Heart failure patients with implantable cardioverter-defibrillator: molecular predictors for risk assessment of adverse events

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Objective. The objectives of the study were to evaluate a multimarker strategy including galectin-3, soluble ST2 (sST2) and NT-proBNP for risk stratification of adverse cardiovascular events (ACE) and death in heart failure (HF) patients with implantable cardioverter-defibrillator (ICD) during the 12-month follow-up period. Methods. A total of 57 patients (41 men, median age of 65 [59; 68] years) of New York Heart Association (NYHA) class II-IV and baseline LVEF of 34% [26; 44]% were enrolled in the study. 71% of patients had prior myocardial infarction and 86% received prior myocardial revascularization (coronary artery bypass graft/stent). Serum levels of sST2, NT-proBNP and galectin-3 were measured using an enzyme immunoassay at baseline. All patients received implantation of cardioverter-defibrillator. Results. After the 12-month follow-up period, all patients were divided into 2 groups: group A (n = 17) comprised patients with ASE, group B (n = 40) comprised those without it. During 12-month follow-up period 15.8% of patients (n = 9) died. The median values of sST2 in group A were higher (p = 0.001) by 51% than in group B (24.42 [22.46; 31.4] and 49.94 [37.4; 58.54] ng/mL, respectively). The median values of galectin-3 in group A (p = 0.002) were 14.7 [9.95; 24.3] ng/L and 9.2 [7.2; 14.7] ng/L in group B. The median values of NT-proBNP were also higher (p = 0.021) by 22% in patients with ASE. Odds ratio for hyperexpression of sST2 was 3.06 (95% CI 2.89-3.17; p <0.0001), 3.79 for galectin-3 (95% CI 2.67-4.11; p < 0.001), and 1.27 for NT-proBNP (95% CI 0.89-2.21; p = 0.036). Reclassification did not significantly benefit after NT-proBNP addition into the full model; some indices even worsened with all 3 biomarkers. Based on ROC-analysis, baseline sST2 concentration of 34.43 ng/mL (sensitivity of 86.7%, specificity of 71.9%, and AUC of 0.78; p < 0.0001) and baseline galectin-3 concentration of 11.6 ng/L (sensitivity of 67.5%, specificity of 70.6%, and AUC of 0.72; p = 0.0014) were identified as a cut-off values predicting adverse cardiac events. The combined evaluation of both biomarkers increased the predictive value of the analysis (sensitivity of 90.1%, specificity of 79.1%, and AUС of 0.84; p < 0.0001). Conclusion. Our data suggest that ST2 and galectin-3 may be used as diagnostic biomarkers in HF patients with ICD. The combined use of sST2 and galectin-3 demonstrated higher diagnostic sensitivity and specificity for prediction of adverse outcomes. However, NT-proBNP in addition to ST2 and galectin-3 biomarkers had a limited effect on risk stratification.