Advances in Research on Treatment of Heart Failure with Yangxinshi Tablet

Jian LI, Zhixiao WANG, Xinling ZHOU, Yihong JIANG

Guangxi International Zhuang Medical Hospital, Nanning 530201, China

Abstract The advances in the treatment of heart failure with Yangxinshi tablet are reviewed in this paper. Yangxinshi tablet has effects of nourishing myocardia, improving myocardial metabolism, reducing myocardial oxygen consumption, dilating coronary artery, improving cardiac blood supply, reducing blood viscosity and improving microcirculation, and it can improve the functions of heart and curative effect of heart failure.

Key words Yangxinshi tablet, Heart failure, Advance, Mechanism, Qi deficiency and blood stasis type, Coronary heart failure, Pulmonary heart disease, Anemic cardiopathy

1 Introduction

Chronic heart failure (CHF) is a syndrome of late manifestations of various heart diseases and is a common manifestation of the development of various heart diseases to the end stage, characterized by ventricular insufficiency caused by abnormal cardiac functions and structure. It is the ultimate fate and main cause of death of most cardiovascular diseases[1]. Heart failure seriously affects the physical health and quality of life of patients. At present, the treatment of heart failure is mainly based on corresponding drugs. Yangxinshi tablet has achieved a positive effect in the prevention and treatment of heart failure. This article reviews the relevant literature on Yangxinshi tablet in the treatment of heart failure as follows.

2 Effects and mechanisms of Yangxinshi tablet in the prevention and treatment of heart failure

2.1 Effects on plasma brain natriuretic peptide (BNP)When heart failure occurs and myocardial cells are stimulated, the synthesis and secretion of BNP in the body will be promoted, resulting in a significant increase in serum BNP level; and with the increase of the degree of heart failure, the plasma BNP level also gradually increases[2]. Zhang Jinlong[3]explored the effect of Yangxinshi tablet on plasma BNP in patients with CHF. A total of 60 patients with heart failure were selected. The patients in the observation group were given conventional treatment plus Yangxinshi tablet, and the patients in the control group were given conventional treatment. The results showed that the plasma BNP levels in the two groups were significantly improved compared with those before treatment, and the improvement effect in the observation group was significantly better than that in the control group, suggesting that Yangxinshi tablet can effectively improve cardiac function and 6-minute walk distance, as well as significantly reduce the plasma BNP level of the patients, and it has obvious therapeutic effect on patients with CHF.

2.2 Effects on vascular endothelial functionLi Qing[4]observed the therapeutic effect of Yangxinshi tablet combined with trimetazidine on coronary heart disease complicated with CHF and its effect on vascular endothelial function. The control group was treated with trimetazidine, and the observation group was treated with Yangxinshi tablet combined with trimetazidine. The curative effect after treatment, as well as the left ventricular function, 6-minute walk distance (6-MWT), basal value of brachial artery diameter at the end of vasodilation (D0), brachial artery diameter after hyperemia (D1), mitochondrial coupling factor 6 (CF6), nitric oxide (NO) and endothelin (ET)-1 levels before and after treatment were observed. The results showed that the total effective rate in the observation group was better than that in the control group (P<0.05); there was no significant difference in left ventricular function, 6-MWT, D0, D1, CF6, NO or ET-1 level between the two groups before treatment (P>0.05); the LVEF, 6-MWT and D1 levels significantly increased (P<0.01), and the CF6 and ET-1 levels significantly reduced (P<0.01) after treatment, and the decreases and increases in the observation group were larger (P<0.01), suggesting that Yangxinshi tablet can improve sexual function and vascular endothelial function and improve the clinical efficacy for coronary heart disease complicated with CHF.

2.3 Effect on C-reactive proteinTang Zhaolietal.[5]observed the effects of Yangxinshi tablet on cardiac function and high-sensitivity C-reactive protein in patients with coronary heart disease. The patients were given conventional treatment and conventional treatment+Yangxinshi tablet for 6 months. Before and after the treatment, the cardiac function was evaluated using Doppler echocardiography (PHILIPSA33), and the level of high-sensitivity C-reactive protein was determined. The results showed that after 6 months of treatment, the left ventricular ejection fraction (P<0.01) increased, relevant indices of left ventricular structure improved (P<0.01), and the level of high-sensitivity C-reactive protein significantly reduced (P<0.01); and there was no significant change in the conventional observation group. It suggests that Yangxinshi tablet can improve left ventricular systolic and diastolic functions and reduce the level of high-sensitivity C-reactive protein in patients with heart disease, and it has a protective effect on the coronary artery.

