Marco Bonifazi and Sergio MondilloFederico Alvino, Angela Malandrino, Paola Palmitesta, Alessandro Zorzi, Domenico Corrado,

Flavio D'Ascenzi, Antonio Pelliccia, Benedetta Maria Natali, Valerio Zacà, Matteo Cameli,Highly Trained Female Athletes

Morphological and Functional Adaptation of Left and Right Atria Induced by Training in

Print ISSN: 1941-9651. Online ISSN: 1942-0080 Copyright © 2014 American Heart Association, Inc. All rights reserved.

Dallas, TX 75231is published by the American Heart Association, 7272 Greenville Avenue,Circulation: Cardiovascular Imaging

doi: 10.1161/CIRCIMAGING.113.0013452014;7:222-229; originally published online January 27, 2014;Circ Cardiovasc Imaging. 

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222

The hemodynamic adaptations associated with exercise conditioning in competitive athletes have been extensively

reported and previous studies have demonstrated that they vary according to the type and intensity of exercise.1–4 Cardiac changes consist of interrelated morphological and functional modifications, involving not only the left ventricle (LV) but also the left atrium (LA).5–7 Furthermore, similar hemody-namic and physiological influences affect both the right and left heart of highly trained athletes, determining a symmetrical cardiac enlargement induced by exercise conditioning.8,9

Clinical Perspective on p 229

Although several echocardiographic studies have investi-gated the effects of training on cardiac geometry and func-tion, most are restricted to male athletes or are not specifically focused on the heart of female athletes.10–14 A previous study

has demonstrated that highly trained female athletes exhibit LV dimensional changes as an adaptation to physical train-ing in comparison with sedentary controls.15 However, most of these studies have a cross-sectional design and longitudi-nal assessment of training-specific cardiac changes has been rarely performed in elite athletes, particularly in women.16,17 Furthermore, only a few studies have investigated the adapta-tion of LA and right atria (RA) to intensive training,8,9,16 even if the investigation of atrial adaptation in the athletic popu-lation is of particular interest, considering the existing con-troversies on the relationship between exercise-induced atrial remodeling and the incidence of atrial fibrillation among competitive athletes.18–20 The majority of previous studies focused on pure endurance or resistance sports. Instead, the most popular team-based sport activities, such as volleyball for women or basketball and soccer for men, incorporate a

Background—Exercise is able to induce atrial remodeling in top-level athletes. However, evidence is mainly limited to men and based on cross-sectional studies. The aim of this prospective, longitudinal study was to investigate whether exercise is able to influence left and right atrial morphology and function also in female athletes.

Methods and Results—Two-dimensional echocardiography was performed before season and after 16 weeks of intensive training in 24 top-level female athletes. Left and right atrial myocardial deformation was assessed by two-dimensional speckle-tracking echocardiography. Left atrial volume index (24.0±3.6 versus 26.7±6.9 mL/m2; P<0.001) and right atrial volume index (15.66±3.09 versus 20.47±4.82 mL/m2; P<0.001) significantly increased after training in female athletes. Left atrial global peak atrial longitudinal strain and peak atrial contraction strain significantly decreased after training in female athletes (43.9±9.5% versus 39.8±6.5%; P<0.05 and 15.5±4.0% versus 13.9±4.0%; P<0.05, respectively). Right atrial peak atrial longitudinal strain and peak atrial contraction strain showed a similar, although non-significant decrease (42.8±10.6% versus 39.3±8.3%; 15.6±5.6% versus 13.1±6.1%, respectively). Neither biventricular E/e′ ratio nor biatrial stiffness changed after training, suggesting that biatrial remodeling occurs in a model of volume rather than pressure overload.

Conclusions—Exercise is able to induce biatrial morphological and functional changes in female athletes. Biatrial enlargement, with normal filling pressures and low atrial stiffness, is a typical feature of the heart of female athletes. These findings should be interpreted as physiological adaptations to exercise and should be considered in the differential diagnosis with cardiomyopathies. (Circ Cardiovasc Imaging. 2014;7:222-229.)

Key Words: athlete’s heart syndrome ◼ atrial function ◼ atrial remodeling ◼ echocardiography ◼ speckle tracking ◼ women

© 2014 American Heart Association, Inc.

Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org DOI: 10.1161/CIRCIMAGING.113.001345

Received June 12, 2013; accepted January 16, 2014.From the Departments of Cardiovascular Diseases (F.D.’A., B.M.N., V.Z., M.C., F.A., A.M., S.M.) and Medicine, Surgery, and NeuroScience (M.B.), University

of Siena, Siena, Italy; Institute of Sports Medicine and Science, Rome, Italy (A.P.); Department of Social, Political, and Cognitive Sciences, University of Siena, Siena, Italy (P.P.); and Division of Cardiology, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy (A.Z., D.C.).

