AAMJ, Vol. 11, N. 1, January, 2013 ‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬

EVALUATION OF LEFT VENTRICULAR MECHANICAL DYSSYNCHRONY IN PATIENTS WITH DILATED CARDIOMYOPATHY BY TWO- DIMENSIONAL SPECKLE TRACKING IMAGING Ayman Sadek*, Ahmed Roza*, Mahmoud Elshahat* and Eman Rashid** Cardiology Department, Male*, Female**- faculty of medicine, Alazhar university, Egypt ‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ ABSTRACT The purpose of this study was to evaluate left ventricular mechanical dyssynchrony in patients with dilated cardiomyopathy referring to normal healthy people by 2D speckle tracking imaging. Furthermore, the relationships between dyssynchrony indices and QRS duration (QRSd).This study included 60 Patients with dilated cardiomyopathy referred from Echocardiography unit of El Sayed Galal University Hospitals between march 2012 and October 2012. Patients included were in Sinus rhythm, QRSd ≥120 milliseconds, (NYHA) cardiac function class II-IV. Patients excluded if they had frequent premature ventricular contraction. Atrial fibrillation, valvular heart disease, congenital heart disease, poor image quality.All subjects were subjected to Informed written consent was taken from all patients.

Complete history taking for

Detection of NYHA grade, hypertension, diabetes mellitus, history of smoking, History of ischemic heart disease.Resting standard 12-leads electrocardiogram searching for rate, rhythm, and QRS duration.Referring to the healthy population, this study calculated statistically based cut-off values for each dyssynchrony index and a comparison of dyssynchrony rates within each CHF subgroup was made.Results: It was noted that no statistically significant differences in studied group as regarding gender age, gender and heart rate (P > 0.05). It’s noted that there is significant statistically difference between three 183

Ayman Sadek et al

‫ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ groups regarding to LVESV, LVEDV, LVEDD, and LVEF. It was noted that no significant differences between two groups of patients with cardiomyopathy regarding to QRS duration.also, no relationship existed between QRS duration and dyssynchrony indices as P >0.005. Conclusion: 2D-speckle tracking imaging is capable of identifying intraventricular mechanical dyssynchrony. Left ventricular systolic function was closely related to mechanical dyssynchrony, whereas QRSd showed no significant correlation.

INTRODUCTION Heart failure is a clinical syndrome which is caused by a large number of cardiac diseases and it is characterized by inability of the heart topump the adequateamount of blood that could satisfy the body's needs for oxygen in proportion to physical activity provided that the venous blood flow to the heart is normal.Mortality from heart failure is highand ranges from 15%-60% per year and the economic impact of morbidity is high. (1) Cardiac resynchronization therapy (CRT) is a new modality that involves synchronization of ventricular contraction and has shown a- lot of promise in managing symptomatic patients of CHF who are on optimal medical therapy and have interventricular conduction delay (IVCD). It has improved exercise tolerance and NYHA functional class in such patients in sinus rhythm and a recent meta-analysis has also shown mortality benefits in CHF.(2) Recently benefits of CRT have also been observed in CHF patients who do not have wide QRS complexes on electrocardiogram (EKG). Recent studies have also focused on the combined use of CRT and implantable cardioverter defibrillator (ICD) and it has shown encouraging results (1) In recent years, several echocardiographic techniques have been adopted to quantify left ventricular mechanical dyssynchrony(LVMD), including tissue Doppler imaging (TDI), real-time three-dimensional Echocardiography (RT184

AAMJ, Vol. 11, N. 1, January, 2013 ‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ 3DE), and two-dimensional speckle tracking imaging (2D-STI). TDI is limited by angle dependence, and RT-3D restricts at low frame rates. However, 2D-STI has overcome these disadvantages. This technique reflects myocardial deformation in three directions: radial thickening, circumferential shortening, and longitudinal shortening(3).

