameter of LA stiff ness [ 2 , 17 ] .

Measurement variability The intraobserver variability for LA mean volume index, LA PALS, and PACS parameters has already been tested in a previous similar study by our echocardiographic laboratory [ 6 , 9 ] .

Statistical analysis Data are shown as mean ± SD. Comparison of values obtained at baseline, after 4 months and after 8 months of training, was per-formed with ANOVA with Bonferroni correction for multiple comparisons. A P-value < 0.05 was considered signifi cant. Analy-ses were performed using the SPSS (Statistical Package for the Social Sciences, Chicago, Illinois) software Release 11.5. To identify signifi cant independent determinants of LA mean volume, LA global PALS, and LA global PACS in the athletes, indi-vidual association with echocardiographic parameters was assessed by multivariable linear regression analysis. The follow-ing parameters were included in the analysis: LVM, LV EDD, LV EDV, LV ESV, LV SV, HR, standard Doppler, and tissue Doppler measurements. These variables were selected according to their potential impact on LA function and structure, as previously demonstrated [ 8 , 9 , 28 ].

Results ▼ Characteristics of the study population 21 male adolescent soccer players were enrolled in the study. 3 participants were excluded because of musculoskeletal injury and withdrawal from training program > 10 days. The fi nal pop-ulation consisted of 18 male adolescent athletes (mean age 17.61 ± 1.04 year). Baseline demographic characteristics and training volume are listed in ● ▶ Table 1 . At baseline, after a period of detraining lasting 2 months, athletes showed a relative high resting heart rate. After 4 months of training program, resting heart rate lowered, and after 8 months a signifi cant reduction of resting heart rate was observed (p < 0.05). No signifi cant diff er-ences were observed in BSA between values obtained at the beginning of the study and those after 8 months (1.87 ± 0.08 vs. 1.88 ± 0.09).

LA volume index Echocardiographic images suitable for a complete analysis were obtained in all participants. Echocardiographic parameters col-lected at the time of enrollment and after 4 and 8 months of training are listed in ● ▶ Table 2 . After a 4-month training period, LA mean volume index signifi -cantly increased (Δ = 5.47 ± 4.38 mL/m 2 , p ≤ 0.0001). After 8 months of training, LA mean volume index showed a further increase with a greater volume in comparison with baseline values (29.13 ± 4.50 mL/m 2 vs. 20.18 ± 4.86 mL/m 2 , respectively, Δ = 8.95 ± 4.47 mL/m 2 , p < 0.0001, ● ▶ Fig. 1 , 2 ). Interestingly, while only 1 subject presented a mild enlargement at the time of enrollment (5.6 % of the study population), after 4 months 5 participants (27.8 %) had a LA mean volume ≥ 29 mL/m 2 . After 8 months of training, 9 participants (50 %) showed an LA enlargement, with 7 athletes presenting a mildly abnormal LA mean volume index and 2 athletes presenting a moderate enlargement of LA. None of the participants showed severe abnormal LA enlargement.

Speckle-tracking echocardiographic analysis Among a total of 648 segments analyzed, the software was able to correctly track 624 (96.4 %) segments. After 4 months of training athletes showed no signifi cant diff erences of global PALS in com-parison with baseline values. However, after 8 months athletes showed a signifi cant lower value of global PALS (37.68 ± 7.66 % vs. 43.92 ± 8.33 %, respectively, Δ = − 9.54 ± 14.83, p ≤ 0.005) in com-parison with baseline values ( ● ▶ Fig. 3 ). Global PACS showed a

Table 1 Baseline demographic characteristics and training volume.

Parameters Athletes (n = 18)

age (years) 17.61 ± 1.04 male gender (n/ %) 18/100 height (cm) 178.35 ± 4.51 weight (kg) 69.56 ± 4.6 BMI 21.85 ± 0.71 BSA (m 2 ) 1.87 ± 0.08 resting HR (beats/min) 70.12 ± 9.08 study period training (h/week) 15 Values are expressed as mean ± SD. BMI, body mass index; BSA, body surface area; HR, heart rate

Table 2 Standard echocardiographic analysis and left atrial speckle-tracking echocardiography: eff ects of an 8-month high-intensity training program.

