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BMC Nephrology

, 20:441 | Cite as

The improvement of QRS-T angle as a manifestation of reverse electrical remodeling following renal transplantation in end-stage kidney disease patients on haemodialysis

  • Andrzej JaroszyńskiEmail author
  • Jacek Furmaga
  • Tomasz Zapolski
  • Tomasz Zaborowski
  • Sławomir Rudzki
  • Wojciech Dąbrowski
Open Access
Research article
  • 129 Downloads
Part of the following topical collections:
  1. Renal transplantation

Abstract

Background

Successful renal transplantation (RT) reverses some of the cardiac changes and reduces cardiac mortality in hemodialysis (HD) patients. Widened QRS-T angle reflects both ventricular repolarization and depolarization. It is considered a sensitive and strong predictor of heart ventricular remodeling as well as a powerful and independent risk stratifier suitable in predicting cardiac events in various clinical settings. The study aimed to assess the influence of the RT on QRS-T angle and to evaluate factors influencing QRS-T changes in renal transplanted recipients (RTRs).

Methods

Fifty-four selected HD patients who have undergone RT were included. Blood chemistry, echocardiography, and QRS-T angle were evaluated 5 times: about 1 week, 3 months, 6 months, 1 year and 3 years after RT.

Results

An improvement of echocardiographic parameters was observed. The dynamics of changes in individual parameters were, however, variable. QRS-T angle correlated with echocardiographic parameters. The biphasic pattern of the decreases of QRS-T angle was observed. The first decrease took place in the third month of follow-up. The second decrease of QRS-T angle was observed after 1 year of follow-up. The QRS-T angle was higher in RTRs compared with controls during each evaluation. Multivariable analysis demonstrated that the decrease of left ventricle enddiastolic volume was an independent predictor of early QRS-T angle improvement. The increase of left ventricle ejection fraction was found to be the independent predictor of the late QRS-T angle improvement.

Conclusions

RT induces biphasic reverse electrical remodeling as assessed by the narrowing of QRS-T angle. Early decrease of QRS-T angle is mainly due to the normalization of volume status, whereas late decrease is associated predominantly with the improvement of cardiac contractile function.

Keywords

QRS-T angle Renal transplantation Hypervolemia Ejection fraction Reverse remodeling 

Abbreviations

CI

Cardiac index

CO

Cardiac output

CV

Cardiovascular

DBP

Diastolic blood pressure

EF

Left ventricle ejection fraction

ESRD

End-stage renal disease

HD

Hemodialysis

HR

Heart rate

LAV

Left atrial volume

LAVI

Left atrial volume index

LVEDV

Left ventricle and enddialstolic volume

LVESV

Left ventricle endsystolic volume

LVM

Left ventricle mass

LVMI

Left ventricle mass index

PP

Pulse pressure

RT

Renal transplantation

RTRs

Renal transplanted recipients

SBP

Systolic blood pressure

SCD

Sudden cardiac death

SI

Stroke index

SV

Left ventricle stroke

Background

The pathology of cardiovascular (CV) disease is complex and multifactorial in patients with end-stage renal disease (ESRD) patients. Both traditional and nontraditional risk factors induce structural as well as functional changes of the myocardium, contributing to myocardial remodeling and cardiomyopathy, resulting in substantially increased cardiac events and death. Successful renal transplantation (RT) reverses some of the cardiac changes observed in end-stage renal disease (ESRD) patients, and reduces CV mortality. CV death, including sudden cardiac death (SCD), however, is still much higher compared with the general population [1, 2, 3, 4, 5, 6, 7].

The QRS-T angle is the spatial angle between the vectors of the T-wave and QRS loops (Fig. 1). A widened QRS-T angle is considered a cumulative measurement of cardiac electrical activity, reflecting ventricular repolarization as well as ventricular depolarization. Depolarization abnormalities reflect pathology of ventricular structures, while repolarization abnormalities reflect myocardial action potential homogeneity abnormalities, resulting in electrical instability [8, 9, 10, 11, 12, 13, 14]. A widened QRS-T angle is considered a sensitive and strong predictor of heart ventricular structural as well as electrical remodeling [15]. Many studies have confirmed that QRS-T angle is an independent and strong predictor of adverse cardiac events both in the general population [10, 13] and other patient groups [11, 14, 16, 17, 18], including dialysis patients [8, 19, 20, 21, 22]. Moreover it is especially useful for the prediction of SCD [9, 10, 11, 12, 13, 14, 15, 16, 17].
Fig. 1

QRS-T angle – the spatial angle between the vectors of the T-wave and QRS loops

To the best of our knowledge there are no data in the literature on the influence of RT on QRS-T angle. The objective of the study was to: (i) assess the influence of the RT on QRS-T angle and (ii) evaluate the possible factors influencing QRS-T changes in a group of selected renal transplanted recipients (RTRs).

