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Background: Pulmonary valve regurgitation is a significant long-term complication in patients with tetralogy of Fallot (TOF)., Objective: This study aims to investigate the effects of pulmonary valve implantation (PVI) on the anatomy and function of the right ventricle (RV) and the long-term evolution of the implanted prosthesis in the pulmonary position., Methods: A single-center retrospective cohort analysis was performed in 56 consecutive patients with TOF who underwent PVI. The study included patients of both sexes, aged ≥ 12 years, and involved assessing clinical and surgical data, pre- and post-operative cardiovascular magnetic resonance imaging, and echocardiogram data more than 1 year after PVI., Results: After PVI, there was a significant decrease in RV end-systolic volume indexed by body surface area (BSA), from 89 mL/BSA to 69 mL/BSA (p < 0.001) and indexed RV end-diastolic volume, from 157 mL/BSA to 116 mL/BSA (p < 0.001). Moreover, there was an increase in corrected RV ejection fraction [ RVEFC = net pulmonary flow (pulmonary forward flow - regurgitant flow) / R V end-diastolic volume ] from 23% to 35% (p < 0.001) and left ventricular ejection fraction from 58% to 60% (p = 0.008). However, a progressive increase in the peak pulmonary valve gradient was observed over time, with 25% of patients experiencing a gradient exceeding 60 mmHg. Smaller prostheses (sizes 19 to 23) were associated with a 4.3-fold higher risk of a gradient > 60 mmHg compared to larger prostheses (sizes 25 to 27; p = 0.029; confidence interval: 1.18 to 17.8)., Conclusion: As expected, PVI demonstrated improvements in RV volumes and function. Long-term follow-up and surveillance are crucial for assessing the durability of the prosthesis and detecting potential complications. Proper sizing of prostheses is essential for improved prosthesis longevity.

Background: Many patients with repaired tetralogy of Fallot require pulmonary valve replacement (PVR) due to significant pulmonary regurgitation (PR). Transcatheter PVR (TPVR) is an equally effective and less invasive alternative to surgical PVR but many native right ventricular outflow tracts (RVOTs) are too large for TPVR at time of referral. Understanding the rate of growth of the RVOT may help optimize timing of referral. This study aims to examine the longitudinal growth of the native RVOT over time in repaired tetralogy of Fallot (TOF)., Methods: A retrospective review of serial cardiac MRI cardiovascular magnetic resonance (CMR) data from 121 patients with repaired TOF and a native RVOT (median age at first CMR 14.7 years, average interval between the first and last CMR of 8.1 years) was performed to measure serial changes in RVOT diameter, cross-sectional area, perimeter-derived diameter, and length., Results: All parameters of RVOT size continued to grow with increasing age but growth was more rapid in the decade after TOF repair (for minimum systolic diameter, mean increase of 5.7 mm per 10 years up to year 12, subsequently 2.3 mm per 10 years). The RVOT was larger with a transannular patch and in patients without pulmonary stenosis (p < 0.001 for both), but this was not associated with rate of growth. More rapid RVOT enlargement was noted in patients with larger right ventricular end-diastolic volume (RVEDV), higher PR fraction, and greater rates of increases in RVEDV and PR (p < 0.001 for all) CONCLUSIONS: in patients with repaired TOF, using serial CMR data, we found that RVOT size increased progressively at all ages, but the rate was more rapid in the first decade after repair. More rapid RVOT enlargement was noted in patients with a larger RV, more PR, and greater rates of increases in RV size and PR severity. These results may be important in considering timing of referral for transcatheter pulmonary valves, in planning transcatheter and surgical valve replacement, and in designing future valves for the native RVOT., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Ashwin Prakash reports a relationship with Moderna Inc that includes: equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess flow energy loss (EL) pattern inside the pulmonary circulation in adult patients with repaired tetralogy of Fallot (TOF), particularly in TOF with pulmonary stenosis (PS) and pulmonary regurgitation (PR), as a cardiac workload parameter and its relationship to symptoms and major adverse cardiovascular events (MACE)., Methods: Prospectively, 51 consecutive TOF adults after intracardiac repair, who underwent four-dimensional flow magnetic resonance imaging, were enrolled. All of them had significant PR (PR regurgitant fraction >25 %). TOF patients who had already reached the conventional criteria were excluded. We defined MACE as the following: 1) fatal arrhythmias, 2) sudden cardiac death, 3) surgical pulmonary valvular repair (PVR), 4) right heart failure (HF) needing diuretics and/or hospitalization within 2 years., Results: A total of 15 patients had MACE; 1) 10 patients underwent PVR within 2 years, 2) 2 patients had ventricular tachycardia, and 3) 6 patients developed right HF (overlapped). Right ventricular (RV) end diastolic volume index (EDVI), RV end systolic volume index (ESVI), average EL/cardiac output (CO), and diastolic EL/CO in patients with MACE were greater than ones without MACE. On a multivariate logistic analysis, the diastolic EL/CO ratio and RVEDVI had the highest odds with MACE in all TOF (odds ratio, 40.7 and 1.15. 95%CI, 1.83-905 and 1.02-13.0; p-value, 0.02 and 0.03). In sub-analysis within 29 patients with moderate PS with PR, and 10 patients with MACE showed higher diastolic EL/CO. Average and diastolic EL/CO negatively correlated with RV ejection fraction (EF) in this sub-analysis., Conclusions: High EL, particularly, high diastolic EL/CO, were the important factors for MACE in adult TOF. Higher diastolic EL/CO was also related to lower RV EF and deteriorated RV function in adult TOF with PS and PR. Right-sided EL can be a sensitive marker of excessive cardiac workload which integrates both afterload and preload in adult patients with TOF, beyond the RV size., Competing Interests: Declaration of competing interest The authors except for K.I. report no relationships that could be construed as a conflict of interest. K.I. has a stock option in Cardio Flow Design Inc., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Repaired Tetralogy of Fallot (rTOF) patients suffer from pulmonary regurgitation and may require pulmonary valve replacement (PVR). Cardiac magnetic resonance imaging (cMRI) guides therapy, but conventional measurements do not quantify the intracardiac flow effects from pulmonary regurgitation or PVR. This study investigates intracardiac flow parameters of the right ventricle (RV) of rTOF by computational fluid dynamics (CFD). cMRI of rTOF patients and controls were retrospectively included. Feature-tracking captured RV endocardial contours from long-axis/short-axis cine. Ventricular motion was reconstructed via diffeomorphic mapping, serving as domain boundary for CFD simulations. Vorticity (1/s), viscous energy loss (ELoss, mJ/L) and turbulent kinetic energy (TKE, mJ/L) were quantified in RV outflow tract (RVOT) and RV inflow. These parameters were normalized against total RV kinetic energy (KE) and RV inflow vorticity to derive dimensionless metrics. Vorticity contours by Q-criterion were qualitatively compared. rTOF patients (n = 15) had mean regurgitant fraction 38 ± 12% and RV size 162 ± 35 mL/m 2 . Compared to controls (n = 12), rTOF had increased RVOT vorticity (142.6 ± 75.6/s vs. 40.4 ± 11.8/s, p < 0.0001), Eloss (55.6 ± 42.5 vs. 5.2 ± 4.4 mJ/L, p = 0.0004), and TKE (5.7 ± 5.9 vs. 0.84 ± 0.46 mJ/L, p = 0.0003). After PVR, there was decrease in normalized RVOT Eloss/TKE (p = 0.0009, p = 0.029) and increase in normalized tricuspid inflow vorticity/KE (p = 0.0136, p = 0.043), corresponding to reorganization of the "donut"-shaped tricuspid ring-vortex. The intracardiac flow in rTOF patients can be simulated to determine the impact of PVR and improve the clinical indications guided by cardiac imaging., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

In patients with repaired tetralogy of Fallot (rTOF), the regurgitant fraction (RF) in left pulmonary artery (LPA) and right pulmonary artery (RPA) is usually unequal. The morphometrics may play a crucial role in this RF discrepancy. Cardiovascular MR of 79 rTOF patients and 20 healthy controls were retrospectively enrolled. Forty-four from the 79 patients were matched in age, sex and body surface area to the 20 controls and were investigated for: (1) phase-contrast flow of main pulmonary artery (MPA), LPA, and RPA; (2) vascular angles: the angles between the thoracic anterior-posterior line (TAPL) with MPA (θ M-AP ), MPA with RPA (θ M-R ), and MPA with LPA (θ M-L ); (3) cardiac angle, the angle between TAPL and the interventricular septum; (4) area ratio of bilateral lung and hemithorax regions. Compared with the 20 controls, the 44 rTOF patients exhibited wider θ M-AP , sharper θ M-L angle, and a smaller θ M-L /θ M-R ratio. In the 79 rTOF patients, LPA showed lower forward, backward, and net flow, and greater RF as compared with RPA. Multivariate analysis showed that the RF of LPA was negatively associated with the θ M-L /θ M-R ratio and the age at surgery (R 2  = 0.255). Conversely, the RF of RPA was negatively associated with the left lung/left hemithorax area ratio and cross-sectional area (CSA) of LPA, and positively associated with CSA of RPA and MPA (R 2  = 0.366). In rTOF patients, the RF of LPA is more severe than that of RPA, which may be related to the vascular morphometrics. Different morphometric parameters are independently associated with the RF of LPA or RPA, which may offer potential insights for surgical strategies., (© 2024. The Author(s).)

