1 Vol.:(0123456789) Scientific Reports | (2021) 11:22532 | https://doi.org/10.1038/s41598-021-02028-1 www.nature.com/scientificreports Right heart exercise‑training‑adaptation and remodelling in endurance athletes Valeria Conti1, Filippo Migliorini2*, Marco Pilone1, María I. Barriopedro3, Juan José Ramos‑Álvarez4, Francisco Javer Calderon Montero4 & Nicola Maffulli1,5,6 Long-term sports training leads to myocardial adaptations, with remodelling of the heart chambers. However, while myocardial adaptations of the left heart are well described, remodelling of the right heart and its impact on the development of arrhythmias is still debated. To conduct a systematic review on right ventricle (RV) and right atrium (RA) structural and functional changes in athletes who participate in long-term endurance training. Systematic review. A systematic literature search was conducted. All the articles reporting right heart echocardiographic (ECHO) and cardiac magnetic resonance (CMR) parameters evaluated in endurance athletes and sedentary subjects were considered eligible. A multivariate analysis was conducted to investigate whether age, sex, body surface area (BSA), intensity of training are associated with RV ECHO, CMR parameters and RA ECHO parameters. A positive association between age and right atrium area (RAA) (P = 0.01) was found. This is a negative association to RV E/A (P = 0.004), and RV end diastolic diameter (RVED) longitudinal (P = 0.01). A positive association between BSA and RVED middle (P = 0.001), as well between BSA and RAA (P = 0.05) was found, along with a negative association with RV E/A (P = 0.002). A positive association between intensity of training and RV end systolic area (RVESA) (P = 0.03), RV end diastolic volume indexed (RVEDVI) (P = 0.01), RV end systolic volume indexed (RVESVI) (P = 0.01) was found, along with a negative association with ejection fraction (EF %) (P = 0.01). Endurance athletes demonstrated an association between RV remodelling and age, BSA and intensity of training. “Athlete’s heart” refers to remodelling of the whole cardiac muscles induced by the high workload of sports training1–10. Heart remodelling is different following endurance training and resistance training11. In endurance training, the left ventricle (LV) undergoes eccentric hypertrophy, while resistance training promotes concentric hypertrophy12. A clear classification is not possible as the overall size of cardiomyocytes increases under both remodelling patterns. In general, the thickness of the LV wall prevails in resistance training as a consequence of chronic volume overload; LV dilatation is a prominent characteristic in endurance-trained heart, mainly determined by chronic systolic pressure overload13. However, exercise-induced changes of the right ventricle (RV) are still debated14. Also, there seems to be an association between RV hypertrophy and Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)15–17, one of the major causes of cardiac death in young athletes18,19. Therefore, it would be interesting to define exercise- induced RV adaptation, and its impact on the onset of arrhythmias16. Endurance training causes greater mor- phological and functional RV changes than any other type of exercise, but the role of variables such as age, sex and BSA has not been established20. Endurance training increases the hemodynamic needs with a consequent OPEN 1Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy. 2Department of Orthopaedic, Trauma, and Recontructive Surgery, RWTH Aachen University Clinic, Pauwelsstraße 30, 52074  Aachen, Germany. 3Faculty of Physical Activity and Sport Sciences, Universidad Politécnica de Madrid, Madrid, Spain. 4Escuela de Medicina Deportiva. Departamento de Radiología, Rehabilitación y Fisioterapia, Universidad Complutense de Madrid, Madrid, Spain. 5Centre for Sports and Exercise Medicine, Barts and The London School of Medicine and Dentistry, Mile End Hospital, Queen Mary University of London, 275 Bancroft Road, London E1 4DG, England, UK. 6Department of Musculoskeletal Disorders, School of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy. *email: Migliorini.md@gmail.com http://crossmark.crossref.org/dialog/?doi=10.1038/s41598-021-02028-1&domain=pdf 2 Vol:.