Study Cohort
This was a single-center study prospectively recruiting patients referred for maintenance hemodialysis between April 2015 to June 2016. The local ethics committees approved the study protocol. Informed consent was obtained from all patients. Patients who had been on MHD for at least six months were enrolled in this study. The exclusion criteria were: congenital heart disease, coronary artery disease, valvular stenosis, severe valvular regurgitation, prosthetic valve replacement, abnormal wall motion, heart failure (LVEF<50%), arrhythmia, pulmonary hypertension caused by lung disease. A total of 92 patients were included in the final analysis, among whom 72 were diagnosed with chronic glomerulonephritis, six with IgA nephropathy, four with polycystic kidney disease, and ten with diabetic nephropathy, according to the National Kidney Foundation Kidney Disease Outcome Quality Initiative clinical practice guidelines[11]. Forty age- and sex-matched healthy subjects served as control, with the following inclusion criteria: no history of cardiac symptoms, hypertension or diabetes, normal physical examination, normal electrocardiogram and echocardiography results, and no medication history.
Clinical data
The height, weight, blood pressure, and heart rate were collected on the non-dialysis day. History of hypertension, diabetes mellitus, and hyperlipidemia, medication, and laboratory data were transcribed from the medical record. Major adverse cardiovascular events included hospitalization for unstable angina or revascularization procedures, acute myocardial infarction (AMI), heart failure (HF), stroke, and cardiovascular mortality. The MHD cohort was followed for at least two years using the institutional electronic medical record system and telephone interviews.
Conventional echocardiographic data
Echocardiography was performed on the non-dialysis day to avoid the impact of hemodialysis in MHD patients. Comprehensive transthoracic echocardiography was performed by experienced sonographers using a Vivid E95 ultrasound system equipped with an M5S 1.7 ~ 3.3 MHz transducer (GE, Horton, Norway). Patients were scanned in the left lateral decubitus position with standard 2D images of three consecutive cardiac cycles and the images were saved in cine-loop digital format for offline analysis. LV end-diastolic and end-systolic diameter(LVEDD/LVESD), interventricular septal thickness (IVST), and posterior wall thickness (PWT) were measured in the parasternal long-axis view. LV mass was calculated from linear measurements obtained and indexed to BSA. LV end-diastolic and end-systolic volumes (LVEDV/LVESV) were measured in the apical two- and four-chamber views and LVEF was calculated using the biplane Simpson method[12]. LV mitral inflow velocities were obtained with the sample volume positioned at mitral leaflet tips by pulsed wave (PW) Doppler. LV mitral annular velocities at both the septal and lateral sides were obtained using PW tissue Doppler imaging. All the recordings and measurements were made according to the American Society of Echocardiography guidelines[12].
GLS and MW analysis
GLS was obtained using two-dimensional speckle-tracking echocardiography[13]. Analysis was performed in LV two-, three, and four-chamber views. Region of interest was adjusted by correcting the endocardial border or width to include the endo-, mid-, and epicardium and myocardial motion was automatically tracked. Mitral and aortic valve event timing were set in the three-chamber view (mitral valve closure, aortic valve opening, aortic valve closure, mitral valve opening). Non-invasive blood pressure values were recorded with brachial artery sphygmomanometry. Quantification of MW indices was performed using the vendor-specific module within the Automated Function Imaging software (EchoPAC V.203, GE), computed by combining non-invasive LV pressure with strain[14]. The area within the loop served as an index of regional and global MW (Fig. 1a, 1b). A bull's eye map with the segmental and global work index (GWI) values was also provided (Fig. 1c, 1d).
Global constructive work (GCW) was defined as work performed during segmental shortening in systole and lengthening in isovolumetric relaxation. Global wasted work (GWW) was defined as work performed during lengthening in systole adding work performed during shortening in isovolumetric relaxation. Global work efficiency (GWE) was calculated as the sum of GCW in all LV segments divided by the sum of GCW and GWW in all segments (Fig. 2). For each case, two readers (G.Y. and S.M.M. with 5 and 12 years of experience reading echocardiographic exams, respectively) independently performed the analyses on the same workstation.
Statistical analysis
Continuous variables were expressed as mean ± SD. Categorical variables were presented as numbers and percentages. The continuous variables with normal distribution were compared using an independent t-test. The Wilcoxon rank-sum test was performed for continuous variables with skewed distribution. Comparisons between the categorical variables were made with the chi-square test. A univariate logistic regression analysis was performed to assess the predictive value of conventional echocardiographic and MW parameters for MACE in the MHD group. Conventional variables with a univariate value < 0.05 were included in the multivariate analysis (baseline model). Two nested models were then created by adding GWE and GLS to the baseline model, each at a time.
Twenty patients were randomly selected and measured by two observers blinded to patient clinical data and each other's results. Intra- and inter-observer variability were assessed using intraclass correlation coefficient (ICC) and Bland–Altman analysis. All statistical analyses were performed using SPSS version 22.0 (SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant.