Clinical intervention effect of Xuefu Zhuyu decoction on chronic heart failure complicated with depression

Abstract

BACKGROUND

The diagnosis and treatment of depression in patients with chronic heart failure (CHF) is challenging, with no ideal treatment at present.

AIM

To analyze the clinical intervention effect of Xuefu Zhuyu decoction (XFZYD) on CHF complicated with depression.

METHODS

The study cohort comprised 116 patients with CHF complicated with depression who received treatment from July 2020 to July 2023, of which 55 received Western medicine (control group) and 61 received XFZYD (research group). Data on clinical effectiveness, traditional Chinese medicine (TCM) syndrome score, cardiac function, negative emotions, and serum inflammatory factors, were collected for comparative analyses.

RESULTS

Compared with the control group, the research group had an evidently higher total effective rate. Furthermore, there were marked reductions in TCM symptom score, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, Self-Rating Depression Scale, Hamilton Depression Scale, high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, and matrix metalloproteinase-9 in the research group after treatment, and these were lower than the corresponding values in the control group. Left ventricular ejection fraction was increased and higher in the research group compared with the control group after treatment.

CONCLUSION

Our findings conclusively proved that XFZYD was considerably superior to Western medicine for treating CHF complicated with depression because it significantly alleviated patients’ symptoms, improved cardiac function, relieved negative emotions, and reduced the levels of serum inflammatory factors.

Key Words: Xuefu Zhuyu decoction; Chronic heart failure; Depression; Cardiac function; Negative emotions

Core Tip: Chronic heart failure (CHF) is a hemodynamic disorder that leads to systolic and diastolic dysfunction and increases the risk of diabetes and chronic kidney disease. Additionally, the risk of depression in patients with CHF can reach up to 60%, and the diagnosis and treatment of depression in this patient population is challenging because there is no ideal therapy for this comorbidity. This study comparatively analyzed the clinical effects of Xuefu Zhuyu decoction (XFZYD) vs Western medicine in patients with CHF complicated with depression from the perspectives of clinical efficacy, traditional Chinese medicine symptom score, cardiac function, negative emotions, and serum inflammatory factor levels. We found that the clinical efficacy of XFZYD was significantly higher than Western medicine for treating CHF complicated with depression and significantly reduced patients’ symptoms, improved cardiac function, alleviated negative emotions, and inhibited serum inflammatory factors. Therefore, XFZYD is highly beneficial for improving the efficacy and clinical outcomes of patients with CHF complicated with depression.

INTRODUCTION

Chronic heart failure (CHF) is a cardiovascular disease with high prevalence and a high frequency of hospitalization and death. CHF symptoms include fatigue, dyspnea, fluid retention, and poor exercise tolerance[1,2]. Because CHF is a hemodynamic disorder, it may lead to systolic and diastolic dysfunction and increase the risk of diabetes and chronic kidney disease[3]. Additionally, the risk of depression in CHF can reach 60%, and it has been associated with worsening patient conditions, particularly in older adults[4,5]. The cause of depression in CHF patients may be related to factors such as limited activities of daily living and functional symptoms, like immobility[6]. The comorbidity mechanism of CHF combined with depression is related to inflammatory overreaction and abnormal cardiac autonomic control and regulation[7]. The diagnosis and treatment of depression in patients with CHF are challenging, and there is currently no ideal treatment for this comorbidity[8,9]. Thus, solving the abovementioned issues will be of great value in improving the treatment effectiveness and clinical outcomes of patients with CHF complicated with depression.

There applications of traditional Chinese medicine (TCM) therapy for patients with CHF complicated with depression are increasing. Cai et al[10] reported that the practice of Tai Chi as a Chinese medicine exercise therapy by patients with CHF complicated with depression significantly alleviated their negative emotions. According to Wang et al[11], Buxin Yiqi decoction, as a TCM therapy, effectively reduced symptoms in patients with CHF and enhanced their prognosis, with a lower risk of adverse reactions compared with Western medicine therapy. Collectively, these findings indicate the high therapeutic potential of TCM therapy for patients with CHF complicated with depression. Xuefu Zhuyu decoction (XFZYD) is a Chinese herbal medicine that was introduced in the Qing Dynasty to regulate qi and disperse stagnation. It is composed of various Chinese herbs, including Poria cocos, Paeonia lactiflora, ginger, Atractylodes macrocephala, Radix Paeoniae Rubra, peach kernel, and Fructus Aurantii[12]. This prescription is used for treating angina pectoris, exerting positive effects on symptom relief, blood lipid metabolism, and quality of life[13]. TCM classifies CHF complicated with depression in the categories of chest obstruction and stagnation syndrome, which mainly manifests as blood stasis syndrome, with etiology associated with blood stasis obstruction of the heart pulse, stagnation of qi activity, and prolonged qi stagnation[14,15]. Therefore, CHF treatment is based on the principle of activating blood, dissolving stasis, regulating qi, and relieving depression, with XFZYD being the best choice.

