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Variations in native T1 values in patients with Duchenne muscular dystrophy with and without late gadolinium enhancement

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Abstract

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder leading to progressive skeletal and cardiac myopathy. Elevated myocardial T1 values correlate with fibrosis in most disease processes, but DMD skeletal and cardiac histopathology is defined by fibrofatty replacement that may result in a decrease in T1 values, due to the low T1 of fat. The study goal was to assess myocardial T1 values in DMD patients with and without late gadolinium enhancement (LGE). A retrospective analysis was performed on all patients with DMD referred for CMR at our institution from 7/5/2017 to 10/24/2018. T1 measurements were performed using breath-held modified Look Locker inversion recovery (MOLLI) sequences at the basal and mid-ventricular levels. The cohort was separated into patients without the presence of LGE (LGE−) and patients with current or previous LGE (LGE+). A total of 207 CMR studies were analyzed. The LGE− group comprised 88 patients while 119 patients were in the LGE+ group. The LGE+ group was older, had larger indexed LV end-diastolic volume and lower LV ejection fraction (LVEF) compared to the LGE− group. T1 values in the LGE+ group were lower compared to the LGE− group (mid T1 1012 ms vs. 1035 ms; p = 0.002), with 5 CMR studies demonstrating mid T1 values < 900 ms. There was no correlation between mid T1 and LVEF in the LGE− group. In the LGE+ cohort, lower T1 values correlated with worse LVEF (r = 0.34, p = 0.0002). The association between mid T1 values and LVEF remained statistically significant on multivariable analysis when accounting for number of LGE segments, LVEDVi, and age (p = 0.009). This is the largest study assessing native T1 values in patients with DMD. The results demonstrate that patients with LGE had lower T1 values than patients without LGE. In the LGE+ group, lower T1 values correlated with worse LV systolic function. These results are consistent with the evolving recognition of fibrofatty replacement in advanced stages of DMD myopathy. Furthermore, our study supports that there is not a simple linear relationship between increasing T1 values and advancing disease progression reported in most other cardiomyopathies.

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Data availability

The data that support the findings of this study are available on request from the corresponding author [SML]. The data are not publicly available due to records which may contain information that could compromise patient confidentiality.

References

  1. Muntoni F, Torelli S, Ferlini A (2003) Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol 2:731–740

    Article  CAS  PubMed  Google Scholar 

  2. Centers for Disease Control and Prevention (2009) Prevalence of Duchenne/Becker muscular dystrophy among males aged 5–24 years—four states, 2007. MMWR Morb Mortal Wkly Rep 58:1119–1122

    Google Scholar 

  3. 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

    Article  PubMed  Google Scholar 

  4. Connuck DM, Sleeper LA, Colan SD, Cox GF, Towbin JA, Lowe AM et al (2008) Characteristics and outcomes of cardiomyopathy in children with Duchenne or Becker muscular dystrophy: a comparative study from the Pediatric Cardiomyopathy Registry. Am Heart J 155:998–1005

    Article  PubMed  PubMed Central  Google Scholar 

  5. Power A, Poonja S, Disler D, Myers K, Patton DJ, Mah JK et al (2017) Echocardiographic image quality deteriorates with age in children and young adults with Duchenne muscular dystrophy. Front Cardiovasc Med 4:82

    Article  PubMed  PubMed Central  Google Scholar 

  6. Soslow JH, Xu M, Slaughter JC, Stanley M, Crum K, Markham LW et al (2016) Evaluation of echocardiographic measures of left ventricular function in patients with Duchenne muscular dystrophy: assessment of reproducibility and comparison to cardiac magnetic resonance imaging. J Am Soc Echocardiogr 29:983–991

    Article  PubMed  PubMed Central  Google Scholar 

  7. American Academy of Pediatrics Section on Cardiology and Cardiac Surgery (2005) Cardiovascular health supervision for individuals affected by Duchenne or Becker muscular dystrophy. Pediatrics 116:1569–1573

    Article  Google Scholar 

  8. Bushby K, Muntoni F, Bourke JP (2003) 107th ENMC international workshop: the management of cardiac involvement in muscular dystrophy and myotonic dystrophy. 7th–9th June 2002, Naarden, the Netherlands. Neuromuscul Disord 13:166–72

    Article  CAS  PubMed  Google Scholar 

  9. Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Case LE et al (2018) Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol 17:347–361

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ong KS, Kinnett K, Soelaeman R, Webb L, Bain JS, Martin AS et al (2018) Evaluating implementation of the updated care considerations for Duchenne muscular dystrophy. Pediatrics 142:S118–S128

    Article  PubMed  Google Scholar 

  11. Feingold B, Mahle WT, Auerbach S, Clemens P, Domenighetti AA, Jefferies JL et al (2017) Management of cardiac involvement associated with neuromuscular diseases: a scientific statement from the American Heart Association. Circulation 136:e200–e231

    Article  PubMed  Google Scholar 

  12. Tandon A, Villa CR, Hor KN, Jefferies JL, Gao Z, Towbin JA, Wong BL et al (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 4:e001338

