Total Thrombotic Occlusion of an Extracardiac Fontan Conduit in a Hemodynamically Stable Patient.

Cardiac and extracardiac complications of single-ventricle physiology are well described and carry significant morbidity and mortality risks. We present the case of a 32-year-old patient with a Fontan circulation who presented to the emergency department with epigastric pain, and with chest computed tomography angiography concerning for total thrombosis of the extracardiac conduit.

Predictors of spontaneous pregnancy loss in single ventricle physiology.

BACKGROUND: Pregnant patients with single ventricle (SV) physiology carry a high risk of spontaneous pregnancy loss (SPL), yet the clinical factors contributing to this risk are not well defined. METHODS: Single-centre retrospective study of pregnant patients with SV physiology seen in cardio-obstetrics clinic over the past 20 years with chart review of their obstetric history. Patients without a known pregnancy outcome were excluded. Univariable Bayesian panel-data random effects logit was used to model the risk of SPL. RESULTS: The study included 20 patients with 44 pregnancies, 20 live births, 21 SPL and 3 elective abortions. All had Fontan palliation except for two with Waterston and Glenn shunts. 10 (50%) had a single right ventricle (RV). 14 (70%) had moderate or severe atrioventricular valve regurgitation (AVVR). Atrial arrhythmias were present in 16 (80%), Fontan-associated liver disease (FALD) in 15 (75%) and FALD stage 4 in 9 (45%). 12 (60%) were on anticoagulation. Average first-trimester oxygen saturation was 93.8% for live births and 90.8% for SPL. The following factors were associated with higher odds of SPL: RV morphology (OR 1.72 (95% credible interval (CrI) 1.0008-2.70)), moderate or severe AVVR (OR 1.64 (95% CrI 1.003-2.71)) and reduced first-trimester oxygen saturation (OR 1.83 (95% CrI 1.03-2.71) for each per cent decrease in O2 saturation. CONCLUSION: Pregnant patients with SV physiology, particularly those with RV morphology, moderate or severe AVVR, and lower first-trimester oxygen saturations, have a higher risk of SPL. Identifying these clinical risk factors can guide preconception counselling by the cardio-obstetrics team.

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

BACKGROUND: 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. OBJECTIVE: 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. MATERIALS AND METHODS: 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 3 months 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. RESULTS: Twenty-two patients (15 males) were included in the study, with a median age of 17 years (IQR is 14.8-20.5 years; age range: 7 years to 30.2 years). The median spleen stiffness was 2.94 m/s (IQR: 2.57-3.61 m/s; range: 1.48-4.27 m/s). The median Fontan pressure was 11 mm Hg (IQR: 10-13.3 mm Hg; range: 7-19 mm Hg) obtained within a median of 10 days (IQR: 1-41 days) 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). CONCLUSIONS: In this preliminary study, SWE spleen stiffness values did not correlate with biopsy-determined scoring of liver fibrosis in patients with Fontan physiology.

Real-World Use and Outcomes of Apixaban for Early Post-Surgical Fontan Thromboprophylaxis.

Patients with Fontan physiology are at heightened risk of thrombosis related to passive venous return leading to increased stasis, as well as acquired thrombophilia from congestive hepatopathy. Variability exists for post-Fontan thromboprophylaxis, with no consensus on best practices. Direct oral anticoagulants offer advantages over conventional anticoagulants including fewer drug-drug interactions, no dietary restrictions, and less frequent monitoring. Herein, we report our single center experience utilizing apixaban thromboprophylaxis in children post-Fontan procedure. Single center, retrospective, cohort study evaluating apixaban thromboprophylaxis dosing strategies, efficacy, and safety in children admitted post-Fontan procedure at Boston Children's Hospital. Between September 2019 and December 2023, 62 children, median age 3.2 years (2.1-10.5 years), weight 13.9 kg (9.5-56.3 kg) received apixaban at a median of 93 days post-Fontan (7-1421 days). Over a total of 93 days of apixaban exposure, there was 1 treatment-related thrombosis event (0.07 per 1000 person-days on apixaban) and 3 combined treatment-related clinically relevant non-major (CRNM) and major bleeding events (0.22 per 1000 person-days on apixaban). Apixaban for post-Fontan thromboprophylaxis was feasible with low rates of bleeding and thrombosis.

