Molecular Pathways and Animal Models of Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with underdevelopment of left-sided heart structures. While previously uniformly fatal, surgical advances now provide highly effective palliation that allows most HLHS patients to survive their critical CHD. Nevertheless, there remains high morbidity and mortality with high risk of heart failure. As hemodynamic compromise from restricted aortic blood flow has been suggested to underlie the poor LV growth, this suggests the possibility of prenatal fetal intervention to recover LV growth. As such interventions have yielded ambiguous results, the optimization of therapy will require more mechanistic insights into the developmental etiology for HLHS. Clinical studies have shown high heritability for HLHS, with an oligogenic etiology indicated in conjunction with genetic heterogeneity. This is corroborated with the recent recovery of mutant mice with HLHS. With availability-induced pluripotent stem cell (iPSC)-derived cardiomyocytes from HLHS mice and patients, new insights have emerged into the cellular and molecular etiology for the LV hypoplasia in HLHS. Cell proliferation defects were observed in conjunction with metaphase arrest and the disturbance of Hippo-YAP signaling. The left-sided restriction of the ventricular hypoplasia may result from epigenetic perturbation of pathways regulating left-right patterning. These findings suggest new avenues for fetal interventions with therapies using existing drugs that target the Hippo-YAP pathway and/or modulate epigenetic regulation.

Hemodynamics During Development and Postnatal Life.

A well-developed heart is essential for embryonic survival. There are constant interactions between cardiac tissue motion and blood flow, which determine the heart shape itself. Hemodynamic forces are a powerful stimulus for cardiac growth and differentiation. Therefore, it is particularly interesting to investigate how the blood flows through the heart and how hemodynamics is linked to a particular species and its development, including human. The appropriate patterns and magnitude of hemodynamic stresses are necessary for the proper formation of cardiac structures, and hemodynamic perturbations have been found to cause malformations via identifiable mechanobiological molecular pathways. There are significant differences in cardiac hemodynamics among vertebrate species, which go hand in hand with the presence of specific anatomical structures. However, strong similarities during development suggest a common pattern for cardiac hemodynamics in human adults. In the human fetal heart, hemodynamic abnormalities during gestation are known to progress to congenital heart malformations by birth. In this chapter, we discuss the current state of the knowledge of the prenatal cardiac hemodynamics, as discovered through small and large animal models, as well as from clinical investigations, with parallels gathered from the poikilotherm vertebrates that emulate some hemodynamically significant human congenital heart diseases.

Human Genetics of Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) is a severe congenital cardiovascular malformation characterized by hypoplasia of the left ventricle, aorta, and other structures on the left side of the heart. The pathologic definition includes atresia or stenosis of both the aortic and mitral valves. Despite considerable progress in clinical and surgical management of HLHS, mortality and morbidity remain concerns. One barrier to progress in HLHS management is poor understanding of its cause. Several lines of evidence point to genetic origins of HLHS. First, some HLHS cases have been associated with cytogenetic abnormalities (e.g., Turner syndrome). Second, studies of family clustering of HLHS and related cardiovascular malformations have determined HLHS is heritable. Third, genomic regions that encode genes influencing the inheritance of HLHS have been identified. Taken together, these diverse studies provide strong evidence for genetic origins of HLHS and related cardiac phenotypes. However, using simple Mendelian inheritance models, identification of single genetic variants that "cause" HLHS has remained elusive, and in most cases, the genetic cause remains unknown. These results suggest that HLHS inheritance is complex rather than simple. The implication of this conclusion is that researchers must move beyond the expectation that a single disease-causing variant can be found. Utilization of complex models to analyze high-throughput genetic data requires careful consideration of study design.

Vectorcardiography signs of a failing Fontan: Heart rate, PR interval, RtQRSvm, QRSvm and SPQRS-T angle as noninvasive markers of late Fontan complications and mortality.

