Conclusions
Repeat investigations have demonstrated that sudden cardiac death in patients with dilated cardiomyopathy and severely diminished LV systolic function is far rarer in the pediatric population than in adults. Despite this, recommendations for ICD implantation in DMD are generally extrapolated from adult data into the pediatric population. Moreover, our advances in heart failure have allowed children with Duchenne cardiomyopathy to grow into adults with Duchenne cardiomyopathy, and the need for evidence-based disease-specific recommendations is great. There is limited evidence to suggest sudden death in Duchenne Muscular Dystrophy is typically from an arrhythmic cause. More likely, pathologic cardiopulmonary interactions manifest as sudden death. The inability to correlate holter findings to cardiac arrest risk make discussions about ICD placement challenging, as there is not significant evidence suggesting placement meaningfully prolongs life in these patients. The placement of an ICD is not without risk; the patient will need anesthesia which may require intubation or other respiratory support. In our institution, our practice is to discuss ICD placement only in presence of both severely decreased ejection fraction and ventricular arrhythmias. While ICDs are an effective method to prevent arrhythmic death in cardiac disease, the absolute risk of sudden cardiac arrest in the dystrophin-deficient cardiomyopathies is low, and the decision to implant an ICD must be thoughtfully discussed with the patient and his caregivers, and in accordance with their goals of care.
1. Buddhe S, Cripe L, Friedland-Little J, et al. Cardiac Management of the Patient With Duchenne Muscular Dystrophy. Pediatrics.2018;142(Suppl 2):S72-S81.
2. Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 2018;17(4):347-361.
3. Melacini P, Fanin M, Danieli GA, et al. Myocardial involvement is very frequent among patients affected with subclinical Becker’s muscular dystrophy. Circulation. 1996;94(12):3168-3175.
4. Hor KN, Taylor MD, Al-Khalidi HR, et al. 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.
5. Bilchick KC, Salerno M, Plitt D, et al. Prevalence and distribution of regional scar in dysfunctional myocardial segments in Duchenne muscular dystrophy. J Cardiovasc Magn Reson. 2011;13:20.
6. Johnston TP, Cripe LH, Mah ML, et al. Young Becker Muscular Dystrophy Patients Demonstrate Fibrosis Associated With Abnormal Left Ventricular Ejection Fraction on Cardiac Magnetic Resonance Imaging. Circ Cardiovasc Imaging. 2019;12(7):e008919.
7. Rajdev A, Groh WJ. Arrhythmias in the muscular dystrophies.Card Electrophysiol Clin. 2015;7(2):303-308.
8. Fitch CW, Ainger LE. The Frank vectorcardiogram and the electrocardiogram in Duchenne progressive muscular dystrophy.Circulation. 1967;35(6):1124-1140.
9. Slucka C. The electrocardiogram in Duchenne progressive muscular dystrophy. Circulation. 1968;38(5):933-940.
10. Das MK, Zipes DP. Fragmented QRS: a predictor of mortality and sudden cardiac death. Heart Rhythm. 2009;6(3 Suppl):S8-14.
11. Cho MJ, Lee JW, Lee J, Shin YB, Lee HD. Relationship Between Fragmented QRS Complexes and Cardiac Status in Duchenne Muscular Dystrophy: Multimodal Validation Using Echocardiography, Magnetic Resonance Imaging, and Holter Monitoring. Pediatr Cardiol.2017;38(5):1042-1048.
12. Gavillet B, Rougier JS, Domenighetti AA, et al. Cardiac sodium channel Nav1.5 is regulated by a multiprotein complex composed of syntrophins and dystrophin. Circ Res. 2006;99(4):407-414.
13. Albesa M, Ogrodnik J, Rougier JS, Abriel H. Regulation of the cardiac sodium channel Nav1.5 by utrophin in dystrophin-deficient mice.Cardiovasc Res. 2011;89(2):320-328.
14. Ebner J, Uhrin P, Szabo PL, et al. Reduced Na(+) current in Purkinje fibers explains cardiac conduction defects and arrhythmias in Duchenne muscular dystrophy. Am J Physiol Heart Circ Physiol.2020;318(6):H1436-H1440.
15. Chenard AA, Becane HM, Tertrain F, de Kermadec JM, Weiss YA. Ventricular arrhythmia in Duchenne muscular dystrophy: prevalence, significance and prognosis. Neuromuscul Disord.1993;3(3):201-206.
16. Juan-Mateu J, Gonzalez-Quereda L, Rodriguez MJ, et al. DMD Mutations in 576 Dystrophinopathy Families: A Step Forward in Genotype-Phenotype Correlations. PLoS One. 2015;10(8):e0135189.
