Normative Reference Values of Right Heart in Competitive Athletes: A Systematic Review and Meta-Analysis

Normative Reference Values of Right Heart in Competitive Athletes: A Systematic Review and Meta-Analysis Flavio D’Ascenzi, MD, PhD, FESC, Antonio Pelliccia, MD, FESC, Marco Solari, MD, Pietro Piu, PhD, Ferdinando Loiacono, MD, Francesca Anselmi, MD, Stefano Caselli, MD, PhD, FASE, FESC, Marta Focardi, MD, PhD, Marco Bonifazi, MD, and Sergio Mondillo, MD, Siena and Rome, Italy

Training-induced right ventricular (RV) enlargement is frequent in athletes. Unfortunately, RV dilatation is also a common phenotypic expression and one of the diagnostic criteria of arrhythmogenic RV cardiomyopathy (ARVC). The current echocardiographic reference values derived from the general population can overestimate the presence of RV dilatation in athletes. We performed a meta-analysis of the literature to derive the proper reference values for assessing RV enlargement in competitive athletes. We conducted systematic review of English-language studies in the MEDLINE, Scopus, and Cochrane databases investigating RV size and function by echocardiography and by cardiac magnetic resonance (CMR) in competitive athletes. In total, 6,806 and 740 competitive athletes were included for the echocardiographic and CMR quantification of the RV, respectively. In this review, we present normal reference values for RV size and function to be applied in competitive athletes according to the disciplines practiced. The reference ranges reported in this review suggest that physicians should be aware that application of the current recommendations for normal population could be misleading when evaluating athletes. We suggest using these normative reference values, obtained in competitive athletes, to avoid the potential for mistakenly concluding, in this specific population, that RV size or function are abnormal. (J Am Soc Echocardiogr 2017;30:845-58.) Keywords: Athlete’s heart, Right ventricle, Normative values, Cut-off, Echocardiography, Cardiac magnetic resonance, Chamber quantification

Right ventricular (RV) enlargement is a common phenotypic expression and one of the established criteria for the diagnosis of arrhythmogenic RV cardiomyopathy (ARVC)1,2; however, this finding is not uncommonly reported in other conditions, including the ‘‘athlete’s heart.’’3-9 Specifically, RV enlargement has been described as a morphologic hallmark in imaging studies of a large proportion of the athletic population, with the extent of remodeling being more marked in individuals engaged in the endurance disciplines.6,8 In these instances, the training-induced dimensional increase of the RV may even overlap with the pathological dilatation of the RV in patients with ARVC, raising the question of a challenging differential diagnosis. The judgment of whether the RV enlargement is consistent with a physiologic adaptation has enormous importance, and, despite several reports having previously described the morphologic characteristics of the RV in athletes,4,6,8,9 a definitive assessment of the

From the Department of Medical Biotechnologies, Division of Cardiology (F.D’A., M.S., F.L., F.A., M.F., S.M.) and Department of Medicine, Surgery, and NeuroScience, University of Siena, Siena (P.P., M.B.); and Institute of Sports Medicine and Science, Rome, Italy (A.P., S.C.). Reprint requests: Flavio D’Ascenzi, MD, PhD, FESC, Department of Medical Biotechnologies, Division of Cardiology, University of Siena, Viale M. Bracci, 16 53100 Siena, Italy (E-mail: [email protected]). 0894-7317/$36.00 Copyright 2017 by the American Society of Echocardiography. http://dx.doi.org/10.1016/j.echo.2017.06.013

reference values for standard echocardiographic measurements of the right heart in competitive athletes is still lacking. Reference values were previously published by the American Society of Echocardiography and the European Association of Echocardiography,10 and revised recommendations have been further released.11,12 Unfortunately, these documents have not included athletes and do not take into account the exercise-induced RV remodeling. Therefore, quantification of RV dimensions in athletes’ cohorts based on these reference values may be misleading and a possible source of misdiagnosis, with potential unwarranted clinical consequences. Therefore, we believed it to be timely and appropriate to conduct a meta-analysis from all available studies referring to athletes, in order to derive the normative reference values for RV dimensions and function by echocardiography and cardiac magnetic resonance (CMR) to be implemented in the clinical evaluation of competitive athletes.

METHODS Data Source and Searches We conducted a systematic literature search of the MEDLINE, Scopus, and Cochrane databases from inception to April 30, 2016. We also included articles published online ahead of print at the time of our search. The primary search used the following keywords: echo or cardiac magnetic resonance (CMR) or CMR imaging, with or without: Doppler, colour, stress, three-dimensional; right heart; right ventricular: dimension, function, size, structure. In addition, the 845

846 D’Ascenzi et al

Abbreviations

ARVC = Arrhythmogenic right ventricular cardiomyopathy

BIC = Bayesian information criterion

BSA = Body surface area CMR = Cardiac magnetic resonance

FAC = Fractional area change

Journal of the American Society of Echocardiography September 2017

population search used the following items: athletes, training, exercise. Where applicable, keywords were searched as the root and truncation symbol (e.g., ventric*). Additionally, we manually searched references from papers about studies, review articles, and meta-analyses. All searches were confined to human studies. Studies not in English were excluded.

LV = Left ventricular

Study Selection We assessed studies for inclusion view by using the following a priori PSAX = Parasternal defined criteria: (1) the study short-axis view explicitly stated that it evaluated competitive athletes, with no RA = Right atrial history of cardiovascular disease; RV = Right ventricular, (2) the study reported at least three ventricle parameters of RV dimensions and RVOT = Right ventricular function, measured by CMR or outflow tract two-dimensional echocardiography according to current clinical TAPSE = Tricuspid annular standards10-12; (3) the mean age plane systolic excursion of the study cohort was set TF = Task force between 18 and 39 years both for echocardiographic and CMR studies; (4) a measure of statistical variance was reported; (5) year of publication S1990 for echocardiographic studies and S2000 for CMR studies. Because of the paucity of CMR data referring to female athletes, for CMR studies only male athletes were analyzed. Study arms that reported populations that potentially overlapped with other studies were excluded. Echocardiographic studies with #20 athletes were also excluded. A flowchart showing the derivation of the reference cohort is shown in Figure 1 for echocardiographic studies and in Figure 2 for CMR studies. PLAX = Parasternal long-axis

Data Collection Each eligible article meeting the inclusion criteria was reviewed by two independent reviewers (M.S. and F.L.) who compared decisionmaking and discussed disagreements. Discrepancies were resolved by consensus. Each data set was reviewed for units and methods of measurement, range checks were performed to identify and exclude biologically implausible values, and summary statistics were crosschecked against published results, where available. Athletes were classified into strength (such as bodybuilders and weightlifters), endurance (such as long-distance runners, swimmers, and cross-country skiers), and combined (such as rowers, cyclists, and speed skaters) groups according to the intensity level of static and dynamic components.13-15 Heterogeneous groups of athletes of different sports classifications were categorized as mixed. In longitudinal studies investigating training-induced RV remodeling, the RV measurements after the longest exercise exposure were used. Data Synthesis, Statistical Analysis, and Development of Reference Values To explore the influence of type of training (endurance, strength, mixed, or combined disciplines), gender, and age on right heart size

