Search

Hypoplastic left heart syndrome (HLHS) is a severe form of single ventricle congenital heart disease characterized by an underdevelopment of the left ventricle. Early serial postmortem examinations revealed high rate of coronary artery abnormalities in HLHS fetal hearts, which may impact ventricular development and intra-cardiac hemodynamics, leading to a poor prognosis after surgical palliations. Previous study reported that endothelial cells (ECs) lining the coronary vessels showed DNA damage in the left ventricle of human fetal heart with HLHS, indicating that EC dysfunction may contribute to the coronary abnormalities in HLHS. To investigate the underlying mechanism of HLHS coronary artery abnormalities, we profiled both human fetal heart with an underdeveloped left ventricle (ULV) and ECs differentiated from induced pluripotent stem cells (iPSCs) derived from HLHS patients at single cell resolution. CD144+/NPR3- vascular ECs were selected and further classified as venous EC (NR2F2high), arterial EC (EFNB2high) and late arterial EC (GJA5high) subclusters based on previously reported marker genes. To study the arterial phenotype, we specifically generated iPSC-arterial ECs (AECs, CD34+CDH5+CXCR4+NT5E-/low) derived from three HLHS patients and three age-matched healthy controls to further dissect the phenotype of HLHS-AECs. As compared to normal human heart and control iPSC-ECs respectively, ULV late arterial EC subcluster and HLHS iPSC-EC arterial clusters showed significantly reduced expression of arterial genes GJA5, DLL4, and HEY1. Pathway enrichment analysis based on differentially expressed genes revealed several defects in late AEC cluster from ULV compared to normal human heart, such as impaired endothelial proliferation, development and Notch signaling. HLHS iPSCs exhibited impaired AEC differentiation as evidenced by the significantly reduced CXCR4+NT5E-/low AEC progenitor population. Consistent with human heart transcriptomic data, matured HLHS iPSC-AECs also showed a lower expression of the arterial genes such as GJA5, DLL4, HEY1 which are also downstream of NOTCH signaling. Additionally, matured HLHS iPSC-AECs showed significantly decreased expression of cell proliferation marker Ki67 and G1/S transition genes (CCND1, CCND2) compared with controls. Interestingly, NOTCH ligand Jag1 treatment significantly rescued this cell proliferation defect in HLHS AECs, accompanied by upregulation of various G1/S transition genes. In summary, we found that coronary AECs from HLHS showed impaired arterial development and proliferation downstream of NOTCH signaling. These functional defects in HLHS coronary AECs could contribute to the vascular structure malformation and impaired ventricular development.

Background This report describes 9 high-risk neonates and infants with hypoplastic left heart syndrome (HLHS) who were stabilized with a combined hybrid approach and ventricular assist device (VAD) insertion (HYBRID+VAD) in preparation for heart transplantation. Methods A total of 9 patients with HLHS (7 neonates, 2 infants) presented with anatomic or physiologic features associated with an increased risk for conventional univentricular palliation with the Norwood operation (large coronary sinusoids or fistulas, severe tricuspid regurgitation, cardiogenic shock, restrictive atrial septum). These patients underwent combined VAD insertion (Berlin EXCOR, Berlin Heart, Inc, Berlin, Germany) and Stage 1 hybrid palliation (application of bilateral pulmonary bands, stent placement in the patent arterial duct, and atrial septectomy if needed). During this same era, at the Congenital Heart Center, University of Florida, Gainesville, Florida, 46 neonates underwent a Norwood operation, 4 neonates underwent a hybrid approach “Stage 1” without VAD, and 3 patients with HLHS were supported with prostaglandin while awaiting heart transplantation. Results At HYBRID+VAD insertion, the median age was 20 days (range, 13 to 143 days), and median weight was 3.25 kg (range, 2.43 to 4.2 kg). Six patients survive (67%), and 3 patients died (33%). Five survivors are at home doing well after successful heart transplantation, and 1 survivor is doing well in the intensive care unit on VAD support while awaiting transplantation. Only 1 of 6 survivors (16.7%) required intubation more than 10 days after HYBRID+VAD insertion. In 8 patients no longer undergoing VAD support, the median length of VAD support was 119.5 days (range, 56 to 196 days). Conclusions High-risk patients with HLHS who are suboptimal candidates for Norwood palliation can be successfully stabilized with pulsatile VAD insertion along with hybrid palliation while awaiting cardiac transplantation. These patients may be extubated and optimized for transplantation while undergoing VAD support.

Some neonates with functionally univentricular hearts are extremely high risk for conventional surgical palliation. Primary cardiac transplantation offers the best option for survival of these challenging neonates; however, waitlist mortality must be minimized. We have developed a comprehensive strategy for the management of neonates with functionally univentricular hearts that includes the selective use of conventional neonatal palliation in standard risk patients, hybrid approaches in neonates with elevated risk secondary to noncardiac etiology, and neonatal palliation combined with insertion of a single ventricular assist device (VAD) in neonates with elevated risk secondary to cardiac etiology. The purpose of this manuscript is to describe our selection criteria, technical details, management strategies, pitfalls, and current outcomes for neonates with functionally univentricular hearts supported with VAD. Our experience documents that extremely high-risk patients with functionally univentricular hearts who are poor candidates for conventional palliation can be successfully stabilized with concomitant palliation and pulsatile VAD insertion while awaiting transplantation.

The Single Ventricle Reconstruction Trial demonstrated increased risk of death or heart transplant 1 year after Norwood among subjects randomly assigned to modified Blalock-Taussig shunts compared with right ventricle to pulmonary artery (RV-PA) shunts. We used the Single Ventricle Reconstruction Trial public use database to evaluate incidence and risk factors for postoperative renal failure and relationships between renal failure, shunt type, and outcomes after Norwood.Postoperative renal failure was defined a priori as a threefold rise in creatinine from baseline, or dialysis use, within 7 days of Norwood. We used multivariate logistic regression to evaluate risk factors for postoperative renal failure and Cox hazard regression to determine the association between postoperative renal failure and 1 year after Norwood mortality.Overall, postoperative renal failure occurred in 8.4% (46 of 544) patients with risk factors including receipt of a modified Blalock-Taussig shunt (adjusted odds ratio [aOR] 3.3, P = .02), low center volume (aOR 2.7, P = .005), two or more preoperative complications (aOR 4.0, P.001), low birth weight (aOR 3.2, P = .002), postoperative heart block (aOR 8.5, P = .001), and delayed sternal closure (aOR 5.3, P = .026). Renal failure was an independent risk factor for 1-year mortality (aHR 1.9, P = .019). Assessing interaction by shunt type, mortality risk associated with renal failure was greatest in the RV-PA shunt group (aHR 3.3 vs RV-PA shunt without renal failure, P = .001), but was also increased in the modified Blalock-Taussig shunt group (aHR 1.9, P = .03).Postoperative renal failure is common after Norwood and is independently associated with mortality. Although renal failure is more common after modified Blalock-Taussig shunt, the highest mortality risk with renal failure occurs after RV-PA shunt.

There are two borderline left-heart phenotypes in the fetus: (1) severe aortic stenosis (AS), which is associated with a 'short, fat', globular left ventricle (LV), LV systolic dysfunction and LV growth arrest; and (2) severe left-heart hypoplasia (LHH), which is associated with a 'long, skinny' LV, laminar flow across hypoplastic mitral and aortic valves and arch hypoplasia. Both phenotypes may be counseled for possible single-ventricle palliation. We aimed to compare the rates of left-sided cardiac structure growth and Z-score change over gestation and to describe the postnatal outcomes associated with these two phenotypes. We hypothesized that the left-sided structures would grow faster in fetuses with LHH compared to those with AS, and that those with LHH would be more likely to achieve biventricular circulation.This was a retrospective cohort study using data collected in an institutional cardiology database between April 2001 and April 2018. We included fetuses with severe AS or severe LHH, and with at least two fetal echocardiograms. Inclusion criteria for the AS group included: aortic-annulus Z-score -2.0, severe AS, depressed LV function, retrograde systolic flow in the aortic arch and endocardial fibroelastosis. Inclusion criteria for the LHH group included: aortic-annulus Z-score -2.0, hypoplastic but apex-forming LV, normal LV function and retrograde systolic flow in the aortic arch. Exclusion criteria were: abnormal cardiac connections, other forms of structural congenital heart disease, cardiomyopathy, history of fetal aortic valvuloplasty and participation in a maternal hyperoxygenation study. Measurements and respective Z-scores for the aortic-valve annulus, mitral-valve annulus, LV long- and short-axis dimensions, along with aortic-arch measurements, were collected longitudinally for each fetus and plotted over time for both cohorts. Mean slopes of change in dimension and Z-scores over gestation were calculated and compared between the two groups using mixed generalized linear regression accounting for repeated measures. A subanalysis was performed, matching six fetuses from each group for initial aortic-annulus Z-score and gestational age, due to the significant differences in these two variables between the original cohorts.In total, 53 fetuses with 158 echocardiograms were included. In the AS cohort, there were 20 (38%) fetuses with 65 echocardiograms, and in the LHH cohort there were 33 (62%) fetuses with 93 echocardiograms. On the first echocardiogram, LHH fetuses had a later gestational age and a larger aortic-annulus diameter. The rate of aortic-annulus growth was greater in the LHH group compared with the AS group (mean ± SD, 0.15 ± 0.01 mm/week for LHH vs 0.07 ± 0.01 mm/week for AS (P 0.001)). While the LHH group had a decrease in aortic-annulus Z-score over time, this was at a slower rate than the decrease in the AS group (mean ± SD, -0.04 ± 0.02/week for LHH vs -0.13 ± 0.02/week for AS (P 0.001)). A similar pattern was seen for the mitral-valve and LV short-axis-dimension Z-scores. Subanalysis of six fetuses from each group matched for initial aortic-annulus Z-score and gestational age demonstrated similar findings, with the LHH group Z-scores decreasing at a slower rate than those in the AS group. Fifty-two of the 53 fetuses were liveborn, one LHH fetus dying in utero. Of the 20 liveborn in the AS cohort, 15 (75%) infants underwent single-ventricle palliation, two (10%) underwent biventricular repair and three (15%) died prior to intervention. Of the 32 liveborn in the LHH cohort, three (9.4%) underwent single-ventricle palliation, 28 (87.5%) achieved biventricular circulation, of which six required no surgery, and one (3.1%) died prior to intervention.The left-sided cardiac structures grow at a faster rate in fetuses with severe LHH than they do in fetuses with severe AS, and the Z-scores decrease at a slower rate in fetuses with severe LHH than they do in those with severe AS. The majority of infants in the LHH group did not undergo single-ventricle palliation. This information can be useful in counseling families on the expected growth potential of the fetus's aortic valve, mitral valve and LV, depending on the cardiac phenotype. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