17. Tandon A, Jefferies JL, Villa CR, et al. Dystrophin genotype-cardiac phenotype correlations in Duchenne and Becker muscular dystrophies using cardiac magnetic resonance imaging. Am J Cardiol.2015;115(7):967-971.
18. Kaspar RW, Allen HD, Ray WC, et al. Analysis of dystrophin deletion mutations predicts age of cardiomyopathy onset in becker muscular dystrophy. Circ Cardiovasc Genet. 2009;2(6):544-551.
19. Yamamoto T, Awano H, Zhang Z, et al. Cardiac Dysfunction in Duchenne Muscular Dystrophy Is Less Frequent in Patients With Mutations in the Dystrophin Dp116 Coding Region Than in Other Regions. Circ Genom Precis Med. 2018;11(1):e001782.
20. Chiang DY, Allen HD, Kim JJ, et al. Relation of Cardiac Dysfunction to Rhythm Abnormalities in Patients With Duchenne or Becker Muscular Dystrophies. Am J Cardiol. 2016;117(8):1349-1354.
21. Altekin RE, Yanikoglu A, Ucar M, Ermis C. Complete AV block and cardiac syncope in a patient with Duchenne muscular dystrophy. J Cardiol Cases. 2011;3(2):e68-e70.
22. Segawa K, Komaki H, Mori-Yoshimura M, et al. Cardiac conduction disturbances and aging in patients with Duchenne muscular dystrophy.Medicine (Baltimore). 2017;96(42):e8335.
23. Villa CR, Czosek RJ, Ahmed H, et al. Ambulatory Monitoring and Arrhythmic Outcomes in Pediatric and Adolescent Patients With Duchenne Muscular Dystrophy. J Am Heart Assoc. 2015;5(1).
24. Punnoose AR, Kaltman JR, Pastor W, McCarter R, He J, Spurney CF. Cardiac Disease Burden and Risk of Mortality in Hospitalized Muscular Dystrophy Patients. Pediatr Cardiol. 2016;37(7):1290-1296.
25. Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Circulation. 2008;117(21):e350-408.
26. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2018;72(14):1677-1749.
27. Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy.N Engl J Med. 2004;350(21):2151-2158.
28. Dimas VV, Denfield SW, Friedman RA, et al. Frequency of cardiac death in children with idiopathic dilated cardiomyopathy. Am J Cardiol. 2009;104(11):1574-1577.
29. Pahl E, Sleeper LA, Canter CE, et al. Incidence of and risk factors for sudden cardiac death in children with dilated cardiomyopathy: a report from the Pediatric Cardiomyopathy Registry. J Am Coll Cardiol. 2012;59(6):607-615.
30. Corrado G, Lissoni A, Beretta S, et al. Prognostic value of electrocardiograms, ventricular late potentials, ventricular arrhythmias, and left ventricular systolic dysfunction in patients with Duchenne muscular dystrophy. Am J Cardiol. 2002;89(7):838-841.
31. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.Eur J Heart Fail. 2016;18(8):891-975.
32. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol.2017;70(6):776-803.
33. Mavrogeni SI, Markousis-Mavrogenis G, Papavasiliou A, Papadopoulos G, Kolovou G. Cardiac Involvement in Duchenne Muscular Dystrophy and Related Dystrophinopathies. Methods Mol Biol. 2018;1687:31-42.
34. Raman SV, Hor KN, Mazur W, et al. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol.2015;14(2):153-161.
35. Raman SV, Hor KN, Mazur W, et al. Stabilization of Early Duchenne Cardiomyopathy With Aldosterone Inhibition: Results of the Multicenter AIDMD Trial. J Am Heart Assoc. 2019;8(19):e013501.
36. Raman SV, Hor KN, Mazur W, et al. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial. Orphanet J Rare Dis. 2017;12(1):39.
37. Tracy CM, Epstein AE, Darbar D, et al. 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. [corrected]. Circulation.2012;126(14):1784-1800.
38. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005;352(3):225-237.
39. Bourke JP, Guglieri M, Duboc D, Group EtWS. 238th ENMC International Workshop: Updating management recommendations of cardiac dystrophinopathyHoofddorp, The Netherlands, 30 November - 2 December 2018. Neuromuscul Disord. 2019;29(8):634-643.
40. Connuck DM, Sleeper LA, Colan SD, 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(6):998-1005.
41. McCulloch MA, Lal AK, Knecht K, et al. Implantable Cardioverter Defibrillator Use in Males with Duchenne Muscular Dystrophy and Severe Left Ventricular Dysfunction. Pediatr Cardiol.2020;41(5):925-931.
42. Hiermeier UM, Baker C, Bourke JP. Exploring the acceptability of implantable defibrillators in patients with cardiac dystrophinopathy and carers. Open Heart. 2020;7(1):e001230.