Risk Factors for Thromboembolic and Bleeding Events in Patients After the Fontan Operation (Insights from the National Database of Health Insurance Claims of Japan).

Risk stratification of thromboembolic events (TEs) and bleeding events is important for the appropriate selection of thromboprophylaxis in patients after the Fontan operation. Therefore, we clarified the risk factors for TEs and bleeding events in patients after the Fontan operation using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. We conducted a retrospective cohort study including 2,515 patients who underwent the Fontan operation between June 2011 and September 2019. The end points were TEs and bleeding events within 1 year of the Fontan operation analysis. We analyzed the risk factors for these end points using a multivariate analysis. In total, 1,903 patients were included in the analysis. The median age at the time of the Fontan operation was 3 (1 to 22) years, and 1,067 patients (56%) were male. The incidence rates of TEs and bleeding events were 12% and 11%, respectively. Age (odds ratio [OR] 1.1 per 1 year older, p <0.05) was an independent risk factor for TEs. Thromboprophylaxis with aspirin after the Fontan operation significantly reduced TEs (OR 0.3, p <0.05). A history of postoperative hemorrhage (OR 1.5, p <0.05) and the use of a potassium channel blocker (OR 2.1, p <0.05) were independent risk factors for bleeding events. In conclusion, aspirin was found to reduce the risk of TEs within 1 year of the Fontan operation. The results of this study will be useful in selecting effective and safe thromboprophylaxis in patients after the Fontan operation.

Long-term neurodevelopmental outcome and serial cerebral magnetic resonance imaging assessment in Fontan patients at school age.

OBJECTIVES: Children with univentricular congenital heart disease undergoing staged surgical palliation are at risk for impaired neurodevelopmental (ND) outcome. Little is known about the long-term effects on brain growth until school age. METHODS: In a prospective two-centre study, consecutive patients undergoing stage I (Hybrid or Norwood) to stage III (Fontan procedure) were evaluated by 2 serial cerebral magnetic resonance imaging examinations, somatic growth and ND testing before Fontan procedure at 2 years of age (Bayley-III) and after Fontan at 6-8 years of age (Wechsler Intelligence Scale for Children-third edition). Magnetic resonance imaging findings were compared with 8 healthy controls. Medical and sociodemographic characteristics were documented and related to cerebral and ND findings. RESULTS: We examined 33 children (16 female) at a mean age of 2.3 (0.35) and 6.8 (± 0.7) years. The mean Bayley-III cognitive scales were 99.1 (9.9), language scales 98.4 (11.9) and motor scales 98.5 (13.8) at the first examination. Follow-up at school age showed a mean total IQ of 86.7 (13.6). The rate of structural brain lesions increased from 39% at 2 years to 58% at school age. Bayley-III language scale (P = 0.021) and mean Wechsler Intelligence Scale for Children-third edition (P = 0.019) were lower in children with pathological MR findings. Total brain volume (P < 0.001), total grey matter volume (P = 0.002), deep grey matter volume (P = 0.001) and white matter volume (P < 0.001) were smaller in patients compared to age- and gender-matched healthy controls. CONCLUSIONS: Smaller brain volumes and structural brain lesions in complex congenital heart defect patients at school age are associated with impaired ND outcome. For the evaluation of predictive surgical or clinical factors, larger multicentre studies are needed.

Non-invasive assessment of liver abnormalities in pediatric Fontan patients.

