Single Ventricle Congenital Heart Disease Research Articles

Abstract 8963: Mitochondrial Dysfunction in Peripheral Blood Mononuclear Cells is Associated With Heart Failure in Patients With Single Ventricle Congenital Heart Disease

Introduction: Heart failure (HF) remains a leading cause of death and indication for heart transplant in children with single ventricle congenital heart disease (SV). The purpose of this study was to evaluate mitochondrial function in circulating peripheral blood mononuclear cells (PBMCs) from failing pediatric SV patients compared to age-matched nonfailing controls (NF). Prior data obtained at the time of cardiac transplant shows associations between SV PBMC mitochondrial function and ex-vivo high-resolution respirometry analysis conducted on permeabilized myocardial fibers, suggesting that PBMCs may be surrogates for myocardial mitochondrial function. Hypothesis: SV patients will have impaired mitochondrial respiratory capacity in circulating PBMCs. Methods: Subjects were recruited from Children’s Hospital Colorado. SV patients ages 0-18 years were included. Healthy children 0-18 years of age with normal biventricular cardiac function were included as a control group. PBMCs were isolated from whole blood (EDTA) using density gradient centrifugation in Histopaque Accuspin tubes. Oxygen consumption rates (OCR) of intact PBMCs were measured using the Seahorse XFe Bioanalyzer (Agilent). OCR is measured under 4 different conditions (Figure 1): baseline, after addition of oligomycin, after addition of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, and after addition of antimycin A and rotenone. Results: Baseline respiratory capacity, coupling efficiency, and mitochondrial oxygen flux were decreased in failing SV PBMCs relative to NF controls (Figure 2). Conclusions: Our results demonstrate impaired mitochondrial respiratory capacity in circulating PBMCs of pediatric SV patients relative to healthy age-matched controls. Combined with our ex vivo data showing decreased mitochondrial function in failing SV myocardium, our findings suggests PBMCs may serve as a viable non-invasive biomarker of myocardial respiratory capacity.

Abstract 13285: Sensitivity to Beta-Adrenergic Stimulation in Pediatric Failing Single Ventricle Myocardium

Introduction: Children with heart failure (HF) in the context of palliated single ventricle congenital heart disease (SV) are treated with various pharmacotherapies, all with limited efficacy. Specifically, outcomes with β-blockade for HF in SV children are disparate from those in adult HF, even with similar downregulation of β 1 -adrenergic receptors (AR) in both populations. Hypothesis: Downregulation of β 1 -AR in pediatric SV subjects results in a unique contractile phenotype. Methods: Hearts were obtained from SV children who underwent transplant between 2010-2020. Non-failing SV (SV-NF) subjects underwent primary transplantation and had no signs of HF at the time of transplant. Failing SV (SV-F) subjects required transplantation due to end-stage HF (including refractory protein losing enteropathy or plastic bronchitis). At the time of transplant, trabeculae are isolated from the right ventricle of the explanted SV heart and mounted in a multi-chamber muscle bath. Ex vivo contractile response of isolated trabeculae is measured in response to the non-selective β-agonist isoproterenol; only trabeculae with an appropriate isoproterenol response are included in analyses. Results: Although β 1 -AR density is decreased in both SV-NF and SV-F myocardium, trabecular contractility assessment demonstrates increased sensitivity to isoproterenol in SV-F compared to SV-NF. Maximal tension generation with isoproterenol is similar between SV-NF and SV-F. Isoproterenol sensitivity in SV-F is comparable to that of non-failing adult hearts (age <40, n=4). Conclusions: Pediatric SV-F trabeculae demonstrate increased sensitivity to β-adrenergic stimulation when compared to SV-NF, but is similar to that of non-failing adult hearts. The preservation of adrenergic responsiveness may suggest that chronic, adverse β 1 -AR signaling is not part of the pathophysiology of failing SV, which may limit the effectiveness of β-blockade for HF indications in this population.

Multi-institution Assessment of the Accuracy of Cardiac Computed Tomography in Preparation for Superior Cavopulmonary Connection.

