Expanding the phenotypic spectrum of NOTCH1 variants: clinical manifestations in families with congenital heart disease.

Pathogenic variants in NOTCH1 are associated with non-syndromic congenital heart disease (CHD) and Adams-Oliver syndrome (AOS). The clinical presentation of individuals with damaging NOTCH1 variants is characterized by variable expressivity and incomplete penetrance; however, data on systematic phenotypic characterization are limited. We report the genotype and phenotype of a cohort of 33 individuals (20 females, 13 males; median age 23.4 years, range 2.5-68.3 years) from 11 families with causative NOTCH1 variants (9 inherited, 2 de novo; 9 novel), ascertained from a proband with CHD. We describe the cardiac and extracardiac anomalies identified in these 33 individuals, only four of whom met criteria for AOS. The most common CHD identified was tetralogy of Fallot, though various left- and right-sided lesions and septal defects were also present. Extracardiac anomalies identified include cutis aplasia (5/33), cutaneous vascular anomalies (7/33), vascular anomalies of the central nervous system (2/10), Poland anomaly (1/33), pulmonary hypertension (2/33), and structural brain anomalies (3/14). Identification of these findings in a cardiac proband cohort supports NOTCH1-associated CHD and NOTCH1-associated AOS lying on a phenotypic continuum. Our findings also support (1) Broad indications for NOTCH1 molecular testing (any familial CHD, simplex tetralogy of Fallot or hypoplastic left heart); (2) Cascade testing in all at-risk relatives; and (3) A thorough physical exam, in addition to cardiac, brain (structural and vascular), abdominal, and ophthalmologic imaging, in all gene-positive individuals. This information is important for guiding the medical management of these individuals, particularly given the high prevalence of NOTCH1 variants in the CHD population.

Surgical Melody Mitral Valve: A Paradigm Shift for Infants With Unrepairable Mitral Valve Disease.

BACKGROUND: The Melody valve (Medtronic, Minneapolis, MN) for mitral valve replacement (MVR) (MelodyMVR) has been an effective strategy to treat unrepairable mitral valve disease in small children. This study analyzed survival, durability, and complications of the MelodyMVR strategy. METHODS: Patients who underwent MelodyMVR between 2014 and 2023 were included. Transplant-free survival was analyzed with Kaplan-Meier analysis. The Fine and Gray subdistribution method was applied to quantify the cumulative incidence. RESULTS: Twenty-five patients underwent MelodyMVR. Median age and weight were 6.3 months (interquartile range, 4.4-15.2 months) and 6.36 kg (interquartile range, 4.41-7.57 kg). Fifteen patients (60%) had congenital mitral valve disease and 13 (52%) had dominant mitral regurgitation. The median diameter of the implanted Melody was 16 mm (interquartile range, 14-18 mm). Mortality at 6 months, 1 year, and 5 years was 8.3% (95% CI, 2.2%-29.4%), 12.5% (95% CI, 4.2%-33.9%), and 17.6% (95% CI, 7.0%-40.7%), respectively. Two hospital survivors (8%) required early Melody replacement. Competing risk analysis showed that ∼50% of patients underwent mechanical MVR by 3.5 years after MelodyMVR. Freedom from bleeding and thrombosis at 4 years was 87.5% (95% CI, 74.2%-100%). Eleven patients underwent subsequent mechanical MVR with no deaths. One (9%) required pacemaker implantation after mechanical MVR. CONCLUSIONS: MelodyMVR provides reasonable early and medium-term survival in small children and a high rate of successful bridge to mechanical MVR. MelodyMVR is associated with minimal pacemaker requirement, bleeding, and thrombosis. Early Melody functional deterioration necessitates early repeat MVR, which can be achieved with minimal morbidity and mortality.

Melody Mitral Valve Is a Promising Alternative to Mechanical Valve Replacement for Young Children.