To review our experience with fetal aortic valvuloplasty (FAV) in fetuses with critical aortic stenosis (CAS) and evolving hypoplastic left heart syndrome (eHLHS), including short- and medium-term postnatal outcome, and to refine selection criteria for FAV by identifying preprocedural predictors of biventricular (BV) outcome.This was a retrospective review of all fetuses with CAS and eHLHS undergoing FAV at our center between December 2001 and September 2020. Echocardiograms and patient charts were analyzed for pre-FAV ventricular and valvular dimensions and hemodynamics and for postnatal procedures and outcomes. The primary endpoints were type of circulation 28 days after birth and at 1 year of age. Classification and regression-tree analysis was performed to investigate the predictive capacity of pre-FAV parameters for BV circulation at 1 year of age.During the study period, 103 fetuses underwent 125 FAVs at our center, of which 87.4% had a technically successful procedure. Technical success per fetus was higher in the more recent period (from 2014) than in the earlier period (96.2% (51/53) vs 78.0% (39/50); P = 0.0068). Eighty fetuses were liveborn after successful intervention and received further treatment. BV outcome at 1 year of age was achieved in 55% of liveborn patients in our cohort after successful FAV, which is significantly higher than the BV-outcome rate (23.7%) in a previously published natural history cohort fulfilling the same criteria for eHLHS (P = 0.0015). Decision-tree analysis based on the ratio of right to left ventricular (RV/LV) length combined with LV pressure (mitral valve regurgitation maximum velocity (MR-Vmax)) had a sensitivity of 96.97% and a specificity of 94.44% for predicting BV outcome without signs of pulmonary arterial hypertension at 1 year of age. The highest probability for a BV outcome was reached for fetuses with a pre-FAV RV/LV length ratio of 1.094 (96.4%) and for those fetuses with a RV/LV length ratio ≥ 1.094 to 1.135 combined with a MR-Vmax of ≥ 3.14 m/s (100%).FAV could be performed with high success rates and an acceptable risk with improving results after a learning curve. Pre-FAV RV/LV length ratio combined with LV pressure estimates were able to predict a successful BV outcome at 1 year of age with high sensitivity and specificity. © 2022 The Authors. Ultrasound in ObstetricsGynecology published by John WileySons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal aortic valvuloplasty (FAV) has become a treatment option for critical fetal aortic stenosis (AS) with the goal of preserving biventricular circulation (BVC); however, to date, it is unclear how many patients undergoing FAV achieve BVC. The aim of this systematic review and meta-analysis was to investigate the type of postnatal circulation achieved following FAV.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. MEDLINE, EMBASE, Web of Science and the Cochrane Library were searched systematically for studies investigating postnatal circulation in patients with AS following FAV. Eligible for inclusion were original papers in the English language, published from 2000 to 2020, with at least 12 months of follow-up after birth. Review papers, abstracts, expert opinions, books, editorials and case reports were excluded. The titles and abstracts of all retrieved literature were screened, duplicates were excluded and the full texts of potentially eligible articles were obtained and assessed. The primary endpoint was type of postnatal circulation. Additional assessed outcomes included fetal death, live birth, neonatal death (NND), termination of pregnancy (TOP) and technical success of the FAV procedure. The quality of articles was assessed using the Critical Appraisal Skills Programme (CASP) tool. To estimate the overall proportion of each endpoint, meta-analysis of proportions was employed using a random-effects model.The electronic search identified 579 studies, of which seven were considered eligible for inclusion in the systematic review and meta-analysis. A total of 266 fetuses underwent FAV with median follow-up per study from 12 months to 13.2 years. There were no maternal deaths and only one case of FAV-related maternal complication was reported. Hydrops was present in 29 (11%) patients. The pooled prevalence of BVC and univentricular circulation (UVC) among liveborn patients was 45.8% (95% CI, 39.2-52.4%) and 43.6% (95% CI, 33.9-53.8%), respectively. The pooled prevalence of technically successful FAV procedure was 82.1% (95% CI, 74.3-87.9%), of fetal death it was 16.0% (95% CI, 11.2-22.4%), of TOP 5.7% (95% CI, 2.0-15.5%), of live birth 78.8% (95% CI, 66.5-87.4%), of NND 8.7% (95% CI, 4.7-15.5%), of palliative care 4.0% (95% CI, 1.9-8.4%) and of infant death 10.3% (95% CI, 3.6-26.1%). The pooled prevalence of BVC and UVC among liveborn patients who had technically successful FAV was 51.9% (95% CI, 44.7-59.1%) and 39.8% (95% CI, 29.7-50.9%), respectively.This study showed a BVC rate of 46% among liveborn patients with AS undergoing FAV, which improved to 52% when subjects underwent technically successful FAV. Given the lack of randomized clinical trials, results should be interpreted with caution. Currently, data do not suggest a true benefit of FAV for achieving BVC. © 2022 The Authors. Ultrasound in ObstetricsGynecology published by John WileySons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Despite recent advances in pediatric diagnosis and surgical intervention, mortality and morbidity continue to be a prevalent issue in both tetralogy of Fallot (ToF) and hypoplastic left heart syndrome (HLHS). Therefore, novel approaches to studying both of these conditions are warranted. Investigating cardiac anatomical features of different species in the animal kingdom that are similar to the defects and complications present in ToF and HLHS (as well as others) could serve as a new avenue for improving the management of congenital heart diseases (CHD). This review reveals that although some structures found in HLHS and ToF are pathological, similar structures can be found in diving mammals and reptiles that are adaptive. Pathological aortic dilation in CHD resembles the aortic bulb present in diving mammals, but the latter is more elastic and distensible compared with the former. The unrepaired HLHS heart resembles the univentricular heart of non-crocodilian reptiles. Right ventricle hypertrophy is pathological in HLHS and ToF, but in contrast, adaptive in crocodilians and diving mammals. Lastly, the increased pulmonary resistance due to pulmonary stenosis in ToF is comparable with increased pulmonary resistance in crocodilians due to the presence of an active valve proximal to the pulmonary valve. Some of these anatomical structures could potentially be adapted for palliative surgery in children with HLHS or ToF. Moreover, further investigating the underlying molecular signals responsible for the adaptive tissue responses seen in other species may also be useful for developing novel strategies for preventing some of the complications that occur after surgical repair in both of these congenital heart diseases.