and function, a meta-analysis was conducted to integrate the results of a set of studies about RV parameters measured by echocardiography and CMR in competitive athletes engaged in different disciplines. Specifically, a meta-regression was used that allowed for betweenstudy heterogeneity. The class of sports activity (i.e., endurance vs nonendurance disciplines) and age were included in the model as moderator variables. Since the levels of the moderators may influence the heterogeneity among the studies, the meta-regression analysis was based on a mixed effects model.16,17 Mixed effects models provided unconditional inference about the average effect in the entire population of studies from which the included studies were assumed to be randomly selected. The Knapp-Hartung adjustment18 to the standard errors of the estimated coefficients was applied in order to adjust the statistics and the confidence intervals of the estimates so that their significance properties are closer to the nominal 5% type I error and the confidence intervals maintain a 95% coverage level. Therefore, the tests on individual coefficients as well as the confidence intervals relied on t distributions with k - 1 degrees of freedom, where k is the number of studies. An underlying heteroskedastic covariance structure was considered in the study-aggregate metaanalysis. The sampling variances were calculated based on large sample approximation. Maximum-likelihood estimation was used when estimating the heterogeneity parameters of meta-analysis. The between-study heterogeneity in the true measurements of the dependent variables was assessed by the parameter t2, and its percentage over the total variability in the effect size estimates was also calculated (I2). A test of the residual heterogeneity (Q statistic) was also applied. For each variable, a sequence of two meta-regressions were implemented, which included the reduced model consisting of the basic random effects model (i.e., a meta-regression without moderators) and the models with the Class moderator. The Bayesian information criterion (BIC) was used for model selection among the above finite set of models. The model with the lowest BIC was preferred. The coefficients from the selected model quantified the direction and magnitude of the relationship between the average ‘‘true’’ outcome in the population of studies and the moderator variable(s) included in the model. The 95% CIs around the estimated average outcome and prediction intervals of new possible data were provided for different levels of the significant moderators. We also reported 99% CIs in order to provide further information. Forest plots gave the graphical overview of the results from the fitted model. Funnel plots were also drawn, and the Egger’s regression test for funnel plot asymmetry indicated whether either publication bias or systematic difference between larger and smaller studies occurred. Significant rejection of the null hypothesis of symmetry therefore would cast doubts on the reliability of the metaregression. The coefficients from the fitted model estimated the direction and magnitude of the relationship between the average true outcome in the population of studies and the moderator variable included in the model. RV reference values were defined at the 95th percentile and lower reference values at the 5th percentile. In accordance with earlier recommendations,10 these values defined 90% of the population as normal, but they allowed for nonnormal distributions. Reference values were derived in male competitive athletes divided according to sports disciplines for RV size (RV outflow tract [RVOT] parasternal long-axis view [PLAX], RVOT parasternal short-axis view [PSAX], RVend-diastolic and end-systolic area, RV basal and midcavity diameter, RA area and their indexed values, and RV wall thickness) and RV function (fractional area change [FAC], tricuspid annular plane systolic excursion [TAPSE], s’ and e’ velocities, and RV strain). Reference

Journal of the American Society of Echocardiography Volume 30 Number 9

D’Ascenzi et al 847

Figure 1 Results of the literature search and disposition of echocardiographic articles screened for inclusion. MRI, Magnetic resonance imaging. values were established in male competitive athletes divided according to sports disciplines also by CMR for RV end-diastolic and end-systolic volumes, RV stroke volume, and RV ejection fraction. In female competitive athletes only the reduced meta-regression model was considered (i.e., reporting only mean values 6 SE). All statistical analysis was carried out with the comprehensive software meta-analysis package for R: metafor 1.9-8 (2015-09-28).19

RESULTS Our search of the literature for echocardiographic studies identified 361 articles for review (Figure 1). Of these, 315 were excluded for

various reasons, most commonly because the RV was not evaluated. Thus, 46 studies2-8,20-58 met the inclusion criteria for the analysis, and a final population of 6,806 athletes were included in the present meta-analysis. We also identified 84 articles for review of CMR studies (Figure 2). Of these, 66 were excluded for various reasons. Thus, 18 studies59-76 met the inclusion criteria for the analysis, and a final population of 740 athletes were included in the present metaanalysis. Table 1 reports the demographic characteristics of the subjects of the articles included in this study. The mean body surface area (BSA) of the overall population was 2.0 6 0.2 m2, while the mean resting heart rate was 56.2 6 0.7 bpm and systolic and diastolic blood pressure were 123 6 2 and 75 6 1 mmHg, respectively. The number of studies and subjects

848 D’Ascenzi et al

Journal of the American Society of Echocardiography September 2017

Figure 2 Results of the literature search and disposition of CMR articles screened for inclusion. available for each echocardiographic and CMR parameter and the results of heterogeneity tests in the final analysis are shown in Table 2. The reference values of RV size by echocardiography in male competitive athletes were reported in Table 3. While RVOT diameters did not differ among the four groups, RV end-diastolic and endsystolic areas were significantly different among the four groups, reaching the greatest value in combined athletes and the lowest in strength-trained athletes. The same findings were observed also for RV end-diastolic and midcavity diameters, while RA area did not differ among the groups. While RV wall thickness was similar between endurance and mixed athletes, athletes engaged in combined disciplines showed the greater value. The reference values

of RV function estimated by echocardiography are reported in Table 4. The FAC was lower in athletes practicing endurance and combined disciplines, but the lower limit of normalcy was the same for all the groups (i.e., 32%), with the exception of the mixed group. Neither TAPSE nor E/A ratio differed among the groups, while s’ velocity and e’ velocity reached the highest value in endurance and strength athletes. We obtained also CMR-derived data of RV size and function in male athletes, and reference values are reported in Table 5. Data of RV size and function are reported separately in Table 6 as mean 6 SE in female competitive athletes, while the number of subjects analyzed for each parameter and the results of heterogeneity tests in female athletes are shown in Table 2.

D’Ascenzi et al 849

Journal of the American Society of Echocardiography Volume 30 Number 9

Table 1 Demographic characteristics of echocardiographic and CMR studies assessing RV size and function in competitive athletes First author, year

Type of sport

n

Gender

Ethnicity

Age, years

Height, cm

BSA, m2

Training regimen

nr

38 6 10

nr

nr

nr

Echocardiographic studies Douglas, 199020

Combined

41

M, F

21

Henriksen, 1996

Endurance

127

M

nr

22 6 1

182 6 1

1.90 6 0.02

nr

Henriksen, 199922

Endurance

42

F

Caucasian

20 6 1

169 6 2

1.65 6 0.03

300-600 hours/year

Mixed

36

M

nr

22 6 4

nr

nr

Endurance

32

M

nr

24 6 2

nr

1.89 6 0.5

15-20 hours/week

Endurance

26

M

nr

22 6 3

nr

1.96 6 0.6

15-20 hours/week

Mixed

52

M

Caucasian

23 6 4

173 6 7

1.79 6 0.13

>10 hours/week

Endurance

20

M, F

nr

34 6 10

nr

nr

42 6 9 miles/wk

Mixed

60

M, F

nr

21 6 3

nr

2.0 6 0.2

15 6 5 hours/week

Combined

20

F

nr

19.6 6 1

172 6 8

1.8 6 0.2

11.3 6 2.4 hours/week

Combined

20

M

nr

19.2 6 1.2

187 6 6

2.1 6 0.1

11.9 6 2.2 hours/week

Combined

24

M

nr

19.1 6 0.5

187 6 7

2.2 6 0.2

13.3 6 3.2 hours/week

La Gerche, 200829

Combined

27

M, F

nr

nr

179 6 8

nr

19.2 6 3.3 hours/week

Poh, 200830

Combined

24

M, F

22 6 3

nr

1.6 6 0.2

Erol, 200223 D’Andrea, 200324 Kasikcioglu, 200525 Neilan, 200626 Koc¸, 200727 Baggish, 200828

Teske, 200931

Baggish, 201032 Bauce, 20102

American, Caucasian and Chinese

11.5 6 3.9 hours/week

nr

Mixed

58

M, F

nr

28 6 5

180 6 7

1.9 6 0.15

9-18 hours/week

Mixed

63

M, F

nr

27 6 5

183 6 8

1.96 6 0.17

>18 hours/week $ 9 hours/week

Mixed

54

M, F

nr

51 6 7

176 6 8

1.87 6 0.18

Combined

20

M

Caucasian

25 6 3

197 6 5

2.3 6 0.1

22 6 6 hours/week

Combined

20

M

Caucasian

20 6 2

186 6 6

2.1 6 0.2

11 6 4 hours/week

Endurance

40

M, F

Caucasian

26 6 5

173 6 20

1.84 6 0.2

7 6 1.7 hours/week 15-20 hours/week

33

D’Andrea, 2010

Endurance

50

M

nr

36 6 8

nr

1.89 6 0.11

D’Andrea, 201134

Endurance

370

M, F

nr

29 6 10

nr

1.84 6 0.5

15-20 hours/week

Strength

245

M, F

nr

29 6 10

nr

1.89 6 0.6

15-20 hours/week

Krol, 201135

Combined

38

M, F

Caucasian

25 6 3

186 6 10

2.1 6 0.2

La Gerche, 201136

Endurance

39

M, F

nr

36 6 8

178 6 6

nr

Popovic, 201137

Combined

21

M

nr

21 6 3

nr

2.12 6 0.09

15 hours/week

Strength

16

M

nr

23 6 3

nr

2.13 6 0.27

17 hours/week

Endurance

220

M, F

nr

28 6 11

nr

1.83 6 0.5

15-20 hours/week

Strength

210

M, F

nr

28 6 9

nr

1.89 6 0.7

15-20 hours/week

D’Andrea, 201238

nr 16.3 6 5.1 hours/week

Endurance

25

M, F

nr

nr

169 6 8

nr

Mixed

102

M, F

nr

36 6 11

178 6 8

2.02 6 0.24

Bernheim, 201340

Combined

38

M, F

nr

38 6 9

nr

1.9 6 0.2

D’Ascenzi, 20135

Endurance

100

M, F

nr

26 6 5

nr

2.05 6 0.23

Combined

18

M

nr

22 6 4

nr

2.1 6 0.1

3-8 low + 2-5 high + more super-high hours/week

Endurance

24

M

nr

24 6 4

nr

2.0 6 0.2

6-10.5 hours/week

Karlstedt, 201239 Oxborough, 20126

41

King, 2013

47 6 7 miles/week 8-24 hours/week 13.5 6 3.5 hours/week >15 hours/week

(Continued )