Liver abnormalities are well known among long-term survivors of Fontan palliation, which remains the definite surgery for complex congenital heart disease and single ventricle physiology. Pediatric data however are scarce. We assessed the prevalence and degree of liver abnormalities in pediatric Fontan patients through non-invasive investigations suitable for longitudinal follow-up. Thirty-five patients with a median age of 11.8 years (5.2-16.6) and median time since Fontan of 6 years (1.17-13.83) were studied. Each child underwent a blood test, liver Doppler ultrasound (US), and transient elastography (TE). Healthy children were used as controls for TE measurement. AST, ALT, γGT, and direct bilirubin were abnormal in respectively 12 (34%), 5 (14%), 24 (69%), and 7 (20%) patients, while platelet count was decreased in 7 (20%). Splenomegaly was present in 7 (20%) patients. Portal vein mean flow velocity was < 15 cm/s in 19 (54%) patients indicative of portal hypertension. Twenty-two patients (63%) showed inferior vena cava collapsibility index values below 17%, indicating venous congestion. Hepatic artery and superior mesenteric artery resistance index were inversely correlated with time post Fontan (p < 0.05). TE values in Fontan patients were significantly higher than controls, with a median of 12.6 versus 4.6 kPa (p < 0.001) and were already increased shortly after Fontan completion. Conclusion: Liver abnormalities are frequently observed in pediatric Fontan patients. The non-invasive investigations used were not able to confirm liver fibrosis or differentiate hepatic congestion from fibrosis. Based on our findings, we propose a prospective screening protocol with serial measurements of laboratory, (Doppler) US, and TE parameters. What is Known: • Hepatic dysfunction is a well-known consequence of the Fontan circulation. • The natural history of Fontan-associated liver disease in the pediatric age group remains unclear. What is New: • Liver abnormalities are frequently observed in pediatric Fontan patients; however, differentiating liver fibrosis and hepatic congestion with non-invasive investigations remains challenging. Sonographic Doppler measurements may improve our insight in both Fontan-associated liver disease development and the functioning of the Fontan circulation. • A prospective screening protocol is proposed to improve our ability to detect Fontan-associated liver disease early on and understand its natural history.

Cross-sectional assessment of haemostatic profile and hepatic dysfunction in Fontan patients.

BACKGROUND: Fontan-associated liver disease is accompanied by a hypercoagulable state. While hepatic dysfunction in Fontan patients is common, its relationship with haemostatic changes and clinical outcomes in this patient population remains unclear. OBJECTIVE: To correlate liver dysfunction and haemostatic profiles with clinical outcomes in the Fontan population. PATIENTS/METHODS: Patients were enrolled in a multicentre, cross-sectional study in Australia and New Zealand. Hepatic structure and function were assessed using serum-based calculations (Fibrotest and model for end-stage liver disease excluding international normalised ratio scores). Haemostatic profiles were assessed by Thrombin Generation. Platelet function was assessed via Platelet Factor 4 (PF4) and P-selectin (P-SEL). Clinical outcomes were obtained from the Australian and New Zealand Fontan Registry. RESULTS: Seventy-three patients participated in the study (mean age 18.9±8.5 years with a mean of 13.5±6.9 years post-Fontan). The Endogenous Thrombin Potential (ETP) for patients who suffered thrombotic events (TE) (1366.4±66.2 nM/min) was higher compared with patients with major bleeding events (1011.1±138.4 nM/min) (p=0.03). Except for a negative correlation between Fibrotest-score and PF4 (p=0.045), PF4 and P-SEL concentrations did not correlate with markers of hepatic dysfunction or structural abnormality. CONCLUSIONS: Increased ETP is associated with TE during clinical follow-up after Fontan. This study reinforces that hepatic dysfunction may contribute to the derangement of coagulation factors, impacting the individual risk of haemostatic complications for the Fontan population.

Noninvasive ultrasound technique for assessment of liver fibrosis and cardiac function in Fontan-associated liver disease: diagnosis based on elastography and hepatic vein waveform type.

PURPOSE: Patients with a Fontan circulation tend to develop liver fibrosis, liver cirrhosis and even hepatocellular carcinoma. A noninvasive ultrasound technique for liver fibrosis and cardiac function assessment in Fontan-associated liver disease (FALD) is needed to evaluate disease progression in real time. This study aimed to evaluate whether hepatic vein (HV) waveform analysis and elastography could be alternative markers to cardiac index (CI) in patients with FALD and assess factors influencing elastography measurements in FALD cases. METHODS: All patients underwent cardiac catheterization, B-mode ultrasound and ultrasound elastography measurement. Moreover, we measured serum markers related to fibrosis and examined HV blood flow using duplex Doppler ultrasonography. RESULTS: Forty-three patients (median age, 17 years; interquartile range, 12-25 years; 29 men, 6 with liver biopsy) were enrolled. The real-time tissue elastography (RTE) value was significantly higher in patients who underwent surgery > 7 years prior, suggesting that this value probably reflects the liver fibrosis due to FALD from the early fibrosis stage. The ultrasound elastography did not significantly correlate with hemodynamic parameters. The area under the receiver operating curve for the diagnosis of CI < 2.2 L/min/m2 using HV waveform was superior to the results from elastography and calculated fibrosis indices. CONCLUSION: HV waveform can be used as a noninvasive measurable surrogate marker for CI. The RTE value increased overtime after the operation and would reflect liver fibrosis. The combination of RTE and HV waveform type could be useful noninvasive tools to evaluate clinical conditions in FALD patients in real time.

