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

  • Hicham Skali
  • Robert Gerwien
  • Timothy E. Meyer
  • James V Snider
  • Scott D. Solomon
  • Craig M. Stolen
Original Article


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.


ST2 Biomarker Heart failure Arrhythmia Sudden cardiac death Implantable cardioverter defibrillator (ICD) Cardiac resynchronization therapy (CRT) Prognosis 


Compliance with Ethical Standards


Boston Scientific funded the MADIT-CRT trial and the specimen collection. Critical Diagnostics funded the ST2 measurements.

Conflict of Interest

HS has no conflicts to disclose. CMS and TEM are employed by Boston Scientific and have stock ownership in Boston Scientific. RG and JVS are employed by Critical Diagnostics, and JVS has ownership interest in Critical Diagnostics. SDS has received research support (>$10,000) and consulting fees (<$10,000) from Boston Scientific.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committees and with the 1964 Helsinki declaration and its later amendments. This article does not contain any studies with animals performed by any of the authors.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12265_2016_9713_MOESM1_ESM.pdf (1.3 mb)
Supplementary Table 1 Baseline characteristics of the cohorts with and without sST2 assessment. (PDF 1.33 MB)
12265_2016_9713_MOESM2_ESM.pdf (1.3 mb)
Supplementary Table 2 (PDF 1.33 MB)
12265_2016_9713_MOESM3_ESM.docx (20 kb)
Supplementary Table 3 (DOCX 20 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Hicham Skali
    • 1
  • Robert Gerwien
    • 2
  • Timothy E. Meyer
    • 3
  • James V Snider
    • 2
  • Scott D. Solomon
    • 1
  • Craig M. Stolen
    • 3
  1. 1.Cardiovascular DivisionBrigham and Women’s HospitalBostonUSA
  2. 2.Critical DiagnosticsSan DiegoUSA
  3. 3.Boston ScientificSt. PaulUSA

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