(1234567890) Scientific Reports | (2021) 11:22532 | https://doi.org/10.1038/s41598-021-02028-1 www.nature.com/scientificreports/ chronic pressure elevation in the cardiac chambers21. As a result, long-term exercise leads to permanent RV structural and functional modifications, with large interindividual variability22. It is important to distinguish between acute and chronic adaptations, and to consider exercise loading and intensity23, which induce different functional and clinical consequences22,23. Immediately after an intense exercise, the serum level of troponin and B-type natriuretic peptide increases17,24. A process of micro injuring and healing occurs, mirroring what take place in skeletal muscles, which, eventually, leads to myocardial adaptation22. This study investigates the structural and functional changes of the right ventricle (RV) and right atrium (RA) in athletes who participate in long-term endurance training, and defines whether the RV ECHO and CMR reference values for the general population are appropriate for endurance athletes. Methods Search strategy.  The present systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recomendations25. We followed the PICO protocol for the preliminary search: • P (Problem): right heart in endurance athletes; • I (Intervention): long-term endurance sport training; • C (Comparator): right heart in sedentary individuals; • O (Outcomes): morphological and functional ECHO and CMR parameters. Literature search and selection.  Two authors (MP; VC) independently performed the literature search in May 2021. The following databases were used for the search: Medline, Scopus and Cochrane. To conduct a comprehensive systematic literature search, we used both controlled vocabulary and free text terms. For our research, the following MESH terms were used: right ventricle, right atrium, right heart, heart chambers, endur- ance, athletes, echocardiography, cardiac magnetic resonance, sport, players, remodelling, adaptation, training, work out. Only studies published from 2000 up to May 2021 were accessed. Resulting titles and abstracts of interests were screened by the two authors independently. The full text of the articles of interest were examined. Disagreements about the eligibility of a study were resolved were solved by a third author (FM). Eligibility criteria.  According to the authors’ language capabilities, articles in English, Italian, French, Ger- man, Portuguese and Spanish were considered. Studies with level of evidence I to III, according to the Oxford Centre for Evidence-Based Medicine (OCEBM), were considered26. Data from national registries were excluded, as well as reviews, letters, expert opinions, case reports, editorials, animal, computational and cadaveric studies. As the aim was to investigate the remodelling of the right heart in endurance athletes, only study which investi- gated athletes who regularly played sports listed on the Mitchel Category class C27 were examined. Only studies reporting right heart ECHO and/or CMR parameters of endurance athletes and a sedentary group as controls were eligible. To evaluate chronic adaptations, only CMR or an ECHO evaluation performed at rest were consid- ered. The exclusions criteria were represented by all the variables which could alter the physiological parameters: the presence of diseases, a family history of pulmonary or cardiac diseases, chronic use of drugs. Data extraction.  Data were extracted by two different authors (MP; VC). Data from the following end- points were collected: • generalities displayed author and publication year and general characteristics of our population: number of athletes, number of sedentary individuals, sex, age, body mass index (BMI), body surface area (BSA), heart rate (HR), training hours and years of training. • ECHO data to assess the morphological and functional parameters of the right heart: basal, middle, longitu- dinal right ventricle end diastolic diameter (RVED) and their values BSA indexed, right ventricle end dias- tolic area (RVEDA), end systolic area (RVESA) and their values BSA indexed, right ventricle wall thickness (RVWT), right ventricle E/A (RV E/A), fractional area change (FAC %), ejection fraction (EF %) tricuspid annular plane excursion (TAPSE), right ventricle outflow tract (RVOT1,RVOT2,RVOT3) and their values BSA indexed, right atrial area (RAA), right atrial volume (RAV) and their value BSA indexed. • CMR data to assess the morphological and functional parameters of the right heart: right ventricle end dias- tolic volume (RVEDV), right ventricle end systolic volume (RVESV), right ventricle stroke volume (RVSV), mass and their value BSA indexed and ejection fraction (EF %). Outcomes of interest.  