Single Ventricle Heart Research Articles

Abstract 10283: Socioeconomic Disparities in Overall and Morbidity Free Survival of Infants With Single Ventricle Heart Disease

Prior studies have demonstrated higher odds of mortality for non-white and lower socioeconomic status patients with single ventricle (SV) heart disease. However, these studies have not examined survival through staged surgical palliation or rates of morbidity in this patient population. We hypothesized that non-white race/ethnicity and lower socioeconomic status were associated with lower overall survival and increased morbidity through 1 st birthday in patients undergoing SV palliation. Patients with SV heart disease, live birth, and planned SV palliation in the National Pediatric Cardiology Quality Improvement Collaborative between January 1, 2016, and December 31, 2020, were included. Race/ethnicity, payer, and neighborhood characteristics were analyzed. Morbidity was defined as acute neurological events, unplanned procedures, renal support, cardiac arrest, extracorporeal life support, necrotizing enterocolitis, or surgical site infection. Morbidity-free survival was defined as survival through each stage of palliation without experiencing one of the above morbidities. Cox proportional hazards and multivariable regression modeling were performed to evaluate the association between socioeconomic variables, race/ethnicity, and overall morbidity-free survival to 1st birthday. There were 2,184 live births with an overall survival to 1st birthday of 76%. There was no difference in survival to 1st birthday between non-Hispanic White, non-Hispanic Black, and Hispanic patients. Patients with government insurance had decreased survival prior to their 1st birthday (HR 0.79, 95% CI 0.64, 0.98 vs commercial insurance). Infants with government insurance had lower morbidity-free survival during stage 1 (OR 0.72, 95% CI 0.59, 0.87) and stage 2 (OR 0.67, 95% CI 0.52, 0.85) hospitalizations. Patients with “Other” race/ethnicity had lower odds of morbidity-free survival to one year of age (OR 0.68 95% CI 0.47, 0.98). Household income and deprivation index were not associated with survival or morbidity. Infants with government insurance experienced decreased survival to 1st birthday, and those of “Other” race/ethnicity had lower morbidity-free survival. Addressing disparities in these patient populations is an area of ongoing need.

Abstract 10776: A Supervised Classification Model Detects Fontan Patients Based on Clinical Notes With Higher Accuracy Than ICD Codes

Introduction: The Fontan operation palliates single ventricle heart defects. As native anatomy varies, Fontan cases cannot always be identified by ICD9 or 10CM codes. Hypothesis: We sought to train and evaluate a supervised machine learning (ML) system to identify Fontan cases based on unstructured clinical notes in a large database. Methods: 160 adult Fontan patients from validated clinical data at a single tertiary referral center with available text notes were studied. The imbalanced data set had more non-Fontan cases than Fontan patients; thus we created multiple datasets with different positive : negative case ratios ranging from 1:2 to 1:10. We used stratified 80-20 training-testing splits of data. Vectorized representations of text notes were used as features. We trained a Support Vector Machine (SVM) model, mostly used for text classification, to identify Fontan cases from notes. For each dataset, we performed random 80-20 data splitting 10 times and reported average F 1 score (harmonic mean of recall/sensitivity & precision/positive predictive value) over the positive class. Results: The model achieved a mean F 1 score of 0.95 for the positive class on the data split with 1:2 positive-negative ratio. Increasing data imbalance from 1:2 to 1:10 did not substantially impact performance. The mean F 1 score over all data splits was 0.94, and SD 0.01. We also computed precision, recall, and F 1 score of ICD codes to identify Fontan patients. Performance comparisons between ICD codes only and Natural Language Processing (NLP)/ML are in Table 1. Conclusions: A supervised classification model more effectively detects Fontan patients based on clinical notes with higher accuracy than ICD codes. The model is robust and insensitive to data imbalance. Findings suggest our model may work effectively in real-world data. Since the sensitivity of ICD codes is high but PPV is low, it may be beneficial to apply ICD codes as a filter prior to applying NLP/ML to improve performance.

