Predictors of cardiac disease in duchenne muscular dystrophy: a systematic review and evidence grading.
Cardiomyopathy
GRADE
Guidelines
Heart
Neuromuscular disease
Treatment
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
28 Sep 2024
28 Sep 2024
Historique:
received:
15
11
2023
accepted:
18
09
2024
medline:
29
9
2024
pubmed:
29
9
2024
entrez:
28
9
2024
Statut:
epublish
Résumé
Duchenne muscular dystrophy (DMD) is a rare disease that causes progressive muscle degeneration resulting in life-threatening cardiac complications. The objective of this systematic literature review was to describe and grade the published evidence of predictors of cardiac disease in DMD. The review encompassed searches of Embase, MEDLINE ALL, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of cardiac disease in DMD. The certainty of evidence (i.e., very low to high) was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. We included 33 publications encompassing 9,232 patients with DMD. We found moderate- to high-quality evidence that cardiac medication (i.e., ACE inhibitors [enalapril and perindopril], β-blockers [carvedilol], and mineralocorticoid receptor antagonists [eplerenone]) are significantly associated with preserved left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular circumferential strain (LVCS). DMD mutations in exons 51 and 52 were found to be significantly associated with lower risk of cardiomyopathy; deletions treatable by exon 53 skipping and mutations in the Dp116 coding region with improved LVEF and prolonged cardiac dysfunction-free survival; and exons 45-50 and 52 with early left ventricular systolic dysfunction (low/very low-quality evidence). We found high-quality evidence that glucocorticoids (deflazacort) are significantly associated with preserved LVEF and improved fractional shortening (FS), and low-quality evidence that glucocorticoids (deflazacort, prednisone, and/or prednisolone) are associated with improved ejection fraction (EF) and lower risk of cardiomyopathy, ventricular dysfunction, and heart failure-related mortality. Full-time mechanical ventilation was found to be significantly correlated with LVEF (low-quality evidence), muscle strength with FS (low-quality evidence), and genetic modifiers (i.e., LTBP4 rs10880 and ACTN3) with LVEF, lower risk of cardiomyopathy and left ventricular dilation (low-quality evidence). Several sources of cardiac disease heterogeneity are well-studied in patients with DMD. Yet, the certainty of evidence is generally low, and little is known of the contribution of non-pharmacological interventions, as well as the impact of different criteria for initiation of specific treatments. Our findings help raise awareness of prevailing unmet needs, shape expectations of treatment outcomes, and inform the design of future research.
Sections du résumé
BACKGROUND
BACKGROUND
Duchenne muscular dystrophy (DMD) is a rare disease that causes progressive muscle degeneration resulting in life-threatening cardiac complications. The objective of this systematic literature review was to describe and grade the published evidence of predictors of cardiac disease in DMD.
METHODS
METHODS
The review encompassed searches of Embase, MEDLINE ALL, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of cardiac disease in DMD. The certainty of evidence (i.e., very low to high) was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework.
RESULTS
RESULTS
We included 33 publications encompassing 9,232 patients with DMD. We found moderate- to high-quality evidence that cardiac medication (i.e., ACE inhibitors [enalapril and perindopril], β-blockers [carvedilol], and mineralocorticoid receptor antagonists [eplerenone]) are significantly associated with preserved left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular circumferential strain (LVCS). DMD mutations in exons 51 and 52 were found to be significantly associated with lower risk of cardiomyopathy; deletions treatable by exon 53 skipping and mutations in the Dp116 coding region with improved LVEF and prolonged cardiac dysfunction-free survival; and exons 45-50 and 52 with early left ventricular systolic dysfunction (low/very low-quality evidence). We found high-quality evidence that glucocorticoids (deflazacort) are significantly associated with preserved LVEF and improved fractional shortening (FS), and low-quality evidence that glucocorticoids (deflazacort, prednisone, and/or prednisolone) are associated with improved ejection fraction (EF) and lower risk of cardiomyopathy, ventricular dysfunction, and heart failure-related mortality. Full-time mechanical ventilation was found to be significantly correlated with LVEF (low-quality evidence), muscle strength with FS (low-quality evidence), and genetic modifiers (i.e., LTBP4 rs10880 and ACTN3) with LVEF, lower risk of cardiomyopathy and left ventricular dilation (low-quality evidence).
CONCLUSION
CONCLUSIONS
Several sources of cardiac disease heterogeneity are well-studied in patients with DMD. Yet, the certainty of evidence is generally low, and little is known of the contribution of non-pharmacological interventions, as well as the impact of different criteria for initiation of specific treatments. Our findings help raise awareness of prevailing unmet needs, shape expectations of treatment outcomes, and inform the design of future research.
