Analysis of the factors influencing the cardiac phenotype in Friedreich's ataxia

Abstract

Friedreich's ataxia (FRDA) has been associated with both cardiac hypertrophy and to a lesser degree dilated cardiomyopathy. We have conducted a cross sectional magnetic resonance imaging (MRI) study of 25 patients with clinically and genetically confirmed FRDA and 24 healthy controls to analyse how disease parameters influence cardiac features in FRDA. MR cine imaging in the long and short axis planes was performed alongside clinical assessments. LV mass was most pronounced in FRDA patients with a larger genetic mutation (GAA1 repeats >600), earlier age of onset (<16years) and a shorter disease duration (<15 years). LV mass decreased with longer disease duration (>15 years), and independent of GAA1 repeat size and age of onset, suggesting cardiac thinning occurred with prolonged disease. Heart function was lower in patients with larger GAA1 repeat number and longer disease duration. Consequently, cardiac hypertrophy was more marked in FRDA patients with a larger GAA1 repeat number and younger age of onset, while prolonged disease duration was associated with lower LV mass and decreased heart function. It is important not only to understand the biochemical basis for these cardiac changes but also allow for these changes when assessing the effect of treatment of FRDA patients.

The Heart in Friedreich Ataxia

“…Because cardiac involvement in FA is commonly described on the basis of data limited to either LV hypertrophy, LV dysfunction, or electric abnormalities, 10,[17][18][19][20] there is still a lack of comprehensive cardiac data sets that allow development of strategies for the reliable detection and assessment of FA-CM. The present cross-sectional study in Ͼ200 patients is thus far the largest in FA to present data on cardiac morphology and function determined by standard echocardiography, CDMI, cMRI, ECG, and exercise testing.…”

Management and therapy for cardiomyopathy in Friedreich’s ataxia

“…As noted above, magnetic resonance spectroscopy has detected alterations in cardiac bioenergetics in FRDA patients even in the absence of cardiac hypertrophy and systolic dysfunction [21][22][23]. Static disease features, such as GAA repeat length and age of disease onset, in cross-sectional studies correlate with cardiac findings by CMR such as LV mass, LV function [67] and relative wall thickness [48]. As for the observation that LV mass is lower in those with longer disease duration [67], longitudinal studies are needed to determine whether cardiac thinning occurs over time, and whether such thinning represents clinical worsening due to fibrosis in FRDA.…”

“…Static disease features, such as GAA repeat length and age of disease onset, in cross-sectional studies correlate with cardiac findings by CMR such as LV mass, LV function [67] and relative wall thickness [48]. As for the observation that LV mass is lower in those with longer disease duration [67], longitudinal studies are needed to determine whether cardiac thinning occurs over time, and whether such thinning represents clinical worsening due to fibrosis in FRDA. An alternative explanation would include a less severe and thus less hypertrophied cardiac phenotype in older subjects.…”

Cardiomyopathy in the Friedreich Ataxia: Clinical Presentation and Diagnostics of Complications

“…Так, при развитии первичной ГКМП увеличивается не только длина и толщина кардиомиоцитов, но меняется и их пространственная ориентация, т. е. кардиомиоциты межжелудочковой перегородки рас-полагаются поперечно, а не продольно. Подобных морфологических признаков при аутопсии не выяв-ляется у пациентов с кардиомиопатией при АФ, что, по всей видимости, и обусловливает низкую частоту развития желудочковых аритмий [8][9][10][11][12][13].…”