BACKGROUND: Limited data exists on interpreting vectorcardiography (VCG) parameters in the Fontan population. OBJECTIVE: The purpose of this study was to demonstrate the associations between ECG/VCG parameters and Fontan failure (FF). METHODS/RESULTS: 107 patients with a Fontan operation after 1990 and without significant ventricular pacing were included. FF and Fontan survival (FS) groups were compared. The average follow-up after Fontan operation was 11.8 years ±7.1 years. 14 patients had FF (13.1%) which was defined as having protein-losing-enteropathy (1.9%), plastic bronchitis (2.8%), Fontan takedown (1.9%), heart transplant (5.6%), NYHA class III-IV (2.8%) or death (0.9%). A 12­lead ECG at last follow up or prior to FF was assessed for heart rate, PR interval, QRS duration, Qtc and left/right sided precordial measures (P-wave, QRS and T-wave vector magnitudes, spatial P-R and QRS-T angles). Transthoracic echocardiogram evaluated atrioventricular valve regurgitation and ventricular dysfunction at FF or last follow up. A cox multivariate regression analysis adjusted for LV dominance, ventricular dysfunction, HR, PR, QTc, Pvm, QRSvm, SPQRST-angle, RtPvm, RtQRSvm and RtTvm. Ventricular dysfunction, increased heart rate and prolonged PR interval were significantly associated to FF at the multivariate analysis. ROC analysis and Kaplan-meier analysis revealed an increased total mortality associated with a heart rate > 93 bpm, PR interval > 155 mv, QRSvm >1.91 mV, RtQRSvm >1.8 mV and SPQRST angle >92.3 mV with p values <0.001 to 0.018. CONCLUSION: We demonstrate the importance of ECG/VCG monitoring in the Fontan population and suggest specific indicators of late complications and mortality.

Duct Stenting in Duct-Dependent Systemic Blood Flow, Past, Present, and Future.

Arterial duct stenting, pioneered in the early 1990s for newborns with a duct-dependent pulmonary and systemic circulation, has evolved significantly over the past decades. This progressive technique has led to the development of novel therapeutic strategies, including the Hybrid approach introduced three decades ago, and more recently, a complete transcatheter approach for treating newborns with hypoplastic left heart syndrome (HLHS). Subsequently, the transcatheter method has been extended to bi-ventricular lesions and patients with pulmonary hypertension, establishing a reverse Potts-shunt pathophysiology. Considering current experiences, this review aims to assess the strengths, weaknesses, and complications associated with ductal stenting, which represents a critical component of these complex treatment strategies. Despite advancements, the mortality rate of Norwood and Hybrid stage-1 procedures has plateaued, underscoring the importance of enhancing the quality of life of affected patients as the primary therapeutic goal. The prerequisite is a gentle, almost atraumatic medicine, particularly during the newborn period. It is essential to recognize that both the Hybrid and total transcatheter approaches demand comparable experience to Norwood surgery. Successful outcomes hinge on much more than merely inserting a stent into the duct; they require meticulous attention to detail and comprehensive management strategies.

Quality analysis of publicly available information about hypoplastic left heart syndrome.

PURPOSE: Publicly available health information is increasingly important for patients and their families. While the average US citizen reads at an 8th-grade level, electronic educational materials for patients and families are often advanced. We assessed the quality and readability of publicly available resources regarding hypoplastic left heart syndrome (HLHS). METHODS: We queried four search engines for "hypoplastic left heart syndrome", "HLHS", and "hypoplastic left ventricle". The top 30 websites from searches on Google, Yahoo!, Bing, and Dogpile were combined into a single list. Duplicates, commercial websites, physician-oriented resources, disability websites, and broken links were removed. Websites were graded for accountability, content, interactivity, and structure using a two-reviewer system. Nonparametric analysis of variance was performed. RESULTS: Fifty-two websites were analysed. Inter-rater agreement was high (Kappa = 0.874). Website types included 35 hospital/healthcare organisation (67.3%), 12 open access (23.1%), 4 governmental agency (7.7%), and 1 professional medical society (1.9%). Median total score was 19 of 39 (interquartile range = 15.8-25.3): accountability 5.5 of 17 (interquartile range = 2.0-9.3), content 8 of 12 (interquartile range = 6.4-10.0), interactivity 2 of 6 (interquartile range = 2.0-3.0), and structure 3 of 4 (interquartile range = 2.8-4.0). Accountability was low with 32.7% (n = 17) of sites disclosing authorship and 26.9% (n = 14) citing sources. Forty-two percent (n = 22) of websites were available in Spanish. Total score varied by website type (p = 0.03), with open access sites scoring highest (median = 26.5; interquartile range = 20.5-28.6) and hospital/healthcare organisation websites scoring lowest (median = 17.5; interquartile range = 13.5-21.5). Score differences were driven by differences in accountability (p = 0.001) - content scores were similar between groups (p = 0.25). Overall readability was low, with median Flesch-Kincaid Grade Level of 11th grade (interquartile range = 10th-12th grade). CONCLUSIONS: Our evaluation of popular websites about HLHS identifies multiple opportunities for improvement, including increasing accountability by disclosing authorship and citing sources, enhancing readability by providing material that is understandable to readers with the full spectrum of educational background, and providing information in languages besides English, all of which would enhance health equity.

