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Background: This study describes the evolving in-hospital management strategies for neonates who are diagnosed with tetralogy of Fallot (ToF)., Methods: The Pediatric Health Information System (PHIS) database was used to identify admitted patients aged 0 to 1 month old with ToF from 2010 through 2019; era 1, 2010 through 2014; and era 2, 2015 through 2019. International Classification of Diseases codes were used to identify related interventions that occurred during this admission but not necessarily as a neonate: full repair, systemic-to-pulmonary shunt, and percutaneous stent in the right ventricular outflow tract and/or patent ductus arteriosus., Results: Among 6021 neonates diagnosed with ToF, 2030 (34%) underwent an intervention: 60% had total repair, 31% systemic-to-pulmonary shunt, and 9% percutaneous stent. In the no-intervention cohort, in-hospital mortality was 9%. In-hospital mortality between repair (6%), shunt (6%), and stent (3%) patients (P = .446) did not differ. Regarding regional practices, no intervention was most frequently used in the Midwest (69% vs 65% average for all other regions [avg], P = .075) while interventions overall were performed most frequently in the West (36% vs 33.5% avg, P = .075). Among the interventions, full repair was most frequent in the Northeast (76% vs 57% avg, P < .001), shunt was most frequent in the Midwest (39% vs 28% avg, P < .001), and stent was most frequent in the South (11% vs 7% avg, P = .083). Between eras 1 and 2, the type of intervention changed: full repair (52% vs 69%, P < .001) and stent (1% vs 16%, P < .001) increased, while shunt decreased (47% vs 15%, P < .001)., Conclusions: Although most neonates admitted with ToF are discharged with no intervention, more than one-third undergo some intervention with a 3% to 6% mortality. The proportion of these patients who undergo an intervention is unchanged during the past decade, but the types of intervention have changed, and significant regional differences exist., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods: Sixty-six patients with rTOF without prior pulmonary valve replacement who underwent CMR (median age 18.5 years) were identified. Twenty-one adult rTOF patients (age range 19-32 years) were compared with 20 age-matched healthy volunteers (age range 19-34 years). 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., Results: 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., Conclusions: 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.

Background Cardiac MRI (CMR) derived ventricular global function index (GFI), a ratio of stroke volume to the sum of mean ventricular cavity and myocardial volumes, has demonstrated improved prediction of clinical outcomes in adults with atherosclerotic disease over ejection fraction. We sought to assess CMR derived GFI and a novel modification that accounts for unique loading conditions in patients with repaired tetralogy of Fallot (rTOF) and determine its correlation with exercise performance. Methods and Results Seventy-five patients with rTOF who underwent CMR were identified. Clinical variables were recorded and biventricular GFI calculated. A right ventricular (RV) effective GFI (eGFI) was derived by incorporating effective stroke volume. Thirty-five pediatric patients were matched with 29 age-matched healthy controls. Twenty-five patients completed cardiopulmonary exercise tests within 6 months of CMR. Stepwise regression models were used to determine univariate and multivariable predictors of indexed and percent predicted peak VO 2 . Median age at CMR was 20 years (interquartile range, 13-28). Pediatric rTOF patients had lower RV eGFI ( P < 0.001), RV ejection fraction ( P =0.002), but higher indexed RV end-diastolic and end-systolic volumes ( P < 0.001, P < 0.001) compared with controls. Univariate analysis demonstrated a correlation between indexed peak VO 2 with RV eGFI ( R 2 =0.32, P =0.004), but with neither RVGFI, RV ejection fraction, indexed RV volumes nor RV mass. RV eGFI remained significantly associated with indexed peak VO 2 during multivariable modeling. Conclusions Reduced RV eGFI was associated with reduced exercise capacity in rTOF patients, while RV GFI, RV ejection fraction, indexed RV volumes and mass were not. Our modification of the GFI, RV eGFI, may be a valuable non-invasive marker of cardiac function in rTOF.

