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Hemodialysis International 2016; 20:564–572 Hemodialysis-induced regional left ventricular systolic dysfunction Yuxin NIE,1,2 Zhen ZHANG,1,2 Jianzhou ZOU,1,2,3 Yixiu LIANG,4 Xuesen CAO,1,2 Zhonghua LIU,1,2 Bo SHEN,1,2 Xiaohong CHEN,1,2 Xiaoqiang DING1,2,3 1 Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, P. R. China; 2Shanghai Institute of Kidney Disease and Dialysis, Shanghai, P. R. China; 3Key Laboratory of Kidney and Blood Purification of Shanghai, Zhongshan Hospital, Fudan University, Shanghai, P. R. China; 4Division of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, P. R. China Abstract Introduction Hemodialysis (HD) patients are under observably elevated cardiovascular mortality. Cardiac dysfunction is closely related to death caused by cardiovascular diseases (CVD). In the general population, repetitive myocardial ischemia induced left ventricular (LV) dysfunction may progress to irreversible loss of contraction step by step, and finally lead to cardiac death. In HD patients, to remove water and solute accumulated from 48 or 72 hours of interdialysis period in a 4-hour HD session will induce myocardial ischemia. In this study, we evaluated the prevalence and potential risk factors associated with HD-induced LV systolic dysfunction and provide some evidences for clinical strategies. Methods We recruited 31 standard HD patients for this study from Fudan University Zhongshan hospital. Echocardiography was performed predialysis, at peak stress during HD (15 minutes prior to the end of dialysis), and 30 minutes after HD. Auto functional imaging (AFI) was used to assess the incidence and persistence of HD-induced regional wall motion abnormalities (RWMAs). Blood samples were drawn to measure biochemical variables. Findings Among totally 527 segments of 31 patients, 93.54% (29/31) patients and 51.40% (276/ 527) segments were diagnosed as RWMAs. Higher cTnT (0.060 6 0.030 vs. 0.048 6 0.015 ng/mL, P 5 0.023), phosphate (2.07 6 0.50 vs. 1.49 6 0.96 mmol/L, P 5 0.001), UFR (11.00 6 3.89 vs. 8.30 6 2.66 mL/Kg/h, P 5 0.039) and lower albumin (37.83 6 4.48 vs. 38.38 6 2.53 g/L, P 5 0.050) were found in patients with severe RWMAs (RWMAs in more than 50% segments). After univariate and multivariate analysis, interdialytic weight gain (IDWG) was found as independent risk factor of severe RWMAs (OR 5 1.047, 95%CI 1.155–4.732, P 5 0.038). Discussion LV systolic dysfunction induced by HD is prevalent in conventional HD patients and should be paid attention to. Patients would benefit from better weight control during interdialytic period to reduce ultrafiltration rate. Key words: Hemodialysis, left ventricle, systolic dysfunction, myocardial injury, myocardial stunning INTRODUCTION Correspondence to: X. Ding, MD, 180 Fenglin Road, Shanghai, 200032, P. R. China, E-mail: ding.xiaoqiang@ zs-hospital.sh.cn Conflict of Interest: The authors declare that they have no conflict of interests. Disclosure of grants or other funding: The authors declare that they have no grants or other funding. Among Hemodialysis (HD) patients, prevalence of CVD and cardiovascular mortality is observably elevated. According to the USRDS annual data report 2015, more than 60% of death were caused by CVD, such as chronic heart failure (CHF), arrhythmia, cardiac arrest, and so forth.1 It is as 30 times higher than the general population at the same age.2 One important reason that may lead to cardiac death is LV C 2016 International Society for Hemodialysis V DOI:10.1111/hdi.12434 564 HD-induced LV systolic dysfunction dysfunction, which is extremely prevalent in HD patients,1 and always represents poor prognosis. In nondialysis patients, cardiac systolic dysfunction caused by transient subclinical myocardial ischemia may persist for a period even perfusion has returned to normal. This delayed recovery of LV function is defined as myocardial stunning.3 Recurrent episodes of stunning are cumulative and contribute to the pathophysiology of heart failure.4 In HD patients, because of the intermittent blood volume reduction due to fluid removal, systemic hypoperfusion, and cardiac ischemia is quite common represented by intradialytic hypotension (IDH).5 This ischemic effect, though transient, could potentially cause myocardial fibrosis in the long term and the subsequent LV kinetic dysregulation.6 The combination of coronary hypoperfusion and resultant myocardial dysfunction culminates in an elevated mortality in chronic HD patients. In this study, we tried to explore the prevalence and risk factors of HD-induced LV systolic dysfunction in HD patients. The study adhered to the Declaration of Helsinki and was approved by the Ethical Committee, Zhongshan Hospital, Fudan University HD parameters Dialysis was conducted using GAMBRO (AK200S, Sweden) with low-flux hollow polysulfone membrane dialyzers, surface area either 1.4 or 1.6 m2, prescriptions depend on patients individually. Dialysate composition was Na1 138 mmol/L, K1 2 mmol/L, Ca21 1.25 mmol/L, Mg21 0.5 mmol/L, and bicarbonate 32 mmol/L. The dialysate flow was set at 500 mL/minutes, and dialysate temperature was set at 378C. Ultrafiltration volume (UF) was set individually according to their IDWG. Blood pump was set at a range from 200 to 250 mL/minutes depends on the patient’s access. Blood pressure (BP) was recorded before the start of dialysis and then per hour during HD session. All HD sessions were 4 hours. Low molecular weight heparin was used for anticoagulation. Echocardiography assessment MATERIALS AND METHODS Patient population Thirty-one standard HD patients agreed to participate in this study from Fudan University Zhongshan hospital hemodialysis unit from November 2014 to April 2015. Patients are dialyzed three times a week for 4-hours per session. Patients with following situations were excluded: (a) Left ventricular ejection fraction (LVEF) < 55% or NYHA class III or IV; (b) Myocardial infarction within last 6 months; (c) Dialysis vintage <3 months; (d) Cancer. Echocardiographs and blood samples were conducted at the end of the longest interdialytic period, since most cardiovascular events occur after the long interdialytic break. Venous blood samples were drawn by phlebotomy immediately before and after each dialysis session. All biochemical analyses including serum albumin, prealbumin, hemoglobin, serum creatinine (SCr), blood urea nitrogen (BUN), uric acid (UA), sodium (Na1), potassium(K1), calcium (Ca21), phosphate, magnesium (Mg21), and ferritin were measured using an automatic analyzer in clinical laboratories. The concentration of high-sensitivity cardiac troponin T (hs-cTnT) was determined using immunoturbidimetry assay. N-terminal proBNP was assessed using enzyme-linked immunosorbent assay (ELISA). Hemodialysis International 2016; 20:564–572 Apical two-dimensional echocardiography was conducted before the start of HD, at peak stress during HD (15 minutes before the end of dialysis) and 30 minutes after the end of HD (GE medical systems, Germany) by a single doctor, who is blinded to the patients’ other clinical results. Images were digitally recorded for subsequent offline analysis (EchoPAC Clinical Workstation Software, GE, Germany). At least three stable consecutive cardiac cycles were recorded for analyze using AFI technic, which can track the wall motion by detect the endocardial borders semiautomatically. Each ventricular was divided into 17 segments as shown in Figure 1.7 All segments were analyzed for their percentage of peak systolic strain (%PSS). Segments those showed reductions of % PSS more than 20% comparing to baseline were defined as RWMAs. HD-induced regional LV systolic dysfunction was defined as new occurrences of RWMAs in at least two LV segments at any time point after the beginning of HD session.8 Wall motion score index (WMSI) was calculated for each patient as well. Statistical analysis SPSS (version 20.0) was used for statistical analysis. Statistical significance level was defined as 0.05. Data were expressed as counts/percentages for discrete variables or as means 6 SDs for continuous variables. Comparison between patients with and without HD-induced LV systolic dysfunction was made by a chi-square test for 565 Nie et al. Comparison between patients with/ without severe RWMAs Figure 1 Left ventricular segmentation. Numbers in the figure represents: 1. Basal anterior; 2. Basal anteroseptal; 