心房颤动（房颤）显著增加心力衰竭（心衰）的发病风险，但其具体机制尚不明确。以节律控制为目标的导管消融显著减少房颤患者心衰的发生和恶化，但手术难度较大，部分患者需要多次消融。对房颤患者的心衰发病风险进行评估将有助于治疗策略的选择。我们前期研究发现，心衰的房颤患者存在HAND1基因的突变，提示HAND1突变可能与心衰发病有关。我们将构建hHAND1点突变质粒和mHand1点突变的基因敲入(Knockin)小鼠，分别在细胞和整体水平，深入研究Hand1基因突变对房颤所致心衰的影响及其可能的机制，明确HAND1基因突变的功能。最后，我们将在已建立的房颤患者病例队列中，验证所发现的HAND1基因点突变对房颤患者心衰发病风险的预测价值。本研究有望建立起房颤患者心力衰竭发病风险的基因学预测指标，有助于心衰高危患者的早期识别，通过与临床相关指标结合，最终为房颤患者的个体化治疗提供理论依据。

Atrial fibrillation is known to increase the incidence of heart failure. However, the exact mechanism by which it affects is still unknown. Catheter ablation, which is used as a rhythm control strategy, greatly decreases the incidence and deterioration to heart failure but the procedure is technically difficult with a number of patients needing several procedures. Risk stratification of atrial fibrillation patients with heart failure will assist in selecting the optimal treatment strategy for this subset of patients. Our previous studies found that atrial fibrillation patients with heart failure have a mutation of HAND1 gene, indicating that HAND1 mutation might be related to developing heart failure. We will construct hHAND1 mutated plasmid and mHAND1 knock-in mice to have a model which will be used to investigate the effects and mechanism of HAND1 gene in the development of heart failure during atrial fibrillation. Clinical studies will be conducted by establishing a case cohort of atrial fibrillation patients which will be used to assess the risk prediction value of HAND1 gene. The study will develop a genetic predictive marker for developing heart failure in atrial fibrillation patients. This will provide evidence for early recognition and personalized management of high risk atrial fibrillation patients.