The Correlation of Skeletal and Cardiac Muscle Dysfunction in Duchenne Muscular Dystrophy

Abstract

Background: Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle and cardiac dysfunction. While skeletal muscle dysfunction precedes cardiomyopathy, the relationship between the progressive decline in skeletal and cardiac muscle function is unclear. This relationship is especially important given that the myocardial effects of many developing DMD therapies are largely unknown.

Objective: Our objective was to assess the relationship between progression of skeletal muscle weakness and onset of cardiac dysfunction in DMD.

Methods: A total of 77 DMD subjects treated at a single referral center were included. Demographic information, quantitative muscle testing (QMT), subjective muscle strength, cardiac function, and current and retrospective medications were collected. A Spearman rank correlation was used to evaluate for an association between subjective strength and fractional shortening. The effects of total QMT and arm QMT on fractional shortening were examined in generalized least square with and without adjustments for age, ambulatory status, and duration of corticosteroids and cardiac specific medications.

Results: We found a significant correlation between maintained subjective skeletal muscle arm and leg strength and maintained cardiac function as defined by fractional shortening (rho=0.47, p=0.004 and rho=0.48, p=0.003, respectively). We also found a significant association between QMT and fractional shortening among non-ambulatory DMD subjects (p=0.03), while this association was not significant in ambulatory subjects.

Conclusions: Our findings allow us to conclude that in this population, there exists a significant relationship between skeletal muscle and cardiac function in non-ambulatory DMD patients. While this does not imply a causal relationship, a possible association between skeletal and cardiac muscle function suggests that researchers should carefully monitor cardiac function, even when the primary outcome measures are not cardiac in nature.

Keywords: Ambulation; Cardiac dysfunction; Cardiomyopathy; Duchenne muscular dystrophy; Skeletal muscle dysfunction.

Figure 1. Relationship between fractional shortening (FS) and quantitative muscle testing (QMT)

Figure 1 demonstrates predicted fractional shortening (FS) from the generalized least square model including the interaction between total quantitative muscle testing (QMT) and ambulatory status with adjustment for age and duration of corticosteroids and cardiac specific medications. To avoid over-fitting, only those risk factors deemed most important were pre-specified. This relationship is modified by ambulatory status (p=0.03 for interaction) such that greater QMT score was associated with a greater FS among non-ambulatory subjects while there is no significant relationship in ambulatory subjects.