Two‐dimensional speckle tracking to image ventricular‐arterial coupling in uremia

Objective To study ventricular‐arterial coupling(VAC) in uremic patients by application of two‐dimensional speckle tracing imaging (2DSTI). Methods One hundred uremic patients were divided into two groups based on left ventricular ejection fraction (LVEF): group 1 with LVEF ≥ 5%, and group 2 with LVEF < 55%. Forty healthy subjects were recruited as a control group. Conventional echocardiography was performed; VAC components and myocardial performance index were calculated. Longitudinal strain (LS) of 17 segments was measured using 2DSTI. Mean base (LSBA), papillary muscle (LSPM), and apex values (LSAP) were calculated. Results Compared to subjects in the control group and group 1, subjects in group 2 exhibited decreased LV end‐diastolic volume (EDV), end‐systolic volume (ESV), LV mass index (LVMI), and VAC (P < 0.05). EF, fractional shortening (FS), end‐systolic elastance (Ees) were significantly higher in group 2 (P < 0.05). SLBA, SLPM, and SLAP differed significantly among the groups (all P < 0.05). SLBA, SLPM, and SLAP correlated positively with Ees, EF, and FS (all P < 0.05) but negatively with arterial elastance (Ea), VAC, systemic vascular resistance index (SVRI), and rate‐pressure product (RPP) (all P < 0.05). Multiple regression analysis revealed that relative wall thickness (RWT), LVMI, LSAP, and stroke works (SW) were independent predictors of VAC (b′ = −0.443, 0.537, −0.470, and −0.491, all P < 0.05). Conclusions In patients with uremia, LV myocardial LS gradually decreased as LV systolic dysfunction decreased. VAC correlated negatively with left ventricular LS, and LSAP was an independent predictor for VAC.

analyze regional and global left ventricular (LV) strain. This modality may be used to objectively assess myocardial deformation and quantitatively analyze regional wall motion abnormalities. 2DSTI is also preferable for evaluation of apical segment movement because the approach used avoids the angle dependence of Doppler technology. 5,6 The aim of this paper was to assess the utility of 2DSTI for evaluation of cardiovascular stiffness and VAC in patients with uremia.

| Studypopulation
This study enrolled 100 patients (52 male, 48 female; mean age ± SD, 48.6 ± 12.8 years; range, 21-63 years) with uremia seen at the Urology Department of our hospital during the period from January 2015 to December 2017. Subjects were divided into 2 groups: group 1 included subjects with normal LV systolic function; group 2 included patients with LV systolic dysfunction. Systolic dysfunction was defined as LV ejection fraction (LVEF) <55%. Patients were excluded if they had valvular disease, coronary heart disease, hypertrophic cardiomyopathy, congenital heart disease, or peripheral arterial disease. All uremic patients were on hemodialysis for 4 hours a day, 3 times a week. Patients without standardized treatment were excluded. Each patient underwent assessment by 2DSTI before hemodialysis.
Forty healthy volunteers (20 male, 20 female; mean age, 44.80 ± 10.76 years; range, 22-65 years) who had no history of renal or cardiovascular disease were included as controls. All subjects included as controls had normal physical examination, echocardiographic, and electrocardiographic results. The study was approved by the Ethics Committee at Gaozhou People's Hospital, and each patient who participated in the study provided written informed consent.

| Echocardiography
Two-dimensional echocardiography was performed with a commercial ultrasound machine (iE33; Philips Healthcare, Andover, MA) equipped with an S5-1 transducer (1-5 MHz). Conventional echocardiography was performed with the patient in the left lateral decubitus position. LV end-diastolic diameter (EDD), LV end-systolic diameter (ESD), LV posterior wall thickness (PWT), and interventricular septum thickness (IVST) were measured according to the criteria provided by the American Society of Echocardiography (Raleigh, NC). These parameters were used to calculate LV mass index (LVMI) 7 and relative wall thickness (RWT). 8 LV end-diastolic volume (EDV) and end-systolic volume (ESV), stroke volume (SV), and EF were measured with the apical biplane method. Cardiac output (CO) was obtained as SV × heart rate (HR), and cardiac index (CI) was derived from the ratio of CO to body surface area (BSA). All parameters above were measured in triplicate and averaged.
LV end-systolic elastance (Ees) was calculated as follows: where V 0 is LV volume when LV pressure = 0.

