Transforming Pulmonary Arterial Hypertension: Key Milestones and Future Perspectives.

Over the past four decades, substantial advances in understanding PAH pathobiology, epidemiology, diagnosis, and treatment have meaningfully improved patient outcomes.

在过去的四十年里，对PAH病理生物学、流行病学、诊断和治疗的深入理解已经显著改善了患者的预后。

The pathobiology of PAH is multifaceted, involving endothelial dysfunction, smooth muscle cell hyperproliferation, inflammation, and dysregulation of key signaling pathways, including the prostacyclin, nitric oxide, endothelin 1, and bone morphogenetic/TGF-β (transforming growth factor β) axes.

PAH的病理生物学是多方面的，涉及内皮功能障碍、平滑肌细胞过度增殖、炎症以及关键信号通路的失调，包括前列环素、一氧化氮、内皮素1和骨形态发生蛋白/转化生长因子β（TGF-β）轴。

Dysregulation of the activin arm of the TGF-β pathway has emerged as a critical driver of vascular remodeling and is the target of sotatercept, the first antiremodeling therapy approved for PAH.

TGF-β通路的激活素分支失调已成为血管重塑的关键驱动因素，并且是首个被批准用于PAH的抗重塑疗法sotatercept的靶点。

Epidemiologically, PAH now more commonly affects older adults with cardiovascular and pulmonary comorbidities compared with historical cohorts.

流行病学上，与历史队列相比，现在肺动脉高压（PAH）更常见于有心血管和肺部共病的老年人群体。

The global burden varies considerably, with methamphetamine-associated PAH rising in North America and schistosomiasis- and HIV-associated PAH prevalent in low- and middle-income countries, where underdiagnosis likely remains substantial. Diagnosis continues to be delayed, with advanced symptoms present at the time of diagnosis for most patients.

全球负担差异显著，北美与甲基苯丙胺相关的肺动脉高压（PAH）发病率上升，而血吸虫病和HIV相关的肺动脉高压在低收入和中等收入国家更为普遍，在这些国家，漏诊可能仍然相当严重。诊断继续延迟，大多数患者在诊断时已出现晚期症状。

Right heart catheterization remains essential for definitive diagnosis.

右心导管检查对于确诊仍然是必不可少的。

Emerging tools, including artificial intelligence applied to electrocardiography, echocardiography, and electronic health records, hold promise for earlier case identification.

新兴工具，包括应用于心电图、超声心动图和电子健康记录的人工智能，对于早期病例识别具有很大的潜力。

Management and prognostication of PAH is based on regular risk stratification using validated multiparameter tools.

PAH的管理和预后判断基于使用经过验证的多参数工具进行定期的风险分层。

The initial therapy choice is up-front combination therapy with 2 oral medications for most patients, with initial triple therapy that includes a parenteral prostacyclin used in high-risk patients.

大多数患者的初始治疗选择是两种口服药物的联合治疗，对于高风险患者，初始治疗包括使用一种静脉注射的前列腺素的三重治疗。

Add-on therapy with sotatercept is now an option for patients not achieving low risk, a strategy that led to improvements in hemodynamics, right heart function, and reduced the risk of adverse clinical outcomes in recent randomized trials.

对于未能达到低风险的患者，现在可以考虑添加索他来曲作为治疗方案，这一策略在最近的随机试验中改善了血流动力学、右心功能，并降低了不良临床结果的风险。

For patients who remain at higher risk despite maximal therapy, lung transplantation remains an important and life-saving option.

对于尽管接受了最大治疗仍然处于高风险的患者，肺移植仍然是一个重要的、救命的选择。

Despite remarkable therapy progress, gaps persist in earlier detection, management of comorbid phenotypes, personalized therapy, and novel therapies targeting right ventricular failure.

尽管治疗进展显著，但在早期检测、共病表型的管理、个性化治疗以及针对右心室衰竭的新疗法开发方面仍存在差距。

Ongoing clinical trials and translational research continue to advance the field toward the goal of normal survival and quality of life for patients with PAH.

正在进行的临床试验和转化研究继续推动该领域向为肺动脉高压患者实现正常生存和生活质量的目标迈进。