Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Myocardial atrophy in children with mitochondrial disease and Duchenne muscular dystrophy

  • Lee, Tae Ho (Divisions of Pediatric Cardiology, Department of Pediatrics, Yonsei University College of Medicine) ;
  • Eun, Lucy Youngmin (Divisions of Pediatric Cardiology, Department of Pediatrics, Yonsei University College of Medicine) ;
  • Choi, Jae Young (Divisions of Pediatric Cardiology, Department of Pediatrics, Yonsei University College of Medicine) ;
  • Kwon, Hye Eun (Divisions of Pediatric Neurology, Department of Pediatrics, Yonsei University College of Medicine) ;
  • Lee, Young-Mock (Divisions of Pediatric Neurology, Department of Pediatrics, Yonsei University College of Medicine) ;
  • Kim, Heung Dong (Divisions of Pediatric Neurology, Department of Pediatrics, Yonsei University College of Medicine) ;
  • Kang, Seong-Woong (Department of Rehabilitation Medicine and Rehabilitation Institute of Muscular Disease, Yonsei University College of Medicine)
  • Received : 2013.09.20
  • Accepted : 2013.10.21
  • Published : 2014.05.15
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Abstract

Purpose: Mitochondrial disease (MD) and Duchenne muscular dystrophy (DMD) are often associated with cardiomyopathy, but the myocardial variability has not been isolated to a specific characteristic. We evaluated the left ventricular (LV) mass by echocardiography to identify the general distribution and functional changes of the myocardium in patients with MD or DMD. Methods: We retrospectively evaluated the echocardiographic data of 90 children with MD and 42 with DMD. Using two-dimensional echocardiography, including time-motion (M) mode and Doppler measurements, we estimated the LV mass, ratio of early to late mitral filling velocities (E/A), ratio of early mitral filling velocity to early diastolic mitral annular velocity (E/Ea), stroke volume, and cardiac output. A "z score" was generated using the lambda-mu-sigma method to standardize the LV mass with respect to body size. Results: The LV mass-for-height z scores were significantly below normal in children with MD ($-1.02{\pm}1.52$, P<0.001) or DMD ($-0.82{\pm}1.61$, P =0.002), as were the LV mass-for-lean body-mass z scores. The body mass index (BMI)-for-age z scores were far below normal and were directly proportional to the LV mass-for-height z scores in both patients with MD (R =0.377, P<0.001) and those with DMD (R =0.330, P=0.033). The LV mass-for-height z score correlated positively with the stroke volume index (R =0.462, P<0.001) and cardiac index (R =0.358, P<0.001). Conclusion: LV myocardial atrophy is present in patients with MD and those with DMD and may be closely associated with low BMI. The insufficient LV mass for body size might indicate deterioration of systolic function in these patients.

