Soluble ST2 and Risk of Arrhythmias, Heart Failure, or Death in Patients with Mildly Symptomatic Heart Failure: Results from MADIT-CRT

Abstract

Soluble ST2 is an established biomarker of heart failure (HF) progression. Data about its prognostic implications in patients with mildly symptomatic HF eligible to receive cardiac resynchronization therapy defibrillators (CRT-D) are limited. In a cohort of 684 patients enrolled in Multicenter Automated Defibrillator Implantation Trial (MADIT)-CRT, levels of soluble ST2 (sST2) were serially assessed at baseline and 1 year (n = 410). In multivariable-adjusted models, elevated baseline sST2 was associated with an increased risk of death, death or HF, and death or ventricular arrhythmia (VA) even when adjusting for baseline brain natriuretic protein (BNP) levels. In addition, patients with lower baseline sST2 levels had greater risk reduction with CRT-D (p = 0.006). Serial assessment revealed increased risk of VA and death or VA (HR per 10 % increase in sST2 1.11 (1.04-1.20), p = 0.004). Among patients with mildly symptomatic HF and eligibility for CRT-D, baseline and serial assessments sST2 may provide important information for risk stratification.

Cardioprotective effects of the estrogen receptors modulators in the conditions of experimental acute myocardial infarction

“…An expected result of such changes was a statistically significant increase of the "soluble" ST2 receptor (sST2) in the plasma of the rats with experimental myocardial infarction. It is known that the receptor ST2 (suppression of tumorigenicity-2) is a representative of the interleukin IL-1 receptors family [12][13][14]. ST2 exists in two isoforms: transmembrane (ST2L) and "soluble" (sST2), which is not bound to the cell or membrane and circulates freely in the circulatory system.…”

“…A number of studies have shown that interleukin-33 (IL-33) is the ligand of the ST2 receptor [12]. Hypoxic damage to cardiomyocytes and fibroblasts, excessive pressure and stretching are the main momentum of the IL-33/ST2 system activation in the heart [14]. IL-33 performs its cardioprotective effect in the interaction with the ST2L receptor [13][14].…”

“…In the heart, ST2 plays a biological role in the innate immune process, and also modulates the cardiac signalling pathway. An important feature of ST2 is the rapid, under ischemia, blockade of IL-33 cardioprotective effect, which contributes to the heart remodeling and fibrosis development [14]. With adequately selected cardioprotective therapy, the concentration of ST2 decreases rapidly, which explains the prospect of its use for cardioprotective properties of the drugs evaluation in the study [12][13][14].…”

Classic and Novel Biomarkers as Potential Predictors of Ventricular Arrhythmias and Sudden Cardiac Death

“…However, in patients with mildly symptomatic HF evaluated during the MADIT-CRT trial, a 10% elevation of sST2 levels alone over one year, was shown to be predictive of increased risk of onset of ventricular arrhythmias and death. Nevertheless, in the same study it was shown, that an elevated sST2 baseline is not directly predictive of ventricular arrhythmias [90].…”

Interleukin-33/suppression of tumorigenicity 2 (IL-33/ST2) axis in idiopathic inflammatory myopathies and its association with laboratory and clinical parameters: a pilot study

“…Despite those facts, it is recommended to start the assessment in clinical practice with cTnT and evaluate cardiac troponin I (cTnI) in those who present increased concentrations of cTnT [14]. sST2 is associated with increased risk of death, heart failure or ventricular arrhythmia, as it reduces protective impact of IL-33 on myocardium [6,17]. Yet, in our study, no correlations were found between IL-33, sST2 and clinical symptoms indicating cardiovascular involvement or biochemical markers of cardiac injury such as CK-MB, troponin T, troponin I or NT-proBNP.…”