850 D’Ascenzi et al

Journal of the American Society of Echocardiography September 2017

Table 1 (Continued ) First author, year

Type of sport

42

Moro, 2013

Endurance

n

17

Gender

Ethnicity

Age, years

M

nr

33 6 8 (overall)

Height, cm

174 6 1

BSA, m2

1.81 6 0.03

Training regimen

24 hours/week

Endurance

19

M

nr

173 6 1

1.78 6 0.02

12-18 hours/week

Endurance

21

M

nr

177 6 1

1.92 6 0.02

26 hours/week

Mixed

80

M

Caucasian

31 6 10

nr

1.98 6 0.15

14.6 6 5.4 hours/week

Strength

28

M

Caucasian

27 6 6

nr

1.95 6 0.21

17.1 6 7.2 hours/week

Schmied, 201343

Endurance

210

M

African

19 6 nr

172 6 6

1.70 6 0.13

Simsek, 201344

Endurance

44

M, F

nr

24 6 3

nr

nr

Vitarelli, 201345

Endurance

35

M

nr

28.7 6 10.7

nr

Strength

35

M

nr

30.3 6 9.4

nr

29.4 6 9.8

Pagourelias, 20133

Zaidi, 20134

Strength

35

M

Mixed

300

M, F

Mixed

375

M, F

nr 14-18 hours/week

1.91 6 0.15

>15 hours/week

1.98 6 0.18

>15 hours/week

1.93 6 0.13

> 15 hours/week

22 6 5

nr

1.97 6 0.2

16.5 6 6.1 hours/week

white

22 6 5

nr

1.94 6 0.2

20.3 6 7.0 hours/week

Black (black African, black Afro-Caribbean, black British)

Mixed

627

M, F

ND

22 6 5

nr

nr

D’Ascenzi, 201447

Endurance

24

F

nr

25 6 4

nr

1.87 6 0.11

Esposito, 201448

Combined

40

M

Caucasian

28 6 10

nr

nr

>30 hours/week for 4 years

Gjerdalen, 201449

Endurance

553

M

504 Caucasian, 49 African

25 6 5

183 6 6

2.0 6 0.1

nr

Combined

54

M

nr

38 6 12

182 6 7

1.97 6 0.14

nr

Combined

33

F

nr

34 6 8

169 6 6

1.70 6 0.13

Zaidi, 201346

Leischik, 201450 Giraldeau, 201551 Grunig, 201552

Mixed

45

M

Caucasian

19 6 1

182 6 7

2.06 6 0.17

Mixed

45

F

Caucasian

19 6 1

168 6 6

1.71 6 0.12

Endurance

395

M, F

nr

nr

nr

nr

Strength

255

M, F

nr

19.8 6 7.5 16 hours/week

nr 15-20 hours/week

nr

Hedman, 201553

Mixed

46

F

nr

21 6 2

1.68 6 0.06

1.69 6 0.1

Jongman, 201554

Combined

24

M

nr

28 6 5

nr

1.9 6 0.1

24.3 6 5.6 hours/week

Mixed

52

M

Caucasian

25 6 5

nr

1.95 6 0.14

18.9 6 6.7 hours/week

Malmgren, 201556

Endurance

33

F

nr

20 6 2

175 6 7

1.90 6 0.1

10.8 6 2.3 hours/week

Utomi, 201557

Endurance

19

M

Caucasian

34 6 5

180 6 10

2.1 6 0.2

12 hours/week

Strength

21

M

Caucasian

29 6 8

180 6 10

2.3 6 0.3

11 hours/week

D’Ascenzi, 201658

Endurance

35

M, F

nr

22 6 7

nr

2.1 6 0.2

>20 hours/week for 4 weeks, then 12 hours/week + 1 or 2 matches/week

D’Ascenzi, 20167

Endurance

29

M, F

nr

21 6 7

nr

2.2 6 0.2

nr

Mixed

262

M, F

Caucasian

24 6 6 (overall)

nr

1.9 6 0.2

nr (Olympic athletes)

Strength

277

nr

1.8 6 0.2

Mixed

216

nr

1.9 6 0.2

Mixed

254

nr

2.0 6 0.2

Major, 201555

8

D’Ascenzi, 2017

13 6 5 hours/week

(Continued )

D’Ascenzi et al 851

Journal of the American Society of Echocardiography Volume 30 Number 9

Table 1 (Continued ) First author, year

Type of sport

n

Gender

Ethnicity

Age, years

Height, cm

BSA, m2

Training regimen

CMR studies Petersen, 200659

Mixed

20

M

nr

25 6 4

185 6 10

2.01 6 0.2

Perseghin, 200760

Endurance

9

M

nr

26 6 5

nr

2.11 6 1.2

nr

Combined

14

M

23 6 3

nr

1.92 6 0.1

nr

Combined

8

M

179.1 6 11.2

nr

11.5 6 3.1

Esch, 201061 62

Prakken, 2010

nr

31 6 9.7

22 6 7

Mixed

83

M

nr

26 6 6.4

186 6 7.3

2 6 0.2

12 6 2.4

Mixed

46

M

nr

26 6 4.9

186 6 7.3

2 6 0.2

24 6 5.6

Scharf, 201063

Endurance

29

M

White

24.6 6 3.9

184 6 4.4

2.03 6 0.8

nr

Scharf, 201064

Combined

26

M

nr

27.9 6 3.5

184 6 5

1.99 6 0.1

nr

Steding, 201065

Luijkx, 201267 Luijkx, 201268

Erz, 201366 Franzen, 201369 Luijkx, 201370

Endurance

11

M

nr

25 6 6

186 6 0.05

2.1 6 0.08

nr

Endurance

18

M

nr

24 6 5

183 6 0.05

2.01 6 0.08

nr

2.03 6 0.1

Combined

12

M

nr

35 6 9

184 6 0.05

Endurance

28

M

European

23 6 4.6

183 6 5.9

Endurance

10

M

African

23 6 2.8

179 6 4.8

1.95 6 0.1

14 6 2.8

Endurance

93

M

nr

24 6 4.3

183 6 6.4

1.97 6 0.15

16 6 6.1

2 6 0.13

>10 hours/week 16 6 4.4

Combined

57

M

nr

27 6 5

186 6 7.3

2.02 6 0.16

23 6 5.9

Strength

27

M

nr

26 6 5.8

181 6 8.2

2.13 6 0.23

13 6 5.1

182 6 4

1.9 6 0.14

13.7 6 5.8

Mixed

18

M

nr

37 6 7.6

Combined

20

M

nr

38.7 6 6.2

181 6 10

1.93 6 0.1

Strength

28

M

nr

27 6 6.5

180 6 7.4

2.13 6 0.21

Combined

52

M

nr

28 6 5.6

185 6 7.0

2 6 0.15

17.1 6 4.5 11.5 hours/week

Mixed

73

M

nr

37.4 6 11.4

181 6 6.1

1.91 6 0.13

13.1 6 4.5

StedingEhrenborg, 201372

Endurance

16

M

nr

25 6 5

183 6 0.05

2.03 6 0.10

nr

Claessen, 201473

Combined

14

M

nr

36 6 6

nr

nr

13 6 5 hours/week

La Gerche, 201574

Combined

10

M

nr

35 6 6

nr

nr

11 (6-15) hours/week

Dupont, 201776

Combined

12

M

nr

32.3 6 7.1

181 6 0.07

1.93 6 0.11

>8 hours/week

StedingEhrenborg, 201675

Endurance

6

M

nr

23 6 3

183 6 8

1.92 6 0.16

71

Mangold, 2013

nr

F, Female; M, male; ND, not distinguished; nr, not reported.

