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Progressive left ventricular dysfunction and myocardial fibrosis in Duchenne and Becker muscular dystrophy: a longitudinal cardiovascular magnetic resonance study

  • Tadao Aikawa
  • Atsuhito Takeda
  • Noriko Oyama-ManabeEmail author
  • Masanao Naya
  • Hirokuni Yamazawa
  • Kazuhiro Koyanagawa
  • Yoichi M. Ito
  • Toshihisa Anzai
Original Article
  • 78 Downloads

Abstract

This study examined the progression of left ventricular dysfunction and myocardial fibrosis in patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) to evaluate the effects of angiotensin-converting enzyme inhibitor (ACEI). Ninety-eight cardiovascular magnetic resonance (CMR) studies in 34 consecutive patients with DMD (n = 21) or BMD (n = 13) were retrospectively reviewed. Left ventricular ejection fraction (LVEF) and the extent of myocardial late gadolinium enhancement (LGE) were semiautomatically quantified. During the study period, five patients had already been treated with ACEI at the first CMR; five were started on ACEI at LVEF ≥ 55% and 10 at LVEF < 55%. All patients had hyperenhanced myocardium on LGE images at the first CMR (median extent, 3.3%; interquartile range 0.1–14.3%). A mixed-effects model for longitudinal data of each patient, adjusted for age, type of muscular dystrophy, steroid use, and ACEI use showed that higher age (β = − 1.1%/year; 95% confidence interval [CI], − 1.8% to − 0.4%; p = 0.005) and no use of ACEI (β = − 3.1%; 95% CI, − 5.4% to − 0.8%; p = 0.009) were significantly associated with a lower LVEF. When ACEI use was stratified by time of initiation (LVEF ≥ 55% vs. < 55%), only ACEI initiation at LVEF < 55% had a beneficial effect on LVEF at each imaging examination (β = 3.7%; 95% CI, 0.9–6.4%; p = 0.010). ACEI use or the time of initiation of ACEI did not significantly affect age-related increase in LGE. ACEI attenuated the age-related decline in LVEF only in patients with DMD or BMD and reduced LVEF, suggesting that further investigation on prophylactic use of cardioprotective therapy in these patients is warranted.

Keywords

Duchenne muscular dystrophy Becker muscular dystrophy Angiotensin-converting enzyme inhibitor Cardiovascular magnetic resonance imaging Late gadolinium enhancement Mixed-effects model 

Notes

Acknowledgements

We thank Drs. Yukitoshi Isikawa and Yuka Ishikawa for providing DMD/BMD-specific knowledge and insight and Kinya Ishizaka for technical assistance.

Funding

This study was funded by the Miyata Cardiac Research Promotion Foundation (to Tadao Aikawa). The funder had no role in the study design, data collection, analysis, interpretation of data, or in the writing of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

