Tager Dany, Highland Kristin B, Aulak Kulwant S, Haber Leora, Tonelli Adriano R
Department of Pulmonary and Critical Care Medicine Integrated Hospital Care Institute Cleveland Ohio USA.
Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Cleveland Ohio USA.
Pulm Circ. 2025 Jul 27;15(3):e70141. doi: 10.1002/pul2.70141. eCollection 2025 Jul.
Pulmonary arterial hypertension (PAH) is a disorder characterized by progressive remodeling of small pulmonary arteries, leading to increased pulmonary vascular resistance, right ventricular failure and premature death (1-2). Over the past 30 years, significant advancements have been made in the treatment of PAH, including the recent approval of sotatercept, a first-in-class fusion protein that acts as a ligand trap for activins and growth differentiation factors, which are key players in the transforming growth factor β (TGF-β) superfamily (3-4). Sotatercept improves exercise capacity, as assessed by 6-min walk distance and World Health Organization (WHO) functional class, reduces pulmonary vascular resistance and NT-pro brain natriuretic peptide, and improves the simplified French risk score while extending the time to death or nonfatal clinical worsening (3). The 7th World Symposium in pulmonary hypertension recommends the addition of sotatercept as an option in PAH patients who have not achieved low risk despite combination therapy with at least an endothelin receptor antagonist and phosphodiesterase type-5 inhibitor, in intermediate or high-risk patients. The STELLAR study of sotatercept in PAH patients demonstrated the efficacy of this medication in patients receiving background therapy (3). In fact, 34% of the patients were on double and 60% of the patients on triple therapy. Interestingly 40% were on prostacyclin infusion therapy (3). Post-hoc analysis of the stellar study showed a beneficial effect for those on double or triple background PAH therapy as well as those receiving prostacyclin infusion at baseline (1,5). It remains unclear if the addition of sotatercept to other PAH treatments may have unexpected complications. It is possible that by rebalancing the proliferative/antiproliferative effects in the pulmonary circulation, the effect of other treatments for PAH may become excessive, particularly when parenteral prostacyclin is used at high doses. This phenomenon may manifest with the typical characteristics of prostacyclin overdose, including enhanced side effects and high cardiac output heart failure. Hereby we describe a patient with PAH on triple PAH-specific therapy, who after the initiation of sotatercept developed a large pericardial effusion and high cardiac output heart failure.
肺动脉高压（PAH）是一种以小肺动脉进行性重塑为特征的疾病，导致肺血管阻力增加、右心室衰竭和过早死亡（1-2）。在过去30年中，PAH的治疗取得了重大进展，包括最近索他西普的获批，这是一种一流的融合蛋白，可作为激活素和生长分化因子的配体陷阱，而激活素和生长分化因子是转化生长因子β（TGF-β）超家族的关键成员（3-4）。索他西普可改善运动能力，通过6分钟步行距离和世界卫生组织（WHO）功能分级评估，降低肺血管阻力和N末端脑钠肽前体，并改善简化的法国风险评分，同时延长至死亡或非致命性临床恶化的时间（3）。第七届世界肺动脉高压研讨会建议，对于尽管联合使用至少一种内皮素受体拮抗剂和5型磷酸二酯酶抑制剂仍未达到低风险的PAH患者，以及中高危患者，可将索他西普作为治疗选择。索他西普在PAH患者中的STELLAR研究证明了这种药物在接受背景治疗的患者中的疗效（3）。事实上，34%的患者接受双重治疗，60%的患者接受三重治疗。有趣的是，40%的患者接受前列环素输注治疗（3）。STELLAR研究的事后分析显示，对于接受双重或三重PAH背景治疗的患者以及基线时接受前列环素输注的患者有有益效果（1,5）。尚不清楚在其他PAH治疗中添加索他西普是否会有意外并发症。有可能通过重新平衡肺循环中的增殖/抗增殖作用，其他PAH治疗的效果可能会变得过度，特别是当高剂量使用胃肠外前列环素时。这种现象可能表现为前列环素过量的典型特征，包括副作用增强和高心输出量心力衰竭。在此，我们描述了一名接受三重PAH特异性治疗的PAH患者，在开始使用索他西普后出现了大量心包积液和高心输出量心力衰竭。
