Single Ventricle Patients Research Articles

T1 mapping of the myocardium and liver in the single ventricle population.

Fontan associated liver disease (FALD) is an increasingly recognized complication of the single ventricle circulation characterized by hepatic venous congestion leading to hepatic fibrosis. Within the Fontan myocardium, fibrotic myocardial remodeling may occur and lead to ventricular dysfunction. Magnetic resonance imaging (MRI) T1 mapping can characterize both myocardial and liver properties. The aim of this study was to compare myocardial and liver T1 between single ventricle patients with and without a Fontan and biventricular controls. A retrospective study of 3 groups of patients: 16 single ventricle patients before Fontan (SVpre 2 newborns, 9 pre-Glenn, 5 pre-Fontan, 31% single right ventricle [SRV]), 16 Fontans (56% SRV) and 10 repaired d-transposition of the great arteries (TGA). Native modified Look-Locker inversion T1 times were measured in the myocardium and liver. Cardiac MRI parameters, myocardial and liver T1 values were compared in the three groups. Correlations were assessed between liver T1 and cardiac parameters. Myocardial T1 was higher in SVpre (1,056 ± 48ms) and Fontans (1,047 ± 41ms) compared to TGA (1,012 ± 48ms, P < 0.05). Increased liver T1 was found in both SVpre (683 ± 82ms) and Fontan (727 ± 49ms) patients compared to TGA patients (587 ± 58ms, P < 0.001). There was no difference between single left ventricle (SLV) versus SRV myocardial or liver T1. Liver T1 showed moderate correlations with myocardial T1 (r = 0.48, confidence interval [CI] 0.26-0.72) and ejection fraction (r = -0.36, CI -0.66-0.95) but not with other volumetric parameters. Increased liver T1 at both pre- and post-Fontan stages suggests there are intrinsic liver abnormalities early in the course of single ventricle palliation. Increased myocardial T1 and its relationship to liver T1 suggest a combination of edema from passive venous congestion and/or myocardial fibrosis occurring in this population. Liver T1 may provide an earlier marker of liver disease warranting further study.

Abstract 10999: Long-Term Outcomes of Atrioventricular Valve Regurgitation and Repair in Patients With Single Ventricle Physiology

Introduction: In single ventricle patients, AV valve regurgitation increases the risk of adverse outcomes, and staged palliation with concomitant AV valve intervention further increases that risk in the post-operative period. Long-term outcomes of valve intervention during stage 2 palliation, however, have not been established. The purpose of this study is to evaluate long-term outcomes after AV valve intervention during stage 2 palliation in patients with RV dominant circulation in a multicenter study utilizing a national public-use database. Methods: The study was performed using the SVR and SVR II public use datasets. From the original cohort of 549 patients, 102 (19%) with moderate or severe tricuspid valve regurgitation as measured by their stage 2 pre-operative core lab echocardiogram were included. Kaplan-Meier curves were performed to describe the association between valve regurgitation and intervention and long-term survival up to 6 years post Fontan. Multivariable Cox proportional-hazards models were used to assess the relationship between valve intervention and survival adjusting for confounding covariates. Results: Patients with moderate or severe valve regurgitation at either stage 1 or 2 had worse long-term survival defined as death or transplant up to 6 years post-Fontan operation ( p &lt; 0.001, p &lt; 0.01). There were 34 patients (33%) of the 102 with significant regurgitation who underwent valve intervention at the time of stage 2 repair. Those who underwent valve intervention at stage 2 surgery were significantly more likely to die or undergo heart transplantation (HR 3.49, CI 1.53-7.94). Of the patients who underwent valve intervention, those who survived were more likely to have none or mild valve regurgitation by the time of stage 3 (78% vs 46%, p = 0.025). Patients with moderate to severe AV valve regurgitation at the time of the Fontan had favorable outcomes regardless of valve intervention with 100% survival. Conclusions: The risks associated with AV valve regurgitation in single ventricle patients are not mitigated by valve intervention at the time of stage 2 palliation. In fact, patients who underwent valve intervention at stage 2 had significantly worse survival as compared to patients with AV valve regurgitation who did not.

Abstract 15009: Detection of a Low Ventricular Stiffness With Preserved Ejection Fraction Phenotype in Single Ventricle Physiology

Introduction: Patients with single ventricle physiology frequently demonstrate decreased exercise tolerance after the Fontan operation. The objective of this study was to investigate the contribution of ventricular stiffness to exercise function in these patients. Hypothesis: We hypothesized that ventricular stiffness, both extremes of high and low stiffness, would be associated with exercise tolerance in Fontan patients. Methods: We previously validated an echocardiographic measure of ventricular stiffness, lateral Doppler E: tissue Doppler e’/end-diastolic volume (lateral E:e’/EDV) in children. Core-lab echocardiograms and exercise test results were obtained from the publicly-available Pediatric Heart Network Fontan Cross-sectional Study database. Exercise function was quantified as % predicted VO 2 . Ejection fraction (EF) was considered abnormal if &lt; 50%. Diastolic function was defined as high stiffness if the lateral E:e’/EDV was &gt; 90th percentile or low stiffness if &lt; 10th percentile. Patients were divided into four groups: 1 = normal EF and normal diastolic function, 2 = decreased EF with normal diastolic function, 3 = normal EF with high ventricular stiffness, and 4 = normal EF with low ventricular stiffness. Results: 239 patients (61% left, 29% right, 10% mixed ventricular dominance) had EF, lateral E:e’/EDV, and VO 2 measured. Differences between groups are reported in the Table. Conclusion: Single ventricle patients with both high and low stiffness and preserved EF had worse exercise capacity than patients with both normal and abnormal EF. To our knowledge, this is the first study detecting a low stiffness heart failure phenotype in single ventricle physiology. Future studies should further investigate the pathophysiologic mechanisms that lead to these extremes of stiffness in Fontan patients.

Abstract 14731: Form and Function: 4D Flow Derived Hemodynamic Parameters in the Ascending Aorta is Reflective of Transverse Aortic Arch Dilation in Patients With Single Ventricle Physiology

Introduction: Reconstructed aortas in patients with single ventricle (SV) can dilate progressively over time, possibly due to abnormal flow patterns. Four-dimensional (4D) flow cardiac magnetic resonance imaging (CMR) can assess advanced hemodynamic parameters. This study utilizes 4D flow CMR to assess the association between ascending aorta (AAo) 4D flow dynamics of vorticity, viscous energy loss (EL) and kinetic energy (KE) with arch anatomy in SV patients. Methods: This was a retrospective single center study of all patients with SV who underwent 4D flow CMR from June 2021-present. Vorticity, KE and EL were calculated over the segmented three-dimensional AAo, and values were normalized to cardiac index (CI). Cross-sectional areas of the aortic root, AAo and transverse aorta were indexed to body surface area. Linear regression was used to determine associations between hemodynamic parameters and arch anatomy. Results: 20 pts met inclusion criteria; 5 were excluded due to incomplete datasets. The remaining 15 pts had a median age of 57 months (IQR 31;117.5). Ten (66%) had a systemic RV, 13 (86%) had a reconstructed aorta and 40% were after the Fontan operation. Peak and mean vorticity in the AAo were positively associated with transverse arch area. Additionally, there was a positive association between both total EL and EL index, and transverse arch area. (see table) Conclusions: Higher vorticity and EL in the AAo are associated with and reflective of higher transverse arch areas (i.e. dilation) in SV pts. In depth research in a prospective, longitudinal cohort is warranted to better understand this relationship and the geometry relative to hemodynamics. Furthermore, correlation of 4D flow metrics with clinical outcomes may provide novel insights into modifiable risk factors in this patient population

Abstract 11846: Factors Influencing Survival in Adult Patients With Congenital Heart Disease Considered for Transplant: A Single Center Study

Introduction: Adult congenital heart disease (ACHD) patients pose unique challenges in identifying time for transplantation and factors influencing outcomes. Hypothesis: Survival outcomes in ACHD patients depend on hemodynamic, functional, and laboratory parameters. Methods: We performed a retrospective chart review of adult patients (&gt;18y) with CHD evaluated for heart or heart+ transplant between November 2004 and July 2014 and evaluated outcomes until December 2020 at University of Pittsburgh Medical Center. Multiple clinical parameters were evaluated to identify factors influencing outcomes for up to 10 years after consideration for transplant. Kruskal-Wallis nonparametric analysis was conducted to compare differences between variables. Results: 58 adult patients with congenital heart disease (CHD), age range 20-55 years were evaluated. D-TGA with atrial switch operation (20.7%), tetralogy of Fallot/pulmonary atresia (15.5%) and tricuspid atresia (13.8%) were the most common diagnosis for transplant. Of the 58 patients, 5 (8.6%) were deferred, 42 (72.4%) were listed for transplant and 11 (18.9%) were declined for transplant. Statistically significant factors affecting listing decision are included in table 1. Declined patients showed the highest 1-year mortality (18.2%), whereas waitlisted patients showed the highest 10-year mortality (84.2%). In the post-transplantation period, 30 day survival was 87.0%, 1-yr was 82.6%, and 5-yr and 10 year was 69.6%. 1-year post-transplant survival was influenced by pre-transplant end diastolic pressures, use of advanced life support, and right atrial pressure. There was no significant difference in post-transplant survival between single ventricle versus bi-ventricular patients. Conclusions: We have identified clinical factors that influence survival outcomes in ACHD patients considered for transplantation, These can applied while making transplant decisions and improve outcomes

Abstract 12034: Diffuse Myocardial Fibrosis, Its Distribution And Relationship To Clinical Outcome And Ventricular Function In Single Ventricles Before And After Fontan: A Cardiac Magnetic Resonance Outcome Study

Introduction: Patients with single ventricle (SV) anatomy are susceptible to myocardial fibrosis as measured by cardiac magnetic resonance (CMR) imaging. This study investigated the association of diffuse myocardial fibrosis prior to Fontan with ventricular function and clinical outcomes after Fontan completion. Methods: Retrospective cohort study of consecutive SV patients who underwent CMR T1 mapping prior to Fontan. Native T1 time and extracellular volume (ECV) of the dominant ventricle and a free wall region of interest (ROI) were measured on CMR pre-Fontan. Longitudinal strain was measured on echocardiography pre- and post-Fontan. Associations between pre-Fontan fibrosis, strain, and clinical outcomes were evaluated using linear and logistic regression. Results: 40 patients were included (table 1). ECV directly correlated to the number of ICU days and post-Fontan strain. The coefficient of variation (CV) of ECV directly correlated to hospital and chest tube days. When limited to single right ventricles (RV), T1 directly correlated to strain pre-Fontan. ECV directly correlated to ICU days as well as strain pre- and post-Fontan. ECV ROI directly correlated to strain post-Fontan. The CV of ECV directly correlated to the number of hospital days (table 2). Conclusions: Myocardial fibrosis prior to Fontan may portend the clinical course after Fontan and should be considered for risk stratification. The CV of ECV is a novel measure of diffuse fibrosis that is associated with clinical outcome. For single RV patients, fibrosis before Fontan is associated with worse ventricular function after. The use of reverse remodeling agents prior to Fontan should be considered.

A computational study of aortic reconstruction in single ventricle patients.

Patients with hypoplastic left heart syndrome (HLHS) are born with an underdeveloped left heart. They typically receive a sequence of surgeries that result in a single ventricle physiology called the Fontan circulation. While these patients usually survive into early adulthood, they are at risk for medical complications, partially due to their lower than normal cardiac output, which leads to insufficient cerebral and gut perfusion. While clinical imaging data can provide detailed insight into cardiovascular function within the imaged region, it is difficult to use these data for assessing deficiencies in the rest of the body and for deriving blood pressure dynamics. Data from patients used in this paper include three-dimensional, magnetic resonance angiograms (MRA), time-resolved phase contrast cardiac magnetic resonance images (4D-MRI) and sphygmomanometer blood pressure measurements. The 4D-MRI images provide detailed insight into velocity and flow in vessels within the imaged region, but they cannot predict flow in the rest of the body, nor do they provide values of blood pressure. To remedy these limitations, this study combines the MRA, 4D-MRI, and pressure data with 1D fluid dynamics models to predict hemodynamics in the major systemic arteries, including the cerebral and gut vasculature. A specific focus is placed on studying the impact of aortic reconstruction occurring during the first surgery that results in abnormal vessel morphology. To study these effects, we compare simulations for an HLHS patient with simulations for a matched control patient that has double outlet right ventricle (DORV) physiology with a native aorta. Our results show that the HLHS patient has hypertensive pressures in the brain as well as reduced flow to the gut. Wave intensity analysis suggests that the HLHS patient has irregular circulatory function during light upright exercise conditions and that predicted wall shear stresses are lower than normal, suggesting the HLHS patient may have hypertension.

Ventricular Assist Device Outcomes in Infants and Children With Stage 1 Single Ventricle Palliation.

Data on ventricular assist device (VAD) outcomes in infants with stage 1 single ventricle (SV) palliation are limited. We examined the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry for outcomes of pre/poststage 1 SV patients undergoing VAD implantation between March 2018 and October 2020. Data are collected from 32 centers and major adverse events undergo central adjudication. During the study period, 30 stage 1 SV patients underwent VAD implant with median age of 0.9 months (range 0.1-25) and weight 3.7 kg (2.4-17). Preimplant illness severity was high: ventilator support (90%), ECMO (30%), prior cerebral vascular accident (CVA, 23%), and dialysis (13%). Devices used included paracorporeal pulsatile (50%), paracorporeal continuous-flow (37%), and multiple devices (13%). Median support duration was 56 days (range 3-246). A positive clinical outcome (transplanted or weaned) was attained in 63% (63% transplanted, 37% mortality, 0% weaned). VAD adverse events included: major infection (43%), neurologic dysfunction (any = 30%; CVA = 20%), major bleeding (17%), renal dysfunction (13%), and device malfunction (3%). In conclusion, stage 1 SV patients undergoing VAD support have high preimplant illness severity and complexity, as well as significant morbidity and mortality postimplant. A variety of devices and strategies are employed by centers to support this challenging population.

HeartWatch: Implementing a Pediatric Heart Center Program to Prevent Cardiac Arrests Outside the ICU.

HeartWatch aims to identify patients not adequately captured by Cardiac Pediatric Early Warning Scores who are at high risk for sudden decompensation. Inclusion criteria were developed and evaluated during pilot and implemented phases (April 2020-April 2021) and then monitored in a sustained phase through June 2022. Our primary outcome was the reduction in the out-of-ICU CA rate. During the 13 months, we enrolled 169 patients, and the CA rate decreased from 0.7 to 0.33 per 1,000 patient days, a 53% reduction. The CA rate further decreased to 0.28 events per 1,000 patient days, a 60% reduction, by June 2022. The most common indications for HeartWatch inclusion were high-risk single-ventricle patients (31%) and patients with diminished ventricular function (20%). Implementation of HeartWatch was associated with a meaningful reduction in CA in the ACCU. Creating shared mental models for high-risk patients is essential for patient safety. Future work will optimize local processes that focus on the sustainability of our gains. We will also evaluate opportunities to adapt and implement a similar framework in other institutions to assess reproducibility.

Somatic growth in single ventricle patients: A systematic review and meta-analysis.

To map somatic growth patterns throughout Fontan palliation and summarise evidence on its key modifiers. Databases were searched for relevant articles published from January 2000 to December 2021. Height and weight z scores at each time point (birth, Glenn procedure, Fontan procedure and >5 years after Fontan completion) were pooled using a random effects meta-analysis. A random effects meta-regression model was fitted to model the trend in z scores over time. Nineteen studies fulfilled eligibility criteria, yielding a total of 2006 participants. The z scores for height and weight were markedly reduced from birth to the interstage period, but recovered by about 50% following the Glenn procedure. At >10 years after the Fontan procedure, the z scores for weight seemed to normalise despite persistent lower height, resulting in increased body mass index. The review revealed a number of modifiers of somatic growth, including aggressive nutritional management, timing of Glenn/Fontan, prompt resolution of complications and obesity prevention programmes in adolescence and adulthood. This review mapped the somatic growth of single ventricle patients and summarised key modifiers that may be amendable to improvement. These data provide guidance on strategies to further optimise somatic growth in this population and may serve as a benchmark for clinical follow-up.

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.

Impaired Neurovascular Function Underlies Poor Neurocognitive Outcomes and Is Associated with Nitric Oxide Bioavailability in Congenital Heart Disease.

We use a non-invasive MRI proxy of neurovascular function (pnvf) to assess the ability of the vasculature to supply baseline metabolic demand, to compare pediatric and young adult congenital heart disease (CHD) patients to normal referents and relate the proxy to neurocognitive outcomes and nitric oxide bioavailability. In a prospective single-center study, resting-state blood-oxygen-level-dependent (BOLD) and arterial spin labeling (ASL) MRI scans were successfully obtained from 24 CHD patients (age = 15.4 ± 4.06 years) and 63 normal referents (age = 14.1 ± 3.49) years. Pnvf was computed on a voxelwise basis as the negative of the ratio of functional connectivity strength (FCS) estimated from the resting-state BOLD acquisition to regional cerebral blood flow (rCBF) as estimated from the ASL acquisition. Pnvf was used to predict end-tidal CO2 (PETCO2) levels and compared to those estimated from the BOLD data. Nitric oxide availability was obtained via nasal measurements (nNO). Pnvf was compared on a voxelwise basis between CHD patients and normal referents and correlated with nitric oxide availability and neurocognitive outcomes as assessed via the NIH Toolbox. Pnvf was shown as highly predictive of PETCO2 using theoretical modeling. Pnvf was found to be significantly reduced in CHD patients in default mode network (DMN, comprising the ventromedial prefrontal cortex and posterior cingulate/precuneus), salience network (SN, comprising the insula and dorsal anterior cingulate), and central executive network (CEN, comprising posterior parietal and dorsolateral prefrontal cortex) regions with similar findings noted in single cardiac ventricle patients. Positive correlations of Pnvf in these brain regions, as well as the hippocampus, were found with neurocognitive outcomes. Similarly, positive correlations between Pnvf and nitric oxide availability were found in frontal DMN and CEN regions, with particularly strong correlations in subcortical regions (putamen). Reduced Pnvf in CHD patients was found to be mediated by nNO. Mediation analyses further supported that reduced Pnvf in these regions underlies worse neurocognitive outcome in CHD patients and is associated with nitric oxide bioavailability. Impaired neuro-vascular function, which may be non-invasively estimated via combined arterial-spin label and BOLD MR imaging, is a nitric oxide bioavailability dependent factor implicated in adverse neurocognitive outcomes in pediatric and young adult CHD.

Analyzing Continuous Physiologic Data to Find Hemodynamic Signatures Associated With New Brain Injury After Congenital Heart Surgery.

IMPORTANCE:Continuous data capture technology is becoming more common. Establishing analytic approaches for continuous data could aid in understanding the relationship between physiology and clinical outcomes.OBJECTIVES:Our objective was to design a retrospective analysis for continuous physiologic measurements and their relationship with new brain injury over time after cardiac surgery.DESIGN, SETTING, AND PARTICIPANTS:Retrospective cohort study in the Cardiac Critical Care Unit at the Hospital for Sick Children in patients after repair of transposition of the great arteries (TGA) or single ventricle (SV) lesions.MAIN OUTCOMES AND MEASURES:Continuously acquired physiologic measurements for up to 72 hours after cardiac surgery were analyzed for association with new brain injury by MRI. Distributions of heart rate (HR), systolic blood pressure (BP), and oxygen saturation (Spo2) for SV and TGA were analyzed graphically and with descriptive statistics over postoperative time for data-driven variable selection. Mixed-effects regression analyses characterized relationships between HR, BP, and Spo2 and new brain injury over time while accounting for variation between patients, measurement heterogeneity, and missingness.RESULTS:Seventy-seven patients (60 TGA; 17 SV) were included. New brain injury was seen in 26 (34%). In SV patients, with and without new brain injury, respectively, in the first 24 hours after cardiac surgery, the median (interquartile range) HR was 172.0 beats/min (bpm) (169.7–176.0 bpm) versus 159.6 bpm (145.0–167.0 bpm); systolic BP 74.8 (67.9–78.5 mm Hg) versus 68.9 mm Hg (61.6–70.9 mm Hg). Higher postoperative HR (parameter estimate, 19.4; 95% CI, 7.8–31; p = 0.003 and BP, 8.6; 1.3–15.8; p = 0.024) were associated with new brain injury in SV patients. The strength of this relationship decreased with time.CONCLUSIONS AND RELEVANCE:Retrospective analysis of continuous physiologic measurements can provide insight into changes in postoperative physiology over time and their relationship with new brain injury. This technique could be applied to assess relationships between physiologic data and many patient interventions or outcomes.

Predictors and Outcomes of Arrhythmiaon Stage I Palliation of SingleVentricle Patients.

Arrhythmias are common in single ventricle patients though their effect on outcomes during stage I palliation (S1P) is unclear. The authors sought to study associated risks for arrhythmia in patients undergoing S1P for single ventricle disease and evaluate the outcome of arrhythmias and their treatment strategies on survival. Retrospective patient, surgical, medication, and arrhythmia data were obtained from the NPC-QIC (NationalPediatric Cardiology Quality Improvement Collaborative) database. Bivariate analysis of variables associated with arrhythmias, as well as those associated with survival, was performed at the time of stage II palliation. Appropriate variables were included in multivariate modeling. Of the 2,048 patients included in the study, 36% had arrhythmia noted during their S1P hospitalization, with supraventricular tachycardia (12%) and focal atrial tachycardia (11%) the most common. At S1P discharge, 11% of patients were on an antiarrhythmic medication. Arrhythmias were associated with lower survival and increased hospital length of stay. Heterotaxy syndrome, younger age at S1P, male sex, and additional anomalies were associated with increased risk of arrhythmia in multivariable modeling (P≤ 0.01). Arrhythmia and female sex were associated with increased mortality, whereas antiarrhythmic medication and digoxin use were associated with decreased mortality (P≤ 0.003, model area under the curve=0.79). The use of antiarrhythmic medications within the subcohort of arrhythmia patients was also associated with decreased risk of mortality (P&lt; 0.0001; odds ratio: 2.0-7.2). Arrhythmias are common during admission for S1P and associated with poor outcomes. Theuseofantiarrhythmic medications may improve survival, though future studies are needed.

Incidence and impact of malnutrition in patients with Fontan physiology.

Single-ventricle patients require a series of surgeries, with the final stage being the Fontan. This form of circulation results in several long-term complications, but the impact and consequences of nutrition status remain unclear. We sought to evaluate the incidence of malnutrition in Fontan patients and the impact on outcomes. This study was a retrospective cohort study of children who underwent Fontan surgery between 1997 and 2018. Clinical, demographic, and nutrition data were collected, including weight, height, body mass index (BMI), and their respective z scores (z score for weight-for-age [WAZ], z score for height-for-age [HAZ], and z score for BMI-for-age [BMIZ]) pre-Fontan, at discharge, 6 months, and 1, 5, and 10 years post-Fontan. Malnutrition status was categorized using the American Society for Parenteral and Enteral Nutrition guidelines and the Michigan MTool. Fontan failure was defined as listing for heart transplant or death. Of the 69 patients, moderate-severe malnutrition occurred at any time point in 11% (n = 8) by WAZ, 16% (n = 11) by HAZ, and 6% (n = 4) by BMIZ. Moderate-severe malnutrition persisted in 6.5%-12.9% at 10 years post-Fontan. Compared with the pre-Fontan period, there was no change in these parameters over time. There was no statistically significant difference in Fontan failure between degrees of pre-Fontan malnutrition. There is a 6%-16% incidence of moderate-severe malnutrition in Fontan patients. Malnutrition is a condition that remains present in follow-up. There was no association with anthropometric parameters and transplant-free survival. A prospective multi-institutional study is needed to understand the impact of malnutrition on long-term outcomes.

Perioperative Management of an Adolescent Fontan Patient with Narrowing of the Aortopulmonary Space for Posterior Scoliosis Surgery

Congenital cardiac patients who received neonatal reconstructive aortic arch surgery are at risk of aortopulmonary space narrowing with compression of the left pulmonary artery and left main bronchus (LMB) later in life. We discuss a challenging adolescent single ventricle patient who presented for surgical treatment of a non-idiopathic thoracic scoliosis (posterior spinal fusion) with severe stenosis of the LMB and left pulmonary artery due to a narrow aortopulmonary space. Careful preoperative imaging, evaluation, and decision making resulted in successful surgical treatment and uneventful perioperative course.

Impact of Total Anomalous Pulmonary Venous Connection in Staged Single Ventricle Palliation

BackgroundTotal anomalous pulmonary venous connection (TAPVC) with a functional single ventricle is a risk factor for mortality during staged palliation. This study aimed to assess TAPVC’s impact on staged palliation outcomes. MethodsIn a total of 602 patients with a functional single ventricle who underwent stage 1 palliation (S1P) at our center between 2001 and 2020, 39 (6.5%) patients were associated with TAPVC. Median age at S1P was 12.0 (interquartile range, 7-21) days with a body weight of 3.1 (interquartile range, 2.8-3.6) kg. Outcomes during staged palliation were compared with the remaining 563 patients without TAPVC. Risk factors for mortality were identified using a Cox proportional hazards regression model. ResultsPrimary diagnosis in functional single-ventricle patients with TAPVC included hypoplastic left heart syndromes (n = 13), unbalanced atrioventricular septal defects (n = 12) tricuspid atresias (n = 2), double inlet left ventricle (n = 1), and others (n = 11). Types of TAPVC were supracardiac (n = 21), cardiac (n = 10), infracardiac (n = 6), and mixed (n = 2). Pulmonary venous obstruction (PVO) was associated in 19 (49%) patients. S1Ps included Norwood (n = 13), aortopulmonary shunt (n = 21), and pulmonary artery banding (n = 5). Thirty-day mortality after S1P was significantly increased in patients with TAPVC vs without TAPVC (43.6% vs 16.3%; P < .001). After bidirectional cavopulmonary shunt and total cavopulmonary connection procedures, mortality was low in both groups, and no statistically significant differences were found. Correction of TAPVC at the time of S1P was not found to be a significant risk factor in univariable Cox regression analysis. In univariate and multivariate analysis, PVO was identified as an independent risk factor for mortality in patients with TAPVC (P < .001). ConclusionsOverall survival is lower in TAPVC single-ventricle patients than in non-TAPVC patients. Most deaths after S1P were associated with TAPVC, but not after S2P. PVO is a mortality risk factor in TAPVC patients.

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.

Subcutaneous Treprostinil Improves Surgical Candidacy for Next Stage Palliation in Single Ventricle Patients With High-Risk Hemodynamics

Single ventricle (SV) patients with pulmonary vascular disease (SV-PVD) are considered poor surgical candidates for Glenn or Fontan palliation. Given limited options for Stage 1 (S1) and Stage 2 (S2) SV patients with SV-PVD, we report on the use of subcutaneous treprostinil (TRE) to treat SV-PVD in this population. This single-center, retrospective cohort study examined SV patients who were not candidates for subsequent surgical palliation due to SV-PVD and were treated with TRE. The primary outcome was ability to progress to the next surgical stage; secondary outcomes included changes in hemodynamics after TRE initiation. Between 3/2014 and 8/2021, 17 SV patients received TRE for SV-PVD: 11 after S1 and 6 after S2 (median PVR 4.1 [IQR 3.2-4.8] WU*m2 and 5.0 [IQR 1.5-6.1] WU*m2, respectively). Nine of 11 (82%) S1 progressed to S2, and 2 (18%) underwent heart transplant (HTx). Three of 6 (50%) S2 progressed to Fontan, 1 underwent HTx and 2 are awaiting Fontan on TRE. TRE significantly decreased PVR in S1 patients with median post-treatment PVR of 2.0 (IQR 1.5-2.6) WU*m2. TRE can allow for further surgical palliation in select pre-Fontan patients with SV-PVD, obviating the need for HTx. Improvement in PVR was significant in S1 patients and persisted beyond discontinuation of therapy for most patients.

Impact and Modifiers of Ventricular Pacing in Patients With Single Ventricle Circulation

BackgroundPalliation of the single ventricle (SV) circulation is associated with a burden of lifelong complications. Previous studies have identified that the need for a permanent ventricular pacing system (PPMv) may be associated with additional adverse long-term outcomes. ObjectivesThe goal of this study was to quantify the attributable risk of PPMv in patients with SV, and to identify modifiable risk factors. MethodsThis international study was sponsored by the Pediatric and Congenital Electrophysiology Society. Centers contributed baseline and longitudinal data for functionally SV patients with PPMv. Enrollment was at implantation. Controls were matched 1:1 to PPMv subjects by ventricular morphology and sex, identified within center, and enrolled at matched age. Primary outcome was transplantation or death. ResultsIn total, 236 PPMv subjects and 213 matched controls were identified (22 centers, 9 countries). Median age at enrollment was 5.3 years (quartiles: 1.5-13.2 years), follow-up 6.9 years (3.4-11.6 years). Median percent ventricular pacing (Vp) was 90.8% (25th-75th percentile: 4.3%-100%) in the PPMv cohort. Across 213 matched pairs, multivariable HR for death/transplant associated with PPMv was 3.8 (95% CI 1.9-7.6; P < 0.001). Within the PPMv population, higher Vp (HR: 1.009 per %; P = 0.009), higher QRS z-score (HR: 1.19; P = 0.009) and nonapical lead position (HR: 2.17; P = 0.042) were all associated with death/transplantation. ConclusionsPPMv in patients with SV is associated with increased risk of heart transplantation and death, despite controlling for increased associated morbidity of the PPMv cohort. Increased Vp, higher QRS z-score, and nonapical ventricular lead position are all associated with higher risk of adverse outcome and may be modifiable risk factors.