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Research Article

Left ventricular long-axis ultrasound strain (GLS) is an ideal indicator for patients with anti-hypertension treatment

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Pages 20-25 | Received 30 Jun 2021, Accepted 15 Aug 2021, Published online: 15 Sep 2021

ABSTRACT

Background

Primary hypertension is one of the most well-known risk factors for cardiovascular disease. Currently, there is still no ideal indicator for left ventricular end-diastolic pressure.

Methods

73 hypertension patients and 37 healthy people were enrolled in this study. Each member was examined with conventional echocardiography including multiple indicators such as Peak mitral valve flow velocity (E, A), E/A, left atrial volume index (LAVl), tissue Doppler (PW-TDI) peak velocities during early and late diastolic mitral valve flow (e ‘), E/e ‘, and GLS. We have collected clinical data from all enrolled members. The above cardiac ultrasound indicators were obtained before the antihypertensive treatment, one month and three months after treatment.

Results

Left ventricular end-diastolic pressure (LVEDP) was positively correlated and negatively correlated with GLS (r = 0.638, P < .01) and E/e’ (r = −0.578, P < .05), respectively. The hypertensives had lower e’ value and higher values of GLS, E/e’, and LAVI than the control group (P < .05). GLS and E/e’ were significantly lower in hypertension group than those in the Control group after one month and three months of treatment (P < .05). The improvement rate of GLS was significantly higher than those in the improvement rate of e’, E/e’, LAVI after treatment (p < .05).

Conclusion

The GLS improvement rate was significantly higher than those of e’, E/e’ after one and three-month treatment. Therefore, GLS might be a potential ideal index for patients with anti-hypertension treatment. The results obtained in this study provide useful information for further study.

Introduction

Primary hypertension is a major risk factor for cardiovascular disease. Hypertensive heart disease and heart failure are serious consequences of damage to important target organs by hypertension. Therefore, early treatment of hypertension is particularly important to prevent the occurrence and development of heart failure (Citation1). Blood pressure regulation is a complex pathophysiological process, which is related to many factors such as sympathetic nerve excitation, vascular endothelial dysfunction, insulin resistance and activation of the renin-angiotensin-aldosterone system (Citation2). In the early stage, the body maintained normal pump function of the heart through neurohumoral regulation. However, long-term hypertension can cause a sustained increase in left ventricular load, which result in an increase in left ventricular filling pressure. In order to maintain normal cardiac function, the myocardial cells compensate for contraction and thicken the wall. This is left ventricular hypertrophy or ventricular remodeling (Citation3). Previous studies have shown that left ventricular diastolic reduction (diastolic function) is earlier than the changes in left ventricular morphology and systolic function in early hypertension (Citation4). Therefore, the treatment and follow-up evaluation of left ventricular diastolic dysfunction in early hypertension is an important issue for clinical and scientific research.

At present, the measurement methods of left ventricular end-diastolic pressure mainly include the following: 1) Cardiac catheterization; 2) Myocardial strain analysis by myocardial magnetic resonance; 3) Echocardiography. For echocardiographic analysis, the main techniques include Mitral valve pulsed blood flow Doppler, Left atrial volume index, Doppler pulsed pulmonary vein blood flow spectrum imaging (mitral flow pattern (MFP)), Pulsed wave Doppler tissue imaging ((PW-DTI) pulsed wave Doppler tissue imaging), 2D-STE (Two-Dimensional Ultrasound Speckle Tracking Imaging), and Real-Time Three-Dimensional Echocardiography (RT-TDE) (Citation5). Studies have revealed that contraction and relaxation of the left ventricle are mainly accomplished by a series of complex dynamic changes in cardiac muscle cells. The shortening, elongation, narrowing, widening, twisting, and untwisting of myocardial fibers can cause changes in the length and shape of the heart muscle. Therefore, multiple myocardial deformation movements can be observed, including GLS (longitudinal axis strain of the left ventricle), GCS (longitudinal axis strain of the left ventricle), and GRS (longitudinal axis strain of the left ventricle) (Citation6,Citation7). The relationship between stress and strain can more sensitively reflect the functional characteristics of myocardial tissue than that in pressure-volume. Therefore, the myocardial strain is a direct and objective indicator of myocardial function (Citation8,Citation9). For example, left ventricular longitudinal long-axis strain (GLS) in patients without systolic dysfunction can be helpful in reflecting changes in diastolic function (Citation10,Citation11). Imbalzano et al. Believe that in patients without left ventricular remodeling, the change of GLS is earlier than diastolic function indexes such as e’, E/e’ (Citation12). Mochizuki et al. suggested that GLS can directly reflect the diastolic function of the left ventricle in patients with ejection fraction-preserving heart failure (Citation13).

