Role of haemodialysis on left ventricular dyssynchrony 2. Maher ER, Young G, Smyth-Walsh B et al.

Aortic and mitral valve calcification in patients with end-stage renal disease. Lancet 1987; 2: 875877 3. Straumann E, Meyer B, Misteli M et al. Aortic and mitral valve disease in patients with end stage renal failure on long-term haemodialysis. Br Heart J 1992; 67: 236239 4. Braun J, Oldendorf M, Moshage W et al. Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis 1996; 27: 394401 5. Ribeiro S, Ramos A, Brandao A et al. Cardiac valve calcification in haemodialysis patients: role of calcium-phosphate metabolism. Nephrol Dial Transplant 1998; 13: 20372040 6. Baglin A, Hanslik T, Vaillant JN et al. Severe valvular heart disease in patients on chronic dialysis. A five-year multicenter French survey. Ann Med Interne (Paris) 1997; 148: 521526 7. Perkovic V, Hunt D, Griffin SV et al. Accelerated progression of calcific aortic stenosis in dialysis patients. Nephron Clin Pract 2003; 94: c40c45 8. Urena P, Malergue MC, Goldfarb B et al. Evolutive aortic stenosis in hemodialysis patients: analysis of risk factors. Nephrologie 1999; 20: 217225 9. Rosenhek R, Binder T, Porenta G et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med 2000; 343: 611617 10. Kume T, Kawamoto T, Akasaka T et al. Rate of progression of valvular aortic stenosis in patients undergoing dialysis. J Am Soc Echocardiogr 2006; 19: 914918 11. Bonow RO, Carabello BA, Chatterjee K et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation 2006; 114: e84e231

1655 12. Bonow RO, Carabello BA, Chatterjee K et al. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2008; 118: e523e661 13. Brinkman WT, Williams WH, Guyton RA et al. Valve replacement in patients on chronic renal dialysis: implications for valve prosthesis selection. Ann Thorac Surg 2002; 74: 3742 discussion 42 14. Brown JM, O'Brien SM, Wu C et al. Isolated aortic valve replacement in North America comprising 108,687 patients in 10 years: changes in risks, valve types, and outcomes in the Society of Thoracic Surgeons National Database. J Thorac Cardiovasc Surg 2009; 137: 8290 15. Kaplon RJ, Cosgrove DM 3rd, Gillinov AM. Cardiac valve replacement in patients on dialysis: influence of prosthesis on survival. Ann Thorac Surg 2000; 70: 438441 16. Herzog CA, Ma JZ, Collins AJ. Long-term survival of dialysis patients in the United States with prosthetic heart valves: should ACC/AHA practice guidelines on valve selection be modified? Circulation 2002; 105: 13361341 17. Hahn HS, Maze SS. Rapid bioprosthetic valve degeneration in a patient undergoing hemodialysis. Ann Intern Med 2000; 132: 847 18. Strom BL, Abrutyn E, Berlin JA et al. Risk factors for infective endocarditis: oral hygiene and nondental exposures. Circulation 2000; 102: 28422848 19. Nucifora G, Badano LP, Viale P et al. Infective endocarditis in chronic haemodialysis patients: an increasing clinical challenge. Eur Heart J 2007; 28: 23072312

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Received for publication: 24.3.10; Accepted in revised form: 6.9.10

Nephrol Dial Transplant (2011) 26: 16551661 doi: 10.1093/ndt/gfq590 Advance Access publication 23 September 2010

Role of haemodialytic therapy on left ventricular mechanical dyssynchrony in patients with end-stage renal disease quantified by speckle-tracking strain imaging
Tomohiro Murata1, Kaoru Dohi2, Katsuya Onishi1, Emiyo Sugiura1, Naoki Fujimoto1, Kazuhide Ichikawa1, Eiji Ishikawa1, Mashio Nakamura1, Shinsuke Nomura1, Hideyuki Takeuchi3, Tsutomu Nobori2 and Masaaki Ito1
Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan, 2Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine,Tsu, Japan and 3Takeuchi Hospital, Tsu, Japan Correspondence and offprint requests to: Kaoru Dohi; E-mail: dohik@clin.medic.mie-u.ac.jp
1