Pretransplantation and Post-Transplantation Liver Disease Assessment in Adolescents Undergoing Isolated Heart Transplantation for Fontan Failure.

OBJECTIVE: To describe the assessment of Fontan-associated liver disease and determine the clinical and imaging measures that may identify hepatic morbidity risk in isolated heart transplantation candidates and trend those measures post-isolated heart transplantation. STUDY DESIGN: Retrospective analysis of pre-isolated heart transplantation and post-isolated heart transplantation Fontan-associated liver disease (FALD) status using blood tests, magnetic resonance imaging (MRI), and liver biopsy analysis within 6 months before isolated heart transplantation and 12 months after isolated heart transplantation in 9 consecutive patients with Fontan. Pre- and post-isolated heart transplantation standard laboratory values; varices, ascites, splenomegaly, thrombocytopenia (VAST) score; Fontan liver MRI score; liver biopsy scores; Model for End-stage Liver Disease (MELD); MELD excluding the International Normalized Ratio (MELD-XI); AST to platelet ratio index, and cardiac catheterization data were compared. RESULTS: Pretransplantation maximum MELD and MELD-XI was 15 and 16, respectively. Central venous pressures and VAST scores decreased significantly post-transplantation. In 5 paired studies, Fontan liver MRI score maximum was 10 pretransplantation and decreased significantly post-transplantation. Arterially enhancing nodules on MRI persisted in 2 patients post-transplantation. Pretransplantation and post-transplantation liver biopsy scores did not differ in 4 paired biopsy specimens. CONCLUSIONS: Patients with FALD and MELD <15, MELD-XI <16, Fontan liver MRI score <10, and VAST score ≤2 can have successful short-term isolated heart transplantation outcomes. Liver MRI and VAST scores improved post-transplantation. Post-transplantation liver biopsy scores did not change significantly. Pretransplantation liver biopsy demonstrating fibrosis alone should not exclude consideration of isolated heart transplantation. The persistence of hepatic vascular remodeling and fibrosis post-isolated heart transplantation suggests that continued surveillance for hepatic complications post-transplantation for patients with Fontan is reasonable.

Serial assessment of somatic and cardiovascular development in patients with single ventricle undergoing Fontan procedure.

BACKGROUND: The palliation of patients with single ventricle (SV) undergoing Fontan procedure led to improved long-term survival but is still limited due to cardiovascular complications. The aim of this study was to describe the somatic and cardiovascular development of Fontan patients until adolescence and to identify determining factors. METHODS: We retrospectively assessed somatic growth, vascular growth of pulmonary arteries, and cardiac growth of the SV and systemic semilunar valve from 0 to 16 years of age using transthoracic echocardiography. The Doppler inflow pattern of the atrioventricular valve was quantified by E-, A-wave and E/A ratio. All data were converted to z-scores and analyzed using linear mixed effect models to identify associations with age at Fontan procedure, gender, and ventricular morphology. RESULTS: 134 patients undergoing Fontan procedure at a median age of 2.4 (IQR 2.12 to 2.8) years were analyzed. A catch-up of somatic growth after Fontan procedure until school age was found, with lower body height and weight z-scores in male patients and patients with systemic right ventricles. An early time of Fontan procedure was favorable for somatic growth, but not for vascular growth. Cardiac development indicated a decrease of SV end-diastolic diameter z-score until adolescence. Despite a trend towards normalization, E-wave and E/A ratio z-scores were diminished over the entire period. CONCLUSIONS: There is a catch-up growth of somatic, vascular and cardiac parameters after Fontan procedure, which in our cohort depends on the time of Fontan procedure, ventricular morphology, and gender. Beside other factors, diastolic function of the SV remains altered.

