Echocardiographic characterization of cardiomyopathy in Friedreich's ataxia with tissue doppler echocardiographically derived myocardial velocity gradients

Abstract

Background - Conventional and tissue Doppler echocardiographically derived myocardial velocity gradients (MVGs) were used to characterize the myocardium in patients with Friedreich's ataxia (FRDA), and the relationship between MVGs and the mutation in the FRDA gene, a GAA triplet repeat expansion, was investigated. Methods and Results - We studied 29 patients with FRDA (10 men, mean age 31±9 years) who were homozygous for the GAA expansion in the FRDA gene and were without cardiac symptoms. A comparison was made with a group of 30 age-matched control subjects. In patients with FRDA, interventricular septal thickness (1.17±0.26 versus 0.85±0.13 cm, P<0.005), posterior left ventricular wall thickness (1.00±0.24 versus 0.88±0.15 cm, P<0.01), and left atrial diameter (3.3±0.5 versus 2.9±0.3 cm, P=0.01) were increased compared with control subjects. MVGs were reduced in FRDA during systole (3.1±1.2 versus 4.5±0.5 s-1, P<0.0001) and in early diastole (4.9±2.7 versus 8.8±1.8 s-1, P<0.0001) but increased in late diastole (2.0±1.3 versus 1.1±0.9 s-1, P<0.01). The strongest relationship was seen between age-corrected early diastolic MVGs and the GAA expansion in the smaller allele of the FRDA gene (r=-0.68, P<0.0001). Conclusions - MVGs offer a means of further characterizing the myocardial abnormalities in patients with FRDA. Early diastolic MVGs appear to relate most closely to the genetic abnormality and the consequential reduction in frataxin protein.