Abstract Background. Abnormal myocardial loading can contribute to left ventricular (LV) mechanical dyssynchrony in

patients with end-stage renal disease (ESRD). The aims of this study were to characterize and quantify LV function and mechanical dyssynchrony in patients with

The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

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ESRD, and to elucidate the impact of haemodialytic (HD) therapy on these parameters by speckle-tracking strain imaging. Methods. Twenty-three patients with ESRD (63 11 years) before (pre-dialysis group) and after HD therapy (postdialysis group) and 28 normal subjects (control group; 60 10 years) were examined by echocardiography. Global and segmental LV peak systolic strain (PSS) were analysed, and LV mechanical dyssynchrony was assessed by calculating the standard deviation of the segmental time-to-PSS over longitudinal, circumferential or radial regions, respectively. Results. Global PSS and LV ejection fraction in the predialysis group were similar to those in the control group, and were not altered by HD therapy. LV mechanical dyssynchronies in the longitudinal and radial directions, but not in the circumferential direction, were significantly greater in the pre-dialysis group than those in the control group [longitudinal direction: 63 15 (P < 0.05 vs. the control group) vs. 49 15 ms, circumferential direction: 44 24 vs. 41 23 ms, and radial direction: 47 29 (P < 0.05 vs. the control group) vs. 16 18 ms]. HD therapy dramatically improved only the radial LV dyssynchrony in the post-dialysis group (23 24 ms, P < 0.05 vs. the pre-dialysis group). Conclusions. The presence of ESRD was associated with longitudinal and radial LV dyssynchronies. In addition, HD therapy dramatically improved radial LV dyssynchrony, which strongly indicates that only radial LV dyssynchrony is preload dependent among the three LV systolic directions.
Keywords: dyssynchrony; echocardiography; haemodialysis; left ventricle

renal disease (ESRD) requiring chronic haemodialytic (HD) therapy. Although a large number of echocardiographic indices have been proposed to determine LV mechanical dyssynchrony using a tissue Doppler imaging technique [7,8], they typically only measure longitudinal wall motion, and ignore radial and circumferential myocardial deformation that may play a pivotal role in the physiology of LV mechanical dyssynchrony [9,10]. Speckle-tracking echocardiography is a new approach to quantify global and segmental LV deformation independently in the longitudinal, circumferential and radial directions [11,12]. In the present study, we investigate the potential contribution of volume overload to the development of LV mechanical dyssynchrony in the longitudinal, circumferential or radial directions, and identify the acute effect of HD therapy in patients with ESRD using speckle-tracking strain echocardiography.
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Materials and methods

Study population From a total of 368 ESRD patients undergoing regular HD therapy in Mie University Hospital and Takeuchi Hospital between June and December 2008, the study group began with 30 consecutive patients with no history of LV systolic dysfunction to focus purposefully on patients with preserved LV systolic function. After enrolment, one patient identified as having a reduced LV ejection fraction <40% by echocardiography was excluded from this study. We also excluded two patients with atrial fibrillation, two patients with severe aortic stenosis, one patient with the presence of a pacing wire in the right ventricle, and one patient with technically inadequate images. Accordingly, the study group consisted of 23 patients (mean age 63 11 years, range 3181 years, 21 males) with preserved LV ejection fraction (62 9%) and was composed of 11 patients with diabetic nephropathy and 12 patients with other disease aetiologies. We also studied 28 age- and gender-matched normal subjects (control group: mean age 60 10 years, range 4479 years, 25 males) who had no history of cardiopulmonary disease, diabetes or hypertension, and no electrocardiographic and echocardiographic abnormalities. Written informed consent was obtained from all patients, and the protocol was approved for use by the Human Studies Subcommittee of Mie University Graduate School of Medicine. Haemodialytic therapy

