Cardiac Issues in Friedreichs Ataxia2nd Annual Friedreichs Ataxia Symposium

Robert E. Shaddy, MD

Jennifer Terker Professor of PediatricsDivision Chief, Pediatric CardiologyMedical Director, Heart Transplant ProgramThe Childrens Hospital of PhiladelphiaUniversity of Pennsylvania School of Medicine

IncidenceMyocardial involvement is eventually evident in 95% of casesTypical findings are thickening of the walls of the heart, particularly the left ventricleCan progress to dilated LVPathogenesis unclearMitochondrial respiratory chain dysfunctionOxidative stress

Hypertrophied Left Ventrcile

Clinical ManifestationsCardiac signs and symptoms typically occur late in the course of the disease, but they may rarely precede the neurologic symptomsExertional dyspneaChest painSome studies suggest that the frequency of cardiomyopathy increases with the size of the GAA repeat in the shorter alleleFilla A et al. Am J Human Gen 1997

Diagnostic TestingECG Commonly abnormal usually left ventricular hypertrophy (LVH)Echocardiography Most sensitive way to assess cardiac involvementLVHCan progress to dilated cardiomyopathy with decreased functionCardiac MRI

Alizad A, Seward JB. J Am Soc Echocardiogr. 2000

Echocardiogram

Cardiac MRI41 adults with FA (29% with atypical phenotype)40% with LVHGAA repeat length had only minor influence on interventricular septal thickness

Meyer C. Movement Disorders 2007

Cardiac MRIMeyer C. Movement Disorders 2007

Idebenone Rustin et al. Free Radical Res 2002Hausse et al. Heart 2002

Neurology 2003

LVPW thickness reduction6 months4.3% idebenone group0.8% placebo group p=0.4312 months8.6% idebenone group2.4% 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

Friedreichs Ataxia:Idebenone Treatment in Early Stage PatientsOpen label trial, 9 patients, 11-19 years5 mg/kg/day for 1 yearNo 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 LVHSlow decrease in LV function over timeNo correlation of cardiac abnormalities with GAA repeats or ambulatory status

Therapy of HypertrophicCardiomyopathy in ChildrenMedicationsBeta-adrenergic receptor blockersCalcium channel blockersDisopyramideAmiodaroneImplantable Cardioverters/DefibrillatorsCan be used if there are significant concerns of arrhythmias

Dilated CardiomyopathyMedicationsAngiotensin converting enzyme (ACE) inhibitorsBeta-adrenergic receptor blockers (beta-blockers)Aldosterone antagonistsDigoxinDiuretics

ConclusionsVentricular hypertrophy is common in patients with Friederichs AtaxiaEchocardiography and MRI are the best methods to follow the progression of LVHIt is uncommon to have symptoms from this during childhoodIdebenone therapy appears to have some potential benefit

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