Robot-assisted laparoscopic hepatectomy for hepatocellular carcinoma with Fontan-associated liver disease: a world-first case report.

BACKGROUND: Fontan-associated liver disease (FALD) encompasses hepatic complications following the Fontan procedure, ranging from fibrosis to hepatocellular carcinoma (HCC). Despite advancements in surgical techniques and perioperative care, robot-assisted laparoscopic hepatectomy (RALH) for HCC in patients with FALD has not been previously reported owing to concerns about the Fontan circulation. CASE PRESENTATION: We present the first case of RALH for recurrent HCC in a 45-year-old man after the Fontan procedure. The preoperative evaluation confirmed good cardiac function. The procedure involved meticulous monitoring and management of central venous pressure and was successfully completed with minimal blood loss. Postoperative recovery was uneventful. With thorough preoperative cardiac assessment and close collaboration between cardiologists and anesthesiologists, RALH can be safely performed in selected patients with FALD. CONCLUSIONS: Even if a patient has a history of FALD, RALH can be safely performed in selected patients under appropriate conditions.

Efficacy and safety of macitentan in Fontan-palliated patients: 52-week randomized, placebo-controlled RUBATO Phase 3 trial and open-label extension.

OBJECTIVES: The efficacy and safety of macitentan, an endothelin receptor antagonist, were assessed in a 52-week, prospective, multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessing the efficacy and safety of macitentan in Fontan-palliated adult and adolescent patients (RUBATO-DB) and an open-label extension trial (RUBATO-OL). METHODS: Patients aged 12 years and older with New York Heart Association functional class II or III underwent total cavopulmonary connection more than 1 year before screening and showed no signs of Fontan failure/clinical deterioration. In RUBATO-DB, the primary efficacy end point was change in peak oxygen consumption from baseline to week 16; secondary end points were change from baseline over 52 weeks in peak oxygen consumption and change in mean count/minute of daily physical activity via accelerometer from baseline to week 16. Safety was assessed throughout both studies. RESULTS: In RUBATO-DB, 137 patients were randomized to macitentan 10 mg (n = 68) or placebo (n = 69); 92.7% completed 52-week double-blind treatment. At week 16, mean ± SD change in peak oxygen consumption was -0.16 ± 2.86 versus -0.67 ± 2.66 mL/kg/minute with macitentan versus placebo (median unbiased treatment difference estimate, 0.62 mL/kg/minute [99% repeated CI, -0.62 to 1.85]; P = .19). No treatment effect was observed in either of the secondary end points. During RUBATO-DB, most common adverse events with macitentan were headache, nasopharyngitis, and pyrexia. Across RUBATO-DB and RUBATO-OL, most common adverse events were COVID-19, headache, and fatigue. RUBATO-OL was prematurely discontinued because RUBATO-DB did not meet its primary or secondary end point. CONCLUSIONS: The primary end point of RUBATO-DB was not met; macitentan did not improve exercise capacity versus placebo in patients with Fontan palliation. Macitentan was generally well tolerated over long-term treatment.

The Long-Term Outcomes and Risk Factors of Complications After Fontan Surgery: From the Korean Fontan Registry (KFR).