Patients with single ventricle (SV) congenital heart disease (CHD) undergo several interventions in the first years of life. Advanced diagnostics are required for interstage assessment of anatomy, but are associated with significant diagnostic risk. We sought to evaluate image quality, risk, and accuracy of cardiac computed tomography (CCT) for evaluation of anatomy prior to superior cavopulmonary connection (SCPC) compared to surgical findings across 2 institutions. A retrospective evaluation of image quality, risk, and accuracy of pre-SCPC CCT was performed at 2 institutions between January 1, 2010 and September 30, 2016. CCT was performed in 90 SV CHD patients with a median age of 4.03 months (interquartile range [IQR] 3.36, 5.33) prior to SCPC. Image quality was optimal (84%) or good (16%) in all patients, without significant discrepancy compared to surgical findings. 7 patients (8%) required interventional cardiac catheterization subsequent to CCT and before surgical intervention. 49% of scans were performed without sedation, 43% of scans were performed with mild to moderate sedation, and 8% of scans were performed with general anesthesia. The median total procedural dose-length product (DLP) was 18 (IQR 14, 26) mGy*cm, estimating an age adjusted radiation dose of 1.4 millisievert (mSv). One minor (1%) adverse event was reported within 24 h of the CCT. Surgical complications were unrelated to the presurgical findings. CCT for pre-SCPC evaluation is safe, with excellent accuracy for anatomy at the time of surgical intervention across 2 institutions. In select patients, noninvasive evaluation with CCT may be indicated.

Socioeconomic Impact on Outcomes During the First Year of Life of Patients with Single Ventricle Heart Disease: An Analysis of the National Pediatric Cardiology Quality Improvement Collaborative Registry.

Socioeconomic status (SES) affects a range of health outcomes but has not been extensively explored in the single ventricle population. We investigate the impact of community-level deprivation on morbidity and mortality for infants with single ventricle heart disease in the first year of life. Retrospective cohort analysis of infants enrolled in the National Pediatric Cardiology Improvement Collaborative who underwent staged single ventricle palliation examining mortality and length of stay (LOS) using a community-level deprivation index (DI). 974 patients met inclusion criteria. Overall mortality was 20.5%, with 15.7% of deaths occurring between the first and second palliations. After adjusting for clinical risk factors, the DI was associated with death (log relative hazard [Formula: see text] = 8.92, p = 0.030) and death or transplant (log relative hazard [Formula: see text] = 8.62, p = 0.035) in a non-linear fashion, impacting those near the mean DI. Deprivation was associated with LOS following the first surgical palliation (S1P) (p = 0.031) and overall hospitalization during the first year of life (p = 0.018). For every 0.1 increase in the DI, LOS following S1P increased by 3.35days (95% confidence interval 0.31-6.38) and total hospitalized days by 5.08days (95% CI 0.88-9.27). Community deprivation is associated with mortality and LOS for patients with single ventricle congenital heart disease. While patients near the mean DI had a higher hazard of one year mortality compared to those at the extremes of the DI, LOS and DI were linearly associated, demonstrating the complex nature of SES factors.

Characteristics and outcomes of acute COVID-19 infection in paediatric and young adult patients with underlying cardiac disease.

To describe outcomes of acute coronavirus disease 2019 in paediatric and young adult patients with underlying cardiac disease and evaluate the association between cardiac risk factors and hospitalisation. We conducted a retrospective single-institution review of patients with known cardiac disease and positive severe acute respiratory syndrome coronavirus 2 RT-PCR from 1 March, 2020 to 30 November, 2020. Extracardiac comorbidities and cardiac risk factors were compared between those admitted for coronavirus disease 2019 illness and the rest of the cohort using univariate analysis. Forty-two patients with a mean age of 7.7 ± 6.7 years were identified. Six were 18 years of age or more with the oldest being 22 years of age. Seventy-six percent were Hispanic. The most common cardiac diagnoses were repaired cyanotic (n = 7, 16.6%) and palliated single ventricle (n = 7, 16.6%) congenital heart disease. Fourteen patients (33.3%) had underlying syndromes or chromosomal anomalies, nine (21%) had chronic pulmonary disease and eight (19%) were immunosuppressed. Nineteen patients (47.6%) reported no symptoms. Sixteen (38.1%) reported only mild symptoms. Six patients (14.3%) were admitted to the hospital for acute coronavirus disease 2019 illness. Noncardiac comorbidities were associated with an increased risk of hospitalisation (p = 0.02), particularly chronic pulmonary disease (p = 0.01) and baseline supplemental oxygen requirement (p = 0.007). None of the single ventricle patients who tested positive required admission. Hospitalisations for coronavirus disease 2019 were rare among children and young adults with underlying cardiac disease. Extracardiac comorbidities like pulmonary disease were associated with increased risk of hospitalisation while cardiac risk factors were not.