3. Basal inferoseptal; 4. Basal inferior; 5. Basal inferolateral; 6. Basal anterolateral; 7. Mid anterior; 8. Mid anteroseptal; 9. Mid inferoseptal; 10. Mid inferior; 11. Mid inferolateral; 12. Mid anterolateral; 13. Apical anterior; 14. Apical septal; 15. Apical inferior; 16. Apical lateral; 17. Apex. categorical variables. For normally distributed continuous variables and non–normally distributed continuous variables, we chose a t test or a Mann–Whitney test, respectively. The Pearson correlation was used to assess linear relationships. Univariate and multivariate logistic regression were used to figure out the risk factors for HDinduced myocardial stunning. Multivariate analysis involved variables showed statistical differences in univariate analysis. We defined RWMAs occurred in more than 50% segments as severe RWMAs. When comparing patients with and without severe RWMAs, we found significant differences of serum phosphate level before dialysis, hs-cTnT and ultrafiltration rate (UFR) between two groups (P 5 0.001, 0.023, 0.039, respectively). What’s more, patients with severe RWMAs showed higher WMSI than another group (1.04 6 0.05 vs. 1.00 6 0.02, P 5 0.021). However, there’s no significant difference of baseline LVEF and other LV structures between two groups (supporting Information Table 2). Serum albumin showed a higher trend in patients without severe RWMAs, although not reaching statistical significance (P 5 0.050; Figure 3). There is no difference of age, gender, history of diabetes and CVD, dialysis vintage, dialysis access, dry weight (DW), IDWG, serum Ca21, serum K1, NT-proBNP level, reduction of mean artery pressure (MAP). Association of candidate predictors with severe RWMAs Using Pearson rank correlation analysis, serum cTnT before hemodialysis (r 5 0.437, P 5 0.014), IDWG (r 5 0.372, P 5 0.039), UF (r 5 0.357, P 5 0.049), UFR (r 5 0.368, P 5 0.042) were positive related with number of RWMAs segments. In univariate regression analysis, IDWG (OR 5 1.047, 95%CI 1.155–4.732, P 5 0.038), RESULTS Characteristics of study participants Of the total 31 patients, there are 19 males and 12 females, with a mean age at 60 years old. The baseline characteristics are listed in supporting Information Table 1. Among totally 527 segments of 31 patients, 93.54% (29/31) patients and 51.40% (276/527) segments were diagnosed as RWMAs. Basal anterior (22/276), apical septal (20/276), apical lateral (20/276) and mid anterior (19/ 276) were the most likely influenced segments. Meanwhile, basal inferoseptal (12/276), mid inferoseptal (13/ 276), mid inferior (13/276) and mid inferolateral (14/ 276) were segments not influenced so much (Figure 2). 566 Figure 2 Distribution of HD-induced RWMAs regions. Numbers in the vertical axis represents: 1. Basal anterior; 2. Basal anteroseptal; 3. Basal inferoseptal; 4. Basal inferior; 5. Basal inferolateral; 6. Basal anterolateral; 7. Mid anterior; 8. Mid anteroseptal; 9. Mid inferoseptal; 10. Mid inferior; 11. Mid inferolateral; 12. Mid anterolateral; 13. Apical anterior; 14. Apical septal; 15. Apical inferior; 16. Apical lateral; 17. Apex. Hemodialysis International 2016; 20:564–572 HD-induced LV systolic dysfunction Figure 3 Comparison between patients with/without severe RWMAs. Due to the wide range of variables’ values (five orders of magnitude difference), the figure is presented by Logarithmic scale axis. Blue bar represents patients with RWMAs less than 50% (n 5 13). Red bar represents patients with RWMAs equals to or more than 50% (n 5 18). Table 1 Detection of hemodialysis-induced myocardial stunning in univariate and multivariate regression analyses Predictor Univariable analysis IDWG (for every additional percentage) UFR (for every additional liter per hour) Phosphorus (for every additional mmol/L) WBC (for every additional count of 109) Multivariable analysis IDWG (for every additional percentage) Odds Ratio (95% CI) 1.047 66.627 3.070 2.177 (1.155–4.732) (1.186–3746.760) (0.091–9.505) (1.095–4.329) 1.047 (1.155–4.732) P value 0.038 0.041 0.052 0.026 0.038 CI 5 Confidence interval; IDWG 5 interdialytic weight gain; UFR 5 Ultrafiltration rate; WBC 5 White blood cell count. UFR (OR 5 1.004, 95%CI 1.001–1.008, P 5 0.041) were