Dapagliflozin has been shown to improve outcomes in adult heart failure (HF) but has not been widely evaluated in pediatrics. The present study describes dapagliflozin use and adverse events (AEs) in infants and children with HF. This descriptive, single-center retrospective review included pediatric patients with HF or recent heart transplant who were started on dapagliflozin and treated for any duration between 9/2020 and 5/2024. Descriptive statistics were used to summarize clinical characteristics, AEs, anthropometrics, and laboratory values during treatment. Of 120 patients (40.8

Quantification of the regurgitation fraction (RF) in pediatric patients requires cardiac magnetic resonance imaging (CMR). Three-dimensional echocardiography (3DE) can be used to measure right and left ventricular volumes and therefore has the potential to calculate the RF by comparison of stroke volumes. 3DE volume acquisitions can be acquired in only a few heartbeats, often as part of a standard pediatric study. This study compared the quantification of single valve regurgitation by 3DE with CMR, the latter serving as the gold standard. Patients < 18 years of age were included in the study if they had mild regurgitation of one valve and a biventricular circulation. Patients were excluded if they had more than mild regurgitation of another valve, or a significant shunt lesion. Full right and left ventricular volume data sets were obtained using a Philips -iE33 or EPIQ CVx machine (X5 or X7 ultrasound probe) as a part of studies done for clinical reasons. 3DE volumes and RFs were analyzed retrospectively by blinded echocardiographers using 4D Cardioview (Tomtec Imaging Systems) and compared with ventricular volumes and RF obtained by CMR. Additionally, 3DE-derived ventricular volume ratios (VVR) were analyzed for correlation and agreement with CMR. Inter- and intra-observer reliability were assessed for 3DE ventricular volumes and RF. 43 patients were included with 7 patients having two separate paired 3DE and CMR studies. The median patient age was 8.4 (IQR; 3.6–12.0) years. Anesthesia, for the CMR study, was used for 20 (40

Importance:Studies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking. Objective:To evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in children after heart transplant. Design, Setting, and Participants:Multicenter, randomized, open-label, clinical trial enrolling 211 patients who were alive 6 months after pediatric heart transplant at 25 US sites from February 2018 to August 2020. The last date of follow-up was April 17, 2023. Interventions:Participants were randomized to receive everolimus and low-dose tacrolimus (n = 107) or standard-dose tacrolimus and mycophenolate mofetil (n = 104) for 30 months. Main Outcomes and Measures:The primary efficacy end point was the MATE-3 score at 30 months, a validated composite ordinal end point including acute cellular rejection, CAV, and CKD. The primary safety end point was the MATE-6 score, encompassing the MATE-3 score plus antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder. Results:Among 211 children randomized, the mean age was 8.2 (SD, 6.3) years, 97 (46%) underwent transplant for congenital heart disease, and 49 (23%) were treated for rejection before 6 months. At 30 months, the mean MATE-3 score did not differ between the 2 treatment groups (mean difference, -0.32; 95% CI, -0.90 to 0.20; P = .16). The mean MATE-6 score was no higher in the everolimus group than in the mycophenolate group (baseline-adjusted mean difference, -0.40; 95% CI, -1.81 to 0.93), meeting the success criterion for safety (noninferiority margin <3). There were no differences in graft survival, MATE-free survival, or freedom from any individual MATE. Everolimus was associated with greater improvement in estimated glomerular filtration rate at 12 months (mean difference, 10.5 mL/min/1.73 m2; 95% CI, 1.09-19.91 mL/min/1.73 m2) and a lower incidence of CMV infection (hazard ratio, 0.50; 95% CI, 0.26-0.93). Conclusions and Relevance:Among 6-month pediatric heart transplant survivors, everolimus and low-dose tacrolimus did not differ from tacrolimus and mycophenolate in preventing the composite of cellular rejection, CAV, and CKD at 30 months. However, everolimus and low-dose tacrolimus appear to be safe based on the total burden of 6 MATEs and may be associated with improved kidney function and less CMV infection. Trial Registration:ClinicalTrials.gov Identifier: NCT03386539.

