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

与非缺血性心肌病室性快速心律失常相关的临床、心电图和心脏磁共振成像危险因素

• 批准号: 9904736
• 负责人: Wojciech Zareba
• 金额: $ 75.58万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904736
• 关键词: Cardiac; Cardiomyopathies; Cessation of life; Clinical; Clinical Data; Clinical Trials; Data; Data Analyses; Devices; EFRAC; Electrocardiogram; Enrollment; Event; Gadolinium; Guidelines; Heart Abnormalities; Heart failure; Hour; Implantable Defibrillators; Lead; Left; Left Ventricular Ejection Fraction; Level of Evidence; Magnetic Resonance; Magnetic Resonance Imaging; Modeling; Modernization; Morphology; Myocardial; Patients; Pharmacology; Primary Prevention; Prospective Studies; Publishing; Randomized; Risk; Risk Factors; Risk stratification; Subgroup; Tachyarrhythmias; Therapeutic; Ventricular; Ventricular Arrhythmia; arm; base; coronary fibrosis; cost; cost effectiveness; cost-effectiveness evaluation; hazard; implantable device; implantation; improved; insight; interest; mortality; myocardial damage; patient population; predictive modeling; preimplantation; risk prediction model; screening; sudden cardiac death

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).

抽象的 用于死亡一级预防的植入式心律转复除颤器 (ICD) 是一种 批准治疗射血分数 (EF) 的非缺血性心肌病 (NICM) 患者 ≤35%。然而，DANISH ICD 试验招募了 1,116 名 NICM 且 EF ≤ 35% 的患者 随机接受 ICD (n=556) 或不接受 ICD (n=560)，显示死亡率不显着 与非 ICD 患者相比，ICD 患者减少（风险比=0.87；p=0.28），但是 心源性猝死的风险显着降低（风险比=0.50；p=0.005）。数据来自 先前导致 NICM 中 ICD 适应症的临床试验显示，不显着，但临床上 死亡率显着降低，心源性猝死显着减少 （确定：458 名患者；HR=0.65；p=0.08，SCD-HeFT 的亚组分析：792 患者; HR=0.73； p=0.06）。丹麦患者接受了最佳药物治疗 58% 拥有 CRT 设备。非 ICD 组的 3 年死亡率约为 10%，而非 ICD 组的 3 年死亡率约为 10 年前进行的 DEFINITE 和 SCD-HeFT 试验中为 20%，反映了 不同的患者群体和不同的基础疗法。 由于致心律失常心肌基质的特点是室性心律失常 在长期心电图记录中检测到，我们分析了 416 NICM 中 MADIT-CRT 试验的数据 NYHA II 级 QRS ≥ 130 ms 的患者被随机分配至 CRT-D，并且具有 24- 设备植入前进行小时动态心电图记录。植入前动态心电图上的 NSVT（在 194 [47%] 患者）的风险比为 3.08 (p<0.001)，增大的 LVESVi >86 ml/m2 与 2.81 (p<0.001) 的风险比相关，并且非 LBBB QRS 形态（在 44 名 (11%) 患者）在预测快速 VT≥188 的多变量模型中风险比为 3.33 (p<0.001) bpm 或 VF。该风险预测模型可以指导有关植入的治疗决策 QRS≥120 ms NICM 心力衰竭患者的 CRT-D、CRT-P 或 ICD 设备。 在本提案的具体目标 1 中，我们建议验证此 MADIT-CRT 风险分层 400 NICM 模型，宽 QRS≥120ms。随着人们对观察的兴趣日益浓厚 心脏 MRI 评估的钆增强与突发性心脏病风险增加相关 在 NICM 患者心源性死亡中，我们还旨在：2）确定心脏磁是否异常 晚期钆增强共振 (CMR) 成像可预测快速 VT/VF 并将进一步改善 QRS≥120 ms NICM 的风险分层，以及 3) 评估成本 所提议的风险分层方法的有效性，导致使用成本较低的风险分层方法 设备（CRTP 与 CERT-D）。