心力衰竭 (HF)

心力衰竭引起的复杂临床综合征主要表现为呼吸困难、疲乏和液体潴留（肺淤血、体循环淤血及外周水肿）等，也是各种心脏疾病的严重表现或晚期阶段。

据估计，全球心力衰竭患者约6400万。在中国25岁以上人群的患病率为1.1%，这意味着中国25岁以上人群中患者人数估计超过1200万，且患病率随着年龄增加而上升。

根据左室射血分数（LVEF），分为射血分数降低的心衰（HFrEF，LVEF≤40%）、射血分数改善的心衰（HFimpEF，既往LVEF≤40%，随访LVEF>40%）、射血分数轻度降低的心衰（HFmrEF，LVEF 41%-49%）和射血分数保留的心衰（HFpEF，LVEF ≥50%）。在中国队列中观察到HFrEF的患者5年死亡率明显高于其他类型。

虽然心衰的防治已经取得了很大进步，但整体预后仍不理想。有数据显示，中国心衰患者出院后30天和1年的再住院率为19%和53%，而出院后30天和1年死亡率分别为14%和29%。考虑到心衰患者的数量，反复住院和最终死亡都给家庭和医疗系统都带来明显的负担。

Aficamten可作为一种射血分数保留的心力衰竭（HFpEF）的候选药物。作为肌球蛋白抑制剂，aficamten通过改善心肌收缩力以调节肌小节功能障碍，并有可能延长心力衰竭患者的寿命。

Omecamtiv mecarbil是一种在研的选择性小分子心肌肌球蛋白激活剂，作为同类首创的靶向肌节的在研新药，可直接靶向作用于心脏的收缩机制，在收缩过程中结合并增加与肌动蛋白相互作用的心肌肌球蛋白头部区域的数量。Omecamtiv mecarbil旨在增加每个心动周期中的肌动蛋白-肌球蛋白活性横桥的数量，从而在射血分数降低的心力衰竭（HFrEF）患者中增强受损的心肌收缩力。临床前研究显示，omecamtiv mecarbil可增强心肌收缩力，且不增加心肌细胞内的钙浓度或心肌耗氧量。

参考文献：

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