Risk Stratification in MADIT II Type Patients

MADIT II 型患者的风险分层

• 批准号: 7071782
• 负责人: Wojciech Zareba
• 金额: $ 74.42万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7071782
• 关键词: atrial fibrillation; bioimaging /biomedical imaging; cardiovascular disorder therapy; clinical research; computer assisted medical decision making; computer program /software; cost effectiveness; electrocardiographic monitor; electrocardiography; human mortality; human subject; implantable defibrillators; mathematical model; medical implant science; model design /development; myocardial infarction; noninvasive diagnosis; patient safety /medical error; prognosis; quality of life; sudden cardiac death; tachycardia; ventricular fibrillation

DESCRIPTION (provided by applicant): Recently, the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) demonstrated that post-infarction patients with advanced left ventricular dysfunction, defined by ejection fraction equal to or < 30%, have a very high 19.6% 20-month mortality which was reduced by 28% with prophylactic implantation of a cardioverter-defibrillators. Over 30% of patients with SCDs receive appropriate therapy for ventricular tachycardia or ventricular fibrillation. Similar reduction in mortality associated with ICD therapy was recently reported from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Since the population of patients eligible for an ICD following MADIT II indications is very large, there is a great interest in developing methods and algorithms for identifying high- and low-risk individuals among MADIT ll-type patients to prioritize them for ICD therapy. Based on previous experience and recent preliminary analyses from the MADIT II data, we hypothesize that a combination of clinical variables and noninvasive ECG parameters, indicating contribution of different mechanisms that predispose to arrhythmias and sudden death, will allow identification of patients with increased benefit and those with little benefit from ICD therapy. Therefore, the primary aims of this study are: 1) to evaluate the predictive value of a multivariate model consisting of pre-specified clinical and ECG parameters for predicting arrhythmic events in MADIT II type postinfarction patients with severe left ventricular dysfunction; 2) to develop a multivariate risk-stratification model, based on a broader spectrum of pre-specified clinical covariates and ECG parameters, and from it a risk-scoring algorithm identifying high-risk and low-risk patient groups; this algorithm will be validated by a cross-validation study. Such an algorithm will enable an ordering of patients who may benefit most, and benefit least, from ICD therapy. The secondary objectives of this study are: 1) to determine the prognostic significance of clinical and noninvasive ECG variables for predicting non-sudden (non-arrhythmic) cardiac mortality in MADIT II type patients; identifying such individuals will further refine clinical practice and cost-effectiveness of primary prevention of SCO with ICD therapy; 2) to identify ECG predictors of inappropriate therapy delivered for episodes of atrial fibrillation or supraventricular tachyarrhythmias and evaluate the association between inappropriate therapy and the risk of ventricular tachyarrhythmias; 3) to determine whether clinical and ECG predictors contribute to identification of patients with worsening quality of life, and compare changes in quality of life of patients experiencing ICD therapy with those who do not, after adjusting for clinical and ECG parameters.

描述（申请人提供）：最近，多中心自动除颤器植入试验 II (MADIT II) 表明，患有晚期左心室功能障碍（定义为射血分数等于或 < 30%）的梗塞后患者，20 个月死亡率高达 19.6%，通过预防性植入心脏复律除颤器可将死亡率降低 28%。超过 30% 的 SCD 患者接受了针对室性心动过速或心室颤动的适当治疗。最近，心力衰竭猝死试验 (SCD-HeFT) 报告了与 ICD 治疗相关的类似死亡率降低。由于符合 MADIT II 适应症的 ICD 患者群体非常大，因此人们对开发用于识别 MADIT ll 型患者中高风险和低风险个体的方法和算法非常感兴趣，以便优先对他们进行 ICD 治疗。根据以前的经验和最近对 MADIT II 数据的初步分析，我们假设临床变量和无创心电图参数的组合表明易导致心律失常和猝死的不同机制的贡献，将允许识别从 ICD 治疗中获益增加的患者和获益很少的患者。因此，本研究的主要目的是： 1）评估由预先指定的临床和心电图参数组成的多变量模型对预测患有严重左心功能不全的 MADIT II 型梗死后患者心律失常事件的预测价值； 2) 基于更广泛的预先指定的临床协变量和心电图参数，开发多变量风险分层模型，并从中识别高风险和低风险患者组的风险评分算法；该算法将通过交叉验证研究进行验证。这样的算法将能够对可能从 ICD 治疗中受益最大和受益最小的患者进行排序。本研究的次要目标是：1) 确定临床和无创心电图变量对于预测 MADIT II 型患者非突发（非心律失常）心脏死亡的预后意义；识别此类个体将进一步完善采用 ICD 治疗的 SCO 一级预防的临床实践和成本效益； 2) 确定心房颤动或室上性快速心律失常发作时不当治疗的心电图预测因素，并评估不当治疗与室性快速心律失常风险之间的关联； 3) 确定临床和心电图预测因子是否有助于识别生活质量恶化的患者，并在调整临床和心电图参数后，比较接受 ICD 治疗的患者与未接受 ICD 治疗的患者的生活质量变化。