ST2 Test Useful For Clinical Information

ST2 Test
Useful For
Aiding in prognosis for patients diagnosed with chronic heart failure
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 interleukin (IL)-33 in modulating cardiac
remodeling and ventricular function via effects in the inflammatory and apoptosis
pathways.(3)

ST2 is a member of the IL-1 receptor family and has 2 isoforms that are directly
implicated in progression of cardiac disease: 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.
Reference Values
Males:
<24 months: not established
2-17 years: < or =43.0 ng/mL
> or =18 years: < or = 52.0 ng/mL

Females:
<24 months: not established
2-17 years: < or =43.0 ng/mL
> or =18 years: < or =38.7 ng/mL
Interpretation
Clinically, ST2 concentrations in the HF-ACTION heart failure study were a significant
predictor of mortality, all-cause hospitalization, mortality due to cardiovascular disease,
and hospitalization due to cardiovascular disease using a cut point of 35 ng/mL. In
addition, mortality risk was significantly higher in patients with ST2 greater than 35
ng/mL.(4) The risk appears early and persists throughout the follow-up period.

Clinical risk categories are substantiated by results from several large chronic heart
failure studies:
-Low risk: < or =35.0 ng/mL
-High risk: >35.0 ng/mL (high risk)

Results should be interpreted in the context of the individual patient presentation.
Elevated ST2 results indicate an increased risk for adverse outcomes and signal the
adverse remodeling and progression of disease.

The reference interval was derived from normal donors without a history of
cardiovascular disease, stroke, diabetes, renal disease, liver disease, or autoimmune
diseases. The reference range is gender dependent; however, it is the clinical cut point
that is recognized as providing the most utility.

Knowledge of ST2 results in a heart failure patient may assist in cardiovascular risk
stratification and lead to more aggressive management. There are no specific ST2
inhibitors available at this time and heart failure patients with elevated ST2
concentrations should be treated and monitored according to established guidelines.
Angiotensin receptor blockers and aldosterone antagonists are thought to be particularly
effective.
Cautions
ST2 has not been shown to be useful in the acute diagnosis of heart failure; natriuretic
peptides (BNP or NT-proBNP) should be utilized for this purpose in the context of
appropriate clinical suspicion of acute heart failure. ST2 and natriuretic peptides are
measures of separate and distinct biological processes, providing independent and
complimentary prognostic information.

There are no significant analytical interferences reported for ST2 from bilirubin,
hemoglobin, triglycerides, cholesterol, or total protein. Forty-nine therapeutic
substances were tested for analytical interference and none had significant interference
with the ST2 assay.(5)

ST2 Test Useful For Clinical Information

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