BACKGROUND >Despite advances in drug development, life expectancy in idiopathic pulmonary arterial hypertension (IPAH) remains unacceptable. Contemporary IPAH characterization is based on criteria that may not adequately capture disease heterogeneity and may be proposed as a possible explanation for why patient outcome is still unfavorable. The aim of this study was to apply cluster analysis to improve phenotyping of patients with IPAH and analyze long-term clinical outcome of derived clusters. METHODS Patients with IPAH from 2 referral centers (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Patients were classified according to cluster analysis and followed for clinical worsening occurrence. RESULTS The cluster analysis identified 4 IPAH phenotypes. Cluster 1 was characterized by young patients, mild pulmonary hypertension (PH), mild right ventricular (RV) dilation and high oxygen (O2) pulse; Cluster 2 by severe PH and RV dilation and high O2 pulse; and Cluster 3 by male patients, severe PH and RV dilation, and low O2 pulse. Cluster 4 patients were older and overweight, with mild PH and RV dilation and low O2 pulse. After a mean follow-up of 995 ± 623 days, 123 (48.8%) patients had clinical worsening. Cluster 1 patients presented the best prognosis, whereas Cluster 3 had the highest rates of clinical worsening. Compared with Cluster 1, risk of clinical worsening ranged from 4.12 (confidence interval [CI] 1.43-11.92; p = 0.009) for Cluster 4 to 7.38 (CI 2.80-19.40) for Cluster 2 and 13.8 (CI 5.60-34.0; p = 0.0001) for Cluster 3. CONCLUSIONS Cluster analysis of clinical variables identified 4 distinct phenotypes of IPAH. Our findings underscore the high degree of disease heterogeneity that exists within patients with IPAH and the need for advanced clinical testing to define phenotypes to improve treatment strategy decision-making. CONDENSED ABSTRACT Idiopathic pulmonary arterial hypertension (IPAH) characterization is based on criteria that may not adequately capture disease heterogeneity. The aim of this study was to apply cluster analysis to improve phenotyping of IPAH. Patients with IPAH (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Within the umbrella category of IPAH, it was the combination of mean pulmonary arterial pressure, right ventricular size, and oxygen pulse that further stratified patients into novel IPAH phenotypes that significantly associate with clinical worsening. These findings underscore the need for novel multidimensional IPAH phenotyping for improved patient care and trial quality.

中文翻译：

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通过聚类分析定义的特发性肺动脉高压表型的临床意义。

背景技术尽管药物开发取得进展，但特发性肺动脉高压（IPAH）的预期寿命仍然无法接受。当代IPAH的表征基于可能无法充分捕捉疾病异质性的标准，并可能被建议作为患者结果仍然不利的可能解释。这项研究的目的是应用聚类分析来改善IPAH患者的表型，并分析衍生聚类的长期临床结果。方法对来自2个转诊中心（n = 252）的IPAH患者进行临床，血液动力学和超声心动图评估以及心肺运动测试。根据聚类分析对患者进行分类，并随访临床恶化情况。结果聚类分析确定了4种IPAH表型。簇1的特点是年轻患者，轻度肺动脉高压（PH），轻度右心室（RV）扩张和高氧（O2）脉搏；簇2受严重的PH和RV扩张和高O2脉冲影响；男性患者，严重的PH和RV扩张以及低的O2脉搏出现在第3组。集群4例患者年龄较大且超重，PH和RV轻度扩张，O2脉冲低。平均随访995±623天后，有123例（48.8％）患者临床恶化。第一组的患者预后最好，而第3组的临床恶化率最高。与群集1相比，群集4的临床恶化风险范围为4.12（置信区间[CI] 1.43-11.92； p = 0.009）至群集2的7.38（CI 2.80-19.40）和13.8（CI 5.60-34.0; p =群集3的0.0001）。结论临床变量的聚类分析确定了4种不同的IPAH表型。我们的发现强调了IPAH患者中存在高度的疾病异质性，并且需要高级临床测试来定义表型以改善治疗策略决策。摘要特发性肺动脉高压（IPAH）的表征基于可能无法充分捕获疾病异质性的标准。这项研究的目的是应用聚类分析来改善IPAH的表型。对IPAH患者（n = 252）进行了临床，血液动力学和超声心动图评估以及心肺运动测试。在IPAH的总括范围内，它是平均肺动脉压，右心室大小，和氧气脉冲进一步将患者分为新的IPAH表型，这些表型与临床恶化密切相关。这些发现强调了需要新颖的多维IPAH表型来改善患者护理和试验质量。