Echocardiographic features and outcome of restrictive foramen ovale in fetuses with and without cardiac malformations: Literature review.

Foramen ovale is a small communication between the left and the right atrium and its restriction is a rare congenital heart anomaly. There is no consensus on diagnosis and management of fetal restrictive foramen ovale (RFO). In our paper we included 11 studies about fetuses affected by isolated RFO, RFO with D-Transposition of the Great Arteries (dTGA) and RFO with hypoplastic left heart syndrome (HLHS). While fetuses affected from HLHS and dTGA with RFO have a poor prognosis, premature RFO in an otherwise structurally normal heart, if found in later gestation, have an overall good outcome.

Hypoplastic Left Heart Syndrome: Signaling & Molecular Perspectives, and the Road Ahead.

Hypoplastic left heart syndrome (HLHS) is a lethal congenital heart disease (CHD) affecting 8-25 per 100,000 neonates globally. Clinical interventions, primarily surgical, have improved the life expectancy of the affected subjects substantially over the years. However, the etiological basis of HLHS remains fundamentally unclear to this day. Based upon the existing paradigm of studies, HLHS exhibits a multifactorial mode of etiology mediated by a complicated course of genetic and signaling cascade. This review presents a detailed outline of the HLHS phenotype, the prenatal and postnatal risks, and the signaling and molecular mechanisms driving HLHS pathogenesis. The review discusses the potential limitations and future perspectives of studies that can be undertaken to address the existing scientific gap. Mechanistic studies to explain HLHS etiology will potentially elucidate novel druggable targets and empower the development of therapeutic regimens against HLHS in the future.

Genome-wide DNA methylation profiling confirms a case of low-level mosaic Kabuki syndrome 1.

Kabuki syndrome is a Mendelian disorder of the epigenetic machinery characterized by typical dysmorphic features, intellectual disability, and postnatal growth deficiency. Pathogenic variants in the genes encoding the chromatin modifiers KMT2D and KDM6A are responsible for Kabuki syndrome 1 (KS1) and Kabuki syndrome 2 (KS2), respectively. In addition, 11 cases of KS1 caused by mosaic variants in KMT2D have been reported in the literature. Some of these individuals display milder craniofacial and growth phenotypes, and most do not have congenital heart defects. We report the case of an infant with severe hypoplastic left heart syndrome with mitral atresia and aortic atresia (HLHS MA-AA), pulmonary vein stenosis, and atypical facies with a somatic mosaic de novo nonsense variant in KMT2D (c.8200C>T, p.R2734*) identified on trio exome sequencing of peripheral blood and present in 11.2% of sequencing reads. KS was confirmed with EpiSign, a diagnostic genome-wide DNA methylation platform used to identify epigenetic signatures. This case suggests that use of this newly available clinical test can guide the interpretation of low-level mosaic variants identified through sequencing and suggests a new lower limit of mosaicism in whole blood required for a diagnosis of KS.

Fetal growth of left-sided structures and postnatal surgical outcome in borderline left heart varies by cardiac phenotype.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Leftward and Posterior Deviation of the Septum Primum Predicts Morbidity in Patients with Hypoplastic Left Heart Syndrome.

Leftward posterior deviation of the atrial septum primum (LDSP) has been reported in up to 64% of patients with hypoplastic left heart syndrome (HLHS) but there are no published data on its impact on neonatal outcomes. We reviewed the prevalence of LDSP and its correlation with neonatal outcomes in our institution. This was a single-center retrospective study of neonates with HLHS from 2001 to 2019. Echocardiograms were reviewed and the presence or absence of LDSP was noted. To quantify the degree of deviation in patients with LDSP, a new measurement, the deviation index (DI) was calculated using both the subcostal long and short-axis views. Of ninety-four patients with HLHS, fifty-seven (61%) patients were noted to have LDSP. There was no statistically significant difference in gestational age (GA), birth weight (BW), or mortality between patients with and without LDSP. Patients with LDSP had an increased incidence of unplanned reoperation (p < 0.01), post-operative cardiac catheterization (p < 0.05), and post-operative infection (p < 0.05). After correction for GA, BW, HLHS subtype, and type of surgery, LDSP predicted reoperation (OR = 3.6, p < 0.01), catheterization (OR = 2.7, p = 0.05), and infection (OR = 3.4, p < 0.05). Higher degree of deviation predicted reoperation (DI > 0.17), catheterization (DI > 0.07), and infection (DI > 0.12). There was excellent inter-observer reproducibility of the DI (ICCabsolute-agreement = 0.82, ICCconsistency = 0.90). Patients with LDSP have a higher prevalence of post-operative morbidity. The degree of deviation was found to be predictive of post-operative complications. Pre-operative echocardiographic evaluation of LDSP in patients with HLHS may be helpful in risk stratification and counseling.

