Effect of Levosimendan injection on plasma NT-proBNP and urocortin II levels in patients with chronic heart failure (CHF)
[Abstract] Objective To observe the effects of Levosimendan (LEV) on plasma NT-proBNP and urocortin II levels in patients with chronic heart failure (CHF), and to evaluate its clinical efficacy and safety. Methods Sixty-four patients with CHF were selected, of which 29 patients in the observation group were treated with levosimendan and 35 patients in the control group were treated with dobutamine. The changes of vital signs, degree of dyspnea, ejection fraction and plasma NT-proBNP and urocortin II biochemical indexes were observed before and after the drug administration in both groups. Results There was no statistical difference in the basic vital indicators between the two groups before drug administration (P0.05). When comparing 24 h after drug discontinuation with 24 h before and after drug administration, levosimendan showed significant differences in increasing ejection fraction and decreasing plasma NT-proBNP and urocortin II levels (P<0.05). There were 2 cases (6.9%) of adverse drug reactions in the observation group and 5 cases (14.3%) in the control group (P0.05), and no serious adverse events occurred in both groups. Conclusion Levosimendan can reduce dyspnea, improve general condition, increase ejection fraction, and significantly decrease plasma NT-proBNP and urocortin II levels in CHF patients. Huangfu Weizhong, Department of Geriatrics, Affiliated Hospital of Inner Mongolia Medical University
[Keywords] Levosimendan; dobutamine; chronic heart failure; NT-proBNP; urocortin II
Effects of Levosimendan on plasma NT-proBNP, urocortin II in patients with chronic heart failure
LI Wen-xia Xu-Yun HUANG Fu-weizhong
(Nongken Nada Hospital in Hainan Province, Danzhou, Hainan 571700 Department of old age, Affiliated Hospital, Inner Mongolia Medical College, Hohhot 010050)
Abstract: Objective To evaluate the efficacy and safety of levosimendan in the treatment of chronic heart failure(CHF) through objective values of NT- proBNP, urocortin II on plasma.Methods Randomized, open, controlled clinical trial was conducted in 64 patients with CHF.29 of the patients were treated with levosimendan in Vital signs, dyspnea, eject fraction (EF), NT-proBNP and urocortin II in blood biochemistry. Vital signs, dyspnea, eject fraction (EF), NT-proBNP and urocortin II in blood biochemical index before and after drug administration were observed . of the EF, in the decrease of NT-proBNP and urocortin II between the trial group and control group, but no significant diferences were found in LVDD.Side effects were found in 2 patients 0f the trial group and 5 patients of the control group.Conclusion Levosimendan is effective in treating CHF and it can Levosimendan is effective in treating CHF and it can relieve dyspnea,improve the general condition ,increase EF,decrease NT-proBNP and urocortin II.
[Key words] Levosimendan;dobutamine;chronic heart failure;NT-proBNP;urocortin II
Chronic heart failure (CHF) is the final destination of most heart diseases and is the most morbid and mortal disease in the world.
Heart failure is one of the most morbid and mortal diseases in the world, and drug interventions with β-adrenergic receptor blockers, angiotensin-converting enzyme and aldosterone receptor antagonists and diuretics have sufficiently increased the survival rate of patients, but the results are still unsatisfactory [1]; the Ca2+ sensitizer, Levosimendan (LEV), is a new class of orthosteric agents used in clinical practice in recent years. Levosimendan (LEV) is a new class of positive inotropic drugs used in clinical practice in recent years, which acts by linking and stabilizing calcium ions leading to conformational changes in troponin C [2] and by opening ATP-sensitive K channels on vascular smooth muscle, thus increasing myocardial contractility without increasing myocardial oxygen consumption, acting as a positive inotropic agent and maintaining hemodynamic stability [3]. It was found [4] that during the formation and development of CHF, the release of brain natriuretic peptide (BNP) and caudal pressin (urocortin II) increases due to hemodynamic abnormalities and neuroendocrine activation as well as myocardial remodeling, which stimulates cardiomyocyte synthesis. In this study, levosimendan was used to treat
In this study, the efficacy and clinical significance of levosimendan in the treatment of CHF were evaluated by measuring the changes of plasma urocortin II, NT-proBNP) and LVDD and LVEF before and after the drug administration.
1 Data and methods
1.1 Clinical data Sixty-four patients with CHF in our hospital from May 2011 to March 2012 met the inclusion criteria and were diagnosed by detailed physical examination, electrocardiogram, X-ray chest film, cardiac ultrasound and blood and urine routine, blood glucose, liver and kidney function, among which 39 were male and 25 were female, and were divided into two groups according to the principle of random assignment: observation group (29 cases) and control group (35 cases).
1.1.1 Inclusion criteria (1) inpatients aged 50-80 years old with no restriction on gender; (2) those with poor conventional treatment; (3) those who conformed to New York Heart Association cardiac function class III-IV or killip classification; (4) those with LVEF less than 40% confirmed by echocardiography; (5) those with pulmonary edema one week after myocardial infarction.
