Study Design

All enrolled subjects were adults (≥18 years old). The hemodialysis group consisted of consecutive patients with ESRD receiving a maintenance hemodialysis program, 4-hour sessions thrice per week, for >3 months at two community hospitals in Taiwan: National Cheng Kung University Hospital Dou-Liou Branch and Catholic Fu-An Hospital. The study protocol was approved by the human research and ethics committee of National Cheng Kung University Hospital (ER-98-073). Participants gave their informed consent.

The exclusion criteria were (1) moderate to severe valvular heart disease (including mitral or aortic regurgitation or stenosis), (2) an active episode of decompensated heart failure presenting with pulmonary edema, (3) acute coronary syndromes or atrial fibrillation, (4) reduced LVEF (<50%), and (5) inadequate echocardiographic image quality.

It was confirmed that all dialysis patients took their medications regularly and were undergoing dialysis on the basis of prescribed dialysis regimens, frequencies, and dosages. Dialysis adequacy, as measure by Kt/V, and creatinine clearance were evaluated on the basis of the recommendations in the Kidney Disease Outcomes Quality Initiative.

Data Collection

Data were collected through medical history and laboratory findings. Medication compliance was ascertained carefully by questionnaire and personal interviews. Blood samples were collected without anticoagulants, and the samples were separated by centrifugation. Sera were frozen and stored at −80°C until analysis. Sera were thawed to measure the levels of cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, plasminogen activator inhibitor–1, and PICP. Serum albumin, calcium, phosphate, total cholesterol, and triglyceride levels were determined using an automatic analyzer at National Taiwan University Hospital Yunlin Branch.

Echocardiographic Measurements

All patients were examined in the left lateral decubitus position, using a commercially available ultrasound system with a 3.5-MHz probe (Vivid I or Vivid 7; GE Vingmed Ultrasound AS, Horten, Norway). Two-dimensional speckle-tracking echocardiography and Doppler tissue imaging were obtained as described elsewhere. According to the recommendation of the American Society of Echocardiography (ASE), we measured LV mass index, LV volume, LVEF, left atrial volume index, and mitral inflow pattern using pulsed-wave Doppler, positioned at the mitral leaflet tips during diastole at end-expiration. These measurements included the peak early (E) and late (A) diastolic velocities, the E/A ratio, and the deceleration time of E velocity. Furthermore, mitral annular calcification (MAC) was defined as the presence of dense echo structure located at the junction of the atrioventricular groove and the posterior or anterior mitral leaflet on the parasternal long-axis, apical four-chamber, or two-chamber view. With regard to the maximal thickness of the dense echo structure, prescribed previously, the severity of MAC was categorized into two groups: mild to moderate (1–4 mm) and severe (>4 mm).

We used color flow imaging to determine the absence or presence of mitral or aortic regurgitation. According to ASE recommendations, the severity of mitral or aortic regurgitation was graded using the following measurements: jet area, vena contracta width, and structural parameters (i.e., mitral and aortic leaflet, left atrial, and LV size). We also measured the pressure half-time of the regurgitant jet for aortic regurgitation severity grading. The results were averages of three measured values.

Pulse Doppler tissue imaging of mitral annular movement was acquired from the apical four-chamber view when a 2-mm sample volume was placed sequentially at the septal and lateral sides of the mitral annulus. To obtain the peak systolic (s′) and early diastolic (e′) velocities, we measured three end-expiratory beats and averaged these values for further analysis. On the basis of ASE recommendations, we used an average e′ velocity, acquired from the septal and lateral sides of the mitral annulus, to calculate the ratio of mitral inflow E velocity to e′ velocity (average E/e′).

Speckle-tracking echocardiographic images were acquired in the three standard apical views (apical four-chamber, apical two-chamber, and apical long-axis) for three consecutive cardiac cycles at a frame rate of 50 to 90 frames/sec and stored digitally for subsequent offline analysis. Peak systolic longitudinal strain was obtained automatically from the three standard apical views by automated function imaging software, and the average value of peak systolic longitudinal strain from the three apical views was regarded as global longitudinal strain. Additionally, systolic longitudinal strain rate was simultaneously acquired from these three apical views and averaged for further analysis. Also, we assessed the six LV segments on the parasternal short-axis view at the midpapillary level to obtain circumferential and radial strain and strain rate. Two cardiologists performed offline analysis using commercial software (EchoPAC workstation, BT08; GE Healthcare, Haifa, Israel) without knowledge of all clinical information.

Inferior Vena Cava (IVC) Diameter Measurement in Patients with ESRD

To evaluate the fluid status of patients with ESRD, we measured IVC diameter twice at the end of expiration in a subxiphoid location and just proximal to the junction of the hepatic veins that lie approximately 0.5 to 3.0 cm proximal to the ostium of the right atium. The average value of the measured end-expiratory IVC diameter was defined as IVCe. It has been reported that IVCe > 1.53 cm is a marker of overhydration in patients with ESRD. Moreover, on the basis of ASE recommendations, right atrial pressure was estimated by IVC diameter and the presence of inspiratory collapse.

Statistical Analysis

Between-group differences were assessed using Student’s t tests or one-way analysis of variance, as appropriate, or using χ ² tests for categorical variables to identify the significant parameters of diastolic dysfunction and PICP level. Multivariate linear regression analysis was used to assess the independent factors of PICP level. Two-sided P values < .05 were considered statistically significant.