Cardiomyopathy
in Muscular Dystrophy Workshop 28–30 September 2003, Tucson, Arizona
Neuroscience
Letters, 2004
Clinical Recomendations:
The European Neuromuscular Centre convened a
meeting in 2002 on Cardiomyopathy and Muscular Dystrophy. Kate Bushby presented
the findings and recommendations from that gathering. At the 2002 meeting and
the present meeting, it was agreed that clinical studies were not available to
provide specific recommendations regarding the management of cardiomyopathy in
muscular dystrophy. The rare nature of these disorders leads to difficulty in
assembling sufficient numbers of subjects for controlled clinical trials. As
such, multicenter-based trials are needed, and multicenter trials are just
beginning. The complexity in conducting these trials also includes the
determination of adequate endpoints and uniformity in performance and
interpretation of noninvasive studies. Carolyn Spencer reviewed the use of
echocardiography as a tool to predict outcome in subjects with cardiomyopathy.
In some studies, left ventricular function has been used as an endpoint for
studies of heart failure, and it may be useful for studies of the heart failure
that accompanies muscle disease. Paula Clemons is working with Cooperative
International Neuromuscular Research Group (CINRG) to begin a study of the
efficacy of Co enzyme Q10 and prednisone in children with DMD. An arm of this
study will evaluate the effect of these medications on cardiac function
including wall stress, shortening fraction, and tissue Doppler imaging. Valerie
Cwik discussed the ongoing MD STARNet study sponsored by the Centers for
Disease Control. Its goals are to determine whether there has been a change in
the prevalence of DMD and to determine what treatment is being offered to
children with DMD. Until controlled clinical trials are available for
cardiomyopathy with muscular dystrophy, recommendations for clinical care
should rely on controlled clinical trials of heart failure and cardiomyopathy.
The mainstay of pharmacologic treatment for left ventricular dysfunction for
adults with cardiomyopathy and CHF relies on (1) afterload reduction with ACE
inhibitors as a first line option and angiotensin receptor blockade if ACE
inhibitors cannot be used, (2) beta adrenergic receptor blockade, (3)
spironolactone, (4) diuretics as needed to manage fluid overload, and (5)
aggressive surveillance for cardiac arrhythmias. The role of additional
pharmacologic agents such as digoxin is not clear. Arrhythmias, if detected or
suspected, can be treated by device implantation and/or pharmacologic therapy
with antiarrhythmic agents. Surveillance should include regular EKGs, Holter
monitoring and/or event monitoring. Syncope, if noted, may warrant treatment
for presumed arrhythmias. Similar therapies in children, with the use of ACE
inhibitors and b-blockers with or without diuretics and digoxin, are first line
approaches. The specific recommendations may be modified with regard to the
precise gene defect. In DMD, heart involvement generally occurs later than
skeletal muscle involvement and may not be present until the late second
decade. It is not known at this time whether early treatment, before the
visible onset of left ventricular dysfunction may slow the course of
cardiomyopathy. Future clinical trials should be designed to determine at what
age and at what stage therapy to prevent cardiomyopathy should be initiated. As
these problems can become evident in the early second decade, monitoring should
begin at that time. Cardiologists, whether specialized in the care of adult or
pediatric patients, should be experienced in caring for subjects with muscular
dystrophy. The Muscular Dystrophy Association may wish to identify a referral
base of cardiologists who work with the MDA clinics throughout the country. In
BMD, cardiac involvement may occur later but may eventually become a prominent
feature. Cardiac transplantation can be offered if pharmacologic therapy fails.
Monitoring should begin in the late second decade for BMD. Finally, female carriers
of dystrophin mutations should be evaluated beginning in their late 3rd to 4th
decade since cardiomyopathy may develop in these subjects.