Left ventricular mass normalization for body size in children based on an allometrically adjusted ratio is as accurate as normalization based on the centile curves method

Autoři: Hubert Krysztofiak aff001;  Marcel Młyńczak aff003;  Łukasz A. Małek aff004;  Andrzej Folga aff002;  Wojciech Braksator aff005
Působiště autorů: Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland aff001;  National Centre for Sports Medicine, Warsaw, Poland aff002;  Warsaw University of Technology, Faculty of Mechatronics, Institute of Metrology and Biomedical Engineering, Warsaw, Poland aff003;  Department of Epidemiology, Cardiovascular Disease Prevention and Health Promotion, National Institute of Cardiology, Warsaw, Poland aff004;  Department of Sports Cardiology and Noninvasive Cardiovascular Imaging, 2nd Medical Faculty, Medical University of Warsaw, Warsaw, Poland aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225287



Normalization for body size is required for reliable left ventricular mass (LVM) evaluation, especially in children due to the large variability of body size. In clinical practice, the allometrically adjusted ratio of LVM to height raised to the power of 2.7 is often used. However, studies presenting normative LVM data for children recommend centile curves as optimal for the development of normative data. This study aimed to assess whether the allometrically adjusted LVM-to-height ratio can reliably reproduce the results of LVM normalization for height based on the centile curves method.


Left ventricular mass was computed for 464 boys and 327 girls, 5–18 years old, based on echocardiographic examination. Normalized data representing LVM for height were developed using the centile curves construction method and two variants of the allometrically adjusted ratio method: one variant with the allometric exponents specific to the study groups, and one variant with the universal exponent of 2.7. The agreement between the allometric methods and the centile curves method was analyzed using the concordance correlation coefficient, sensitivity, and specificity.


For both the specific allometric variant and the universal variant, the analysis of concordance has indicated high reproducibility compared to the centile curves method. The respective coefficient values were 0.9917 and 0.9916 for girls, and 0.9886 and 0.9869 for boys. The sensitivity and specificity test has also shown high agreement. However, for girls, the sensitivity was higher for the specific variant (100% vs. 90.9%).


The results of the study show that allometric scaling of LVM for height can very reliably reproduce the results of LVM normalization for height based on the centile curves method. However, the analysis of sensitivity and specificity indicates greater agreement for the allometric normalization with the group-specific allometric exponents.

Klíčová slova:

Adolescents – Database and informatics methods – Echocardiography – Children – Physiological parameters – Statistical data


1. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, et al. Echocardiographic assessment of left ventricular hypertrophy: Comparison to necropsy findings. Am J Cardiol 1986; 57: 450–458. doi: 10.1016/0002-9149(86)90771-x 2936235

2. 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.e14. doi: 10.1016/j.echo.2014.10.003 25559473

3. De Simone G, Gottdiener JS, Chinali M, Maurer MS. Left ventricular mass predicts heart failure not related to previous myocardial infarction: the Cardiovascular Health Study. Eur Heart J 2008; 29: 741–747. doi: 10.1093/eurheartj/ehm605 18204091

4. Bluemke DA, Kronmal RA, Lima JA, Liu K, Olson J, Burke GL, et al. The relationship of left ventricular mass and geometry to incident cardiovascular events: the MESA (Multi-Ethnic Study of Atherosclerosis) study. J Am Coll Cardiol 2008; 52: 2148–2155. doi: 10.1016/j.jacc.2008.09.014 19095132

5. Krysztofiak H, Petkow-Dimitrow P. Differentiating physiology from pathology in elite athletes. Left ventricular hypertrophy versus hypertrophic cardiomyopathy. Kardiol Pol 2016; 74(8):705–716. doi: 10.5603/KP.a2016.0084 27221963

6. Galderisi M, Cardim N, D'Andrea A, Bruder O, Cosyns B, Davin L, et al. The multi-modality cardiac imaging approach to the Athlete's heart: an expert consensus of the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2015; 16: 353. doi: 10.1093/ehjci/jeu323 25681828

