# Application of Combined Detection of Echocardiography and Serum NT-ProBNP in the Diagnosis of Diastolic Heart Failure and Its Effect on Left Ventricular Morphology and Diastolic Function

Authors: Wei Yang; Zhonghua Zhang; Defeng Liang
Journal: Evidence-Based Complementary and Alternative Medicine
 (2022)

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## Abstract

Objective. This study is to assess the application of combined detection of echocardiography and serum N-terminal pro B-type natriuretic peptide (NT-ProBNP) in the diagnosis of diastolic heart failure (DHF) and its effect on left ventricular morphology and diastolic function. Methods. Thirty patients with DHF with enrolled in our hospital between January 2019 and January 2021 were included in the experimental group, and thirty healthy individuals during the same period were included in the control group. The blood pressure, heart rate (HR), left ventricular morphology, diastolic function, and serum NT-ProBNP levels were compared between the two groups. Results. DHF was associated with higher levels of diastolic blood pressure (DBP), systolic blood pressure (SBP), HR, left ventricular diameter (LVD), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), left atrial volume index (LAVI), left ventricular end-diastolic volume (LVEDV), serum NT-ProBNP, maximum early ventricular filling velocity/early diastolic velocity of the mitral annulus (E/Ea) ratio, and aortic regurgitation (AR) and lower levels of left ventricular ejection fraction (LVEF), flow propagation velocity (VP), and systolic/diastolic (S/D) ratio versus healthy subjects (all at P<0.05). Conclusion. The combined detection of echocardiography and serum NT-ProBNP yields a high clinical value in the diagnosis of DHF deficiency, as it can accurately evaluate the patient's left heart morphology and diastolic function, so it is worthy of clinical promotion and application.


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## Body

## 1. Introduction

Diastolic heart failure (DHF) is a heart failure that occurs due to impaired filling of the left ventricle during diastole, reduced stroke volume, and increased left ventricular end-diastolic pressure, as a result of impaired active relaxation of the left ventricle in diastole, reduced myocardial compliance, and cardiomyocyte hypertrophy with interstitial fibrosis. DHF usually precedes systolic heart failure and is closely related to cardiomyopathy, pulmonary hypertension, and atrial fibrillation [1–5]. DHF is a complex clinical syndrome in which the ventricular pumping capacity and cardiac output are reduced, resulting in failure to meet the metabolic needs of the body.Echocardiography is a key method to evaluate the structure and function of the heart. It is noninvasive and can accurately evaluate the heart function and structural information, which is of great significance in the diagnosis of heart failure [6, 7]. Human B-type brain natriuretic peptide (BNP) is secreted from the heart, and brain natriuretic peptide N-terminal precursor peptide (NT-ProBNP) is the amino-terminal fragment cleaved during the secretion of BNP, which can better reflect the heart function [8, 9]. BNP can promote sodium excretion, diuresis, and vasodilation and can counteract the vasoconstrictive effects of the renin-angiotensin-aldosterone system. Cardiac dysfunction (changes in ventricular load and ventricular wall tension) considerably activates the natriuretic peptide system, and increased ventricular load leads to the release of BNP. BNP is widely distributed in the brain, spinal cord, heart, and lung tissues, with the highest content in the heart but not in the left ventricle. The high expression of BNP in the left ventricle is attributable to the elevated ventricular wall retraction, and therefore, BNP can be used as a clinically reliable and population-based indicator to evaluate the prognosis of DHF. This article analyzed the application of combined detection of echocardiography and serum NT-ProBNP in the diagnosis of diastolic heart failure and its impact on left heart morphology and diastolic function. The report is presented as follows.


## 2. Materials and Methods

### 2.1. General Information

Thirty patients with DHF admitted to our hospital from January 2019 to January 2021 were included in the experimental group, and 30 healthy patients during the same period after physical examination were included in the control group. In the experimental group, there were 18 males and 12 females, ranging from 52 to 70 years, with an average age of (64.5 ± 4.7) years; among them, there were 13 cases of ischemic heart disease, 8 cases of hypertensive heart disease, and 9 cases of dilated cardiomyopathy. According to the New York Heart Academy (NYHA) cardiac function classification, there were 14 cases in class II, 10 cases in class III, and 6 cases in class IV. In the control group, there were 14 males and 16 females, ranging from 50 to 73 years, with an average age of (65.1 ± 4.9) years. The two groups presented no significant difference regarding the general informationP>0.05. This study was approved by the Xianghe County People’s Hospital, No. 90717s/19.


