Undergone Fontan Palliation Research Articles

Health related quality of life in children following Fontan surgery: A Malaysian perspective

BackgroundChildren with Fontan circulation suffer from morbidities and physical limitations that affect their quality of life. The study examined the health-related quality of life (HRQoL) of children in Malaysia following the Fontan procedure. MethodsAll patients who are 8 years and older and who had undergone Fontan palliation for at least 1 year were assessed using electronically distributed, aged-based Pediatric Quality of Life Inventory™ (PedsQL) Generic and Cardiac modules. The scores from the patients were compared with those of aged-match students in the Klang Valley and patient's parents. ResultsA total of 133 patients [time after Fontan: 6.24 years (IQR: 2.54, 8.54); SpO2: 92 % (IQR: 88, 95)] and parents and 130 normal subjects participated in the study. Fontan patients have reduced HRQOL scores compared to their healthy peers in almost all domains. Patients with NYHA class I demonstrated higher PedsQL scores in almost all domains. Patients with SpO2 < 95 % and taking more medication had lower PedsQL scores in total and physical score. Similarly, those with many complications show significantly low PedsQL scores in all domains. There was poor agreement between patients' and parents' perceived HRQoL in most of the domains in the generic module, but the difference was not as explicit in the cardiac module. ConclusionsFontan patients had a lower perceived quality of life compared to healthy controls. Physical ability and Fontan complications influenced the perceived quality of life, especially in younger children. Parents generally underestimate the impact of Fontan towards their children's quality of life.

Spleen shear wave elastography measurements do not correlate with histological grading of liver fibrosis in Fontan physiology: a preliminary investigation.

Elevated spleen stiffness may be seen in patients with portal hypertension due to cirrhosis. In patients with Fontan physiology, elevated liver stiffness has been shown to correlate poorly with liver fibrosis. It is unknown whether spleen stiffness may instead serve as a surrogate marker of liver fibrosis in these patients. To compare spleen stiffness determined by shear wave elastography (SWE) with histological findings of an ultrasound-guided liver biopsy in patients who had undergone Fontan palliation as a potential surrogate for Fontan-associated liver disease. This was an IRB-approved single-center, retrospective study. Patients with Fontan palliation who had undergone both a spleen SWE study and a percutaneous liver biopsy between 2016 and 2020 were included. Biopsy, performed during cardiac catheterization, within 3months of the SWE was required for inclusion. Using Kruskal-Wallis tests, spleen stiffness was compared with three liver biopsy scoring methods: Ishak, METAVIR, and congestive hepatic fibrosis score (CHFS). When available, Pearson's correlation was also used to compare collagen deposition determined using Sirius Red stain (%SR) with SWE values. A P-value < 0.05 was considered statistically significant. Twenty-two patients (15 males) were included in the study, with a median age of 17years (IQR is 14.8-20.5years; age range: 7years to 30.2years). The median spleen stiffness was 2.94m/s (IQR: 2.57-3.61m/s; range: 1.48-4.27m/s). The median Fontan pressure was 11mm Hg (IQR: 10-13.3mm Hg; range: 7-19mm Hg) obtained within a median of 10days (IQR: 1-41days) of SWE. Splenic stiffness did not correlate with the extent of fibrosis determined by histology (all P > 0.05). There was also no statistically significant correlation between the %SR staining and SWE-determined spleen stiffness (Pearson's correlation of 0.165, P = 0.59, n = 13). In this preliminary study, SWE spleen stiffness values did not correlate with biopsy-determined scoring of liver fibrosis in patients with Fontan physiology.

Additive value of invasive haemodynamic assessment for predicting post-operative outcomes after Fontan.