Background: Robust data on changes in pulmonary valve replacement (PVR) procedural volume and predictors of bioprosthetic pulmonary valve (BPV) durability in patients with tetralogy of Fallot (TOF) are scarce., Objectives: This study sought to assess temporal trends in PVR procedural volume and BPV durability in a nationwide, retrospective TOF cohort., Methods: Data were obtained from patient records. Robust linear regression was used to assess temporal trends in PVR procedural volume. Piecewise exponential additive mixed models were used to estimate BPV durability, defined as the time from implantation to redo PVR with death as a competing risk, and to assess risk factors for reduced durability., Results: In total, 546 PVR were performed in 384 patients from 1976 to 2021. The annual number of PVR increased from 0.4 to 6.0 per million population (P < 0.001). In the last decade, the transcatheter PVR volume increased by 20% annually (P < 0.001), whereas the surgical PVR volume did not change significantly. The median BPV durability was 17 years (Q1: 10-Q3: 10 years-not applicable). There was no significant difference in the durability of different BPV after adjustment for confounders. Age at PVR (HR: 0.78 per 10 years from <1 year; 95% CI: 0.63-0.96; P = 0.02) and true inner valve diameter (9-17 mm vs 18-22 mm HR: 0.40; 95% CI: 0.22-0.73; P = 0.003 and 18-22 mm vs 23-30 mm HR: 0.59; 95% CI: 0.25-1.39; P = 0.23) were associated with reduced BPV durability in multivariate models., Conclusions: The PVR procedural volume has increased over time, with a greater increment in transcatheter than surgical PVR during the last decade. Younger patient age at PVR and a smaller true inner valve diameter predicted reduced BPV durability., Competing Interests: Funding Support and Author Disclosures This study was funded by the Danish Heart Foundation, Copenhagen, Denmark, and the Novo Nordisk Foundation, Hellerup, Denmark. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with repaired Tetralogy of Fallot (rTOF) often develop pulmonary regurgitation (PR) and right ventricle (RV) dysfunction, experiencing increased mortality and morbidity rates in adulthood. Pulmonary valve replacement (PVR) timing to address PR is controversial. Cardiac Magnetic Resonance (CMR) is the gold standard for morpho-functional evaluation of complex cardiopathies. This study aims to identify CMR parameters predictive of adverse outcomes to help defining the best therapeutic management of rTOF patients., Methods: 130 rTOF patients who underwent CMR (2006-2019) were enrolled in this retrospective single-center study. CMR, clinical, ECG and exercise data were analyzed. Univariate and multivariate analyses identified clinical and CMR parameters predictive of adverse outcomes both individually (e.g., death, arrhythmias, heart failure (HF), pharmacological therapy, QRS ≥ 160ms) and as composite outcome., Results: Univariate analysis confirmed RV volumes and RV ejection fraction corrected for PR as adverse outcome predictors and identified interesting correlations: pulmonary artery bifurcation geometry and abnormal interventricular septum (IVS) motion with arrhythmias (p < .001; p = .037), HF (p = .049; p = .005), composite outcome (p = .039; p = .009); right atrium (RA) dimensions with the composite outcome and the outcomes individually (p < .001). The best predictive models by multivariate analysis included sex (male), RV and RA dilation for QRS ≥ 160ms, time form repair to CMR, age at TOF repair and IVS fibrosis for pharmacological therapy., Conclusions: Besides RV volumes, new adverse prognostic factors could guide rTOF therapeutic management: pulmonary arteries morphology, abnormal IVS motion, RV dysfunction, RA dilation. Perspective multicentric evaluation is needed to specify their effective role., (© 2023. The Author(s).)

