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CLINICAL RESEARCH: BIOMARKERS

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

Domingo A. Pascual-Figal, MD, PhD^_*,_*, Jordi Ordoñez-Llanos, MD, PhD, Pedro L. Tornel, PhD, Rafael Vázquez, MD, PhD^||, Teresa Puig, MD, PhD, Mariano Valdés, MD, PhD^_*, Juan Cinca, MD, PhD, Antoni Bayes de Luna, MD, PhD^¶, Antoni Bayes-Genis, MD, PhD on behalf of the MUSIC Investigators

^_* Cardiology Service, Virgen de la Arrixaca Hospital and Department of Medicine, University of Murcia, Murcia, Spain
Biochemistry Service, Sant Pau Hospital and Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Barcelona, Spain
Cardiology Service, Sant Pau Hospital, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
Biochemistry Service, Virgen de la Arrixaca Hospital, Murcia, Spain
^|| Cardiology Service, Hospital Universitario Puerta del Mar, Cádiz, Spain
^¶ Institut Català de Ciències Cardiovasculars, Barcelona, Spain

Manuscript received June 9, 2009; accepted July 8, 2009.

^_* Reprint requests and correspondence: Dr. Domingo A. Pascual-Figal, Heart Failure Unit, Cardiology Department, University Hospital Virgen de la Arrixaca Ctra Madrid-Cartagena s/n, 30120 Murcia, Spain (Email: dapascual{at}servicam.com).

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 Súbita en Insuficiencia Cardíaca) 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.

Key Words: soluble ST2 • sudden cardiac death • chronic heart failure • B-type natriuretic peptide • biomarkers

Abbreviations and Acronyms   BNP = B-type natriuretic peptide   CI = confidence interval   HF = heart failure   IL = interleukin   IQR = interquartile range   LV = left ventricle/ventricular   LVEF = left ventricular ejection fraction   NT-proBNP = N-terminal pro–B-type natriuretic peptide   OR = odds ratio   ROC = receiver-operator characteristic   SCD = sudden cardiac death   sST2 = soluble ST2

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