Fontan associated liver disease (FALD) has been recognized as a potentially serious sequela of the Fontan circulation. Prevalence of FALD among different age groups and risk factors for advanced changes were assessed. FALD screening included abdominal ultrasound and laboratory tests. A "liver disease score (LDS)" incorporating items from ultrasound and blood testing was calculated to grade FALD severity (5 items each, maximum score 10 points). 240 patients (male: n = 139, female: n = 101, systemic right ventricle: n = 160) underwent FALD screening 10 (IQR 7-15) years after Fontan surgery. Ultrasound was abnormal in 184 (76.6%) patients (surface nodularity / blunted liver edge: n = 133, 55.4%; heterogeneous parenchyma: n = 93, 38.8%; splenomegaly: n = 68, 28.3%; ascites: n = 23, 9.6%). At least one abnormal laboratory test was detected in 218 (90.8%) patients. Gamma-glutamyl-transpeptidase was elevated in the majority of patients (n = 206, 85.8%). Median LDS was 3 (2-4). Scores ≥5 were observed in 32 (13.3%) patients. Longer follow-up (15 (11-20) vs 9 (6-14) years, P0.001), higher central venous (13 (11-15) vs 10 (9-12) mmHg, P0.001) and end-diastolic pressure (8 (5-10) vs 6 (5-7) mmHg, P = 0.001), impaired ventricular function and absence of sinus rhythm were associated with LDS ≥5. Longer follow-up (OR 1.2 (1.1-1.3), P0.001) and higher central venous pressure (OR 1.6 (1.3-2.1), p0.001) were the only independent predictors of advanced FALD. Abdominal ultrasound and laboratory abnormalities suggestive of FALD are common during routine follow-up already in childhood and adolescence irrespective of ventricular morphology. More advanced findings are associated with longer follow-up and higher central venous pressure.

Thrombus formation is a feared complication following bidirectional cavopulmonary shunt (BCPS). We aimed to investigate the effect of thrombus formation on outcome. BCPS was performed in 525 patients at our center between 1998 and 2018. The impacts of thrombus formation on survival and probability of Fontan completion were analyzed, and risk factors for thrombus formation were examined. Thrombus formation occurred in 30 patients (5.7%). Compared with the remaining 495 patients, there was no significant difference in the median age at BCPS (4.9 vs 4.7 months; P = 0.587). However, unbalanced atrioventricular septal defects (17 vs 5%; P = 0.008) and preoperative ventricular dysfunction (23.3 vs 8%; P = 0.004) were more frequent in patients who developed a thrombus. Thrombolytic therapy was performed in all patients and surgical thrombus removal was required in 13 patients. In-hospital mortality was higher in patients with thrombus (30.0 vs 2.2%; P0.001). Of 505 hospital survivors, an estimated survival at 1 year after hospital discharge following BCPS was 84.4% (95% CI, 76.1-92.7%) in patients with thrombus and 96.8% (95% CI, 96.0-97.6%) in those without (P0.001). Cumulative incidence of Fontan completion at 3 years after BCPS was 52.8% (95% CI, 30.3-75.2%) in patients with thrombus and 90.1% (95% CI, 87.2-92.9%) in those without (P = 0.004). Higher left atrial pressure (OR = 1.165; P = 0.029) and longer cardiopulmonary bypass time (OR = 1.013, P = 0.001) at BCPS were independent risk factors for thrombus formation after BCPS. Thrombus formation after BCPS poses a significant risk for survival and Fontan completion. Preoperative higher left atrial pressure and longer cardiopulmonary bypass time are significant risk factors.

It is crucial to have an adequate-size unobstructed branch pulmonary artery architecture to achieve an ideal cavopulmonary circulation. Branch pulmonary artery distortion, stenosis, or hypoplasia is a common problem following the stage I Norwood procedure for infants with hypoplastic left heart syndrome regardless of the shunt type. This technical review describes the surgical principle and techniques of the extensive hilum to hilum branch pulmonary artery reconstruction at the time of stage II palliation, bidirectional cavopulmonary shunt in infants with hypoplastic left heart syndrome.

The article discusses the possible diagnostic errors in the hypoplastic left heart syndrome (HLHS) with mitral atresia and intact interventricular septum. “Atrioventricular canal defects” can be commonly and mistakenly diagnosed the prenatal period in such cases. The aspects and possibilities of differential diagnosis of these defects in the prenatal period are discussed. Ultrasound sign is presented in the article, we have named it “hockey stick with puck” that characterizes the retrograde blood flow in the aortic arch. This sign is diagnosed by color Doppler mapping of the sagittal section of the ductus arteriosus and can serve as a marker of mitral/aortic atresia.

Objective The Norwood neoaortic arch biomechanical properties are abnormal due to reduced vessel wall compliance and abnormal geometry. Others have previously described neoaortic geometric distortion by the degree of diameter reduction (tapering) and associated this with mismatched ventricular-neoaortic coupling, abnormal flow hemodynamic parameters, and worse patient outcome. Our purposes were to investigate the influence of neoaortic tapering (ie, diameter reduction) on flow-mediated viscous energy loss (EL') in post-Norwood palliated hypoplastic left heart syndrome patients, and correlate flow-geometry with single ventricle power generation. Methods Twenty-six palliated hypoplastic left heart syndrome patients underwent comprehensive cardiac evaluation with 4-dimensional-flow magnetic resonance imaging. Patients were grouped into high- (group H, n = 13) and low- (group L, n = 13) degree neoaortic tapering using the median cutoff value of neoaortic diameter variance. EL' was calculated along standardized segments using 4-dimensional-flow magnetic resonance imaging. Flow-mediated power loss as a percentage of total power generated by the single ventricle was determined. Results Group H had a higher prevalence of abnormal recirculating flow in the neoaorta and elevated neoaortic EL' in the ascending aorta (1.0 vs 0.6 mW; P = .004). Group H EL' was increased across the entire thoracic aorta (2.6 vs 1.3 mW; P = .002) and accounted for 0.7% of generated ventricular power versus 0.3% in group L (P = .024). EL' directly correlated with the degree of ascending aortic dilation (R = 0.49; P = .012). Conclusions Patients with high degree neoaortic tapering have more perturbed flow through the neoaorta and increased EL'. Flow-mediated energy loss due to abnormal flow represents irreversibly wasted power generated by the single right ventricle. In patients with high-degree neoaortic tapering, EL' was more than 2-fold greater than low-degree tapering patients. These data suggest that oversizing the Norwood neoaortic reconstruction should be avoided and that patients with distorted neoaortic geometry may warrant increased surveillance for single-ventricle deterioration.

BACKGROUND The impact of the striking perinatal circulatory changes on blood flow distribution have not to date been well examined in hypoplastic left heart syndrome (HLHS). This study aimed to document perinatal redistribution of cardiac output in HLHS compared with healthy control subjects, to further understand the impact of the perinatal transition on cerebral and systemic blood flow. METHODS Prospectively recruited HLHS case subjects (n = 31) and healthy control subjects (n = 19) underwent serial echocardiography from late fetal stages to 96 hours after birth. Combined cardiac output (CCO), systemic, pulmonary, cerebrovascular, and splanchnic flow data were compared between neonates with HLHS and control subjects, and the impact of vasoactive support and positive pressure ventilation in HLHS patients was examined. RESULTS In late gestation, CCO was similar between HLHS and control subjects, whereas middle cerebral artery (MCA) pulsatility index (PI) in HLHS was consistent with low cerebral vascular resistance. In the 96 hours after birth, CCO and pulmonary blood flow progressively increased in HLHS compared with control subjects (P < 0.001), and CCO was further increased in neonates with HLHS receiving vasoactive support (P = 0.01). Neonates with HLHS had reduced systemic and 6-24-hour superior vena cava (SVC) flow compared with control subjects (P < 0.001). Low systemic flow was further suggested by increased MCA and celiac artery PI at 6-48 hours in neonates with HLHS (P < 0.001). Systemic and SVC flow did not differ between those with and without vasoactive support. CONCLUSIONS We provide quantitative echocardiographic evidence associating impaired cerebral and systemic blood flow with perinatal hemodynamic changes in the preoperative neonate with HLHS.

The presence of a genetic condition is a risk factor for increased mortality in hypoplastic left heart syndrome (HLHS). Speckle tracking strain analysis in interstage echocardiograms have shown promise in identifying patients with HLHS at increased risk of mortality. We hypothesized that fetuses with a genetic condition and HLHS have impaired right ventricular global longitudinal strain compared with fetuses with HLHS and no evident genetic condition. We performed a retrospective analysis of 60 patients diagnosed in fetal life with HLHS from 11/2015 to 11/2019. We evaluated presenting echocardiograms and calculated right ventricular global longitudinal strain (RV GLS) and fractional area of change (FAC) using post-processing software. We first compared RV GLS and FAC between those with genetic conditions to those without. We examined the secondary outcome of mortality among those with and without genetic conditions and among HLHS subgroups. Of the 60 patients with available genetic testing, 11 (18%) had an identified genetic condition. Neither RV GLS nor FAC was significantly different between patients with and without genetic conditions. There was no difference in RV GLS or FAC among HLHS phenotype or those who died or survived as infants. However, patients with a genetic syndrome had increased neonatal and overall mortality. In this cohort, RV GLS did not differ between those with and without a genetic diagnosis, among HLHS phenotypes, or between those surviving and dying as infants. Further analysis of strain throughout gestation and after birth could provide insight into the developing heart in fetuses with HLHS.