### 2.2. Inclusion Criteria and Exclusion Criteria

Inclusion criteria were as follows: ① patients who met the DHF diagnostic criteria in the “Chinese Guidelines for the Diagnosis and Treatment of Heart Failure 2014”; ② those with typical symptoms and signs of congestive heart failure such as exertional dyspnea; ③ those with left ventricular ejection fraction (LVEF) > 50%; ④ those with evidence of left ventricular diastolic dysfunction confirmed by echocardiography; ⑤ those without heart valve disease confirmed by echocardiography.


### 2.3. Treatment

The patients received baseline treatment with diuretics (furosemide tablets 20 mg 1–2 times/day), ACEI (perindopril tablets 2–4 mg 1 time/day),β-blockers (metoprolol succinate tablets 23.75–47.5 mg 1 time/day), and sodium and water restriction and oxygenation. The efficacy was evaluated after two weeks of continuous treatment.


### 2.4. Detection Method

Before the examination, the diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) of the two groups were measured. PHLIPS IU elite Color Doppler ultrasound system was used, with a sector probe frequency of 1–5 MHz. The long-axis view of the left ventricle next to the sternum was used to detect the left ventricular diameter (LVD), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), and left ventricular end-diastolic volume (LVEDV). The dynamic images of the apical four-chambered heart and two-chambered heart were used to measure the left atrial volume index (LAVI) and LVEF. The apical four-chambered section was used to determine the flow propagation velocity (VP), maximum early ventricular filling velocity/early diastolic velocity of the mitral annulus (E/Ea) ratio, systolic/diastolic (S/D) ratio, and aortic regurgitation (AR).Serum NT-ProBNP level determination: 4 ml of morning peripheral venous blood was collected after the patients fasted for 12 hours, placed in a heparin anticoagulation tube, and centrifuged at 4000 r/min for 5 minutes to separate the serum. Fluorescence immunoassay (Access automatic biochemical analyzer, Beckman, USA) was used to determine the serum NT-ProBNP levels. The operation was carried out in strict accordance with the instructions of the kit.


### 2.5. Outcome Measures

(1) The DBP, SBP, and HR were compared between the two groups. (2) The LVD, IVST, LVPWT, LVEDV, LAVI, LVEF, VP, E/Ea ratio, S/D ratio, and AR were compared between the two groups. (3) The serum NT-ProBNP levels were compared between the two groups.


### 2.6. Statistical Processing

In this research, the data were processed by SPSS20.0 and GraphPad Prism 7 (GraphPad Software, San Diego, USA) was used to plot the graphics. The research included count data and measurement data. The measurement data were represented by (‾x ± s), using a t-test. The count data were represented by (n(%)), using the X2 test. P<0.05 indicated that the difference was statistically significant.


## 2.1. General Information

Thirty patients with DHF admitted to our hospital from January 2019 to January 2021 were included in the experimental group, and 30 healthy patients during the same period after physical examination were included in the control group. In the experimental group, there were 18 males and 12 females, ranging from 52 to 70 years, with an average age of (64.5 ± 4.7) years; among them, there were 13 cases of ischemic heart disease, 8 cases of hypertensive heart disease, and 9 cases of dilated cardiomyopathy. According to the New York Heart Academy (NYHA) cardiac function classification, there were 14 cases in class II, 10 cases in class III, and 6 cases in class IV. In the control group, there were 14 males and 16 females, ranging from 50 to 73 years, with an average age of (65.1 ± 4.9) years. The two groups presented no significant difference regarding the general informationP>0.05. This study was approved by the Xianghe County People’s Hospital, No. 90717s/19.


## 2.2. Inclusion Criteria and Exclusion Criteria

Inclusion criteria were as follows: ① patients who met the DHF diagnostic criteria in the “Chinese Guidelines for the Diagnosis and Treatment of Heart Failure 2014”; ② those with typical symptoms and signs of congestive heart failure such as exertional dyspnea; ③ those with left ventricular ejection fraction (LVEF) > 50%; ④ those with evidence of left ventricular diastolic dysfunction confirmed by echocardiography; ⑤ those without heart valve disease confirmed by echocardiography.


## 2.3. Treatment

The patients received baseline treatment with diuretics (furosemide tablets 20 mg 1–2 times/day), ACEI (perindopril tablets 2–4 mg 1 time/day),β-blockers (metoprolol succinate tablets 23.75–47.5 mg 1 time/day), and sodium and water restriction and oxygenation. The efficacy was evaluated after two weeks of continuous treatment.


