Abstract 2735: Genomic, Proteomic and Functional Associations with Left Ventricular Mass in a Young Cohort with Friedreich’s Ataxia
Background: Previous studies have reported an association between the number of GAA repeats on the frataxin gene on the short chromosome 9 with left ventricular mass (LVM) in patients with Friedreich’s ataxia (FA). We compared GAA repeats with LVM as well as ventricular function and proteomic markers in a neurologically symptomatic pediatric population with FA.
Methods: We performed genetic sampling, two-dimensional echocardiographic examinations, including pulsed, tissue Doppler and color flow propagation markers of diastolic function, and measured serum brain natriuretic peptide (BNP), an indicator of LV filling pressure, on 48 FA subjects (25 males, 23 females, mean age=13 ± 2) undergoing examination within a 48 hour period at the NIH Clinical Center.
Results: Based on historical threshold values, LV hypertrophy was present in 45% of cases by M mode echo-determined mass indexed by cubed height while LV concentric remodeling was found in 73% of subjects as indicated by relative wall thickness (RWT)≥ 0.42. Mean 2D biplane LV ejection fraction and Doppler-derived cardiac indices were normal at 71 ± 9% and 3.6 liters/minute/meter2, respectively. All measures of LVM including RWT, height indexed M-mode, 2D myocardial cross-sectional area and 2D biplane bullet method were significantly associated with prolonged isovolumic relaxation (r=0.41, p≤0.005, r=0.40, p≤0.01,r=0.33, p≤0.05 r=0.37, p≤0.01, respectively) and decreased early mitral annular tissue velocity (r=0.61, 0.61, 0.59; p<0.0001 and r=0.49, p≤0.005,respectively) but not early/late velocity (E/A) ratio. Mass indices also correlated with early transmitral velocity/annular tissue Doppler velocity ratio (r=0.53, 0.57, 0.60 and 0.56, respectively, p<0.0001 for all) but not serum BNP. GAA repeat number did not correlate with measures of LVM, diastolic function or BNP.
In this pediatric population, up to 73% of FA subjects with neurological symptoms had evidence of cardiomyopathy with disease.
LVM correlated with markers of impaired early LV filling but not ventricular systolic function or BNP.
Frataxin gene GAA repeats were not associated with LVM, diastolic LV filling abnormalities or elevations of BNP in this stage of the disease.