Background Mortality in cohorts with a single ventricle remains high with multiple associated factors. The effect of heart block during stage I palliation remains unclear. Objective The purpose of this study was to study patient and surgical risks of heart block and its effect on 12-month transplant-free survival in patients with a single ventricle. Methods Patient, surgical, outcome data and heart block status (transient and permanent) were obtained from the National Pediatric Cardiology Quality Improvement Collaborative single ventricle database. Bivariate analysis was performed comparing patients with and without heart block, and multivariate modeling was used to identify variables associated with block. One-year outcomes were analyzed to identify variables associated with lower 12-month transplant-free survival. Results In total, 1423 patients were identified, of whom 28 (2%) developed heart block (second degree or complete) during their surgical admission. Associated risk factors for block included heterotaxy syndrome (odds ratio [OR] 6.4) and atrial flutter/fibrillation (OR 3.8). Patients with heart block had lower 12-month survival, though only in patients with complete heart block as opposed to second degree block. At 12 months of age, 43% (12/28) of patients with heart block died and were more likely to experience mortality at 12 months than patients without block (OR 4.9; 95% confidence interval 1.4–17.5; P = .01). Conclusion Although rare, complete heart block after stage I palliation represents an additional risk of poor outcomes in this high-risk patient population. Heterotaxy syndrome was the most significant risk factor for the development of heart block after stage I palliation. The role of transient block in outcomes and potential rescue with long-term pacing remains unknown and requires additional study.

Background Tricuspid valve regurgitation (TR) is a risk factor for morbidity and mortality in children with hypoplastic left heart syndrome (HLHS). Surgical tricuspid valve (TV) repair is common, but durable repair remains challenging. The aim of this study was to examine mechanisms of TR requiring surgery, features associated with unsuccessful repair, and TV changes after surgical repair. Methods Thirty-six patients with HLHS requiring TV repair (TVR) and 36 matched control subjects with HLHS were assessed using two-dimensional and three-dimensional echocardiography. Using three-dimensional echocardiography, TV coordinates from the annulus, leaflet, and ventricle were used to measure annular, leaflet, prolapse, and tethering values and anterior papillary muscle angle. TR grade and ventricular size, function, and shape were assessed using two-dimensional echocardiography. Results Patients requiring TVR had greater total leaflet prolapse, larger TV annular and leaflet areas, and flatter annuli, with no difference in tethering, coaptation index, or anterior papillary muscle angle. In patients with HLHS, successful TVR at follow-up (58%) was associated with preoperative total leaflet prolapse (especially posterior). Unsuccessful repair was associated with preoperative tethering of the septal leaflet. TVR in patients with HLHS caused a reduction of total annular and leaflet size and reduced prolapse and tethering of the posterior leaflet but did not affect anterior leaflet prolapse or septal leaflet tethering. Conclusions Features associated with TVR include a flattened and dilated TV annulus with leaflet prolapse. The additional presence of a tethered septal leaflet before TVR is associated with significant postoperative TR. Current surgical techniques, predominantly posterior annuloplasty and commissuroplasty, adequately address annular size and posterior leaflet pathology, but not septal leaflet tethering. Individualized and innovative surgical techniques are vital to improve surgical repair success.

There are conflicting data on how delivery location impacts outcomes in neonates with ductal-dependent heart disease. Our goal was to evaluate the impact of delivery location on hospital length of stay and survival in infants with prenatally diagnosed hypoplastic left heart syndrome (HLHS) after stage 1 palliation (S1P). A multicenter cohort study was performed utilizing the National Pediatric Cardiology Quality Improvement Collaborative dataset for infants with prenatally diagnosed HLHS who underwent S1P from August 2016 to December 2018. Univariate comparisons of demographics, clinical, and outcome data were made and multivariable logistic regression was performed between groups stratified by distance from surgical center. A total of 790 patients from 33 centers were analyzed: 85% were born

Minimal data exist about the incidence and risk factors for arch intervention after comprehensive stage II (CSII). Goal of this study was to document incidence of arch interventions after CSII and determine if any differences existed between those who underwent an arch intervention (aiCSII) versus those did not have an intervention. Single-center retrospective chart review of all hypoplastic left heart syndrome patients who underwent a CSII between 6/1/2005 and 2/1/2020 was performed. Univariate analysis was conducted in addition to principal components analysis (PCA). One hundred patients were evaluated. Sixteen patients underwent 24 arch interventions. Age at initial arch reintervention was 1.3 ± 1.2 years (median 1.0 years, range 0.5-2.2 years). Univariate analysis showed that the aiCSII group were more likely to be female, to have had a retrograde arch intervention post-hybrid procedure, and to be younger at time of CSII. On echocardiograms, aiCSII group had significantly higher pre-CSII patent ductus arteriosus velocities, arch velocities on their 1st post-operative and discharge study post-CSII, and arch velocities pre-Fontan. Gradients were higher in the aiCSII via pre-Fontan catheterization. With PCA, echocardiographic and catheterization data remained significantly associated with aiCSII versus those who did not undergo an arch intervention (OR = 4.5 (1.9, 19.8), p = 0.008). Incidence of arch intervention post-CSII was 16%. Echocardiographic arch velocities during the CSII hospitalization were the strongest predictors for subsequent aortic arch interventions. Further studies are needed to determine any modifiable variables that may reduce the incidence of arch interventions.

Graphical abstract, Highlights • Native aortic root thrombus is a life-threatening complication in patients with HLHS. • Echo evaluation of the native aortic root is an important consideration. • Echo monitoring is a useful tool for assessment of thrombus response to therapy.

NPC-QIC Registry data showed that angiotensin-converting enzyme inhibitors were described in almost 38% for patients with single ventricle physiology after stage-I Norwood palliation. However, mortality and ventricular dysfunction or atrioventricular valve insufficiency seems to be not improved by oral application of angiotensin-converting enzyme inhibitors. The final conclusion was that despite limited evidence of benefit for patients with hypoplastic left heart syndrome, prescription of angiotensin-converting enzyme inhibitors during interstage is still common. Taking into account of the predominant cardiovascular regulation in newborns and young infants by circulating catecholamines, no real improvement is to be expected from angiotensin-converting enzyme inhibitor monotherapy. The goals of drug therapy after stage-I Norwood palliation in hypoplastic left heart syndrome are prevention of systemic right ventricle failure, balancing pulmonary and systemic blood flow, and reduction of oxygen consumption with regard to limitations of oxygen supply by the single ventricle, furthermore, avoiding harmful effects of endogenous catecholamine production in the long term on somatic and cognitive development. In this light of knowledge, we want to recommend the use of a long-acting and highly specific ß1-adrenoreceptor blocker for almost all patients after stage-I Norwood palliation and a combination with angiotensin-converting enzyme inhibitors only by indication after exclusion of potential side effects.

While the Norwood operation is the most common palliative surgery for neonates with hypoplastic left heart syndrome (HLHS), initial hybrid strategy aiming to restrict pulmonary blood flow and maintain systemic output is necessary when Norwood is contraindicated or at high risk. The traditional mainstay of initial hybrid palliation is surgical pulmonary artery branch banding (PABB) plus interventional ductal stenting. We present a case of a transcatheter approach for pulmonary flow restriction (PFR) that was accomplished by modifying a Medtronic microvascular plug (MVP)™. The patient is a 2.4 kg neonate diagnosed with HLHS, dysplastic tricuspid and pulmonary valves with pulmonary stenosis, tricuspid stenosis, and regurgitation. He was not considered a candidate for surgical intervention. He started developing sequelae of unbalanced pulmonary and systemic blood flow; therefore, he underwent placement of transcatheter PFR as alternative to PABB. He underwent successful orthotopic heart transplant 104 days after index procedure. This case demonstrates the significant complexity that can occur in patients with HLHS and abnormal right sided valves. Additionally, it is another example that transcatheter branch pulmonary artery flow restriction can be a safe and feasible alternative to PABB as initial palliation strategy. It may benefit patients in whom primary Norwood procedure would have increased risks or who will undergo primary transplant.

Objective Although the right ventricle (RV) to pulmonary artery conduit in stage 1 Norwood operation results in improved interstage survival, the long-term effects of the ventriculotomy used in the traditional technique remain a concern. The periscopic technique (PT) of RV to pulmonary artery conduit placement has been described as an alternative technique to minimize RV injury. A retrospective study was performed to compare the effects of traditional technique and PT on ventricular function following Norwood operation. Methods A retrospective study of all patients who underwent Norwood operation from 2012 to 2019 was performed. Patients with baseline RV dysfunction and significant tricuspid valve regurgitation were excluded. Prestage 2 echocardiograms were reviewed by a blinded experienced imager for quantification of RV function (sinus and infundibular RV fractional area change) as well as for regional conduit site wall dysfunction (normal or abnormal, including hypokinesia, akinesia, or dyskinesia). Wilcoxon rank-sum tests were used to assess differences in RV infundibular and RV sinus ejection fraction and the Fisher exact test was used to assess differences in regional wall dysfunction. Results Twenty-two patients met inclusion criteria. Eight underwent traditional technique and 14 underwent PT. Median infundibular RV fractional area change was 49% and 37% (P = .02) and sinus RV fractional area change was 50% and 41% for PT and traditional technique (P = .007) respectively. Similarly qualitative regional RV wall function was better preserved in PT (P = .002). Conclusions The PT for RV to pulmonary artery conduit in Norwood operation results in better preservation of early RV global and regional systolic function. Whether or not this benefit translates to improved clinical outcome still needs to be studied.