Given the current scanty research on the therapeutic effect of XFZYD in patients with CHF complicated with depression, we performed this study to confirm the clinical effectiveness of this TCM therapy in such patients.

MATERIALS AND METHODS

Patients and general data

We enrolled 116 patients with CHF complicated with depression who received treatment at Cangzhou Central Hospital, China, between July 2020 and July 2023. The control group (n = 55) was administered Western medicine, and the research group (n = 61) was treated with XFZYD.

Criteria for patient enrollment and exclusion

All patients met the diagnostic criteria for CHF[16], with the syndrome of blood stasis and qi stagnation diagnosed by referring to the Guidelines for the Diagnosis and Treatment of Common Internal Diseases in Chinese Medicine[17]. The inclusion criteria were New York Heart Association (NYHA) classification grade II–III and TCM symptoms of depression, impatience, headache, insomnia, forgetfulness, pain in the chest and hypochondrium, chills or fever in a certain part of the body, a dark purple tongue or a tongue with petechiae and ecchymosis, and a stringy or uneven pulse. The exclusion criteria were as follows: use of other TCM decoctions 1 wk prior to enrollment or antidepressant medications within 1 month of enrollment; coagulation or immune dysfunction; uncontrollable hypertension and hyperglycemia; severe heart failure, severe ventricular arrhythmia, or constrictive pericarditis; other organ dysfunction; history of heart surgery; history of mental illness; infectious or blood system diseases; pregnancy or lactation; and incomplete clinical data.

Treatment methods

All patients received conventional treatment according to the European Society of Cardiology 2016 Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure, as well as conventional psychological care interventions[18].

The control group was treated with Western medicine (flupentixol and melitracen tablets administered in the morning and at noon, one tablet at a time). The research group received XFZYD. The prescription comprised 12 g peach kernel; 9 g each of Carthamus tinctorius L., angelica, Radix Rehmanniae, and Achyranthis Bidentatae; 10 g each of chuanxiong rhizome and Platycodon grandiflorus; 6 g each of Radix Paeoniae Rubra, Fructus Aurantii, and licorice; and 15 g of Radix Bupleuri. The above components were boiled in 500 mL of clear water and simmered to reduce the volume to 400 mL. The drug was taken warm, with 200 mL in the morning and evening, respectively, for a course of treatment of 4 weeks. Both groups were treated for two consecutive courses.

Endpoints

Efficacy: The therapeutic effectiveness of both groups was observed and recorded. Marked effectiveness was defined as the basic or complete disappearance of clinical symptoms, including the evaluation of cardiac function as NYHA grade I or an improvement by more than two grades and a ≥ 70% reduction in the TCM symptom score. Effectiveness was defined as an obvious improvement of clinical symptoms, including an improvement of cardiac function by one grade but not by up to two grades, and a reduction of 30%–70% in the TCM symptom score. Ineffectiveness was defined as no significant improvement or deterioration of clinical symptoms, improvement of cardiac function by less than one grade or worsening of cardiac function, and a reduction of < 30% in the TCM symptom score or a higher score than before treatment. The total effective rate was the sum of the marked effectiveness rate and effectiveness rate.

TCM symptom score: All patients were scored by the same physician before and after treatment for seven symptoms: Depression, frequent sighing, palpitations, fatigue, shortness of breath and weakness, pale complexion, and cold hands and feet, with a total score of 7–21, proportional to the symptoms and signs.

Cardiac function: The left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD) were measured by echocardiography before and after treatment.

Negative emotions: The depressive mood of the patients was assessed using the Self-Rating Depression Scale (SDS), which comprises 20 items with a score of 0–80. Patients’ depression was also evaluated using the Hamilton Depression Scale (HAMD), which comprises 17 items, with a score of 0–68. For both the SDS and HAMD, the higher the score, the more serious the depression.

Serum inflammatory factors: We collected 5 mL of venous blood before and after treatment. The serum was obtained after centrifugation and used to determine the levels of high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), and matrix metalloproteinase-9 (MMP-9) by enzyme-linked immunosorbent assay.