The primary outcome of interest was to investigate the association between right heart remodelling and age, sex, BSA and intensity of training. The second outcome of interest was to compare the mean values of endurance athletes morphological and functional parameters. To underline the different adapta- tion of RV in male and female among CMR studies, five studies were selected, in which parameters referred to male athletes, male sedentary, female athletes, female sedentary were reported separately. In these studies, the difference of the means between male athletes-male sedentary subjects and female athletes-female sedentary subjects were compared. Methodological quality assessment.  The same two reviewers who extracted data (MP; VC) assessed the risk of bias of the included studies using the Newcastle Ottawa Scale (NOS)28. The NOS evaluates three parameters, namely selection, comparability and exposure. The parameter selection domain includes 4 items 3 Vol.:(0123456789) Scientific Reports | (2021) 11:22532 | https://doi.org/10.1038/s41598-021-02028-1 www.nature.com/scientificreports/ useful to check definition and representativeness of cases and controls; the comparability domain includes 1 item to compare cases and controls based on the study design or analysis; the exposure domain includes 3 items to evaluate methods adopted in the study to ascertain exposure for cases and controls28. The maximum score for each study is nine points, and a study with lesser than five points is considered at high risk of bias. The NOS has been described as a reliable tool to assess the quality of case control studies and cohort studies29. Statistical analysis.  For the multivariate analyses, the STATA/MP 16.1 (StataCorp, College Station, TX) was used, with a multiple linear model regression diagnostic. For pairwise correlation, the Pearson Product- Moment Correlation Coefficient (r) was used. The final effect was evaluated according to the Cauchy–Schwarz inequality: + 1 (positive linear correlation) and − 1 (negative linear correlation). Values of 0.1 <| r |< 0.3, 0.3 <| r |< 0.5, and | r |> 0.5 were considered to have small, medium, and strong correlation, respectively. The test of over- all significance was performed through the χ2 test, with values of P < 0.05 considered statistically significant. For continuous variable, mean and standard deviation was evaluated. The T test was performed, with P < 0.05 considered statistically significant. Results Search results.  The search resulted in 2280 articles. After removing duplicates (N = 696), a total of 1584 articles were screened. A further 1166 articles were excluded because of: the type of the study (N = 508), the absence of sedentary controls (N = 193), sports not listed on the Mitchel Category class C (N = 131), language limitations (N = 7), evaluation after an acute stress (N = 118), presence of diseases (N = 209). Another 364 studies were excluded because they did not match the topic of interest or did not report quantitative data on outcome of interest. Finally, 54 articles were included in the analysis: 32 articles reporting ECHO parameters, 20 reporting CMR parameters, 2 reporting both. The flowchart of the literature search is shown in Fig. 1. Methodological quality assessment.  The NOS scale evidenced an overall high quality of the included studies. Studies eligibility criteria and sports category were well described, as were the selection criteria of con- trol groups. The intensity of training was seldom reported. Demographic characteristics were often exhaustively described. The procedure to assess outcomes was overall clearly described. The description of ECHO and CMR results was also comprehensive. A NOS scale score > 8 was achieved by all the included studies. Population demographic.  In ECHO studies, data from 2102 athletes and 1311 sedentary practice were col- lected. The mean age of athletes and sedentary was 26.6 ± 8.6 and 26.6 ± 7.6, respectively. The BSA was 1.86 ± 0.2 and 1.82 ± 0.15, respectively. The BMI of athletes was 24.8 ± 2.01 and BMI of sedentary was 22.89 ± 1.32. HR was 57.3 ± 7.06 and 69.6 ± 5.26, respectively. In CMR studies, data from 1257 athletes and 909 sedentary subjects were collected. The mean age of athletes and sedentary was 31.5 ± 9.8 and 31.9 ± 8.8, respectively. The BSA was 1.89 ± 0.19 and 1.87 ± 0.15, respectively. The BMI of athletes was 22.4 ± 0.5, and that of sedentary participants was 24.4 ± 1.1. HR was 57.3 ± 7.06 and 63.4 ± 6.9, respectively. Population demographics is shown in Table 1 and in Table 2. Outcome of interest.  