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

描述(申请人提供)：心肌梗塞(MI)后心源性猝死(SCD)的发生率保持不变，在MI后第一年最显著。在梗死区周围观察到的显著的细胞各向异性被报道为室性心律失常的潜在原因。心脏磁共振成像(CMR)可以表征心肌梗死后心肌组织的变化和心功能。最近，我们小组证明了使用对比增强CMR(PIZCMR)量化梗塞周围区域范围的临床可行性，并报道了其与MI后全因死亡率的强烈相关性。(3)在一项针对144名MI患者的研究中，我们使用了一种新的自动化技术，根据信号强度阈值将晚期强化区域量化为核心和梗塞周围区域(PIZCMR)(分别比远程正常心肌高3个SD和2到3个SD)。PIZCMR以绝对质量(MDE外围)和占总强化区域的百分比(%MDE外围)进行量化。我们发现，随着患者年龄和左心室射血分数(LVEF)的增加，%MDE外周是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)在检测不稳定的电生理底物方面使心肌梗死后患者暴露于SCD。在治疗方面，在大规模随机临床试验中，omega-3多不饱和脂肪酸()-3 FA对恶性心律失常的膜稳定作用的强有力的实验证据已被显著降低冠心病患者的SCD所证实。这些已发表的发现为目前的提议提供了动力，以阐明观察到的PIZCMR和心肌梗死后死亡率之间的预后关联的致病基础。这一建议的中心假设是，PIZCMR含有产生折返性室性心动过速所必需的结构和电底物，并且)-3 FA可以促进其愈合，从而降低SCD和/或需要除颤的重大室性心律失常事件的风险。因此，我们计划将414名急性心肌梗死患者随机分为两组，分别补充)-3 FA(每天4 gm，持续9个月)或安慰剂，以检验以下假设：1)直接心肌定量PIZCMR可提供较LVEF和Mtwa更高的预后关联；2)口服补充3 FA可有益地改变PIZCMR与MACE的预后关联；3)急性MI且PIZCMR较大的患者，通过Mtwa表现出伴随的电学异质性；4)与安慰剂对照组相比，对急性心肌梗死患者口服-3-FA可减少PIZCMR的心肌范围并使MTWA正常化。 项目简介：心脏性猝死(SCD)是心脏病发作患者最常见的死亡原因。虽然植入自动内部心律转复除颤器(AICD)可以有效地终止SCD，但目前仅通过评估心功能来选择患者接受AICD装置的标准是不准确的，可能导致巨大的医疗成本和可能的严重设备故障并发症。因此，需要一种更好的非侵入性方法来识别高危患者，对他们来说，AICD治疗是最合适的。众所周知，心脏病发作后疤痕周围的区域(梗死区周围)在产生危及生命的心律失常方面起着关键作用，这种心律失常可能导致心脏病发作后的SCD。磁共振成像是一种不需要使用有害辐射的成像技术，它可以比传统技术更好地显示组织特征的差异。我们团队最近设计了一种新的方法，通过使用心脏磁共振成像(CMR)来测量144名心脏病发作患者的心脏梗塞周围区域。此外，当我们在CMR研究后4年跟踪这些患者的临床病程时，我们发现这个梗死区的大小可以预测心脏病发作后患者的死亡。因此，目前提出的研究旨在评估CMR是否能够提供重要的心肌信息，从而改善SCD或其他严重后果的预测，而不是目前使用心功能的非特异性标准。此外，我们还计划确定从CMR获得的信息是否与心脏节律问题有关，这一点由一种名为微伏T波交替的技术证明。大量证据表明，摄入omega-3多不饱和脂肪酸(鱼油)是安全的，耐受性良好，可以稳定心脏的电信号，降低SCD的风险。我们还建议研究omega-3脂肪酸是否可以促进最近心脏病发作的患者的梗塞周围区域的愈合。此外，这项研究的结果将为无创性MRI是否可以改善对采用AICD治疗的SCD高危患者的识别提供洞察力。

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. Project Narrative: Sudden cardiac death (SCD) is the most common cause of death in patients who have suffered a heart attack. While SCD can be effectively aborted by the implantation of an automatic internal cardiovertion-defibrillaton (AICD) device, the current criteria for selecting patients to receive an AICD device using assessment of heart function alone is inaccurate and can result in enormous healthcare costs and possible serious complications from device malfunction. A better noninvasive method is therefore needed to identify high risk patients for whom AICD therapy can be most appropriately utilized. The region surrounding the scar of a heart attack (peri-infarct zone) has been known to be critical in generating life-threatening arrhythmias that can lead to SCD after a heart attack. Magnetic resonance imaging is an imaging technology that does not require the use of harmful radiation and it can demonstrate differences in tissue characteristics better than conventional technology. Our group has recently devised a new way of measuring the peri-infarct zone of the heart in 144 patients who suffered a heart attack by using magnetic resonance imaging of the heart (CMR). Moreover, we showed that the size of this peri-infarct zone predicts patient death after a heart attack when we followed these patients clinical course up to 4 years after the CMR study. The current proposed study therefore aims to assess whether CMR can provide important information of the heart muscle which can improve the prediction of SCD or other serious outcomes, beyond the current non-specific criteria using heart function. In addition, we also plan to determine if the information gained from the CMR is related to heart rhythm problem as demonstrated by a technology called microvolt T-wave alternans. A large body of evidence suggests that intake of omega-3 polyunsaturated fatty acids (fish oils) is safe, well-tolerated, and can serve to stabilize the electrical signals of the heart and reduce the risk to SCD. We also propose to investigate whether healing of the peri-infarct zone can be promoted by omega-3 fatty acids in patients who have suffered a recent heart attack. In addition, the results of this study will provide insight if noninvasive MRI can improve the identification of patients at high risk of SCD who are best managed with AICD therapy.