Abstract
Background
Chronic kidney disease is a disorder of epidemic proportions that impairs cardiac function. Cardiovascular diseases are the leading cause of death in hemodialysis patients, and the understanding of new nontraditional predictors of mortality could improve their outcomes. Right ventricular systolic dysfunction (RVSD) has recently been recognized as a predictor of cardiovascular death in heart failure and hemodialysis patients. However, the factors contributing to RVSD in hemodialysis patients remain unknown. The aim of this study was to evaluate the clinical and echocardiographic factors associated with RVSD in hemodialysis patients.
Methods
A cross-sectional study was conducted in which 100 outpatients with end-stage renal disease on chronic hemodialysis were evaluated. A transthoracic echocardiographic examination was performed at optimal dry weight. Right ventricular systolic function was evaluated using tricuspid annular plane systolic excursion (TAPSE). Clinical and echocardiographic data were recorded for each patient. A multivariate linear logistic regression was created using RVSD (TAPSE <14 mm) as the dependent variable.
Results
Fifteen patients with RVSD and 85 patients without RVSD were analyzed. TAPSE had a positive correlation with left ventricular ejection fraction (LVEF) and myocardial relaxation velocity. Independent contributors to RVSD were LVEF (OR 1.14, 95% CI 1.05-1.26), left ventricular mass index (OR 1.02, 95% CI 1.00-1.04), and myocardial relaxation velocity (OR 1.81, 95% CI 1.18-3.19).
Conclusions
Echocardiographic factors were significant contributors to RVSD. These measurements could be included as part of the routine workup in all end-stage renal disease patients on hemodialysis.
Key Words: Tricuspid annular plane systolic excursion, Right ventricular dysfunction, Hemodialysis, Chronic kidney disease
Introduction
Chronic kidney disease is a multisystemic disorder of epidemic proportions that negatively affects cardiac function (type 4 cardiorenal syndrome) [1,2]. The incidence of structural heart disease is high in end-stage renal disease (ESRD) patients [3] and has been reported to be more frequent in hemodialysis patients [4].
Cardiovascular diseases are the leading cause of death in chronic kidney disease patients on hemodialysis. Traditional risk factors do not completely explain this high risk [5]; thus, an understanding of new nontraditional predictors of mortality could improve treatment and increase the survival of chronic kidney disease patients.
Right ventricular systolic dysfunction (RVSD) has recently been shown to be a predictor of cardiovascular death in patients with chronic systolic heart failure and coronary artery disease [6,7,8]. Moreover, right ventricular systolic function has been shown to inversely correlate with glomerular filtration rate in chronic kidney disease patients [9] and has been poorer in hemodialysis patients than in healthy controls [10]. However, it remains unknown which factors contribute to RVSD in ESRD patients on hemodialysis.
The aim of this study was to evaluate the clinical and echocardiographic factors associated with RVSD in ESRD patients on hemodialysis.
Methods
Study Population
A cross-sectional study was conducted between April 2013 and January 2014 in the Cardiology and Nephrology Departments of the Hospital Central ‘Dr. Ignacio Morones Prieto’ in San Luis Potosí, México. An evaluation was performed on a total of 100 outpatients with ESRD on chronic hemodialysis (minimum 3 months).
Exclusion criteria were a history of renal graft, a history of heart failure, a history of ischemic heart disease, presence of a prosthetic heart valve, moderate to severe aortic or mitral valve disease, pericardial effusion, and oxygen-dependent lung disease. Clinical and echocardiographic data were recorded for each patient. Every participant provided informed consent, and all procedures were approved by our institute's Bioethics Committee (reference 30-13).
Clinical Data Collection
Previous to echocardiographic evaluation, participants were interviewed about some clinical data. Age, gender, diabetes diagnosis, hemodialysis time, and arteriovenous fistula time (length of time the fistula was in place) were recorded. All patients were dialyzed in the same center with bicarbonate dialysate solution (NaturaLyte 4000, Fresenius Medical Care). Medical records were reviewed to confirm the data obtained.
Echocardiographic Evaluation
Transthoracic echocardiographic examination was performed with a Philips IE 320 ultrasound instrument and a 3.5-MHz transducer. Echocardiography was performed after hemodialysis while the patients were at optimal dry weight. Dry weight was ascertained by clinical examination. Left ventricular ejection fraction (LVEF) was calculated from apical two- and four-chamber views using the modified Simpson's rule. Right ventricular systolic function was evaluated using tricuspid annular plane systolic excursion (TAPSE) [11,12]. TAPSE was assessed by M-mode at the junction of the tricuspid valve and right ventricle free wall in the apical four-chamber view (fig. 1). Left ventricular mass index was calculated as recommended by the American Society of Echocardiography [13]. Myocardial relaxation velocity was evaluated by tissue Doppler ultrasound, calculating the mean value between the septum and left ventricle free wall (E’ wave). Estimated pulmonary artery systolic pressure was obtained from the apical four-chamber view by calculating the pressure gradient between the right ventricle and the right atrium through tricuspid regurgitation flow and by adding the estimated value of pressure in the right atrium.