Methods

Patients

The study included adult patients transplanted in Lublin center (Poland). The exclusion criteria were: manifest coronary artery disease, implanted pacemaker or implantable cardioverter defibrillator, atrial fibrillation, and unstable graft function during the follow-up. Unstable graft function was defined as delayed graft function of more then 3 days, acute graft rejection, and acute kidney injury defined by the RIFLE criteria.

All patients gave written consent, and the studies were conducted in accordance with the Declaration of Helsinki, and approved by members of the Bioethics Committee of Medical University in Lublin, Poland (KE-254/125/2011).

Patients were followed for 3 years after the day of RT. All patients were evaluated 5 times: about 1 week, 3 months, 6 months, 1 year and 3 years after RT. During the subsequent phases the following measurements were performed:

Echocardiographic examination

Transthoracic echocardiographic examination was performed (according to the recommendations of the American Society of Echocardiography) by an cardiologist, who was blinded to the clinical data of the study subjects [23, 24]. On the basis of the planimetric measurements, the following parameters were calculated: left ventricle endsystolic and enddialstolic volumes (LVESV and LVEDV, respectively), left ventricle stroke volume (SV), stroke index (SI), cardiac output (CO), cardiac index (CI), left ventricle ejection fraction (EF), left ventricle mass (LVM), and left ventricle mass index (LVMI), left atrial volume (LAV), LA volume index (LAVI). The body surface area was calculated according to the Gehan and George formula [25].

ECG, derived vectorcardiogram (VCG)

Surface 12-lead resting ECG was recorded using a Cardiax device (IMED Co Ltd., Budapest, Hungary). The recordings were automatically transformed into three orthogonal leads X, Y and Z according to the inverse Dower method. Next, the value for the QRS/T angle was automatically calculated from the maximum spatial QRS and T vectors by using Cardiax commercial software. An abnormal spatial QRS-T angle was defined as a spatial QRS-T angle > 116 for females and a spatial QRS-T angle > 130 in male subjects [26]. The QRS-T angle was also evaluated in 60 healthy controls (hospital employees) who came for routine physical check-ups. The controls did not show any abnormalities in the physical examination, ECG, and laboratory test. The group’s gender distribution and age range were similar to the group of patients. In the control group, the QRS-T angle value was evaluated at the same intervals as in patients.

Statistical analysis

The Kolmogorov-Smirnov test was used to test the normality of the distribution of the results. Normally distributed variables were expressed as mean ± SD, while non-normally distributed variables were expressed as median and range. Continuous data were compared using the Student t-test for paired data when normally distributed and using Mann-Whitney U-test when non-normally distributed. In order to compare the results between more than two groups, one-way ANOVA was used. Linear regression analysis was performed by using the Pearson test. Multivariable logistic regression analysis was performed to identify the independent determinants of QRS-T changes induced by the RT process. Explanatory variables with a p value ≤0.15 in the univariate analysis were entered into a multivariate analysis. A p-value < 0.05 was considered significant.

Results

Of the total of 92 available RTRs patients that were transplanted in the last 4 years in our center, 38 patients were excluded due to unstable graft function, manifest coronary artery disease, lack of all echocardiographic measurements, implanted pacemaker or implantable cardioverter defibrillator as well as less than 3 years follow-up. The remaining 54 patients, aged 44.6 ± 8.9 years, including 28 women aged 46.7 ± 9.4 years and 26 men aged 42.6 ± 8.7 years were followed-up for 3 years. The causes of ESRD were: glomerulonephritis (n = 20), diabetes (n = 9), obstructive nephropathy (n = 6), tabulo-interstitial nephritis (n = 4), vasculitis (n = 2), polycystic kidney disease (n = 3) and unknown/uncertain (n = 10). All patients have undergone RT from unrelated deceased donors. The immunosuppresion regimen included methylprednisolone (100%), mycophenolate mofetil (96,3%) and cyclosporine (35.2%) or tacrolimus (64.8%). Table 1 lists the baseline characteristics of the study population.
Table 1

Baseline characteristics (n = 54)

Characteristic

Value

age [years]

44.6 ± 8.9

gender (men/women) [n (%)]

26 (48.1)/28 (51.9)

time on dialysis until RT [months]

36.65 (±19.34)

haemoglobin [g/dL]

12.43 (±2.89)

sodium [mmol/L]

138.4 (±2.01)

potassium [mmol/L]

4.74 (±1.20)

magnesium [mmol/L]

0.98 (±0.25)

calcium [mmol/L]

2.49 (±0.26)

phosphorus [mmol/L]

1.63 (±0.47)

parathormone [pg/mL]

695.3 (±666.8)

creatinine [μmol/L]

567.2 (±229.3)

urea [mmol/L]

9.54 (±5.34)

total protein [g/L]

74.8 (±13.8)

albumin [g/L]

4.5 (±1.11)

hs-CRP [mg/L]

3.42 (±2.02)

total cholesterol [mg/dL]

223.0 (±62.2)

LDL-cholesterol [mg/dL]

138.0 (±42.18)

HDL-cholesterol [mg/dL]

68.0 (±22.05)

triglycerides [mg/dL]

211.2 (±65.69)

glucose [mg/dL]

