RT In Patients Research Articles

Prediction of Ventricular Mechanics After Pulmonary Valve Replacement in Tetralogy of Fallot by Biomechanical Modeling: A Step Towards Precision Healthcare.

Clinical indicators of heart function are often limited in their ability to accurately evaluate the current mechanical state of the myocardium. Biomechanical modeling has been shown to be a promising tool in addition to clinical indicators. By providing a patient-specific measure of myocardial active stress (contractility), biomechanical modeling can enhance the precision of the description of patient's pathophysiology at any given point in time. In this work we aim to explore the ability of biomechanical modeling to predict the response of ventricular mechanics to the progressively decreasing afterload in repaired tetralogy of Fallot (rTOF) patients undergoing pulmonary valve replacement (PVR) for significant residual right ventricular outflow tract obstruction (RVOTO). We used 19 patient-specific models of patients with rTOF prior to pulmonary valve replacement (PVR), denoted as PSMpre, and patient-specific models of the same patients created post-PVR (PSMpost)-both created in our previous published work. Using the PSMpre and assuming cessation of the pulmonary regurgitation and a progressive decrease of RVOT resistance, we built relationships between the contractility and RVOT resistance post-PVR. The predictive value of such in silico obtained relationships were tested against the PSMpost, i.e. the models created from the actual post-PVR datasets. Our results show a linear 1-dimensional relationship between the in silico predicted contractility post-PVR and the RVOT resistance. The predicted contractility was close to the contractility in the PSMpost model with a mean (± SD) difference of 6.5 (± 3.0)%. The relationships between the contractility predicted by in silico PVR vs. RVOT resistance have a potential to inform clinicians about hypothetical mechanical response of the ventricle based on the degree of pre-operative RVOTO.

Echocardiographic assessment of right ventricular volume in repaired tetralogy of Fallot: a novel approach to an older technique.

In repaired tetralogy of Fallot (rTOF), right ventricular (RV) enlargement leads to poor outcomes. However, evaluating the RV has limitations; cardiac magnetic resonance (CMR) and 3D echocardiography have barriers including cost and accessibility. Traditional echocardiography is limited given the complex geometry and anterior location of the RV. We propose a novel echocardiographic evaluation of RV volume using 2 separate views. This is a retrospective study of rTOF patients with echocardiogram, CMR, and exercise tests. By echocardiogram, we collected RV length in parasternal long axis (PLAX), area in 4-chamber (4C) view, and measurements per standard guidelines. RV end-diastolic and end-systolic volume (RVEDV and RVESV) were calculated as 5/9 (4C area * PLAX length). Forty-five patients with 66 sets of CMR, echocardiogram, and exercise tests were included (mean age 13.3 ± 3.2years). The echocardiographic RVEDV and RVESV showed strong correlation with CMR parameters (r = 0.81 and 0.72; p≤ 0.0001), and moderate correlation with peak oxygen pulse (0.63 and 0.49; p≤0.0001). Guideline measurements had no significant correlation. Echocardiographic RVEDV and RVESV were higher in those requiring subsequent pulmonary valve replacement. Indexed echocardiographic RVEDV of 93ml/m2 had 92% sensitivity and 50% specificity (area under curve 0.75 (p = 0.001)) in predicting CMR RV/LV EDV ratio > 2, which is an early indicator for pulmonary valve replacement. This novel technique correlates strongly with CMR, better than traditional parameters. While echocardiogram will not replace CMR, this method would be useful in predicting the RV volume, progression of dilation, and timing of CMR.

