Right ventricular dysfunction in patients with end-stage renal disease on regular hemodialysis

11 vs. 25.23± 3.99, P o 0.001). There were no statistically significant correlations between systolic pulmonary pressure and RV dimensions or RV function indices.


Introduction
Chronic renal failure (CRF) is associated with significantly increased morbidity and mortality.Chronic renal failure affects almost every system of the body and results in various functional and structural abnormalities.Cardiovascular complications are the main cause of death in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD) therapy [1,2], accounting for 40% of deaths in international registries [3].
The traditional risk factors for cardiovascular disease do not completely explain this high risk, which seems to be influenced by the so-called nontraditional risk factors associated with CKD [4].This set of factors accelerates the course of coronary artery disease [5] and is associated with a higher prevalence of ventricular hypertrophy, myocardial fibrosis, valvulopathies, arrhythmias, and sudden death [6].
The prevalence of clinical manifestations of cardiac disease at the start of end-stage renal disease (ESRD) therapy is high and these manifestations predict death independently [7,8].More than 50% of the individuals starting a dialysis program present some type of pre-existent cardiovascular disease [9].Clinical manifestations of cardiovascular disease were highly prevalent at the start of ESRD therapy: 14% had coronary artery disease, 19% had angina pectoris, 31% had cardiac failure, 7% had dysrhythmia, and 8% had peripheral vascular disease [10].
There is increasing evidence of the pivotal role of echocardiography in the improvement of quality of global clinical evaluation of advanced CKD patients.The current literature and clinical practice have emphasized the usefulness of the method for the diagnosis of clinical and subclinical cardiac dysfunction, the prediction of cardiovascular risk, and in the orientation and follow-up of treatment strategies.Guidelines recommend the echocardiogram for all HD patients 1-3 months after the start of renal replacement therapy and in intervals of 3 years subsequently, irrespective of the symptoms [11].
ESRD is associated with a variety of cardiac alterations including left ventricular hypertrophy (LVH), left ventricular (LV) dilation, and reduction in systolic and diastolic function, with only 16% of new dialysis patients presenting with normal cardiac morphology and function [12] On echocardiography, 15% had systolic dysfunction, 32% had LV dilatation, and 74% had LVH [13].Patients undergoing chronic HD show an increased prevalence of pulmonary hypertension during treatment, 15-20% [1,2].However, although most available studies focused on LV function in dialysis patients, the impact of dialysis treatments on the development of right ventricular dysfunction (RVD) has not been fully investigated.However, recently, a retrospective study in which Paneni et al. [14] investigated the impact of different dialysis treatments on right ventricular (RV) function showed that compared with peritoneal dialysis, HD increases the risk of RVD, particularly in the presence of brachial ateriovenous fistula (AVF).A limitation of this study is its retrospective design.

Patients and methods
This is a prospective study that included 50 patients with end-stage renal failure on regular HD (group I).They were recruited from the nephrology and dialysis department, Cairo University (Kasr El-Ainy) hospital, from May 2011 to December 2011.We also included 24 agematched and sex-matched healthy volunteers (without any cardiac or renal diseases) who served as the control group (group II).

Selection of patients
Patients on HD had been on regular 4 h HD sessions three times per week for at least 3 months using bicarbonate-buffered dialysate.All patients underwent full clinical evaluation and they also underwent chest radiography, standard 12-lead ECG, and arterial blood gas analysis.The exclusion criteria were defined by clinical or echocardiographic evidence of ischemic heart disease, LV dysfunction, valvulopathy, or previous renal transplantation.We also excluded patients with clinical conditions that might predispose to pulmonary hypertension (chronic obstructive pulmonary disease, interstitial lung diseases, connective tissue disorders, chronic thromboembolic disease, congenital left-to-right shunts, and primary pulmonary hypertension).Every participant provided informed consent and all the diagnostic procedures were approved by our institute's ethics committee.

Echocardiography
The entire study population underwent transthoracic echocardiography, including both conventional and tissue Doppler imaging (TDI) of the LV and the RV.Echocardiography was performed within 1 h after the completion of HD while the patients were at optimal dry weight to avoid any overestimation of pulmonary pressure because of volume overload.Images were obtained using a Philips iE33 (Philips Healthcare, Massachusetts, USA) with 2 and 2.5 MHz sector transducer equipped with the TDI mode.The study was carried out according to the criteria of the American Society of Echocardiography [15].LV volumes were estimated using the z-derived method.Ejection fraction (EF) of the LV was calculated using the Teicholz formula [16] and further confirmed using Simpson's technique in the four-chamber view.The maximal tricuspid regurgitation velocity was measured by continuous wave Doppler echocardiography from the apical four-chamber view.The highest peak velocity was recorded and the average peak velocities from three beats were calculated.RV diameters were measured in the long axis view.EF of the RV was calculated using Simpson's formula from the apical four-chamber view.