92.56 (±42.18)

troponin T [μg/L]

0.019 (±0.035)

treatment prior to RT

 ACE-inhibitors/sartans [n (%)]

36 (66.7)

 calcium blockers [n (%)]

42 (77.8)

 beta-blockers [n (%)]

41 (75.9)

 alfa-blockers [n (%)]

4 (7.4)

 clonidine [n (%)]

2 (3.7)

 statins [n (%)]

26 (48.1)

immunosuppression

 methylprednisolone [n (%)]

54 (100)

 mycophenolate mofetil [n (%)]

52 (96.3)

 cyclosporine [n (%)]

18 (33.3)

 tacrolimus [n (%)]

36 (66.6)

hs-CRP – high-sensitivity C-reactive protein; ACE- inhibitors –angiotensin converting enzyme inhibitors; sartans - angiotensin 2 receptor blockers

An analysis of changes in heart rate (HR) and blood pressures are depicted in Table 2. During the follow-up regular decrease of HR was observed and at the end of the observation HR was lower than at the baseline. During the follow-up systolic blood pressure (SBP) steadily decreased, while diastolic blood pressure (DBP) did not change. As a result, the pulse pressure (PP) decrease was noted.
Table 2

Heart rate and blood pressures in patients after RT (n = 54)

parameter

1 week after RT

(1)

3 months after RT

(2)

6 months after RT

(3)

1 year after RT

(4)

3 years after RT

(5)

p

1vs2

1vs3

1vs4

1vs5

2vs3

3vs5

4vs5

HR [n/min]

77.2 ± 8.9

75.1 ± 7.7

75.3 ± 7.9

73.2 ± 8.0

71.6 ± 7.3

0.378

0.381

0.098

0.014

0.872

0.062

0.373

SBP [mmHg]

138.2 ± 12

135.3 ± 12

135.8 ± 11

134.2 ± 14

132.9 ± 10

0.019

0.021

0.005

< 0.001

0.692

0.109

0.112

DBP [mmHg]

87.2 ± 8.0

86.9 ± 9.3

86.5 ± 8.8

86.9 ± 8.7

87.1 ± 7.5

0.691

0.543

0.552

0.569

0.782

0.577

0.853

PP [mmHg]

51.1 ± 8.9

51.6 ± 8.2

49.3 ± 9.2

47.2 ± 8.1

45.7 ± 5.3

0.864

0.231

0.002

< 0.001

0.267

0.012

0.203

HR Heart rate, SBP Systolic blood pressure, DBP Diastolic blood pressure, PP Pulse pressure

The analysis of drug treatment is shown in Table 3. During observation, a reduction in the use of calcium channel blockers was observed. We did not observe differences in the use of both beta-blockers and angiotensin-converting enzyme inhibitors/aldosterone receptors blockers.
Table 3

Pharmacological treatment in patients after RT (n = 54)

parameter

1 week after RT

(1)

3 months after RT

(2)

6 months after RT

(3)

1 year after RT

(4)

3 years after RT

(5)

p

1vs2

1vs3

1vs4

1vs5

2vs3

3vs5

4vs5

ACEI/ARB [n(%)]

37 (68.5)

38 (70.1)

38 (70.1)

37 (68.5)

39 (72.2)

0.791

0.731

1.000

0.572

1.000

0.795

0.6576

CCB [n(%)]

40 (74.1)

36 (66.6)

33 (61.1)

35 (64.8)

32 (59.2)

0.104

0.017

0.009

< 0.001

0.108

0.423

0.073

BB [n(%)]

41 (75.9)

39 (72.2)

39 (72.2)

39 (72.2)

40 (74.1)

0.512

0.512

0.512

0.517

1.000

0.789

0.790

ACEI Angiotensin-converting enzyme inhibitors, ARB Aldosterone receptors blockers, BB Beta-blockers

Gradually reduction of planimetric parameters of the LV was observed. At the end of the observation, all evaluated parameters were lower in comparison with the baseline, however, the dynamics of changes in individual parameters varied depending on the parameters evaluated in subsequent observation periods (Table 4). Reduction of planimetric dimensions was associated by the change of LVH parameters, however, these changes started to be significant only after 1 year of observation (Table 4). Due to the planimetric indices reduction, the decrease in LV volumetric parameters was noted. The dynamics of changes in individual parameters were, however, variable (Table 4). Contractility parameters of LV also improved, but the significance of these changes started after 1 years of follow-up (Table 4).
Table 4

Echocardiographic parameters in patients after RT (n = 54)

parameter

1 week after RT

(1)

3 months after RT

(2)

6 months after RT

(3)

1 year after RT

(4)

3 years after RT

(5)

p

1vs2

1vs3

1vs4

1vs5

2vs3

3vs5

4vs5

LV dimensions

 LVEDd [mm]

52.3 ± 5.0

49.8 ± 4.4

50.0 ± 4.7

49.9 ± 4.6

49.5 ± 4.7

0.012

0.016

0.001

< 0.001

0.953

0.079

0.232

 LVESd [mm]