Introduction
It is widely recognized that abnormal electrical activation sequences of the heart, often with left bundle branch block, can induce an abnormal onset of myocardial contraction resulting in consequent left ventricular (LV) mechanical dyssynchrony, which further deteriorates pump function and pump efficiency in patients with congestive heart failure [15]. However, recent studies have demonstrated significant LV mechanical dyssynchrony among patients with narrow QRS and preserved LV systolic function, providing further insight into the mechanisms governing LV mechanical dyssynchrony in various disease states [6,7]. In this context, LV mechanical dyssynchrony can be caused not only by abnormal electrical activation, but also by the heterogeneity of myocardial tissue damage, the non-uniformity of the ventricular wall structure, and abnormal loading conditions [7]. Abnormal loading such as excessive volume overload can worsen LV mechanical dyssynchrony by intensifying imbalances in the regional stretching and shortening of myocardial fibres following abnormal stress to myocardial tissue, especially in patients with end-stage
All patients underwent HD therapy three times a week using polysulphone (18 patients), polymethyl methacrylate (3 patients), cellulose triacetate (1 patient) and polyester polymer alloy (1 patient) dialysers. HD was performed for 35h (QB 150250 mL/min and QD 500 mL/min) using acetate-buffered dialysate with potassium 2.0 0.1 mmol/L (range 2.0 2.1 mmol/L), sodium 141 1 mmol/L (range 138143 mmol/L) and bicarbonate 26.7 2.4 mmol/L (range 24.029.4 mmol/L). The median (interquartile range) vintage time on dialysis was 10 (266)months. Twenty patients were dialysed via native arteriovenous fistula, and three patients were dialysed via graft. Amezinium metilsulphate was administered at the beginning of each HD therapy in two patients. During each dialysis session, excess fluid was removed to achieve the patient's clinically determined dry weight, and the mean reduction of body weight was 1.9 0.9 kg. Echocardiography All subjects received a complete transthoracic echocardiography using a Vivid 7 ultrasound system (GE-Vingmed Ultrasound AS, Horten, Norway). Patients with ESRD underwent a repeat echocardiography within 30 min before (pre-dialysis group) and after HD therapy (postdialysis group). LV volume and ejection fraction were assessed using the biplane Simpsons rule [13]. Stroke volume was calculated using pulsed Doppler from the apical long-axis view [8]. The LV mass index was

Role of haemodialysis on left ventricular dyssynchrony calculated using the arealength method [13]. The ratio of peak early-tolate diastolic transmitral flow velocity (mitral E/A) was calculated by pulsed Doppler echocardiography [14]. Colour-coded tissue Doppler cine loops from three consecutive beats were obtained from the apical 4-, 2-, and long axis for offline analysis of LV myocardial and mitral annular velocities. The ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity (E/Ea) at the lateral site was calculated as the Doppler parameter of LV filling pressure [15,16]. All echocardiographic values represent the average of three beats. Speckle-tracking strain imaging Digital routine B-mode grey-scale cine-loops from three consecutive beats were obtained from the apical 4-, 2-, long axis and mid-LV shortaxis views for offline analysis of myocardial strain using commercially available software (EchoPAC, GE-Vingmed) [1,11]. A frame rate of 76 17 Hz was used for this study. To generate myocardial strain data for evaluating myocardial dynamics, a line was loosely traced along the LV endocardium at the frame in which it was best defined. On the basis of this line, the myocardium was automatically tracked by the algorithm and divided into six segments in the apical 4-, 2-, long axis and mid-LV short-axis views, respectively (Figure 1). Segmental peak systolic strain (PSS) obtained from timestrain curves was defined as an index of regional LV myocardial systolic shortening or thickening (Figure 2). Global strain data were calculated for the entire U-shaped length of the LV myocardium from apical views for longitudinal function, and circular length from parasternal short-axis views for circumferential function [1719]. Global strain (%) = [L (end-systole) L (end-diastole)]/L (end-diastole) 100%, where L is entire length of LV myocardium. Global PSS was defined as an index of global LV myocardial systolic shortening. Global radial strain was assessed by averaging the six-site radial strain data. Quantification of left ventricular mechanical dyssynchrony The strain-derived dyssynchrony index was assessed by calculating the standard deviation of the segmental time-to-PSS over longitudinal (18 segments), circumferential (6 segments) or radial regions (6 segments), and were normalized by RR interval. Delayed contraction was defined if the maximal myocardial systolic shortening or thickening occurred after aortic valve closure; the number of the delayed segments was counted in the longitudinal, circumferential and radial directions in each group. To assess longitudinal LV mechanical dyssynchrony, we also calculated the standard deviation of the time-to-peak myocardial systolic velocity of the 12 LV segments (Ts-SD) during the ejection phase from the apical 4-, 2- and long axis using colour-coded tissue Doppler imaging [20].