BACKGROUND AND OBJECTIVES: This study aimed to analyze the outcomes of Fontan surgery in the Republic of Korea, as there were only a few studies from Asian countries. METHODS: The medical records of 1,732 patients who underwent Fontan surgery in 10 cardiac centers were reviewed. RESULTS: Among them, 1,040 (58.8%) were men. The mean age at Fontan surgery was 4.3±4.2 years, and 395 (22.8%) patients presented with heterotaxy syndrome. According to the types of Fontan surgery, 157 patients underwent atriopulmonary (AP) type; 303, lateral tunnel (LT) type; and 1,266, extracardiac conduit (ECC) type. The overall survival rates were 91.7%, 87.1%, and 74.4% at 10, 20, and 30 years, respectively. The risk factors of early mortality were male, heterotaxy syndrome, AP-type Fontan surgery, high mean pulmonary artery pressure (mPAP) in pre-Fontan cardiac catheterization, and early Fontan surgery year. The risk factors of late mortality were heterotaxy syndrome, genetic disorder, significant atrioventricular valve regurgitation (AVVR) before Fontan surgery, high mPAP in pre-Fontan cardiac catheterization, and no fenestration. CONCLUSIONS: In Asian population with a high incidence of heterotaxy syndrome, the heterotaxy syndrome was identified as the poor prognostic factors for Fontan surgery. The preoperative low mPAP and less AVVR are associated with better early and long-term outcomes of Fontan surgery.

The Fontan Circulation in Pregnancy: Hemodynamic Challenges and Anesthetic Considerations.

Pregnancy in patients with Fontan physiology presents unique challenges due to altered cardiovascular dynamics inherent to both conditions. The Fontan procedure reroutes venous blood directly to the pulmonary arteries, bypassing the heart, and necessitating precise regulation of pulmonary venous resistance and systemic venous pressure to maintain effective cardiac output. The significant cardiovascular adaptations required during pregnancy to meet the metabolic demands of the mother and fetus can overburden the limited preload capacity and venous compliance in Fontan patients, predisposing them to a spectrum of potential complications, including arrhythmias, heart failure, thromboembolism, and obstetric and fetal risks. This review delineates the essential physiological adaptations during pregnancy and the challenges faced by Fontan patients, advocating for a comprehensive care approach involving multidisciplinary collaboration, vigilant monitoring, tailored anesthetic management, and postpartum care. Understanding the complex dynamics between Fontan physiology and pregnancy is crucial for anesthesiologists to develop and execute individualized management strategies to minimize risks and optimize outcomes for this high-risk population.

Augmented Biphasic Breathing Using Sniff and an Oral Positive Expiratory Pressure Device (Sniff-PEP) in Fontan Patients.

The use of an oral positive expiratory pressure device (oPEP) with sniff breathing (Sniff-PEP) mimics biphasic ventilation. Biphasic ventilation increases pulmonary blood flow and cardiac output in Fontan patients. The aim of this study was to assess the effect of Sniff-PEP on Fontan flow velocities. A single-center, pilot, prospective study was carried out in 15 subjects with Fontan circulation enrolled to use the oPEP device for 1 month. Subjects were instructed on Sniff-PEP and to use the device for 10-15 min 3-4 times a day. Measurements of flow velocity and cardiac output were measured via echocardiogram and quality of life assessments were performed at baseline and 4-6 weeks later. The mean age at enrollment was 19.9 ± 8.7 years (age range of 10-37 years). 7 patients (47%) had dominant left ventricle and 8 (53%) had an open fenestration. There was a statistically significant increase in flow velocities in the hepatic vein from 27.5 ± 7.6 to 35.1 ± 11.3 cm/s (p = 0.003), left pulmonary artery from 51.6 ± 16.6 to 57.6 ± 21.1 cm/s (p = 0.01), and right pulmonary artery from 43.1 ± 14.2 to 45.8 ± 17.2 cm/s (p = 0.04). With chronic use, the mean fenestration gradient slightly decreased from 4.5 ± 1.6 to 4.1 ± 1.9 mmHg but the difference was not statistically significant (p = 0.14). oPEP device therapy increased flow velocity in several areas in the Fontan circulation with acute use. Further studies are needed to assess the effects long term.Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT03251742.

Patient Reported Outcome Measures in Adults with Fontan Circulatory Failure.

