Late Gadolinium Enhancement on Cardiac MRI Associated With Increased Fatigue in Women Carriers of Dystrophinopathies

A single-center retrospective cohort study presented at the 2026 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 9-11, in Orlando, Florida, reported that women carriers of Duchenne muscular dystrophy (MD) and Becker MD with late gadolinium enhancement (LGE) on cardiac MRI had significantly higher fatigue. However, findings showed no significant differences in left ventricular ejection fraction (LVEF) or walking performance between carriers with and without LGE.¹

"[LGE] may precede measurable declines in [LVEF], suggesting that myocardial fibrosis develops before systolic dysfunction becomes apparent,” lead author Audrey McKennitt, BS, a MD candidate at UMass Chan Medical School, and colleagues wrote.¹ “Reliance on LVEF alone may underestimate early cardiac involvement in [women] dystrophinopathy carriers. The presence of LGE, even in the setting of preserved LVEF, supports continued use of contrast-enhanced cardiac MRI to detect subclinical myocardial disease.”

This study aimed to assess whether LGE on cardiac MRI in women carriers of Duchenne or Becker was associated with cardiac function, exercise capacity, and self-reported fatigue. Investigators enrolled into the study 38 genetically confirmed women carriers of DMD or BMD from the UMass Chan Medical School clinic registry between February 2019 and June 2025. Researchers compared LVEF, distance on the 6-minute walk test (6MWT), and total fatigue scores between carriers with (LGE+) and without LGE (LGE–) using Welch t tests. In addition, comorbidities and medication use were compared between groups descriptively.

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Among 35 carriers who underwent at least 1 cardiac MRI assessments (LGE+, n = 15; LGE–, n = 20, the mean LVEF was numerically lower among LGE+ carriers compared with LGE– carriers (56.0 ± 9.1 vs 58.2 ± 4.9; P = .41). In addition, distance on the 6MWT was numerically greater in the LGE+ group (569.0 [±82.7] m vs 535.7 [±102.7] m; P = .30). Notably, fatigue scores, however, were significantly higher among LGE+ carriers compared with those without LGE (21.3 [±17.4] vs 8.2 [±5.2]; P = .02). Authors noted that the LGE+ and LGE– groups did not differ significantly in age, comorbidities, or medication use.

“Prospective longitudinal studies should determine whether LGE predicts subsequent decline in LVEF or functional capacity. Quantitative assessment of LGE burden, rather than binary LGE status, may provide a more sensitive marker of early myocardial remodeling,”McKennitt et al noted.¹ “Future studies incorporating advanced imaging may better detect early myocardial changes, improve risk stratification and inform earlier cardioprotective intervention before systolic dysfunction emerges.”

All told, women heterozygotes of Duchenne MD mutations could be at risk for cardiac disease, even in the absence of skeletal muscle symptoms.^2,3 Despite this risk, authors noted that women carriers have been under investigated, and no evidence-based surveillance guidelines currently exist for this population.⁴ Researchers also highlighted that cardiac MRI with LGE can detect myocardial fibrosis in these individuals, although the association between these imaging findings, cardiac function, and gross motor performance had not been fully established.

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REFERENCES
1. McKennitt A, Offord E, Chrzanowski S, et al. Cardiac MRI and Functional Outcomes in Female Carriers of Dystrophinopathies. Presented at: MDA Clinical & Scientific Conference; March 8-11, 2026; Orlando, Florida. Abstract 19.
2. Mah ML, Cripe L, Slawinski MK, et al. Duchenne and Becker muscular dystrophy carriers: Evidence of cardiomyopathy by exercise and cardiac MRI testing. Int J Cardiol. 2020;316:257-265. doi:10.1016/j.ijcard.2020.05.052
3. Lim KRQ, Sheri N, Nguyen Q, Yokota T. Cardiac Involvement in Dystrophin-Deficient Females: Current Understanding and Implications for the Treatment of Dystrophinopathies. Genes (Basel). 2020;11(7):765. Published 2020 Jul 8. doi:10.3390/genes11070765
4. Sarkozy A, Quinlivan R, Bourke JP, Ferlini A; ENMC 263rd Workshop Study Group. 263rd ENMC International Workshop: Focus on female carriers of dystrophinopathy: refining recommendations for prevention, diagnosis, surveillance, and treatment. Hoofddorp, The Netherlands, 13-15 May 2022. Neuromuscul Disord. 2023;33(3):274-284. doi:10.1016/j.nmd.2023.01.003