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sST2 Has Independent Prognostic Value for Patients with Chronic Heart Failure

Key findings

  • In a large, international population of patients with chronic heart failure, sST2 concentrations were predictive of three clinically relevant endpoints, independently of NT-proBNP and hs-TnT
  • sST2 was an independent predictor of outcomes across most patient subgroups
  • The risks increased approximately in parallel with the number of elevated biomarkers

For patients with chronic heart failure (HF), determining an accurate prognosis is important to guide therapeutic decision-making and follow-up care. American College of Cardiology/American Heart Association guidelines give a class I recommendation for using a natriuretic peptide and troponin testing for prognosis.

Soluble suppression of tumorigenesis-2 (sST2), in contrast, has a class IIb recommendation. So far only one study, a subanalysis of the PARADIGM-HF trial, has suggested that sST2 has independent prognostic significance beyond N-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT).

To investigate the prognostic value of sST2, James L. Januzzi, Jr, MD, director, Dennis and Marilyn Barry Fellowship in Cardiology Research, led a team that conducted a large patient-level meta-analysis. In the Journal of the American College of Cardiology, the team reports that sST2 provided substantial and important prognostic information for patients with chronic HF that was independent of the traditional biomarkers.

The researchers identified 4,268 patients in Medline, EMBASE, the Cochrane Library and Scopus from five clinical trials who had data available on NT-proBNP, hs-TnT and sST2. They divided the patients according to median concentrations of the three biomarkers, which were 1,360 ng/L for NT-proBNP, 18 ng/L for hs-TnT and 27 ng/mL for sST2.

There were significant differences between patients whose biomarkers fell above or below the medians with regard to the risks of death from any cause, cardiovascular death and HF-related hospitalization.

Measuring sST2 in addition to measuring NT-proBNP and hs-TnT had substantial prognostic value.

Compared with patients who had no biomarker concentration above or equal to the median:

  • Patients who had sST2 concentrations above or equal to the median had a doubled risk of all-cause death, a 50% higher risk of cardiovascular death and a 10% higher risk of HF hospitalization
  • Patients who had all three biomarker concentrations above or equal to the median had 850%, 640% and 590% higher risks of all-cause death, cardiovascular death and HF hospitalization, respectively
  • Patients who had both sST2 and hs-TnT concentrations above or equal to the median had a greater risk of all-cause death

Moreover, compared with patients who had only NT-proBNP and hs-TnT elevated, patients who had all three biomarkers elevated were at 2.4-fold, 1.7-fold and 1.5-fold higher risk of all-cause death, cardiovascular death and HF hospitalization, respectively.

sST2 was an independent predictor of outcome in most subgroups studied, including patients in all left ventricular ejection fraction categories, as well as in those with or without important comorbidities (diabetes, chronic obstructive pulmonary disease and hypertension) or systemic inflammation.

The researchers theorize that sST2 has additive prognostic value because its pathophysiology differs from that of NT-proBNP and hs-TnT. Natriuretic peptide concentrations reflect mainly myocardial wall stress and hemodynamic function, they explain, and troponin release results from ongoing cardiac stress and damage. By comparison, sST2 is associated with the activation of inflammatory and pro-fibrotic pathways.

sST2 also has advantages over natriuretic peptides, Dr. Januzzi's team comments. It has a narrower range of biological variation, and its plasma concentrations are less influenced by age, sex, body mass index and comorbidities, including chronic kidney disease. For these reasons, the authors conclude that sST2 deserves to be included in a multimarker panel along with NT-proBNP and hs-TnT.

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James Januzzi, MD, director of the Dennis and Marilyn Barry Fellowship in Cardiology Research, discusses his team’s focus on the role of biomarker testing to diagnose the presence of cardiovascular disease and to establish prognosis or course of the disease.