Cardiac Issues in Friedreich’s Ataxia 2 nd Annual Friedreich’s Ataxia Symposium Robert E....
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Transcript of Cardiac Issues in Friedreich’s Ataxia 2 nd Annual Friedreich’s Ataxia Symposium Robert E....
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 2002Hausse 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 HypertrophicCardiomyopathy 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– 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