BACKGROUND:Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes.METHODS:Patients diagnosed with PAH between January 1999 and December 2018 at 15 pulmonary hypertension centers were included and analyzed retrospectively. In accordance with current guidelines, acute vasoreactivity response was defined by a decrease of mean pulmonary artery pressure by ≥10 mm Hg to reach <40 mm Hg, without a decrease in cardiac output. Long-term response to CCBs was defined as alive with unchanged initial CCB therapy with or without other initial PAH therapy and World Health Organization functional classification I/II or low European Society of Cardiology/European Respiratory Society risk status at 12 months after initiation of CCBs. Patients were followed for up to 5 years; clinical measures, outcome, and subsequent treatment patterns were captured.RESULTS:Of 3702 patients undergoing right heart catheterization for PAH diagnosis, 2051 had idiopathic, hereditary, or drug-induced PAH, of whom 1904 (92.8%) underwent acute vasoreactivity testing. A total of 162 patients fulfilled acute vasoreactivity response criteria and received an initial CCB alone (n=123) or in combination with another PAH therapy (n=39). The median follow-up time was 60.0 months (interquartile range, 30.8–60.0), during which overall survival was 86.7%. At 12 months, 53.2% remained on CCB monotherapy, 14.7% on initial CCB plus another initial PAH therapy, and the remaining patients had the CCB withdrawn or PAH therapy added. CCB long-term response was found in 54.3% of patients. Five-year survival was 98.5% in long-term responders versus 73.0% in nonresponders. In addition to established vasodilator responder criteria, pulmonary artery compliance at acute vasoreactivity testing, low risk status and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels at early follow-up correlated with long-term response and predicted survival.CONCLUSIONS:Our data display heterogeneity within the group of vasoresponders, with a large subset failing to show a sustained satisfactory clinical response to CCBs. This highlights the necessity for comprehensive reassessment during early follow-up. The use of pulmonary artery compliance in addition to current measures may better identify those likely to have a good long-term response.

中文翻译：

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肺动脉高压的阳性血管反应性检测：现代管理时代的治疗后果、治疗模式和结果

背景：在肺动脉高压（PAH）患者中，右心导管插入术期间的急性血管反应性测试可能会识别急性血管反应，建议使用大剂量钙通道阻滞剂（CCB）治疗。然而，当前时代的长期结果仍然很大程度上未知。我们试图评估急性血管反应性反应对 CCB 长期反应和其他结果的影响。方法：纳入并回顾性分析 1999 年 1 月至 2018 年 12 月期间在 15 个肺动脉高压中心诊断为 PAH 的患者。根据现行指南，急性血管反应性反应的定义是平均肺动脉压降低≥10 mm Hg，达到<40 mm Hg，且心输出量不降低。 CCB 的长期缓解被定义为在开始 CCB 后 12 个月时，初始 CCB 治疗未改变，无论有或没有其他初始 PAH 治疗，并且世界卫生组织功能分类 I/II 或欧洲心脏病学会/欧洲呼吸学会低风险状态，仍存活。 。对患者进行长达 5 年的随访；结果：在 3702 名接受右心导管检查诊断 PAH 的患者中，2051 名患有特发性、遗传性或药物诱发的 PAH，其中 1904 名 (92.8%) 接受了急性血管反应性检测。共有 162 名患者符合急性血管反应性反应标准，并接受单独初始 CCB (n=123) 或与另一种 PAH 治疗联合治疗 (n=39)。中位随访时间为 60.0 个月（四分位数范围，30.8-60.0），在此期间总生存率为 86.7%。 12 个月时，53.2% 仍接受 CCB 单药治疗，14.7% 接受初始 CCB 加另一种初始 PAH 治疗，其余患者撤回 CCB 或添加 PAH 治疗。 54.3% 的患者发现 CCB 长期缓解。长期缓解者的五年生存率为 98.5%，而无缓解者的五年生存率为 73.0%。除了既定的血管舒张反应标准外，急性血管反应性测试中的肺动脉顺应性、低风险状态和早期随访时的 NT-proBNP（N 端 B 型利钠肽前体）水平与长期反应和预测生存相关结论：我们的数据显示血管反应组内的异质性，其中很大一部分未能显示出对 CCB 持续令人满意的临床反应。这凸显了在早期随访期间进行全面重新评估的必要性。除了当前的措施之外，使用肺动脉顺应性可以更好地识别那些可能具有良好长期反应的患者。