Fontan Patients Research Articles

Paraganglioma and phaeochromocytoma in adult Fontan patients.

The purpose of this study was to address the gap in knowledge in the incidence, presentation and imaging features of PPGL in Fontan patients. It has been hypothesised in the literature that Fontan circulation patients have an increased incidence of these tumours. This study is the largest cohort of adult Fontan patients in North America. The Fontan procedure is a palliative procedure for single ventricle congenital heart disease where the systemic venous return is directed into the pulmonary circulation. Fontan patients are at increased risk of developing several extracardiac complications including phaeochromocytoma and paraganglioma (PPGL). This retrospective single-centre study includes all adult patients who were treated between 1 September 2015 and 1 September 2022 in a tertiary referral centre for adult congenital heart disease. Imaging and electronic medical records were retrospectively searched for the presence of PPGL. Five hundred and forty-seven Fontan patients were included in the study. Three patients had PPGL with an incidence of 0.5%. Two patients were diagnosed with paraganglioma and one with phaeochromocytoma. All patients were female. Median age of Fontan procedure was 1.8 years (range: 1.75-27 years). Median age of PPGL diagnosis was 19 years (range: 12-39 years). Median time from Fontan operation to diagnosis of PPGL was 12 years (range: 10.3-17.2 years). Fontan patients are at increased risk of PPGL. Clinically, the diagnosis of PPGL is challenging as symptoms and serum markers can be confounding in this population; however, the imaging features of PPGL remain typical making the role of the radiologist crucial.

Mountains and Waves: Fontan Circulation in Different Environmental Conditions.

As surgical options and medical care for patients with univentricular heart physiology continue to improve, leading to increased life expectancy and quality of life, a new population of Fontan patients is growing up with the desire to participate in leisure activities, including aquatic activities, high-altitude stays, and air travel. Due to significant data gaps and insufficient experience, current guidelines do not provide clear recommendations, leading to uncertainty and sometimes restrictive patient management. This review summarizes new insights and the current state of research on this subject and provides an overview of the long overdue change in policies toward less restrictive counseling for Fontan patients regarding swimming, diving, high-altitude stays, and air travel. The current review summarizes the physiologic impact of aquatic and high-altitude activities on the cardiovascular system and presents currently available data on this topic in Fontan patients. Patients with Fontan circulation in good clinical shape can tolerate activities in the water and in the mountains as well as air traveling without critical events. In order to be able to make general recommendations, further studies with larger numbers of cases must be carried out.

Abstract 4137186: No Room for Chronotropic Incompetence in Living Fontan Patients: Enhanced Heart Rate Increase in Response to Exercise to Compensate Low Stroke Volume Reserve

Background: Fontan patients reveal decreased peak exercise performance in combination with low peak heart rate (HR), which is frequently interpreted as chronological incompetence. This is counterproductive as HR increase has to be enhanced to compensate limited stroke volume increase in Fontan physiology. Methods: Cardiopulmonary exercise testing (CPET) data in asymptomatic Fontan patients and age-matched control subjects were retrospectively studied. Peak and submaximal CPET parameters were obtained by cycle ergometer. Chronotropic capacity was assessed by peak HR/peak [WR/kg] and submaximal slope of HR/[work rate (WR)/kg] (ΔHR/Δ[WR/kg]) for males and females, separately. Results: Table 1 presents CPET data of Fontan patients (51) and controls (65). Fontan patients showed significantly lower peak HR, peak WR, peak oxygen consumption (VO2)/kg, %predicted maximum VO2, and peak oxygen pulse (pOP)/kg than controls in both sexes whereas peak HR/peak [WR/kg] was significantly higher in Fontan patients, indicating higher HR at the maximum effort in Fontan patients than in controls. Fontan patients showed higher ΔHR/Δ[WR/kg], a marker for HR-dependency, and lower Δ[VO2/kg]/ΔHR, a surrogate of stroke volume, suggesting higher HR was compensating lower stroke volume during submaximal phase of exercise in Fontan patients. Figure 1 demonstrates a linear relationship between ΔHR/ΔWR and peak HR/peak WR in both sexes. Male Fontan patients revealed a comparable trend with controls, whereas female Fontan patients showed higher HR increase at the peak exercise effort than controls with the same ΔHR/ΔWR, suggesting more limited stroke volume reserve than male Fontan patients. Conclusions: Fontan patients showed higher HR-response to exercise than controls in both sexes due to limitation in stroke volume increase. Our data indicate that lower peak HR in Fontan patients results from early exhaustion due to limited stroke volume reserve rather than primary chronotropic incompetence.

Abstract 4138238: A Tense Race: Correlation of Liver Stiffness with Ultrasound Elastography and Hemodynamics in Fontan Patients.