PURPOSE: The purpose of this study was to compare outcomes of Melody mitral valve to mechanical mitral valve replacement (MVR) for young children. DESCRIPTION: Children who underwent Melody MVR from 2014 to 2020 were case-matched to mechanical MVR patients. Transplant-free survival and cumulative incidence of reintervention were compared. A subanalysis was performed for infants aged < 1 year (9 Melody MVRs and their matches). EVALUATION: Twelve children underwent Melody MVR. Two children (17%) salvaged from mechanical support died. Five of 10 survivors (50%) had subsequent MVR. At 1 and 3 years, transplant-free survival (Melody: 83%, 83%; mechanical: 83%, 67%; P = .180) and reintervention (Melody: 9%, 39%; mechanical: 0%, 18%; P = .18) were equivalent between groups. For children < 1 year of age, Melody MVR had a modest survival benefit (Melody: 89%, 89%; mechanical: 80%, 60%; P = .046), while rate of reintervention remained equivalent (Melody: 13%, 32%; mechanical: 0%, 22%; P = .32). CONCLUSIONS: For patients < 1 year old, Melody MVR offers a promising alternative and is a reasonable bridge to mechanical MVR, which can be performed safely at an older age. Further studies are necessary to corroborate these findings.

Biventricular Repair in Borderline Left Hearts: Insights From Cardiac Magnetic Resonance Imaging.

Background: Cardiac magnetic resonance imaging (CMR) may augment 2-dimensional (2D) echocardiography in decision-making for biventricular repair in borderline hypoplastic left hearts. Objectives: This study evaluates: 1) the relationship between 2D echocardiography and CMR; 2) imaging variables affecting assignment to biventricular vs non-biventricular management; and 3) variables affecting transplant-free biventricular survival. Methods: We reviewed clinical, echocardiographic, and CMR data in 67 infants, including CMR-determined ascending aortic (AAo) flow and comparable left ventricular end-diastolic volume indexed (LVEDVi) by 2D-echocardiography and CMR. Results: Treatment assignment to biventricular repair was either direct (BV, n = 45) or with a bridging hybrid procedure (H1-BV, n = 12). Echocardiographic LVEDVi was <20 mL/m2 in 83% of biventricular repair infants and underestimated CMR-LVEDVi by 16.8 mL/m2. AAo flows had no/weak correlation with aortic and mitral valve z-scores or LVEDVi. AAo flows differed between BV, H1-BV, and single-ventricle groups (median): 2.1, 1.7, and 0.7 L/min/m2, respectively. Important variables for treatment assignment were presence of endocardial fibroelastosis, AAo flow, and mitral valve z-score. Biventricular repair was achieved in 54. The median follow-up was 8.0 (0.1-16.4) years. Transplant-free biventricular survival was 96%, 82%, and 77% at 1, 5, and 10 years, respectively. Patients without aortic coarctation repair were at higher risk of death, transplantation, or single-ventricle conversion (HR: 54.3; 95% CI: 6.3-47.1; P < 0.001) during follow-up. AAo flow had a smaller nonlinear effect with hazard ratio increasing at lower flows. Conclusions: Historical 2D echocardiographic criteria would have precluded many patients from successful biventricular repair. AAo flow, an integrative index of left heart performance, was important in assigning patients to a biventricular circulation and affected survival. Biventricular survival was strongly associated with the need for aortic coarctation repair.

Current-Era Outcomes of Balloon Aortic Valvotomy in Neonates and Infants.

Background: The optimal initial treatment pathway for aortic valve stenosis remains debated. Objectives: The objective of this study was to review current outcomes of balloon aortic valvotomy (BAV) in neonates and infants. Methods: Neonates and infants with a biventricular circulation treated with BAV between 2004 and 2019 were reviewed. Results: One hundred thirty-nine infants (48% neonates) with median (Q1, Q3) age of 33(7, 84) days and weight 4.0 (3.4, 5.1) kg were followed up for 7.1 (3.3, 11.0) years. BAV reduced peak-to-peak gradient from mean (SD) 52 (16) mmHg to 18 (12) mmHg; P < 0.001. Aortic regurgitation (AI) increased with time after BAV. Three children died during follow-up. Fifty-one reinterventions (26 BAV, 19 aortic valve replacements [AVRs], and 6 surgical valvotomies) were performed on 40 children. Freedom from AVR (95% CI) was 96% (93%-99%) at 1, 91% (86%-96%) at 5, and 86% (79%-93%) at 10 years. The predictors of AVR were a unicommissural valve (hazard ratio [HR] [95% CI]: 3.7 [1.4-9.6]; P = 0.007) and moderate to severe AI after index BAV (HR [95% CI]: 3.3 [1.1-9.7]; P = 0.029). Freedom from reintervention was 84% (78%-90%) at 1, 76% (69%-83%) at 5, and 69% (60-78%) at 10 years. Main predictors of reintervention were age below 1 month (HR [95% CI]: 2.1 [1.1-4.1]; P = 0.032) and postdilation peak-to-peak gradient (per 10-mmHg increase; HR [95% CI]: 1.36 [1.02-1.79]; P = 0.032). Conclusions: BAV is a safe and effective treatment for aortic valve stenosis in neonates and infants. Outcomes are competitive with contemporary published data on aortic valve repair in relation to mortality, gradient relief, long-term AVR, and reintervention rates. In the absence of significant AI, surgery can be reserved for those with gradients resistant to valve dilation.

