Angiotensin-converting enzyme inhibitors and beta-blockers in cardiacasymptomatic patients with Duchenne muscular dystrophy
A. FAYSSOIL,
Raymond Poincare Hospital, critical care medicine Garches,FRANCE

Manuscrit

 DMD is an X-linked recessive disorder caused by the absence of dystrophin. This disease affects one in 3500 male births (1). Dystrophin is a sarcolemmal protein which links the cytoskeleton to the extra cellular matrix by interacting with a large number of membrane proteins. The lack of this protein leads to progressive fiber damage and membrane leakage which alters muscle. DMD is characterized by skeletal and cardiac muscle degeneration with fibrous tissue replacement and fatty infiltration. The onset of this disease occurs in early childhood, and most patients die of respiratory failure and / or congestive heart failure at approximately 20 years of age. About 90% of the patients disclose cardiomyopathy because of cardiac muscle degeneration leading progressively to heart failure (1). Most DMD patients remain asymptomatic for years in spite of the progression of cardiac dysfunction because of their limited daily activities. However, it is possible to detect latent myocardial involvement by using cardiac tissular Doppler imaging. Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are traditionally recommended in heart failure (2). ACE inhibitors are recommended as first-line treatment in all patients with reduced left ventricular (LV) systolic function (LV ejection fraction = 35 – 40%) (2). ACE inhibitors block the conversion of angiotensin-I to angiotensin-II and thus reduce the level of angiotensin-II. Moreover, they inhibit kininase-II and increase bradykinin concentration. Mechanisms underlying benefits’ effects in heart failure include decrease of peripheral vascular resistance, improvement of endothelial function, myocardial fibrosis and after-load reducing (3,4). Beta - blockers (carvedilol, bisoprolol, and metoprolol succinate) decrease the rate of hospitalisations and mortality and lead to improvement of functional class. The mechanisms of the beneficial effects of beta-blockers in heart failure include suppression of oxygen consumption, upregulation of beta-adrenergic receptors, anti-arrhythmic effects, decrease of cardiac norepinephrine and improvement of ventricular diastolic function (5). The combination of beta-blockers and ACE inhibitors can improve the LV systolic function in DMD patients (4). Duboc et al. reported that ACE inhibitors (perindopril) may improve cardiac function in young DMD patients (6). Moreover, perindopril can delay the onset and the progression of LV dysfunction (6). In the study reported by Ogata H. et al. (7), asymptomatic

patients treated by ACE inhibitors and beta-blockers had a 5-year survival rate of 97% and a 7-survival rate of 84%. Early detection of myocardial involvement by using echocardiography-Doppler completed by tissular Doppler imaging in asymptomatic DMD patients will provides informations  for the prescription of  ACE inhibitors and beta-blockers (8).

References
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2) Task Force for Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of European Society of Cardiology, Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Strömberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K; ESC Committee for Practice Guidelines, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J. 2008 Oct;29(19):2388-442
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5) Packer M, Coats AJS, Fowler MB, Katus HA, Krum H, Mohacsi P, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651– 1658.
6) Duboc D, Meune C, Lerebours G, Devaux JY, Vaksmann G, Bécane HM. Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J Am Coll Cardiol. 2005 Mar 15;45(6):855-7
7) Ogata H, Ishikawa Y, Ishikawa Y, Minami R. Beneficial effects of beta-blockers and angiotensin-converting enzyme inhibitors in Duchenne muscular dystrophy. J Cardiol. 2009 Feb;53(1):72-8.
8) Towbin JA. A non-invasive means of detecting preclinical cardiomyopathy in Duchenne muscular dystrophy? J Am Coll Cardiol 2003;42: 317–8.

Correspondence:Dr A. FAYSSOIL, Raymond Poincare Hospital, critical care medicine, AP-HP, Garches, FRANCE
Email: fayssoil2000@yahoo.fr