The Data Supplement is available at http://circimaging.ahajournals.org/lookup/suppl/doi:10.1161/CIRCIMAGING.113.001345/-/DC1.Correspondence to Flavio D’Ascenzi, MD, Department of Cardiovascular Diseases, University of Siena, Viale M. Bracci, 16 53100 Siena, Italy. E-mail

flavio.dascenzi@libero.it

Morphological and Functional Adaptation of Left and Right Atria Induced by Training in Highly Trained

Female AthletesFlavio D’Ascenzi, MD; Antonio Pelliccia, MD; Benedetta Maria Natali, MD;

Valerio Zacà, MD; Matteo Cameli, MD; Federico Alvino, MD; Angela Malandrino, MD; Paola Palmitesta, PhD; Alessandro Zorzi, MD; Domenico Corrado, MD, PhD;

Marco Bonifazi, MD; Sergio Mondillo, MD

Atrial Structure and Function

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D’Ascenzi et al Training-Induced Cardiac Adaptation in Women 223

combination of endurance (dynamic), strength/resistance (static), and celerity training.21

The aim of this study was to investigate prospectively whether an intensive combined training program can significantly influ-ence LA and RA morphology and function in competitive female volleyball players and whether this adaptation is asso-ciated with an improvement or a worsening of atrial function.

MethodsStudy PopulationTwenty-six female volleyball players, members of 2 elite sports teams, were enrolled in this study. Pretraining echocardiographic ex-amination was collected after 3 months of detraining. Detraining was defined as the partial or complete loss of anatomic, physiological, and performance adaptations induced by training, as a consequence of usual training regime suspension22; during this period, none of the athletes practiced >3 hours/wk of exercise. Post-training examination was performed after 16 weeks of supervised intensive training, con-sisting of 16 hours/wk, distributed in 8 sessions/wk. Training sessions were comparable between the 2 teams in aerobic–anaerobic compo-nents, kind of exercise, and hours of training per week.

Athletes were excluded from the study if they withdrew from the training program >10 days for musculoskeletal injuries. For this rea-son, 2 athletes were excluded, and the final population of this study consisted of 24 athletes.

Twenty-four age- and sex-matched healthy sedentary subjects were enrolled and used as controls. The same design of data collection was performed in a group of 12 male, basketball athletes, playing in a top team and practicing a high-volume training program to provide a ref-erence group of men undergoing similar training regimens. A detailed analysis, including the evaluation of echocardiographic predictors of biatrial remodeling, was not performed in the athletic group of men because of the small sample size of this group and according to the fact that the present study aimed to investigate the training-induced adaptation of both atria primarily in female athletes.

Participants were asymptomatic and showed a negative family history of cardiac disease or sudden cardiac death. None of the athletes had cardiovascular structural or functional abnormalities, hypertension, and type I diabetes mellitus. Participants underwent complete physical examination, ECG, standard echocardiography, and treadmill ECG test. After the rationale and the study protocol were explained, the participants gave informed consent. The inves-tigational protocol was approved by the local ethical committee.

Echocardiographic MeasurementsEchocardiographic examination was performed by 1 cardiologist using a high-quality echocardiograph (Vivid 7; GE Healthcare, Milwaukee, WI), equipped with an M4S 1.5-MHz to 4.0-MHz trans-ducer, and a 1-lead ECG was continuously displayed. Subjects were studied in the steep left-lateral decubitus position. Offline data analy-sis, from 3 stored cycles, was performed by an experienced reader, blinded to the study time point, using a dedicated software (EchoPac; GE Healthcare). Heart rate (HR) was measured from the superim-posed ECG obtained during the echocardiographic examination.

Size Quantification of Left and Right Heart ChamberLA and RA dimensions were measured at the end of LV systole, when these chambers get to their maximum size during cardiac cycle, as recommended.23,24 RA and LA area and volume were calculated by biplane method of disks (modified Simpson rule) in the apical 4-chamber view for the former and both 4- and 2-chamber views for the latter, obtaining an average value. LA size was assessed excluding the pulmonary veins and LA appendage from LA tracing. The plane of mitral annulus was used as inferior border.23 A mild enlargement of the LA was defined as LA volume ≥29 mL/m2, a moderate as ≥34 mL/m2, and a severe as ≥40 mL/m2.23

RA dimension was measured excluding the area between the leaf-lets and the annulus, after the RA endocardium, excluding the inferior and superior vena cava and RA appendage.24 RA enlargement was defined as an RA end-systolic area >18 cm2.24 Biatrial volumes were indexed to body surface area (BSA), calculated using the Dubois and Dubois formula.25 Right ventricular (RV) end-diastolic chamber size was assessed using the measurement of basal and midcavity diam-eters from the apical 4-chamber view at end diastole.24

To identify potential predictors of atrial remodeling associated with training, LV volumes, LV mass (LVM), and LVM index were obtained as recommended.23

Standard and Tissue Doppler ImagingPulsed-wave and tissue Doppler imaging analyses were performed to determine LV and RV diastolic function, according to the current recommendations (Data Supplement).24,26 The mitral and tricuspid E/e′ ratio was calculated and considered as a reliable index of LA and RA filling pressures.24,26–28

Speckle-Tracking Echocardiography of RA and LATwo-dimensional (2D) speckle-tracking echocardiography was obtained and recorded using conventional 2D gray-scale echocardiography dur-ing breath holding with stable electrocardiographic tracing, as described previously for LA and RA.9,29,30 Offline analysis was performed using a commercially available semiautomated 2D strain software (EchoPAC PC, version 112, rev. 1.1; GE Healthcare), obtaining peak atrial longitu-dinal strain (PALS) and peak atrial contraction strain (PACS), measures of atrial reservoir and atrial active conduit, respectively.