## 2.4. Detection Method

Before the examination, the diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) of the two groups were measured. PHLIPS IU elite Color Doppler ultrasound system was used, with a sector probe frequency of 1–5 MHz. The long-axis view of the left ventricle next to the sternum was used to detect the left ventricular diameter (LVD), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), and left ventricular end-diastolic volume (LVEDV). The dynamic images of the apical four-chambered heart and two-chambered heart were used to measure the left atrial volume index (LAVI) and LVEF. The apical four-chambered section was used to determine the flow propagation velocity (VP), maximum early ventricular filling velocity/early diastolic velocity of the mitral annulus (E/Ea) ratio, systolic/diastolic (S/D) ratio, and aortic regurgitation (AR).Serum NT-ProBNP level determination: 4 ml of morning peripheral venous blood was collected after the patients fasted for 12 hours, placed in a heparin anticoagulation tube, and centrifuged at 4000 r/min for 5 minutes to separate the serum. Fluorescence immunoassay (Access automatic biochemical analyzer, Beckman, USA) was used to determine the serum NT-ProBNP levels. The operation was carried out in strict accordance with the instructions of the kit.


## 2.5. Outcome Measures

(1) The DBP, SBP, and HR were compared between the two groups. (2) The LVD, IVST, LVPWT, LVEDV, LAVI, LVEF, VP, E/Ea ratio, S/D ratio, and AR were compared between the two groups. (3) The serum NT-ProBNP levels were compared between the two groups.


## 2.6. Statistical Processing

In this research, the data were processed by SPSS20.0 and GraphPad Prism 7 (GraphPad Software, San Diego, USA) was used to plot the graphics. The research included count data and measurement data. The measurement data were represented by (‾x ± s), using a t-test. The count data were represented by (n(%)), using the X2 test. P<0.05 indicated that the difference was statistically significant.


## 3. Results

### 3.1. Comparison of Blood Pressure and HR

The experimental group obtained higher DBP, SBP, and HR levels than the control groupP<0.05 (Table 1).Table 1
Comparison of blood pressure and HR (‾x ± s).
GroupsnDBP (mmHg)SBP (mmHg)HR (beats/min)Control group3078.52 ± 3.10119.34 ± 3.3167.34 ± 2.51Experimental group3091.64 ± 7.23156.75 ± 14.2297.55 ± 9.37t value9.13514.03417.058P value<0.05<0.05<0.05


### 3.2. Comparison of LVD, IVST, and LVPWT Levels

Higher levels of LVD, IVST, and LVPWT levels were observed in the experimental group than in the control groupP<0.05 (Table 2).Table 2
Comparison of LVD, IVST, and LVPWT levels (‾x ± s).
GroupsnLVD (mm)IVST (mm)LVPWT (mm)Control group3032.13 ± 3.429.04 ± 0.878.57 ± 1.16Experimental group3044.28 ± 3.3411.88 ± 1.9611.49 ± 1.43t value13.9217.2548.686P value<0.05<0.05<0.05


### 3.3. Comparison of LAVI, LVEDV, and LVEF Levels

The LAVI level of the experimental group exceeded that of the control group. Strong evidence of the higher LVEDV level in the experimental group was found versus the control group; a lower level of LVEF was seen in the experimental group than in the control groupP<0.05 (Table 3).Table 3
Comparison of LAVI, LVEDV, and LVEF levels (x ± s).
GroupLAVI (ml/m2)LVEDV (ml)LVEF (%)Experimental group32 ± 8182.35 ± 16.2555.40 ± 4.45Control group26 ± 5173.38 ± 16.7964.13 ± 4.07t value3.4842.1037.929P value0.0090.040＜0.01


### 3.4. Comparison of Serum NT-ProBNP Levels

The experimental group showed a remarkably higher NT-ProBNP level than the control groupP<0.05 (Figure 1).Figure 1
Comparison of serum NT-ProBNP levels (‾x ± s). The abscissa represents the control group and the experimental group, and the ordinate represents the serum NT-ProBNP level (pg/ml). The serum NT-ProBNP level of the control group is (184.68 ± 18.47) pg/ml. The serum NT-ProBNP level of the experimental group is (2034.52 ± 211.45) pg/ml. The symbol ∗ indicates that there is a significant difference in the NT-ProBNP level between the two groups (t = 47.735, P≤0.001).


