Serial assessment of echocardiographic measures in Friedreich ataxia.

Background: Cardiomyopathy is the most common cause of death in Friedreich ataxia (FRDA), but the relationship between genetic factors, disease course, echocardiographic measures, and clinical outcomes is not completely defined. Methods: Data on echocardiographic results and disease status were obtained from records from a large cohort of subjects followed at the Children's Hospital of Philadelphia (CHOP) or other locations. We compared clinical features with long term clinical outcomes and echocardiographic markers of cardiomyopathy using correlation and linear regression. Results: Overall, FRDA hearts initially showed mild hypertrophy with normal systolic function, and a decrease in systolic function up to 30 years later in the disease course. Markers of maximal hypertrophy, in particular septal wall thickness (IVSTd), moderately correlated with genetic severity (GAA1). GAA1 values predicted later stage cardiac disease manifestations in FRDA (presence of arrhythmias, decreases in ejection fraction to less than 50%). Among echocardiographic parameters, early elevations in septal and posterior wall thickness and a hyperdynamic ejection fraction predicted later adverse outcomes including arrhythmias, decreases in ejection fraction, and death. Conclusions: The present data are consistent with the prevailing pathophysiological hypothesis that decreased levels of frataxin lead to early hypertrophy, with later cardiac problems manifesting as decreased systolic function, arrhythmias, and death.