BACKGROUND: Female carriers of dystrophin gene mutations (DMD-FC) were previously considered non-manifesting, but in recent decades, cardiomyopathy associated with muscular dystrophy and myocardial fibrosis has been described. Our study aimed to assess prospectively myocardial fibrosis in asymptomatic DMD-FC compared to a sex-matched control group (CG) with similar age distribution using native T1 mapping and extracellular volume (ECV) quantification by cardiovascular magnetic resonance (CMR) imaging. MATERIALS AND METHODS: 38 DMD-FC with verified genetic mutation and 22 healthy volunteers were included. Using CMR, native T1 relaxation time and ECV quantification were determined in each group. Late gadolinium enhancement (LGE) was assessed in all cases. RESULTS: There were 38 DMD-FC (mean age 39.1 ± 8.8 years) and 22 healthy volunteers (mean age 39.9 ± 12.6 years) imagined by CMR. The mean global native T1 relaxation time was similar for DMD-FC and CG (1005.1 ± 26.3 ms vs. 1003.5 ± 25.0 ms; p-value = 0.81). Likewise, the mean global ECV value was also similar between the groups (27.92 ± 2.02% vs. 27.10 ± 2.89%; p-value = 0.20). The segmental analysis of mean ECV values according to the American Heart Association classification did not show any differences between DMD-FC and CG. There was a non-significant trend towards higher mean ECV values of DMD-FC in the inferior and inferolateral segments of the myocardium (p-value = 0.075 and 0.070 respectively). CONCLUSION: There were no statistically significant differences in the mean global and segmental native T1 relaxation times and the mean global or segmental ECV values. There was a trend towards higher segmental mean ECV values of DMD-FC in the inferior and inferolateral walls of the myocardium.

1st Department of Internal Medicine Cardioangiology St Anne's University Hospital Faculty of Medicine Masaryk University Brno Czech Republic

Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Biomedical Engineering University of Technology Brno Czech Republic

Department of Medical Imaging St Anne's University Hospital Brno Czech Republic

Department of Paediatric Neurology University Hospital Brno Czech Republic

Department of Pathophysiology Faculty of Medicine Masaryk University Brno Czech Republic

International Clinical Research Centre St Anne's University Hospital Brno Czech Republic

Orphanet J Rare Dis. 2023 Oct 19;18(1):331. doi: 10.1186/s13023-023-02922-z. PubMed

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Kamdar F, Garry DJ. Dystrophin-Deficient Cardiomyopathy. J Am Coll Cardiol. 2016;67(21):2533–46. doi: 10.1016/j.jacc.2016.02.081. PubMed DOI

Hermans MCE, Pinto YM, Merkies ISJ, de Die-Smulders CEM, Crijns HJGM, Faber CG. Hereditary muscular dystrophies and the heart. Neuromuscul Disord NMD. 2010;20(8):479–92. doi: 10.1016/j.nmd.2010.04.008. PubMed DOI

Feingold B, Mahle WT, Auerbach S, Clemens P, Domenighetti AA, Jefferies JL, et al. Management of Cardiac involvement Associated with Neuromuscular Diseases: A Scientific Statement from the American Heart Association. Circulation. 2017;136(13):e200–31. doi: 10.1161/CIR.0000000000000526. PubMed DOI

McNally EM, Kaltman JR, Benson DW, Canter CE, Cripe LH, Duan D, et al. Contemporary cardiac issues in Duchenne muscular dystrophy. Working Group of the National Heart, Lung, and Blood Institute in collaboration with parent project muscular dystrophy. Circulation. 2015;131(18):1590–8. doi: 10.1161/CIRCULATIONAHA.114.015151. PubMed DOI PMC

Demos J, Dreyfus JC, Schapira F, Schapira G. [Biological anomalies in the apparently healthy transmitters of muscular dystrophy] Rev Can Biol. 1962;21:587–97. PubMed

Aikawa T, Takeda A, Oyama-Manabe N, Naya M, Yamazawa H, Koyanagawa K, et al. Progressive left ventricular dysfunction and myocardial fibrosis in Duchenne and Becker muscular dystrophy: a longitudinal cardiovascular magnetic resonance study. Pediatr Cardiol. 2019;40(2):384–92. doi: 10.1007/s00246-018-2046-x. PubMed DOI

Mccaffrey T, Guglieri M, Murphy AP, Bushby K, Johnson A, Bourke JP. Cardiac involvement in female carriers of duchenne or becker muscular dystrophy. Muscle Nerve. 2017;55(6):810–8. doi: 10.1002/mus.25445. PubMed DOI

Lang SM, Shugh S, Mazur W, Sticka JJ, Rattan MS, Jefferies JL, et al. Myocardial fibrosis and left ventricular dysfunction in Duchenne muscular dystrophy carriers using Cardiac magnetic resonance imaging. Pediatr Cardiol. 2015;36(7):1495–501. doi: 10.1007/s00246-015-1192-7. PubMed DOI