Intrahepatic Dynamic Contrast-Enhanced Magnetic Resonance Lymphangiography: Potential Imaging Signature for Protein-Losing Enteropathy in Congenital Heart Disease.

BackgroundProtein‐losing enteropathy (PLE) is a significant cause of morbidity and mortality in congenital heart disease patients with single ventricle physiology. Intrahepatic dynamic contrast‐enhanced magnetic resonance lymphangiography (IH‐DCMRL) is a novel diagnostic technique that may be useful in characterizing pathologic abdominal lymphatic flow in the congenital heart disease population and in diagnosing PLE. The objective of this study was to characterize differences in IH‐DCMRL findings in patients with single ventricle congenital heart disease with and without PLE.Methods and ResultsThis was a single‐center retrospective study of IH‐DCMRL findings and clinical data in 41 consecutive patients, 20 with PLE and 21 without PLE, with single ventricle physiology referred for lymphatic evaluation. There were 3 distinct duodenal imaging patterns by IH‐DCMRL: (1) enhancement of the duodenal wall with leakage into the lumen, (2) enhancement of the duodenal wall without leakage into the lumen, and (3) no duodenal involvement. Patients with PLE were more likely to have duodenal involvement on IH‐DCMRL than patients without PLE (P<0.001).ConclusionsIH‐DCMRL findings of lymphatic enhancement of the duodenal wall and leakage of lymph into the duodenal lumen are associated with PLE. IH‐DCMRL is a useful new modality for characterizing pathologic abdominal lymphatic flow in PLE and might be useful as a risk‐assessment tool for PLE in at‐risk patients.

Role of Transient Elastography to Stage Fontan-Associated Liver Disease (FALD) in Adults with Single Ventricle Congenital Heart Disease Correction.

Fontan-associated liver disease (FALD) is an arising clinical entity that can occur long after a successful Fontan operation for correction of single ventricle (SV) congenital heart disease (CHD). Occurrence of FALD is characterized by liver cirrhosis and other hepatic complications, and determinates an increased morbidity and mortality. Currently, there is no consensus on how to stage FALD. We report here our experience by an observational study in 52 patients with SV-CHD after Fontan operation that were recruited through a period of 36 ± 9.3 months. All cases underwent lab tests and liver and cardiac imaging evaluation, including liver stiffness (LS) measurement by transient elastography (TE) (FibroScan®). According to selective criteria for liver disease, we identified 23/43 (53.5%) cases with advanced FALD that showed: older age (p < 0.05), larger hepatic and cava veins diameter (p < 0.05), worsened NYHA class (p < 0.05), abnormal lymphocytes (p < 0.01), platelet count (p < 0.05), and GGT, prothrombin time (INR), albumin and cystatin C levels (p < 0.05), with respect to cases without advanced FALD. LS values were significantly increased in cases with advanced FALD, at cut-off values higher than 22 kPa (p < 0.001). LS, and its combined score with spleen diameter and platelet count (LSPS) successfully helped to detect 100% of cases with portal hypertension (p < 0.001). In conclusion, LS can be effective to stage FALD and to uncover cases with severe risk of complications, avoiding higher morbidity and mortality related to advanced FALD.

