Myocardial Viability and Remodeling in the OAT

描述（由申请人提供）： 正在进行的NHLBI资助的闭塞动脉试验（OAT）旨在检验以下假设：MI后3-28天开放闭塞的梗死相关动脉（伊拉）将降低3年随访期间死亡率、复发性MI和NYHA IV级心力衰竭的复合终点。 OAT目前已在24个国家的240个中心随机分配了约1100例患者。 在提出的解释晚期血运重建获益的机制中，由于恢复存活心肌的血流而恢复LV功能和减轻LV重构是最合理的。 我们建议进行一项OAT的辅助研究，以评估心肌存活对MI后左心室重构的影响，并探讨梗死区保留存活、左心室重构与OAT干预反应、伊拉晚期PCI之间的关系。 为此，我们建议在OAT辅助研究（OAT-NUC）中招募200例患者。 本研究的主要具体目的是：1）检验以下假设：与表现出主要梗死的患者相比，在梗死区内表现出存活能力保留的患者将表现出更少的进行性重构; 2）检验以下假设：存活能力保留将改变AMI后3-28天伊拉闭塞的MI后患者随机化至晚期血运重建的治疗效果。 所有患者将在基线时进行静息门控Tc-99 m sestamibi SPECT成像，并在1年后再次进行。 梗死区内的基线活力参数以及LV体积变化和功能的系列测量将由Tufts-New England Medical Center的心脏成像核心实验室集中评估，该实验室是一个在多中心临床试验中分析心脏成像数据具有丰富经验的小组。 解决假设的主要研究终点将是LV舒张末期容积的连续变化，基于定义的梗死区内存活力的保持程度。样本量计算基于同一组在相似数量的临床试验机构研究的相似数量患者的数据。 因此，样本量预测对于当前试验是稳健和适当的，并且研究小组具有高质量开展拟定研究的经验。 OAT-NUC是OAT的唯一可行性辅助研究，因此在评估OAT结果的潜在机制方面具有关键需求。

DESCRIPTION (provided by applicant): The ongoing NHLBI-funded Occluded Artery Trial (OAT) is designed to test the hypothesis that opening an occluded infarct related artery (IRA) 3-28 days following an MI will reduce the composite endpoint of mortality, recurrent MI, and NYHA class IV heart failure over three-year follow-up. OAT has currently randomized approximately 1100 patients in 240 centers in 24 countries. Among the mechanisms proposed to explain benefit of late revascularization, recovery of LV function and attenuation of LV remodeling due to restoration of blood flow to viable myocardium is the most plausible. We propose an ancillary study of OAT to assess the effect of myocardial viability on LV remodeling post-MI, and to explore the relationships between retained viability of the infarct zone, LV remodeling, and the response to the OAT intervention, late PCI of the IRA. To this end, we propose to enroll 200 patients in the Viability and Remodeling in OAT Ancillary Study (OAT-NUC). The primary specific aims of this study are 1) to test the hypothesis that patients who demonstrate preservation of viability within the infarct zone will evidence less progressive remodeling compared to patients exhibiting predominant infarct, and 2) to test the hypothesis that preservation of viability will modify the treatment effect of randomization to late revascularization of post-MI patients with an occluded IRA 3-28 days after an AMI. All patients will have resting gated Tc-99m sestamibi SPECT imaging at baseline, and again 1 year later. Parameters of baseline viability within the infarct zone, and serial measures of LV volume change and function will be centrally assessed by the Cardiac Imaging Core Laboratory at Tufts-New England Medical Center, a group with substantial experience analyzing cardiac imaging data in multicenter clinical trials. The major study endpoint to address the hypotheses will be serial change in LV end-diastolic volume, based on the degree of preservation of viability within the defined infarct zone. Sample size calculations are based on data evaluated by the same group from a similar number of patients studied at a similar number of clinical sites. Hence, sample size projections are robust and appropriate for the current trial, and the investigative group has the experience to carry out the proposed study with high quality. OAT-NUC is the only viability ancillary study of OAT, and thus serves a critical need in assessing potential mechanisms of the findings in OAT.