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: 10176259
• 负责人: Wojciech Zareba
• 金额: $ 74.38万
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10176259
• 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; 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; risk stratification; 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 用于主要预防死亡率的可植入的心脏逆变器除颤器（ICD）是 批准的非缺血性心肌病（NICM）射血分数患者（EF）的疗法 ≤35％。但是，丹麦ICD试验招募了1,116例NICM和EF≤35％的患者 随机分配给ICD（n = 556）或没有ICD（n = 560），证明缺乏显着死亡率 与非ICD患者相比，ICD患者的减少（危险比= 0.87； P = 0.28），但 突然心脏死亡的风险显着降低（危险比= 0.50； p = 0.005）。来自 先前的临床试验导致NICM中的ICD适应症显示出非显着但在临床上 死亡率的有意义降低，心脏猝死大幅降低 （确定：458例患者； HR = 0.65； P = 0.08和SCD-HEFT的亚组分析：792 患者; HR = 0.73; p = 0.06）。丹麦患者正在接受最佳药理治疗 58％的CRT设备。他们在非ICD ARM中的3年死亡率约为10％。 在10年前进行的20％和SCD-HEFT试验，反映 不同的患者人群和不同的潜在疗法。 由于心律失常心肌底物的特征是心室心律不齐 在长期ECG记录中检测到，我们分析了416 NICM中MADIT-CRT试验的数据 NYHA II级的患者QRS≥130ms，他们被随机分为CRT-D并且具有24-的患者 设备植入之前的小时Holter ECG记录。 NSVT在植入前抛光方面（在 194 [47％]患者）与3.08（p <0.001）的危险比相关，LVESVI> 86 mL/m2 与2.81（p <0.001）和非LBBB QRS形态相关（在 在多变量模型中，危险比为3.33（p <0.001）的44（11％）患者预测快速VT≥188 BPM或VF。这种风险预测模型可以指导有关植入的热决策 NICM心力衰竭患者的CRT-D，CRT-P或ICD设备，QRS≥120毫秒。 在本提案的特定目的1中，我们建议验证此MADIT-CRT风险分层 型号为400 NICM，QRS≥120ms。对迟到的观察越来越兴趣 在心脏MRI中评估的Gadolinium增强功能与突然的风险增加有关 NICM患者的心脏死亡，我们还旨在：2）确定是否异常心脏磁 与晚期增强的共振（CMR）成像将预测快速VT/VF 并将进一步改善QRS≥120毫秒的NICM的风险分层，3）评估成本 - 拟议的风险分层方法的有效性导致利用较低的成本 设备（CRTP与CERT-D）。