PMID- 21812510
OWN - NLM
STAT- MEDLINE
DCOM- 20120119
LR  - 20110913
IS  - 1179-187X (Electronic)
IS  - 1175-3277 (Linking)
VI  - 11
IP  - 5
DP  - 2011 Oct 1
TI  - Pathophysiology and therapy of cardiac dysfunction in Duchenne muscular 
      dystrophy.
PG  - 287-94
LID - 10.2165/11594070-000000000-00000 [doi]
AB  - Cardiac dysfunction is a frequent manifestation of Duchenne muscular dystrophy 
      (DMD) and a common cause of death for individuals with this condition. Early 
      diastolic dysfunction and focal fibrosis proceed to dilated cardiomyopathy (DCM), 
      complicated by heart failure and arrhythmia in most patients. Improvements in the 
      management of respiratory insufficiency in DMD have improved lifespan and overall 
      prognosis, but heart failure and sudden death continue to impact survival and 
      quality of life for people with DMD. Since the specific mechanisms resulting in 
      heart failure for people with DMD are poorly understood, current treatments are 
      not targeted, but rely on approaches that are considered standard for DCM. These 
      approaches include angiotensin-converting enzyme (ACE) inhibitors and 
      beta-adrenoceptor antagonists. Data from one trial in DMD support the use of ACE 
      inhibitors before the onset of left ventricular dysfunction. Angiotensin receptor 
      blockers have shown similar efficacy to ACE inhibitors in numerous studies of 
      dilated cardiomyopathy, and are a good choice for patients who cannot tolerate 
      ACE inhibition. The pathogenesis of DMD-associated cardiomyopathy may be similar 
      to other genetic disorders of the cytoskeletal complex of ventricular myocytes, 
      though unique features offer targeted opportunities to impact treatment. Novel 
      areas of investigation are focused on the regulatory role of dystrophin in 
      relation to neuronal nitric oxide synthase (nNOS) and transient receptor 
      potential canonical channels (TRPC). Inhibition of phosphodiesterase-5 (PDE5) 
      addresses several aspects of regulatory dysfunction induced by dystrophin 
      deficiency, and studies with PDE5-inhibitors have shown benefits in murine models 
      of DMD. PDE5-inhibitors are currently under investigation in at least one study 
      in humans. This article focuses on mechanisms of cardiac dysfunction, as well as 
      potential targets for pharmacologic manipulation to prevent or improve 
      cardiomyopathy in DMD.
FAU - Judge, Daniel P
AU  - Judge DP
AD  - Division of Cardiology/Medicine, Johns Hopkins University, Baltimore, MD 21205, 
      USA. djudge@jhmi.edu
FAU - Kass, David A
AU  - Kass DA
FAU - Thompson, W Reid
AU  - Thompson WR
FAU - Wagner, Kathryn R
AU  - Wagner KR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - New Zealand
TA  - Am J Cardiovasc Drugs
JT  - American journal of cardiovascular drugs : drugs, devices, and other 
      interventions
JID - 100967755
SB  - IM
MH  - Animals
MH  - Heart/*drug effects/*physiopathology
MH  - Humans
MH  - Muscular Dystrophy, Duchenne/*drug therapy/*physiopathology
EDAT- 2011/08/05 06:00
MHDA- 2012/01/20 06:00
CRDT- 2011/08/05 06:00
PHST- 2011/08/05 06:00 [entrez]
PHST- 2011/08/05 06:00 [pubmed]
PHST- 2012/01/20 06:00 [medline]
AID - 10.2165/11594070-000000000-00000 [doi]
PST - ppublish
SO  - Am J Cardiovasc Drugs. 2011 Oct 1;11(5):287-94. doi: 
      10.2165/11594070-000000000-00000.