A Clinical Coordinating Center for VEST and PREDICTS

描述(由申请人提供)：尽管心肌梗死(ML)后前2个月猝死的发生率很高，但目前植入式心脏转复除颤器(ICD)指南建议对射血分数(EF)低的患者在ML后延迟植入(&gt；40天)。延迟植入会在ICD植入前留下一个增加猝死风险的无保护窗口。此外，只有左心室射血分数(EF)被用来决定Mi后患者随后是否应该接受ICD以一级预防猝死。在这种情况下，在接下来的5年里，只有20%的患者会出现需要ICD电击的自发性室性心律失常。需要一种更经济有效的方法来选择患者进行一级预防ICD植入。针对这两个不足，我们提出了早期猝死试验(VEST)和ICD治疗预测研究(Predicts)。该提案寻求为临床协调中心提供资金，Linked R01(Pi Hulley)为数据协调中心，其余资金(80%)将来自行业。VEST是一项多中心、随机、对照试验，旨在确定非侵入性可穿戴除颤器背心是否将降低左心功能不全患者在注射后头60天内的总死亡率(EF&lt；35%)。Predicts是这种随机干预的后续行动，在该干预中，穿着背心的参与者将在放置ICD之前接受一系列风险分层测试，包括T波交替、压力反射敏感性、Holter监测和其他7个可能的预测指标。然后，参与者将在未来5年内接受ICD休克和其他临床结果的监测。这些数据将被用来开发和验证多变量风险分层工具，该工具可以预测“可电击”室性心律失常的发生，并有效地识别ICD最具成本效益的高风险患者(以及不需要ICD的低风险患者)。来自这两项研究的生物样本和数据将被储存起来，并提供给外部调查人员用于未来的研究。我们预计，通过测试一种可能保护极高风险的Mi后早期患者的干预措施，以及通过确定风险分层策略来识别风险最高和风险最低的患者，并使ICD植入更具成本效益，Vest and Predicts将对美国每年50万人的猝死产生重大影响。

DESCRIPTION (provided by applicant): Despite the high rate of sudden death in the first 2 months following a myocardial infarction (Ml), current guidelines for implantable cardioverter defibrillators (ICDs) recommend delayed implantation (>40 days) after an Ml in patients with low ejection fraction (EF). Delaying implantation leaves an unprotected window of increased sudden death risk prior to ICD implantation. In addition, only left ventricular ejection fraction (EF) is used to decide whether a post-Mi patient should subsequently receive an ICD for primary prevention of sudden death. In this setting, only 20% of patients will have spontaneous ventricular arrhythmias requiring ICD shocks in the next 5 years. A more cost-effective method for selecting patients for primary prevention ICD implantation is needed. To address these two deficiencies, we propose the Vest prevention of Early Sudden death Trial (VEST) and the PREDiction of ICd Therapies Study (PREDICTS). This proposal seeks funding for a Clinical Coordinating Center, the linked R01 (PI Hulley) is for a Data Coordinating Center, and the remaining funding (80%) will come from industry. VEST is a multicenter, randomized, controlled trial to determine whether a non-invasive wearable defibrillator vest will reduce overall mortality during the first 60 days following an Ml in patients with left ventricular dysfunction (EF<35%). PREDICTS is a follow-up to this randomized intervention, in which participants in VEST will undergo a battery of risk stratification tests including T wave alternans, baroreflex sensitivity, Holter monitoring and 7 other likely predictors before placement of an ICD. Participants will then be monitored for ICD shocks and other clinical outcomes over the next 5 years. These data will be used to develop and validate a multivariable risk stratification tool that predicts the occurrence of "shockable" ventricular arrhythmias and efficiently identifies high-risk patients in whom an ICD would be most cost-effective (and low-risk patients in whom an ICD is not necessary). Biological samples and data from both studies will be stored and made available to outside investigators for future studies. We anticipate that VEST and PREDICTS will have a major impact on the 500,000 annual sudden deaths in the US by testing an intervention that may protect the very highest-risk early post-Mi patients, and by identifying a risk stratification strategy to identify those at highest and lowest risk and make ICD implantation more cost-effective.