Hibernating Myocardium and Sudden Cardiac Death

冬眠心肌与心脏性猝死

• 批准号: 6757623
• 负责人: John M Canty
• 金额: $ 68.74万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6757623
• 关键词: ammonia; bioimaging /biomedical imaging; clinical research; glucose metabolism; heart disorder diagnosis; heart function; heart imaging /visualization /scanning; heart revascularization; human subject; implantable defibrillators; myocardial infarction; myocardial ischemia /hypoxia; patient oriented research; positron emission tomography; sudden cardiac death; tachycardia

DESCRIPTION (provided by applicant): Currently available electrophysiological approaches are limited in their ability to identify the majority of patients with CAD and LV dysfunction that succumb to sudden cardiac death (SCD). Over half of the patients developing SCD are not inducible at EP testing underscoring the need for new ways to identify substrates leading to arrhythmic death. Viable chronically dysfunctional or hibernating myocardium, not amenable to revascularization, appears to be a major risk factor for subsequent cardiac death and is present in up to 60 percent of patients with ischemic cardiomyopathy. Revascularization improves survival but most patients with hibernating myocardium are managed medically due to prohibitive procedural risks or technical limitations. Cause specific mortality data is limited but appears to be arrhythmic rather than from fatal MI or progressive CHF. In support of this, swine with hibernating myocardium develop SCD from VT/VF in the absence of MI or CHF. Potential triggers of lethal arrhythmias include regional reductions in SR calcium uptake and release proteins, myocyte hypertrophy and altered sympathetic innervation. The central hypothesis of this proposal is that the presence of hibernating myocardium as opposed to scar identifies a large subset of patients with ischemic cardiomyopathy that are at high risk for SCD. We further hypothesize that this risk is related to inhomogeneity in sympathetic innervation arising from chronic repetitive ischemia. We propose a prospective observational study that will enroll 360 patients with CAD, Class I-III CHF and an EF <= 35 percent. Using positron emission tomography (PET), the prevalence and amount ofhibemating myocardium will be quantified in patients that are not candidates for coronary revascularization. Aim 1 will determine whether imaging the mismatch between viability (preserved ( 18)F-2-deoxyglucose) and reduced resting flow (13)N-ammonia can predict an increased risk of SCD (or ICD discharge for VT/VF as a surrogate end-point) in hibernating myocardium. Aim 2 will image norepinephrine uptake using ( 11)C-hydroxyephedrine to determine whether inhomogeneity in myocardial sympathetic innervation predicts SCD risk better than viability testing. Aim 3 will identify whether the substrate identified by PET is stable after an aborted SCD event by evaluating temporal changes in function, viability and sympathetic innervation in patients with an ICD. Our long-term objective is to develop better approaches to identify patients with CAD who are most likely to benefit from primary prevention of SCD with placement of an ICD.

描述（由申请人提供）：目前可用的电生理学方法在识别大多数患有 CAD 和 LV 功能障碍并死于心源性猝死 (SCD) 的患者方面能力有限。 超过一半的发生 SCD 的患者在 EP 测试中无法诱导，这强调需要新的方法来识别导致心律失常死亡的底物。 存活的慢性功能障碍或冬眠心肌不适合血运重建，似乎是随后心源性死亡的主要危险因素，并且存在于高达 60% 的缺血性心肌病患者中。 血运重建可提高生存率，但由于手术风险或技术限制，大多数冬眠心肌患者都需要接受医学治疗。 具体原因死亡率数据有限，但似乎是心律失常所致，而不是致命性心肌梗死或进行性心力衰竭。 为了支持这一点，具有冬眠心肌的猪在没有 MI 或 CHF 的情况下从 VT/VF 发展为 SCD。 致命性心律失常的潜在诱因包括 SR 钙摄取和释放蛋白的局部减少、肌细胞肥大和交感神经支配改变。 该提议的中心假设是，与疤痕相反，冬眠心肌的存在可以识别出一大部分患有 SCD 的高风险缺血性心肌病患者。 我们进一步假设这种风险与慢性重复性缺血引起的交感神经支配的不均匀性有关。 我们提出一项前瞻性观察性研究，将招募 360 名 CAD、I-III 类 CHF 且 EF <= 35% 的患者。 使用正电子发射断层扫描（PET），将量化不适合冠状动脉血运重建的患者中冬眠心肌的患病率和数量。 目标 1 将确定对活力（保留的 (18)F-2-脱氧葡萄糖）和减少的静息流量 (13)N-氨之间的不匹配进行成像是否可以预测 SCD（或 VT/VF 的 ICD 放电作为替代终点）的风险增加-点）在冬眠心肌中。 目标 2 将使用 (11)C-羟基麻黄碱对去甲肾上腺素摄取进行成像，以确定心肌交感神经支配的不均匀性是否比活力测试更好地预测 SCD 风险。 目标 3 将通过评估 ICD 患者功能、活力和交感神经支配的时间变化来确定 PET 识别的底物在 SCD 事件中止后是否稳定。 我们的长期目标是开发更好的方法来识别最有可能受益于放置 ICD 的 SCD 一级预防的 CAD 患者。