Variable Baseline 4 months 8 months

LA mean volume index (mL/m 2 )

20.18 ± 4.86 25.65 ± 4.68* 29.13 ± 4.50*

heart rate (beats/min) 70.12 ± 9.08 64.47 ± 11.58 63.4 ± 7.37† peak E velocity (m/s) 0.84 ± 0.13 0.94 ± 0.15* 0.94 ± 0.10* peak A velocity (m/s) 0.46 ± 0.08 0.43 ± 0.10 0.40 ± 0.09 e’ peak (m/s) 0.19 ± 0.02 0.23 ± 0.03‡ 0.25 ± 0.04* a’ peak (m/s) 0.08 ± 0.02 0.07 ± 0.03 0.07 ± 0.01 E/e’ ratio 4.42 ± 1.03 4.10 ± 0.57† 3.78 ± 0.61‡ global PALS ( %) 43.92 ± 8.33 40.78 ± 6.97 37.68 ± 7.66‡ global PACS ( %) 12.89 ± 4.05 11.26 ± 4.02 10.86 ± 3.57* (E/e’)/global PALS 0.10 ± 0.03 0.10 ± 0.02 0.11 ± 0.03 Values are expressed as mean ± SD. LA, left atrial; PALS, peak atrial longitudinal strain; PACS, peak atrial contraction strain. *p ≤ 0.0001 vs. baseline; † p < 0.05 vs. baseline; ‡ p ≤ 0.005 vs. baseline

Fig. 1 Left atrial (LA) volumetric variations reported in each participant at the time of enrolment, after 4 months, and after 8 months of training.

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similar trend during the study period with a non-signifi cant reduction after 4 months and with signifi cant lower values after 8 months of training in comparison with baseline measurements (12.89 ± 4.05 % vs. 10.86 ± 3.57 %, Δ = − 2.96 ± 6.47, p ≤ 0.0001).

Standard Doppler and tissue Doppler imaging analysis Athletes showed a signifi cantly higher LV peak E velocity after 4 months in comparison with baseline values (p ≤ 0.0001), while peak E velocity was relatively unchanged between data obtained at 4 months and data collected at 8 months ( ● ▶ Fig. 4 ). Peak A velocity showed a trend toward reduction during the study period, however no signifi cant diff erences were observed at 8 months in comparison with baseline values. Athletes showed a higher e’ peak at 4 months (p ≤ 0.005) and a further increase in e’ peak at 8 months in comparison with baseline values (0.19 ± 0.02 m/s vs 0.25 ± 0.04 m/s, p ≤ 0.0001, ● ▶ Fig. 4 ). The a’ peak was relatively unchanged after 8 months in comparison with baseline values. Interestingly, E/e’ ratio signifi cantly low-ered from baseline to 4 months values (p < 0.05) and 8 month measurements demonstrated a further reduction in comparison with baseline values (4.42 ± 1.03 vs 3.78 ± 0.61, p ≤ 0.005). LA stiff ness derived parameter did not signifi cantly vary during the study.

Correlation of LA mean volume index and LA strain indices with echocardiographic parameters Stepwise multivariate regression analysis identifi ed heart rate (β = − 0.580, p < 0.0001), LV indexed mass (β = 0.215, p < 0.0001) and indexed stroke volume (β = 0.181, p = 0.0002) as parameters strongly correlate with LA mean volume index. The model explained 54.7 % of the variability in LA mean volume index (overall model p < 0.0001). Heart rate showed the strongest cor-relation, accounting for 46.5 % of the total variability explained by the model. Of note, in the present model, E/e’ ratio did not emerge as an independent determinant of LA mean volume index. Regarding global PALS and global PACS correlations, in stepwise multivariate regression analysis, heart rate showed to be the strongest independent determinant (β = 0.570, p < 0.0001 and β = 0.697, p < 0.0001, respectively; overall model p < 0.0001). The models explained 59.5 % and 70.2 % of the variability in global PALS and global PACS, respectively. Heart rate was the principal determinant, accounting for 47.4 % and 69.3 % of the total varia-bility of the two models, respectively.

Discussion ▼ Several cross-sectional studies have demonstrated in athletes a process of LA remodelling associated with intensive exercise

Fig. 3 Speckle-tracking echocardiographic analysis. Peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) values obtained at the beginning of the study (left panel) and after 8 months of training (right panel). Typical case of an adolescent competitive soccer player showing a signifi cant reduction of PALS and PACS values after 8 months of physical conditioning.

Fig. 2 Left atrial (LA) volume obtained at the beginning of the study, after 2 months of detraining (left panel). LA volume obtained at the end of the study, after 8 months of training (right panel). In this representative case, LA mean volume index increased from 26.7 mL/m 2 to 32.9 mL/m 2 , with a Δ = 6.2 mL/m 2 .

