Assessing left atrial volume and function in dyslipidemia patients using three-dimensional speckle tracking imaging

Introduction

Dyslipidemia is considered a risk factor for increased cardiovascular disease morbidity and mortality, and may negatively affect myocardial function, as well as left ventricular (LV) and left atrial (LA) functions (1,2). Echocardiography is a noninvasive, economical, accurate, and efficient imaging method, which evaluates the changes of cardiac morphology and function. At present, there are many techniques for evaluating LA function, but they all have their own advantages and disadvantages. Traditional echocardiography is susceptible to a variety of physiological and pathological factors. In addition, single-plane echocardiography is not comprehensive enough to evaluate myocardial function and cannot be used as a diagnostic basis for evaluating LA dysfunction in patients with hypertension. Three-dimensional speckle tracking imaging (3D-STI) is a newly developed technique in the field of ultrasound diagnosis. Off-line detection and analysis of full-volume images allow the trajectory of myocardial acoustic spots to be followed in three dimensions, and objective parameters such as atrioventricular volume and myocardial strain can be obtained to accurately assess atrioventricular cavity function and myocardial motion. Compared to traditional ultrasound techniques such as spectral Doppler and two-dimensional (2D)-STI, 3D-STI technology is not angle dependent and overcomes the limitations of tracking myocardial motion trajectories in the 2D plane. It aligns better with the mechanical motion of the heart and shows a strong correlation with magnetic resonance imaging (MRI) and other tests. Currently, this technology has been used to evaluate the cardiac function of patients with heart diseases. At present, there are few studies on early changes in LA function in patients with dyslipidemia. Considering this, this study aims to apply 3D-STI to evaluate changes in LA volume and function in patients with dyslipidemia, and to explore its application value in the field, to provide a reference basis for the diagnosis, treatment, and prognosis of the disease. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1077/rc).

Methods

Study subjects

The study size was determined by the number of cases examined during the study period. A total of 102 dyslipidemia patients, initially treated at The Affiliated Hospital of Qingdao University between September 2020 and December 2023, were chosen, comprising 54 men and 48 women, aged between 22 and 66 (42.90±9.61) years.

The inclusion criteria were developed according to the 2016 Chinese guideline for the management of dyslipidemia in adults (3). The patients were on a normal diet and were not taking any medications that affect lipid levels: (I) fasting serum total cholesterol (TC) concentration ≥5.2 mmol/L (200 mg/dL) on two recent occasions (more than 2 weeks apart), or low-density lipoprotein cholesterol (LDL-C) ≥3.4 mmol/L (130 mg/L), or triglyceride (TG) ≥1.7 mmol/L (200 mg/dL), or high-density lipoprotein cholesterol (HDL-C) <1.0 mmol/L (40 mg/dL); (II) LV ejection fraction (LVEF) >50%.

Exclusion criteria were: individuals diagnosed with tumors, liver and kidney deficiencies, hepatitis, cardiomyopathy, congenital heart conditions, and diabetes mellitus through medical records, physical exams, and lab tests; those receiving consistent lipid-reducing treatment (e.g., lipid-lowering drugs); those whose lipid counts had returned to normal through dietary modifications or increased physical activity.

Patients were classified into the high TC group (TC ≥5.2 mmol/L or LDL-C ≥3.4 mmol/L), the high TG group (TG ≥1.7 mmol/L), the low HDL-C group (HDL-C <1.0 mmol/L), and the mixed dyslipidemia group (TC ≥5.2 mmol/L, LDL-C ≥3.4 mmol/L, TG ≥1.7 mmol/L, and HDL-C <1.0 mmol/L). Another 30 healthy individuals, comparable in age and gender, were chosen for the control group, comprising 20 men and 10 women, aged between 25 and 57 years (40.13±8.36). No cardiac and other underlying diseases were detected in the control group. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University (ethical approval No. QYFY WZLL 27724), and all patients gave informed consent.