Non-invasive biomarkers of Fontan-associated liver disease

Background & AimsFontan-associated liver disease (FALD) has emerged as an important morbidity following surgical palliation of single ventricle congenital heart disease. In this study, non-invasive biomarkers that may be associated with severity of FALD were explored.MethodsA retrospective cohort of paediatric patients post-Fontan who underwent liver biopsy at a high volume at a paediatric congenital heart disease centre was reviewed.ResultsAmong 106 patients, 66% were male and 69% were Hispanic. The mean age was 14.4 ± 3.5 years, and biopsy was performed 10.8 ± 3.6 years post-Fontan. The mean BMI was 20.8 ± 5 kg/m2, with 27.4% meeting obesity criteria. Bridging fibrosis was observed in 35% of patients, and 10.4% of all patients had superimposed steatosis. Bridging fibrosis was associated with lower platelet counts (168.3 ± 58.4 vs. 203.9 ± 65.8 K/μl for congestive hepatic fibrosis score [CHFS] 0–2b, p = 0.009), higher bilirubin (1.7 ± 2.2 vs. 0.9 ± 0.7 mg/dl, p = 0.0090), higher aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] scores (APRI: 0.5 ± 0.3 vs. 0.4 ± 0.1, p <0.01 [AUC: 0.69] and FIB-4: 0.6 ± 0.4 vs. 0.4 ± 0.2, p <0.01 [AUC: 0.69]), and worse overall survival (median 2 years follow-up post-biopsy, p = 0.027). Regression modelling of temporal changes in platelet counts before and after biopsy correlated with fibrosis severity (p = 0.005).ConclusionsIn this large, relatively homogeneous adolescent population in terms of age, ethnicity, and Fontan duration, bridging fibrosis was observed in 35% of patients within the first decade post-Fontan. Bridging fibrosis was associated with worse survival. Changes in platelet counts, even years before biopsy, and APRI/FIB-4 scores had modest discriminatory power in identifying patients with advanced fibrosis. Steatosis may represent an additional risk factor for disease progression in obese patients. Further prospective studies are necessary to develop strategies to screen for FALD in the adolescent population.Lay summaryIn this study, the prevalence of Fontan-associated liver disease (FALD) in the young adult population and clinical variables that may be predictive of fibrosis severity or adverse outcomes were explored. Several lab-based, non-invasive markers of bridging fibrosis in FALD were identified, suggesting that these values may be followed as a prognostic biomarker for FALD progression in the adolescent population.

Acute neurological injury in pediatric patients with single-ventricle congenital heart disease.

Single-ventricle congenital heart disease (CHD) in pediatric patients with Glenn and Fontan physiology represents a unique physiology requiring the surgical diversion of the systemic venous return from the superior vena cava (Glenn) and then the inferior vena cava (Fontan) directly to the pulmonary arteries. Because many of these patients are on chronic anticoagulation therapy and may have right-to-left shunts, arrhythmias, or lymphatic disorders that predispose them to bleeding and/or clotting, they are at risk of experiencing neurological injury requiring intubation and positive pressure ventilation, which can significantly hamper pulmonary blood flow and cardiac output. The aim of this study was to describe the complex neurological and cardiopulmonary interactions of these pediatric patients after acute central nervous system (CNS) injury. The authors retrospectively analyzed the records of pediatric patients who had been admitted to a quaternary children's hospital with CHD palliated to bidirectional Glenn (BDG) or Fontan circulation and acute CNS injury and who had undergone intubation and mechanical ventilation. Patients who had been admitted from 2005 to 2019 were included in the study. Clinical characteristics, surgical outcomes, cardiovascular and pulmonary data, and intracranial pressure data were collected and analyzed. Nine pediatric single-ventricle patients met the study inclusion criteria. All had undergone the BDG procedure, and the majority (78%) were status post Fontan palliation. The mean age was 7.4 years (range 1.3-17.3 years). At the time of acute CNS injury, which included traumatic brain injury, intracranial hemorrhage, and cerebral infarct, the median time interval from the most recent cardiac surgical procedure was 3 years (range 2 weeks-11 years). Maintaining normocarbia to mild hypercarbia for most patients during intubation periods did not cause neurological deterioration, and hemodynamic profiles were more favorable as compared to periods of hypocarbia. Hypocarbia was associated with unfavorable hemodynamics but was necessary to decrease intracranial hypertension. Most patients were managed using low mean airway pressure (MAWP) in order to minimize the impact on preload and cardiac output. The authors highlight the complex neurological and cardiopulmonary interactions with respect to partial pressure of arterial CO2 (PaCO2) and MAWP when pediatric CHD patients with single-ventricle physiology require mechanical ventilation. The study data demonstrated that tight control of PaCO2 and minimizing MAWP with the goal of early extubation may be beneficial in this population. A multidisciplinary team of pediatric critical care intensivists, cardiac intensivists and anesthesiologists, and pediatric neurosurgeons and neurologists are recommended to ensure the best possible outcomes.