Background: Ultrasound elastography (USE) is a non-invasive tool to diagnose and monitor liver fibrosis. Patients with Fontan physiology are predisposed to congestive hepatopathy, progressive liver fibrosis, and end-stage liver disease. We sought to determine whether hemodynamics pre- and post-Fontan are associated with increased liver stiffness on USE. Methods: A single-center retrospective study included Fontan patients who had one or more USE between 06/2008-03/2024. Liver stiffness was reported as shear wave elastography (SWE) in m/s. Hemodynamic data pre- and post-Fontan and recent echocardiographic data were collected. Data was analyzed as continuous (linear regression model) and as a dichotomous variable (t-test). Results: A total of 78 post-Fontan USE results in 56 patients were analyzed. Table 1 describes the demographics of our patient population. The spectrum of fibrosis based on USE was normal (3.8%), mild (10.3%), moderate (55.1%) and severe (30.8%). In patients with more than one USE, the average increase in SWE was 0.04m/s per month. Pre-Fontan median Glenn pressure was 12mmHg [IQR 13, 15] (p=0.83). On post-Fontan catheterization, median Fontan pressure was 18mmHg [16, 21] (p=0.86). We did not find a significant correlation between hemodynamics and severity of liver stiffness on USE (Tables 2&3). No correlation was seen between USE and severity of ventricular function or atrioventricular valve regurgitation. SWE as a function of time from Fontan operation (<5 yr, 5-10 yrs, >10 yrs) did not vary significantly. Conclusions: USE as a marker of liver congestion does not correlate with hemodynamics pre- or post-Fontan. Further studies are necessary to determine the clinical utility of USE in Fontan patients.

Abstract 4125294: Fontan-Related Lymphatic Complications are Associated with Extracardiac Outcomes and Morbidity

Background: Patients born with single ventricle anatomy palliated with the Fontan procedure are at risk of lymphatic complications (LC), including plastic bronchitis, protein losing enteropathy, ascites, and hypoalbuminemia. The mechanism of LC, associated risk factors, and impact on outcomes are not well understood. Aim: We aimed to describe the prevalence of Fontan-related LC, expand on their association with previously reported risk factors, and explore the impact on mortality and transplantation. Methods: We performed a single-center, retrospective, cross-sectional cohort study of patients with Fontan circulation seen between 2009-2022, including those with cardiac catheterization and echocardiography within six months. Univariate comparisons were completed comparing those with and without LC. Results: A total of 144 Fontan patients were included with mean age of 23.6±11.9 years, with average of 18.8±10.5 years after their Fontan. Of those, 68 patients (48.6%) had at least one LC. There was no difference in demographic or anthropometric data in those with versus without LC, however patients with LC had their Fontan at an older age (5.6 vs 3.8 years, p =0.001). The presence of LC was associated with higher likelihood of thromboembolism (25% vs 7.9%, p =0.005), arrhythmia (45.6% vs 21.1%, p =0.002), lower estimated glomerular filtration rate (102.0±25.5 vs 111.6±17.9, p =0.02) and higher Fontan mean pressures noted on catheterization (14.8±3.8 vs 12.1±3.8 mmHg, p <0.001). Notably, LC were not related to the presence of moderate to severe ventricular dysfunction or moderate to severe atrioventricular valve regurgitation. Fontan patients with LC had higher rates of transplantation (25.4% vs 4%, p <0.001) and mortality (18% vs 4%, p =0.006). Conclusions: Fontan-related LC are associated with extra-cardiac morbidities and greater transplant and mortality rates. Our study suggests that LC are associated with venous congestion and not necessarily dependent on cardiac function.

Abstract 4145857: The effect of homebase exercise training on single ventricle heart (SVH) function, exercise performance, body composition and quality of Life in children and adolescents living with a Fontan circulation

Objectives: Fontan patients have impaired exercise capacity. Exercise training has been shown to improve exercise performance. We aim to determine the effect of exercise training on SVH function, and its correlation with exercise capacity, body composition and self-reported QOL. Methods: 31 paediatric Fontan patients were prospectively recruited to complete 3x30 minute homebased HIIT sessions per week for 20 weeks. Baseline physical activity levels, including structured sports participation, daily step-counts and active-zone-minutes (AZM) were recorded by accelerometer (Fitbit inspire3). Patients were considered active if they met 2 of the 3 criteria: 1/Structured sports training ≥ 2 per week (moderate-vigorous intensity >30 minutes) 2/Daily steps ≥ 10k 3/AZM ≥60 minutes per day Bio-impedance-analysis, cardiopulmonary exercise tests, echocardiography including deformation imaging and PedQL questionnaires were performed at baseline and upon completion. Results: 28 participants completed the programme. 86% had good compliance (completed >45/60 sessions). 17 male (60.7%), mean age 14.3±2.03 years, 14 LV-dominant, 14 non-LV dominant (9RV, 5BiV). No serious adverse events reported. The exercise duration improved from 7.56±2.6 to 9.16±2.5 minutes, p<0.001 and peak workload from 110±43.6 to 129±45.8 watts, p<0.001. Indexed oxygen consumption (VO 2 /kg peak) improved from 30.9±7.1 to 32.2±7ml/min/kg, p=0.003 and oxygen pulse, O 2 pulse peak from 9.1±2.6 to 9.7±3 mL/beat, p<0.001. Submaximal analysis showed normal %predicted VO2 (>40%) and improvement of O 2 pulse, p=0.024. LV systolic function showed improved MAPSE from 1.65±0.2 to 1.86±0.2, p=0.017, and improved apical rotation from 2.3±3.8 to 5.9±3.1, p=0.043. RV systolic function showed improved TAPSE of 1.4±0.2 to 1.6±0.3, p=0.032 and FAC of 44±5.6% to 49±10.5%, p=0.170. Self-reported QOL scores were higher in Fontan children who were physically active at baseline, with a downward trend noted when poor compliance was evident (Child’s QOL V3.0 91.21±0.7 to 86.1±5.2, p=0.018 (Table 2). Although no significant change in body composition, a higher appendicular skeletal muscle mass, SMMa% and lower body fat% were noted pre and post exercise training in the active Fontan group (Table 3), Conclusions: We observed significant improvements in both the submaximal and peak exercise performance in paediatric Exercise training associated with improvement of single ventricle longitudinal systolic function and ventricular mechanics.

