Glucocorticoid Therapy for Duchenne Cardiomyopathy: A Hobson's Choice?

As if receiving a diagnosis of Duchenne muscular dystrophy (DMD) were not terrible enough, consider the impact when a parent learns of the disease’s progressive and inexorable effects on their son’s heart. A relentless search for effective therapies against relentless cardiomyopathy ensues. Those with access to well-informed teams at centers dedicated to interdisciplinary DMD care may get timely and sensitive screening for cardiac involvement, with institution of agents such as angiotensin-converting enzyme inhibitors and b-blockers that benefit a broad spectrum of myocardial diseases. Those without access to such centers may themselves have to educate less-experienced clinicians on appropriate diagnostic testing and medical therapy, armed with evidence collected from advocacy organizations or their own web-based searches. Crucial to decision-making are published data from high-quality clinical trials, ideally based on mechanistically insightful preclinical investigations, that provide evidence in favor of or against a particular treatment. In this issue of JAHA, Tandon and colleagues describe their analysis of clinically-acquired cardiac magnetic resonance scans in conjunction with steroid use recorded from the medical record in a large, single-center DMD patient cohort. Two major findings are reported. First, they confirm prior results showing that increasing age is a risk factor for worsening left ventricular systolic function. As more damaged myocardium is less likely to function properly, increasing late gadolinium enhancement (LGE) abnormality in parallel with declining left ventricular ejection fraction should not come as a surprise. Their second finding describes an association between steroid use and change over time in number of LGEpositive myocardial segments. When considering the sequelae of chronic corticosteroid therapy, the conclusion that longer steroid treatment duration confers lower age-related increase in myocardial damage warrants closer examination. In particular, what evidence does the scientific literature offer on glucocorticoid therapy for DMD cardiomyopathy? Randomized controlled trials over the last several decades have established glucocorticoids as the therapy to prolong ambulatory function; unfortunately, none included any cardiac end points. Evidence from a number of studies associate prednisone and deflazacort use with better cardiac function and outcomes in boys with DMD. However, the designs of these retrospective observational studies incur inherent biases that make interpretation of even a large amount of data potentially erroneous. Data of similar caliber suggesting that one may retard scoliosis and preserve pulmonary function have been used to justify continued prescription of high-dose glucocorticoids even after loss of ambulation. What is not uncertain are the well-documented adverse effects of chronic, high-dose prednisone and, to a lesser extent, deflazacort therapy in DMD: personality changes, weight gain, cataracts, growth hormone and testosterone deficiencies, diabetes, gastrointestinal complications, and bone fractures. Notably, glucocorticoid use remains outside of the realm of both pediatric and adult guidelines for heart failure management. Even in conditions such as viral myocarditis and cardiac sarcoidosis, the scrutiny of systematic review has exposed the limitations of data generated from observational and retrospective studies, precluding endorsement of efficacy. Given the authors’ implication that longer steroid use is beneficial to the heart in this vulnerable patient population, it is important to carefully consider the limitations of the current study. It is well established that there exists extreme variability in steroid dosing regimens for the treatment of DMD. In addition, many patients elect to be treated with deflazacort, a glucocorticoid not yet available in the United The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Division of Cardiovascular Medicine, Ohio State University, Columbus, OH (S.V.R.); Nationwide Children’s Hospital Heart Center, Coloumbus, OH (L.H.C). Correspondence to: Subha V. Raman, MD, MSEE, Davis Heart and Lung Research Institute, The Ohio State University, 473 W. 12th Ave, Suite 200, Columbus, OH 43210. E-mail: [email protected] J Am Heart Assoc. 2015;4:e001896 doi: 10.1161/JAHA.115.001896. a 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.