Statistical analysis

Continuous variables were described as mean ± SD, with intergroup and intragroup comparisons performed using t-test and paired t-test, respectively. Categorical variables were described as numbers and percentages, and intergroup comparisons were performed using χ² test. SPSS v24.0 software was used for statistical analysis. P values < 0.05 were considered statistically significant.

RESULTS

General information

The two groups were similar in sex, age, CHF course, NYHA grade, and the course and degree of depression (P > 0.05; Table 1).

Table 1 General information.

Indicators	Control group (n = 55)	Research group (n = 61)	χ2/t-test	P value
Sex (male/female)	35/20	37/24	0.109	0.741
Age (yr)	58.00 ± 5.97	58.77 ± 7.06	0.631	0.530
CHF course (yr)	3.89 ± 0.66	3.84 ± 0.82	0.359	0.720
NYHA classification (II/III)	31/24	35/26	0.012	0.912
Depression course (months)	4.53 ± 0.77	4.67 ± 0.94	0.872	0.385
Depression degree (mild/moderate)	17/38	20/41	0.047	0.829

CHF: Chronic heart failure; NYHA: New York Heart Association.

Clinical effectiveness

The total effective cases in the control and research groups were 43 and 58, respectively, indicating a significantly higher total effective rate in the research group compared with the control group (P < 0.05; Table 2).

Table 2 Clinical efficacy.

Indicators	Control group (n = 55)	Research group (n = 61)	χ2	P value
Marked effectiveness	16 (29.09)	22 (36.07)
Effectiveness	27 (49.09)	36 (59.02)
Ineffectiveness	12 (21.82)	3 (4.92)
Total effective rate	43 (78.18)	58 (95.08)	7.337	0.007

Results are presented as n (%).

TCM symptom score

We calculated the TCM symptom scores of both groups before and after treatment. There were no significant differences between groups before treatment (P > 0.05). However, the scores decreased significantly (P < 0.05) after treatment in both groups, particularly in the research group (Figure 1).

Figure 1 Traditional Chinese medicine symptom score. ^aP < 0.05 and ^bP < 0.01 vs before treatment; ^cP < 0.05 vs control group.

Cardiac function

The main evaluation indices of cardiac function were LVEF, LVEDD, and LVESD. The two groups did not differ markedly in the pretreatment levels of these three indices (P > 0.05). However, LVEF significantly increased (P < 0.05) in both groups after treatment, with an even higher increase in the research group. Furthermore, LVEDD and LVESD were significantly reduced (P < 0.05) after treatment and were lower in the research group than in the control group (Figure 2).

Figure 2 Cardiac function. A: Left ventricular ejection fraction in both groups increased significantly after treatment; B: Left ventricular end-diastolic diameter in both groups decreased significantly after treatment; C: Both groups showed significantly reduced Left ventricular end-systolic diameter after treatment. ^aP < 0.05 and ^bP < 0.01 vs before treatment; ^cP < 0.05 vs control group. LVEF: Left ventricular ejection fraction; LVEDD: Left ventricular end-diastolic diameter; LVESD: Left ventricular end-systolic diameter.

Negative emotions

We used the SDS and HAMD scales to evaluate changes in depressive mood in the two groups. No notable intergroup differences were identified in the two scale scores before treatment (P > 0.05). A significant reduction (P < 0.05) was observed in SDS and HAMD scores in both groups after treatment, and these were more significantly decreased in the research group compared with the control group (Figure 3).

Figure 3 Negative emotions. A: Both groups had significantly reduced Self-Rating Depression Scale scores after treatment; B: Both groups had significantly reduced Hamilton Depression Scale scores after treatment. ^aP < 0.05 and ^bP < 0.01 vs before treatment; ^cP < 0.05 vs control group. HAMD: Hamilton Depression Scale; SDS: Self-Rating Depression Scale.

Serum inflammation

We measured the levels of the major serum inflammatory factors hs-CRP, MCP-1, and MMP-9. There were no significant intergroup differences before treatment (P > 0.05). After treatment, both the research and control groups showed markedly lowered hs-CRP, MCP-1, and MMP-9 Levels, and the levels in the research group were lower than those in the control group (P < 0.05; Figure 4).