2.4 Effects on myocardial apoptosisGuo Zhigangetal.[6]explored the effects of Yangxinshi tablet on myocardial apoptosis in rats with heart failure and its mechanism. The rats were randomly divided into normal control group and Yangxinshi tablet group. The rats in the Yangxinshi tablet group were treated with Yangxinshi tablet. After 6 weeks, the heart rate (HR) and left ventricular function of the rats were measured. The blood of the posterior common carotid artery was collected for biochemical analysis. Collagen fibrosis and morphology were observed using Masson staining; apical phosphorylated connexin (P-Cx) 43 and β-actin levels were detected by Western blotting; and apoptosis of myocardia was detected using TUNEL detection kit. The results showed that the levels of BNP, troponin (cTn) I, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and HW/BW in the Yangxin tablet group were significantly lower than those in the model group (P<0.05); the level of BNP in Yangxinshi tablet group was significantly higher than that in digoxin group (P<0.05); the myocardial collagen volume fraction and myocardial apoptosis index of cardiomyocytes in the Yangxinshi tablet group were significantly lower than those in the model group (P<0.05); the P-Cx43/β-actin level in the Yangxinshi tablet group was significantly lower than that in the blank group (P<0.05); and the level of P-Cx43/β-actin was positively correlated with myocardial cell apoptosis (P<0.05). It is suggested that Yangxinshi tablet can improve cardiac function, and reduce myocardial cell fibrosis and ventricular remodeling in rats. The mechanism is achieved by regulating the expression of P-Cx43 to improve myocardial apoptosis in rats with heart failure.

2.5 Effects on reperfusion injuryGao Yueetal.[7]conducted experimental research on the effects of Yangxinshi tablet on the prevention and treatment of chronic ischemic heart failure and acute myocardial ischemia-reperfusion injury. Rat model of chronic ischemic heart failure and myocardial infarctional mouse model with acute myocardial ischemia and reperfusion (coronary artery ligation) were established. The animals were randomly divided into sham operation group, model group, positive drug group and low, medium and high-dose Yangxinshi tablet groups. Through pre-administration and post-modeling administration, the ultrasonic cardiogram, ACE, ACD, mouse myocardial infarction area, CK, LDH, SOD and related factors were measured, and the morphological changes of cardiac pathological sections were observed. The results showed that compared with the sham operation group, the biochemical parameters of the model group were statistically different (P<0.001); and compared with the model group, the biochemical indexes changed significantly (P<0.001,P<0.01,P<0.05), the area of myocardial infarction significantly reduced (P<0.01,P<0.05), the edema degree of cardiomyocytes significantly improved, and cell infiltration reduced in the positive drug group and the high-dose Yangxinshi tablet group. It indicates that Yangxinshi tablet has significant prevention and therapeutic effects on chronic ischemic heart failure and acute myocardial ischemia-reperfusion injury.