Age showed evidence of statistically significant moderate negative association to RV E/A in athletes (P = 0.009, r = − 0.63). Age showed also a statistically significant negative and strong associa- tion to RVED longitudinal in athletes (P = 0.01, r = − 0.7). Age showed evidence of statistically significant strong positive association with an increased rate of progression to RAA both in the athletes and sedentary controls (P = 0.04, r = 0.77, P = 0.02, r = 0.85, respectively). BSA showed statistically significant strong positive association with an increased rate of progression to RVED middle in athletes (P = 0.001, r = 0.71), while in sedentary subject there was evidence of statistically significant moderate positive association with an increased rate of progression (P = 0.05, r = 0.54). Also, BSA showed statistically significant strong positive association with an increased rate of progression to RAA both in athletes and sedentary controls (P = 0.05, r = 0.82, P = 0.04, r = 0.83, respectively). Notably, BSA showed statistically significant strong negative association to ratio RV E/A in athletes (P = 0.002, r = − 0.72). With regard to ECHO data, intensity of training showed evidence of statistically significant strong positive association with an increased rate of progression to RVESA (P = 0.03, r = 0.85). Considering CMR data, the intensity of training presented statistically significant positive and, respectively, strong moderate associa- tion to RVEDVI and RVESVI (P = 0.01, r = 0.65, P = 0.01, r = 0.70, respectively). Moreover, evidence of a statisti- cally significant moderate negative association was found between the intensity of training and EF % (P = 0.01, r = − 0.60). The multivariate analysis is shown in Table 3 and supplemental Table 1 (ECHO data) and in Table 4 (CMR data). A statistically significant difference was observed between RVEDVI means difference values in male and RVEDVI means difference values in female (P = 0.001), as shown in Table 5. A statistically significant difference was found between all RV ECHO and CMR means in endurance athletes and RV reference means. Results are shown in Table 6 and in Table 7. In athletes, EF % showed evidence of a statistically significant strong negative association to RVEDV and RVESV (P = 0.01, r = − 0.70, P = 0.0003, r =  − 0.89, respectively). Data are reported in Table 8. Discussion Endurance athletes demonstrated a statistically significant association between RV remodelling and age, BSA and intensity of training. 2-D ECHO is the easiest way to assess morphological and functional parameters of the right heart, and CMR became fundamental to evaluate the RV morphology23. In fact, it is currently used 4 Vol:.(1234567890) Scientific Reports | (2021) 11:22532 | https://doi.org/10.1038/s41598-021-02028-1 www.nature.com/scientificreports/ to diagnose ARVC, although normal range values of both ECHO and CMR parameters in endurance athletes have not been established yet30. Right cardiac chambers remodelling depends on many factors. To analyse the differences between male and female RV adaptation to exercise training, five CMR studies in which data were separated for sex were selected. Changes in morphological and functional parameter both in males (athletes versus sedentary) and in females (athletes versus sedentary) were analysed. There are no differences in the kinetics of trend of adaptation between males and females, with the exception of RVEDV, and all the other parameters showed a similar trend of adaptation both in female and male endurance athletes. Age and increased BSA in athletes are linked to a decrease in diastolic function with a reduction in RV E/A. The intensity of exercise train- ing is associated with heart morphological remodelling. The studies show that 6–8 h/w are sufficient to induce remodelling evident on ECHO and CMR31–33. Another goal of this systematic review was to discuss whether the normal RV reference values fitted the RV characteristics in endurance athletes. Athletes involved in endurance sport have different ECHO parameters from those of the general population20. Comparing the studies’ results with the reference values, the mean values of all considered parameters in endurance athletes are higher than those of the general population indicated by the American Society of Echocardiography and the European Association of Cardiovascular Imaging34. Furthermore, there is a difference between the reference mean values adopted for CMR parameters and the mean values in endurance athletes35. This is in accordance with an earlier systematic review, which underlines how endurance sport induces the most significant modification in the right heart, with eccentric hypertrophy12. Such structural changes could lead to incorrectly diagnose ARVC. Ar�cles screen (N = 1584) Ar�cles removed because duplicated (N = 696) Articles identified through the database search (N = 2280) Articles excluded because not- matching the eligibility criteria (N = 1166) Articles included in quantitativesynthesis (N = 54) Ar�cles excluded because la of quantitative data (N = 364) Full-text articles assessed for eligibility (N = 418) In cl us io n El ig ib ili ty Sc re en in g Id en tif ic at io n Figure 1.   