Shenmai Injection Improves Energy Metabolism in Patients With Heart Failure: A Randomized Controlled Trial

Abstract

Background: In recent years, the application of Shenmai (SM) injection, a traditional Chinese medicine (TCM), to treat heart failure (HF) has been gradually accepted in China. However, whether SM improves energy metabolism in patients with HF has not been determined due to the lack of high-quality studies. We aimed to investigate the influence of SM on energy metabolism in patients with HF.

Methods: This single-blind, controlled study randomly assigned 120 eligible patients equally into three groups receiving SM, trimetazidine (TMZ), or control in addition to standard medical treatment for HF for 7 days. The primary endpoints were changes in free fatty acids (FFAs), glucose, lactic acid (LA), pyroracemic acid (pyruvate, PA) and branched chain amino acids (BCAAs) in serum. The secondary outcomes included the New York Heart Association (NYHA) functional classification, TCM syndrome score (TCM-s), left ventricular injection fraction (LVEF), left ventricular internal diastolic diameter (LVIDd), left ventricular internal dimension systole (LVIDs), and B-type natriuretic peptide (BNP).

Results: After treatment for 1 week, the NYHA functional classification, TCM-s, and BNP level gradually decreased in the patients in all three groups, but these metrics were significantly increased in the patients in the SM group compared with those in the patients in the TMZ and control groups (P < 0.05). Moreover, energy metabolism was improved in the NYHA III-IV patients in the SM group compared with those in the patients in the TMZ and control groups as evidenced by changes in the serum levels of FFA, LA, PA, and BCAA.

Conclusions: Integrative treatment with SM in addition to standard medical treatment for HF was associated with improved cardiac function compared to standard medical treatment alone. The benefit of SM in HF may be related to an improvement in energy metabolism, which seems to be more remarkable than that following treatment with TMZ.

Keywords: Shenmai injection; cardiac function; energy metabolism; heart failure; traditional Chinese medicine.

Figure 1

HPLC fingerprint of Shenmai injection and the ginsenosides Re, Rg1, and Rb1 as reference standards. A. Chromatogram of the reference standards: 1 represents ginsenoside Re; 2 represents ginsenoside Rg1; 3 represents ginsenoside Rb1. B. Representative chromatogram of Shenmai injection samples: No. 1–3 represent the common peaks with the reference standards Re, Rg1, and Rb1.

Figure 2

Flow chart of the patients included throughout the study. FAS, full analysis set.

Figure 3

The effects of the SM, TMZ, and control treatments on the NYHA functional classification in HF patients. *P < 0.01 and ^#P < 0.05 vs. the control (7 days), *P < 0.01 compared with the TMZ group (7 days).

Figure 4

The effects of the SM, TMZ, and control treatments on C-BNP in HF patients. (A) Levels of BNP at baseline and after 7 days of treatment in the SM, TMZ, and control groups; *P <0.01 vs. the baseline of SM; ^#P < 0.01 vs. the baseline of TMZ; the control group (7 days), P < 0.01 vs. the baseline of control; *P < 0.05 and ^#P > 0.05 compared with the control group (7 days); (B) C-BNP ratio in the SM, TMZ, and control groups after 7 days; *P < 0.01 or ^#P < 0.01 vs. the control group (7 days). C-BNP ratio=log₁₀(10^baseline-10^7d)/baseline. 7d, 7days.

Figure 5

The effects of the SM, TMZ, and control treatments on CTCM-s in patients with HF. (A) CTCM-s at baseline and after 7 days of treatment in the SM, TMZ, and control groups; *P <0.01 vs. the baseline of SM; ^#P < 0.01 vs. the baseline of TMZ; the control group (7 days), P < 0.01 vs. the baseline of control; *P < 0.01 and ^#P > 0.05 compared with the control group (7 days), *P < 0.05 compared with the TMZ group (7 days); (B) CTCM-s in the SM, TMZ, and control groups after 7 days; *P < 0.01 or ^#P > 0.05 vs. the control group (7 days); *P < 0.05 vs. the TMZ group (7 days). CTCM-s ratio= (baseline-7 days)/baseline.

Figure 6

The effects of the SM, TMZ and control treatments on metabolism substrates in the serum in patients with HF. (A) Changes in serum FFAs in patients with HF; *P <0.01 vs. the baseline of SM; ^#P < 0.05 vs. the baseline of TMZ; control group (7 days), P < 0.05 vs. the baseline of control; *P < 0.05 and ^#P > 0.05 compared with the control group (7 days). (B) Changes in serum glucose in patients with HF; *P > 0.05 or ^#P > 0.05 compared with the control group (7 days). (C) Changes in serum LA in patients with HF; *P <0.05 vs. the baseline of SM; ^#P < 0.05 vs. the baseline of TMZ; the control group (7 days), P < 0.05 vs. the baseline of control; *P > 0.05 or ^#P > 0.05 compared with the control group (7 days). (D) Changes in serum PA in patients with HF; *P <0.05 vs. the baseline of SM; *P > 0.05 or ^#P > 0.05 compared with the control group (7 days). (E) Changes in serum BCAAs in patients with HF; *P <0.05 vs. the baseline of SM; *P < 0.05 or ^#P > 0.05 compared with the control group (7 days).