risk factors of severe RWMAs. Then we toke covariables associated with outcome with P < 0.1, after multivariate logistic regression, only IDWG remained as independent risk factor (Table 1). Figure 4 Sensitivity analysis using different methods to define RWMAs. WMSI 5 Wall motion score index; WMS 5 Wall motion score; SF 5 Shortening fraction. Hemodialysis International 2016; 20:564–572 DISCUSSION HD-induced LV systolic dysfunction is quite prevalent in maintenance HD patients. In our study, about 90% patients and more than half segments were diagnosed as RWMAs. However, the percentage of RWMAs varies quite different from study to study. The widely range is mainly due to different methods used in different studies. Burton et al evaluated RWMAs by shortening fraction (SF), and defined RWMA as the region showed a decline in SF more than 20% from baseline, and the prevalence of RWMAs in his study was 74%;9 Assa et al defined RWMA as region showed an increase in WMSI, and reported the prevalence of RWMAs in at least 2 out of 17 LV regions as 29%;8 while Dubin et al defined RWMA as an increase of sum of wall motion score (WMS) in all LV segments, and they found the prevalence of RWMAs as 23%.10 When we used the other three methods mentioned above for a sensitivity analysis, the results varied from 30% to 90%, as shown in Figure 4. Comparing to these methods, the region was defined as RWMA as long as it showed a decline of %PSS more than 20% from baseline 567 Nie et al. according to the AFI method (strain echocardiography) used in our study. Sometimes the systolic function is still within the normal range even after the decline. At this time, the region is defined as RWMA if using “strain” method, but non-RWMA if using WMS or WMSI. Similarly, when comparing methods using %PSS and %SF, the latter one only represents global LV systolic function, while %PSS could represents regional segment function. If a heart shows changes of %PSS in a few LV segment with preserved global systolic function, it is defined as RWMA if using %PSS, but non-RWMA if using %SF. As a result, it leads to a higher prevalence of RWMAs when choosing strain echocardiography than choosing WMS or %SF. Since there is no standard criterion for HD-induced LV systolic dysfunction yet, it is hard to judge which method is better than others. Strain echocardiography is more sensitive to detect early stage reduction of cardiac function. What is more, it has been proved that even among patients with reserved LV functions, strain echocardiography is still reliable and powerful.11 Some researchers found that patients with HD-induced cardiac dysfunction were under worse baseline cardiac functions.8,10 In our study, the baselines LVEFs for patients without and with severe RWMAs were 63.46% 6 7.38% and 64.59% 6 5.83%, respectively (P 5 0.979), and WMSI were 1.00 6 0.02 and 1.04 6 0.05, respectively (P 5 0.021). There’s just a slightly higher WMSI with similar LVEF in patients with severe RWMAs. The reason why we failed to find association between baseline cardiac function and occurrence of RWMAs may be due to the different study population. In Assa’s study, 35.2% patients have baseline LVEF<50%, and 40% patients have WMSI > 1. Similarly, in Dubin’s study, 12.5% patients had heart failure with average baseline LVEF of 40%, and some degrees of diastolic dysfunction. While in our study, we excluded patients with LVEF<55%, and our baseline LVEF was 64%, with only 25% patients had WMSI>1, which means our study’s population was under a better baseline cardiac function. As a result, there showed no significant differences of LVEF between patients with and without severe RWMAs. Further studies including patients with worse heart functions would be more comprehensive and representative, and should be considered for a better illustration. Besides systolic function, diastolic function is an important part of the cardiac function as well, which represents the ability of the heart to expand and refill the ventricles. It was determined by the intrinsic ventricular properties, such as stiffness and relaxation. When the ventricles systole, the cardiac muscles both contract and twist, the circumferential muscles distort to