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: 8214588
• 负责人: Raymond Y Kwong
• 金额: $ 37.67万
• 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 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8214588
• 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

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.

心肌梗死（MI）后心源性猝死（SCD）的发生率一直居高不下 无变化，在MI后第一年最显著。观察到显著的细胞各向异性 据报道，心肌梗塞周围区域的心肌梗塞是室性心律失常的潜在原因。心脏 磁共振成像（CMR）可以表征心肌组织变化和心室 MI后的功能最近，我们的研究小组证明了量化的程度的临床可行性， 使用对比剂增强的CMR（PIZDMR）检查梗死周围区，并报告了其强预后 与心肌梗死后全因死亡率相关。(3)在一项对144名心肌梗死患者的研究中，我们使用了一种新的 自动化技术定量晚期增强区的核心和周围梗死（PIZCMR） 基于信号强度阈值的区域（> 3SD和高于远程正常值2 - 3 SD 心肌）。PIZCMR以绝对质量（MDE外周）定量，并作为 占总增强区的百分比（%MDE外周）。我们发现，%MDE外围是一个 全因死亡率随患者年龄和左心室射血分数增加而增加的有力预测因子 （LVEF）。随着数字信号处理的最新进展， 检测使MI后患者暴露于SCD的不稳定电生理底物。上 治疗方面，强有力的实验证据表明，膜稳定作用的ω-3 多不饱和脂肪酸（<$-3 FA）对恶性心律失常已被证实， 在大规模随机化研究中， 临床试验这些已发表的研究结果为本提案提供了动力，以阐明 PIZCMR与MI后死亡率之间的预后相关性的致病基础。的 该建议的中心假设是PIZCMR包含结构和电基底 对于折返性室性心动过速的产生至关重要，并且可以促进其愈合 通过<$-3 FA，转化为SCD和/或显著室性心律失常事件的风险降低 需要除颤。因此，我们计划将414例急性心肌梗死患者随机分配至 补充<$-3 FA（4 gm/天，持续9个月）或安慰剂旨在测试 假设：1）PIZCMR的直接心肌定量提供增量预后 除LVEF和MTWA外，与MACE相关; 2）口服补充<$-3 FA可 有益地改变PIZCMR与MACE的预后相关性; 3）患有 急性MI并具有大的PIZCMR，通过MTWA表现出伴随的电异质性;以及4）口服 对急性心肌梗死患者补充FA可降低心肌梗死的程度， 与安慰剂对照组相比，PIZCMR使MTWA正常化。

项目成果

Role of transcytolemmal water-exchange in magnetic resonance measurements of diffuse myocardial fibrosis in hypertensive heart disease.

• DOI: 10.1161/circimaging.112.979815
• 发表时间: 2013-01-01
• 期刊: Circulation. Cardiovascular imaging
• 作者: Coelho-Filho OR;Mongeon FP;Mitchell R;Moreno H Jr;Nadruz W Jr;Kwong R;Jerosch-Herold M
• 通讯作者: Jerosch-Herold M

Multimodality imaging in the assessment of myocardial viability.

• DOI: 10.1007/s10741-010-9201-7
• 发表时间: 2011-07
• 期刊: HEART FAILURE REVIEWS
• 影响因子: 4.6
• 作者: Partington, Sara L.;Kwong, Raymond Y.;Dorbala, Sharmila
• 通讯作者: Dorbala, Sharmila

Lessons learned from MPI and physiologic testing in randomized trials of stable ischemic heart disease: COURAGE, BARI 2D, FAME, and ISCHEMIA.

• DOI: 10.1007/s12350-013-9773-4
• 发表时间: 2013-12
• 期刊: JOURNAL OF NUCLEAR CARDIOLOGY
• 影响因子: 2.4
• 作者: Phillips, Lawrence M.;Hachamovitch, Rory;Berman, Daniel S.;Iskandrian, Ami E.;Min, James K.;Picard, Michael H.;Kwong, Raymond Y.;Friedrich, Matthias G.;Scherrer-Crosbie, Marielle;Hayes, Sean W.;Sharir, Tali;Gosselin, Gilbert;Mazzanti, Marco;Senior, Roxy;Beanlands, Rob;Smanio, Paola;Goyal, Abhi;Al-Mallah, Mouaz;Reynolds, Harmony;Stone, Gregg W.;Maron, David J.;Shaw, Leslee J.
• 通讯作者: Shaw, Leslee J.

Quantification of extracellular matrix expansion by CMR in infiltrative heart disease.

• DOI: 10.1016/j.jcmg.2012.04.006
• 发表时间: 2012-09
• 期刊: JACC-CARDIOVASCULAR IMAGING
• 影响因子: 14
• 作者: Mongeon, Francois-Pierre;Jerosch-Herold, Michael;Coelho-Filho, Otavio Rizzi;Blankstein, Ron;Falk, Rodney H.;Kwong, Raymond Y.
• 通讯作者: Kwong, Raymond Y.

Cardiac magnetic resonance imaging as a prognostic tool in patients with nonischemic cardiomyopathy.

心脏磁共振成像作为非缺血性心肌病患者的预后工具。

• DOI: 10.3810/hp.2010.11.343
• 发表时间: 2010
• 期刊: Hospital practice (1995)
• 作者: Partington,SaraL;Seabra,LucianaF;Kwong,RaymondY
• 通讯作者: Kwong,RaymondY