Abstract 9950: Right Ventricular Hemodynamic Forces: Linking Pulmonary Insufficiency to Wall Motion in Repaired Tetralogy of Fallot Patients

Introduction: Patients with repaired Tetralogy of Fallot (rTOF) will develop right ventricle (RV) dysfunction from chronic pulmonary insufficiency (PI). Cardiac magnetic resonance (CMR) biomarkers informs timing of pulmonary valve replacement (PVR), but do not clarify the direct impact of PI on myocardial biomechanics. 4D flow studies have shown that RV hemodynamic forces (HDF) are altered in rTOF. In this study, we derived HDF in rTOF, exclusively using RV wall motion from conventional cine. Methods: This was a retrospective study using CMR of rTOF patients who had no PVR at time of imaging. Feature-tracking (QStrain, Medis) was used to capture RV wall motion from cine imaging. A novel diffeomorphic mapping technique was used to calculate 3D RV kinematic models (Figure 1A) and global HDF vector generated throughout the cardiac cycle. The RVOT-to-Diaphragm HDF vector was isolated for analysis. Global longitudinal strain, QRS duration and RV size/function were collected. Repeat analysis was performed on subgroup of rTOF who had subsequent PVR and follow-up CMR. Results: 44 rTOF studies (21±11 years) were included with regurgitant fraction (PR%) 33±15%, RV ejection fraction 50±5%, and RV end-diastolic volume 144±37 mL/m 2 . PR% correlated with RVOT-to-Diaphragm HDF vector in diastole (Figure 1B). Higher diastolic:systolic HDF ratio correlated with lower RV ejection fraction (R = -0.31, p = 0.04), lower global longitudinal strain (R = -0.38, p = 0.009), and longer QRS duration (R = 0.44, p = 0.004). 9 rTOF patients had follow-up CMR after PVR and demonstrated decrease in RVOT-to-Diaphragm HDF (Figure 1C). Conclusions: PI in rTOF patients is correlated to diastolic HDF exerted along the direction of the RVOT. Diastolic HDF correlates with RV dysfunction in rTOF patients, and as a global parameter can be captured by RV wall motion without the need to analyze 4D flow details. HDF is a potential biomarker that may provide early detection of RV dysfunction and inform PVR timing.

Abstract 10282: Biventricular Shape Markers in Repaired Tetralogy of Fallot Associate with Pulmonary Valve Replacement Better Than Standard Clinical Indices

Introduction: Current indications for pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF) rely on global ventricular measurements but are inconsistently applied, lead to mixed outcomes, and are widely debated. Hypothesis: We aimed to test the hypothesis that specific regional markers of biventricular shape can discriminate differences in ventricular remodeling between rTOF patients that were and were not designated for follow-up PVR better than standard clinical indices. Methods: In this cross-sectional retrospective study, biventricular shape models were fit 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 marker and clinical index associations with subsequent intervention status (PVR, n=48 vs. No-PVR, n=36) while accounting for confounders. Clustering analysis was then used to test the ability of statistically significant shape markers and clinical indices to discriminate PVR status as evaluated by Matthews correlation coefficient (MCC). Geometric strain analysis was also conducted to assess shape marker associations with systolic function. Results: PVR status correlated with shape markers associated with RV apical dilation and LV dilation (p<0.001), RV basal bulging and LV conicity (p<0.02), and pulmonary valve dilation (p<0.002). PVR status also correlated with RV EF (p<0.03) and non-significantly correlated with LV ESVi (p<0.06). Clustering analysis revealed that shape markers discriminated PVR status better than clinical indices (MCC=0.49 and MCC=0.28, respectively). These shape markers were also significantly associated with RV and LV radial strain. Conclusions: Biventricular shape markers discriminated PVR status better than standard and current use clinical indices for PVR. These specific, regional features of cardiac morphology can provide mechanistic insight into adaptive vs. maladaptive types of ventricular remodeling that provide the foundation for clinical decision-making but may be overlooked when relying solely on global ventricular measurements.

The Interplay between Myocardial Fibrosis, Strain Imaging and Collagen Biomarkers in Adults with Repaired Tetralogy of Fallot.

