Clinical Information

Heart failure is a chronic, progressive, complex cardiovascular disorder with a variety of etiologies and heterogeneity with respect to the clinical presentation of the patient. Heart failure is significantly increasing in prevalence with an aging population and is associated with high short- and long-term mortality rate. Over 80% of patients diagnosed and treated for acute heart failure syndromes in the emergency department are readmitted within the forthcoming year, incurring costly treatments and therapies.(1)

The development and progression of heart failure is a clinically silent process until manifestation of the disorder, which typically occurs late and irreversibly into its progression. Mechanistically heart failure, whether due to systolic or diastolic dysfunction, is thought to progress primarily through adverse cardiac remodeling and fibrosis in response to cardiac injury or stress.(2) Soluble ST2 (sST2) is a biomarker that appears to be actively involved with IL-33 in modulating cardiac remodeling and ventricular function via effects in the inflammatory and apoptosis pathways.(3)

ST2 is a member of the interleukin-1 receptor family and has 2 isoforms that are directly implicated in progression of cardiac disease: soluble ST2 (sST2) and a transmembrane-bound form, ST2 ligand (ST2L). IL-33 is the hormone that interacts with ST2L, protecting against left ventricular hypertrophy and myocardial fibrosis to effectively preserve cardiac function. Therefore, when sST2 concentrations are high, IL-33 is unavailable for cardioprotective signaling, leaving the heart vulnerable to the effects of sST2. High concentrations of sST2 result in cellular death, tissue fibrosis, reduced cardiac function, and an increase in the rate of disease progression.