Download Hypertrophic Cardiomyopathy

Cardiac Issues in Friedreich’s Ataxia
2nd Annual Friedreich’s Ataxia Symposium
Robert E. Shaddy, MD
Jennifer Terker Professor of Pediatrics
Division Chief, Pediatric Cardiology
Medical Director, Heart Transplant Program
The Children’s Hospital of Philadelphia
University of Pennsylvania School of Medicine
Incidence
• Myocardial involvement is eventually
evident in 95% of cases
• Typical findings are thickening of the walls
of the heart, particularly the left ventricle
• Can progress to dilated LV
• Pathogenesis unclear
– Mitochondrial respiratory chain dysfunction
– Oxidative stress
Hypertrophied Left Ventrcile
Clinical Manifestations
• Cardiac signs and symptoms typically occur
late in the course of the disease, but they may
rarely precede the neurologic symptoms
– Exertional dyspnea
– Chest pain
• Some studies suggest that the frequency of
cardiomyopathy increases with the size of the
GAA repeat in the shorter allele
Filla A et al. Am J Human Gen 1997
Diagnostic Testing
• ECG
– Commonly abnormal usually left ventricular hypertrophy (LVH)
• Echocardiography
– Most sensitive way to assess cardiac involvement
– LVH
– Can progress to dilated cardiomyopathy with decreased function
• Cardiac MRI
Alizad A, Seward JB. J Am Soc Echocardiogr. 2000
Echocardiogram
Cardiac MRI
• 41 adults with FA (29% with atypical
phenotype)
• 40% with LVH
• GAA repeat length had only minor influence
on interventricular septal thickness
Meyer C. Movement Disorders 2007
Cardiac MRI
Meyer C. Movement Disorders 2007
Idebenone
Rustin et al. Free Radical Res 2002
Hausse et al. Heart 2002
Neurology 2003
• LVPW thickness reduction
– 6 months
• 4.3% idebenone group
• 0.8% placebo group p=0.43
– 12 months
• 8.6% idebenone group
• 2.4% control group p=0.18
Kearney et al. Cochrane Rev 2009
• “No research on the clinical relevance of
this heart change has been done.”
Kearney et al. Cochrane Rev 2009
Friedreich’s Ataxia:
Idebenone Treatment in Early Stage Patients
• Open label trial, 9 patients, 11-19 years
• 5 mg/kg/day for 1 year
• No differences observed in echo
measurements after the start of therapy
Artuch et al. Neuropediatrics 2002
• 28 children from 1974 through 2004
Pediatric Cardiology 2008
• High incidence of LVH
• Slow decrease in LV function over time
• No correlation of cardiac abnormalities with
GAA repeats or ambulatory status
Therapy of Hypertrophic
Cardiomyopathy in Children
• Medications
– Beta-adrenergic receptor blockers
– Calcium channel blockers
– Disopyramide
– Amiodarone
• Implantable Cardioverters/Defibrillators
– Can be used if there are significant concerns of
arrhythmias
Dilated Cardiomyopathy
• Medications
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Angiotensin converting enzyme (ACE) inhibitors
Beta-adrenergic receptor blockers (beta-blockers)
Aldosterone antagonists
Digoxin
Diuretics
Conclusions
• Ventricular hypertrophy is common in
patients with Friederich’s Ataxia
• Echocardiography and MRI are the best
methods to follow the progression of LVH
• It is uncommon to have symptoms from this
during childhood
• Idebenone therapy appears to have some
potential benefit