Background The aims of this study were to investigate the dynamic changes in the vena contracta (VC) and proximal isovelocity surface area (PISA) through systole in patients with hypoplastic left heart syndrome and tricuspid regurgitation and to identify the stage of systole (early, mid, or late) in which VC and PISA radius are optimal. Methods Twenty-eight patients with hypoplastic left heart syndrome were prospectively studied using continuous two-dimensional (2D) and three-dimensional (3D) echocardiography. Two-dimensional VC width, 3D VC area, and PISA radii (2D and 3D) were measured frame by frame throughout systole. The maximal 2D VC width, 3D VC area, and PISA radii in the first, middle, and last thirds of systole were compared, and correlations were explored with 3D tricuspid annular areas, right atrial volumes, and right ventricular volumes. Results In all, 35 data sets that met inclusion criteria were analyzed. On frame-by-frame analysis, maximal 2D VC width and 3D VC area were found in the first third of systole in 17% and 20% of studies, in the second third in 34% and 31%, and in the final third in 49% and 49%. Similarly, the maximal 2D and 3D PISA radii were found in the first third of systole in 26% and 17% of studies, in the second third in 28% and 34%, and in the final third in 46% and 49%. Conclusions In hypoplastic left heart syndrome, detailed temporal analysis of tricuspid regurgitation–associated VC and PISA by 2D and 3D echocardiography reveals no reliable pattern predicting when in systole these parameters peak. Frame-by-frame measurement is necessary for identification of maximal VC and PISA radius on 2D and 3D color Doppler echocardiography because the severity of tricuspid regurgitation could be underestimated because of temporal variability in VC and PISA.

We investigated the incidence and predictors of failure to undergo the Fontan in children with hypoplastic left heart syndrome who survived superior cavopulmonary connection.The cohort consists of all patients with hypoplastic left heart syndrome who survived to hospital discharge after superior cavopulmonary connection between 1988 and 2017. The primary outcome was attrition, which was defined as death, nonsuitability for the Fontan, or cardiac transplantation before the Fontan. Subjects were excluded if they were awaiting the Fontan, were lost to follow-up, or underwent biventricular repair. The study period was divided into 4 eras based on changes in operative or medical management. Attrition was estimated with 95% confidence intervals, and predictors were identified using adjusted, logistic regression models.Of the 856 hospital survivors after superior cavopulmonary connection, 52 died, 7 were deemed unsuitable for Fontan, and 12 underwent or were awaiting heart transplant. Overall attrition was 8.3% (71/856). Attrition rate did not change significantly across eras. A best-fitting multiple logistic regression model was used, adjusting for superior cavopulmonary connection year and other influential covariates: right ventricle to pulmonary artery shunt at Norwood (P .01), total support time at superior cavopulmonary connection (P .01), atrioventricular valve reconstruction at superior cavopulmonary connection (P = .02), performance of other procedures at superior cavopulmonary connection (P = .01), and length of stay after superior cavopulmonary connection (P .01).In this study spanning more than 3 decades, 8.3% of children with hypoplastic left heart syndrome failed to undergo the Fontan after superior cavopulmonary connection. This attrition rate has not decreased over 30 years. Use of a right ventricle to pulmonary artery shunt at the Norwood procedure was associated with increased attrition.

Our aim was to evaluate the results of stage 2 palliation by means of bidirectional cavopulmonary shunt (BCPS) and to identify risk factors for failed Fontan completion.Between 1998 and 2018, BCPS was performed on 525 patients with functional single ventricle. Patient demographics, surgical data, and echocardiographic and cardiac catheterization measurements were analyzed, and outcomes after BCPS were evaluated.The median age at BCPS was 4.7 months (interquartile range, 3 to 7.4). Hypoplastic left heart syndrome was the most frequent diagnosis. The median follow-up after BCPS was 3.4 years (interquartile range, 1.5 to 8.7); 407 patients underwent the Fontan procedure, 50 were waiting for Fontan completion, 47 died, 6 were considered not suitable for Fontan completion, and 15 were lost to follow-up. Of the 407 patients who underwent Fontan completion, there were 5 early deaths. Freedom from failed Fontan completion (mortality before, unsuitability for, and early mortality after the Fontan procedure) at 1, 2, and 3 years was 91.9%, 87.3%, and 86.1%, respectively. Risk factor analysis for failed Fontan completion revealed hypoplastic left heart syndrome (hazard ratio [HR] 4.1, P = .001), unbalanced atrioventricular septal defect (HR 10.1, P.001), higher pulmonary artery pressure (HR 1.1, P = .040), and reduced ventricular function (HR 4.2, P = .001) as risks.Stage 2 palliation can be performed with minimal risk and provides excellent subsequent Fontan completion. Hypoplastic left heart syndrome, unbalanced atrioventricular septal defect, high pulmonary artery pressure, and reduced ventricular function at the time of BCPS were identified as risk factors for failure to successfully complete the Fontan procedure.

OBJECTIVESRight ventricular dysfunction predicts death in patients with hypoplastic left heart syndrome (HLHS), but differences in morphology and loading conditions make calculation of the ejection fraction (EF), a challenging measure of its function. Our goal was to evaluate how strain measurements with cardiac magnetic resonance feature tracking could be used to evaluate right ventricular function in patients with HLHS.METHODSA systematic search of the literature was performed by 2 independent researchers using the terms ‘population’, ‘intervention’, ‘comparison’, ‘outcome’ and ‘time criteria’. PubMed and the Ovid database were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.RESULTSOur review included 8 studies with 608 participants with ventricular strain values obtained using cardiac magnetic resonance feature tracking. After stage I palliation, global strain was reduced in patients after a hybrid procedure and a right ventricle-to-pulmonary artery conduit compared with a modified Blalock–Taussig shunt despite similar EFs. Global longitudinal strain did not differ between stage II and stage III (Fontan) palliation. Fontan patients had significantly impaired global longitudinal and circumferential strain compared to the left ventricular strain of the controls. Studies of Fontan patients that included patients with HLHS who were part of a cohort with a single right ventricle showed impaired global circumferential strain compared with the cohort with a single left ventricle, with controls, and over time. In this group, impaired global circumferential strain was associated with major adverse cardiac events.CONCLUSIONSCardiac magnetic resonance feature tracking can be used in patients with HLHS to evaluate RV strain and demonstrate differences between surgical strategies, over time and compared with controls. It could be used alongside clinical symptoms and EF values to detect ventricular dysfunction.

Background Norwood palliation for hypoplastic left heart syndrome typically results in retrograde perfusion of the native aortic root. This may predispose to native aortic root thrombosis (NART). Methods Patients who underwent stage 1 Norwood palliation at Children’s Hospital Colorado between 2003 and 2019 were retrospectively reviewed for NART. Additional patients were identified by a systematic literature review. Patient factors, operative details, presentation, diagnostic methods, treatments, and outcomes were analyzed. Results Three patients with NART were identified among 241 patients who had undergone stage 1 Norwood palliation at Children’s Hospital Colorado (mean follow-up, 48 months). A fourth patient identified at Children’s Hospital Colorado had undergone stage 1 palliation elsewhere. The systematic literature review identified 12 additional patients. Among the 16 patients, patients presented with new arrhythmias (38% [n = 6]), evidence of ischemia (31% [n = 5]), incidentally (19% [n = 3]), inability to wean from postoperative support (6% [n = 1]), and cardiac arrest (6% [n = 1). The diagnosis was made by transthoracic echocardiography (TTE) in 50% (n = 8), transesophageal echocardiography in 19% (n = 3), cardiac catheterization in 25% (n = 4), and cardiac computed tomography in 6% (n = 1). Importantly, 44% (n = 7) of patients were missed by TTE and subsequently diagnosed by other methods. Treatment strategies were surgical thrombectomy in 38% (n = 6), anticoagulation alone in 38% (n = 6), direct catheter thrombolysis in 19% (n = 3), and systemic thrombolysis in 6% (n = 1). The rate of mortality or transplant listing was 44% (n = 7). Conclusions NART is an underappreciated complication of Norwood palliation with high mortality. There should be a high index of suspicion for NART in patients after Norwood palliation with an unexplained complicated clinical course. Importantly, NART is frequently missed by TTE.