Purpose: Pulmonary valve (PV) monocusp reconstruction in transannular patch (TAP) right ventricular outflow tract (RVOT) repair for Tetralogy of Fallot has variable clinical outcomes across different surgical approaches. The study purpose was to systematically evaluate how monocusp leaflet design parameters affect valve function in-vitro., Methods: A 3D-printed, disease-specific RVOT model was tested under three infant physiological conditions. Monocusps were sewn into models with the native main pulmonary artery (MPA) forming backwalls that constituted 40% and 50% of the reconstructed circumference for z-score zero PV annulus and MPA diameters (native PV z-score - 3.52 and - 2.99 for BSA 0.32m 2 ). Various leaflet free edge lengths (FEL) (relative to backwall), positions (relative to PV STJ), and scallop depths were investigated across both models. Pressure gradient, regurgitation, and coaptation were analyzed with descriptive statistics and regression models., Results: Increasing FEL beyond 100% of the MPA backwall decreased gradient but mildly increased regurgitation to a peak of 25%. Positioning the free edge 2 mm past the STJ mildly increased gradient for each FEL without significantly changing regurgitation compared to STJ placement. Scalloping leaflets trivially affected performance. Pre-folding leaflets improved mobility and slightly reduced gradient., Conclusions: Balancing gradient, regurgitation, and oversizing for growth, a set of leaflet designs have been selected for pre-clinical evaluation. Designs with leaflet widths 140-160% in the 40% backwall model (110-120% in the 50% backwall), positioned at or 2 mm past the STJ, demonstrated the best results. The next stage of ex-vivo testing will additionally consider native RVOT distensibility, native leaflet interactions, and TAP characteristics., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: Patients with repaired tetralogy of Fallot (rTOF) experience long-term chronic pulmonary valve regurgitation resulting in right ventricular (RV) dilatation. According to current guidelines, the evaluation of patients with rTOF for RV dilatation should be based on cardiac magnetic resonance (CMR). However, for many asymptomatic patients, routine CMR is not practical. Our study aims to identify screening methods for CMR based on echocardiographic data, with the goal of establishing a more practical and cheap method of screening for severity of RV dilatation in patients with asymptomatic rTOF., Methods: Thirty two rTOF patients (mean age, 21(10.5) y, 21 males) with moderate to severe pulmonary regurgitation (PR) were prospectively recruited. Each patient received CMR and echocardiogram examination within 1 month prior to operation and collected clinical data, and then received echocardiogram examination at discharge and 3-6 months post-surgery., Results: RV moderate-severe dilatation was defined as right ventricular end-diastolic volume index (RVEDVI) ≥ 160 ml/m2 or right ventricular end-systolic volume index (RVESVI) ≥ 80 ml/m2 in 15 of 32 patients (RVEDVI, 202.15[171.51, 252.56] ml/m2, RVESVI, 111.99 [96.28, 171.74] ml/m2). The other 17 (RVESDI, 130.19 [117.91, 139.35] ml/m2, RVESVI = 67.91 [63.35, 73.11] ml/m2) were defined as right ventricle mild dilatation, i.e., RVEDVI < 160 ml/m2 and RVESVI < 80 ml/m2, and the two parameters were higher than normal values. Compared with the RV mild dilatation group, patients of RV moderate-severe dilatation have worse cardiac function before surgery (right ventricular ejection fraction, 38.92(9.19) % versus 48.31(5.53) %, p < 0.001; Left ventricular ejection fraction, 59.80(10.26) versus 66.41(4.15), p = 0.021). Patients with RV moderate-severe dilatation faced longer operation time and more blood transfusion during operation (operation time, 271.53(08.33) min versus 170.53(72.36) min, p < 0.01; Intraoperative blood transfusion, 200(175) ml versus 100(50) ml, p = 0.001). Postoperative RV moderate-severe dilatation patients have poor short-term prognosis, which was reflected in a longer postoperative hospital stay (6.59 [2.12] days versus 9.80 [5.10] days, p = 0.024) and a higher incidence of hypohepatia (0[0] % versus 4[26.7] %, p = 0.023). Patients with RV dilatation score > 2.35 were diagnosed with RV moderate-severe dilatation (AUC = 0,882; Sensitivity = 94.1%; Specificity = 77.3%)., Conclusions: RV moderate-severe dilatation is associated with worse preoperative cardiac function and short-term prognosis after PVR in rTOF patients with moderate to severe PR. The RV dilatation score is an effective screening method. When RV dilatation score > 2.35, the patient is indicated for further CMR examination and treatment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Competing Interests: Funding Support and Author Disclosures Dr Seckeler has received funding support from PANDA (People Acting Now Discover Answers) for the University of Arizona Congenital Cardiac 3D Printing Program. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Pulmonary valve replacement is recommended in patients with repaired tetralogy of Fallot based on cardiac magnetic resonance imaging (MRI) criteria. This procedure is performed by surgical or transcatheter approaches., Objective: We aimed to investigate the differences in preprocedural MRI characteristics (volume, function, strain) and morphology of the right ventricular outflow tract and branch pulmonary arteries in patients for whom surgical or transcatheter pulmonary valve replacement was planned., Materials and Methods: Cardiac MRI of 166 patients with tetralogy of Fallot were analyzed. Of these, 36 patients for whom pulmonary valve replacement was planned were included. Magnetic resonance imaging characteristics, right ventricular outflow tract morphology, branch pulmonary artery flow distribution and diameter were compared between surgical and transcatheter groups. Spearman correlation and Kruskal-Wallis tests were performed., Results: Circumferential and radial MRI strain for the right ventricle were lower in the surgical group (P=0.045 and P=0.046, respectively). The diameter of the left pulmonary artery was significantly lower (P=0.021) and branch pulmonary artery flow and diameter ratio were higher (P=0.044 and P = 0.002, respectively) in the transcatheter group. There was a significant correlation between right ventricular outflow tract morphology and right ventricular end-diastolic volume index and global circumferential and radial MRI strain (P=0.046, P=0.046 and P= 0.049, respectively)., Conclusion: Preprocedural MRI strain, right-to-left pulmonary artery flow, diameter ratio and morphological features of the right ventricular outflow tract were significantly different between the two groups. A transcatheter approach may be recommended for patients with branch pulmonary artery stenosis, since both pulmonary valve replacement and branch pulmonary artery stenting can be performed in the same session., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Residual lesions following Fallot repair are primarily pulmonary regurgitation and right ventricular outflow tract obstruction. These lesions may impact exercise tolerance, particularly because of a poor increase in left ventricular stroke volume. Pulmonary perfusion imbalance is also common, but its effect on cardiac adaptation to exercise is not known., Aim: To assess the association between pulmonary perfusion asymmetry and peak indexed exercise stroke volume (pSVi) in young patients., Methods: We retrospectively studied 82 consecutive patients with Fallot repair (mean age 15.2±3.8 years) who underwent echocardiography, four-dimensional flow magnetic resonance imaging and cardiopulmonary testing with pSVi measurement by thoracic bioimpedance. Normal pulmonary flow distribution was defined as right pulmonary artery perfusion between 43 and 61%., Results: Normal, rightward and leftward flow distributions were found in 52 (63%), 26 (32%) and four (5%) patients, respectively. Independent predictors of pSVi were right pulmonary artery perfusion (β=0.368, 95% confidence interval [CI] 0.188 to 0.548; P=0.0003), right ventricular ejection fraction (β=0.205, 95% CI 0.026 to 0.383; P=0.049), pulmonary regurgitation fraction (β=-0.283, 95% CI -0.495 to -0.072; P=0.006) and Fallot variant with pulmonary atresia (β=-0.213, 95% CI -0.416 to -0.009; P=0.041). The pSVi prediction was similar when the categorical variable right pulmonary artery perfusion>61% was used (β=0.210, 95% CI 0.006 to 0.415; P=0.044)., Conclusion: In addition to right ventricular ejection fraction, pulmonary regurgitation fraction and Fallot variant with pulmonary atresia, right pulmonary artery perfusion is a predictor of pSVi, in that rightward imbalanced pulmonary perfusion favours greater pSVi., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Accurate detection of significant pulmonary regurgitation (PR) is critical in management of patients after right ventricular (RV) outflow reconstruction in Tetralogy of Fallot (TOF) patients, because of its influence on adverse outcomes. Although pressure half time (PHT) of PR velocity is one of the widely used echocardiographic markers of the severity, shortened PHT is suggested to be seen in conditions with increased RV stiffness with mild PR. However, little has been reported about the exact characteristics of patients showing discrepancy between PHT and PR volume in this population., Methods: Echocardiography and cardiac magnetic resonance imaging (MRI) were performed in 74 TOF patients after right ventricular outflow tract (RVOT) reconstruction [32 ± 10 years old]. PHT was measured from the continuous Doppler PR flow velocity profile and PHT < 100 ms was used as a sign of significant PR. Presence of end-diastolic RVOT forward flow was defined as RV restrictive physiology. By using phase-contrast MRI, forward and regurgitant volumes through the RVOT were measured and regurgitation fraction was calculated. Significant PR was defined as regurgitant fraction ≥ 25%., Results: Significant PR was observed in 54 of 74 patients. While PHT < 100 ms well predicted significant PR with sensitivity of 96%, specificity of 52%, and c-index of 0.72, 10 patients showed shortened PHT despite regurgitant fraction < 25% (discordant group). Tricuspid annular plane systolic excursion and left ventricular (LV) ejection fraction were comparable between discordant group and patients showing PHT < 100 ms and regurgitant fraction ≥ 25% (concordant group). However, discordant group showed significantly smaller mid RV diameter (30.7 ± 4.5 vs. 39.2 ± 7.3 mm, P < 0.001) and higher prevalence of restrictive physiology (100% vs. 42%, P < 0.01) than concordant group. When mid RV diameter ≥ 32 mm and presence of restrictive physiology were added to PHT, the predictive value was significantly improved (sensitivity: 81%, specificity: 90%, and c-index: 0.89, P < 0.001 vs. PHT alone by multivariable logistic regression model)., Conclusion: Patients with increased RV stiffness and non-enlarged right ventricle showed short PHT despite mild PR. Although it has been expected, this was the first study to demonstrate the exact characteristics of patients showing discrepancy between PHT and PR volume in TOF patients after RVOT reconstruction., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease. After surgical repair, the excellent survival rate has led to long-term complications dominated by pulmonary regurgitation (PR). Our study aimed to identify echocardiographic criteria for assessment of right ventricular (RV) function and quantification of PR correlated with cardiac MRI indices., Methods: We conducted a descriptive study between June 2021 and March 2022 including patients followed for repaired ToF since 2016 or earlier. All patients were seen for clinical, electrocardiographic, and ultrasound evaluation. Cardiac MRI was performed with a maximum delay of 1 month from Doppler echocardiography., Results: 38 patients were included, with a mean age at imaging of 18 ± 9 years. Our study showed that the echocardiographic parameters of PR quantification correlated with a pulmonary regurgitation fraction on MRI greater than 40% were: the PHT value (p = 0.005) and the ratio of PR jet width to pulmonary valve annulus diameter (p = 0.032). The only ultrasound parameter estimating RV systolic function correlated with RVEF on cardiac MRI was FAC, with p = 0.007., Conclusion: Quantitative assessment of RV parameters in patients followed for repaired ToF, as well as the assessment of the severity of PR, is feasible with a standardized ultrasound examination, with good correlation with cardiac MRI., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Current indications for pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF) rely on cardiovascular magnetic resonance (CMR) image-based indices but are inconsistently applied, lead to mixed outcomes, and remain debated. This study aimed to test the hypothesis that specific markers of biventricular shape may discriminate differences between rTOF patients who did and did not require subsequent PVR better than standard imaging indices. In this cross-sectional retrospective study, biventricular shape models were customized to CMR images from 84 rTOF patients. A statistical atlas of end-diastolic shape was constructed using principal component analysis. Multivariate regression was used to quantify shape mode and imaging index associations with subsequent intervention status (PVR, n = 48 vs. No-PVR, n = 36), while accounting for confounders. Clustering analysis was used to test the ability of the most significant shape modes and imaging indices to discriminate PVR status as evaluated by a Matthews correlation coefficient (MCC). Geometric strain analysis was also conducted to assess shape mode associations with systolic function. PVR status correlated significantly with shape modes associated with right ventricular (RV) apical dilation and left ventricular (LV) dilation (p < 0.01), RV basal bulging and LV conicity (p < 0.05), and pulmonary valve dilation (p < 0.01). PVR status also correlated significantly with RV ejection fraction (p < 0.05) and correlated marginally with LV end-systolic volume index (p < 0.07). Shape modes discriminated subsequent PVR better than standard imaging indices (MCC = 0.49 and MCC = 0.28, respectively) and were significantly associated with RV and LV radial systolic strain. Biventricular shape modes discriminated differences between patients who did and did not require subsequent PVR better than standard imaging indices in current use. These regional features of cardiac morphology may provide insight into adaptive vs. maladaptive types of structural remodeling and point toward an improved quantitative, patient-specific assessment tool for clinical use., (© 2023. The Author(s).)