Background Reduced biventricular global function index (BVGFI) is associated with adverse outcomes in repaired tetralogy of Fallot (rTOF). The change in BVGFI associated with pulmonary valve replacement (PVR) is unknown. Objectives To characterize BVGFI following PVR in rTOF and identify pre-PVR factors associated with severely depressed post-PVR BVGFI. Methods Single-center retrospective cohort study of rTOF patients with a cardiac magnetic resonance (CMR) examination within 1 year before and 2 years after their first PVR and no interval cardiac procedures (n=133). CMR parameters between rTOF and normal controls (n=136) were compared. BVGFI was categorized as normal (≥46.2), mild-moderately depressed (40.0-46.1), or severely depressed (<40.0). Pre- vs. post-PVR changes and pre-PVR correlates of severely depressed post-PVR BVGFI were explored. Results When adjusted for age and sex, pre-PVR BVGFI was lower in patients with rTOF compared to controls (47.7±0.6 vs. 56.0±0.5, p<0.001), with 48% of rTOF patients having subnormal pre-PVR BVGFI. Overall, compared with pre-PVR values, mean BVGFI did not change after PVR (46.6±7.7 vs. 45.6±6.7, p=0.28), while RVGFI declined from 49.6±10.2 pre-PVR to 46.1±9.0 post-PVR (p=0.003). Among patients with normal pre-PVR BVGFI (n=69), 64% remained normal, whereas 36% declined. Of those with severely depressed pre-PVR BVGFI (n=24), 50% remained severely depressed, and only 4% achieved normalization of BVGFI after PVR. Factors independently associated with severely depressed post-PVR BVGFI were lower pre-PVR BVGFI, male sex, moderate or severe pulmonary regurgitation (PR), and higher left ventricular end-systolic volume index (LVESVi). Type of pre-PVR hemodynamic load was not associated with the odds of severely depressed BVGFI post-PVR. Conclusions BVGFI is depressed in about half of rTOF patients pre-PVR and did not significantly change post-PVR remaining stable in most patients. Lower pre-PVR BVGFI, male sex, moderate or severe PR, and higher LVESVi are independently associated with severely depressed post-PVR BVGFI.

OBJECTIVES Parachute left atrioventricular valve (LAVV) complicates atrioventricular septal defect (AVSD) repair. We evaluate outcomes of AVSD patients with parachute LAVV and identify risk factors for adverse outcomes.METHODS We evaluated all patients undergoing repair of AVSD with parachute LAVV from 2012 to 2021. The primary outcome was a composite of time-to-death, LAVV reintervention and development of greater than or equal to moderate LAVV dysfunction (greater than or equal to moderate LAVV stenosis and/or LAVV regurgitation). Event-free survival for the composite outcome was estimated using Kaplan-Meier methodology and competing risks analysis. Cox proportional hazards regression was used to identify predictors of the primary outcome.RESULTS A total of 36 patients were included with a median age at repair of 4 months (interquartile range 2.3-5.5 months). Over a median follow-up of 2.6 years (interquartile range 1.0-5.6 years), 6 (17%) patients underwent LAVV reintervention. All 6 patients who underwent LAVV reintervention had right-dominant AVSD. Sixteen patients (44%) met the composite outcome, and all did so within 2 years of initial repair. Transitional AVSD (versus complete), prior single-ventricle palliation, leaving the cleft completely open and greater than or equal to moderate preoperative LAVV regurgitation were associated with a higher risk of LAVV reintervention in univariate analysis. In multivariate analysis, leaving the cleft completely open was associated with the composite outcome.CONCLUSIONS Repair of AVSD with parachute LAVV remains a challenge with a significant burden of LAVV reintervention and dysfunction in medium-term follow-up. Unbalanced, right-dominant AVSDs are at higher risk for LAVV reintervention. Leaving the cleft completely open might independently predict poor overall outcomes and should be avoided when possible.Clinical trial registration number IRB-P00041642 Repair of atrioventricular septal defects (AVSDs) is now routinely performed in infancy with good surgical outcomes and a low risk of reoperation [1-3].

BACKGROUND:Late hypertension (HTN) after coarctation of the aorta (CoA) repair contributes to higher morbidity and mortality. An association between transverse aortic arch (TAA) hypoplasia and HTN has been found, but its relationship with surgical strategy is unclear. We studied the association between late HTN and initial surgical strategy pertaining to the TAA. METHODS:We retrospectively reviewed patients who underwent surgical repair of CoA during infancy with at least 10 years of follow-up, excluding those with atypical coarctation, major associated heart defects, and residual isthmic narrowing. TAA diameter z-score immediately postrepair was measured as a marker of surgical strategy. Systemic HTN at latest follow-up was assessed using standard criteria. RESULTS:A total of 130 patients underwent surgical repair of CoA (76% via thoracotomy, 24% via sternotomy) with resection and end-to-end anastomosis (62%), extended end-to-end anastomosis (30%), subclavian flap (5%), or arch repair with patch (4%), at a median age of 14 days (interquartile range [IQR], 7-62 days). The median postrepair TAA diameter z-score was -2.04 (IQR, -2.69 to 1.24). At a mean follow-up of 17.3 years, 43 of the 130 patients (33%) developed HTN. After controlling for age at repair, sex, and presence of a genetic syndrome, HTN was not associated with immediate postrepair TAA diameter z-score (P = .41), type of surgical incision (P = .99), or type of surgical repair (P = .66). CONCLUSIONS:In patients undergoing surgical repair of CoA during infancy, late HTN was not associated with immediate postrepair TAA size or surgical strategy pertaining to the TAA. These results suggest that factors other than surgical strategy, such as differential growth of the TAA during childhood, may be important.