Abstract 4124293: Exercise Capacity in Patients with Fontan Physiology

Introduction/Background: In the absence of a sub-pulmonary ventricle in the Fontan circulation, augmentation of pulmonary blood flow and filling of the systemic ventricle during exercise are limited. Cardiopulmonary exercise testing (CPET) is a reliable method for evaluation of aerobic capacity, gas exchange, and other physiologic parameters used for risk stratification in this population. Despite the ubiquitous use of CPET, reference ranges for patients with Fontan physiology are limited. The purpose of this study is to describe exercise characteristics and their relationship with different characteristics of Fontan physiology, imaging, and hemodynamics. Methods/Approach: In this retrospective cohort study, CPET results were reviewed for adult Fontan patients at the University of Washington between May 2021 and February 2024. Demographics, comorbidities, medications, type of Fontan conduit, imaging characteristics, hemodynamics, and exercise characteristics were included. Results were compared to a large previously published cohort of Fontan patients. Univariate linear regression was used to identify associations between demographics, cardiac anatomy, and exercise parameters. A p-value of less than 0.05 was considered statistically significant. Results/Data: Baseline demographics were notable for an older patient population (31±7 years) with lower indexed peak VO 2 (20.5±5.6 mL/kg/min) and greater V E /VCO 2 slope (37±7) compared to the historic cohort. Indexed peak VO2 was associated with age, BMI, type of Fontan conduit, FEV1, FVC, resting oxygen saturation, peak systolic blood pressure, and peak heart rate. Indexed peak VO 2 was notably not significantly associated with sex, systemic ventricular morphology, ventricular systolic function, Fontan pressure, or the presence of conventional heart failure medical therapy. Conclusions: In the growing population of older patients with Fontan physiology, development of age-specific population normative data may increase the clinical utility of CPET. Further investigation of the relationship between imaging characteristics, hemodynamics, and exercise parameters is needed in the Fontan population.

Abstract 4134460: Application of Principal Component Analysis to Heterogenous Fontan Registry Data to Identify Independent Contributing Factors to Decline

Introduction: Single ventricle heart disease is a severe and life-threatening illness, and improvements in clinical outcomes of those with Fontan circulation have not yet yielded acceptable survival over the past two decades. Patients are at risk of developing a diverse variety of Fontan-associated comorbidities that may ultimately require heart transplant. Goal: Our study goal was to determine if principal component analysis (PCA), which determines unique directions of data variance, applied to data collected from a pediatric Fontan cohort can predict functional decline (N=140). Methods: Heterogeneous data broadly consisting of measures of cardiac and vascular function, exercise (VO 2max ), lymphatic biomarkers, and blood biomarkers were collected over 9 years at a single site as part of a prospectively applied clinical care pathway; in that time, 16 events occurred that are considered here in a composite adverse outcome measure. After standardization and PCA, principal components (PCs) representing >5% of total variance were thematically labeled based on their constituents and tested for association with the composite outcome. Results: Our main findings suggest that the 6 th PC (PC6), representing 7.1% percent of the total variance in the set, is greatly influenced by albumin, alkaline phosphatase, total protein, BUN and BNP max and is a superior measure of proportional hazard compared to EF; it displayed the greatest accuracy for classifying Fontan patients as determined by AUC. In bivariate hazard analysis, we found that models combining systolic function (EF or PC5) and blood biomarkers (PC6) were most predictive, with the former having the greatest AIC, and the latter having the highest c-statistic. Conclusion: Our findings support the hypothesis that a broad, prospectively collected, multiorgan system model analyzed by way of unsupervised machine learning methods will improve prognosis of adverse outcomes in a Fontan cohort.