Background: Annulus-sparing repair of tetralogy of Fallot (TOF) carries a potential increased risk of reoperation for restenosis and unproven benefits on right ventricular (RV) geometry., Methods: Primary TOF repairs (n = 434) between 2000 and 2012 were studied using risk-adjusted parametric techniques. Progression of cardiac dimensions was analyzed using repeated measures regression using reports of all 2,103 echocardiograms undertaken throughout the study period, to a maximum follow-up of 13.7 years., Results: Repair was at a mean age of 180 days: AS approach in 296 (68%) patients; and transannular patch in 138 (32%). Intraoperative revisions (for residual stenosis) were required in 135 patients (29%). There have been 4 deaths (survival 99%). Surgical reoperation for recurrent right ventricular outflow tract stenosis was occasionally required in both groups at comparable rates (transannular patch, 5 of 136 [4%]; annulus-sparing repair, 14 of 296 [5%]; p = 0.83). Larger increases in RV end-diastolic dimensions were evident in transannular patch patients versus annulus-sparing repair patients (p < 0.0001). Other risks for RV dilation included worse grade of postoperative pulmonary regurgitation, larger right ventricular end-diastolic dimension at the time of diagnosis, and higher operative weight (all p < 0.0001). Factors associated with successful annulus-sparing repair included (1) pulmonary annulus greater than 7 mm, right ventricular end-diastolic dimension greater than 1.2 cm, and tricuspid annulus greater than 1.4 cm (all preoperatively); and (2) right ventricular outflow tract diameter greater than 10 mm and right ventricular systolic pressure less than 50 mm Hg (both intraoperatively after repair)., Conclusions: Pursuit of annulus-sparing repair strategies can lower the use of transannular patch to approximately 30% with low risk of reoperation for the patient. Annulus-sparing repair is associated with significantly reduced long-term RV dilation. Pulmonary valve enlargement to approximately 10 mm and right ventricular systolic pressure less than 50 mm Hg during annulus-sparing repair are associated with low risk of recurrent stenosis., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The left pulmonary artery (LPA) contributes more than the right (RPA) to total pulmonary regurgitation (PR) in patients after tetralogy of Fallot (TOF) repair, but the mechanism of this difference is not well understood. This study aimed to analyze the interplay between heart and lung size, mediastinal geometry, and differential PR., Methods: Forty-eight Cardiovascular Magnetic Resonance (CMR) studies in patients after TOF repair were analyzed. In addition to the routine blood flow and ventricular volume quantification cardiac angle between the thoracic anterior-posterior line and the interventricular septum, right and left lung areas as well as right and left hemithorax areas were measured on an axial image. Statistical analysis was performed to compare flow parameters between RPA and LPA and to assess correlation among right ventricular volume, pulmonary blood flow parameters and lung area., Results: There was no difference between LPA and RPA diameters. The LPA showed significantly less total forward flow (2.49 ± 0.87 L/min/m(2) vs 2.86 ± 0.89 L/min/m(2); p = 0.02), smaller net forward flow (1.40 ± 0.51 vs 1.89 ± 0.60 mL/min/m(2); p = <0.001), and greater regurgitant fraction (RF) (34 ± 10 % vs 43 ± 12 %; p = 0.001) than the RPA. There was no difference in regurgitant flow volume between RPA and LPA (p = 0.29). Indexed right ventricular end-diastolic volume (RVEDVi) correlated with LPA RF (R = 0.48, p < 0.001), but not with RPA RF (p = 0.09). Larger RVEDVi correlated with a more leftward cardiac axis (R = 0.46, p < 0.001) and with smaller left lung area (R = -0.58, p < 0.001). LPA RF, but not RPA RF, correlated inversely with left lung area (R = -0.34, p = 0.02). The follow-up CMRs in 20 patients showed a correlation of the rate of RV enlargement with the rates of LPA RF worsening (R = 0.50, p = 0.03), and of increasing left lung compression (R = -0.55, p = 0.012)., Conclusion: An enlarged and levorotated heart is associated with left lung compression and impaired flow into the left lung.