BACKGROUND:The interstage period after discharge from stage 1 palliation carries high morbidity and mortality. The impact of social determinants of health on interstage outcomes is not well characterized. We assessed the relationship between childhood opportunity and acute interstage outcomes. METHODS:Infants discharged home after stage 1 palliation in the National Pediatric Quality Improvement Collaborative Phase II registry (2016-2022) were retrospectively reviewed. Zip code-level Childhood Opportunity Index (COI), a composite metric of 29 indicators across education, health and environment, and socioeconomic domains, was used to classify patients into 5 COI levels. Acute interstage outcomes included death or transplant listing, unplanned readmission, intensive care unit admission, unplanned catheterization, and reoperation. The association between COI level and acute interstage outcomes was assessed using logistic regression with sequential adjustment for potential confounders. RESULTS:The analysis cohort included 1837 patients from 69 centers. Birth weight (P<0.001) and proximity to a surgical center at birth (P=0.02) increased with COI level. Stage 1 length of stay decreased (P=0.001), and exclusive oral feeding rate at discharge increased (P<0.001), with higher COI level. More than 98% of patients in all COI levels were enrolled in home monitoring. Death or transplant listing occurred in 101 (5%) patients with unplanned readmission in 987 (53%), intensive care unit admission in 448 (24%), catheterization in 345 (19%), and reoperation in 83 (5%). There was no difference in the incidence or time to occurrence of any acute interstage outcome among COI levels in unadjusted or adjusted analysis. There was no interaction between race and ethnicity and childhood opportunity in acute interstage outcomes. CONCLUSIONS:Zip code COI level is associated with differences in preoperative risk factors and stage 1 palliation hospitalization characteristics. Acute interstage outcomes, although common across the spectrum of childhood opportunity, are not associated with COI level in an era of highly prevalent home monitoring programs. The role of home monitoring in mitigating disparities during the interstage period merits further investigation.

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. (Am Heart J 2024;274:95- 101.)

Background Robust risk assessment is crucial for the growing repaired tetralogy of Fallot population at risk of major adverse clinical outcomes; however, current tools are hindered by lack of validation. This study aims to develop and validate a risk prediction model for death in the repaired tetralogy of Fallot population. Methods and Results Patients with repaired tetralogy of Fallot enrolled in the INDICATOR (International Multicenter Tetralogy of Fallot Registry) cohort with clinical, arrhythmia, cardiac magnetic resonance, and outcome data were included. Patients from London, Amsterdam, and Boston sites were placed in the development cohort; patients from the Toronto site were used for external validation. Multivariable Cox regression was used to evaluate factors associated with time from cardiac magnetic resonance until the primary outcome: all‐cause death. Of 1552 eligible patients (n=1221 in development, n=331 in validation; median age at cardiac magnetic resonance 23.4 [interquartile range, 15.6–35.6] years; median follow up 9.5 years), 102 (6.6%) experienced the primary outcome. The multivariable Cox model performed similarly during development (concordance index, 0.83 [95% CI, 0.78–0.88]) and external validation (concordance index, 0.80 [95% CI, 0.71–0.90]) and identified older age at cardiac magnetic resonance, obesity, type of tetralogy of Fallot repair, higher right ventricular end‐systolic volume index, and lower biventricular global function index as independent predictors of death. A risk‐scoring algorithm dividing patients into low‐risk (score ≤4) versus high‐risk (score >4) groups was validated to effectively discriminate risk of death (15‐year survival of 95% versus 74%, respectively; P <0.001). Conclusions This externally validated mortality risk prediction algorithm can help identify vulnerable patients with repaired tetralogy of Fallot who may benefit from targeted interventions.