Duct stenting versus modified Blalock-Taussig shunt in neonates and infants with duct-dependent pulmonary blood flow: A systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis is to evaluate whether duct stenting is associated with better survival and other clinical outcomes compared with the modified Blalock-Taussig shunt in infants with duct-dependent pulmonary flow. METHODS: A systematic search of the Medline, Embase, and Cochrane databases was performed by 4 independent reviewers from inception to March 2019. Meta-analysis was performed using the DerSimonian and Laird method with inverse-variance weighting. The quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation framework. RESULTS: Six comparative observational studies were included, of which 3 were rated low risk of bias. There was no difference in 30-day mortality between the Blalock-Taussig shunt and duct stenting groups (risk ratio, 1.02; 95% confidence interval, 0.46-2.27; P = .96; I2 = 0%). However, there was benefit in favor of duct stenting for medium-term mortality (risk ratio, 0.63; 95% confidence interval, 0.40-0.99; P = .05; I2 = 0%). Duct stenting demonstrated a reduced risk for procedural complications compared with the Blalock-Taussig shunt (risk ratio, 0.50; 95% confidence interval, 0.31-0.81; P = .005; I2 = 0%). However, there was an increased risk for unplanned reintervention for duct stenting (risk ratio, 1.77; 95% confidence interval, 1.39-2.26; P < .00001; I2 = 10%). Duct stenting demonstrated shorter mean intensive care unit length of stay (mean difference, -4.69 days; 95% confidence interval, -7.30 to -2.07; P = .0004; I2 = 80%), as well as shorter hospital length of stay (mean difference, -5.78 days; 95% confidence interval, -9.27 to -2.28; P = .0009, I2 = 75%). The overall quality of evidence was rated low using the Grading of Recommendations, Assessment, Development, and Evaluation framework. CONCLUSIONS: Duct stenting demonstrated comparable early mortality, lower medium-term mortality, lower risk of procedural complications, and higher risk of reintervention compared with the Blalock-Taussig shunt.

Balloon Angioplasty for Native Aortic Coarctation in 3- to 12-Month-Old Infants.

BACKGROUND: Balloon angioplasty for native coarctation of the aorta (CoA) is successful in children and adults but in neonates results in frequent restenosis. The efficacy of balloon angioplasty for native CoA during infancy beyond the neonatal period was examined in infants aged 3 to 12 months of age. METHODS: A retrospective review of 68 infants who underwent balloon angioplasty for native CoA. 95% CI are in parentheses. RESULTS: Procedural age was (mean±SD) 6±3.4 months and weight was 7±1.8 kg. Balloon angioplasty produced a large decrease in both the noninvasive arm-to-leg blood pressure gradient (41.2±18.7 to 5.6±9.6 mm Hg) and the invasive peak systolic pressure gradient (34±12 to 11±9 mm Hg). Balloon angioplasty increased the CoA diameter from 2.7±1 mm to 4.6±1.2 mm. One patient was lost to follow-up. A catheter reintervention was required in 11.8% and surgery in 10.3%. The hazard of reintervention was highest early. Median freedom from reintervention was 89% (95% CI, 80%-96%) at 1 year, 83% (95% CI, 73%-92%) at 5 years, and 81% (95% CI, 69%-90%) at 10 years. Femoral artery thrombosis was documented in 6 (9%) infants without any long-term consequence. One patient developed a small aortic aneurysm late and has not required treatment. A robust estimate of the frequency of aortic aneurysms remains to be determined as the majority of subjects have not had cross-sectional imaging. CONCLUSIONS: Balloon angioplasty of native CoA is effective and safe in infants aged 3 to 12 months with outcomes comparable to those in older children and adults. Catheter reinterventions can avoid the need for surgery in most patients.

An Overview of Contemporary Outcomes in Fetal Cardiac Intervention: A Case for High-Volume Superspecialization?