Abstract 4144560: Phase 2 Open-label, Single-arm, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Camostat Mesylate in Patients with Protein-losing Enteropathy after Fontan Operation-Preliminary Outcome

Introduction: Protein-losing enteropathy (PLE) is a multifaceted condition that profoundly affects the systemic health and quality of life of Fontan patients. Despite medical progress, the treatment of PLE remains a significant challenge. This study investigates the efficacy and safety of Camostat Mesylate for managing PLE patients who have undergone the Fontan operation. Hypothesis: We hypothesize that Camostat Mesylate will enhance the gut environment, resulting in increase of serum albumin levels and decrease of stool alpha-1 antitrypsin levels in PLE patients following Fontan operation. Methods: This phase 2, multicenter, open-label, single-arm trial included patients over 4 years old diagnosed with PLE following Fontan operation. Camostat Mesylate was added to conventional treatments, with follow-up assessments at 1, 3, and 6 months, and a final evaluation one month after discontinuation. Efficacy was measured by changes in serum albumin, stool alpha-1 antitrypsin levels, and PLE symptoms such as diarrhea, edema, weight changes, and ascites. Results: Nineteen patients were enrolled in the study, of whom fifteen patients completed follow-up as per protocol. The median age was 15 years (interquartile range, 12.0-21.3). The median time between the Fontan operation and PLE diagnosis was 2.4 years. Serum albumin levels increased from 2.5 to 2.6 g/dL (p=0.504), and stool alpha-1 antitrypsin levels decreased significantly from 280.0 to 172.1 mg/dL (p=0.033). Notably, patients with diarrhea at baseline showed substantial improvement in both parameters, with increased serum albumin levels from 1.8 to 2.2 g/dL and decreased stool alpha-1 antitrypsin levels from 220.3 to 80.2 mg/dL. No serious adverse events were reported during study period. Conclusions: Camostat Mesylate demonstrated safety and efficacy, reducing stool alpha-1 antitrypsin in PLE patients after Fontan operation, especially those with diarrhea at baseline. Therefore, Camostat Mesylate could be considered as an additional treatment option for patients with PLE following Fontan operation. Key words: Camostat mesylate; protein-losing enteropathy; Fontan operation Source of Funding: This research was funded by SNUH Lee Kun-hee Child Cancer&Rare Disease Project, Republic of Korea.

Magnetic resonance elastography is useful to determine the severity of liver fibrosis according to liver biopsy in post-fontan patients.

The reliability of various modalities for assessing and monitoring Fontan-associated liver disease compared to liver biopsy remains an intriguing subject of inquiry. Our objective was to assess the efficacy of multiple modalities in comparison to liver histology for evaluating liver fibrosis in post-Fontan patients. We conducted a cross-sectional study involving Fontan patients without known liver disease. Eligible patients underwent cardiac and hepatic evaluations, including ultrasound liver elastography, magnetic resonance elastography (MRE) of the liver, computerized tomography (CT) scan of the upper abdomen, echocardiography, cardiac catheterization, and liver biopsy. The severity of liver fibrosis was categorized using the METAVIR score derived from liver biopsy results: F0/F1 indicated no or mild fibrosis, F2 indicated significant fibrosis, F3 indicated advanced fibrosis and F4 indicated cirrhosis. A total of 38 patients (mean age 21 ± 6.5 years, 52.6% female) were included in the cross-sectional study, with a mean time elapsed since the Fontan operation of 13 years. Parameters obtained from echocardiography, ultrasound liver elastography, and CT scan of the upper abdomen did not exhibit significant differences among the groups. Notably, liver biopsy revealed advanced cirrhosis in 23 out of 38 patients and none were diagnosed with hepatocellular carcinoma. Multivariate logistic regression analysis demonstrated that the factor significantly associated with significant liver fibrosis or cirrhosis in post-Fontan patients was liver stiffness with MRE > 4.4kPa [OR 13.5 (95% CI 1.2-152.2)]. Our findings suggest that post-Fontan patients with liver stiffness of MRE > 4.4kPa should undergo further investigation. These results contribute to understanding the liver fibrosis assessment in post-Fontan patients and highlight the importance of MRE in predicting significant liver disease.

Cardiac Rehabilitation for Fontan Circulation Patients: A Systematic Review, and Meta-Analysis

Background and Objectives: Despite advances in the surgical management of patients with Fontan circulation, their exercise capacity and quality of life remain significantly impaired. Exercise-based cardiac rehabilitation (CR) offers promising improvements in these areas, but the implementation and adherence to these programmes are often inconsistent. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Materials and Methods: A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted on 24 August 2023. Studies were screened and assessed for quality using the Cochrane RoB Tool 2 and STROBE checklist. Meta-analysis was performed using a continuous random-effects model to determine the effectiveness of various CR interventions, including aerobic exercise training (AET), resistance training, and inspiratory muscle training (IMT). Results: A total of 26 studies (7 RCTs, 19 cohorts) comprising 22 distinct cohorts were included, with a total sample size of 428 Fontan patients. The interventions ranged from 4 weeks to 24 months and included AET (18 studies), resistance training (11 studies), and IMT (6 studies). The meta-analysis revealed significant improvements in exercise capacity, with a pooled mean difference in peak VO2 of 1.947 (95% CI: 1.491 to 2.402, p < 0.001). Subgroup analyses showed that combined AET and resistance training had the most robust effect, with a mean difference of 2.11 (95% CI: 1.57 to 2.65, p < 0.001). Home-based interventions showed significant benefits, while supervised and hybrid interventions did not show statistically significant differences. Publication bias was identified, particularly in home-based interventions, where smaller studies demonstrated larger effect sizes, as confirmed by Egger’s test (Intercept = 2.417, 95% CI: 1.498 to 3.337, p = 0.001). However, no significant bias was detected in supervised or hybrid interventions, which displayed symmetrical distributions in funnel plots and non-significant Egger’s test results. Conclusions: CR appears to be an effective intervention for improving exercise capacity in Fontan patients, particularly when combining AET with resistance training. Home-based programmes offer promising results, though the potential for publication bias, especially in smaller studies, warrants cautious interpretation of these findings. Further research is needed to refine protocols, explore long-term outcomes, and determine the underlying mechanisms, particularly for patients with more severe clinical presentations. The low incidence of adverse events across the studies reinforces the safety of these interventions.