Solheim TA, Fornander F, Raja AA, Møgelvang R, Poulsen NS, Dunø M, et al. Cardiac involvement in women with pathogenic dystrophin gene variants. Front Neurol. 2021;12:707838. Available from: https://www.frontiersin.org/articles/. 10.3389/fneur.2021.707838. PubMed PMC

Soltanzadeh P, Friez MJ, Dunn D, von Niederhausern A, Gurvich OL, Swoboda KJ, et al. Clinical and genetic characterization of manifesting carriers of DMD mutations. Neuromuscul Disord NMD. 2010;20(8):499–504. doi: 10.1016/j.nmd.2010.05.010. PubMed DOI PMC

Wexberg P, Avanzini M, Mascherbauer J, Pfaffenberger S, Freudenthaler B, Bittner R, et al. Myocardial late gadolinium enhancement is associated with clinical presentation in Duchenne muscular dystrophy carriers. J Cardiovasc Magn Reson off J Soc Cardiovasc Magn Reson. 2016;18(1):61. PubMed PMC

Florian A, Rösch S, Bietenbeck M, Engelen M, Stypmann J, Waltenberger J, et al. 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(3):326–33. doi: 10.1093/ehjci/jev161. PubMed DOI

Mewton N, Liu CY, Croisille P, Bluemke D, Lima JAC. Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol. 2011;57(8):891–903. doi: 10.1016/j.jacc.2010.11.013. PubMed DOI PMC

Florian A, Ludwig A, Rösch S, Yildiz H, Sechtem U, Yilmaz A. Myocardial fibrosis imaging based on T1-mapping and extracellular volume fraction (ECV) measurement in muscular dystrophy patients: diagnostic value compared with conventional late gadolinium enhancement (LGE) imaging. Eur Heart J Cardiovasc Imaging. 2014;15(9):1004–12. doi: 10.1093/ehjci/jeu050. PubMed DOI

Starc JJ, Moore RA, Rattan MS, Villa CR, Gao Z, Mazur W, et al. Elevated myocardial extracellular volume fraction in Duchenne muscular dystrophy. Pediatr Cardiol. 2017;38(7):1485–92. doi: 10.1007/s00246-017-1690-x. PubMed DOI

Soslow J, Damon S, Crum K, Lawson M, Slaughter J, Xu M et al. Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy. J Cardiovasc Magn Reson. 2015;18. PubMed PMC

Panovský R, Pešl M, Máchal J, Holeček T, Feitová V, Juříková L, et al. Quantitative assessment of left ventricular longitudinal function and myocardial deformation in Duchenne muscular dystrophy patients. Orphanet J Rare Dis. 2021;16(1):57. doi: 10.1186/s13023-021-01704-9. PubMed DOI PMC

Soslow JH, Damon SM, Crum K, Lawson MA, Slaughter JC, Xu M, et al. Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy. J Cardiovasc Magn Reson. 2016;18(1):5. doi: 10.1186/s12968-016-0224-7. PubMed DOI PMC

Mah ML, Cripe L, Slawinski MK, Al-Zaidy SA, Camino E, Lehman KJ, et al. Duchenne and Becker muscular dystrophy carriers: evidence of cardiomyopathy by exercise and cardiac MRI testing. Int J Cardiol. 2020;316:257–65. doi: 10.1016/j.ijcard.2020.05.052. PubMed DOI

Koyanagawa K, Kobayashi Y, Aikawa T, Takeda A, Shiraishi H, Tsuneta S, et al. Myocardial T(1)-mapping and extracellular volume quantification in patients and putative carriers of muscular dystrophy: early experience. Magn Reson Med Sci MRMS off J Jpn Soc Magn Reson Med. 2021;20(3):320–4. PubMed PMC

Jerosch-Herold M, Kwong RY. Cardiac T(1) imaging. Top Magn Reson Imaging TMRI. 2014;23(1):3–11. doi: 10.1097/RMR.0000000000000013. PubMed DOI PMC

Schulz-Menger J, Bluemke DA, Bremerich J, Flamm SD, Fogel MA, Friedrich MG, et al. Standardized image interpretation and post-processing in cardiovascular magnetic resonance – 2020 update: Society for Cardiovascular magnetic resonance (SCMR): Board of Trustees Task Force on standardized post-processing. J Cardiovasc Magn Reson off J Soc Cardiovasc Magn Reson. 2020;22(1):19. PubMed PMC

Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation. 2002;105(4):539–42. doi: 10.1161/hc0402.102975. PubMed DOI