### 3.5. Comparison of Left Ventricular Diastolic Function

As shown in Table4, the experimental group yielded higher E/Ea ratio and AR levels and lower VP and S/D ratio levels, than the control group P<0.05.Table 4
Comparison of left ventricular diastolic function (‾x ± s).
GroupsnE/EaVP (cm/s)S/DAR (cm/s)Control group307.41 ± 3.240.68 ± 0.091.45 ± 0.3420.56 ± 6.36Experimental group3016.57 ± 2.10.40 ± 0.130.98 ± 0.2633.44 ± 7.90t value12.9949.6996.0146.956P value<0.05<0.05<0.05<0.05


## 3.1. Comparison of Blood Pressure and HR

The experimental group obtained higher DBP, SBP, and HR levels than the control groupP<0.05 (Table 1).Table 1
Comparison of blood pressure and HR (‾x ± s).
GroupsnDBP (mmHg)SBP (mmHg)HR (beats/min)Control group3078.52 ± 3.10119.34 ± 3.3167.34 ± 2.51Experimental group3091.64 ± 7.23156.75 ± 14.2297.55 ± 9.37t value9.13514.03417.058P value<0.05<0.05<0.05


## 3.2. Comparison of LVD, IVST, and LVPWT Levels

Higher levels of LVD, IVST, and LVPWT levels were observed in the experimental group than in the control groupP<0.05 (Table 2).Table 2
Comparison of LVD, IVST, and LVPWT levels (‾x ± s).
GroupsnLVD (mm)IVST (mm)LVPWT (mm)Control group3032.13 ± 3.429.04 ± 0.878.57 ± 1.16Experimental group3044.28 ± 3.3411.88 ± 1.9611.49 ± 1.43t value13.9217.2548.686P value<0.05<0.05<0.05


## 3.3. Comparison of LAVI, LVEDV, and LVEF Levels

The LAVI level of the experimental group exceeded that of the control group. Strong evidence of the higher LVEDV level in the experimental group was found versus the control group; a lower level of LVEF was seen in the experimental group than in the control groupP<0.05 (Table 3).Table 3
Comparison of LAVI, LVEDV, and LVEF levels (x ± s).
GroupLAVI (ml/m2)LVEDV (ml)LVEF (%)Experimental group32 ± 8182.35 ± 16.2555.40 ± 4.45Control group26 ± 5173.38 ± 16.7964.13 ± 4.07t value3.4842.1037.929P value0.0090.040＜0.01


## 3.4. Comparison of Serum NT-ProBNP Levels

The experimental group showed a remarkably higher NT-ProBNP level than the control groupP<0.05 (Figure 1).Figure 1
Comparison of serum NT-ProBNP levels (‾x ± s). The abscissa represents the control group and the experimental group, and the ordinate represents the serum NT-ProBNP level (pg/ml). The serum NT-ProBNP level of the control group is (184.68 ± 18.47) pg/ml. The serum NT-ProBNP level of the experimental group is (2034.52 ± 211.45) pg/ml. The symbol ∗ indicates that there is a significant difference in the NT-ProBNP level between the two groups (t = 47.735, P≤0.001).


## 3.5. Comparison of Left Ventricular Diastolic Function

As shown in Table4, the experimental group yielded higher E/Ea ratio and AR levels and lower VP and S/D ratio levels, than the control group P<0.05.Table 4
Comparison of left ventricular diastolic function (‾x ± s).
GroupsnE/EaVP (cm/s)S/DAR (cm/s)Control group307.41 ± 3.240.68 ± 0.091.45 ± 0.3420.56 ± 6.36Experimental group3016.57 ± 2.10.40 ± 0.130.98 ± 0.2633.44 ± 7.90t value12.9949.6996.0146.956P value<0.05<0.05<0.05<0.05


