Molecular Pathways and Animal Models of Tetralogy of Fallot and Double Outlet Right Ventricle.

Tetralogy of Fallot and double-outlet right ventricle are outflow tract (OFT) alignment defects situated on a continuous disease spectrum. A myriad of upstream causes can impact on ventriculoarterial alignment that can be summarized as defects in either i) OFT elongation during looping morphogenesis or ii) OFT remodeling during cardiac septation. Embryological processes underlying these two developmental steps include deployment of second heart field cardiac progenitor cells, establishment and transmission of embryonic left/right information driving OFT rotation and OFT cushion and valve morphogenesis. The formation and remodeling of pulmonary trunk infundibular myocardium is a critical component of both steps. Defects in myocardial, endocardial, or neural crest cell lineages can result in alignment defects, reflecting the complex intercellular signaling events that coordinate arterial pole development. Importantly, however, OFT alignment is mechanistically distinct from neural crest-driven OFT septation, although neural crest cells impact indirectly on alignment through their role in modulating signaling during SHF development. As yet poorly understood nongenetic causes of alignment defects that impact the above processes include hemodynamic changes, maternal exposure to environmental teratogens, and stochastic events. The heterogeneity of causes converging on alignment defects characterizes the OFT as a hotspot of congenital heart defects.

Transcatheter-Based Interventions for Tetralogy of Fallot Across All Age Groups.

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. Palliative procedures, either surgical or transcatheter, aim to improve oxygen saturation, affording definitive procedures at a later stage. Transcatheter interventions have been used before and after surgical palliative or definitive repair in children and adults. This review aims to provide an overview of the different catheter-based interventions for TOF across all age groups, with an emphasis on palliative interventions, such as patent arterial duct stenting, right ventricular outflow tract stenting, or balloon pulmonary valvuloplasty in infants and children and transcatheter pulmonary valve replacement in adults with repaired TOF, including the available options for a large, dilated native right ventricular outflow tract.

The Ongoing Debate: Longevity of Biological Valves in Pulmonary Position.

BACKGROUND: In patients with tetralogy of Fallot (ToF) or ToF-like anatomy, factors possibly impacting the longevity of biological valves in the pulmonary position were investigated. METHOD: Between 1997 and 2017, 79 consecutive hospital survivors with a median age of 8.7 years (range: 0.2-56.1 years; interquartile range [IQR]: 14.8 years) with ToF or ToF-like anatomy underwent surgical implantation of Contegra (n = 34), Hancock (n = 23), Perimount (n = 9), pulmonary homograft (n = 9), and miscellaneous (n = 4) conduits. The median internal graft diameter was 19 mm (range: 11-29 mm; IQR: 8 mm) which refers to a median z-score of 0.6 standard deviation (SD) (range: -1.8 to 4.0 SD; IQR: 2.1 SD). RESULTS: The median time of follow-up was 9.4 years (range: 1.1-18.8 years; IQR: 6.0 years). Thirty-nine patients (49%) underwent surgical (n = 32) or interventional (n = 7) pulmonary valve re-replacement. Univariate Cox regression revealed patient age (p = 0.018), body surface area (p = 0.004), internal valve diameter (p = 0.005), and prosthesis z-score (p = 0.018) to impact valve longevity. Multivariate Cox regression analysis, however, did not show any significant effect (likely related to multicollinearity). Subgroup analysis showed that valve-revised patients have a higher average z-score (p = 0.003) and younger average age (p = 0.007). CONCLUSION: A decreased longevity of biological valves in the pulmonary position is related to younger age, lower valve diameter, and higher z-score. Because valve size (diameter and z-score) can be predicted by age, patient age is the crucial parameter influencing graft longevity.

Tetralogy of Fallot regurgitation energetics and kinetics: an intracardiac flow analysis of the right ventricle using computational fluid dynamics.

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/m2. 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.

The effects of pregnancy in subjects with repaired tetralogy of Fallot.

