Presence of Late Gadolinium Enhancement Predicts Global Ventricular Dysfunction and Disease Progression in Becker Muscular Dystrophy Patients Over Time by Cardiac Magnetic Resonance Imaging

Background: Cardiomyopathy is the leading cause of mortality for Becker Muscular Dystrophy (BMD). Risk stratification is challenging due to the wide variation of cardiomyopathy onset, progression, and severity; with cardiomyopathy developing independent of skeletal myopathy progression. We have been performing cardiac magnetic resonance imaging (CMR) routinely by 10 years of age. We hypothesized that BMD patients with late gadolinium enhancement have worse left ventricular ejection fraction (LVEF) and have greater decline on follow-up CMR study

Methods: We retrospectively reviewed the CMR studies performed between June 2013 and June 2025 and only included patients with at least two studies. The patients were dichotomized into two groups based on LGE findings of the initial CMR study. We collected LGE status, LVEF and age were collected at each study to calculated time between studies, change in LVEF and rate of decline per year. Statistical analysis was performed using Student’s t-test between groups.

Results: There were 75 BMD patients who underwent 150 CMR studies with LGE assessment with CMR date shown in Table 1. The average age of the first CMR study was 14.8±6.2 (range 8-40) and follow-up at 17.9±6.4 years (9-41). Of these 45/75 (60%) patients had negative LGE and 30/75 (40%) had positive LGE on the first study. The LGE positive group was significantly older (p< 0.0001) with average age 18.5±7.4 years (range 9-40 years) compared to 12.3±7.9 years (range 8-22 years). Patients who were LGE positive had a lower mean initial LVEF compared with LGE negative patients (55.1±8.0% vs 62.2±5.3% p-value < 0.0001) and decline in LVEF on follow-up study (48.3±11.1% vs 60.3±6.7% p-value < 0.0001) with no difference in mean follow-up time (2.7±2.0 vs 3.4±2.0 years, p= 0.05), Figure 1 and Figure 2. Of the LGE negative patients 13/45 (28.9%) became positive over a 4.2±1.9 years a decline in LVEF from 65.2±5.2% to 55.8±6.9% over a 4.2±1.9-year period. In serial follow up, LGE positive patients showed a statistically significant decline in LVEF of -6.8%±7.8 vs -2.8±6.0%, p =0.007 for an average yearly decline of -3.7±8% per year versus -0.4±2.1% per year, p=0.005, Figure 3. Interestingly, the 13 patients that converted had a decline in LVEF from 65.2±5.2 to 55.8±6.9% with an average LVEF decreased of -9.4% for a decline of 2.4% per year who those who remained negative did not decline +1.7% for a 0.4% positive LVEF change per year.

Conclusion: Our study reported many BMD patients with LGE positive findings on their first study. Like prior DMD studies, the presence of LGE results in both lower LVEF and more rapid progression. CMR studies should be considered in BMD patients when sedation is no longer required. Escalation of medical therapy should be considered for patients who demonstrate evidence of fibrosis. Future study, should consider more detail LGE assessment to delineate the impact of fibrosis burden and impact on cardiomyopathy progression.

Table 1: Patient CMR Findings at Baseline and Follow-Up Study

Patient Characteristics  (n = 75)	Study Group	LGE Negative Initial CMR	LGE Positive Initial CMR	P-Value (LGE - vs LGE +)
Number  of Subjects, n (%)	75 (100%)	45 (60%)	30 (40%)	N/A
Age at Baseline CMR (Years)	14.8±6.2	12.3±3.7	18.5±7.4	< 0.0001
Age at Follow-up CMR (Years)	17.9±6.4	15.8±4.5	21.2±7.4	0.0001
Time Between CMR (Years)	3.1±2.0	3.4±2.0	2.7±2.0	0.05
LGE - on all CMR, n (%)	32 (42.7%)	32 (42.7)	N/A	N/A
Conversion from LGE - to LGE +,n (%)	13 (17.3%)	13 (17.3%)	N/A	N/A
LGE + on all CMR, n (%)	30 (40%)	N/A	30 (40%)	N/A
Baseline LVEF (%)	59.9±7.6	63.1±5.4	55.1±8.0	< 0.0001
Follow-up LVEF (%)	55.5±10.5	60.3±6.7	48.3±11.1	< 0.0001
Change in LVEF (%) from Baseline to Follow-Up (%)	(-) 4.4±7.0	(-) 2.8±6.0	(-) 6.8±7.8	0.007
Decline in LVEF% per Year	(-) 1.7±5.5	(-) 0.4±2.1	(-) 3.7±8.0	0.005

Table 1: Patient CMR Findings at Baseline and Follow-Up Study

Patient Characteristics (n = 75)	Study Group	LGE Negative Initial CMR	LGE Positive Initial CMR	P-Value (LGE - vs LGE +)
Number of Subjects, n (%)	75 (100%)	45 (60%)	30 (40%)	N/A
Age at Baseline CMR (Years)	14.8±6.2	12.3±3.7	18.5±7.4	< 0.0001
Age at Follow-up CMR (Years)	17.9±6.4	15.8±4.5	21.2±7.4	0.0001
Time Between CMR (Years)	3.1±2.0	3.4±2.0	2.7±2.0	0.05
LGE - on all CMR, n (%)	32 (42.7%)	32 (42.7)	N/A	N/A
Conversion from LGE - to LGE +, n (%)	13 (17.3%)	13 (17.3%)	N/A	N/A
LGE + on all CMR, n (%)	30 (40%)	N/A	30 (40%)	N/A
Baseline LVEF (%)	59.9±7.6	63.1±5.4	55.1±8.0	< 0.0001
Follow-up LVEF (%)	55.5±10.5	60.3±6.7	48.3±11.1	< 0.0001
Change in LVEF (%) from Baseline to Follow-Up (%)	- 4.4±7.0	- 2.8±6.0	- 6.8±7.8	0.007
Decline in LVEF% per Year	- 1.7±5.5	- 0.4±2.1	- 3.7±8.0	0.005

Figure 1: Serial LVEF by CMR in BMD Patients showing initial (blue) and follow-up (red) LVEF changes in LGE positive versus LGE negative patients over time.
Figure 2: Longitudinal Scatter Plot of LGE Negative (blue lines), LGE negative converted to LGE positive (yellow lines) an LGE positive patients (red lines)
Figure 2: Yearly LVEF Decline in LGE Negative (blue) compared to LGE positive (red) BMD patients