DOI QR코드

DOI QR Code

The Effect of Enalapril and Carvedilol on Left Ventricular Dysfunction in Middle Childhood and Adolescent Patients With Muscular Dystrophy

  • Kwon, Hye-Won (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Kwon, Bo-Sang (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Kim, Gi-Beom (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Chae, Jong-Hee (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Park, June-Dong (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Bae, Eun-Jung (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Noh, Chung-Il (Department of Pediatrics, Seoul National University Children's Hospital)
  • Published : 2012.03.31

Abstract

Background and Objectives: In Duchenne and Becker muscular dystrophies, cardiac function deteriorates with time resulting in heart failure which is often fatal. We prospectively evaluated the effect of enalapril and carvedilol on left ventricular (LV) dysfunction in middle childhood and adolescent patients with muscular dystrophy. Subjects and Methods: Twenty-three patients with LV dysfunction (22 with Duchenne muscular dystrophy, 1 with Becker muscular dystrophy) were enrolled. We prescribed enalapril (13 patients) or carvedilol (10 patients) randomly from July 2008 to August 2010 and followed up the patients until September 2011. The changes in LV function parameters before and after the treatment were evaluated by echocardiography. Results: The mean age at the start of treatment with enalapril or carvedilol was 12.6${\pm}$3.7 years (median 13 years), and mean follow-up duration was 20.1${\pm}$8.9 months. In the enalapril group, LV fractional shortening (FS) increased from 25.8${\pm}$2.1 to 26.6${\pm}$3.0 (p=0.241). In the carvedilol group, LV FS increased from 26.4${\pm}$1.1 to 28.6${\pm}$4.2 (p=0.110). In all 23 patients, LV FS significantly increased from 26.1${\pm}$1.7 (before) to 27.6${\pm}$3.7 (after treatment) (p<0.046). Indexed LV dimension at end diastole and LV end-diastolic volume decreased slightly, but without statistical significance by tri-plane volumetry. LV diastolic functional parameters were maintained during follow-up period. Conclusion: Enalapril or carvedilol could improve LV systolic function in middle childhood and adolescent patients with muscular dystrophy without significant adverse effects.