35.2 ± 5.4

34.1 ± 3.6

34.3 ± 4.2

33.8 ± 4.8

32.2 ± 4.6

0.093

0.108

0.009

0.002

0.580

0.015

0.016

 PWDd [mm]

12.2 ± 1.4

12.0 ± 1.4

11.7 ± 1.3

11.7 ± 1.7

11.0 ± 1.3

0.872

0.009

0.016

< 0.001

0.684

0.011

0.072

 PWSd [mm]

15.4 ± 1.1

16.2 ± 1.6

16.4 ± 2.0

16.1 ± 2.1

17.2 ± 2.1

0.129

0.098

0.353

0.001

0.657

0.011

0.016

 IVSDd [mm]

13.5 ± 1.3

13.2 ± 0.8

13.1 ± 0.8

12.0 ± 0.7

11.7 ± 1.2

0.362

0.245

0.002

< 0.001

0.421

0.017

0.048

 IVSSd [mm]

16.2 ± 1.4

16.4 ± 1.2

17.8 ± 2.2

16.9 ± 2.1

17.5 ± 1.8

0.675

0.002

0.021

< 0.001

0.173

0.534

0.426

LVM indices

 LVM [g]

321 ± 70

323 ± 74

320 ± 71

309 ± 73

281 ± 65

0.866

0.354

0.011

< 0.001

0.191

< 0.001

0.003

 LVMI [g/m2]

171 ± 36

171 ± 33

170 ± 34

162 ± 33

1459 ± 31

0.884

0.443

0.009

< 0.001

0.124

< 0.001

0.002

LV volumetric parameters

 LVEDV [ml]

135 ± 28

125 ± 30

122 ± 29

121 ± 34

117 ± 29

0.004

0.005

0.002

0.001

0.764

0.043

0.121

 LVESV [m]

53.9 ± 19.9

50.1 ± 13.5

50.4 ± 15.6

48.5 ± 18.5

42.3 ± 15.3

0.059

0.118

0.021

0.005

0.439

0.008

0.011

 SV [ml]

81.6 ± 17.1

78.2 ± 14.4

77.6 ± 17.1

76.4 ± 21.0

76.1 ± 18.3

0.009

0.011

0.014

0.008

0.489

0.706

0.601

Cardiac output parameters

 CO [l/min]

6.09 ± 0.73

5.80 ± 0.69

5.72 ± 0.70

5.51 ± 0.78

5.51 ± 0.63

0.031

0.010

0.008

0.003

0.664

0.212

0.923

 CI [l/min/m2]

3.31 ± 0.49

3.11 ± 0.55

3.09 ± 0.47

2.96 ± 0.46

2.96 ± 0.52

0.019

0.014

0.011

0.006

0.821

0.263

0.976

Contractility parameters

 EF [%]

60.9 ± 9.9

59.1 ± 8.8

60.8 ± 9.1

65.3 ± 8.9

65.5 ± 8.8

0.892

0.859

0.002

0.001

0.233

0.002

0.601

LVEDd Left ventricle enddiastolic diameter, LVESd Left ventricle endsystolic diameter, PWSd Posterior wall systolic diameter; PWDd Posterior wall diastolic diameter, IVSSd Interventricular septum systolic diameter, IVSDd Interventricular septum diastolic diameter, LVESV Left ventricle endsystolic volume, LVEDV Left ventricle enddiastolic volume, SV Left ventricle stroke volume, SI Stroke index, CO Cardiac output, CI Cardiac index, EF Left ventricle ejection fraction, LVM Left ventricle mass, LVMI Left ventricle mass index

A detailed analysis of the changes in the LA planimetric as well as volumetric indices are shown in Table 3. During the follow-up planimetric parameters showed a constant and progressive reduction in dimensions. The volumetric indices followed the described changes confirming a significant reduction in the LA dimensions (Table 4).

A detailed analysis of changes in QRS-T angle are depicted in Fig. 2. At baseline abnormal QRS-T angle was found in 10 (18.5%) patients. In 32 (59.3%) patients QRS-T angle was > 50° and lower than abnormal value, whereas in 12 (22.2%) patients it was < 50°. The biphasic pattern of the decreases of QRS-T angle was observed. The first decrease took place in the 3 month of follow-up. Next, QRS-T angle remained stable to 1 year after RT. The second decrease of QRS-T angle was observed after 1 year of follow-up. Abnormal QRS-T angle was then found in 7 (13.0%) patients (all patients had abnormal QRS-T angle at baseline). In 33 (61.1%) patients QRS-T angle was > 50 and lower than abnormal value, whereas in 14 (25.9%) patients it was < 50°. In the final phase of follow-up an unsignificant increase of QRS-T angle was found. The QRS-T angle was lower in controls (51.4 ± 11.3) compared with RTRs at the beginning of the observation and throughout the entire observation (p < 0.001 in all cases). In the control group, no significant changes in QRS-T angle values were observed during observation (Fig. 2).
Fig. 2

