Soluble ST2 for Predicting Sudden Cardiac Death in Patients With Chronic Heart Failure and Left Ventricular Systolic Dysfunction

Objectives We studied whether the measurement of the soluble form of ST2 (sST2), an interleukin-1 receptor family member, could identify heart failure (HF) patients at risk of sudden cardiac death (SCD). Background The prediction of SCD remains an important challenge in patients with mild-to-moderate chronic HF. Concentrations of sST2 have been found increased and related to worse long-term outcomes in patients with acute HF. Whether sST2 has a prognostic role in SCD is unknown. Methods A nested case-control study was performed on 36 cases of SCD and 63 control patients (matched for age, sex, and left ventricular ejection fraction) obtained from the MUSIC (MUerte Subita en Insuficiencia Cardiaca) registry, a 3-year multicenter registry of ambulatory HF patients (New York Heart Association functional class II to III, left ventricular ejection fraction <= 45%). Demographic, clinical, echocardiographic, electrical, and biochemical data were collected at enrollment. Results Concentrations of sST2 were greater among decedents (0.23 ng/ml [interquartile range 0.16 to 0.43 ng/ml] vs. 0.12 ng/ml [interquartile range 0.06 to 0.23 ng/ml], p = 0.001) and were predictive of experiencing SCD (+0.1 ng/ml, odds ratio: 1.39, 95% confidence interval: 1.09 to 1.78, p = 0.006). On the basis of a combined biomarker status, only 4% of patients experienced SCD for neither sST2 nor N-terminal pro-B-type natriuretic peptide (NT-proBNP) above receiver-operator characteristic-derived cut-off points (0.15 ng/ml and 2,000 ng/l, respectively), 34% for either biomarker above, and 71% for both biomarkers above (p < 0.001 for trend). This combined variable added incremental prognostic value to the multivariable regression model (p < 0.001). Conclusions Elevated sST2 concentrations are predictive of SCD in patients with chronic HF and provide complementary information to NT-proBNP levels. A combined biomarker approach may have an impact on clinical decision-making. (J Am Coll Cardiol 2009;54:2174-9) (C) 2009 by the American College of Cardiology Foundation