Evaluation of cardiac functions in children with Duchenne Muscular Dystrophy
A prospective case-control study
Keywords:
Duchenne muscular dystrophy (DMD), Echocardiography, Electrocardiography (ECG), Cardiac evaluationsAbstract
Background: Duchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy. The incidence of cardiomyopathy in DMD increases with age, so its early detection is important because institution of cardioprotective medical therapies may slow adverse remodeling and attenuate heart failure symptoms in these patients.
Objective: To assess the cardiac functions in children clinically suspected to have DMD.
Methods: Over a one-year period, 28 male children aged from 3 to 18 years old, who met the criteria for diagnosis of DMD compared to 47 healthy controls children, were approached to participate in the study. The included children were subjected to full clinical examination, and blood samples were collected to determine creatinine phosphokinase (CPK), troponin I enzyme, myoglobin and lactate dehydrogenase (LDH) enzyme level. Echocardiography and 12-leads electrocardiogram (ECG) were also done for children in both groups. Data were analyzed using Independent-samples t-test, Mann-Whitney U, Chi square, and Fisher's exact test.
Results: The mean age of the cases group was 7.29±3.24 years versus 8.06±2.86 years for controls. In DMD group, 25% had positive family history of DMD while 35.7% of them had positive consanguinity. All cases had elevated CPK level while CPK level in controls was normal (p<0.0001). LDH level was elevated in 19 cases (67.86%) of DMD while all controls children had normal LDH level (p<0.0001). Furthermore, the mean serum myoglobin level of DMD patients was higher relative to that of healthy controls (39.39±7.25 versus 33.68 ±12.38 ng/ml respectively) (p=0.01). Echocardiography of our patients revealed that seven cases (25%) had low ejection fraction (EF) and fraction shortening (FS). In addition, all controls children had normal EF (p<0.0001) and normal FS (p<0.0001). Interestingly, ECG showed that 28.57% of cases had sinus tachycardia vs. 6.88% for controls (p=0.0001). Prolonged QTc interval was present in 39.29% of cases (mean 431.39±43.60) while all controls had normal QTc duration for age (mean of 415.17±25.2) (p<0.0001).
Conclusion: ECG manifestations in children with DMD in the form of sinus tachycardia and prolonged QTc interval are an early alarm for developing cardiomyopathy before overt echocardiographic findings appear.
References
Emery AE. Population frequencies of inherited neuromuscular diseases – a world survey.
NeuromusculDisord. 1991;1(1):19–29. doi: 10.1016/0960-8966(91)90039-U
Mah JK, Korngut L, Dykeman J, Day L, Pringsheim T, Jette N. A systematic review and meta-analysis on
the epidemiology of Duchenne and Becker muscular dystrophy. NeuromusculDisord. 2014;24(6):482–491.
doi: 10.1016/j.nmd.2014.03.008
Matsumura K, Tomé FM, Collin H, Azibi K, Chaouch M, Kaplan JC, Fardeau M, Campbell KP.
Deficiency of the 50K dystrophin-associated glycoprotein in severe childhood autosomal recessive
muscular dystrophy.Nature. 1992;359(6393):320-2. doi: 10.1038/359320a0, PMid: 1406935
Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L et al. Diagnosis and management of
Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial
management.Lancet Neurol. 2010;9(1):77-93. doi: 10.1016/S1474-4422(09)70271-6
Pane M, Lombardo ME, Alfieri P, et al. Attention deficit hyperactivity disorder and cognitive function in
Duchenne muscular dystrophy: phenotype-genotype correlation. J Pediatr. 2012;161(4):705.e1–709.e1. doi:
1016/j.jpeds.2012.03.020, PMid: 22560791
McDonald CM, Henricson EK, Abresch RT, et al. The cooperative international neuromuscular research
group Duchenne natural history study – a longitudinal investigation in the era of glucocorticoid therapy:
design of protocol and the methods used. Muscle Nerve. 2013;48(1):32–54. doi: 10.1002/mus.23807,
PMid: 23677550, PMCid: PMC4147958
Kieny P, Chollet S, Delalande P, et al. Evolution of life expectancy of patients with Duchenne muscular
dystrophy at AFM Yolaine de Kepper Centre between 1981 and 2011. Ann PhysRehabil Med.