Routine pre-Fontan cardiac catheterization remains standard practice at most centres. However, with advances in non-invasive risk assessment, an invasive haemodynamic assessment may not be necessary for all patients.Using retrospective data from patients undergoing Fontan palliation at our institution, we developed a multivariable model to predict the likelihood of a composite adverse post-operative outcome including prolonged length of stay ≥ 30 days, hospital readmission within 6 months, and death and/or transplant within 6 months. Our baseline model included non-invasive risk factors obtained from clinical history and echocardiogram. We then incrementally incorporated invasive haemodynamic data to determine if these variables improved risk prediction.Our baseline model correctly predicted favourable versus adverse post-Fontan outcomes in 118/174 (68%) patients. Covariates associated with adverse outcomes included the presence of a systemic right ventricle (adjusted adds ratio [aOR] 2.9; 95% CI 1.4, 5.8; p = 0.004), earlier surgical era (aOR 3.1 for era 1 vs 2; 95% CI 1.5, 6.5; p = 0.002), and performance of concomitant surgical procedures at the time of Fontan surgery (aOR 2.5; 95% CI 1.1, 5.0; p = 0.026). Incremental addition of invasively acquired haemodynamic data did not improve model performance or percentage of outcomes predicted.Invasively acquired haemodynamic data does not add substantially to non-invasive risk stratification in the majority of patients. Pre-Fontan catheterization may still be beneficial for angiographic evaluation of anatomy, for therapeutic intervention, and in select patients with equivocal risk stratification.

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

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

Abstract 13272: Acute Effects of Enhanced External Counterpulsation in Adults With Fontan Circulation

Background: Patients who have undergone Fontan palliation for single ventricle CHD exhibit reduced cardiac output. Aims: To study the safety and acute hemodynamic effects of enhanced external counterpulsation (EECP) in a cohort of Fontan patients. Methods: Pilot study of adult Fontan patients recruited through the ambulatory clinic at a single, large-volume ACHD center. Patients underwent TTE and measurement of pulmonary blood flow (PBF), a surrogate for cardiac output, followed by 1 hour of EECP divided into 20-minute stages (80 mmHg, 160 mmHg, 240 mmHg). TTE and PBF measurement were repeated at each stage and 15-30 minutes after completion of EECP. Patients were monitored for symptoms throughout the visit. A repeated measures linear-mixed-model (robust to non-normality) was used to estimate the mean at each time point and to test for differences across time points. Results: There were 23 patients enrolled (52% male, 91% cis-gender, 74% White). Mean age at enrollment and at Fontan completion was 33.0 ± 7.8 years and 5.1 ± 4.1 years, respectively. Six patients (26%) had a pacemaker. Twenty-two (96%) completed a full hour of EECP. Pressure was reduced in the third stage for 3 patients due to discomfort. No patients reported chest pain or increased dyspnea during EECP. PBF was increased at each stage of EECP compared to baseline and returned to baseline post-EECP (Fig. 1). There was a small qualitative improvement in ventricular systolic function in the second and third stages of EECP compared to baseline (160 mmHg: p=0.048; 240 mmHg: p=0.024). O 2 saturation was increased at each stage of EECP compared to baseline (baseline: 93.0%, 80 mmHg: 94.3% [p=0.008], 160 mmHg: 94.6% [p=&lt;0.001], 240 mmHg: 94.6% [p=&lt;0.001]). Mean arterial pressure and heart rate did not change. Conclusions: EECP is well-tolerated in adult Fontan patients and acutely improves PBF at pressures as low as 80 mmHg. Further study is warranted to explore long-term therapeutic effects of EECP in these patients.

The Effect of Udenafil on Heart Rate and Blood Pressure in Adolescents With the Fontan Circulation