Background: Patient reported outcomes (PROs) are important measures in acquired heart disease but have not been well defined in Adult Congenital Heart Disease (ACHD). Our aim was to explore the discriminatory capacity of PRO survey tools in Fontan circulatory failure (FCF). Methods: Consecutive adults were enrolled from our ambulatory clinics. Inclusion criteria were age ≥18 years, a Fontan circulation or a hemodynamically insignificant shunt lesion, and sufficient cognitive/language abilities to complete PROs. A comprehensive package of PRO measures, designed to assess perceived health-related quality of life (HRQOL) was administered (including the Kansas City Cardiomyopathy Questionnaire [KCCQ-12], EuroQol-5-dimension [EQ5D], Short Form Health Status Survey [SF-12], self-reported New York Heart Association [NYHA] Functional Class, and Specific Activity Scale [SAS]). Results: We compared 54 Fontan patients (35 ± 10 years) to 25 simple shunt lesion patients (34 ± 11 years). The KCCQ-12 score was lower in Fontan versus shunt lesion patients (87 [IQR 79, 95] versus 100 [IQR 97, 100], p-value < 0.001). The FCF subgroup was associated with lower KCCQ-12 scores as compared with the non-FCF subgroup (82 [IQR 56, 89] versus 93 [IQR 81, 98], p-value = 0.002). Although the KCCQ-12 had the best discriminatory capacity for determination of FCF of all PRO tools studied (c-statistic 0.75 [CI 0.62, 0.88]), superior FCF discrimination was achieved when the KCCQ-12 was combined with all PRO tools (c-statistic 0.82 [CI 0.71, 0.93]). Conclusions: The KCCQ-12 questionnaire demonstrated good discriminatory capacity for the identification of FCF, which was further improved through the addition of complementary PRO tools. Further research will establish the value of PRO tools to guide management strategies in ACHD.

Effect of liver abnormalities on mortality in Fontan patients: a systematic review and meta-analysis.

BACKGROUND: Fontan-associated liver disease (FALD) is one of the most common complications following Fontan procedure, but the impact of FALD on survival outcomes remains controversial. The aim of this systematic review and meta-analysis was to examine and quantify the influence of liver disease on the survival of Fontan patients. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed, and relevant human studies published from inception up to 12 August 2022 were searched. Stata (version 17.0) was applied to perform the meta-analysis, using random effects (Mantel-Haenszel) models. The I2 statistic was used to assess the heterogeneity. Subgroup analysis and meta-regression were employed to explore the potential sources of heterogeneity and sensitivity analysis was performed to determine the potential influence of each study on the overall pooled results. RESULTS: A total of 312 records were initially identified and 8 studies involving 2,466 patients were selected for inclusion. Results revealed a significant association between the severity of liver disease following Fontan procedure and mortality, which was confirmed by sensitivity analysis and subgroup analysis assessing post-HT mortality. Meta-regression showed that diagnostic methods for liver disease may be a source of heterogeneity. After removal of the FALD patients identified by international classification of disease codes, heterogeneity was markedly reduced, and the positive association between all-cause mortality and the severity of liver disease became significant. CONCLUSIONS: This meta-analysis showed the severity of liver disease following the Fontan procedure has a significant association with mortality. Lifelong follow-up is necessary and imaging examinations are recommended for routine surveillance of liver disease. Among patients with failing Fontan and advanced liver disease, combined heart-liver transplantation may provide additional survival benefits.

Preliminary report of a thoracic duct-to-pulmonary vein lymphovenous anastomosis in swine: A novel technique and potential treatment for lymphatic failure.