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[ 8 , 9 , 28 ]. However, few longitudinal data focused on LA adapta-tion to the exercise conditioning and no data on LA function assessed by 2D STE were prospectively collected [ 5 ] . This is the fi rst longitudinal study investigating by standard echocardiography and by 2D STE the process of LA remodelling in athletes. We demonstrated that an 8-month training program is associated with a dimensional and functional LA adaptation in adolescent elite soccer players. The LA structural changes observed in our study are in agreement with previous data reported by Baggish and colleagues, demonstrating that 90 days of team training were associated with a signifi cant increase in LA volumes, with a Δ = 2.4 ± 1.5 mL/m 2 [ 33 ] . The relatively long-term observational period of the present study allowed us to demon-strate a more pronounced LA enlargement in competitive soccer players. Previous studies found a relatively high prevalence of mild LA enlargement in athletes, also when gold standard imag-ing techniques were used to assess atrial size, such as cardiac magnetic resonance imaging (MRI) [ 8 , 20 , 28 ]. The present study confi rmed these fi ndings and provided the additional evidence that a dynamic process of LA enlargement is seen also in sub-jects in whom underlying adaptations are already present. Car-diac chamber size and cardiac output increases with increasing body size during normal growth and development [ 25 ] . Some authors reported that in children and adolescents increased car-diac size is directly proportional to increases in body height [ 11, 26 ] , while some others demonstrated that BMI has the greatest impact on LA size in childhood [ 4 ] . Increasing age among children does not appear to be associated with trend towards an increase in corrected LA size, confi rming that an increase in body size in children is associated with an increase in LA size [ 25 ] . Moreover, Nidorf et al. demonstrated that, after puberty, the rate of cardiac growth slows and signifi cant increases in cardiac dimensions are not seen after 15 years of age

[ 26 ] . In a population of junior athletes, George and colleagues reported a general progression in cardiac size across the age range, although it occurs in close association with an increased body size [ 14 ] . In the present study we demonstrated a signifi -cant increase of LA volumes through the season in competitive adolescent athletes, despite non-signifi cant variations of BSA values. 2-dimensional echocardiography is known to be limited by the use of geometric models to determine the volume of a nonsym-metric chamber and by possible errors due to foreshortening, thus it tends to underestimate LA volumes compared to cardiac MRI and to 3-dimensional methods [ 20 ] . Therefore, our results, based on 2-dimensional echocardiographic acquisitions, may have underestimated the longitudinal process of LA enlarge-ment in adolescent athletes. Considering that LA anteroposterior dimensions on M-mode are recognized as an inaccurate repre-sentation of the true LA size [ 19 ] , we chose LA volume as the referred measurement to identify the asymmetric dimensional remodelling of LA chamber [ 18 ] . Moreover, because body size and composition signifi cantly aff ect cardiac morphology inde-pendently of other factors [ 30 ] , LA size was indexed to BSA, as recommended [ 18 ] . Scharf et al. demonstrated that elite triathletes have signifi cantly greater LA and LV volumes than control subjects, as assessed by cardiac MRI [ 29 ] . The authors hypothesized that an increased LA fi lling pressure due to a higher vagal tone may contribute to atrial enlargement. Wilhelm et al. demonstrated that athletes with an early repolarization pattern had an increased E/e’ ratio, refl ecting a higher LA fi lling pressure, and reported that, even if underlying mechanisms for structural changes of the LA in endurance athletes are not entirely understood, an increased LA pressure may lead to atrial remodelling and dilation [ 34 ] . In fact, an increase in LA size is most commonly related to increased

Fig. 4 Pulsed-wave (PW) Doppler (top fi gures) and Doppler tissue imaging analysis (bottom fi gures). Diastolic function of a representative athlete analyzed at the beginning of the study (left fi gures) and at the end of the study (right fi gures). This athlete had trivial mitral regurgitation, which was captured by PW Doppler.