7. Sharma S, Maron BJ, Whyte G, Firoozi S, Elliott PM, McKenna WJ. Physiologic limits of left ventricular hypertrophy in elite junior athletes: relevance to differential diagnosis of athlete's heart and hypertrophic cardiomyopathy. J Am Coll Cardiol 2002; 40: 1431–6. doi: 10.1016/s0735-1097(02)02270-2 12392833

8. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013; 34: 2159–2219. doi: 10.1093/eurheartj/eht151 23771844

9. Armstrong AC, Gidding S, Gjesdal O, Wu C, Bluemke DA, Lima JAC. LV Mass Assessed by Echocardiography and CMR, Cardiovascular Outcomes, and Medical Practice. JACC Cardiovasc Imaging 2012; 5(8): 837–848. doi: 10.1016/j.jcmg.2012.06.003 22897998

10. Lopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK, et al. Recommendations for Quantification Methods During the Performance of a Pediatric Echocardiogram: A Report From the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr 2010; 23: 465–495. doi: 10.1016/j.echo.2010.03.019 20451803

11. Krysztofiak H, Młyńczak M, Małek ŁA, Folga A, Braksator W. Left ventricular mass is underestimated in overweight children because of incorrect body size variable chosen for normalization. PLoS ONE 2019; 14(5): e0217637. doi: 10.1371/journal.pone.0217637 31141818

12. de Simone G, Daniels SR, Devereux RB, Meyer RA, Roman MJ, de Divitiis O, et al. Left ventricular mass and body size in normotensive children and adults: Assessment of allometric relations and impact of overweight. J Am Coll Cardiol 1992; 20: 1251–1260. doi: 10.1016/0735-1097(92)90385-Z 1401629

13. de Simone G, Devereux RB, Daniels SR, Koren MJ, Meyer RA, Laragh JH. Effect of growth on variability of left ventricular mass: assessment of allometric signals in adults and children and their capacity to predict cardiovascular risk. J Am Coll Cardiol 1995; 25: 1056–62. doi: 10.1016/0735-1097(94)00540-7 7897116

14. de Simone G, Kizer JR, Chinali M, Roman MJ, Bella JN, Best LG, et al; Strong Heart Study Investigators. Normalization for body size and population-attributable risk of left ventricular hypertrophy: The Strong Heart Study. Am J Hypertens 2005; 18: 191–196. doi: 10.1016/j.amjhyper.2004.08.032 15752946

15. Foster BJ, Mackie AS, Mitsnefes M, Ali H, Mamber S, Colan SD. A novel method of expressing left ventricular mass relative to body size in children. Circulation 2008; 117(21): 2769–2775. doi: 10.1161/CIRCULATIONAHA.107.741157 18490525

16. Foster BJ, Gao T, Mackie AS, Zemel BS, Ali H, Platt RW, et al. Limitations of expressing left ventricular mass relative to height and to body surface area in children. J Am Soc Echocardiogr 2013; 26: 410–418. doi: 10.1016/j.echo.2012.11.018 23267782

17. Foster BJ, Khoury PR, Kimball TR, Mackie AS, Mitsnefes M. New reference centiles for left ventricular mass relative to lean body mass in children. J Am Soc Echocardiogr 2016; 29: 441–447.e2. doi: 10.1016/j.echo.2015.12.011 26850680

18. Mawad W, Drolet C, Dahdah N, Dallaire F. A review and critique of the statistical methods used to generate reference values in pediatric echocardiography. J Am Soc Echocardiogr 2013; 26: 29–37. doi: 10.1016/j.echo.2012.09.021 23140845

19. WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards: Length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: Methods and development. Geneva: World Health Organization, 2006 (312 pages). Available from: https://www.who.int/childgrowth/standards/technical_report/en/