BACKGROUND: Previous reports reveal inconsistent findings of right ventricular (RV) changes following pregnancy in subjects with repaired tetralogy of Fallot (rTOF). METHODS: A two-center, retrospective cohort study which included women with rTOF who completed pregnancy that were matched to nulliparous women with rTOF by age at the time of baseline cardiac magnetic resonance (CMR), RV ejection fraction (RVEF), and indexed RV end-diastolic volume (RVEDVi). Pre-pregnancy and postpartum cardiac magnetic resonance (CMR) were analyzed and compared to sequential CMR of nulliparous subjects with rTOF. RESULTS: Thirty-six women with rTOF who completed pregnancy were matched to 72 nulliparous women with rTOF. Over a mean period of 3.1 years for the pregnancy group and 2.7 years for the comparison group, there was no significant change in the RVEDVi, RVEF, RV mass, pulmonary regurgitation severity, left ventricular (LV) volumes, LV ejection fraction (LVEF), or LV mass when comparing the baseline CMR and the follow-up CMR in either of the groups. There was a slight increase in RV indexed end-systolic volume (RVESVi) when comparing the baseline CMR and the follow-up CMR in the pregnancy group (68.93, SD 23.34 ml/m2 at baseline vs. 72.97, SD 25.24 mL/m2 at follow-up, P = .028). Using a mixed effects model for CMR parameters change over time; when adjusted for time between baseline and follow-up CMR there was no significant difference in rate of change between the pregnancy and comparison groups. CONCLUSIONS: Most ventricular remodeling parameters measured by CMR did not significantly change in subjects with rTOF who completed pregnancy or in nulliparous subjects with rTOF. In the pregnancy group, RVESVi is larger in those individuals who have undergone pregnancy without a significant change in ventricular function. These patients should be followed longitudinally to determine the long-term ventricular and clinical effects of pregnancy.

Multidetector Computed Tomography Assessment of Anatomical Ventricular Tachycardia Isthmuses in Repaired Tetralogy of Fallot.

BACKGROUND: Tetralogy of Fallot (TOF) is associated with risk for sustained monomorphic ventricular tachycardia (VT). Preemptive electrophysiology study before transcatheter pulmonary valve placement is increasing, but the value of MDCT for anatomical VT isthmus assessment is unknown. OBJECTIVES: The purpose of this study was to determine the impact of multidetector computed tomography (MDCT) in the evaluation of sustained monomorphic VT for repaired TOF. METHODS: Consecutive pre-transcatheter pulmonary valve MDCT studies were identified, and anatomical isthmus dimensions were measured. For a subset of patients with preemptive electrophysiology study, MDCT features were compared with electroanatomical maps. RESULTS: A total of 61 repaired TOFs with MDCT were identified (mean 35 ± 14 years, 58% men) with MDCT electroanatomical map pairs in 35 (57%). Calcification corresponding to patch material was present in 46 (75%) and was used to measure anatomical VT isthmuses. MDCT wall thickness correlated positively with number of ablation lesions and varied with functional isthmus properties (blocked isthmus 2.6 mm [Q1, Q3: 2.1, 4.0 mm], slow conduction 4.8 mm [Q1, Q3: 3.3, 6.0 mm], and normal conduction 5.6 mm [Q1, Q3: 3.9, 8.3 mm]; P < 0.001). A large conal branch was present in 6 (10%) and a major coronary anomaly was discovered in 3 (5%). Median ablation lesion distance was closer to the right vs the left coronary artery (10 mm vs 15 mm; P = 0.01) with lesion-to-coronary distance <5 mm in 3 patients. CONCLUSIONS: MDCT identifies anatomical structures relevant to catheter ablation for repaired TOF. Wall thickness at commonly targeted anatomical VT isthmuses is associated with functional isthmus properties and increased thermal energy delivery.

Flow pattern analysis of right ventricular outflow tract in repaired tetralogy of Fallot through 4D flow MRI.