The Fontan Udenafil Exercise Longitudinal (FUEL) trial showed that treatment with udenafil was associated with improved exercise performance at the ventilatory anaerobic threshold in children with Fontan physiology. However, it is not known how the initiation of phosphodiesterase 5 inhibitor therapy affects heart rate and blood pressure in this population. These data may help inform patient selection and monitoring after the initiation of udenafil therapy. The purpose of this study is to evaluate the effects of udenafil on vital signs in the cohort of patients enrolled in the FUEL trial. This international, multicenter, randomized, double-blind, placebo-controlled trial of udenafil included adolescents with single ventricle congenital heart disease who had undergone Fontan palliation. Changes in vital signs (heart rate [HR], systolic [SBP] and diastolic blood pressure [DBP]) were compared both to subject baseline and between the treatment and the placebo groups. Additional exploratory analyses were performed to evaluate changes in vital signs for prespecified subpopulations believed to be most sensitive to udenafil initiation. Baseline characteristics were similar between the treatment and placebo cohorts (n=200 for each). The groups demonstrated a decrease in HR, SBP, and DBP 2 hours after drug/placebo administration, except SBP in the placebo group. There was an increase in SBP from baseline to after 6-min walk test in the treatment and placebo groups, and the treatment group showed an increase in HR (87.4 ± 15.0 to 93.1 ± 19.4 beats/min, p <0.01) after exercise. When comparing changes from baseline to the 26-week study visit, small decreases in both SBP (-1.9 ± 12.3 mm Hg, p=0.03) and DBP (-3.0 ± 9.6 mm Hg, p <0.01) were seen in the treatment group. There were no clinically significant differences between treatment and placebo group in change in HR or blood pressure in the youngest age quartile, lightest weight quartile, or those on afterload-reducing agents. In conclusion, initiation of treatment with udenafil in patients with Fontan circulation was not associated with clinically significant changes in vital signs, implying that for patients similar to those enrolled in the FUEL trial, udenafil can be started without the requirement for additional monitoring after initial administration.

Clinical course after Fontan palliation: Single center experience

BackgroundThe Fontan procedure has been the standard palliation for single-ventricle patients. We aimed to investigate the short- and midterm outcomes of patients who underwent Fontan palliation. ObjectivesTo assess and analyze the clinical course, including length of stay, complications, and mortality of single ventricle patients undergoing Fontan Palliation. MethodsRetrospective review of all patients who underwent Fontan palliation at the University of Minnesota, 2006–2020. The primary outcomes measured were length of stay, complications, and Fontan failure. ResultsOf the 55 patients the median age of Fontan was 3.9 yrs [2.63, 4.19] and the most common diagnoses were hypoplastic left heart syndrome (n = 20, 36 %), double inlet left ventricle (n = 11, 20 %) and double outlet right ventricle (n = 8, 15 %). Twenty-Seven were right ventricle dominant, 23 were left ventricle dominant, and 5 had biventricular morphology. The median hospital stay was 11 days [8, 17.5], an ICU stay of 6.5 days [4,9]. Fourteen late complications occurred in 10 patients. Three, all with HLHS, had Fontan failure leading to heart transplant. Four died: two prior to hospital discharge, one 6.7 yrs post-Fontan, and one 27 days after transplantation. Right ventricle morphology was associated with prolonged ICU (P 0.05), prolonged hospital stay (P < 0.01), and complications resulting in Fontan failure (P < 0.01). ConclusionThe survival following Fontan completion in the current era is excellent, with an overall and transplant-free survival at 5 and 10 years were at 96 % and 93 %. However, it is clear that univentricular physiology continues to present challenges, and patients remain at risk for morbidity, especially for patients with right ventricle morphology.

Association of post-operative ICU requirements with early extubation in the fontan procedure.

This study investigated the association between early extubation (EE) and the degree of postoperative intensive care unit (ICU) support after the Fontan procedure, specifically evaluating the volume of postoperative intravenous fluid (IVF) and vasoactive-inotropic score (VIS). Retrospective analysis of patients who underwent Fontan palliation from 2008 to 2018 at a single center was completed. Patients were initially divided into pre-institutional initiative towards EE (control) and post-initiative (modern) cohorts. Differences between the cohorts were assessed using t-test, Wilcoxon, or chi-Square. Following stratification by early or late extubation, four groups were compared via ANOVA or Kruskal-Wallis Test. There was a significant difference in the rate of EE between the control and modern cohorts (mean 42.6 versus 75.7%, p = 0.01). The modern cohort demonstrated lower median VIS (5 versus 8, p = 0.002), but higher total mean IVF (101±42 versus 82 ±27 cc/kg, p < 0.001) versus control cohort. Late extubated (LE) patients in the modern cohort had the highest VIS and IVF requirements. This group received 67% more IVF (140 ± 53 versus 84 ± 26 cc/kg, p < 0.001) and had a higher median VIS at 24 hours (10 (IQR, 5-10) versus 4 (IQR, 2-7), p < 0.001) versus all other groups. In comparison, all EE patients had a 5-point lower median VIS when compared to LE patients (3 versus 8, p= 0.001). EE following the Fontan procedure is associated with reduced post-operative VIS. LE patients in the modern cohort received more IVF, potentially identifying a high-risk subgroup of Fontan patients deserving of further investigation.