Flow-chart of literature search. 5 Vol.:(0123456789) Scientific Reports | (2021) 11:22532 | https://doi.org/10.1038/s41598-021-02028-1 www.nature.com/scientificreports/ Author name N Athletes N Sedentary M% Athletes Age Athletes Age sedentary BMI athletes (h/m2) BMI Sedentary (h/m2) BSA Athletes (m2) BSA Sedentary (m2) HR Athletes HR Sedentary Intensity of training (h/w) Years of training Baggish 201038 20 20 100% 25 ± 3 21 ± 2 NA NA 2.3 ± 0.1 2.0 ± 0.1 56 ± 7 72 ± 8 22 ± 6 9 ± 4 Baggish 201038 ◄ 20 100% 20 ± 2 NA NA 2.1 ± 0.2 60 ± 5 11 ± 4 5 ± 2 Bauce 200831 40 40 70% 26 ± 5 28 ± 12 NA NA 1.84 ± 0.2 1.80 ± 0.1 NA NA 7 ± 1.4 5.2 Bernheim 20131 39 23 82% 36 (31–43) 36 (31–43) NA NA 1.3(1.8– 2.0) 1.98 (1.75–2.05) 56(50–64) 73 (65–81) 13.5 ± 3.5 NA Bjerring 2018°39 76 25 63% 12.1 ± 0.2 12.1 ± 0.3 17.5 ± 1.5 19.9 ± 4.0 1.32 ± 0.12 1.43 ± 0.21 72 ± 12 80 ± 20 7 ± 2.3 5.4 ± 1.2 D’Andrea20133 395 230 61% 28.8 ± 10.1 27.5 ± 11.3 NA NA 1.84 ± 0.5 1.83 ± 0.6 52.1 ± 4.4 70.5 ± 10.6 15–20  > 4 D’Ascenzi 201240 100 78 76% 25.91 ± 4.61 25.20 ± 3.92 NA NA 2.05 ± 0.23 1.82 ± 0.18 60.69 ± 9.63 72.16 ± 13.1  > 15 5 D’Ascenzi 201641° 57 37 100% 10.8 ± 0.2 10.2 ± 0.2 NA NA 1.34 ± 0.20 1.33 ± 0.20 78 ± 11 67 ± 9  > 10 NA De Luca 201342 25 20 100% 20 ± 3 18.3 ± 3.6 NA NA NA NA 70.3 ± 9.04 77.9 ± 8.52  > 10 10 ± 3 Doronina 2018 15 15 0% 24 ± 4 23 ± 2 21.4 ± 1.2 20.5 ± 2.8 1.8 ± 0.1 1.6 ± 0.1 69 ± 14 82 ± 7 24 ± 8 12.1 ± 4.6 Esposito 201443 40 43 100% 28 ± 9.5 29.0 ± 5.8 24.2 ± 2.5 23.2 ± 3.0 NA NA 55.3 ± 8.0 68.5 ± 10.6  > 30  > 4 Eun 201644 29 29 100% 27 ± 4.1 26 ± 6.5 NA NA 1.97 ± 0.1 1.87 ± 0.2 54.2 ± 10.1 73.3 ± 10.7 ELITE NA Hedman 201445 46 48 0% 21 ± 2 21 ± 2 NA NA 1.69 ± 0.10 1.63 ± 0.09 54 ± 8 71 ± 10 13 ± 2 6 ± 2 King201346 24 17 100% 24.3 ± 4.2 27.06 ± 3.5 NA NA 2.0 ± 0.2 1.93 ± 0.2 61.29 ± 9.31 71.71 ± 9.31  > 10 NA King201346◄ 18 100% 22.38 ± 3.7 NA NA 2.08 ± 0.13 61.72 ± 8.59  > 8 NA Koc 20072 60 60 90% 20.7 ± 2.5 21.3 ± 2.6 NA NA 2.0 ± 0.2 1.9 ± 0.2 65.4 ± 8.7 77.0 ± 7.8 15 ± 5  > 5 Koore- man201947 37 31 0% 19 ± 1 19 ± 1 22.1 ± 2.3 23.5 ± 3.5 1.8 ± 0.2 1.7 ± 0.2 NA NA ELITE NA La Gerche 201516 10 7 100% 35 ± 6 34 ± 16 22.9 ± 1.5 23.2 ± 1.7 NA NA 52 ± 8 62 ± 12 11 (6- 1 5) 9 (6–17) Lakatos 201848 30 20 100% 18.9 ± 4.0 19.9 ± 3.8 NA NA 2.2 ± 0.2 1.9 ± 0.2 67.2 ± 11.5 68.4 ± 9.1 17 ± 6 10 ± 5 Lakatos201848 ♀ 30 20 0% 19.0 ± 3.7 19.5 ± 2.3 NA NA 1.8 ± 0.1 1.6 ± 0.1 71.1 ± 12.1 84.2 ± 19.2 17 ± 6 10 ± 5 Leischik 201649 33 37 0% 34.3 ± 6.3 31.2 ± 6.3 21.6 ± 2.3 23.7 ± 4.0 1.70 ± 0.13 1.81 ± 0.16 61.6 ± 8.6 69.7 ± 12.3 15.5 7.6 ± 5.8 Major 20155 52 25 100% 24.6 ± 5.1 26.5 ± 5.4 22.9 ± 2.4 23.7 ± 3.3 1.95 ± 0.14 1.96 ± 0.18 54.8 ± 9.3 68.4 ± 10.9 18.9 ± 6.7  > 6 Mirea 201650° 30 22 100% 17.8 ± 4 20.1 ± 4.6 18.8 ± 2.2 21.8 ± 2.2 1.61 ± 0.2 1.77 ± 0.2 64 ± 12 69 ± 15 13.6 5.3 ± 3.8 Moro 201351 21 36 100% 22 30 24.3 ± 0.41 23.8 ± 0.33 1.92 ± 0.02 1.95 ± 0.03 56.5 ± 4.92 68.4 ± 9.31 26 NA Moro 201351 ◄ 19 100% 43 21.9 ± 0.45 1.78 ± 0.02 55.3 ± 9.18 15 NA Moro 201351 ◄ 17 100% 26 22.3 ± 0.43 1.81 ± 0.03 55.5 ± 6.50 24 NA Pagourelias 201352 80 26 100% 31.3 ± 10.4 26.6 ± 5.6 21.9 ± 2.5 21.2 ± 2.8 1.98 ± 0.15 2.01 ± 0.16 50 ± 7 65 ± 9 14.6 ± 5.4 11.3 ± 8.3 Pelà 200410 20 15 100% 26 ± 5 26 ± 2 NA NA 1.98 ± 0.10 1.90 ± 0.10 55 ± 11 69 ± 9 ELITE NA Popple 201853 100 20 100% 25 ± 5 25 ± 4 NA NA 2.0 ± 0.1 2.0 ± 0.1 NA NA  > 20 NA Popple 201853° 100 19 100% 16 ± 1 16 ± 1 NA NA 1.9 ± 0.1 1.8 ± 0.1 NA NA  > 15 NA Rimensberger 201454 26 33 100% 44 ± 9 41 ± 7 22.8 ± 1.6 23.6 ± 2.1 1.9 ± 0.2 1.9 ± 0.1 56 ± 8 60 ± 7  > 10  > 5 Rundqvist 201755° 27 27 ND 15.5 (13–19) 15.4 (13–19) NA NA 1.66 (1.37– 1.98) 1.72(1.26– 2.23) 63 (42–85) 71 (49–88)  > 2.5  > 2 Sanchis-Gor- mar 201656 42 18 100% 55 ± 9 58 ± 5 NA NA NA NA 54 ± 9 63 ± 8 10.6 ± 4.2 24 ± 9 Sanchis-Gor- mar 201656 ◄ 11 100% 54 ± 4 NA NA NA NA 58 ± 8 10.6 ± 3.1 24 ± 9 Sanz-Dela- garza201757 20 20 100% 38 ± 3.5 36.2 ± 3.5 NA NA 1.88 ± 0.09 1.91 ± 0.17 57.5 ± 8.1 66.5 ± 8.9 13.5 ± 1.6 10.2 ± 3.4 Sanz-Dela- garza201757 ♀ 20 20 0% 37.4 ± 6.3 36.9 ± 4.6 NA NA 1.60 ± 0.10 1.62 ± 0.11 59.9 ± 5.1 74.9 ± 7.6 13.2 ± 1.4 10.8 ± 4.0 Simsek 201358 44 30 73% 24.10 ± 2.90 23.80 ± 2.10 22.6 ± 2.2 23.1 ± 2.4 NA NA 55.22 ± 5.20 66.40 ± 5.80 14 – 18 NA Sitges 201759 100 50 100% 25 ± 6 25 ± 4 NA NA 2.02 ± 0.21 1.92 ± 0.12 58 ± 10 65 ± 10 18  > 5 Teske 20094 59 62 51% 27 ± 5.4 27.9 ± 5.6 NA NA 1.90 ± 0.15 1.88 ± 0.25 50.7 ± 7.3 59.3 ± 10.6 12.4 ± 2.3  > 5 Teske 20094 ◄ 62 71% 27 ± 4.7 NA NA 1.96 ± 0.17 50.4 ± 9.0 24.4 ± 5.4  > 5 Teske 20094 ◄ 54 32 72% 50 ± 6.5 45.5 ± 4.3 NA NA 1.96 ± 0.17 1.89 ± 0.20 50.1 ± 11.1 59.8 ± 8.6 11.9 ± 3.8  > 12 Continued 6 Vol:.