Heart Rhythm. 2018 Oct;15(10):e253-e274. doi: 10.1016/j.hrthm.2017.10.037. Epub 2017 Nov 4.
Although large randomized clinical trials have found that primary prevention use of an implantable cardioverter-defibrillator (ICD) improves survival in patients with cardiomyopathy and heart failure symptoms, patients who receive ICDs in practice are often older and have more comorbidities than patients who were enrolled in the clinical trials. In addition, there is a debate among clinicians on the usefulness of electrophysiological study for risk stratification of asymptomatic patients with Brugada syndrome.
Our analysis has 2 objectives. First, to evaluate whether ventricular arrhythmias (VAs) induced with programmed electrostimulation in asymptomatic patients with Brugada syndrome identify a higher risk group that may require additional testing or therapies. Second, to evaluate whether implantation of an ICD is associated with a clinical benefit in older patients and patients with comorbidities who would otherwise benefit on the basis of left ventricular ejection fraction and heart failure symptoms.
Traditional statistical approaches were used to address 1) whether programmed ventricular stimulation identifies a higher-risk group in asymptomatic patients with Brugada syndrome and 2) whether ICD implantation for primary prevention is associated with improved outcomes in older patients (>75 years of age) and patients with significant comorbidities who would otherwise meet criteria for ICD implantation on the basis of symptoms or left ventricular function.
Evidence from 6 studies of 1138 asymptomatic patients were identified. Brugada syndrome with inducible VA on electrophysiological study was identified in 390 (34.3%) patients. To minimize patient overlap, the primary analysis used 5 of the 6 studies and found an odds ratio of 2.3 (95% CI: 0.63-8.66; p=0.2) for major arrhythmic events (sustained VAs, sudden cardiac death, or appropriate ICD therapy) in asymptomatic patients with Brugada syndrome and inducible VA on electrophysiological study versus those without inducible VA. Ten studies were reviewed that evaluated ICD use in older patients and 4 studies that evaluated unique patient populations were identified. In our analysis, ICD implantation was associated with improved survival (overall hazard ratio: 0.75; 95% confidence interval: 0.67-0.83; p<0.001). Ten studies were identified that evaluated ICD use in patients with various comorbidities including renal disease, chronic obstructive pulmonary disease, atrial fibrillation, heart disease, and others. A random effects model demonstrated that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.72; 95% confidence interval: 0.65-0.79; p<0.0001), and a second "minimal overlap" analysis also found that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.61-0.82; p<0.0001). In 5 studies that included data on renal dysfunction, ICD implantation was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.60-0.85; p<0.001).
尽管大型随机临床试验发现,对有心肌病和心力衰竭症状的患者进行植入式心脏复律除颤器(ICD)的一级预防使用可改善生存,但在实践中接受 ICD 的患者通常比临床试验中纳入的患者年龄更大,合并症更多。此外,临床医生对电生理研究在 Brugada 综合征无症状患者中的风险分层的有用性存在争议。
我们的分析有两个目标。首先,评估 Brugada 综合征无症状患者中程控电刺激诱导的室性心律失常(VA)是否可以识别出更高危的群体,这些患者可能需要进一步的检查或治疗。其次,评估 ICD 的植入是否与年龄较大的患者和有合并症的患者的临床获益相关,如果基于左心室射血分数和心力衰竭症状,这些患者将从中受益。
使用传统的统计方法来解决以下问题:1)程控心室刺激是否可以识别 Brugada 综合征无症状患者中的高危群体,2)ICD 一级预防植入是否与改善年龄较大的患者(>75 岁)和有合并症的患者的预后相关,如果基于症状或左心室功能,这些患者符合 ICD 植入的标准。
确定了 6 项涉及 1138 例无症状患者的研究中的证据。在 390 例(34.3%)患者中发现 Brugada 综合征伴有电生理研究诱导的 VA。为了尽量减少患者重叠,主要分析使用了 6 项研究中的 5 项,发现 Brugada 综合征伴有电生理研究诱导的 VA 的无症状患者发生主要心律失常事件(持续性 VA、心源性猝死或适当的 ICD 治疗)的优势比为 2.3(95%置信区间:0.63-8.66;p=0.2),而无电生理研究诱导的 VA 的患者则无。评估了 10 项研究中 ICD 在老年患者中的应用,确定了 4 项评估独特患者人群的研究。在我们的分析中,ICD 植入与生存率的提高相关(总风险比:0.75;95%置信区间:0.67-0.83;p<0.001)。评估了 ICD 在包括肾功能不全、慢性阻塞性肺疾病、心房颤动、心脏病等多种合并症的患者中的应用的 10 项研究。随机效应模型表明,ICD 应用与全因死亡率降低相关(总风险比:0.72;95%置信区间:0.65-0.79;p<0.0001),第二次“最小重叠”分析也发现,ICD 应用与全因死亡率降低相关(总风险比:0.71;95%置信区间:0.61-0.82;p<0.0001)。在包括肾功能不全数据的 5 项研究中,ICD 植入与全因死亡率降低相关(总风险比:0.71;95%置信区间:0.60-0.85;p<0.001)。