Objectives: Velocity vector imaging allows quantitation of myocardial strain and strain rate from 2-dimensional images based on speckle tracking echocardiography. The aim of this study was to analyze the changes in myocardial strain and strain rate patterns in patients with end-stage renal disease and renal transplant recipients.
Materials and Methods: We studied 33 patients with end-stage renal disease on hemodialysis (19 men; mean age, 36 ± 8 y), 24 renal transplant recipients with functional grafts (21 men; mean age, 36 ± 7 y) and 26 age- and sex-matched control subjects. Longitudinal peak systolic strain and strain rate for basal, mid, and apical segments of the left ventricular wall were determined by velocity vector imaging from apical 4- and 2-chamber views. The average longitudinal strain and strain rate for the left ventricle were noted. From short-axis views at the level of papillary muscles, average circumferential, and radial strain, and strain rate were assessed.
Results: Mean heart rate and systolic and diastolic blood pressure during imaging were similar between the groups. Longitudinal peak systolic strain and strain rate at basal and mid-segments of the lateral wall were significantly higher in renal transplant recipients and control groups than end-stage renal disease patients. Average longitudinal systolic strain from the 4-chamber view was highest in control subjects (-14.5% ± 2.9%) and was higher in renal transplant recipients (-12.5% ± 3.0%) than end-stage renal disease patients (-10.2% ± 1.6%; P ≤ .001). Radial and circumferential strain and strain rate at the level of the papillary muscle were lower in patients with end-stage renal disease than other groups.
Conclusions: Differences in myocardial function in patients with end-stage renal disease, renal transplant recipients, and normal controls can be quantified by strain imaging. Myocardial function is improved in renal transplant recipients compared with end-stage renal disease patients.
Key words : Chronic kidney disease, Heart, Myocardium, Strain, Strain rate
Cardiovascular diseases are the leading causes of death in patients with end-stage renal disease (ESRD).1,2 Changes in left ventricular function are common in these patients and are predictors of outcome.3 Renal transplant improves prognosis in renal transplant recipients (RTR). Several studies have demonstrated improvement in left ventricular systolic function after successful transplant.4,5 Even in advanced systolic heart failure, renal transplant leads to an increase in left ventricular ejection fraction (EF) and improves functional status of patients.6
Subclinical myocardial disease can be assessed with advanced echocardiographic methods including measurement of tissue velocities, strain, and strain rate (SR). Strain and SR provide accurate measurements of contractility, unaffected by myocardial tethering or translation.7 A feature tracking algorithm incorporating speckle and endocardial border tracking, velocity vector imaging (VVI), provides myocardial velocity, strain, and SR based on 2-dimensional images, independent of Doppler angle.
In this study, we sought to define changes in regional and global left ventricular function in terms of myocardial velocity, systolic strain, systolic SR, and dyssynchrony indices in ESRD patients and RTR with preserved EF using speckle tracking echocardiography. We compared ESRD patients, RTR, and normal controls regarding parameters indicating subclinical myocardial function.
Materials and Methods
In this study, we enrolled 33 patients with ESRD (age > 18 y) on maintenance hemodialysis therapy, 24 RTR with a functioning graft, and 26 age- and sex-matched healthy controls. Patients with clinical coronary artery disease were not included in the study. Coronary artery disease was defined as the presence of one of the following: typical angina, ST segment, or T wave changes specific for myocardial ischemia, or Q waves on electrocardiogram, wall motion abnormality on echocardiography, a noninvasive stress test revealing ischemia or any perfusion abnormality, or history of a myocardial infarction and/or revascularization. Patients with moderate or severe mitral or aortic regurgitation or stenosis, atrial fibrillation, hypertrophic cardiomyopathy, or poor echocardiographic image quality were excluded from the study.
Demographic data including risk factors for coronary artery disease and cardiovascular medications were evaluated from patient charts. Mean duration of maintenance hemodialysis for ESRD patients, total time on dialysis before transplant, and mean interval between renal transplant and echocardiographic assessment for RTR were noted. Fasting venous blood samples were obtained for biochemical analyses. The institutional review board approved the study protocol, and all patients gave informed consent before enrollment. All of the protocols conformed with the ethical guidelines of the 1975 Helsinki Declaration. Written informed consent was obtained from all subjects.