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Soslow JH, Damon SM, Crum K, Lawson MA, Slaughter JC, Xu M et al (2016) Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy. J Cardiovasc Magn Reson 18:5

    Article  PubMed  PubMed Central  Google Scholar 

  14. Schelbert EB, Messroghli DR (2016) State of the art: clinical applications of cardiac T1 mapping. Radiology 278:658–676

    Article  PubMed  Google Scholar 

  15. Haaf P, Garg P, Messroghli DR, Broadbent DA, Greenwood JP, Plein S (2016) Cardiac T1 mapping and extracellular volume (ECV) in clinical practice: a comprehensive review. J Cardiovasc Magn Reson 18:89

    Article  PubMed  PubMed Central  Google Scholar 

  16. Messroghli DR, Moon JC, Ferreira VM, Grosse-Wortmann L, He T, Kellman P et al (2017) Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: a consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI). J Cardiovasc Magn Reson 19:75

    Article  PubMed  PubMed Central  Google Scholar 

  17. Flett AS, Hayward MP, Ashworth MT, Hansen MS, Taylor AM, Elliott PM et al (2010) Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation 122:138–144

    Article  PubMed  Google Scholar 

  18. Starc JJ, Moore RA, Rattan MS, Villa CR, Gao Z, Mazur W et al (2017) Elevated myocardial extracellular volume fraction in Duchenne muscular dystrophy. Pediatr Cardiol 38:1485–1492

    Article  PubMed  Google Scholar 

  19. Olivieri LJ, Kellman P, McCarter RJ, Cross RR, Hansen MS, Spurney CF (2016) Native T1 values identify myocardial changes and stratify disease severity in patients with Duchenne muscular dystrophy. J Cardiovasc Magn Reson 18:72

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bish LT, Yarchoan M, Sleeper MM, Gazzara JA, Morine KJ, Acosta P et al (2011) Chronic losartan administration reduces mortality and preserves cardiac but not skeletal muscle function in dystrophic mice. PLoS ONE 6:e20856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chun JL, O’Brien R, Berry SE (2012) Cardiac dysfunction and pathology in the dystrophin and utrophin-deficient mouse during development of dilated cardiomyopathy. Neuromuscul Disord 22:368–379

    Article  PubMed  Google Scholar 

  22. Quinlan JG, Hahn HS, Wong BL, Lorenz JN, Wenisch AS, Levin LS (2004) Evolution of the mdx mouse cardiomyopathy: physiological and morphological findings. Neuromuscul Disord 14:491–496

    Article  PubMed  Google Scholar 

  23. Klingler W, Jurkat-Rott K, Lehmann-Horn F, Schleip R (2012) The role of fibrosis in Duchenne muscular dystrophy. Acta Myol 31:184–195

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Burakiewicz J, Sinclair CDJ, Fischer D, Walter GA, Kan HE, Hollingsworth KG (2017) Quantifying fat replacement of muscle by quantitative MRI in muscular dystrophy. J Neurol 264:2053–2067

    Article  PubMed  PubMed Central  Google Scholar 

  25. Tsai WC, Kao KJ, Chang KM, Hung CF, Yang Q, Lin CE et al (2017) B1 field correction of T1 estimation should be considered for breast dynamic contrast-enhanced MR imaging even at 1.5 T. Radiology 282:55–62

    Article  PubMed  Google Scholar 

  26. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ et al (2002) 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. Int J Cardiovasc Imaging 18:539–542

    PubMed  Google Scholar 

  27. Lang SM, Alsaied T, Moore RA, Rattan M, Ryan TD, Taylor MD (2019) Conservative gadolinium administration to patients with Duchenne muscular dystrophy: decreasing exposure, cost, and time, without change in medical management. Int J Cardiovasc Imaging 35(12):2213–2219

    Article  PubMed  Google Scholar 

  28. Niss O, Fleck R, Makue F, Alsaied T, Desai P, Towbin JA et al (2017) Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia. Blood 130:205–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Puntmann VO, Voigt T, Chen Z, Mayr M, Karim R, Rhode K et al (2013) Native T1 mapping in differentiation of normal myocardium from diffuse disease in hypertrophic and dilated cardiomyopathy. JACC Cardiovasc Imaging 6:475–484

    Article  PubMed  Google Scholar 

  30. Puntmann VO, Peker E, Chandrashekhar Y, Nagel E (2016) T1 mapping in characterizing myocardial disease: a comprehensive review. Circ Res 119:277–299

    Article  CAS  PubMed  Google Scholar 

  31. Panovsky R, Pesl M, Holecek T, Machal J, Feitova V, Mrazova L et al (2019) Cardiac profile of the Czech population of Duchenne muscular dystrophy patients: a cardiovascular magnetic resonance study with T1 mapping. Orphanet J Rare Dis 14(1):10