Abstract 13196: Inter-Stage Infants With Single Ventricle Heart Disease Show Prominent Dysregulation in Multiple Metabolic Pathways: A Targeted Metabolomics Analysis

Objectives: To evaluate the circulating metabolome of interstage infants with single ventricle heart disease (SVHD) and determine whether metabolite levels were associated with pulmonary vascular inadequacy. Background: Infants with SVHD experience morbidity related to pulmonary vascular inadequacy. Metabolomic analysis involves a systems biology approach to identifying novel biomarkers and pathways in complex diseases. The metabolome of infants with SVHD is not well understood and no prior study has evaluated the relationship between metabolite levels and pulmonary vascular readiness for staged SVHD palliation. Methods: Prospective cohort study of 52 infants with SVHD undergoing Stage 2 palliation and 48 healthy infants. Targeted metabolomic phenotyping (n=175 metabolites) performed by tandem mass spectrometry on SVHD pre-Stage 2, post-Stage 2, and control serum samples. Clinical variables were extracted from the medical record. Results: Random Forest analysis readily distinguished between cases and controls (Figure), and pre-op and post-op samples. Seventy-four of 175 metabolites differed between SVHD and controls. Twenty-seven of 39 metabolic pathways were altered including pentose phosphate and arginine metabolism. Seventy-one metabolites differed in SVHD patients between timepoints. Thirty-three of 39 pathways were altered post-operatively including arginine and tryptophan metabolism. We found trends towards increased pre-operative methionine metabolites in patients with higher pulmonary vascular resistance and higher post-operative tryptophan metabolites in patients with greater post-operative hypoxemia. Conclusions: The circulating metabolome of interstage SVHD infants differs significantly from controls and is further disrupted after Stage 2. Several metabolites showed promising trends towards association with adverse outcomes. Metabolic dysregulation may be an important factor in early SVHD pathobiology.

Abstract 13643: Examining the Association Between Social Determinants of Health and Health-Related Quality of Life Among Children With Cardiac Conditions

Introduction: Patient-reported outcomes like health-related quality of life (HRQOL) measure the health and well-being of patients, providing insights not communicated by traditional outcomes. The degree to which social determinants of health (SDOH) influence HRQOL is under-studied. Methods: A cross-sectional analysis of subjects aged 8-18 years referred for cardiac catheterization from 1/1/18-12/31/21 was performed, evaluating the association between HRQOL (measured through child and caregiver-proxy reports of cardiac-specific HRQOL (Pediatric Cardiac Quality of Life Inventory (PCQLI)) and general HRQOL (Pediatric Quality of Life Inventory (PedsQL))) and a panel of potential SDOH. Potential SDOH measures were calculated at subject’s neighborhood level by linking their addresses to block group/census tract data. SDOH measures included Childhood Opportunity Index, which measures neighborhood resources supporting child development, and Social Deprivation Index, which measures neighborhoods’ levels of disadvantage. Linear regression was used to evaluate the association between SDOH and HRQOL (PCQLI and PedsQL total scores), adjusting for presence of cardiac symptoms (New York Heart Association Class). Results: In total, 111 subjects (age 12.8±2.9 years, of which 89% identified as White, 5% Black, and 8% Hispanic, and 27% Medicaid-insured) were studied. Primary cardiac diagnoses included single ventricle heart disease (19%), complex biventricular repairs (20%), and orthotopic heart transplantation (12%). The majority (69%) denied having symptoms. Out of a potential 100, subject-reported scores were 67±18 on the PCQLI and 74±19 on the PedsQL. Caregiver-proxy reported scores were 70±17 on the PCQLI and 71±19 on the PedsQL. Worse SDOH was consistently associated with lower HRQOL adjusted for presence of symptoms (Table 1). Conclusions: Worse SDOH was associated with worse HRQOL in pediatric cardiac patients independent of symptoms severity

Abstract 12509: Characterization and Risk Factors for Death or Transplant After Stage Ii/glenn Palliation in Infants With Single Ventricle Heart Disease