Echocardiographic image acquisition
All subjects underwent resting echocardiography with an ultrasonography system (ACUSON Sequoia 256, Siemens, Mountain View, CA, USA) and a 3.5-MHz transducer. For patients with ESRD, echocardiography was performed on days between dialysis. Images were acquired from apical 4-chamber, 2-chamber, parasternal long-axis, and parasternal short-axis views at the level of papillary muscles. The 2-dimensional, M-mode, spectral, and color Doppler examinations were performed. Left ventricular end-diastolic and end-systolic diameters, interventricular septal and posterior wall thicknesses, early (E) and late (A) mitral inflow velocities, and deceleration time for mitral E wave were measured. Left ventricular mass was determined using the method of Devereux, and EF was calculated by Simpson biplane method of disks.8 For each image, 2 to 3 cardiac cycles were acquired at a frame rate of 45 to 50 Hz. Images were stored and transferred to a computer for off-line VVI analysis.
Velocity vector imaging
The off-line software (syngo Velocity Vector Imaging technology, Siemens) provided velocity, strain, and SR from 2-dimensional images. The VVI incorporates speckle tracking, mitral annulus motion, tissue-blood border detection, and periodicity of the cardiac cycle using R-R intervals. Strain assessment by this method was validated in an animal study against sonomicrometry.9
Longitudinal systolic velocity, strain, and SR were recorded for lateral, septal, anterior, and inferior walls for each patient. Each wall was divided into basal, mid, and apical segments automatically. In addition to segmental strain and SR, average strain and SR values from 4- and 2-chamber views were noted. Average strain curves obtained from 4-chamber views for patients with ESRD and RTR are shown in Figure 1. Time from onset of QRS to peak systolic velocity, peak systolic strain, and SR for basal, septal, and basal lateral walls were measured, and opposing wall delays were calculated for peak systolic velocity, strain and SR as dyssynchrony indices. From short-axis views at the level of papillary muscles, average circumferential and radial strain and SR were assessed (Figure 2). The average time needed for the analysis by VVI was 4 to 5 minutes for each acquisition.
Variables were presented as mean ± SD. Echocardiographic variables from 3 groups were compared using 1-way analysis of variance with Bonferroni adjustment and post hoc analysis. Clinical characteristics of the groups were compared with chi-square test. Values for P ≤ .05 were considered statistically significant. Multivariate linear regression analysis was performed to investigate parameters associated with average strain. The analyses were performed using statistical software (Statistical Package for the Social Sciences, Version 11.0, SSPS Inc., Chicago, IL, USA).
Mean age of patients with ESRD was 36 ± 6 years and RTR was 36 ± 7 years. Prevalence of hypertension was significantly lower in the control group than patients with ESRD and RTR (Table 1). Mean duration of maintenance hemodialysis for ESRD patients was 107 ± 79 months. Total time on dialysis prior to transplant was 62 ± 35 months, and mean interval between renal transplant and echocardiographic assessment was 51 ± 41 months for patients with a functioning graft kidney.
Standard echocardiography showed that mean EF was similar between the study groups (Table 2). Peak systolic velocities of basal segments of septal, lateral, and anterior walls were significantly lower in ESRD patients than controls, but similar between RTR and controls (Table 3). Peak systolic strain values from basal, mid, and apical segments of septal, lateral, anterior, and inferior walls were lower in patients with ESRD than controls, and similar patterns of changes were observed for systolic SR (Table 4).
Average systolic strain from 4-chamber and 2-chamber views were highest in control subjectsand were higher in RTR than in ESRD patients (4-chamber: control, -14.5% ± 2.9%; RTR, -12.5% ± 3.0%; ESRD, -10.2% ± 1.6%; P ≤ .001) (2-chamber: control, -15.9% ± 2.7%; RTR,-13.4% ± 2.4%; ESRD, -11.4% ± 2.2%; P ≤ .001) (Figure 3). Average systolic SR was similar between controls and RTR and lower in ESRD patients (4-chamber: control, -0.76 ± 0.17 s-1; RTR, -0.77 ± 0.21 s-1; ESRD,-0.62 ± 0.13 s-1; P ≤ .001) (2-chamber: control, 0.85 ± 0.15 s-1; RTR, -0.78 ± 0.19 s-1; ESRD, -0.65 ± 0.12 s-1; P ≤ .001) (Figure 3). Radial and circumferential strain and SR at the level of papillary muscle were lower in patients with ESRD than the other groups (Table 5).