References

  1. 1.
    Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K (2002) Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul Disord 12:926–929.  https://doi.org/10.1016/S0960-8966(02)00140-2 CrossRefPubMedGoogle Scholar
  2. 2.
    Melacini P, Fanin M, Danieli GA, Villanova C, Martinello F, Miorin M, Freda MP, Miorelli M, Mostacciuolo ML, Fasoli G, Angelini C, Volta SD (1996) Myocardial involvement is very frequent among patients affected with subclinical Becker’s muscular dystrophy. Circulation 94:3168–3175.  https://doi.org/10.1161/01.CIR.94.12.3168 CrossRefPubMedGoogle Scholar
  3. 3.
    Jefferies JL, Eidem BW, Belmont JW, Craigen WJ, Ware SM, Fernbach SD, Neish SR, Smith EO, Towbin JA (2005) Genetic predictors and remodeling of dilated cardiomyopathy in muscular dystrophy. Circulation 112:2799–2804.  https://doi.org/10.1161/CIRCULATIONAHA.104.528281 CrossRefPubMedGoogle Scholar
  4. 4.
    Melacini P, Fanin M, Danieli GA, Fasoli G, Villanova C, Angelini C, Vitiello L, Miorelli M, Buja GF, Mostacciuolo ML, Pegoraro E, Volta SD (1993) Cardiac involvement in Becker muscular dystrophy. J Am Coll Cardiol 22:1927–1934.  https://doi.org/10.1016/0735-1097(93)90781-U CrossRefPubMedGoogle Scholar
  5. 5.
    Silva MC, Meira ZM, Gurgel Giannetti J, da Silva MM, Campos AF, Barbosa Mde M, Starling Filho GM, Ferreira Rde A, Zatz M, Rochitte CE (2007) Myocardial delayed enhancement by magnetic resonance imaging in patients with muscular dystrophy. J Am Coll Cardiol 49:1874–1879.  https://doi.org/10.1016/j.jacc.2006.10.078 CrossRefPubMedGoogle Scholar
  6. 6.
    Tandon A, Villa CR, Hor KN, Jefferies JL, Gao Z, Towbin JA, Wong BL, Mazur W, Fleck RJ, Sticka JJ, Benson DW, Taylor MD (2015) 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.  https://doi.org/10.1161/JAHA.114.001338 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Feingold B, Mahle WT, Auerbach S, Clemens P, Domenighetti AA, Jefferies JL, Judge DP, Lal AK, Markham LW, Parks WJ, Tsuda T, Wang PJ, Yoo SJ, American Heart Association Pediatric Heart Failure Committee of the Council on Cardiovascular Disease in the Young; Council on Clinical Cardiology; Council on Cardiovascular Radiology and Intervention; Council on Functional Genomics and Translational Biology; and Stroke Council (2017) Management of cardiac involvement associated with neuromuscular diseases: a scientific statement From the American Heart Association. Circulation 136:e200–e231.  https://doi.org/10.1161/CIR.0000000000000526 CrossRefGoogle Scholar
  8. 8.
    Silva MC, Magalhaes TA, Meira ZM, Rassi CH, Andrade AC, Gutierrez PS, Azevedo CF, Gurgel-Giannetti J, Vainzof M, Zatz M, Kalil-Filho R, Rochitte CE (2017) Myocardial fibrosis progression in Duchenne and Becker muscular dystrophy: a randomized clinical trial. JAMA Cardiol 2:190–199.  https://doi.org/10.1001/jamacardio.2016.4801 CrossRefPubMedGoogle Scholar
  9. 9.
    Duboc D, Meune C, Pierre B, Wahbi K, Eymard B, Toutain A, Berard C, Vaksmann G, Weber S, Becane HM (2007) Perindopril preventive treatment on mortality in Duchenne muscular dystrophy: 10 years’ follow-up. Am Heart J 154:596–602.  https://doi.org/10.1016/j.ahj.2007.05.014 CrossRefPubMedGoogle Scholar
  10. 10.
    Aikawa T, Naya M, Obara M, Oyama-Manabe N, Manabe O, Magota K, Ito YM, Katoh C, Tamaki N (2017) Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study. Eur J Nucl Med Mol Imaging 44:1897–1905.  https://doi.org/10.1007/s00259-017-3760-y CrossRefPubMedGoogle Scholar
  11. 11.
    Aikawa T, Oyama-Manabe N, Naya M, Ohira H, Sugimoto A, Tsujino I, Obara M, Manabe O, Kudo K, Tsutsui H, Tamaki N (2017) Delayed contrast-enhanced computed tomography in patients with known or suspected cardiac sarcoidosis: a feasibility study. Eur Radiol 27:4054–4063.  https://doi.org/10.1007/s00330-017-4824-x CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Nassenstein K, Breuckmann F, Bucher C, Kaiser G, Konorza T, Schafer L, Konietzka I, de Greiff A, Heusch G, Erbel R, Barkhausen J (2008) How much myocardial damage is necessary to enable detection of focal late gadolinium enhancement at cardiac MR imaging? Radiology 249:829–835.  https://doi.org/10.1148/radiol.2493080457 CrossRefPubMedGoogle Scholar