;56(6):443–454. doi: 10.1016/j.rehab.2013.06.002, PMid: 23876223
Boland BJ, Silbert PL, Groover RV, Wollan PC, Silverstein MD. Skeletal, cardiac, and smooth muscle
failure in Duchenne muscular dystrophy.Pediatr Neurol. 1996;14(1):7-12. doi: 10.1016/0887- 8994(95)00251-0
Tuffery-Giraud S, Béroud C, Leturcq F, Yaou RB, Hamroun D, Michel-Calemard L et al. Genotype- phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of
nationwide knowledgebase.Hum Mutat. 2009;30(6):934-45. doi: 10.1002/humu.20976, PMid: 19367636
Goyenvalle A, Seto JT, Davies KE, Chamberlain J. Therapeutic approaches to muscular dystrophy.Hum
Mol Genet. 2011;20(R1):R69-78. doi: 10.1093/hmg/ddr105, PMid: 21436158, PMCid: PMC3095062
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 Disord2003; 13:166–172. doi: 10.1016/S0960-8966(02)00213-4
Wagner KR, Lechtzin N, Judge DP. Current treatment of adult Duchenne muscular
dystrophy.BiochimBiophysActa. 2007;1772(2):229-37. doi: 10.1016/j.bbadis.2006.06.009
Kwon SW, Kang SW, Kim JY, Choi EY, Yoon YW, Park YM et al. Outcomes of cardiac involvement in
patients with late-stage Duchenne muscular dystrophy under management in the pulmonary rehabilitation
center of a tertiary referral hospital.Cardiology. 2012;121(3):186-93. doi: 10.1159/000336810, PMid:
Shirokova N., Niggli E. Cardiac phenotype of duchenne muscular dystrophy: Insights from cellular studies.
J. Mol. Cell. Cardiol. 2013;58:217–224. doi: 10.1016/j.yjmcc.2012.12.009, PMid: 23261966, PMCid:
PMC3615054
Nigro G., Comi L.I., Politano L., Bain R.J. The incidence and evolution of cardiomyopathy in duchenne
muscular dystrophy. Int. J. Cardiol. 1990;26:271–277. doi: 10.1016/0167-5273(90)90082-G
Hor K.N., Taylor M.D., Al-Khalidi H.R., Cripe L.H., Raman S.V., Jefferies J.L., O’Donnell R., Benson
D.W., Mazur W. Prevalence and distribution of late gadolinium enhancement in a large population of
patients with duchenne muscular dystrophy: Effect of age and left ventricular systolic function. J.
Cardiovasc. Magn. Reson. 2013;15:107. doi: 10.1186/1532-429X-15-107, PMid: 24359596, PMCid:
PMC3896985
Mazur W., Hor K.N., Germann J.T., Fleck R.J., Al-Khalidi H.R., Wansapura J.P., Chung E.S., Taylor
M.D., Jefferies J.L., Benson D.W., et al. Patterns of left ventricular remodeling in patients with duchenne
muscular dystrophy: A cardiac mri study of ventricular geometry, global function, and strain. Int. J.
Cardiovasc. Imaging. 2012;28:99–107. doi: 10.1007/s10554-010-9781-2, PMid: 21222036
Hermans M.C., Pinto Y.M., Merkies I.S., de Die-Smulders C.E., Crijns H.J., Faber C.G. Hereditary
muscular dystrophies and the heart. Neuromusc. Disord. 2010;20:479–492. doi:
1016/j.nmd.2010.04.008, PMid: 20627570
Yanagisawa A., Miyagawa M., Yotsukura M., Tsuya T., Shirato C., Ishihara T., Aoyagi T., Ishikawa K.
The prevalence and prognostic significance of arrhythmias in duchenne type muscular dystrophy. Am.
Heart J. 1992;124:1244–1250. doi: 10.1016/0002-8703(92)90407-M
Chenard A.A., Becane H.M., Tertrain F., de Kermadec J.M., Weiss Y.A. Ventricular arrhythmia in
duchenne muscular dystrophy: Prevalence, significance and prognosis. Neuromusc. Disord. 1993;3:201–
doi: 10.1016/0960-8966(93)90060-W
Hampton JR. The ECG Made Easy. 7th edition. London: Churchill Livingstone 2008.