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kellman P, Bandettini WP, Mancini C, Hammer-Hansen S, Hansen MS, Arai AE (2015) Characterization of myocardial T1-mapping bias caused by intramyocardial fat in inversion recovery and saturation recovery techniques. J Cardiovasc Magn Reson 17:33

    Article  PubMed  PubMed Central  Google Scholar 

  33. Mordi I, Radjenovic A, Stanton T, Gardner RS, McPhaden A, Carrick D et al (2015) Prevalence and prognostic significance of lipomatous metaplasia in patients with prior myocardial infarction. JACC Cardiovasc Imaging 8:1111–1112

    Article  PubMed  Google Scholar 

  34. Reiter U, Reiter C, Krauter C, Fuchsjager M, Reiter G (2018) Cardiac magnetic resonance T1 mapping. Part 2: diagnostic potential and applications. Eur J Radiol 109:235–247

    Article  PubMed  Google Scholar 

  35. Baroldi G, Silver MD, De Maria R, Parodi O, Pellegrini A (1997) Lipomatous metaplasia in left ventricular scar. Can J Cardiol 13:65–71

    CAS  PubMed  Google Scholar 

  36. Pouliopoulos J, Chik WW, Kanthan A, Sivagangabalan G, Barry MA, Fahmy PN et al (2013) Intramyocardial adiposity after myocardial infarction: new implications of a substrate for ventricular tachycardia. Circulation 128:2296–2308

    Article  PubMed  Google Scholar 

  37. Kim HK, Serai S, Lindquist D, Merrow AC, Horn PS, Kim DH et al (2015) Quantitative skeletal muscle MRI: part 2, MR spectroscopy and T2 relaxation time mapping-comparison between boys with Duchenne muscular dystrophy and healthy boys. AJR Am J Roentgenol 205:W216–W223

    Article  PubMed  Google Scholar 

  38. Hasuwa T, Kawano H, Fukae S, Arakawa S, Maemura K (2020) Fat infiltration in myocardium in Duchenne muscular dystrophy with atrial tachycardia. Eur Heart J Cardiovasc Imaging 21(8):922

    Article  PubMed  Google Scholar 

  39. Dabir D, Child N, Kalra A, Rogers T, Gebker R, Jabbour A et al (2014) Reference values for healthy human myocardium using a T1 mapping methodology: results from the International T1 Multicenter cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 16:69

    Article  PubMed  PubMed Central  Google Scholar 

  40. Piechnik SK, Ferreira VM, Lewandowski AJ, Ntusi NA, Banerjee R, Holloway C et al (2013) Normal variation of magnetic resonance T1 relaxation times in the human population at 1.5 T using ShMOLLI. J Cardiovasc Magn Reson 15:13

    Article  PubMed  PubMed Central  Google Scholar 

  41. Rauhalammi SM, Mangion K, Barrientos PH, Carrick DJ, Clerfond G, McClure J et al (2016) Native myocardial longitudinal (T1) relaxation time: regional, age, and sex associations in the healthy adult heart. J Magn Reson Imaging 44:541–548

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kanda T, Fukusato T, Matsuda M, Toyoda K, Oba H, Kotoku J et al (2015) Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology 276:228–232

    Article  PubMed  Google Scholar 

  43. Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D (2014) High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology 270:834–841

    Article  PubMed  Google Scholar 

  44. Kanda T, Matsuda M, Oba H, Toyoda K, Furui S (2015) Gadolinium deposition after contrast-enhanced MR imaging. Radiology 277:924–925

    Article  PubMed  Google Scholar 

  45. Kanda T, Oba H, Toyoda K, Kitajima K, Furui S (2016) Brain gadolinium deposition after administration of gadolinium-based contrast agents. Jpn J Radiol 34:3–9

    Article  CAS  PubMed  Google Scholar 

  46. Hor KN, Taylor MD, Al-Khalidi HR, Cripe LH, Raman SV, Jefferies JL et al (2013) 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 15:107

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to acknowledge the Heart Institute and the Heart Institute Research Core at Cincinnati Children’s Hospital Medical Center for their support of the project.

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Authors and Affiliations

  1. Heart Institute, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 2003, Cincinnati, OH, 45229, USA

    Sean M. Lang, Tarek Alsaied, Philip R. Khoury, Thomas D. Ryan & Michael D. Taylor

  2. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA

    Sean M. Lang, Tarek Alsaied, Thomas D. Ryan & Michael D. Taylor

  3. Heart Institute Research Core, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, USA

    Philip R. Khoury

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  1. Sean M. Lang
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Correspondence to Sean M. Lang.

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This study was approved by the Institutional Review Board at Cincinnati Children’s Hospital Medical Center.

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Lang, S.M., Alsaied, T., Khoury, P.R. et al. Variations in native T1 values in patients with Duchenne muscular dystrophy with and without late gadolinium enhancement. Int J Cardiovasc Imaging 37, 635–642 (2021). https://doi.org/10.1007/s10554-020-02031-z

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  • DOI: https://doi.org/10.1007/s10554-020-02031-z

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