Background: Identification of risk factors for biventricular (BiV) repair in children with hypoplastic left ventricles (HLV) has been challenging. We sought to identify preoperative cardiovascular magnetic resonance (CMR) predictors of outcome in patients with HLVs who underwent BiV repair, with a focus on the mitral valve (MV). Methods: Single-center retrospective analysis of preoperative CMRs on patients with HLV (<= 50 mL/m2) and no endocardial fibroelastosis who underwent BiV repair from 2005-2022. CMR measurements included MV orifice area in diastole. The primary composite outcome included time to death, transplant, BiV takedown, heart failure admission, left atrial decompression, or unexpected reoperation; and the secondary outcome included more than or equal to moderate mitral stenosis and/or regurgitation. Results: Median follow-up was 0.7 (interquartile range 0.1, 2.2) years. Of 122 patients [59 atrioventricular canal (AVC) and 63 non-AVC] age 3 +/- 2.8 years at the time of BiV repair, freedom from the primary outcome at 2 years was 53% for AVC and 69% for non-AVC (log rank p = 0.12), and freedom from the secondary outcome at 2 years was 49% for AVC and 79% for non-AVC (log rank p < 0.01). Independent predictors of primary outcome for AVC patients included MV orifice area z-score < -2 and transitional AVC; for non-AVC patients, predictors included MV orifice area z-score < -2, abnormal MV anatomy, and conal-septal ventricular septal defect. Independent predictors of secondary outcome for AVC patients included older age at surgery, transitional AVC, and transposition of the great arteries. Conclusion: In children with HLV, low MV orifice area and pre-existing MV pathology are risk factors for adverse outcome after BiV repair.

Background:FAV is offered to fetuses with severe aortic valve stenosis and evolving hypoplastic left heart syndrome. An inferential analysis of TS and SAE in a large series has not been reported. Objectives:The purpose of this study was to determine factors associated with fetal aortic valvuloplasty (FAV) technical success (TS) and serious adverse events (SAEs). Methods:Retrospective, single-center, cohort analysis of attempted FAV from March 1, 2000, to December 31, 2020. The primary outcome was the TS of FAV, and the secondary outcome was the presence of an SAE. Results:A total of 165 FAVs were attempted in 163 patients with a median gestational age of 24.6 weeks (IQR: 22.9-27.1 weeks). FAV TS was 85% (141/165) and was higher in the 2010 to 2020 era (94% [85/90] vs 75% [56/75]; P < 0.001). Pre-FAV echocardiographic left ventricle (LV) long axis dimension z-score >-0.10 (P < 0.001) and higher LV ejection fraction (P = 0.037) were independently associated with a higher odds of TS. There were 117 SAEs in 67 attempted FAVs (41%), 13 of which were fetal deaths (7.9%). By classification and regression tree analysis, gestational age <21 weeks or in older fetuses, a procedure time of ≥39.6 minutes was associated with higher SAE rate. In the multivariable logistic regression model correcting for gestational age, fetuses with an LV end-diastolic volume <4.09 mL had an age-adjusted OR of 4.71 (95% CI: 1.67-13.29; P = 0.004) for experiencing an SAE. Conclusions:TS of FAV has improved over time, and failure is associated with smaller fetal left heart sizes. SAEs are common and are associated with smaller left hearts and longer procedure times.

Background:The right ventricle (RV) has complex geometry and function, with motion along three separate axes-longitudinal, radial, and anteroposterior. Quantitative assessment of RV function by two-dimension echocardiography (2DE) has been limited as a consequence of this complexity, whereas newer three dimensional (3D) analysis offers the potential for more comprehensive assessment of the contributors to RV function. The aims of this study were to quantify the longitudinal, radial and anteroposterior components of global RV function using 3D echocardiography in a cohort of healthy children and to examine maturational changes in these parameters. Methods:Three-dimensional contours of the RV were generated from a cohort of healthy pediatric patients with structurally normal hearts at two centers. Traditional 2D and 3D echo characteristics were recorded. Using offline analysis of 3D datasets, RV motion was decomposed into three components, and ejection fractions (EF) were calculated (longitudinal-LEF; radial-REF; and anteroposterior-AEF). The individual decomposed EF values were indexed against the global RVEF. Strain values were calculated as well. Results:Data from 166 subjects were included in the analysis; median age was 13.5 years (range 0 to 17.4 years). Overall, AEF was greater than REF and LEF (29.2 ± 6.2% vs. 25.1 ± 7.2% and 25.7 ± 6.0%, respectively; p < 0.001). This remained true when indexed to overall EF (49.8 ± 8.7% vs. 43.3 ± 11.6% and 44.4 ± 10%, respectively; p < 0.001). Age-related differences were present for global RVEF, REF, and all components of RV strain. Conclusions:In healthy children, anteroposterior shortening is the dominant component of RV contraction. Evaluation of 3D parameters of the RV in children is feasible and enhances the overall understanding of RV function, which may allow improvements in recognition of dysfunction and assessment of treatment effects in the future.