Identifiants
pubmed: 39342355
doi: 10.1186/s13023-024-03372-x
pii: 10.1186/s13023-024-03372-x
doi:
Types de publication
Systematic Review
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
359Informations de copyright
© 2024. The Author(s).
Références
Emery AE. The muscular dystrophies. Lancet. 2002;359(9307):687–95.
pubmed: 11879882
doi: 10.1016/S0140-6736(02)07815-7
Landfeldt E, Thompson R, Sejersen T, McMillan HJ, Kirschner J, Lochmüller H. Life expectancy at birth in Duchenne muscular dystrophy: a systematic review and meta-analysis. Eur J Epidemiol. 2020;35(7):643–53.
pubmed: 32107739
pmcid: 7387367
doi: 10.1007/s10654-020-00613-8
Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Brumbaugh D, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018;17(3):251–67.
pubmed: 29395989
pmcid: 5869704
doi: 10.1016/S1474-4422(18)30024-3
Landfeldt E, Edström J, Buccella F, Kirschner J, Lochmüller H. Duchenne muscular dystrophy and caregiver burden: a systematic review. Dev Med Child Neurol. 2018;60(10):987–96.
pubmed: 29904912
doi: 10.1111/dmcn.13934
Landfeldt E, Lindgren P, Bell CF, Guglieri M, Straub V, Lochmüller H, et al. Health-related quality of life in patients with Duchenne muscular dystrophy: a multinational, cross-sectional study. Dev Med Child Neurol. 2016;58(5):508–15.
pubmed: 26483095
doi: 10.1111/dmcn.12938
Landfeldt E, Lindgren P, Bell CF, Schmitt C, Guglieri M, Straub V, et al. The burden of Duchenne muscular dystrophy: an international, cross-sectional study. Neurology. 2014;83(6):529–36.
pubmed: 24991029
pmcid: 4141999
doi: 10.1212/WNL.0000000000000669
Villa C, Auerbach SR, Bansal N, Birnbaum BF, Conway J, Esteso P, et al. Current practices in treating cardiomyopathy and heart failure in duchenne muscular dystrophy (DMD): understanding care practices in order to optimize DMD heart failure through ACTION. Pediatr Cardiol. 2022;43(5):977–85.
pubmed: 35024902
pmcid: 8756173
doi: 10.1007/s00246-021-02807-7
Birnkrant DJ, Bushby K, Bann CM, Alman BA, Apkon SD, Blackwell A, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 2018;17(4):347–61.
pubmed: 29395990
pmcid: 5889091
doi: 10.1016/S1474-4422(18)30025-5
Finsterer J, Cripe L. Treatment of dystrophin cardiomyopathies. Nat Rev Cardiol. 2014;11(3):168–79.
pubmed: 24419258
doi: 10.1038/nrcardio.2013.213
Bello L, Pegoraro E. The, “Usual Suspects”: genes for inflammation, fibrosis, regeneration, and muscle strength modify duchenne muscular dystrophy. J Clin Med. 2019;8(5):63.
doi: 10.3390/jcm8050649
Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2003;2(12):731–40.
pubmed: 14636778
doi: 10.1016/S1474-4422(03)00585-4
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372: n71.
pubmed: 33782057
pmcid: 8005924
doi: 10.1136/bmj.n71
Guyatt GH, Oxman AD, Schünemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol. 2011;64(4):380–2.
pubmed: 21185693
doi: 10.1016/j.jclinepi.2010.09.011
Aikawa T, Takeda A, Oyama-Manabe N, Naya M, Yamazawa H, Koyanagawa K, et al. Prophylactic use of angiotensin converting enzyme inhibitor in patients with duchenne and becker muscular dystrophy. Eur Heart J. 2018;39(Supplement 1):299.
Barber BJ, Andrews JG, Lu Z, West NA, Meaney FJ, Price ET, et al. Oral corticosteroids and onset of cardiomyopathy in Duchenne muscular dystrophy. J Pediatr. 2013;163(4):1080-4.e1.
pubmed: 23866715
doi: 10.1016/j.jpeds.2013.05.060
Barp A, Bello L, Politano L, Melacini P, Calore C, Polo A, et al. Genetic modifiers of duchenne muscular dystrophy and dilated cardiomyopathy. PLoS ONE. 2015;10(10):e0141240.
pubmed: 26513582
pmcid: 4626372
doi: 10.1371/journal.pone.0141240
Batra A, Barnard AM, Lott DJ, Willcocks RJ, Forbes SC, Chakraborty S, et al. Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging. BMC Cardiovasc Disord. 2022;22(1):260.
pubmed: 35681116
pmcid: 9185987
doi: 10.1186/s12872-022-02688-5
Biggar WD, Harris VA, Eliasoph L, Alman B. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord. 2006;16(4):249–55.
pubmed: 16545568
doi: 10.1016/j.nmd.2006.01.010
Cirino RHD, Scola RH, Ducci RD, Wermelinger ACC, Kay CSK, Lorenzoni PJ, et al. Predictors of early left ventricular systolic dysfunction in DMD patients. J Neuromusc Dis. 2018;5(Supplement 1):S106–7.
