Hypoplastic Left Heart Syndrome Research Articles

Transforming congenital heart disease management: Advances in fetal cardiac interventions.

This review addresses the transformative advancements in fetal cardiac interventions (FCI) for congenital heart diseases (CHD), with a particular focus on aortic stenosis with evolving hypoplastic left heart syndrome, pulmonary atresia with an intact ventricular septum, and HLHS with an intact atrial septum (HLHS-IAS). We outline the specific FCI techniques employed, the refined criteria for selecting appropriate fetal and maternal candidates, and the promising yet varied outcomes associated with these procedures. Procedural strategies and clinical decision-making are examined as we take into account the fetal pathophysiology and the benefits and risks of early intervention. We highlight the role of multidisciplinary teams in improving technical success and managing immediate procedural complications, which have led to significant improvements in procedural outcomes. Additionally, the review discusses the long-term outcomes, challenges, and future research directions in FCI, emphasizing the necessity for continuous innovation and collaboration across specialties to advance the management of CHD. The integration of new technologies and research findings holds the promise of further enhancing FCI success rates and patient outcomes.

Native aortic root thrombus leading to myocardial infarction in a single ventricle patient.

We report a 14-month-old male with hypoplastic left heart syndrome, mitral stenosis, and aortic stenosis with native aortic root thrombus. He developed a wide complex ventricular tachycardia and ST-segment elevation myocardial infarction with troponin I levels peaking at 388 ng/mL. He was treated safely with systemic alteplase with a resolution of his regional wall motion abnormality 18 hours later.

Children with Congenital Heart Diseases Exhibit Altered Deep Gray Matter Structures.

Children with congenital heart diseases (CHDs) have an increased risk of developing neurologic deficits, even in the absence of apparent brain pathology. The aim of this work was to compare quantitative macro- and microstructural properties of subcortical gray matter structures of pediatric CHD patients with normal appearing brain magnetic resonance imaging to healthy controls. We retrospectively reviewed children with coarctation of the aorta (COA) and hypoplastic left heart syndrome (HLHS) admitted to our hospital. We identified 24pediatric CHD patients (17COA, 7HLHS) with normal-appearing brain MRI. Using an atlas-based approach, the volume and apparent diffusion coefficient (ADC) were determined for the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, nucleus accumbens, cerebral white matter, cerebral cortex, and brainstem. Multivariate statistics were used to compare the extracted values to reference values from 100 typically developing children without any known cardiac or neurological diseases. Multivariate analysis of covariance using the regional ADC and volume values as dependent variables and age and sex as co-variates revealed asignificant difference between pediatric CHD patients and healthy controls (p < 0.001). Post-hoc comparisons demonstrated significantly reduced brain volumes in most subcortical brain regions investigated and elevated ADC values in the thalamus for children with CHD. No significant differences were found comparing children with COA and HLHS. Despite normal appearing brain MRI, children with CHD exhibit wide-spread macro-structural and regional micro-structural differences of subcortical brain structures compared to healthy controls, which could negatively impact neurodevelopment, leading to neurological deficits in childhood and beyond.