Echocardiographic Strain to Predict Need for Transplant or Mortality in Fontan Patients with Hypoplastic Left Heart Syndrome.

Despite recent advances, hypoplastic left heart syndrome (HLHS) patients subsequent to the Fontan still have significant morbidity and mortality. Some require heart transplant due to systemic ventricular dysfunction. Limited data exist on timing for transplant referral. This study aims to correlate systemic ventricular strain by echocardiography to transplant-free survival. HLHS patients who had Fontan palliation at our institution were included. Patients were divided into: 1) Required transplant or experienced mortality (composite end point); 2) Did not require transplant or survived. For those who experienced the composite endpoint, the last echocardiogram prior to the composite outcome was used, while for those who did not experience the composite endpoint the last echocardiogram obtained was used. Several qualitative and quantitative parameters were analyzed with focus on strain parameters. Ninety-five patients with HLHS Fontan palliation were identified. Sixty-six had adequate images and eight (12%) experienced transplant or mortality. These patients had greater myocardial performance index by flow Doppler (0.72 versus 0.53, p = 0.01), higher systolic/diastolic duration ratio (1.51 versus 1.13, p = 0.02), lower fractional area change (17.65 versus 33.99, p < 0.01), lower global longitudinal strain (GLS) (-8.63 versus -17.99, p < 0.01), lower global longitudinal strain rate (GLSR) (-0.51 versus -0.93, p < 0.01), lower global circumferential strain (GCS) (-6.68 versus -18.25, p < 0.01), and lower (GCSR) global circumferential strain rate (-0.45 versus -1.01, p < 0.01). ROC analysis demonstrated predictive value for GLS -7.6 (71% sensitive, 97% specific, AUC 81%), GLSR -0.58 (71% sensitive, 88% specific, AUC 82%), GCS -10.0 (86% sensitive, 91% specific, AUC 82%), and GCSR -0.85 (100% sensitive, 71% specific, AUC 90%). GLS and GCS can help predict transplant-free survival in patients with hypoplastic left heart syndrome having undergone Fontan palliation. Higher strain values (closer to zero) may be a helpful tool in determining when transplant evaluation is warranted in these patients.

Corazón univentricular sin cirugía de Fontan: el tipo de paliación importa

Introduction and objectivesThere is scarce information on patients with single ventricle physiology (SVP) and restricted pulmonary flow not undergoing Fontan circulation. This study aimed to compare survival and cardiovascular events in these patients according to the type of palliation. MethodsSVP patient data were obtained from the databases of the adult congenital heart disease units of 7 centers. Patients completing Fontan circulation or developing Eisenmenger syndrome were excluded. Three groups were created according to the source of pulmonary flow: G1 (restrictive pulmonary forward flow), G2 (cavopulmonary shunt), and G3 (aortopulmonary shunts±cavopulmonary shunt). The primary endpoint was death. ResultsWe identified 120 patients. Mean age at the first visit was 32.2 years. Mean follow-up was 7.1 years. Fifty-five patients (45.8%) were assigned to G1, 30 (25%) to G2, and 35 (29.2%) to G3. Patients in G3 had worse renal function, functional class, and ejection fraction at the first visit and a more marked ejection fraction decline during follow-up, especially when compared with G1. Twenty-four patients (20%) died, 38 (31.7%) were admitted for heart failure, and 21 (17.5%) had atrial flutter/fibrillation during follow-up. These events were more frequent in G3 and significant differences were found compared with G1 in terms of death (HR, 2.9; 95%CI, 1.14-7.37; P=.026) and atrial flutter/fibrillation (HR, 2.9; 95%CI, 1.11-7.68; P=.037). ConclusionsThe type of palliation in patients with SVP and restricted pulmonary flow not undergoing Fontan palliation identifies distinct profiles. Patients palliated with aortopulmonary shunts have an overall worse prognosis with higher morbidity and mortality.