Fetal cardiac interventions (FCI) offer the opportunity to rescue a fetus at risk of intrauterine death, or more ambitiously to alter disease progression. Most of these fetuses require multiple additional postnatal procedures, and it is difficult to disentangle the effect of the fetal procedure from that of the postnatal management sequence. The true clinical impact of FCI may only be discernible in large-volume institutions that can commit to a standardized postnatal approach and have sufficient case volume to overcome their FCI learning curve.

Haploinsufficiency of vascular endothelial growth factor related signaling genes is associated with tetralogy of Fallot.

PURPOSE: To determine disease-associated single-gene variants in conotruncal defects, particularly tetralogy of Fallot (TOF). METHODS: We analyzed for rare loss-of-function and deleterious variants in FLT4 (VEGFR3) and other genes in the vascular endothelial growth factor (VEGF) pathway, as part of a genome sequencing study involving 175 adults with TOF from a single site. RESULTS: We identified nine (5.1%) probands with novel FLT4 variants: seven loss-of-function, including an 8-kb deletion, and two predicted damaging. In ten other probands we found likely disruptive variants in VEGF-related genes: KDR (VEGFR2; two stopgain and two nonsynonymous variants), VEGFA, FGD5, BCAR1, IQGAP1, FOXO1, and PRDM1. Detection of VEGF-related variants (19/175, 10.9%) was associated with an increased prevalence of absent pulmonary valve (26.3% vs. 3.4%, p < 0.0001) and right aortic arch (52.6% vs. 29.1%, p = 0.029). Extracardiac anomalies were rare. In an attempt to replicate findings, we identified three loss-of-function or damaging variants in FLT4, KDR, and IQGAP1 in ten independent families with TOF. CONCLUSION: Loss-of-function variants in FLT4 and KDR contribute substantially to the genetic basis of TOF. The findings support dysregulated VEGF signaling as a novel mechanism contributing to the pathogenesis of TOF.

Right ventricular fibrosis is associated with cardiac remodelling after pulmonary valve replacement.

OBJECTIVE: The relationship between right ventricular (RV) fibrosis and right heart reverse remodelling following pulmonary valve replacement (PVR) has not been well studied in adults with repaired tetralogy of Fallot (rTOF). Our aims were to histologically quantify RV fibrosis and to explore the relationship between fibrosis severity and cardiac remodelling post-PVR. METHODS: Adults with rTOF and pre-PVR cardiovascular (CMR) imaging were consented to procurement of RV muscle during PVR. Samples were stained with picrosirius red to quantify collagen volume fraction. Clinical data at baseline and at last follow-up were reviewed. Adverse cardiovascular outcomes included death, sustained arrhythmia and heart failure. RESULTS: Fifty-three patients (male 58%, 38±11 years) were studied. Those with severe fibrosis (collagen volume fraction >11.0%, n=13) had longer aortic cross-clamp times at initial repair compared with the remainder of the population (50 vs 33 min, p=0.018) and increased RV mass:volume ratio pre-PVR (0.20 vs 0.18 g/mL, p=0.028). Post-PVR, the severe fibrosis group had increased indexed RV end-systolic volume index (RVESVi) (74 vs 66 mL/m2, p=0.044), decreased RVESVi change (Δ29 vs Δ45 mL/m2, p=0.005), increased RV mass (34 vs 25 g/m2, p=0.023) and larger right atrial (RA) area (21 vs 17 cm2, p=0.021). A trend towards increased heart failure events was observed in the severe fibrosis group (15% vs 0%, p=0.057). CONCLUSIONS: Severe RV fibrosis was associated with increased RVESVi, RV mass and RA area post-PVR in rTOF. Further study is required to define the impact of fibrosis and persistent right heart enlargement on clinical outcomes.

Percutaneous Fetal Atrial Balloon Septoplasty for Simple Transposition of the Great Arteries With an Intact Atrial Septum.

We report the first ultrasonographically guided percutaneous balloon atrial septoplasty (BAS), to our knowledge, in a fetus with transposition of the great arteries and an intact ventricular and atrial septum (37 + 2 weeks). After vaginal delivery at 38 weeks, the infant had an elective septostomy (day 1) and an arterial switch procedure (day 7), with an uneventful postoperative course. For centres with experience in fetal cardiac interventions, fetal BAS is a superior management option compared with the alternatives for this high-risk physiology.

Abnormal Myocardial Contractility After Pediatric Heart Transplantation by Cardiac MRI.