the helical orientation, 568 which varies from endocardium to epicardium by 1608.12 During this process, elastic energy is stored in myocytes.13 When diastolic period starts, the stored energy is released to “untwist” the ventricles, and create suction pressures, which initiate the ventricles filling.14,15 In the general population, studies showed that the ischemia and periischemia regions caused by coronary artery occlusion represented ischemia-induced diastolic dysfunction, which could be relieved after a period of reperfusion.16,17 Similarly, during HD sessions, diastolic dysfunction caused by HD-induced ischemia has been proved using conventional echocardiography and Tissue Doppler Imaging (TDI) methods.18–20 What is more, diastolic dysfunction has been proved closely related with poor outcome, even in patients with preserved systolic function.21 However, as HD patients are usually with rapidly blood volume changes during HD sessions, evaluate the diastolic function by conventional methods, such as early mitral flow velocity and atrial filling, might not be accurate.22 AFI conducted by two-dimensional speckle tracking echocardiography (STE) is a more sensitive and reliable method to measure diastolic function.23,24 Further research focus on diastolic strain abnormalities should be considered for the assessment of HD-induced diastolic dysfunction. According to our results, we found that segments with single coronary artery blood supply were more prone to be impacted during HD, such as basal anterior, apical septal, apical lateral, and mid anterior segments. In a recent study, Huang et al also found that apical inferior, mid anterior, basal anterior and basal lateral segments showed a trend toward higher strain value at peak dialysis compared with it before dialysis.25 Since in Huang’s study, the author divided LV chamber into 12 segments, while we divided it into 17 segments, although the names of influenced segments are not exactly the same, they showed highly similar distribution in a bulls-eye display. What is more, Huang et al also found that the segmental longitudinal strains (SLS) of the mid septal and apical septal segments, as well as apical, inferior and septal arears were associated with survival outcome. The authors attributed the anatomically vulnerable regions to the mismatch of perfusion/ischemia. McIntyre et al reported that when using H2-15O positron emission tomography to assess myocardial blood flow (MBF), LV segments dysfunction could be induced by decline of MBF.26 However, the reason why some segments are more “fragile” than others is remain unclear. It has been reported that there is a reduction of the number of capillaries per volume among HD patients due to the uremic toxins and cardiac structural abnormal.27,28 As a result, it shows a mismatch of myocytes and capillaries.22 Besides that the increased Hemodialysis International 2016; 20:564–572 HD-induced LV systolic dysfunction vascular calcification and arterial stiffness29 result impaired microperfusion of the heart. Thus, the ability to adapt the hemodynamic pressure induced by HD is decreased. It has been widely recognized that IDH plays an important role in elevated CV mortality in HD patients. Beyond the fluid removal during HD sessions, another hypothesis for IDH is defective vasoregulation.22 Several risk factors may contribute to this deficiency. Chesterton et al reported impaired baroreflex sensitivity due to autonomic dysfunction in HD patients.30 Meanwhile, endothelium as the key regulator of vascular function was damaged as a consequence of the combination of inflammation,31,32 endotoxins,33 and oxidative stresses.34 Eventually, multiple factors lead to abnormal perfusion of the end organs and vulnerable vascular beds, especially when under increasing circulatory stress induced by HD.22 In the general population, the most popular hypothesis about the mechanisms of ischemia induced cardiac dysfunction is “Oxyradical Hypothesis.”35 Thus, it mostly occurs during the first few minutes of reperfusion with arterial blood.35,36 However, according to our study and some other research,9,37 HD-induced LV systolic dysfunction mostly happens during the dialysis session (before the