Association of Body Mass Index With Clinical Features and Outcomes in Adults With Fontan Palliation.

Background With improving survival of patients with single ventricle physiology who underwent Fontan palliation, there is also an increase in the prevalence of overweight and obesity in these patients. This tertiary care single-center study aims to determine the association of body mass index (BMI) with the clinical characteristics and outcomes in adults with Fontan. Methods and Results Adult patients (aged ≥18 years) with Fontan who were managed at a single tertiary care center between January 1, 2000, and July 1, 2019, and had BMI data available were identified via retrospective review of medical records. Univariate and multivariable (after adjusting for age, sex, functional class, and type of Fontan) linear and logistic regression, as appropriate, were utilized to evaluate associations between BMI and diagnostic testing and clinical outcomes. A total of 163 adult patients with Fontan were included (mean age, 29.9±9.08 years), with a mean BMI of 24.2±5.21 kg/m2 (37.4% of patients had BMI ≥25 kg/m2). Echocardiography data were available for 95.7% of patients, exercise testing for 39.3% of patients, and catheterization for 53.7% of patients. Each SD increase in BMI was significantly associated with decreased peak oxygen consumption (P=0.010) on univariate analysis and with increased Fontan pressure (P=0.035) and pulmonary capillary wedge pressure (P=0.037) on multivariable analysis. In addition, BMI ≥25 kg/m2 was independently associated with heart failure hospitalization (adjusted odds ratio [AOR], 10.2; 95% CI, 2.79-37.1 [P<0.001]) and thromboembolic complications (AOR, 2.79; 95% CI, 1.11-6.97 [P=0.029]). Conclusions Elevated BMI is associated with poor hemodynamics and worse clinical outcomes in adult patients with Fontan. Whether elevated BMI is the cause or consequence of poor clinical outcomes needs to be further established.

Long-term outcomes of patients with single ventricle who do not undergo Fontan palliation

BackgroundPatients with single ventricle (SV) without Fontan palliation are uncommon, and their long-term outcomes remain unclear. MethodsRetrospective study of 35 adult patients with SV without Fontan from two tertiary centers. Primary outcome was mortality. ResultsMedian age at first follow-up was 31 years (IQR: 20–40). Most common defect was double inlet left ventricle (34%), and 69% had left ventricular morphology. Patients were unoperated (46%), had systemic-to-pulmonary artery shunt (31%) or bidirectional cavopulmonary shunt (23%) as final palliation. Most common reasons for not progressing to Fontan palliation were pulmonary vascular disease (54%), patient refusal (17%), Fontan takedown (14%), and hypoplastic pulmonary arteries (11%). Baseline mean hemoglobin was 195 ± 29 g/L, mean O2 saturation 83 ± 6.9%, and 4 patients in NYHA Class III‒IV. After a mean follow-up of 10 ± 8.3 years, there were 9 deaths with heart failure being the leading cause (n = 6). Age-adjusted survival of these adult SV survivors was 73% and 53% at 40 and 50 years of age, respectively. Deceased patients more frequently had renal impairment (50% vs 0%) and QRS prolongation (75% vs 16%) at baseline (all p < 0.05). During follow-up, 40% had a new arrhythmia (atrial: n = 14, ventricular: n = 3), 34% had one or more hospitalizations for heart failure, and 17% had a stroke. A greater proportion of patients with pre-existing or new atrial/ventricular arrhythmia died compared to those without (42% vs 6%, p = 0.02). ConclusionsPatients with SV without Fontan have high mortality and a substantial burden of cardiovascular complications, particularly arrhythmia. QRS prolongation and renal impairment were associated with mortality.