Background: We sought to assess the interplay between right ventricle (RV) fibrosis, biventricular dysfunction based on global longitudinal strain (GLS) analysis, and biomarkers such as Galectin-3 (Gal-3), procollagen type III (PCIII), and NTproBNP. Methods: We studied 35 adult patients with rToF. All patients underwent a cardiac magnetic resonance (CMR) scan including feature tracking for deformation imaging. Blood biomarkers were measured. Results: LGE RV was detected in all patients, mainly at surgical sites. Patients with the highest RV LGE scoring had greater RV dilatation and dysfunction whereas left ventricular (LV) function was preserved. LV GLS correlated with RV total fibrosis score (p = 0.007). A LV GLS value of −15.9% predicted LGE RV score > 8 (AUC 0.754 (p = 0.02)). Neither RV GLS nor biomarker levels were correlated with the extent of RV fibrosis. A cut-off value for NTproBNP of 145.25 pg/mL predicted LGE RV score > 8 points (AUC 0.729, (p = 0.03)). A cut-off value for Gal-3 of 7.42 ng/mL predicted PR Fraction > 20% [AUC 0.704, (p = 0.05)]. Conclusions: A significant extent of RV fibrosis was mainly detected at surgical sites of RV, affecting RV performance. CMR-FT reveals subtle LV dysfunction in rToF patients, due to decreased performance of the fibrotic RV. Impaired LV function and elevated NTproBNP in rToF reflect a dysfunctional fibrotic RV.

Substrate characterization of the right ventricle in repaired tetralogy of Fallot using late enhancement cardiac magnetic resonance.

Three-dimensional (3D) substrate characterization by high-resolution late gadolinium enhancement cardiac magnetic resonance (LE-CMR) is useful for guiding ventricular tachycardia ablation of the left ventricle in ischemic heart disease. The purpose of this study was to validate the substrate characterization and 3D reconstruction of LE-CMR images of the right ventricle (RV) in patients with repaired tetralogy of Fallot (rTOF) and to identify the algorithm that best fits with electroanatomic mapping (EAM). RV LE-CMR images were compared with RV EAM in 10 patients with rTOF. RV LE-CMR images were postprocessed and analyzed to identify fibrotic tissue on 3D color maps. The 3D RV substrate reconstructions were created using an adjustable percentage of the maximum voxel signal intensity (MSI) of the scar region to define the threshold between core, transitional zone (TZ), and healthy tissue. Extensions of the core and TZ areas were compared with the scar (<0.5 mV) and low-voltage (0.5-1.5 mV) areas obtained by RV EAM. Agreement on anatomic isthmi identification was quantified. The best match between core and scar was obtained at 65% MSI cutoff (mean areas 17.4 ± 9.9 cm2 vs 16.9 ± 10.0 cm2, respectively; r = 0.954; P <.001). Agreement on anatomic isthmi identification was best at 60% MSI cutoff, which identified 95% of isthmi and achieved a total fit in 90% of patients. This study demonstrates that characterization of the RV substrate by postprocessing LE-CMR images in rTOF patients is feasible and validates the technique against RV EAM, which could help in planning target ablation.

Prioritized Optimization of Total Toxicity Burden for Head and Neck Cancer Patients

Head and neck cancer (HNC) RT typically results in high doses to organs-at-risk (OARs), contributing to decreased quality-of-life (QOL) seen in patient reported outcomes (PRO). Current RT planning methods are driven by singular dosimetric trade-offs that may be inconsistent with improving a patient's overall predicted total toxicity burden (TTB). We developed an aggregate toxicity assessment over time including PROs that represents a paradigm shift over informal summary of individual toxicity. Here we introduce a treatment planning approach to directly optimize and reduce the predicted TTB-PRO of a patient's RT plan.We implemented a prioritized approach to TTB optimization using an in-house optimization plugin linked to a commercial treatment planning system. Prioritized TTB (P-TTB) plans were optimized using a two-stage hierarchal method for inverse IMRT planning. In the first stage, TTB, defined as the weighted-sum of NTCPs, is minimized subject to high-priority OAR dose limits, target prescription, and target coverage requirements. Weights for the toxicities directly represent the relative undesirability of toxicities. In the second stage, a weighted-sum dose-metric objective is minimized, similar to current clinical practice. This stage is subject to the same constraints as the first stage, but an additional constraint for TTB is incorporated based on the optimal solution of the first stage. Using this approach, we retrospectively generated plans for 5 HNC patients and compared the resulting plans to IMRT plans generated without the added TTB constraint. Both plans consisted of 9 equally spaced beams with the same OAR dose limits and dose-metric objective. Target dose requirements were based on simultaneous integrated boost prescriptions of 70 and 56 Gy delivered in 35 fractions. TTB was calculated using previously published NTCP models for dysphagia and xerostomia. Dysphagia was based on increase in aspiration or HNQOL score > 81 as a function of pharyngeal constrictor (PC) mean dose. Xerostomia was based on parotid flow ratio < 25% of pretreatment (grade 4) or xerostomia questionnaire > 73 as a function of parotid gland (PG) mean dose.Our optimization engine successfully generated P-TTB plans for all five patients while maintaining similar target coverage to the standard dosimetrically optimized plans. P-TTB plans resulted in average absolute NTCP reductions of 15.5% (range: 0.2 - 53.4) for dysphagia and 20.5% (1.9 - 68.5) for xerostomia. These changes correlate to average mean dose decreases of 6.9 Gy (0.2 - 22.7) for PC and 10.2 Gy (1.2 - 33.5) for PGs. P-TTB planning resulted in greater fluence modulation and higher doses to OARs not included in the calculation of TTB.The P-TTB planning method offers an intuitive optimization approach to balancing trade-offs between various treatment outcomes and has the ability to directly reduce and redistribute predicted toxicity which may aid in improving QOL for HNC patients receiving RT.