In a multivariate regression model including age, serum creatinine level, left ventricular EF, and hypertension as confounding parameters, average strain was independently associated with creatinine level (β = 0.31; P ≤ .009) and EF (β = -0.41; P ≤ .002).
Opposing wall delay in peak systolic velocity, strain, and SR for septal-lateral walls were 30 ± 24 ms, 19 ± 18 ms, and 33 ± 35 ms for controls. Other study groups demonstrated prolongation of this delay, which was more pronounced in patients with ESRD (43 ± 51 ms, 59 ± 49 ms, and 56 ± 54 ms for RTR, and 62 ± 54 ms, 55 ± 44 ms, and 72 ± 68 ms for ESRD patients, P ≤ .03, P ≤ .001 and P ≤ .03 for 3 group comparisons). There was no statistically significant difference between ESRD and RTR groups on post hoc analysis.
This study demonstrated that indices of subclinical myocardial disease, including longitudinal, circumferential, and radial strain and SR determined by a new feature tracking algorithm, are impaired in ESRD patients with preserved EF and without overt coronary artery disease. These parameters were improved in subjects who underwent renal transplant.
Cardiovascular diseases are the main cause of death in patients with ESRD, and development of congestive heart failure is the most common complication. Approximately one-third of the patients have cardiac failure at the beginning of dialysis.10 Myocardial function has been studied extensively using conventional echocardiography parameters. However, because fluid status may show considerable variation in patients with ESRD, it may not be accurate to use load-dependent parameters such as EF. It has been shown that, using tissue Doppler imaging, both systolic and diastolic dysfunction could be demonstrated in hemodialysis patients.11 In addition, tissue Doppler imaging in comparison with conventional echocardiography was a more sensitive method for the detection of left ventricular diastolic dysfunction and provided additional information in predialysis chronic kidney disease patients.12 In a substudy of the Multi-Ethnic Study of Atherosclerosis, patients with mild to moderate renal insufficiency and without evidence of clinical heart disease had impaired regional systolic and diastolic function, which was assessed by tagged magnetic resonance imaging.13
Edwards and colleagues demonstrated that abnormal longitudinal systolic deformation was present in asymptomatic individuals with early chronic kidney disease without clinical evidence of heart disease.14 More recently, in a study using 2-dimensional speckle tracking echocardiography with strain analysis, it was demonstrated that global peak longitudinal and circumferential strain were decreased in chronic kidney disease patients.15 Worsening renal function was associated with a reduction of strain; moreover, hemodialysis patients had better left ventricular systolic function than moderate-advanced chronic kidney disease patients. Wang and associates also confirmed that in hemodialysis patients, myocardial function was impaired in the longitudinal and circumferential directions, despite preserved EF.16 Similarly, using 2-dimensional speckle tracking echocardiography, we have demonstrated in our study that longitudinal and circumferential strain and SR are impaired in ESRD patients with preserved global systolic function. Furthermore, our study extends these findings, demonstrating that strain in the radial direction and synchronous contraction of the left ventricle were impaired in this patient population. Additionally, we have shown that the above-mentioned indices of regional myocardial function are improved in patients who underwent renal transplant.