Background: The prevalence and determinants of tricuspid regurgitation (TR) in patients with repaired Tetralogy of Fallot (rTOF) remain incompletely understood., Objectives: To explore the prevalence of and factors associated with TR in patients with rTOF, specifically, the relationship of right ventricular (RV) dilatation with TR severity., Methods: Patients (≥17 yrs) with rTOF referred to our service (2000-2019) were identified. Those with severe pulmonary stenosis, significant shunt, or previous tricuspid valve surgery were excluded. Using standard cardiac MRI protocols, RV, right atrial (RA) and tricuspid valve (TV) parameters were measured and compared., Results: 68 consecutively eligible patients with rTOF were included in the study (27 ± 9 yrs., 35% female). Despite substantial RV volume overload (mean RVEDVi 153 mL/m 2 ), the majority of the cohort (78%) had no or only mild TR. RA volumes, tenting height/area and annular diameter were normal (4.9 ± 2.0 mm, 1.1 ± 1.0 cm 2 and 32.4 ± 6.2 mm, respectively). There was no significant correlation of TR fraction with RVEDVi (r = 0.13; p = 0.30), RVEF (r = 0.09; p = 0.44) or tricuspid annular diameter (r = 0.07; p = 0.62). Only RAVi showed a weak but significant correlation with TR fraction (0.29; p = 0.03). In a pooled cohort analysis, including both rTOF patients and adults with a dilated RV from pre-tricuspid shunt lesions, only rTOF was independently associated with higher TR fraction (p = 0.017)., Conclusion: Despite substantial RV dilatation in a cohort with rTOF, there was surprisingly little TR. We found poor correlation between RVEDVi, RA volumes, tricuspid annular dilatation and the presence of significant TR. These findings question commonly held notions regarding the pathophysiology of functional TR in these patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Patients with tetralogy of Fallot (TOF) may undergo pulmonary valve replacement (PVR) after initial full repair. We investigated indices of biventricular function, work and efficiency of TOF patients' using noninvasive pressure-volume (PV) loop analysis on cardiovascular magnetic resonance (CMR) images and compared pre-and post PVR groups. Biventricular segmentations of steady state free precession CMR images were performed using custom validated software (Segment version 2.0 R7067). Brachial cuff pressure estimated left ventricular (LV) systolic pressure. Right ventricular (RV) inputs were obtained from pre-PVR cardiac catheterization data. Biventricular PV loops were then derived using a time-varying elastance model. Twenty seven patients were studied: (22 pre-PVR, 5 post-PVR), mean age of 20±10.5 years and 83% male. RV stroke volume significantly differed before and after PVR (73.2±25 ml vs. 41±10 mL, P =0.01). RV stroke work (SW) and mean external power (MEP) were significantly less post-PVR, but there were no significant differences in the LV hemodynamic indices. TOF patients have reduced RV SW and MEP post-PVR suggesting improved hemodynamics. Noninvasive biventricular PV loop analysis shows potential for integration into standard CMR imaging of TOF and provides hemodynamic data that could influence management decisions., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Maladaptive remodelling mechanisms occur in patients with repaired tetralogy of Fallot (rToF) resulting in a cycle of metabolic and structural changes. Biventricular shape analysis may indicate mechanisms associated with adverse events independent of pulmonary regurgitant volume index (PRVI). We aimed to determine novel remodelling patterns associated with adverse events in patients with rToF using shape and function analysis., Methods: Biventricular shape and function were studied in 192 patients with rToF (median time from TOF repair to baseline evaluation 13.5 years). Linear discriminant analysis (LDA) and principal component analysis (PCA) were used to identify shape differences between patients with and without adverse events. Adverse events included death, arrhythmias, and cardiac arrest with median follow-up of 10 years., Results: LDA and PCA showed that shape characteristics pertaining to adverse events included a more circular left ventricle (LV) (decreased eccentricity), dilated (increased sphericity) LV base, increased right ventricular (RV) apical sphericity, and decreased RV basal sphericity. Multivariate LDA showed that the optimal discriminative model included only RV apical ejection fraction and one PCA mode associated with a more circular and dilated LV base (AUC = 0.77). PRVI did not add value, and shape changes associated with increased PRVI were not predictive of adverse outcomes., Conclusion: Pathological remodelling patterns in patients with rToF are significantly associated with adverse events, independent of PRVI. Mechanisms related to incident events include LV basal dilation with a reduced RV apical ejection fraction., (© 2022. The Author(s).)

Background: Serum biomarkers of myocardial fibrosis are considered markers of adverse outcome in adults with heart disease. Associations between biomarkers and clinical parameters in tetralogy of Fallot (TOF) has been understudied. We compared serum biomarker profiles with clinical and cardiac magnetic resonance (CMR) parameters of ventricular remodeling in patients with repaired TOF., Methods: Serum biomarkers [metalloproteinases MMP1 and MMP9, galectin-3, micro-RNA21 (miR21)), ST2, procollagen type I carboxy-terminal propeptide (PICP), and NTproBNP] were measured in TOF patients undergoing CMR. Associations between biomarkers and clinical and CMR variables were assessed using correlation coefficients, and linear and logistic regression., Results: Sixty patients were investigated, of which 47% were male. Age at CMR and TOF repair was 15 years [interquartile range (IQR) 9, 22] and 3.2 months (IQR 0.8, 6.2), respectively. Twelve (20%) had prior pulmonary valve replacement (PVR). MMP1 values were higher among those with prior PVR (16.7 (IQR 7.9, 25.5) vs 14.4 (IQR 9.9, 24.9), p = 0.02). When stratifying MMP1 into low and high groups, higher MMP1 was associated with higher indexed right (RV) and left ventricular (LV) mass and RV mass:volume ratios after adjusting for PVR. No other associations between biomarkers and CMR parameters were identified., Conclusions: Only MMP1 was associated with markers of RV remodeling after TOF repair. As an enzyme involved in extracellular matrix degradation, MMP1 could be associated with fibrotic processes underlying RV remodeling, including dilation and hypertrophy. The additional biomarkers may not be specific towards cardiac remodeling. These findings merit further correlations with myocardial fibrosis measurements by CMR., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In the surgical repair of the tetralogy of Fallot with a narrow pulmonary valve annulus, the transannular patch method is used for right ventricular outflow tract repair. To prevent pulmonary regurgitation and valve calcification, we created and applied a new transannular patch method using pedicled own pericardium in a 5-month-old boy with tetralogy of Fallot. After closing the ventricular septal defect as usual with a 0.4 mm Gore-Tex sheet, we decided that the pulmonary valve could not be spared, because the pulmonary valve opening size was 6 mm. After removing the right ventricular abnormal myocardium, each edge of the pedicled own pericardium patch was sewn from 5 mm above the pulmonary valve commissures toward the basis of the pulmonary valve ring. The transannular patch was created using a Gore-Tex graft sawn to the right ventricular outflow tract. Echocardiography performed 6 months post surgery showed no pulmonary stenosis and trivial pulmonary insufficiency., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Right ventricular (RV) dysfunction caused by chronic pulmonary regurgitation (PR) is a major determinant of clinical outcome in adults with repaired tetralogy of Fallot (rTOF). However, the accurate assessment of RV function by conventional echocardiography remains challenging. This study tested the feasibility and usefulness of RV free-wall (RVFW) strain obtained by two-dimensional (2D) speckle-tracking echocardiography (STE) in evaluation of RV function in adults with rTOF by comparing cardiac magnetic resonance (CMR) imaging. We enrolled 22 consecutive patients (male/female, 8/14; mean age, 25.0 years) with rTOF who underwent transthoracic echocardiography at Tohoku University Hospital from July 2016 to June 2019. We measured RVFW strain by STE and compared them with 22 hemodynamically normal subjects (NOR) (male/female, 9/13; mean age, 32.0 years). The correlation between RV strain and CMR-derived RV ejection fraction (RVEF) or PR fraction (PRF) were also evaluated. All rTOF patients had more than moderate PR but were near asymptomatic. RVFW longitudinal strain (RVFW-LS) was significantly decreased in the rTOF group compared with that in the NOR group (-19.6 vs. -24.7, P < 0.01). In the rTOF group, RVFW-LS correlated with PRF (r = 0.44, P < 0.05), whereas RVFW circumferential strain at the mid-ventricular level correlated with RVEF (r = 0.57, P < 0.01). Intra-observer variability of RVFW strain was acceptable. These results indicate that RV systolic function and PR severity in rTOF could be assessed by RVFW strain measured by 2D STE. This method is feasible and can be used as a complement to CMR imaging.

Tetralogy of Fallot is the most common cyanotic congenital heart defect, accounting for 10% of all CHD. Despite most patients now surviving well into adulthood, morbidity and mortality rates continue to be high. Surgical and percutaneous pulmonary valve replacement are procedures that are performed to prevent long-term complications from occurring. Unfortunately, pulmonary valve replacement based on current CMR criteria does not prevent postoperative ventricular arrhythmia, heart failure, and sudden cardiac death. Thus, a more advanced and comprehensive hemodynamic evaluation is needed to better understand right ventricular (dys)function in tetralogy of Fallot patients and to optimize the timing of valve replacement. Recently, four-dimensional flow CMR has emerged as a promising and non-invasive imaging technique that can provide comprehensive quantitative evaluation of flow in an entire volume within the chest in a single imaging session. With velocity-encoding in all three spatial directions throughout the complete cardiac cycle, it can provide analysis of cardiac, pulmonary artery and aortic flow volumes, flow velocities, flow patterns, as well as more advanced hemodynamic parameters. Four-dimensional flow CMR could therefore provide insights into the complex hemodynamics of tetralogy of Fallot and could potentially provide novel criteria for pulmonary valve replacement in these patients. The aim of this review is to provide an overview of available research on four-dimensional flow CMR research in tetralogy of Fallot patients.

