Myocardial Viability and Remodeling in the OAT

描述(由申请人提供)： 正在进行的由NHLBI资助的闭塞动脉试验(OAT)旨在测试这样一个假设，即在心肌梗死后3-28天开放闭塞的梗塞相关动脉(IRA)将在三年的随访中降低死亡率、复发性心肌梗死和NYHA IV级心力衰竭的综合终点。OAT目前已经在24个国家的240个中心随机调查了大约1100名患者。在解释晚期血管重建术的益处的机制中，最可信的机制是通过恢复存活心肌的血流量来恢复左室功能和减轻左室重构。我们建议进行一项OAT的辅助研究，以评估心肌存活率对MI后左室重构的影响，并探讨梗死区存活率、左室重构与OAT干预、IRA晚期经皮冠状动脉介入治疗的反应之间的关系。为此，我们建议招募200名患者参加OAT辅助研究中的生存和重塑(OAT-NUC)。这项研究的主要具体目的是：1)检验这样一种假设，即与主要梗死区患者相比，在梗死区内表现出生存能力保留的患者的进展性重塑较少；2)验证这样一种假设，即保留生存能力将改变随机化对急性心肌梗死后IRA闭塞患者3-28天晚期血运重建的治疗效果。所有患者都将在基线时进行静息门控~(99m)Tc-Sestamibi SPECT显像，并在1年后再次进行。位于塔夫茨-新英格兰医学中心的心脏成像核心实验室将对梗死区内基线生存能力的参数以及左室容量变化和功能的一系列测量进行集中评估，该小组拥有在多中心临床试验中分析心脏成像数据的丰富经验。解决这些假设的主要研究终点将是根据确定的梗死区内存活能力的保存程度，左室舒张末期容量的连续变化。样本量的计算是基于同一组从相同数量的临床站点研究的相似数量的患者评估的数据。因此，样本量预测是稳健的，适合目前的试验，调查小组有经验高质量地开展拟议的研究。燕麦-NUC是燕麦片唯一的可行性辅助研究，因此在评估燕麦片研究结果的潜在机制方面是至关重要的。

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.