Effect of Luhong formula on the cardiac rehabilitation of patients with chronic heart failure

Abstract

BACKGROUND

Current treatments for chronic heart failure (CHF) are therapeutically ineffective. The optimization of treatments for this disease needs to be explored and analyzed.

AIM

To analyze the effect of using Luhong Formula in the cardiac rehabilitation of patients with CHF and its influence on cardiopulmonary function (CPF) and prognosis.

METHODS

In total, 160 patients with CHF admitted between June 2022 and June 2023 were selected, including 75 receiving perindopril (control group) and 85 receiving Luhong Formula (research group). We conducted comparative analyses on the curative effects of traditional Chinese medicine (TCM) syndromes and cardiac function, CPF [oxygen consumption at the anaerobic threshold (VO₂ AT) and at peak exercise (peak VO₂)], echocardiographic indexes [left atrial volume index (LAVI), left ventricular muscle mass index (LVMI), left ventricular ejection fraction (LVEF)], and prognosis [major adverse cardiovascular events (MACEs) at 6 months follow-up].

RESULTS

The research group showed markedly higher curative effects of TCM syndromes and cardiac function than the control group. In addition, post-treatment VO₂ AT, peak VO₂, LVMI and LVEF in the research group were significantly higher, whereas LAVI was significantly lower, than those of the control group. Furthermore, fewer patients in the research group developed MACEs at the 6-month follow-up.

CONCLUSION

Luhong Formula is more therapeutically effective than perindopril for the cardiac rehabilitation of patients with CHF, specifically in enhancing CPF and prognosis.

Key Words: Luhong formula; Chronic heart failure; Cardiopulmonary function; Cardiac rehabilitation; Prognosis

Core Tip: Traditional Chinese medicine (TCM) has great potential and clinical value in the treatment of chronic heart failure (CHF). This study analyzed the clinical efficacy of Luhong formula in the treatment of patients with CHF in terms of its curative effects on TCM syndromes and cardiac function, cardiopulmonary function (CPF), echocardiographic indexes, and prognosis. Luhong Formula showed a significantly better therapeutic effect on cardiac rehabilitation for CHF than perindopril, specifically in improving CPF and prognosis. The findings demonstrate the potential of Luhong formula as an effective TCM-based treatment option that can be integrated into cardiac rehabilitation strategies for CHF.

INTRODUCTION

Chronic heart failure (CHF) is a hemodynamic disorder characterized by pathological and physiological abnormalities, such as abnormal cardiac output, myocardial contractility, and filling pressure[1]. It can increase the risk of diabetes mellitus (DM), chronic kidney disease, and comorbidities[2]. Risk factors include obesity, type 2 DM, hypertension, and coronary atherosclerotic cardiopathy, all of which can accelerate cardiovascular aging[3]. The number of heart failure (HF) cases worldwide is nearly 40 million, with approximately 900000 new cases annually[4,5]. Although the prognosis of patients with HF has improved, it is still not ideal. Over 23% of patients experience rehospitalization within 60–90 d after discharge and < 50% surviving more than 5 years[6,7]. The negative impact of CHF on the body mainly manifests as fatigue and breathing difficulties, which impose limitations on daily activities. Current treatments for CHF are mainly aimed at cardiopulmonary rehabilitation to improve cardiopulmonary function (CPF) and prognosis[8].

Pharmacologic treatments for CHF, such as angiotensin-converting enzyme inhibitors, β-adrenergic blockers, and diuretics, can cause electrolyte depletion, fluid depletion, hypotension, and other adverse events[9,10]. However, the substitutability of new drugs, such as levosimendan (Simendan), angiotensin receptor-neprilysin inhibitors, and SGLT-2 inhibitors, for traditional drugs still lacks evidence-based medical evidence[11-13]. To further optimize CHF treatment, this study investigated traditional Chinese medicine (TCM) therapy as the preferred treatment, which are more costeffective, have few side effects, and exhibit good curative effects on syndrome differentiation[14]. In TCM, the main syndromes of CHF are Qi deficiency, blood stasis, water stagnation, Yin deficiency, and phlegm turbidity. Therefore, TCM treatment of CHF is based on replenishing Qi, promoting blood circulation to remove blood stasis, and reducing swelling[15]. In this study, Luhong formula evaluated for its effectiveness in cardiac rehabilitation, enhancement of CPF, and improvement of prognosis in CHF.

Research remains limited on the clinical application of Luhong formula in the treatment of CHF. We believe that this study can broaden the current understanding of Luhong formula and shed new insights into the treatment options for CHF.