Mavrogeni S, Papavasiliou A, Giannakopoulou K, Markousis-Mavrogenis G, Pons MR, Karanasios E et al. Oedema-fibrosis in Duchenne muscular dystrophy: role of cardiovascular magnetic resonance imaging. Eur J Clin Invest. 2017;47(12). PubMed

Hor KN, Taylor MD, Al-Khalidi HR, Cripe LH, Raman SV, Jefferies JL, 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 off J Soc Cardiovasc Magn Reson. 2013;15(1):107. PubMed PMC

van Woerden G, van Veldhuisen DJ, Gorter TM, Willems TP, van Empel VPM, Peters A, et al. The clinical and prognostic value of late Gadolinium enhancement imaging in heart failure with mid-range and preserved ejection fraction. Heart Vessels. 2022;37(2):273–81. doi: 10.1007/s00380-021-01910-2. PubMed DOI PMC

Xu K, Xu H, Xu R, Xie L, jun, Yang Z gang, Yu L et al. Global, segmental and layer specific analysis of myocardial involvement in Duchenne muscular dystrophy by cardiovascular magnetic resonance native T1 mapping. J Cardiovasc Magn Reson. 2021;23(1):110. PubMed PMC

Maforo NG, Magrath P, Moulin K, Shao J, Kim GH, Prosper A, et al. T(1)-Mapping and extracellular volume estimates in pediatric subjects with Duchenne muscular dystrophy and healthy controls at 3T. J Cardiovasc Magn Reson off J Soc Cardiovasc Magn Reson. 2020;22(1):85. PubMed PMC

Olivieri LJ, Kellman P, McCarter RJ, Cross RR, Hansen MS, Spurney CF. Native T1 values identify myocardial changes and stratify disease severity in patients with Duchenne muscular dystrophy. J Cardiovasc Magn Reson. 2016;18(1):72. doi: 10.1186/s12968-016-0292-8. PubMed DOI PMC

Frankel KA, Rosser RJ. The pathology of the heart in progressive muscular dystrophy: epimyocardial fibrosis. Hum Pathol. 1976;7(4):375–86. doi: 10.1016/S0046-8177(76)80053-6. PubMed DOI

Everett RJ, Stirrat CG, Semple SIR, Newby DE, Dweck MR, Mirsadraee S. Assessment of myocardial fibrosis with T1 mapping MRI. Clin Radiol. 2016;71(8):768–78. doi: 10.1016/j.crad.2016.02.013. PubMed DOI

Messroghli DR, Radjenovic A, Kozerke S, Higgins DM, Sivananthan MU, Ridgway JP. Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Reson Med. 2004;52(1):141–6. doi: 10.1002/mrm.20110. PubMed DOI

Puntmann VO, Voigt T, Chen Z, Mayr M, Karim R, Rhode K, et al. Native T1 mapping in differentiation of normal myocardium from diffuse disease in hypertrophic and dilated cardiomyopathy. JACC Cardiovasc Imaging. 2013;6(4):475–84. doi: 10.1016/j.jcmg.2012.08.019. PubMed DOI

Kincl V, Panovský R, Pešl M, Máchal J, Juříková L, Haberlová J, et al. Echocardiographic signs of subclinical cardiac function impairment in Duchenne dystrophy gene carriers. Sci Rep. 2020;10(1):20794. doi: 10.1038/s41598-020-77882-6. PubMed DOI PMC

Masárová L, Pisciotti MM-L, Panovský R, Kincl V. Decreased global strains of LV in Asymptomatic Female Duchenne muscular dystrophy gene carriers using CMR-FT. JACC Cardiovasc Imaging. 2021;14(5):1070–2. doi: 10.1016/j.jcmg.2020.09.016. PubMed DOI

Silva MC, Meira ZMA, Gurgel Giannetti J, da Silva MM, Campos AFO, de Barbosa M. Myocardial delayed enhancement by magnetic resonance imaging in patients with muscular dystrophy. J Am Coll Cardiol. 2007;49(18):1874–9. doi: 10.1016/j.jacc.2006.10.078. PubMed DOI

Puchalski MD, Williams RV, Askovich B, Sower CT, Hor KH, Su JT, et al. Late gadolinium enhancement: precursor to cardiomyopathy in Duchenne muscular dystrophy? Int J Cardiovasc Imaging. 2009;25(1):57–63. doi: 10.1007/s10554-008-9352-y. PubMed DOI PMC

von Knobelsdorff-Brenkenhoff F, Prothmann M, Dieringer MA, Wassmuth R, Greiser A, Schwenke C, et al. Myocardial T1 and T2 mapping at 3 T: reference values, influencing factors and implications. J Cardiovasc Magn Reson off J Soc Cardiovasc Magn Reson. 2013;15(1):53. PubMed PMC

Correction: Myocardial native T1 mapping and extracellular volume quantification in asymptomatic female carriers of Duchenne muscular dystrophy gene mutations