Univentricular hearts not undergoing Fontan: the type of palliation matters

Introduction and objectivesThere is scarce information on patients with single ventricle physiology (SVP) and restricted pulmonary flow not undergoing Fontan circulation. This study aimed to compare survival and cardiovascular events in these patients according to the type of palliation. MethodsSVP patient data were obtained from the databases of the adult congenital heart disease units of 7 centers. Patients completing Fontan circulation or developing Eisenmenger syndrome were excluded. Three groups were created according to the source of pulmonary flow: G1 (restrictive pulmonary forward flow), G2 (cavopulmonary shunt), and G3 (aortopulmonary shunts±cavopulmonary shunt). The primary endpoint was death. ResultsWe identified 120 patients. Mean age at the first visit was 32.2 years. Mean follow-up was 7.1 years. Fifty-five patients (45.8%) were assigned to G1, 30 (25%) to G2, and 35 (29.2%) to G3. Patients in G3 had worse renal function, functional class, and ejection fraction at the first visit and a more marked ejection fraction decline during follow-up, especially when compared with G1. Twenty-four patients (20%) died, 38 (31.7%) were admitted for heart failure, and 21 (17.5%) had atrial flutter/fibrillation during follow-up. These events were more frequent in G3 and significant differences were found compared with G1 in terms of death (HR, 2.9; 95%CI, 1.14-7.37; P=.026) and atrial flutter/fibrillation (HR, 2.9; 95%CI, 1.11-7.68; P=.037). ConclusionsThe type of palliation in patients with SVP and restricted pulmonary flow not undergoing Fontan palliation identifies distinct profiles. Patients palliated with aortopulmonary shunts have an overall worse prognosis with higher morbidity and mortality.

Combined heart-liver transplantation practices survey in North America: Evaluation and organ listing practices.

We conducted a web-based survey to characterize liver transplant (LT) evaluation and listing practices for patients being evaluated for combined heart-liver transplantation (CHLT), with a specific emphasis on patients with congenital heart disease (CHD), around transplant centers in North America. Very few protocols for liver evaluation and listing in patients undergoing combined heart-liver transplantation are published, and no guidelines currently exist on this topic. A subject of intense debate in the transplant community is the decision of which patients with CHD and liver disease benefit from CHLT compared with heart transplantation. A focus group from the American Society of Transplantation Liver-Intestine Community of Practice Education Subcommittee developed a web-based survey that included questions (1) respondee demographic information; (2) LT evaluation practices in CHLT; (3) liver organ listing practices in CHLT, and (4) 4 clinical vignettes with case-based scenarios in CHLT liver listings among CHD patients who underwent Fontan palliation. The survey was distributed to medical and surgical LT program directors of 47 centers that had completed at least 1 CHLT up to July 2021 in the US and the University of Toronto, Canada. The survey had an excellent 83% response rate (87% for centers that completed at least 1 CHLT in the past 5y). Total 66.7% used transjugular liver biopsy with HVPG measurements, 30% used percutaneous liver biopsy with no consensus on the use of a fibrosis staging system, 95% mandated contrasted cross-sectional imaging, and 65% upper endoscopy. The following isolated findings evaluation mandated CHLT listing: isolated elevated HVPG (61.5%); the presence of portosystemic collaterals on imaging (67.5%); the endoscopic presence of esophageal or gastric varices (75%), and the presence of HCC (80%), whereas the majority of centers did not feel that the presence of isolated splenomegaly (100%), thrombocytopenia (81.6%), endoscopic findings of portal hypertensive gastropathy (66.7%), or highly sensitized patients (84.6%) justified CHLT. In our survey of North American centers that had performed at least 1 CHLT in the past 5 years, we observed heterogeneity in practices for both evaluation and listing protocols in these patients.

Altered white matter connectivity in children with congenital heart disease with single ventricle physiology

Children born with congenital heart disease (CHD) have seen a dramatic decrease in mortality thanks to surgical innovations. However, there are numerous risk factors associated with CHD that can disrupt neurodevelopment. Recent studies have found that psychological deficits and structural brain abnormalities persist into adulthood. The goal of the current study was to investigate white matter connectivity in early school-age children (6–11 years), born with complex cyanotic CHD (single ventricle physiology), who have undergone Fontan palliation, compared to a group of heart-healthy, typically developing controls (TPC). Additionally, we investigated associations between white matter tract connectivity and measures on a comprehensive neuropsychological battery within each group. Our results suggest CHD patients exhibit widespread decreases in white matter connectivity, and the extent of these decreases is related to performance in several cognitive domains. Analysis of network topology showed that hub distribution was more extensive and bilateral in the TPC group. Our results are consistent with previous studies suggesting perinatal ischemia leads to white matter lesions and delayed maturation.