In this study, we recruited hypertensive patients with negative coronary angiography. Left ventricular end-diastolic pressure (LVEDP) was measured through a cardiac catheter. Meanwhile, we had analyzed the correlations between LVEDP and indexes of echocardiography (E/A, LAVI, e’, E/e’, and GLS). Moreover, we had recorded and analyzed mitral valve blood flow Doppler (E/A), left atrial volume index (LAVI), tissue Doppler (e’, E/e’), and left ventricular longitudinal long axis strain (GLS) after antihypertensive treatment. To explore the subclinical impairment of left the results obtained in this article will be helpful in exploring the subclinical impairment of left ventricular function in early hypertension.

Method and materials

Research object

The Research Ethics Committee of the Xiangya Hospital of Central South University had approved this study. All participating members had carefully read and signed informed consent. All enrolled members were divided into three groups, including 1) hypertensive treatment experimental group: 56 patients with newly diagnosed essential hypertension were followed up. 3) Healthy control group: 37 normal volunteers from the physical examination center were collected. The inclusion criteria are as follows: 1) Newly diagnosed essential hypertension. The diagnostic criteria included not taking antihypertensive drugs, measuring blood pressure three times on a different day, systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg (Citation14); 2) 2) Patients with the previous diagnosis of hypertension and poor blood pressure control. After taking antihypertensive drugs, blood pressure was measured three times on a different day. The systolic blood pressure ≥140 mmHg and/or diastolic blood pressure≥90 mmHg. Moreover, exclusion criteria were as follows: 1) Patients have diagnosed as coronary heart disease; 2) Patients with various types of valvular heart disease; 3) Patients with various types of cardiomyopathy; 4) Patients with atrial fibrillation and atrial flutter; 5) Patients were previously diagnosed with primary and secondary pulmonary hypertension; 6) Patients with secondary hypertension; 7) LVEF <50% of patients with hypertension; 8) Patients with diabetes; 9) Patients with atrioventricular block of IIIII degree; 10) Patients with bradycardia sinus; 11) Patients with bronchial asthma, pulmonary heart disease, hyperthyroid heart disease, hepatic and renal insufficiency, pericardial disease patient, severe anemia, infection, fever, and poor echocardiographic image quality.

Experimental instruments and methods

In this experiment, the instruments used in left ventricular catheter manometry and coronary angiography include MCS type angiography machine (Philips Company, USA), Philips EPIQ 7 color Doppler ultrasound system (probe) Frequency 2.5 MHZ (Philips Company, USA), and Q-Lab11 ultrasound image analysis software. Seventeen patients with hypertension underwent coronary angiography and echocardiography examination. The electrocardiogram was connected during coronary angiography. LVEDP is the left ventricular pressure, which corresponds to the onset of the QRS complex. We measured LVEDP three times and calculated the average. The specific measurement process is as follows: During transthoracic echocardiography, the subjects breathed calmly and their left side was lying. We connected and displayed the ECG measurements of the mitral valve mouth diastolic early and late blood flow spectrum (E peak and A peak). We measured the left atrial diameter through the long-axis section of the left ventricle next to the sternum. Meanwhile, we used the Simpson ’s method to measure the maximum left atrial volume and calculate the left atrial volume index. In the TDI model, we had obtained the peak motion velocity (e’) at various aspects of the early diastolic mitral valve annulus. We calculated the average e ‘and E/e’ values for the four segments of the mitral valve annulus. In the two-dimensional echocardiography mode, we obtained the standard cardiac section of the four-chamber apex, the standard section of the two-chamber apex, and the standard section of the three-chamber cardiogram. Five cardiac cycles were collected each. The above data is saved in DICOM (Digital Imaging and Communications in Medicine) mode and imported into Q-Lab software. We set two basal tracking points and apical tracking points on the four-chamber heart, two-chamber heart, and three-chamber heart sections, and the Q-Lab software automatically analyzes the strain values obtained from the above three sections. Meanwhile, the overall longitudinal long axis strain of the left ventricle is automatically analyzed. 56 patients with hypertension were followed up for 1–3 months to observe the antihypertensive effect. We had re-tested the above-mentioned echocardiographic indicators during the follow-up period.