Time-to-peak longitudinal strain and time-to-peak contraction strain were also obtained for both the LA and RA and indexed to relative risk interval (ms). The E/e′ ratio was used in conjunction with PALS to derive a noninvasive dimensionless parameter of LA and RA stiffness, as previously reported (Data Supplement).9,31,32

Statistical AnalysisNormal 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 appropriate. Categorical variables are ex-pressed as percentages. The unpaired t test and the Mann–Whitney U test were used according to data distribution to assess between-groups significance. The paired t test and the Wilcoxon matched-pair test were used to assess the within-subjects significance of pretraining and post-training measurements, as appropriate for data distribution. A P value <0.05 was considered significant. Correlation analysis was performed to find association between continuous variables using the Spearman and Pearson methods, as appropriate for data distribution. Univariate linear regression analysis was performed to identify predictors of atrial remod-eling. Statistics were performed using SPSS version 14.0 software for Windows (Statistical Package for the Social Sciences Inc, Chicago, IL).

ResultsThe demographic characteristics of female athletes and female controls are reported in Table 1. The mean age of the female athletic population was 24.9±4.1 years. As expected, female athletes significantly increased their weight and BSA (P<0.05), whereas the resting HR significantly decreased (P<0.05) after training. The mean age of the reference group of male athletes was 26.0±4.2 years, BSA was 2.3±0.1 m2, and resting HR was 54.2±4.8 bpm. During the study period, none of the male and female athletes experienced palpitations or symptoms, requiring further investigations.

LA AdaptationDifferences in left heart measurements between pretraining data collected in female athletes and data measured in controls and between pretraining and post-training data obtained in female

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224 Circ Cardiovasc Imaging March 2014

athletes are reported in Table 2. Although E/e′ ratio did not dif-fer between pretraining measurements obtained in female ath-letes and data collected in controls, female athletes had a higher pretraining LA volume index when compared with sedentary subjects (P=0.008). Furthermore, female athletes showed dif-ferences in pretraining LV volumes and pretraining LA strain, even if the PALS/PACS ratio was comparable between female athletes and controls. Pretraining LV end-diastolic volume (LVEDV) index was higher in female athletes when compared with that in controls (52.1±8.7 versus 45.3±6.9 mL/m2, respec-tively; P=0.012); conversely, pretraining LVM index was com-parable between female athletes and controls (66.6±11.3 versus 61.0±15.9 g/m2, respectively; P=0.80).

LA morphology and function did change after 16 weeks of intensive training in female athletes: LA volume and LA volume index increased significantly when compared with pretraining data (P<0.001; Figure 1). Before training, 95% of female athletes showed a normal LA volume index and 5% a mild LA enlarge-ment. After training, 45% of female athletes showed a LA volume index ≥29 mL/m2, with 30% presenting a mild LA enlargement and 15% a moderate enlargement. None of the female athletes experienced a severe LA enlargement during the study.

Although LA size increased in female athletes, E/e′ ratio did not vary during the study (P=0.96). Although s′ peak did

not change (10.6±1.1 versus 10.6±1.6 cm/s; P=0.47), e′ peak increased (16.4±1.8 versus 17.6±2.4 cm/s; P=0.025) and a′ decreased (8.6±1.4 versus 7.7±1.7 cm/s; P=0.015) after train-ing in female athletes. The morphological remodeling was accompanied in female athletes by a significant reduction in LA global PALS and LA global PACS (P<0.05; Figure 1). Neither the PALS/PACS ratio nor LA stiffness index signifi-cantly varied with training in women.

In competitive male athletes, LA volume (65.9±21.2 versus 73.8±30.8 mL; P=0.17) and LA volume index (28.3±7.7 ver-sus 31.4±11.7 mL/m2; P=0.20) tended to increase during the observation period, although no statistically significant differ-ences were found between pretraining and post-training data. E/e′ ratio (5.4±1.1 versus 4.8±0.4; P=0.068), LA global PALS (36.2±4.0% versus 37.5±4.1%; P=0.51), LA global PACS (11.5±2.2% versus 12.2±2.1%; P=0.42), and PALS/PACS ratio (3.2±0.6 versus 3.1±0.5; P=0.72) did not vary signifi-cantly, whereas LVM index increased significantly after train-ing (100.0±15.7 versus 157.3±26.8 g/m2; P<0.001).

RA AdaptationAs reported in Table 3, no significant differences were observed between pretraining data collected in female ath-letes and data measured in controls on RA morphology and

Table 1. Demographic Characteristics of Female Controls and Elite Female Volleyball Players Observed Before Season and After 16 Weeks of Supervised Training Program

Variable Controls (n=24)

Female Competitive Athletes (n=24) P Value Athletes vs Controls

P Value Pretraining vs Post- TrainingPretraining Post-Training

Age, y 24.4±3.2 24.9±4.1 25.2±4.1 NS NS

BSA, m2 1.68±0.14 1.86±0.11 1.87±0.11 0.000 0.012

Resting HR, bpm 76.6±9.9 68.1±10.5 64.4±10.8 0.011 0.026

BSA indicates body surface area; HR, heart rate; and NS, nonsignificant.