## 4. Discussion

Clinically, heart failure can be divided into systolic heart failure and DHF according to different pathologies, with growing morbidity in recent years [10]. The pathogenesis of DHF is calcium ion dysfunction, which is triggered by abnormal calcium ion “evacuation” function. Factors that can cause intracellular calcium uptake and efflux will result in calcium overload, thereby compromising the patient’s ventricular diastolic function [11–13]. In addition, cardiomyocyte stiffness, left ventricular pressure overload, volume reduction, and heart rate changes are also associated with DHF [14, 15]. Echocardiography is a widely used diagnostic method in clinical practice that can objectively and accurately evaluate the cardiac function of patients and monitor the changes in cardiac function in real time, with the advantages of noninvasiveness, easy operation, and repeatability. BNP is a peptide cardiogenic hormone in the natriuretic family and is synthesized and secreted by ventricular myocytes [16–18]. NT-ProBNP is an inactive peptide fragment produced 1 : 1 with BNP and exists in the blood circulation. With a long half-life, high content, stable concentration, and fewer interference factors, NT-ProBNP possesses a high sensitivity and negative predictive value [19, 20]. Serum NT-ProBNP regulates the cardiovascular system, and damage to the ventricular structure and dysfunction will increase serum NT-ProBNP. Therefore, the aberrant serum NT-ProBNP levels are associated with the severity of cardiac function damage [21, 22].Heart failure is a progressive disease that can be monitored by conventional echocardiography, but patients with an atrial cavity, ventricular wall thickening, valve damage, or systolic-diastolic function during disease progression show normal echocardiographic performance. In the presence of risk factors, the septum thickens and the left atrium enlarges [6], and in patients with abnormal diastolic function but normal systolic function, the echocardiogram shows an increase in the degree of cardiac remodeling and a positive correlation with the degree of disease exacerbation [7]. It has been established that Em and Am are accurate indices of diastolic function in echocardiographic testing with high sensitivity [8] and there is a correlation between E/Ea and filling pressures, mostly found in patients with mitral fusion and atrial fibrillation. Research by Aquaro et al. [23] showed that the blood pressure and heart rate levels of patients with DHF had abnormally high levels, which is correlated with the patient’s cardiac dysfunction. In the present study, the experimental group showed higher levels of DBP, SBP, HR, LVD, IVST, and LVPWT than the control group (all P<0.05, suggesting that echocardiography can accurately reflect the left heart morphology of patients with heart failure). The study by Deanacristian et al. [24] has confirmed that LAVI is an independent predictor of heart failure and atrial fibrillation, and it is also a key structural change in DHF. Here, higher LAVI, LVEDV, and NT-ProBNP levels and lower LVEF levels of the experimental group were observed than of the control group (all P<0.05), and the NT-ProBNP levels were positively correlated with the LVEDV levels. It demonstrates that the heart function of patients with DHF is correlated with the level of serum NT-ProBNP and the combination of echocardiography and serum NT-ProBNP is more accurate in the detection of DHF. The experimental group had higher E/Ea ratio and Ar levels but lower VP and S/D ratio levels than the control group P<0.05, which was consistent with the results of a prior study [25], indicating that in the event of abnormal diastolic function of patients with DHF, E/Ea can accurately evaluate the left ventricular filling pressure and the increase in AR is closely related to the ventricular filling. The decrease in VP and S/D ratio levels is attributable to their independence from cardiac preload.Ophiopogonis Radix exhibits stabilizing and positive inotropic effects on cardiac myocyte membranes [5], and Fructus Schisandrae chinensis inhibits the activity of Na +-K + - adenosine triphosphatase to affect Na +-K + and Na +-Ca2 + exchange and increase Ca2 + inward flow, increasing the concentration of cardiac calmodulin bound to Ca2 +, which is conducive to enhancing myocardial contractility, improving microcirculation, and correcting the pathological abnormalities in heart failure [6, 7]. Ginseng polysaccharides and ginsenosides are the main active components of ginseng with positive inotropic effects, protecting ischemic myocardium and enhancing ventricular contractile function [8, 9]. Astragali Radix can protect cardiomyocytes and reverse ventricular hypertrophy [10, 11]. Therefore, the components selected in this formula are supported by good evidence from modern pharmacological studies for controlling the progression of heart failure and improving clinical treatment. It was found that microRNA-21 expression was upregulated in cardiac fibroblasts of heart failure patients, which was significantly higher than its expression in normal cardiomyocytes. Under stressful conditions, microRNA-21 overexpression in cardiac fibroblasts can significantly activate ERK-MAPK pathway proteins and promote fibroblast proliferation and fibrosis [26].


## 5. Conclusion

The combined detection of echocardiography and serum NT-ProBNP yields a high clinical value in the diagnosis of DHF, as it can accurately evaluate the patient's left heart morphology and diastolic function, so it is worthy of clinical promotion and application. The innovation of this study lies in the use of combined echocardiography combined with the serum NT-ProBNP test in the diagnosis of diastolic heart failure, which provides promising medical guidance. The limitation lies in the absence of diagnostic efficacy and the lack of evaluation of the specificity and sensitivity of the combined detection of the two methods in the present study, which will be further investigated in the future to obtain more reliable clinical data.



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