Speckle tracking echocardiography before and after Surgical pulmonary valve replacement in Tetralogy of Fallot patients: Can STE elucidate early left ventricular dysfunction?

Objectives: TOF is the most common cyanotic CHD. We investigated left ventricular (LV) function after surgical pulmonary valve replacement (sPVR) in patients with repaired Tetralogy of Fallot (rTOF) by Speckle Tracking Echocardiography (STE). Methods: 58 volunteers participated in this study who divided into 3 groups including 22 PVR patients (mean age 18.96±7 year), 16 repaired Tetralogy of Fallot and 20 healthy age match control. For all patients, we performed 2D echocardiography and STE. Results: 2D echocardiography in all groups showed normal LV ejection fraction without a significant statistical difference (64% sPVR, 60% in repaired Tetralogy of Fallot and 62.5% in the control group). However, the mean global longitudinal strains (GLS) of LV were significantly reduced in both sPVR (-17.5±2.5%) and repaired Tetralogy of Fallot (-17.1±4.7%) patients rather than control group (-20.2±0.7%) (P = 0.003). But GLS had no statistically significant difference between repaired Tetralogy of Fallot and sPVR patients (P=0.9). Segmental analysis of longitudinal strain (LS) showed a significant decrease in sPVR patients and repaired Tetralogy of Fallot group in basal anterior, basal septal, basal anterolateral segments, mid-anterior and anterolateral segments. Except for lower LS in the apical-anteroseptal segment, this level was mostly spared in both sPVR and repaired Tetralogy of Fallot patients. Conclusion: LVEF was within normal range after sPVR patients, but the pattern of impaired segmental LS and GLS did not change as compared with rTOF. Surgical PVR in patients with repaired TOF may not have a significant effect on the improvement of LV function assessed by STE. LV damage which happens during surgical


Introduction
Tetralogy of Fallot is the most common form of congenital cyanotic heart disease, and despite the introduction of many surgical and interventional treatments, pulmonary regurgitation is the main cause of morbidity in long term management of these patients. It is well known that pulmonary regurgitation is progressive and may lead to right ventricle failure and then impaired left ventricle function(1-5).
Pulmonary valve replacement (PVR) was suggested as an effective option to improve and ameliorate the volume overload resulting from pulmonary valve regurgitation (2,6). Pulmonary valve replacement leads to improvement in functional class, exercise capacity, decreases QRS duration, interventricular interaction and quality of life and etc (7). As reported, the left ventricle dysfunction is a major determinant of clinical outcome in these patients, hence evaluation of left ventricle is important (4,(8)(9)(10). Although some studies have stated the importance of left ventricle function and size in repaired Tetralogy of Fallot patients, its usage as prognostic value is not adequate (4). In recent years, assessing myocardial motion strain by using Speckle tracking echocardiography is an emerging echocardiographic technique, increasingly used in heart disease diagnosis and management. Hence, it is useful for detecting subtle and early cardiac dysfunctions in several clinical conditions that cannot be discovered or diagnosed by conventional 2D echocardiography (11). In this study we focused on left ventricle parameters and the aim of this study was to identify patterns of systolic myocardial deformation in repaired Tetralogy of Fallot patients after surgical pulmonary valve replacement, using 2D speckle tracking echocardiography to assess left ventricle function and remodeling that might be undetectable by conventional 2D echocardiography.

