Relationship of soluble ST2 to pulmonary hypertension severity in patients undergoing cardiac resynchronization therapy

Jonathan Beaudoin, Jackie Szymonifka, Zachary Lavender, Roderick C. Deaño, Qing Zhou, James L. Januzzi, Jagmeet P. Singh, Quynh A. Truong

Abstract

Background: Pulmonary hypertension (PH) is an adverse prognostic marker in patients undergoing cardiac resynchronization therapy (CRT). We sought to determine the relation of biomarkers of fibrosis [soluble ST2 (sST2), galectin-3], wall stretch [amino terminal pro-brain natriuretic peptide (NT-proBNP)], and necrosis [high-sensitivity troponin-I (hsTnI)] to PH severity in CRT patients.
Methods: Biomarkers and right ventricular systolic pressure (RVSP) were measured at CRT implant and 6-month later (n=111). PH was categorized into 3 groups based on RVSP: no (<35 mmHg), mild-moderate (35–60 mmHg), and severe (>60 mmHg). Patients were categorized as progressors (worsened PH), persistent PH (no change) and regressors (improved PH). Endpoints were 6-month CRT response and 2-year major adverse cardiac event (MACE).
Results: RVSP was associated with CRT nonresponse (P=0.02) and MACE (P=0.03). Severe PH patients had 5-fold increase risk for CRT nonresponse (OR 5.0, P=0.04) and MACE (HR 5.7, P=0.04) over non-PH patients. Progressors and persistent PH patients had >2-fold odds for CRT non-response (OR 2.8, P=0.45) and >11-fold increase in MACE compared to no PH patients or regressors (HR 11.6, P=0.02). Only NT-proBNP and sST2 were discernable between PH groups, with graded increase based on PH severity (both P≤0.02), and lower values in regressors versus non-regressors (both P≤0.01). Levels of sST2 decreased at 6 months in regressors (15 ng/mL, P=0.03) and increased slightly (3–8 ng/mL) in non-regressors, without difference for NT-proBNP (P=0.08).
Conclusions: sST2 levels are related with PH severity in CRT patients. Serial sST2 changes after CRT implant suggests potential role to monitor PH after CRT.