Critical Organ Dysfunction and Preoperative Mortality in Newborns with Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) is fatal without surgical intervention. An important subset of HLHS patients die prior to surgical intervention, but this population is underevaluated. The neonatal sequential organ failure assessment score (nSOFA) is an operational definition of organ dysfunction that can identify those with a high risk of mortality among neonatal intensive care unit (NICU) patients. The utility of the nSOFA to predict preoperative mortality in the unique HLHS population is unknown and could inform care, particularly care provided by neonatology staff. We performed a multicenter retrospective cohort study of HLHS cases across three level IV NICUs from January 1, 2009 to December 3, 2023. Patients were classified as either survived or died prior to surgical intervention. Demographic variables were curated from medical records including the maximum nSOFA (nSOFAmax) before surgical intervention or death. We identified 265 patients with HLHS over the study period. The nSOFAmax was greater in patients who died preoperatively (14/265; 5%) compared with survivors to surgical intervention (median 8 [interquartile range, 6, 12] vs. 2 [0, 4]; p < 0.001). The area under receiver operating characteristics curve for the nSOFAmax to discriminate for mortality was 0.93 (95% confidence interval, 0.88-0.98; p < 0.001). Compared with an nSOFAmax of 0, the likelihood ratio for preoperative death doubled at 2, tripled at 4, and was 10-fold at 9. This is the first demonstration of nSOFA utility in specific to congenital heart disease and HLHS. The nSOFAmax represents a novel, electronic health record-compatible, and generalizable method to identify patient-level organ dysfunction and risk for preoperative mortality in HLHS patients. KEY POINTS: · An important subset of HLHS patients die preoperatively.. · nSOFA can be used to measure preoperative HLHS severity.. · nSOFA predicts preoperative mortality risk in HLHS patients..

Mesenchymal Stem Cells improve phenotype of induced pluripotent stem cell (iPSC)-derived cardiomyocytes in Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). We previously demonstrated that genetic variants in the alpha myosin heavy chain (MYH6) gene are significantly associated with HLHS as well as poor outcomes in patients. Additionally, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) carrying an MYH6-R443P head domain variant demonstrated an impaired CM phenotype including dysmorphic sarcomere structure, altered contractility, and upregulated MYH7 expression. Mesenchymal stem cells (MSCs) and their secretome are currently being explored as a potential therapeutic for cardiac injury. In this study, a possible treatment strategy for iPSC-CMs with a MYH6 tail domain variant was examined through investigation of co-culturing umbilical cord tissue derived MSCs from a healthy newborn. iPSC-CMs from an unaffected family member were included as a normal control to compare cellular RNA and protein changes observed in the MYH6-E1584K line. The MYH6-E1584K variant line demonstrated significant upregulation of sarcomere, calcium channel, and inflammation/immune related gene expression in both mRNA and protein levels. Co-culturing with MSCs rescued expression of several genes and was confirmed through label free proteomic analysis. Co-culturing iPSC-CMs with MSCs also significantly improved contraction (contraction maximum displacement and velocity) in MYH6-E1584K iPSC-CMs. Finally, measurements of microRNA, cytokines, and exosomes secreted into cultured media indicated significant changes. This study suggests that MSC secreted factors improve CM expression and function and may elucidate a new mechanistic target for patients with HLHS. AHW/HHI Innovation Pilot Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects: A Randomized Clinical Trial.

Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. ClinicalTrials.gov Identifier: NCT02133573.

Comparison of MYOCYTER and MUSCLEMOTION in the analysis of Induced Pluripotent Stem Cell Derived Cardiomyocyte Contractility

Patient-specific induced pluripotent stem cells (iPSCs) differentiated into cardiomyocytes (CMs) offer tremendous opportunities for cardiac disease modeling and advancements in precision medicine. There is a need for technologies that allow noninvasive and precise measurements of CM function, such as contractility, to increase throughput for drug screening and testing efforts. Hypoplastic Left Heart Syndrome (HLHS) is a rare and complex congenital heart defect characterized by hypoplasia of the left ventricle, proximal aorta, as well as stenosis or atresia of the mitral and/or aortic valves. Previously it was demonstrated that iPSC-CMs from an HLHS patient with a genetic variant in the alpha myosin heavy chain ( MYH6 gene) exhibited an impaired cardiomyocyte phenotype (dysmorphic sarcomere structure, compensatory expression of MYH7, and altered contractility). Gene editing using CRISPR/Cas9 rescued the phenotype, demonstrating the utility of MYH6 iPSC-CMs as a useful disease model for HLHS. Critical parameters of CM function include contraction and relaxation, assessing systolic and diastolic dysfunction, respectively, in iPSC-CMs. The aim of this study is to compare features from two open-source macros for ImageJ: MYOCYTER and MUSCLEMOTION. MYOCYTER improves upon previous plugins available by allowing for users to select parameters. Both methods allow measurement of movement from high-speed movies. MYOCYTER enables the user to select an optimal threshold, size, and cell count to minimize disturbances such as cellular fragments, background noise, and floating bubbles, to maximize precision during analysis. MUSCLEMOTION allows rapid and easy measurement of movement from high- speed videos and can measure and compare relative or absolute parameters. This study will determine whether a systolic or diastolic dysfunction phenotype is observed under different magnification settings and evaluate the effect of dosing with pharmaceutical compounds. Finally, benefits and drawbacks of both macros will be investigated. Children's Research Institute. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiac biomarkers in patients with hypoplastic left heart syndrome and Fontan circulation: The effects of aerobic exercise training on single ventricle circulation