Analysis and statistics

SPSS22.0 statistical software was used to analyze the data. Measurement data are expressed by mean ± standard deviation. The comparison of before and after self-index was analyzed by paired T-test. The independent-sample t-test is used to compare the measurement data between the groups showing a normal distribution and homogeneity of variance. For group-to-group comparisons with uneven variance, the independent sample approximation t-test was used. Bivariate measurement data were analyzed by the paired rank-sum. The screening of influencing factors of cardiac ultrasonography was performed by stepwise multiple linear regression analysis (αout = 0.15, αin = 0.10). Pearson correlation analysis was used to analyze the correlation between LVEDP and other cardiac ultrasound indicators. P < .05 was statistically significant.

Results

Clinical characteristics comparison between the control group and the hypertensive group

In this study, we have collected multiple clinical characteristics, including Age, height, weight, Body Mass Index(BMI), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Pulse Pressure(PP), Mean Arterial Pressure (MAP), Heart rate, Low-Density Lipoprotein (LDL), Triglyceride (TG), and Total Cholesterol (TC), from the patients in the control group and the hypertensive group (). The results showed that SBP, DBP, PP, and MAP in the hypertensive group were significantly higher than those in the control group (P < .01). Based on the above results, we have further probed the characteristics of the ultrasonic cardiogram of patients in different groups. All data were collected by the same experienced ultrasound physician who was unaware of the patient’s condition. Data from 15 patients with hypertension were used to analyze the peak velocities (E, A peaks), LAVI, and tissue Doppler early mitral valve ankle peak velocity (e ‘peak). The GLS was measured by two observers five times in a row and averaged, and the paired t-test was performed. Baselines of multiple indicators in the healthy group were listed as following: LVEDP = 11.18 ± 3.54 mmHg, E/A = 1.01 ± 0.27, e’cm/s = 7.25 ± 2.20, E/e’ = 11.7 ± 3.28, LAVI = 30.8 ± 5.30 ml/m2, and GLS(%) = −18.3 ± 2.49. There was no significant difference in the data between the observers. showed the left ventricular end-diastolic pressure and echocardiogram parameters of the patients in the left heart catheterization experimental group. Meanwhile, suggested that LVEDP was positively correlated with GLS and E/e ‘(r = 0.638, P < .01; r = 0.574, P < .01;). However, LVEDP was negatively correlated with e ‘(r = −0.578, p = .011). There was no significant correlation between LVEDP and LAVI and E/A values. In addition, we have further analysis of the echocardiographic indicators comparison of the hypertensive group and the Healthy control group. indicated that E, A, E/A, E/e,’ LAVI, GLS, and LVMI in the hypertensive group were significantly higher than that in the Healthy control group (P < .01). However, e’ in the hypertensive group was significantly lower than that in the Healthy control group (P < .01). no difference of LVMI and EF could be retrieved between both groups. In summary, the evidence mentioned above suggested that multiple differences could be calculated between the control group and the hypertensive group.

Table 1. Comparison of clinical information between the antihypertensive treatment experimental group and the healthy control group

Table 2. Left ventricular end-diastolic pressure and echocardiogram parameters of the patients in the hypertensive experimental group and the healthy control group

Table 3. Echocardiographic indicators comparison of the hypertensive experimental group and the healthy control group

