Martinelli-Filho Martino, Marin-Neto José A, Scanavacca Mauricio Ibrahim, de Paola Angelo Amato Vincenzo, Medeiros Paulo de Tarso Jorge, Owen Ruth, Pocock Stuart J, de Siqueira Sergio Freitas
Department of Cardiology, Instituto do Coração, Hospital das Clínicas da Universidade de São Paulo, São Paulo, Brazil.
Department of Interventional Cardiology, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
JAMA Cardiol. 2024 Dec 1;9(12):1073-1081. doi: 10.1001/jamacardio.2024.3169.
Over 10 000 people with Chagas disease experience sudden cardiac death (SCD) annually, mostly caused by ventricular fibrillation. Amiodarone hydrochloride and the implantable cardioverter-defibrillator (ICD) have been empirically used to prevent SCD in patients with chronic Chagas cardiomyopathy.
To test the hypothesis that ICD is more effective than amiodarone therapy for primary prevention of all-cause mortality in patients with chronic Chagas cardiomyopathy and moderate to high mortality risk, assessed by the Rassi score.
DESIGN, SETTING, AND PARTICIPANTS: CHAGASICS is an open-label, randomized clinical trial. The study enrolled patients from 13 centers in Brazil from May 30, 2014, to August 13, 2021, with the last follow-up November 8, 2021. Patients with serological findings positive for Chagas disease, a Rassi risk score of at least 10 points (intermediate to high risk), and at least 1 episode of nonsustained ventricular tachycardia were eligible to participate. Data were analyzed from May 3, 2022, to June 16, 2023.
Patients were randomized 1:1 to receive ICD or amiodarone (with a loading dose of 600 mg after randomization).
The primary outcome was all-cause mortality, and secondary outcomes included SCD, hospitalization for heart failure, and necessity of a pacemaker during the entire follow-up.
The study was stopped prematurely for administrative reasons, with 323 patients randomized (166 in the amiodarone group and 157 in the ICD group), rather than the intended 1100 patients. Analysis was by intention to treat at a median follow-up of 3.6 (IQR, 1.8-4.4) years. Mean (SD) age was 57.4 (9.8) years, 185 patients (57.3%) were male, and the mean (SD) left ventricular ejection fraction was 37.0% (11.6%). There were 60 deaths (38.2%) in the ICD arm and 64 (38.6%) in the amiodarone group (hazard ratio [HR], 0.86 [95% CI, 0.60-1.22]; P = .40). The rates of SCD (6 [3.8%] vs 23 [13.9%]; HR, 0.25 [95% CI, 0.10-0.61]; P = .001), bradycardia requiring pacing (3 [1.9%] vs 27 [16.3%]; HR, 0.10 [95% CI, 0.03-0.34]; P < .001), and heart failure hospitalization (14 [8.9%] vs 28 [16.9%]; HR, 0.46 [95% CI, 0.24-0.87]; P = .01) were lower in the ICD group compared with the amiodarone arm.
In patients with chronic Chagas cardiomyopathy at moderate to high risk of mortality, ICD did not reduce the risk of all-cause mortality. However, ICD significantly reduced the risk of SCD, pacing need, and heart failure hospitalization compared with amiodarone therapy. Further studies are warranted to confirm the evidence generated by this trial.
ClinicalTrials.gov Identifier: NCT01722942.
每年有超过10000名恰加斯病患者经历心源性猝死（SCD），主要由室颤引起。盐酸胺碘酮和植入式心脏复律除颤器（ICD）已被经验性地用于预防慢性恰加斯心肌病患者的心源性猝死。
检验以下假设，即对于慢性恰加斯心肌病且死亡风险为中度至高度（通过拉西评分评估）的患者，ICD在全因死亡一级预防方面比胺碘酮治疗更有效。
设计、设置和参与者：CHAGASICS是一项开放标签的随机临床试验。该研究于2014年5月30日至2021年8月13日招募了来自巴西13个中心的患者，最后一次随访于2021年11月8日进行。恰加斯病血清学检查结果呈阳性、拉西风险评分至少为10分（中度至高度风险）且至少有1次非持续性室性心动过速发作史的患者符合参与条件。数据于2022年5月3日至2023年6月16日进行分析。
患者按1:1随机分组，分别接受ICD或胺碘酮治疗（随机分组后给予600mg负荷剂量）。
主要结局为全因死亡，次要结局包括心源性猝死、因心力衰竭住院以及整个随访期间对起搏器的需求。
由于管理原因，该研究提前终止，共随机分配了323例患者（胺碘酮组166例，ICD组157例），而非计划的1100例患者。分析采用意向性分析，中位随访时间为3.6（四分位间距，1.8 - 4.4）年。平均（标准差）年龄为57.4（9.8）岁，185例患者（57.3%）为男性，平均（标准差）左心室射血分数为37.0%（11.6%）。ICD组有60例死亡（38.2%），胺碘酮组有64例死亡（38.6%）（风险比[HR]，0.86[95%置信区间，0.60 - 1.22]；P = 0.40）。与胺碘酮组相比，ICD组的心源性猝死发生率（6[3.8%]对23[13.9%]；HR，0.25[95%置信区间，0.10 - 0.61]；P = 0.001）、需要起搏的心动过缓发生率（3[1.9%]对27[16.3%]；HR，0.10[95%置信区间，0.03 - 0.34]；P < 0.001）以及心力衰竭住院率（14[8.9%]对28[16.9%]；HR，0.46[95%置信区间，0.24 - 0.87]；P = 0.01）均较低。
对于中度至高度死亡风险的慢性恰加斯心肌病患者，ICD并未降低全因死亡风险。然而，与胺碘酮治疗相比，ICD显著降低了心源性猝死风险、起搏需求以及心力衰竭住院率。有必要进行进一步研究以证实该试验所产生的证据。
ClinicalTrials.gov标识符：NCT01722942。