Abnormal left-sided blood volume, wall shear stress &amp; energy loss in patients with repaired Tetralogy of Fallot identified by 4D flow MRI

Abstract Introduction Tetralogy of Fallot (TOF) occurs in 4 of every 10,000 live births and is the most common form of cyanotic congenital heart disease. Patients with repaired TOF (rTOF) require long-term and frequent monitoring for many complications that may arise. The hemodynamic alterations that contribute to the quality of life and outcomes for these patients are understudied and poorly understood. Purpose The objective of this study was to use 4D Flow MRI to assess flow hemodynamics in patients with rTOF to better identify and predict altered hemodynamic patterns to assist with future interventions. We hypothesized, patients with rTOF will have abnormal left-sided flow hemodynamics compared to healthy controls resulting in poorer hemodynamic patterns even after post-repair. Methods A total of 20 rToF patients (age = 34.5±11.2, female = 5) and 20 healthy controls (age = 37.0±12.1, female = 6) were enrolled in this study and underwent standard cardiac MRI followed by 4D Flow MRI acquisition. Figure 1 demonstrates the workflow of the analysis that was performed using cvi42 v5.11 (Circle Cardiovascular Imaging Inc., Calgary, Canada). The Aorta and LV were segmented, flow visualization and quantitative flow analysis were performed by placing analysis planes perpendicular to the flow of interest as shown in Figure 1. Total volume (TV), Wall Shear Stress Axial (WSSax), circumferential (WSScirc) and energy loss (EL) were calculated. Statistics were analyzed using IBM SPSS Statistics, version 27. An independent-samples t-test was used to compare parameters and identify significant differences between controls and patients. A P-value &amp;lt;0.05 was considered significant. Results In comparison to controls, TV of the STJ (66.89±17.33 vs. 82.28±18.77, p=0.011), Aao (56.05±10.71 vs. 73.04±19.66, p=0.002), and 1st Aortic Arch (AAr) (56.88±12.97 vs. 69.52±18.65, p=0.017) were lower in rTOF patients. In addition, patients with rTOF had higher average WSSax in the LVOT (0.13±0.05 vs. 0.10±0.03, p=0.049), STJ (0.10±0.02 vs. 0.07±0.02, p=0.001), and Aao (0.10±0.03 vs. 0.08±0.02, p&amp;lt;0.000) compared to controls. Moreover, average WSScirc in the LVOT (0.07±0.02 vs. 0.05±0.01, p=0.010), STJ (0.07±0.02 vs. 0.05±0.01, p=0.006), Aao (0.07±0.02 vs. 0.05±0.01, p=0.004), and 1st AAr (0.06±0.02 vs. 0.05±0.01, p=0.017) were higher in patients compared to controls. Lastly, EL in the Aao was lower in patients compared to controls (1.87±0.83 vs. 2.47±1.03, p=0.049). Significant results are demonstrated in Table 1, red illustrating lower values in patients compared to controls and green illustrating higher values. Conclusion This study unveiled abnormal left-sided blood flow in rToF patients with reduced TV and increased WSSax, average WSScirc and EL. These new hemodynamic insights obtained from 4D flow MRI may help to inform future individualized decision-making for patients with rTOF. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): University of Calgary

