Patients and methods: This prospective study included a total of 38 patients (24 males, 14 females; mean age: 60.8±13.8 years; range, 31 to 82 years) who were on chronic HD for at least six months and had a LV ejection fraction of ≥50% between December 2021 and January 2022. The clinical and echocardiographic features of the patients were recorded before and after HD. The GLS was calculated using two-dimensional speckle-tracking method.

Results: The mean dialysis time of the patients was 6.3±3.9 years. The left atrial volume index was significantly lower after HD than before (30.1±10.0 vs. 27.5±8.2 mL/m², p=0.005). Pulsed Doppler echocardiography showed significantly decreased E and A wave peak velocity after HD (99.3±38.2 vs. 80.4±27.8 cm/s, p=0.001 and 99.4±23.2 vs. 90.4±25.5 cm/s, p=0.022), but no significant change in the E/A ratio (1.1±0.5 vs. 1±0.6, p=0.660). There was no significant change on the LV GLS between before and after HD (-17.3±2.6 vs. -16.9±2.6%, p=0.088).

Conclusion: Hemodialysis has no significant effect on LV GLS in the acute phase in patients with end-stage chronic renal disease.

Despite a high prevalence of cardiovascular insults and progressive symptoms of heart failure, left ventricular ejection fraction (LVEF) remains preserved in the majority of patients with chronic kidney disease (CKD).[4] Speckle-tracking echocardiography with myocardial deformation (two-dimensional [2D] strain) analysis is a quantitative method for the assessment of subtle left ventricular (LV) dysfunction, which cannot be evaluated by semiquantitative conventional echocardiography.[5] Left ventricular global longitudinal strain (GLS) has been proposed to be a new indicator of systolic function. However, using speckle-tracking echocardiography to assess acute effects of HD on cardiac function has resulted in contradictory results.[6] Although some studies have reported that HD improves cardiac functions in the acute period, others have shown that it affects them negatively.[7-10] In the current study, we aimed to investigate the acute effect of HD on LV GLS in chronic HD patients with preserved LVEF.

Echocardiography was performed immediately before and immediately after HD in all patients included in the study. Two-dimensional conventional and speckle-tracking echocardiography data of the patients were recorded. Clinical information on comorbidities, medical history, and current cardiovascular medication was obtained by careful review of each patient’s medical record and a self-reported questionnaire. All patients were assured to receive adequate clearance by dialysis. The blood pressure and pulse rate values of the patients were recorded before and after HD. The patients were weighed before and after HD and their body weights were recorded. Hemodialysis times, ultrafiltration volumes, and rates of all patients were noted. Baseline blood values taken before the HD session at the beginning of the week were recorded. The body mass index (BMI) of the patients was calculated with the formula: body weight/height in meters squared.

Echocardiography
The Philips EPIQ echocardiography instrument (EPIQ 7, Philips Medical Systems, USA) with a X5-1 probe (Q-lab digital software version 10) was used together with a Q-Lab digital software (Philips Medical Systems, USA) for offline analysis. All echocardiographic parameters were measured offline in batches by two experienced cardiologists blinded to clinical and outcome data. Echocardiography was performed immediately before and immediately after HD.

Two-dimensional echocardiography
Left ventricular ejection fraction was assessed using the biplane Simpson’s method from apical four- and two-chamber views. Preserved LVEF was defined as ≥50%. Left ventricular diastolic and systolic diameters were measured from the parasternal long axis view. Peak early (E) and late (A) diastolic velocities of the mitral inflow were evaluated by pulse wave Doppler. Tricuspid regurgitation velocity (TRV) and right atrial pressure were used to estimate pulmonary artery systolic pressure (PASP). Left atrial volume index (LAVI) was measured using the biplane area length method and was indexed to body surface area.

Two-dimensional speckle-tracking echocardiography
Apical four-, three-, and two-chamber views were acquired with high frame rate (>50 fps) for 2D speckle-tracking strain analysis. Offline analyses were performed using Automated Cardiac Motion Quantification software on Q-lab version 10 (Philips Medical Systems, USA). To define the region of interest, the endocardial surface was identified by manually placing at least 15 markings in all apical views. Systolic longitudinal strain was automatically obtained from the three standard apical views (Figure 1). The average systolic longitudinal strain value from the three apical views was regarded as the GLS (Figure 2).

Figure 1: Two-dimensional speckle-tracking echocardiography for left ventricular 4-chamber longitudinal strain.

Figure 2: The average left ventricular global longitudinal strain (bull’s eye plot).

Statistical analysis
Statistical analysis was performed using the SPSS for Windows version 15.0 software (SPSS Inc., Chicago, IL, USA). The Kolmogorov-Smirnov test was used to check for normality of distribution for continuous variables. Continuous variables were presented in mean ± standard deviation (SD) or median (min-max), while categorical variables were presented in number and frequency. Paired samples t-test was used to compare continuous variables before and after HD. Categorical variables were compared using the Pearson chi-square and Fisher exact test. A p value of <0.05 was considered statistically significant.