PATIENTS AND METHODS This study included 60 Patients with dilated cardiomyopathy referred from Echocardiography unit ofSayed Galal University Hospitalbetween march 2012 and october 2012. Etiology of CHF included idiopathic dilated cardiomyopathy and ischaemic cardiomyopathy. Selection criteria were as follows:  Sinus rhythm instandard 12-lead electrocardiography (ECG).  QRSd≥120milliseconds  New York Heart Association (NYHA)cardiac function class II-IV. Exclusion criteria were asfollows:  Atrial fibrillation.  Valvularheartdisease.  Congenital heart disease.  Poor Echo window. Population of the study classified into three subgroups: (1) LVEF ≤ 35% (group I). (2) 35% < LVEF < 50% (groupII). (3) A totalof 20 healthy individuals with similar age and gendercomprised the control group (group III). Echocardiographic Examination All the patients will be examined in the left lateral decubitus position. Echocardiographic images will be acquired from the standard views (parasternal 185

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‫ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ long-axis, parasternal short axis at level of basal and mid-level, apical four– chambers, apical two-chambers). Recordings and calculations of different cardiac chambers and ejection fractions will be made according to the recommendations of the American Society of Echocardiography(4). Standard echocardiography examinations were performedby a commercially available system (iE33, Philips MedicalSystem) using a 1-5 MHz transducer. Afterconnecting the ECG, M-mode and two-dimensional imageswere acquired with the participants in the left lateraldecubitus position. According

to

recommendation

of

American

Society

of

Echocardiographyall images were obtained according recommendation during breathholding and stored in three consecutive cardiac cycles. Gain, depth, and focal range were adjusted to ensure optimal leftventricular border display and high frame rate (> 110 fps).Left ventricular end-diastolic diameters (LVEDDs) and

Left

ventricular

end-systolic

diameters

(LVESDs)linear

internal

measurements of the left ventricle and its walls be performed in the parasternal long-axis view. Values should be carefully obtained perpendicular to the LV long axis and measured at or immediately below the level of the mitral valve leaflet tips. In this regard, the electronic calipers should be positioned on the interface between the myocardial wall and cavity and the interface between the wall and the pericardium. Internal dimensions can be obtained with a two dimensional (2D) echocardiography (2DE)–guided M-mode approach, although linearmeasurements obtained from 2D echocardiographic images are preferred to avoid oblique sections of the ventricle. Left

ventricularend-systolic

volumes

(LVESVs)

and

end-diastolic

volumes(LVEDVs) were usually based on tracings of the interface between the compacted myocardium and the LV cavity.At the mitral valve level, the contour is closed by connecting the two opposite sections of the mitral ring with a straight line. LV length is defined as the distance between the bisector of this 186

AAMJ, Vol. 11, N. 1, January, 2013 ‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ line and the apical point of the LV contour, which is most distant to it. The use of the longer LV length between the apical two- and four-chamber views is recommended. LV volumes should be measured from the apical four- and twochamber views. Two-dimensional echocardiographic image acquisition should aim to maximize LV areas, while avoiding foreshortening of the left ventricle, which results in volume underestimation. Acquiring LV views at a reduced depth to focus on the LV cavity will reduce the likelihood of foreshortening and minimize errors in endocardial border tracings.(11) 2D-STI and dyssynchrony indices Post-processing was performed using Qlab software(Version 9.0, Philips Medical Systems). For speckle trackinganalysis, standard two-dimensional images were recordedin apical two-, three-, and four-chamber views as well asthe parasternal short-axis views of basal level and mid-level. First, three points, at the cardiac apex and the twosides of mitral valve, were marked on the endocardiumcavity interface in apical views; and a center point of theendocardium cavity was marked in short-axis views. Afterthat, the whole left ventricular myocardium was identifiedas the region of interest automatically. A total of 12 segments of basal level and mid-level inboth apical and shortaxis views were selected. The timeinterval from Q-wave of the ECG to peak systolic strain/strain rate was measured for each segment. For each typeof deformation analysis, two dyssynchrony indices wereobtained: standard deviation (SD) of time to peak systolicstrain/strain rate in 12 segments (Ts12SD) and the maximaltime delay between peak systolic strain/strain rate of 2segments in 12 segments (Ts-12Diff).(10) Statistics: The collected data were revised, organized, tabulated and statistically analyzed using statistical package for social sciences (SPSS) version 22.0 for windows. Data are presented as the Mean ± standard deviation (SD), frequency, 187

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‫ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ and percentage. Categorical variables were compared using the chi-square (χ2) and Fisher's exact tests (if required). Continuous variables were compared by the Student t test (two-tailed) and one – way ANOVA test for parametric data. Mann-Whitney U and Kruskal – Wallis tests for nonparametric data. Pearson and spearman correlation was used to study the correlation between the studied variables. Cut – off value for each index of the normal populationwas calculated using the ROC curve. The level of significance was accepted if the P value < 0.05.

RESULTS The population enrolled in this study composed of 80 individuals (60 patients and 20 controls). The studied sample was classified according to ejection fraction(EF) into the following groups: First group

Ejection fraction ≤ 35 %.