Background: Infants with single ventricle heart disease have a 20% mortality rate during the first year of life with most deaths occurring prior to Stage II/Glenn. Although the time after the Stage II procedure is believed to be a lower risk period, significant morbidity and mortality may occur during this time. Methods: Retrospective cohort analysis of infants enrolled in the National Pediatric Cardiology Improvement Collaborative who underwent staged single ventricle palliation from 2016-2021 and survived to Stage II operation. Multivariable logistic regression and classification and regression tree analysis were performed to identify risk factors for the composite of mortality or transplantation between Stage II surgery and the first birthday. Candidate variables (n=75) included sociodemographic, prenatal, birth, anatomic, stage I intra- and post-operative, interstage course, and Stage II operative characteristics. Results: Of the 1455 patients in the cohort who survived to Stage II, the overall event rate was 7% (76 (5%) died and 34 (2%) were referred for transplant). Overall event rates at 30 and 100 days after Stage 2 were 2% and 5%, respectively ( Figure 1A ). Independent risk factors for mortality and transplantation included shunt type and AV valve repair at Stage I, ECMO and reintubation after Stage I, pre-operative weight and ≥ moderate AV valve regurgitation prior to Stage II, Stage II cross-clamp time, and comprehensive Stage II surgery ( Figure 1B). Patient race/ethnicity and socioeconomic status were not associated with worse outcome. Conclusions: Mortality rates after Stage II surgery to 1 year of age remain high ~5%. Some of the risk factors identified have been shown to also predict interstage mortality, whereas others (reintubation, pre-operative weight, and Stage II characteristics) may be unique to the period after Stage II. Further research is needed to understand whether risk factor modification results in improved transplant-free survival.

Abstract 15694: Mitochondrial Dysfunction and Fatty Acid Metabolism Derangement in Pediatric Single Ventricle Congenital Heart Disease

Introduction: Cardiac dysfunction is a common complication in pediatric patients with single ventricle (SV) physiology. While many factors contribute to the development of SV heart failure (HF), metabolic switch from fatty acid utilization to carbohydrate metabolism has been shown to contribute to cardiac dysfunction in adult HF. Hypothesis: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from pediatric SV HF patients exhibit reduced fatty acid utilization and decreased contractility when compared with hiPSC-CMs from healthy control individuals. Methods: We differentiated iPSCs from pediatric patients with hypoplastic left heart syndrome (HLHS) who developed early onset HF and from healthy control individuals to generate hiPSC-CMs. We plated hiPSC-CMs on hydrogel micropattern for single-cell plating and measured their contractile phenotype using the Sony SI8000 cell motion imaging system. We used Seahorse XF assay to measure metabolism in hiPSC-CMs. Furthermore, we performed metabolomic profiling of day 20 and day 45 hiPSC-CMs. Results: HLHS hiPSC-CMs demonstrated metabolic derangement with significant reduction in ATP production (p <0.001) and in basal and maximal respiration (p <.001). We also found that HLHS hiPSC-CMs have impaired contractility when compared to WT hiPSC-CMs. Contraction force and acceleration were decreased on HLHS hiPSC-CMs compared to WT hiPSC-CMs (p<0.01). Our metabolomic profiling identified a reduction of tricarboxylic acid (TCA) cycle metabolites such as succinyl carnitine (p = 0.002) and alpha-ketoglutarate (p = 0.056) in HLHS cells compared to healthy controls at day 20 and day 45 of differentiation. In addition, succinate, fumarate, malate, itaconate and citraconate/ glutaconate were also significantly reduced in day 20 media of HLHS hiPSC-CMs and trended lower in day 45 HLHS hiPSC-CMs. Conclusions: The disrupted fatty acid metabolism in hiPSC-CMs from patients with SV HF provides new insight into the pathogenesis of this disease and may help to develop novel metabolic biomarkers that may be useful for identifying pediatric patients at an earlier stage of SV HF.

Abstract 11605: Association of Patient Characteristics and Center on Age of Fontan Completion: A Retrospective Cohort Study Using the Pediatric Health Information Systems Database