Abstract 14813: Insulin Resistances in Patients With Fontan Palliations

Introduction: Patients (pts) with single ventricles who have undergone Fontan palliation are surviving longer and at increased risk for acquired morbidly. Insulin resistance (IR) and abnormal glucose metabolism are known to be predictors of cardiac morbidity and mortality. Limited studies suggest that IR and metabolic syndrome occur in individuals following Fontan palliation. This study aimed to evaluate IR in Fontan pts. Methods: In this prospective, single-center, case-control study, Fontan pts and controls were recruited during clinic or catheterization visits between 6/2021 - 2/2022. Individuals with diabetes mellitus, pregnancy, steroid use, inotropic support, or surgery within the last 6 months were excluded. Control subjects were eligible if they had 2 ventricle circulation and did not have heart failure or systemic illness. Demographic and clinical data were collected via chart review. Fasting serum glucose and insulin were acquired at their visit. Group comparisons were made in IR via natural log-transformed homeostasis model assessment, ln(HOMA-IR), and QUICKI (1/[log(Insulin) + log(Glucose)]), without/with adjusting for age. Results: In total 89 pts (59 Fontan and 30 controls) were included, with median age of 20.2 yrs (interquartile range 15-28.1). Fontan pts showed significant elevation of ln(HOMA-IR) (0.82±0.62 vs 0.24±0.44) and decrease in QUICKI (0.34±0.03 vs 0.37±0.02) compared to controls (both p&lt;.0001); this remained significant even controlling for age (both p≤0.02). Analysis excluding Fontan pts with obesity still showed significant elevation of ln(HOMA-IR) and reduction of QUICKI in Fontan pts compared to controls when adjusting for age (both p&lt;0.05). With older age there was an increase in ln(HOMA-IR) (mean 0.2 in age &lt; 13 yrs vs. 0.53 in age 13-18 yrs vs. 0.78 in ag &gt; 18 yrs, p=0.01). Using a QUICKI &lt; 0.339 defining IR, there was an increase proportion of IR with older age (7% in age &lt; 13 yrs vs. 26% in age 13-18 yrs vs. 48% in age &gt; 18 yrs, p=0.01). Conclusions: Fontan pts had significant elevation in IR compared to controls using standard clinical IR serum testing that was independent of age. Additionally, IR continues to increase with age. Further evaluation is needed to understand risk for IR in pts undergoing Fontan palliation.

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.

Outcomes of Biventricular and Single Ventricle Heterotaxy Patients: A Single Center Five-Decade Experience

BackgroundSurgical palliation of patients with heterotaxy syndrome has proven challenging. Long-term outcomes have historically been poor. Factors contributing to these outcomes are not completely understood. MethodsThe institutional databases were queried for patients with heterotaxy syndrome from 1973 to 2021. Comparisons were made between patients managed with single ventricle physiology and biventricular physiology. ResultsHeterotaxy syndrome was identified in 230 patients (polysplenia, 47%; asplenia, 53%). In all, 199 patients had single ventricle physiology; 180 (78%) had undergone Fontan palliation. Thirty-one patients had biventricular physiology, including 20 (9%) with surgical intervention and 11 (5%) without surgical intervention. Median age at Fontan was 7.5 years (interquartile range, 8.8). Median follow-up was 20 years (interquartile range, 21). Kaplan-Meier analysis showed decreased survival with single ventricle physiology (53% ± 4%, vs biventricular 93% ± 5% at 30 years; P = .001), as well as asplenia compared with polysplenia (49% ± 5% vs 68% ± 5% at 30 years; P < .001). Polysplenia patients with biventricular physiology demonstrated the best survival (100% alive, vs 53% ± 25% of asplenia biventricular at 30 years; P < .001). Overall, 8 patients (3.5%) underwent cardiac transplantation at a median age of 17 years. On multivariable analysis, risk factors associated with mortality included single ventricle physiology (odds ratio [OR] 7.2; 95% CI, 2.4-21.7), no prior Glenn (OR 3.6; 95% CI, 1.9-6.7), need for permanent pacemaker (OR 2.3; 95% CI, 1.2-4.6), and asplenia (OR 2.7; 95% CI, 1.5-5.0). ConclusionsOverall, patients with asplenia demonstrated decreased survival compared with patients with polysplenia; and single ventricle physiology had decreased survival compared with biventricular. Patients with biventricular physiology and polysplenia had the best survival.