(1234567890) Scientific Reports | (2021) 11:22532 | https://doi.org/10.1038/s41598-021-02028-1 www.nature.com/scientificreports/ The ARVC is a group of cardiomyopathies with a similar phenotype and tendency to ventricular arrhythmias. Mutations encoding desmosomal genes are associated to ARVC. In some individuals the phenotypical expres- sion can be triggered by endurance exercise training15. The mean values of RVEDVI are 132.25 ± 9.63 mL/m2 and 109.5 ± 9.35 mL/m2 respectively for males and females, and they are both over the limit of the major criteria for diagnosis of ARVC (≥ 110 mL/m2 for males and ≥ 100 mL/m2 for females)30. The value of 30.24 ± 1.11 mm for RVOT1 is below the limit of major criteria (≥ 32 mm) but it is included in the minor criteria limit (≥ 29 to ≤ 32 mm), while the BSA indexed value (20.18 ± 4 mm/m2) is just above the major criteria limit (≥ 19 mm/ m2). The value of 31.83 ± 2.34 mm for RVOT2 is above the limit of the minor criteria (> 32 mm), and the RVOT2/ BSA (22.3 ± 3.15 mm/m2) is beyond the limit of the major criteria (> 21 mm/m2). Functional parameters (FAC % and EF %) are not over the limit for diagnosis of ARVC (> 33% to ≤ 40% and > 40% to ≤ 45%, respectively)28. A low value of RV E/A is a sign of diastolic disfunction36. As highlighted in previous studies, age affects diastolic function, with proliferation of extracellular matrix and crosslinking of collagen fibres4. The present study shows that a negative association is evident among athletes, but not among sedentary subjects. Some chronic cardiac microinjuries can emphasise the physiological mechanisms of extracellular matrix rearrangement and fibrotic alteration that normally occur with aging. This leads to a decrease in right heart wall compliance with a reduction in diastolic function. Low values in EF % are related to ventricular chamber dilatation, as shown in Table 8, with a negative association with EDV and ESV. EF % exhibits a negative association with the intensity of training. The more an athlete trains, the more the EF % decreases. Actually, in the case of ventricle dilatation, a lower EF % is necessary to obtain the same SV22.Although EF% decreases, this is not sufficient to justify a systolic disfunction or any other pathological condition, and it should be regarded as a physiological adaptation to the increase in EDV and ESV. To make a correct diagnosis of ARVC, it is important to examine the family history, and to fulfil the other Task Force criteria30. Pathology should be suspected when ECHO shows akinesia, dyskinesia, or an aneurysm, because they are not features of athlete’s heart37. Indeed, the remodelling induced by endurance sport could resemble a cardiomyopathy, but the real impact on future morbidity is still unknown. However, if a subject has a latent ARVC, sport-induced adaptation could deteriorate this condition15,16. Cardiac remodelling is evident in both sexes, but the lack of studies investigating separately ECHO parameters in male and female athletes does not allow to thoroughly assess similarity and differences. Also, atrial adapta- tions should be considered, but there are still few studies which analyse atrial chamber remodelling in athletes. A positive association was shown between RAA and age, and between RAA and BSA, but the data available on RA were fewer than data on RV: other studies should be conducted to assess the impact of RA remodelling in endurance athletes. Similarly, years of training were not taken into account because of the lack of relevant data, and further investigations could be conducted to ascertain how many years of training induce permanent RV modifications. The impact of systolic and diastolic disfunction should be analysed considering a longer follow-up period to estimate the incidence of cardiovascular diseases in endurance athletes. Future studies should overcome these limitations to offer a more complete overview. Conclusion Endurance athletes exhibit an association between RV remodelling and age, BSA and intensity of training. In particular, RV E/A is an age-related functional parameter, and it should be carefully evaluated because it is a marker of diastolic dysfunction. The systolic function of the RV is decreased in endurance athletes. This is a normal adaptation to exercise, induced by structural changes, and it is within the normal limits. RV