Drug treatments influences

In this study, we have formulated different antihypertensive treatment schemes for different patients with hypertension: 1) CCB drugs treatment. 2) CCB drugs + ARB drugs (or ACEIs) treatment. 3) CCB drugs + ARB drugs (or ACEIs) + β blockers (or α, β blockers) (oral) treatment. According to the patient’s blood pressure level, the above-mentioned schemes are selected. When the standard is not reached within four weeks, another antihypertensive drug is selected. showed that the values of SBP, DBP, PP, MAP, BMI, E/A, e’, E/e’, GLS, LAVI, and LVMI in the hypertensive group, hypertensive group with one-month treatment, and hypertensive group with three-month treatment. The results suggested that the value of SBP, DBP, PP, MAP, E/e’, and GLS in the hypertensive group with one-month treatment were significantly lower than those in the hypertensive group before treatment (P < .05). However, the values of e’ in the hypertensive group with one-month treatment were significantly higher than those in the hypertensive group before treatment (P < .05). Meanwhile, the value of SBP, DBP, PP, MAP, E/e’, and GLS in the hypertensive group with three-month treatment were also significantly lower than those in the hypertensive group before treatment (P < .05). Meanwhile, the values of e’ in the hypertensive group with three-month treatment were significantly higher than those in the hypertensive group before treatment (P < .05). Moreover, we have employed Paired Rank Sum Test method to analysis the changes of multiple cardiac ultrasound indexes after 1 and 3 Months of hypertensive treatment. revealed that significant differences of LAVIc-GLSc, E/ec-GLSc, and ec-GLSc could be retrieved between the hypertensive group, the hypertensive group with one-month treatment, and hypertensive group with three-month treatment. Meanwhile, the changes of the average GLS value is significantly higher than the changes of the average values of LAVIc, e’c, and E/e’c (P < .05).

Table 4. Changes of clinical parameters before and after hypertensive treatment

Table 5. Paired rank sum test of changes in cardiac ultrasound indexes after 1 and 3 months of hypertensive treatment

Multivariate analysis of the magnitude of GLS changes after treatment

In this study, We used GLSc after one and three months of treatment as the dependent variable. Type of medication (CCB assigned value of 1, CCB + ACEI/ARB assigned value of 2, CCB + ACEI/ARB + β receptor blocker/α, β receptor blocker assigned 3), change rate of systolic blood pressure, change rate of diastolic blood pressure, change rate of pulse pressure difference, change rate of mean pulse pressure difference, change rate of heart rate, change rate of EF, and change rate of BMI were independent variables. Multiple stepwise linear regression analysis was performed to determine its clinical influence factors. The multivariate stepwise linear regression equation for GLScone month is GLSc one month = 0.054 × medicine type + 0.016. The determination coefficient R2 = 0.067, indicating that the percentage of the dependent variable explained by the independent variable is 6.7%. The analysis of variance showed that F = 4.942, P = .030 was statistically significant (P < .05) (F test) ( and ). Furthermore, we have also employed Multiple stepwise linear regression analysis to determine its clinical influence factors after three-month treatments. The results suggested that GLSc three month multivariate stepwise linear regression equation is GLSc three month = 0.068 × medicine type + 0.14. The determination coefficient R2 = 0.092, indicating that the percentage of the dependent variable explained by the independent variable is 9.2%. The analysis of variance showed that F = 4.862, P = .034 was statistically significant (P < .05) (F test) ( and ).

Table 6. Correlation coefficient between GLS and medication type after one month of treatment

Table 7. Multivariate stepwise linear regression analysis with GLS as dependent variable after 1 month of treatment

Table 8. Correlation coefficient between GLS and medication type after three months of treatment

Table 9. Multivariate stepwise linear regression analysis with GLS as dependent variable after three months of treatment

Discussion

Long-term uncontrolled hypertension will lead to a variety of adverse events, including increased left ventricular afterload, subintimal myocardial ischemia, increased myocardial oxygen consumption, increased energy consumption, myocardial retardation, and early left ventricular diastolic function (Citation15). The treatment of hypertension has many positive significances, including protecting target organs, reducing the occurrence of cardiovascular and cerebrovascular events, and preventing the occurrence of heart failure (Citation16). Therefore, the study of left ventricular diastolic function assessment indicators in early hypertension is of great significance for the prevention and treatment of hypertension.