Table A1 reports the reference range of RV dimensional and functional echocardiographic parameters for male competitive athletes defined as 99% CI.

DISCUSSION RV enlargement is a common phenotypic expression and one of the essential components of the diagnostic criteria for ARVC.1,2 However, this finding is not uncommonly observed in clinically benign conditions, such as athlete’s heart, and a relevant proportion of competitive athletes exhibit absolute RV enlargement, which is dimensionally compatible with ARVC.4 Thus, an accurate definition of the normal limits of RV size in athletes is essential to guide the differential diagnosis between ARVC and athlete’s heart. The present systematic review and meta-analysis was planned to derive specific reference values for echocardiographic and CMR assessment of RV dimensions and function in athletes. We report the mean values and the 95% CI for RV size and function in competitive athletes. Indeed, in order to define appropriate reference values

for those athletes presenting the most marked and extreme physiologic RV remodeling, we further derived the normal range from this selected athletes’ cohort. In comparison with normative values of the current recommendations,11,12 we found that male competitive athletes had higher upper limits for RVOT PLAX, RV end-diastolic and end-systolic areas, RA area, and RV basal and midcavity diameter. Conversely, the reference values in athletes were similar to normal subjects for RVOT PSAX. Notably, the upper limit of RV wall thickness was within the normal range for endurance and strength athletes but not for athletes practicing combined disciplines, suggesting that physiological adaptation to exercise usually is not associated with RV hypertrophy, with the exception of athletes engaged in sports with high static, high dynamic demand such as rowing or canoeing. In 2010, Marcus et al. proposed a modification of the task force (TF) criteria for the diagnosis of ARVC.1 This revised document, based on data derived from patients with an established diagnosis of the disease, provides major and minor diagnostic criteria. Although these criteria require RV dilatation to be accompanied by wall motion abnormalities, visual assessment of these may be challenging in athletes

852 D’Ascenzi et al

Journal of the American Society of Echocardiography September 2017

Table 2 Number of studies and subjects used to derive each parameter in male competitive athletes Studies (n)

Subjects (n)

I2

Q

P value Q

Male athletes RV echocardiographic parameters RVOT PLAX

8

355

58.9

22.0

RVOT PLAX index

4

191

0

2.2

.0002

RVOT PSAX

6

299

0

0.19

.91

RVOT PSAX index

4

191

0

2.0

.16

.14

RVOT distal diameter

4

217

0

0.90

.64

RVOT distal diameter index

3

167

0

0.74

.39

16

1221

0

8.2

.76 .48

RV end-diastolic area RV end-diastolic area index RV end-systolic area RV end-systolic area index RV basal diameter RV basal diameter index RV midcavity diameter RV midcavity diameter index

9

746

0

4.5

12

890

0

5.0

.76

5

637

0

0.75

.68

12

1031

0

7.5

.49

7

788

0

9.9

.04

18

1210

0

13.4

.50

5

744

49.2

9.0

.01

RA area

5

895

0

1.2

.27

RV wall thickness

8

852

0

1.6

.90

15

732

0

12.8

.31

8

245

0

2.8

.59

s’

14

451

0

10.8

.37

e’

15

482

0

8.2

.69

e’/a’ ratio

11

434

58.8

19.9

.006

RV strain

12

430

0

2.7

.95

End-diastolic volume

18

398

40.6

28.6

.02

End-systolic volume

12

302

6.3

10.6

.30

FAC TAPSE

RV parameters derived by CMR

Stroke volume Ejection fraction

9

128

32.2

12.8

.04

23

704

33.6

32.7

.03

Demographic characteristics BSA

28

1679

20.2

27.0

.31

Resting heart rate

26

1367

0

11.6

.96

Height

29

1720

95.0

843.6

<.0001

Female athletes RVOT PLAX

6

285

0.34

6.71

.15

RVOT PLAX index

5

252

0

3.15

.37

RVOT PSAX

4

206

0

1.42

.49

RVOT PSAX index

4

206

0

0.55

.76

RV end-diastolic area

7

465

0

0.31

.99

RV end-systolic area

2

49

0

0.1

.75

RV basal diameter

7

312

0

0.68

.98

RV midcavity diameter

6

266

0

2.01

.73

RA area

6

258

0

1.66

.8

RV FAC

3

111

0

0.69

.41

s’ velocity

4

123

56.8

8.7

.03

e’ velocity

4

74

4.4

4.4

.21

exhibiting a significant RV remodeling. As a consequence, in clinical practice, the demonstration of a dilated RV plays a major role in raising suspicion of ARVC and may lead to false-positive results in low-risk

populations, such as competitive athletes. Indeed, athletes usually exhibit large RV dimensions, and this morphological remodeling is influenced by the hemodynamic changes induced by the increase in

D’Ascenzi et al 853

Journal of the American Society of Echocardiography Volume 30 Number 9

Table 3 Normal values for two-dimensional echocardiographic parameters of RV size in male competitive athletes Mean (95% CI)

RVOT PLAX (mm)

Table 3 (Continued ) Mean (95% CI)

P value for class of sport

.69

P value for class of sport

RV end-systolic area (cm2) Endurance

13 (10-15)

Reference

Combined

17 (14-20)

.02

Endurance

29 (26-33)

Mixed

13 (8-18)

.79

Combined

29 (26-33)

Strength

10 (8-13)

.18

Mixed

29 (26-33)

Strength

29 (26-33) 2

RVOT PLAX index (mm/m ) Endurance

Endurance .79

17 (15-18)

Combined

17 (15-18)

Mixed

17 (15-18)

Strength

17 (15-18)

RVOT PSAX (mm) 34 (32-35)

Combined

34 (32-35)

Mixed

34 (32-35)

Strength

34 (32-35)

RVOT PSAX index (mm/m2)

9 (7-10)

Combined

9 (7-10)

Mixed

9 (7-10)

Strength

9 (7-10)

RV basal diameter (mm) .17

Endurance

.67

RV end-systolic area index (cm2/m2)

Endurance

40 (38-42)

Reference

Combined

44 (39-49)

.14

Mixed

43 (41-44)

.02

Strength

38 (31-45)

.59

RV basal diameter index (mm/m2) Endurance

.46 23 (19-26)

Combined

23 (19-26)

Endurance

18 (16-20)

Mixed

23 (19-26)

Combined

18 (16-20)

Strength

23 (19-26)

Mixed

18 (16-20)

Strength

18 (16-20)

.74

RVOT distal diameter (mm)

RV midcavity diameter (mm)

.10

Endurance

29 (27-30)

Reference

Combined

41 (37-46)

<.0001

Endurance

31 (27-34)

Mixed

36 (35-37)

<.0001

Combined

31 (27-34)

Strength

26 (23-29)

.07

Mixed

31 (27-34)

Strength

31 (27-34)

RVOT distal diameter index (mm/m2)

.80

Endurance

16 (15-18)

Combined

16 (15-18)

Mixed

16 (15-18) 2

RV end-diastolic area (cm ) Endurance

23 (20-27)

Combined

32 (29-35)

Endurance

18 (14-22)

Combined

18 (14-22)

Mixed

18 (14-22)

Strength

18 (14-22)

RA area (cm2)

16 (15-18)

Strength

.69

RV midcavity diameter index (mm/m2)

Reference .002

.60

Endurance

18 (14-23)

Combined

18 (14-23)

Mixed

18 (14-23)

Strength

18 (14-23)

RV wall thickness (mm)

Mixed

30 (28-31)

.005

Strength

21 (17-25)

.33

Endurance

4.2 (3.9-4.4)

.95

Combined

7.0 (5-8)

RV end-diastolic area index (cm2/m2)

Mixed

Endurance

15 (14-16)

Combined

15 (14-16)

Mixed

15 (14-16)

Strength

15 (14-16)

Strength

Reference .01

nd

nd

4.0 (3-5)

.60

BSA (m2) Endurance

1.89 (1.80-1.97)

Reference (Continued )

(Continued )

854 D’Ascenzi et al

Journal of the American Society of Echocardiography September 2017

Table 3 (Continued ) Mean (95% CI)

P value for class of sport

Combined

2.01 (1.99-2.20)

<.0001

Mixed

1.93 (1.77-2.08)

.57

Strength

2.00 (1.82-2.17)

.20

Heart rate (bpm)

Table 4 Normal values for two-dimensional echocardiographic parameters of RV function in male competitive athletes Mean (95% CI)

FAC (%) Endurance

35 (32-38)

Reference

Combined

36 (32-40)

