NEUROBEHAVIORAL SEQUELAE OF CARDIAC SURGERY

申请人描述：虽然与先天性心脏病手术修复相关的死亡率有所下降，但这些患者中不良术后神经系统后遗症（从局灶性损伤到细微的神经行为功能障碍）的患病率却有所上升。一些与心脏手术相关的脑损伤可能归因于术中用于保护重要器官的程序，特别是心肺转流（CPB）。试图确定与CPB相关的神经风险的研究由于难以组建一个适当的对照组而受到阻碍，对照组是修复手术不涉及CPB的可比患者。介入心脏病学的最新进展使患有先天性心脏缺陷的患者可以通过经导管封堵术进行修复，而无需体外循环。与这种修复策略相关的潜在神经风险尚不清楚。然而，一项回顾性（非随机）初步研究的数据表明，经导管封堵术修复房间隔缺损（ASD）的患者在全量表智商、操作智商和视觉空间技能方面的得分显著高于手术修复ASD的患者。该研究是一项前瞻性单中心随机试验，涉及3至15岁11个月的ASD修复患者。患者将被随机分配到两个治疗组，通过标准心脏直视手术方法（包括一段时间的轻度低温CPB）或通过经导管输送器械进行闭合。目标样本量为每个治疗组20例患者，将在3.5年期间入组。每名患者将在ASD闭合前接受一组适合年龄的神经行为测试，并在闭合后12个月接受相同的测试。主要终点是全量表IQ。假设是，在意向治疗分析中，基线和闭合后评估之间的全量表智商变化将因治疗组而异，手术患者的表现明显差于器械患者。要测量的次要终点包括视觉空间技能、注意力/警惕性、精细运动功能、新学习、学术技能和行为。如果结果表明，即使是短暂的CPB也与随后神经行为功能障碍的风险增加有关，那么对许多先天性心脏病患者的临床管理将具有重大意义。

APPLICANT'S DESCRIPTION: Although the mortality associated with surgical repair of congenital heart defects has declined, the prevalence of adverse post-operative neurological sequalae, ranging from focal injury to subtle neurobehavioral dysfunctions is elevated among these patients. Some of the brain injury associated with cardiac surgery may be attributable to the procedures used intra-operatively to protect vital organs, particularly cardiopulmonary bypass (CPB). Studies attempting to determine the neurological risks associated with CPB have been hampered by the difficulty of assembling an appropriate control group of comparable patients whose repair procedure does not involve CPB. Recent advances in interventional cardiology have made available patients with congenital heart defects that can be repaired by means of transcatheter closure, without the need for CPB. The potential neurological risks associated with this repair strategy are not yet clear. Data from a retrospective (nonrandomized) pilot study suggested, however, that patients with an atrial septal defect (ASD) repaired by transcatheter closure scored significantly higher than patients with an ASD repaired surgically in terms of Full-Scale IQ, Performance IQ, and visual-spatial skills. The proposed study is a prospective single-center randomized trial involving patients 3 to 15 years 11 months of age presenting for repair of an ASD. Patients will be randomly assigned to two treatment groups, closure by means of standard open-heart surgical methods that involve a period of mildly hypothermic CPB, or by means of a transcatheter delivered device. The target sample size is 20 patients per treatment group, to be enrolled over a 3.5-year period. Each patient will be administered a battery of age-appropriate neurobehavioral tests prior to ASD closure and the same battery of tests 12 months after closure. The primary endpoint is Full-Scale IQ. The hypothesis is that, in intention-to-treat analyses, change in Full-Scale IQ between the baseline and post-closure assessments will differ depending on treatment group, with surgical patients performing significantly worse than device patients. Secondary endpoints to be measured include visual-spatial skills, attention/vigilance, fine motor function, new learning, academic skills, and behavior. Implications for the clinical management of many patients with congenital heart defects will be substantial if the results indicate that even a brief period of CPB is associated with an increased risk of subsequent neurobehavioral dysfunction.