Effects of systemic ventricular assist in failing Fontan patients: a theoretical analysis using a computational model

Mechanical circulatory support is a potential treatment for failing Fontan patients. In this study, we performed a theoretical analysis using a computational model to clarify the effects of systemic ventricular assist device (VAD) in failing Fontan patients. Cardiac chambers and vascular systems were described using the time-varying elastance model and modified Windkessel model, respectively. A VAD was simulated as a nonlinear function. In systolic and diastolic ventricular dysfunction and atrioventricular valve regurgitation models, systemic VAD increased the cardiac index and decreased the central venous pressure (CVP). However, in the high pulmonary vascular resistance model, CVP became extremely high above 15 mmHg to maintain the cardiac index when the pulmonary vascular resistance index (PVRI) was above 5 Wood units m2. In Fontan patients with ventricular dysfunction or atrioventricular valve regurgitation, systemic VAD efficiently improves the hemodynamics. In Fontan patients with PVRI of > 5 Wood units m2, systemic VAD seems ineffective.

Active Machine Learning for Pre-procedural Prediction of Time-Varying Boundary Condition After Fontan Procedure Using Generative Adversarial Networks.

The Fontan procedure is the definitive palliation for pediatric patients born with single ventricles. Surgical planning for the Fontan procedure has emerged as a promising vehicle toward optimizing outcomes, where pre-operative measurements are used prospectively as post-operative boundary conditions for simulation. Nevertheless, actual post-operative measurements can be very different from pre-operative states, which raises questions for the accuracy of surgical planning. The goal of this study is to apply machine leaning techniques to describing pre-operative and post-operative vena caval flow conditions in Fontan patients in order to develop predictions of post-operative boundary conditions to be used in surgical planning. Based on a virtual cohort synthesized by lumped-parameter models, we proposed a novel diversity-aware generative adversarial active learning framework to successfully train predictive deep neural networks on very limited amount of cases that are generally faced by cardiovascular studies. Results of 14 groups of experiments uniquely combining different data query strategies, metrics, and data augmentation options with generative adversarial networks demonstrated that the highest overall prediction accuracy and coefficient of determination were exhibited by the proposed method. This framework serves as a first step toward deep learning for cardiovascular flow prediction/regression with reduced labeling requirements and augmented learning space.

Predictive Role of Atrial Strain, Aortic Stiffness, and Muscle-Related Factors for Maximal and Submaximal Exercise Capacity in Fontan Patients.

Fontan patients' exercise capacity and associated risks of morbidity and mortality necessitate a comprehensive study. We aim to explore maximal and submaximal exercise capacity, assessing the impact of cardiovascular and peripheral factors, including atrial strain, aortic stiffness, and muscle-related factors. Fontan patients and matched controls were examined. Clinical details were recorded, and atrial strain and aortic stiffness were measured using echocardiography. Hand grip and knee extensor strength were assessed, and muscle oxygenation was recorded. Cardiopulmonary exercise test determined exercise capacity, with peak oxygen uptake/kg (VO2/kg) and oxygen uptake efficiency slope/kg (OUES/kg) as markers for maximal and submaximal capacity, respectively. Thirty-one Fontan patients (median age = 18, range = 7-31years) and 30 controls (median age = 18, range = 7-32years) were studied. No significant differences in body composition and muscle strength were observed between Fontan patients and controls (p > 0.05). Fontan patients exhibited lower peak VO2/kg and OUES/kg (p < 0.001 for both), along with decreased atrial strain and increased aortic stiffness compared to controls (p < 0.001). Aortic pulse wave velocity (PWV), left atrial strain contractile phase (LASct), and knee extensor strength independently predicted peak VO2/kg (R2 = 0.514) and OUES/kg (R2 = 0.486) in Fontan patients; age was a predictor for peak VO2/kg. Atrial contractile strain, aortic stiffness, and knee extensor muscle strength are predictors of submaximal exercise capacity; furthermore, age, along with these variables, serves as predictors of maximal exercise capacity in Fontan patients. Evaluating hemodynamic, vascular, and muscular parameters, in conjunction with assessing both maximal and submaximal exercise capacities, is crucial for optimizing disease management in Fontan patients. Clinicaltrials.gov registration: NCT05011565.