OBJECTIVE: The thoracic duct is the largest lymphatic vessel in the body, and carries fluid and nutrients absorbed in abdominal organs to the central venous circulation. Thoracic duct obstruction can cause significant failure of the lymphatic circulation (i.e., protein-losing enteropathy, plastic bronchitis, etc.). Surgical anastomosis between the thoracic duct and central venous circulation has been used to treat thoracic duct obstruction but cannot provide lymphatic decompression in patients with superior vena cava obstruction or chronically elevated central venous pressures (e.g., right heart failure, single ventricle physiology, etc.). Therefore, this preclinical feasibility study sought to develop a novel and optimal surgical technique for creating a thoracic duct-to-pulmonary vein lymphovenous anastomosis (LVA) in swine that could remain patent and preserve unidirectional lymphatic fluid flow into the systemic venous circulation to provide therapeutic decompression of the lymphatic circulation even at high central venous pressures. METHODS: A thoracic duct-to-pulmonary vein LVA was attempted in 10 piglets (median age 80 [IQR 80-83] days; weight 22.5 [IQR 21.4-26.8] kg). After a right thoracotomy, the thoracic duct was mobilized, transected, and anastomosed to the right inferior pulmonary vein. Animals were systemically anticoagulated on post-operative day 1. Lymphangiography was used to evaluate LVA patency up to post-operative day 7. RESULTS: A thoracic duct-to-pulmonary vein LVA was successfully completed in 8/10 (80.0%) piglets, of which 6/8 (75.0%) survived to the intended study endpoint without any complication (median 6 [IQR 4-7] days). Initially, 2/10 (20.0%) LVAs were aborted intraoperatively, and 2/10 (20.0%) animals were euthanized early due to post-operative complications. However, using an optimized surgical technique, the success rate for creating a thoracic duct-to-pulmonary vein LVA in six animals was 100%, all of which survived to their intended study endpoint without any complications (median 6 [IQR 4-7] days). LVAs remained patent for up to seven days. CONCLUSION: A thoracic duct-to-pulmonary vein LVA can be completed safely and remain patent for at least one week with systemic anticoagulation, which provides an important proof-of-concept that this novel intervention could effectively offload the lymphatic circulation in patients with lymphatic failure and elevated central venous pressures.

Iron deficiency in patients with a Fontan circulation and its impact on exercise capacity.

BACKGROUND: Iron deficiency (ID) has been reported in patients with congenital heart disease. There is, however, a scarcity of data on its prevalence in patients with a Fontan circulation. The aim of this study is to investigate the prevalence of ID in Fontan patients and to investigate the association between ID and exercise capacity in this population. METHODS AND RESULTS: Blood count and haematological parameters were determined in plasma of 61 Fontan patients (51% female, mean age 29±9 years). ID was defined as transferrin saturation (TSAT) ≤19.8%. The prevalence of ID was 36% (22/61 patients). Especially among women, the diagnosis of ID was highly prevalent (52%) despite normal haemoglobin levels (153.7±18.4 g/L). Mean ferritin levels were 98±80 µg/L and mean TSAT levels were 22%±12%. Cardiopulmonary exercise testing was performed in 46 patients (75%). Patients with ID had a lower peak oxygen uptake (V̇O2peak) (1397±477 vs 1692±530 mL/min; p=0.039), although this relationship was confounded by sex. The presence of ID increased the likelihood of not achieving a respiratory exchange ratio (RER) ≥1.1 by 5-fold (p=0.035). CONCLUSION: ID is highly prevalent among patients with a Fontan circulation. V̇O2peak is lower in patients with ID. Fontan patients with ID are less likely to achieve an RER≥1.1 during cardiopulmonary exercise testing.

Role and Applications of Experimental Animal Models of Fontan Circulation.

Over the last four decades, the Fontan operation has been the treatment of choice for children born with complex congenital heart diseases and a single-ventricle physiology. However, therapeutic options remain limited and despite ongoing improvements in initial surgical repair, patients still experience a multiplicity of cardiovascular complications. The causes for cardiovascular failure are multifactorial and include systemic ventricular dysfunction, pulmonary vascular resistance, atrioventricular valve regurgitation, arrhythmia, development of collaterals, protein-losing enteropathy, hepatic dysfunction, and plastic bronchitis, among others. The mechanisms leading to these late complications remain to be fully elucidated. Experimental animal models have been developed as preclinical steps that enable a better understanding of the underlying pathophysiology. They furthermore play a key role in the evaluation of the efficacy and safety of new medical devices prior to their use in human clinical studies. However, these experimental models have several limitations. In this review, we aim to provide an overview of the evolution and progress of the various types of experimental animal models used in the Fontan procedure published to date in the literature. A special focus is placed on experimental studies performed on animal models of the Fontan procedure with or without mechanical circulatory support as well as a description of their impact in the evolution of the Fontan design. We also highlight the contribution of animal models to our understanding of the pathophysiology and assess forthcoming developments that may improve the contribution of animal models for the testing of new therapeutic solutions.