ECHO and CMR values in endurance athletes are slightly different from the reference values established in the general population. This could lead to an incorrect diagnosis of ARVC. Author name N Athletes N Sedentary M% Athletes Age Athletes Age sedentary BMI athletes (h/m2) BMI Sedentary (h/m2) BSA Athletes (m2) BSA Sedentary (m2) HR Athletes HR Sedentary Intensity of training (h/w) Years of training Utomi 201560 19 21 100% 34 ± 5 27 ± 8 NA NA 2.1 ± 0.2 2.1 ± 0.2 56 ± 11 63 ± 10  > 12  > 11 Vitarelli 201361 35 35 100% 28.7 ± 10.7 28.3 ± 11.4 22.7 ± 6 22.4 ± 2 1.91 ± 0.15 1.89 ± 0.23 54.1 ± 5.6 69.5 ± 9.1  > 15 9.6 ± 2.9 Results 2102 1311 76% 26.6 ± 8.6 26.6 ± 7.6 24.8 ± 2.01 22.89 ± 1.32 1.86 ± 0.20 1.82 ± 0.15 57.3 ± 7.06 69.6 ± 5.26 Table 1.   Population demographics in ECHO studies. ♀Data on female extracted from article with mixed population (including both sex). °Data on athletes aged < 18 extracted from article with age mixed population. ◄Different athletes population analysed in the same article with the same sedentary control. NA, not available; M%, percentage ofmale. h/w = hours/week. 7 Vol.:(0123456789) Scientific Reports | (2021) 11:22532 | https://doi.org/10.1038/s41598-021-02028-1 www.nature.com/scientificreports/ Author name N Athletes N Sedentary M% Athletes Age Athletes Age Sedentary BMI Athletes (h/m2) BMI Sedentary (h/m2) BSA Athletes (m2) BSA Sedentary (m2) HR Athletes HR Sedentary Intensity of training (h/w) Years of training Arvidd- son 20177 14 25 43% 24 (18–30) 28 (23–63) NA NA 1.7 (1.46– 2.10) 1.82 (1.45–2.29) 50 (38–69) 62 (52–65) ELITE ND Barczuk- Falecka 201832° 36 24 100% 10 ± 1.4 10.4 ± 1.7 NA NA 1.18 ± 0.21 1.23 ± 0.22 ND ND 2 × 90 minxweek +  1 × 60 min  > 2 Ber- nardino 20206 89 77 47% 34 ± 6.1 33 ± 3.8 NA NA 1.78 ± 0.19 1.86 ± 0.20 65.5 ± 10.2 54.4 ± 11.9  > 10  > 5 Bohm 20168 33 33 100% 47 ± 8 46 ± 9 NA NA 1.96 ± 0.1 2.00 ± 0.1 48 ± 7 65 ± 11 16.7 ± 4.4 23 ± 8 Brosnan 201562 68 41 ND 35.0 ± 8.1 36.9 ± 12.6 NA NA 1.9 ± 0.1 1.9 ± 0.2 55 ± 9 69 ± 15  > 10 10 ± 9 Dome- nech- Ximenos 202063 49 42 100% 37 ± 5.5 34.5 ± 3.4 NA NA 1.91 ± 0.13 1.98 ± 0.14 63.6 ± 10.3 77.3 ± 11.4  > 12 13.33 ± 7.6 Domo- nech- Ximenos 202063 ♀ 44 30 0% 34 ± 5.8 33 ± 3.7 NA NA 1.63 ± 0.09 1.67 ± 0.12 60.15 ± 10.4 81.8 ± 13.4  > 12 14.2 ± 7.9 Dupont 201764 12 12 100% 32.3 ± 7.1 33.1 ± 8.8 22.60 ± 1.06 24.9 ± 3.98 1.93 ± 0.11 2.00 ± 0.18 55 ± 11 73 ± 11 9.67 ± 2.43 ND Esch 201065 8 8 100% 31.0 ± 9.7 33.0 ± 7.3 NA NA NA NA 57.3 ± 6.2 68.4 ± 15.3 11.5 ± 3.1 11.1 ± 4.5 La Gerche 201121 39 14 90% 36 ± 8 38 ± 6 NA NA NA NA 59 ± 9 71 ± 10 16.3 ± 5.1 10 ± 9 La Gerche 201516 10 7 100% 35 ± 6 34 ± 16 22.9 ± 1.5 23.2 ± 1.7 NA NA 52 ± 8 62 ± 12 11 (6–15) 9 (6–17) Luijkx 201266 93 56 100% 24 ± 4.3 27 ± 5.1 NA ND 1.95 ± 0.15 2.00 ± 0.14 NA NA 16 ± 6.1 NA Luijkx 201266 ♀ 51 58 0% 23 ± 5.9 26 ± 5.8 NA NA 1.74 ± 0.11 1.74 ± 0.11 NA NA 13 ± 5.1 NA Luijkx 201266 ♀ ◄ 24 0% 27 ± 4.4 NA NA 1.83 ± 0.13 NA NA 21 ± 4.3 NA Luijkx 201266 ◄ 57 100% 27 ± 5 NA NA 2.02 ± 0.16 NA NA 23 ± 5.9 NA Lukasz A Malek 201967 30 10 100% 40.9 ± 6.6 40.0 ± 8.2 22.7 ± 1.5 26.1 ± 1.5 1.89 ± 0.07 2.00 ± 0.11 54.9 ± 9.2 69.6 ± 11.0 ELITE 6 (5–8) Perseghin 20079 9 10 100% 26 ± 5 25 ± 2 21.1 ± 1.2 22.4 ± 1.7 1.83 ± 0.13 1,93 ± 0.12 46 ± 11 64 ± 15 ELITE NA Prakken 201068 3 100% 26 ± 6.4 26 ± 5.2 NA NA 2.0 ± 0.2 2.0 ± 0.1 59 ± 9.7 66 ± 12 12 ± 2.4 5.1 ± 4.7 Prakken 201068◄ 46 100% 26 ± 4.9 NA NA 2.0 ± 0.2 58 ± 11 24 ± 5.6 7.5 ± 4.0 Prakken 201068 ♀ 60 58 0% 25 ± 5.3 26 ± 5.9 NA NA 1.8 ± 0.1 1.7 ± 0.1 58 ± 9.9 67 ± 9.8 13 ± 2.4 4.4 Prakken 201068 ♀ ◄ 33 0% 25 ± 4.2 NA NA 1.9 ± 0.1 57 ± 8.6 22 ± 3.5 8.8 ± 3.7 Prakken 201169 55 32 100% 50 ± 6.6 47 ± 6.6 NA NA 1.9 ± 0.1 2.1 ± 0.2 57 ± 10 62 ± 8.9 13 ± 2.9  > 1 Prakken 201169 ♀ 23 33 0% 50 ± 6.5 48 ± 5.2 NA NA 1.7 ± 0.1 1.8 ± 0.1 10 ± 1.8  > 1 Sanchis- Gormar 201656 42 18 100% 55 ± 9 58 ± 5 NA NA NA NA 54 ± 9 63 ± 8 10.6 ± 4.2 24 ± 9 Sanchis- Gormar 201656 ◄ 11 100% 54 ± 4 NA NA NA NA 58 ± 8 10.6 ± 3.1 29 ± 9 Scharf 201033 29 29 100% 24.6 ± 3.9 27.0 ± 3.7 NA NA 2.03 ± 0.8 1.99 ± 0.2 56.0 ± 8.5 69.3 ± 10.3  > 3  > 10 Scharhag 200270 21 21 100% 27 ± 5 26 ± 3 NA NA 1,87 ± 0.14 1.88 ± 0.14 53 ± 6 66 ± 8 ELITE NA Schiros 201371 19 24 53% 39 ± 10 45 ± 8 NA NA 1.78 ± 0.23 1.91 ± 0.17 55 ± 9 67 ± 11 ELITE  > 2 Steding- Ehrenborg 201572 8 7 100% 64 ± 4 66 ± 4 NA NA 1.91 ± 0.15 1.98 ± 0.11 NA NA  > 5 30 Continued 8 Vol:.