Flow vorticity relationships with right ventricular geometry in adult tetralogy of Fallot

Abstract Background Repaired tetralogy of Fallot adults (rToF) undergo right ventricular (RV) remodeling, in part due to volume overload of residual pulmonary regurgitation volume (PRV). Time-resolved phase-contrast cardiac magnetic resonance imaging (4D Flow MRI) enables the qualitative and quantitative measurement of altered blood flow patterns, including vorticity. Cardiac atlases allow for complex three-dimensional heart shapes to be expressed as morphometric scores. Those scores show the extent of geometrical shift and can help explore uncharted relationships between vorticity and architecture. Purpose We aimed to quantify vorticity, incorporating deep learning to enhance 4D Flow data, and correlate this with global cardiac parameters and morphometric scores. Methods 12 Adult rToF patients and 10 age-matched controls underwent 4D flow MRI and cine imaging. RV interventricular vorticity was calculated for outflow and inflow tracts. EDV, ESV and SV were computed from cines which were also used to build three-dimensional shape models. The biventricular models were projected onto an atlas generated from 95 rToF patients, and twenty-one principal component analysis shape modes were correlated with cardiac metrics and vorticity to identify global shape variations. Association between biventricular shape and vorticity was further analysed using multivariate multiple regression models. Results Strong correlation was found between PRV and the right ventricular outflow tract (RVOT) vorticity. PRV and RVOT vorticity both correlated with the same 3 shape modes (r=−0.55, −0.50 and 0.6 (p&amp;lt;0.05) respectively for PR and r=0.63, −0.82 and 0.60 (p&amp;lt;0.05) respectively for vorticity) i.e., the RV dilates with an increase in basal bulging, apical bulging and tricuspid annulus tilting with more severe regurgitation, as well as a smaller LV, and a paradoxical movement of the septum (Figure 1). However, RV vorticity correlated with 2 modes that did not correlate with PRV, (r=−0.62, −0.69, p&amp;lt;0.05). With higher vorticity the RV was longer, increased tilting of the tricuspid annulus and an increased basal bulge around the tricuspid area. The multivariate analysis model demonstrated that higher vorticity was associated with displacement of the pulmonary valve and change in the RVOT length and direction. A septal displacement towards the left ventricle was observed and increased apical flatness of the RV (Figure 1). Qualitatively, vorticity in rToF group was more heterogeneous than controls (Figure 2). Conclusions Vorticity is a novel marker based on the influence of blood motion providing new insight into early diagnosis and prognosis of cardiac disease. This is the first study to examine the relationships between vorticity and regional RV shape changes in rToF. Mode associations with vorticity were different to associations with PRV. More longitudinal studies are required for standardization of change in vorticity with the disease process. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The New Zealand heart foundation Mode variations and morphometric modelVorticity visualization and analysis

Pulmonary valve replacement in women with repaired tetralogy of Fallot. Contrasting indications compared with men

Abstract Background Recent data suggest that in pulmonary regurgitation (PR) after repair of Tetralogy of Fallot (rToF) sex may influence right ventricular (RV) size, mass and function. We hypothesized that women with rToF and PR constitute a patient population with different preoperative clinical characteristics and different postoperative outcomes compared with men. Methods We collected retrospectively demographic data, clinical variables, imaging and functional variables in a cohort of 166 rToF patients (50% males; median age 35; IQR 26–41 years) with at least moderate PR. A transannular patch was used in 73 and 79% of men and women, respectively. The most recent data preceding death and pulmonary valve replacement (PVR) were requested. Variables were compared between men and women. Results Over follow-up, none of the patients died but 35 (42.7%) men and 23 (27.4%) women underwent PVR (p=0.05) at a median age of 32.5 (IQR 23.7–42.7 years). Women are more likely to undergo surgery after developing symptoms, while the criterion for surgery in men was ventricular size. At surgery, women were nearly twice as likely to have class III or IV symptoms preoperatively as men. Although PR fraction was similar between the two groups, indexed ventricular volumes were substantially higher and RV function was lower in males, compared to females. 20% of women had a RVEDVi ≥160ml and a RVESVi ≥80ml, compared with 35 and 32% of men, respectively (p=0.06), and only 6% of woman had an RVEDVi &amp;gt;180ml, compared with 18% of men (p=0.01). Fibrosis detected on late gadolinium was observed in 100% of men but only in 20% of women (p=0.009). Conclusions Under comparable loading conditions, a striking difference was noted in the condition leading to the surgical indication. These results suggest that the generalization of the RV dimension surgical criteria results in criteria almost never reached by women. Recommendations need more focus on sex differences. Funding Acknowledgement Type of funding sources: None.