Anesthetic management for the peripartum care of women with Fontan physiology

BackgroundAs outcomes for surgical palliation have improved, women with single ventricle congenital heart disease are surviving into their reproductive years and may become pregnant. The cardiovascular changes of pregnancy may stress the Fontan circulation and pose significant risk to the mother and fetus. MethodsPregnant women with Fontan physiology were identified from the Ahmanson/UCLA Adult Congenital Heart Disease Center database. A total of 37 pregnancies were identified between 2000 and 2019. Twenty live births from 19 patients were reviewed and compared for cardiac history, obstetric history, anesthetic management and cardiovascular outcomes. ResultsMedian gestational age at delivery was 35 weeks. Ten of 20 births were by cesarean delivery. An epidural technique was used as the primary anesthetic for 19 deliveries and general anesthesia was used for one cesarean delivery. An arterial line was placed in the peripartum period for three deliveries. Central venous access was established in the peripartum period for one patient. The mean blood loss for cesarean deliveries was 626 mL (range 240–1200 mL). The mean net peri-operative intake/output was positive 93.5 mL. Three patients were briefly transferred to the intensive care unit postpartum for higher level monitoring and care. ConclusionEpidural anesthesia is safe and effective for both vaginal and cesarean deliveries. Judicious fluid management is critical in minimizing postpartum cardiovascular complications. Many patients do not require a higher level of care, invasive monitoring or central venous access during the peripartum period.

Reaching consensus for unified medical language in Fontan care

AimsThe Fontan operation has resulted in improved survival in patients with single‐ventricle congenital heart disease. As a result, there is a growing population of teenagers and adults with a Fontan circulation. Many co‐morbidities have been increasingly recognized in this population due to the unique features of the Fontan circulation. Standardization of how Fontan co‐morbid conditions are defined will help facilitate understanding, consistency and interpretability of research and clinical experience. Unifying common language usage in Fontan is a critical precursor step for data comparison of research findings and clinical outcomes and ultimately accelerating improvements in management for this growing group of patients. This manuscript aimed to create unified definitions for morbidities seen after the Fontan palliation.MethodsIn association of many congenital heart disease organizations, this work used Delphi methodology to reach a broad consensus among recognized experts regarding commonly used terms in Fontan care and research. Each definition underwent at least three rounds of revisions to reach a final definition through surveys sent to experts in the field of single‐ventricle care.ResultsThe process of reaching a consensus on multiple morbidities associated with the Fontan procedure is summarized in this manuscript. The different versions that preceded reaching the consensus are also presented in the Supporting Information. Table 1 represents the final definitions according to the consensus.ConclusionsWe propose the use of these definitions for clinical care, future research studies, registry development and clinical trials.

PRO3 Systematic Literature Review (SLR) of Evidence on Clinical, Humanistic, and Economic Burden for Patients Who Have Undergone the Fontan Procedure

Fontan procedure surgically palliates abnormal anatomy in functional single ventricle congenital heart disease (CHD), a rare, serious condition. Post-surgery, patients may experience exercise intolerance, thrombosis, arrhythmias, and liver disease; clinical worsening (CW) related to pulmonary hypertension can be significant even with small increases in pulmonary vascular resistance (PVR). No therapies are approved to modulate PVR post-Fontan. We explored published evidence on post-Fontan clinical, humanistic, and economic burden.

