Dados do Trabalho

Título

Long-term Cardiac magnetic resonance imaging study in Friedreich’s Ataxia

Resumo

Background: Friedreich’s ataxia (FRDA) is an autosomal recessively inherited disorder related to abnormally expanded GAA repeat in intron 1 of FXN gene (9q21.11), and characterized by cerebellar ataxia, spasticity and areflexia of lower limbs and loss of position and vibration sense. The disease is also related to cardiomyopathy in about two thirds of individuals, and heart failure is the main cause of death in these patients. There is a lack of biomarkers for clinical care and assessment in clinical trials, and previous data might suggest that cardiac magnetic resonance imaging (cMRI) might be sensitive for early damage and clinical follow-up.
Objective: The present study aimed to assess the usefulness of cMRI as a clinical marker in FRDA.
Methods: Eighteen healthy controls and 42 FRDA patients were included. cMRI was performed in a 3T Phillips scanner. Among patients, 17 also underwent a 5 year-interval repeat cMRI. The following imaging data were assessed: left ventricle ejection fraction (LVEF), mass and volumes, late gadolinium enhancement (LGE), extracellular volume fraction (ECV) and intracellular water-lifetime (τic). The FRDA rating scale (FARS) was determined to quantify neurological decline. An ANCOVA test, using age, sex and follow-up time as covariates, was performed between groups, and also a Pearson correlation coefficient to determine relationship between clinical and imaging data.
Results: The FRDA group had increased LV volumes and thickness, ECV and τi, with preserved LVEF, when compared to controls in cross-sectional analyses. Nine patients (21,9%) had epicardial LGE. FARS scores did correlate LV volumes. Follow-up analyses evinced an increase of the LV diastolic volume and decrease of the LV volume/mass ratio, but no significant LV decline. Also, 5 additional patients presented epicardial LGE.
Conclusion: FRDA patients have an expansion of the myocardial interstitium and an increase in cardiomyocyte size, with increased LV volumes and thickness, and a preserved LVEF. The cMRI might be useful not only for cardiac assessment but for general clinical evaluation in FRDA since LV volumes correlate with ataxia severity. The follow-up analyses indicate a switch from a hypertrophic cardiomyopathy phenotype towards a dilated cardiomyopathy phenotype, suggesting progressive heart damage. Thus, our data suggest that cMRI might be a useful biomarker in FRDA.

Palavras Chave

cardiac MRI, Longitudinal, Friedreich's Ataxia

Área

Neurogenética