Introduction: Little is known regarding optimal timing of the Fontan operation and whether timing affects outcomes in patients with single-ventricle heart disease. The association of patient-level factors with age at the Fontan operation and the degree of practice variation among surgical centers have not been quantified in large studies. Methods: A retrospective cohort study of patients who underwent a Fontan operation between 1/1/2007 and 12/31/2017 at Pediatric Health Information Systems Database centers was performed to evaluate associations between patient characteristics and center on timing of Fontan operation. Mixed-effects multivariable linear regression was used to adjust for patient characteristics and center-level covariance. Results: In all, 7,840 patients (41% male, 57% white) at 46 centers were included. Median age at Fontan was 3.3 years (IQR 2.5-4.3). In an adjusted model hypoplastic left heart syndrome (-16 months, 95% CI -18 to -13), heterotaxy (-9 months, 95% CI -13 to -5), and ECMO history (-11 months, 95% CI -17 to -5) were associated with younger age at Fontan. Non-cardiac diagnoses (+4 months, 95% CI 0.1-9) and technology-dependence (+21 months, 95% CI 16-25) were associated with older age at Fontan ( Figure 1A ). There was no evidence of racial differences in Fontan timing. Children with Medicaid insurance were significantly younger at Fontan than counterparts with other insurance. We observed center effects on age at Fontan (p<0.001, ICC 0.03 95% CI 0.02-0.05) with youngest median age of 0.9 years (IQR 0.6-2.8) at one center and oldest median age of 5.0 years (IQR 4.6-5.9) at another center ( Figure 1B ). Conclusion: In this study, age at Fontan was significantly associated with cardiac anatomy, non-cardiac diagnoses, ECMO history, and insurance but not race. There was practice variation between centers in Fontan timing. Future studies will examine associations between timing of Fontan and patient outcomes.

Determinants and Prognostic Implications of Hepatorenal Dysfunction in Adults With Congenital Heart Disease.

There are limited data on the prognostic role of hepatorenal function indices in ambulatory patients with congenital heart disease (CHD). The purpose of this study was to determine the prevalence, risk factors, and prognostic implications of hepatorenal dysfunction, as measured by Model for End-Stage Liver Disease Excluding International Normalised Ratio (MELD-XI) score, in adults with CHD. In this retrospective study of CHD patients with comprehensive metabolic panels (2003-2019), mild/moderate and severe hepatorenal dysfunction was defined as MELD-XI 11-15 and > 15, respectively. Of 4977 patients, 1376 (28%) had hepatorenal dysfunction (mild/moderate: n= 935 [19%]; severe: n= 441 [9%]). Hepatorenal dysfunction was most common in Fontan/unrepaired single ventricle (46%) and right heart disease (31%). Baseline MELD-XI was associated with all-cause mortality (HR 1.27, CI 1.21-1.33; P < 0.001) after adjustment for age, sex, and congenital heart lesion. In 3864 patients with serial MELD-XI data, there was a temporal increase in MELD-XI, and this was associated with an increased risk of mortality (HR 1.24, CI 1.15-1.36, per unit increase in MELD-XI; P= 0.004), independently from the baseline MELD-XI score. In the subset of 1856 patients that underwent surgical/transcatheter interventions, there was a postoperative reduction in MELD-XI, and this was associated with a lower risk of mortality (HR 0.94, CI 0.90-0.98, per unit decrease in MELD-XI; P= 0.008), independently from the baseline MELD-XI score. Hepatorenal dysfunction was common in adults with CHD. Both baseline MELD-XI score and temporal changes in MELD-XI were associated with clinical outcomes, and therefore could be used to monitor therapeutic response to interventions and for deterioration in clinical status.

Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure

Patients with single ventricle heart defects requires a series of staged open-heart procedures, termed Fontan palliation. However, while lifesaving, these operations are associated with significant morbidity and early mortality. The attendant complications are thought to arise in response to the abnormal hemodynamics induced by Fontan palliation, although the pathophysiology underlying these physicochemical changes in cardiovascular and other organs remain unknown. Here, we investigated the microRNA (miRNA) content in serum and serum-derived extracellular vesicles (EVs) by sequencing small RNAs from a physiologically relevant sheep model of the Fontan operation. The differential expression analysis identified the enriched miRNA clusters in (1) serum vs. serum-derived EVs and (2) pre-Fontan EVs vs. post-Fontan EVs. Metascape analysis showed that the overexpressed subset of EV miRNAs by Fontan procedure target liver-specific cells, underscoring a potentially important pathway involved in the liver dysfunction that occurs as a consequence of Fontan palliation. We also found that post-Fontan EV miRNAs were associated with senescence and cell death, whereas pre-Fontan EV miRNAs were associated with stem cell maintenance and epithelial-to-mesenchymal transition. This study shows great potential to identify novel circulating EV biomarkers from Fontan sheep serum that may be used for the diagnosis, prognosis, and therapeutics for patients that have undergone Fontan palliation.