Cardiac biomarkers in patients with hypoplastic left heart syndrome and Fontan circulation: The effects of aerobic exercise training on single ventricle circulation

Reprint of: How He Did It – The James S. Tweddell Approach to Single Ventricle Palliation in Patients With Hypoplastic Left Heart Syndrome

This article will detail Dr. James Tweddell's operative technique and considerations for 26 all three stages of SVP in patients with HLHS. This will include the Norwood Procedure with 27 Right-Ventricle-to-Pulmonary-Artery Conduit (Sano Modification), Bidirectional Glenn 28 (Superior Cavopulmonary Connection), and Extracardiac, Fenestrated Fontan Completion (Total 29 Cavopulmonary Connection). These techniques are the culmination of over 20 years of experience 30 and represent the final techniques he employed at both Children's Hospital of Wisconsin and 31 Cincinnati Children's Hospital Medical Center.

The Burden of Stroke in Neonates Undergoing Congenital Heart Surgery: A Large Multicenter Analysis

BACKGROUNDStroke affects surgical decision making and outcomes of neonatal cardiac surgery(CHS). We sought to assess the burden of stroke in this population from a large multi-center database. METHODSWe analyzed neonates undergoing CHS with cardiopulmonary bypass from the Pediatric Health Information System database(2004-2022). The cohort was divided into stroke-group which included pre/post-op ischemic, hemorrhagic-subtypes and grade III-IV intraventricular hemorrhages and compared in-hospital and follow-up outcomes to non-stroke group. RESULTSOf 14,228 neonates, 800(5.6%) had a peri-operative stroke. Stroke-group was more likely to have hypoplastic left-heart syndrome (HLHS)(30.5% vs 20.7%), born pre-term(19.4% vs 11.7%), low-birthweight(17.8% vs 11.9%) and require ECMO(48.8% vs 13.8%)(all, p<0.001). Outcomes comparing stroke vs no-stroke were, mortality:33.1% vs 8.9%, non-home discharge:12.5% vs 6.9%, length of stay:41 vs 24 days, hospitalization-costs:$354,521 vs $180,489(all, p<0.05). Stroke increased odds of mortality by two-fold[OR 2.20(1.75-2.77), p<0.001] after adjusting for ECMO, prematurity among other significant factors. On follow-up, stroke-group had higher incidence of hydrocephalus(9.5% vs 1.3%), cerebral palsy (6.2% vs 1.3%), autism spectrum disorder(7.1% vs 3.5%) and had higher one- and five- year mortality among survivors of index admission(5.3% and 11.3% vs 3.3% and 5.9%, respectively) (all p<0.05). CONCLUSIONSNeonatal CHS patients born prematurely, diagnosed with HLHS or those requiring ECMO are disproportionately affected by stroke. The occurrence of stroke is marked by significantly higher mortality. Future research should seek to identify factors leading to stroke, in order to increase rescue after stroke and for improvement of long-term outcomes.

Myocardial biomechanical effects of fetal aortic valvuloplasty.