Cardiac magnetic resonance imaging (CMR) often shows discrepancies between right ventricular outflow tract (RVOT) flow and left ventricular outflow tract flow in patients with late-stage repaired tetralogy of Fallot (rTOF), leading to potential errors in pulmonary regurgitation fraction (PRF) assessment. This study aimed to identify the conditions under which RVOT flow can be acutely evaluated using four-dimensional (4D) flow CMR. Twenty-seven consecutive patients with rTOF underwent both two-dimensional phase-contrast (2D PC) and 4D flow CMR between 2016 and 2018, excluding those with peripheral pulmonary artery stenosis, RVOT conduit replacement, unknown surgical method, and an aortic valve regurgitation greater than 20%. Seven healthy controls also underwent only 4D Flow CMR. All healthy controls and fifteen patients with rTOF showed laminar RVOT flow, while seven patients exhibited helical, and four patients exhibited vortical RVOT flow in 4D flow CMR visualization. Flow-volume concordance between the pulmonary artery and aortic flow was significantly lower in patients with rTOF and PRF > 40% in 2D PC CMR. This concordance rate in the suprapulmonary valve was high in both the TOF and control groups, comparing at five RVOT locations in 4D flow CMR. Regarding RVOT flow regurgitation in 4D flow, the whole bulk evaluation exhibited greater variation depending on the flow type compared to the whole pixel-wise evaluation. The study confirmed the flow volume at the upper section of the pulmonary valve as the most accurate correlate of aortic flow volume. Furthermore, the 4D flow CMR using the pixel-wise method demonstrated superior accuracy compared to the traditional bulk flow method.

Growth of the right ventricular outflow tract in repaired tetralogy of Fallot: A longitudinal CMR study.

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.

Comparison of management strategies for neonates with symptomatic tetralogy of Fallot and weight <2.5 kg.

OBJECTIVE: To compare management strategies for neonates <2.5 kg with tetralogy of Fallot and symptomatic cyanosis who either undergo staged repair (SR) (initial palliation followed by later complete repair) or primary repair (PR). METHODS: Consecutive neonates with tetralogy of Fallot and symptomatic cyanosis weighing <2.5 kg at initial intervention and between 2005 and 2017 were retrospectively reviewed from the Congenital Cardiac Research Collaborative. Primary outcome was mortality and secondary outcomes included component (eg, initial palliation, complete repair, or primary repair) and cumulative (SR: initial palliation followed by later complete repair) hospital and intensive care unit lengths of stay, durations of ventilation, inotrope use, cardiopulmonary bypass time, procedural complications, and reintervention. Outcomes were compared with propensity score adjustments with PR as the reference group. RESULTS: The cohort included 76 SR (initial palliation: 53 surgical and 23 transcatheter) and 44 PR patients. The observed risk of overall mortality was similar between SR and PR groups (15.8% vs 18.2%: P = .735). The adjusted hazard of mortality remained similar between groups overall (hazard ratio, 0.59; 95% confidence interval, 0.26-1.36; P = .214), as well as during short-term (<4 months: hazard ratio, 0.37; 95% confidence interval, 0.13-1.09; P = .071) and midterm (>4 months: hazard ratio, 1.32; 95% confidence interval, 0.30-5.79; P = .717) follow-up. Reintervention in the first 18 months was common in both groups (53.2% vs 48.4%; hazard ratio, 1.69; 95% confidence interval, 0.96-2.28; P = .072). Adjusted procedural complications and neonatal morbidity burden were overall lower in the SR group. Cumulative secondary outcome burdens largely favored the PR group. CONCLUSIONS: In this study comparing SR and PR treatment strategies for neonates with tetralogy of Fallot and symptomatic cyanosis and weight <2.5 kg, mortality and reintervention burden was high and independent of treatment strategy. Other potential advantages were observed with each approach.

Unchanged right ventricular strain in repaired tetralogy of Fallot after pulmonary valve replacement with radial long-axis cine magnetic resonance images.