Dittrich S, Graf E, Trollmann R, Neudorf U, Schara U, Heilmann A, et al. Effect and safety of treatment with ACE-inhibitor Enalapril and β-blocker metoprolol on the onset of left ventricular dysfunction in Duchenne muscular dystrophy-a randomized, double-blind, placebo-controlled trial. Orphanet J Rare Dis. 2019;14(1):105.
pubmed: 31077250
pmcid: 6509833
doi: 10.1186/s13023-019-1066-9
Duboc D, Meune C, Lerebours G, Devaux JY, Vaksmann G, Becane HM. Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J Am Coll Cardiol. 2005;45(6):855–7.
pubmed: 15766818
doi: 10.1016/j.jacc.2004.09.078
Fayssoil A, Ogna A, Chaffaut C, Lamothe L, Ambrosi X, Nardi O, et al. Natural history of cardiac function in Duchenne and Becker muscular dystrophies on home mechanical ventilation. Medicine (United States). 2018;97(27):e11381.
Houde S, Filiatrault M, Fournier A, Dubé J, D’Arcy S, Bérubé D, et al. Deflazacort use in Duchenne muscular dystrophy: an 8-year follow-up. Pediatr Neurol. 2008;38(3):200–6.
pubmed: 18279756
doi: 10.1016/j.pediatrneurol.2007.11.001
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.
pubmed: 16246949
doi: 10.1161/CIRCULATIONAHA.104.528281
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.
pubmed: 16864930
doi: 10.1253/circj.70.991
Kelley EF, Cross TJ, Johnson BD. Influence of beta1 adrenergic receptor genotype on longitudinal measures of left ventricular ejection fraction and responsiveness to s-blocker therapy in patients with duchenne muscular dystrophy. J Cardiac Fail. 2022;28(5 Supplement):S86.
doi: 10.1016/j.cardfail.2022.03.216
Kim S, Zhu Y, Romitti PA, Fox DJ, Sheehan DW, Valdez R, et al. Associations between timing of corticosteroid treatment initiation and clinical outcomes in Duchenne muscular dystrophy. Neuromuscul Disord. 2017;27(8):730–7.
pubmed: 28645460
pmcid: 5824693
doi: 10.1016/j.nmd.2017.05.019
Koeks Z, Bladen CL, Salgado D, van Zwet E, Pogoryelova O, McMacken G, et al. Clinical outcomes in duchenne muscular dystrophy: a study of 5345 patients from the TREAT-NMD DMD global database. J Neuromuscul Dis. 2017;4(4):293–306.
pubmed: 29125504
pmcid: 5701764
doi: 10.3233/JND-170280
Kwon HW, Kwon BS, Kim GB, Chae JH, Park JD, Bae EJ, et al. The effect of enalapril and carvedilol on left ventricular dysfunction in middle childhood and adolescent patients with muscular dystrophy. Korean Circ J. 2012;42(3):184–91.
pubmed: 22493613
pmcid: 3318090
doi: 10.4070/kcj.2012.42.3.184
Markham LW, Kinnett K, Wong BL, Woodrow Benson D, Cripe LH. Corticosteroid treatment retards development of ventricular dysfunction in Duchenne muscular dystrophy. Neuromuscul Disord. 2008;18(5):365–70.
pubmed: 18436445
doi: 10.1016/j.nmd.2008.03.002
Markham LW, Spicer RL, Khoury PR, Wong BL, Mathews KD, Cripe LH. Steroid therapy and cardiac function in Duchenne muscular dystrophy. Pediatr Cardiol. 2005;26(6):768–71.
pubmed: 15990951
doi: 10.1007/s00246-005-0909-4
Matsumura T, Tamura T, Kuru S, Kikuchi Y, Kawai M. Carvedilol can prevent cardiac events in duchenne muscular dystrophy. Intern Med. 2010;49(14):1357–63.
pubmed: 20647648
doi: 10.2169/internalmedicine.49.3259
Mavrogeni S, Papavasiliou A, Douskou M, Kolovou G, Papadopoulou E, Cokkinos DV. Effect of deflazacort on cardiac and sternocleidomastoid muscles in Duchenne muscular dystrophy: a magnetic resonance imaging study. Eur J Paediatr Neurol. 2009;13(1):34–40.