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References

  1. Darin N, Oldfors A, Moslemi AR, Holme E, Tulinius M. The incidence of mitochondrial encephalomyopathies in childhood: clinical features and morphological, biochemical, and DNA anbormalities. Ann Neurol 2001;49:377-83.
  2. Debray FG, Lambert M, Chevalier I, Robitaille Y, Decarie JC, Shoubridge EA, et al. Long-term outcome and clinical spectrum of 73 pediatric patients with mitochondrial diseases. Pediatrics 2007; 119:722-33.
  3. Haas RH, Parikh S, Falk MJ, Saneto RP, Wolf NI, Darin N, et al. Mitochondrial disease: a practical approach for primary care physicians. Pediatrics 2007;120:1326-33.
  4. Moser H. Duchenne muscular dystrophy: pathogenetic aspects and genetic prevention. Hum Genet 1984;66:17-40.
  5. Pasternak C, Wong S, Elson EL. Mechanical function of dystrophin in muscle cells. J Cell Biol 1995;128:355-61.
  6. Bushby K, Muntoni F, Bourke JP. 107th ENMC international workshop: the management of cardiac involvement in muscular dystrophy and myotonic dystrophy. 7th-9th June 2002, Naarden, the Netherlands. Neuromuscul Disord 2003;13:166-72.
  7. Holmgren D, Wahlander H, Eriksson BO, Oldfors A, Holme E, Tulinius M. Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings. Eur Heart J 2003;24:280-8.
  8. Connuck DM, Sleeper LA, Colan SD, Cox GF, Towbin JA, Lowe AM, et al. Characteristics and outcomes of cardiomyopathy in children with Duchenne or Becker muscular dystrophy: a comparative study from the Pediatric Cardiomyopathy Registry. Am Heart J 2008;155:998-1005.
  9. Kessler KM, Pina I, Green B, Burnett B, Laighold M, Bilsker M, et al. Cardiovascular findings in quadriplegic and paraplegic patients and in normal subjects. Am J Cardiol 1986;58:525-30.
  10. Shapiro F, Sethna N, Colan S, Wohl ME, Specht L. Spinal fusion in Duchenne muscular dystrophy: a multidisciplinary approach. Muscle Nerve 1992;15:604-14.
  11. 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;117:2769-75.
  12. Morava E, van den Heuvel L, Hol F, de Vries MC, Hogeveen M, Rodenburg RJ, et al. Mitochondrial disease criteria: diagnostic applications in children. Neurology 2006 28;67:1823-6.
  13. Koenig MK. Presentation and diagnosis of mitochondrial disorders in children. Pediatr Neurol 2008;38:305-13.
  14. Koenig M, Beggs AH, Moyer M, Scherpf S, Heindrich K, Bettecken T, et al. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet 1989;45:498-506.
  15. Foster BJ, Platt RW, Zemel BS. Development and validation of a predictive equation for lean body mass in children and adolescents. Ann Hum Biol 2012;39:171-82.
  16. Teichholz LE, Kreulen T, Herman MV, Gorlin R. Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence of absence of asynergy. Am J Cardiol 1976;37:7-11.
  17. 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;57:450-8.
  18. de Simone G, Devereux RB, Daniels SR, Mureddu G, Roman MJ, Kimball TR, et al. Stroke volume and cardiac output in normotensive children and adults. Assessment of relations with body size and impact of overweight. Circulation 1997;95:1837-43.
  19. 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; 26:410-8.
  20. Sluysmans T, Colan SD. Theoretical and empirical derivation of cardiovascular allometric relationships in children. J Appl Physiol (1985) 2005;99:445-57.
  21. Fleming S, Thompson M, Stevens R, Heneghan C, Pluddemann A, Maconochie I, et al. Normal ranges of heart rate and respiratory rate in children from birth to 18 years of age: a systematic review of observational studies. Lancet 2011;377:1011-8.
  22. Hurwitz RA, Treves S, Kuruc A. Right ventricular and left ventricular ejection fraction in pediatric patients with normal hearts: first-pass radionuclide angiocardiography. Am Heart J 1984;107:726-32.
  23. Ostman-Smith I, Devlin AM. A simple method for assessing the regression or progression of ventricular hypertrophy in the growing child and adult: the value of left ventricular wall-to-cavity ratios. Eur J Echocardiogr 2001;2:22-30.
  24. Eidem BW, McMahon CJ, Cohen RR, Wu J, Finkelshteyn I, Kovalchin JP, et al. Impact of cardiac growth on Doppler tissue imaging velocities: a study in healthy children. J Am Soc Echocardiogr 2004;17:212-21.
  25. Finsterer J, Stollberger C. The heart in human dystrophinopathies. Cardiology 2003;99:1-19.
  26. Daniels SR, Kimball TR, Morrison JA, Khoury P, Witt S, Meyer RA. Effect of lean body mass, fat mass, blood pressure, and sexual maturation on left ventricular mass in children and adolescents. Statistical, biological, and clinical significance. Circulation 1995; 92:3249-54.
  27. Wolny S, McFarland R, Chinnery P, Cheetham T. Abnormal growth in mitochondrial disease. Acta Paediatr 2009;98:553-4.
  28. Shimizu-Fujiwara M, Komaki H, Nakagawa E, Mori-Yoshimura M, Oya Y, Fujisaki T, et al. Decreased resting energy expenditure in patients with Duchenne muscular dystrophy. Brain Dev 2012;34: 206-12.
  29. Hyams LC, Langley GN, Shoffner JM. Relationship between metabolic rate measurements, mitochondrial protein chemistry, and mitochondrial DNA (mtDNA) mutations. Neurology 2009;72:A17-8.
  30. Okada K, Manabe S, Sakamoto S, Ohnaka M, Niiyama Y. Protein and energy metabolism in patients with progressive muscular dystrophy. J Nutr Sci Vitaminol (Tokyo) 1992;38:141-54.
  31. Brandi G, Brambilla I. Artero-venous difference of oxygen, cardiac output and stroke volume in function of the energy consumption. Int Z Angew Physiol 1961;19:130-3.
  32. Sharma KR, Mynhier MA, Miller RG. Muscular fatigue in Duchenne muscular dystrophy. Neurology 1995;45:306-10.
  33. Griggs RC, Karpati G. Muscle pain, fatigue, and mitochondriopathies. N Engl J Med 1999;341:1077-8.
  34. Karason K, Wallentin I, Larsson B, Sjostrom L. Effects of obesity and weight loss on left ventricular mass and relative wall thickness: survey and intervention study. BMJ 1997;315:912-6.

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