Background: According to numerous studies, from 30% to 50% of patients with chronic heart failure (CHF) are resistant to cardiac resynchronization therapy (CRT) and cardiac contractility modulation (CCM), despite their careful selection in accordance with current guidelines. It is of interest to study neurohormones characterizing myocardial (NT-proBNP) and fibrosis (sST2) as potential additional markers of CHF patients' “response” to CRT and CCM.Aim: To evaluate the potential to use NT-proBNP and sST2 biomarkers in CHF patients combined with transthoracic echocardiography (Echo) and contrast magnetic resonance imaging (MRI) parameters of the heart to predict a positive response to CRT and CCM devices.Materials and methods: The study included 51 patients (41 men, 10 women) aged 58 ± 12 years (26 to 79 years) with ischemic heart disease post acute myocardial infarction (n = 22) or non-ischemic cardiomyopathy (n = 29), left ventricle (LV) ejection fraction (EF) < 35%, and CHF II–III NYHA functional class despite ≥ 3 months of optimized medical therapy. The patients were assessed by serum biomarkers NT-proBNP and sST2 measurements, transthoracic Echo, and contrast- enhanced cardiac MRI. After the diagnostic assessment, CRT defibrillators (CRT-D) were implanted to 39 patients and CCM to 12 patients. After prospective follow-up of the patients for 18 to 24 months, predictors of the response to each device type were analyzed in univariate, multivariate, and ROC analysis.Results: The response to CRT-D was found in 21 (54%) patients, to CCM in 7 (58%) patients. Multivariate analysis showed the following predictors of the response of patients to CRT-D were: 1) sST2 < 50 ng/mL, 2) NT-proBNP < 3900 pg/mL, 3) < 3 LV segments with fibrosis (by MRI) and 4) anteroposterior dimension of the left atrium < 4.8 cm (by Echo). Any 2 of these 4 characteristics made it possible to predict the response to CRT with an accuracy of 87% (sensitivity 90%, specificity 83%). The predictors of the response to CCM were: 1) sST2 < 30 ng/ml, 2) LV end diastolic diameter < 78 mm (Echo), 3) age < 56 years, 4) body mass index < 27 kg/m2. Any 2 of these 4 characteristics predicted the positive response to CCM with an accuracy of 92% (sensitivity 86%, specificity 100%).Conclusion: The preoperative sST2 level was the only universal marker of the response to either CRT (< 50 ng/mL) or CCM (< 30 ng/mL) devices in CHF patients with reduced LVEF. The results indicate the potential for improved efficacy of these devices with their earlier implantation after the onset of the heart disease, as well as provided that maximal control CHF in these patients has been achieved.