pubmed: 18406648
doi: 10.1016/j.ejpn.2008.02.006
Nagai M, Awano H, Yamamoto T, Bo R, Matsuo M, Iijima K. The ACTN3 577XX null genotype is associated with low left ventricular dilation-free survival rate in patients with duchenne muscular dystrophy. J Cardiac Fail. 2020;26(10):841–8.
doi: 10.1016/j.cardfail.2020.08.002
Porcher R, Desguerre I, Amthor H, Chabrol B, Audic F, Rivier F, et al. Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy-analysis of registry data. Eur Heart J. 2021;42(20):1976–84.
pubmed: 33748842
doi: 10.1093/eurheartj/ehab054
Posner AD, Soslow JH, Burnette WB, Bian A, Shintani A, Sawyer DB, et al. The correlation of skeletal and cardiac muscle dysfunction in duchenne muscular dystrophy. J Neuromuscul Dis. 2016;3(1):91–9.
pubmed: 27182492
pmcid: 4864001
doi: 10.3233/JND-150132
Raman SV, Hor KN, Mazur W, Halnon NJ, Kissel JT, He X, et al. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2015;14(2):153–61.
pubmed: 25554404
doi: 10.1016/S1474-4422(14)70318-7
Schram G, Fournier A, Leduc H, Dahdah N, Therien J, Vanasse M, et al. All-cause mortality and cardiovascular outcomes with prophylactic steroid therapy in Duchenne muscular dystrophy. J Am Coll Cardiol. 2013;61(9):948–54.
pubmed: 23352781
doi: 10.1016/j.jacc.2012.12.008
Servais L, Montus M, Guiner CL, Ben Yaou R, Annoussamy M, Moraux A, et al. Non-ambulant duchenne patients theoretically treatable by exon 53 skipping have severe phenotype. J Neuromuscul Dis. 2015;2(3):269–79.
pubmed: 27858743
pmcid: 5240539
doi: 10.3233/JND-150100
Silva MC, Magalhaes TA, Meira ZMA, Rassi CHRE, Andrade ACDS, Gutierrez PS, et al. Myocardial fibrosis progression in Duchenne and Becker muscular dystrophy: a randomized clinical trial. JAMA Cardiol. 2017;2(2):190–9.
pubmed: 27926769
doi: 10.1001/jamacardio.2016.4801
Silversides CK, Webb GD, Harris VA, Biggar DW. Effects of deflazacort on left ventricular function in patients with Duchenne muscular dystrophy. Am J Cardiol. 2003;91(6):769–72.
pubmed: 12633823
doi: 10.1016/S0002-9149(02)03429-X
Tandon A, Villa CR, Hor KN, Jefferies JL, Gao Z, Towbin JA, et al. Myocardial fibrosis burden predicts left ventricular ejection fraction and is associated with age and steroid treatment duration in duchenne muscular dystrophy. J Am Heart Assoc. 2015;4(4):63.
doi: 10.1161/JAHA.114.001338
Trucco F, Domingos JP, Tay CG, Ridout D, Maresh K, Munot P, et al. Cardiorespiratory progression over 5 years and role of corticosteroids in duchenne muscular dystrophy: a single-site retrospective longitudinal study. Chest. 2020;158(4):1606–16.
pubmed: 32387519
doi: 10.1016/j.chest.2020.04.043
Viollet L, Thrush PT, Flanigan KM, Mendell JR, Allen HD. Effects of angiotensin-converting enzyme inhibitors and/or beta blockers on the cardiomyopathy in Duchenne muscular dystrophy. Am J Cardiol. 2012;110(1):98–102.
pubmed: 22463839
doi: 10.1016/j.amjcard.2012.02.064
Yamamoto T, Awano H, Zhang Z, Sakuma M, Kitaaki S, Matsumoto M, 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.
pubmed: 29874176
pmcid: 6319568
doi: 10.1161/CIRCGEN.117.001782
Zhang L, Liu Z, Hu KY, Tian QB, Wei LG, Zhao Z, et al. Early myocardial damage assessment in dystrophinopathies using (99)Tc(m)-MIBI gated myocardial perfusion imaging. Ther Clin Risk Manag. 2015;11:1819–27.
pubmed: 26677332
pmcid: 4677759
Bourke JP, Watson G, Spinty S, Bryant A, Roper H, Chadwick T, et al. Preventing cardiomyopathy in DMD: a randomized placebo-controlled drug trial. Neurol Clin Pract. 2021;11(5):e661–8.
pubmed: 34840880
pmcid: 8610500
doi: 10.1212/CPJ.0000000000001023
Landfeldt E. Gene therapy for neuromuscular diseases: health economic challenges and future perspectives. J Neuromuscul Dis. 2022;9(6):675–88.
pubmed: 36314216
pmcid: 9697054
doi: 10.3233/JND-221540