Paediatrician's guide to post-operative care for functionally univentricular CHD: a review.

Single ventricle CHD affects about 5 out of 100,000 newborns, resulting in complex anatomy often requiring multiple, staged palliative surgeries. Paediatricians are an essential part of the team that cares for children with single ventricle CHD. These patients often encounter their paediatrician first when a complication arises, so it is critical to ensure the paediatrician is knowledgeable of these issues to provide optimal care. We reviewed the subtypes of single ventricle heart disease and the various palliative surgeries these patients undergo. We then searched the literature to detail the general paediatrician's approach to single ventricle patients at different stages of surgical palliation. Single ventricle patients undergo staged palliation that drastically changes physiology after each intervention. Coordinated care between their paediatrician and cardiologist is requisite to provide excellent care. This review highlights what to expect when these patients are seen by their paediatrician for either well child visits or additional visits for parental or patient concern.

Intranasal dexmedetomidine for transthoracic echocardiography in infants with shunt-dependent single ventricle heart disease.

We investigated the efficacy and complication profile of intranasal dexmedetomidine for transthoracic echocardiography sedation in patients with single ventricle physiology and shunt-dependent pulmonary blood flow during the high-risk interstage period. A single-centre, retrospective review identified interstage infants who received dexmedetomidine for echocardiography sedation. Baseline and procedural vitals were reported. Significant adverse events related to sedation were defined as an escalation in care or need for any additional/increased inotropic support to maintain pre-procedural haemodynamics. Minor adverse events were defined as changes from baseline haemodynamics that resolved without intervention. To assess whether sedation was adequate, echocardiogram reports were reviewed for completeness. From September to December 2020, five interstage patients (age 29-69 days) were sedated with 3 mcg/kg intranasal dexmedetomidine. The median sedation onset time and duration time was 24 minutes (range 12-43 minutes) and 60 minutes (range 33-60 minutes), respectively. Sedation was deemed adequate in all patients as complete echocardiograms were accomplished without a rescue dose. When compared to baseline, three (60%) patients had a >10% reduction in heart rate, one (20%) patient had a >10% reduction in oxygen saturations, and one (20%) patient had a >30% decrease in blood pressure. Amongst all patients, no significant complications occurred and haemodynamic changes from baseline did not result in need for intervention or interruption of study. Intranasal dexmedetomidine may be a reasonable option for echocardiography sedation in infants with shunt-dependent single ventricle heart disease, and further investigation is warranted to ensure efficacy and safety in an outpatient setting.

Influence of intraoperative residual lesions and timing of extracorporeal membrane oxygenation on outcomes following first-stage palliation of single-ventricle heart disease

BackgroundData regarding the influence of intraoperative residual lesions on extracorporeal membrane oxygenation (ECMO) following the Norwood procedure are limited. Moreover, the significance of postoperative ECMO timing on in-hospital outcomes remains incompletely characterized. MethodsThis was a single-center, retrospective review of consecutive patients who underwent the Norwood operation from January 1997 to November 2017. Patients with at least minor residual lesions based on the intraoperative postcardiopulmonary bypass echocardiogram were identified. The association between residual lesions and postoperative ECMO was assessed with logistic regression, adjusting for age, weight, prematurity, various preoperative system-specific and procedural risk factors, shunt type, and era. Among patients receiving ECMO, associations between late ECMO (≥3 days post-Norwood) and in-hospital mortality or transplant, postoperative hospital length-of-stay, and cost of hospitalization were evaluated using logistic regression or generalized linear models with a gamma distribution and logarithmic link. ResultsAmong 500 patients, 78 (15.6%) received ECMO postoperatively. On multivariable analysis, the presence of at least minor residual lesions (odds ratio, 4.4; 95% CI, 2.1-9.3; P < .001) was associated with postoperative ECMO. In the ECMO subpopulation, there were 44 (56.4%) deaths or transplants. Late ECMO was associated with increased risk of in-hospital mortality or transplant (adjusted odds ratio, 6.2; 95% CI, 1.5-26.0), longer postoperative hospital length of stay (regression coefficient, 0.7; 95% CI, 0.3-1.1), and greater cost (regression coefficient, 0.6; 95%, CI 0.4-0.7), versus early ECMO (all P values < .05). ConclusionsThe presence of even minor intraoperative residua significantly increases the risk of ECMO following the Norwood operation. Among patients receiving ECMO postoperatively, early institution of ECMO is associated with lower mortality and resource utilization.

