Abstract
Background Chronic thromboembolic pulmonary hypertension (CTEPH) leads to right heart failure. Pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) restore pulmonary haemodynamics and allow cardiac recovery. This study examined the relationship of copeptin and mid-regional pro-atrial natriuretic peptide (MR-proANP) levels to disease severity and therapy response.
Methods This observational cohort study included 125 patients (55 PEA/70 BPA) who underwent treatment and completed a 6-/12-month follow-up. Biomarkers, measured at baseline, prior to every BPA and at follow-up, were compared to 1) severe disease at baseline (right atrial pressure (RAP) ≥8 mmHg and cardiac index ≤2.4 L·min−1·m−2) and 2) optimal therapy response (no persistent pulmonary hypertension combined with a normalised RAP (mean PAP ≤25 mmHg, pulmonary vascular resistance (PVR) ≤3 WU and RAP ≤6 mmHg) or a reduction in mean PAP ≥25%, PVR ≥35% and RAP ≥25%).
Results Severely diseased patients had higher levels of MR-proANP (320 (246–527) pmol·L−1 versus 133 (82–215) pmol·L−1; p=0.001) and copeptin (12.7 (7.3–20.6) pmol·L−1 versus 6.8 (4.4–12.8) pmol·L−1; p=0.015) at baseline than the rest of the cohort. At baseline, MR-proANP (area under the curve (AUC) 0.91; cut-off value 227 pmol·L−1; OR 56, 95% CI 6.9–454.3) and copeptin (AUC 0.70; cut-off value 10.9 pmol·L−1; OR 1.5, 95% CI 1.2–1.9) identified severely diseased patients. After PEA/BPA, levels of MR-proANP (99 (58–145) pmol·L−1; p<0.001) and copeptin (6.3 (3.7–12.6) pmol·L−1; p=0.009) decreased and indicated optimal therapy response (MR-proANP <123 pmol·L−1 (AUC 0.70) and copeptin <10.1 pmol·L−1 (AUC 0.58)).
Conclusion MR-proANP and copeptin levels are affected in CTEPH and decrease after therapy. MR-proANP identifies a severe disease status and optimal therapy response.
Abstract
The assessment of cardiac stress and impact of therapy is crucial in CTEPH. Serum levels of MR-proANP are associated with haemodynamic disease severity and therapy response, and might thus support individualised patient management. https://bit.ly/2QKwb7x
Footnotes
Conflict of interest: S.D. Kriechbaum has nothing to disclose.
Conflict of interest: L. Scherwitz has nothing to disclose.
Conflict of interest: C.B. Wiedenroth reports personal fees from Actelion, Bayer, MSD, Pfizer and BTG outside the submitted work.
Conflict of interest: F. Rudolph has nothing to disclose.
Conflict of interest: S. Wolter has nothing to disclose.
Conflict of interest: M. Haas reports personal fees from Daiichi-Sankyo and Pfizer outside the submitted work.
Conflict of interest: U. Fischer-Rasokat has nothing to disclose.
Conflict of interest: A. Rolf reports personal fees from Astra Zeneca, Boehringer Ingelheim and Pfizer-Bristol-Myers Squibb outside the submitted work;.
Conflict of interest: C.W. Hamm reports personal fees from BRAHMS/Thermo Fisher outside the submitted work.
Conflict of interest: E. Mayer reports grants from Deutsche Forschungsgesellschaft during the conduct of the study; and personal fees from Actelion, Bayer, MSD and Pfizer outside the submitted work.
Conflict of interest: S. Guth reports personal fees from Actelion, Bayer, GSK, MSD and Pfizer outside the submitted work.
Conflict of interest: T. Keller reports personal fees from Abbott and Brahms outside the submitted work.
Conflict of interest: S.V. Konstantinides reports grants from German Federal Ministry of Education and Research (BMBF 01EO1503) during the conduct of the study; and grants and personal fees from Bayer, personal fees from Pfizer Bristol Myers Suqibb, grants and personal fees from Boehringer Ingelheim, personal fees from Daiichi Sankyo and MSD, and grants from Actelion, outside the submitted work;.
Conflict of interest: M. Lankeit reports grants from German Federal Ministry of Education and Research (BMBF 01EO1503) during the conduct of the study; and grants and personal fees from Bayer, personal fees from Pfizer Bristol Myers Squibb, personal fees from Daiichi Sankyo and MSD, grants and personal fees from Thermo Fisher Scientific, and personal fees from Actelion, outside the submitted work.
Conflict of interest: C. Liebetrau reports personal fees from Bayer, Pfizer-Bristol-Myers Squibb, GSK, Abott, AstraZeneca, Berlin Chemie, Daiichi-Sankyo and Boehringer Ingelheim outside the submitted work.
Support statement: This research project is based on a cohort that is part of the Kerckhoff Biomarker Registry (Bioreg) that is financially supported by the Kerckhoff Heart Research Institute (KHFI) and the German Center for Cardiovascular Research (DZHK). We are also grateful to the William G. Kerckhoff Foundation (Bad Nauheim, Germany) for research funding. The current evaluation is supported by the grant of the Kerckhoff Foundation and is associated with the collaborative research centre 1213 (SFB 1213). The sponsors had no influence on the study design, statistical analyses or drafting of the manuscript. The work of M. Lankeit and S.V. Konstantinides was supported by the German Federal Ministry of Education and Research (BMBF 01EO1503). The authors are responsible for the contents of this publication. BRAHMS GmbH, part of Thermo Fisher Scientific (Hennigsdorf/Berlin, Germany) provided the assays for MR-proANP and copeptin measurements. The sponsor was neither involved in biomarker measurements, statistical analyses, writing of the manuscript nor had any influence on the scientific contents of this publication. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received June 5, 2020.
- Accepted August 18, 2020.
- Copyright ©ERS 2020
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