The Longitudinal Course of Cardiomyopathy in Friedreich's Ataxia During Childhood
The Longitudinal Course of Cardiomyopathy in Friedreich's Ataxia During Childhood
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DOI：
10.1007/s00246-008-9305-1
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发表时间：
2009-04-01
影响因子：
1.6
通讯作者：
Blume, Elizabeth D.
中科院分区：
文献类型：
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作者：
Kipps, Alaina;Alexander, Mark;Blume, Elizabeth D.
背景临床心脏病在Friedreich‘s共济失调(FA)的最初描述中被认识。据报道，这种进行性神经系统疾病的心脏表现包括肥厚型心肌病、扩张型心肌病和电生理障碍。儿童病例的纵向数据有限。本研究旨在明确儿童时期诊断为FA的心脏异常的纵向病程，以及心肌病的存在与临床和遗传因素的相关性。方法采用前瞻性、盲法对超声心动图和心电图进行回顾性分析。从1974年到2004年，所有确诊为FA的患者都被纳入了这项研究。结果本研究共对28例患者进行了113次超声心动图检查。总体而言，该组患者左心室肥厚，收缩功能正常，质量z积分中位数为2.48(范围-3.8~35.6)，射血分数(EF)中位数为61%(范围23~81%)。在28例患者中，23例(82%)有两次或两次以上的超声心动图。最近一次超声心动图的中位随访时间为5.1年(范围为0.4-16.5年)。在这一纵向随访队列中，许多人(57%)至少在一次超声心动图上显示肥厚性心肌病，最后一次随访评估显示38%的患者存在收缩功能障碍。随着年龄的增加，心脏收缩功能呈缓慢的非线性下降，平均EF下降更快(p=0.02)，EF维持在正常范围直到22岁。在12名有收缩功能障碍和随访超声心动图的患者中，10名患者至少有一次超声心动图显示EF正常范围改善，5名患者在最后一次研究中保持正常。心功能和心形态方面的趋势与Frataxin GAA重复长度(FA的主要遗传缺陷)或步行状态无关。一名患者需要植入除颤器。没有死亡或心脏移植。结论总体而言，FA患者在整个童年期间都保留了心功能，但心脏重量增加。由于许多收缩功能受抑的患者在随后的研究中表现出改善，因此应该对心力衰竭的潜在可逆原因进行评估。儿童时期的相对临床稳定性和在第二个十年中保持正常的收缩功能可能有助于父母和患者的教育。
Background Clinical heart disease was recognized in the first descriptions of Friedreich's ataxia (FA). Cardiac manifestations reported for this progressive neurologic disease include hypertrophic cardiomyopathy, dilated cardiomyopathy, and electrophysiologic disturbances. Longitudinal data for childhood cases are limited. This study aimed to define the longitudinal course of the cardiac abnormalities with FA diagnosed during childhood and to correlate the presence of cardiomyopathy with clinical and genetic factors. Methods A retrospective chart review was conducted, with prospective, blinded interpretation of echocardiograms and electrocardiograms. All the patients with a diagnosis of FA referred to the cardiology department of a single institution from 1974 to 2004 were included in the study. Results This study investigated a total of 113 echocardiograms for 28 patients. Overall, the group had left ventricular hypertrophy and normal systolic function, with a median mass z-score of 2.48 (range, -3.8 to 35.6) and a median ejection fraction (EF) of 61% (range, 23-81%). Of the 28 patients, 23 (82%) had two or more echocardiograms. The median follow-up time to the most recent echocardiogram was 5.1 years (range, 0.4-16.5 years). Many in this longitudinal follow-up cohort (57%) showed hypertrophic cardiomyopathy on at least one echocardiogram, with the last follow-up assessment showing systolic dysfunction for 38% of these patients. There was a slow nonlinear decline in systolic function over time, with the mean EF decreasing more rapidly as age increased (p = 0.02) and maintenance of EF in the normal range until the age of 22 years. Of the 12 patients with systolic dysfunction and follow-up echocardiograms, 10 showed improvement to the normal EF range on at least one echocardiogram, and 5 remained normal through the last study. None of the trends in cardiac function and morphology correlated with frataxin GAA repeat length (the primary genetic defect in FA) or ambulatory status. One patient required an implantable defibrillator. There were no deaths or heart transplantations. Conclusions Overall, patients with FA have preserved cardiac function with increased mass throughout childhood. Because many patients who experience depressed systolic function show improvement in subsequent studies, evaluation for potentially reversible causes of heart failure should be conducted. Relative clinical stability during childhood and maintenance of normal systolic function into the second decade may be helpful for parent and patient education.