Background: Potential surgical strategies for hypoplastic branch pulmonary arteries (BPAs) during tetralogy of Fallot repair include (1) extensive patch augmentation to the hilum (PATCH), (2) limited extension arterioplasty to the proximal pulmonary artery (EXTENSION), or (3) leaving the native vessels unaugmented (NATIVE). We explored the effect of these strategies on reintervention and BPA growth., Methods: From 2000 to 2012, 434 children underwent complete tetralogy of Fallot repair. Risk-adjusted parametric models were used to analyze the risk of BPA reintervention for (1) all children, (2) children with BPAs of 4 mm or smaller, and (3) children with BPAs of 3 mm or smaller. Repeated-measures analysis of more than 2,000 echocardiograms was used to characterize postoperative BPA growth and right ventricular pressure by using nonlinear mixed models., Results: Overall survival (99% [3 deaths]) was excellent. The 10-year freedom from BPA reintervention was 84%. In risk-adjusted models (including baseline BPA z-score), PATCH had a decreased freedom from reintervention (73%; p < 0.01) vs EXTENSION (87%) or NATIVE (91%). For children with BPAs of 4 mm or smaller (28 PATCH, 60 EXTENSION, 75 NATIVE), baseline characteristics were similar. The risk-adjusted 5-year freedom from reintervention was 68% for PATCH, 76% for EXTENSION, and 85% for NATIVE. PATCH trended toward an increased risk of reintervention (p = 0.07). For children with BPAs of 4 mm or smaller left in their NATIVE state, only ∼15% required reintervention. After adjustment for baseline BPA z-score, the time-related BPA growth was decreased (p < 0.014) and right ventricular pressure was increased (p = 0.03) for the PATCH group., Conclusions: Aggressive PATCH augmentation of hypoplastic BPAs improves the short-term geometry but may lead to late stenosis and higher rates of reintervention. Hypoplastic BPAs in tetralogy of Fallot tend (∼85%) to grow well without instrumentation., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Long-term biventricular systolic performance is a key determinant of clinical outcomes late after tetralogy of Fallot (TOF) repair. A need exists for early indices of both left ventricular (LV) and right ventricular (RV) compromise in this population., Methods: Twenty-nine children (age range, 5-18 years) with repaired TOF and 44 healthy controls were prospectively evaluated. M-mode and tissue Doppler data were obtained for each ventricle and the RV outflow tract at rest and during semisupine bicycle exercise. By making measurements of myocardial acceleration during isovolumic contraction during exercise, at increasing heart rates, LV force-frequency curves were constructed. Patients also underwent cardiac magnetic resonance imaging, cardiopulmonary exercise testing, and measurement of serum neurohormonal markers., Results: Children with repaired TOF had dilated right ventricles (RV end-diastolic volume index = 153 ± 37.3 mL/m(2)) but normal ejection fractions as measured on magnetic resonance imaging (LV ejection fraction = 59.3 ± 6.2%, RV ejection fraction = 50.2 ± 8.5%) and normal serum neurohormonal markers. Detailed resting echocardiography detected abnormal ventricular function, worst in the right ventricle and RV outflow tract. Exercise exacerbated these findings and provoked significant decline in LV indices. The LV force-frequency curves of patients were attenuated, with an early plateau and inadequate increase of isovolumic contraction. Correlations were seen between peak exercise LV isovolumic contraction and percentage predicted peak oxygen uptake (r = 0.51, P = .02), LV and RV ejection fractions (r = 0.41, P = .03), and RV and LV long-axis fractional shortening (r = 0.44, P = .02)., Conclusions: The postsurgical pathophysiology of TOF begins early after repair. At a time when clinically well and while routine indices of heart function remain normal, children with repaired TOF exhibit RV dilatation and subtle, interlinked biventricular abnormalities on resting echocardiography. Exercise echocardiography provides additional information and reveals abnormal LV excitation-contractile coupling that may be linked to impaired exercise capacity., (Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Chronic hemodynamically relevant pulmonary regurgitation (PR) resulting in important right ventricular dilation and ventricular dysfunction is commonly seen after tetralogy of Fallot (TOF) repair. Late adverse clinical outcomes, including exercise intolerance, arrhythmias, heart failure and/or death accelerate in the third decade of life and are cause for considerable concern. Timing of pulmonary valve replacement (PVR) to address chronic PR is controversial, particularly in asymptomatic individuals, and effect of PVR on clinical measures has not been determined., Methods: Canadian Outcomes Registry Late After Tetralogy of Fallot Repair (CORRELATE) is a prospective, multicentre, Canada-wide cohort study. Candidates will be included if they are ≥ 12 years of age, have had surgically repaired TOF resulting in moderate or severe PR, and are able to undergo cardiovascular magnetic resonance imaging. Enrollment of > 1000 individuals from 15 participating centres (Toronto, Montreal, Quebec City, Sherbrooke, Halifax, Calgary, Edmonton, and Vancouver) is anticipated. Clinical data, health-related quality of life metrics, and adverse outcomes will be entered into a web-based database. A central core lab will analyze all cardiovascular magnetic resonance studies (PR severity, right ventricular volumes, and ventricular function). Major adverse outcomes (sustained ventricular tachycardia and cardiovascular cause of death) will be centrally adjudicated., Results: To the best of our knowledge, CORRELATE will be the first prospective pan-Canadian cohort study of congenital heart disease in children and adults., Conclusions: CORRELATE will uniquely link clinical, imaging, and functional data in those with repaired TOF and important PR, thereby enabling critical evaluation of clinically relevant outcomes in those managed conservatively compared with those referred for PVR., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Right ventricular (RV) volume overload results in RV dilatation and dysfunction in patients with pulmonary regurgitation after tetralogy of Fallot (ToF) repair, affecting left ventricular (LV) function because of ventricular interaction. The aim of this study was to assess the effect of chronic RV volume loading on LV myocardial mechanics in patients after ToF repair by combining cardiac magnetic resonance imaging with echocardiography., Methods: Seventy-five subjects were studied: 50 patients after ToF repair and 25 age-matched controls. All patients with ToF and controls underwent echocardiography at the time of clinically indicated cardiac magnetic resonance imaging. Myocardial deformation, including LV torsion, was analyzed using speckle-tracking echocardiography., Results: RV free wall global and segmental longitudinal strain and strain rate were significantly lower in patients with ToF compared with controls (P < .001). All LV longitudinal, strain, and torsion parameters were significantly reduced in patients with ToF (P < .01). Basal rotation was particularly abnormal, with 38% of patients with ToF having reversed basal rotation. In contrast, apical rotation was reduced but not reversed. On multivariate regression analysis, the only significant predictor of counterclockwise basal rotation was RV strain, suggesting that RV function more than dilatation influences abnormal LV torsion., Conclusion: Patients with ToF have abnormal LV myocardial mechanics, as demonstrated by speckle-tracking echocardiography. The most striking changes were noted in LV torsion, especially related to abnormal LV basal rotation. RV dysfunction seems the most important determinant of abnormal LV rotation. The clinical significance and potential prognostic implications of these observations remain to be determined., (Copyright © 2014 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Adverse ventricular remodeling after tetralogy of Fallot (TOF) repair is associated with diffuse myocardial fibrosis., Objective: The goal of this study was to measure post-contrast myocardial T1 in pediatric patients after TOF repair as surrogates of myocardial fibrosis., Materials and Methods: Children after TOF repair who underwent cardiac magnetic resonance imaging with T1 mapping using the modified look-locker inversion recovery (MOLLI) sequence were included. In addition to routine volumetric and flow data, we measured post-contrast T1 values of the basal interventricular septum, the left ventricular (LV) lateral wall, and the inferior and anterior walls of the right ventricle (RV). Results were compared to data from age-matched healthy controls., Results: The scans of 18 children who had undergone TOF repair and 12 healthy children were included. Post-contrast T1 values of the left ventricular lateral wall (443 ± 54 vs. 510 ± 77 ms, P = 0.0168) and of the right ventricular anterior wall (333 ± 62 vs. 392 ± 72 ms, P = 0.0423) were significantly shorter in children with TOF repair than in controls, suggesting a higher degree of fibrosis. In children with TOF repair, but not in controls, post-contrast T1 values were shorter in the right ventricle than the left ventricle and shorter in the anterior wall of the right ventricle than in the inferior segments. In the TOF group, post-contrast T1 values of the RV anterior wall correlated with the RV end-systolic volume indexed to body surface area (r = 0.54; r(2) = 0.30; P = 0.0238)., Conclusion: In children who underwent tetralogy of Fallot repair the myocardium of both ventricles appears to bear an abnormally high fibrosis burden.