Risk Factors of Right Ventricular Dysfunction and Adverse Cardiac Events in Patients with Repaired Tetralogy of Fallot.

Aim: This study evaluates the risk factors associated with right ventricular (RV) dilation and dysfunction leading to pulmonary valve replacement (PVR) or adverse cardiac events in repaired Tetralogy of Fallot (rToF) patients. Methods: Data from all rToF patients who underwent magnetic resonance imaging (MRI) evaluation at our hospital between February 2007 and September 2020 were collected. Results: Three hundred and forty-two patients (60% males, 42% older than 18 years), with a median age of 16 years (IQR 13–24) at the time of MRI, were included. All patients underwent complete repair at a median age of 8 months (IQR 5–16), while palliation was performed in 56 patients (16%). One hundred and forty-four patients (42%) subsequently received pulmonary valve replacement (PVR). At the multivariate analysis, male gender was an independent predictor for significant RV dilation, RV and left ventricular (LV) dysfunction. Transventricular ventricular septal defect (VSD) closure and previous palliation significantly affected LV function and RV size, respectively. Male gender and the transventricular VSD closure were independent predictors for PVR. Conclusions: Male gender and surgical history (palliation, VSD closure approach) significantly affected the long-term outcomes in rToF patients and should be taken into consideration in the follow-up management and in PVR timing in this patient population.

Blood biomarkers in patients with repaired Tetralogy of Fallot (rTOF); A systematic review and meta-analysis

Background: The clinical use and prognostic value of plasma brain natriuretic peptide (NT-proBNP) and soluble suppression of tumourigenicity-2 (sST2) levels are not known in patients with repaired Tetralogy of Fallot (rTOF).Objectives: We evaluated blood biomarkers in rTOF patients by combining the available evidence, focussing on prognosis, adverse echocardiographic findings and exercise intolerance.Methods: This systematic review and meta-analysis were carried out in accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. For the primary prognostic outcomes, a meta-analysis was performed. For hemodynamic outcomes, a pooled meta-analysis of correlation coefficients (r) was performed. The study protocol was registered with PROSPERO(CRD42020211897).Results: We analysed 1479 patients with repaired TOF in 23 studies. Mean age was 22.7 ​± ​8.3 years. The mean value of NT-proBNP was 174.4.1 ​± ​56.4 ​pg/ml while ST2 drawn from two investigations was 26.95 ​ng/ml. There was no difference in mean NT-proBNP between older and younger subjects (160.4 ​± ​37.7 vs190.6 ​± ​72.9, pg/ml, respectively; p ​> ​.05). NT-proBNP levels were higher in TAP studies than others with other RVOT intervention (191.6 ​± ​57 vs 151 ​± ​46, pg/ml, p ​< ​.05). Elevated NT-proBNP levels were associated with an increased risk of adverse cardiovascular outcomes including death, arrhythmias and acute heart failure with a hazard ratio (HR) of 1.18 (95% CI 1.07–1.31, p.001). We noted a moderate correlation between NT-proBNP levels and exercise intolerance, RV structural and volumetric changes (r ​= ​−.52, r ​= ​0.41, P ​< ​.001).Conclusions: NT-proBNP levels are elevated in patients with surgically repaired TOF and are associated with an increased risk of cardiovascular adverse outcomes and exercise intolerance.