Insights from 3D Echocardiography in Hypoplastic Left Heart Syndrome Patients Undergoing TV Repair.

BACKGROUND: Tricuspid regurgitation (TR) in hypoplastic left heart syndrome (HLHS) is associated with morbidity and mortality. TR mechanisms and the impact of tricuspid valve repair (TVR) are unclear. We examined HLHS TR mechanisms, TVR's impact on tricuspid valve (TV), and features of poor TVR durability. METHODS: We retrospectively compared 35 HLHS TVR cases and 35 age/stage-matched HLHS controls who do not undergo TVR. Pre-operative 3-dimensional echocardiography (3DE) assessed overall TV morphology (prolapse, normal, tethered), leaflet morphology, vena contracta area, and TR location. Two-dimensional echocardiography measured TV annulus diameter, RV fractional area change (RVFAC), sphericity, and TR grade at three time points (pre-op, early post-op, and latest follow-up). RESULTS: Pre-op, TVR group, and controls had no difference in age, RV function or shape, or TV dimension. TVR group most commonly had anterior leaflet prolapse followed by septal leaflet prolapse or tethering. TR jet arises centrally (63%) and anterior septally (26%). Posterior annuloplasty (69%), commissuroplasty (37%), and leaflet repair (37%) were surgical techniques commonly performed. At early post-op, TR grade and TV annulus decreased. At latest follow-up, TV annulus remained reduced; however, 50% had significant TR. 25% required TV reoperation. Larger vena contracta at TVR was associated with significant TR. CONCLUSION: HLHS patients undergoing TVR had more anterior leaflet prolapse and central TR. While TVR initially reduces annular size and TR grade, 50% redevelop significant TR despite maintained annular reduction. The association of greater TR severity prior to repair with post-op recurrence raises the consideration for earlier repair of TR in HLHS patients.

Identifying gaps in parental support for families of children with hypoplastic left heart syndrome.

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.

Growth and Nutritional Intake of Infants with Univentricular Circulation.

OBJECTIVES: To evaluate the nutritional status and early nutritional intake of infants with univentricular congenital heart disease. STUDY DESIGN: The included infants underwent a Norwood procedure or hybrid intervention (stage 1) within the first 6 weeks of life, between January 2014 and January 2019, at Children's Health Ireland at Crumlin. Demographic, anthropometric, nutritional intake, and morbidity data were collected. RESULTS: Data were collected on 90 infants and 1886 neonatal admission days. There was a significant drop in mean weight-for-age z-score (WAZ) between measurements at birth, -0.01 and on discharge post stage 1 surgery -1.45 (P < .01). On hospital discharge (median hospital stay, 25 days) 32% of infants had a WAZ <-2 and 11% had a WAZ <-3. Pre-stage 1, 26% received trophic feeds and 39% received parenteral nutrition. Basal metabolic requirements and target caloric intake (120 kcal/kg) were met on 56% and 13% of admission days, respectively. Infants referred to a dietitian had a shorter time to any form of nutrition support, enteral feeds, and target caloric intake (P < .001, P = .016, and P = .048, respectively). At stage 3 (Fontan) surgery, 15% of infants were classified as stunted (length-for-age z-score [LAZ] <-2). CONCLUSIONS: The greatest decline in nutritional status occurs in the neonatal period, followed by significant growth stunting by the time of the Fontan procedure. Early involvement of dietitians is critical in the care of this nutritionally fragile group. With the currently low rate of preoperative nutritional support, there may be opportunities to improve intake at this critical stage.

Early prenatal diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins due to a 16q24.1 deletion.

First trimester ultrasound screening is an essential fetal examination performed generally at 11-13 weeks of gestation (WG). However, it does not allow for an accurate description of all fetal organs, partly due to their development in progress. Meanwhile, increased nuchal translucency (INT) is a widely used marker known to be associated with chromosomal deleterious rearrangements. We report on a 14 WG fetus with an association of INT and univentricular congenital heart malformation (CHM) leading to chorionic villous sampling (CVS). Cytogenetic investigations performed using array-Comparative Genomic Hybridization (CGH) and fluorescence in situ hybridization (FISH) demonstrated a 1.17 Mb deletion in 16q24.1 encompassing FOXF1 arisen de novo on maternal inherited chromosome. Fetopathological study confirmed CHM with hypoplastic left heart syndrome (HLHS) associating aortic atresia, mitral stenosis, and left ventricular hypoplasia and revealed in addition specific lung lesions corresponding to alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). This is so far the first case of first trimester prenatal diagnosis of ACDMPV due to the deletion of FOXF1 gene. An interpretation of the complex genomic data generated by ultrasound markers is facilitated considerably by the genotype-phenotype correlations on fetopathological examination.