Clinical update on the hybrid comprehensive stage II operation

ObjectiveWe previously described the hybrid comprehensive stage II operation as an alternate surgical procedure for a subset of patients with single ventricle congenital heart disease with adequate native ascending aortic outflow. Here we provide a clinical update on the 4 patients who have undergone this procedure. MethodsAfter undergoing a hybrid approach to the stage I Norwood palliation, the hybrid comprehensive stage II procedure was performed with an incision to the main pulmonary artery (PA), dilation of the ductal stent, creation of a stented baffle between the branch PAs, and a bidirectional Glenn connection. With this approach, dissection of the distal arch and creation of a Damus-Kaye-Stansel anastomosis was avoided. A standard Fontan procedure was planned after the usual period of growth. ResultsThe first patient, who had trisomy 21 and elevated PA pressures, died postoperatively due to left PA thrombosis. The subsequent 3 patients survived the procedure and remain clinically well. All have required catheterizations for reintervention on their stented intrapulmonary baffles and ductal arches, and all have undergone successful completion of their Fontan procedures. ConclusionsThe hybrid comprehensive stage II is a feasible, less complex alternative to the conventional comprehensive stage II operation in a subset of patients with single ventricle physiology. Early postoperative anticoagulation therapy to avoid PA thrombosis is recommended, and restenting of the ductal arch is anticipated. Although the long-term consequences of separate outflow tracts supplying the upper and lower body is unknown, the 3 surviving patients with this circulation are doing well with their Fontan circulation at midterm follow-up.

Characteristics of Interstage Death After Discharge from Stage I Palliation.

Interstage mortality (IM) remains high for patients with single-ventricle congenital heart disease (SVCHD) in the period between Stage 1 Palliation (S1P) and Glenn operation. We sought to characterize IM. This was a descriptive analysis of 2184 patients with SVCHD discharged home after S1P from 60 National Pediatric Cardiology Quality Improvement Collaborative sites between 2008 and 2015. Patients underwent S1P with right ventricle-pulmonary artery conduit (RVPAC), modified Blalock-Taussig-Thomas shunt (BTT), or Hybrid; transplants were excluded. IM occurred in 153 (7%) patients (median gestational age 38weeks, 54% male, 77% white), at 88 (IQR 60,136) days of life, and 39 (IQR 17,84) days after hospital discharge; 13 (8.6%) occurred ≤ 30days after S1P. The mortality rate for RVPAC was lower (5.2%; 59/1138) than BTT (9.1%; 65/712) and Hybrid (20.1%; 27/134). More than half of deaths occurred at home (20%) or in the emergency department (33%). The remainder occurred while inpatient at center of S1P (cardiac intensive care unit 36%, inpatient ward 5%) or at a different center (5%). Fussiness and breathing problems were most often cited as harbingers of death; distance to surgical center was the biggest barrier cited to seeking care. Cause of death was unknown in 44% of cases overall; in the subset of patients who underwent post-mortem autopsy, the cause of death remained unknown in 30% of patients, with the most common diagnosis being low cardiac output. Most IM occurred in the outpatient setting, with non-specific preceding symptoms and unknown cause of death. These data indicate the need for research to identify occult causes of death, including arrhythmia.

The Direct Route, Alternative Paths, and Informing the Future Directions of Single Ventricle Palliation

The treatment of single ventricle congenital heart disease through staged, surgical palliation to Fontan circulation is now widely accepted as the best route to years of high-quality life. The recent era’s improved survival through and following Fontan palliation is a remarkable achievement for pediatric cardiothoracic surgeons and cardiologists. The short- and midterm outcomes AFTER Fontan palliation are now such that proponents of the main alternative pathway for single ventricle diseases, primary heart transplant, are relatively infrequently heard from for standard risk disease.

