Prevalence and clinical outcomes of dystrophin-associated dilated cardiomyopathy without severe skeletal myopathy
Por:
Restrepo-Cordoba, M, Wahbi, K, Florian, A, Jimenez-Jaimez, J, Politano, L, Arad, M, Climent-Paya, V, Garcia-Alvarez, A, Hansen, R, Larranaga-Moreira, J, Kubanek, M, Lopes, L, Ros, A, Jurcut, R, Rasmussen, T, Ruiz-Guerrero, L, Pribe-Wolferts, R, Palomino-Doza, J, Bilinska, Z, Rodriguez-Palomares, J, Van Loon, R, Elorz, M, Quarta, G, Inarritu, M, Verdonschot, J, Stojkovic, T, Shomanova, Z, Bermudez-Jimenez, F, Palladino, A, Freimark, D, Garcia-Alvarez, M, Jorda, P, Dominguez, F, Ochoa, J, Girolami, F, Brugada, R, Meder, B, Barriales-Villa, R, Mogensen, J, Laforet, P, Yilmaz, A, Elliott, P, Garcia-Pavia, P and European Genetic Cardiomyopathies
Publicada:
1 ago 2021
Ahead of Print:
1 jun 2021
Resumen:
Aims 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.
Methods and results 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.
Conclusions 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.
Filiaciones:
Restrepo-Cordoba, M:
Hosp Univ Puerta Hierro, Dept Cardiol, Heart Failure & Inherited Cardiac Dis Unit, Manuel Falla 2, Madrid 28222, Spain
Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain
European Reference Network Rare & Low Prevalence, Amsterdam, Netherlands
Wahbi, K:
Sorbonne Paris Cite Univ, Cochin Hosp, APHP, Cardiol Dept,FILNEMUS,Paris Descartes, Paris, France
Florian, A:
Univ Hosp Muenster, Dept Cardiol 1, Div Cardiovasc Imaging, Munster, Germany
Jimenez-Jaimez, J:
Hosp Univ Virgen Nieves, Cardiol Dept, Granada, Spain
Politano, L:
Univ Campania Luigi Vanvitelli, Cardiomyol & Med Genet, Naples, Italy
Arad, M:
Tel Aviv Univ, Sheba Med Ctr, Leviev Heart Ctr, Tel Aviv, Israel
Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
:
Hosp Gen Univ Alicante, Cardiol Dept, Alicante, Spain
Inst Hlth & Biomed Res ISABIAL, Alicante, Spain
Garcia-Alvarez, A:
Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain
Univ Barcelona, Hosp Clin, Inst Clin Cardiovasc, IDIBAPS, Barcelona, Spain
Hansen, R:
Odense Univ Hosp, Dept Cardiol, Odense, Denmark
Larranaga-Moreira, J:
Univ A Coruna, Complexo Hosp Univ A Coruna, Inst Invest Biomed A Coruna INIBIC,Serv Galego Sa, Inherited Cardiovasc Dis Unit,Cardiol Serv, La Coruna, Spain
Kubanek, M:
Inst Clin & Expt Med, Dept Cardiol, Prague, Czech Republic
Lopes, L:
European Reference Network Rare & Low Prevalence, Amsterdam, Netherlands
Barts Hlth NHS Trust, St Bartholomews Hosp, Barts Heart Ctr, London, England
UCL, Inst Cardiovasc Sci, Ctr Heart Muscle Dis, London, England
Ros, A:
Univ Hosp Germans Trias & Pujol, Clin Genet Dept, Cardiogenet Unit, Badalona, Spain
Jurcut, R:
European Reference Network Rare & Low Prevalence, Amsterdam, Netherlands
Emergency Inst Cardiovasc Dis Prof Dr CC Iliescu, Expert Ctr Rare Cardiovasc Genet Dis, Cardiol Dept 3, Bucharest, Romania
Rasmussen, T:
Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark
Ruiz-Guerrero, L:
IDIVAL, Hosp Univ Marques de Valdecilla, Dept Cardiol, Santander, Spain
Pribe-Wolferts, R:
Univ Hosp Heidelberg, Inst Cardiomyopathies Heidelberg, Heidelberg, Germany
Palomino-Doza, J:
Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain
Inst Invest 12 Madrid Spain, Hosp Univ 12 Octubre, Cardiol Dept, Inherited Cardiac Dis unit, Madrid, Spain
Bilinska, Z:
