Feasibility and Reproducibility of Echocardiographic Measures in Children with Muscular Dystrophies

Abstract

Background: Cardiac disease is a major cause of death in patients with muscular dystrophies. The use of feasible and reproducible echocardiographic measures of cardiac function is critical to advance the field of therapeutics for dystrophic cardiomyopathy.

Methods: Participants aged 8 to 18 years with genetically confirmed Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, or limb-girdle muscular dystrophy were enrolled at five centers, and standardized echocardiographic examinations were performed. Measures of systolic and diastolic function and speckle-tracking echocardiography-derived cardiac strain were reviewed independently by two central readers. Furthermore, echocardiographic measures from participants with DMD were compared with those from retrospective age-matched control subjects from a single site to assess measures of myocardial function.

Results: Forty-eight participants (mean age, 13.3 ± 2.7 years) were enrolled. Shortening fraction had a greater interobserver correlation (intraclass correlation coefficient [ICC] = 0.63) compared with ejection fraction (ICC = 0.49). One reader could measure ejection fraction in only 53% of participants. Myocardial performance index measured by pulse-wave Doppler and Doppler tissue imaging showed similar ICCs (0.55 and 0.54). Speckle-tracking echocardiography showed a high ICC (0.96). Focusing on participants with DMD (n = 33), significantly increased mitral A-wave velocities, lower E/A ratios, and lower Doppler tissue imaging mitral lateral E' velocities were observed compared with age-matched control subjects. Speckle-tracking echocardiography demonstrated subclinical myocardial dysfunction with decreased average circumferential and longitudinal strain in three distinct subgroups: participants with DMD with normal shortening fractions, participants with DMD aged < 13 years, and participants with DMD with myocardial performance index scores < 0.40 compared with control subjects.

Conclusions: In a muscular dystrophy cohort, assessment of cardiac function is feasible and reproducible using shortening fraction, diastolic measures, and myocardial performance index. Cardiac strain measures identified early myocardial disease in patients with DMD.

Keywords: Cardiac strain; Cardiomyopathy; Echocardiography; Muscular dystrophy.

Figure 1

Agreement of percent shortening fraction (SF%) measures within and between readers (Panel A: shows agreement within the same reader (blue is measure #1 and red is measure #2) and Panel B shows agreement between readers separated by diagnosis (blue = DMD, red = BMD, black = LGMD); for both panels, the closer the values are to the identity line, the smaller the discrepancy between the two reads.

Figure 2

Assessment of variability in percent shortening fraction (SF%) measurements across SF% magnitudes (Panel A; a rolling average with standard deviation (SD) bars across the range of observed SF% values) and across different patient ages (Panel B; average with SD bars shown by 2 year intervals) with reader#1 in blue and reader #2 in red.

Figure 3

Agreement between MPI via PWD and TDI. Blue dots represent participants deemed normal by both PWD and TDI; Red dots represent participants deemed abnormal by both PWD and TDI; Black dots represent participants where PWD and TDI MPI disagreed.

Figure 4

Bland-Altman plots demonstrate variability of inter-observer measures for: percent shortening fraction (SF%, Panel A); percent ejection fraction (EF%, Panel B); myocardial performance index (MPI, inter-observer differences in Panel C and inter-method (PWD vs. TDI) in Panel D); average circumferential (CS%, Panel E) and longitudinal strain (LS%, Panel F). The red dashed line represents the mean bias and the shaded area indicates the area between the limits of agreement.