  13. 13.
    Allen HD, Flanigan KM, Thrush PT, Dvorchik I, Yin H, Canter C, Connolly AM, Parrish M, McDonald CM, Braunlin E, Colan SD, Day J, Darras B, Mendell JR (2013) A randomized, double-blind trial of lisinopril and losartan for the treatment of cardiomyopathy in duchenne muscular dystrophy. PLoS Curr.  https://doi.org/10.1371/currents.md.2cc69a1dae4be7dfe2bcb420024ea865 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Viollet L, Thrush PT, Flanigan KM, Mendell JR, Allen HD (2012) Effects of angiotensin-converting enzyme inhibitors and/or beta blockers on the cardiomyopathy in Duchenne muscular dystrophy. Am J Cardiol 110:98–102.  https://doi.org/10.1016/j.amjcard.2012.02.064 CrossRefPubMedGoogle Scholar
  15. 15.
    Duboc D, Meune C, Lerebours G, Devaux JY, Vaksmann G, Becane HM (2005) Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J Am Coll Cardiol 45:855–857.  https://doi.org/10.1016/j.jacc.2004.09.078 CrossRefPubMedGoogle Scholar
  16. 16.
    Schram G, Fournier A, Leduc H, Dahdah N, Therien J, Vanasse M, Khairy P (2013) All-cause mortality and cardiovascular outcomes with prophylactic steroid therapy in Duchenne muscular dystrophy. J Am Coll Cardiol 61:948–954.  https://doi.org/10.1016/j.jacc.2012.12.008 CrossRefPubMedGoogle Scholar
  17. 17.
    Lonn EM, Yusuf S, Jha P, Montague TJ, Teo KK, Benedict CR, Pitt B (1994) Emerging role of angiotensin-converting enzyme inhibitors in cardiac and vascular protection. Circulation 90:2056–2069.  https://doi.org/10.1161/01.CIR.90.4.2056 CrossRefPubMedGoogle Scholar
  18. 18.
    Mewton N, Liu CY, Croisille P, Bluemke D, Lima JA (2011) Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol 57:891–903.  https://doi.org/10.1016/j.jacc.2010.11.013 CrossRefPubMedGoogle Scholar
  19. 19.
    Hor KN, Wansapura J, Markham LW, Mazur W, Cripe LH, Fleck R, Benson DW, Gottliebson WM (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.  https://doi.org/10.1016/j.jacc.2008.12.032 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Soslow JH, Damon SM, Crum K, Lawson MA, Slaughter JC, Xu M, Arai AE, Sawyer DB, Parra DA, Damon BM, Markham LW (2016) Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy. J Cardiovasc Magn Reson 18:5.  https://doi.org/10.1186/s12968-016-0224-7 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Maisel AS, Bhalla V, Braunwald E (2006) Cardiac biomarkers: a contemporary status report. Nat Clin Pract Cardiovasc Med 3:24–34.  https://doi.org/10.1038/ncpcardio0405 CrossRefPubMedGoogle Scholar
  22. 22.
    Price JF, Thomas AK, Grenier M, Eidem BW, O’Brian Smith E, Denfield SW, Towbin JA, Dreyer WJ (2006) B-type natriuretic peptide predicts adverse cardiovascular events in pediatric outpatients with chronic left ventricular systolic dysfunction. Circulation 114:1063–1069.  https://doi.org/10.1161/circulationaha.105.608869 CrossRefPubMedGoogle Scholar
  23. 23.
    Cheeran D, Khan S, Khera R, Bhatt A, Garg S, Grodin JL, Morlend R, Araj FG, Amin AA, Thibodeau JT, Das S, Drazner MH, Mammen PPA (2017) Predictors of death in adults with Duchenne muscular dystrophy-associated cardiomyopathy. J Am Heart Assoc.  https://doi.org/10.1161/jaha.117.006340 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Raman SV, Hor KN, Mazur W, Halnon NJ, Kissel JT, He X, Tran T, Smart S, McCarthy B, Taylor MD, Jefferies JL, Rafael-Fortney JA, Lowe J, Roble SL, Cripe LH (2015) Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 14:153–161.  https://doi.org/10.1016/s1474-4422(14)70318-7 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Tadao Aikawa
    • 1
  • Atsuhito Takeda
    • 2
  • Noriko Oyama-Manabe
    • 3
    Email author
  • Masanao Naya
    • 1
  • Hirokuni Yamazawa
    • 2
  • Kazuhiro Koyanagawa
    • 1
  • Yoichi M. Ito
    • 4
  • Toshihisa Anzai
    • 1
  1. 1.Department of Cardiovascular MedicineHokkaido University HospitalSapporoJapan
  2. 2.Department of PediatricsHokkaido University HospitalSapporoJapan
  3. 3.Department of Diagnostic and Interventional RadiologyHokkaido University HospitalSapporoJapan
  4. 4.Department of Biostatistics, Faculty of Medicine, Graduate School of MedicineHokkaido UniversitySapporoJapan

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