Risk Stratification in MADIT II Type Patients

描述（由申请人提供）：最近，多中心自动除颤器植入试验II （MADIT II）表明，梗死后晚期左心室功能障碍患者（射血分数等于或< 30%）的20个月死亡率高达19.6%，预防性植入心律转复除颤器可降低28%。超过30%的SCDs患者接受适当的室性心动过速或心室颤动治疗。最近在心力衰竭的心源性猝死试验（SCD-HeFT）中也报道了与ICD治疗相关的死亡率的类似降低。由于符合MADIT II适应症的ICD患者人数非常多，因此开发方法和算法来识别MADIT II型患者中的高风险和低风险个体，以优先考虑他们的ICD治疗非常有兴趣。根据以往的经验和最近对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结合，表明易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较少的患者。因此，本研究的主要目的是：1)评估由预先指定的临床和ECG参数组成的多变量模型对伴有严重左心室功能障碍的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，建立多变量风险分层模型，并以此为基础建立识别高风险和低风险患者群体的风险评分算法；该算法将通过交叉验证研究进行验证。这样的算法将能够排序哪些患者可能从ICD治疗中获益最多，哪些获益最少。本研究的次要目的是：1)确定临床和无创心电图变量对预测MADIT II型患者非突发性（非心律失常）心脏死亡率的预后意义；识别这些个体将进一步完善临床实践和使用ICD治疗初级预防SCO的成本效益；2)确定心房颤动或室上性心动过速发作的不适当治疗的心电图预测因素，并评估不适当治疗与室性心动过速风险之间的关系；3)确定临床和心电图预测指标是否有助于识别生活质量恶化的患者，并比较接受ICD治疗与未接受ICD治疗的患者在调整临床和心电图参数后的生活质量变化。

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.