1657 Intra- and inter-observer variability of time-to-PSS over longitudinal, circumferential or radial regions were analysed in 10 randomly selected echocardiographic examinations and expressed as the mean percentage error (difference/mean). Statistical analysis Data in the text and table were presented as mean standard deviation. The association among indices of cardiovascular function was investigated using regression analysis. Between-group comparisons were assessed using analysis of variance for continuous variables, and Fishers exact test for categorical data. The Bonferroni correction was applied for multiple comparisons. A P-value <0.05 was accepted as significant. Analyses were performed using SPSS for Windows, version 11.5 (SPSS, Inc., Chicago, IL, USA).

Results
Clinical and echocardiographic characteristics and effects of haemodialytic therapy Clinical characteristics of the study participants are provided in Table 1. Body weight was similar between the control group and the pre-dialysis group. Systolic, diastolic, and mean blood pressure were significantly higher in the pre-dialysis group compared with the control group. Body weight decreased after HD therapy; however, blood pressures and heart rate were statistically unchanged after HD in the post-dialysis group. The QRS duration was similar in the pre-dialysis group and the control group. The pre-dialysis group had a high prevalence of coexisting hypertension, diabetes mellitus, coronary artery disease and history of heart failure. Table 2 shows the echocardiographic characteristics of the study participants. LV volume indices and stroke volume were larger in the pre-dialysis group compared with the control group, but LV ejection fraction was similar in the two groups. HD therapy reduced LV volume indices and stroke volume without affecting LV ejection fraction. The LV mass index was higher in the pre-dialysis group compared with the control group. The pre-dialysis group had a mitral E/A similar to the control group; however,

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Fig. 1. Digital routine B-mode grey-scale cine-loop was obtained, and a six-segmental model of the left ventricle from each view was created by the tracking algorithm after manual delineation of the endocardial border in the apical (left) and short-axis views (right), respectively.

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Fig. 2. Typical longitudinal (left), circumferential (middle) and radial (right) timestrain curves in subjects from the control group (top) and the predialysis group (bottom).

E/Ea was significantly higher in the pre-dialysis group compared with the control group. HD therapy reduced mitral E/A but not E/Ea.

Assessment of global strain and left ventricular mechanical dyssynchrony Figure 2 shows typical examples of timestrain curves in subjects from the control group and pre-dialysis group. The group data for global PSS are summarized in Table 2. Global PSS was similar in the control group and the predialysis group, and HD therapy did not affect global PSS in the longitudinal, circumferential or radial directions. The group data comparing the strain-derived dyssynchrony index are shown in Figure 3. Dyssynchrony indices in the longitudinal and radial directions, but not in the circumferential direction, were significantly greater in the pre-dialysis group compared with the control group [longitudinal direction: 63 15 (P < 0.05 vs. the control group) vs. 49 15 ms, circumferential direction: 44 24 vs. 41 23 ms, and radial direction: 47 29 (P < 0.05 vs. the control group) vs. 16 18 ms]. HD therapy dramatically reduced only the radial LV dyssynchrony index [longitudinal direction: 60 14 ms (P < 0.05 vs. the control group), circumferential direction: 40