Table 1: Baseline characteristics of the patients (n=38)

Table 2: Laboratory characteristics of the patients (n=38)

While there was no significant difference in the mean heart rate before and after HD (73.1±8.6 vs. 74.5±8.9 bpm, p=0.194), mean systolic and diastolic blood pressures were significantly lower after HD (136.1±29.1 vs. 111.9±20.6 mmHg, p<0.001 and 77.1±14.7 vs. 69±12.8 mmHg, p<0.001, respectively). The clinical parameters of the patients before and after HD are presented in Table III.

Table 3: Clinical parameters before and after hemodialysis

Of the echocardiographic parameters, the mean LV end-diastolic volume and end-systolic volume were significantly decreased after HD (97.02±20.19 vs. 92.0±17.9 mL, p=0.002 and 40.1±11.1 vs. 37.9±10.5 mL, p=0.008, respectively). Similarly, left atrial area, left atrial volume, and LAVI were significantly lower after HD than before (17.7±4.5 vs. 16.5±3.5 cm², p=0.001, 54.7±17.1 vs. 49.7±15.5 mL, p=0.002, and 30.1±10.0 vs. 27.5±8.2 mL/m², p=0.005, respectively). Pulsed Doppler echocardiography showed significantly decreased E and A wave peak velocity (99.3±38.2 vs. 80.4±27.8 cm/s, p=0.001 and 99.4±23.2 vs. 90.4±25.5 cm/s, p=0.022), but no significant change in the E/A ratio (1.1±0.5 vs. 1±0.6, p=0.660). There was no significant change on the LV GLS between before and after HD (-17.3±2.6% vs. -16.9±2.6%, p=0.088). The echocardiographic parameters of the patients are presented in Table IV.

Table 4: Echocardiographic parameters before and after hemodialysis

Chronic kidney disease is a unique risk factor for cardiac remodeling. An experiment in mice showed that early subendocardial changes were worse in those with CKD than in those without.[11] The LVEF measures predominantly radial contraction, while GLS represents the function of subendocardial longitudinal myocardial fibers, which are more sensitive to decreased coronary perfusion and increased wall stress.[12,13] The GLS reflects the longitudinal contraction of the myocardium and its accuracy has been validated against tagged magnetic resonance imaging.[14] The GLS not only provides a quantitative assessment of myocardial function, but also reflects changes in the myocardial interstitium, including myocardial fibrosis.[15] Compared to the general population, the incidence of cardiovascular death in HD patients is 10 to 20 times higher.[1,16] In the general population, GLS was shown to be a superior predictor of cardiac events and all-cause mortality compared to LVEF.[17] Kramann et al.[15] showed that strain parameters were independent risk factors for cardiovascular and all-cause mortality.

Many previous studies have reported that HD adversely affects LV GLS and LVEF.[7,18,19] Indeed, LV functions are expected to improve after HD due to reduced preload and afterload, but there are different mechanisms that affect LV GLS. In addition, hemodynamic changes experienced during HD may worsen LV function by causing myocardial ischemia, myocardial damage or stunning. In a study conducted by Unlu et al.,[9] troponin-T increased with the decline of GLS after HD. In contrast, Liu et al.[10] found that patients with ESRD who received HD had better LV GLS than those who did not. It was stated that the reason for this was the elimination of the negative effects of renal failure on LV functions by HD.

In some studies similar to our study results, it has been shown that HD does not have a significant effect on LV systolic functions.[20,21] In a different study, Amoozgar et al.[22] found no notable change in LV GLS after HD in children receiving HD, and believed that children’s LV GLS was preload independent. The most important cause of deterioration in LV functions during HD is rapid intravascular volume changes. Other possible causes that increase this deterioration are changes in ionized calcium concentration, sympathetic hyperactivity, increased oxidative stress during HD, and low-resistant vessels. In our study, the mean dialysis time was 4 h and controlled ultrafiltration was performed without causing sudden hypotension. This is the most important reason why there was no significant change in LV GLS before and after HD in our study.

In the current study, a decrease in left atrial and ventricular volumes, which are indicators of preload, was found after HD, similar to the findings of Wang et al.[7] However, there was no significant change in LVEF. Furthermore, we found that HD-associated volume reduction changed mitral valve inflow parameters. Both E-wave and A-wave decreased significantly after HD, but there was no significant decrease in E/A ratio. The E/A ratio is an important indicator of LV filling and diastolic function. There was no significant change in the E/A ratio reflecting diastolic functions after HD, just as in LV GLS reflecting systolic functions.

This study has some limitations. The study has a single-center design with a relatively small sample size, and its results need to be further confirmed by a more rigorous and large-sample prospective study. In addition, LV GLS changes after HD according to the ultrafiltration volumes of the patients were not examined separately, which may have affected the LV GLS results.

In conclusion, HD has no significant effect on LV systolic and diastolic functions in the acute phase in patients with chronic ESRD. Avoiding rapid blood volume changes with controlled ultrafiltration during HD may prevent deterioration of LV functions.

Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The authors received no financial support for the research and/or authorship of this article.