Background Right ventricle-to-pulmonary artery (RV-PA) shunt as a part of the Norwood procedure underwent many modifications. We present our experience with a commercially available polytetrafluoroethylene vascular graft with cobra-head cuff as an RV-PA shunt. Methods A consecutive series of 52 children with hypoplastic left heart syndrome (median age 8 [range, 2-68] days, median weight 3200 [range, 2060-4400] g) underwent the Norwood procedure with a cobra-head cuffed RV-PA shunt (6 mm). The cuffed end was used for the central PA reconstruction. A retrospective analysis of clinical results, PAs development, and shunt-related complications, interventions, and technique of Glenn operation was performed. The study endpoint was Glenn operation with shunt removal or interstage death. Results The hospital and late interstage mortality was 3.8% (n = 2 of 52) and 4% (n = 2 of 50), respectively, and was not shunt-related. During mean follow of 3.7 ± 2.5 years, 48 (92.3%) children underwent Glenn operation at a median age of 6 (range, 2.6-9.1) months. Angiography before the second stage revealed satisfactory branch PAs development (maximum and minimum McGoon ratio of 1.95 ± 0.36 and 1.38 ± 0.38, respectively). The mean maximal diameter of the left PA was smaller than that of the right PA (7.13 ± 2.1 mm vs 8.42 ± 2.2 mm; P = .017), without differences in mean minimal diameter. Two infants required stent implantation in proximal shunt end and 1 required urgent Glenn operation because distal shunt thrombosis. During Glenn operation, 11 (22.9%) children required patch reconstruction of central PAs. Conclusions The cobra-head cuffed graft allowed easy and reproducible reconstruction of the central PA during the Norwood procedure. Using this technique, the development of PAs is satisfactory, the rate of shunt-related complications and interventions is low, and the second stage can be performed without patch material.

We report a 15-year-old male with hypoplastic left heart syndrome (HLHS) after Fontan operation with recurrent, drug-resistant atrial tachycardia. With the use of electro-anatomical mapping system (EnSite) an atrial flutter (AFl) with reentry activation around the tricuspid valve was diagnosed. Successful radiofrequency catheter ablation (RFCA) was performed.

OBJECTIVES The aim of this study was to assess single right ventricular (RV) function in a large cohort of hypoplastic left heart syndrome (HLHS) patients after the completion of total cavopulmonary connection by analysing serial cardiovascular magnetic resonance (CMR) studies. METHODS CMR studies from 95 HLHS patients were analysed. RV end-diastolic and end-systolic volumes (RVEDV, RVESV), ejection fraction (RVEF) and long-axis strain (LAS) were measured from cine images. RESULTS All 95 patients had at least 2 CMR scans and 35 patients had 3 CMR scans. The median age (first quartile–third quartile) at the 3 examinations was 4.2 (3.3–6.1), 9.4 (6.1–11.4) and 14.6 (11.8–16.8) years. RV indexed volumes (RVEDVi and RVESVi) increased from first to the second and from the first and second examination to the third examination in patients with >10 years of age (P CONCLUSIONS Serial assessment of CMR studies in HLHS patients after total cavopulmonary connection completion demonstrate an increase in indexed RV volumes in older HLHS patients but only mild reduction in RVEF and LAS. The correlation of indexed RV volumes with RVEF and LAS together with the significant increase in RV volumes over time suggests that indexed RV volumes might be superior to RV functional markers to monitor the RV in HLHS patients.

Introduction:CHD affects over 1 million children in the United States. Studies show decreased mortality from CHD with newborn cardiac screening. California began a screening programme on 1 July, 2013. We evaluated the effect of mandatory screening on surgical outcomes at Loma Linda University Children’s Hospital since 1 July, 2013.Methods:We evaluated all infants having congenital heart surgery at Loma Linda University Children’s Hospital between 1 July, 2013 and 31 December, 2018. Primary target diagnoses include hypoplastic left heart syndrome, pulmonary atresia with intact ventricular septum, tetralogy of Fallot, total anomalous pulmonary venous return, transposition of the great arteries, tricuspid atresia, and truncus arteriosus. Secondary target diagnoses include aortic coarctation, double outlet right ventricle, Ebstein anomaly, interrupted aortic arch, and single ventricle. Patients were stratified by timing of diagnosis (pre-screen, screen positive, and screen negative). Primary end points were post-operative length of stay, operative mortality, absolute mortality, and actuarial survival.Results:The cohort included 274 infants. Of these, 79% were diagnosed prior to screening (46% prenatally). Only 38% of those screened were positive, with 13% of the cohort having a “missed diagnosis.”Conclusions:Primary targets were more likely to be diagnosed by screening (53%), while secondary targets were unlikely to be diagnosed by screening (10%) (p = 0.004). Outcomes such as length of stay, operative mortality, and actuarial survival were not different based on timing of diagnosis (p > 0.05). Despite late diagnosis, those not diagnosed until after screening did not have adverse outcomes.

Objectives To investigate the correlation between prenatal ultrasound (US) and autopsy findings in pregnancies terminated due to isolated congenital heart defects (CHDs), including CHDs associated with heterotaxy syndrome. Materials and methods The material consists of 67 fetuses with prenatally detected isolated CHDs or CHDs associated with heterotaxy syndrome at a tertiary center in Norway between 1985 and 2014. The main CHDs were categorized into subdiagnoses of CHDs in accordance with ICD-10. The US and autopsy findings were categorized according to degree of concordance. Results Gestational age at termination was 12 + 0–22 + 6 weeks. Hypoplastic left heart syndrome was the most common main diagnosis among the 67 fetuses (32.8%). There was full agreement between US and autopsy findings in 97.4% (222/228) of all subdiagnoses. The discrepant findings in three fetuses had no influence on the decision to terminate the pregnancy. Conclusions The correlation was high between prenatal US and postmortem findings in fetuses with isolated CHDs. Meticulous assessment of cardiac anatomy is particularly necessary when the decision to terminate relies on isolated CHDs. The trend of earlier termination challenges verification of diagnoses at autopsy. Consequently, the fetus should be examined at a tertiary center with fetal medicine specialists, pediatric cardiologists and perinatal pathologists.

Overall survival of patients with hypoplastic left heart syndrome (HLHS) has shown continued improvement. Right ventricular (RV) dysfunction, in the long term, adversely affects prognosis in these patients. This study examines changes in echocardiographic markers of RV function in a longitudinal cohort. We retrospectively reviewed patients with HLHS managed at our institution from 7/1994 to 1/2016. Follow-up included surgical and clinical data, and echocardiographic measures. Measures of RV function preceding and following all three stages of single ventricular palliation were collected. Freedom from transplant-free survival was assessed by Kaplan–Meier analysis. Multivariable associations with time to death or transplant were explored using the Cox proportional hazards model. A total of 120 patients with HLHS were identified. Norwood operation was performed in all patients. The probability of survival for the cohort was 71 ± 4.4%, 69 ± 4.5% and 66 ± 4.7% at 1, 2 and 5 years respectively after stage I Norwood operation. RV fractional area change (FAC), compared to post-Norwood was decreased at all subsequent stages with the greatest change noted post-superior cavo-pulmonary shunt from 40.7 ± 9.3% to 31.1 ± 8.3% (p 35% and TAPSE Z-score > -5, patients with RV FAC ≤ 35% and TAPSE Z-score ≤ -5 had a significantly lower transplant-free survival (p

BACKGROUND: The impact of published evidence on clinical practice has been understudied in pediatric cardiology. OBJECTIVE: We sought to assess changes in prescribing behavior for angiotensin-converting enzyme inhibitor (ACEI) and digoxin at discharge after initial palliation of infants with single ventricle (SV) physiology following the publication of two large studies: The Pediatric Heart Network Infant Single Ventricle (PHN-ISV) trial showing no benefit with routine ACEI use and the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) analysis showing an association between digoxin and survival. METHODS: ICD 9–10 codes identified SV infants from the Pediatric Health Information System (1/2004 to 1/2018) and charge codes identified medications at discharge. Generalized estimating equations implementing segmented logistic regressions modelled medication use, before and after (with a 3-month washout period) the relevant publication (ACEI 7/1/2010; digoxin 4/1/2016). A subgroup analysis was performed for hypoplastic left heart syndrome (HLHS). RESULTS: ACEI use (37 centers, n=4,700) at discharge did not change over time during the pre-publication period. After publication of the PHN-ISV trial, ACEI use decreased (OR: 0.61, CI 0.44–0.84, p=0.003). Digoxin use (43 centers, n=4,778) decreased by 1% monthly before publication. After the NPC-QIC publication, digoxin use increased (OR: 2.07, CI 1.05–4.08, p=0.04) with an ongoing increase of 9% per month. Results were similar for the HLHS subgroup. CONCLUSIONS: Prescribing behavior changed congruently after publication of evidence-based studies, with decreased ACEI use and increased digoxin use at discharge following initial palliation of SV infants. Our findings suggest scientific findings were rapidly implemented into clinical practice.