In post-operative Tetralogy of Fallot (TOF) patients cMRI data are used for determining right ventricle (RV) dilation to justify the pulmonary valve placement. Echocardiogram analysis of RV volumes has inherent accuracy issues. There are no data exploring the relationship of transthoracic echocardiography tricuspid valve (TV) annulus size and cMRI RV dilation. Retrospective study in post-operative TOF patients. Patients less than 21 years old and with high-quality transthoracic echocardiogram and MRI within 6 months of each other were included. We collected demographic data, type of initial repair, echocardiographic, and cMRI data. A single reviewer measured echocardiogram TV size. Boston z-scores were used. 77 echocardiogram and cMRI pairs were analyzed. Average age was 14 years old. There is not a strong linear relationship between TV z-score and indexed right ventricular end diastolic volume (RVEDVi) (R 2  = 0.31). Twenty patients had RVEDVi's of greater than 150 ml/m 2 . From those 20 patients, 9 patients had a TV z-score of > 2. No patient had a TV z-score > 2 and a normal RVEDVi. For a TV z-score < 2, there was a positive predictive value of 100%, a negative predictive value of 83%, specificity of 100%, and sensitivity of 45%. In our study population, the TV z-score is not sufficient to predict RV dilation. However, TV z-score > 2 has a high positive predictive value for an RVEDVi of > 150 ml/m 2 . This would suggest that a cMRI should be done if the TV z-score is > 2 on echocardiography., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This new and easily reproducible pulmonary valve-sparing technique for the correction of Tetralogy of Fallot is based on a conservative management of the native pulmonary valve to preserve its growth potential. From July 2015 to December 2019, 67 children presenting with a Tetralogy of Fallot were operated consecutively in a single centre using this technique in all cases. A T-shaped infundibulotomy is used to release the anterior pulmonary annulus from any muscular attachment. After myocardial resection and ventricular septal defect closure, an extensive commissurotomy is achieved. Finally, the right ventricular outflow tract remodelling is completed by a shield-shaped bovine patch with an oversized square superior edge, attached directly on the pulmonary valve annulus, with an effect of systolic traction. Sixty patients (89.5%) had a Tetralogy of Fallot repair with preservation of the pulmonary valve. To date, with a median follow-up of 38.2 [14-64] months, no patient has needed a surgical or interventional procedure for pulmonary valve stenosis or regurgitation, with low residual gradients. This procedure could provide a significant increase in native pulmonary valve preservation. Long-term studies are needed to assess pulmonary valve growth and the consequent reduction in surgical or interventional reoperations., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Purpose: Patients with repaired Tetralogy of Fallot (rTOF) will develop dilation of the right ventricle (RV) from chronic pulmonary insufficiency and require pulmonary valve replacement (PVR). Cardiac MRI (cMRI) is used to guide therapy but has limitations in studying novel intracardiac flow parameters. This pilot study aimed to demonstrate feasibility of reconstructing RV motion and simulating intracardiac flow in rTOF patients, exclusively using conventional cMRI and an immersed-boundary method computational fluid dynamic (CFD) solver., Methods: Four rTOF patients and three normal controls underwent cMRI including 4D flow. 3D RV models were segmented from cMRI images. Feature-tracking software captured RV endocardial contours from cMRI long-axis and short-axis cine stacks. RV motion was reconstructed via diffeomorphic mapping (Deformetrica, deformetrica.org), serving as the domain boundary for CFD. Fully-resolved direct numerical simulations were performed over several cardiac cycles. Intracardiac vorticity, kinetic energy (KE) and turbulent kinetic energy (TKE) was measured. For validation, RV motion was compared to manual tracings, results of KE were compared between CFD and 4D flow., Results: Diastolic vorticity and TKE in rTOF patients were 4.12 ± 2.42 mJ/L and 115 ± 27/s, compared to 2.96 ± 2.16 mJ/L and 78 ± 45/s in controls. There was good agreement between RV motion and manual tracings. The difference in diastolic KE between CFD and 4D flow by Bland-Altman analysis was - 0.89910 to 2 mJ/mL (95% limits of agreement: - 1.351 × 10 -2 mJ/mL to 1.171 × 10 -2 mJ/mL)., Conclusion: This CFD framework can produce intracardiac flow in rTOF patients. CFD has the potential for predicting the effects of PVR in rTOF patients and improve the clinical indications guided by cMRI., (© 2021. Biomedical Engineering Society.)

Background: Right ventricle-pulmonary artery (RV-PA) coupling is a strong prognostic marker in several clinical settings, but few studies have focused on its role in repaired tetralogy of Fallot (rToF) with pulmonary regurgitation., Aim: To assess whether differences exist in RV-PA coupling, estimated by echocardiography, between patients with rToF and pulmonary regurgitation with or without an indication for pulmonary valve replacement (PVR)., Methods: The study population included 40 patients with rToF, who were allocated to two groups: 20 with an indication for PVR (i-PVR group); and 20 without an indication for PVR (ni-PVR group). Forty healthy controls were also included. All subjects underwent echocardiography, and cardiac magnetic resonance (CMR) was available in 27/40 patients with rToF. RV-PA coupling was assessed by echocardiographic tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) and right ventricular stroke volume/right ventricular end-systolic volume (RVSV/RVESV) by CMR., Results: TAPSE was similar in the i-PVR and ni-PVR groups (19.0±3.4 vs 18.8±2.7mm; P=0.97) whereas RV-PA coupling was significantly worse in the i-PVR group versus the ni-PVR group (TAPSE/PASP 0.8±0.3 vs 1.1±0.5mm/mmHg; P=0.001), and in the i-PVR group versus the control group (P=0.02); there was no difference between the ni-PVR and control groups (P=0.29). CMR data confirmed the echocardiography results, with a significant difference in RV-PA coupling between the i-PVR and ni-PVR groups (RVSV/RVESV 0.9±0.2 vs 1.2±0.3mL/min/mL; P=0.01)., Conclusions: This study demonstrates worse RV-PA coupling, despite normal RV systolic function, in patients with rToF with an indication for PVR. RV-PA coupling could be a sensitive marker of a progressive maladaptive RV response to long-standing volume overload in rToF before the onset of clinical symptoms and RV systolic dysfunction., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