1) Cheung AK, Sarnak MJ, Yan G, Berkoben M, Heyka R, Kaufman A, et al. Cardiac diseases in maintenance hemodialysis patients: Results of the HEMO Study. Kidney Int 2004;65:2380-9.

2) Schärer K, Schmidt KG, Soergel M. Cardiac function and structure in patients with chronic renal failure. Pediatr Nephrol 1999;13:951-65.

3) London G. Pathophysiology of cardiovascular damage in the early renal population. Nephrol Dial Transplant 2001;16 Suppl 2:3-6.

4) Edwards NC, Hirth A, Ferro CJ, Townend JN, Steeds RP. Subclinical abnormalities of left ventricular myocardial deformation in early-stage chronic kidney disease: The precursor of uremic cardiomyopathy? J Am Soc Echocardiogr 2008;21:1293-8.

5) Zoccali C, Benedetto FA, Tripepi G, Mallamaci F, Rapisarda F, Seminara G, et al. Left ventricular systolic function monitoring in asymptomatic dialysis patients: A prospective cohort study. J Am Soc Nephrol 2006;17:1460-5.

6) Mendes L, Ribeiras R, Adragão T, Lima S, Horta E, Reis C, et al. Load-independent parameters of diastolic and systolic function by speckle tracking and tissue doppler in hemodialysis patients. Rev Port Cardiol 2008;27:1011-25.

7) Wang X, Hong J, Zhang T, Xu D. Changes in left ventricular and atrial mechanics and function after dialysis in patients with end-stage renal disease. Quant Imaging Med Surg 2021;11:1899-908.

8) Kovács A, Tapolyai M, Celeng C, Gara E, Faludi M, Berta K, et al. Impact of hemodialysis, left ventricular mass and FGF-23 on myocardial mechanics in end-stage renal disease: A three-dimensional speckle tracking study. Int J Cardiovasc Imaging 2014;30:1331-7.

9) Ünlü S, Şahinarslan A, Sezenöz B, Uludağ OM, Gökalp G, Seçkin Ö, et al. High-sensitive troponin T increase after hemodialysis is associated with left ventricular global longitudinal strain and ultrafiltration rate. Cardiol J 2020;27:376-83.

10) Liu YW, Su CT, Huang YY, Yang CS, Huang JW, Yang MT, et al. Left ventricular systolic strain in chronic kidney disease and hemodialysis patients. Am J Nephrol 2011;33:84-90.

11) Bongartz LG, Braam B, Gaillard CA, Cramer MJ, Goldschmeding R, Verhaar MC, et al. Target organ cross talk in cardiorenal syndrome: Animal models. Am J Physiol Renal Physiol 2012;303:F1253-63.

12) Buckberg G, Hoffman JI, Mahajan A, Saleh S, Coghlan C. Cardiac mechanics revisited: The relationship of cardiac architecture to ventricular function. Circulation 2008;118:2571-87.

13) Carabello BA, Spann JF. The uses and limitations of endsystolic indexes of left ventricular function. Circulation 1984;69:1058-64.

14) Amundsen BH, Helle-Valle T, Edvardsen T, Torp H, Crosby J, Lyseggen E, et al. Noninvasive myocardial strain measurement by speckle tracking echocardiography: Validation against sonomicrometry and tagged magnetic resonance imaging. J Am Coll Cardiol 2006;47:789-93.

15) Kramann R, Erpenbeck J, Schneider RK, Röhl AB, Hein M, Brandenburg VM, et al. Speckle tracking echocardiography detects uremic cardiomyopathy early and predicts cardiovascular mortality in ESRD. J Am Soc Nephrol 2014;25:2351-65.

16) Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol 1998;9(12 Suppl):S16-23.

17) Cho GY, Marwick TH, Kim HS, Kim MK, Hong KS, Oh DJ. Global 2-dimensional strain as a new prognosticator in patients with heart failure. J Am Coll Cardiol 2009;54:618-24.

18) Choi JO, Shin DH, Cho SW, Song YB, Kim JH, Kim YG, et al. Effect of preload on left ventricular longitudinal strain by 2D speckle tracking. Echocardiography 2008;25:873-9.

19) Ibrahim SS, Koura MA, Emara AA, Kamel M, Abd El-Wahed WA. The effect of hemodialysis-induced preload changes on the left ventricular function: A speckle-tracking echocardiographic study. Menoufia Medical Journal 2016;29:406-11.

20) Huang SH, Crowley LE, Jefferies HJ, Eldehni MT, Odudu A, McIntyre CW. The impact of hemodialysis on segmental and global longitudinal myocardial strain. Can J Cardiol 2014;30:1422-8.

21) Wu B-T, Tsai-Pai M-A, Hsu H-Y, Lin P-S, Lin C-H, Chen Y-T. Effect of preload reduction by hemodialysis on left ventricular mechanical parameters by three-dimensional speckle tracking echocardiography. Acta Cardiol Sin 2012;28:25-33.

22) Amoozgar H, Naghshzan A, Basiratnia M, Ahmadipoor M. Effect of hemodialysis on global and regional cardiac function in children with end-stage renal disease. Iran J Kidney Dis 2018;12:48-52.