Value of Serial ST2 in Acute Heart Failure

Study Questions:

What is the prognostic value of baseline and repeated ST2 measurements in acute heart failure (HF) patients?

Methods:

The TRIUMPH (Translational Initiative on Unique and novel strategies for Management of Patients with Heart failure) study cohort was comprised of 496 acute HF patients enrolled from 14 hospitals in The Netherlands, between 2009 and 2014. Repeated blood samples (seven) were obtained during the 1-year follow-up period. ST2 [an IL-1 receptor family member with membrane-bound (ST2L) and soluble (sST2) isoforms] and N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels were measured. The primary endpoint was the composite of all-cause mortality and HF re-hospitalization. Associations between repeated biomarker measurements and the primary endpoint were assessed using a joint model (a model that combines a mixed-effects linear regression model for the serial measurements with a Cox proportional hazards model for the risk of the specified study endpoints).

Results:

The median age of the study cohort was 74 years (interquartile range [IQR], 65-80 years) and 37% were women. Forty percent of the cohort (n = 188 patients) reached the primary endpoint during a median follow-up of 325 days (IQR, 85-401). This corresponds with an incidence rate of 55.9 per 100 patient-years for the primary endpoint. Median systolic blood pressure was 125 mm Hg (IQR, 110-147) and median left ventricular ejection fraction was 30% (IQR, 21-42). The majority were HF patients with a reduced ejection fraction (83%). Median baseline ST2 level was 71 ng/ml (IQR, 46-102) and NT-proBNP was 4152 pg/ml (IQR, 2089-9387). The study investigators found that after adjusting for clinical factors and NT-proBNP, baseline ST2 was associated with an increased risk of the primary endpoint, hazard ratio (HR) per 1 standard deviation (SD) increase of the baseline ST2 level (on the log2 scale) was 1.30 (95% confidence interval [CI], 1.08-1.56; p = 0.005). When they took repeated measurements into account, the adjusted HR per 1 SD increase of the ST2 level (on the log2 scale) during follow-up increased to 1.85 (95% CI, 1.02-3.33; p = 0.044), adjusted for clinical factors and repeated measurements of NT-proBNP. Interestingly, they found that ST2 levels appear to elevate several weeks prior to the time of the primary endpoint.

Conclusions:

The study investigators concluded that repeated ST2 measurements are a strong predictor of outcome in acute HF patients, independent of repeatedly measured NT-proBNP. Therefore, ST2 may be helpful in clinical practice for prognostication and treatment monitoring.

Perspective:

This is an important study because it suggests that ST2 measurements provide incremental value to NT-proBNP measurements. These findings now should be validated in large, multicenter studies. In the future, it is probable that a panel of biomarkers rather than one biomarker may be utilized to diagnose, prognosticate, and guide therapy.

Clinical Topics: Anticoagulation Management, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Biological Markers, Blood Pressure, Geriatrics, Heart Failure, Natriuretic Peptide, Brain, Peptide Fragments, Prognosis, Receptors, Interleukin-1, Stroke Volume


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