Background: Right ventricular (RV) volume overload results in RV dilatation in patients with atrial septal defect (ASD) and after tetralogy of Fallot (ToF) repair with pulmonary regurgitation., Aim: Study the differential effects of chronic RV volume loading on regional and global RV deformation in patients with ASD and after TOF repair., Methods: We studied 85 subjects: 50 patients after ToF repair, 15 patients with unrepaired ASD and 20 age-matched controls. The ToF patients and controls underwent an echocardiography at the time of a clinically indicated MRI. The ASD patients had a routine echocardiogram including RV volume calculations. Longitudinal deformation was analyzed using 2-D speckle tracking echocardiography., Results: RV free wall global and segmental longitudinal deformation was significantly lower in ToF patients compared with ASD and controls (p<0.001). In ToF patients, there was a progressive decrease in strain values from base to apex (p<0.001), while in the ASD group there was a progressive increase (p=0.04). We found strong negative correlations between RV size and RV longitudinal strain measurements, strongest with RV length (R=0.72). When corrected for RV size, all ASD patients had normal or higher deformation values while half of the TOF patients had significantly lower values., Conclusion: Global and regional myocardial RV deformation is differently affected by chronic volume loading in ASD versus TOF patients, especially regarding the apical function. This suggests a different adaptation mechanism in both diseases. Our data also suggest that strain measurements are strongly influenced by ventricular size, which should be taken into consideration when interpreting strain values., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: The presence of end-diastolic forward flow (EDFF) in the pulmonary arteries is commonly regarded as a hallmark of restrictive physiology of the right ventricle (RV) which, in turn, has been associated with a better long-term prognosis in patients after TOF repair. However, controversy persists over the beneficial clinical consequences of restrictive physiology. We aimed at determining the clinical relevance of restrictive physiology late after TOF repair., Methods: Fifty magnetic resonance examinations of 50 patients (age 13.0 ± 2.8 years, 26 males) with repaired TOF were evaluated. The patients were divided into: Group-1 with and Group-2 without EDFF; Group-A with smaller RVs (<170 ml/m2) and Group-B with larger RVs (≥ 170 ml/m2). Maximum oxygen consumption as percent of predicted (VO2max-pred) at a recent exercise test was recorded., Results: Groups-1 and 2 did not differ with regard to their right ventricular end-diastolic volume, pulmonary regurgitant volume, or QRS duration. Patients in Group-1 had a higher VO2max-pred than patients in Group-2 (70.3% versus 54.7% of predicted, p<0.01). In Group-1A versus 2A (RV<170 ml/m(2), with and without EDFF) this difference persisted, but in Group B there was no difference in VO2max-pred between patients with and without EDFF. The flow volume of EDFF correlated with VO2max-pred (r=0.444, p=0.007)., Conclusions: End-diastolic forward flow measured by magnetic resonance is present in patients with small and large RVs. The presence of EDFF is associated with better exercise tolerance, but only in patients with relatively small RVs., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Adverse ventricular-ventricular interactions have been recognized in those with repaired tetralogy of Fallot (TOF) and severe pulmonary regurgitation., Objective: We aimed to examine the impact of pulmonary valve replacement (PVR) on the left heart late after TOF repair., Methods and Results: Left ventricular (LV) volumes and ejection fractions (EF) were analyzed in adults with severe pulmonary regurgitation after TOF repair with cardiac magnetic resonance imaging (CMR) before and after PVR. Thirty-nine patients (median age 33[20-65] years) were reviewed. Post-PVR, LVEF improved significantly in the entire cohort (50 ± 9%→54 ± 7%, p<0.001) and in those with moderately impaired (defined as LVEF ≤ 45%) preoperative LVEF (38 ± 5%→47 ± 6%, p<0.0001), but was not statistically different in those with relatively preserved (defined as LVEF >45%) preoperative LVEF. By multivariate linear regression analysis to evaluate independent CMR predictors of improved LVEF post-PVR for the entire cohort, the only CMR variable to emerge was preoperative LVEF (p=0.012, regression coefficient -0.54, SE 0.13). Whereas PVR resulted in increased LV filling in patients with relatively preserved preoperative LVEF reflected by an increase in LV end-diastolic volumes (77 ± 10→82 ± 16 mL/m(2), p=0.05), LV end-systolic volumes decreased after PVR in patients with impaired preoperative LVEF (65 ± 12→54 ± 10 mL/m(2), p=0.001) but LV end-diastolic volumes were not significantly changed., Conclusion: When LVEF is decreased after TOF repair, PVR appears to have a salutary effect on postoperative LVEF, thereby supporting the concept of recovery of adverse right-left heart interactions. Mechanisms of left heart improvement post-PVR differ depending on degree of preoperative LV systolic dysfunction., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Hypoxia-inducible factor (HIF1A) regulates the myocardial response to hypoxia and hemodynamic load. We investigated the association of HIF1A variants with right-ventricular (RV) remodeling after tetralogy of Fallot (TOF) repair., Methods: Children with TOF were genotyped for three single-nucleotide polymorphisms in HIF1A. Genotypes were analyzed for association with RV myocardial protein expression and fibrosis at complete repair (n = 42) and RV dilation, fractional area change, and freedom from pulmonary valve/conduit replacement on follow-up., Results: In 180 TOF patients, mean age at repair was 1.0 ± 0.8 y with follow-up at 9.0 ± 3.5 y; 82% had moderate to severe pulmonary insufficiency. Freedom from RV reinterventions at 5, 10, and 15 y was 92, 84, and 67%, respectively. Patients with more functioning HIF1A alleles had higher transforming growth factor β1 expression and more fibrosis at initial repair as compared with controls (P < 0.05). During follow-up, patients with more functioning HIF1A alleles showed less RV dilation, better preservation of RV function, and greater freedom from RV reinterventions (P < 0.05). This was confirmed in a replication cohort of 69 patients., Conclusion: In children who have had TOF repair, a lower number of functioning HIF1A alleles was associated with RV dilation and dysfunction, suggesting that hypoxia adaptation in unrepaired TOF may influence RV phenotype after repair.

