基于当代射血分数降低的心力衰竭患者心脏性猝死风险预测模型的建立和验证

心脏性猝死(SCD)是射血分数降低的心力衰竭(HFrEF)患者常见死亡原因。植入式心律转复除颤器(ICD)是预防SCD的有效措施，但ICD费用高且其适应症对猝死高危患者甄别能力有限。因此，ICD的实际应用远低于其适应证范围。我们前期研究发现，HFrEF患者SCD发生率在过去近20年下降了44%，且这一趋势与神经内分泌抑制剂的累积使用有关。当前ICD所降低的SCD风险或已不足以转变为总生存获益，因此，对符合ICD适应证的HFrEF患者进一步完善SCD危险分层具有重要意义。本项目拟基于当代国际多中心临床试验，采用竞争风险模型建立HFrEF患者SCD预测模型，评价模型的区分度和校准度等指标，对模型进行验证以评价模型的稳定性和外推性，并基于预测模型建立网页工具和手机APP，作为猝死风险与ICD获益的量化评估工具，以期提高ICD的临床应用和成本获益比，促进精准医疗的实施和医疗资源的合理配置。

Sudden cardiac death (SCD) is one of the leading causes of death in patients with heart failure and reduced ejection fraction (HFrEF). Implantable cardioverter defibrillator (ICD) is an effective method to prevent SCD, though ICDs are costly and its indications are of low capacity to identify those at higher risk of SCD. Therefore, the use of ICD in clinical practice is far below its indications. Our previous study showed that the rate of SCD has decreased by 44% in patients with HFrEF over a nearly 20-year period, in parallel with a cumulative use of the guideline-recommended neurohumoral medications. The reduced risk of SCD by ICD implantation may not be able to translate into an overall survival benefit. Therefore, it is of great importance to further stratify the risk of SCD in patients with HFrEF who meet the current indications for ICD. In this project, we aim to develop and validate a predictive model for SCD in patients with HFrEF based on the contemporary cohorts from international multicenter clinical trials, with the use of competing risk model, and to assess the derived model’s discrimination and calibration. We would validate the model to examine its stability and generalizability, and build its online calculators and mobile phone applications as a calculation tool for sudden death risk and ICD benefit. This would improve the clinical use and cost-effectiveness of ICD, and promote the implementation of precision medicine and reasonable allocation of medical resources.