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wall tension as a result of increased LV fi lling pressure and the adverse outcomes associated with increased LA dimensions are more strongly associated with increased LV fi lling pressures [ 1,34 ] . However, the present study demonstrates that LV fi lling pressures, as assessed by E/e’ ratio, not only did not increase during the observation period, but also signifi cantly lowered, due to higher values of e’. Thus, our fi ndings suggest that an increase in the LV fi lling pressures cannot be implicated as a cause in the determination of LA enlargement in adolescent ath-letes after 8 months of training. Moreover, even if the use of car-diac fi lling pressures with indices of LA function (e. g. strain) to calculate LA stiff ness is novel and worth exploring [ 23 ] , we observed that in soccer players the noninvasive parameter of LA stiff ness did not change during the study period. In this particu-lar population, LA enlargement does not represent a marker of magnitude of LA pressure elevation, as previously described in patients with cardiovascular disease [ 1,31 ] . Thus, concepts related to the pathology of myocardial dysfunction cannot exhaustively explain the physiology of athlete’s heart and LA remodelling might be interpreted as an adaptive modifi cation more than a preclinical disease. Interestingly, our results dem-onstrated that LA remodelling occurs in association with LV remodelling, as demonstrated by the stepwise multivariate regression analysis that identifi ed indexed LV mass and indexed LV SV as parameters strongly related to LA mean volume index. Thus, LA enlargement represents the physiologic consequence of a global cardiac adaptation to the increased SV associated with chronic and intensive exercise conditioning [ 8,28 ] . 2-dimensional STE has been demonstrated to be a useful tool to allow a direct assessment of LA endocardial contractility and passive deformation [ 23 ] . Moreover, we previously demon-strated that this new echocardiographic technique may contrib-ute to elucidate the role of LA in the context of athlete’s heart remodelling [ 9 ] . In the present study, 2D STE allowed us to dem-onstrate that LA remodelling in athletes encompasses not only dimensional but also functional adaptations, as suggested by the signifi cant reduction of global PALS and global PACS after 8 months of training. As demonstrated by stepwise multivariate regression analysis, HR showed to be the strongest independent determinant of global PALS and global PACS. Thus, these fi ndings support the hypothesis that an increased parasympathetic tone, a recognized marker of the athlete’s heart, may play a central role in the functional cardiovascular remodelling of athletes. In the present study, signifi cant variations in HR occurred in close association with cardiac chamber enlargement, as demonstrated by the association between LA mean volume index and HR. This phenomenon, together with the ability to generate a large SV, is a direct result of exercise training. Athletes involved in sports with a high dynamic component are known to predominantly develop an increase in chamber size, caused by volume overload, and able to maintain, even in a condition of bradycardia, an ade-quate high cardiac output at rest [ 12 ] . Moreover, the increase in chamber size, e. g. the LV end-diastolic volume, is able to enhance SV during exercise and, together with the increase in HR, is responsible for cardiac output augmentation. Further longitudi-nal studies with larger samples are needed to confi rm our fi nd-ings and to clarify the determinants of the reduction of global PALS and global PACS associated with training and with HR vari-ations. Athletes are known to present with an improvement in diastolic properties of LV in comparison with normal subjects, with a higher peak E velocities, a higher e’peak, a lower peak A velocity,

and a lower a’ peak, resulting in a shift of LV diastolic fi lling period toward early diastole [ 7 , 12 ] . This supernormal aspect determines a peculiar pattern of LA deformation dynamics, with a reduction of global PACS in athletes, as compared with normal subjects [ 9 ] . The present study demonstrates that an further improvement in LV diastolic properties can occur after training also in athletes already presenting with features of athlete’s heart. However, training-induced bradycardia is able to prolong the diastolic fi lling period and to lengthen the diastasis during mid-diastole, increasing the E/A ratio and making the interpre-tation of diastolic function complex. Thus, the demonstration of an improvement in diastolic properties in the present study should be interpreted with caution considering that diastolic function in athletes depends not only on training per se , but it is also infl uenced by other factors, such as exercise-induced bradycar-dia. The strength of the present study is represented by the longitu-dinal design, based on repeated measurements on the same cohort of selected elite athletes. The study design was intended to evaluate the dynamic nature of LA remodelling in soccer play-ers, showing a gradual LA volumetric increase during an 8-month training program. We provided a novel analysis of LA function based on STE, demonstrating that this new echocardio-graphic technique is able to detect in athletes longitudinal mod-ifi cations of myocardial deformation dynamics associated with training. Interestingly, the present fi ndings indicate that the variability in LA structure and function and in LV diastolic properties through the training season may constitute a possible source of error in cross-sectional studies that do not evaluate athletes at the top of their training program. Therefore, when an echocardiographic evaluation is performed in athletes, in order to correctly evalu-ate the measurements obtained, we have to take into account not only the training volume, the previous years of practice, and the sport the athlete is engaged in, but also the period in which the examination is performed.

Limitations ▼ The main limitation of the present study is represented by the lack of a echocardiographic examination after a detraining period. Thus, we cannot establish whether this process of remodelling might continue to evolve after further months of training and whether a period of detraining might be able to produce changes in cardiac parameters in a converse manner. Further limitations are represented by the small sample size and the lack of a control group of untrained adolescents. Considering that BSA did not signifi cantly vary during the study period, it would appear reasonable to surmise that changes in LA size are specifi -cally related to the exercise conditioning. However, the lack of a control group of adolescent sedentary subjects does not allow to defi nitively exclude the contribution of variations related to the development.

Conclusions ▼ We present novel longitudinal fi ndings concerning LA remodel-ling in athletes suggestive that an 8-month training program is associated with LA dimensional and functional training-specifi c adaptations in competitive adolescent soccer players. Moreover,

801Training & Testing

D’Ascenzi F et al. Left Atrial Remodelling in … Int J Sports Med 2012; 33: 795–801

in the present study we demonstrate that LV diastolic properties can improve after training in a specifi c manner also in competi-tive athletes already presenting cardiac adaptations to exercise conditioning.

Acknowledgements ▼ Authors wish to thank Chairman of Siena Football Club, Massimo Mezzaroma, vice-chairwoman Valentina Mezzaroma, all mem-bers of medical and coaching staff , athletes, managers, Giorgio D’Urbano, and Domenico Di Mambro, medical doctor of Siena Football Club Academy, for their support in the study.

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