Objective: We hypothesized that spontaneous inspiratory effort transmitted to the pleural space during airway pressure release ventilation would result in increased lung perfusion after surgery for tetralogy of Fallot or following a cavopulmonary shunt as a consequence of transient decreases in intrapleural pressure., Design: Prospective crossover cohort study., Setting: A tertiary care cardiac pediatric intensive care unit., Patients: Children after tetralogy of Fallot repair, cavopulmonary shunt, or Fontan operation., Interventions: Lung perfusion and cardiac output were measured during airway pressure release ventilation and pressure control ventilation with pressure support, both with and without spontaneous ventilation. Oxygen consumption was measured (mass spectrometer) and lung perfusion/cardiac output calculated (Fick equation). Constant levels of CO₂ and mean airway pressure were targeted in all study phases., Measurements and Main Results: Twenty patients were enrolled in the study, nine after repair of tetralogy of Fallot and 11 after a cavopulmonary shunt. In the absence of spontaneous ventilation, there were no differences in lung perfusion or any of the measured gas exchange or hemodynamic parameters. In the presence of spontaneous ventilation for all patients, mean pulmonary blood flow increased from 2.4 to 2.9 L·min⁻¹M⁻² (p = .02). Oxygen delivery increased from 594 to 774 mL/min/m² (p = .05) in the patients with tetralogy of Fallot patients and from 473 to 518 L·min⁻¹M⁻² (p = .07) in the cavopulmonary shunt group., Conclusion: Ventilation with airway pressure release ventilation (at comparable mean airway pressure) improves lung perfusion compared with pressure control ventilation in children after tetralogy of Fallot repair and cavopulmonary shunt operations. Although this study focused on tetralogy of Fallot and cavopulmonary shunt operations, the improved cardiopulmonary interactions may be beneficial in other situations in which hemodynamics are impaired by positive pressure ventilation.

Background: Diastolic dysfunction of the right ventricle (RV) is common after repair of tetralogy of Fallot. While restrictive physiology in late diastole has been well known, dysfunction in early diastole has not been described. The present study sought to assess the prevalence and mechanism of early diastolic dysfunction of the RV defined as delayed onset of the tricuspid valve (TV) flow after TOF repair., Methods: The study population consisted of 31 children with repaired TOF (mean age ± SD, 12.3 ± 4.1 years) who underwent postoperative cardiovascular magnetic resonance (CMR). The CMR protocol included simultaneous phase-contrast velocity mapping of the atrioventricular valves, which enabled direct comparison of the timing and patterns of tricuspid (TV) and mitral (MV) valve flow. The TV flow was defined to have delayed onset when its onset was > 20 ms later than the onset of the MV flow. The TV and MV flow from 14 normal children was used for comparison. The CMR results were correlated with the findings on echocardiography and electrocardiography., Result: Delayed onset of the TV flow was observed in 16/31 patients and in none of the controls. The mean delay time was 64.81 ± 27.07 ms (8.7 ± 3.2% of R-R interval). The delay time correlated with the differences in duration of the TV and MV flow (55.94 ± 32.88 ms) (r = 0.90, p < 0.001). Delayed onset was associated with prolongation of the RV ejection time in 9 and delayed onset and cessation of the pulmonary arterial flow in 4. Delayed onset was not associated with timing changes in the pulmonary artery in 3. The patients with delayed onset showed reduced RV ejection fraction (p = 0.01). However, the two groups did not show significant differences in TV E/A ratio, ventricular end-diastolic volumes, left ventricular ejection fraction, pulmonary regurgitant fraction, heart rate, PR interval and QRS duration., Conclusions: Early diastolic dysfunction with delayed onset of TV flow is common after TOF repair, and is associated with reduced RV ejection fraction. It is a further manifestation of interventricular dyssynchrony and represent an additional mechanism of ventricular diastolic dysfunction.