MATERIALS AND METHODS

Patient information

The study population comprised 160 patients with CHF admitted from June 2022 to June 2023, including 75 treated with perindopril (control group), and 85 treated with Luhong formula (research group).

Eligibility and exclusion criteria

The inclusion criteria were as follows: Diagnosis of CHF confirmed by X-ray and two-dimensional echocardiography[16]; New York Heart Association (NYHA) classification grade II–III [17]; left ventricular ejection fraction (LVEF) < 40%; stable condition ≥ 1 month; no contraindications for medication; and complete clinical data.

The exclusion criteria were as follows: Severe heart, lung, liver, or kidney dysfunction; infective endocarditis, constrictive pericarditis, and other heart diseases; thyroid dysfunction; acute myocardial infarction or unstable angina pectoris; malignant tumors; and inability to communicate normally due to mental illness or cognitive impairment.

Methods

The control group received perindopril (4 mg per tablet) once a day before breakfast, for 2 wk of treatment. The research group was treated with Luhong formula. The prescription of Luhong formula was composed of Cornu Cervi Pantotrichum, Carthamus tinctorius L., Herba Epimedii, Fructus Psoraleae, Fructus Corni, Fructus Ligustri Lucidi, and Aquilaria agallocha Roxb., prepared according to the ratio of 15:9:30:20:15:30:6. Cornu Cervi Pantotrichum and C. tinctorius L. were decocted with water twice: 10 times the volume (2 h) on the first extraction and eight times the volume (1 h) on the second. The decoctions obtained were then mixed, filtered, and concentrated into an extract with a relative density of 1.20 (60°C) for later use. A. agallocha Roxb. was soaked in 80% ethanol ten times its volume for 48 h and filtered. The filtrate was concentrated under reduced pressure to recover ethanol and remove the alcohol odor to obtain A. agallocha Roxb. leachate. Next, Herba Epimedii, Fructus Psoraleae, Fructus Corni, and Fructus Ligustri Lucidi were also decocted in water ten times their volume for 2 h for the first extraction and eight times their volume for 1 h for the second extraction. The decoctions were combined and filtered, and the filtrate was concentrated to a relative density of 1.10. After cooling the filtrate to room temperature, 95% ethanol was added to bring the alcohol content to approximately 70%. The mixture was then stirred and allowed to stand for 24 h. The supernatant was then collected and recovered under reduced pressure until it had no ethanol odor. The abovementioned spare liquid and A. agallocha Roxb. extract were combined and concentrated into an extract with a relative density of 1.35. One part of the extract was added with an appropriate amount of auxiliary materials for preparing into granules (1000 g), which was dried below 90°C, granulated, and packed (5 g/bag) for later use. The drug was taken after meals twice daily.

Outcome measures

Curative effects on TCM syndromes: The clinical symptoms before and after treatment and recovery of the control and research groups were comparatively analyzed. Marked effectiveness was defined as the basic or complete disappearance of the primary and secondary TCM syndromes and the reduction of the syndrome score by ≥ 70%. Effectiveness was defined as the significant reduction of the primary and secondary TCM syndromes as indicated by a 30%–69% reduction in the syndrome score. Ineffectiveness was defined as no marked alleviation in the primary and secondary TCM syndromes and a < 30% reduction in the syndrome score. Exacerbation was defined as the aggravation of the primary and secondary TCM syndromes compared with baseline and an increase in the syndrome score.

Curative effects on cardiac function: The evaluation was conducted using the NYHA cardiac function classification. Marked effectiveness indicates that the CHF clinical symptoms are basically controlled or an improvement in NYHA classification by ≥ 2 grades. Effectiveness indicates improvement in the clinical symptoms and signs of CHF and in the NYHA cardiac function classification by 1 grade but not to grade I. Ineffectiveness indicates no significant changes in the clinical symptoms and signs of CHF and an improvement in the NYHA classification < 1 grade. Exacerbation indicates that the clinical symptoms and signs of CHF are aggravated and the NYHA classification worsened by ≥ 1 grade; (3) CPF. CPF was evaluated before and after treatment by measuring oxygen consumption at the anaerobic threshold (VO₂ AT) and peak exercise (Peak VO₂) during the cardiopulmonary exercise test.

Echocardiographic indexes: The left atrial volume index (LAVI), left ventricular muscle mass index (LVMI), and LVEF were measured using a Philips EPZQ-7C echocardiogram before and after intervention.

Prognosis: All patients were followed up for 6 months after discharge by telephone, QQ mobile app, WeChat lifestyle app, and email. Major adverse cardiovascular events (MACEs) were compared between the two groups, including sudden cardiac death, ventricular arrhythmia, and rehospitalization for HF.

