STICH TRIAL - NEUROHORMONAL/ CYTOKINE/ GENETIC CORE LAB

缺血性心力衰竭的外科治疗（ST 1CH）多中心国际随机试验涉及两个特定的 在冠状动脉粥样硬化性心脏病（CHF）和左心室（LV）功能障碍患者中的主要假设 适合手术血运重建的疾病（CAD）：1）冠状动脉旁路移植术（CABG）， 与单独强化药物治疗相比，MED治疗可改善长期生存率; 2）在局部LV患者中， 功能障碍，手术心室恢复（SVR）到更正常的LV大小和形状可以提高生存率，无后续并发症。 与单纯CABG相比，反映发病率、成本和生活质量的重要次要终点 将被评估。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）研究将确保一致的检测实践， 标准化数据，以确定致命的病人，并解决与主要假设有关的具体问题。 在三年内，50个临床研究中心将招募2,800名同意的HF、LV射血分数（EF）< .35和CAD患者。 适合CABG。这些患者首先将通过心绞痛强度或左主干冠状动脉狭窄的存在来表征， 仅适用于外科治疗或同时适用于内科和外科治疗。将对AH患者进行进一步评价， 收缩末期容积指数（ESVI）> 60 ml/m2和单个LV区域功能障碍表明SVR适当。 600例估计有资格接受SVR但无资格随机接受药物治疗的患者将平均分配至 随机接受CABG伴或不伴SVR。在2,200名同意接受内科或外科治疗的病人中， 非SVR死亡将在仅MED和MED联合CABG之间均匀随机分配。这600名患者也符合条件 对于SVR，将在仅MED、MED + CABG或MED + CABG + SVR的三种治疗之间均匀随机分配。 将保留合格但拒绝参加试验的患者的临床信息登记。AH随机化和 一些登记患者将每隔四个月接受一次门诊随访，至少持续三年。适当 随机分组患者的亚组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/遗传学核心将检验三个假设：1）术前神经激素、利钠素、 肽和促炎细胞因子将有助于预测最有可能受益于 手术血运重建和/或手术血运重建伴SVR; 2）术后 神经激素/细胞因子/利钠肽激活将预测接受手术或非手术治疗的患者的长期结局。 血运重建和/或SVR血运重建，并将提供这些变化的生理学依据;以及3） 具有有利基因型的患者（例如ACE基因表达低或腺苷水平高）最有可能 从CABG或CABG伴SVR中获得长期获益。

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.