Fontan-associated liver disease.

Fontan-associated liver disease.

610 Fontan associated kidney and liver disease: can we predict organ involvement with echocardiographic assessment of systolic function and atrioventricular valve insufficiency?

Abstract Aims Fontan operation represents the surgical palliative option for congenital heart disease with single ventricle physiology. With the improvement of surgical and percutaneous technique, we are facing a growing population of patients with an unique pathophysiology and potential complications. Methods and results Patients that underwent Fontan palliation in our centre between 1993 and 2016 were included in this prospective study. We excluded patients with major congenital renal anomalies, those that underwent cardiac transplantation, and redo-Fontan patients. All the subjects underwent clinical evaluation, laboratory exams with complete renal and hepatic function, transient hepatic elastography, and complete cardiac evaluation. We used Schwartz equation for estimating glomerular filtration rate in patients younger than 18 years, and CDK-EPI equation for adult patients. We enrolled 35 patients, 46% female (N = 16), and 54% male (N = 19). Medium age was 17 years old, median age 15 years old (range: 10–31 years old). Medium time from Fontan completion was 160 months (range: 57–340 months). Regarding to cardiac anatomy, 10 patients had functional single left ventricle (FSLV, 28.5%) and 21 a functional single right ventricle (FSRV, 60%); 4 patients had undetermined single ventricle (11.5%). Total cavo-pulmonary connection (TCPC) with intracardiac lateral tunnel was performed in 7 patients (20%, N = 7), whereas 28 patients had TCPC with external conduit (80%). Data from echocardiographic evaluation showed a medium EF established with Simpson’s method of 60% in patients with FSLV; patients with a FSRV or undetermined single ventricle had a medium FAC of 41.1%, with 15.1% having a reduced FAC &amp;lt; 35%. No FSLV patients had an EF &amp;lt; 50%. When using creatinine-based formula, data about renal function in our population showed a stage 2 chronic kidney disease (eGFR: 60–89 ml/min 1.73 mq) in 11% of total population (N = 4), that became 26% when using cystatin C-based equation (N = 9), with one patient showing a moderate reduced loss of kidney function (eGFR: 40–59 ml/min 1.73 mq). Urinalysis showed 29% (N = 10) of patients having microalbuminuria (microalbumin/creatinine ratio between 30 and 300 mg/g). Statistical analysis demonstrated a negative correlation between systolic function (TAPSE for FSRV) and cystatin C blood levels (Pearson’s R −0.428, P = 0.053), and between systolic function (FAC and Simpson) and microalbuminuria (Pearson’s R −0.414 with P = 0.049 and Pearson’s R −0.754 with P = 0.019, respectively). Transient elastography reported 10 patients (29.4%) with abnormal hepatic stiffness for Fontan patients. That condition appeared to be more frequent in patients with higher grade of AV valve insufficiency (P &amp;lt; 0.05). Conclusions Our population showed an higher prevalence of FSRV Fontan patients, with an expected lower systolic function compared with FSLV. 2D evaluation of systolic function showed a linear inverse correlation with renal function, suggesting that Fontan patients need a closer renal monitoring. Hepatic stiffness, which is a warning sign of potential hepatic cirrhosis need to be monitored in all Fontan patients, especially those with a worse AV valve insufficiency.