STICH TRIAL - NEUROHORMONAL/ CYTOKINE/ GENETIC CORE LAB

缺血性心力衰竭的外科治疗(ST1CH)多中心国际随机试验涉及两个具体的 有冠状动脉的临床心力衰竭(HF)和左心功能不全(LV)患者的主要假设 适合外科血运重建的疾病(CAD)：1)冠状动脉旁路移植术(CABG) 与单独的强化药物治疗相比，治疗(MED)可提高长期存活率；2)局部LV患者 功能障碍，外科心室重建术(SVR)恢复到更正常的左心室大小和形状可提高存活率，而不会有后续的 住院时间与单纯冠脉搭桥术相比。反映发病率、成本和生活质量的重要次要终点 将会被评估。心脏磁共振(CMR)、超声心动图(ECHO)、 神经激素/细胞因子/遗传(NCG)和放射性核素(RN)研究将确保一致的测试实践和 对必要的数据进行标准化，以确定符合条件的患者并解决与主要假设相关的具体问题。 在三年的时间里，50个临床站点将招募2800名同意接受心衰、左心室射血分数(EF)和.35；冠心病的患者 服从冠脉搭桥术。这些患者首先将以心绞痛强度或存在左主干狭窄为特征 仅适用于外科治疗或内科和外科两种治疗方法。将对AH患者进行进一步的评估 SVR的适宜性由收缩末期容量指数(ESVI)、60ml/m2和单个LV区域的功能障碍来指示。 据估计，600名有资格接受SVR但没有资格随机接受药物治疗的患者将平均 随机分为冠脉搭桥术组和非冠脉搭桥组。在2,200名同意接受内科或外科治疗的患者中，1,600名 不符合SVR条件的患者将在单纯MED和MED伴CABG之间随机均分。剩下的600名患者也符合条件 对于SVR，将在仅MED、MED CABG或MED CABG SVR的三种治疗方法之间均匀随机进行。 将保留符合条件但拒绝试验进入的患者的临床信息登记。AH随机化和 一些登记的患者将在至少三年内每隔四个月进行一次诊所访问。恰如其分 随机分组的患者将在指定的随访间隔重复进行核心实验室研究。 神经激素/细胞因子/遗传核心将检验三个假设：1)术前神经激素、利钠水平 多肽和促炎细胞因子将有助于预测最有可能受益于 外科血管重建术和/或外科血管重建术中的SVR；2)手术后的有益变化 神经激素/细胞因子/利钠肽激活将预测接受任何一种手术的患者的长期结果 SVR的血运重建和/或血运重建，将为这些变化提供生理学基础； 具有有利基因型别(如ACE基因低表达或腺苷水平高)的患者最有可能 从冠脉搭桥术或冠脉搭桥术和SVR中获得长期收益。

The Surgical Treatment for Ischemic Heart Failure (ST1CH) multicenter international randomized trial addresses two specific primary hypotheses in patients with clinical heart failure (HF) and left ventricular (LV) dysfunction who have coronary artery disease (CAD) amenable to surgical revascularization: 1) Coronary artery bypass grafting (CABG) with intensive medical therapy (MED) improves long-term survival compared to intensive medical therapy alone; 2) In patients with regional LV dysfunction, surgical ventricular restoration (SVR) to a more normal LV size and shape improves survival free of subsequent hospitalization in comparison to CABG alone. Important secondary endpoints reflecting morbidity, cost, and quality of life will be assessed. Core laboratories for cardiac magnetic resonance (CMR), echocardiography (ECHO), neurohormonal/cytokine/genetic (NCG), and radionuclide (RN) studies will ensure consistent testing practices and standardization of data necessary to identify eligiblepatients and address specific questions related to the primary hypotheses. Over three years, 50 clinical sites will recruit 2,800 consenting patients with HF, LV ejection fraction (EF) < .35, and CAD amenable to CABG. These patients first will be characterized by angina intensity or presence of left main coronary stenosis as appropriate for only surgical therapy or both medical and surgical therapy. AH patients will be evaluated further for appropriateness of SVR indicated by an end-systolic volume index (ESVI) > 60 ml/m2 and dysfunction in a single LV region. The 600 patients estimated to be eligible for SVR but ineligible for randomization to medical therapy will be evenly randomized to CABG with or without SVR. Of the 2,200 consenting patients eligiblefor medical or surgical therapy, the 1,600 not SVR eligiblewill be evenly randomized between MED only and MED with CABG. The remaining600 patients also eligible for SVR will be evenly randomized between three treatments of MED only, or MED + CABG, or MED + CABG + SVR. Registries of clinical information will be maintained on patients who are eligible but decline trial entry. AHrandomized and some registry patients will be followed by a clinic visit at four-month intervals for a minimum of three years. Appropriate subgroups of randomized patients will have core laboratory studies repeated at specified follow-up intervals. The neurohormone/cytokine/genetic core will test three hypothesis: 1) pre-operative levels of neurohormones, natriuretic peptides, and pro-inflammatory cytokines will be useful in predicting that group of patients who will most likely benefit from either surgical revascularization and/or surgical revascularization with SVR; 2) salutary changes post-operatively in neurohormonal/cytokine/natriuretic peptide activation will predict long term outcomes in patients undergoing either surgical revascularization and/or revascularization with SVR and will provide the physiologic rationale for these changes; and 3) patients having a favorable genotype (eg.Low expression of ACE gene or high levels of adenosine) will be most likely to achieve long-term benefit from either CABG or CABG with SVR.