Abstract P1120: Project Singular: Building A Large-scale Genetics Dataset To Fuel Research Towards Curative Solutions For Single Ventricle Heart Disease

Objective: Single ventricle (SV) heart disease is a set of rare conditions occurring in 5 out of 100,000 births. Forty years ago, such diagnoses were universally fatal, but surgical advances have enabled most patients to live into their thirties. However, SV patients face a lifetime of expensive, invasive clinical care for complications and co-morbidities and decreased life expectancy and quality of life. The cause of SV heart disease is still unknown; believed to be both Mendelian and non-Mendelian, multigenic and multifactorial. To date, four genes have been linked to SV disease; however, the penetrance is low, and none are causal. Project Singular aims to uncover the cause(s) of SV by sequencing at least 5,000 SV patients and immediate family members, in conjunction with collecting important medical data, creating the largest genetic dataset available to date in this disease community and make it available free of charge to all qualified researchers. Methods: Subjects will be recruited and consented virtually through an online portal and will receive a biospecimen collection kit (saliva or buccal) by mail to return to the Broad Institute of MIT and Harvard. Samples will be processed, quality-controlled, and whole genome-sequenced using Illumina HiSeq at 30X coverage, with methylation arrays conducted on a subset. Sequences will be aligned to the human genome, annotated, deidentified, and securely deposited into the Terra.bio platform. Participants will fill out a survey on demographics and medical history, and patients will provide medical records. Deidentified phenotypic and genotypic data will be made available for free to qualified researchers globally. Integration with other SV-related registries will be undertaken where possible to increase the power of the study. Conclusion: Project Singular is the first genetics sequencing initiative of its size and depth focused specifically on SV, the most complex of all congenital heart defects. By enabling patients and families to participate from their homes, Project Singular will reduce barriers of travel and cost to increase diversity of participants. Data democratization of the dataset will fuel discovery in single ventricle etiology and lead to new targeted treatments and potentially curative solutions.

Liver Disease Assessment in Children with Fontan and Glenn Surgeries for Univentricular Hearts—The Role of Elastography and Biochemical Fibrosis Markers

Background: Children born with single-ventricle hearts require surgery in order to survive. Liver fibrosis is a known complication of Fontan surgery for univentricular hearts. Methods: In this study on 13 post-Fontan and 21 post-Glenn patients, we used elastography (shearwave and transient elastography) as well as serum biochemical fibrosis markers to evaluate the degree of liver fibrosis in comparison to 32 controls. Results: The mean Emedian and Vmedian values determined by shear wave elastography in the Fontan Group were significantly higher than the controls (4.85 kPa vs. 3.91 kPa and 1.25 m/s vs. 1.12 m/s, respectively). Fontan patients had significantly increased Fibrotest, Actitest, AST-to-Platelet Ratio index, ALT and GammaGT levels compared to controls. For post-Glenn patients, the mean Emedian and Vmedian values were similar to healthy controls, whereas the Fibrotest, Actitest and AST-to-Platelet Ratio index were significantly increased. Using transient elastography, we found significantly higher values for Emedian and Vmedian in Fontan patients compared to Glenn patients. Conclusions: Elastography and biochemical fibrosis markers are valuable non-invasive tools for screening and monitoring liver fibrosis in patients with Fontan and Glenn interventions.

Prenatal Diagnosis and Management of Single-Ventricle Heart Disease.