Purpose:The purpose of this study is to identify gaps in support for parents of children with Hypoplastic Left Heart Syndrome.Design and methods:Using a mixed-methods approach, the researchers first studied the parental and care team experience through interviews of Hypoplastic Left Heart Syndrome mothers and members of the inter-professional care team and then conducted an international survey of 690 Hypoplastic Left Heart Syndrome primary caregivers to validate the qualitative findings.Results:Parental and care team interviews revealed three main gaps in parental support, including lack of open communication, unrealistic parental expectations, and unclear inter-professional team roles. Survey results found that parents whose children were diagnosed with Hypoplastic Left Heart Syndrome after birth indicated significant dissatisfaction with the care team’s open communication and welcoming of feedback (p = 0.008). As parents progress through the stages of surgical intervention, they also indicate significant dissatisfaction with the care team’s anticipation of parental emotional needs and provision of coping resources (p = 0.003).Conclusions:Parental support interventions should focus on providing resources to help parents cope, helping the care team model open communication, and welcoming feedback on the parental experience.Practice implications:Interventions should be piloted with parents who are in the later stages of the surgical intervention timeline or whose children were diagnosed after birth as they are the populations who perceived the least support within this study.

OBJECTIVES With improvements in early survival after the stage I palliation (S1P) Norwood procedure for hypoplastic left heart syndrome (HLHS) and its variants, inter-stage death accounts for an increasing proportion of mortality. Our aim was to identify the risk factors for inter-stage mortality. METHODS The records of 322 neonates with HLHS or a variant who underwent the Norwood procedure at our centre between 2001 and 2019 were retrospectively analysed. RESULTS The diagnoses included 271 neonates with HLHS (84%) and 51 with variants (16%). Aortic atresia was observed in 138 (43%) patients, mitral atresia in 91 (28%), extracardiac anomalies in 42 (13%) and genetic disorder in 14 (4%). The median age and weight of the patients at the S1P Norwood procedure were 9 (interquartile range: 7–12) days and 3.2 (2.9–3.5) kg, respectively. The median cardiopulmonary bypass time was 137 (107–163) min. Modified Blalock–Taussig shunts were used in 159 (49%) and unvalved right ventricle-to-pulmonary artery shunts in 163 (51%) patients. The number of inter-stage deaths was as follows: between S1P and stage II palliation (S2P), 61 including 38 early (30 days) deaths, and between S2P and stage III palliation, 32 deaths. Low birth weight ( CONCLUSIONS The risk factors for inter-stage attrition after the Norwood procedure were different between each stage. Preoperative factors, including birth weight, restrictive atrial septum and extracardiac anomalies, adversely affected the inter-stage mortality.

Background Mortality after stage 1 palliation of hypoplastic left heart syndrome remains significant. Both cardiac output (CO) and systemic vascular resistance (SVR) contribute to hemodynamic vulnerability. Simultaneous measures of mean arterial pressure and somatic regional near infrared spectroscopy saturation can classify complex hemodynamics into 4 distinct states, with a low-CO state of higher risk. We sought to identify interventions associated with low-CO state occupancy and transition. Methods Perioperative data were prospectively collected in an institutional review board–approved database. Hemodynamic state was classified as high CO, high SVR, low SVR, and low CO using bivariate analysis. Associations of static and dynamic support levels and state classifications over 48 postoperative hours were tested between states and across transitions using mixed regression methods in a quasi-experimental design. Results Data from 10,272 hours in 214 patients were analyzed. A low-CO state was observed in 142 patients for 1107 hours. Both low CO and extracorporeal membrane oxygenation had increased mortality risk. The low-CO state was characterized by lower milrinone but higher catecholamine dose. Successful transition out of low CO was associated with increased milrinone dose and hemoglobin concentration. Increasing milrinone and hemoglobin levels predicted reduced risk of low CO in future states. Conclusions Bivariate classification objectively defines hemodynamic states and transitions with distinct support profiles. Maintaining or increasing inodilator and hemoglobin levels were associated with improved hemodynamic conditions and were predictive of successful future transitions from the low-CO state.

The hypoplasia of left-sided heart structures shows great variability and complexity. What the many variants have in common is that their heart structures are neither fully developed before nor after birth. Fetuses and newborns require an individual therapy depending on anatomy and function of the heart. Fetal interventions focus on improving left heart structures by catheter-based interventions and maternal hyperoxygenation which promotes growth as the left ventricular preload and blood flow within the cavity increase. Stage-I management of newborns with single ventricle physiology is usually based on the Norwood/Sano surgery or the Hybrid approach. Two more steps are required to ultimately achieve a Fontan circulation. Some centers also use the Hybrid approach for subsequent Norwood operation beyond the neonatal period. After the Hybrid approach, a comprehensive stage-II or corrective surgery is performed, the latter if a bi-ventricular circulation is possible. With progressively improved catheter-based interventions, particularly ductal stenting and manipulations of the atrial septum, the next advance is to develop a bespoke flow restrictor that can be easily inserted into the branches of the pulmonary artery. The main goal is to avoid complex heart operations under general anesthesia, followed by substantial intensive care in the neonatal period, especially for patients with complex heart defects. Based on the current state of the art of surgical treatment of hypoplastic left heart syndrome and variants with the Norwood surgery or the Hybrid approach, our main focus is on an alternative percutaneous transcatheter technique in the sense of a completely non-surgical stage-I approach.

Background Pericardial patches are often used for repair of congenital cardiac defects. The aim of this study was to describe our initial experience with the use of equine pericardium and its safety and advantages and disadvantages compared to bovine pericardium. Methods We designed a retrospective cohort study of 111 patients who were surgically treated for congenital heart disease between 2017 and 2020. Equine pericardium was used in 58 patients and bovine pericardium was used in 53 patients. Recorded variables included demographic data, preoperative cardiac pathology, site of patch insertion, morbidity and mortality. Results The overall survival rate was 94.5% and no deaths were related to patch insertion. None of our patients were reoperated on for patch related complications. Postoperative transcatheter intervention was needed in 2 patients (1.8%): one for dilatation of aortic arch stenosis after repair of hypoplastic left heart syndrome with equine pericardium and one for dilatation of pulmonary artery branches after repair of tetralogy of Fallot using bovine pericardium. Conclusions Equine pericardium is a safe patch material for reconstruction in congenital heart surgery. It may be preferable to bovine pericardium in cases requiring a complex shape or a pliable patch as in in arch reconstruction or for valve reconstruction.

Re-Norwood operation is technically difficult to perform and is a high risk procedure due to the underlying hypocardiac function. Herein, we describe our successful re-Norwood operation approach in a 6-month old infant with persistent severe cyanosis and aortic re-coarctation. Our procedure was performed using femoral artery cannulation to protect cerebrospinal and lower body perfusion. Safe reopening of the chest was achieved, despite strong adhesions due to prior surgeries. Our repair and anastomosis techniques are described in detail. Cardiac circulation and function improved post-surgery. The patient was maintained on anti-heart failure drug therapy after surgery while awaiting a Glenn procedure.

Hypoplastic left heart syndrome is a form of congenital heart disease that is associated with significant lifelong morbidity and mortality. Although rarely reported together, the prognosis for patients with hypoplastic left heart syndrome and congenital anomalies of the airway or lung, such as congenital diaphragmatic hernia, has been shown to be very poor. The outcomes for patients with hypoplastic left heart syndrome and congenital lobar emphysema specifically is currently unknown. Reported herein is the first case of a child with a rare combination of hypoplastic left heart syndrome and congenital lobar emphysema, and a discussion of his presentation, diagnosis, management and outcome to date.

Hypoplastic left heart syndrome (HLHS) is one of the most complicated congenital heart defects which leads to the inevitable fatal outcome in the natural course of the disease. Currently, Norwood procedure and fetal aortic valvuloplasty are considered the major approaches for surgical treatment of HLHS. However, the prognosis of such surgeries is often unpredictable. The aim. To study morphological variations of the left ventricle (LV) in HLHS and evaluate the prognostic significance of each of them in the choice of surgical approach. Materials. The main group included 63 hearts of newborns with HLHS, the comparison group included 53 hearts of newborns without cardiac pathology. Methods. The methods used were survey microscopy, as well as macro- and micromorphometry of various parameters of the heart, calculation of the ratio of their absolute values (indices) with subsequent statistical data processing. Results. Five types of LV were identified in HLHS patients based on the size and shape of the cavity, wall thickness, presence or absence of fibroelastosis: slit-like hypoplastic (Type I) (n = 10; 15.9%); slit-like hypertrophic (Type II) (n = 19; 30.2%); cylindrical (Type III) (n = 22; 34.9%); lacunar (Type IV) (n = 6; 9.5% ); lacunar-cylindrical (Type V) (n = 6; 9.5%). In Type I left ventricles, the interventricular index (IVI) (the ratio of the areas of the free walls of the left and right ventricles on the cross sections of the heart) was the smallest: 0.13 ± 0.03 units versus normal 1.96 ± 0.31 units. In Type II left ventricles, the value was equal to 1.69 ± 0.23 units; in Type III it was 1.59 ± 0.64 units; in Type IV it was 1.31 ± 0.03 units; in Type V it was 1.05 ± 0.52 units. The index of the working area of the right ventricular myocardium (RVI) (the ratio of the area of the free wall of the right ventricle to the sum of the areas of the free wall and interventricular septum) in Type I LV was the highest: 81.3 ± 5.7% versus normal 57.1 ± 2.02%; in Type II it was 49.7 ± 6.4%; in Type III it was 39.8 ± 2.9%; in Type IV it was 69.7 ± 16.1%; in Type V it was 41.3 ± 24.4%.Type III–V LVs have always been associated with fibroelastosis, in contrast to Type I and II LVs. Conclusions. In HLHS, Type I hearts are the most eligible for the Norwood procedure, since the LV, due to its minimal size, is not an excess ballast for the working right ventricle. Type II LV is optimal for the fetal aortic valvuloplasty, since during the II-III trimesters of gestation they can join the circulatory system due to remodeling. HLHS with LV fibroelastosis (Types III, IV, V) seem to be the least favorable for both pre- and postnatal surgery, especially in the presence of fibroelastosis of the right ventricle.