We assessed right ventricular (RV)-pulmonary arterial (PA) coupling in patients with repaired tetralogy of Fallot (TOF). Sixty patients (34 males) aged 18.6 ± 8.3 years at 14.8 ± 7.4 years after repair and 60 controls were studied. Two-dimensional, tissue Doppler and speckle tracking echocardiography and colour flow mapping were performed to assess RV end-systolic (ESA) and -diastolic areas, tricuspid valve Doppler and myocardial velocities, left ventricular (LV) and RV deformation and pulmonary (PR), tricuspid regurgitation (TR), respectively. The ratios of RV area change to ESA and peak tricuspid annular systolic (s) velocity to RV ESA indexed to body surface area reflected RV-PA coupling. Patients had greater RV areas and reduced tricuspid annular and myocardial velocities, LV and RV myocardial mechanics compared to controls (all p < 0.05). Both RV area change/ESA ratio and peak tricuspid annular s velocity/indexed RV ESA ratio were reduced in patients (all p < 0.001). Sixty-one and 100% of patients had, respectively, RV area change/ESA ratio and peak tricuspid annular s velocity/indexed RV ESA ratio < -2SD of controls. Indices of RV-PA coupling correlated positively with tricuspid myocardial velocities, LV and RV deformation and inversely with PR and TR (all p < 0.05). Multivariate analysis showed RV systolic strain rate, PR and TR as independent predictors of both RV-PA coupling indices, whilst age, gender and LV systolic strain were also predictors of peak tricuspid annular s velocity/indexed RV ESA ratio (all p < 0.05). In conclusion, RV-PA coupling is impaired and is associated with RV and LV mechanics and severity of PR and TR in patients with repaired TOF., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Fragmented QRS is an abnormal sign in an ECG resulting from ventricular dyssynchrony. The presence of fragmented QRS (fQRS) is related to mortality in patients with repaired tetralogy of Fallot (rTOF). This study aimed to analyze the correlations between fQRS and ventricular function parameters from cardiac magnetic resonance (CMR) images. A total of 54 patients with rTOF or repaired DORV, TOF type who had been investigated by CMR at Songklanagarind Hospital from January 2012 to August 2019 were retrospectively reviewed. Most of the patients (47 patients, 87%) were diagnosed with TOF and most of these (57.4%) were treated with a transannular patch (TAP) on the right ventricular outflow tract (RVOT). Forty-four patients (81%) had fQRS. The median time interval between EKG and CMR was 4.2 months (IQR 1.1, 6.9). Patients with fQRS had significantly higher RVEDVi (145.6 [IQR 121.1, 173.1) vs. 115.9 [IQR 96.2, 146.9] mL/m 2 , p = 0.037), higher RVESVi (82.5 [IQR 62.9, 100.8] vs. 58.6 [IQR 46, 77.2] mL/m 2 , p = 0.032) and higher RVEDV/LVEDV ratio [1.6 (IQR 1.4, 1.9) vs. 1.4 (IQR 1.3, 1.5), p = 0.026]. The extent of fQRS was significantly associated with an increase in RVEDVi (r = 0.39, p = 0.004) and RVESVi (r = 0.45, p < 0.001) but a decrease in RVEF (r =  - 0.37, p = 0.006). Fragmented QRS had higher sensitivity and lower specificity than prolonged QRS duration (≥ 160 ms) to predict all of the parameters indicating pulmonary valve replacement (PVR). Patients with rTOF who had fQRS were significantly associated with RV dilatation. The extent of fQRS had only low to moderate correlation with right ventricular parameters (RVEDVi, RVESVi and RVEF). Fragmented QRS could be used for early detection of RV dilatation and the need for PVR in patients with rTOF., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Growth differentiation factor-15 is a novel biomarker of increasing importance in cardiovascular diseases. This study aimed to evaluate the relationship between ventricular measurements assessed by cardiac magnetic resonance imaging (MRI) and serum growth differentiation factor-15 levels in children with surgically corrected tetralogy of Fallot., Materials and Method: Serum growth differentiation factor-15 levels were measured in 40 patients (mean age: 15.2 ± 2.9 years; 52.5% male; 87.5% NYHA I). End-diastolic volume index, end-systolic volume index, and ejection fractions of both ventricles and pulmonary regurgitation fraction were measured on cardiac MRI. The correlation between growth differentiation factor-15 levels and cardiac MRI parameters of the patients was investigated. Also, growth differentiation factor-15 levels of the patients were compared with healthy controls since reference values have not been determined in children., Results: The mean growth differentiation factor-15 level was 254.9 ± 6.3 pg/ml in the patient group. There was no correlation between growth differentiation factor-15 levels and cardiac MRI parameters in patients. Also, there was no significant difference in growth differentiation factor-15 levels between the patients and control groups., Conclusion: The serum levels of growth differentiation factor-15 were uncorrelated with ventricular size, function, and pulmonary regurgitation fraction assessed by cardiac MRI in children with operated tetralogy of Fallot. Moreover, growth differentiation factor-15 levels were not different in these patients from healthy children.

Right ventricular (RV) volumetric cardiac magnetic resonance (CMR) criteria serve as indicators for pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF). Myocardial deformation and tricuspid valve displacement parameters may be more sensitive measures of RV dysfunction. This study's aim was to describe rTOF RV deformation and tricuspid displacement patterns using novel CMR semi-automated software and determine associations with standard CMR measures. Retrospective study of 78 pediatric rTOF patients was compared to 44 normal controls. Global RV longitudinal and circumferential strain and strain rate (SR) and tricuspid valve (TV) displacement were measured. Correlation analysis between strain, SR, TV displacement, and volumes was performed between and within subgroups. The sensitivity and specificity of strain parameters in predicting CMR criteria for PVR was determined. Deformation variables were reduced in rTOF compared to controls. Decreased RV strain and TV shortening were associated with increased RV volumes and decreased RVEF. Longitudinal and circumferential parameters were predictive of RVESVi (> 80 ml/m2) and RVEF (< 47%), with circumferential strain (> - 15.88%) and SR (> - 0.62) being most sensitive. Longitudinal strain was unchanged between rTOF subgroups, while circumferential strain trended abnormal in those meeting PVR criteria compared to controls. RV deformation and TV displacement are abnormal in rTOF, and RV circumferential strain variation may reflect an adaptive response to chronic volume or pressure load. This coupled with associations of ventricular deformation with traditional PVR indications suggest importance of this analysis in the evolution of rTOF RV assessment., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Improved survival has led to a growing population of adults with congenital heart disease (CHD), followed by numerous reports of late complications. Liver disease is a known complication in some patients, with most studies focusing on Fontan associated liver disease. Whether liver disease also exists in other patients with CHD is not fully investigated. Elevated central venous pressure is considered pivotal in the development of liver disease in Fontan associated liver disease, and other patients with alterations in central venous pressure may also be at risk for developing liver fibrosis. We wanted to see if liver fibrosis is present in patients with tetralogy of Fallot. Many patients with tetralogy of Fallot have severe pulmonary regurgitation, which can lead to elevated central venous pressure. Patients with tetralogy of Fallot may be at risk of developing liver fibrosis., Materials and Methods: Ten patients (24-56 years) with tetralogy of Fallot and pulmonary regurgitation were investigated for liver fibrosis. All patients were examined with magnetic resonance elastography of liver, hepatobiliary iminodiacetic acid scan, indocyanine green elimination by pulse spectrophotometry, elastography via FibroScan, abdominal ultrasound including liver elastography, and blood samples including liver markers., Results: Three out of ten patients had findings indicating possible liver fibrosis. Two of these had a liver biopsy performed, which revealed fibrosis stage 1 and 2, respectively. The same three patients had an estimated elevated central venous pressure in previous echocardiograms., Conclusions: Mild liver fibrosis was present in selected patients with tetralogy of Fallot and may be related to elevated central venous pressure.

Background: Relationships between right ventricular (RV) and left ventricular (LV) shape and function may be useful in determining optimal timing for pulmonary valve replacement in patients with repaired tetralogy of Fallot (rTOF). However, these are multivariate and difficult to quantify. We aimed to quantify variations in biventricular shape associated with pulmonary regurgitant volume (PRV) in rTOF using a biventricular atlas., Methods: In this cross-sectional retrospective study, a biventricular shape model was customized to cardiovascular magnetic resonance (CMR) images from 88 rTOF patients (median age 16, inter-quartile range 11.8-24.3 years). Morphometric scores quantifying biventricular shape at end-diastole and end-systole were computed using principal component analysis. Multivariate linear regression was used to quantify biventricular shape associations with PRV, corrected for age, sex, height, and weight. Regional associations were confirmed by univariate correlations with distances and angles computed from the models, as well as global systolic strains computed from changes in arc length from end-diastole to end-systole., Results: PRV was significantly associated with 5 biventricular morphometric scores, independent of covariates, and accounted for 12.3% of total shape variation (p < 0.05). Increasing PRV was associated with RV dilation and basal bulging, in conjunction with decreased LV septal-lateral dimension (LV flattening) and systolic septal motion towards the RV (all p < 0.05). Increased global RV radial, longitudinal, circumferential and LV radial systolic strains were significantly associated with increased PRV (all p < 0.05)., Conclusion: A biventricular atlas of rTOF patients quantified multivariate relationships between left-right ventricular morphometry and wall motion with pulmonary regurgitation. Regional RV dilation, LV reduction, LV septal-lateral flattening and increased RV strain were all associated with increased pulmonary regurgitant volume. Morphometric scores provide simple metrics linking mechanisms for structural and functional alteration with important clinical indices., (© 2021. The Author(s).)