22 ms, and radial direction: 23 24ms (P < 0.05 vs. the pre-dialysis group), respectively, Figures 3 and 4]. The percentage of myocardial segments exhibiting delayed contraction in the six radial segments were significantly higher in the pre-dialysis group than those in the control group (50 31 vs. 29 39%, P < 0.05 vs. the conTable 1. Clinical characteristics of the study subjects Control (n = 28) Mean age (years) Male gender (%) Height (cm) Weight (kg) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Mean blood pressure (mmHg) Heart rate (beats/min) QRS duration (ms) Hypertension (%) Diabetes mellitus (%) CAD (%) History of heart failure (%) 60 10 25 (89) 165 9 62 9 122 14 72 10 89 10 65 9 95 13 0 0 0 0 Pre-dialysis Post-dialysis (n = 23) (n = 23) 63 11 21 (91) 164 8 63 8 154 18* 81 11* 106 12* 73 14 93 16 87* 56* 35* 26*

61 146 75 99 75

8** 23* 14 16* 17*

ESRD, end-stage renal disease; CAD, coronary artery disease. *P < 0.05 vs. the control group and **P < 0.05 vs. the pre-dialysis group, with Bonferroni's correction.

Role of haemodialysis on left ventricular dyssynchrony Table 2. Echocardiographic data of the study subjects Control LV end-diastolic volume index (mL/m2) LV end-systolic volume index (mL/m2) LV ejection fraction (%) Stroke volume (mL) LV mass index (g/m2) Mitral E/A E/Ea Global longitudinal peak systolic strain (%) Global circumferential peak systolic strain (%) Global radial peak systolic strain (%) Ts-SD (ms) 44 9 15 5 65 63 76 1.1 9 19 6 12 8 0.4 2 2 Pre-dialysis 54 19* 21 11* 62 73 121 1.0 12 18 9 14* 24* 0.5 6* 4 Post-dialysis 48 18** 18 10** 64 7 67 16** 0.9 0.4** 10 4 18 4 24 5 44 17 30 23

1659

the LV end-diastolic volume index and the reduction of the delayed segments, but not with the reduction of the mean blood pressure or the extent of volume removal after HD therapy [r = 0.54 (P < 0.05), 0.58 (P < 0.05), 0.24 and 0.26, respectively]. Inter-observer and intra-observer variability of timeto-PSS over longitudinal, circumferential and radial segments were 3.7 4.9% and 4.0 5.5%, 6.6 7.2% and 6.9 7.9%, and 6.2 6.3% and 6.9 6.5%, respectively.

Discussion
This is the first study to characterize and quantify global LV function and mechanical dyssynchrony in patients with ESRD, and to elucidate the effects of HD therapy on these parameters by speckle-tracking strain echocardiography. Speckle-tracking strain echocardiography revealed that LV mechanical dyssynchrony is frequently present in patients with ESRD and preserved LV systolic function, especially in the radial and longitudinal directions, and that HD therapy dramatically improved only radial LV dyssynchrony among the three LV systolic directions, which strongly indicates that radial LV dyssynchrony is sensitive to and is modulated by alterations in volume status. The existence of LV mechanical dyssynchrony may have the potential to contribute to the high incidence of cardiac events or deaths in patients with ESRD receiving HD therapy since the non-uniformity of LV contraction impairs systolic performance. Therefore, it is clinically important to identify LV mechanical dyssynchrony and to address its underlying mechanisms in such a population. It is widely recognized that abnormal electrical activation sequences of the heart can induce the abnormal onset of myocardial contraction resulting in LV mechanical dyssynchrony in patients with congestive heart failure [1,2]. However, LV mechanical dyssynchrony can be caused not only by abnormal electrical activation but also by the heterogeneity of myocardial tissue damage and the non-uniformity of the ventricular wall structure [7]. Therefore, the mechanisms of LV mechanical dyssynchrony in ESRD patients with a normal QRS duration and maladaptive LV hypertrophy can be different from those associated with LV systolic dysfunction and abnormal electrical activation