Objectives The Super Glenn procedure involves targeted increased in blood flow to left sided heart structures with fenestrated atrial septation. The objective of this study was to examine the outcomes of patients who had this procedure as a part of biventricular staging and specifically evaluate the effect on dimensions of left heart structures. Methods Data for patients who had this procedure between 2005 and 2019 were retrospectively identified. Results Thirty-seven patients were identified. Most common diagnosis was hypoplastic left heart syndrome in 40% (n = 15). On echocardiography, the median mitral valve z score was −2.26. On cardiac magnetic resonance imaging, median indexed left ventricular end-diastolic volume was 31.5 ml/m2 and mitral/tricuspid inflow ratio was 0.35. The median age at Super Glenn was 2.3 years (interquartile range 1.5–3.6) while median weight was 12 kg (interquartile range 9.8–14). There were no early/hospital deaths. The median intensive care unit length of stay was 4 days, and median hospital length of stay was 10 days. Median follow-up for the entire cohort was 3 years (range 15 days to 13.2 years). There was a statistically significant increase in indexed left ventricular dimensions. There were 5 deaths (14%). Three patients (8%) underwent heart transplant. Freedom from death/transplant was 79% at 5 years. Seven patients (19%) needed a reoperation. Twenty-three patients (62%) underwent biventricular conversion after a median of 11.3 months after Super Glenn. Conclusions The Super Glenn procedure achieves consistent increase in left ventricular dimensions. This may be a useful strategy to help achieve a successful biventricular circulation in patients with borderline left ventricle. The superiority/non-inferiority of this approach over the conventional Fontan pathway is unclear.

Background:Pulmonary arteriovenous malformations in single ventricle congenital heart disease are poorly understood. Previous studies investigating pulmonary arteriovenous malformations predominantly focus on patients with heterotaxy syndrome and interrupted inferior caval vein. It is unknown if development and resolution of pulmonary arteriovenous malformations are similar for patients with and without heterotaxy syndrome.Methods:In this retrospective single-institution study, we identified patients with a history of single ventricle congenital heart disease and Fontan palliation. We then matched patients with heterotaxy syndrome (intact and interrupted inferior caval vein) and non-heterotaxy hypoplastic left heart syndrome. To compare development of pulmonary arteriovenous malformations, we identified the frequency of positive diagnoses pre-Fontan. To compare resolution of pulmonary arteriovenous malformations, we recorded oxygen saturation changes for 12 months following Fontan.Results:A total of 124 patients were included. Patients with heterotaxy and interrupted inferior caval vein were more likely to have a pre-Fontan contrast echocardiogram performed (p < 0.01) and more likely to be diagnosed with pulmonary arteriovenous malformations pre-Fontan (p < 0.01). There was no difference in oxygen saturation prior to Fontan, yet all patient groups had increased their oxygen saturations in the first year after Fontan discharge.Conclusions:Pulmonary arteriovenous malformations are variably diagnosed prior to Fontan palliation; however, all study groups had increased oxygen saturations after Fontan discharge, potentially indicating resolution of pulmonary arteriovenous malformations in all groups. The prevalence of pulmonary arteriovenous malformations pre-Fontan is likely underestimated. A quantitative, systematic approach to diagnosis and follow-up of pulmonary arteriovenous malformations is needed to better understand susceptibility and pathophysiology.

Die Mortalitat von Patienten mit isoliert auftretenden angeborenen Zwerchfellhernien liegt in spezialisierten Zentren bei 20–40%. Wesentliche, das Outcome beeinflussende Faktoren, sind die bestehende Lungenhypoplasie, eine daraus resultierende pulmonale Hypertonie, sowie das Vorliegen weiterer Fehlbildungen. Begleitfehlbildungen wie angeborene Herzfehler treten bei ca. 18% aller Neonaten mit Zwerchfellhernie auf. Schwere angeborene Herzfehler wie das hypoplastische Linksherz Syndrom zeigen sich in ca. 8% der Falle. In einer retrospektiven Analyse des Patientenkollektivs unserer Klinik zwischen 01/2012 und 12/2018 wurde das pra- und postnatale Management, sowie das Outcome von Neugeborenen mit der Kombination aus angeborenen Herzfehlern und Zwerchfellhernien untersucht. Im Studienzeitraum wurden in unserer Klinik 156 Neugeborene mit Zwerchfellhernie behandelt. Bei 10 Patienten (6,4%) lag zusatzlich ein schwerer, bei 11 Patienten (7,1%) ein moderater Herzfehler vor. 6/21 Patienten verstarben im Verlauf des Krankenhausaufenthaltes, davon 3 am ersten Lebenstag. Es zeigte sich eine deutlich geringere Mortalitat bei Patienten mit Zwerchfellhernie und moderatem Herzfehler im Vergleich zu schwerem Herzfehler (9 vs. 50%). Besonders hoch lag die Mortalitat bei Kindern mit einem univentrikularen Herzen. Trotz einer deutlich reduzierten Prognose bei der Kombination aus angeborenem Herzfehler und Zwerchfellhernie muss nicht generell mit einer infausten Prognose gerechnet werden. In spezialisierten Zentren kann ein kurativer Ansatz erfolgen. The mortality of patients with isolated congenital diaphragmatic hernia (CDH) in specialized centers is 20–40%. The main factors influencing the outcome are the underlying pulmonary hypoplasia, the resulting pulmonary hypertension and the presence of other malformations. Concomitant malformations such as congenital heart defects occur in around 18% of all neonates with a diaphragmatic hernia. Serious congenital heart defects such as hypoplastic left heart syndrome occur in approximately 8% of cases. In a retrospective analysis of the patient collective of our hospital between 01/2012 and 12/2018, the prenatal and postnatal management as well as the outcome of newborns with a combination of congenital heart defects and diaphragmatic hernias were examined. During the study period, 156 newborns with diaphragmatic hernias were treated at our institution. In 10 patients (6.4%) there was also a severe, and in 11 patients (7.1%) a moderate heart defect. 6/21 patients died during their hospital stay, 3 of them on the first day of life. There was a significantly lower mortality in patients with diaphragmatic hernia and moderate heart defects compared to severe heart defects (9 vs. 50%). The mortality in children with a univentricular heart was particularly high. Despite a significantly reduced prognosis for the combination of congenital heart defects and diaphragmatic hernia, generally a poor prognosis does not have to be expected. A curative approach can be achieved in specialized centers.

Accurate assessment of the right ventricular (RV) volume and function is important in patients with hypoplastic left heart syndrome (HLHS). We sought to investigate the effect of ventriculotomy on the correlation of RV functional assessments by two-dimensional echocardiography (2DE) to cardiac magnetic resonance (CMR)-derived RV ejection fraction (EF) in patients with HLHS. A retrospective re-analysis of CMR imaging with matched 2DE was performed from the institutional HLHS registry. Echocardiographic RV functional parameters were analyzed and correlated with CMR-derived EF. Intraclass correlation coefficient was used to determine interobserver reliability. A total of 58 matched echocardiograms and CMR imaging studies from 46 patients was evaluated. Median duration between CMR imaging and echocardiogram was 1 day (range 0–6 days). No significant difference was seen in CMR RV EF between patients with and without a ventriculotomy (EF − 43.6% vs 44.7%, p = 0.85). The presence of a ventriculotomy significantly decreased the correlation of biplane FAC (r = 0.86 vs 0.52; p = 0.02), triplane FAC (r = 0.84 vs 0.49; p = 0.03), and 2DE visually estimated EF (r = 0.83 vs 0.49; p = 0.02). The correlation of circumferential and longitudinal strains to CMR-derived EF was not significantly affected by the presence of a ventriculotomy. A prior ventriculotomy significantly affected correlation between 2DE FAC and visually estimated EF with CMR-derived EF. The dyskinetic myocardial segment due to ventriculotomy, which is often not visualized by 2DE, may be the reason for this discrepancy.