Cluster analysis identifies novel real-world lung disease-pulmonary hypertension sub-phenotypes: implications for treatment response
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Published:2024-02-29
Issue:
Volume:
Page:00959-2023
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ISSN:2312-0541
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Container-title:ERJ Open Research
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language:en
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Short-container-title:ERJ Open Res
Author:
Johnson Shelsey W.,Wang Rui-Sheng,Winter Michael R.,Gillmeyer Kari R.,Zeder Katarina,Klings Elizabeth S.,Goldstein Ronald H.,Wiener Renda Soylemez,Maron Bradley A.
Abstract
BackgroundClinical 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.MethodsTwo 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.ResultsThree 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.ConclusionsCluster 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.
Funder
National Heart, Lung, and Blood Institute
Publisher
European Respiratory Society (ERS)