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) can progress to a univentricular (UV) birth malformation. Catheter-based fetal aortic valvuloplasty (FAV) can resolve stenosis and reduce the likelihood of malformation progression. However, we have limited understanding of the biomechanical impact of FAV and subsequent LV responses. Therefore, we performed image-based finite element (FE) modeling of 4 CAS-eHLHS fetal hearts, by performing iterative simulations to match image-based characteristics and then back-computing physiological parameters. We used pre-FAV simulations to conduct virtual FAV (vFAV) and compared pre-FAV and post-FAV simulations. vFAV simulations generally enabled partial restoration of several physiological features toward healthy levels, including increased stroke volume and myocardial strains, reduced aortic valve (AV) and mitral valve regurgitation (MVr) velocities, reduced LV and LA pressures, and reduced peak myofiber stress. FAV often leads to aortic valve regurgitation (AVr). Our simulations showed that AVr could compromise LV and LA depressurization but itcould alsosignificantly increase stroke volume and myocardial deformational stimuli. Post-FAV scans and simulations showed FAV enabled only partial reduction of the AV dissipative coefficient. Furthermore, LV contractility and peripheral vascular resistance could change in response to FAV, preventing decreases in AV velocity and LV pressure, compared with what would be anticipated from stenosis relief. This suggested that case-specific post-FAV modeling is required to fully capture cardiac functionality. Overall, image-based FE modeling could provide mechanistic details of the effects of FAV, but computational prediction of acute outcomes was difficult due to a patient-dependent physiological response to FAV.

Fetal aortic valvuloplasty as the first step in a complex therapeutic strategy.

Fetal aortic valvuloplasty (FAV) is proposed to prevent hypoplastic left heart syndrome due to fetal critical aortic stenosis. to report our experience on FAV as the first step in a complex therapeutic strategy. Series of patients with FAV over an 18-year period. 27 FAVs were performed in 26 fetuses, with technical success in 82% (22/27) and periprocedural fetal demise in 22% (6/27), decreasing to 15% in the second half-cohort. Loss to follow-up was due to birth or postnatal therapy in other centers (5) and termination of pregnancy (1), A normal-sized LV at birth was observed in 46% (6/13), 4 neonates underwent aortic valvuloplasty and 2 cardiac surgeries, with 5/6 achieving biventricular circulation at 28days, and 3 transplant-free survival at mid-term follow-up. The 7/13 born with a borderline LV underwent LV rehabilitation strategy, with survival at 28days in 4/7 and at mid-term in 3: one with biventricular circulation, one with a ventricle-and-a-half repair, and one lost to follow-up. FAV was feasible in most cases, with no maternal complications, and biventricular circulation at 28days in ∼40% of survivors. After FAV, a diverse range of postnatal cardiac interventions are performed, reflecting the challenging innovation in current cardiovascular therapy.

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.

Fetal Echocardiographic Evaluation of Tricuspid Valve and Right Ventricular Function Including Global Longitudinal Strain in Hypoplastic Left Heart Syndrome and Association with Postnatal Outcomes.

Despite significant advancements in the care of patients with hypoplastic left heart syndrome (HLHS) morbidity and mortality remain high. Postnatal right ventricular dysfunction and tricuspid regurgitation (TR) are associated with worse outcomes in HLHS. We aim to determine if right ventricle functional parameters and TR on fetal echocardiogram are associated with postnatal outcomes in HLHS patients. Retrospective review was performed on all fetuses with HLHS from 2014 to 2022 at our institution. Initial and follow up fetal echocardiogram measurements of right ventricular myocardial performance index (MPI), fractional area change (FAC) and global longitudinal strain (GLS) were retrospectively measured. The presence and severity of TR was recorded from the fetal echocardiogram reports. Postnatal outcomes including transplant-free survival, hospital length of stay > 30days after initial palliation and need for bidirectional Glenn at < 4months were reviewed. Forty-three subjects met inclusion criteria. Mean gestational age at presentation was 26.1 ± 5.9weeks. Nine subjects died and 3 required heart transplantation. Initial fetal echocardiogram MPI was significantly lower (better) (0.36 ± 0.06 vs 0.44 ± 0.11; p = < 0.001) and FAC was significantly higher (better) (45 ± 6% vs 40 ± 8%; p = 0.035) in transplant-free survivors. Fetal right ventricular GLS and presence of mild TR were not associated with postnatal outcome. In fetuses with HLHS, abnormal MPI and right ventricular FAC are associated with decreased transplant-free survival. There was no observed association between GLS and postnatal outcomes. To our knowledge this is the first study examining fetal right ventricular function and GLS in HLHS patients and its link to postnatal outcomes.