Statistical analysis

Statistical analysis was performed using SPSS 21.0. Continuous variables were expressed as mean ± SD. Inter- and intra-group comparisons (before and after intervention) were performed using the independent sample and paired t-tests, respectively. The χ² test was used for the intergroup comparison of categorical variables, which are expressed as number and percentage [n (%)]. Statistical significance was reported at P < 0.05.

RESULTS

Baseline data

The research and control groups did not differ significantly in sex, age, disease course, NYHA cardiac function classification, hypertension, DM, and hyperlipidemia (P > 0.05; Table 1).

Table 1 Baseline information.

Indicators	Control group (n = 75)	Research group (n = 85)	χ2/t value	P value
Sex (male/female)	45/30	49/36	0.091	0.763
Age (yr)	56.97 ± 10.01	57.41 ± 9.02	0.292	0.770
Disease course (yr)	6.04 ± 1.16	5.88 ± 1.44	0.767	0.444
NYHA cardiac function classification (II/III)	34/41	40/45	0.048	0.827
Hypertension (with/without)	38/37	36/49	1.108	0.293
DM (with/without)	25/50	31/54	0.172	0.678
Hyperlipidemia (with/without)	28/47	35/50	0.247	0.620

DM: Diabetes mellitus; NYHA: New York Heart Association.

Curative effects on TCM syndromes

The total therapeutic efficacy rate on TCM syndromes was higher in the research group than in the control group (97.65% vs 85.33%, respectively; P < 0.05; Table 2).

Table 2 Curative effects of traditional Chinese medicine syndromes, n (%).

Indicators	Control group (n = 75)	Research group (n = 85)	χ2 value	P value
Marked effectiveness	24 (32.00)	44 (51.76)
Effectiveness	40 (53.33)	39 (45.88)
Ineffectiveness	8 (10.67)	2 (2.35)
Exacerbation	3 (4.00)	0 (0.00)
Total effective rate	64 (85.33)	83 (97.65)	8.093	0.004

Curative effects on cardiac function

The research group also showed a higher total therapeutic efficacy rate than the control group in terms of improvement in cardiac function (95.29% vs 82.67%, respectively; P < 0.05; Table 3).

Table 3 Curative effects of cardiac function, n (%).

Indicators	Control group (n = 75)	Research group (n = 85)	χ2 value	P value
Marked effectiveness	23 (30.67)	43 (50.59)
Effectiveness	39 (52.00)	38 (44.71)
Ineffectiveness	11 (14.67)	4 (4.71)
Exacerbation	2 (2.67)	0 (0.00)
Total effective rate	62 (82.67)	81 (95.29)	6.690	0.010

CPF

The major CPF indexes assessed were VO₂ AT and Peak VO₂. No significant intergroup difference was found in VO₂ AT and Peak VO₂ before the intervention (P > 0.05). However, both indexes increased significantly in the two groups after intervention (P < 0.05), with even higher levels observed in the research group (P < 0.05; Figure 1).

Figure 1 Comparative analysis of anaerobic threshold and peak exercise before and after intervention. A: Oxygen consumption at the anaerobic threshold (VO₂ AT) before and after intervention; B: Oxygen consumption at peak exercise (peak VO₂) before and after intervention. ^aP < 0.05 vs before intervention. ^bP < 0.01 vs before intervention. ^cP < 0.05 vs control group. VO₂ AT: Oxygen consumption at the anaerobic threshold; Peak VO₂: Oxygen consumption at peak exercise.

Echocardiographic indexes

LAVI, LVMI, and LVEF were the echocardiographic indexes evaluated. We also found no significant intergroup difference in these three indexes before the intervention (P > 0.05). After the intervention, the LAVI in both groups decreased significantly, whereas the LVMI and LVEF increased significantly. Moreover, a lower LAVI and higher LVMI and LVEF was observed in the research group compared with those of the control group (P < 0.05; Figure 2).

Figure 2 Comparative analysis of left atrial volume index, left ventricular muscle mass index, and left ventricular ejection fraction before and after intervention. A: Left atrial volume index before and after intervention; B: Left ventricular muscle mass index before and after intervention; C: Left ventricular ejection fraction before and after intervention. ^aP < 0.05 vs before intervention. ^bP < 0.01 vs before intervention. ^cP < 0.05 vs control group. LAVI: Left atrial volume index; LVMI: Left ventricular muscle mass index; LVEF: Left ventricular ejection fraction.

