STICH TRIAL - NEUROHORMONAL/ CYTOKINE/ GENETIC CORE LAB

STICH 试验 - 神经激素/细胞因子/遗传核心实验室

• 批准号: 7497233
• 负责人: ARTHUR M FELDMAN
• 金额: $ 4.68万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497233
• 关键词: Address; Adenosine; Affect; Apoptosis; Biological; Biological Markers; Cardiac; Cardiac Myocytes; Clinic Visits; Clinical; Clinical Trials; Consent; Coronary Arteriosclerosis; Coronary Artery Bypass; Coronary Stenosis; Cytokine Activation; Data; Development; Dilatation - action; Disease Progression; Echocardiography; Elevation; End Point; Endothelin; Ensure; Experimental Models; Extracellular Matrix; Failure; Functional disorder; General Population; Genes; Genetic; Genetic Determinism; Genetic Polymorphism; Genetic Variation; Genotype; Heart; Heart Transplantation; Heart failure; Hospitalization; Individual; Inflammatory; Injury; International; Intervention; Investigation; Laboratories; Laboratory Study; Left; Left Ventricular Dysfunction; Left Ventricular Ejection Fraction; Left Ventricular Function; Living Wills; Magnetic Resonance; Mechanics; Mediator of activation protein; Medical; Morbidity - disease rate; Mutation; Myocardial Ischemia; Myocardium; Natriuretic Peptides; Neurohormones; Norepinephrine; Numbers; Operative Surgical Procedures; Outcome; Pathological Dilatation; Pathway interactions; Patients; Peptides; Personal Satisfaction; Phenotype; Physiological; Plasma; Play; Population; Postoperative Period; Production; Quality of life; Radioisotopes; Randomized; Randomized Controlled Clinical Trials; Recruitment Activity; Registries; Research Personnel; Role; Shapes; Specific qualifier value; Standardization; Stretching; Subgroup; Testing; Therapeutic; Time; Upper arm; Variant; Ventricular; base; clinical research site; cost; cytokine; follow-up; hemodynamics; improved; indexing; outcome forecast; patient registry; programs; protein expression; restoration; size

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.

缺血性心力衰竭（ST1CH）多中心国际随机试验的手术治疗涉及两个特定的特定 患有冠状动脉的临床心力衰竭（HF）和左心室（LV）功能障碍的患者的主要假设 疾病（CAD）可容纳手术血运重建：1）冠状动脉搭桥术（CABG）与密集型医学 与仅强化医疗疗法相比，治疗（MED）可改善长期生存； 2）在区域LV患者中 功能障碍，手术心室恢复（SVR）至更正常 与仅CABG相比，住院。重要的次要终点反映了发病率，成本和生活质量 将被评估。心脏磁共振的核心实验室（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 确定合格患者并解决与主要假设相关的特定问题所必需的数据标准化。 在三年的时间里，有50个临床部位将招募2,800名同意患者HF，LV射血分数（EF）<.35和CAD患者 适合CABG。这些患者首先以心绞痛强度或左主冠状动脉狭窄的存在为特征 仅适用于手术疗法或医学和外科疗法。 AH患者将进一步评估 SVR的适当性通过单个LV区域中的末端音量体积指数（ESVI）> 60 mL/m2和功能障碍表示。 估计有600名患者有资格获得SVR，但没有资格进行医疗治疗的资格将均匀 随机分配到有或没有SVR的情况下。在有资格医疗或外科疗法的2200名同意患者中，有1,600名 不是SVR符合条件将均匀地随机在MED和MED之间与CABG均匀。剩下的600名患者也有资格 因为SVR仅在MED或MED + CABG或MED + CABG + SVR之间均匀随机。 临床信息的注册将对符合条件但下降试验的患者进行维护。 ahrandomemed和 一些注册表患者将在至少三年的时间内进行四个月的诊所就诊。合适的 随机患者的亚组将在特定的随访间隔内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）术前神经激素水平，NATIRETER 肽和促炎性细胞因子将有助于预测一组最有可能受益的患者 通过SVR进行手术血运重建和/或手术血运重建； 2）术后有益的变化 神经激素/细胞因子/亚钠肽激活将预测接受这两种手术的患者的长期结局 SVR的血运重建和/或血运重建，将为这些变化提供生理原理； 3） 具有良好基因型的患者（例如，ACE基因的低表达或高水平的腺苷）最有可能 使用SVR从CABG或CABG中获得长期收益。

项目成果

Cost-Effectiveness of Coronary Artery Bypass Surgery Versus Medicine in Ischemic Cardiomyopathy: The STICH Randomized Clinical Trial.

• DOI: 10.1161/circulationaha.121.056276
• 发表时间: 2022-03-15
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Chew DS;Cowper PA;Al-Khalidi H;Anstrom KJ;Daniels MR;Davidson-Ray L;Li Y;Michler RE;Panza JA;Piña IL;Rouleau JL;Velazquez EJ;Mark DB;STICH Investigators
• 通讯作者: STICH Investigators

Myocardial viability and survival in ischemic left ventricular dysfunction.

• DOI: 10.1056/nejmoa1100358
• 发表时间: 2011-04-28
• 期刊: The New England journal of medicine
• 作者: Bonow RO;Maurer G;Lee KL;Holly TA;Binkley PF;Desvigne-Nickens P;Drozdz J;Farsky PS;Feldman AM;Doenst T;Michler RE;Berman DS;Nicolau JC;Pellikka PA;Wrobel K;Alotti N;Asch FM;Favaloro LE;She L;Velazquez EJ;Jones RH;Panza JA;STICH Trial Investigators
• 通讯作者: STICH Trial Investigators

The emerging role of pharmacogenomics in the treatment of patients with heart failure.

药物基因组学在心力衰竭患者治疗中的新兴作用。

• DOI: 10.1016/j.athoracsur.2003.09.004
• 发表时间: 2003
• 期刊: The Annals of thoracic surgery
• 作者: Feldman,ArthurM

Genetic variants are not associated with outcome in patients with coronary artery disease and left ventricular dysfunction: results of the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials.

• DOI: 10.1159/000368221
• 发表时间: 2015
• 期刊: Cardiology
• 影响因子: 1.9
• 作者: Feldman AM;She L;McNamara DM;Mann DL;Bristow MR;Maisel AS;Wagner DR;Andersson B;Chiariello L;Hayward CS;Hendry P;Parker JD;Racine N;Selzman CH;Senni M;Stepinska J;Zembala M;Rouleau J;Velazquez EJ;Lee KL
• 通讯作者: Lee KL

Severity of Remodeling, Myocardial Viability, and Survival in Ischemic LV Dysfunction After Surgical Revascularization.

• DOI: 10.1016/j.jcmg.2015.03.013
• 发表时间: 2015-10
• 期刊: JACC. Cardiovascular imaging
• 作者: Bonow RO;Castelvecchio S;Panza JA;Berman DS;Velazquez EJ;Michler RE;She L;Holly TA;Desvigne-Nickens P;Kosevic D;Rajda M;Chrzanowski L;Deja M;Lee KL;White H;Oh JK;Doenst T;Hill JA;Rouleau JL;Menicanti L;STICH Trial Investigators
• 通讯作者: STICH Trial Investigators