Postnatal Cerebral Hemodynamics and Placental Vascular Malperfusion Lesions in Neonates With Congenital Heart Disease

BackgroundNeonates with congenital heart disease (CHD) have smaller brain volume at birth. High rates of placental vascular malperfusion lesions may play a role in disrupted brain development. MethodsThis is a single-center retrospective cohort study of infants born between 2010 and 2019 who were diagnosed with a major cardiac defect requiring surgery in the first year of life. Doppler ultrasound RI of the middle cerebral artery (MCA) and anterior cerebral artery were calculated within the first 72 hours of life. Placentas were evaluated using a standardized approach. ResultsOver the study period, there were 52 patients with hypoplastic left heart syndrome (HLHS), 22 with single-ventricle right ventricular outflow tract obstruction (SV-RVOTO), 75 with a two-ventricle cardiac defect (2V), and 25 with transposition of the great arteries (TGA). MCA Doppler RI were significantly higher for all subgroups of CHD compared with control subjects (0.68 ± 0.11 in control subjects compared with 0.78 ± 0.13 in HLHS, P = 0.03; 0.77 ± 0.10 in SV-RVOTO, P = 0.002; 0.78 ± 0.13 in 2V, P = 0.03; and 0.80 ± 0.14 in TGA; P = 0.001) with the highest average MCA RI in the TGA group. In subgroup analyses, placental fetal vascular malperfusion in the 2V group was associated with higher MCA RI, but this relationship was not present in other subgroups, nor in regards to maternal vascular malperfusion. ConclusionsMajor forms of CHD are associated with significantly higher cerebral artery RI postnatally, but placental vascular malperfusion lesions may not contribute to this hemodynamic adaptation.

Congenital Diaphragmatic Hernia Patients with Left Heart Hypoplasia and Left Ventricular Dysfunction Have Highest Odds of Mortality

To describe the scope of left ventricular (LV) dysfunction and left heart hypoplasia (LHH) in infants with congenital diaphragmatic hernia (CDH), to determine associations with CDH severity, and to evaluate the odds of extracorporeal membrane oxygenation (ECMO) and death with categories of left heart disease. Demographic and clinical variables were collected from a single-center, retrospective cohort of CDH patients from January 2017 through May 2022. Quantitative measures of LV function and LHH were prospectively performed on initial echocardiograms. LHH was defined as ≥2 of the following: Z-score ≤ -2 of any left heart structure or LV end-diastolic volume <3 mL. LV dysfunction was defined as shortening fraction <28%, ejection fraction <60%, or global longitudinal strain <20%. The exposure was operationalized as a four-group categorical variable (LV dysfunction +/-, LHH +/-). Logistic regression models evaluated associations with ECMO and death, adjusting for CDH severity. One-hundred and eight-two patients (80.8% left CDH, 63.2% liver herniation, 23.6% ECMO, 12.1% mortality) were included. Twenty percent demonstrated normal LV function and no LHH (LV dysfunction-/LHH-), 37% normal LV function with LHH (LV dysfunction-/LHH+), 14% LV dysfunction without LHH (LV dysfunction+/LHH-), and 28% both LV dysfunction and LHH (LV dysfunction+/LHH+). There was a dose-response effect between increasing severity of left heart disease, ECMO use, and mortality. LV dysfunction+/LHH+ infants had the highest odds of ECMO use and death, after adjustment for CDH severity [OR (95% CI); 1.76 (1.20,2.62) for ECMO, 2.76 (1.63, 5.17) for death]. In our large single-center cohort, CDH patients with LV dysfunction+/LHH+ had the highest risk of ECMO use and death.

