Prevalence and clinical outcomes of dystrophin-associated dilated cardiomyopathy without severe skeletal myopathy.
DMD
Dilated cardiomyopathy
Dystrophin
Heart failure
Myopathy
Journal
European journal of heart failure
ISSN: 1879-0844
Titre abrégé: Eur J Heart Fail
Pays: England
ID NLM: 100887595
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
12
04
2021
received:
31
12
2020
accepted:
18
05
2021
pubmed:
30
5
2021
medline:
25
9
2021
entrez:
29
5
2021
Statut:
ppublish
Résumé
Dilated cardiomyopathy (DCM) associated with dystrophin gene (DMD) mutations in individuals with mild or absent skeletal myopathy is often indistinguishable from other DCM forms. We sought to describe the phenotype and prognosis of DMD associated DCM in DMD mutation carriers without severe skeletal myopathy. At 26 European centres, we retrospectively collected clinical characteristics and outcomes of 223 DMD mutation carriers (83% male, 33 ± 15 years). A total of 112 individuals (52%) had DCM at first evaluation [n = 85; left ventricular ejection fraction (LVEF) 34 ± 11.2%] or developed DCM (n = 27; LVEF 41.3 ± 7.5%) after a median follow-up of 96 months (interquartile range 5-311 months). DCM penetrance was 45% in carriers older than 40 years. DCM appeared earlier in males and was independent of the type of mutation, presence of skeletal myopathy, or elevated serum creatine kinase levels. Major adverse cardiac events (MACE) occurred in 22% individuals with DCM, 18% developed end-stage heart failure and 9% sudden cardiac death or equivalent. Skeletal myopathy was not associated with survival free of MACE in patients with DCM. Decreased LVEF and increased left ventricular end-diastolic diameter at baseline were associated with MACE. Individuals without DCM had favourable prognosis without MACE or death during follow-up. DMD-associated DCM without severe skeletal myopathy is characterized by incomplete penetrance but high risk of MACE, including progression to end-stage heart failure and ventricular arrhythmias. DCM onset is the major determinant of prognosis with similar survival regardless of the presence of skeletal myopathy.
Substances chimiques
Dystrophin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1276-1286Subventions
Organisme : Medical Research Council
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 European Society of Cardiology.
Références
Pinto YM, Elliott PM, Arbustini E, Adler Y, Anastasakis A, Böhm M, Duboc D, Gimeno J, Groote P, Imazio M, Heymans S, Klingel K, Komajda M, Limongelli G, Linhart A, Mogensen J, Moon J, Pieper PG, Seferovic PM, Schueler S, Zamorano JL, Caforio ALP, Charron P. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J 2016;37:1850-1858.
Hershberger RE, Hedges DJ, Morales A. Dilated cardiomyopathy: the complexity of a diverse genetic architecture. Nat Rev Cardiol 2013;10:531-547.
Diegoli M, Grasso M, Favalli V, Serio A, Gambarin FI, Klersy C, Pasotti M, Agozzino E, Scelsi L, Ferlini A, Febo O, Piccolo G, Tavazzi L, Narula J, Arbustini E. Diagnostic work-up and risk stratification in X-linked dilated cardiomyopathies caused by dystrophin defects. J Am Coll Cardiol 2011;58:925-934.
Kamdar F, Garry DJ. Dystrophin-deficient cardiomyopathy. J Am Coll Cardiol 2016;67:2533-2546.
Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol 2010;9:177-189.
Tandon A, Jefferies JL, Villa CR, Hor KN, Wong BL, Ware SM, Gao Z, Towbin JA, Mazur W, Fleck RJ, Sticka JJ, Benson DW, Taylor MD. Dystrophin genotype-cardiac phenotype correlations in Duchenne and Becker muscular dystrophies using cardiac magnetic resonance imaging. Am J Cardiol 2015;115:967-971.
D'Amario D, Amodeo A, Adorisio R, Tiziano FD, Leone AM, Perri G, Bruno P, Massetti M, Ferlini A, Pane M, Niccoli G, Porto I, D'Angelo GA, Borovac JA, Mercuri E, Crea F. A current approach to heart failure in Duchenne muscular dystrophy. Heart 2017;103:1770-1779.
