Background

A small proportion of patients undergoing primary prophylactic implantation of implantable cardioverter defibrillators (ICDs) experiences malignant arrhythmias. We postulated that periodic repolarisation dynamics, a novel marker of sympathetic-activity-associated repolarisation instability, could be used to identify electrically vulnerable patients who would benefit from prophylactic implantation of ICDs by way of a reduction in mortality.

Methods

We did a prespecified substudy of EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD), a prospective, investigator-initiated, non-randomised, controlled cohort study done at 44 centres in 15 EU countries. Patients aged 18 years or older with ischaemic or non-ischaemic cardiomyopathy and reduced left ventricular ejection fraction (≤35%) were eligible for inclusion if they met guideline-based criteria for primary prophylactic implantation of ICDs. Periodic repolarisation dynamics from 24-h Holter recordings were assessed blindly in patients the day before ICD implantation or on the day of study enrolment in patients who were conservatively managed. The primary endpoint was all-cause mortality. Propensity scoring and multivariable models were used to assess the interaction between periodic repolarisation dynamics and the treatment effect of ICDs on mortality.

Findings

Between May 12, 2014, and Sept 7, 2018, 1371 patients were enrolled in our study. 968 of these patients underwent ICD implantation, and 403 were treated conservatively. During follow-up (median 2·7 years [IQR 2·0–3·3] in the ICD group and 1·2 years [0·8–2·7] in the control group), 138 (14%) patients died in the ICD group and 64 (16%) patients died in the control group. We noted a 43% reduction in mortality in the ICD group compared with the control group (adjusted hazard ratio [HR] 0·57 [95% CI 0·41–0·79]; p=0·0008). Periodic repolarisation dynamics significantly predicted the treatment effect of ICDs on mortality (adjusted p=0·0307). The mortality benefits associated with ICD implantation were greater in patients with periodic repolarisation dynamics of 7·5 deg or higher (n=199; adjusted HR 0·25 [95% CI 0·13–0·47] for the ICD group vs the control group; p<0·0001) than in those with periodic repolarisation dynamics less than 7·5 deg (n=1166; adjusted HR 0·69 [95% CI 0·47–1·00]; p=0·0492; p _interaction=0·0056). The number needed to treat was 18·3 (95% CI 10·6–4895·3) in patients with periodic repolarisation dynamics less than 7·5 deg and 3·1 (2·6–4·8) in those with periodic repolarisation dynamics of 7·5 deg or higher.

Interpretation

Periodic repolarisation dynamics predict mortality reductions associated with prophylactic implantation of ICDs in contemporarily treated patients with ischaemic or non-ischaemic cardiomyopathy. Periodic repolarisation dynamics could help to guide treatment decisions about prophylactic ICD implantation.

Funding

The European Community's 7th Framework Programme.

中文翻译：

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基于定期复极动态对除颤器进行预防性植入患者的死亡率预测：一项前瞻性，对照，多中心队列研究

背景

一小部分正在接受预防性植入式心脏复律除颤器（ICD）植入的患者发生恶性心律不齐。我们假设周期性的复极动力学是一种与交感神经活动相关的复极不稳定性的新标志，可以用来鉴定易受电的患者，这些患者可以通过降低死亡率来预防性植入ICD。

方法

我们对EUropean比较有效性研究进行了预先指定的子研究，以评估使用主要的预防性植入式心脏复律除颤器（EU-CERT-ICD），这是一项由研究人员发起，由研究人员发起的，非随机，对照的队列研究，其研究对象是15个欧盟国家的44个中心。18岁或以上患有缺血性或非缺血性心肌病且左心室射血分数降低（≤35％）的患者，如果符合ICD一级预防性植入的基于指南的标准，则符合入选条件。在植入ICD的前一天或研究入选当天保守治疗的患者中，盲人评估了24小时动态心电图记录的周期性复极动态。主要终点是全因死亡率。

发现

在2014年5月12日至2018年9月7日之间，我们的研究招募了1371名患者。这些患者中有968位接受了ICD植入，其中403位接受了保守治疗。随访期间（ICD组中位2·7年[IQR 2·0–3·3]和对照组1·2年[0·8–2·7]），138名患者（14％）在ICD组中死亡，对照组中有64例（16％）患者死亡。我们注意到，与对照组相比，ICD组的死亡率降低了43％（危险比[HR] 0·57 [95％CI 0·41-0·79]； p = 0·0008）。周期性复极动力学显着预测了ICD对死亡率的治疗效果（调整后的p = 0·0307）。周期性复极动态为7·5度或更高的患者，与ICD植入相关的死亡率收益更大（n = 199； ICD组的校正后HR 0·25 [95％CI 0·13-0·47]与对照组相比；p <0·0001）小于周期性复极动力学小于7·5度（n = 1166；调整后的HR 0·69 [95％CI 0·47-1·00]； p = 0·0492； p_{相互作用）} = 0·0056）。周期性复极动力学低于7·5度的患者需要治疗的人数为18·3（95％CI 10·6–4895·3），周期性复极动力学低于7·5度的患者需要治疗的人数为3·1（2·6–4·8）再极化动力学为7·5度或更高。

解释

周期性复极动力学预测，在接受缺血性或非缺血性心肌病治疗的患者中，预防性植入ICD会降低死亡率。周期性复极动力学可以帮助指导有关预防性ICD植入的治疗决策。

资金

欧洲共同体的第七框架计划。