Figure 4 Serum inflammatory factors. A: Levels of high-sensitivity C-reactive protein in both groups decreased significantly after treatment; B: Levels of monocyte chemoattractant protein-1 in both groups decreased significantly after treatment; C: Levels of matrix metalloproteinase-9 in both groups decreased significantly after treatment. ^aP < 0.05 and ^bP < 0.01 vs before treatment; ^cP < 0.05 vs control group. hs-CRP: High-sensitivity C-reactive protein; MCP-1: Monocyte chemoattractant protein-1; MMP-9: Matrix metalloproteinase-9.

DISCUSSION

Depression is a debilitating mental illness characterized by persistent low spirits, reduced enthusiasm for daily life, and a dulled ability to experience happiness[19]. The disease is common in patients with CHF and is not only harmful to patient recovery but also increases the risk of suicide[20]. This study analyzed the clinical intervention effect of XFZYD on CHF complicated with depression, with the aim of improving the curative effect in such patients.

The total effective rate in the research group was 95.08%, which was significantly higher than that of the control group (78.18%), indicating that the use of XFZYD in patients with CHF and depression is conducive to a significant improvement in clinical efficacy. The peach kernel used in XFZYD has the effect of expelling blood stasis, promoting stagnation, and moistening dryness[21]. Carthamus tinctorius L., Radix Paeoniae Rubra, and Achyranthes bidentata promote blood circulation, eliminate blood stasis, and relieve pain[22]. Platycodon grandiflorus and Fructus Aurantii, which are responsible for regulating ascending and descending qi, respectively, alleviate mental depression and promote qi circulation[23]. Radix Bupleuri targets the liver-gallbladder meridian, and when used together with Platycodon grandiflorus and Fructus Aurantii, it plays a synergistic role in soothing the liver and relieving depression[24]. Radix Rehmanniae and Angelica sinensis nourish the blood, regulate the qi flowing in the channels, and ensure the therapeutic effects of many drugs by preventing qi-regulating drugs from ascending, dispersing, and damaging yin and blood[25]. Licorice functions as a harmonizer of various drugs to ensure the full extent of curative effects[26]. All the above Chinese herbal medicines work synergistically to treat CHF complicated with depression, exerting a therapeutic effect by activating blood, removing blood stasis, and promoting qi circulation by removing blood stasis and stagnation. The results of TCM symptom scores showed that the research group scored significantly better than the control group in all seven symptoms (depression, frequent sighing, palpitations, fatigue, shortness of breath and weakness, pale complexion, and cold hands and feet) after treatment, indicating that XFZYD was significantly more effective in relieving symptoms in patients with CHF complicated with depression compared with conventional Western medicine. Our evaluation of cardiac function revealed a notable reduction in LVEDD and LVESD in the research group after treatment, which were lower than the LVEDD and LVESD in the control group, whereas the LVEF was markedly elevated and higher in the research group compared with the control group, indicating that XFZYD has a positive mediating and stabilizing effect on cardiac function abnormalities in patients with CHF complicated with depression. Similar to our research results, Zhang et al[27], reported that XFZYD significantly shortened the duration of angina pectoris in patients with coronary heart disease, effectively improved their vascular endothelial function, and significantly reduced TCM symptom scores. Qi et al[28] confirmed that XFZYD showed higher efficacy than Western medicine for treating patients with various types of angina pectoris, which is related to the fact that the target network and cross-targets of XFZYD are closer to the target network of various types of angina compared with Western medicine. In terms of changes in depression, the research group exhibited greatly reduced SDS and HAMD scores after treatment, and these were lower than the pretreatment levels and those in the control group, suggesting that treatment with XFZYD in patients with CHF complicated with depression plays a prominent role in alleviating depression. Wang et al[29] reported that as a therapy for regulating qi and promoting blood circulation, XFZYD had a significant alleviating effect on depressive symptoms in patients with stable angina pectoris, which is consistent with our research results. Finally, the post-treatment levels of hs-CRP, MCP-1, and MMP-9 in the research group were significantly reduced and lower compared with those in the control group, indicating that XFZYD significantly inhibited serum inflammatory responses in patients with CHF complicated with depression, thereby hindering disease progression and playing an active therapeutic role.

CONCLUSION

In summary, XFZYD is superior to Western medicines such as flupentixol and melitracen in treating patients with CHF complicated with depression and exerts a significant therapeutic effect. Besides significantly relieving clinical TCM symptoms and enhancing cardiac function, this TCM therapy also relieves depression and markedly inhibits the levels of serum inflammatory factors. Our findings provide an optimized direction for the treatment of patients with CHF complicated with depression, as evidenced by changes in certain clinical values.