QRS-T angle in patients after RT and in the control group

Correlations between QRS-T angle and some echocardiographic indices (both 1 week after RT and 1 year after RT) are depicted in Table 5. Both 1 week after RT and 1 year after RT significant correlations were found between QRS-T angle and LVEDV, LVMI, SV, CI, and EF.
Table 5

Correlations of QRS-T angle with LV structural indices 1 week as well as 1 year after RT

 

QRS-T angle

1 week after RT

1 year after RT

r

p

r

p

LVEDV

0.53

< 0.001

0.51

< 0.001

LVMI

0.39

0.008

0.37

0.011

SV

- 0.33

0.026

- 0.31

0.029

EF

- 0.57

< 0.001

- 0.59

< 0.001

LVEDV Left ventricle enddiastolic volume, LVMI Left ventricle mass index, SV Left ventricle stroke volume, EF Left ventricle ejection fraction

Multivariable logistic regression analysis was performed to indentify determinants of QRS-T angle changes observed 3 months as well as 1 year after RT. The results are shown in Table 6. Multivariable analysis demonstrated that the decrease of LVEDV was the independent predictor of QRS-T angle improvement 3 months after the RT. One year after the RT the increase of LVEF was found to be the independent predictor of QRS-T angle improvement.
Table 6

Multivariable logistic regression analysis in order to indentify determinants of QRS-T angle changes induced after (A) 3 months as well as after (B) 1 year of RT

Parameter

Univariate

p

Multivariate

p

A

 Age

1.23 (0.89–1.1.81)

0.013

1.31 (1.05–2.62)

0.101

 Beta-blockers

1.29 (0.78–2.87)

0.211

  

 Δ Systolic blood pressure

1.14 (0.72–1.65)

0.143

1.18 (0.69–2.35)

0.237

 Baseline troponin T

2.89 (2.03–3.65)

0.126

2.43 (1.78–3.97)

0.198

 Δ LVEDd

2.35 (1.09–3.26)

0.201

  

 Δ LVEDV

1.38 (1.11–1.67)

0.004

1.29 (0.88–1.49)

0.006

 Δ LVESV

2.09 (0.93–3.33)

0.241

  

 Δ SV

0.99 (0.66–1.22)

0.011

1.12 (0.69–1.59)

0.126

 Δ CO

1.47 (0.75–2.36)

0.231

  

B

 Diabetes mellitus

1.37 (0.88–2.06)

0.137

1.25 (0.74–2.99)

0.314

 Δ LVM

1.71 (1.07–2.34)

0.228

  

 Δ LVEDd

1.09 (0.78–2.17)

0.233

  

 Δ LVEF

2.67 (1.89–2.45)

0.006

2.11 (1.72–2.63)

0.002

 Δ LAVI

2.34 (1.86–2.82)

0.023

1.98 (1.54–2.33)

0.213

LVEDd Left ventricle enddiastolic diameter, LVESV Left ventricle endsystolic volume, LVEDV Left ventricle enddiastolic volume, SV Left ventricle stroke volume, CO Cardiac output, CI Cardiac index, LVM Left ventricular mass, LVEF Left ventricular ejection fraction, LAVI left atrium volume index. Exclusively parameters with a p value < 0.15 at the univariate analysis are shown in order to improve readability

Discussion

Three key findings were generated in our study: (i) RT improves QRS-T angle in a biphasic manner, however, QRS-T values are still higher than in controls, (ii) the first decrease takes place in the short term after RT, and is associated with the improvement of volume dependent parameters, (iii) the second QRS-T angle decrease occurs 1 year after RT, and is predominantly associated with the improvement of cardiac contractile function.

QRS-T angle is a strong, independent and reliable predictor of CV mortality in various populations, including HD patients. It provides greater prognostic value than any of the commonly utilized ECG indicators [8, 9, 17, 27], however, that there is no consensus on the methods for the calculation of the QRS-T angle and the cut-point value that defines abnormal QRS-T angle depends on the method of QRS-T angle estimation. It may cause difficulties in comparing results of different studies. To our knowledge, ours is the first study that shows that RT improves QRS-T angle, however, its values are still higher than in controls, suggesting persistent higher CV risk. It is in agreement with previous studies showing that RT reduce cardiac mortality, however, it is still higher in RTRs compared to the general population [2, 3, 4].

Given the high CV risk of RTR patients, it is of clinical importance to identify not only patients at high risk but also to identify determinants of an abnormal QRS-T angle that potentially might represent therapeutic targets to improve prognosis in this patients’ population.