Effect of Fontan circulation on body composition and correlation with exercise capacity

Abstract Background There is growing attention to body composition in Fontan patients (FP) and preliminary results suggest that FP have an increased fat mass and a decreased muscle mass compared to the healthy population. FP also have reduced exercise capacity compared to health peers. However, data are still limited. Purpose The aim of our study was to compare the body composition (BC) of adult patients with Fontan circulation and healthy controls and to assess the correlation with functional capacity. Material and Methods Case control study on adult patients with Fontan circulation (FP) and age and gender matched healthy controls (HC). The following characteristics were recorded: age, gender, morphology of the systemic ventricle, type of Fontan circulation, level of physical activity (PAR, 0-7 points, 0 = sedentary - 7 = running &amp;gt; 3hours/week). S-score muscle, T-score bone, fat mass (FM%), intra-muscular adipose tissue (IMAT), abdominal adipose tissue (AAT), intracellular water (ICW), extracellular water (ECW), total body water (TBW), were measured through multi-frequency bioelectrical impedance technology in the FP and in the HC. Correlation was made for FP between body composition and oxygen consumption at peak exercise (VO2 peak), VE/VCO2 slope and NYHA class as indicator of functional capacity. Results Thirty Fontan patients (FP, mean age 24±6 yrs, 70% males) and 30 matched healthy controls (HC) were recruited in the study. The systemic ventricle was dominant left in 14 patients (47%), dominant right in 16 (53%). Four patients had atrio-pulmonary connection, the remaining were palliated with a lateral tunnel (n=26, 87%). The analysed parameters are summarised in Table 1. PAR was reduced in FP compared to HC (median 4.0 points in FP versus 7.0 points in HC, p 0.024). There was no difference in the BMI, fat mass, and body water between FP and HC. However, FP showed significantly lower S and T scores compared to the HC (S-score: -0,75 in FP versus 0,0 in HC, p 0.003. T-score: -0.9 in FP versus -0.25 in HC, p 0.001). In FP, NYHA Class was I in 28 patients (93%), II in 1 (3,5%) and III in 1 (3.5%) patient. The mean VO2 was 23.4±5.4mlO2/kg/min and mean VE/VCO2 slope 32±7. There was a direct correlation between VO2 peak and the PAR (rho 0.443, p 0.044). No correlation was found between the VO2 peak, the VE/VCO2 slope or the NYHA Class and the analysed parameters of body composition. Conclusion FP have reduced muscle mass, and bone density compared to HC. In addition to the known reduced efficiency of the cardiac pump during exercise in FP, the lower level of conditioning contributes to the reduced exercise capacity in this population. Programs aiming to encourage physical activity are key and should be part of patients’ care.

Outcomes and management of Haemoptysis in the Fontan population

Abstract Background Patients with a Fontan circulation for palliation of a univentricular congenital heart defect commonly possess pulmonary vascular abnormalities including arteriovenous malformations (AVM), aortopulmonary and venous-venous collaterals (1). These vessels are prone to haemorrhage which may result in life-threatening haemoptysis (2). This risk is increased with oral anticoagulant medication, given to reduce the risk of thromboembolism in Fontan patients (3). Management of these patients is difficult, and strategies vary across institutions. Purpose We aim to describe our experience with managing adult Fontan patients presenting with haemoptysis in a tertiary centre with a large Fontan cohort. Methods We retrospectively reviewed the records of 410 adult Fontan patients. Individuals admitted to our institution with an episode of haemoptysis were included. Details relating to anticoagulation regimens, interventions and mortality of patients were captured. Results From a cohort of 410 Fontan patients, 35 haemorrhagic events were observed in 11 patients (2.68%). The median age at initial haemoptysis was 24.5 years (range 19 to 43 years). 6 of the 11 patients were female (54.5%). Haemoptysis recurred in 8 of the 11 patients (72.7%). 2 out of 11 had a prior history of haemoptysis in childhood. All patients were administered with oral vitamin K antagonists at presentation. 24 of the 35 events were managed conservatively with IV fluids, anticoagulation reversal and tranexamic acid (66.7%). 11 events required catheter-based interventions, with coil and/or plug embolization of bleeding vessels. Prior to intervention, CT successfully identified potential bleeding sites in 10 of the 11 events (90.9%) but could not visualise all vessels that were subsequently embolized. The most common culprits for haemoptysis were aortopulmonary collaterals, followed by AVMs and venous-venous collaterals. In severe cases, more extensive management was required including transfusions, bronchoscopy, intubation, surgical exploration (1 patient) and pneumonectomy (1 patient). 3 patients died following recurrent severe haemoptysis (27.3%), and 2 patients died of subsequent Fontan failure and sudden cardiac death respectively. Total mortality of the cohort is 5 out of 11 (45.5%) with a median follow up of 10.75 years (range 3 days to 27 years). Conclusions Haemoptysis is a rare but potentially fatal complication in patients who have undergone a Fontan procedure. The variability in presentation of this condition mandates an individualised approach to management with involvement of a multidisciplinary team. There is a high rate of recurrence following haemoptysis and a comprehensive assessment of all potential bleeding sites is necessary. CT is a useful tool to help facilitate this and guide further management. Our policy is to close all potential sources of bleeding as CT and invasive angiography rarely identifies an active point of bleeding.