Nigro G, Comi LI, Politano L, Limongelli FM, Nigro V, De Rimini ML, Giugliano MAM, Petretta VR, Passamano L, Restucci B, Fattore L, Tebloev K, Comi L, De Luca F, Raia P, Esposito MG. Evaluation of the cardiomyopathy in Becker muscular dystrophy. Muscle Nerve 1995;18:283-291.
Jefferies JL, Eidem BW, Belmont JW, Craigen WJ, Ware SM, Fernbach SD, Neish SR, Smith EO, Towbin JA. Genetic predictors and remodeling of dilated cardiomyopathy in muscular dystrophy. Circulation 2005;112:2799-2804.
Frank DE, Schnell FJ, Akana C, El-Husayni SH, Desjardins CA, Morgan J, Charleston JS, Sardone V, Domingos J, Dickson G, Straub V, Guglieri M, Mercuri E, Servais L, Muntoni F. Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology 2020;94:e2270-e2282.
D'Amario D, Gowran A, Canonico F, Castiglioni E, Rovina D, Santoro R, Spinelli P, Adorisio R, Amodeo A, Perrucci G, Borovac J, Pompilio G, Crea F. Dystrophin cardiomyopathies: clinical management, molecular pathogenesis and evolution towards precision medicine. J Clin Med 2018;7:291.
Garry DJ, Alexy T. Emerging therapies for dystrophic cardiomyopathy. JACC Basic Transl Sci 2019;4:792-794.
Akhtar MM, Lorenzini M, Cicerchia M, Ochoa JP, Hey TM, Sabater Molina M, Restrepo-Cordoba MA, Dal Ferro M, Stolfo D, Johnson R, Larrañaga-Moreira JM, Robles-Mezcua A, Rodriguez-Palomares JF, Casas G, Peña-Peña ML, Lopes LR, Gallego-Delgado M, Franaszczyk M, Laucey G, Rangel-Sousa D, Basurte M, Palomino-Doza J, Villacorta E, Bilinska Z, Limeres Freire J, Garcia Pinilla JM, Barriales-Villa R, Fatkin D, Sinagra G, Garcia-Pavia P, Gimeno JR, Mogensen J, Monserrat L, Elliott PM. Clinical phenotypes and prognosis of dilated cardiomyopathy caused by truncating variants in the TTN gene. Circ Heart Fail 2020;13:e006832.
Domínguez F, Cuenca S, Bilińska Z, Toro R, Villard E, Barriales-Villa R, Ochoa JP, Asselbergs F, Sammani A, Franaszczyk M, Akhtar M, Coronado-Albi MJ, Rangel-Sousa D, Rodriguez-Palomares JF, Jiménez-Jáimez J, Garcia-Pinilla JM, Ripoll-Vera T, Mogollón-Jiménez MV, Fontalba-Romero A, Garcia-Medina D, Palomino-Doza J, Gonzalo-Calvo D, Cicerchia M, Salazar-Mendiguchia J, Salas C, Pankuweit S, Hey TM, Mogensen J, Barton PJ, Charron P, Elliott P, Garcia-Pavia P; European Genetic Cardiomyopathies Initiative Investigators. Dilated cardiomyopathy due to BLC2-associated athanogene 3 (BAG3) mutations. J Am Coll Cardiol 2018;72:2471-2481.
Lopez-Sainz A, Dominguez F, Lopes LR, Ochoa JP, Barriales-Villa R, Climent V, Linschoten M, Tiron C, Chiriatti C, Marques N, Rasmussen TB, Espinosa MÁ, Beinart R, Quarta G, Cesar S, Field E, Garcia-Pinilla JM, Bilinska Z, Muir AR, Roberts AM, Santas E, Zorio E, Peña-Peña ML, Navarro M, Fernandez A, Palomino-Doza J, Azevedo O, Lorenzini M, García-Álvarez MI, Bento D, Jensen MK, Méndez I, Pezzoli L, Sarquella-Brugada G, Campuzano O, Gonzalez-Lopez E, Mogensen J, Kaski JP, Arad M, Brugada R, Asselbergs FW, Monserrat L, Olivotto I, Elliott PM, Garcia-Pavia P; European Genetic Cardiomyopathies Initiative Investigators. Clinical features and natural history of PRKAG2 variant cardiac glycogenosis. J Am Coll Cardiol 2020;14:186-197.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-424.