Keywords

References

  1. Emery AE. The muscular dystrophies. Lancet 2002;359:687-95. https://doi.org/10.1016/S0140-6736(02)07815-7
  2. Emery AE. Population frequencies of inherited neuromuscular diseases: a world survey. Neuromuscul Disord 1991;1:19-29. https://doi.org/10.1016/0960-8966(91)90039-U
  3. Finsterer J, Stollberger C. The heart in human dystrophinopathies. Cardiology 2003;99:1-19. https://doi.org/10.1159/000068446
  4. McNally EM. Duchenne muscular dystrophy: how bad is the heart? Heart 2008;94:976-7. https://doi.org/10.1136/hrt.2007.138461
  5. Kaspar RW, Allen HD, Montanaro F. Current understanding and management of dilated cardiomyopathy in Duchenne and Becker muscular dystrophy. J Am Acad Nurse Pract 2009;21:241-9. https://doi.org/10.1111/j.1745-7599.2009.00404.x
  6. Jefferies JL, Eidem BW, Belmont JW, et al. Genetic predictors and remodeling of dilated cardiomyopathy in muscular dystrophy. Circulation 2005;112:2799-804. https://doi.org/10.1161/CIRCULATIONAHA.104.528281
  7. Duboc D, Meune C, Lerebours G, Devaux JY, Vaksmann G, Bécane HM. Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J Am Coll Cardiol 2005; 45:855-7. https://doi.org/10.1016/j.jacc.2004.09.078
  8. Duboc D, Meune C, Pierre B, et al. Perindopril preventive treatment on mortality in Duchenne muscular dystrophy: 10 years' follow-up. Am Heart J 2007;154:596-602 https://doi.org/10.1016/j.ahj.2007.05.014
  9. Giglio V. Left ventricular function and response to enalapril in patients with Duchenne muscular dystrophy during the second decade of life. Am J Cardiol 2007;99:147-8. https://doi.org/10.1016/j.amjcard.2006.10.008
  10. Saito T, Matsumura T, Miyai I, Nozaki S, Shinno S. Carvedilol effectiveness for left ventricular-insufficient patients with Duchenne muscular dystrophy. Rinsho Shinkeigaku 2001;41:691-4.
  11. Reisner SA, Lysyansky P, Agmon Y, Mutlak D, Lessick J, Friedman Z. Global longitudinal strain: a novel index of left ventricular systolic function. J Am Soc Echocardiogr 2004;17:630-3. https://doi.org/10.1016/j.echo.2004.02.011
  12. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072-83. https://doi.org/10.1161/01.CIR.58.6.1072
  13. Garcia MJ, Thomas JD, Klein AL. New Doppler echocardiographic applications for the study of diastolic function. J Am Coll Cardiol 1998; 32:865-75. https://doi.org/10.1016/S0735-1097(98)00345-3
  14. Tei C, Ling LH, Hodge DO, et al. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function: a study in normals and dilated cardiomyopathy. J Cardiol 1995;26:357-66.
  15. Sohn DW, Chai IH, Lee DJ, et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 1997;30:474-80. https://doi.org/10.1016/S0735-1097(97)88335-0
  16. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man: anatomic validation of method. Circulation 1977; 55:613-8. https://doi.org/10.1161/01.CIR.55.4.613
  17. Lamparter S, Sun Y, Weber KT. Angiotensin II receptor blockade during gestation attenuates collagen formation in the developing rat heart. Cardiovasc Res 1999;43:165-72. https://doi.org/10.1016/S0008-6363(99)00111-X
  18. Bernal J, Pitta SR, Thatai D. Role of the renin-angiotensin-aldosterone system in diastolic heart failure: potential for pharmacologic intervention. Am J Cardiovasc Drugs 2006;6:373-81. https://doi.org/10.2165/00129784-200606060-00004
  19. Ramaciotti C, Heistein LC, Coursey M, et al. Left ventricular function and response to enalapril in patients with Duchenne muscular dystrophy during the second decade of life. Am J Cardiol 2006;98:825-7. https://doi.org/10.1016/j.amjcard.2006.04.020
  20. Francis GS, Benedict C, Johnstone DE, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure: a substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation 1990;82:1724-9. https://doi.org/10.1161/01.CIR.82.5.1724
  21. Cha DH, Cha YS, Kook JH, et al. Clinical efficacy of carvedilol in patients with moderate to severe congestive heart failure. Korean Circ J 1998; 28:523-31.
  22. Bruns LA, Chrisant MK, Lamour JM, et al. Carvedilol as therapy in pediatric heart failure: an initial multicenter experience. J Pediatr 2001;138: 505-11. https://doi.org/10.1067/mpd.2001.113045
  23. Ishikawa Y, Bach JR, Minami R. Cardioprotection for Duchenne's muscular dystrophy. Am Heart J 1999;137:895-902. https://doi.org/10.1016/S0002-8703(99)70414-X
  24. Kajimoto H, Ishigaki K, Okumura K, et al. Beta-blocker therapy for cardiac dysfunction in patients with muscular dystrophy. Circ J 2006;70: 991-4. https://doi.org/10.1253/circj.70.991
  25. Ogata H, Ishikawa Y, Ishikawa Y, Minami R. Beneficial effects of betablockers and angiotensin-converting enzyme inhibitors in Duchenne muscular dystrophy. J Cardiol 2009;53:72-8. https://doi.org/10.1016/j.jjcc.2008.08.013
  26. American Academy of Pediatrics Section on Cardiology and Cardiac Surgery. Cardiovascular health supervision for individuals affected by Duchenne or Becker muscular dystrophy. Pediatrics 2005;116:1569-73. https://doi.org/10.1542/peds.2005-2448
  27. Bahler RC, Mohyuddin T, Finkelhor RS, Jacobs IB. Contribution of Doppler tissue imaging and myocardial performance index to assessment of left ventricular function in patients with Duchenne's muscular dystrophy. J Am Soc Echocardiogr 2005;18:666-73. https://doi.org/10.1016/j.echo.2004.10.003
  28. Giatrakos N, Kinali M, Stephens D, Dawson D, Muntoni F, Nihoyannopoulos P. Cardiac tissue velocities and strain rate in the early detection of myocardial dysfunction of asymptomatic boys with Duchenne's muscular dystrophy: relationship to clinical outcome. Heart 2006;92:840-2.
  29. Ogata H, Nakatani S, Ishikawa Y, et al. Myocardial strain changes in Duchenne muscular dystrophy without overt cardiomyopathy. Int J Cardiol 2007;115:190-5. https://doi.org/10.1016/j.ijcard.2006.02.013
  30. Tsutamoto T, Wada A, Maeda K, et al. Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction. Circulation 1997;96:509-16. https://doi.org/10.1161/01.CIR.96.2.509
  31. Mori K, Manabe T, Nii M, Hayabuchi Y, Kuroda Y, Tatara K. Plasma levels of natriuretic peptide and echocardiographic parameters in patients with Duchenne's progressive muscular dystrophy. Pediatr Cardiol 2002; 23:160-6. https://doi.org/10.1007/s00246-001-0040-0

Cited by

  1. Dysregulation of calcium homeostasis in muscular dystrophies vol.16, pp.None, 2012, https://doi.org/10.1017/erm.2014.17
  2. Treatment of dystrophin cardiomyopathies vol.11, pp.3, 2012, https://doi.org/10.1038/nrcardio.2013.213
  3. Prediction of gene-based drug indications using compendia of public gene expression data and PubMed abstracts vol.12, pp.3, 2012, https://doi.org/10.1142/s0219720014500073
  4. Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association vol.136, pp.13, 2012, https://doi.org/10.1161/cir.0000000000000526
  5. Risk Stratification of Genetic, Dilated Cardiomyopathies Associated With Neuromuscular Disorders : Role of Cardiac Imaging vol.137, pp.23, 2018, https://doi.org/10.1161/circulationaha.117.031110
  6. Randomised placebo-controlled trial of combination ACE inhibitor and beta-blocker therapy to prevent cardiomyopathy in children with Duchenne muscular dystrophy? (DMD Heart Protection Study): a protoc vol.8, pp.12, 2012, https://doi.org/10.1136/bmjopen-2018-022572
  7. Left Ventricular End-Diastolic Diameter and Cardiac Mortality in Duchenne Muscular Dystrophy vol.16, pp.None, 2012, https://doi.org/10.2147/ndt.s235166
  8. Duchenne Muscular Dystrophy: the Heart of the Matter vol.17, pp.3, 2012, https://doi.org/10.1007/s11897-020-00456-0
  9. Role of the Renin–Angiotensin–Aldosterone System in Dystrophin-Deficient Cardiomyopathy vol.22, pp.1, 2012, https://doi.org/10.3390/ijms22010356
  10. Abnormal Calcium Handling in Duchenne Muscular Dystrophy: Mechanisms and Potential Therapies vol.12, pp.None, 2021, https://doi.org/10.3389/fphys.2021.647010
  11. Preventing Cardiomyopathy in DMD : A Randomized Placebo-Controlled Drug Trial vol.11, pp.5, 2012, https://doi.org/10.1212/cpj.0000000000001023