.62

Mixed

43 (36-51)

.04

41 (32-49)

.22

Endurance

55 (53-57)

Reference

Combined

59 (56-64)

.04

Strength

Mixed

52 (43-60)

.42

TAPSE (mm)

Strength

60 (54-66)

.10

Endurance

25 (22-28)

Combined

25 (22-28)

Height (cm)

.11

Endurance

182 (180-185)

Combined

182 (180-185)

Mixed

182 (180-185)

Strength

182 (180-185)

nd, Not definable.

cardiac preload, gender, BSA, type of training, period of the agonistic season when the evaluation is performed (i.e., low-training vs peaktraining), and, according to some investigators, also age.4,6,7 The present review and meta-analysis is intended to support clinicians in the difficult task of differential diagnosis between physiologic and pathologic RV remodeling, by providing the reference limits of RV dimensions in competitive athletes. Notably, comparing our results with the current echocardiographic TF criteria for the diagnosis of ARVC, we can observe that the upper limits of RVOT PLAX diameter are beyond both the minor and major diagnostic criteria for ARVC (33 vs 29 mm or vs 32 mm, respectively), and the same finding was observed also for RVOT PSAX diameter (35 vs 32 mm or vs 36 mm, respectively). Conversely, if we compared the upper limit derived from this population for RVOT PLAX indexed to BSA to the echocardiographic criteria for ARVC, we found that, while the limit was greater than that recommended as minor diagnostic criteria for ARVC (18 vs 16 mm/m2), the upper limit of normalcy found in athletes was within the normal range if we considered the major criteria for the diagnosis of ARVC (18 vs 19 mm2). The same results were found also for RVOT PLAX index. Thus, according to the current results, we suggest applying in competitive athletes only the major echocardiographic criteria for the diagnosis of ARVC in order to prevent unwarranted false-positive results. We further confirm that the criteria of RV enlargement proposed by the American Society of Echocardiography11 cannot be properly applied to the athletic population. When RV functional indexes are examined, the lower limit of normalcy of RV FAC in all the groups of athletes—with the exception of the mixed group—was lower than that proposed by the recommendations to be applied for the general population.11,12 Notably, the lower limit of normality for endurance-, combined-, and strengthtrained male athletes was lower than the limits proposed as minor or major diagnostic criteria for ARVC (32% vs 40% and 33%, respectively). Therefore, the present results suggest that healthy athletes can show a slightly lower RV function at rest and confirm the uncertainties regarding the strict application of functional criteria for the diagnosis of ARVC based on FAC. Although a slight reduction in RV FAC could be interpreted as a physiological consequence of the extreme RV remodeling induced by exercise, in subsets of endurance and ultraendurance

P value for class of sport

.24

Mixed

25 (22-28)

Strength

25 (22-28)

Strain (%)

.06

Endurance

24.7 (22.9-26.4)

Combined

24.7 (22.9-26.4)

Mixed

24.7 (22.9-26.4)

Strength

24.7 (22.9-26.4)

s’ velocity (m/sec) Endurance

0.17 (0.13-0.20)

Reference

Combined

0.11 (0.09-0.13)

.04

Mixed

0.14 (0.10-0.19)

.36

Strength

0.17 (0.13-0.22)

.72

Endurance

0.18 (0.14-0.22)

Reference

Combined

0.12 (0.10-0.14)

.009

Mixed

0.16 (0.12-0.20)

.46

Strength

0.18 (0.16-0.20)

.86

e’ velocity (m/sec)

E/A ratio

.92

Endurance

1.71 (1.57-1.84)

Combined

1.71 (1.57-1.84)

Mixed

1.71 (1.57-1.84)

Strength

1.71 (1.57-1.84)

athletes, a possible detrimental effect of intensive training on the RV systolic function has been hypothesized and future studies are needed to investigate the cumulative effect of chronic exercise on RV function estimated by RV FAC.26,77,78 Therefore, further studies with a large sample of athletes observed over a long-term period are needed to confirm whether a slight decrease of RV function can still be considered a physiological consequence or rather is it a sign of an incipient negative effect of strenuous exercise training on RV function. While echocardiography remains the primary imaging modality for athletes with suspected RV pathology, the use of CMR for the assessment of RV size and function has dramatically increased in the last years. Accordingly, in the present meta-analysis we derive also reference values for RV size and function. Our results did not find significant differences among the four sports categories, although the small number of studies currently available could have influenced the results of this analysis. In a meta-analysis

D’Ascenzi et al 855

Journal of the American Society of Echocardiography Volume 30 Number 9

Table 5 Normal values for parameters of RV size and function obtained by CMR in male competitive athletes Mean (95% CI)

End-diastolic volume (mL)

Table 6 Echocardiographic data of RV size and function in female competitive athletes

P value for class of sport

.89

Mean 6 SE

RVOT PLAX (mm)

28 6 2

RVOT PLAX index (mm/m2)

17 6 1 30 6 1

Endurance

232 (228-247)

RVOT PSAX (mm)

Combined

232 (228-247)

RVOT PSAX index (mm/m2)

18 6 1

Mixed

232 (228-247)

RV end-diastolic area (cm2)

23.0 6 0.1

Strength

232 (228-247)

RV end-systolic area (cm2)

Not definable

Ene-systolic volume (mL)

.24

Endurance

100 (89-112)

Combined

100 (89-112)

Mixed

100 (89-112)

Strength

100 (89-112)

RV stroke volume (mL)

RV basal diameter (mm)

35.7 6 0.2

RV mid-cavity diameter (mm)

29.1 6 0.3

RA area (cm2)

16 6 1

RV FAC (%)

39 6 4

s’ velocity (m/sec)

0.13 6 0.015

e’ velocity (m/sec)

0.15 6 0.01

.92

Endurance

124 (111-137)

Combined

124 (111-137)

Mixed

124 (111-137)

Strength

124 (111-137)

Ejection fraction (%)

.45

Endurance

54 (52-57)

Combined

54 (52-57)

Mixed

54 (52-57)

Strength

54 (52-57)

investigating the influence of training mode on LV morphology and function in male athletes’ hearts, Utomi and colleagues reported RV structural and functional data obtained by CMR in endurance athletes.79 Our results are in agreement with those by Utomi et al., with similar values of RV end-diastolic volume and RV stroke volume. We further extend these findings, reporting also RV endsystolic volume and RV ejection fraction. In comparison with the normative values proposed for the general population, the mean values of RV volumes and stroke volume found in athletes were greater, while the upper limits were similar.80 Notably, while RV function estimated by echocardiography with FAC was lower in comparison with the diagnostic criteria of ARVC and with the normal range proposed for the general population, in healthy athletes RV function was within the range of normalcy when CMR was used,80 calling into question the use of RV FAC as a single parameter for estimating right heart function. Notably, although technical advances in the imaging modalities have improved the capability to image the RV with reproducible measurements of RV size and function, the diagnosis of ARVC currently relies also on structural, histological, electrocardiographic, arrhythmic, and familial features. Therefore, as recommended by the TF criteria,1 for the diagnosis of ARVC the parameters derived by imaging modalities should be integrated in a comprehensive clinical assessment including family history and the demonstration of structural, functional, and electrophysiological abnormalities that are caused by or reflect the underlying histological changes. Furthermore, comprehensive testing using widely available techniques can effectively help physicians in differentiating borderline cases.81

Finally, in the present meta-analysis, athletes were divided into four groups according to the intensity level of the static and dynamic components of their training according to Mitchell’s classification13 and with the mixed group representing heterogeneous groups of different sports. We found that combined athletes (i.e., athletes engaged in disciplines such as triathlon, rowing, or canoeing) exhibited the greater values of RV areas and basal and midcavity diameters as well as greater values of RV wall thickness. Conversely, strength athletes had the lowest values of RV areas and basal and midcavity diameters. Notably, RVOT diameters did not differ among the groups. These findings are partly in agreement with previous studies demonstrating that endurance athletes had the greatest RV size, while strength athletes had the lowest.6,9 Most of the previous studies were limited to the dichotomous distinction between endurance and strength disciplines, while in a recent study we analyzed RV remodeling in a large cohort of Olympic athletes, with sports disciplines divided into endurance, mixed, power, and skill.8 Olympic athletes practicing endurance sports demonstrated the highest degree of RV remodeling, while power and skill disciplines were accompanied by the lowest degree of RVenlargement.8 However, these previous findings are partly comparable to the current results because the classification of sports was different and in the present study combined sports were distinguished from endurance disciplines. The present meta-analysis suggests that the extent of RV remodeling is particularly evident in combined sports; therefore clinicians should be aware about the potential misleading interpretation of echocardiographic RV assessment with a possible source of misdiagnosis in these athletes. Limitations The extent of RV remodeling differs according to gender: therefore, in this study data were presented separately for men and women. Unfortunately, the small number of studies available in the existing literature reporting RV measurements in female athletes precluded meaningful statistical analysis of reference values, because it might influence the covariant distribution, making the composition of the group of female athletes imbalanced. Furthermore, the small sample size of female athletes could potentially determine a large error in the estimates, causing wider confidence intervals, as it is affected by the uncertainty of sample estimates of mean and variance.82 Thus, considering the potential to mislead by adopting normal ranges