We measured right ventricular (RV) strain by applying a novel postprocessing technique to conventional short-axis cine magnetic resonance imaging in the repaired tetralogy of Fallot (TOF) and investigated whether pulmonary valve replacement (PVR) changes the RV strain. Twenty-four patients with repaired TOF who underwent PVR and 16 healthy controls were enrolled. Global maximum and minimum principal strains (GPSmax, GPSmin) and global circumferential and longitudinal strains (GCS, GLS) were measured from short-axis cine images reconstructed radially along the long axis. Strain parameters before and after PVR were compared using paired t-tests. One-way ANOVA with Tukey post-hoc analysis was used for comparisons between the before and after PVR groups and the control group. There were no differences in strain parameters before and after PVR. The GPSmax before PVR was lower than that in the control group (P = 0.002). Before and after PVR, GCSs were higher and GLSs were lower than those in the control group (before and after GCSs: P = 0.002 for both, before and after GLSs: P < 0.0001 and P = 0.0003). RV strains from radially reconstructed short-axis cine images revealed unchanged myocardial motion after PVR. When compared to the control group, changes in GCS and GLS in TOF patients before and after PVR might be due to RV remodeling.

Biventricular Global Function Index Is Associated With Adverse Outcomes in Repaired Tetralogy of Fallot.

INTRODUCTION: Cardiac magnetic resonance (CMR) derived biventricular global function index (BVGFI) is a new CMR parameter that integrates biventricular volumes, mass, and function using clinically available CMR parameters. The associations of BVGFI with clinical outcomes in repaired tetralogy of Fallot are unknown. METHODS: Patients with repaired tetralogy of Fallot who had a CMR before the occurrence of a composite outcome of death, resuscitated sudden death, or sustained ventricular tachycardia were studied. BVGFI was calculated as the average of right and left GFI. GFI was defined as (ventricular stroke volume×100)/(ventricular mean cavity volume + total ventricular myocardial volume). Ventricular mean cavity volume was defined as ([end-diastolic + end-systolic volume]/2). Cox multivariable regression analysis and classification and regression tree methodology were used. RESULTS: Of the 736 eligible subjects (mean age at CMR 25.4±14.5 years), with a median follow-up of 28 months, 55 subjects (7.4%) reached the composite outcome (46 deaths and 9 sustained ventricular tachycardia). Independent associations with the composite outcome were as follows: BVGFI <37 (hazard ratio, 2.52; P=0.004), right ventricular end-systolic volume index >85 mL/m2 (hazard ratio, 3.25; P<0.001), atrial tachycardia (hazard ratio, 2.03; P=0.021), and age at repair >2.5 years (hazard ratio, 3.37; P<0.001). Classification and regression tree analysis identified BVGFI as the most discriminatory CMR parameter associated with a high risk for adverse outcomes. CONCLUSIONS: BVGFI, a novel CMR-derived imaging biomarker combining biventricular volumes, mass, and function, may improve risk stratification for adverse clinical outcomes in patients with repaired tetralogy of Fallot.

Impaired Exercise Tolerance in Repaired Tetralogy of Fallot Is Associated With Impaired Biventricular Contractile Reserve: An Exercise-Stress Real-Time Cardiovascular Magnetic Resonance Study.

BACKGROUND: Correction of tetralogy of Fallot (cTOF) often results in pulmonary valve pathology and right ventricular (RV) dysfunction. Reduced exercise capacity in cTOF patients cannot be explained by these findings alone. We aimed to explore why cTOF patients exhibit impaired exercise capacity with the aid of a comprehensive cardiopulmonary exercise testing (CPET) and real-time cardiovascular magnetic resonance exercise testing (CMR-ET) protocol. METHODS: Thirty three cTOF patients and 35 matched healthy controls underwent CPET and CMR-ET in a prospective case-control study. Real-time steady-state free precession cine and phase-contrast sequences were obtained during incremental supine in-scanner cycling at 50, 70, and 90 W. RV and left ventricle (LV) volumes and pulmonary blood flow (Qp) were calculated. Differences of CPET and CMR-ET between cTOF versus controls and correlations between CPET and CMR-ET parameters in cTOF were evaluated statistically for all CMR exercise levels using Mann-Whitney U and Spearman rank-order correlation tests. RESULTS: CPET capacity was significantly lower in cTOF than in controls. cTOF patients exhibited not only significantly reduced Qp and RV function but also lower LV function on CMR-ET. Higher CPET values in cTOF correlated with higher Qp (Qp 90 W versus carbon dioxide ventilatory equivalent %: R=-0.519, P<0.05), higher LV-end-diastolic volume indexed to body surface area (LV-end-diastolic volume indexed to body surface area at 50 W versus oxygen uptake in % at maximum exercise on CPET R=0.452, P<0.05), and change in LV ejection fraction (EF; LV-EF at 90 W versus Watt %: r=-0.463, P<0.05). No correlation was found with regard to RV-EF. Significant RV-LV interaction was observed during CMR-ET (RV-EF versus LV-EF at 50 W and 70 W: r=0.66, P<0.02 and r=0.52, P<0.05, respectively). CONCLUSIONS: Impaired exercise capacity in cTOF resulted from a reduction in not only RV, but also LV function. cTOF with good exercise capacity on CPET demonstrated higher LV reserve and pulmonary blood flow during incremental CMR-ET. Apart from RV parameters, CMR-ET-derived LV function could be a valuable tool to stratify cTOF patients for pulmonary valve replacement.

