Prognostic Impact and Arrhythmic Potential of Peri-infarct Zone by Cardiac MRI

心脏 MRI 对梗死周围区域的预后影响和心律失常可能性

• 批准号: 7837521
• 负责人: Raymond Y Kwong
• 金额: $ 38.49万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7837521
• 关键词: Acute myocardial infarction; Affect; Age; Animal Welfare; Anisotropy; Arrhythmia; Bibliography; Cardiac; Cardiac Death; Clinical; Clinical Trials Design; Complication; Control Groups; Coronary Arteriosclerosis; Country; Digital Signal Processing; Double-Blind Method; Electric Countershock; Environment; Environmental Impact; Equipment; Event; Exhibits; Favorable Clinical Outcome; Fibrosis; Generations; Healed; Heterogeneity; IACUC; Implantable Defibrillators; Incidence; Infarction; Intake; International; Left Ventricular Ejection Fraction; Life; Magnetic Resonance; Magnetic Resonance Imaging; Malignant - descriptor; Membrane; Multi-Institutional Clinical Trial; Muscle Cells; Myocardial; Myocardial Infarction; Myocardial tissue; Myocardium; Myristica fragrans; Names; Omega-3 Fatty Acids; Oral; Patients; Placebo Control; Placebos; Principal Investigator; Publishing; Randomized; Randomized Clinical Trials; Reporting; Research; Research Ethics Committees; Resources; Risk; Secondary to; Selection Criteria; Side; Signal Transduction; Supplementation; Techniques; Testing; Therapeutic; Tissues; Translating; Ventricular; Ventricular Arrhythmia; Ventricular Function; Ventricular Tachycardia; Vertebrates; abstracting; base; cohort; design; expiration; healing; high risk; human subject; improved; mortality; novel; outcome forecast; pre-clinical; prognostic; programs; protective effect; randomized placebo controlled trial; sudden cardiac death; tool

The incidence of sudden cardiac death (SCD) after myocardial infarction (MI) has remained unchanged and is most significant in the first year after MI. The marked cellular anisotropy observed in the peri-infarct zone has reported to be a potential cause of ventricular arrhythmias. Cardiac magnetic resonance imaging (CMR) can characterize myocardial tissue changes and ventricular function after MI. Recently, our group demonstrated the clinical feasibility of quantifying the extent of the peri-infarct zone using contrast-enhanced CMR (PIZCMR) and also reported its strong prognostic association with post-MI all-cause mortality.(3) In a study of 144 patients with MI, we used a novel automated technique to quantify the late-enhancing region into the core and peri-infarct (PIZCMR) regions based on signal-intensity threshold (>3SDs and 2 to 3 SDs above remote normal myocardium, respectively). PIZCMR was quantified in absolute mass (MDEperiphery) and as a percentage of the total enhancing region (%MDEperiphery). We found that %MDEperiphery was a powerful predictor of all-cause mortality incremental to patient age and left ventricular ejection fraction (LVEF). With recent advances in digital signal processing, microvolt T-wave alternans (MTWA) in detecting unstable electrophysiological substrate that exposes post-MI patients to SCD. On the therapeutic side, strong experimental evidence of membrane stabilization effects of omega-3 polyunsaturated fatty acids ()-3 FA) against malignant arrhythmias has been substantiated by a remarkable reduction of SCD in patients with coronary artery disease in large-scale randomized clinical trials. These published findings provide the impetus for the present proposal to elucidate the pathogenic basis underlying the observed prognostic association of PIZCMR and post-MI mortality. The central hypothesis of this proposal is that PIZCMR contains the structural and electrical substrate essential for the generation of reentrant ventricular tachycardia, and that its healing can be promoted by )-3 FA, translating to a reduced risk of SCD and/or significant ventricular arrhythmic events requiring defibrillation. Accordingly, we plan to randomized 414 patients with acute MI to supplementation with either )-3 FA (4 gm/day for 9 months) or placebo is designed to test the hypotheses that 1) Direct myocardial quantitation of PIZCMR provides incremental prognostic association, beyond LVEF and MTWA, with MACE; 2) Oral supplementation with )-3 FA can beneficially modify the prognostic association of the PIZCMR with MACE; 3) Patients who suffered an acute MI and have a large PIZCMR, exhibit concomitant electrical heterogeneity by MTWA; and 4) Oral )-3 FA supplementation to patients who suffered an acute MI, reduces the myocardial extent of PIZCMR and normalizes MTWA, compared to the placebo control group.

心源性猝死（SCD）发生率 心肌梗死 (MI) 保持不变，并且在 MI 后的第一年最为显着。这 据报道，在梗塞周围区域观察到的明显细胞各向异性是导致梗死的潜在原因。 室性心律失常。心脏磁共振成像（CMR）可以表征心肌 MI 后的组织变化和心室功能。近期，我们课题组展示了临床 使用对比增强 CMR (PIZCMR) 量化梗塞周围区域范围的可行性以及 还报告了其与 MI 后全因死亡率的强烈预后相关性。(3) 在一项针对 144 名患者的研究中 对于 MI 患者，我们使用了一种新颖的自动化技术将晚期增强区域量化为 基于信号强度阈值（>3SD 和 2 至 3 SD）的核心和梗塞周围 (PIZCMR) 区域 分别位于远端正常心肌上方）。 PIZCMR 以绝对质量进行量化 (MDEperiphery) 以及占总增强区域的百分比 (%MDEperiphery)。我们发现 %MDEperiphery 是随患者年龄和左侧增加的全因死亡率的有力预测因子 心室射血分数（LVEF）。随着数字信号处理的最新进展，微伏 T 波 交替（MTWA）用于检测不稳定的电生理底物，使心肌梗死后患者暴露于 SCD。在治疗方面，膜稳定作用的有力实验证据 omega-3 多不饱和脂肪酸 ()-3 FA) 对抗恶性心律失常已被证实 在大规模随机研究中，冠状动脉疾病患者的 SCD 显着减少 临床试验。这些发表的研究结果为当前的提案提供了动力，以阐明 观察到的 PIZCMR 与 MI 后死亡率的预后关联的致病基础。这 该提案的中心假设是 PIZCMR 包含结构和电气基板 对于折返性室性心动过速的产生至关重要，并且可以通过以下方式促进其愈合 )-3 FA，意味着发生 SCD 和/或需要接受治疗的重大室性心律失常事件的风险降低 除颤。因此，我们计划将 414 名急性心肌梗死患者随机分为补充 )-3 FA（4 克/天，持续 9 个月）或安慰剂旨在测试以下假设：1) 直接 PIZCMR 的心肌定量提供了超越 LVEF 和 LVEF 的增量预后关联 MTWA，与 MACE； 2) 口服补充 )-3 FA 可以有益地改变预后 PIZCMR 与 MACE 的关联； 3) 患有急性心梗且脑容量大的患者 PIZCMR，通过 MTWA 表现出伴随的电不均匀性； 4) 口服 )-3 FA 补充 患有急性 MI 的患者，减少 PIZCMR 的心肌范围并使 MTWA 正常化， 与安慰剂对照组相比。