Table 2. Differences in Left Heart Measurements Between Female Athletes and Female Sedentary Controls and Between Pretraining and Post-Training Data Collected in Female Competitive Athletes

Variable Controls (n=24)

Female Competitive Athletes (n=24) P Value Athletes vs

ControlsP Value Pretraining vs

Post-Training Mean Change (95% CI)Pretraining Post-Training

LA area, cm2 14.2±1.9 16.4±1.6 17.3±2.6 0.000 0.010 0.8 (−0.1, 1.7)

LA volume, mL 34.3±8.8 46.0±7.2 52.9±12.1 0.000 0.001 7.0 (3.6, 10.4)

LA volume index, mL/m2 20.5±4.9 24.6±3.0 28.1±5.5 0.003 0.001 3.5 (1.8, 5.2)

E/A ratio 1.7±0.4 1.8±0.4 1.8±0.3 0.68 0.33 0.1 (−0.1, 0.2)

e′/a′ ratio 2.2±0.4 2.0±0.4 2.4±0.6 0.063 0.001 0.4 (0.2, 0.7)

E/e′ ratio 5.0±0.8 5.0±1.0 5.0±0.9 0.99 0.96 −0.01 (−0.5, 0.5)

LA global PALS, % 39.4±10.0 43.9±9.5 39.8±6.5 0.18 0.037 −4.2 (−8.3, −0.1)

LA global PACS, % 13.9±3.0 15.5±4.0 13.9±4.0 0.19 0.033 −1.8 (−3.4, −0.2)

LA stiffness index 0.15±0.05 0.12±0.04 0.13±0.04 0.031 0.306 0.01 (0.2, 0.7)

LA PALS/PACS ratio 3.0±1.3 2.9±0.4 3.0±0.7 0.56 0.23 0.2 (−0.1, 0.4)

LA TPLS, ms 351.4±72.5 374.1±40.9 390.1±34.3 0.23 0.13 12.1 (−8.3, 32.4)

LA TPCS, ms 588.0±159.1 755.8±160.9 809.5±164.2 0.002 0.055 54.4 (−3.7, 112.6)

LA TPLS/RR ratio 0.45±0.11 0.41±0.05 0.41±0.05 0.25 0.81 −0.01 (−0.04, 0.02)

LA TPCS/RR ratio 0.75±0.19 0.82±0.06 0.84±0.07 0.071 0.42 −0.01 (−0.03, 0.06)

CI indicates confidence interval; LA, left atrial; PACS, peak atrial contraction strain; PALS, peak atrial longitudinal strain; RR, relative risk; TPCS, time-to-peak contraction strain; and TPLS, time-to-peak longitudinal strain.

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function, with the exception of a higher RA PALS value in the control group. Conversely, both pretraining RV midcavity and basal end-diastolic diameter (EDD) were higher in female athletes when compared with those in sedentary subjects (28.8±4.1 versus 22.5±2.2 mm; P<0.001; 36.0±4.5 versus 30.1±3.2 mm; P<0.005, respectively).

After 16 weeks of intensive training, a significant increase in RA area, RA volume, and RA volume index was observed in female athletes (P<0.001; Table 3; Figure 2). Although none of the athletic women had an RA enlargement before training, 10% of female athletes exhibited a mild RA enlargement after 16 weeks of training. None of the athletes experienced a mod-erate or severe RA enlargement after training.

Although a trend toward decrease was observed after 16 weeks of training, no significant differences were found between pretraining and post-training measurements in RA PALS and RA PACS in female athletes (Table 3; Figure 2). As was observed for the LA, neither RA PALS/PACS nor RA stiff-ness index varied significantly after training. s′ peak (13.6±1.9 versus 13.6±2.1 cm/s; P=0.10), e′ peak (15.6±3.2 versus 15.9±3.0 cm/s; P=0.86), and a′ peak (10.1±2.2 versus 10.6±2.8 cm/s; P=0.66) did not change with training in female athletes.

In competitive male athletes, RA area (19.7±3.9 versus 21.1±3.3 cm2; P<0.05), RA volume index (24.9±8.0 versus 27.7±7.2 mL/m2; P<0.05), and RV basal EDD (39.9±4.3 versus

43.7±6.3 mm; P<0.05) increased significantly after training. Conversely, neither RA PALS (39.8±8.0% versus 40.9±4.4%; P=0.73) nor RA PACS (12.1±2.5% versus 12.7±2.7%; P=0.64) changed in male athletes, with PALS/PACS ratio remaining stable after training (3.3±0.7 versus 3.3±0.8; P=0.99).

See Table I in the Data Supplement for biventricular changes in morphology and myocardial deformation observed in female athletes before and after training.

Predictors of Biatrial Volumes in Female AthletesLeft AtriumUnivariate predictors of pretraining LA volume included BSA (β=0.75; adjusted R2=0.54; P<0.001), LVEDV (β=0.57; adjusted R2=0.28; P=0.009), RV midcavity EDD (β=0.53; adjusted R2=0.24; P=0.015), resting HR (β=−0.53; adjusted R2=0.24; P=0.017), inferior vena cava diameter (β=0.51; adjusted R2=0.21; P=0.26), and RR interval (β=0.47; adjusted R2=0.18; P=0.036). Univariate predictors of post-training LA volume included LVEDV (β=0.66; adjusted R2=0.41; P=0.001), BSA (β=−0.62; adjusted R2=0.35; P=0.004), LV systolic volume (β=0.50; adjusted R2=0.21; P=0.025), and RR interval (β=0.44; adjusted R2=0.15; P=0.048).