Long-term assessment of clinical outcomes and disease progression in patients with corrected Tetralogy of Fallot.

Understanding changes of right ventricular (RV) geometry and function in repaired Tetralogy of Fallot (rToF) patients can improve decision-making for pulmonary valve replacement. Therefore, we aimed to assess the magnitude and clinical correlations of RV changes in rToF patients. Clinical and MRI data of rToF patients who underwent repeated cardiac magnetic resonance imaging (MRI) at two centers between December 2003 and September 2020 were analyzed together with anatomical factors, including RV outflow tract obstruction, pulmonary artery branch stenosis, and tricuspidregurgitation. Adverse cardiac events and/or NYHA class worsening were documented and correlated with MRI changes. QRS length was reported at each MRI. Two-hundred-and-nineteen rToF patients (53% males, aged 20.2 ± 10.1 years) were enrolled. An increase of ventricular dimensions, except LVEDVi, and worsening of right and left ejection fractions were found over an average period of 5 years of follow-up. These changes were statistically significant but within 10% of the initial value. No significant changes were reported on a year-to-year basis, except in a small group of patients (6%) in whom no predictive factors were identified. Despite similar RV dimensions at the first examination, younger patients had a higher RV ejection fraction and a different annual rate of change of ventricular dimensions compared to older ones. Patients with arrhythmias (20%) were more frequently older and had larger RV dimensions but showed no significant correlations with MRI changes/years. Changes in RV dimensions and function occur rarely and very slowly in rToF patients. A small percentage of patients experience a significant worsening in a short time interval without any recognized risk factors. Arrhythmias appear to occur in a small percentage of cases in the late follow-up.

Characterization of Flow Dynamics in the Pulmonary Bifurcation of Patients With Repaired Tetralogy of Fallot: A Computational Approach.

The hemodynamic environment of the pulmonary bifurcation is of great importance for adult patients with repaired tetralogy of Fallot (rTOF) due to possible complications in the pulmonary valve and narrowing of the left pulmonary artery (LPA). The aim of this study was to computationally investigate the effect of geometrical variability and flow split on blood flow characteristics in the pulmonary trunk of patient-specific models. Data from a cohort of seven patients was used retrospectively and the pulmonary hemodynamics was investigated using averaged and MRI-derived patient-specific boundary conditions on the individualized models, as well as a statistical mean geometry. Geometrical analysis showed that curvature and tortuosity are higher in the LPA branch, compared to the right pulmonary artery (RPA), resulting in complex flow patterns in the LPA. The computational analysis also demonstrated high time-averaged wall shear stress (TAWSS) at the outer wall of the LPA and the wall of the RPA proximal to the junction. Similar TAWSS patterns were observed for averaged boundary conditions, except for a significantly modified flow split assigned at the outlets. Overall, this study enhances our understanding about the flow development in the pulmonary bifurcation of rTOF patients and associates some morphological characteristics with hemodynamic parameters, highlighting the importance of patient-specificity in the models. To confirm these findings, further studies are required with a bigger cohort of patients.

Branch Pulmonary Artery Regurgitation in Repaired Tetralogy of Fallot: Correlation with Pulmonary Artery Morphology, Distensibility, and Right Ventricular Function.

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.

Global and regional right ventricular mechanics in repaired tetralogy of Fallot with chronic severe pulmonary regurgitation: a three-dimensional echocardiography study

BackgroundData 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.MethodsWe 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.ResultsCorresponding 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).Conclusions3DTE 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.

Cardiac MRI-Derived Myocardial Deformation Parameters Correlate with Pulmonary Valve Replacement Indications in Repaired Tetralogy of Fallot.

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 (> 80ml/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.

Computational Modeling of Right Ventricular Motion and Intracardiac Flow in Repaired Tetralogy of Fallot.

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. 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. Diastolic vorticity and TKE in rTOF patients were 4.12 ± 2.42mJ/L and 115 ± 27/s, compared to 2.96 ± 2.16mJ/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 2mJ/mL (95% limits of agreement: -1.351 × 10-2 mJ/mL to 1.171 × 10-2 mJ/mL). 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.