3 Efficacy of Yangxinshi tablet in the treatment of heart failure

3.1 Therapeutic effect on CHFQu Jiawuetal.[8]found that Yangxinshi tablet provides a new method for the treatment of CHF, and its mechanism is achieved by improving the heart function of patients with heart failure. Yang Kaietal.[9]explored the clinical efficacy of Qishen Yiqi drop pill combined with Yangxinshi tablet in treating CHF. The study found that the combined application of the two drugs can significantly improve cardiac function and increase exercise tolerance, and can be promoted in clinical applications. Pan Feng[10]combined conventional western medicine and Yangxinshi tablet in treatment of diastolic heart failure. Both the two groups were treated for 30 d. Compared with the control group, the observation group significantly improved the clinical symptoms of patients with diastolic heart failure and extended 6-minute walk distance to improve clinical efficacy. Xu Wei[11]conducted a prospective randomized controlled study. The control group received conventional anti-heart failure treatment. In the observation group, trimetazidine and Yangxinshi tablet were added on the basis of conventional treatment. The results show that after one month of treatment, the left ventricular ejection fraction in the observation group was not significantly different from that before treatment and in the control group; and after one year of treatment, the left ventricular ejection fraction in the observation group significantly improved compared with that before treatment and in the control group, the total effective rate was 82.2% in the observation group and 50% in the control group, and the one-year hospitalization rate and mortality rate in the observation group decreased by 65% and 75% compared with those in the control group. The above research showed that the combination of trimetazidine and Yangxinshi tablet on the basis of conventional treatment can significantly improve the clinical efficacy of CHF and reduce mortality. Huang Minetal.[12]observed the clinical effect of Yangxinshi tablet on diastolic heart failure (DHF). A total of 125 cases were randomly divided into two groups. The 62 cases in the control group were treated with basic western medicine, and the 63 patients in the observation group were treated with Yangxinshi tablet on the basis of western medicine. The changes in clinical efficacy, TCM syndrome score, and rehospitalization rate in the two groups were observed. The results showed that the total effective rate in the observation group was 92.1%, which was higher than that (80.6%) in the control group (P<0.05); the TCM symptom scores decreased in both groups after treatment; the scores of various indicators in the observation group after treatment significantly improved compared with those before treatment (P<0.05,P<0.01); and compared with the control group, the scores of symptoms such as shortness of breath, chest tightness, anorexia, dark lips, pale tongue, dark tongue, weak pulse and intermittent pulse were significantly reduced (P<0.05). In short, Yangxinshi tablet had obvious effect in the treatment of DHF on the basis of western medicine treatment, the patients’ symptoms improved significantly, and the rate of rehospitalization decreased, suggesting that Yangxinshi tablet can improve the diastolic function of patients, and it has a good effect on the adjuvant treatment of DHF.

3.2 Therapeutic effect on CHF with Qi deficiency and blood stasisSun Mingliangetal.[13]found through clinical research that Yangxinshi tablet could improve the clinical symptoms of patients, increase left ventricular ejection fraction, significantly improve cardiac function in patients with CHF, and improve patients’ quality of life. Patient compliance was better, and there were no obvious adverse reactions during the treatment. Therefore, Yangxinshi tablet is worthy of clinical application. Zhang Weietal.[14]found that Yangxinshi tablet could improve cardiac function and improve symptoms in patients with CHF from coronary heart disease, without obvious adverse reactions, and it is an effective drug for treating CHF with Qi deficiency and blood stasis. Zhang Hangetal.[15]Observed the clinical effect of Yangxinshi tablet in treating DHF with qi deficiency and blood stasis. The results showed that Yangxinshi tablet combined with conventional western medicine was more effective in treating patients with DHF of qi deficiency and blood stasis type than conventional western medicine; Yangxinshi tablet showed effect-enhancing and toxicity-reducing effect in the treatment of DHF of qi deficiency and blood stasis type; and Yangxinshi tablet is very beneficial for patients who have long been affected by adverse reactions to western medicine, and it has obvious advantages compared with conventional western medicine treatment. In order to evaluate the clinical efficacy of Yangxinshi tablet in treating coronary heart disease of qi deficiency and blood stasis, Lin Xin[16]randomly divided 96 patients with coronary heart disease of qi deficiency and blood stasis type into control group (Western medicine treatment) and Yangxinshi tablet group (Western medicine treatment + Yangxinshi tablet), 48 cases in each group. The course of treatment was 3 months. The symptoms and signs of TCM, angina pectoris, electrocardiogram, hs-CRP, NT-pro BNP, Hcy, lipids and adverse reactions in the two groups were observed and compared. The results are as follows. (i) After treatment, the total effective rate of symptoms and signs of TCM in the observation group was 92.8%, and that in the control group was 75.1%. There was a statistically significant difference between the two groups (P<0.05). (ii) After treatment, the total effective rate of angina pectoris improvement in the Yangxinshi tablet group was 93.75%, higher than 83.33% of the control group (P<0.05). (iii) In terms of electrocardiogram, the total effective rate of the observation group was 81.25%,and that of the control group was 70.83% (P<0.05). (iv) The hs-CRP, NT-pro BNP and Hcy in the Yangxinshi tablet group were lower than those in the control group (P<0.05). (v) The incidence of adverse reactions in the Yangxinshi tablet group was 8.33%, lower than 14.58% of the control group (P<0.05). In the treatment of CHD with qi deficiency and blood stasis, the efficacy of Yangxinshi tablet in combination with commonly used western medicine for symptoms and signs of TCM, angina pectoris, electrocardiogram, hs-CRP, NTpro BNP, Hcy, blood lipids,etc. Was better compared with that of western medicine alone, and Yangxinshi tablet significantly reduced adverse reactions (P<0.05), and to a certain extent, it had played a role in enhancing effectiveness, reducing toxicity and improving patient compliance.