Brandt T, Sack LM, Arjona D, Tan D, Mei H, Cui H, Gao H, Bean LJH, Ankala A, Del Gaudio D, Knight Johnson A, Vincent LM, Reavey C, Lai A, Richard G, Meck JM. Adapting ACMG/AMP sequence variant classification guidelines for single-gene copy number variants. Genet Med 2020;22:336-344.
Kumar S, Baldinger SH, Gandjbakhch E, Maury P, Sellal JM, Androulakis AFA, Waintraub X, Charron P, Rollin A, Richard P, Stevenson WG, Macintyre CJ, Ho CY, Thompson T, Vohra JK, Kalman JM, Zeppenfeld K, Sacher F, Tedrow UB, Lakdawala NK. Long-term arrhythmic and nonarrhythmic outcomes of lamin A/C mutation carriers. J Am Coll Cardiol 2016;68:2299-2307.
Ortiz-Genga MF, Cuenca S, Dal Ferro M, Zorio E, Salgado-Aranda R, Climent V, Padrón-Barthe L, Duro-Aguado I, Jiménez-Jáimez J, Hidalgo-Olivares VM, García-Campo E, Lanzillo C, Suárez-Mier MP, Yonath H, Marcos-Alonso S, Ochoa JP, Santomé JL, García-Giustiniani D, Rodríguez-Garrido JL, Domínguez F, Merlo M, Palomino J, Peña ML, Trujillo JP, Martín-Vila A, Stolfo D, Molina P, Lara-Pezzi E, Calvo-Iglesias FE, Nof E, Calò L, Barriales-Villa R, Gimeno-Blanes JR, Arad M, García-Pavía P, Monserrat L. Truncating FLNC mutations are associated with high-risk dilated and arrhythmogenic cardiomyopathies. J Am Coll Cardiol 2016;68:2440-2451.
Florian A, Ludwig A, Engelen M, Waltenberger J, Rösch S, Sechtem U, Yilmaz A. Left ventricular systolic function and the pattern of late-gadolinium-enhancement independently and additively predict adverse cardiac events in muscular dystrophy patients. J Cardiovasc Magn Reson 2014;16:81.
Klem I, Klein M, Khan M, Yang EY, Nabi F, Ivanov A, Bhatti L, Hayes B, Graviss EA, Nguyen DT, Judd RM, Kim RJ, Heitner JF, Shah DJ. The relationship of LVEF and myocardial scar to long-term mortality risk and mode of death in patients with non-ischemic cardiomyopathy. Circulation 2021;143:1343-1358.
Halliday BP, Cleland JGF, Goldberger JJ, Prasad SK. Personalizing risk stratification for sudden death in dilated cardiomyopathy: the past, present, and future. Circulation 2017;136:215-231.
Gigli M, Merlo M, Graw SL, Barbati G, Rowland TJ, Slavov DB, Stolfo D, Haywood ME, Dal Ferro M, Altinier A, Ramani F, Brun F, Cocciolo A, Puggia I, Morea G, McKenna WJ, La Rosa FG, Taylor MRG, Sinagra G, Mestroni L. Genetic risk of arrhythmic phenotypes in patients with dilated cardiomyopathy. J Am Coll Cardiol 2019;74:1480-1490.
Adachi K, Hashiguchi S, Saito M, Kashiwagi S, Miyazaki T, Kawai H, Yamada H, Iwase T, Akaike M, Takao S, Kobayashi M, Ishizaki M, Matsumura T, Mori-Yoshimura M, Kimura E. Detection and management of cardiomyopathy in female dystrophinopathy carriers. J Neurol Sci 2018;386:74-80.
Ishizaki M, Kobayashi M, Adachi K, Matsumura T, Kimura E. Female dystrophinopathy: review of current literature. Neuromuscul Disord 2018;28:572-581.
Florian A, Rösch S, Bietenbeck M, Engelen M, Stypmann J, Waltenberger J, Sechtem U, Yilmaz A. Cardiac involvement in female Duchenne and Becker muscular dystrophy carriers in comparison to their first-degree male relatives: a comparative cardiovascular magnetic resonance study. Eur Heart J Cardiovasc Imaging 2016;17:326-333.
Papa AA, D'Ambrosio P, Petillo R, Palladino A, Politano L. Heart transplantation in patients with dystrophinopathic cardiomyopathy: review of the literature and personal series. Intractable Rare Dis Res 2017;6:95-101.