Shelsey W. Johnson, Rui-Sheng Wang, Michael R. Winter, K. R. Gillmeyer, Katarina Zeder, E. Klings, Ronald H. Goldstein, R. Wiener, Bradley A Maron
{"title":"Cluster analysis identifies novel real-world lung disease-pulmonary hypertension sub-phenotypes: implications for treatment response","authors":"Shelsey W. Johnson, Rui-Sheng Wang, Michael R. Winter, K. R. Gillmeyer, Katarina Zeder, E. Klings, Ronald H. Goldstein, R. Wiener, Bradley A Maron","doi":"10.1183/23120541.00959-2023","DOIUrl":null,"url":null,"abstract":"Clinical trials repurposing pulmonary arterial hypertension (PAH) therapies to patients with lung disease- or hypoxia-pulmonary hypertension (Group 3 PH) have failed to show a consistent benefit. However, Group 3 PH clinical heterogeneity suggests robust phenotyping may inform detection of treatment-responsive subgroups. We hypothesized that cluster analysis would identify sub-phenotypes with differential responses to oral PAH therapy.Two k-means analyses were performed on a national cohort of U.S. Veterans with Group 3 PH; an inclusive model (I) of all treated patients (n=196) and a hemodynamic model (H) limited to patients with right heart catheterisations (RHC) (n=112). The primary outcome was organ failure or all-cause mortality by cluster. An exploratory analysis evaluated within-cluster treatment effects.Three distinct clusters of Group 3 PH patients were identified. In the “inclusive model” (C1I=43, 21.9%; C2I=102, 52.0%; C3I=51, 26.0%) lung disease and spirometry drove cluster assignment whereas RHC data surpassed the importance of these variables in the hemodynamic model (C1H=44, 39.3%; C2H=43, 38.4%; C3H=25, 22.3%). In the hemodynamic model, compared to C3H, C1Hexperienced the greatest hazard for respiratory failure or death (HR 6.1 [95% CI 3.2, 11.8]). In an exploratory analysis, cluster determined treatment response (p=0.006). Conclusions regarding within-cluster treatment responses were limited by significant differences between select variables in the treated and untreated groups.Cluster analysis identifies novel real-world sub-phenotypes of Group 3 PH patients with distinct clinical trajectories. Future studies may consider this methodologic approach to identify subgroups of heterogeneous patients that may be responsive to existing pulmonary vasodilatory therapies.","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ERJ Open Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1183/23120541.00959-2023","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0
Abstract
Clinical trials repurposing pulmonary arterial hypertension (PAH) therapies to patients with lung disease- or hypoxia-pulmonary hypertension (Group 3 PH) have failed to show a consistent benefit. However, Group 3 PH clinical heterogeneity suggests robust phenotyping may inform detection of treatment-responsive subgroups. We hypothesized that cluster analysis would identify sub-phenotypes with differential responses to oral PAH therapy.Two k-means analyses were performed on a national cohort of U.S. Veterans with Group 3 PH; an inclusive model (I) of all treated patients (n=196) and a hemodynamic model (H) limited to patients with right heart catheterisations (RHC) (n=112). The primary outcome was organ failure or all-cause mortality by cluster. An exploratory analysis evaluated within-cluster treatment effects.Three distinct clusters of Group 3 PH patients were identified. In the “inclusive model” (C1I=43, 21.9%; C2I=102, 52.0%; C3I=51, 26.0%) lung disease and spirometry drove cluster assignment whereas RHC data surpassed the importance of these variables in the hemodynamic model (C1H=44, 39.3%; C2H=43, 38.4%; C3H=25, 22.3%). In the hemodynamic model, compared to C3H, C1Hexperienced the greatest hazard for respiratory failure or death (HR 6.1 [95% CI 3.2, 11.8]). In an exploratory analysis, cluster determined treatment response (p=0.006). Conclusions regarding within-cluster treatment responses were limited by significant differences between select variables in the treated and untreated groups.Cluster analysis identifies novel real-world sub-phenotypes of Group 3 PH patients with distinct clinical trajectories. Future studies may consider this methodologic approach to identify subgroups of heterogeneous patients that may be responsive to existing pulmonary vasodilatory therapies.
期刊介绍:
ERJ Open Research is a fully open access original research journal, published online by the European Respiratory Society. The journal aims to publish high-quality work in all fields of respiratory science and medicine, covering basic science, clinical translational science and clinical medicine. The journal was created to help fulfil the ERS objective to disseminate scientific and educational material to its members and to the medical community, but also to provide researchers with an affordable open access specialty journal in which to publish their work.