Techniques and methods

A Philips EPIQ 7C color Doppler ultrasound diagnostic instrument was used, equipped with an S5-1 2D probe with a frequency of 1–5 MHz, an X5-1 3D probe with a frequency of 1.9–3.8 MHz, and an external 3D quantitative analysis software (4D LV-Analysis 3.0, Tom-Tec Imaging Systems, Munich, Germany).

Patients’ clinical data and echocardiographic parameters were recorded. (I) Clinical data: age, gender, height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were recorded, and TC, TG, LDL-C, and HDL-C levels were also tested. (II) Conventional echocardiographic parameters: patients were instructed to lie on their left side and hooked up the electrocardiogram. 2D echocardiograms were obtained using the S5-1 probe in the LV long-axis view, LA diameter (LAD) was obtained at the end-systolic end of the left ventricle in the LV long-axis view, LA area (LAA) was obtained in the apical 4-chamber view, and Simpson’s method was used to measure LA maximal volume and LA minimal volume, and then to calculate LA maximal volume index (LAVi_max) and LA minimal volume index (LAVi_min). Also, LVEF was calculated. The LA volume index was obtained from the ratio of the LA volume to the body surface area. Early diastolic transmitral velocity (E), late diastolic transmitral velocity (A), and early diastolic tissue velocity (e’) were measured by Doppler in the apical 4-chamber view. Then, E/A and E/e’ were calculated. (III) 3D-STI parameters: In the apical four-chamber view, the X5-1 probe was used to obtain clear 2D images. Upon stabilization of the Electrocardiogram (ECG), the full-volume mode was activated, and the dynamic raw data set of 4 consecutive stabilized cardiac cycles (20–30 frames/second) was acquired as the patient held breath at the end of expiration, and then imported into the Tom-Tec workstation for offline analysis. LA strain parameters, volume curves, and strain maps were thereafter generated (Figure 1). 3D-STI was applied to measure and calculate 3D-STI parameters of the left atrium in different phases, including LA maximum volume, LA minimum volume, LAVi_max, LAVi_min, LA presystolic volume, and LA presystolic volume index (LAVip). LAEF = (LAVi_max − LAVi_min)/LAVi_max. Passive LA emptying fraction (pLAEF) = (LAVi_max − LAVip)/LAVi_max, active LA emptying fraction (aLAEF) = (LAVip − LAVi_min)/LAVip. LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were calculated. A comparison was made of the correlation between the 3D strain parameters, and LA strain parameters measured by 3D-STI were tested for intra-observer and inter-observer agreement.

Figure 1 3D-STI of LA. (A) Analysis process of 3D-STI. Dotted line, positioning line; green line, LA intimal surface depicted by the software; yellow arrow, cardiac cycle; green arrow, frame; purple arrow, 3D simulation of the left atrium. (B) LA time-volume curve of control group. (C) LA strain curve of control group. (D) LA time-volume curve of dyslipidemia patients. (E) LA strain curve of dyslipidemia patients. (B,D) X-axis, time; Y-axis, LA volume; green line, dynamic timeline. (C,E) X-axis, time; Y-axis, strain; green line, dynamic timeline; colored dots, average strain of each segment; color coding, the color range corresponding to the strain. 3D, three-dimensional; 3D-STI, three-dimensional speckle tracking imaging; EDV, end diastolic volume; EF, ejection fraction; ESV, end systolic volume; GCS, global circumferential strain; GLS, global longitudinal strain; LA, left atrial; SV, stroke volume.

The images of 10 healthy individuals and 10 patients with dyslipidemia were randomly selected, and the above indices were measured offline by two physicians skilled in 3D-STI analysis software alone, with the difference between the two reflecting the inter-observer error. The above indices were measured repeatedly by one of the physicians after 2 weeks. The difference between the two measurement results reflected the intra-observer error.

