Lise Legrand1, Jonathan W Weinsaft2, Francoise Pousset1, Claire Ewenczyk3, Perrine Charles3, Stéphane Hatem4, Anna Heinzmann3, Marie Biet3, Alexandra Durr3, Alban Redheuil5. 1. Cardiology Department, Pitié-Salpêtrière Hospital (AP-HP), Sorbonne Université, 75013 Paris, France; ICAN Institute of Cardiometabolism and Nutrition, 75013 Paris, France. 2. Weill Cornell Medicine, New York 10021, USA. 3. Paris Brain Institute (ICM), INSERM, CNRS, Pitié-Salpêtrière Hospital (AP-HP), Sorbonne Université, 75646 Paris cedex 13, France. 4. Cardiology Department, Pitié-Salpêtrière Hospital (AP-HP), Sorbonne Université, 75013 Paris, France; ICAN Institute of Cardiometabolism and Nutrition, 75013 Paris, France; ICT Cardiothoracic Imaging Unit, Pitié-Salpêtrière Hospital (AP-HP), Laboratoire d'Imagerie Biomédicale, Sorbonne Université, Inserm, CNRS, 47-83, boulevard de l'hôpital, 75013 Paris, France. 5. ICAN Institute of Cardiometabolism and Nutrition, 75013 Paris, France; ICT Cardiothoracic Imaging Unit, Pitié-Salpêtrière Hospital (AP-HP), Laboratoire d'Imagerie Biomédicale, Sorbonne Université, Inserm, CNRS, 47-83, boulevard de l'hôpital, 75013 Paris, France. Electronic address: alban.redheuil@aphp.fr.
Abstract
BACKGROUND: Friedreich's ataxia is an autosomal recessive mitochondrial disease caused by a triplet repeat expansion in the frataxin gene (FXN), exhibiting cerebellar sensory ataxia, diabetes and cardiomyopathy. Cardiac complications are the major cause of early death. AIMS: To characterize the cardiac phenotype associated with Friedreich's ataxia, and to assess the evolution of the associated cardiopathy over 1 year. METHODS: This observational single-centre open label study consisted of two groups: 20 subjects with Friedreich's ataxia and 20 healthy controls studied over two visits over 1 year. All subjects had transthoracic echocardiography, cardiac magnetic resonance imaging, cardiopulmonary exercise testing, quantification of serum cardiac biomarkers and neurological assessment. RESULTS: Patients with Friedreich's ataxia had left ventricular hypertrophy, with significantly smaller left ventricular diastolic diameters and volumes and increased wall thicknesses. Cardiac magnetic resonance imaging demonstrated significant concentric left ventricular remodelling, according to the mass/volume ratio, and focal myocardial fibrosis in 50% of patients with Friedreich's ataxia. Cardiopulmonary exercise testing showed alteration of left ventricular diastolic filling in patients with Friedreich's ataxia, with an elevated VE/VCO2 slope (ventilatory flow/exhaled volume of carbon dioxide). High-sensitivity troponin T plasma concentrations were higher in subjects with Friedreich's ataxia. None of the previous variables changed at 1 year. Neurological assessments remained stable for both groups, except for the nine-hole pegboard test, which was altered over 1 year. CONCLUSIONS: The multivariable characterization of the cardiac phenotype of patients with Friedreich's ataxia was significantly different from controls at baseline. Over 1 year there were no clinically significant changes in patients with Friedreich's ataxia compared with healthy controls, whereas the neurological severity score increased modestly.
BACKGROUND: Friedreich's ataxia is an autosomal recessive mitochondrial disease caused by a triplet repeat expansion in the frataxin gene (FXN), exhibiting cerebellar sensory ataxia, diabetes and cardiomyopathy. Cardiac complications are the major cause of early death. AIMS: To characterize the cardiac phenotype associated with Friedreich's ataxia, and to assess the evolution of the associated cardiopathy over 1 year. METHODS: This observational single-centre open label study consisted of two groups: 20 subjects with Friedreich's ataxia and 20 healthy controls studied over two visits over 1 year. All subjects had transthoracic echocardiography, cardiac magnetic resonance imaging, cardiopulmonary exercise testing, quantification of serum cardiac biomarkers and neurological assessment. RESULTS: Patients with Friedreich's ataxia had left ventricular hypertrophy, with significantly smaller left ventricular diastolic diameters and volumes and increased wall thicknesses. Cardiac magnetic resonance imaging demonstrated significant concentric left ventricular remodelling, according to the mass/volume ratio, and focal myocardial fibrosis in 50% of patients with Friedreich's ataxia. Cardiopulmonary exercise testing showed alteration of left ventricular diastolic filling in patients with Friedreich's ataxia, with an elevated VE/VCO2 slope (ventilatory flow/exhaled volume of carbon dioxide). High-sensitivity troponin T plasma concentrations were higher in subjects with Friedreich's ataxia. None of the previous variables changed at 1 year. Neurological assessments remained stable for both groups, except for the nine-hole pegboard test, which was altered over 1 year. CONCLUSIONS: The multivariable characterization of the cardiac phenotype of patients with Friedreich's ataxia was significantly different from controls at baseline. Over 1 year there were no clinically significant changes in patients with Friedreich's ataxia compared with healthy controls, whereas the neurological severity score increased modestly.