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

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

• Lee GY
• Choi JO
• Ju ES
• Lee YJ
• Jeon ES

• KMID: 2355457
• DOI: http://doi.org/10.4070/kcj.2016.46.6.811

Abstract

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.

Keyword

Biomarkers; ST2 protein; Heart transplantation; Graft rejection

MeSH Terms

Allografts
Biomarkers
Biopsy
Graft Rejection
Heart Transplantation
Heart*
Hemodynamics
Humans
Lung
Troponin I
Biomarkers
Troponin I

Figure

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  Fig. 1 Scattered plots showing correlation of sST2 with other continuous variables. (A) WBC count, (B) lymphocytes count, (C) cardiac troponin I (cTnI), and (D) NT-proBNP. WBC: white blood cell, NT-proBNP: N-terminal pro-B-type natriuretic peptide.

• 

  Fig. 2 Scatter plots of sST2 values according to the time after heart transplant. (A) sST2 measured in entire population of 494 blood samples (B) sST2 measured in 381 samples at the specific time point after heart transplant (0.5, 1, 2, 3, 6, 9, and 12 months). Median value and interquartile range of sST2 are presented as horizontal lines in whisker form. Some extreme cases of sST2 levels (arrows in Fig. 2B) reflected critical events other than acute allograft rejection that occurred within several days; 1) generalized seizure suspected as posterior reversible encephalopathy syndrome (PRES), 2) ischemic injury noted in endomyocardial biopsy, and 3) septic shock.

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  Fig. 3 Scattered plots of sST2 grouped by the rejection grades of concomitant endomyocardial biopsy. (A) sST2 categorized by groups according to International Society of Heart and Lung Transplant (ISHLT) rejection score. (B) sST2 categorized by the presence of significant rejection. Median value of sST2 in each group is marked with a horizontal line.

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  Fig. 4 Scatter plots of sST2 grouped by the pathologic grades of concomitant endomyocardial biopsy. (A) early (≤90 days) and (B) late (>90 days) periods after heart transplant. Median value of sST2 in each group is marked with a horizontal line. ISHLT: International Society of Heart and Lung Transplant.

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  Fig. 5 Scattered plots of sST2 measured at pre-rejection, at the time of rejection, and after a treatment of significant rejection. (A) Overall patients. (B) Early (≤90 days) and (C) later (>90 days) postoperative days. Measurement values of each individual case were connected by a line.

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