| 2Dspeckletrackinganalysis
Offline strain measurements were performed with Qlab 8.0 software. Apical four-, two-, and three-chamber views were obtained with frame rates >60 frame/sec. The regional four-chamber view of the left ventricular apex was analyzed first. Three points were selected for analysis. The software program automatically provided an outline of the endocardium to produce a region of interest (ROI). ROI width was adjusted manually to reflect myocardial thickness. 13 The system automatically generated longitudinal strain values for 5 or 6 segments. The same method was used to analyze the data provided in apical two-and three-chamber views. The

| Statisticalanalysis
Statistical analyses were performed using SPSS 20.0 software (SPSS Inc, Chicago, IL). All data are expressed as mean values ± SD. Analysis of variance for multiple comparisons was used to assess betweengroup differences. Pearson's correlation coefficients were applied to evaluate correlations between variables of interest. Multiple linear regression analysis was performed to explore the determinants of VAC. P < 0.05 was considered statistically significant.

| Clinicalcharacteristics
Descriptive characteristics of the patient population are presented in Table 1. There were no significant differences among the 3 groups in terms of age or gender. However, systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were higher in the 2 groups with uremia than in the control group. Body mass index (BMI) was lower in the 2 groups with uremia than in the control group (P < 0.05) ( Table 1).

| Conventionalechocardiographic parametersandLVlongitudinalstrain
RWT and LVMI were higher in group 1, compared with the control group (P < 0.05). LS BA , LS PM , and LS AP were lower in group 1 (P < 0.05), compared with the control group. LVEDV, LVESV, and LVMI were significantly higher in group 2, compared with the control group and group 1 (P < 0.05). EF, FS, LS BA , LS PM , and LS AP were significantly lower in group 2 than in the control group and group 1 (P < 0.05). RWT was slightly higher in group 2 than in the control group, but this trend was not statistically significant. There were no differences across groups in SV, CO, or CI (

| VACcomponentsandmyocardial performanceindex
With respect to VAC, Ea was significantly higher in group 2, com- RPP and SW were significantly higher in the 2 disease groups, compared with the control group. SVRI did not differ significantly among the 3 groups (Table 3).

| Correlationanalysis
Pearson correlation analysis was conducted to investigate the rela-   F I G U R E 1 2D longitudinal peak strain, presented as a "bull's eye" display. Representative image of a control subject F I G U R E 2 2D longitudinal peak strain, presented in a "bull's eye" display. Representative image from a uremic patient with normal LV systolic function F I G U R E 3 2D longitudinal peak strain, presented as a "bull's eye" display. Representative image from a uremic patient with LV systolic dysfunction

| D ISCUSS I ON
The principal finding of this observational study was that in patients Previous studies of cardiovascular disease in uremic patients have shown that age is a risk factor for cardiovascular-related death. 16 There was no significant difference in age or gender among the three groups included in our study, demonstrating that the factors above did not affect the research results.
With respect to components of the VAC, Ea is an integrated index of the net arterial load imposed on the LV. Numerous disease states are characterized by elevated Ea. 10 Ees is a measure of myocardial contractility reflecting the ability of the LV to eject blood, in opposition to a given pressure. An increase in Ees is usually associated with enhanced myocardial contractility. In addition, chronic changes in Ees also reflect passive myocardial stiffening and chamber geometry. 17  In uremic patients, vascular sclerosis increases myocardial oxygen; myocardial stiffness further enhances this effect. Table 3 shows that RPP, a sensitive index of myocardial oxygen consump-

| LI M ITATI O N S
This study had some limitations. Firstly, the duration of uremia should be an important parameter when analyzing the effects of uremia on cardiac function and VAC. However, this study failed to analyze the duration of illness in uremic patients, as some patients did not know how long they had been suffering from uremia.
Secondly, during dialysis treatment, blood biochemical parameters associated with uremia changed dynamically. This study did not include laboratory analysis. It is expected that in future studies, changes in cardiac function and VAC during this dynamic process will be analyzed. Finally, future studies should investigate global LS in uremic patients.

| CON CLUS ION
In conclusion, LV myocardial LS decreased gradually as LV systolic dysfunction decreased in patients with uremia. VAC was normal in uremic patients with normal LV systolic function but abnormal in patients with LV systolic dysfunction. VAC correlated negatively with left ventricular LS, and LS AP was an independent predictor for VAC.