Acute cellular rejection (ACR) compromises graft function after heart transplantation (HTX). The purpose of this study was to describe systolic myocardial deformation in pediatric HTX and to determine whether it is impaired during ACR. Eighteen combined cardiac magnetic resonance imaging (CMR)/endomyocardial biopsy (EMBx) examinations were performed in 14 HTX patients (11 male, age 13.9 ± 4.7 years; 1.2 ± 1.3 years after HTX). Biventricular function and left ventricular (LV) circumferential strain, rotation, and torsion by myocardial tagging CMR were compared to 11 controls as well as between patients with and without clinically significant ACR. HTX patients showed mildly reduced biventricular systolic function when compared to controls [LV ejection fraction (EF): 55 ± 8% vs. 61 ± 3, p = 0.02; right ventricular (RV) EF: 48 ± 7% vs. 53 ± 6, p = 0.04]. Indexed LV mass was mildly increased in HTX patients (67 ± 14 g/m2 vs. 55 ± 13, p = 0.03). LV myocardial deformation indices were all significantly reduced, expressed by global circumferential strain (-13.5 ± 2.3% vs. -19.1 ± 1.1%, p < 0.01), basal strain (-13.7 ± 3.0% vs. -17.5 ± 2.4%, p < 0.01), mid-ventricular strain (-13.4 ± 2.7% vs. -19.3 ± 2.2%, p < 0.01), apical strain (-13.5 ± 2.8% vs. -19.9 ± 2.0%, p < 0.01), basal rotation (-2.0 ± 2.1° vs. -5.0 ± 2.0°, p < 0.01), and torsion (6.1 ± 1.7° vs. 7.8 ± 1.1°, p < 0.01). EMBx demonstrated ACR grade 0 R in 3 HTX cases, ACR grade 1 R in 11 HTX cases and ACR grade 2 R in 4 HTX cases. When comparing clinically non-significant ACR (grades 0-1 R vs. ACR 2 R), basal rotation, and apical rotation were worse in ACR 2 R patients (-1.4 ± 1.8° vs. -4.2 ± 1.4°, p = 0.01 and 10.2 ± 2.9° vs. 2.8 ± 1.9°, p < 0.01, respectively). Pediatric HTX recipients demonstrate reduced biventricular systolic function and decreased myocardial contractility. Myocardial deformation indices by CMR may serve as non-invasive markers of graft function and, perhaps, rejection in pediatric HTX patients.

Histological validation of cardiovascular magnetic resonance T1 mapping markers of myocardial fibrosis in paediatric heart transplant recipients.

BACKGROUND: Adverse fibrotic remodeling is detrimental to myocardial health and a reliable method for monitoring the development of fibrotic remodeling may be desirable during the follow-up of patients after heart transplantation (HTx). Quantification of diffuse myocardial fibrosis with cardiovascular magnetic resonance (CMR) has been increasingly applied and validated histologically in adult patients with heart disease. However, comparisons of CMR findings with histological fibrosis burden in children are lacking. This study aimed to compare native T1 times and extracellular volume fraction (ECV) derived from CMR with the degree of collagen on endomyocardial biopsy (EmBx), and to investigate the association between myocardial fibrosis and clinical as well as functional markers in children after HTx. METHODS: EmBx and CMR were performed on the same day. All specimens were stained with picrosirius red. The collagen volume fraction (CVF) was calculated as ratio of stained collagen area to total myocardial area on EmBx. Native T1 values and ECV were measured by CMR on a mid-ventricular short axis slice, using a modified look-locker inversion recovery approach. RESULTS: Twenty patients (9.9 ± 6.2 years of age; 9 girls) after HTx were prospectively enrolled, at a median of 1.3 years (0.02-12.6 years) post HTx, and compared to 24 controls (13.9 ± 2.6 years of age; 12 girls). The mean histological CVF was 10.0 ± 3.4%. Septal native T1 times and ECV were higher in HTx patients compared to controls (1008 ± 32 ms vs 979 ± 24 ms, p < 0.005 and 0.30 ± 0.03 vs 0.22 ± 0.03, p < 0.0001, respectively). CVF showed a moderate correlation with native T1 (r = 0.53, p < 0.05) as well as ECV (r = 0.46, p < 0.05). Native T1 time, but not ECV and CVF, correlated with ischemia time (r = 0.46, p < 0.05). CONCLUSIONS: CMR-derived fibrosis markers correlate with histological degree of fibrosis on EmBx in children after HTx. Further, native T1 times are associated with longer ischemia times.