23 4 52 12 23 13

22 5 47 13 42 23*

ESRD, end-stage renal disease; LV, left ventricular; Mitral E/A, ratio of peak early to late diastolic transmitral flow velocity; E/Ea, ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity; TsSD, the standard deviation of the time to peak myocardial systolic velocity during ejection phase of the 12 LV segments. *P < 0.05 vs. the control group and **P < 0.05 vs. the pre-dialysis group, with Bonferroni's correction.

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trol group), and HD therapy significantly reduced this delay to 23 36% (P < 0.05 vs. the pre-dialysis group). The percentage of myocardial segments exhibiting delayed contraction in the 18 longitudinal segments were significantly higher in the pre-dialysis group than those in the control group (45 19 vs. 32 11%, P < 0.05 vs. the control group). However, HD therapy did not reduce the delayed segments in the longitudinal direction (41 13%, P = NS vs. the pre-dialysis group). The number of delayed segments was similar among the three groups in the circumferential direction (data not shown). Ts-SD was greater in the pre-dialysis group compared with the control group; however, it was not significantly improved statistically after HD therapy (Table 2). There were no significant correlations between indices of LV dyssynchrony in the longitudinal, circumferential, or radial directions and mean blood pressure in all subjects (data not shown). Improvement of the radial LV dyssynchrony index modestly correlated with the reduction of

Fig. 3. Plots showing comparisons of left ventricular mechanical dyssynchrony in the control group (open circle; n = 28), the pre-dialysis group (grey circle; n = 23), and the post-dialysis group (black circle; n = 23) in the longitudinal (left), circumferential (middle) and radial (right) directions. *P < 0.05 vs. the control group; **P < 0.05 vs. the pre-dialysis group.

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Fig. 4. Typical example of radial timestrain curves in a patient with end-stage renal disease before (left: pre-dialysis) and after (right: post-dialysis) haemodialytic therapy.

sequences. By measuring the onsets of regional peak systolic velocity at the LV basal segments, Pai et al. first demonstrated that hypertensive LVH was associated with LV mechanical dyssynchrony despite the absence of intraventricular conduction delays and regional wall motion abnormalities [21]. In the present study, patients with ESRD and LVH had significant radial as well as longitudinal LV dyssynchronies assessed by using speckle-tracking strain echocardiography. The presence of systolic dyssynchrony and the absence of a conduction abnormality suggest the probability of heterogeneities in electromechanical coupling consequent to myocardial disease or subendocardial ischaemia caused by LV hypertrophy, which may account for the prominent delayed segmental contraction. Excessive volume overload can also worsen LV mechanical dyssynchrony by intensifying the imbalance in regional stretching and shortening of myocardial fibres following abnormal stress to myocardial tissue [6]. Hayashi et al. demonstrated the frequent coexistence of LV dyssynchrony in patients with ESRD using tissue Doppler velocity imaging and revealed that the severity of LV dyssynchrony correlates with LV end-diastolic diameter, an echocardiographic marker of LV preload [7]. In the present study, HD therapy profoundly reduced radial LV dyssynchrony, which modestly correlated with a reduction in LV volume after HD therapy. These data suggest that preload reduction plays a key role in the amelioration of radial LV dyssynchrony. Consistent with our observations, Park et al. recently demonstrated that radial LV dyssynchrony, defined as the maximal difference in time-to-peak radial strain among six myocardial segments, was significantly reduced by preload reduction after the administration of sublingual nitroglycerine in patients with non-ischaemic cardiomyopathy [22]. HD therapy also has the potential to improve LV dyssynchrony via afterload reduction [23]; however, changes in mean blood pressure after HD therapy did not correlate with the improvement of radial LV dyssynchrony in the present study.