3.3 Therapeutic effect on heart failure from coronary heart diseaseGu Jialinetal. observed the clinical effect of Yangxinshi tablet on patients with coronary heart disease and heart failure. It was found that the addition of Yangxinshi tablet in the therapy further reduced plasma BNP levels and improved TCM symptoms and heart function in the patients, indicating that the combination of conventional western medicine and Yangxinshi tablet can further improve heart function. Lu Weixingetal.[17]conducted clinical observation on Yangxinshi tablet in treating heart failure of qi deficiency and blood stasis type caused by coronary heart disease. The results showed that Yangxinshi tablet has a better effect on improving cardiac function in patients with CHF from coronary heart disease. After treatment, the plasma BNP level in the Yangxinshi tablet group decreased significantly. In terms of comparison of efficacy for TCM syndromes between the two groups of patients, the observation group showed a significantly better effect on the reduction of total score of TCM symptoms and signs than the control group. There were significant differences in the improvement fatigue, spontaneous sweating and other symptoms between the two groups (P<0.05). It showed that the observation group was better than the control group in improving the symptoms of fatigue and spontaneous sweating, and it could significantly improve the quality of life of patients.

3.4 Therapeutic effect on heart failure from dilated cardiomyopathyQian Guoquanetal.[18]observed 112 patients with dilated cardiomyopathy, and 56 of them were treated with Yangxinshi tablet, and significant results were achieved. The inclusion of Yangxinshi tablet improved patient compliance, and significantly improved left ventricular ejection fraction and clinical symptoms in patients with chronic congestive heart failure. Fu Pengetal. randomly divided 126 patients with dilated cardiomyopathy into an observation group and a control group. The control group was treated with conventional drugs for heart failure. In the observation group, Yangxinshi tablet was added on the basis of the control group, 3 tablets/time, 3 times/d. The results showed that the left ventricular ejection fraction, N-terminal natriuretic peptide precursor level, and cardiac function classification in the observation group were better than those in the control group (P<0.05). indicating that Yangxinshi tablet can significantly improve the efficacy and prognosis of patients with dilated cardiomyopathy.

3.5 Therapeutic effect on hypothyroid heart diseasePan Wei found that Yangxinshi tablet and Youjiale improved the symptoms of hypothyroid heart disease quickly, and the effect was significant. No obvious adverse reactions were found. The combined application of the two drugs promptly and appropriately intervened in the treatment of hypothyroid heart disease. When they started to be used at a lower dose of levothyroxine sodium, aggravation of heart failure was avoided, thyroid function and heart function were better improved, symptoms were improved quickly, the course of disease was shortened, and no obvious adverse reactions were found, so they can be promoted and applied clinically.

3.6 Therapeutic effect on pulmonary heart diseaseSu Qingzhuetal. evaluated the clinical efficacy of Yangxinshi tablet in the treatment of pulmonary heart disease. It was found that Yangxinshi tablet could significantly improve clinical symptoms and blood lipids, increase LVEF and reduce hs-CRP, NT-proBNP and adverse reactions, with high safety and clinical guiding significance. In this clinical study, Yangxinshi tablet in combination with isosorbide mononitrate was used to treatment pulmonary heart disease complicated with heart failure. The total effective rate of improvement of clinical symptoms and the improvement of LVEF, hs-CRP, NTproBNP, and blood lipids in the Yangxinshi tablet group were significantly better than those in the control group. What’s more, Yangxinshi tablet significantly reduced the adverse reactions caused by western medicine (P<0.05), and to a certain extent, it had played a role in enhancing effectiveness and reducing toxicity, thereby improving patient compliance. Chen Xin[19]observed the clinical efficacy of Yangxinshi adjuvant treatment for pulmonary heart disease, as well as its effects on serum high-sensitivity C-reactive protein (hdCRP) and interleukin-8 (IL-8) levels in patients. A total of 50 patients with pulmonary heart disease were selected as the research object. They were randomly divided into observation group and control group with 25 cases each. The patients in both groups were given standard medicine for pulmonary heart disease. On the basis of this, the observation group was treated with Yangxinshi tablet. After treatment, the levels of hsCRP and IL-8 in the two groups were significantly lower than those before treatment (P<0.01). After treatment, the levels of hsCRP and IL-8 were significantly different between the groups (P<0.01). There were no serious adverse events during the treatment in the two groups. It shows that Yangxinshi tablet is an adjunct to the treatment of pulmonary heart disease on the basis of conventional drug treatment, and it can further reduce serum hsCRP and IL-8 levels in patients, improve cardiopulmonary function, and improve exercise endurance.

