Monash Cardiovascular Research Centre, MonashHeart and Department of Medicine (School of Clinical Sciences at Monash Health), Monash University and Monash Health, Clayton, Victoria, Australia.
Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
PLoS One. 2018 Dec 31;13(12):e0209410. doi: 10.1371/journal.pone.0209410. eCollection 2018.
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative condition which also has effects on the heart. In 96% of affected individuals FRDA is due to homozygosity of a GAA repeat expansion in intron 1 of the frataxin (FXN) gene. The number of GAA repeats have been shown to relate to disease severity in FRDA, this thought to be via an inverse relationship of GAA repeat number and cellular frataxin levels. We investigated the effects of FRDA on regional long axis function of the left and right ventricles, and also the relationship of long axis systolic (s) and early diastolic (e
) peak velocities with GAA repeat number on the shorter (GAA1) and longer FXN alleles (GAA2).
The study group of 78 adult subjects (age 32±9 years) with FRDA and normal left ventricular (LV) ejection fraction were compared to 54 healthy control subjects of similar age, sex and body size. Tissue Doppler imaging (TDI) signals were recorded at the mitral annulus for measurement of sand e
of the septal, lateral, anterior and inferior walls and at the tricuspid annulus for measurement of right ventricular (RV) sand e
.
All the regional LV sand e
, and both RV sand RV e
, were lower in individuals with FRDA compared to controls (p<0.001 for all). On multivariate analysis, which included LV septal wall thickness (SWT), RV sand RV e
were both inversely correlated with GAA1 (β = -0.32 & -0.33, respectively, p = 0.01), but not with GAA2, whereas anterior and lateral swere both inversely correlated with GAA2 (β = -0.25 and β = -0.28, p = 0.02) but not with GAA1. Increasing SWT was the most consistent LV structural correlate of lower s
and e, whereas age was a consistent inverse correlate of e
but not of s`.
There are generalized abnormalities of both LV regional and RV long axis function in FRDA, but there are also regional differences in the association of this dysfunction with the smaller and larger GAA repeats in the FXN gene.
弗里德赖希共济失调(FRDA)是一种常染色体隐性神经退行性疾病,也会对心脏产生影响。在 96%的受影响个体中,FRDA 是由于 FXN 基因内含子 1 中的 GAA 重复扩增的纯合性所致。已经表明 GAA 重复数与 FRDA 中的疾病严重程度有关,这被认为是通过 GAA 重复数与细胞 FXN 水平的反比关系。我们研究了 FRDA 对左、右心室长轴功能的影响,以及长轴收缩期(s)和早期舒张期(e
)峰值速度与较短(GAA1)和较长 FXN 等位基因(GAA2)中 GAA 重复数的关系。
本研究组纳入了 78 名 FRDA 成年患者(年龄 32±9 岁),这些患者均具有正常的左心室(LV)射血分数,与 54 名年龄、性别和体型相似的健康对照组进行了比较。应用组织多普勒成像(TDI)技术在二尖瓣环记录 s和 e
,测量间隔、侧壁、前壁和下壁的运动,在三尖瓣环记录 s和 e
,测量右心室(RV)的运动。
与对照组相比,FRDA 个体的所有 LV 节段 s和 e
以及 RV 的 s和 RV e
均较低(所有 P<0.001)。多元分析包括 LV 间隔壁厚度(SWT),RV s和 RV e
均与 GAA1 呈负相关(β=-0.32 和-0.33,P=0.01),但与 GAA2 无关,而前壁和侧壁 s均与 GAA2 呈负相关(β=-0.25 和-0.28,P=0.02),但与 GAA1 无关。SWT 的增加是 LV 节段 s
和 e降低的最一致的结构相关因素,而年龄是 e
降低的一致负相关因素,但不是 s`降低的负相关因素。
FRDA 患者存在左心室局部和右心室长轴功能的广泛异常,但这种功能障碍与 FXN 基因中较小和较大 GAA 重复的相关性存在区域性差异。