BackgroundFor infants with single ventricle heart disease, the time after stage 2 procedure (S2P) is believed to be a lower risk period compared with the interstage period; however, significant morbidity and mortality still occur.ObjectivesThis study aimed to identify risk factors for mortality or transplantation referral between S2P surgery and the first birthday.MethodsRetrospective cohort analysis of infants in the National Pediatric Cardiology Quality Improvement Collaborative who underwent staged single ventricle palliation from 2016 to 2022 and survived to S2P. Multivariable logistic regression and classification and regression trees were performed to identify risk factors for mortality and transplantation referral after S2P.ResultsOf the 1,455 patients in the cohort who survived to S2P, 5.2% died and 2.3% were referred for transplant. Overall event rates at 30 and 100 days after S2P were 2% and 5%, respectively. Independent risk factors for mortality and transplantation referral included the presence of a known genetic syndrome, shunt type at stage 1 procedure (S1P), tricuspid valve repair at S1P, longer time to extubation and reintubation after S1P, ≥ moderate tricuspid regurgitation prior to S2P, younger age at S2P, and the risk groups identified in the classification and regression tree analysis (extracorporeal membrane oxygenation after S1P and longer S2P cardiopulmonary bypass time without extracorporeal membrane oxygenation).ConclusionsMortality and transplantation referral rates after S2P to 1 year of age remain high ∼7%. Many of the identified risk factors after S2P are similar to those established for interstage factors around the S1P, whereas others may be unique to the period after S2P.

Objective A subset of patients with borderline hypoplastic left heart may be candidates for single to biventricular conversion, but long-term morbidity and mortality persist. Prior studies have shown conflicting results regarding the association of preoperative diastolic dysfunction and outcome, and patient selection remains challenging. Methods Patients with borderline hypoplastic left heart undergoing biventricular conversion from 2005 to 2017 were included. Cox regression identified preoperative factors associated with a composite outcome of time to mortality, heart transplant, takedown to single ventricle circulation, or hemodynamic failure (defined as left ventricular end-diastolic pressure >20 mm Hg, mean pulmonary artery pressure >35 mm Hg, or pulmonary vascular resistance >6 international Woods units). Results Among 43 patients, 20 (46%) met the outcome, with a median time to outcome of 5.2 years. On univariate analysis, endocardial fibroelastosis, lower left ventricular end-diastolic volume/body surface area (when <50 mL/m2), lower left ventricular stroke volume/body surface area (when <32 mL/m2), and lower left:right ventricular stroke volume ratio (when <0.7) were associated with outcome; higher preoperative left ventricular end-diastolic pressure was not. Multivariable analysis demonstrated that endocardial fibroelastosis (hazard ratio, 5.1, 95% confidence interval, 1.5-22.7, P = .033) and left ventricular stroke volume/body surface area 28 mL/m2 or less (hazard ratio, 4.3, 95% confidence interval, 1.5-12.3, P = .006) were independently associated with a higher hazard of the outcome. Approximately all patients (86%) with endocardial fibroelastosis and left ventricular stroke volume/body surface area 28 mL/m2 or less met the outcome compared with 10% of those without endocardial fibroelastosis and with higher stroke volume/body surface area. Conclusions History of endocardial fibroelastosis and smaller left ventricular stroke volume/body surface area are independent factors associated with adverse outcomes among patients with borderline hypoplastic left heart undergoing biventricular conversion. Normal preoperative left ventricular end-diastolic pressure is insufficient to reassure against diastolic dysfunction after biventricular conversion.

Optimal reverse remodeling of the right ventricle (RV), a sentinel goal of pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot, is not fully predicted by volume-based pre-PVR parameters. Our objectives were to characterize novel geometric RV parameters in patients receiving PVR and in controls, and to identify associations between these parameters and chamber remodeling post-PVR. Secondary analysis was performed on cardiac magnetic resonance (CMR) data from 60 patients enrolled in a randomized trial of PVR with and without surgical RV remodeling. 20 healthy age-matched subjects served as controls. The primary outcome was optimal post-PVR RV remodeling (end-diastolic volume index (EDVi) ≤ 114 ml/m2 and ejection fraction (EF) ≥ 48