Clinical effect of recombinant human brain natriuretic peptide in the treatment of heart failure in elderly patients

Abstract

Background

Heart failure in elderly individuals poses significant challenges due to the decline in cardiac function associated with aging. This study aimed to investigate the clinical efficacy of recombinant human brain natriuretic peptide (rhBNP) for the treatment of heart failure, especially in elderly patients.

Methods

This was a retrospective case control study of the medical records of 60 elderly patients with heart failure admitted to our hospital between December 2020 and December 2023. Patients were divided into two groups based on treatment. The control group (n = 30) received diuretics, digitalis, and β receptor blockers, while the observation group (n = 30) received lyophilized rhBNP in addition to the control group treatment. Changes in BNP levels and clinical outcomes were compared between the two groups.

Results

Posttreatment BNP levels were significantly lower in the observation group than in the control group (p < 0.05), and the total clinical effective rate was greater in the observation group (p < 0.05). Additionally, the left ventricular diameter, left atrial diameter, left ventricular shortening fraction, diastolic flow signal and cardiac output in the observation group were lower than those in the control group (p < 0.05), while the thickness of the aortic root diameter in the observation group was greater than that in the control group (p < 0.05).

Conclusion

RhBNP demonstrated ideal clinical efficacy in elderly patients with heart failure, improving symptoms and indicating potential for widespread use in the future.

Background

Heart failure in elderly individuals represents a significant health challenge characterized by a gradual decline in cardiac function, leading to an inability to meet the body’s physiological demands [1]. As medical technology advances and living standards improve, the aging population continues to grow, resulting in a rising prevalence of heart failure among elderly people [2, 3]. The prevalence of heart failure worldwide is approximately 1–2%, and it is estimated to exceed 10% in subjects over 70 years of age [4]. In China, studies have indicated that the prevalence of heart failure is 0.57% among individuals aged 25 to 64 years, 3.86% among those aged 65 to 79 years, and 7.55% among those aged 80 years and above [5]. Effective treatment strategies for elderly patients with heart failure are imperative to mitigate symptoms and improve prognosis. Although current pharmacological interventions aim to inhibit ventricular remodeling, enhance myocardial blood circulation, and repair damaged cardiomyocytes, their clinical efficacy remains limited. Consequently, there is a pressing need for innovative therapies to address the complex pathophysiology of heart failure in the elderly population [6].

Clinical studies have demonstrated the significance of brain natriuretic peptide (BNP) in heart failure management, with elevated levels observed following the onset of the disease [7]. However, the rapid degradation and diminished physiological activity of endogenous BNP necessitate supplementation with exogenous BNP [8]. Recombinant human BNP (rhBNP) has emerged as a promising therapeutic agent due to its natural antioxidant and anti-inflammatory effects, and it offers multifaceted benefits for cardiac function and patient well-being [9]. Nevertheless, further investigation is warranted to elucidate the specific effects and safety profile of rhBNP in treating heart failure among the elderly population. Prior studies have focused on the general efficacy of BNP in heart failure management, but there is a lack of comprehensive data specifically addressing the elderly demographic, which is more vulnerable to the adverse impacts of heart failure and may respond differently to treatment due to age-related physiological changes.

This paper aimed to evaluate the therapeutic efficacy of rhBNP in elderly patients with heart failure by utilizing a comparative analysis of 60 patients treated at our hospital from December 2020 to December 2023. By elucidating the clinical outcomes of rhBNP supplementation, this study endeavors to provide valuable insights for optimizing drug regimens and enhancing clinical management strategies for elderly patients with heart failure.

Method

Participant

This is a retrospective case-control study. Sixty elderly patients with heart failure who were treated at Jingxian Hospital between December 2020 and December 2023 were selected for this research. The medical records of the patients were retrospectively analyzed, and the patients were categorized based on the treatment plans. Thirty patients were included in both the control and observation groups. All participants and their families were informed about the survey’s objectives, voluntarily signed the consent form, and actively participated in the research activities. This study was approved by the Ethics Committee of Jing County Hospital (Approval No. 2024-31). No significant differences were found in the data or information between the two groups of elderly heart failure patients (P > 0.05). Further details can be found in Table 1.

Table 1 Comparison of clinical data of two groups of elderly sufferers with heart failure

The inclusion criteria were as follows: (1) the presence of symptoms such as orthopnea, shortness of breath, dyspnea, and hemoptysis, consistent with the diagnostic criteria for heart failure in elderly individuals outlined in the Guidelines for Heart Failure and Treatment in China; (2) age 60 years and older; (3) no history of relevant drug treatment in the past 2 months; and (4) normal consciousness and cognitive function. The exclusion criteria included (1) abnormal blood coagulation; (2) severe infectious diseases and malignant tumors; (3) acute myocardial infarction; (4) recent history of surgical treatment; (5) severe allergic reactions to study-related drugs; (6) hypotension (systolic blood pressure/diastolic blood pressure below 90 mmHg/60 mmHg); and (7) heart valve disease, hypertrophic cardiomyopathy, acute myocarditis, among others.