Second group 50% > Ejection fraction > 35 % Third group Ejection fraction ≥ 50 %. Demographic and clinical characteristics of the studied group. It was noted that female patients were more than male patients, mean age was 55.08 ± 7.15and mean HR was 73.01 ± 8.52. It was noted that no statistically significant differences in studied group as regarding gender age, gender and heart rate (P > 0.05). table (1)

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AAMJ, Vol. 11, N. 1, January, 2013 ‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ Table (1): Demographic and clinical characteristics of the studied sample. Frequency

Variable

Percent

(N= 80)

Gender

39

48.8

41

51.3

Age (years) (M ± SD)

55.08 ± 7.15

----

HR (beats/min) (M ± SD)

73.01 ± 8.52

----

Male Female

Echocardiographic characteristics of the studied sample It was noted that mean LVESV78.09 ± 46.57, meanLVEDV126.85 ± 55.18, mean LVEDD60.48 ± 9.15, and mean LVEF (%) 43.02± 12.62. Comparison between some echocardiographic parameters among the studied different groups. It’s noted that there is significant statistically difference between three groups regarding to LVESV, LVEDV, LVEDD, and LVEF. table (2) Table (2): Comparison between some echocardiographic parameters among the studied different groups. Group ≤ 35

> 35 – 49.9

≥ 50

(N= 30)

(N = 30)

(N= 20)

LVESV (ml)

128.13± 28.63

64.80± 14.31

22.95± 4.64

< 0.001

LVEDV (ml)

180.47 ± 36.08

120.83± 20.02

55.45± 9.97

< 0.001

LVEDD (mm)

68.63± 4.20

60.94 ± 4.34

47.55± 3.33

< 0.001

LVEF (%)

28.87

46.29± 2.67

59.35± 3.96

< 0.001

Variable

P

Comparison between some dyssynchrony indices of three groups. It’s noted that regarding to TSLSD; there was significant statistically difference between the studied group except between 1stand 2nd group there was 189

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≤ 35

> 35 – 49.9

≥ 50

(N= 30)

(N = 30)

(N= 20)

P

P1 = 0.481 Tsls12 SD

98.40 ± 34.40

88.10 ± 28.38

42.60 ± 13.21

P2 < 0.001 P3 < 0.001 P < 0.001 P1< 0.001

Tslsr12 SD

105.80 ± 25.65

84.07 ± 17.33

60.25 ± 15.19

P2< 0.001 P3 = 0.001 P < 0.001 P1 < 0.001

Tscs12 SD

73.60 ± 24.13

45.27 ± 17.04

35.25 ± 13.97

P2 < 0.001 P3 = 0.233 P< 0.001 P1 = 0.053

Tscsr12 SD

67.60 ± 20.70

60 ± 16.47

45.90 ± 13.47

P2 < 0.001 P3 = 0.114 P< 0.001

P1: Comparison of 1st group with 2nd group.P2: Comparison of 1stgroup with 3rdgroup. P3: Comparison of 2nd group with 3rd group.P: Comparison of all groups with each other. 190

AAMJ, Vol. 11, N. 1, January, 2013 ‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ Cs = circumferential strain; csr = circumferential strain rate; ls = longitudinal strain; lsr = longitudinal strain rate; Ts-12SD = the standard deviation of time to peak systolic strain/strain rate in 12 segment. Comparison of otherdyssynchrony indices among the studied different groups. As regarding to Tsls-12 Diffthere was significant statistically difference in Comparison of all groups except Comparison of 1st group with 2nd group, there was no significant statistically difference. As regarding to Tslsr-12 Diffthere was significant statistically difference in comparison of all groups except comparison of 1st group with 2nd group there was no significant statistically difference.As regarding to Tscs-12 Diff there was significant statistically difference in Comparison of all studied groupsexcept comparison of 2nd group with 3rd group there was no significant statistically difference.As regarding to Tscsr-12 Diffthere was no significant statistically difference in Comparison of all studied groups. table (3) Table (3): Comparison of other dyssynchrony indices among the studied different groups. Variable

≤ 35 (N= 30)

Group > 35 – 49.9 (N = 30)

≥ 50 (N= 20)