Long-term outcomes of heart transplantation in adults with congenital heart disease: The impact of single-ventricle versus biventricular physiology

ObjectiveCongenital heart disease is a risk factor for mortality after orthotopic heart transplantation; however, the impact of preoperative circulation type and primary congenital heart disease diagnosis remains poorly delineated. MethodsWe retrospectively reviewed patients with adult congenital heart disease aged 16 years or more who underwent orthotopic heart transplantation at our institution between 2008 and 2022. Patients were categorized as having single-ventricle or biventricular circulation. The primary end point was 5-year post-transplant survival. ResultsSixty-one patients with adult congenital heart disease (single-ventricle: n = 26 [42.6%], biventricular: n = 35 [57.4%]) underwent orthotopic heart transplantation at 33.7 [interquartile range, 19.1-48.7] years. The most common congenital heart disease diagnosis was hypoplastic left heart syndrome (n = 11, 42.3%) in the single-ventricle group and congenitally corrected transposition of the great arteries (n = 7, 20.0%) in the biventricular group. Twenty-four patients previously underwent Fontan palliation. At transplant, patients in the single-ventricle group were younger (18.5 [interquartile range, 17.6-32.3] years vs 45.0 [interquartile range, 33.0-52.2] years, P < .001) and more likely to have biopsy-proven cirrhosis (46.2% vs 14.3%, P = .01) and protein-losing enteropathy (42.3% vs 2.9%, P < .001). Patients in the single-ventricle group also had longer bypass times (223.4 ± 65.3 minutes vs 187.4 ± 59.5 minutes, P = .03) and longer durations of mechanical ventilatory support (3.5 [interquartile range, 2.0-6.0] days vs 1.0 [interquartile range, 1.0-2.0] days, P < .001). Operative mortality was comparable (11.5% vs 8.6%, P = 1). Median follow-up was 6.0 [interquartile range, 2.4-10.0] years. Five-year survival was worse in the single-ventricle group (66.0% ± 10.0% vs 91.3% ± 4.8%, P = .03), as was freedom from major rejection (58.3% ± 10.2% vs 84.0% ± 6.6%, P = .02). In univariable analysis, hypoplastic left heart syndrome and Fontan circulation were risk factors for post-transplant mortality (hypoplastic left heart syndrome: hazard ratio, 5.0, P < .001; Fontan: hazard ratio, 3.5, P = .03). ConclusionsAdult patients with congenital heart disease undergoing heart transplant with single-ventricle physiology experienced a more complicated post-transplant course, with worse long-term survival and freedom from rejection. Multicenter studies are required to guide orthotopic heart transplantation decision-making in this complex cohort.

The anatomic repair of recurrent aortic arch obstruction in children and adolescents

ObjectiveSurgery for recurrent aortic arch obstruction is highly challenging and publications are rare. The aim of this retrospective, single-center study was to evaluate mortality, complications, and reintervention rate after an anatomic repair. MethodsBetween 1999 and 2022, in total 946 operations on the aortic arch were performed at the Children's Heart Center Linz. In 39 cases, the indication was a recurrent or residual aortic arch obstruction or coarctation in a patient aged 18 years or younger. This is our study cohort. The aorta was reconstructed by a direct anastomosis/autograft in 20 patients, patch in 17 patients, and interposition graft in 2 adolescents. In 32 procedures, cardiopulmonary bypass with whole body perfusion was employed, in 4, antegrade cerebral perfusion was employed, in 2, a left heart bypass was employed, and in 1 no cardiopulmonary bypass was used. ResultsMedian (Q1, Q3) age at operation was 253 days (100, 2198 days), weight 7.5 kg (4.5, 17.8 kg). Median cardiopulmonary bypass time was 177 minutes (115, 219 minutes), crossclamp time 73 minutes (49, 102 minutes). Three infants died during the hospital stay: 1 with Williams syndrome, 1 with hypoplastic left heart syndrome, and 1 with heterotaxia. There was no death due to an arch complication. The main complications were 1 neurologic injury after postoperative resuscitation (Williams syndrome) and 1 permanent recurrent laryngeal nerve paralysis. During the follow-up period of median 8.1 years (2.6, 12 years) 1 re-reintervention on the aortic arch was necessary. ConclusionsSophisticated reoperations on the aortic arch could be performed safely. In children, the growth potential of all segments of the aorta could be sustainably preserved by avoiding interposition or extra-anatomic bypass grafts.