Our study has revealed that the short term QRS-T angle decrease is associated with the improvement of LVEDV. In HD patients it is well established that chronic fluid overload leads to increased CV mortality due to hypertension, left ventricular dysfunction, heart failure, and arrhythmias, including SCD [28, 29, 30]. Widespread consensus exists that LVEDV is a volumetric parameter of the left ventricle and reflects preload. Greater LVEDV values cause greater distention of the ventricle. Myocardial stretch due to volume overload leads to electrophysiological abnormalities in refractoriness and conduction, essential components of both re-entry and proarrhythmia, and can provoke arrhythmias [31, 32]. Increased LVEDV reflecting the presence of a dilated ventricle has been associated with increased risk of CV death both in HD patients and in RTRs [28, 33]. In HD patients hypervolemia is universal, however, both the prevalence and consequences of fluid overload in RTRs have not been intensively investigated. Chan et al. [31] using multifrequency bioimpedance analysis have found that hypervolemia is common among clinically stable RTRs, and is observed in 30% of them, with 5% classified as severe hypervolemia. Given that hydration status is a potentially modifiable factor the relation between QRS-T angle and LVEDV is of interest. Its clinical significance, however, needs further prospective follow-up investigations.

In the present study we have observed the improvement of LV structural parameters, suggesting myocardial reverse remodeling process due to RT. We have also demonstrated that late QRS-T angle decrease is predominantly associated with the improvement of cardiac contractile function. The restoration of the renal function following RT, induces myocardial reverse remodelling, the reparative processes leading to partial restitution of the myocardial structure and function [5, 34]. However, LV structural indices correlated with QRS-T angle only moderately. This may suggest that LV structural improvement is only partly responsible for the reverse of inhomogeneities of the myocardium repolarisation phase in RTRs. This implies that other mechanisms should be considered as responsible for electrical remodeling, independently from structural changes. This issue needs further investigation.

Most, however, not all studies [35] show that RT improves EF, functional status of heart failure as well as increases RTRs survival [1, 5, 34, 36, 37]. In our study we found slight, however significant improvement of LVEF after 1 year after RT. Growing evidence suggests that the greatest benefit of RT in relation to the LVEF refers to RTRs with advanced systolic heart failure [23, 34]. In the present study LVEF was in normal range in most RTRs, thus the increase of LVEF was slight only. The relation between LVEF and QRS-T angle have been commonly observed both in the general population and in HD patients [8, 9, 11]. Recently published study using MRI showed that QRS-T angle is associated with left ventricle function, mass as well as myocardial scar burden [15]. It has also been suggested that widened spatial QRS-T angle may be a sensitive and strong predictor of heart ventricular electrical remodelling, which may display early, before ECG or echocardiographic signs of left heart damage become evident [15]. The relationship found in our study between the slight increase of EF and the improvement of QRS-T angle values suggests that even slight improvement of left ventricular function remains of importance and might represent a potential therapeutic target.

The present study has some limitations. First, in this study we did not assess outcome data. Given the previously established relationship between the spatial QRS-T angle and cardiac events, and especially SCD we can only present a hypothesis that the QRS-T angle improvement may reflect the reverse of inhomogeneities of the myocardium repolarisation phase in RTRs. Further studies using clinical endpoints would allow for more definitive conclusions. Second, present study is a clinical cohort study, thus election bias may have played a role in influencing the results. Third, the numbers of patients was relatively small, nevertheless was large enough to demonstrate that RT improves QRS-T angle.

Conclusions

RT induce biphasic reverse electrical remodeling as assessed by the narrowing of QRS-T angle. Early decrease of QRS-T angle is mainly due to the normalization of volume status, whereas late decrease is associated predominantly with the improvement of cardiac contractile function.

Notes

Acknowledgments

Not applicable

Authors’ contributions

AJ conceived of the study, designed and coordination of the study, wrote the manuscript; JF conceived of the study, participated in all transplantations; TZapolski carried out echocardiography, analyzed and interpreter data; TZaborowski analyzed and interpreter data; SR participated in the study design; WD analyzed and interpreted data, participated in design of the study. Authors read and approved the manuscript.

Funding

Medical University of Lublin. Award number 232. Recipient – Andrzej Jaroszyński. The funding was used for data collection.

Ethics approval and consent to participate

All patients gave written consent, and the studies were conducted in accordance with the Declaration of Helsinki, and approved by members of the Bioethics Committee of Medical University in Lublin, Poland (KE-254/125/2011).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