Method

Upon admission, all patients received oxygen inhalation and standard treatment, including diuretics, antiplatelet aggregation drugs, and β-receptor blockers.

The subjects in the control group were administered furosemide (H41020435 Tianfang Pharmaceutical Co., Ltd., 20 mg) and digoxin (H33021657 Hangzhou Minsheng Pharmaceutical Co., Ltd., 0.125 mg). Furosemide (20 mg) was taken orally once a day, and digoxin (0.125 ∼ 0.25 mg) was taken orally once a day. The patients were treated for 10 days.

In the observation group, the patients in this group were treated with new activin (0.5 mg/branch of Chengdu Nuodikang Biological Pharmaceutical Co., Ltd., S20050033). First, 0.5 mg of new activin was dissolved in 0.9% 50 ml of sodium chloride solution (H20066533 Shijiazhuang Fourth Pharmaceutical Co., Ltd.). The solution was micropumped and then pumped into 3 min at a rate of 1.5 μg/kg. The drug was then given through the vein at a rate of 0.01 μg/(kg·min) for 72 h, after which the drug treatment was stopped. The patients received a total of 10 days of medication.

Observation indicators

(1) Changes in BNP levels in two groups of elderly patients with heart failure included in the statistical investigation. Five milliliters of venous blood from the elbow of the patients was collected before and after treatment, and all the blood samples were collected 30 min after collection. In this study, an enzyme-linked immunosorbent assay kit produced by the MarkInc Company in the United States was used with an automatic enzyme labeling instrument (produced by SunriseRomte, Austria). The instrument used was a TouchScreen. The BNP level was detected.

(2) The clinical efficacy of the two groups was analyzed, expressed as the total clinical effective rate and expressed as the total clinical effective rate (the sum of the markedly effective rate and the effective rate). The effective criteria were as follows: symptoms such as shortness of breath, sitting breath and the ability to cough pink foam sputum were significantly improved after treatment, and the severity of cardiac function decreased by more than 2 grades compared with that before treatment. According to the effective criteria, disease-related symptoms improved after treatment, and cardiac function decreased by 1 grade compared with that before treatment. Invalid criteria: disease-related symptoms did not improve after treatment, cardiac function grade did not change, and even the disease further developed [10].

(3) Changes in cardiac function indices between groups were recorded. The left ventricular diameter (LV), left atrial diameter (LA), interventricular septum (IVS), left ventricular posterior wall thickness (LVPW), left ventricular shortening fraction (FS), cardiac diastolic blood flow signal (Vd), cardiac output (CO) and cardiac functional end-diastolic volume (SV) were measured by B-ultrasound before and after treatment.

Statistical processing

After the analysis and summary, the relevant data in the study were entered into the statistical software SPSS 22.0 for processing. Categorical data between groups are presented as percentages (%), while normally distributed data are presented as the mean ± standard deviation (SD). Chi-square tests were used for categorical data comparisons, whereas t tests were used for normally distributed measurement data. Statistically significant differences between test data were defined as P < 0.05.

Results

Comparison of the BNP index among the groups

Based on the data presented in Fig. 1, no significant difference was observed in the BNP levels between the two groups before treatment (p = 0.977). However, following treatment, the BNP levels in the observation group were significantly lower than those in the control group (p = 0.001).

Fig. 1

Comparison of the changes in BNP index levels between the two groups of elderly patients with heart failure

Comparison of clinical efficacy between groups

As depicted in Table 2, the overall clinical effectiveness rate among subjects in the observation group was significantly greater than that in the control group (p = 0.023).

Table 2 Compare the clinical efficacy of two groups of elderly patients with heart failure [n (%)]

Comparison of cardiac function indices between groups

Table 3 shows that before the implementation of the treatment, there was no significant difference between the measured values of LV, LA, AO, IVS, LVPW, FS, Vd, SV and CO in the observation group and the control group (p > 0.05). After therapy, the measured values of LV, LA, FS, Vd, SV and CO in the observation group were significantly lower than those in the control group (p < 0.05), and the AO values in the observation group were significantly greater than those in the control group (p < 0.05). No significant difference was found in the IVS or LVPW between the two groups and the control group.

Table 3 Comparison of cardiac function indexes between the two groups of elderly sufferers with heart failure

Discussion

Heart failure in elderly individuals presents significant challenges due to its adverse impact on health and quality of life. The main findings of this study indicate that recombinant human brain natriuretic peptide (rhBNP) significantly improves clinical outcomes in elderly patients with heart failure. Specifically, we observed that patients in the observation group, who received rhBNP treatment, demonstrated markedly lower BNP levels post-treatment compared to the control group. Additionally, the overall clinical effectiveness rate and cardiac function indices such as LV, LA, FS, Vd, SV, and CO were significantly better in the observation group after therapy. These results underscore the potential of rhBNP as an effective therapeutic option for managing heart failure in the elderly population, addressing the limitations of current pharmacological interventions.