Background: tetralogy of Fallot (TOF) is a complex congenital heart disease with clinical and genetic heterogeneity. Of the few known causes, 22q11.2 deletion syndrome (22q11DS) is the most common. We sought to define other clinical subgroups by focusing on cardiac and extracardiac features., Methods: we prospectively screened a cohort of adults with TOF using an established protocol by which subjects were categorized as "syndromic" if they had at least 2 of 3 features: dysmorphic facies, learning difficulties, or voice abnormalities. We then compared the prevalence of cardiac and extracardiac features between subjects in the syndromic group (n = 56) and 112 age- and gender-matched subjects who did not meet our syndromic criteria., Results: the syndromic group was more likely than the nonsyndromic group to have pulmonary atresia and/or major aortopulmonary collateral arteries (25% vs 13%, P = .04). There was a trend toward a higher prevalence of one or more major congenital extracardiac anomalies, primarily involving the musculoskeletal and genitourinary systems (25% vs 13%, P = .06). Later-onset conditions, including neuropsychiatric disorders (32% vs 17%, P = .03), thyroid disorders (20% vs 4%, P = .001), and hearing deficits (20% vs 0, P < .001), were more common in the syndromic group. The syndromic group tested (n = 50) had neither 22q11.2 deletions nor karyotypic anomalies., Conclusion: similar to 22q11DS, adults with TOF meeting screening criteria for a possible genetic syndrome are enriched for more severe cardiac disease and late-onset extracardiac features. Increased awareness of this subgroup with a multisystem condition may be helpful for identifying individuals for referral to medical genetics and optimizing management.

Objective: The mechanisms underlying adverse electro-mechanical interaction after tetralogy of Fallot (TOF) repair remain unclear. This study investigated biventricular dyssynchrony in children with TOF and its relationship to exercise, QRS duration (QRSd) and ventricular mechanics., Methods: 29 asymptomatic children (5-18 years) with repaired TOF were prospectively evaluated by MRI, cardiopulmonary exercise testing and echocardiography at rest and during bicycle exertion. Their dyssynchrony results were compared with those of 44 resting and 27 exercising, age- and sex-matched controls. An intraventricular dyssynchrony index was calculated from the SD of regional time intervals in 12 left ventricular (LV) 'Ts LV-12SD' and eight right ventricular (RV) 'Ts RV-8SD' segments. Ventricular size, volumes, ejection fractions, pulmonary regurgitant volumes and peak oxygen consumption and N-terminal BNP levels were quantified in the patients., Results: Despite moderate RV dilatation (median indexed RV end-diastolic volume 145.2 ml/m(2)) and right bundle branch block (median QRSd 130 ms) compared with controls, children with TOF demonstrated neither RV nor LV dyssynchrony at rest (Ts RV-8SD, 37.9±10.2 vs 44.3±10.3, 95% CI -11.8 to -0.99, p=0.02; Ts LV-12SD, 38.6±16.8 vs 34.0±10.8, 95% CI -1.8 to 11.0, p=0.16). Exercise stress induced biventricular dyssynchrony in patients with TOF but not in controls (Ts RV-8SD, 59.9±34.4 vs 28.2±10.4, p<0.0001, 95% CI 17.2 to 46.3; Ts LV-12SD, 48.0±18.6 vs 31.9±10.7, 95% CI 7.9 to 24.4, p=0.002). This was unrelated to QRSd, ventricular volumes and function, or peak oxygen consumption., Conclusion: Exercise induces biventricular mechanical dyssynchrony in children with TOF.

Tetralogy of Fallot is the most common form of cyanotic congenital heart disease, and one of the first to be successfully repaired by congenital heart surgeons. Since the first procedures in the 1950s, advances in the diagnosis, perioperative and surgical treatment, and postoperative care have been such that almost all those born with tetralogy of Fallot can now expect to survive to adulthood. The startling improvement in outcomes for babies born with congenital heart disease in general-and for those with tetralogy of Fallot in particular-is one of the success stories of modern medicine. Indeed, in many countries adults with tetralogy of Fallot outnumber children. Consequently, new issues have emerged, ranging from hitherto unpredicted medical complications to issues with training for caregivers and resource allocation for this population of survivors. Therefore, evolution of treatment, recognition of late complications, research on disease mechanisms and therapies-with feedback to changes in care of affected children born nowadays-are templates on which the timely discussion of organisation of care of those affected by congenital heart diseases from the fetus to the elderly can be based. Here, we focus on new developments in the understanding of the causes, diagnosis, early treatment, and late outcomes of tetralogy of Fallot, emphasising the continuum of multidisciplinary care that is necessary for best possible lifelong treatment of the 1% of the population born with congenital heart diseases.

