Cardiac Remodeling Biomarker May Identify High Risk Patients With PAH

gloved hand holding test tubes, biomarkers
Suppressor of tumorigenicity 2 may function as a biomarker to identify patients with pulmonary arterial hypertension with higher REVEAL risk scores.

Suppressor of tumorigenicity (ST-2) may function as a biomarker to identify patients with pulmonary arterial hypertension (PAH) with higher REVEAL risk scores, according to research being presented at the 39th Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation held in Orlando, Florida.

In a post hoc analysis of the 24-week open-label, uncontrolled Phase 3B clinical trial RESPITE ( Identifier: NCT02007629), researchers assessed ST-2 as a biomarker of the likelihood of response in patients who switched from PDE5 inhibitors to riociguat as well as the association of ST-2 with the REVEAL risk score.

Participants underwent a washout period before they received riociguat which was adjusted up to 2.5 mg 3 times daily. At week 24, responder status was defined as freedom from clinical worsening, experiencing an improvement of ≥30 meters in the 6-minute walking distance test, and being classified as World Health Organization functional class I or II.

ST-2 was 21±15 ng/mL at baseline in the overall population (n=53) and the 16 responders had lower ST-2 levels compared with the 35 nonresponders (17±8 vs 23±17 ng/mL).

When patients were grouped by REVEAL risk score, ST-2 levels were lowest in low-risk patients (REVEAL risk score, 0-6; n=24) and highest in high-risk patients (REVEAL risk score, 9-13; n=17) both at baseline (33±20 ng/mL) and at week 24 (25±12 ng/mL). The researchers found a significant positive correlation between ST-2 levels and REVEAL risk score at baseline and at week 24 (r=0.71; P <.0001 and r=0.61; P <.0001, respectively). However, there were no significant changes in ST-2 levels in the overall population (P =.10), responders (P =.09), or nonresponders (P =.22) from baseline to week 24.

While there were slight increases in ST-2 in both the low- and intermediate-risk groups (+0.86 and +0.22 ng/mL, respectively), ST-2 levels decreased by 10 ng/mL in the high-risk group at week 24.

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“ST-2 levels at baseline correlated with [REVEAL risk score] at both baseline and week 24 in RESPITE, and were lower in responders at baseline. Therefore, there may be potential for ST-2 as a biomarker to identify patients who may be at higher risk at treatment commencement,” the researchers concluded.


Benza RL, Klinger JR, Ghofrani HA, et al. Suppressor of tumorigenicity 2 as biomarker in pulmonary arterial hypertension and its association with REVEAL risk score in riociguat-treated patients in the RESPITE study. J Heart Lung Transplant. 2019;38(4S):S96.