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

Article type: Research Article

Authors: Posner, Andrew D.^{a; 1; 2} | Soslow, Jonathan H.^{b; 1; *} | Burnette, W. Bryan^c | Bian, Aihua^d | Shintani, Ayumi^d | Sawyer, Douglas B.^e | Markham, Larry W.^b

Affiliations: [a] Vanderbilt University, Nashville, TN, USA | [b] Department of Pediatrics, Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN, USA | [c] Department of Pediatrics, Division of Pediatric Neurology, Vanderbilt University Medical Center, Nashville, TN, USA | [d] Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA | [e] Department of Cardiac Services, Maine Medical Center, Portland, ME, USA

Correspondence: [*] Correspondence to: Jonathan H. Soslow, MD, MSCI, Department of Pediatrics, Division of Pediatric Cardiology, Vanderbilt University Medical Center, 2200 Children’s Way, Suite 5230 DOT, Nashville, TN 37232, USA. Tel: +1 615 322 7447; Fax: +1 615 322 2210; E-mail: jonathan.h.soslow@vanderbilt.edu.

Note: [1] First author disclaimer: Recognizing the importance of being listed as first author in various search engines and to career advancement, both A. Posner and Dr. Soslow deserve this distinction based on their individual contributions to the generation of this work and are listed here in alphabetical order.

Note: [2] Present address: University of Maryland Medical Center, 22. S. Greene St.Baltimore, MD 21201-1595

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: Duchenne muscular dystrophy, cardiac dysfunction, cardiomyopathy, skeletal muscle dysfunction, ambulation

DOI: 10.3233/JND-150132

Journal: Journal of Neuromuscular Diseases, vol. 3, no. 1, pp. 91-99, 2016