Statistical analysis

SPSS 22.0 software was used to test for normality. Measurement data were expressed as mean ± standard deviation (SD). Data in homogeneity of variance were compared using one-way analysis of variance (ANOVA) and least significant difference (LSD) test. Otherwise, data were comparatively analyzed using Kruskal-Wallis test and Dunnett’s T3 test. Enumeration data were expressed as frequencies and/or percentages, and the χ² test was applied for comparisons. The sensitivity of each index was analyzed by plotting the receiver operating characteristic (ROC) curve. Bland-Altman test was applied to test the agreement of the results. GraphPad Prism7 software was applied for plotting. Differences were considered statistically significant at P<0.05.

Results

Clinical parameters between groups of patients

There were statistically significant differences in TG, TC, and HDL-C among groups (P<0.05), and no statistical differences were observed in age, gender, and blood pressure (P>0.05). The high TC group exhibited elevated TC or LDL-C levels compared to the control, TG, and low HDL-C groups; TG levels were higher in the TG group and mixed dyslipidemia groups than in the control, high TC, and low HDL-C groups; HDL-C levels were reduced in the low HDL-C group compared to other groups; HDL-C levels were lower in the mixed dyslipidemia group than in the control, high TG, and high TC groups, and TG levels in the mixed dyslipidemia group were higher than in the control group, high TC group, and low HDL-C group, TC levels in the mixed dyslipidemia group were higher than in the control group, high TG group, and low HDL-C group, LDL-C levels in the mixed dyslipidemia group were higher than in the control group and high TG group, and SBP and DBP levels in the mixed dyslipidemia group were higher than in the other groups (P<0.05) (Table 1).

Conventional 2D parameters in each group of patients

There were no statistically significant differences in interventricular septal thickness (IVST), LV posterior wall thickness (LVPWT), LVEF, and E/A among groups, and statistically significant differences were seen in LAD, LAVi_max’, LAVi_min’, and E/e’ among groups (P<0.05). LAD, LAVi_max’, LAVi_min’, and E/e’ were higher in patients with dyslipidemia than those without dyslipidemia (P<0.05), and LAD, LAVi_max’, and LAVi_min’ were higher in the mixed dyslipidemia group than in the high TC group, high TG group, and low HDL-C group, and E/e’ was higher in the mixed dyslipidemia group than in the high TG group and low HDL-C group (P<0.05) (Table 2).

3D-STI-related parameter values between groups of patients

The differences in LAVi_max, LAVi_min, LAVip, LAEF, and pLAEF were statistically significant among patients (P<0.05), and the difference in aLAEF was not statistically significant (P>0.05). In the high TC, high TG, low HDL-C, and mixed dyslipidemia groups, LAVi_max, LAVi_min, and LAVip were elevated, while LAEF and pLAEF were reduced, compared to the control group. In the mixed dyslipidemia group, LAVip, LAVi_max, and LAVi_min were elevated, while LAEF was reduced, compared to the high TC, high TG, and low HDL-C groups. Additionally, pLAEF in the mixed dyslipidemia group was lower compared to the high TG and low HDL-C groups; similarly, pLAEF was reduced in the high TC group compared to the low HDL-C group (P<0.05) (Table 3).

3D-STI-related parameters between groups of patients

The differences in GLS, GCS, and GRS were statistically significant (P<0.05) among patients. Compared to the control group, the high TC group, high TG group, low HDL-C group, and mixed dyslipidemia group exhibited reduced GLS and GCS, while the high TC group, high TG group, and mixed dyslipidemia group showed lower GRS. The mixed dyslipidemia group exhibited reduced GLS compared to the high TC, high TG, and low HDL-C groups, while the mixed dyslipidemia group had lower GCS than the high TG and low HDL-C groups (P<0.05) (Table 4).

ROC curve analysis

ROC curve analysis revealed that the area under the curve (AUC) values of GLS, GRS, and GCS were 0.740, 0.725, and 0.681, respectively. When the threshold of GLS was set at 27.59%, the sensitivity reached 80.00%, and the specificity was 64.71%. The AUC values for GLS and LAEF were 0.740 and 0.787, respectively, while the combined index GLS-LAEF had an AUC of 0.796, surpassing the AUC of the two. The highest approximate index of GLS-LAEF was 0.484, the corresponding sensitivity was 78.40%, and the specificity was 70.00%. These results suggest that the combined index GLS-LAEF has higher diagnostic efficacy in identifying patients with dyslipidemia (Figure 2).

