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Cardiac Involvement in Duchenne Muscular Dystrophy and Related Dystrophinopathies

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Duchenne Muscular Dystrophy

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1687))

Abstract

Dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy (XLCM), and facioscapulohumeral muscular dystrophy (FSHD). DMD/BMD are X-linked recessive disorders, related to the synthesis of dystrophin. Most of DMD after the third decade of their age develop cardiomyopathy that remains silent, due to relative physical inactivity. Cardiac disease in female carriers presents with hypertrophy, arrhythmias or dilated cardiomyopathy, clinically overt by increasing age.

In ECG, DMD presents increased R/S ratio in the right precordial leads, deep Q waves in the lateral leads, conduction abnormalities, and arrhythmias. Echocardiography, although widely available and inexpensive, is highly depended on the acoustic window and operator’s experience. Tissue Doppler can be used to identify early changes of cardiomyopathy and detect progressive cardiac damage. CMR, a noninvasive, nonradiating technique, by evaluation of cardiac volumes, mass, ejection fraction, inflammation, and fibrosis, is ideal for early diagnosis. Subepicardial fibrosis in the inferolateral wall is the typical CMR lesion in DMD/BMD.

Early initiation of angiotensin converting enzyme inhibitors (ACEI) treatment, such as perindopril, was associated with lower mortality in DMD with normal LV ejection fraction at study entry. Other studies documented that a beta-blocker (BB), in addition to ACEI, improves LV systolic function in MD. These encouraging results recommend initiation of ACEI and/or BB early after diagnosis of the muscular dystrophy, especially in DMD.

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References

  1. Hoffman EP, Brown RH Jr, Kunkel LM (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51:919–928

    Article  CAS  PubMed  Google Scholar 

  2. Monaco AP, Bertelson CJ, Liechti-Gallati S et al (1988) An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 2:90–95

    Article  CAS  PubMed  Google Scholar 

  3. Bushby K, Finkel R, Birnkrant DJ et al (2010) Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol 9:177–189

    Article  CAS  PubMed  Google Scholar 

  4. Rafael JA, Cox GA, Corrado K et al (1996) Forced expression of dystrophin deletion constructs reveals structure-function correlations. J Cell Biol 134:93–102

    Article  CAS  PubMed  Google Scholar 

  5. Corrado K, Rafael JA, Mills PL et al (1996) Transgenic mdx mice expressing dystrophin with a deletion in the actin-binding domain display a “mild Becker” phenotype. J Cell Biol 134:873–884

    Article  CAS  PubMed  Google Scholar 

  6. Petrof BJ, Shrager JB, Stedman HH et al (1993) Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci U S A 90:3710–3714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wallace GQ, McNally EM (2009) Mechanisms of muscle degeneration, regeneration and repair in the muscular dystrophies. Annu Rev Physiol 71:37–57

    Article  CAS  PubMed  Google Scholar 

  8. Bushby KM, Thambyayah M, Gardner-Medwin D (1991) Prevalence and incidence of Becker muscular dystrophy. Lancet 337:1022–1024

    Article  CAS  PubMed  Google Scholar 

  9. Emery AE, Skinner R (1976) Clinical studies in benign (Becker type) X-linked muscular dystrophy. Clin Genet 10:189–201

    Article  CAS  PubMed  Google Scholar 

  10. Bradley WG, Jones MZ, Mussini JM et al (1978) Becker-type muscular dystrophy. Muscle Nerve 1:111–132

    Article  CAS  PubMed  Google Scholar 

  11. Bushby KM, Gardner-Medwin D (1993) The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy. I Natural history. J Neurol 240:98–104

    Article  CAS  PubMed  Google Scholar 

  12. Hoogerwaard EM, de Voogt WG, Wilde AA et al (1997) Evolution of cardiac abnormalities in Becker muscular dystrophy over a 13-year period. J Neurol 244:657–663

    Article  CAS  PubMed  Google Scholar 

  13. Towbin JA, Hejtmancik JF, Brink P et al (1993) X linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. Circulation 87:1854–1865

    Article  CAS  PubMed  Google Scholar 

  14. van Dijk GP, van der Kooi E, Behin A et al (2014) High prevalence of incomplete right bundle branch block in facioscapulohumeral muscular dystrophy without cardiac symptoms. Funct Neurol 29(3):159–165

    PubMed  PubMed Central  Google Scholar 

  15. McNally EM (2007) New approaches in the therapy of cardiomyopathy in muscular dystrophy. Annu Rev Med 58:75–88

    Article  CAS  PubMed  Google Scholar 

  16. Ashwath ML, Jacobs IB, Crowe CA et al (2014) Left ventricular dysfunction in duchenne muscular dystrophy and genotype. Am J Cardiol 114(2):284–289