In the current era, most single-ventricle heart disease (SVHD) is diagnosed prenatally by means of fetal echocardiography. Disparities exist, however, by socioeconomic status and remote location, which require further attention. Prenatal diagnosis affords the opportunity to counsel expectant parents regarding the life-long course of children with SVHD, including the stages of single-ventricle palliation and challenges of the Fontan circulation; to discuss pregnancy management options; and to optimise delivery planning and perinatal care. Prognosis may be refined by specific features on the fetal echocardiogram, such as ventricular morphology, total anomalous pulmonary venous return, and atrioventricular valve regurgitation. Expectant mothers should be referred for evaluation of extracardiac anomalies and/or a genetic syndrome, which also significantly affect outcome. Fetuses with SVHD should be cared for by a multidisciplinary team and ideally delivered at term at or near a cardiac surgical center. Serial echocardiograms refine the anticipated postnatal physiology to optimise transitional care, including the need for prostaglandin or urgent atrial septal intervention in fetuses with hypoplastic left heart syndrome. In selected patients, there may be a role for fetal cardiac intervention to improve mortality or achieve a biventricular circulation after birth. Together, these strategies enhance the preoperative status of the neonate. Recent advances in fetal cardiovascular magnetic resonance imaging have focused on studying the relationships between cardiovascular physiology and fetal growth and development. These novel techniques allow for the exploration of the physiologic effects of SVHD on the brain and open avenues for the investigation of neuroprotective therapies.

Predicting Hemodynamic Performance of Fontan Operation for Glenn Physiology using Computational Fluid Dynamics: Ten Patient-specific Cases.

Single ventricle hearts have only one ventricle that can pump blood effectively and the treatment requires three stages of operations to reconfigure the heart and circulatory system. At the second stage, Glenn procedure is performed to connect superior vena cava (SVC) to the pulmonary arteries (PA). For the third and most complex operation, called Fontan, an extracardiac conduit is used to connect inferior vena cava (IVC) to the PL and thereafter no deoxygenated blood goes to the heart. Predicting Hemodynamic Performance of Fontan Operation using computational fluid dynamics (CFD) is hypothesized to improve outcomes and optimize this treatment planning in children with single-ventricle heart disease. An important reason for this surgical planning is to reduce the development of pulmonary arteriovenous malformations (PAVM) and the need to perform Fontan revisions. The purpose of this study was to develop amodel for Fontan surgical planning and use this model to compare blood circulation in two designed graft types of Fontan operation known as T-shape and Y-graft. The functionality of grafts was compared in terms of power loss (PL) and hepatic flow distribution (HFD), a known factor in PAVM development. To perform this study, ten single-ventricle children with Glenn physiology were included and a CFD model was developed to estimate the blood flow circulation to the left and right pulmonary arteries. The estimated blood flow by CFD was compared with that measured by cardiovascular magnetic resonance. Results showed that there was an excellent agreement between the net blood flow in the right and left pulmonary arteries computed by CFD and CMR (ICC= 0.98, P-value ≥0.21). After validating the accuracy of each CFD model, Fontan operations using T-shape and Y-graft conduits were performed in silico for each patient and the developed CFD model was used to predict the post-surgical PL and HFD. We found that the PL in the Y-graft was significantly lower than in the T-shape (P-value ≤0.001) and HFD was significantly better balanced in Y-graft compared to the T-shape (P-value=0.004).

Neonatal ventricular assist device implantation for high-risk hypoplastic left heart syndrome: How we do it.

Neonatal ventricular assist device implantation for high-risk hypoplastic left heart syndrome: How we do it.

Virtual Reality Cardiac Surgical Planning Software (CorFix) for Designing Patient-Specific Vascular Grafts: Development and Pilot Usability Study.