Catheter-Based Palliation in an Infant With Obstructed Cor Triatriatum.

A 33-day-old infant with obstructed cor triatriatum sinister and partial anomalous pulmonary venous drainage presented with respiratory distress and fever. Her suprasystemic pulmonary hypertension was relieved by opening the connection to the right atrium using balloon atrial septoplasty and septostomy, and to the inferior chamber using balloon dilation of a fenestration in the dividing membrane. This enabled extubation and discharge, with elective surgical repair at 2 months. To our knowledge, this is the youngest patient to receive a catheter intervention for obstructed cor triatriatum sinister, providing relief of pulmonary hypertension and postponement of surgical repair.

Magnetic resonance imaging of the transplanted pediatric heart as a potential predictor of rejection.

AIM: To evaluate cardiac magnetic resonance imaging (CMR) as a non-invasive tool to detect acute cellular rejection (ACR) in children after heart transplant (HT). METHODS: Thirty pediatric HT recipients underwent CMR at the time of surveillance endomyocardial biopsy (EMB) and results were compared to 14 non-transplant controls. Biventricular volumes, ejection fractions (EFs), T2-weighted signal intensities, native T1 times, extracellular volumes (ECVs) and presence of late gadolinium enhancement (LGE) were compared between patients and controls and between patients with International Society of Heart and Lung Transplantation (ISHLT) grade ≥ 2R rejection and those with grade 0/1R. Heart rate (HR) and brain natriuretic peptide (BNP) were assessed as potential biomarkers. RESULTS: Significant ACR (ISHLT grade ≥ 2R) was an infrequent event in our population (5/30, 17%). Ventricular volumes, EFs, LGE prevalence, ECVs, native T1 times, T2 signal intensity ratios, HR and BNP were not associated with the presence of ≥ 2R ACR. CONCLUSION: In this pilot study CMR did not reliably identify ACR-related changes in pediatric HT patients.

Pulmonary artery stenosis in hybrid single-ventricle palliation: High incidence of left pulmonary artery intervention.

OBJECTIVE: Pulmonary artery growth is an important determinant of outcome in single-ventricle strategies. Higher rates of pulmonary artery intervention have been reported with hybrid-based palliation when compared with Norwood palliation. METHODS: We performed a retrospective review of pulmonary artery growth and clinical outcomes in patients undergoing hybrid-based single-ventricle palliation. RESULTS: The stage I hybrid procedure was performed in 72 patients between 2004 and 2012, of whom 54 were on a Fontan palliative pathway. Thirty-four infants completed stage II, and 20 infants underwent the Fontan operation. The mean diameters of the right pulmonary artery (5.6 ± 1.9 mm) and left pulmonary artery (5.6 ± 2.1 mm) were similar before stage II. After stage II, the right and left pulmonary artery diameters were 8.5 ± 2.1 mm and 5.8 ± 1.3 mm, respectively (P < .001), and after the Fontan operation, these were 8.8 ± 2.0 mm and 6.4 ± 1.1 mm, respectively (P = .002). The mean right pulmonary artery z score was normal throughout, but the left pulmonary artery did not maintain a normal size. The cumulative pulmonary artery intervention rate was 50% at any time after stage II. Fifteen interventions (88%) were performed after stage II (35% during the same hospitalization, 71% <60 days). The most intervened site was the midsection of the left pulmonary artery (41%). Initial pulmonary artery intervention was balloon dilation in 59% of patients and stent implantation in 41% of patients. Half of patients with initial balloon dilation required reintervention. CONCLUSIONS: There is significant risk of left pulmonary artery compromise after the second stage of hybrid palliation associated with a high intervention rate.

Surgical palliation strategy does not affect interstage ventricular dysfunction or atrioventricular valve regurgitation in children with hypoplastic left heart syndrome and variants.