Objectives: The clinical significance of persistent end-diastolic forward flow (EDFF) after pulmonary valve replacement (PVR) remains unclear in patients with repaired tetralogy of Fallot. This study aimed to identify the characteristics of these patients and the impact of persistent EDFF on outcomes., Methods: Of 46 consecutive patients who underwent PVR for moderate to severe pulmonary regurgitation between 2003 and 2019, 23 (50%) did not show EDFF before PVR [group (-)]. In the remaining 23 patients with EDFF before PVR, EDFF was diminished after PVR in 13 (28%) [group (+, -)] and persisted in 10 (22%) [group (+, +)]. The following variables were compared between these 3 groups: (i) preoperative right ventricular (RV) and right atrial volumes measured by magnetic resonance imaging, haemodynamic parameters measured by cardiac catheterization and the degree of RV myocardial fibrosis measured by RV biopsy obtained at PVR and (ii) the post-PVR course, development of atrial arrhythmia and need for intervention., Results: A high RV end-diastolic pressure, a greater right atrial volume index and a greater RV end-systolic volume index before PVR and a high degree of RV fibrosis were significantly associated with persistent EDFF 1 year after PVR. Persistent EDFF was a significant risk factor for postoperative atrial tachyarrhythmia, and catheter ablation and pacemaker implantation were required more frequently in these patients., Conclusions: Persistent EDFF after PVR could predict a worse prognosis, especially an increased risk of arrhythmia. Close follow-up is required in patients with persistent EDFF for early detection of arrhythmia and prompt reintervention if necessary., Clinical Trial Registration Number: Institutional review board of Osaka University Hospital, number 16105., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The present study was conducted to investigate the decrease in left ventricular stroke volume index (LVSVI) that is caused by pulmonary regurgitation-induced right heart dysfunction and its clinical implications before and after pulmonary valve replacement (PVR)., Methods: Between January 2010 and December 2019, 30 adults who underwent surgical PVR for chronic pulmonary regurgitation with right ventricular dilation late after tetralogy of Fallot (TOF) repair were included. All patients were evaluated using cardiac magnetic resonance before PVR. The median interval from TOF repair to PVR was 29 [25th, 75th percentile: 25, 37] years. The median pulmonary regurgitation fraction and right ventricular end-diastolic volume index were 56 [48, 66] % and 203 [187, 239] ml/m2. Twenty-three patients (76.7%) were re-evaluated 1 year after PVR., Results: Before PVR, the median LVSVI was 40 [35, 46] ml/beat/m2. A lower LVSVI was associated with a longer interval from TOF repair to PVR (r = -0.40, P = 0.029) and a lower right ventricular ejection fraction (r = 0.52, P = 0.004). A lower LVSVI was not associated with a higher right ventricular end-diastolic volume index. LVSVI remained unchanged after PVR. The patients were subdivided into Normal-stroke volume index (SVI) and Subnormal-SVI groups using the preoperative LVSVI cut-off value of 35 mL/beat/m2. Compared with the Normal-SVI group, the Subnormal-SVI group had a higher incidence of ablation therapy before PVR (4.7 vs 2.3 patient-years, P = 0.044). After PVR, LVSVI in the Subnormal-SVI group was still lower (40 [34, 42] vs 44 [42, 47] ml/beat/m2, P = 0.038) despite the right ventricular end-diastolic volume index normalization. There was no difference in the clinical event incidence between the 2 groups during the follow-up period. Brain natriuretic peptide level in the Subnormal-SVI group was higher within 3 years after PVR (P = 0.046)., Conclusions: Reduced left ventricular stroke volume did not fully recover after PVR. PVR for patients with repaired TOF should be performed before the left ventricular stroke volume begins to decrease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The aim was to determine the effect of pulmonary artery (PA) morphology on the branch pulmonary artery-regurgitation fraction (BPA-RF), the relationship of pulmonary insufficiency (PI) to BPA-RF and PA-distensibility, and factors (BPA-RF and PA-distensibility) associated with right ventricular function (RVF) in repaired tetralogy of Fallot (rTOF)., Methods: A total of 182 rTOF patients (median age 17.1 years) were analyzed for length, angle of PA, BPA-RF, PI, and PA-distensibility, using magnetic resonance imaging., Results: The left PA had a significant greater RF than the right PA (median (interquartile range)): LPA 43.1% (32.6-51.5) and RPA 35.2% (24.7-44.7), p < 0.001. The LPA was shorter with a narrower angle than the RPA ( p < 0.001). The anatomy of the branch-PA was not a factor for the greater LPA-RF (odds ratio, 95% confidence interval: CI, p -value): length 0.44 (0.95-2.00), p = 0.28; angle 0.63 (0.13-2.99), p = 0.56. There was a strong positive correlation between PI and BPA-RF-coefficients (95% CI), p -value: LPA 0.78% (0.70-0.86), p < 0.001; RPA 0.78% (0.71-0.84), p < 0.001 and between BPA-RF and distensibility-coefficients (95%CI), p -value: LPA 0.73% (0.37-1.09), p < 0.001; RPA 1.63% (1.22-2.03), p < 0.001, respectively. The adjusted BPA-RF did not predict RVF, RPA ( p = 0.434), LPA ( p = 0.268)., Conclusions: PA morphology is not a significant factor for the differential BPA-RF. The vascular wall in rTOF patients responds to chronic increased intravascular volume by increasing distensibility. BPA-RF is not a determinant of RVF.

Background: Although valve-sparing repair remains ideal for patients with tetralogy of Fallot, the durability of valve-sparing repair and which patients may have been better served with a transannular patch remain unclear., Methods: Retrospective review was performed of tetralogy of Fallot operations at our institution from January 2008 to December 2018. Standard demographic data were collected, including echocardiographic parameters, operative details, and clinical outcomes. Statistical analysis was performed comparing the transannular patch and valve-sparing repair groups., Results: Sixty-seven patients underwent tetralogy of Fallot repair with a median age of 4.5 (3.2-6.0) months and weight of 5.8 (5.2, 6.7) kg. Seventeen (25%) patients underwent transannular patch repair and 50 (75%) patients underwent valve-sparing repair. There was no difference in age or weight between patients who underwent a transannular patch repair and those who underwent a valve-sparing repair. At last follow-up (median 42 months), there was a trend of a higher peak pulmonary valve/right ventricular outflow tract gradient ( P = .06) in the valve-sparing group, but no difference in the pulmonary valve annulus z -scores. Additionally, the pulmonary valve z -scores in the valve-sparing group decreased from -2.3 ± 1.0 on predischarge echocardiogram of to -1.2 ± 1.6 on last follow-up, with the peak gradient on predischarge 23 (0-37) mm Hg remaining stable on last follow-up at 18 (0-29) mm Hg. There was one reoperation: pulmonary valve replacement six years after a transannular patch., Conclusions: Obtaining a postrepair pulmonary valve z -score of -2 yields satisfactory, stable valve-sparing repair with pulmonary valve growth, acceptable gradients, minimal regurgitation, and high freedom from reintervention during follow-up.

We present a surgical case of native pulmonary valve (PV) restoration in a 16-year-old boy with a previous history of transannular patch repair of tetralogy of Fallot in infancy. The PV was restored by approximation of split anterior commissure in the presence of developed and pliable leaflets well preserved after initial surgery. Postoperative echocardiogram showed a competent valve with peak velocity of 2.8 m/s. At six-week follow-up, the patient remained well, and echocardiogram demonstrated a competent PV with decreased velocity of 2.1 m/s across it. We encourage a mindful preservation of PV leaflets whenever it is possible at time of initial repair to implement this relatively easy operation to restore PV function later in life.

Background: The global effect of chronic pulmonary regurgitation (PR) on right ventricular (RV) dilation and dysfunction in repaired Tetralogy of Fallot (rTOF) patients is well studied by cardiovascular magnetic resonance (CMR). However, the links between PR in the RV outflow tract (RVOT), RV dysfunction and exercise intolerance are not clarified by conventional measurements. Not all patients with RV dilation share the same intracardiac flow characteristics, now measurable by time resolved three-dimensional phase contrast imaging (4D flow). In our study, we quantified regional vorticity and energy loss in rTOF patients and correlated these parameters with RV dysfunction and exercise capacity., Methods: rTOF patients with 4D flow datasets were retrospectively analyzed, including those with transannular/infundibular repair and conduit repair. Normal controls and RV dilation patients with atrial-level shunts (Qp:Qs > 1.2:1) were included for comparison. 4D flow was post-processed using IT Flow (Cardioflow, Japan). Systolic/diastolic vorticity (ω, 1/s) and viscous energy loss (VEL, mW) in the RVOT and RV inflow were measured. To characterize the relative influence of diastolic vorticity in the two regions, an RV Diastolic Vorticity Quotient (ω RVOT-Diastole /ω RV Inflow-Diastole, RV-DVQ) was calculated. Additionally, RVOT Vorticity Quotient (ω RVOT-Diastole /ω RVOT-Systole , RVOT-VQ) and RVOT Energy Quotient (VEL RVOT-Diastole /VEL RVOT-Systole , RVOT-EQ) was calculated. In rTOF, measurements were correlated against conventional CMR and exercise stress test results., Results: 58 rTOF patients, 28 RV dilation patients and 12 controls were included. RV-DVQ, RVOT-VQ, and RVOT-EQ were highest in rTOF patients with severe PR compared to rTOF patients with non-severe PR, RV dilation and controls (p < 0.001). RV-DVQ positively correlated with RV end-diastolic volume (0.683, p < 0.001), PR fraction (0.774, p < 0.001) and negatively with RV ejection fraction (- 0.521, p = 0.003). Both RVOT-VQ, RVOT-EQ negatively correlated with VO 2-max (- 0.587, p = 0.008 and - 0.617, p = 0.005) and % predicted VO 2-max (- 0.678, p = 0.016 and - 0.690, p = 0.001)., Conclusions: In rTOF patients, vorticity and energy loss dominate the RVOT compared to tricuspid inflow, correlating with RV dysfunction and exercise intolerance. These 4D flow-based measurements may be sensitive biomarkers to guide surgical management of rTOF patients., (© 2021. The Author(s).)