BackgroundPatients with single ventricle heart defects receive 3 stages of operations culminating in the Fontan procedure. During the Fontan procedure, a vascular graft is sutured between the inferior vena cava and pulmonary artery to divert deoxygenated blood flow to the lungs via passive flow. Customizing the graft configuration can maximize the long-term benefits. However, planning patient-specific procedures has several challenges, including the ability for physicians to customize grafts and evaluate their hemodynamic performance.ObjectiveThe aim of this study was to develop a virtual reality (VR) Fontan graft modeling and evaluation software for physicians. A user study was performed to achieve 2 additional goals: (1) to evaluate the software when used by medical doctors and engineers, and (2) to explore the impact of viewing hemodynamic simulation results in numerical and graphical formats.MethodsA total of 5 medical professionals including 4 physicians (1 fourth-year resident, 1 third-year cardiac fellow, 1 pediatric intensivist, and 1 pediatric cardiac surgeon) and 1 biomedical engineer voluntarily participated in the study. The study was pre-scripted to minimize the variability of the interactions between the experimenter and the participants. All participants were trained to use the VR gear and our software, CorFix. Each participant designed 1 bifurcated and 1 tube-shaped Fontan graft for a single patient. A hemodynamic performance evaluation was then completed, allowing the participants to further modify their tube-shaped design. The design time and hemodynamic performance for each graft design were recorded. At the end of the study, all participants were provided surveys to evaluate the usability and learnability of the software and rate the intensity of VR sickness.ResultsThe average times for creating 1 bifurcated and 1 tube-shaped graft after a single 10-minute training session were 13.40 and 5.49 minutes, respectively, with 3 out 5 bifurcated and 1 out of 5 tube-shaped graft designs being in the benchmark range of hepatic flow distribution. Reviewing hemodynamic performance results and modifying the tube-shaped design took an average time of 2.92 minutes. Participants who modified their tube-shaped graft designs were able to improve the nonphysiologic wall shear stress (WSS) percentage by 7.02%. All tube-shaped graft designs improved the WSS percentage compared to the native surgical case of the patient. None of the designs met the benchmark indexed power loss.ConclusionsVR graft design software can quickly be taught to physicians with no engineering background or VR experience. Improving the CorFix system could improve performance of the users in customizing and optimizing grafts for patients. With graphical visualization, physicians were able to improve WSS percentage of a tube-shaped graft, lowering the chance of thrombosis. Bifurcated graft designs showed potential strength in better flow split to the lungs, reducing the risk for pulmonary arteriovenous malformations.

Factors associated with caregiver adherence to mobile health interstage home monitoring in infants with single ventricle or biventricular shunt-dependent heart disease.

Mobile health technology is an emerging tool in interstage home monitoring for infants with single ventricle heart disease or biventricular shunt-dependent defects. This study sought to describe adherence to mobile health monitoring and identify factors and outcomes associated with adherence to mobile health monitoring. This was a retrospective, single-institution study of infants who were followed in a mobile health-based interstage home monitoring programme between February 2016 and October 2020. The analysis included 105 infants and subjects were grouped by frequency of adherence to mobile health monitoring. Within the study cohort, 16 (15.2%) had 0% adherence, 25 (23.8%) had <50% adherence, and 64 (61.0%) had >50% adherence. The adherent groups had a higher percentage of infants who were male (p = 0.02), white race (p < 0.01), non-Hispanic or non-Latinx ethnicity (p < 0.01) and had mothers with primary English fluency (p < 0.01), married marital status (p < 0.01), and a prenatal diagnosis of faetal cardiac disease (p = 0.03). Adherent groups also had a higher percentage of infants with non-Medicaid primary insurance (p < 0.01) and residence in a neighbourhood with a higher median household income (p < 0.04). Frequency of adherence was not associated with interstage mortality, unplanned cardiac reinterventions, or hospital readmissions. Impact of mobile health interstage home monitoring on caregiver stress as well as use of multi-language, low literacy, affordable mobile health options for interstage home monitoring warrant further investigation.

Caregiving for Interstage Infants: A Continuous Process of Compromise During the Pandemic.

Background: Infants born with single ventricle heart disease require in-home medicalized care during the interstage period (time between the first and second staged heart surgery). These caregivers rely on extended family, friends, and hired caretakers to provide respite time. However, the coronavirus pandemic removed these families’ options due to stay-at-home and social distancing directives. We explored the caregivers’ experiences during the interstage period, including impacts on their lifestyle, as they managed their infants’ critical needs during the coronavirus disease 2019 pandemic. Method: In-person or telephonic interviews of 14 caregivers interviewed once or twice were conducted between November 2019 and July 2020. Constructivist Grounded Theory methodology guided both data collection and analysis for the inductive and abductive exploration of caregivers’ experiences. Results: Data analysis led to the development of 2 concepts: Accepting and adapting to a restrictive home environment and Reconciling what is and what is yet to come. Refinement of the relationship between the 2 concepts led to the development of a theory grounded in the words and experiences of the participants called: A Continuous Process of Compromise. Conclusions: Our findings increase understanding of caregivers’ experiences related to psychosocial and lifestyle impacts and the need for additional support during the interstage period.