Contemporary Outcomes in Tetralogy of Fallot With Absent Pulmonary Valve After Fetal Diagnosis.

Background Tetralogy of Fallot with absent pulmonary valve is associated with high mortality, but it remains difficult to predict outcomes prenatally. We aimed to identify risk factors for mortality in a large multicenter cohort. Methods and Results Fetal echocardiograms and clinical data from 19 centers over a 10-year period were collected. Primary outcome measures included fetal demise and overall mortality. Of 100 fetuses, pregnancy termination/postnatal nonintervention was elected in 22. Of 78 with intention to treat, 7 (9%) died in utero and 21 (27%) died postnatally. With median follow-up of 32.9 months, no deaths occurred after 13 months. Of 80 fetuses with genetic testing, 46% had chromosomal abnormalities, with 22q11.2 deletion in 35%. On last fetal echocardiogram, at a median of 34.6 weeks, left ventricular dysfunction independently predicted fetal demise (odds ratio [OR], 7.4; 95% CI 1.3, 43.0; P=0.026). Right ventricular dysfunction independently predicted overall mortality in multivariate analysis (OR, 7.9; 95% CI 2.1-30.0; P=0.002). Earlier gestational age at delivery, mediastinal shift, left ventricular/right ventricular dilation, left ventricular dysfunction, tricuspid regurgitation, and Doppler abnormalities were associated with fetal and postnatal mortality, although few tended to progress throughout gestation on serial evaluation. Pulmonary artery diameters did not correlate with outcomes. Conclusions Perinatal mortality in tetralogy of Fallot with absent pulmonary valve remains high, with overall survival of 64% in fetuses with intention to treat. Right ventricular dysfunction independently predicts overall mortality. Left ventricular dysfunction predicts fetal mortality and may influence prenatal management and delivery planning. Mediastinal shift may reflect secondary effects of airway obstruction and abnormal lung development and is associated with increased mortality.

Finding the Optimal Timing for Repair of Standard Tetralogy of Fallot: Analysis of Cardiac Magnetic Resonance and Echocardiography Parameters Related to Intermediate Term Outcomes in a Pediatric Population.

INTRODUCTION: Right ventricular (RV) dilatation is the determining prognostic factor in the long-term follow up of patients with repaired Tetralogy of Fallot (TOF). The objective of this study is to analyze whether the results vary depending on the timing of the complete repair and on the surgical technique applied. MATERIAL-METHODS: This is a retrospective longitudinal study in which patients with standard TOF were divided into 3 groups depending on their age at surgical repair: group 1 = Early repair (n = 12,1-8 months), group 2 = Late repair (n = 26, > 8 months), and group 3 = Late repair with previous palliative surgery (n = 17, > 8 months). Clinical, echocardiographic and cardiac magnetic resonance (CMR) data from patients that had received complete reparative surgery in our institution from January 2000 to March 2014 were analyzed and compared. RESULTS: 55 patients with echocardiogram and CMR studies (13.39 ± 3.59 years) were reviewed. All patients had at least moderate pulmonary regurgitation (PR). We observed a positive correlation between PR and right ventricular end-diastolic volume (r2 = 0.418; p = 0,004). Group 3 had more severe right ventricular dilatation than patients in groups 1 and 2 (p = 0.001). No differences in right ventricular end-diastolic volume, PR, and pulmonary trunk dimensions were observed between groups 1 and 2. Patients in group 3 had a longer hospital stay. CONCLUSIONS: Although all patients from our cohort had significant PR, age at surgery was not related to RV or pulmonary trunk dilatation. Previous palliative surgery was associated with more severe right ventricular dilatation and longer hospital stays. No differences were observed between early and late repair groups. Our study suggests that postponing TOF repair to a late stage does not improve the degree of PR or long-term morbidity from RV dilatation. Palliative surgery should be avoided if possible.