The current gold standard for evaluating left ventricular diastolic function is cardiac catheterization. This technology has a variety of disadvantages, including invasive operation and inconvenience of repeated operations, The noninvasive gold indicator is cardiac MRI. However, there are still many disadvantages of cardiac MRI, including the complexity of calculations, the high price, and the subjective differences among observers. Echocardiography is widely used in the assessment of left ventricular diastolic function because of its convenience and noninvasive advantages. Mitral valve blood flow Doppler (E/A), LAVI (left atrial volume index), and mitral valve tissue Doppler ultrasound (e ‘, E/e’) are the main indicators for evaluating left ventricular diastolic function. Mitral valve blood flow Doppler is limited in its clinical use because of its susceptibility to pseudonormalization. Tissue Doppler makes up for the shortcomings of false normalization of the mitral valve blood flow spectrum. However, it is greatly affected by the incident angle of the echocardiogram sound beam and heart swing, which cannot reflect the myocardial deformation well (Citation17). GLS can accurately track the movement of myocardial speckles and overcome the effects of factors such as the incident angle of the echocardiogram sound beam and cardiac swing. Therefore, GLS is a better indicator of left ventricular function (Citation9). In this study, the left ventricle end-diastolic pressure measured by cardiac catheterization was used as the gold standard. Correlation between traditional echocardiographic indicators, including GLS and left ventricular end-diastolic pressure (LVEDP) was measured by cardiac catheters. The results show that LVEDP has a good correlation with E/e ’and GLS. The correlation between GLS and left ventricular end-diastolic pressure is the best, which was adopted to the previous studies (Citation18,Citation19). Meanwhile, GLS has the best correlation with LVEDP, suggesting that GLS may be a new reliable indicator for evaluating left ventricular diastolic function.

In this study, e’, LAVI, E/e ‘, and GLS were significantly different between patients receiving hypertension treatment and normal. This results suggested that there is a phenomenon of diastolic function in the left atrium in hypertension patients with normal ejection fraction (Citation20,Citation21). After antihypertensive treatment, LAVI, e, ’ E/e’, and GLS were improved with different degrees. Among them, GLS has the earliest and most significant improvement, which is in line with the perspective of Motoki et al (Citation22).

Studies have shown that GLS is most sensitive to hypoxia and interstitial fibrosis (Citation23). Long-term uncontrolled blood pressure can lead to long-axis myocardial hypoxia and impaired deformation movement (Citation13). Myocardial relaxation is an active energy-consuming process. Diastolic function is limited by hypoxia and interstitial fibrosis. Study has confirmed that blood pressure reduction of CCB drugs can promote blood vessel regeneration, improve myocardial ischemia, and improve myocardial deformation and movement (Citation24). ACEI combined with ARB has a variety of functions, including arterial and venous relaxation, reducing peripheral resistance, antagonizing the RAS system, reducing aldosterone, antagonizing myocardial hypertrophy and vascular fibrosis caused by aldosterone (Citation25). Most patients in this study are older and have high blood pressure. It is difficult to achieve blood pressure control with a single drug to lower blood pressure (Citation26). Therefore, most of the patients in this study were treated with multiple antihypertensive drugs for antihypertensive treatment. For patients with faster basal heart rate, β-receptor antagonists or αβ-receptor antagonists are used. Studies have shown that combined use of β-receptor antagonists or αβ receptor antagonists can further lower blood pressure (Citation27). Therefore, multiple stepwise linear regression analysis was performed to calculate the GLS changes in patients with one month and three-month treatment. The results showed that the antihypertensive drug treatment was an influencing factor of GLSc in one month and three-month treatment.

Although this study can explain some problems, we feel that the study still has the following deficiencies: 1) The follow-up time for this study is still relatively short. Follow-up patients have a certain rate of lost follow-up. The number of follow-up follow-ups was small. 2) The results of this study show that changes in GLS are not associated with decreased blood pressure. We speculate that this may be due to the small sample size and short tracking time. We have planed to expand the sample size and the follow-up time in further research.

Conclusion

In summary, hypertensives had a lower value of e’ and a higher value of LAVI, E/e’, and GLS. GLS is positively correlated with LVEDP. Moreover, the therapeutic regimen was an independent impact factor for the improvement of GLS. In addition, the GLS improvement rate was significantly higher than those of e’, E/e’ after 1 month treatment. Therefore, GLS might be a potential ideal index for patients with anti-hypertension treatment. The results obtained in this study provide useful information for further study.

Disclosure statement

All authors declare that they have no conflict of interest.

References