Material and methods
This study was approved by the local ethics committee of Shiraz University of Medical Sciences and written informed consent was obtained from all the participants or their guardian before recruitment. It was a single-center retrospective observational cross-sectional study that was performed off-line by a single observer. The assessment of ventricular function was done by left ventricular speckle tracking and conventional 2D transthoracic echocardiography with the Vivid S6 GE ultrasound machine. The study population included three groups: group 1, patients with repaired Tetralogy of Fallot after surgical pulmonary valve replacement, group 2, repaired Tetralogy of Fallot without pulmonary valve replacement and group 3 who were healthy individuals. We studied three groups including Tetralogy of Fallot with pulmonary valve replacement, repaired Tetralogy of Fallot and healthy volunteers who were matched in gender and age (Table 1).
Inclusion criteria for repaired Tetralogy of Fallot group were: Age > 5 years, any form of Tetralogy of Fallot or Tetralogy of Fallot -like (Double outlet right ventricle + severe pulmonary stenosis) lesion who had total surgical correction without homograft and acceptance to participate in this study. For the pulmonary valve replacement group, we included cases with Tetralogy of Fallot or Tetralogy of Fallot like lesion with mechanical or biological valve who had accepted to participate in this study. For the control group, healthy volunteers without a history of ischemic or congenital heart disease or major surgery were included.
Also, the following exclusion criteria were applied for all groups: any history of Kawasaki or coronary artery abnormality, history of uncontrolled tachyarrhythmia, significant residual shunt, inadequate imaging for off-line analysis, transposition of great arteries, and implanted pacemakers.
After ECG connection to each patient, two-dimensional grayscale harmonic images were obtained in the left lateral decubitus position with a probe S4-1 (3-7 MHz) at a frame rate of 60-90 frames/s and appropriate frequency for the age. We used the guidelines of the American Society of Echocardiography for chamber measurements, the apical segment usually not completely visualized and tracking in this area has many limitations. We took care and gathered multiple clips for each view to minimizing low-quality tracing. (11,12) All statistical analysis was done using IBM SPSS V. 24. The data are described using mean ± standard deviation (± SD), median and ranges, when possible. Categorical variables were described using count and percentages. Box plot was drawn to show the upper and lower agreement between variables. The ANOVA test was used to compare different groups and a P-value less than 0.05 was considered to be statistically significant.  Table 1. Among the pulmonary valve replacement group, there were 12(55%) male and 10 (45%) females. Surgical pulmonary valve replacement was performed at mean age of 14.8 ± 6.6 years (range from 6 to 29 years) and total correction of Tetralogy of Fallot at 3.2 ± 1.3 years. In the PVR group, 14 were on medication such as antiplatelet and anti-coagulation but in the rTOF group, only 3 patients were on medication including digoxin, captopril and furosemide. In the surgical pulmonary valve replacement group, 16 cases (72.7%) had a bioprosthetic valve, 6(27.3%) had a mechanical valve. In pulmonary valve replacement group,12 (55%) had one operation prior to surgical pulmonary valve replacement (total correction of Tetralogy of Fallot) and 8(36%) had 2 operations (modified Blalock Taussig shunt + total correction of Tetralogy of Fallot) and remaining 2(9%)had more than two operations.  Standard echocardiographic parameters are shown in Table 2. The presence of pulmonary regurgitation and right ventricular outflow tract gradient were assessed by color Doppler and continuous wave Doppler. It revealed moderate or greater pulmonary regurgitation in all repaired Tetralogy of Fallot but only mild pulmonary valve regurgitation in the surgical pulmonary valve replacement group. Pulmonary valve replacement group had a higher right ventricular outflow tract peak gradient (RVOT PG) rather than repaired Tetralogy of Fallot (18.6 ± 12 mmHg vs 12.7 ± 8 mmHg; P-value = 0.02) but both groups had no significant residual stenosis regard of surgical or interventional approach. The right ventricle dimensions was significantly lower in the surgical PVR group rather than repaired Tetralogy of Fallot as shown in Fig. 1 and Table 2. Both TAPSE and FAC% after surgical pulmonary valve replacement were significantly higher as compared with repaired Tetralogy of Fallot (Table 2 ).

Result
Although there was a significant difference in right ventricle 2D echocardiographic parameters, the left ventricle 2D echocardiographic parameter didn't show significant abnormality in either repaired TOF or pulmonary valve replacement groups (Table 2). Interestingly, 2D echocardiography reports normal ejection fraction (EF > 55%) in both repaired Tetralogy of Fallot and pulmonary valve replacement group. Mean global longitudinal systolic strain of left ventricle was significantly lower in both PVR (-17.5 ± 2.5) and repaired TOF (-17.1 ± 4.7) compared to normal (-20.2 ± 0.7) group with p-value < 0.003. (Table 3) The segmental analysis also showed a significant statistical difference in most segments between the normal group and those of repaired TOF and surgical PVR patients; All basal segments had a lower longitudinal strain (LS), except in basal inferior and inferolateral segments ( Table 3). The apical level is the most spared area. In mid-level, both anterior and anterolateral segments had a lower longitudinal strain (Table 3). Pulmonary valve replacement did not change the segmental strain pattern and we did not observe any improvement in the global or segmental longitudinal strain compare with the repaired TOF group.

Discussion
To best of our knowledge, this is one of the few studies that has focused on the left ventricle function by using 2D speckle tracking echocardiography in repaired  The bullseye schematic and global strain in a sPVR, repaired Tetralogy of Fallot and a norma