Tsls-12 Diff

286.10 ± 80.93

255.17 ± 88.46

129.15 ± 57.42

Tslsr-12 Diff

286.30 ± 48.00

265.73± 59.51

182.90 ± 55.33

P P1 = 0.399 P2 < 0.001 P3 < 0.001 P < 0.001 P1 = 0.441 P2 < 0.001 P3 < 0.001 P < 0.001 P1 < 0.001 P2 < 0.001

Tscs-12 Diff

224.90 ± 67.26

139.77 ± 54.78

100.00 ± 51.04 P3 = 0.066 P < 0.001

Correlation between EF and dyssynchrony indices:

191

Ayman Sadek et al

‫ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ It was noted that, there wasa significantly negative linear correlation between LVEF andTsls-12 SD, Tslsr-12 SD, Tscs-12 SD, Tscs-12 SD,Tsls-12 Diff,Tslsr-12 Diff, Tscs-12 Diff, Tscsr-12 Diff. Results revealed that significant differences were noted within both 1st and 2nd groups according to Tscs-12 SD and Tscs-12 Diff (p = 0.005 and 0.024, respectively). Comparison of QRSduration between patients with cardiomyopathy: It was noted that no significant differences between two groups of patients with cardiomyopathy regarding to QRS duration. Correlation between QRSd and dyssynchrony indices: It was noted that no relationship existed between QRSduration and dyssynchrony indices as P >0.005.

DISCUSSION In recent years, several Echocardiographic techniques have been adopted to quantify left ventricular mechanical dyssynchrony (LVMD), including tissue Doppler imaging (TDI), real-time three-dimensional echocardiography (RT3DE), and two-dimensional speckle tracking imaging (2D-STI). TDI is limited by angle dependence, and RT-3D restricts at low frame rates. However, 2D-STI has overcome these disadvantages. This technique reflects myocardial deformation in three directions: radial thickening, circumferential shortening, and longitudinal shortening (7). At present, there is no gold standard to assess LVMD and the results for the different echocardiographic methods are inconclusive(8). A total of 12 segments of basal level and mid-level in both apical and short-axis views were selected. The time interval from Q-wave of the ECG to peak systolic strain/strain rate was measured for each segment. For each type of deformation analysis, two dyssynchrony indices were obtained: standard 192

AAMJ, Vol. 11, N. 1, January, 2013 ‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ deviation (SD) of time to peak systolic strain/strain rate in 12 segments (Ts12SD) and the maximal time delay between peak systolic strain/strain rate of 2 segments in 12 segments (Ts-12Dif). CHF patients usually showed left ventricular remolding, which mean cardiac chamber enlargement and cardiac apex roundout. These special changes make it difficult to completely include apex and apical cap in echocardiographic images. For the correctness of the results, this study selected the remaining 12 segments in the left ventricle, eliminating unstable factors(8). In our study, age and sex did not differ among the study population as the control group had age and sex matched with other groups. It was noted that mean LVESV (78.09 ± 46.57) ml, mean LVEDV (126.85 ± 55.18) ml, mean LVEDD (60.48 ± 9.15) mm, and mean LVEF (%) (43.02±12.62). LVESV, LVEDV, and LVEDD in CHF patients (Groups 1 and 2) were remarkably higher than those in the control group (3) as (p < 0.01). The values of LVESV and LVEDV in Group 1 were significantly higher than those in Group (2) as (p < 0.05). There was significant statistically difference between three groups regarding to LVESV, LVEDV, LVEDD, and LVEF this result was concordant with the result of Feng-Xia et al., 2012 they examined 78 patients and 60 healthy individuals (group 3) were enrolled. The patients were classified into two subgroups: LVEF ≤ 35% (group 1), 35% < LVEF < 50% (group 2). All participants underwent two-dimensional Echocardiography, he found that in CHF patients LVESV, LVEDV, and LVEDD in CHF patients (Groups 1 and 2) were remarkably higher than those in the control group (3) The values of LVESV and LVEDV in Group 1 were significantly higher than those in Group (2)