Left Ventricular Recruitment in Patients With Hypoplastic Left Heart Syndrome.

Hypoplastic left heart complex with "borderline left ventricle" and intact ventricular septum is a clinical conundrum for the congenital heart surgeon. The choice between neonatal biventricular repair and single ventricle palliation can be challenging, and the current tools to aid in the decision-making process fail to account for the morbidity associated with intermediate and late diastolic dysfunction. Staged ventricular recruitment, consisting of valvular repair techniques, resection of endocardial fibroelastosis, atrial septal restriction, and augmentation of pulmonary blood flow, has been shown to improve left ventricular size and function culminating in eventual biventricular circulation. Despite staged ventricular recruitment, some patients cannot undergo biventricular conversion. Strategies to address these complex patients, including the "reverse" double switch, are the next frontier in biventricular repair.

Perioperative Milrinone Infusion Improves One-Year Survival After the Norwood-Sano Procedure.

OBJECTIVES: The aim of this study was to investigate whether milrinone infusion improved one-year survival in patients who underwent the Norwood-Sano procedure. DESIGN: A retrospective observational study. SETTING: A single-institution university hospital. PARTICIPANTS: Children who underwent the Norwood-Sano procedure from January 2008 to December 2014. INTERVENTIONS: Patients were categorized into two groups: group E+D, who received routine epinephrine and dopamine infusion, and group M, who received routine milrinone infusion for intra- and postoperative inotropic support. MEASUREMENTS AND MAIN RESULTS: The primary outcome of this study was one-year survival after the Norwood-Sano procedure. A total of 45 patients were included (group E+D, 22; group M, 23). One-year survival in group M was significantly higher than that in group E+D (95.7% [22/23] v 72.7% [16/22], p = 0.03). A Kaplan-Meier curve also showed that one-year survival in group M was significantly higher than that in group E+D (p = 0.04), from the result of the log-rank test. The number of patients who had any arrhythmias in the intensive care unit (ICU) was significantly lower in group M than in group E+D (21.7% [5/23] v 50% [11/22], p = 0.03). The duration of ICU stay did not have statistical difference between groups (group M 19; interquartile range [IQR], 15-28) v group E+D 19.5 (IQR, 16.3-35.5) days, p = 0.57). CONCLUSIONS: Perioperative milrinone infusion improved the mortality after the Norwood-Sano procedure. Potential advantages of milrinone compared with epinephrine are fewer arrhythmias and better systemic perfusion, which could decrease lethal cardiac events in the ICU.

A milestone in congenital cardiac surgery: Four decades of the Norwood procedure.

Hypoplastic left heart syndrome (HLHS) was first described by Lev in 1952, but it was not until 1958 that it received a name from Noonan and Nadas. For the next several decades, the defect was considered untreatable. In 1979, William Norwood and his colleagues from Boston initiated a program to evaluate staged surgical management for infants with HLHS. The Norwood operation has became a milestone in the effective palliation for neonates born with HLHS. Today, the Norwood procedure is the first step of a three-stage heart surgery aimed at creating a new circulatory pathway (i.e., the Fontan pathway).

Cognitive and Attentional Function in Children with Hypoplastic Left Heart Syndrome: A Pilot Study.

While survival for children with hypoplastic left heart syndrome (HLHS) has improved, compromised cardiac output and oxygen delivery persist, and children show cognitive deficits. Most research has assessed young children on broad cognitive indices; less is known about specific indices in older youth. In this pilot study, cognitive function and attention in youth ages 8 to 16 years with HLHS (n = 20) was assessed with the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) and NIH Toolbox Cognition Battery (NTCB); parents completed the Child Behavior Checklist. Children scored significantly lower than normative means on the WISC-V Full Scale IQ, Verbal Comprehension, Visual Spatial, Working Memory, and Processing Speed indices, and the NTCB Fluid Cognition Composite; effect sizes ranged from medium to large. Attention problems had a large significant effect. Child age corresponded to lower visual spatial scores. Findings highlight the importance of assessing multiple cognitive indices for targeted intervention and investigating age and disease factors as potential correlates in larger samples.

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.