The pathophysiologic mechanism underlying the association between renal failure and myocardial dysfunction appears to be multifactorial. The uremic state, characterized by metabolic aberrations, is harmful for cardiac function and structure.17 Among metabolic alterations, secondary hyperparathyroidism and anemia were proposed as important correlates of cardiac function.18 Parathyroid hormone stimulates proliferation of cardiac fibroblasts, resulting in myocardial fibrosis.19 Other potential mechanisms include oxidative stress and inflammation.20 Microvascular dysfunction, as assessed by impaired coronary flow reserve, also has been implicated in patients with ESRD, which could cause subclinical regional myocardial dysfunction.21
A study by Rakhit and coworkers demonstrated that ESRD patients without congestive heart failure have subclinical myocardial disease, and this is associated with adverse outcome.22 In patients who were dialysis dependent on follow-up, SR significantly decreased and strain remained similar to baseline. For patients who had undergone transplant, mean strain increased and SR did not change significantly compared with baseline. Patients who underwent renal transplant showed reduction of wall thickness, reduction of left ventricular volumes, and increases in diastolic tissue velocity and strain. In our study, in addition to longitudinal strain and SR, circumferential and radial strain were investigated and they were all lower in ESRD patients than controls; patients who had renal transplant had values between these 2 groups. In multivariate regression analysis, serum creatinine level was independently associated with longitudinal strain, suggesting that normalization of renal function has favorable effects on left ventricular systolic function.
Recently, in a retrospective analysis of 447 patients, it was shown that global longitudinal strain was an important predictor of all-cause mortality in chronic kidney disease patients.23 Glomerular filtration rate was independently associated with global longitudinal strain in follow-up at 5 years.
In addition to altered deformation in patients with ESRD, we also found that opposing wall contraction delay (septal-lateral walls) was prolonged in patients with ESRD than normal controls. Gedikli and associates investigated systolic asynchrony in patients with chronic kidney disease using tissue synchronization imaging, and they reported that prevalence of systolic asynchrony was significantly higher in this patient group than in normal controls.24 Geometric alteration in patients with ESRD related to hypertension, volume overload, and myocardial fibrosis may contribute to the development of systolic dyssynchrony in these patients.
The mechanism by which renal transplant normalizes myocardial function remains a matter of speculation. Successful renal transplant improves uremia, anemia, hyperparathyroidism, and volume overload. Because newer echocardiographic parameters such as strain and SR, as assessed in our study, are relatively load-independent, we speculate that improvement in these parameters in RTR may reflect normalization of subclinical regional myocardial function.
Study limitations include the cross-sectional study design; therefore, we do not present follow-up data of patients with ESRD after they had renal transplant. Similarly, deformation measurements of RTR cannot be compared with these parameters in the same patients when they were on regular hemodialysis before transplant. Because not all patients had coronary angiography, we excluded coronary artery disease clinically in the study patients; however, we do not believe that this limitation would interfere with the comparison of ESRD patients with RTR because clinical characteristics were similar between these groups.
In summary, patients with ESRD who were on regular hemodialysis had subclinical left ventricular systolic dysfunction determined by speckle tracking echocardiography, even when they had preserved EF. Patients who underwent renal transplant had improvement in longitudinal, circumferential, and radial deformation indices. Furthermore, systolic dyssynchrony observed in ESRD patients may improve after renal transplant, but this issue should be tested in further studies.
Volume : 13
Issue : 1
Pages : 235 - 241
DOI : 10.6002/ect.mesot2014.P40
From the Departments of 1Cardiology, 2Nephrology, and
3General Surgery, Baskent University Faculty of Medicine, Ankara,
Acknowledgements: The authors have no conflicts of interest to declare. All support for this study came from institutional and departmental resources. This study was presented in part at the Middle East Society for Organ Transplantation Congress, 2014, Istanbul, Turkey.
Corresponding author: Bahar Pirat, MD, Baskent Universitesi Hastanesi, Kardiyoloji Anabilim Dali, 10. sok No. 45 Bahcelievler 06490 Ankara, Turkey
Phone: +90 312 212 6868 ext. 1375
Fax: +90 312 223 8697
Figure 1. Longitudinal Segmental Strain Curves
Figure 2. Average and Segmental Circumferential Strain Curves of a Renal Transplant Recipient Obtained From Short-Axis View
Figure 3. Average Strain (A) and Strain Rate (B) of the Groups From 4-Chamber (4C) and 2-Chamber (2C) Views
Table 1. Baseline Clinical Characteristics of the Groups
Table 2. Standard Echocardiographic Findings of the Groups
Table 3. Peak Systolic Velocities of Basal Segments of 4 Walls of the Study Groups
Table 4. Segmental Strain Values of the Groups
Table 5. Radial and Circumferential Strain and Strain Rate at the Level of Papillary Muscle for Each Group