Longitudinal Changes in Native T1 Mapping Identifies Occult Cardiomyopathy in a Prospective Cohort of Female Duchenne and Becker Muscular Dystrophy Carriers

Presenting Author(s)

• 

  Megan Gunsaulus, MD

  Physician, pediatric cardiology
  Nationwide Children's Hospital
  Columbus, Ohio, United States

Primary Author(s)

• 

  Megan Gunsaulus, MD

  Physician, pediatric cardiology
  Nationwide Children's Hospital
  Columbus, Ohio, United States

Co-Author(s)

• MM

  May Ling Mah, MD, MSc

  Nationwide Children's Hospital, United States
• SC

  Sara Conroy, PhD

  Biostatistician, principal investigator I
  Nationwide Children's Hospital, United States
• CR

  Carson Richardson, MSc

  Statistics and Biostatistics Analyst 2
  Nationwide Children's Hospital, United States
• LL

  Lauren Ledingham, MD

  Pediatric Cardiology Fellow
  Boston Children's Hospital, United States
• AB

  Amulya Buddhavarapu, MD

  Assistant Professor
  Nationwide Children's Hospital, United States
• 

  Hannah Jacobs, DO

  Advanced Noninvasive Cardiac Imager
  Nationwide Children's Hospital
  Columbus, Ohio, United States
• 

  Marc Lee, MD

  Assistant Professor of Pediatrics
  Nationwide Children's Hospital
  Columbus, Ohio, United States
• 

  Rachel Tonnis, MD

  Pediatric Advanced Cardiovascular Imaging Fellow
  Nationwide Children's Hospital and The Ohio State University
  Columbus, Ohio, United States
• 

  Kan N. Hor, MD

  Director, Advanced Cardiovascular Imaging and Fellowship Program, Associate Division Chief for Research
  Nationwide Children's Hospital and The Ohio State University
  Columbus, OH, USA, Ohio, United States

Background: Female carriers of Duchenne and Becker muscular dystrophy (MDC) have heterozygous dystrophin mutations that may lead to clinical manifestations of cardiomyopathy, although this remains poorly understood. Our group previously demonstrated that, within the same prospective MDC cohort analyzed in this study, approximately 50% of patients had evidence of late gadolinium enhancement (LGE) on their baseline CMR. None of the patients without LGE at baseline developed new LGE over the two-year study period, suggesting that focal fibrosis may progress slowly in MDC. However, this also raises the possibility of more subtle or diffuse myocardial changes not captured by segmental LGE assessment. Native T1 mapping has emerged as a valuable cardiac MRI (CMR) technique for detecting diffuse myocardial changes and has been shown to predict adverse cardiovascular outcomes in patients with cardiomyopathy. This study aimed to assess whether native T1 mapping can offer additional insight into the development of occult cardiomyopathy in MDC patients without overt ventricular dysfunction or macroscopic fibrosis on LGE.

Methods: This was a prospective study involving 77 genetically confirmed MDC and 22 non-carriers, identified through genetic testing, who underwent CMR at three time points approximately 12 months apart. An abnormal Native T1 value was defined as >1297 ms based on previously published normative data using a 3-Tesla CMR scanner in healthy controls (mean 1235 ± 31 ms); values exceeding two standard deviations above the mean were considered abnormal. Linear mixed regression models included the main effects and interaction for visit and carrier status to estimate mean native T1 values and 95% confidence intervals by carrier status across visits.

Results: Follow-up CMRs were completed in 88 participants at visit two and 66 participants at visit three. Across all time points, mean native T1 values were higher in MDC compared to non-carriers. In the non-carrier group, mean native T1 values remained stable over the two-year period. In contrast, MDC demonstrated an increase in mean Native T1 from 1254 ms (95% CI: 1245-1262) at enrollment to a peak of 1266 ms (95% CI 1257, 1275) at year 1 (Figure 1). The prevalence of abnormal native T1 values ( >1297 ms) also increased over time for MDC. At enrollment, only 2.6% (1/38) of MDC had elevated T1; this proportion rose to 8.3% (3/36) at year one and reached 22% (5/23) at year two. In comparison, only one non-carrier had an elevated T1 value, and it was observed only at year 1 (Figure 2).

Conclusion: Native T1 values were higher in MDC compared to non-carriers and increased over time, with a growing proportion exceeding the abnormal threshold. These findings suggest that native T1 mapping may offer added value in the early detection and longitudinal monitoring of subclinical cardiomyopathy in this population.

Linear mixed regression model demonstrating longitudinal changes in native T1 values among female carriers of Duchenne and Becker muscular dystrophy (MDC) and non-carriers at each timepoint. Data are presented as mean (95% confidence interval).
Box-and-whisker plot demonstrating the distribution of native T1 values among female carriers of Duchenne and Becker muscular dystrophy (MDC) and non-carriers at each timepoint. The horizontal black reference line indicates the threshold for an abnormal native T1 value (>1297 ms).