BACKGROUND: All 3 palliation strategies, Norwood, Sano, and Hybrid, currently used for hypoplastic left heart syndrome pose a risk of myocardial injury at different times and through different mechanisms. We sought to compare these strategies to understand longitudinal differences in interstage ventricular dysfunction and their subsequent impact on transplant-free survival and atrioventricular valve regurgitation (AVVR) as well as the relationship between adverse events and ventricular function. METHODS AND RESULTS: Serial echocardiographic reports and clinical data were reviewed for 138 children with hypoplastic left heart syndrome who underwent stage I surgical palliation (Sano: 11; Norwood: 73; Hybrid: 54) between 2004 and 2011. Stage II palliation was achieved in 92 (67%) patients (Sano: 7; Norwood: 51; Hybrid: 34). Interstage transplant-free survival, ventricular dysfunction, and AVVR were equivalent among palliation strategies. Patients with preserved ventricular function had a higher rate of transplant-free survival and freedom from AVVR, regardless of palliation strategy. Patients who had cardiac arrest, cardiopulmonary resuscitation, or extracorporeal membrane oxygenation (adverse events) experienced more transient and persistent ventricular dysfunction compared to those without adverse events. Surgical palliation strategies were not identified as risk factors for ventricular dysfunction or AVVR. CONCLUSIONS: Surgical palliation strategy does not affect mortality, interstage ventricular function, or interstage AVVR in children with hypoplastic left heart syndrome. Therefore, the different timing and mechanisms of myocardial injury among palliation strategies do not affect outcomes. Ventricular dysfunction adversely affects transplant-free survival and atrioventricular valve function. Adverse events are associated with the development of ventricular dysfunction. To improve outcomes, interstage treatment should focus on the preservation of ventricular function.

Fetal stenting of the atrial septum: technique and initial results in cardiac lesions with left atrial hypertension.

BACKGROUND: Hypoplastic left heart syndrome with a highly restrictive or intact atrial septum (HLHS-RAS) has a very high mortality. Fetal left atrial (LA) hypertension results in abnormal lung development with lymphangiectasia and pulmonary vein muscularization. We report our initial experience with percutaneous ultrasound-guided stenting of the fetal atrial septum to decompress the LA. METHODS: Retrospective review of fetuses with HLHS-RAS or a variant that underwent active perinatal management from 2000 to 2012. RESULTS: Ten fetuses were identified. Two died in utero (33, 29 weeks). Four required the urgent creation of an atrial communication immediately after birth but died subsequently (5-54 days). Four fetuses (28-36 weeks) underwent percutaneous stenting of the atrial septum, with ultrasound guidance and intravenous maternal sedation. Elevated LA pressure, pulmonary vein dilation and MRI estimated pulmonary perfusion all improved after stenting. Three of four stented fetuses were delivered vaginally. Atrial septectomy was performed within 48 h of delivery to ensure complete LA decompression, rather than for hypoxemia. Intraoperative lung biopsy demonstrated muscularized pulmonary veins and lymphangiectasia in all four. Two fetuses developed stent stenosis in utero and died after birth, from pulmonary hypertension and sepsis respectively. Two are alive, representing an improved outcome over our previous experience (p=0.03). CONCLUSION: Fetal atrial septal stenting is feasible without maternal complications and allows vaginal delivery of a more stable neonate. Fetal LA decompression ameliorates rather than reverses lung injury, and is one component of an approach that may improve survival in HLHS-RAS.

Hybrid versus Norwood strategies for single-ventricle palliation.

BACKGROUND: Hybrid and Norwood strategies differ substantially in terms of stage II palliative procedures. We sought to compare these strategies with an emphasis on survival and reintervention after stage II and subsequent Fontan completion. METHODS AND RESULTS: Of 110 neonates with functionally single-ventricle physiology who underwent stage I palliation between 2004 and 2010, 75 (69%) infants (Norwood, n=43; hybrid, n=32) who subsequently underwent stage II palliation were studied. Survival and reintervention rates after stage II palliation, anatomic and physiologic variables at pre-Fontan assessment, and Fontan outcomes were compared between the groups. Predictors for reintervention were analyzed. Freedom from death/transplant after stage II palliation was equivalent between the groups (Norwood, 80.4% versus hybrid, 85.6% at 3 years, P=0.66). Hybrid patients had a higher pulmonary artery (PA) reintervention rate (P=0.003) and lower Nakata index at pre-Fontan evaluation (P=0.015). Aortic arch and atrioventricular valve reinterventions were not different between the groups. Ventricular end-diastolic pressure, mean PA pressure, and ventricular function were equivalent at pre-Fontan assessment. There were no deaths after Fontan completion in either group (Norwood, n=25, hybrid, n=14). CONCLUSIONS: Survival after stage II palliation and subsequent Fontan completion is equivalent between the groups. The hybrid group had a higher PA reintervention rate and smaller PA size. Both strategies achieved adequate physiology for Fontan completion. Evolution of the hybrid strategy requires refinement to provide optimal PA growth.