Exercise capacity and muscle strength in patients who have undergone the Fontan procedure: a retrospective follow-up study.

BACKGROUND: Due to their relationship with clinical progression, follow-up of exercise capacity and muscle strength is important for optimal disease management in patients who have undergone the Fontan procedure. We aimed to retrospectively analyze exercise capacity and muscle strength trajectory over approximately 2 years. METHODS: Exercise capacity was assessed using an exercise stress test with the modified Bruce protocol on a treadmill, hand grip and knee extensor strength using a hand dynamometer, and body composition using a bioelectrical impedance device. Exercise capacity, muscle strength, and body composition follow-up data recorded between 2020 and 2022 were compared. RESULTS: Fifteen patients [median age from 17 (first assessment) to 18 years (last assessment), 5 females)] with a 20-month median follow-up time were analyzed retrospectively. There was an increase in weight, height, body mass index, and body fat weight (p<0.05). There was a tendency for increased handgrip strength (%) (p=0.069), but no significant difference was observed in the knee extensor strength of patients during the follow-up period (p>0.05). The changes in heart rate (HR) and oxygen saturation were higher in the last test than in the first test (p<0.05). Maximum HR (HRmax), % predicted HRmax and HR reserve recorded during the test and HR 1 minute after the test were similar between the first and last tests (p>0.05). CONCLUSIONS: After 20 months of follow-up, exercise capacity and muscle strength did not decline; instead, the body mass index and fat weight increased. Patients who have undergone the Fontan procedure may not be experiencing a decline in exercise capacity and muscle strength over relatively short time periods during childhood, adolescence, and early adulthood.

The Prevalence of Scoliosis after Fontan Circulation Surgery Followed-Up to Adolescence.

Introduction: The advancement of surgical techniques and perioperative management for congenital heart disease (CHD) has increased life expectancy. The surgical creation of the Fontan circulation maintains pulmonary blood flow without relying on an effective pump from the abnormal heart, relying on peripheral vascular resistance to maintain effective flow through the lungs. Unfortunately, this delicate mechanism is compromised when scoliosis restricts ventilation, leading to Fontan failure and a poor prognosis for life. This report describes the prevalence of scoliosis with Fontan completion surgery and the role of screening and surgical correction. Methods: Ninety-six consecutive Japanese patients undergoing Fontan completion surgery for CHD between 2000 and 2017 were identified in our institutional records. The inclusion criterion was at least 7 years of follow-up after Fontan completion surgery, while the exclusion criteria were congenital, syndromic, and neuromuscular scoliosis. Radiographic and clinical parameters, including cardio-thoracic ratio (CTR) for cardiomegaly and cyanosis saturation, were compared between with and without scoliosis. Results: There were 23 and 40 patients in the scoliosis and no scoliosis groups, respectively. The mean age at the final follow-up was 18.5 and 16.7 years in the scoliosis and no scoliosis groups, respectively (p=0.02). Mean CTR was 43.7% and 39.4% in the scoliosis and no scoliosis groups (p=0.016), and the mean saturation in room air at the final follow-up was 88.8% and 93.2%, respectively (p=0.036). There were no significant differences to clarify the risk factors with multivariate logistic regression analysis. Conclusions: The prevalence of scoliosis with Fontan completion surgery was 36.5%. Screening for scoliosis is important for children with Fontan circulation surgery as part of their routine follow-up at least until they reach adolescence.Evidence Level: 4.