BACKGROUND Multicomponent improvement (MCI) is a novel endpoint for predicting survival in patients with pulmonary arterial hypertension (PAH), included in the sotatercept clinical program. For the first time, we investigated the prognostic value of MCI, ESC/ERS 4-strata risk (4SR) assessment, and the non-invasive French risk stratification score (FRS), for predicting survival in PAH patients in Sweden. All risk prediction models are based on three parameters: WHO-FC (World Health Organization Functional Class), NT-proBNP, and 6MWD (6-minute walk distance). METHODS Data from the Swedish PAH & CTEPH Registry (SPAHR) collected 2008-2021 were used for the analyses. The association of MCI achievement, 4SR, and FRS calculated at 6 months (6M), with transplant-free (TF) survival was investigated in the whole cohort, as well as categorized by age (<65 and ≥65 years). All risk prediction models are based on three parameters: WHO-FC (World Health Organization Function Class), NT-proBNP, and 6MWD (6-minute walk distance). Kaplan-Meier estimate/Log-Rank test and Cox proportional model were used for survival analyses. RESULTS The study included 411 patients (70% women) with a median [IQR] age of 66y.21 At 6M, the mean (SD) NT-proBNP decrease was 808 (603) and the mean 6MWD increase was 44 (11) meters. Median survival/follow-up time was 3.5y [1.7, 5.4]. After adjustment for sex and comorbidities, achievement of MCI independently predicted TF-survival; one MCI-criterion met (HR 0.65; CI 0.46-0.92, p=0.015); two MCI-criteria met (HR 0.45; CI 0.31-0.66, p<0.001); all three MCI-criteria met (HR 0.32; CI 0.21-0.52, p<0.001). Likewise, 4SR and FRS demonstrated a strong association with TF-survival with patients achieving lower risk scores exhibiting longer survival compared to those with higher risk scores. Patients ≥65Y more often had connective tissue disease-associated PAH, lower DLCO, more pronounced comorbidity burden, higher risk at baseline, less improvement during follow-up, and worse TF-survival then patients <65Y. CONCLUSION All models were found to have prognostic relevance for TF-survival. Risk prediction was incremental with the number of low-risk criteria met, while improvements in only one of 6MWD, NT-proBNP, or FC showed a modest association with survival. The risk assessment tools predicted outcome in patients across both age categories.

中文翻译：

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肺动脉高压的风险评估模型和生存率：SPAHR 分析。


背景 多组分改善 （MCI） 是预测肺动脉高压 （PAH） 患者生存率的新终点，包含在 sotatercept 临床计划中。我们首次研究了 MCI 、ESC/ERS 4 层风险 （4SR） 评估和非侵入性 French 风险分层评分 （FRS） 对预测瑞典 PAH 患者生存率的预后价值。所有风险预测模型都基于三个参数：WHO-FC（世界卫生组织功能分类）、NT-proBNP 和 6MWD（6 分钟步行距离）。方法：从2008-2021年收集的瑞典PAH和CTEPH登记处（SPAHR）收集的数据被用于分析。在整个队列中调查了 6 个月 （6M） 时计算的 MCI 成就、 4SR 和 FRS 与无移植 （TF） 生存率的关联，并按年龄 （<65 和 ≥65 岁） 分类。所有风险预测模型都基于三个参数：WHO-FC（世界卫生组织功能等级）、NT-proBNP 和 6MWD（6 分钟步行距离）。采用 Kaplan-Meier 估计/Log-Rank 检验和 Cox 比例模型进行生存分析。结果 该研究包括 411 名患者 （70% 为女性），中位 [IQR] 年龄为 66 岁.21 在 6 米时，平均 （SD） NT-proBNP 降低为 808 （603），平均 6MWD 增加 44 （11） 米。中位生存期/随访时间为 3.5 年 [1.7， 5.4]。在调整性别和合并症后，MCI 的实现独立预测 TF 生存期;满足 1 项 MCI 标准 （HR 0.65;CI 0.46-0.92，p=0.015）;满足两项 MCI 标准 （HR 0.45;CI 0.31-0.66，p<0.001）;所有三个 MCI 标准均满足 （HR 0.32;CI 0.21-0.52，p<0.001）。 同样，4SR 和 FRS 与 TF 生存期密切相关，与风险评分较高的患者相比，获得较低风险评分的患者表现出更长的生存期。与患者 <65Y 相比，≥65Y 患者更常具有结缔组织病相关 PAH 、较低的 DLCO、更明显的合并症负担、更高的基线风险、更高的随访期间改善较少和 TF 生存率更差。结论 发现所有模型都与 TF 生存期具有预后相关性。随着满足低风险标准的数量，风险预测是递增的，而 6MWD 、 NT-proBNP 或 FC 中只有一种的改善与生存率呈适度关联。风险评估工具预测了两个年龄组患者的结局。