Hibernating Myocardium and Sudden Cardiac Death

冬眠心肌与心脏性猝死

• 批准号: 7071227
• 负责人: John M Canty
• 金额: $ 67.64万
• 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/7071227
• 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）：目前可用的电生理方法的限制是识别大多数CAD和LV功能障碍患者屈服于猝死（SCD）的能力。 在EP测试中，超过一半的患者无法诱导，强调了鉴定导致心律失常死亡的新方法的需求。 可行的慢性功能失调或冬眠心肌（不适合血运重建）似乎是随后心脏死亡的主要危险因素，并且有多达60％的缺血性心肌病患者出现。 血运重建可提高生存率，但大多数冬眠心肌的患者由于程序性的风险过高或技术限制而受到医学管理。 导致特定的死亡率数据受到限制，但似乎是心律不齐的，而不是致命的MI或进行性CHF。 为此，在没有MI或CHF的情况下，带有冬眠心肌的猪会从VT/VF开发SCD。 致命性心律失常的潜在触发因素包括SR钙吸收和释放蛋白质的区域减少，心肌肥大和交感神经的改变。 该提议的中心假设是，冬眠心肌的存在与疤痕相反，识别出大部分缺血性心肌病患者，这有SCD高风险。 我们进一步假设，这种风险与慢性重复缺血引起的同情神经上的不均匀性有关。 我们提出了一项前瞻性观察性研究，该研究将招募360例CAD，I-III类CHF和EF <= 35％的患者。 使用正电子发射断层扫描（PET），将在不是冠状动脉血运重建的候选患者中量化的心肌的患病率和量。 AIM 1将确定成像生存能力（保留（18）F-2-脱氧葡萄糖）与静息流量降低（13）N- ammonia之间的不匹配是否可以预测在冬眠心肌中SCD的风险增加（VT/VF作为替代点的ICD排放）。 AIM 2将使用（11）C-羟基甲肾上腺素对去甲肾上腺素的摄取进行成像，以确定心肌交感神经神经的不均匀性是否比可行性测试更好地预测SCD风险。 AIM 3将通过评估ICD患者的功能，生存力和交感神经的时间变化，确定PET鉴定的底物是否在流产的SCD事件后是否稳定。 我们的长期目标是开发更好的方法来识别CAD患者，这些患者最有可能在ICD的放置下从初级预防SCD中受益。