856 D’Ascenzi et al

obtained from biased samples, while mean and confidence intervals were reported for the overall population, reference values were reported only for the most remodeled athletes, that is, males. The limitation of scarce data on female athletes prompts further studies in this area. A paucity of studies specify the ethnic origin of the population, and ethnicity was reported in Table 1 for each study included in the metaanalysis—when available—but was not taken into account in the present study. Despite the limitation imposed by the current literature, the lack of data on ethnicity can be at least in part overcome by the recent demonstration that the impact of ethnicity is minimal, obviating the need for race-specific RV reference values.4

CONCLUSION Physicians should be aware that the application of the current recommendations for the normal population could be misleading when evaluating athletes. In the present systematic review and metaanalysis, we derived normative values for RV echocardiographic and CMR dimensions to be applied in competitive athletes to properly assess the presence and extent of RV dilatation. The extent of RV remodeling is particularly evident in athletes practicing combined disciplines. The application of the proposed cutoffs would prevent misleading interpretation of echocardiographic RV assessment and unwarranted exclusion from sports participation in athletes exhibiting physiologic RV enlargement. Conversely, measurements greatly exceeding the athlete-derived limits here reported are unlikely to represent a uniquely physiologic adaptation to training and should raise suspicion of a pathological cardiac condition.

SUPPLEMENTARY DATA Supplementary data related to this article can be found at http://dx. doi.org/10.1016/j.echo.2017.06.013.

REFERENCES 1. Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Eur Heart J 2010;31: 806-14. 2. Bauce B, Frigo G, Benini G, Michieli P, Basso C, Folino AF, et al. Differences and similarities between arrhythmogenic right ventricular cardiomyopathy and athlete’s heart adaptations. Br J Sports Med 2010;44:148-54. 3. Pagourelias ED, Kouidi E, Efthimiadis GK, Deligiannis A, Geleris P, Vassilikos V. Right atrial and ventricular adaptations to training in male Caucasian athletes: an echocardiographic study. J Am Soc Echocardiogr 2013;26:1344-52. 4. Zaidi A, Ghani S, Sharma R, Oxborough D, Panoulas VF, Sheikh N, et al. Physiological right ventricular adaptation in elite athletes of African and Afro-Caribbean origin. Circulation 2013;127:1783-92. 5. D’Ascenzi F, Cameli M, Padeletti M, Lisi M, Zaca V, Natali B, et al. Characterization of right atrial function and dimension in top-level athletes: a speckle tracking study. Int J Cardiovasc Imaging 2013;29:87-94. 6. Oxborough D, Sharma S, Shave R, Whyte G, Birch K, Artis N, et al. The right ventricle of the endurance athlete: the relationship between morphology and deformation. J Am Soc Echocardiogr 2012;25:263-71. 7. D’Ascenzi F, Pelliccia A, Corrado D, Cameli M, Curci V, Alvino F, et al. Right ventricular remodelling induced by exercise training in competitive athletes. Eur Heart J Cardiovasc Imaging 2016;17:301-7.

Journal of the American Society of Echocardiography September 2017

8. D’Ascenzi F, Caselli S, Di Paolo FM, Spataro A, Pelliccia A. Right ventricular remodelling in Olympic athletes. JACC Cardiovascular Imaging 2017; 10:385-93. 9. D’Andrea A, Riegler L, Golia E, Cocchia R, Scarafile R, Salerno G, et al. Range of right heart measurements in top-level athletes: the training impact. Int J Cardiol 2013;164:48-57. 10. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18: 1440-63. 11. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010;23: 685-713. 12. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015;28:1-39. 13. Levine BD, Baggish AL, Kovacs RJ, Link MS, Maron MS, Mitchell JH, et al. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 1: classification of sports: dynamic, static, and impact: a scientific statement from the American Heart Association and American College of Cardiology. Circulation 2015;132:e262-6. 14. Iskandar A, Thompson PD. A meta-analysis of aortic root size in elite athletes. Circulation 2013;127:791-8. 15. Iskandar A, Mujtaba MT, Thompson PD. Left atrium size in elite athletes. JACC Cardiovasc Imaging 2015;8:753-62. 16. Viechtbauer W, Lopez-Lopez JA, Sanchez-Meca J, Marin-Martinez F. A comparison of procedures to test for moderators in mixed-effects metaregression models. Psychol Meth 2015;20:360-74. 17. Viechtbauer W. Bias and efficiency of meta-analytic variance estimators in the random-effects models. J Educ Behav Stat 2005;30:261-93. 18. Knapp G, Hartung J. Improved tests for a random effects meta-regression with a single covariate. Stat Med 2013;22:2693-710. 19. Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Software 2010;36:1-48. 20. Douglas PS, O’Toole ML, Hiller WD, Reichek N. Different effects of prolonged exercise on the right and left ventricles. JACC 1990;15:64-9. 21. Henriksen E, Landelius J, Wesslen L, Arnell H, Nystr€ om-Rosander C, Kangro T, et al. Echocardiographic right and left ventricular measurements in male elite endurance athletes. Eur Heart J 1996;17:1121-8. 22. Henriksen E, Landelius J, Kangro T, Arnell H, Nystrom-Rosander C, Kangro T, et al. An echocardiographic study of right and left ventricular adaptation to physical exercise in elite female orienteers. Eur Heart J 1999;20:309-16. 23. Erol MK, Karakelleoglu S. Assessment of right heart function in the athlete’s heart. Heart Vessels 2002;16:175-80. 24. D’Andrea A, Caso P, Sarubbi B, Limongelli G, Liccardo B, Cice G, et al. Right ventricular myocardial adaptation to different training protocols in top-level athletes. Echocardiography 2003;20:329-36. 25. Kasikcioglu E, Oflaz H, Akhan H, Kayserilioglu A. Right ventricular myocardial performance index and exercise capacity in athletes. Heart Vessels 2005;20:147-52. 26. Neilan TG, Yoerger DM, Douglas PS, Kayserilioglu A. Persistent and reversible cardiac dysfunction among amateur marathon runners. Eur Heart J 2006;27:1079-84. 27. Koc M, Bozkurt A, Akpinar O, Ergen N, Acarturk E. Right and left ventricular adaptation to training determined by conventional echocardiography and tissue Doppler imaging in young endurance athletes. Acta Cardiol 2007;62:13-8.