Rijnbeek PR, Witsenburg M, Schrama E, Hess J, Kors JA. New normal limits for the paediatric
electrocardiogram.Eur Heart J. 2001;22(8):702-11. doi: 10.1053/euhj.2000.2399, PMid: 11286528
Emery AEH. :Duchenne muscular dystrophy or Meryon’s disease. In:The Muscular Dystrophies. 2nd
edition. Oxford: Oxford University Press, 55–71, 1993. doi: 10.1016/0960-8966(93)90018-F
Melacini P, Vianello A, Villanova C, Fanin M, Miorin M, Angelini C et al. Cardiac and respiratory
involvement in advanced stage Duchenne muscular dystrophy.NeuromusculDisord. 1996;6(5):367-76. doi:
1016/0960-8966(96)00357-4
Duboc D, Meune C, Pierre B, Wahbi K, Eymard B, Toutain A et al. Perindopril preventive treatment on
mortality in Duchenne muscular dystrophy: 10 years' follow-up.Am Heart J. 2007;154(3):596-602. doi:
1016/j.ahj.2007.05.014, PMid: 17719312
Jefferies JL, Eidem BW, Belmont JW, Craigen WJ, Ware SM, Fernbach SD et al. Genetic predictors and
remodeling of dilated cardiomyopathy in muscular dystrophy.Circulation. 2005;112(18):2799-804. doi:
1161/CIRCULATIONAHA.104.528281, PMid: 16246949
Kajimoto H, Ishigaki K, Okumura K, Tomimatsu H, Nakazawa M, Saito K et al. Beta-blocker therapy for
cardiac dysfunction in patients with muscular dystrophy.Circ J. 2006;70(8):991-4. doi:
1253/circj.70.991, PMid: 16864930
Ramaciotti C, Heistein LC, Coursey M, Lemler MS, Eapen RS, Iannaccone ST 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(6):825-7. doi: 10.1016/j.amjcard.2006.04.020, PMid: 16950195
Gesmar Volga Haddad Herdy, Roberta Duarte BezerraPinto,Guilherme de Almeida Costa, Ana
FlaviaMalheirosTorbey, VivianneGalante Ramos, MarcioMoacyrVasconcelos. Clinical and molecular
study on Duchenne muscular dystrophy. International Journal of Cardiovascular Sciences2015;28(3):173- 180, 2015.
Ohlendieck K. Proteomic identification of biomarkers of skeletal muscle disorders.Biomark Med.
;7(1):169-86. doi: 10.2217/bmm.12.96, PMid: 23387498
Carp SJ, Barr AE, Barbe MF. Serum biomarkers as signals for risk and severity of work-related
musculoskeletal injury.Biomark Med. 2008 Feb;2(1):67-79. doi: 10.2217/17520363.2.1.67, PMid:
Brancaccio P, Lippi G, Maffulli N. Biochemical markers of muscular damage.ClinChem Lab Med.
;48(6):757-67. doi: 10.1515/CCLM.2010.179
Hathout Y, Brody E, Clemens PR, Cripe L, DeLisle RK, Furlong P et al. Large-scale serum protein
biomarker discovery in Duchenne muscular dystrophy.ProcNatlAcadSci U S A. 2015;112(23):7153-8. doi:
1073/pnas.1507719112, PMid: 26039989, PMCid: PMC4466703
Markham LW, Michelfelder EC, Border WL, Khoury PR, Spicer RL, Wong BL et al. Abnormalities of
diastolic function precede dilated cardiomyopathy associated with Duchenne muscular dystrophy.J Am
SocEchocardiogr. 2006 ;19(7):865-71. doi: 10.1016/j.echo.2006.02.003, PMid: 16824995
Thrush PT, Allen HD, Viollet L, Mendell JR. Re-examination of the electrocardiogram in boys with
Duchenne muscular dystrophy and correlation with its dilated cardiomyopathy.Am J Cardiol.
;103(2):262-5. doi: 10.1016/j.amjcard.2008.08.064, PMid: 19121448
Thomas TO, Morgan TM, Burnette WB, Markham LW. Correlation of heart rate and cardiac dysfunction in
Duchenne muscular dystrophy.PediatrCardiol. 2012;33(7):1175-9. doi: 10.1007/s00246-012-0281-0
Spurney CF.Cardiomyopathy of Duchenne muscular dystrophy: current understanding and future
directions.Muscle Nerve. 2011;44(1):8-19. doi: 10.1002/mus.22097, PMid: 21674516
Martin AB, Garson A Jr, Perry JC. Prolonged QT interval in hypertrophic and dilated cardiomyopathy in
children.Am Heart J. 1994;127(1):64-70. doi: 10.1016/0002-8703(94)90510-X
Published
Issue
Section
License
Copyright (c) 2020 KNOWLEDGE KINGDOM PUBLISHING
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