Prognosis

Prognosis was assessed by evaluating the 6-month MACEs, specifically sudden cardiac death, ventricular arrhythmias, and rehospitalization for HF. The research group had significantly fewer MACEs than the control group (P < 0.05; Table 4).

Table 4 Major adverse cardiovascular events at 6-month follow-up, n (%).

Indicators	Control group (n = 75)	Research group (n = 85)	χ2 value	P value
Sudden cardiac death	3 (4.00)	2 (2.35)
Ventricular arrhythmia	6 (8.00)	3 (3.53)
Rehospitalization for heart failure	10 (13.33)	3 (3.53)
MACEs	19 (25.33)	8 (9.41)	7.200	0.007

MACEs: Major adverse cardiovascular events.

DISCUSSION

This study investigated the clinical application of Luhong formula in the treatment of CHF. In previous studies, TCM therapies, such as Xinmailong, Wenxin granule, and Shenmai injection, have been used in the treatment of CHF, all of which demonstrating excellent efficacy and safety, indicating the great potential and clinical value of TCM in the treatment of CHF[18-20]. Although CHF-related terms have no equivalent in TCM theory, CHF symptoms can be generally categorized into edema, palpitations, and dyspnea. The disease is often induced by improper diet, overwork, and repeated attacks of exogenous pathogens, among others. These factors result in conditions that can be explained by the TCM symptoms heart-Qi deficiency and heart-Yang deficiency[21,22]. Our study revealed that the curative effects of Luhong formula on TCM syndromes and cardiac function were significantly better in the research group than in the control group, indicating the significant advantages of Luhong formula in relieving CHF symptoms and improving cardiac function. The main pathogenesis of CHF in TCM diagnosis is heart-kidney Yang deficiency, which is caused by fluid-Qi disharmony and enduring fluid retention and stasis. Luhong formula can supplement Qi to warm Yang, activate blood circulation, and promote diuresis[23]. Cornu Cervi Pantotrichum, a component of Luhong formula, can warm the liver and kidneys and nourish essence and blood[24]; C. tinctorius L. can promote blood circulation to remove blood stasis and menstruation, cool the blood, and detoxify[25]. Fructus Psoraleae can reinforce the kidneys to strengthen Yang and absorb Qi to relieve asthma, and if used together with Epimedium brevicornu Maxim. and Cornu Cervi Pantotrichum, can tonify the liver and kidneys[26]. Both Fructus Corni and Fructus Ligustri Lucidi can nourish liver–kidney Yin[27,28]. A. agallocha Roxb. warms the kidneys, absorbs Qi, calms the adverse-rising energy, and relieves asthma[29]. Post-intervention VO₂ AT and Peak VO₂ were significantly higher in the research group than in the control group, indicating that Luhong formula has a significant positive effect on improving the CPF in patients with CHF. Zhao et al[30] found that velvet antlers have several health-promoting functional components (such as velvet antler peptide sVAP32) that exerts an anticardiac fibrosis effect by blocking the transforming growth factor β1 pathway in cardiac fibroblasts. Jia et al[31] reported the cardioprotective effect of C. tinctorius L. extract, which occurs by inducing cardiomyogenic H9C2 cell autophagy and inhibiting apoptosis. The properties of these individual components demonstrate the therapeutic mechanism of Luhong formula in promoting cardiac rehabilitation in patients with CHF. Echocardiographic data indicated markedly reduced LAVI in the research group, lower than baseline and that of the control group, as well as significantly increased LVMI and LVEF that were higher than baseline and those of the control group. The significant improvement in echocardiographic indexes confirms the significant effect of Luhong formula intervention in improving CPF. MACEs at 6 months after intervention were evaluated to assess the effect of prognosis after treatment. The 6-month MACEs (cardiac sudden death, ventricular arrhythmia, and rehospitalization for HF) were notably fewer in the research group than in the control group, indicating the positive impact of Luhong formula intervention on prognosis.

This study has some limitations. First, the assessment period was too short, and the long-term efficacy and prognostic impact of Luhong formula could not be verified. Second, because the sample size was small, information bias may have affected the accuracy of results. Third, no indepth analysis was performed on the prognostic factors affecting 6-month MACEs. Supplementary analysis needs to be performed to address these limitations and strengthen the robustness of the findings.

CONCLUSION

Luhong formula for CHF exerted a curative effect on TCM syndromes and improved cardiac function, which improved CPF and facilitated cardiopulmonary rehabilitation. Furthermore, Luhong formula intervention reduced the risk MACEs at the 6-month follow-up and thus may improve prognosis. Our results present clinical evidence indicating the potential of Luhong formula as an effective treatment option for promoting cardiac rehabilitation in CHF.