Fig. 1.
Low TAPSE assessed by M-mode transthoracic echocardiography.
Reproducibility
Prior to the study, echocardiographic measurements were repeated by two echocardiography cardiologists in 16 ESRD subjects to assess interobserver agreement. The Linn correlation coefficient was 0.94 for LVEF, 0.99 for pulmonary artery systolic pressure, 0.97 for left ventricular mass index, and 0.86 for TAPSE.
Statistical Analysis
Descriptive methods were used with continuous variables presented as means ± SD and categorical variables presented as frequency (%). Patients were divided into two groups: RVSD (TAPSE <14 mm) and normal right ventricular systolic function (TAPSE ≥14 mm), as has been established previously [7,9]. Differences between the groups were tested using the χ2 test for categorical variables and the Student t test for continuous variables. Correlation between TAPSE and other parameters was performed using the Spearman rank correlation test and the Pearson correlation test, as appropriate. A multiple linear regression model was created using TAPSE as the dependent variable. Curved linear relationships of the covariates were tested and then quadratic terms added if appropriate. A multivariate linear logistic regression was also created using RVSD as the dependent variable. Both models were tested for multicollinearity. Statistical analysis was performed using R version 3.1.0 for Windows [14]. A value of p < 0.05 was considered statistically significant.
Results
The analysis included 15 patients with RVSD (TAPSE <14 mm) and 85 patients without RVSD (TAPSE ≥14 mm). The mean age of the study population was 41.2 ± 18 years, the mean time on hemodialysis was 36.3 ± 35 months, and there were 56 males (56%). Clinical and echocardiographic characteristics of the study population are shown in table 1. Compared with the group of normal TAPSE, patients with low TAPSE had less time with their arteriovenous fistula, lower values of LVEF, and a lower myocardial relaxation velocity. Other clinical and echocardiographic characteristics between the groups were not statistically significant.
Table 1.
Clinical and echocardiographic characteristics of the study population
| TAPSE <14 mm (n = 15) | TAPSE ≥14 mm (n = 85) | p | |
|---|---|---|---|
| Age, years | 40.8 ± 16.1 | 41.3 ± 18.4 | 0.92* |
| Gender, male | 8 (53.3) | 48 (56.4) | 0.82† |
| Diabetes | 7 (46.6) | 23 (27.0) | 0.22† |
| HD time, months | 37.9 ± 32.3 | 36.1 ± 35.7 | 0.85* |
| AVF time, months | 4.2 ± 9.6 | 17.8 ± 25.2 | 0.04* |
| PASP, mm Hg | 34.1 ± 13.7 | 34.9 ± 13.3 | 0.82* |
| PAH | 8 (53.3) | 52 (61.1) | 0.77† |
| LVEF | 42.4 (11.3) | 53.4 (11.5) | 0.001* |
| Left ventricular mass index, g/m2 CS | 162.4 ± 60.1 | 167.2 ± 48.2 | 0.73* |
| Myocardial relaxation velocity, cm/s | 4.9 ± 1.6 | 6.3 ± 1.7 | 0.004* |
| TAPSE, mm | 11.5 ± 1.3 | 20.4 ± 3.6 | <0.0001* |
Categorical variables are reported as frequency (%) and continuous variables as means ± SD. HD = Hemodialysis; AVF = arteriovenous fistula; PASP = pulmonary artery systolic pressure; PAH = pulmonary artery hypertension (PASP >30 mm Hg); CS = corporal surface.
Student's t test;
χ2 test.
Correlation between TAPSE and other Parameters
TAPSE had a positive correlation with LVEF and myocardial relaxation velocity. There was a negative correlation between TAPSE and diabetes. Correlations between TAPSE and other parameters were not statistically significant (table 2).
Table 2.
Correlation between TAPSE and other parameters
| r (95% CI) | p | |
|---|---|---|
| Diabetes | −0.26 (−0.43 to −0.06) | 0.008* |
| LVEF | 0.24 (0.05 to 0.42) | 0.01† |
| Myocardial relaxation velocity | 0.46 (0.28 to 0.60) | <0.0001* |
Spearman rank correlation test;
Pearson correlation test.