Neurologic Events Following Pediatric Heart Transplantation

PurposeThe last decade has seen a considerable rise in ventricular assist device (VAD) support as bridge to heart transplant (HT) coupled with increasing transplantation for single ventricle congenital heart disease (SV CHD). Neurologic events (NE) are common in both patient groups. We sought to describe NE before and after HT in the modern era among children and young adults.MethodsWe performed a single center retrospective review of patients who underwent HT between 1/2013 and 4/2020. NE included seizures, stroke, subdural hemorrhage (SDH) and posterior reversible encephalopathy syndrome (PRES). Clinical characteristics were compared between patients with and without post-HT NE.ResultsOverall 163 patients met study criteria, of whom 54 (33%) had a pre-HT NE and 29 (18%) had at least one post-HT NE. Post-HT NE included seizures in 23/163 (14%), strokes in 10/163 (6%), SDH in 9/163 (6%), and PRES in 7/163 (4%). Median time from HT to first post-HT NE was 24 days (IQR 3, 277). Post-HT NE were associated with SDH (6/29 (21%) vs 9/134 (7%), p=0.03), pre-HT ICU admission (11/29 (38%) vs 21/134 (16%), p=0.009), and allograft ischemic time (250 min (IQR 221, 224) vs 223 min (IQR 189, 250), p=0.001), and not with pre-HT NE, SV CHD, or VAD support. ICU admission was an independent predictor of post-HT NE on multivariate analysis (hazard ratio 2.87 (CI 1.09, 7.62), p=0.03). Post-HT NE were associated with significantly decreased survival.ConclusionPost-HT NE are common in children and young adults and occur early post-HT. They are associated with ICU status at time of HT, and not with SV CHD or pre-HT VAD support. Post-HT neurologic events portend a poor prognosis, with 50% mortality by 5 years. The last decade has seen a considerable rise in ventricular assist device (VAD) support as bridge to heart transplant (HT) coupled with increasing transplantation for single ventricle congenital heart disease (SV CHD). Neurologic events (NE) are common in both patient groups. We sought to describe NE before and after HT in the modern era among children and young adults. We performed a single center retrospective review of patients who underwent HT between 1/2013 and 4/2020. NE included seizures, stroke, subdural hemorrhage (SDH) and posterior reversible encephalopathy syndrome (PRES). Clinical characteristics were compared between patients with and without post-HT NE. Overall 163 patients met study criteria, of whom 54 (33%) had a pre-HT NE and 29 (18%) had at least one post-HT NE. Post-HT NE included seizures in 23/163 (14%), strokes in 10/163 (6%), SDH in 9/163 (6%), and PRES in 7/163 (4%). Median time from HT to first post-HT NE was 24 days (IQR 3, 277). Post-HT NE were associated with SDH (6/29 (21%) vs 9/134 (7%), p=0.03), pre-HT ICU admission (11/29 (38%) vs 21/134 (16%), p=0.009), and allograft ischemic time (250 min (IQR 221, 224) vs 223 min (IQR 189, 250), p=0.001), and not with pre-HT NE, SV CHD, or VAD support. ICU admission was an independent predictor of post-HT NE on multivariate analysis (hazard ratio 2.87 (CI 1.09, 7.62), p=0.03). Post-HT NE were associated with significantly decreased survival. Post-HT NE are common in children and young adults and occur early post-HT. They are associated with ICU status at time of HT, and not with SV CHD or pre-HT VAD support. Post-HT neurologic events portend a poor prognosis, with 50% mortality by 5 years.

Increases in oxygen saturation following discharge from Fontan palliation - an indicator of resolution of pulmonary arteriovenous malformations?

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. 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. 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. 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.

Defining a new normal: A qualitative exploration of the parent experience during the single ventricle congenital heart disease interstage period.

To explore parents' experience of transition in the period between the palliative cardiac surgeries (i.e., the interstage period) of an infant with single ventricle congenital heart disease. We conducted an exploratory naturalistic inquiry using a qualitative descriptive approach. A purposive sample of 11 parents of children with single ventricle disease was selected among families that participated in an interstage-period parental home monitoring program during the past 2years. Interviews and field observations were conducted September-October 2019, and data were analyzed for themes. Analysis of data was inductive, although study questions and the interpretation of results were informed by Meleis' transition theory. Parents described the experience of transition in interstage as a striving for normality, a theme that was clustered in subthemes of home, self, and infant. Parents' experiences of striving for normality indicated a need for more targeted efforts to address parents' psychosocial needs during the highly stressful interstage transition. This research underscored the complexity of parents' psychosocial support needs on returning home after their child's first palliative surgery. The findings also suggest need for examination of the transition following the second palliative heart surgery, when the home monitoring program is withdrawn. Understanding parent needs will help guide healthcare teams in developing ways to support parents as they adjust to home, self, and child.