Aims: Pulmonary regurgitation (PR) is an important determinant of outcome after tetralogy of Fallot (TOF) repair. The physiologic impact of PR on the right ventricle remains incompletely understood. We hypothesized that a volumetric expression of PR would be a better measure of ventricular preload and a more accurate reflection of degree of insufficiency., Methods and Results: Patients (n = 64) with magnetic resonance imaging after TOF repair were identified. PR was quantified using: (i) phase contrast (PC) analysis of main pulmonary artery flow and (ii) differential right and left ventricular stroke volumes. PR was expressed as a volume (PR(volume)) and percentage of total forward flow (PR(fraction)). The median PC(PR volume) was 19 mL/m(2) (range 0-63 mL/m(2)) and PC(PR fraction) was 29% (range 0-58%). PR(fraction) was found to be highly variable in terms of absolute PR(volume). In those with significant PR, PR(volume) was better than PR(fraction) for the identification of severe RV dilation (receiver-operator curve area: 0.83 vs. 0.71, P = 0.003). PR(volume) using PC analysis was better at differentiating moderate from severe RV dilation (P = 0.005) as compared with PR(fraction) (P = 0.064)., Conclusion: PR(volume) and PR(fraction) are not interchangeable. PR(volume) may be a more accurate reflection of RV preload and may better represent physiologically significant PR as compared with PR(fraction).

Left ventricular (LV) dysfunction is a predictor of adverse outcomes in patients with repaired tetralogy of Fallot (TOF). However, the mechanisms for LV dysfunction are not well understood. The aim of the study was to determine whether the prolonged QRS duration of right branch bundle block was associated with adverse LV mechanics. Seventy-five patients (mean age 31 +/- 2 years) with repaired TOF were studied. LV and right ventricular (RV) volumes and ejection fractions (EFs) were assessed using cardiac magnetic resonance imaging. Vector velocity imaging was used to assess longitudinal strain and intraventricular dyssynchrony. Prolonged QRS duration was associated with increased RV and LV dimensions (p = 0.01) and decreased function (RVEF r = -0.60, p <0.001 and LVEF r = -0.77, p <0.001). In addition, prolonged QRS duration was associated with heterogeneous ventricular mechanical activation and reduced strain in the lateral and septal left ventricle walls. Degree of intraventricular dyssynchrony correlated with LVEF (r = -0.59, p <0.001), QRS duration (r = 0.74, p <0.001), and septal strain (r = 0.70, p <0.001). In conclusion, LV dysfunction and dyssynchrony were observed in patients with TOF and were associated with QRS duration. It was possible that abnormal LV mechanics in combination with RV dysfunction may explain the relation between QRS duration and adverse cardiac outcomes.

Background: Adult patients with repaired tetralogy of Fallot (rTOF) often have diminished exercise capacity. The primary objective of this study was to examine whether abnormalities of biventricular function play a role in exercise limitation in patients with rTOF., Methods: This was a retrospective review of 99 adult patients with rTOF. Right ventricular (RV) and left ventricular (LV) function were assessed echocardiographically using the myocardial performance index (MPI). Maximal oxygen consumption (VO(2) Max) was measured during a level 1 cardiopulmonary exercise test., Results: The mean age of the cohort was 34 +/- 11 years (50% females). Although most of the patients reported good functional capacity, the peak Vo(2)max was decreased at 22 +/- 6 mL/kg per minute (66% +/- 13% predicted Vo(2)max for age and sex). The mean RV and LV MPI were 0.30 +/- 0.07 and 0.42 +/- 0.09, respectively. In the multivariate model, higher RV MPI (P = .04) and LV MPI (P = .005) values, representing impaired ventricular function, were associated with diminished Vo(2)max. There was a significant correlation between the RV and LV MPI (r = 0.54, P = .001)., Conclusions: Impairment of RV and LV function, as measured by MPI, is associated with diminished exercise capacity in patients with repaired tetralogy of Fallot. Furthermore, there is a linear relationship between the RV and LV function suggesting that ventricular interactions are contributing to the limited exercise capacity in this group of patients. Strategies aimed at preserving biventricular function or improving adverse ventricular interactions could help to improve functional capacity in these patients.

This article describe the primary determinants of pulmonary regurgitation after the repair of tetralogy of Fallot. Furthermore, the methods by which pulmonary regurgitation is measured and some of the pitfalls therein are highlighted.

The physiopathology of right ventricular failure after repair of tetralogy of Fallot is complex. While primarily reflecting chronic volume overload resulting from pulmonary regurgitation, its determinants reflect a varied contribution of different boundary conditions. The competence of the outflow tract, right ventricular afterload, and the integrity of right ventricular diastolic performance are all crucial elements to the long-term responses of the right ventricle. When adverse, chronic right ventricular volume overload may lead to exercise intolerance, congestive cardiac failure, and both atrial and ventricular arrhythmia. Indeed, there appears to be a close relationship between the mechanical properties of the right ventricle and its electrical stability. In this chapter the determinants of pulmonary incompetence and its secondary effects on right ventricular function and performance, and mechano-electric interactions will be discussed.

With increasing follow-up of patients after surgical repair of tetralogy of Fallot, the long-term complications of chronic pulmonary regurgitation (PR), ventricular dilation, electrical inhomogeneity and myocardial scarring are becoming apparent. In this article we review the existing literature regarding the deleterious effects of chronic PR in these patients and the current data regarding the timing and mode of intervention.

