Role of Soluble ST2 as a Marker for Rejection after Heart Transplant

Korean Circ J. 2016 Nov;46(6):811-820. doi: 10.4070/kcj.2016.46.6.811. Epub 2016 Nov 1.


Background and objectives: Endomyocardial biopsy is obligatory during the first year after heart transplant (HTx) for the surveillance of acute rejection. Previous attempts using cardiac biomarkers for the detection of rejection failed to show enough evidence to substitute endomyocardial biopsy. Therefore, this study sought the possibility of using soluble ST2 (sST2), a novel cardiovascular marker, as a surrogate marker for acute allograft rejection after HTx.

Subjects and methods: A total of 494 blood samples acquired at the time of endomyocardial biopsy were analyzed in 67 HTx cases from September 2006 to August 2014. Significant rejection was defined as International Society of Heart and Lung Transplant (ISHLT) score ≥2R and humoral rejection accompanied by hemodynamic instability.

Results: Twenty cases of HTx with 22 blood samples showed significant rejection in endomyocardial biopsy at 4.0 (2.0-9.0) months after HTx. The level of sST2 showed positive correlation with cardiac troponin I, and N-terminal pro-B-type natriuretic peptide (all p<0.001), and negative correlation with post-HTx months (p<0.001). The levels of sST2 according to the ISHLT scores were 36 (19-98), 28 (18-62), 15 (16-37), and 191 (85-343) ng/mL, consecutively 0R, 1R, 2R, and 3R+ (3R plus hemodynamically-unstable humoral rejection) (p=0.003). However, when we studied within-subject effects of sST2 using a mixed model, the sST2 level according to the predefined time point was not different according to the presence of significant rejection (p for interaction=0.94).

Conclusion: Although sST2 is known as a promising predictor for cardiovascular events, its role in HTx patients to predict acute allograft rejection seems to be limited.

Keywords: Biomarkers; Graft rejection; Heart transplantation; ST2 protein.