CVRN-Risk with ICD Placement and Outcomes in Kidney Disease (CVRN-RISK) Study

描述（由申请人提供）：使用植入式心律转复除颤器（ICD）作为心源性猝死（SCD）的一级预防策略，显著降低了选定患者人群的死亡率。随机对照试验表明，在左心室射血分数（LVEF）降低的心力衰竭（HF）患者中，与标准药物治疗相比，预防性ICD植入通过检测和治疗恶性室性心律失常提高了生存率。然而，由于ICD植入会带来重大风险且成本高昂，因此在试验参与者之外和高风险亚组中使用该疗法及其相关结局是患者、临床医生和政策制定者的重要关注点。慢性肾脏疾病（CKD）定义为估计肾小球滤过率（eGFR）<60 ml/min/1.73 m2，影响美国570万心力衰竭（HF）成人中的约三分之一。在HF患者中，肾功能下降已被证明是SCD的最有力预测因素。尽管HF患者的肾功能降低具有高负担和高风险，但大多数先前的一级预防ICD植入试验和研究已排除肾功能降低的患者，或研究力度不足。因此，一级预防ICD植入术的风险和受益在肾功能降低患者与肾功能保留患者之间是否存在差异尚不清楚，但对这一高风险、不断增长的患者人群具有重要的治疗意义。我们计划在正在进行的NHLBI资助的心血管研究网络（CVRN）中合并两个独特的队列，CVRN是一个由15个卫生系统组成的全国性、大型、特殊特征的患者登记处，以解决这些知识差距：（1）HF和LVEF<50%的患者队列（CVRN-HF-REF）和（2）植入式心律转复除颤器（LSICD）的纵向研究，一组接受一级预防ICD置入的患者。合并这两个重叠的队列，我们将创建CVRN-RISK（肾脏疾病中ICD放置和结局的CVRN-RISK）队列，以实现以下特定目标。在目标1中，我们将评估肾功能水平与接受ICD作为心力衰竭伴LVEF降低患者心源性猝死一级预防的可能性之间的相关性。在目标2中，我们将确定植入一级预防ICD患者的植入前肾功能与植入后感染/血肿和不当电击的相关性。在目标3中，我们将评价肾功能是否改变了LVEF降低的HF患者中接受与未接受一级预防ICD对HF住院和死亡的比较有效性。最后，在目标4中，我们将开发一个决策和成本效益模型，以评价LVEF降低的HF患者在不同肾功能水平下植入一级预防ICD的净受益与损害。

DESCRIPTION (provided by applicant): The use of implantable cardioverter defibrillator (ICD) as a primary prevention strategy for sudden cardiac death (SCD) has dramatically reduced mortality in selected patient populations. Randomized controlled trials have shown that in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF), prophylactic ICD implantation improves survival compared with standard medical therapy by detection and treatment of malignant ventricular arrhythmias. However because ICD implantation poses significant risk and is costly, the use and outcomes associated with this therapy outside trial participants and in high-risk subgroups is an important focus by patients, clinicians and policy-makers alike. Chronic kidney disease (CKD), defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, affects approximately one-third of the 5.7 million adults with heart failure (HF) in the U.S. Among HF patients, reduced kidney function has been shown to be the most powerful predictor of SCD. Despite a high burden of and high risk associated with reduced kidney function among HF patients, most previous trials and studies of primary prevention ICD implantation have excluded or have been underpowered to study patients with reduced kidney function. Thus, whether the risks and benefits of primary prevention ICD implantation differs among patients with reduced kidney function compared with those with preserved kidney function remains unclear, but has critical therapeutic implications for this high-risk, growing patient population. We plan to merge two unique cohorts within the ongoing NHLBI-funded Cardiovascular Research Network (CVRN), a national, large, exceptionally-characterized patient registry of 15 health systems to address these gaps in knowledge: (1) a cohort of patients with HF and LVEF<50% (CVRN-HF-REF) and (2) the Longitudinal Study of Implantable Cardioverter-Defibrillators (LSICD), a cohort of patients undergoing primary prevention ICD placement. Merging these two overlapping cohorts, we will create the CVRN-RISK (CVRN-Risks with ICD placement and outcomeS in Kidney disease) cohort to accomplish the following specific aims. In Aim 1, we will evaluate the association between level of kidney function and likelihood of receiving an ICD for primary prevention of sudden cardiac death among patients with HF with reduced LVEF. In Aim 2, we will determine the association of pre-implantation kidney function with post-implantation infections/hematomas and inappropriate shocks among patients receiving a primary prevention ICD. In Aim 3, we will evaluate if kidney function modifies the comparative effectiveness of receipt versus no receipt of a primary prevention ICD on HF hospitalizations and death among HF patients with reduced LVEF. Finally in Aim 4, we will develop a decision and cost-effectiveness model to evaluate the net benefit versus harm associated with primary prevention ICD placement at different levels of kidney function among patients with HF with reduced LVEF.