    Article  PubMed  PubMed Central  Google Scholar 

  17. Raman SV, Hor KN, Mazur W et al (2014) Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 14:153–161. pii: S1474–4422(14)70318–7

    Article  PubMed  PubMed Central  Google Scholar 

  18. Melacini P, Fanin M, Danieli GA et al (1996) Myocardial involvement is very frequent among patients affected with subclinical Becker’s muscular dystrophy. Circulation 94:3168–3175

    Article  CAS  PubMed  Google Scholar 

  19. Politano L, Nigro V, Nigro G et al (1996) Development of cardiomyopathy in female carriers of Duchenne and Becker dystrophy. JAMA 275:1335–1338

    Article  CAS  PubMed  Google Scholar 

  20. Nolan MA, Jones OD, Pedersen RL et al (2003) Cardiac assessment in childhood carriers of Duchenne and Becker muscular dystrophies. Neuromuscul Disord 13:129–132

    Article  CAS  PubMed  Google Scholar 

  21. Hoogerwaard EM, Bakker E, Ippel PF et al (1999) Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in The Netherlands: a cohort study. Lancet 353:2116–2119

    Article  CAS  PubMed  Google Scholar 

  22. Hoogerwaard EM, van der Wouw PA, Wilde AA et al (1999) Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy. Neuromuscul Disord 9:347–351

    Article  CAS  PubMed  Google Scholar 

  23. Grain L, Cortina-Borja M, Forfar C et al (2001) Cardiac abnormalities and skeletal muscle weakness in carriers of Duchenne and Becker muscular dystrophies and controls. Neuromuscul Disord 11:186–191

    Article  CAS  PubMed  Google Scholar 

  24. Melacini P, Fanin M, Angelini A et al (1988) Cardiac transplantation in a Duchenne muscular dystrophy carrier. Neuromuscul Disord 8:585–590

    Article  Google Scholar 

  25. Davies JE, Winokur TS, Aaron MF et al (2001) Cardiomyopathy in a carrier of Duchenne’s muscular dystrophy. J Heart Lung Transplant 20:781–784

    Article  CAS  PubMed  Google Scholar 

  26. Weiss RM, Kerber RE, Jones JK et al (2010) Exercise-induced left ventricular systolic dysfunction in women heterozygous for dystrophinopathy. J Am Soc Echocardiogr 23(8):848–853

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mavrogeni S, Bratis K, Papavasiliou A et al (2013) CMR detects subclinical cardiomyopathy in mother-carriers of Duchenne and Becker muscular dystrophy. JACC Cardiovasc Imaging 6(4):526–528

    Article  PubMed  Google Scholar 

  28. Darras BT, Miller DT, Urion DK 1993–2014. Dystrophinopathies. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Smith RJH, Stephens K, editors Gene reviews [Internet]. Seattle, WA: University of Washington, Seattle

    Google Scholar 

  29. Berko BA, Swift M (1987) X-linked dilated cardiomyopathy. N Engl J Med 316:1186–1191

    Article  CAS  PubMed  Google Scholar 

  30. McMurray JJ, Ostergren J, Swedberg K, CHARM Investigators and Committees et al (2003) Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM added trial. Lancet 362:767–771

    Article  CAS  PubMed  Google Scholar 

  31. Duboc D, Meune C, Pierre B et al (2007) Perindopril preventive treatment on mortality in Duchenne muscular dystrophy: 10 years’ follow- up. Am Heart J 154:596–602

    Article  CAS  PubMed  Google Scholar 

  32. Kajimoto H, Ishigaki K, Okumura K et al (2006) Beta-blocker therapy for cardiac dysfunction in patients with muscular dystrophy. Circ J 70:991–994

    Article  CAS  PubMed  Google Scholar 

  33. Menon SC, Etheridge SP, Liesemer KN et al (2014) Predictive value of myocardial delayed enhancement in Duchenne muscular dystrophy. Pediatr Cardiol 35:1279–1285

    Article  PubMed  Google Scholar 

  34. Bleeker GB, Kaandorp TA, Lamb HJ et al (2006) Effect of posterolateral scar tissue on clinical and echocardiographic improvement after cardiac resynchronization therapy. Circulation 113:969–976

    Article  PubMed  Google Scholar 

  35. Silver MA, Maisel A, Yancy CW et al (2004) BNP consensus panel 2004: a clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases. Congest Heart Fail 10:1–30

    Article  CAS  Google Scholar 

  36. Thrush PT, Allen HD, Viollet L et al (2009) Re-examination of the electrocardiogram in boys with Duchenne muscular dystrophy and correlation with its dilated cardiomyopathy. Am J Cardiol 103:262–265