Figure 2 ROC curves of 3D-STI strain parameters in patients with abnormal lipid metabolism. 3D-STI, three-dimensional speckle tracking imaging; GCS, global circumferential strain; GLS, global longitudinal strain; GRS, global radial strain; LAEF, left atrial ejection fraction; ROC, receiver operating characteristic.

Correlation analysis

3D-STI measurements of LAVi_max and LAVi_min were correlated with the Simpson method measurements of LAVi_max’ and LAVi_min’ (r=0.936, r=0.911, P<0.05) (Figure 3).

Figure 3 Correlation analysis between 2D and 3D volume parameters. 2D, two-dimensional; 3D, three-dimensional; LAVi_max, LA maximal volume index; LAVi_min, LA minimal volume index.

Bland-Altman analysis

The LA parameters determined by 3D-STI technique demonstrated strong intra- and inter-observer agreement (Figure 4).

Figure 4 Intra-observer (left) and inter-observer (right) agreement for GLS. GLS, global longitudinal strain; SD, standard deviation.

Discussion

Traditional 2D ultrasound can only infer the atrial volume from the LAA, which is inherently subject to large error, and cannot quantitatively assess myocardial function (4). 2D-STI offers a partial solution to the drawbacks of traditional 2D ultrasound and, due to its angle independence, enables more rapid evaluation of LA volume and myocardial function (5). Loss of functional information from the myocardium during 2D-STI is a common issue, causing measurement errors and affecting the accuracy of LA function measurements (6). With 3D-STI, measurement errors caused by information loss are solved, allowing more precise and complex assessments of the left atrium. 3D-STI has been applied to the assessment of LA function in a variety of diseases such as hypertension, diabetes, atrial fibrillation, chronic kidney disease, and hypertrophic cardiomyopathy (7-9). In this study, 3D-STI was utilized to evaluate LA function in patients with different types of dyslipidemia.

Dyslipidemia typically develops over a prolonged period and is a known risk factor for cardiovascular disease and death (10-12). A case-control study conducted in 52 countries found that dyslipidemia was associated with the highest number of disease deaths (13). It increases blood flow reserve in the myocardium, increases capillary endothelial cell apoptosis after ischemia and reperfusion, and alters the metabolism of cardiomyocytes, resulting in structural and functional LA changes. Dyslipidemia is mainly characterized by elevated serum levels of TC, TG, and LDL-C, and decreased levels of HDL-C (14). These markers are commonly used to assess cardiovascular risk. However, there are few studies on the relationship between changes in cardiac structure and function and blood lipids. Therefore, we first tested and categorized TC, LDL-C, TG, and HDL-C levels in patients for further investigation.

Conventional echocardiographic analysis showed increased LAD, E, and E/e’ in the mixed dyslipidemia group. The LV structure of patients changes as the disease progresses and the type of disease changes. Nonetheless, the traditional method of assessing the left atrium using echocardiography is flawed due to issues like angle, heart rate, and image quality, which cause inconsistencies in measurement values and challenges in accurately representing LA 3D data (15).

3D-STI is a new ultrasound diagnostic technique developed in recent years, which is not affected by the angle, respiration, and anterior and posterior cardiac loads (16, 17), and it significantly improves the accuracy and utility in the assessment of cardiovascular diseases. CLS, GCS, and GRS are 3D strain parameters of 3D-STI technology, in which GCS indicates circular motion in the short-axis, and a decrease in its value indicates that myocardial ischemia is involved in the intermediate layer; GLS indicates myocardial deformation in the long-axis, which can reflect the contractile function in the long-axis; and GRS reflects the radial myocardial deformation that corresponds to systolic thickening (18-20). ROC curve analysis showed that in patients with dyslipidemia, the AUC for diagnosing LA dysfunction was 0.740 for GLS, 0.725 for GRS, and 0.681 for GCS, with GLS showing the highest diagnostic efficacy. Consistent with the study by Shin et al. (21), the present study found that GLS, GRS, and GCS of 3D-STI were highly correlated with LA in dyslipidemic patients.