Neither E/e′ ratio nor LA stiffness were identified as predictors of pretraining and post-training LA volumes. Furthermore, no significant correlations were observed among

Figure 1. Left atrial (LA) volumes (top) and LA longitudinal myocardial deformation dynamics by 2-dimensional speckle-tracking echocar-diography (bottom). A representative case of a female athlete showing an increase of LA size and a reduction of LA strains after training. PACS indicates peak atrial contraction strain; and PALS, peak atrial longitudinal strain.

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226 Circ Cardiovasc Imaging March 2014

ΔLA volume (post-training versus pretraining) and the other echocardiographic parameters expressed as Δ.

Right AtriumUnivariate predictors of pretraining RA volume included transtricuspid E wave (β=−0.61; adjusted R2=0.33; P=0.015), RV midcavity EDD (β=0.60; adjusted R2=0.33; P=0.005), and RV basal EDD (β=0.57; adjusted R2=0.29; P=0.008). Uni-variate predictors of post-training RA volume included LVM (β=0.51; adjusted R2=0.26; P=0.027) and RV basal EDD (β=0.49; adjusted R2=0.24; P=0.035).

Neither E/e′ ratio nor RA stiffness were identified as predic-tors of pretraining and post-training RA volumes. No significant correlations were observed between RA strains and resting HR and between ΔRA volume (post-training versus pretraining) and the other echocardiographic parameters, expressed as Δ.

We additionally performed correlations between LV and RV dimensional parameters. A significant correlation was found between baseline RV basal EDD and LVEDV (R=0.67; P<0.005) and LV stroke volume index (R=0.54; P<0.05), whereas baseline RV midcavity EDD correlated with LVM (R=0.49; P<0.05) and with LVEDV (R=0.46; P<0.05).

DiscussionExercise Training and Biatrial Morphological AdaptationPrevious cross-sectional echocardiographic studies have observed that women demonstrate a significant cardiovascu-lar remodeling in response to physical training.15,33 Although cross-sectional studies provide useful information to differ-entiate the echocardiographic features of athletes and nonath-letes, they cannot be taken as definitive proof of a cause-effect relationship between training and an adaptive cardiac remod-eling. Longitudinal training studies with repeated measures

within individuals may, at least in part, overcome these draw-backs. Nonetheless, even if prospective studies have analyzed the longitudinal adaptations of the LV to exercise condition-ing,16,17,34 few longitudinal investigations have been conducted on LA dimensional and functional changes occurring during the training program, and no prospective, longitudinal data on RA changes are available, particularly in female athletes. The present study provides longitudinal data demonstrating signif-icant training-induced changes in biatrial size after a 16-week sport-specific training program in competitive female volley-ball players. We observed an exercise-induced biatrial remod-eling with a significant increase in atrial size for both the LA and RA, which correlated with biventricular dimensions. Interestingly, although a relevant percentage of the study population experienced a mild atrial enlargement, only a few athletes exhibited a moderate LA enlargement, and none of the participants experienced a severe biatrial dilatation.

Exercise Training and Biatrial Functional AdaptationIn this study, a 16-week intensive training program was able to induce in female athletes morphological as well as functional adaptations on both left and right heart. Two-dimensional speckle-tracking echocardiography allowed us to find that both left and right PALS and PACS decreased after training. A peculiar pattern of myocardial deformation dynamics has been observed in athletes in comparison with that in sedentary subjects with reduction of LA and RA atrial strain values7,9; furthermore, this typical pattern has been confirmed in a lon-gitudinal study investigating the effects of an 8-month train-ing program on LA, demonstrating that an exercise-induced reduction of LA strain values can be observed in competitive adolescent soccer players.16 In this study, we confirmed these previous findings in female athletes as well. Even if a reduction of PALS and PACS values can be observed in comparison with

Table 3. Differences in Right Heart Measurements Between Female Athletes and Female Sedentary Controls and Between Pretraining and Post-Training Data Collected in Female Competitive Athletes

Variable Controls (n=24)

Female Competitive Athletes (n=24) P Value Athletes vs

ControlsP Value Pretraining vs

Post-Training Mean Change (95% CI)Pretraining Post-Training

RA area, cm2 12.8±1.6 12.4±1.5 14.5±2.0 0.35 0.001 2.8 (1.8, 3.8)

RA volume, mL 31.5±6.2 29.0±5.8 38.5±9.4 0.18 0.001 10.4 (5.1, 15.8)

RA volume index, mL/m2

18.4±4.4 15.6±3.1 20.6±4.9 0.05 0.001 5.4 (2.6, 8.3)

E/A ratio 1.9±0.4 1.7±0.3 2.1±0.7 0.10 0.20 0.3 (−0.1, 0.8)

E/e′ ratio 4.0±0.8 4.0±1.4 3.7±1.0 0.81 0.39 −0.01 (−0.74, 0.71)

RA PALS, % 50.9±10.7 42.8±10.6 39.3±8.3 0.022 0.22 −2.5 (−9.2, 4.2)