end of dialysis session) instead of the period of reperfusion (after the end of dialysis session). This might in some levels explain the increased risk of sudden cardiac death during and immediately after hemodialysis.38 Different occurrence times imply that cardiac dysfunction in HD patients might have different mechanisms from general population, which are still not well demonstrated and needs further research. When comparing patients without severe RWMAs, hscTnT is statistically higher in patients with severe RWMAs. Higher hs-cTnT as a biomarker represents severer myocardial injury, so even there is neither symptom, such as chest pain; nor difference of basic cardiac structures and functions between two groups, potential insufficiency of coronary artery blood reserve and subclinical myocardial injury may already exists. During HD, because of the quick removal of fluid and instable of hemodynamics, myocardial dysfunction was induced. Higher UFR is a risk factor of HD-induced RWMAs. During dialysis session, overload volume accumulated in two to three interdialytic days is removed in 4 hours. Consequently, it brings strong stress to the heart. Previous studies demonstrated that both larger IDWG39 and higher UFR40 were associated with poor survival. HD-induced cardiac dysfunction may present a new idea to explain why this would happen. When giving more frequent or extended HD treatments, the dysfunction could be lessened by the reduction of UFR, which provides further eviHemodialysis International 2016; 20:564–572 dences for it.41 According to this finding, personalized dialysis target to minimize UFR either by more frequent dialysis scheduling or by extended dialysis should be considered, to prevent HD-induced RWMAs and improve long-term cardiovascular outcomes. Albumin is in a lower lever in patients with severe RWMAs, although not meeting a statistical significance (P 5 0.05). This might because of the limit of sample size. Lower albumin represents of malnutrition status and inflammation, which have been well demonstrated with atherosclerosis and poor survival.42 More inflammatory markers such as C-reactive protein, IL-6 and IL-33 and so on could provide more clues about inflammation and HD-induced cardiac dysfunction. In clinical practice, maintaining albumin level at an appropriate range should always be highly focused. In patients with severe RWMAs, they were found under a higher serum phosphate level. Elevated phosphate level is well known associated with adverse cardiovascular outcomes. Suzuki and his coworkers found that in spontaneously hypertensive rats, high phosphate and zinc-free diet markedly reduced their left ventricular systolic and diastolic function and cause severe myocardial fibrosis histopathologically.43 Liu et al. described that high phosphate level is related with increased secretion of ANP and BNP in cardiac myoblast.44 Hyperphosphate may cause cardiomyocytes abnormalities both in structural and functional. When during HD, under stresses caused by changes in electrolytes, acid-base balance, and blood volume on a heart that is already in a nonhealthy state, myocardial dysfunction is induced. It has been well illustrated that HD-induced regional LV systolic dysfunction is closely related to a poor longterm cardiac function and an elevated mortality rate.8,9,11 Thus, strategies to prevent the occurrence of HD-induced cardiac injuries could contribute to a better survival. The protective effects of cooler dialysate on cardiac have been well studied by many researchers. Selby et al reported that when comparing patients using dialysate with temperatures of 37 (HD [37]) and 35 (HD [35]) degree centigrade, less regional LV systolic dysfunction was induced during HD session with more stable hemodynamic parameters in patients with HD (37).37 Further study attributes the protective effect of cool dialysate to the improvement of baroreflex variability.45 Although, the effectiveness of cool dialysate has been acknowledged, the intolerable temperature is still a big problem. As a result, individualized cool dialysate was demonstrated. Jefferies et al proved that dialysate with the temperature 0.58 lower than the patients’ core temperature was as