Meanwhile, GLS in the mixed dyslipidemia group was significantly lower than that in the control group, pointing to myocardial damage and impaired contractile function in the left atrium. This is because the longitudinal fibers are located in the subendocardium, which faces higher pressure during heart contractions and is prone to abnormal diastolic contractions from the myocardium (22,23). The assessment of GLS is more effective because abnormal changes in this direction appear earlier than in other directions during myocardial injury.

Furthermore, LA structure and function can be used to evaluate LV diastolic function laterally. When myocardial structure and function in the left atrium are impaired early on, LVEF does not significantly differ among patient groups, suggesting it is not a sensitive indicator of LV systolic function. This is due to the fact that the enhancement of contraction in the undamaged myocardium to maintain LVEF significantly affects the assessment of LV function (24,25). Additionally, using standard 2D techniques, it was found that patients with normal LVEF had statistically significant increases in E/e, which suggested that LV diastolic function was compromised due to increased LV filling pressures. As structural and functional abnormalities in the left atrium typically appear before those in the left ventricle, using 3D-STI to assess GLS, GRS, and GCS allows for faster and more accurate diagnoses than 2D-STI. Furthermore, the ROC curves of GLS and LAEF were analyzed, and the combined index GLS-LAEF had higher diagnostic efficacy than any index of GLS, GRS, and GCS in identifying patients with dyslipidemia (AUC =0.796).

Increased LA volume has been confirmed to have a strong association with myocardial disease events (26-28). The left atrium is more susceptible to volume changes than the left ventricle. More importantly, LA storage, conduit, and contraction functions assist in LV filling, reflecting changes in diastolic function, with abnormalities in structure and function typically appearing before those in the left ventricle (29,30). As a result, pathological changes in the left atrium can impact venous reflux and the function of the left ventricle to different extents.

LA volume indices LAVi_min and LAVi_max are more valuable to reflect LA storage function. The results of this experiment found that in cases where LV diastolic function was abnormal, patients with dyslipidemia showed increased LAVi_min and LAVi_max, particularly those with mixed dyslipidemia, indicating impaired LA storage and pumping functions (31,32). This is due to the fact that both preload and afterload of the left atrium will increase to varying degrees, stretching the atrial muscle and causing the LA volume to expand as compensation, which then leads to impaired LA function. When LVEF is in the normal range, the accuracy of E/e’ alone to evaluate LV diastolic function is poor.

In contrast, 2D-STI measures myocardial strains across different cardiac cycles and views, but its asynchronous acquisition can be influenced by cardiac rhythms, leading to inaccuracies. By integrating real-time 3D echocardiography with 2D-STI technology, 3D-STI can track myocardial speckle movement in all directions, providing a realistic and objective 3D view of the left atrium for more accurate assessment.

This research primarily explored the influence of different dyslipidemia types on LA function, without further grouping by dyslipidemia severity. It is necessary to increase the sample size of this study in order to make improvements. 3D-STI demands high-quality 2D images, and it is crucial to clearly display the endocardial membranes to guarantee measurement accuracy, which involves some uncertainty.

Conclusions

In conclusion, 3D-STI technology can detect myocardial damage at an early stage and provide a valuable reference. Patients with different dyslipidemia types experience varying levels of damage to the LA structure, resulting in weakened storage and pumping functions. Additionally, 3D-STI allows early detection of myocardial damage, whilst GLS has some predictive value. The combination of GLS and LAEF can better identify patients with dyslipidemia.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-1077/rc

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1077/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University (ethical approval No. QYFY WZLL 27724), and all patients gave informed consent.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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