D’Ascenzi et al 857

Journal of the American Society of Echocardiography Volume 30 Number 9

28. Baggish AL, Wang F, Weiner RB, Elinoff JM, Tournoux F, Boland A, et al. Training-specific changes in cardiac structure and function: a prospective and longitudinal assessment of competitive athletes. J Appl Physiol 2008;104:1121-8. 29. La Gerche A, Connelly KA, Mooney DJ, MacIsaac AI, Prior DL. Biochemical and functional abnormalities of left and right ventricular function after ultra-endurance exercise. Heart 2008;94:860-6. 30. Poh KK, Ton-Nu TT, Neilan TG, Tournoux FB, Picard MH, Wood MJ. Myocardial adaptation and efficiency in response to intensive physical training in elite speedskaters. Int J Cardiol 2008;126:346-51. 31. Teske AJ, Prakken NH, De Boeck BW, Velthuis BK, Doevendans PA, Cramer MJ. Effect of long term and intensive endurance training in athletes on the age related decline in left and right ventricular diastolic function as assessed by Doppler echocardiography. Am J Cardiol 2009;104: 1145-51. 32. Baggish AL, Yared K, Weiner RB, Wang F, Demes R, Picard MH, et al. Differences in cardiac parameters among elite rowers and subelite rowers. Med Sci Sports Exerc 2010;42:1215-20. 33. D’Andrea A, Caso P, Bossone E, Scarafile R, Riegler L, Di Salvo G, et al. Right ventricular myocardial involvement in either physiological or pathological left ventricular hypertrophy: an ultrasound speckle-tracking twodimensional strain analysis. Eur J Echocardiogr 2010;11:492-500. 34. D’Andrea A, Naeije R, D’Alto M, Argiento P, Golia E, Cocchia R, et al. Range in pulmonary artery systolic pressure among highly trained athletes. Chest 2011;139:788-94. 35. Krol W, Braksator W, Kasprzak JD, Kuch M, Mamcarz A, Chybowska B, et al. The influence of extreme mixed exertion load on the right ventricular dimensions and function in elite athletes: a tissue Doppler study. Echocardiography 2011;28:753-60. 36. La Gerche A, Heidbuchel H, Burns AT, Mooney DJ, Taylor AJ, Pfluger HB, et al. Disproportionate exercise load and remodeling of the athlete’s right ventricle. Med Sci Sports Exerc 2011;43:974-81. 37. Popovic D, Damjanovic S, Markovic V, Vujisic-Tesic B, Petrovic M, Nedeljkovic I, et al. Systolic right ventricular adaptive changes in athletes as predictors of the maximal functional capacity: a pulsed tissue Doppler study. J Sports Med Phys Fitness 2011;51:452-61. 38. D’Andrea A, Riegler L, Morra S, Scarafile R, Salerno G, Cocchia R, et al. Right ventricular morphology and function in top-level athletes: a three-dimensional echocardiographic study. J Am Soc Echocardiogr 2012;25:1268-76. 39. Karlstedt E, Chelvanathan A, Da Silva M, Cleverley K, Kumar K, Bhullar N, et al. The impact of repeated marathon running on cardiovascular function in the aging population. J Cardiovasc Magn Reson 2012;14:58. 40. Bernheim AM, Attenhofer Jost CH, Zuber M, Pfyffer M, Seifert B, De Pasquale G, et al. Right ventricle best predicts the race performance in amateur Ironman athletes. Med Sci Sports Exerc 2013;45:1593-9. 41. King G, Almuntaser I, Murphy RT, La Gerche A, Mahoney N, Bennet K, et al. Reduced right ventricular myocardial strain in the elite athlete may not be a consequence of myocardial damage. ‘‘Cream masquerades as skimmed milk.’’. Echocardiography 2013;30:929-35. 42. Moro AS, Okoshi MP, Padovani CR, Okoshi K. Doppler echocardiography in athletes from different sports. Med Sci Monit 2013;19:187-93. 43. Schmied C, Di Paolo FM, Zerguini AY, Dvorak J, Pelliccia A. Screening athletes for cardiovascular disease in Africa: a challenging experience. Br J Sports Med 2013;47:579-84. 44. Simsek Z, Tas MH, Gunay E, Degirmenci H. Speckle-tracking echocardiographic imaging of the right ventricular systolic and diastolic parameters in chronic exercise. Int J Cardiovasc Imaging 2013;29:1265-71. 45. Vitarelli A, Capotosto L, Placanica G, Caranci F, Pergolini M, Zardo F, et al. Comprehensive assessment of biventricular function and aortic stiffness in athletes with different forms of training by three-dimensional echocardiography and strain imaging. Eur Heart J Cardiovasc Imaging 2013;14:1010-20. 46. Zaidi A, Ghani S, Sheikh N, Gati S, Bastiaenen R, Madden B, et al. Clinical significance of electrocardiographic right ventricular hypertrophy in athletes: comparison with arrhythmogenic right ventricular cardiomyopathy and pulmonary hypertension. Eur Heart J 2013;34:3649-56. 47. D’Ascenzi F, Pelliccia A, Natali BM, Zaca V, Cameli M, Alvino F, et al. Morphological and functional adaptation of left and right atria induced

48.

49.

50.

51.

52.

53.

54.

55.

56.

57.

58.

59.

60.

61.

62.

63.

64.

by training in highly trained female athletes. Circ Cardiovasc Imaging 2014;7:222-9. Esposito R, Galderisi M, Schiano-Lomoriello V, Santoro A, De Palma D, Ippolito R, et al. Nonsymmetric myocardial contribution to supranormal right ventricular function in the athlete’s heart: combined assessment by speckle tracking and real time three-dimensional echocardiography. Echocardiography 2014;31:996-1004. Gjerdalen GF, Hisdal J, Solberg EE, Andersen TE, Radunovic Z, Steine K. The Scandinavian athlete’s heart; echocardiographic characteristics of male professional football players. Scand J Med Sci Sports 2014;24: e372-80. Leischik R, Spelsberg N. Endurance sport and ‘‘cardiac injury’’: a prospective study of recreational Ironman athletes. Int J Environ Res Public Health 2014;11:9082-100. Giraldeau G, Kobayashi Y, Finocchiaro G, Wheeler M, Perez M, Kuznetsova T, et al. Gender differences in ventricular remodeling and function in college athletes, insights from lean body mass scaling and deformation imaging. Am J Cardiol 2015;116:1610-6. Grunig E, Biskupek J, D’Andrea A, Ehlken N, Egenlauf B, Weidenhammer J, et al. Reference ranges for and determinants of right ventricular area in healthy adults by two-dimensional echocardiography. Respiration 2015;89:284-93. Hedman K, Tamas E, Henriksson J, Bjarnegard N, Brudin L, Nylander E. Female athlete’s heart: systolic and diastolic function related to circulatory dimensions. Scand J Med Sci Sports 2015;25:372-81. Jongman JK, Zaidi A, Muggenthaler M, Sharma S. Relationship between echocardiographic right-ventricular dimensions and signal-averaged electrocardiogram abnormalities in endurance athletes. Europace 2015;17: 1441-8. Major Z, Csajagi E, Kneffel Z, Kovats T, Szauder I, Sido Z, et al. Comparison of left and right ventricular adaptation in endurance-trained male athletes. Acta Physiol Hung 2015;102:23-33. Malmgren A, Dencker M, Stagmo M, Gudmundsson P. Cardiac dimensions and function in female handball players. J Sports Med Phys Fitness 2015;55:320-8. Utomi V, Oxborough D, Ashley E, Lord R, Fletcher S, Stembridge M, et al. The impact of chronic endurance and resistance training upon the right ventricular phenotype in male athletes. Eur J Appl Physiol 2015;115: 1673-82. D’Ascenzi F, Solari M, Biagi M, Cassano F, Focardi M, Corrado D, et al. P-wave morphology is unaffected by training-induced biatrial dilatation: a prospective, longitudinal study in healthy athletes. Int J Cardiovasc Imaging 2016;32:407-15. Petersen SE, Hudsmith LE, Robson MD, Doll HA, Francis MJ, Wiesman F, et al. Sex-specific characteristics of cardiac function, geometry, and mass in young adult elite athletes. J Magn Reson Imaging 2006;24:297-303. Perseghin G, De Cobelli F, Esposito A, Lattuada G, Terruzzi I, La Torre A, et al. Effect of the sporting discipline on the right and left ventricular morphology and function of elite male track runners: a magnetic resonance imaging and phosphorus 31 spectroscopy study. Am Heart J 2007;154:937-42. Esch BT, Scott JM, Haykowsky MJ, Paterson I, Warburton DER, ChengBaron J, et al. Changes in ventricular twist and untwisting with orthostatic stress: endurance athletes versus normally active individuals. J Appl Physiol 2010;108:1259-66. Prakken NH, Velthuis BK, Teske AJ, Mosterd A, Mali WP, Cramer MJ. Cardiac MRI reference values for athletes and nonathletes corrected for body surface area, training hours/week and sex. Eur J Cardiovasc Prev Rehabil 2010;17:198-203. Scharf M, Brem MH, Wilhelm M, Schoepf UJ, Uder M, Lell MM. Cardiac magnetic resonance assessment of left and right ventricular morphologic and functional adaptations in professional soccer players. Am Heart J 2010;159:911-8. Scharf M, Brem MH, Wilhelm M, Schoepf UJ, Uder M, Lell MM. Atrial and ventricular functional and structural adaptations of the heart in elite triathletes assessed with cardiac MR imaging. Radiology 2010;257:71-9.