Data management and statistical analysis
The data were coded and entered on an IBM compatible computer using the statistical package SPSS version 16.0 (IBM Corporation, Armonk, New York, USA).All data sets were assessed for normality and distribution and appropriate tests were used accordingly.Descriptive statistics using the suitable measures of central tendency and dispersion were calculated to summarize the given data sets.The mean and the SD were mostly used for quantitative data.For qualitative data sets, percentages were used.Inferential statistics were used to assess differences between the studied groups and their comparison.Student's t-test was used to assess differences between two unrelated groups in normally distributed quantitative variables.Qualitative variables were assessed using the w 2 -test.The association between two quantitative variables was tested using the univariate analysis approach for quantitative variables, namely, simple linear correlation -regression.The Pearson correlation coefficient (r) was used to test the strength of the relationship, which varies from -1 to 1, where 0 indicates no relationship and 1 indicates a perfect linear relationship.The sign identifies the direction of the relationship, whether direct in case of a positive sign or inverse in case of a negative sign.All the abovementioned statistical levels rejected the null hypothesis at a P value less than 0.05.

Results
No statistically significant differences were found among the groups in their age, sex, BMI and smoking, and systolic blood pressure; however, there was a significant increase in diastolic blood pressure and heart rate (Table 1).
Laboratory investigations showed a significant increase in blood urea, serum creatinine, potassium, and phosphors in the HD group compared with the control group and a statistically significant decrease in blood hemoglobin and calcium (Table 2).
From Table 8, it is clear that there were positive correlations between RV long, right atrium (RA) major, RA minor diameters and E and E/A.Also, there were positive correlations between RV mid cavity, proximal right ventricle outflow tract, RA minor diameters and left atrium diameter.
Patients on HD had statistically significantly higher systolic pulmonary pressure (SPAP) compared with those in the control group (32.75 ± 10.11 vs. 25.23 ± 3.99, Po0.001) (Table 9).There were no correlations between SPAP and EF, IVST, and PWT.There were no statistically significant correlations between SPAP and RV dimensions or RV function indices (Table 10).

Discussion
Cardiovascular disease is the leading cause of mortality in patients undergoing dialysis, accounting for 50% of deaths [17].In particular, congestive heart failure is the most common finding in these patients and is associated with a poor prognosis [18].
HD, which is usually carried out through a surgically created native AVF, has been associated with an increased risk of pulmonary hypertension.In HD patients, AVF causes a left-to-right shunt, leading to chronic volume overload, independent of the increase in total body water, thus worsening RV overload [2].

