Clinical, Electrocardiographic, and Cardiac Magnetic Resonance Imaging Risk Factors Associated with Ventricular Tachyarrhythmias in Nonischemic Cardiomyopathy

摘要 植入式心律转复除颤器（ICD）用于死亡率的一级预防， 射血分数（EF）的非缺血性心肌病（NICM）患者的获批治疗 ≤ 35%。然而，DANISH ICD试验入组了1，116例NICM和EF ≤35%的患者 随机分配至ICD组（n=556）或无ICD组（n=560），显示无显著死亡率 与非ICD患者相比，ICD患者减少（风险比=0.87; p=0.28），但 心源性猝死风险显著降低（风险比=0.50; p=0.005）。数据从 既往导致ICD适应症的NICM临床试验显示， 死亡率显著降低，心源性猝死显著减少 （定义：458例患者; HR=0.65; p=0.08，SCD-HeFT的亚组分析：792例 患者; HR=0.73; p=0.06）。DANISH患者接受最佳药物治疗 58%的人有CRT设备。非ICD组的3年死亡率约为10%， 在10年前进行的DEFINITE和SCD-HeFT试验中为20%，反映了 不同的患者人群和不同的基础治疗。 由于致心律失常性心肌基质的特征是室性心律失常 在长期心电图记录中检测到，我们分析了416例NICM患者的MADIT-CRT试验数据 随机分配至CRT-D组且24- 30岁的NYHA II级QRS ≥130 ms的患者 器械植入前1小时霍尔特ECG记录。植入前霍尔特上的NSVT（在 194例[47%]患者）与风险比3.08（p<0.001）相关，LVESVi增大>86 ml/m2 与2.81的风险比（p<0.001）和非LBBB QRS形态（在 多变量模型预测快速VT≥188的风险比为3.33（p<0.001） bpm或VF。这种风险预测模型可以指导关于植入 QRS≥120 ms的NICM心力衰竭患者使用CRT-D、CRT-P或ICD器械。 在本提案的具体目标1中，我们建议验证该MADIT-CRT风险分层 宽QRS≥ 120 ms的400 NICM模型。随着对观测的兴趣越来越大， 在心脏MRI中评估的钆增强与心脏骤停风险增加相关。 在NICM患者的心源性死亡中，我们还旨在：2）确定是否有异常的心脏磁 具有晚期钆增强的磁共振（CMR）成像将预测快速VT/VF 并将进一步改善QRS≥120 ms的NICM的风险分层，以及3）评价成本- 建议的风险分层方法的有效性，导致使用成本较低的 设备（CRTP与CERT-D）。

Abstract Implantable cardioverter defibrillator (ICD) for primary prevention of mortality is an approved therapy in nonischemic cardiomyopathy (NICM) patients with ejection fraction (EF) ≤35%. However, the DANISH ICD trial enrolled 1,116 patients with NICM and EF ≤35% randomized to ICD (n=556) or no ICD (n=560), demonstrated lack of significant mortality reduction in ICD patients when compared to non-ICD patients (hazard ratio=0.87; p=0.28), but significant reduction in the risk of sudden cardiac death (hazard ratio=0.50; p=0.005). Data from prior clinical trials leading to ICD indications in NICM showed a nonsignificant but clinically meaningful reduction in mortality, and significant reductions in sudden cardiac death (DEFINITE: 458 patients; HR=0.65; p=0.08 and a subgroup analysis of the SCD-HeFT: 792 patients; HR=0.73; p=0.06). The DANISH patients were on optimal pharmacological therapy and 58% had CRT devices. Their 3-year mortality in non-ICD arm was around 10% vs. around 20% in DEFINITE and SCD-HeFT trials, which were conducted 10 years earlier, a reflection of different patient populations and different underlying therapies. Since arrhythmogenic myocardial substrate is characterized by ventricular arrhythmias detected in long-term ECG recordings, we analyzed data from MADIT-CRT trial in 416 NICM patients in NYHA class II with QRS ≥130 ms who were randomized to CRT-D and who had a 24- hour Holter ECG recording prior to device implantation. NSVT on preimplantation Holter (observed in 194 [47%] patients) was associated with hazard ratio of 3.08 (p<0.001), enlarged LVESVi >86 ml/m2 was associated with hazard ratio of 2.81 (p<0.001), and Non-LBBB QRS morphology (observed in 44 (11%) patients) with hazard ratio of 3.33 (p<0.001) in a multivariate model predicting fast VT≥188 bpm or VF. This risk prediction model could guide therapeutic decisions regarding implantation of CRT-D, CRT-P, or ICD devices in NICM heart failure patients with QRS≥120 ms. In specific aim 1 of this proposal, we propose to validated this MADIT-CRT risk stratification model in 400 NICM with wide QRS≥120ms. With an increasing interest in observations that late gadolinium enhancement assessed in cardiac MRI is associated with increased risk of sudden cardiac death in NICM patients, we also aim to: 2) determine whether abnormal cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement will be predictive for fast VT/VF and will further improve risk stratification in NICM with QRS≥120 ms, and 3) to evaluate cost- effectiveness of the proposed risk stratification approach leading to utilization of less costly devices (CRTP vs. CERT-D).