Natl Inst Cardiol, Unit Screening Studies Inherited Cardiovasc Dis, Warsaw, Poland
Rodriguez-Palomares, J:
Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain
Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Dept Cardiol, Vall dHebron Inst Recerca VHIR, Barcelona, Spain
Van Loon, R:
Univ Utrecht, Univ Med Ctr Utrecht, Dept Genet, Utrecht, Netherlands
Elorz, M:
Complejo Hosp Navarra, Heart Area, Pamplona, Spain
Quarta, G:
ASST Papa Giovanni XXIII, Cardiol Dept, Bergamo, Italy
Inarritu, M:
Hosp Univ Araba Txagorritxu, Vitoria, Spain
Verdonschot, J:
Maastricht Univ, Dept Cardiol, Med Ctr, Maastricht, Netherlands
Maastricht Univ, Dept Clin Genet, Med Ctr, Maastricht, Netherlands
Stojkovic, T:
Hop La Pitie Salpetriere, Myol Inst, Referral Ctr Neuromuscular Dis, Paris, France
Shomanova, Z:
Univ Hosp Muenster, Dept Cardiol 1, Div Cardiovasc Imaging, Munster, Germany
Bermudez-Jimenez, F:
Hosp Univ Virgen Nieves, Cardiol Dept, Granada, Spain
Palladino, A:
Univ Campania Luigi Vanvitelli, Cardiomyol & Med Genet, Naples, Italy
Freimark, D:
Tel Aviv Univ, Sheba Med Ctr, Leviev Heart Ctr, Tel Aviv, Israel
Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
:
Hosp Gen Univ Alicante, Cardiol Dept, Alicante, Spain
Inst Hlth & Biomed Res ISABIAL, Alicante, Spain
Jorda, P:
Univ Barcelona, Hosp Clin, Inst Clin Cardiovasc, IDIBAPS, Barcelona, Spain
Dominguez, F:
Hosp Univ Puerta Hierro, Dept Cardiol, Heart Failure & Inherited Cardiac Dis Unit, Manuel Falla 2, Madrid 28222, Spain
Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain
European Reference Network Rare & Low Prevalence, Amsterdam, Netherlands
Ochoa, J:
Hosp Univ Puerta Hierro, Dept Cardiol, Heart Failure & Inherited Cardiac Dis Unit, Manuel Falla 2, Madrid 28222, Spain
Hlth Code, Cardiol Dept, La Coruna, Spain
Girolami, F:
Meyer Childrens Hosp, Dept Paediat Cardiol, Florence, Italy
Brugada, R:
Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain
Hosp Univ Dr Josep Trueta, Dept Cardiol, Inherited Cardiac Dis Unit, Girona, Spain
Univ Girona, Sch Med, Med Sci Dept, Girona, Spain
Meder, B:
Univ Hosp Heidelberg, Inst Cardiomyopathies Heidelberg, Heidelberg, Germany
Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA
Barriales-Villa, R:
Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain
Univ A Coruna, Complexo Hosp Univ A Coruna, Inst Invest Biomed A Coruna INIBIC,Serv Galego Sa, Inherited Cardiovasc Dis Unit,Cardiol Serv, La Coruna, Spain
Mogensen, J:
Odense Univ Hosp, Dept Cardiol, Odense, Denmark
Laforet, P:
Hop Raymond Poincare, APHP, Ctr Reference Malad Neuromusculaires Nord Est Ile, Garches, France
Yilmaz, A:
Univ Hosp Muenster, Dept Cardiol 1, Div Cardiovasc Imaging, Munster, Germany
Elliott, P:
European Reference Network Rare & Low Prevalence, Amsterdam, Netherlands
Barts Hlth NHS Trust, St Bartholomews Hosp, Barts Heart Ctr, London, England
UCL, Inst Cardiovasc Sci, Ctr Heart Muscle Dis, London, England
Garcia-Pavia, P:
Hosp Univ Puerta Hierro, Dept Cardiol, Heart Failure & Inherited Cardiac Dis Unit, Manuel Falla 2, Madrid 28222, Spain
Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid, Spain
European Reference Network Rare & Low Prevalence, Amsterdam, Netherlands
Univ Francisco Vitoria, Pozuelo De Alarcon, Spain
Ctr Nacl Invest Cardiovasc, Madrid, Spain
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