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‫ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ Also this result was concordant with the result of Suffoletto et al., 2006,they studied 369 consecutive patients with heart failure (HF) with low ejection fraction (EF) and widened QRS receiving CRT. Radial dyssynchrony (septal-posterior radial peak strain delay ≥130 ms by speckle tracking) assessment was possible in 318 patients (86%). Associations with left ventricular end-systolic volume (LVESV) changes were examined using linear regression, and clinical outcomes analyzed using Cox regression adjusted for multiple established outcome correlates. In our study, the dyssynchrony indices was performed between healthy controls and patients with dilated cardiomyopathy The results showed that all indices in group I were higher than those in group III, whereas some indices in group II were higher than those in group III. This implied that CHF patients had different degrees of LVMD. This was concordant with Takeshi Mauro et al., 2009, they used The Speckle Tracking Imaging for the assessment of cardiac resynchronization therapy (START) study was a multicenter prospective cohort study of patients undergoing CRT in Japan.This study was based on criteria that included congestive heart failure refractory to optimal medical therapy and QRS duration ≥ 120 MS, NYHA class II, III or IV and left ventricular (LV) ejection fraction ≤35%. Patients were scheduled to undergo echocardiographic studies with NYHA functional class assessment before and at 1 week and 6 months after CRT. Dyssynchrony parameters by STE time from QRS onset to maximum strain (T max) and to first peak in the multiple strain peaks (T first) were measured in each segment The 3 dyssynchrony parameters in each of T max and T first were calculated as follows: first, standard deviation of T max (T max-SD) and T first (T first-SD) in the 6 segments for RS and CS and the 18 segments for LS; second, time difference (TD) between the smallest T max and largest T max(T 194

AAMJ, Vol. 11, N. 1, January, 2013 ‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ max-TD) and between the smallest T first and largest T first (T first-TD) among the 6 segments for RS and CS and the 18 segments for LS; and third, TD between the septum and lateral wall (T max-TDSL, T first TDSL) for RS, CS, and LS. In the calculations of dyssynchrony parameters with T first, T max was substituted in the segments with a single peak. The study revealed strong feasibility of dyssynchrony assessments by STE, which may improve the ability to predict CRT responders. Also our result was concordant with the result of Feng-Xia et al., 2012 in which dyssynchrony indices derived from 2D-STI were calculated. According to statistical principles, the cut-off value of LVMD was defined as mean ± 1.645 SD of the normal population. Dyssynchrony rates were calculated in CHF subgroups and compared within each subgroup, respectively. Compared with group 3, all indices in group 1 were remarkably higher (p < 0.05), and some of the indices in group 2 were significantly higher (p < 0.05). Moreover, there was a significantly negative linear correlation between LVEF and all indices in CHF subgroups, which implied that systolic function deteriorated as mechanical dyssynchrony motion worsened. These results are concordant with the resultsofFeng-Xia et al., 2012 The current recommendation for CRT candidates mainly focuses on QRSd (5). In our study, we found that no relationship existed between QRSd and dyssynchrony indices as P > 0.005. These results are concordant with the resultsofBleeker et al., 2004 discussed the relationship between QRSd and LVMD in patients with end-stage heart failure, they study 33 consecutive patients with a narrow QRS complex were prospectively compared with 33 consecutive patients with a wide QRS complex. Inclusion criteria were NYHA functional class III or IV, LVEF ≤ 35%, and signs of LV dyssynchrony on TDI (maximum delay between peak systolic velocities among the four walls within the LV ≥ 65 ms). No significant 195

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‫ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬ relationship between baseline QRS duration and LV dyssynchrony was observed, and improvement in clinical symptoms (NYHA functional class, 6minute walk distance, quality of life) or LV reverse remodeling (LV endsystolic volume reduction, increase in LVEF) was similar in both groups after 6 months of CRT. Also our result was concordant with result of Yu CM et al., 2006, they studied 102 HF patients with functional NYHA class III or IV, TDI (SD of the time to peak systolic velocity in 12 LV segments > 32.6 ms) was used to depict subjects with mechanica;2l LV dyssynchrony among 51 patients with a narrow QRS. A reduction in LV end systolic volume was observed in the narrow and wideQRS patient group 3 months after CRT implantation; improvements in NYHA functional class, maximal exercise capacity, 6-minute walk distance, LVEF, and mitral regurgitation were also detected. In contrast, with holding CRT for 4 weeks resulted in loss of echocardiographic benefits. In both groups, LV reverse remodeling was determined to a similar extent by the degree of baseline mechanical dyssynchrony. In our study we found that circumferential indices were better indicators for LVMD than longitudinal indices this was agreement with the study done by Takeshi Mauro et al., 2009,they found that circumferential indices were better indicators for mechanical dyssynchrony, but our result was disagreement with the result of Feng-Xia et al., 2012 they found that longitudinal indices were better indicators for LVMD than radial indices or circumferential indices.

RECOMMENDATIONS 1-More efforts should be done in a big study with larger number of patients 2 -Use of radial strain to compare with other dyssynchrony indices.

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