Mental Health Disorders in Children With Congenital Heart Disease.

Data on anxiety, depression, and attention-deficit/hyperactivity disorder (ADHD) are lacking for youth with congenital heart disease (CHD), particularly those with simple CHD. This study aims to characterize these disorders in youth with CHD compared to those without CHD. A comparative cross-sectional study was conducted by using the electronic medical records of a large tertiary care hospital between 2011 and 2016. Inclusion criteria were youth aged 4 to 17 years with >1 hospitalization or emergency department visits. Exclusion criteria were patients with arrhythmias or treatment with clonidine and/or benzodiazepines. The primary predictor variable was CHD type: simple, complex nonsingle ventricle, and complex single ventricle. The primary outcome variable was a diagnosis and/or medication for anxiety and/or depression or ADHD. Data were analyzed by using logistic regression (Stata v15; Stata Corp, College Station, TX). We identified 118 785 patients, 1164 with CHD. Overall, 18.2% (n = 212) of patients with CHD had a diagnosis or medication for anxiety or depression, compared with 5.2% (n = 6088) of those without CHD. All youth with CHD had significantly higher odds of anxiety and/or depression or ADHD. Children aged 4 to 9 years with simple CHD had ∼5 times higher odds (odds ratio: 5.23; 95% confidence interval: 3.87-7.07) and those with complex single ventricle CHD had ∼7 times higher odds (odds ratio: 7.46; 95% confidence interval: 3.70-15.07) of diagnosis or treatment for anxiety and/or depression. Minority and uninsured youth were significantly less likely to be diagnosed or treated for anxiety and/or depression or ADHD, regardless of disease severity. Youth with CHD of all severities have significantly higher odds of anxiety and/or depression and ADHD compared to those without CHD. Screening for these conditions should be considered in all patients with CHD.

Reduced hippocampal volumes and memory deficits in adolescents with single ventricle heart disease.

IntroductionAdolescents with single ventricle congenital heart disease (SVHD) show functional deficits, particularly in memory and mood regulation. Hippocampi are key brain structures that regulate mood and memory; however, their tissue integrity in SVHD is unclear. Our study aim is to evaluate hippocampal volumes and their associations with memory, anxiety, and mood scores in adolescents with SVHD compared to healthy controls.MethodsWe collected brain magnetic resonance imaging data from 25 SVHD (age 15.9 ± 1.2 years; 15 male) and 38 controls (16.0 ± 1.1 years; 19 male) and assessed memory (Wide Range Assessment of Memory and Learning 2, WRAML2), anxiety (Beck Anxiety Inventory, BAI), and mood (Patient Health Questionnaire 9, PHQ‐9) functions. Both left and right hippocampi were outlined and global volumes, as well as three‐dimensional surfaces were compared between groups using ANCOVA and associations with cognitive and behavioral scores with partial correlations (covariates: age and total brain volume).ResultsThe SVHD group showed significantly higher BAI (p = .001) and PHQ‐9 (p < .001) scores, indicating anxiety and depression symptoms and significantly reduced WRAML2 scores (p < .001), suggesting memory deficits compared with controls. SVHD group had significantly reduced right global hippocampal volumes (p = .036) compared with controls, but not the left (p = .114). Right hippocampal volume reductions were localized in the CA1, CA4, subiculum, and dentate gyrus. Positive correlations emerged between WRAML2 scores and left (r = 0.32, p = .01) and right (r = 0.28, p = .03) hippocampal volumes, but BAI and PHQ‐9 did not show significant correlations.ConclusionAdolescents with SVHD show reduced hippocampal volumes, localized in several sites (CA1, CA4, subiculum, and dentate gyrus), which are associated with memory deficits. The findings indicate the need to explore ways to improve memory to optimize academic achievement and ability for self‐care in the condition.