Conventional drug therapies have shown efficacy in alleviating symptoms and improving quality of life for elderly individuals with chronic heart failure. Diuretics, ACE inhibitors (ACEIs), β-blockers, and digitalis are commonly used to treat chronic heart failure in elderly individuals. Diuretics help reduce edema and cardiac load, thereby improving symptoms such as dyspnea. ACE inhibitors and β-blockers reduce cardiac load and oxygen consumption, leading to improved cardiac function [11]. Digitalis drugs enhance cardiac contractility and pumping capacity, further enhancing treatment outcomes. However, conventional treatments have limitations. Elderly patients often present with multiple complications requiring multidrug therapy, which can increase the risk of drug interactions. Diuretics may cause electrolyte imbalances, while ACE inhibitors and β-blockers may lead to hypotension and renal function impairment. Additionally, age-related changes in drug metabolism and excretion necessitate dose adjustments. Moreover, while conventional therapies alleviate symptoms, they may not halt disease progression entirely, and patients may experience gradual deterioration over time. Furthermore, the presence of arrhythmias and atrial fibrillation in most elderly heart failure patients adds complexity to treatment [12]. Some drugs in conventional regimens may exacerbate arrhythmias or interact with antiarrhythmic agents, impacting treatment efficacy.

Heart failure progresses rapidly in elderly individuals, and regular monitoring is required to detect exacerbations [13]. Elevated BNP levels indicate severe myocardial damage and a heightened risk of poor prognosis. Monitoring BNP levels helps evaluate the condition and prognosis of elderly heart failure patients, guiding treatment plans accordingly. The study findings revealed significantly lower BNP levels in the observation group than in the control group, suggesting that therapy reduces BNP levels and mitigates myocardial damage. RhBNP likely achieves this by inhibiting BNP synthesis in cardiac cells and promoting its degradation by regulating enzyme activity [14]. Given that heart failure is characterized by reduced cardiac pumping function and increased cardiac load, rhBNP may enhance myocardial contractility, reduce load, and improve diastolic function, thereby decreasing BNP levels. Additionally, rhBNP may mitigate cardiac fibrosis, improve myocardial tissue structure and function, and further reduce BNP levels [15].

The results demonstrated a notably greater total clinical effectiveness rate in the observation group than in the control group, accompanied by superior cardiac function indices, indicating the efficacy of rhBNP in improving symptoms and cardiac function in elderly chronic heart failure patients. This improvement can be attributed to the ability of rhBNP to enhance cardiomyocyte energy metabolism and function, addressing the weakened myocardial function observed in these patients. By increasing cardiomyocyte contractility and improving cardiac pumping function, rhBNP effectively alleviates heart failure symptoms associated with diminished myocardial contractility. Furthermore, rhBNP treatment reduces myocardial fibrosis, a key pathological feature of heart failure in elderly individuals, thereby preserving myocardial tissue structure and function [16]. The antioxidative properties of rhBNP mitigate oxidative stress-induced cardiomyocyte damage, a common consequence of heart failure pathology. By reducing free radical production and subsequent cardiomyocyte injury, rhBNP attenuates heart failure symptoms. Additionally, rhBNP improves glomerular artery contractile function, enhances the renal tubular filtration rate, and promotes sodium excretion, thereby reducing cardiac load. Moreover, rhBNP modulates sympathetic excitability, inhibits neuroendocrine hormone secretion, and exerts protective effects on vascular endothelial cells, enhancing coronary microcirculation and ameliorating disease symptoms.

Our study has several strengths. It focuses on an elderly population often underrepresented in research. The case-control design provides a robust comparison between treatment and control groups. Comprehensive data on population characteristics, including LVEF, comorbidities, and medications, enhance the generalizability of our findings. We provide detailed insights into rhBNP’s therapeutic potential and safety for elderly patients. Lastly, our statistically validated results ensure reliability and clinical relevance. The limitations of this study should be acknowledged. First, the sample size was relatively small, which may affect the generalizability of the findings. Additionally, this was a retrospective analysis of medical records, which inherently carries the risk of bias and incomplete data. Furthermore, long-term follow-up studies to assess the sustained effects of rhBNP therapy on elderly patients with chronic heart failure are lacking. Last, the study did not explore potential adverse effects or safety concerns associated with rhBNP treatment. These limitations highlight the need for larger prospective studies with longer follow-up periods to validate the efficacy and safety of rhBNP therapy in this population.

Conclusion

In conclusion, rhBNP shows promise for treating heart failure in elderly patients. Our study highlights the potential of rhBNP to improve symptoms and cardiac function in this population. However, further research is needed to address several gaps in the current knowledge. Future initiatives should focus on larger-scale studies to confirm these findings, elucidate optimal dosing regimens, and assess long-term safety and efficacy. Additionally, exploring the potential mechanisms underlying the therapeutic effects of rhBNP in elderly heart failure patients could provide valuable insights for clinical practice.