Previous studies on the relation between pulmonary hypertension and dialysis have mostly investigated the impact of volume overload on TDI indices of LV function,
showing an increased prevalence of diastolic dysfunction in these patients [19].However, although most available studies focused on LV function in dialysis patients, the impact of dialysis treatments on the development of RVD has not fully been investigated.However, in 2010, a retrospective study in which Paneni et al. [14] investigated the impact of different dialysis treatments on RV function showed that HD increases the risk of RVD, particularly in the presence of brachial AVF.One of the important limitations of that study was its retrospective nature.
In the present study, we investigated RV involvement in HD patients, in an attempt to determine the prevalence of RV dysfunction in these patients and find the correlates of RV dysfunction.Our study was prospective and was designed to investigate the impact of chronic dialysis therapy on RV function.
Patients on HD in our study showed a significant increase in LV mass index compared with the controls (117.43 ± 46.72 vs. 80.13 ± 13.40 g/m 2 , Po0.001); also, in our study, it was found that HD patients, compared with controls, showed a statistically significant increase in both IVST (0.99 ± 0.21 vs. 0.83 ± 0.13 cm, Po0.001) and PWT   Copyright © The Egyptian Society of Internal Medicine.Unauthorized reproduction of this article is prohibited.
(1.01 ± 0.17 vs. 0.83 ± 0.13 cm, Po0.001).This finding was similar to that of the study of Said et al. [20] who found that HD led to an increase in IVST (1.1 vs.No difference in RV dimensions was found between the two groups of our study, except for the long dimension of RV, which was higher in the HD group compared with the controls (7.23 ± 0.87 vs. 6.36 ± 0.79 cm, Po0.001).
More importantly, a positive correlation was found between E/A and RV long diameters (P = 0.005).This means that diastolic dysfunction of LV had an impact on RV dimensions.
The TAPSE is a good parameter to evaluate the RV function and it correlates closely with RVEF and RVFAC in a variety of patient populations [22].In our study, TAPSE was reduced (o1.6 cm) in 28% of the patients in the HD group.This may not only have been because of the effects of uremia on RV function but also the effect of hyperdynamic circulation because of AVF [23].
RVFAC is another measure of RV systolic function that has been shown to correlate well with RV EF by MRI [24].RVFAC was reduced in 20 patients (40%) of the HD group.
A statistically significant decrease in RVFAC in the HD group than the control group was observed (37.54 ± 9.86 vs. 43.5 ± 4.8%, respectively, Po0.001).However, no correlation was detected between RVFAC and duration of HD, SPAP, LVEF, LV mass index, or E/A.Thus, the reduction in RVFAC was independent of LVH, diastolic dysfunction of the LV, and pulmonary hypertension.Further studies are needed to explore the cause for reduction in RVFAC in HD patients.
Twelve HD patients (24%) showed an abnormal decrease in lateral TDIS In the current study, on the basis of the Pearson linear correlation coefficient, there was a positive correlation between SPAP and left atrium (P = 0.019), E wave (P = 0.001), E/A ratio (P = 0.027), right ventricle outflow tract proximal diameter (P = 0.012), and septal TDIS 0 (P = 0.009).However, no significant correlation was found between SPAP and systolic right indices, RVFAC (P = 0.223), LTDIS 0 (P = 0.335), TAPSE (P = 0.223), or LVEF% (P = 0.072).This means that the increased SPAP in the HD population could be attributed to left atrium and LV diastolic dysfunction, and may also be because of AVF, which causes a left-to-right shunt, leading to chronic volume overload.

Conclusion
This study confirmed a high prevalence of pulmonary hypertension among HD patients and that is not significantly associated with RV dysfunction in these patients.Subclinical RV dysfunction, as estimated by RV

Table 1
Characteristics of the study population

Table 2
Laboratory data of the study population Bold values indicate a significant increase in blood urea, serum creatinine, potassium, and phosphors in the HD group compared with the control group and a statistically significant decrease in blood hemoglobin and calcium.FBG, fasting blood glucose; HD, hemodialysis.

Table 3
Left-side echocardiographic parameters in the study population Bold values indicate a statistically significant increase in left ventricle dimensions and thickness in hemodialysis patients.EF, ejection fraction; HD, hemodialysis; IVST, interventricular septal thickness; LV, left ventricular; mitral A wave, atrial filling wave velocity; mitral E wave, early diastolic wave velocity; PWT, posterior ventricular wall thickness.

Table 4
Sensitivity and specificity of ECG for the determination LVH

Table 5
Right ventricular dimensions in the study population HD, hemodialysis; RV, right ventricular; RVOT, right ventricle outflow tract.Rt. ventricular dysfunction in CRF patients on hemodialysis Momtaz et al. 129

Table 7
Right ventricular function parameters in the study population

Table 8
Correlations between RV indices and left ventricle indices Bold values indicates there were positive correlations between RV long, RA major, RA minor diameters and E and E/A.EF, ejection fraction; IVST, interventricular septal thickness; PWT, posterior ventricular wall thickness; RA, right atrium; RV, right ventricular; RVFAC, right ventricle fractional area change; TAPSE, tricuspid plane systolic excursion.

Table 9
Comparison of SPAP between the HD group and the control group [20]atients with HD had statistically significant lower lateral TDIS 0 compared with the controls (11.86 ± 2.86, 16.04 ± 3.60 cm/s, Po0.001).Similar results were obtained by Paneni et al.[14]and Said et al.[20].Similar to the reduction in RVFAC, the decrease in lateral TDIS 0 in the HD group was also independent of LVH, LV diastolic dysfunction, and pulmonary hypertension.

Table 10
Correlations between SPAP and right-side, left-side parameters Bold values indicates there were no correlations between SPAP and EF, IVST, and PWT.There were no statistically significant correlations between SPAP and RV dimensions or RV function indices.EF, ejection fraction; IVST, interventricular septal thickness; LA, left atrium; PWT, posterior ventricular wall thickness; RA, right atrium; RV, right ventricular; RVFAC, right ventricle fractional area change; RVOT, right ventricle outflow tract; SPAP, systolic pulmonary pressure; TAPSE, tricuspid plane systolic excursion.