Impairment of left atrial function in pediatric patients with repaired tetralogy of Fallot: a cardiovascular magnetic resonance imaging study.

We aimed to assess left atrial (LA) strain before LA dilatation in patients with repaired tetralogy of Fallot (rTOF) compared with healthy controls. We also determined the effects of right atrial (RA) dilatation on LA performance using cardiovascular magnetic resonance-feature tracking (CMR-FT). Forty-nine pediatric patients with rTOF and 36 age- and sex-matched healthy controls were prospectively recruited between June 2017 and August 2019. Balanced steady-state free precession (2D b-SSFP) cine, 2D late gadolinium enhancement (LGE) and phase-contrast (PC) sequences were acquired on 1.5 and 3.0 Tesla scanners. Both ventricular and atrial volumes and ejection fraction were measured. Left ventricular (LV) strain and diastolic strain rates were evaluated between the rTOF patient and control groups. LA reservoir (Ɛs), conduit (Ɛe), and booster strain (Ɛa) were determined at LV end-systole, LV diastasis, and pre-LA systole, respectively. The first derivatives of the respective strains yielded corresponding peak strain rates. Statistical analysis was performed using the t-test and Mann-Whitney test for parametric and non-parametric variables, respectively. Correlations were assessed using Pearson's correlation coefficient for normally distributed variables and Spearman's correlation coefficient for non-parametric data. Intra-observer and inter-observer variabilities of LA strain and strain rate measurements were determined from ten randomly selected rTOF patients and ten control subjects. LA strain was significantly lower in patients with rTOF compared with controls (Ɛs, P < 0.001; Ɛe, P = 0.002; Ɛa, P < 0.001). The correlations between LA strain and RA stroke volume indices (SVi) and RA ejection fraction (EF) were moderate (Ɛs and SVi, r = 0.538, P < 0.001; Ɛs and RA EF, r = 0.493, P < 0.001; Ɛe and SVi, r = 0.532, P < 0.001; Ɛe and RA EF, r = 0.466, P < 0.001). LA strain and strain rates had good reproducibility in intra-observer and inter-observer analyses. LA strain and strain rates decreased in pediatric patients with rTOF compared with controls before LA enlargement. A dysfunction in LA performance might precede LV dysfunction in patients with rTOF, even in the early stages after repair.

Left Atrial Strain in the Repaired Tetralogy of Fallot Population: Comparisons to Biventricular Function, Native T1 Values, Exercise Parameters and Healthy Controls.

Non-invasive imaging markers in patients with repaired tetralogy of Fallot (rTOF) are still being investigated to inform clinical decision making. Atrial function is a prognostic indicator in many acquired and congenital heart diseases. We sought to examine the relationship between cardiac MRI (CMR)-derived indices of left atrial (LA) function, native left ventricular (LV) T1 values, biventricular systolic function, and exercise capacity in rTOF. Sixty-six patients with rTOF without prior pulmonary valve replacement who underwent CMR (median age 18.5years) were identified. Twenty-one adult rTOF patients (age range 19-32years) were compared with 20 age-matched healthy volunteers (age range 19-34years). LA reservoir, conduit, and pump global longitudinal strain (GLS) and strain rate (SR) were determined by tissue tracking. Native LV T1 values were measured on rTOF patients. Pearson correlations were performed to determine bivariate associations. Adult rTOF patients had higher pump GLS, pump:conduit, and pump:reservoir GLS ratios, and lower conduit:reservoir GLS ratio, LV ejection fraction (EF), and right ventricular EF compared to controls (p < 0.001 for each comparison). LA conduit:reservoir GLS and pump:reservoir GLS had correlations to native LV T1 (ρ = 0.26, p = 0.03 and ρ = - 0.26, p = 0.03, respectively). LA reservoir SR had positive correlation to RV EF (ρ = 0.27, p = 0.03). There were no statistically significant correlations between LA function and exercise capacity. LA function is altered in adolescent and young adult patients with rTOF indicating worse diastolic function and relates to increasing native LV T1 values. Future studies are indicated to investigate the progression of adverse atrial-ventricular interactions and poor outcomes in this population.