3.7 Therapeutic effect on anemic heart diseaseDai Xingbinetal.[20]observing the clinical effect of Yangxinshi tablet in treating anemic heart disease. The patients treated conventionally were given primary disease treatment, oxygen inhalation, blood transfusion,etc. On the basis of conventional treatment, Yangxinshi tablet was added in the observation group. The efficacy was evaluated referring toGuidingPrinciplesforClinicalResearchofNewChineseMedicine. The scores of TCM symptoms in the two groups were compared. The total effective rate (93.76%) and recent cure rate (21.88%) of the Yangxinshi tablet observation group were higher than those of the control group (85.18% and 14.81%). Yangxinshi tablet could significantly reduce shortness of breath, palpitations and other symptoms. On the basis of conventional treatment, the addition of Yangxinshi tablet improved the clinical symptoms, efficacy, and quality of life in elderly patients with anemic heart disease. Yangxinshi tablet was found to be safe during treatment, and it deserves further study.

4 Conclusions

Yangxinshi tablet is composed of Radix Astragali, Radix Codcnopsitis Pilosulas, Radix Salviae Miltiorrhizae, Radix Puerariae, Herba Epimedii, hawthorn, Radix Rehmanniae, Radix Angelicae Sinensis, Rhizoma Coptidis, Rhizoma Corydalis, Lucid Ganoderma, Radix Ginseng and Radix Glycyrrhizae Preparata, and it is a pure Chinese medicine preparation. According to modern medicine, Radix Ginseng, Radix Astragali, Radix Codcnopsitis Pilosulas and Radix Angelicae Sinensis can improve myocardial ischemia and reperfusion of the heart, promote myocardial production and prostaglandin release, and inhibit the production of thromboxane A2, thus exerting a protective effect on hypoxia and glucose-deficient cardiomyocytes. Radix Salviae Miltiorrhizae, Radix Puerariae, hawthorn and Lucid Ganoderma can expand coronary arteries, lower blood pressure, increase myocardial contractility and reduce myocardial oxygen consumption, and at the same time, they have the effects of preventing platelet aggregation, regulating blood lipids, lowering serum total cholesterol, triacylglycerol and low density lipoprotein, and elevating serum high density lipoprotein cholesterol. Among them, Radix Puerariae also acts as a β-blocker to slow heart rate. Rhizoma Corydalis can directly dilate blood vessels, improve microcirculation and reduce peripheral vascular resistance to reduce cardiac preload. Radix Salviae Miltiorrhizae, Radix Codcnopsitis Pilosulas and Lucid Ganoderma have the effects of strengthening heart, lowering blood pressure, expanding coronary arteries, regulating blood lipids and inhibiting anti-platelet aggregation to reduce blood viscosity. They can also improve blood flow, thereby alleviating symptoms of myocardial ischemia. At the same time, Chinese medicine believes that Radix Ginseng, Radix Codcnopsitis Pilosulas and Radix Astragali have the effects of tonifying qi, strengthening exterior, arresting sweating, relieving desertion, promoting granulation and inducing diuresis for removing edema. Radix Salviae Miltiorrhizae, Radix Puerariae, Radix Angelicae Sinensis and Rhizoma Corydalis have the effects of promoting blood circulation, removing stasis, promoting qi circulation and relieving pain. Radix Glycyrrhizae Preparata, Radix Puerariae, Radix Rehmanniae and Lucid Ganoderma can engender liquid, nourish yin, calm the heart and tranquilize the mind[21]. The prescription can strengthen and consolidate body resistance, benefit qi for activating blood circulation, reliev pain and regulate the functions of the heart and the whole body. In the treatment of CHF, Yangxinshi tablet has the following effects: nourishing myocardia, improving myocardial metabolism, reducing myocardial oxygen consumption, dilating coronary arteries, improving the blood supply to the heart, significantly improving myocardial contraction and diastolic functions, increasing myocardial contractility, increasing cardiac output, reducing myocardial cell apoptosis, improving heart function, preventing ventricular remodeling, reducing inflammatory responses, and improving the efficacy for heart failure. It is expected to become a proprietary Chinese medicine for treating heart failure with unique curative effect.