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).

摘要 植入型心律转复除颤器(ICD)是一种一级预防死亡的方法 非缺血性心肌病(NICM)患者射血分数(EF)的批准治疗 ≤为35%。然而，丹麦的ICD试验招募了1,116名患有NICM和EF≤的患者，患者的比例为35%。 随机分为ICD组(n=556)和非ICD组(n=560)，结果显示无显著死亡率 ICD患者与非ICD患者相比减少(风险比=0.87；p=0.28)，但 显著降低心脏性猝死的风险(危险比=0.5；p=0.005)。数据来自 先前导致NICM中ICD指征的临床试验显示，一个没有意义但临床上 死亡率显著降低，心源性猝死显著减少 (确定：458名患者；HR=0.65；p=0.08，SCD-HeFT亚组分析：792 患者；HR=0.73；P=0.06)。丹麦患者正在接受最理想的药物治疗 58%的人拥有CRT设备。他们在非ICD组的3年死亡率约为10%，而非ICD组的死亡率约为 在10年前进行的确定性和SCD-HeFT试验中，20%反映了 不同的患者群体和不同的潜在治疗方法。 由于致心律失常的心肌基质以室性心律失常为特征 在长期的心电记录中检测到的，我们分析了416个NICM的MADIT-CRT试验的数据 心功能分级II级、QRS-≥为130ms的患者被随机分配到CRT-D组，并有24- 植入术前1小时动态心电图记录。植入前动态心电图的NSVT(观察到 4 4例(47%)，危险比为3.0 8(p&lt；0.001)，左心室增大86ml/m2 与2.81%的危险比相关(p&lt；0.001)，以及非LBBB QRS形态(观察到 在预测FAST VT≥188时的多变量模型中，风险比为3.33P&lt；0.001的患者44(11%) BPM或VF。这种风险预测模型可以指导有关植入的治疗决策。 ≥为120ms的心力衰竭患者的CRT-D、CRT-P或ICD装置。 在本提案的具体目标1中，我们建议验证这种MADIT-CRT风险分层 型号为400NICM，QRS≥为120ms。随着人们对晚些时候的观察越来越感兴趣 心脏MRI评估的Gd增强与猝发风险增加相关 NICM患者的心源性死亡，我们还旨在：2)确定异常的心脏磁化 晚期Gd增强的磁共振(CMR)成像可预测快速VT/VF 并将使用QRS≥120ms进一步改进NICM中的风险分层，以及3)评估成本- 拟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)。