Cardiovascular magnetic resonance-assessed fast global longitudinal strain parameters add diagnostic and prognostic insights in right ventricular volume and pressure loading disease conditions.

BACKGROUND: Parameters of myocardial deformation may provide improved insights into right ventricular (RV) dysfunction. We quantified RV longitudinal myocardial function using a fast, semi-automated method and investigated its diagnostic and prognostic values in patients with repaired tetralogy of Fallot (rTOF) and pulmonary arterial hypertension (PAH), who respectively exemplify patients with RV volume and pressure overload conditions. METHODS: The study enrolled 150 patients (rTOF, n = 75; PAH, n = 75) and 75 healthy controls. RV parameters of interest were fast global longitudinal strain (GLS) and strain rates during systole (GLSRs), early diastole (GLSRe) and late diastole (GLSRa), obtained by tracking the distance from the medial and lateral tricuspid valve insertions to the RV epicardial apex on cine cardiovascular magnetic resonance (CMR). RESULTS: The RV fast GLS exhibited good agreement with strain values obtained by conventional feature tracking approach (bias - 4.9%, error limits (± 2·standard deviation) ± 4.3%) with fast GLS achieving greater reproducibility and requiring reduced analysis time. Mean RV fast GLS was reduced in PAH and rTOF groups compared to healthy controls (PAH < rTOF < healthy controls: 15.1 ± 4.9 < 19.3 ± 2.4 < 24.4 ± 3.0%, all P < 0.001 in pairwise comparisons). In rTOF patients, RV fast GLS was significantly associated with metabolic equivalents, peak oxygen consumption (PVO2) and percentage of predicted PVO2 achieved during cardiopulmonary exercise testing. Lower RV fast GLS was associated with subnormal exercise capacity in rTOF (area under the curve (AUC) = 0.822, sensitivity = 72%, specificity = 91%, cut-off = 19.3%). In PAH patients, reduced RV fast GLS was associated with RV decompensated hemodynamics (AUC = 0.717, sensitivity = 75%, specificity = 58%, cut-off = 14.6%) and higher risk of clinical worsening (AUC = 0.808, sensitivity = 79%, specificity = 70 %, cut-off = 16.0%). CONCLUSIONS: Quantitative RV fast strain and strain rate parameters assessed from CMR identify abnormalities of RV function in rTOF and PAH and are predictive of exercise capacity, RV decompensation and clinical risks in these patients. Trial registry Clinicaltrials.gov: NCT03217240.

Effect of cardiopulmonary bypass reoxygenation on myocardial dysfunction following pediatric tetralogy of Fallot repair.