Significant longitudinal dyssynchronies assessed by both speckle-tracking strain echocardiography and tissue Doppler imaging were observed in patients with ESRD before HD therapy; however, amelioration of these longitudinal dyssynchronies was not achieved by a single HD therapy in the present study. Delgado et al. revealed that only radial LV dyssynchrony profoundly improved after cardiac resynchronization therapy at 6-month follow-up, whereas the changes in the same parameters assessed with longitudinal or circumferential strain were insignificant in patients with heart failure [11]. Therefore, the assessment of longitudinal or circumferential dyssynchrony by calculating time-to-peak regional contraction may not be suitable to identify whether a certain therapeutic intervention is able to improve LV mechanical dyssynchrony. Our study demonstrated the high prevalence of the segments with delayed contraction in patients with ESRD before HD therapy in the longitudinal and radial directions compared with normal subjects. Delayed myocardial contraction occurs in a few disease conditions of the heart including myocardial ischaemia, stunning or hibernation. Recently, it was also found to be a potentially useful surrogate marker of LV mechanical dyssynchrony in patients with heart failure and wide QRS complexes [24,25]. In the present study, improvement of radial LV dyssynchrony correlated significantly with a reduction in the number of segments exhibiting delayed contraction after HD therapy. Although the mechanisms underlying delayed contraction remain unclear, HD therapy restores radial LV synchrony in part by normalizing the time sequence of regional deformation in the myocardial segments with delayed contraction. A technical limitation is that speckle-tracking echocardiography is dependent on frame rate, as well as image resolution [1]. Low frame rates result in inconsistent speckle patterns, which prevent the precise characterization of regional myocardial motion and impact the overall temporal resolution of the regional strain map. In contrast, increas-

