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Treatment-related Biomarkers in Pulmonary Hypertension Patients on Oral Therapies

Publication ,  Journal Article
Swaminathan, AC; Zhu, H; Tapson, V; Lokhnygina, Y; Poms, A; Kelleher, Z; Gaspard, E; Kennedy, K; Fee, B; Fortin, T; Mason, SN; Parikh, K; McMahon, T
August 24, 2020

Multiple classes of oral therapy are available for the treatment of pulmonary arterial hypertension (PAH), but there is little to guide clinicians in choosing a specific regimen or therapeutic class. We aimed to investigate whether treatment-relevant blood biomarkers can predict therapy response in prevalent PAH patients.This prospective cohort study longitudinally assessed biomarkers along the endothelin-1 (ET-1) and nitric oxide (cGMP, ADMA, SDMA, nitrite, and S-nitrosohemoglobin) pathways along with the cGMP/NT-proBNP ratio over 12 months in patients with WHO Group 1 PAH on oral PAH-specific therapies. The relationship between biomarkers and 6MWD at the same and future visits was examined using mixed linear regression models. As cGMP can be elevated when NT-proBNP is elevated, we also tested the relationship between 6MWD and the cGMP/NT-pro BNP ratio. Patients with PAH with concomitant heart or lung disease or chronic thromboembolic pulmonary hypertension (CTEPH) were included in a sensitivity analysis. The study cohort included 58 patients with PAH treated with either an endothelin receptor antagonist (27.6%), phosphodiesterase-5 inhibitor (29.3%) or a combination of the two (43.1%). Among biomarkers along the current therapeutic pathways, ET-1 and the cGMP/NT-proBNP ratio associated with same visit 6MWD (p = 0.04 and p=0.009 respectively). ET-1 (p=0.01) and cGMP/NT-proBNP ratio (p < 0.001) also predicted future 6MWD in the larger cohort (n = 108) of PAH patients with concomitant left heart disease (n = 17), lung disease (n = 20), or CTEPH (n = 13). Finally, in the larger cohort, SDMA associated with 6MWD at the same visit (p = 0.003) in all subgroups and ADMA associated with 6MWD in PAH patients with concomitant lung disease (p=0.027) and PAH patients on ERA therapy (p = 0.01). : ET-1, cGMP/NTproBNP ratio, and dimethylarginines ADMA and SDMA are mediators along pathways targeted by oral PAH therapies that associate with or predict 6MWD.

Duke Scholars

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Publication Date

August 24, 2020
 

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Swaminathan, A. C., Zhu, H., Tapson, V., Lokhnygina, Y., Poms, A., Kelleher, Z., … McMahon, T. (2020). Treatment-related Biomarkers in Pulmonary Hypertension Patients on Oral Therapies. https://doi.org/10.21203/rs.3.rs-63089/v1
Swaminathan, Aparna C., Hongmei Zhu, Victor Tapson, Yuliya Lokhnygina, Abby Poms, Zachary Kelleher, Elijah Gaspard, et al. “Treatment-related Biomarkers in Pulmonary Hypertension Patients on Oral Therapies,” August 24, 2020. https://doi.org/10.21203/rs.3.rs-63089/v1.
Swaminathan AC, Zhu H, Tapson V, Lokhnygina Y, Poms A, Kelleher Z, et al. Treatment-related Biomarkers in Pulmonary Hypertension Patients on Oral Therapies. 2020 Aug 24;
Swaminathan, Aparna C., et al. Treatment-related Biomarkers in Pulmonary Hypertension Patients on Oral Therapies. Aug. 2020. Crossref, doi:10.21203/rs.3.rs-63089/v1.
Swaminathan AC, Zhu H, Tapson V, Lokhnygina Y, Poms A, Kelleher Z, Gaspard E, Kennedy K, Fee B, Fortin T, Mason SN, Parikh K, McMahon T. Treatment-related Biomarkers in Pulmonary Hypertension Patients on Oral Therapies. 2020 Aug 24;

DOI

Publication Date

August 24, 2020