BACKGROUND: Little is known regarding the effect of cardiopulmonary bypass (CPB) reoxygenation on cardiac function following tetralogy of Fallot repair. We hypothesized that hyperoxic reoxygenation would be more strongly associated with myocardial dysfunction in children with tetralogy of Fallot. METHODS: We investigated the association of perfusate oxygenation (PpO2) associated with myocardial dysfunction among children aged 6-72 months who underwent complete repair of tetralogy of Fallot in 2012-2018. Patients were divided into two groups: lower PpO2 group (≤ 250 mmHg) and higher PpO2 (> 250 mmHg) group based on the highest value of PpO2 during aortic occlusion. The odd ratio (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models. RESULTS: This study included 163 patients perfused with lower PpO2 and 213 with higher PpO2, with median age at surgery 23.3 (interquartile range [IQR] 12.5-39.4) months, 164 female (43.6%), and median body mass index 15.59 (IQR 14.3-16.9) kg/m2. After adjustment for baseline, clinical and procedural variables, patients with higher PpO2 were associated with higher risk of myocardial dysfunction than those with lower PpO2 (OR 1.770; 95% CI 1.040-3.012, P = 0.035). Higher PpO2, lower SpO2, lower pulmonary annular Z-score, and longer CPB time were independent risk factors for myocardial dysfunction. CONCLUSIONS: Association exists between higher PpO2 and myocardial dysfunction risk in patients with tetralogy of Fallot, highlighting the modulation of reoxygenation during aortic occlusion to reduce cardiovascular damage following tetralogy of Fallot repair. TRIAL REGISTRATION: Clinical Trials. gov number NCT03568357. June 26, 2018.

The Effect of Geometric and Hemodynamic Parameters on Blood Flow Efficiency in Repaired Tetralogy of Fallot Patients.

Surgical repair of Tetralogy of Fallot (TOF) involves a series of steps to remove right ventricular outflow tract and pulmonary artery obstruction. However, the large degree of anatomic variability among preoperative TOF patients may impact the effectiveness of different repair strategies and, subsequently, different geometric modifications for different patients. This study investigates the relationships between geometric and hemodynamic parameters and mechanical energy efficiency for a patient-specific dataset of 16 postoperative TOF repairs, using morphometric and statistical shape analyses, as well as computational fluid dynamics simulations with physiologically-relevant inlet and outlet boundary conditions. Quantitatively, negative correlations were found between the right and left pulmonary artery centerline tract cumulative torsion and energy efficiency (r = - 0.65, p = 0.01, for both). A positive correlation was also found for a statistical shape mode associated with skewing of the geometric sub-regions (r = 0.61, p = 0.01). Qualitatively, medium- and low-efficiency geometries exhibit disturbed flow and much more proximal vortex formation as compared to a high-efficiency geometry. Thus, it is recommended, as much as possible, to both relieve and avoid the introduction of torsion into the patient's anatomy during surgical repair of TOF.

Hidden pulmonary arteries in tetralogy of Fallot and pulmonary artery pressure in patients operated with a pulmonary artery.

INTRODUCTION: The absence of a pulmonary artery is a rare congenital anomaly that occurs isolated or with other congenital cardiac disorders, particularly tetralogy of Fallot (TOF); meanwhile, a hidden pulmonary artery might exist and originate from a closed ductus arteriosus (DA), which can be stented to reach the artery. MATERIAL AND METHODS: This prospective study describes cardiac catheterization of nine TOF patients diagnosed with the absence of the left pulmonary artery before the operation. The patients were stratified into three groups: group one, whose closed DA was found and connected to the hidden pulmonary artery with a stent; group two, whose hidden pulmonary arteries were found via the pulmonary vein angiography; and group three, for whom we could not find the remnant of the DA, or our attempt to stent the DA to the hidden pulmonary artery was not successful. We also evaluated outcomes of six other surgically-corrected TOF patients who were operated with the absent left pulmonary artery. RESULTS: The first group included the patients aged 1, 24, and 30 months, whose CT angiography 6-9 months after stenting showed acceptable left pulmonary artery diameter for surgical correction, and the pulmonary vein angiography of the second group showed a hidden left pulmonary artery with a suitable diameter for surgical correction. However, we were unable to find or stent the DA of group three patients, aged 12, 38, 60, and 63 months. Earlier Angiography might have increased the chance of access to the hidden vessel. Apart from these three groups, follow-ups of six other patients previously corrected with only the right pulmonary artery revealed pulmonary artery hypertension in all patients. CONCLUSION: The concealed pulmonary artery might be found, and stenting of the closed DA to it might be performed to improve the diameter of the diminutive pulmonary artery. This procedure may allow TOF total surgical correction with two pulmonary arteries. Besides, pulmonary vein angiography can reveal the hidden pulmonary artery.