  1. 1.
    Chen S, Huang J, Su H, Chiu Y, Chang J, Hwang S, Chen H. Prognostic cardiovascular markers in chronic kidney disease. Kidney Blood Press Res. 2018;43:1388–407.CrossRefGoogle Scholar
  2. 2.
    Stoumpos S, Jardine A, Mark P. Cardiovascular morbidity and mortality after kidney transplantation. Transpl Int. 2015;28:10–21.CrossRefGoogle Scholar
  3. 3.
    Jardine A, Gaston R, Fellstrom B, Holdaas H. Prevention of cardiovascular disease in adult recipients of kidney transplants. Lancet. 2011;378:1419–27.CrossRefGoogle Scholar
  4. 4.
    Marcassi A, Yasbek D, Pestana J, Fachini F, De Lira FE, et al. Ventricular arrhythmia in incident kidney transplant recipients: prevalence and associated factors. Transpl Int. 2011;24:67–72.CrossRefGoogle Scholar
  5. 5.
    Hawwa N, Shrestha K, Hammadah M, Yeo P, Fatica R, Tang W. Reverse remodeling and prognosis following kidney transplantation in contemporary patients with cardiac dysfunction. J Am Coll Cardiol. 2015;66:1779–87.CrossRefGoogle Scholar
  6. 6.
    Chrapko B, Tomaszewski A, Jaroszyński A, Furmaga J, Wysokiński A, Rudzki S. Takotsubo syndrome in a patient after renal transplantation. Med Sci Monit. 2012;18:26–30.CrossRefGoogle Scholar
  7. 7.
    Jaroszynski A, Ksiazek A. Comparative study of adequacy of dialysis and health-related quality of life in patients on CADO and APD. Perit Dial Int. 2008;28:542–U7.Google Scholar
  8. 8.
    Tereshchenko L, Kim E, Oehler A, Meoni L, Ghafoori E, Rami T, et al. Electrophysiologic Substrate and Risk of Mortality in Incident Hemodialysis. J Am Soc Nephrol. 2016;27:3413–20.CrossRefGoogle Scholar
  9. 9.
    Oehler A, Feldman T, Henrikson C, Tereshchenko G. QRS-T angle: a review. Ann Noninvasive Electrocardiol. 2014;19:534–42.CrossRefGoogle Scholar
  10. 10.
    Yamazaki T, Froelicher V, Myers J, Chun S, Wang P. Spatial QRS-T angle predicts cardiac death in a clinical population. Heart Rhythm. 2005;2:73–8.CrossRefGoogle Scholar
  11. 11.
    Gleeson S, Liao Y, Dugo C, Cave A, Zhou L, Ayar Z, et al. ECG-derived spatial QRS-T angle is associated with ICD implantation, mortality and heart failure admissions in patients with LV systolic dysfunction. PLoS One. 2017;12(3):e0171069.  https://doi.org/10.1371/journal.pone.0171069 eCollection 2017.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Poulikakos D, Hnatkova K, Skampardoni S, Green D, Kalra P, Malik M. Sudden cardiac death in Dialysis: arrhythmic mechanisms and the value of non-invasive electrophysiology. Front Physiol. 2019;10:144.  https://doi.org/10.3389/fphys.2019.00144.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Zhang X, Zhu Q, Zhu L, Jiang H, Xie J, Huang W, et al. Spatial/frontal QRS-T angle predicts all-cause mortality and cardiac mortality: a meta-analysis. PLoS One. 2015;10:e0136174.CrossRefGoogle Scholar
  14. 14.
    Malik M, Birnbaum Y, MacLeod R, Shusterman V. Markers of impaired repolarization. J Electrocardiol. 2007;40:54–7.CrossRefGoogle Scholar
  15. 15.
    Shi B, Ferrier K, Sasse A, Harding S, Larsen P. Correlation between vectorcardiographic measures and cardiac magnetic resonance imaging of the left ventricle in an implantable cardioverter defibrillator population. J Electrocardiol. 2014;47:52–8.CrossRefGoogle Scholar
  16. 16.
    Cortez D, Graw S, Mestroni L. In Hypertrophic Cardiomyopathy, the Spatial Peaks QRS-T Angle Identifies Those With Sustained Ventricular Arrhythmias. Clin Cardiol. 2016;39:459–63.CrossRefGoogle Scholar
  17. 17.
    Lingman M, Hartford M, Karlsson T, Herlitz J, Rubulis A, Caidahl K, Bergfeldt L. Value of the QRS-T area angle in improving the prediction of sudden cardiac death after acute coronary syndromes. Int J Cardiol. 2016;218:1–11.CrossRefGoogle Scholar
  18. 18.
    Rautaharju P, Kooperberg C, Larson J, LaCroix A. Electrocardiographic abnormalities that predict coronary heart disease events and mortality in postmenopausal women: the Women's Health Initiative. Circulation. 2006;113:473–80.CrossRefGoogle Scholar
  19. 19.
    Jaroszyński A, Wysokiński A, Bednarek-Skublewska A, Głowniak A, Książek P, Sodolski T, et al. The effect of a single dialysis session on spatial QRS-T angle in haemodialysis patients. Nephrol Dial Transplant. 2010;25:3723–9.CrossRefGoogle Scholar
  20. 20.
    de Bie M, Koopman M, Gaasbeek A, Dekker F, Maan A, Swenne C, et al. Incremental prognostic value of an abnormal baseline spatial QRS-T angle in chronic dialysis patients. Europace. 2013;15:290–6.CrossRefGoogle Scholar
  21. 21.
    Zapolski T, Jaroszyński A, Drelich-Zbroja A, Furmaga J, Wysokiński A, Książek A, et al. Left atrial volume index as a predictor of ventricle repolarization abnormalities in adult dialyzed patients. Hemodial Int. 2012;16:220–32.CrossRefGoogle Scholar