Background: Data about the right ventricular (RV) mechanics adaptation to volume overload in patients with repaired tetralogy of Fallot (rToF) are limited. Accordingly, we sought to assess the mechanics of the functional remodeling occurring in the RV of rToF with severe pulmonary regurgitation., Methods: We used three-dimensional transthoracic echocardiography (3DTE) to obtain RV data sets from 33 rToF patients and 30 age- and sex- matched controls. A 3D mesh model of the RV was generated, and RV global and regional longitudinal (LS) and circumferential (CS) strain components, and the relative contribution of longitudinal (LEF), radial (REF) and anteroposterior (AEF) wall motion to global RV ejection fraction (RVEF) were computed using the ReVISION method., Results: Corresponding to decreased global RVEF (45 ± 6% vs 55 ± 5%, p < 0.0001), rToF patients demonstrated lower absolute values of LEF (17 ± 4 vs 28 ± 4), REF (20 ± 5 vs 25 ± 4) and AEF (17 ± 5 vs 21 ± 4) than controls (p < 0.01). However, only the relative contribution of LEF to global RVEF (0.39 ± 0.09 vs 0.52 ± 0.05, p < 0.0001) was significantly decreased in rToF, whereas the contribution of REF (0.45 ± 0.08 vs 0.46 ± 0.04, p > 0.05) and AEF (0.38 ± 0.09 vs 0.39 ± 0.04, p > 0.05) to global RVEF was similar to controls. Accordingly, rToF patients showed lower 3D RV global LS (-16.94 ± 2.9 vs -23.22 ± 2.9, p < 0.0001) and CS (-19.79 ± 3.3 vs -22.81 ± 3.5, p < 0.01) than controls. However, looking at the regional RV deformation, the 3D CS was lower in rToF than in controls only in the basal RV free-wall segment (p < 0.01). 3D RV LS was reduced in all RV free-wall segments in rToF (p < 0.0001), but similar to controls in the septum (p > 0.05)., Conclusions: 3DTE allows a quantitative evaluation of the mechanics of global RVEF. In rToF with chronic volume overload, the relative contribution of the longitudinal shortening to global RVEF is affected more than either the radial or the anteroposterior components., (© 2021. The Author(s).)

We used 4D-flow MRI to investigate circulation, an area integral of vorticity, in the main pulmonary artery (MPA) as a new hemodynamic parameter for assessing patients with a repaired Tetralogy of Fallot (TOF). We evaluated the relationship between circulation, right ventricular (RV) function and the pulmonary regurgitant fraction (PRF). Twenty patients with a repaired TOF underwent cardiac MRI. Flow-sensitive 3D-gradient sequences were used to obtain 4D-flow images. Vortex formation in the MPA was visualized, with short-axis and longitudinal vorticities calculated by software specialized for 4D flow. The RV indexed end-diastolic/end-systolic volumes (RVEDVi/RVESVi) and RV ejection fraction (RVEF) were measured by cine MRI. The PR fraction (PRF) and MPA area were measured by 2D phase-contrast MRI. Spearman ρ values were determined to assess the relationships between circulation, RV function, and PRF. Vortex formation in the MPA occurred in 15 of 20 patients (75%). The longitudinal circulation (11.7 ± 5.1 m 2 /s) was correlated with the RVEF (ρ = - 0.85, p = 0.0002), RVEDVi (ρ = 0.62, p = 0.03), and RVESVi (ρ = 0.76, p = 0.003) after adjusting for the MPA size. The short-axis circulation (9.4 ± 3.4 m 2 /s) in the proximal MPA was positively correlated with the MPA area (ρ = 0.61, p = 0.004). The relationships between the PRF and circulation or RV function were not significant. Increased longitudinal circulation in the MPA, as demonstrated by circulation analysis using 4D flow MRI, was related to RV dysfunction in patients with a repaired TOF.

Background: In repaired tetralogy of Fallot (rTOF), abnormal left ventricular (LV) rotational mechanics are associated with adverse clinical outcomes. We performed a comprehensive analysis of LV rotational mechanics in rTOF patients using cardiac magnetic resonance (CMR) prior to and following surgical pulmonary valve replacement (PVR)., Methods: In this single center retrospective study, we identified rTOF patients who (1) had both a CMR ≤ 1 year before PVR and ≤ 5 years after PVR, (2) had no other intervening procedure between CMRs, (3) had a body surface area > 1.0 m 2 at CMR, and (4) had images suitable for feature tracking analysis. These subjects were matched to healthy age- and sex-matched control subjects. CMR feature tracking analysis was performed on a ventricular short-axis stack of balanced steady-state free precession images. Measurements included LV basal and apical rotation, twist, torsion, peak systolic rates of rotation and torsion, and timing of events. Associations with LV torsion were assessed., Results: A total of 60 rTOF patients (23.6 ± 7.9 years, 52% male) and 30 healthy control subjects (20.8 ± 3.1 years, 50% male) were included. Compared with healthy controls, rTOF patients had lower apical and basal rotation, twist, torsion, and systolic rotation rates, and these parameters peaked earlier in systole. The only parameters that were correlated with LV torsion were right ventricular (RV) end-systolic volume (r = - 0.28, p = 0.029) and RV ejection fraction (r = 0.26, p = 0.044). At a median of 1.0 year (IQR 0.5-1.7) following PVR, there was no significant change in LV rotational parameters versus pre-PVR despite reductions in RV volumes, RV mass, pulmonary regurgitation, and RV outflow tract obstruction., Conclusion: In this comprehensive study of CMR-derived LV rotational mechanics in rTOF patients, rotation, twist, and torsion were diminished compared to controls and did not improve at a median of 1 year after PVR despite favorable RV remodeling.

Background: Pregnant women with repaired tetralogy of Fallot (rTOF) are at increased risk of adverse outcomes. Although pre-pregnancy pulmonary valve replacement (PVR) may be considered in some women to attenuate risk, published data to support this practice are lacking. Our objective was to explore the impact of pre-pregnancy PVR on pregnancy outcomes in rTOF., Methods: Women with rTOF and cardiovascular magnetic resonance imaging (CMR) before and after pregnancy were included if CMR studies were completed within 3 years of pregnancy. Subjects were compared according to presence (+) or absence (-) of PVR at pre-pregnancy CMR. Pregnancy outcomes (cardiovascular, obstetric, and fetal/neonatal) were documented., Results: Of the 29 study women identified, 7 were PVR+ and 22 were PVR-. Post-pregnancy, the PVR- group demonstrated interval increase in indexed right ventricular end-diastolic volumes (RVEDVi) (157 ± 28 versus 166 ± 33 ml/m 2 , p = 0.003) and end-systolic volumes (RVESVi) (82 ± 17 versus 89 ± 20 ml/m 2 , p = 0.003) as compared with pre-pregnancy, but no significant change in RV ejection fraction, RV mass, or left ventricular measurements. In the PVR+ group, there were no interval changes in RV measurements pre-versus post pregnancy. Interval rate of change in RVESVi of PVR- exceeded PVR+ women (+3.7 ± 5.0 versus -2.2 ± 5.0 ml/m 2 /year, p = 0.03). Pregnancy outcomes did not differ in PVR+ versus PVR- women., Conclusions: Pregnancy outcomes did not differ according to PVR status in our cohort. While RV volumes remained unchanged in PVR+ women, interval RV dilation was observed in PVR- women. Additional study of a larger population with longer follow-up may further inform clinical practice regarding pre-pregnancy PVR., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: The prevention of pulmonary insufficiency (PI) is a crucial part of the tetralogy of Fallot repair. Many techniques have been introduced to construct valves from different materials for the right ventricular outflow tract, including the most commonly constructed monocusp valves. We are introducing a new bicuspid valve made intraoperatively using the autologous right atrial appendage (RAA) to prevent PI in these patients., Methods: The RAA valve was constructed and used in 21 patients with tetralogy of Fallot. The effective preservation of the native valve was impossible in all patients because of either a severe valve deformity or a small annulus. The RAA valve was created after ventricular septal defect closure and right ventricular outflow tract myectomy and was covered with a bovine transannular pericardial patch. The perioperative data were evaluated, and the echocardiography results were assessed immediately after operations and in follow-up with a median of 10.5 months. The data were retrospectively compared with 10 other patients with similar demographic data but with only transannular patches., Results: The mean age of the patients was 13.3 months. No mortality or related morbidity occurred after repair using the RAA valve. The PI severity early after the operation was trivial or no PI in 18 patients, and mild PI was observed in 3 patients, which progressed to moderate PI in one of them in the mean 12-month follow-up period. Fifteen patients had mild or no pulmonary stenosis, while moderate pulmonary stenosis was observed in 6 others. Compared with the other 10 patients with only transannular patches, the RAA valve patients had prolonged operative and clamping times, but no difference in postoperative course and shorter hospital stays. The degree of PI was, of course, significantly less in the RAA valve patients, but pulmonary stenosis was the same., Conclusions: The RAA valve construction is a safe and effective technique to prevent PI after the tetralogy of Fallot repair, at least in terms of short- and mid-term results. A longer follow-up period is needed to confirm if this new valve can eliminate or significantly delay the need for pulmonary valve replacement in these patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)