Clinical and Echocardiographic Factors Associated with Right Ventricular Systolic Function
Clinical and echocardiographic data that could contribute to right ventricular systolic function were entered into the multiple linear regression model. The final model is shown in table 3. Independent contributors to right ventricular systolic function were LVEF, left ventricular mass index, and myocardial relaxation velocity. The R2 of the model was 0.38, and 0.35 with Bootstrap validation. Other covariates were not statistically significant.
Table 3.
Multiple linear regression showing factors independently associated with right ventricular systolic function
| Regression coefficient (β) | 95% CI of β | ε2 | p | |
|---|---|---|---|---|
| LVEF | 17.15 | 8.24 to 26.06 | 0.07 | <0.001 |
| LVEF2 | −8.16 | −15.74 to −0.59 | 0.02 | 0.03 |
| Left ventricular mass index | 0.03 | 0.01 to 0.05 | 0.10 | <0.001 |
| Myocardial relaxation velocity | 1.26 | 0.82 to 1.70 | 0.20 | <0.001 |
Covariates entered in the initial model: age, gender, diabetes, hemodialysis time, quadratic term of hemodialysis time, arteriovenous fistula time, quadratic term of arteriovenous fistula time, pulmonary artery systolic pressure, LVEF, LVEF2, ventricular mass index, and myocardial relaxation velocity. Validated R2 = 0.38, p < 0.001. LVEF2 = Quadratic term of left ventricular ejection fraction.
Known risk factors for RVSD were entered into the multivariate linear logistic regression model. The final model is shown in table 4. Independent contributors to RVSD were arteriovenous fistula time, LVEF, left ventricular mass index, and myocardial relaxation velocity. Other covariates were not statistically significant. The accuracy of the model by cross validation was 87%.
Table 4.
Logistic regression showing factors independently associated with RVSD
| Regression coefficient (β) | OR (95% CI) | p | |
|---|---|---|---|
| AVF time | 0.05 | 1.05 (1.00–1.14) | 0.002 |
| LVEF | 0.13 | 1.14 (1.05–1.26) | 0.003 |
| Myocardial relaxation velocity | 0.59 | 1.81 (1.18–3.19) | 0.01 |
| Left ventricular mass index | 0.02 | 1.02 (1.00–1.04) | 0.02 |
Covariates entered in the initial model: age, gender, hemodialysis time, AVF time, pulmonary artery systolic pressure, ejection fraction, ventricular mass index, and myocardial relaxation velocity. Validated accuracy of the model = 87%. AVF = Arteriovenous fistula.
Discussion
Cardiovascular complications are the leading cause of death in chronic hemodialysis patients. Being elderly, smoking status, diabetes, hypertension, and left ventricular heart failure are major contributors recognized. However, nontraditional risk factors for cardiac disease (such as RVSD) have been poorly addressed.
RVSD is a significant predictor of mortality in heart failure patients, regardless of left ventricular systolic dysfunction and valvular disease [7,15,16]. However, it has been poorly studied in hemodialysis patients.
In our study, it was found that LVEF, left ventricular mass index, and myocardial relaxation velocity are major contributors to right ventricular systolic function measured as TAPSE. Additionally, arteriovenous fistula time, LVEF, left ventricular mass index, and myocardial relaxation time were found to be independent factors associated with RVSD in hemodialysis patients.
Hemodialysis therapy increases the risk of RVSD, particularly in the presence of brachial arteriovenous fistula. The arteriovenous fistula causes a left-to-right shunt, leading to chronic volume overload and right ventricle function impairment [10,17].
The left ventricular mass index contributes to left ventricular diastolic dysfunction, and delayed myocardial relaxation velocity is an expression of it. Left ventricular diastolic function impairment produces an increase in left ventricular pressure and in pulmonary pressure and, therefore, a decrease in right ventricular function [18,10]. Through these mechanisms, left ventricular dysfunction (systolic and diastolic) could be the main contributor to RVSD.
Strengths and Limitations
The validation and reproducibility of echocardiographic measurements and the statistical analysis without missing data are some significant strengths of this study. However, our study also has several limitations. First, it is a single-center study. Second, the cross-sectional design does not allow assuming causal relationships between echocardiographic factors and RVSD. Finally, a low rate of RVSD was observed in the study population; so, the logistic regression analysis could be performed only as an approximation.
Conclusion
In our study, only echocardiographic factors were significant contributors to RVSD. The evaluation of LVEF, left ventricular mass index, and myocardial relaxation velocity are simple and noninvasive measurements performed by transthoracic echocardiography. These parameters should be included and reported in every patient on hemodialysis.
Disclosure Statement
The authors have no conflicts of interest to declare.
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