In vivo study of pulmonary artery remodeling and pulsatility in long Fontan patient

Abstract Background Pulmonary vasculopathy associated with Fontan circulation is a relatively unexplored entity that could have clinical and therapeutic implications. Purpose Our aim was to evaluate the physiology of the pulmonary artery in patients with Fontan circulation using conventional right heart catheterization (RHC) and intravascular ultrasound (IVUS). Methods From December 2022 to January 2024, data from all consecutive Fontan patients undergoing RHC were prospectively collected at a tertiary referral center for adult congenital heart disease. Pressures and pulmonary artery wall high-definition IVUS recordings (OptiCrossTM, 60 MHz, Boston Scientific) were recorded at rest and during apnea. Pathological Fontan pressure was defined when as exceeding 15 mmHg. IVUS pulsatility index was defined as [(systolic lumen area - diastolic lumen area)/(diastolic lumen area) ×100], Peterson's elastic modulus as (pulmonary pulse pressure/IVUS pulsatility index), and area of wall thickness as [(wall area - lumen area)/(lumen area) x100)]. In the literature, the mean ± standard deviation (SD) normal values of elastic modulus and wall thickness area have been reported as 21 ± 1.7 mmHg and 1.4 ± 1.3%, respectively, in healthy patients without pulmonary hypertension (1: doi: 10.1186/s12931-017-0568-z). We define an alteration in intrinsic pulmonary arterial wall viscoelastic properties as an elastic modulus &amp;gt; 70 mmHg, and we define structural pulmonary wall remodeling as an increase in wall thickness area greater than 5%. Results 13 patients were studied. Median age was 28.1 years interquartile range (IQR) (25.6- 41.4), 7 (53.9%) were female, and 4 (30,8%) were in functional New York Heart Associtation (NYHA) class I. RHC and pulmonary arterial wall IVUS values are presented in Figure 1. 6 (46.2%) had Fontan abnormal pressures at rest. All patients showed minimal pulse pressure in the pulmonary arteries synchronized with heart rate, median pulmonary pulse pressure (IQR) 3 (2-4) mmHg. This pulsatility was detected in the IVUS study in all patients, pulsatility index (median (IQR) 4.8 (3.3-10.1)) and elastic modulus (median (IQR) 51.5 (20.5-101.6) mmHg). All of them had some degree of structural pulmonary wall remodeling (&amp;gt;5% wall thickness area), and 10 (76.9%) of them had marked remodeling (&amp;gt; 10%). The median (IQR) of wall thickness area was 13.6 (10.5-18.3) % (Figure 2). We think that the pseudo-normality of the elastic modulus is due to a low pulmonary pulse pressure, however, structural remodeling could be secondary to the endothelial dysfunction present and described in arteries with very low pulsatility. Conclusions The IVUS evaluation of the pulmonary artery in Fontan patients may be useful for revealing significant information regarding pulmonary physiology. Pulmonary wall thickening has been observed, providing insight into altered structural remodeling of the pulmonary arteries in this population.

Optimising liver screening in patients with a Fontan circulation: a cost-effective approach to detection of Fontan associated liver disease which enhances patient care

Abstract Introduction Patients with Fontan circulation, require screening for liver cirrhosis and malignancy, to which they are susceptible with time. Surveillance biopsies reveal nearly all adult Fontan patients develop asymptomatic fibrosis, and a majority have abnormal liver function tests (LFTs). This presents significant financial healthcare burden and psychological stress with testing for patients. Objective We aim to present "real-world" liver screening data, from a leading Adult Congenital Heart Disease (ACHD) centre, to propose a cost-reducing testing regimen, which delivers effective screening, while taking account of the challenges of current guidance, patient compliance, and clinical practice. Methods We analysed liver screening data for Fontan patients at a leading ACHD centre, focusing on biochemical tests (bilirubin, ALT, GGT) and imaging. We evaluated the 10-year financial impact of current practices, versus a hypothetical model based on age and risk factors, alongside biannual and annual screening strategies. Tariffs for biochemical test were provided by the local pathology service and we used NHS HRG tariffs for imaging and phlebotomy. Results We included data from 114 patients with a Fontan circulation (median age 32 range 19-56, 42% females). Eighteen patients developed liver cirrhosis diagnosed on imaging (median age 32, range 22-48). None developed hepatocellular carcinoma. A lack of clear and agreed local screening guidelines (over years) resulted in vastly different investigations for FALD, with inconsistent time intervals for testing. Bilirubin was elevated in 59% (55% in age 18-29), ALT was elevated in 41% (31% in age 18-29), GGT was elevated in 83% (80% in age 18-29). We found 3 cases of cirrhosis in the age group 18-29, all with hypoplastic left heart; 4 cases of cirrhosis in age group 30-34 - all had significant comorbidities; 33% had normal bilirubin, LFT and GGT, potentially not requiring further screening until the age of 35. Eleven patients (22%) age 35+ had confirmed cirrhosis (Figure 1). Performing full FALD screening with biochemistry and liver ultrasound every 12-24 months would increase the cost of screening three- to six-fold. We propose rationalising liver screening by age and underlying risk (Figure 2) to minimise the economic burden and equally the psychological impact of frequent testing on patients. Conclusions Our analysis underscores the necessity for an optimised liver screening protocol in Fontan patients, balancing diagnostic accuracy with cost-efficiency. By integrating this data, we have identified a pathway to streamline screening, tailoring it to individual risk profiles and age groups, thereby reducing unnecessary tests, lowering costs and reducing the impact of testing on patients. This approach not only fosters better patient care, but also provides a framework for developing clearer, cost-effective screening guidelines, to monitor liver health, in these complex CHD patients.