RA PACS, % 17.1±5.4 15.6±5.6 13.1±6.1 0.41 0.083 −2.8 (−7.1, 1.6)

RA stiffness index 0.09±0.02 0.09±0.04 0.10±0.03 0.60 0.81 −0.01 (−0.04, 0.03)

RA PALS/PACS ratio 3.2±1.0 3.0±0.9 3.9±3.2 0.55 0.16 0.8 (−0.3, 1.9)

RA TPLS, ms 367.1±37.8 363.7±53.0 386.7±63.4 0.82 0.24 8.4 (−31.2, 48.2)

RA TPCS, ms 638.1±84.6 752.9±190.2 784.6±199.9 0.024 0.52 14.5 (−67.9, 97.0)

RA TPLS/RR ratio 0.46±0.06 0.40±0.07 0.41±0.10 0.010 0.76 −0.01 (−0.06, 0.03)

RA TPCS/RR ratio 0.81±0.08 0.82±0.12 0.81±0.16 0.84 0.96 −0.02 (−0.09, 0.05)

CI indicates confidence interval; PACS, peak atrial contraction strain; PALS, peak atrial longitudinal strain; RA, right atrial; RR, relative risk; TPCS, time-to-peak contraction strain; and TPLS, time-to-peak longitudinal strain.

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D’Ascenzi et al Training-Induced Cardiac Adaptation in Women 227

control subjects, none of the athletes showed pathological val-ues of LA/RA myocardial deformation. Indeed, the observed value of LA PALS was significantly higher when compared with data reported in patients with early hypertension or pul-monary hypertension.35,36 Even if a direct comparison between athletes and patients with paroxysmal atrial fibrillation has not been performed in this study, recent research by Yoon et al37 reported that global LA strain in subjects having par-oxysmal atrial fibrillation was 27.3±7.2%, with LA stiffness being 0.41±0.24. Conversely, athletes in this study exhibit a clearly high value of global LA strain and a markedly lower value of LA stiffness, even lower when compared with con-trols by Yoon et al,37 being 0.29±0.10. Furthermore, even if biatrial size increased after training, LA and RA stiffness did not vary, and the PALS/PACS ratio remained constant after 16 weeks of intensive training because of a balanced reduc-tion of both PALS and PACS. Of note, a slight improvement of left and right diastolic function has been observed during the study, particularly at tissue Doppler imaging analysis, with LV filling pressures, estimated by E/e′ ratio, being stable and within the range of normality. Taken together, these findings indicate that the reduction of atrial myocardial deformation should be regarded as an adaptive phenomenon physiologi-cally induced by training, and the correlation between resting HR and time-to-peak longitudinal and contraction atrial strain seems to suggest a resting atrial functional reserve, indicative of an economized heart function at rest, which likely can be

recruited during the effort, similarly to the training-related modulation of the HR.

Heart of Athletes and Training Stimulus: Female Versus MaleUncertainties persist about the ability of the female heart to adapt in response to exercise conditioning. Rubal et al38 dem-onstrated that sedentary college women exhibit significant changes in LV wall thickness, LVM, and LV end-diastolic dimension after a 10-week endurance conditioning period, whereas Haykowsky et al39 reported that 10 weeks of com-bined endurance/strength training are an insufficient stimulus to elicit alterations in active but not in well-trained female volunteers. In a study primarily investigating biventricular adaptation induced by a 90-day training program in university athletes, Baggish et al17 documented a significant increase in LA and RA dimensions in a mixed population of male and female rowers. In this study, we demonstrated that changes in biatrial size can be observed after 16 weeks of intensive train-ing in highly trained female athletes with previous training experience, suggesting that atrial remodeling can be observed not only in men but also in women practicing sports at a high level. A recent study by Mosén and Steding-Ehrenborg,40 aim-ing to compare atrial volumes obtained in male and female ath-letes directly, reported that atrial adjustment to training is more modest in women. Our study aimed to investigate the training-induced biatrial remodeling in women primarily, and a direct

Figure 2. Right atrial (RA) volumes (top) and RA longitudinal myocardial deformation dynamics by 2-dimensional speckle-tracking echo-cardiography (bottom). A representative case of a female athlete showing an increase of RA size and a reduction of RA strains after train-ing. PACS indicates peak atrial contraction strain; and PALS, peak atrial longitudinal strain.

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228 Circ Cardiovasc Imaging March 2014

comparison between male and female athletes was beyond the scope of the present study. However, we observed in a lon-gitudinal study a significant exercise-induced morphological remodeling of both RA and LA in female athletes, and, albeit not significantly different in men, the variation in LA and RA volumes after training was similar between female and male athletes, being greater for RA volume in women (LA volume, Δ=8 mL in men and Δ=7 mL in women; RA volume, Δ=7 mL in men and Δ=10 mL in women). Although sex differences in the cardiac adaptation between male and female athletes have been primarily attributed to the effect of androgenic hormones on cardiac protein synthesis,41 other determinants might play central roles in sex differences in cardiac adaptation, such as muscle mass, training volume, and blood volume expansion, all variables conditioned by sex as well as by the discipline the athletes were engaged in. Whether these determinants might influence the in-seasonal cardiovascular changes more than sex remains a challenge for future investigations.