Injection Laryngoplasty for Children with Dysphagia after Cardiac Surgery.

To determine whether injection laryngoplasty (IL) resolves thin liquid aspiration among children with unilateral vocal cord paralysis (UVCP) after cardiac surgery. Retrospective case-control. Tertiary children's hospital. Consecutive children (<5 years) between 2012 and 2022 with UVCP after cardiac surgery were included. Resolution of thin liquid aspiration after IL versus observation was determined for children obtaining videofluoroscopic swallow studies (VFSS). A total of 32 children with left UVCP after cardiac surgery met inclusion. Initial surgeries were N = 9 (28%) patent ductus arteriosus ligations, N = 7 (22%) aortic arch surgeries, N = 9 (28%) surgeries for hypoplastic left heart syndrome, and N = 7 (22%) other cardiac surgeries. The mean age at initial surgery was 1.8 months (SD: 3.7). All children had a VFSS obtained after surgery that confirmed aspiration. There were 17 children that obtained an IL at 33.6 months (SD: 20.9) after cardiac surgery and 15 children observed without IL procedure. No surgical complications after IL were noted. The rate of aspiration resolution based on postoperative VFSS was N = 14 (82%) for the IL group and N = 9 (60%) for the control group P = .24. Documented VFSS aspiration resolution after cardiac surgery occurred by 9.6 months (SD: 10.0) in the observation group and 47.4 months (SD: 24.1) in the IL group (P < .001). IL can help treat aspiration in children with UVCP after cardiac surgery but the benefit beyond observation remains unclear. Future studies should continue to explore the utility for IL in managing dysphagia in this pediatric population.

Increased utilization of the hybrid procedure is not associated with improved early survival for newborns with hypoplastic left heart syndrome: a single-centre experience.

The primary objectives were to examine utilization of the Hybrid versus the Norwood procedure for patients with hypoplastic left heart syndrome or variants and the impact on hospital mortality. The Hybrid procedure was 1st used at our institution in 2004. Review of all subjects undergoing the Norwood or Hybrid procedure between 1 January 1984 and 31 December 2022. The study period was divided into 8 eras: era 1, 1984-1988; era 2, 1989-1993; era 3, 1994-1998; era 4, 1999-2003; era 5, 2004-2008; era 6, 2009-2014; era 7, 2015-2018 and era 8, 2019-2022. The primary outcome was in-hospital mortality. Mortality rates were computed using standard binomial proportions with 95% confidence intervals. Rates across eras were compared using an ordered logistic regression model with and adjusted using the Tukey-Kramer post-hoc procedure for multiple comparisons. In the risk-modelling phase, logistic regression models were specified and tested. The Norwood procedure was performed in 1899 subjects, and the Hybrid procedure in 82 subjects. Use of the Hybrid procedure increased in each subsequent era, reaching 30% of subjects in era 8. After adjustment for multiple risk factors, use of the Hybrid procedure was significantly and positively associated with hospital mortality. Despite the increasing use of the Hybrid procedure, overall mortality for the entire cohort has plateaued. After adjustment for risk factors, use of the Hybrid procedure was significantly and positively associated with mortality compared to the Norwood procedure.