Late outcomes of Fontan operation from the EUROFONTAN experience

Abstract Background Fifty years after the first Fontan operation, the persisting challenges and evolving landscape of post-Fontan complications are explored in the EUROFONTAN experience. Aim of the study is the evaluation of long term outcomes of a large cohort of Fontan patients, focusing on age at Fontan and onset of Fontan-associated liver disease (FALD). Methods A retrospective clinical study across 21 european congenital cardiac centers across Europe. Clinical and operative data of patients who underwent Fontan operation between January 1990 and December 2022 were gathered through a RedCap online database. Results 2606 patients were included in this analysis (M/F: 59%/41%, median age and median weight at Fontan of 4.3 y.o (IQR 3.3-6.4), and 16kg (IQR 14-20), respectively. Most frequent cardiac anomaly were tricuspid atresia and pulmonary atresia with intact ventricular septum (781, 30%). Ventricular morphology was left in 1379 patients (53%), and right in 1029 patients (40%). Extra cardiac conduit (ECC) was performed in the majority of patients (2335, 90%), with a median conduit size of 20mm (IQR 18-20). Early post-operative complications were present in 52% (1340), with an early reintervention in 349 patients (249 surgical , 99 catheter driven) At a median follow-up median of 10 years (IQR 4-15), there were 79 late deaths (3%). Adverse events occurred in 49% (1288 , non-surgical in 962 , surgical in 249). The clinical status was stage A in 60% (1288 patients), while only a minority (1.3%) was in status D. Systemic Ventricular function was normal in 1898 patients (73%), while absent or mild Atrioventricular Valve regurgitation was presnet in 86% (1816). Of note, FALD was detected in 388 (15 %) , and sinus rhythm was present in 99%. Statistical analysis shows that late death and adverse events are significantly associated right ventricular morphology of the systemic ventricle (p-value 0.019). Of note, when compared to lateral tunnel, TCPC extracardiac conduit demonstrated lower late mortality (2.3% vs 8.2%, p-value &amp;lt;0.001) and complication rates (60% vs 48%, p-value 0.001). Analyzing age at Fontan, a linear relationship exists between age and late mortality, whereby mortality increases with advancing age (graph 1). However, concerning the development of late adverse events, the risk decreases with age at Fontan up to 7 years; beyond 7 years, the risk increases with advancing age (graph 2). The analysis demonstrated growing FALD-prevalence with increasing time from Fontan completion (significant especially after 10 years). Conclusion current long term outcomes of Fontan operation are highly satisfactory. However, the longer survival is associated to an increasing incidence of late term extracardiac complications (namely FALD) which are more evident if Fontan is performed at older age.Data of Fontan PatientsCorrelation between age at Fontan and AE

Segmental MRI pituitary and hypothalamus volumes post Fontan: An analysis of the Australian and New Zealand Fontan registry

ObjectiveShort stature, central hypothyroidism and infertility are common in those with a Fontan circulation. Given that the Fontan circulation often results in hepatic portal venous congestion, we hypothesize that the hypothalamic-pituitary portal circulation is also affected, contributing to subsequent hypothalamic-pituitary axis dysfunction. MethodsMRI data from the Australian and New Zealand Fontan Registry (86 cases) was compared to 86 age- and sex-matched normal published controls. Total pituitary volumes (both anterior and posterior glands) were measured using a manual tracing segmentation method, and hypothalamic (and subunit) volumes using an automated segmentation tool. Measured gland volume was normalized to total brain volumes. A generalized linear model was used for statistical analysis. ResultsNormalized total pituitary volumes (nTPV) were increased in Fontan patients compared to controls (p < 0.0001), due to an increase in anterior pituitary volumes (nAPV) (p < 0.0001), with no difference in normalized posterior pituitary volumes (p = 0.7). Furthermore, normalized anterior and tubular hypothalamic subunit groups) were increased in Fontan patients compared to the controls (p < 0.01 and p < 0.0001, respectively).The time between Fontan and MRI was positively related to nTPV, nAPV and bilateral hypothalamic volumes. nTPV increased with age, and the increase in nAPV was greater in Fontan patients. ConclusionsSegmental MRI Pituitary and Hypothalamus volumes post Fontan are increased and are related to the time since Fontan procedure. These findings are consistent with venous congestion of the anterior hypothalamic-pituitary portal venous system and may explain the high frequency of endocrine dysfunction in this patient group.