1.1.2 Exclusion criteria: no major organ diseases such as brain, liver, kidney, lung and endocrine, and exclude patients with combined tumor.
1.2 Drug administration method Anti-HF treatment was routinely given, including removal of precipitating factors, restriction of fluid intake, rest, treatment of primary diseases, administration of vasodilators and diuretics, etc. Observation group: The initial loading dose of levosimendan (12.5 mg*5 ml, produced by Qilu Pharmaceutical Co., Ltd.) was 12 μg/kg, and the intravenous injection time was >10 min, and then it was pumped continuously for 24 h at 0.075 μg- kg-1.min-1 by micro-pump. Control group: dobutamine (20 mg*2 ml, produced by Shanghai Ltd.) was initially administered intravenously at 2 μg.kg-1.min-1 and then increased to 4 μg.kg-1.min-1 after lh and continued for 24h.
1.3 Vital signs were monitored and signs of respiratory distress and pulmonary rales, jugular venous angina, hepatomegaly, lower limb edema and weakness were observed. The serum was extracted and stored in polypropylene tubes at -80°C. Serum urocortin II was measured using the Human Urocortin II ELISA kit (detection range: 6.25-400 ng/L), provided by Cusabio Biotechnology Co. The procedure was carried out strictly according to the instructions. Serum NT-proBNP levels were measured using Elecsys 2010 from Roche (Switzerland), and the kit was the Roche Elecsys proBNP kit (detection range: 5 to 35 000 ng/L).) , LVEF, LVDD values were monitored by echocardiography.
1.4 Determination of efficacy The efficacy was determined after 24 h of treatment. Significant effect: symptoms and signs of dyspnea disappeared or basically disappeared, and cardiac function improved > grade II; effective: symptoms were reduced, and cardiac function improved grade I; ineffective: symptoms were basically the same as before treatment or did not reach the above criteria, and cardiac function did not change or deteriorated.
1.5 Statistical methods SPSS16.0 software was applied for statistical analysis. The measurement data were expressed as mean±standard deviation (x±s), and the t-test was used for comparison between groups; the count data were expressed as rate (%), and the x2 test was used for comparison between groups. P
2.1 Basic information
Table 1 Comparison of basic information between the observation group and the control group n(%)
Item
Observation group
Control group
Male
17 (58.6%)
19 (54.3%)
Female
12 (41.4%)
16 (45.7%)
Age
66.2±4.5
67.3±5.7
Height
159.6±6.0
158.5±5.0
Body weight
65.6±12.6
66.6±10.4
Hypertensive disease
14 (48.3%)
15 (42.9%)
Coronary heart disease
10 (34.5%)
12 (28.6%)
Myocardial infarction
5 (17.2%)
8 (18.5%)
Duration of disease
9.8±4.5
9.6±5.6
Cardiac function
Class III
Class IV
16 (55.2%)
13 (44.8%)
20 (57.1%)
15 (42.9%)
NT-proBNP(ng/L)
4327±310.24
3983±279.63
Urocortin II(ng/L)
12.8±3.6
12.7±3.8
LVDD(mm)
76.1±6.7
76.5±3.9
LVEF (%)
30.2±5.1
31.1±4.7
2.2 Clinical efficacy: the clinical efficacy of the observation group was 55.2%, the efficiency rate was 37.9%, and the inefficiency rate was 6.9%; the clinical efficacy rate of the control group was 34.3%, the efficiency rate was 51.4%, and the inefficiency rate was 14.3%, and the difference between the two groups was statistically significant (P<0.05).
Table 2 Comparison of clinical efficacy of the two groups
Group
Number of cases
Apparent effect
Effective
Ineffective
Adverse reaction
Observation group
29
16 (55.2)
11 (37.9)
2 (6.9)
2 (6.9)
Control group
35
12 (34.3)
18 (51.4)
5 (14.3)
5 (14.3)
Note: Compared with the control group, *P<0.05
2.2 Comparison of markers and ultrasound Blood NT-proBNP and urocortin II levels were significantly reduced in the observation group and the control group after 24 h of treatment, and the reduction was more obvious in the observation group (P<0.01);] LVEF was elevated in both groups 24 h after treatment compared with that before treatment, and it was obvious in the observation group, and both were statistically significant (P<0.05); however, in the observation group and the control group, there was no significant change in LVDD after 24 h after treatment, there was no significant change in LVDD, and there was no significant difference (P>0.05) (see Table 3).
