Galectin-3, GDF-15, and sST2 for the assessment of disease severity and therapy response in patients suffering from inoperable chronic thromboembolic pulmonary hypertension

Abstract

Purpose

This study examined sST2, GDF-15, and galectin-3 as indicators of disease severity and therapy response in chronic thromboembolic pulmonary hypertension (CTEPH).

Methods

This study included 57 inoperable CTEPH patients who underwent balloon pulmonary angioplasty and 25 controls without cardiovascular disease. Biomarker levels were examined in relation to advanced hemodynamic impairment [tertile with worst right atrial pressure (RAP) and cardiac index], hemodynamic therapy response [normalized hemodynamics (meanPAP ≤25 mmHg, PVR ≤3 WU and RAP ≤6 mmHg) or a reduction of meanPAP ≥25%; PVR ≥ 35%, RAP ≥25%].

Results

GDF-15 [820 (556–1315) pg/ml vs. 370 (314–516) pg/ml; p < 0.001] and sST2 [53.7 (45.3–74.1) ng/ml vs. 48.7 (35.5–57.0) ng/ml; p = 0.02] were higher in CTEPH patients than in controls. At baseline, a GDF-15 level ≥1443 pg/ml (AUC 0.88; OR 31.4) and a sST2 level ≥65 ng/ml (AUC 0.80; OR 10.9) were associated with advanced hemodynamic impairment. At follow-up GDF-15 ≤ 958 pg/ml (AUC = 0.74, OR 18) identified patients with optimal hemodynamic therapy response and ≤760 pg/ml (AUC = 0.79, OR 14).

Conclusion

GDF-15 and sST2 levels are higher in CTEPH and identified patients with advanced hemodynamic impairment. Further, decreased GDF-15 levels at follow-up were associated with hemodynamic therapy response. The diagnostic strength was not superior to NT-proBNP.

Keywords:

• Galectin-3
• GDF-15
• ST2
• BPA
• CTEPH
• biomarker
• remodelling

Acknowledgements

The authors thank Elizabeth Martinson, PhD, from the KHFI Editorial Office for her editorial assistance.

Disclosure statement

CBW received consultant honoraria and/or speaker fees from Actelion, Bayer AG, MSD, Pfizer and BTG; MH received lecture honoraria from Daiichi-Sankyo and Pfizer; SG received speaker fees from Actelion, Bayer, GSK and Pfizer; AJR received financial grant/travel support from Biotest an Servier, consultant honoraria and/or speaker fees from Actelion and Novartis; AR received lecture honoraria from Astra Zeneca, Boehringer Ingelheim and Pfizer-Bristol-Myers Squibb; CWH received lecture or consulting honoraria from BRAHMS and Thermo Fisher; EM received lecture or consulting honoraria from Actelion, Bayer, MSD, GSK, Pfizer and MSD; TK received speaker fees from Abbott; CL received lecture or consulting honoraria from Abbott, Astra Zeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Daiichi-Sankyo and Pfizer-Bristol-Myers Squibb. SDK, KP, MAB, RA, JSW and FCR have nothing to declare.

Data availability statement

The data underlying this article cannot be shared publicly due to the privacy of individuals that participated in the study. Sharing the underlying data is not in line with the written informed consent of the patients in this study. The data will be shared on reasonable request to the corresponding author.

Additional information

Funding

This work was supported by the SFB 1213 area CP-01 project and the William G. Kerckhoff-Foundation, Bad Nauheim, Germany.