20. Díaz A, Zócalo Y, Bia D. Reference Intervals and Percentile Curves of Echocardiographic Left Ventricular Mass, Relative Wall Thickness and Ejection Fraction in Healthy Children and Adolescents. Pediatr Cardiol 2019; 40: 283–301. doi: 10.1007/s00246-018-2000-y 30288599

21. Cole TJ, Green PJ. Smoothing reference centile curves: The lms method and penalized likelihood. Stat Med 1992; 11: 1305–1319. doi: 10.1002/sim.4780111005 1518992

22. Albrecht GH, Gelvin BR, Hartman SE. Ratios as a size adjustment in morphometrics. Am J Phys Anthropol 1993; 91(4): 441–468. doi: 10.1002/ajpa.1330910404 8372935

23. Lin LI. A concordance correlation coefficient to evaluate reproducibility. Biometrics. 1989 Mar; 45(1): 255–68. 2720055

24. Pluim BM, Zwinderman AH, van der Laarse A, van der Wall EE. The athlete's heart. A meta-analysis of cardiac structure and function. Circulation 2000; 101: 336–44. doi: 10.1161/01.cir.101.3.336 10645932

25. 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: 1727–1733. doi: 10.1136/heartjnl-2012-303465 23474689

26. Whalley GA, Doughty RN, Gamble GD, Oxenham HC, Walsh HJ, Reid IR, et al. Association of fat-free mass and training status with left ventricular size and mass in endurance-trained athletes. J Am Coll Cardiol 2004; 44: 892–896. doi: 10.1016/j.jacc.2004.04.051 15312877

27. Pressler A, Haller B, Scherr J, Heitkamp D, Esefeld K, Boscheri A, et al. Association of body composition and left ventricular dimensions in elite athletes. Eur J Prev Cardiol 2012; 19: 1194–1204. doi: 10.1177/1741826711422455 21885466

28. Gutgesell HP, Rembold CM. Growth of the human heart relative to body surface area. Am J Cardiol 1990; 65(9): 662–668. doi: 10.1016/0002-9149(90)91048-b 2309636

29. Huxley JS, Tessier G. Terminology of relative growth. Nature 1936; 137: 780–781. doi: 10.1038/137780b0

30. Gould SJ. Geometric Similarity in Allometric Growth: A Contribution to the Problem of Scaling in the Evolution of Size. Am Nat 1971; 105:942: 113–136.

31. Sluysmans T, Colan SD. Theoretical and empirical derivation of cardiovascular allometric relationships in children. J Appl Physiol (1985) 2005; 99(2): 445–457. doi: 10.1152/japplphysiol.01144.2004 15557009

32. Chirinos JA, Segers P, De Buyzere ML, Kronmal RA, Raja MW, De Bacquer D, et al. Left ventricular mass: Allometric scaling, normative values, effect of obesity, and prognostic performance. Hypertension 2010; 56: 91–98. doi: 10.1161/HYPERTENSIONAHA.110.150250 20458004

33. Chinali M, Emma F, Esposito C, Rinelli G, Franceschini A, Doyon A, et al. Left Ventricular Mass Indexing in Infants, Children, and Adolescents: A Simplified Approach for the Identification of Left Ventricular Hypertrophy in Clinical Practice. J Pediatr 2015; 170: 193–198. doi: 10.1016/j.jpeds.2015.10.085 26670053

34. de Simone G, Devereux RB. Method Errors or Unexplained Biological? Hypertension 2010; 56:e177–e178. doi: 10.1161/HYPERTENSIONAHA.110.163964 21041700

35. Zaki R, Bulgiba A, Ismail R, Ismail NA. Statistical Methods Used to Test for Agreement of Medical Instruments Measuring Continuous Variables in Method Comparison Studies: A Systematic Review. PLoS ONE 2012; 7(5): e37908. doi: 10.1371/journal.pone.0037908 22662248

Článek vyšel v časopise


2019 Číslo 11