Global Exercise-Induced Cardiac RemodelingIn this study, the training-induced increase in LA and RA dimensions parallels LV and RV enlargement, respectively, as demonstrated by the significant correlation among LA, LVEDV, and LV stroke volume and among RA, RV basal, and midcavity diameters, confirming the interactive and dynamic relationship between atria and ventricles. Furthermore, a cor-relation was found among LV and RV dimensional parameters, supporting the concept that cardiac remodeling in athletes is a balanced, biventricular phenomenon, with an interdependence between right and LV cavities, which is well known to be increased particularly in the case of volume overload.42

Even if exercise conditioning is able to induce an adapta-tion of all cardiac chambers, the increase in biatrial volumes occurred in our study population with a greater extent when compared with the increase in biventricular dimensions, with a 15.0% and 32.7% post-training increase in LA and RA size, respectively, and a 7.5% and 13.5% increase in LV and RV dimensions, respectively. These findings should be explained by the anatomic features of the ventricles and by the thin wall structure of the atria, able to respond to a greater extent to the hemodynamic adaptations induced by exercise conditioning.

Because RV filling is primarily affected by the increased venous return, we demonstrated a significant training-induced increase of the inferior vena cava diameter, supporting the hypothesis that in female athletes volleyball training induces a myocardial remodeling in the form of exercise-induced hemo-dynamic overload, which likely plays a relevant role in the mechanistic cascade for RV adaptation.

LimitationsThe small sample size is the main limitation of this study. How-ever, we studied a selected cohort of athletes, and pooling data from additional teams to extend the sample size could result in uncontrollable differences across subjects in factors such as ath-letic skill, coaching practices, or competitive setting, and it may well have presented greater threats to validity. Furthermore, the population of men athletes is composed of basketball players, and although metabolic and cardiovascular similarities exist between volleyball and basketball, this represents a limitation

of the study. Finally, even if a good reproducibility has been demonstrated for echocardiographic measurements of the right heart,24,43 a RV-focused apical 4-chamber view has to show the maximum diameter of the RV without foreshortening and making sure that the crux and apex of the heart are viewed, as recommended.24 However, repeated-measures studies stress the difficulty to image the RV in the same angle in the same subject.

ConclusionsIn female athletes, a 16-week intensive training program is able to induce a physiological adaptation of the heart, which is associated with a regular and harmonious remodeling of the 4 chambers. Biatrial enlargement, with normal filling pressures, low biatrial stiffness, and normal biatrial longitudinal strains, is a typical feature of the heart of female athletes. These find-ings may contribute to the differential diagnosis with car-diomyopathies and should be interpreted as a physiological adaptation to intensive training.

AcknowledgmentsWe thank Chairmen of Santa Croce Volleyball Club, San Mariano Volleyball Club, and Mens Sana Basket Siena, all members of medi-cal and coaching staff, athletes, and managers for their support in the study.

DisclosuresNone.

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CLINICAL PERSPECTIVEAlthough several echocardiographic studies have investigated the effects of training on cardiac geometry and function, most are restricted to male athletes or are not specifically focused on the heart of female athletes. Particularly, the investigation of left atrial morphological and functional adaptation to exercise conditioning is crucial, considering the existing controversies on the relationship between training-induced atrial remodeling and the incidence of atrial fibrillation among competitive ath-letes. In this prospective and longitudinal study, we investigated the adaptation of both the right and left atrium in competi-tive female athletes, demonstrating that 16 weeks of intensive training are able to induce significant biatrial morphological changes, with greater biatrial volumes after training when compared with pretraining data. Conversely, intracavity filling pressures were normal in competitive athletes and did not vary after training, supporting the hypothesis that the increase in biatrial size occurs in athletes in a model of volume rather than pressure overload. Furthermore, a regular and harmonious remodeling of the 4 cardiac chambers was demonstrated, with the biatrial adaptation that parallels the balanced, biventricular remodeling. Thus, biatrial enlargement, with normal filling pressures, low biatrial stiffness, and normal biatrial longitudinal strains, is a typical feature of the heart of female athletes. These findings may contribute to the differential diagnosis of car-diomyopathies and should be interpreted as a physiological adaptation to intensive training.

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SUPPLEMENTAL  MATERIAL  

 

SUPPLEMENTAL  METHODS  

 

Standard  and  Tissue  Doppler  Imaging  

PW  Doppler  analysis  was  performed   in   the  apical  4-­‐chamber  view  to  obtain  mitral  and  tricuspid  

inflow  velocities  to  assess  LV  and  RV  inflow.  For  LV  a  1-­‐mm  to  3-­‐mm  sample  volume  was  placed  

between  mitral  leaflet  tips  during  diastole,  as  recommended  (25).  For  the  RV  the  sample  volume  

was   placed   at   the   tips   of   the   tricuspid   leaflets   (23).   Care   was   taken   to   measure   at   held   end-­‐

expiration  taking  an  average  of  3  consecutive  beats.  Early  filling  (E-­‐wave),   late  diastolic  filling  (A-­‐

wave)  velocities  and  their  ratio  E/A  were  obtained  for  the  LV  and  the  RV.    