Table 3 Comparison of markers and ultrasound in the 2 groups (x±s)
Group
Number of cases
NT-proBNP(ng/L)
Urocortin II(ng/L)
LVDD(mm)
LVEF(%)
Observation group
29
Before treatment
4327±310.24
12.8±3.6
76.1±6.7
30.2±5.1
24h after treatment
3816±260.15*
10.4±3.9*
75.5±5.4
37.2±6.3*
Control group
35
Before treatment
4292±294.35
12.7±3.8
76.5±3.9
31.1±4.7
24h after treatment
4021±281.42*
11.2±3.2*
75.1±7.1
36.5±5.2*
Note: Compared with pre-treatment, * P<0.05, # P<0.01; compared with control group, △ P<0.05, ☆ P<0.01
Compared with 24 hours after treatment, P<0.05, statistically different.
2.3 Adverse reactions There was one case of headache in the observation group, which was still tolerable; one case of mild decrease in blood pressure, which gradually increased after levosimendan was reduced to 0.005 μg.kg-1.Min-1. In the control group, there were 2 cases of nausea and palpitations, which improved after relevant treatment; both groups successfully completed the treatment, and there was no withdrawal in the middle of the treatment.
3 Discussion
The ultimate goal of CHF treatment is to relieve symptoms, prevent the occurrence of acute loss of CHF, reduce the rehospitalization rate, improve the quality of life of patients, and improve the prognosis. The pathophysiological mechanisms are abnormal hemodynamic changes and abnormal neuroendocrine activation [1]. Abnormal hemodynamic changes in heart failure patients are often accompanied by abnormal neuroendocrine activation and are the main mechanism of heart failure deterioration development, promoting and maintaining the onset and development of myocardial remodeling, which leads to a progressive deterioration development process of heart failure. The hot spots in the treatment of heart failure are improvement of myocardial hemodynamic deterioration and blocking of the neuroendocrine system. The common denominator of the clinically applied traditional positive inotropic drugs digitalis, β-agonists and phosphodiesterase inhibitors is to increase the contractility of cardiac myocytes by increasing the intracellular calcium ion concentration.
The new calcium sensitizer levosimendan (LS) improves cardiac function through a mechanism of action different from that of traditional orthostatic drugs, increasing the sensitivity of cell contractile proteins to Ca2+ and the opening of K+ channels with both cardiotonic and vasodilatory effects, and Ls does not increase myocardial oxygen consumption when cardiotonic [4], making it suitable for cardiotonic therapy in patients with heart failure [5]; it has a unique dual mode of action that increases cardiac output and vasodilation, antagonizing neuroendocrine, anti-inflammatory, anti-apoptotic, and anti-myocardial tonus effects [5]. It does not increase heart rate while improving cardiac pump function [6], providing effective symptomatic relief and improving prognosis without affecting myocardial diastole or increasing the risk of malignant arrhythmias. It improves the hemodynamic parameters and clinical status of CHF low cardiac output syndrome without increasing myocardial oxygen consumption, shortens the duration of intensive care and reduces hospitalization costs, is well tolerated by patients with heart failure and has a low incidence of adverse effects.
NT-proBNP is one of the few blood biochemical markers that have been shown to have diagnostic value in cardiovascular disease, to guide the treatment and prognosis of patients with heart failure, and to have initial clinical application [7], and is now the consensus of the medical community. Plasma NT-proBNP can accurately reflect the decompensation status of heart failure patients and is an important supplement to evaluate the functional status of the heart [8]. urocortin II is a novel cardioprotective peptide that can play a good anti-heart failure role by regulating the pressure-volume homeostasis in heart failure [9]. Some scholars have found that urocortin II increases cardiac output, reduces peripheral vascular resistance and arterial blood pressure, and improves cardiac function during the development of heart failure. It is a powerful therapeutic target for patients with heart failure [10]; blood samples from patients with heart failure may help to identify the different stages of heart failure, and it has been suggested that both UCN II, NT-proBNP may be one of the independent predictors of chronic heart failure. Therefore, simultaneous monitoring of plasma NT-proBNP, urocortin II levels in this trial can more accurately assess the therapeutic effect of levosimendan and provide stronger blood biochemical evidence for the clinical treatment of heart failure patients.
The results showed that the clinical significant rate and efficiency of the observation group were statistically significant compared with the control group, and levosimendan treatment for CHF, could significantly alleviate the symptoms and signs of dyspnea and improve the cardiac function and hemodynamic indexes. By monitoring the biochemical indexes such as plasma NT-proBNP and urocortin II and objective indexes such as left ventricular end-diastolic diameter (LVDD) and LVEF before and 24h after treatment, it was confirmed that levosimendan continued to exert its positive inotropic effect after 24h of treatment, improving myocardial contractility, increasing LVEF, improving cardiac function, and significantly reducing plasma NT-proBNP, urocortin II and LVEF. proBNP and urocortin II levels, further elucidating the dichotomous effects of levosimendan and its scientific assessment of patient prognosis, with fewer adverse effects and longer-lasting effects on cardiac function compared with the control group. However, the sample size of this trial was small and the long-term efficacy and biochemical parameters were not monitored.
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