effective as HD (35), and without compromising tolerability.46 A most recently randomized controlled trial 569 Nie et al. involved 73 incident HD patients with 12 months followup, and evaluated the patients’ systolic and diastolic function by cardiac magnetic resonance imaging, and left ventricular mass as well. It confirmed the benefit of individualized cool dialysate for cardiac protection over a 12-month period.47 Beyond the cardio-protection, the strategy of individualized cool dialysate also represents multi end organs protection.48 Using individualized cooled dialysate is an effective intervention with no additional cost, and is easy to accept and widely use. An alternative option to reduce HD-induced cardiac dysfunction is to minimize the UFR by more frequent HD scheduling. A cross-sectional study has proved the effectiveness of this strategy to reduce HD-induced cardiac injury.41 Besides that patients undergoing frequent HD, such as daily HD or nocturnal dialysis, may also benefit from better clearance of endotoxin.49,50 However, frequent HD may leads to additional cost and inconvenience, which limits its utilization. It also has been reported that the blood flow of arteriovenous fistula (AVF) is associated with HD-induced cardiac injury. In patients with higher AVF flow, both the number of regions of RWMAs and the severity of RWMAs were significantly less than patients with lower AVF flow.51 The benefit of high AVF flows maybe due to better distal microcirculation, and lead to a remote preconditioning. Beyond these strategies, the Sodium Lowering in Dialysate (SoLID) trial is a multicenter, randomized, controlled 3year trial in New Zealand, which is still keep going to clarify the effect of dialysate sodium concentration on the cardiovascular risks among HD patients. We look forward to the information and results brought by this trial.52 HD-induced myocardial dysfunction is common in HD patients, especially in those with higher hs-cTnT, serum phosphate, and UFR, and lower albumin level patients. Transient myocardial ischemia caused by HD can lead to temporary LV dysfunction and stunning, and repeat episodes of stunning may lead to structural and functional abnormalities, and eventually heart failure. There are some limitations. First of all, we performed echocardiography at three time points: predialysis, at peak stress during HD (15 minutes before the end of dialysis) and 30 minutes into the recovery period, so we were lack of data when RWMAs were exactly happened, and when were fully recovered. Second, because of the sample size, our ability to reach statistical significance is limited, for example, albumin level. Third, we did not include evaluation of diastolic function, which is also a key component of cardiac function and prognosis. Further study including the assessment of diastolic function should be considered. 570 CONCLUSIONS HD-induced myocardial regional systolic dysfunction is a common phenomenon among conventional HD patients, which may lead to poor survival and quality of life and should be paid attention to. Better control of weight gains during interdialytic period to reduce UFR might be benefit to patients. Maintain phosphate and albumin level at an appropriate range would also be helpful. More frequent HD scheduling, extended HD, and individualized dialysate temperature setting are indicators of personalized treatments for better organ protection. ACKNOWLEDGMENTS The authors are grateful to all of the staff at the Blood Purification Center, Zhongshan Hospital, Fudan University. Manuscript received December 2015; revised March 2016. REFERENCES 1 United States Renal Data System. 2015 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. Bethesda (MD): National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2015. 2 Foley RN. Clinical epidemiology of cardiac disease in dialysis patients: Left ventricular hypertrophy, ischemic heart disease, and cardiac failure. Semin Dial. 2003; 16:111–117. 3 Braunwald E, Kloner RA. The stunned myocardium: Prolonged, postischemic ventricular dysfunction. Circulation. 1982; 66:1146–1149. 4 Wijns W, Vatner SF, Camici PG. Hibernating myocardium. 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