858 D’Ascenzi et al

65. Steding K, Engblom H, Buhre T, Carlsson M, Mosen H, Wohlfart B, et al. Relation between cardiac dimensions and peak oxygen uptake. J Cardiovasc Magn Reson 2010;12:8. 66. Erz G, Mangold S, Franzen E, Claussen CD, Niess AM, Burgstahler C, et al. Correlation between ECG abnormalities and cardiac parameters in highly trained asymptomatic male endurance athletes: evaluation using cardiac magnetic resonance imaging. Int J Cardiovasc Imaging 2013;29:325-34. 67. Luijkx T, Cramer MJ, Zaidi A, Rienks R, Senden PJ, Sharma S, et al. Ethnic differences in ventricular hypertrabeculation on cardiac MRI in elite football players. Neth Heart J 2012;10:389-95. 68. Luijkx T, Cramer MJ, Prakken NH, Buckens CF, Mosterd A, Rienks R, et al. Sport category is an important determinant of cardiac adaptation: an MRI study. Br J Sports Med 2012;46:1119-24. 69. Franzen E, Mangold S, Erz G, Claussen CD, Niess AM, Kramer U, et al. Comparison of morphological and functional adaptations of the heart in highly trained triathletes and long-distance runners using cardiac magnetic resonance imaging. Heart Vessels 2013;28:626-31. 70. Luijkx T, Velthuis BK, Backx FJG, Buckens CFM, Prakken NHJ, Rienks R, et al. Anabolic androgenic steroid use is associated with ventricular dysfunction on cardiac MRI in strength trained athletes. Int J Cardiol 2013;167:664-8. 71. Mangold S, Kramer U, Franzen E, Erz G, Bretschneider C, Seeger A, et al. Detection of cardiovascular disease in elite athletes using cardiac magnetic resonance imaging. Rofo 2013;185:1167-74. 72. Steding-Ehrenborg K, Carlsson M, Stephensen S, Arheden H. Atrial aspiration from pulmonary and caval veins is caused by ventricular contraction and secures 70% of the total stroke volume independent of resting heart rate and heart size. Clin Physiol Funct Imaging 2013;33:233-40. 73. Claessen G, Claus P, Ghysels S, Vermeersch P, Dymarkowski S, La Gerche A, et al. Right ventricular fatigue developing during endurance ex-

Journal of the American Society of Echocardiography September 2017

74.

75.

76.

77.

78.

79.

80.

81.

82.

ercise: an exercise cardiac magnetic resonance study. Med Sci Sports Exerc 2014;46:1717-26. La Gerche A, Claessen G, Dymarkowski S, Voigt JU, De Buck F, Vanhees L, et al. Exercise-induced right ventricular dysfunction is associated with ventricular arrhythmias in endurance athletes. Eur Heart J 2015;36:1998-2010. Steding-Ehrenborg K, Arvidsson PM, Toger J, Rydberg M, Heiberg E, Carlsson M, et al. Determinants of kinetic energy of blood flow in the four-chambered heart in athletes and sedentary controls. Am J Physiol Heart Circ Physiol 2016;310:113-22. Dupont AC, Poussel M, Hossu G, Marie PY, Chenuel B, Felblinger J, et al. Aortic compliance variation in long male distance triathletes: a new insight into the athlete’s artery? J Sci Med Sport 2017;20:539-42. Heidbuchel H, La Gerche A. The right heart in athletes. Evidence for exercise-induced arrhythmogenic right ventricular cardiomyopathy. Herzschrittmacherther Elektrophysiol 2012;23:82-6. La Gerche A, Burns AT, Mooney DJ, Inder WJ, Taylor AJ, Bogaert J, et al. Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes. Eur Heart J 2012;33:998-1006. Utomi V, Oxborough D, Whyte GP, Somauroo J, Sharma S, Shave R, et al. Systematic review and meta-analysis of training mode, imaging modality and body size influences on the morphology and function of the male athlete’s heart. Heart 2013;99:1727-33. Kawel-Boehm N, Maceira A, Valsangiacomo-Buechel ER, VogelClaussen J, Turkbey EB, Williams R, et al. Normal values for cardiovascular magnetic resonance in adults and children. J Cardiovasc Magn Reson 2015;17:29. Zaidi A, Sheikh N, Jongman JK, Gati S, Panoulas VF, Carr-White G, et al. Clinical differentiation between physiological remodeling and arrhythmogenic right ventricular cardiomyopathy in athletes with marked electrocardiographic repolarization anomalies. J Am Coll Cardiol 2015;65:2702-11. Jolicoeur P. Introduction to biometry. New York: Springer; 2012. pp. 61-2.

D’Ascenzi et al 858.e1

Journal of the American Society of Echocardiography Volume 30 Number 9

APPENDIX

Table A1 Normal values for two-dimensional echocardiographic parameters of RV size in male competitive athletes

Table A1 (Continued ) Mean (99% CI)

Mean (99% CI)

Mixed

13 (6-20)

Strength

10 (7-14)

RV end-systolic area index (cm2/m2)

RVOT PLAX (mm) Endurance

29 (24-34)

Endurance

9 (7-10)

Combined

29 (24-34)

Combined

9 (7-10)

Mixed

29 (24-34)

Mixed

9 (7-10)

Strength

29 (24-34)

Strength

9 (7-10)

RVOT PLAX index (mm/m2)

RV basal diameter (mm)

Endurance

17 (14-20)

Endurance

40 (37-43)

Combined

17 (14-20)

Combined

44 (36-52)

Mixed

17 (14-20)

Mixed

43 (39-46)

Strength

17 (14-20)

Strength

38 (28-48)

RV basal diameter index (mm/m2)

RVOT PSAX (mm) Endurance

34 (32-36)

Endurance

23 (18-27)

Combined

34 (32-36)

Mixed

34 (32-36)

Combined Mixed

23 (18-27) 23 (18-27)

Strength

34 (32-36)

Strength

23 (18-27)

RVOT PSAX index (mm/m2)

RV midcavity diameter (mm)

Endurance

18 (15-22)

Endurance

29 (26-31)

Combined

18 (15-22)

Combined

41 (35-47)

Mixed

18 (15-22)

Mixed

36 (35-37)

Strength

18 (15-22)

Strength

26 (21-30)

RV midcavity diameter index (mm/m2)

RVOT distal diameter (mm) Endurance

31 (27-34)

Endurance

18 (12-24)

Combined

31 (27-34)

Combined

18 (12-24)

Mixed

31 (27-34)

Mixed

18 (12-24)

Strength

31 (27-34)

Strength

18 (12-24)

RVOT distal diameter index (mm/m2)

RA area (cm2)

Endurance

16 (14-19)

Endurance

18 (11-28)

Combined

16 (14-19)

Combined

18 (11-28)

Mixed

16 (14-19)

Mixed

18 (11-28)

Strength

16 (14-19)

Strength

18 (11-28)

RV end-diastolic area (cm2)

RV wall thickness (mm)

Endurance

23 (19-28)

Endurance

4.2 (3.8-4.6)

Combined

32 (28-37)

Combined

7.0 (4.1-9.9)

Mixed

30 (27-32)

Mixed

Strength

21 (15-27)

Strength

RV end-diastolic area index (cm2/m2)

nd 4.0 (2.6-5.4)

FAC (%)

Endurance

15 (14-17)

Endurance

35 (30-39)

Combined Mixed

15 (14-17) 15 (14-17)

Combined

36 (30-42)

Mixed

43 (32-54)

Strength

15 (14-17)

Strength

41 (28-53)

RV end-systolic area (cm2)

TAPSE (mm)

Endurance

13 (9-16)

Endurance

25 (21-30)

Combined

17 (13-22)

Combined

25 (21-30)

(Continued )

(Continued )

858.e2 D’Ascenzi et al

Journal of the American Society of Echocardiography September 2017

Table A1 (Continued ) Mean (99% CI)

Mixed

25 (21-30)

Strength

25 (21-30)

Strain (%) Endurance

24.7 (22.2-27.2)

Combined

24.7 (22.2-27.2)

Mixed

24.7 (22.2-27.2)

Strength

24.7 (22.2-27.2)

s’ velocity (m/sec) Endurance

0.17 (0.12-0.21)

Combined

0.11 (0.08-0.14)

Mixed

0.14 (0.09-0.20)

Strength

0.17 (0.12-0.24)

e’ velocity (m/sec) Endurance

0.18 (0.12-0.24)

Combined

0.12 (0.09-0.14)

Mixed

0.16 (0.11-0.22)

Strength

0.18 (0.15-0.21)

E/A ratio Endurance

1.71 (1.51-1.90)

Combined

1.71 (1.51-1.90)

Mixed

1.71 (1.51-1.90)

Strength

1.71 (1.51-1.90)

nd, Not definable.