Background: The importance of pulmonary regurgitation (PR) after repair of tetralogy of Fallot (TOF) is increasingly recognized, but little is known regarding its underlying mechanisms. This phase-contrast cine magnetic resonance (PC MR) study was performed to evaluate the relative contribution of each lung to total regurgitant volume., Methods and Results: Twenty-two patients with significant PR underwent a PC MR 3 to 16 years after repair of TOF. Regurgitant fraction of the main pulmonary artery was 39+/-10%. Regurgitant fraction of the left pulmonary artery (LPA; 46+/-18%) was greater than that of the right pulmonary artery (34+/-16%; P=0.002). The average contribution of the LPA to the total regurgitant flow volume was 54+/-19%, whereas its average contribution to the total forward flow volume was 44+/-13% (P=0.002). In 4 patients, regurgitant flow in the LPA accounted for 75% to 100% of the total regurgitant flow. There was a linear relationship between regurgitant fraction and fraction of the regurgitant flow duration in the main pulmonary artery (P<0.001) and right pulmonary artery (P=0.001) but not in the LPA (P=0.129)., Conclusions: PR after repair of TOF is commonly associated with differential regurgitation in the branch pulmonary arteries, which is usually greater in the LPA. Although the cause of this disparity requires further investigation, those patients with a significant unilateral contribution to total PR may be amenable to localized techniques to reduce regurgitation.

Abstract Background Diastolic dysfunction of the right ventricle (RV) is common after repair of tetralogy of Fallot. While restrictive physiology in late diastole has been well known, dysfunction in early diastole has not been described. The present study sought to assess the prevalence and mechanism of early diastolic dysfunction of the RV defined as delayed onset of the tricuspid valve (TV) flow after TOF repair. Methods The study population consisted of 31 children with repaired TOF (mean age ± SD, 12.3 ± 4.1 years) who underwent postoperative cardiovascular magnetic resonance (CMR). The CMR protocol included simultaneous phase-contrast velocity mapping of the atrioventricular valves, which enabled direct comparison of the timing and patterns of tricuspid (TV) and mitral (MV) valve flow. The TV flow was defined to have delayed onset when its onset was > 20 ms later than the onset of the MV flow. The TV and MV flow from 14 normal children was used for comparison. The CMR results were correlated with the findings on echocardiography and electrocardiography. Result Delayed onset of the TV flow was observed in 16/31 patients and in none of the controls. The mean delay time was 64.81 ± 27.07 ms (8.7 ± 3.2% of R-R interval). The delay time correlated with the differences in duration of the TV and MV flow (55.94 ± 32.88 ms) (r = 0.90, p < 0.001). Delayed onset was associated with prolongation of the RV ejection time in 9 and delayed onset and cessation of the pulmonary arterial flow in 4. Delayed onset was not associated with timing changes in the pulmonary artery in 3. The patients with delayed onset showed reduced RV ejection fraction (p = 0.01). However, the two groups did not show significant differences in TV E/A ratio, ventricular end-diastolic volumes, left ventricular ejection fraction, pulmonary regurgitant fraction, heart rate, PR interval and QRS duration. Conclusions Early diastolic dysfunction with delayed onset of TV flow is common after TOF repair, and is associated with reduced RV ejection fraction. It is a further manifestation of interventricular dyssynchrony and represent an additional mechanism of ventricular diastolic dysfunction.

The right ventricle has frequently been described as the forgotten ventricle in the circulation. However, its importance both in acquired and congenital heart disease is now unquestioned. This recognition has led to improved risk stratification and development of algorithms for intervention, which incorporate measurements of right ventricular function as key components of the assessment of many conditions. Indeed, such has been the emphasis on characterizing right ventricular dysfunction; the contribution of left ventricular dysfunction to the outcomes of diseases traditionally thought of as right sided has perhaps been underappreciated. In this review, we remind ourselves of the biventricular nature of almost all cardiovascular diseases and, in particular, how the left ventricle can both be a culprit in causation of, and a potential therapeutic target for, late morbidity and mortality in congenital heart disease. [ABSTRACT FROM AUTHOR]

The article discusses the various situations in which pulmonary regurgitation occurs, including repaired Tetralogy of Fallot. It has been found that many patients with right ventricle to pulmonary artery conduit will develop a combination of obstruction and regurgitation across the conduit. Valvar pulmonary stenosis treated with balloon dilatation or surgery can lead to significant pulmonary regurgitation that requires valve replacement.

The physiopathology of right ventricular failure after repair of tetralogy of Fallot is complex. While primarily reflecting chronic volume overload resulting from pulmonary regurgitation, its determinants reflect a varied contribution of different boundary conditions. The competence of the outflow tract, right ventricular afterload, and the integrity of right ventricular diastolic performance are all crucial elements to the long-term responses of the right ventricle. When adverse, chronic right ventricular volume overload may lead to exercise intolerance, congestive cardiac failure, and both atrial and ventricular arrhythmia. Indeed, there appears to be a close relationship between the mechanical properties of the right ventricle and its electrical stability. In this chapter the determinants of pulmonary incompetence and its secondary effects on right ventricular function and performance, and mechano-electric interactions will be discussed. [Copyright &y& Elsevier]