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: 8017408
• 负责人: Raymond Y Kwong
• 金额: $ 37.91万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-05 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8017408
• 关键词: Acute myocardial infarction; Affect; Age; Anisotropy; Arrhythmia; Cardiac; Cause of Death; Cessation of life; Characteristics; Cicatrix; Clinical; Clinical Trials Design; Complication; Control Groups; Coronary Arteriosclerosis; Devices; Digital Signal Processing; Double-Blind Method; Electric Countershock; Event; Exhibits; Favorable Clinical Outcome; Fibrosis; Fish Oils; Generations; Goals; Healed; Health Care Costs; Heart; Heterogeneity; Imaging technology; Implantable Defibrillators; Incidence; Infarction; Intake; Lead; Left Ventricular Ejection Fraction; Life; Magnetic Resonance; Magnetic Resonance Imaging; Malignant - descriptor; Measures; Membrane; Methods; Multi-Institutional Clinical Trial; Muscle Cells; Myocardial; Myocardial Infarction; Myocardial tissue; Myocardium; Omega-3 Fatty Acids; Oral; Outcome; Patients; Placebo Control; Placebos; Publishing; Radiation; Randomized; Randomized Clinical Trials; Reporting; Risk; Sample Size; Secondary to; Selection Criteria; Side; Signal Transduction; Supplementation; Techniques; Technology; Testing; Therapeutic; Tissues; Translating; Ventricular; Ventricular Arrhythmia; Ventricular Function; Ventricular Tachycardia; base; cohort; design; healing; heart function; heart rhythm; high risk; implantation; improved; insight; mortality; novel; outcome forecast; pre-clinical; prognostic; protective effect; randomized placebo controlled trial; sudden cardiac death; tool

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：心肌梗死（MI）后心源性猝死（SCD）的发生率保持不变，并且在 MI 后第一年最为显着。据报道，在梗塞周围区域观察到的显着细胞各向异性是室性心律失常的潜在原因。心脏磁共振成像（CMR）可以表征 MI 后心肌组织的变化和心室功能。最近，我们小组证明了使用对比增强 CMR (PIZCMR) 量化梗死周围区域范围的临床可行性，并报告了其与 MI 后全因死亡率的强烈预后相关性。(3) 在一项针对 144 名 MI 患者的研究中，我们使用一种新颖的自动化技术将后期增强区域量化为核心和梗死周围 (PIZCMR) 区域 信号强度阈值（分别高于远端正常心肌 >3SD 和 2 至 3 SD）。 PIZCMR 以绝对质量 (MDEperiphery) 和总增强区域的百分比 (%MDEperiphery) 进行量化。我们发现 %MDEperiphery 是随患者年龄和左心室射血分数 (LVEF) 增加的全因死亡率的有力预测因子。随着数字信号处理的最新进展，微伏 T 波交替 (MTWA) 可以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，大规模随机临床试验中，omega-3 多不饱和脂肪酸 ()-3 FA) 对恶性心律失常具有细胞膜稳定作用，这已通过显着减少冠状动脉疾病患者的 SCD 得到证实。这些发表的发现为目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。该提案的中心假设是 PIZCMR 包含产生折返性室性心动过速所必需的结构和电基质，并且 )-3 FA 可以促进其愈合，从而降低发生 SCD 和/或需要除颤的重大室性心律失常事件的风险。因此，我们计划对 414 名急性 MI 患者进行随机补充，补充 )-3 FA（每天 4 克，持续 9 个月）或安慰剂，目的是检验以下假设：1) PIZCMR 直接心肌定量可提供除 LVEF 和 MTWA 之外与 MACE 的增量预后关联； 2) 口服补充 )-3 FA 可以有益地改变 PIZCMR 与 MACE 的预后关联； 3) 患有急性 MI 且 PIZCMR 较大的患者，MTWA 表现出伴随的电异质性； 4) 与安慰剂对照组相比，急性 MI 患者口服 )-3 FA 补充剂可减少 PIZCMR 的心肌范围并使 MTWA 正常化。