Introduction

Becker muscular dystrophy (BMD) is a genetic neuromuscular disease characterized by an alteration of the dystrophin protein affecting primarily striated muscle cells. The management of cardiac involvement is central for BMD patients since heart failure represents the most frequent cause of death in this population¹. Quantitative cardiac magnetic resonance (CMR) offers a large range of possibilities for characterizing patients with dystrophin-related cardiomyopathy. The purpose of this prospective study was to perform a comprehensive evaluation of functional and structural myocardial alterations in BMD and to establish the prognosis value of quantitative relaxometry in a population presenting a broad range of cardiac involvement.

Methods

Eighty-eight adult BMD patients (age = 38.7 ± 13.6 yrs, male = 88), and 36 gender and age matched healthy volunteers (age = 39.7 ± 13.1 yrs, male = 36) underwent CMR examination at 3T (Trio, Siemens) using the body coil for RF transmission and a set of flexible matrix coils for signal reception. Seventy-two BMD patients had a follow-up visit after a mean period of (3.0±0.3 yrs) at 3T (Prisma^Fit, Siemens). All subjects underwent venous blood sampling for haematocrit (HTC) determination on the day of CMR. Blood NT-proBNP was also assayed in BMD patients. Cine images were acquired using a balanced steady-state-free precession (bSSFP) sequence in a stack of short-axis oriented slices encompassing the left ventricle (TE/TR = 1.51/33.22 ms, resolution = 1.7 mm², acquisition time = 12 R-R cycles per slice). Images were retrospectively reconstructed with a scheme of 20 phases per RR cycle to calculate left and right-ventricular ejection fraction (LV- and RV-EF, respectively). T2 maps were obtained in short axis orientation with a T2-prepared bSSFP sequence² (TE/TR = 1.3/2.6 ms, 3 T2-preparation times: 0/25/75 ms, resolution = 2.1 mm², acquisition time = 12 R-R cycles). For T1 mapping, a MOLLI sequence was acquired with a standard implementation³ consisting of 3 inversion sets of 3, 3 and 5 images (TE/TR = 1.25/2.5 ms, TI1 = 100 ms, ΔTI = 80 ms, resolution = 2.1 mm², 3 R-R cycles recovery period and acquisition time = 17 R-R cycles). T1 maps were acquired before and 15 minutes after intravenous contrast agent injection (0.2 mmol/kg Dotarem) for ECV quantification⁴.

Results

Figure 1 summarizes the main CMR variables measured at baseline in BMD patients and healthy controls. LV-EF was significantly reduced in BMD patients (61.6 ± 12.2 % vs 69.1 ± 6.5 %; p<0.001). A total of 26% of the BMD patients had a LV-EF below the cutoff lower value determined on healthy volunteers (LV-EF < 56.1%). RV-EF was similar and within the normal range in the two groups (38.7± 8.8% vs 38.3 ± 9.3, p = 0.836). Globally, native T1, T2 and ECV values were significantly higher in BMD patients than in healthy volunteers. A segmental analysis (based on AHA-segmentation) depicted that abnormal segments were found in the inferior, infero-lateral and antero-lateral region (p<0.05, figure 2). Mean native T1 correlated with T2 (R = 0.77, p<0.001) and ECV (R = 0.81, p<0.001, figure 3). Consequently, T2 and ECV were also correlated (R = 0.72, p<0.001). Mean native T1, T2 and ECV correlated with LV-EF values (R = -0.79, -0.70 and -0.71 respectively; p<0.001) and also with NT-proBNP (R = 0.511, 0.58 and 0.44 respectively, p<0.001). No correlations were observed between native T1, T2, ECV and age. After 3 years, 50% of BMD patients had a reduced LV-EF (DLV-EF <0) compared to baseline and 50% had an identical or increased LV-EF (DLV-EF<0). Patients with DLV-EF< 0 had a significantly higher native T1, T2 and ECV than patients with DLV-EF≥0 (figure 4).

Discussion & Conclusion

In this protocol involving a large cohort of BMD subjects, we demonstrated that native T1 and T2 mapping were able to detect subtle variations of tissue structure in patients with BMD. We also demonstrated that native T1 and T2 mapping could provide biomarkers related to inflammation and fibrosis processes that stratify disease severity in BMD patients with the same sensitivity as quantitative contrast-enhanced CMR. Avoiding gadolinium injection could represent a significant benefit for these subjects who are prone to experience multiple examination through their lifespans. Quantitative CMR may serve to detect subtle degradations in BMD patients and initiate appropriate therapy at early stages of heart failure. Our results encourage a more systematic inclusion of CMR examination in the standard of care applied to BMD patients for monitoring cardiac involvement.

Acknowledgements

No acknowledgement found.