    Article  PubMed  Google Scholar 

  37. Muntoni F (2003) Cardiomyopathy in muscular dystrophies. Curr Opin Neurol 16:577–583

    Article  PubMed  Google Scholar 

  38. D'Orsogna L, O'Shea JP, Miller G (1988) Cardiomyopathy of Duchenne muscular dystrophy. Pediatr Cardiol 9:205–213

    Article  PubMed  Google Scholar 

  39. Santos MA, Costa Fde A, Travessa AF et al (2010) Duchenne muscular dystrophy: electrocardiographic analysis of 131 patients. Arq Bras Cardiol 94(5):620–624

    Article  PubMed  Google Scholar 

  40. Kirchmann C, Kececioglu D, Korinthenberg R et al (2005) Echocardiographic and electrocardiographic findings of cardiomyopathy in Duchenne and Becker-Kiener muscular dystrophies. Pediatr Cardiol 26:66–72

    Article  CAS  PubMed  Google Scholar 

  41. Eriksson P, Po H, Eriksson H et al (1998) Bundle-branch block in a general male population: the study of men born 1913. Circulation 98:2494–2500

    Article  CAS  PubMed  Google Scholar 

  42. Mori K, Hayabuchi Y, Inoue M et al (2007) Myocardial strain imaging for early detection of cardiac involvement in patients with Duchenne’s progressive muscular dystrophy. Echocardiography 24:598–608

    Article  PubMed  Google Scholar 

  43. Giatrakos N, Kinali M, Stephens D et al (2006) 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 92(6):840–842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mavrogeni S, Tzelepis GE, Athanasopoulos G et al (2005) Cardiac and sternocleidomastoid muscle involvement in Duchenne muscular dystrophy: an MRI study. Chest 127:143–148

    Article  PubMed  Google Scholar 

  45. Schalla S, Nagel E, Lehmkuhl H et al (2001) Comparison of magnetic resonance real-time imaging of LV function with conventional magnetic resonance imaging and echocardiography. Am J Cardiol 87:95–99

    Article  CAS  PubMed  Google Scholar 

  46. Ashford MW, Liu W, Lin SJ et al (2005) Occult cardiac contractile dysfunction in dystrophin-deficient children revealed by cardiac magnetic resonance strain imaging. Circulation 112:2462–2467

    Article  PubMed  Google Scholar 

  47. Mavrogeni S, Markousis-Mavrogenis G, Papavasiliou A et al (2015) Cardiac involvement in Duchenne and Becker muscular dystrophy. World J Cardiol 7(7):410–414

    Article  PubMed  PubMed Central  Google Scholar 

  48. Hor KN, Wansapura J, Markham LW et al (2009) Circumferential strain analysis identifies strata of cardiomyopathy in Duchenne muscular dystrophy: a cardiac magnetic resonance tagging study. J Am Coll Cardiol 53:1204–1210

    Article  PubMed  PubMed Central  Google Scholar 

  49. Hagenbuch SC, Gottliebson WM, Wansapura J et al (2010) Detection of progressive cardiac dysfunction by serial evaluation of circumferential strain in patients with Duchenne muscular dystrophy. Am J Cardiol 105:1451–1455

    Article  PubMed  Google Scholar 

  50. Mavrogeni S, Papavasiliou A, Skouteli E et al (2010) Cardiovascular magnetic resonance imaging evaluation of two families with Becker muscular dystrophy. Neuromuscul Disord 20(11):717–719

    Article  PubMed  Google Scholar 

  51. Duboc D, Meune C, Lerebours G et al (2005) Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J Am Coll Cardiol 45:855–857

    Article  CAS  PubMed  Google Scholar 

  52. Silva MC, Meira ZM, Gurgel Giannetti J et al (2007) Myocardial delayed enhancement by magnetic resonance imaging in patients with muscular dystrophy. J Am Coll Cardiol 49:1874–1879

    Article  PubMed  Google Scholar 

  53. Dittrich S, Tuerk M, Haaker G et al (2015) Cardiomyopathy in Duchenne muscular dystrophy: current value of clinical, electrophysiological and imaging findings in children and teenagers. Klin Padiatr 227(4):225–231

    Article  CAS  PubMed  Google Scholar 

  54. Turkbey EB, Gai N, Lima JA et al (2012) Assessment of cardiac involvement in myotonic muscular dystrophy by T1 mapping on magnetic resonance imaging. Heart Rhythm 9(10):1691–1697