  22. 22.
    Poulikakos D, Hnatkova K, Banerjee D, Malik M. Association of QRS-T angle and heart rate variability with major cardiac events and mortality in hemodialysis patients. Ann Noninvasive Electrocardiol. 2018;23(6):e12570.  https://doi.org/10.1111/anec.12570.CrossRefPubMedGoogle Scholar
  23. 23.
    Lang R, Badano L, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1–39.CrossRefGoogle Scholar
  24. 24.
    Zapolski T, Furmaga J, Jaroszyński A, Wysocka A, Rudzki S, Wysokiński A. The reverse remodeling of the aorta in patients after renal transplantation - the value of aortic stiffness index: prospective echocardiographic study. BMC Nephrol. 2017;18:33.CrossRefGoogle Scholar
  25. 25.
    Gehan E, George S. Estimation of human body surface area from height and weight. Cancer Chemother Rep. 1970;54:225–35.PubMedGoogle Scholar
  26. 26.
    Scherptong R, Henkens I, Man S, Le Cessie S, Vliegen H, Draisma H, et al. Normal limits of the spatial QRS-T angle and ventricular gradient in 12-lead electrocardiograms of young adults: dependence on sex and heart rate. J Electrocardiol. 2008;41:648–55.CrossRefGoogle Scholar
  27. 27.
    Zhang Z, Prineas R, Case D, Soliman E, Rautaharju P, ARIC Research Group. Comparison of the prognostic significance of the electrocardiographic QRS/T angle in predicting incident coronary heart disease and total mortality (from the atherosclerosis risk in communities study). Am J Cardiol. 2007;100:844–9.CrossRefGoogle Scholar
  28. 28.
    Zoccali C, Benedetto F, Mallamaci F, Tripepi G, Giacone G, Cataliotti A, et al. Prognostic value of echocardiographic indicators of left ventricular systolic function in asymptomatic dialysis patients. J Am Soc Nephrol. 2004;15:1029–37.CrossRefGoogle Scholar
  29. 29.
    Chan C, Greene T, Chertow G, Kliger A, Stokes J, Beck G, et al. Frequent Hemodialysis Network Trial Group. Effects of frequent hemodialysis on ventricular volumes and left ventricular remodeling. Clin J Am Soc Nephrol. 2013;8:2106–16.CrossRefGoogle Scholar
  30. 30.
    Ahmadmehrabi S, Tang W. Hemodialysis-induced cardiovascular disease. Semin Dial. 2018;31:258–67.CrossRefGoogle Scholar
  31. 31.
    Chan W, Bosch J, Jones D, McTernan P, Inston N, Moore S, et al. Hypervolemia and blood pressure in prevalent kidney transplant recipients. Transplantation. 2014;98:320-7.CrossRefGoogle Scholar
  32. 32.
    Chen-Izu Y, Izu L. Mechano-chemo-transduction in cardiac myocytes. J Physiol. 2017;595:3949–58.CrossRefGoogle Scholar
  33. 33.
    Kim E, Chang S, Kim S, Huh K, Kang S, Choi Y. Predictive value of echocardiographic abnormalities and the impact of diastolic dysfunction on in-hospital major cardiovascular complications after living donor kidney transplantation. Int J Med Sci. 2016;13:620–8.CrossRefGoogle Scholar
  34. 34.
    Hewing B, Dehn A, Staeck O, Knebel F, Spethmann S, Stangl K, et al. Improved left ventricular structure and function after successful kidney transplantation. Kidney Blood Press Res. 2016;41:701–9.CrossRefGoogle Scholar
  35. 35.
    Patel R, Mark P, Johnston N, Mcgregor E, Dargie H, Jardine H. Renal transplantation is not associated with regression of left ventricular hypertrophy: a magnetic resonance study. Clin J Am Soc Nephrol. 2008;3:1807–11.CrossRefGoogle Scholar
  36. 36.
    Wali R, Wang G, Gottlieb S, Bellumkonda L, Hansalia R, Ramos E, et al. Effect of kidney transplantation on left ventricular systolic dysfunction and congestive heart failure in patients with end-stage renal disease. J Am Coll Cardiol. 2005;45:1051–60.CrossRefGoogle Scholar
  37. 37.
    Hensen L, Goossens K, Delgado V, Abou R, Rotmans J, Jukema J, Bax J. Prevalence of left ventricular systolic dysfunction in pre-dialysis and dialysis patients with preserved left ventricular ejection fraction. Eur J Heart Fail. 2018;20:560–8.CrossRefGoogle Scholar

Copyright information

© The Author(s). 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors and Affiliations

  • Andrzej Jaroszyński
    • 1
    • 2
    Email author
  • Jacek Furmaga
    • 3
  • Tomasz Zapolski
    • 4
  • Tomasz Zaborowski
    • 5
  • Sławomir Rudzki
    • 3
  • Wojciech Dąbrowski
    • 5
  1. 1.Institute of Medical Sciences, Jan Kochanowski University in KielceKielcePoland
  2. 2.Department of Family MedicineMedical University of LublinLublinPoland
  3. 3.Department of General and Transplant Surgery and Nutritional TreatmentMedical University of LublinLublinPoland
  4. 4.Department of CardiologyMedical University of LublinLublinPoland
  5. 5.Department of Anesthesiology and Intensive CareMedical University of LublinLublinPoland

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