To   perform   TDI   analysis,   an   apical   4-­‐chamber   view  was   used.   For   the   left   ventricle,   the   sample  

volume  was  positioned  at  or  1  cm  within  the  septal  and  the  lateral  insertion  sites  of  mitral  leaflets  

to  cover  the  longitudinal  excursion  of  the  mitral  annulus  in  both  systole  and  diastole  (25).  For  the  

RV,   to   perform   TDI   analysis   of   the   right   side,   an   apical   4-­‐chamber   view  was   used  with   a   tissue  

Doppler  mode   region   of   interest   highlighting   the   RV   free  wall   (23).   The   pulsed  Doppler   sample  

volume  was  placed   in  either  the  tricuspid  annulus  or  the  middle  of  the  basal  segment  of  the  RV  

free   wall.   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   and   basal   RV   longitudinal   function.   e’   and   the   derived   e’/a’   ratio   were   used   as   load-­‐

independent  markers  of  ventricular  diastolic  relaxation.  

 

Speckle  tracking  echocardiography  

Care  was  taken  to  obtain  true  apical  images  using  standard  anatomic  landmarks  in  each  view  and  

not   foreshorten   the   left   and   right   atria,   allowing   a   more   reliable   delineation   of   the   atrial  

endocardial   border. The   optimal   frame   rate   for   the   2-­‐dimensional   image   acquisition   was   set  

between  60  and  80  frames  per  second.  Off-­‐line  analysis  was  performed  by  one  experienced  and  

independent  operator  who  was  not  directly  involved  in  the  image  acquisition  and  was  blinded  to  

the   study   period,   using   a   commercially   available   semi-­‐automated   2-­‐dimensional   strain   software  

(EchoPac,  GE,  USA).  

Endocardial  surfaces  were  manually  traced  in  both  4-­‐  and  2-­‐chamber  views  for  the  left  atrium  and  

only   in   4-­‐chamber   view   for   the   right   atrium,   by   a   point-­‐and-­‐click   approach   in   order   to   create   a  

region   of   interest   (ROI)   with   the   automatic   adjustment   of   the   system.   All   measurements   were  

taken   from   the  onset   of  QRS   complex,   as   previously   described   for   left   and   right   atria   (9,28,29).  

After  a  manual  adjustment  of  the  tracked  area,  the  software  divides  the  ROI  into  6  segments,  and  

the  resulting  tracking  quality   for  each  segment  was  automatically  scored  as  either  acceptable  or  

non-­‐acceptable,   with   the   possibility   of   further   manual   correction.   Segments   with   no   adequate  

image   quality   have   been   excluded   and   the   final   value   was   obtained   with   the   remaining   atrial  

sections.    

PALS  and  PACS  were  obtained  for  both  LA  and  RA,  calculating  the  average  of  all  segments  and  the  

average  values  obtained  from  4-­‐chamber  and  2-­‐chamber  view  for  the  left  atrium  (LA  global  PALS  

and  global  PACS).  LA  and  RA  PALS  were  used  to  estimate  LA  and  RA  reservoir  function,  while  LA  

and  RA  PACS  were  used  to  measure  the  phase  of  LA  and  RA  active  conduit  in  late  diastole  during  

atrial  contraction.    

Inter-­‐observer   and   intra-­‐observer   variability   was   assessed   in   previous   studies   by   our   research  

group  for  both  left  and  right  atria  (7,29).  In  this  study,  the  software  was  able  to  correctly  track  97%  

of  the  segments  analyzed  for  the  left  atrium  and  in  the  92%  of  the  segments  for  the  right  atrium,  

with  the  basal  lateral  segment  being  the  more  complicated  segment  to  trace.  

LV  and  RV  longitudinal  strain  were  determined  as  recommended  (29).  For  the  right  ventricle,  both  

free  wall  and  septal  longitudinal  strain  were  determined.  

SUPPLEMENTAL  TABLE  

 

Supplemental  table  1.  Changes  in  biventricular  dimensions  and  longitudinal  deformation  observed  

pre-­‐training   and   after   16  weeks   of   intensive   supervised   training   program   in   competitive   female  

athletes.    

Competitive  female  athletes  (n  =  24)  

Variable   Pre-­‐training   Post-­‐training   P  value  

LV  mass  index,  g/m2   65.9  ±  11.2   74.7  ±  14.4   .004  

LV  EDV  index,  mL/m2   52.1  ±  8.7   55.7  ±  9.5   .14  

LV  mass/LV  EDV  ratio   1.32  ±  0.33   1.36  ±  0.39   .53  

Global  LV  longitudinal  strain,  %   -­‐19.7  ±  1.8   -­‐20.5  ±  2.1   .25  

RV  EDD  basal,  mm   36.0  ±  4.6   38.2  ±  4.4   .038  

RV  EDD  mid  cavity,  mm   28.7  ±  4.2   32.6  ±  3.7   .001  

RV  free  wall  longitudinal  strain,  %   -­‐24.2  ±  6.3   -­‐27.9  ±  5.8   .026  

Global  RV  longitudinal  strain  (including  interventricular  septum),  %   -­‐22.0  ±  4.0   -­‐23.9  ±  4.1   .079  

IVC  diameter,  mm   17.0  ±  3.3   20.8  ±  4.6   .004  

 

LV,   left  ventricular;  EDV,  end-­‐diastolic  volume;  RV,  right  ventricular;  EDD,  end-­‐diastolic  diameter;  IVC,  inferior  vena  cava.