(1234567890) Scientific Reports | (2021) 11:22532 | https://doi.org/10.1038/s41598-021-02028-1 www.nature.com/scientificreports/ Author name N Athletes N Sedentary M% Athletes Age Athletes Age Sedentary BMI Athletes (h/m2) BMI Sedentary (h/m2) BSA Athletes (m2) BSA Sedentary (m2) HR Athletes HR Sedentary Intensity of training (h/w) Years of training Swoboda 201673 35 35 77% 31.3 ± 7.6 30.6 ± 8.5 22.3 ± 1.9 24.5 ± 3.3 NA NA NA NA 11.5 ± 3.7 8.4 ± 6.0 Szelid 201574 94 109 100% 26.9 ± 5.7 27.1 ± 5.2 25.8 ± 2.2 24.1 ± 4.6 2.38 ± 0.1 2.08 ± 0.3 NA NA NA  > 10 Szelid 201574 ♀ 32 46 0% 24.9 ± 5.3 28.0 ± 5.7 23.4 ± 2.5 21.6 ± 3.9 1.89 ± 0.3 1.74 ± 0.2 NA NA NA  > 10 Results 1257 909 72% 31.5 ± 9.8 31.9 ± 8.8 22.4 ± 0.5 24.4 ± 1.1 1.89 ± 0.19 1.87 ± 0.15 57.7 ± 4.35 63.4 ± 6.9 Table 2.   Population demographics in CMR studies. ♀Data on female extracted from article with mixed population (including both sex). °Data on athletes aged < 18 extracted from article with age mixed population. ◄Different athletes population analysed in the same article with the same sedentary control. NA, not available; M%, percentage of male; h/w, hours/week. Table 3.   Multivariate analysis of ECHO data. Only statistically significant data were shown. NA, not available; h/w, hours/week. Dimension AGE BSA (m2) Intensity of training (h/w) Athletes Sedentary Athletes Sedentary Athletes P value r P value r P value r P value r P value r RVED longitudinal (mm) 0.0114 − 0.6992 0.6259 − 0.5544 0.706 0.5556 0.743 − 0.112 0.886 0.0609 RVESA (cm) 0.3132 0.3184 0.2724 0.4105 0.1785 0.1309 0.1959 0.555 0.0308 0.853 RVESAI (cm2/m2) 0.3663 − 0.8389 0.3182 − 0.8777 0.0415 − 0.9979 0.0117 − 0.9998 NA NA RV E/A 0.0091 − 0.6284 0.106 − 0.4898 0.0016 − 0.7212 0.078 − 0.5275 0.1688 0.4059 RAA (cm2) 0.0438 0.768 0.0166 0.8455 0.0457 0.8199 0.0423 0.8269 0.4773 − 0.7319 Table 4.   Multivariate analysis of CMR data. NA, not available; h/w, hours/week. Dimension AGE BSA Intensity of training (h/w) Athletes Sedentary Athletes Sedentary Athletes P value r P value r P value r P value r P value r RVEDV (ml) 0.9485 0.0146 0.5797 − 0.1695 0.0569 0.5883 0.2967 0.392 0.1159 0.5017 RVEDVI (ml/m2) 0.726 − 0.0951 0.4515 − 0.1876 0.0887 0.3715 0.349 0.2345 0.0084 0.6524 RVESV (ml) 0.5942 − 0.1096 0.3029 − 0.4179 0.1133 0.7109 0.596 0.404 0.0751 0.5859 RVESVI (ml/m2) 0.1387 − 0.4762 0.1221 − 0.3896 0.1318 0.3584 0.3421 0.2638 0.0072 0.7043 RVSV (ml) 0.0671 − 0.3973 0.8966 0.069 0.8888 − 0.1112 0.8364 0.1636 0.874 0.1966 RVSVI (ml/m2) 0.9695 − 0.0203 0.0674 − 0.5987 0.4555 0.2861 0.7691 0.1146 NA NA EF % 0.6754 − 0.1518 0.1485 0.3111 0.7527 − 0.0712 0.5675 − 0.1444 0.0103 − 0.6035 Mass 0.0524 0.3703 0.9772 − 0.0152 0.2925 − 0.4655 0.7043 0.2344 0.9712 − 0.0226 Mass index 0.2581 0.4543 0.2318 − 0.3417 0.1315 0.3809 0.2845 0.3212 0.3042 0.3414 Table 5.   Comparison between increment of CMR values among sex (only studies with both male and female data were shown separately). 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Author contributions M.P.: collection, analysis, interpretation of the data, writing of the paper; F.M.: analysis, interpretation of the data, writing of the paper; V.C.: collection, interpretation of the data, writing of the paper; M.I.B.: conceptualisation, interpretation of the data, writing of the paper; J.J.R.-Á.: conceptualisation, interpretation of the data, critical revision; F.J.C.M.: conceptualisation, interpretation of the data, writing of the paper; N.M.: conceptualisation, interpretation of the data, writing of the paper, critical revision. Funding Open Access funding enabled and organized by Projekt DEAL. Competing interests  The authors declare no competing interests. Additional information Supplementary Information The online version contains supplementary material available at https://​doi.​org/​ 10.​1038/​s41598-​021-​02028-1. Correspondence and requests for materials should be addressed to F.M. Reprints and permissions information is available at www.nature.com/reprints. https://doi.org/10.1016/j.amjcard.2012.12.027 https://doi.org/10.1016/j.amjcard.2012.12.027 https://doi.org/10.1038/s41598-021-02028-1 https://doi.org/10.1038/s41598-021-02028-1 www.nature.com/reprints 12 Vol:.(1234567890) Scientific Reports | (2021) 11:22532 | https://doi.org/10.1038/s41598-021-02028-1 www.nature.com/scientificreports/ Publisher’s note  Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. © The Author(s) 2021 http://creativecommons.org/licenses/by/4.0/ Right heart exercise-training-adaptation and remodelling in endurance athletes Methods Search strategy. Literature search and selection. Eligibility criteria. Data extraction. Outcomes of interest. Methodological quality assessment. Statistical analysis. Results Search results. Methodological quality assessment. Population demographic. Outcome of interest. Discussion Conclusion References Acknowledgements