Role of haemodialysis on left ventricular dyssynchrony

1661 8. Gorcsan J, Kanzaki H, Bazaz R et al. Usefulness of echocardiographic tissue synchronization imaging to predict acute response to cardiac resynchronization therapy. Am J Cardiol 2004; 93: 11781181 9. Dohi K, Suffoletto MS, Schwartzman D et al. Utility of echocardiographic radial strain imaging to quantify left ventricular dyssynchrony and predict acute response to cardiac resynchronization therapy. Am J Cardiol 2005; 96: 112116 10. Arita T, Sorescu GP, Schuler BT et al. Speckle-tracking strain echocardiography for detecting cardiac dyssynchrony in a canine model of dyssynchrony and heart failure. Am J Physiol Heart Circ Physiol 2007; 293: H735H742 11. Delgado V, Ypenburg C, van Bommel RJ et al. Assessment of left ventricular dyssynchrony by speckle tracking strain imaging comparison between longitudinal, circumferential, and radial strain in cardiac resynchronization therapy. J Am Coll Cardiol 2008; 51: 19441952 12. Bertola B, Rondano E, Sulis M et al. Cardiac dyssynchrony quantitated by time-to-peak or temporal uniformity of strain at longitudinal, circumferential, and radial level: implications for resynchronization therapy. J Am Soc Echocardiogr 2009; 22: 665671 13. Daimon M, Watanabe H, Abe Y et al. JAMP Study Investigators. Normal values of echocardiographic parameters in relation to age in a healthy Japanese population: the JAMP study. Circ J 2008; 72: 18591866 14. Nishimura RA, Tajik AJ. Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiography in the clinicians Rosetta stones. J Am Coll Cardiol 1997; 30: 818 15. Garcia MJ, Rodriguez L, Ares M et al. Differentiation of constrictive pericarditis from restrictive cardiomyopathy: assessment of left ventricular diastolic velocities in longitudinal axis by Doppler tissue imaging. J Am Coll Cardiol 1996; 27: 108114 16. Nagueh SF, Middleton KJ, Kopelen HA et al. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997; 30: 15271533 17. Reisner SA, Lysyansky P, Agmon Y et al. Global longitudinal strain: a novel index of left ventricular systolic function. J Am Soc Echocardiogr 2004; 17: 630633 18. Chan J, Hanekom L, Wong C et al. Differentiation of subendocardial and transmural infarction using two-dimensional strain rate imaging to assess short-axis and long-axis myocardial function. J Am Coll Cardiol 2006; 48: 20262033 19. Takamura T, Dohi K, Onishi K et al. Left ventricular contractionrelaxation coupling in normal, hypertrophic, and failing myocardium quantified by speckle-tracking global strain and strain rate imaging. J Am Soc Echocardiogr 2010; 23: 747754 20. Yu CM, Fung JW, Zhang Q et al. Tissue Doppler imaging is superior to strain rate imaging and postsystolic shortening on the prediction of reverse remodeling in both ischemic and nonischemic heart failure after cardiac resynchronization therapy. Circulation 2004; 110: 6673 21. Pai RG, Gill KS. Amplitudes, durations, and timings of apically directed left ventricular myocardial velocities: II. Systolic and diastolic asynchrony in patients with left ventricular hypertrophy. J Am Soc Echocardiogr 1998; 11: 112118 22. Park HE, Chang SA, Kim HK et al. Impact of loading condition on the two-dimensional speckle tracking-derived left ventricular dyssynchrony index in non-ischemic dilated cardiomyopathy. Circ Cardiovasc Imaging 2010; 3: 272281 23. Miura T, Bhargava V, Guth BD et al. Increased afterload intensifies asynchronous wall motion and impairs ventricular relaxation. J Appl Physiol 1993; 75: 389396 24. Yu CM, Bax JJ, Monaghan M et al. Echocardiographic evaluation of cardiac dyssynchrony for predicting a favorable response to cardiac resynchronization therapy. Heart 2004; 90: vi17vi22 25. Sogaard P, Egeblad H, Kim WY et al. Tissue Doppler imaging predicts improved systolic performance and reversed left ventricular remodeling during long-term cardiac resynchronization therapy. J Am Coll Cardiol 2002; 40: 723730 Received for publication: 13.4.10; Accepted in revised form: 2.9.10

ing the frame rate reduces scan-line density, which reduces the image resolution. Accordingly, we found frame rates of 76 17 Hz suitable for speckle-tracking analysis. Invasive pressure measurements were not involved in the present study; therefore, evaluations of LV end-diastolic pressure or pulmonary wedge pressure were not possible. Accordingly, E/Ea at the lateral site was recruited as a marker of LV filling pressure in the present study. This Doppler-derived pressure estimation is widely recognized to correlate with simultaneous catheter-derived measurements [16]. We did not assess toxic accumulation or electrolyte imbalances in uraemia, which may affect the mechanism of LV synchronicity disturbances. Finally, evaluations of clinical outcomes were not involved in the present study. Long-term effects on morbidity and mortality warrant further investigation. In conclusion, the existence of ESRD was associated with longitudinal and radial LV dyssynchronies, and HD therapy dramatically improved only radial LV dyssynchrony. These clinical observations strongly indicate that only radial LV dyssynchrony is preload dependent among the three LV systolic directions. Therefore, the assessment of radial LV dyssynchrony may provide important additional information for better risk stratification and guide the therapeutic strategy in patients with ESRD receiving HD therapy.
Acknowledgements. This work was supported in part by grants-in-aid for Scientific Research from the Ministry of Education, Science, Technology, Sports and Culture, Japan (to K.D.). The authors are grateful to GE Healthcare for technical support. Conflict of interest statement. None declared.

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