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Objectives: The impact of high thoracic sympathetic block (HTSB) on myocardial fibrosis in chronic heart failure (HF) is unclear. Myocardial collagen synthesis can be assessed by measuring circulating biomarkers. Weobserved the effect of HTSB on serum collagen biomarkers in HF. Methods: Forty-four patients were randomized to a control and a HTSB group. They received routine medications. Repeated epidural injections were given to the HTSB group for 4 weeks. Echocardiography and measurements of serum carboxy-terminal propeptide of procollagen type I (PICP) and amino-terminal propeptide of procollagen type III (PIIINP) were performed at baseline and 4 weeks later. Results: There were significant reductions in left atrial diameter, left ventricular (LV) diameter and volume, LV weight index (LVWI) and serum PICP and PIIINP levels in the HTSB group (p < 0.05). The changes in LV end-systolic volume and ejection fraction (LVEF) were greater in the HTSB group than in the control group (p < 0.05). In the HTSB group, the decreases in PICP and PIIINP were correlated with the decrease in LVWI (PICP: r = 0.695, p = 0.000; PIIINP: r = 0.642, p = 0.001), and the decrease in PICP was negatively associated with the rise in LVEF (r = -0.813, p = 0.000). Conclusion: HTSB reduces myocardial fibrosis in HF, which may accompany the improvement of LV hypertrophy anddysfunction.