    Article  PubMed  PubMed Central  Google Scholar 

  55. van Westrum S, Dekker L, de Haan R et al (2013) Brain natriuretic peptide is not predictive of dilated cardiomyopathy in Becker and Duchenne muscular dystrophy patients and carriers. BMC Neurol 13:88

    Article  Google Scholar 

  56. Kim RJ, Fieno DS, Parrish TB et al (1999) Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 100:1992–2002

    Article  CAS  PubMed  Google Scholar 

  57. Kwong RY, Chan AK, Brown KA et al (2006) Impact of unrecognized myocardial scar detected by cardiac magnetic resonance imaging on event-free survival in patients presenting with signs or symptoms of coronary artery disease. Circulation 113:2733–2743

    Article  PubMed  Google Scholar 

  58. Perazzolo Marra M, De Lazzari M, Zorzi A et al (2014) Impact of the presence and amount of myocardial fibrosis by cardiac magnetic resonance on arrhythmic outcome and sudden cardiac death in nonischemic dilated cardiomyopathy. Heart Rhythm 11(5):856–863

    Article  PubMed  Google Scholar 

  59. Badorff C, Knowlton KU (2004) Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside. Med Microbiol Immunol 193:121–126

    Article  CAS  PubMed  Google Scholar 

  60. Mavrogeni S, Papavasiliou A, Spargias K et al (2010) Myocardial inflammation in Duchenne muscular dystrophy as a precipitating factor for heart failure: a prospective study. BMC Neurol 10:33

    Article  PubMed  PubMed Central  Google Scholar 

  61. Dennert R, Crijns HJ, Heymans S (2008) Acute viral myocarditis. Eur Heart J 29:2073–2082

    Article  PubMed  PubMed Central  Google Scholar 

  62. Cooper LT, Baughman KL, Feldman AM, et al (2007). American Heart Association, American College of Cardiology, European Society of Cardiology, Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol 50:1914–1931

    Google Scholar 

  63. Friedrich MG, Sechtem U, Schulz-Menger J et al (2009) International consensus group on cardiovascular magnetic resonance in myocarditis. Cardiovascular magnetic resonance in myocarditis: a JACC white paper. J Am Coll Cardiol 53(17):1475–1487

    Article  PubMed  PubMed Central  Google Scholar 

  64. Bertaso AG, Bertol D, Duncan BB et al (2013) Epicardial fat: definition, measurements and systematic review of main outcomes. Arq Bras Cardiol 101(1):e18–e28

    PubMed  PubMed Central  Google Scholar 

  65. Frankel KA, Rosser RJ (1976) The pathology of the heart in progressive muscular dystrophy: epimyocardial fibrosis. Hum Pathol 7:375–386

    Article  CAS  PubMed  Google Scholar 

  66. Florian A, Ludwig A, Rösch S et al (2014) Myocardial fibrosis imaging based on T1-mapping and extracellular volume fraction (ECV) measurement in muscular dystrophy patients: diagnostic value compared with conventional late gadolinium enhancement (LGE) imaging. Eur Heart J Cardiovasc Imaging 15(9):1004–1012

    Article  PubMed  Google Scholar 

  67. McNally EM, Kaltman JR, Benson DW, et al (2015). Working Group of the National Heart, Lung, and Blood Institute; Parent Project Muscular Dystrophy. Contemporary cardiac issues in Duchenne muscular dystrophy. Working Group of the National Heart, Lung, and Blood Institute in collaboration with parent project muscular dystrophy. Circulation.131(18):1590–598

    Google Scholar 

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Authors and Affiliations

  1. Onassis Cardiac Surgery Center, 50 Esperou Street, 175-61 P.Faliro, Athens, Greece

    Sophie I. Mavrogeni, George Markousis-Mavrogenis & Genovefa Kolovou

  2. Pentelis Children’s Hospital, Athens, Greece

    Antigoni Papavasiliou

  3. Agia Sofia Children’s Hospital, Athens, Greece

    George Papadopoulos

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  1. Sophie I. Mavrogeni
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  2. George Markousis-Mavrogenis
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  3. Antigoni Papavasiliou
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  4. George Papadopoulos
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  5. Genovefa Kolovou
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Correspondence to Sophie I. Mavrogeni .

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  1. Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, Roma, Italy

    Camilla Bernardini

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Mavrogeni, S.I., Markousis-Mavrogenis, G., Papavasiliou, A., Papadopoulos, G., Kolovou, G. (2018). Cardiac Involvement in Duchenne Muscular Dystrophy and Related Dystrophinopathies. In: Bernardini, C. (eds) Duchenne Muscular Dystrophy. Methods in Molecular Biology, vol 1687. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7374-3_3

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  • DOI: https://doi.org/10.1007/978-1-4939-7374-3_3

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7373-6

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