Non-invasive assessment of haemodynamic parameters in patients after Fontan procedure.

INTRODUCTION AND OBJECTIVE: Single ventricle anomaly is one of the complex congenital heart defects. A dependable non-invasive method of evaluation of Fontan circulation haemodynamics for early diagnosing unstable patients is hardly available in routine clinical practice. The aim of the study is non-invasive evaluation of the haemodynamic parameters in patients after Fontan operation. MATERIAL AND METHODS: The study involved 11 participants (age 24.4±4.3 years) with functionally univentricular hearts after Fontan operation. Evaluation of haemodynamic parameters was performed in supine and sitting positions using the impedance cardiography method. RESULTS: In comparative analysis, heart rate (70.1 vs.78.3 1/min; p=0.001), diastolic blood pressure (73.9 vs. 76.7 mm Hg; p=0.026), mean arterial blood pressure (84.5 vs. 88.0 mm Hg; p=0.013), systemic vascular resistance (1284.8 vs. 1334.9 dyn*s*cm-5; p=0.024), systemic vascular resistance index (2178.7 vs. 2272.8 dyn*s*cm-5*m2 ; p=0.018), pre-ejection period (124.2 vs. 136.2 ms; p=0.009), systolic time ratio (0.43 vs. 0.53; p=0.0001), and Zo (26.2 vs. 28.7 Ω; p<0.00001), were significantly higher in the sitting position. Stroke volume (75.4 vs. 68.5 ml; p=0.013), stroke index (42.7 vs. 39.0 ml*m-2; p=0.014), thoracic fluid content (38.5 vs. 35.4 1*kΩ-1; p=<0.00001), thoracic fluid content index (22.8 vs. 21.0 1*kΩ-1*m-2; p=<0.00001), and leftventricular ejection time 291.1 vs. 260.1 ms; p <0.00001, were significantly higher in the supine position. CONCLUSIONS: In patients after Fontan procedure, impedance cardiography can be a useful tool the assessment of shortterm haemodynamic changes provoked by postural changes. Its clinical value in patients with congenital heart defects should be further investigated.

Progressive stiffening and relatively slow growth of the dilated ascending aorta in long-term Fontan survivors-Serial assessment for 15 years.

BACKGROUND: A stiffened, dilated ascending aorta may represent an important predictor of cardiovascular mortality, and has been reported in patients with congenital heart disease, including single ventricle. However, the serial conformational changes and determinants of reduced distensibility in ascending aorta have not been clarified. METHODS: This retrospective study investigated 115 postoperative Fontan survivors (median age at Fontan: 3.7 years). All patients underwent cardiac catheterization before and 1, 5, 10, and 15 years after the Fontan operation. We measured Z-scores for diameters and stiffness indexes (ß) of the ascending aorta and descending aorta from angiograms. We also reviewed the clinical profiles, hemodynamic parameters, and exercise capacities of patients and compared them with results from 47 control subjects. RESULTS: Fontan survivors displayed significantly larger Z-score and ß of the ascending aorta from before to 15 years after surgery than controls, whereas values for the descending aorta were comparable. Z-score for the ascending aorta was decreased, but ß was elevated significantly according to the trend test. In multivariable analysis, ß of the ascending aorta at 15 years after Fontan operation and its increasing trend were associated with older age at Fontan operation and elevated ventricular end-diastolic pressure. Reduced exercise capacity also correlated with stiffening of the ascending aorta. CONCLUSIONS: Fontan survivors showed progressive stiffening and relatively slow growth of the dilated ascending aorta. Progressive stiffening of the ascending aorta may be coupled to diastolic dysfunction and reduced exercise capacity, suggesting the importance of lifelong management of subclinical Fontan pathophysiology.

Reintervention and survival in 1428 patients in the Australian and New Zealand Fontan Registry.

OBJECTIVE: Patients undergoing single-ventricle palliation have experienced significant improvement in survival in the recent era. However, a substantial proportion of these patients undergo reoperations. We performed a review of the Australia and New Zealand (ANZ) Fontan Registry to determine the overall reintervention and reoperative burden in these patients. METHODS: A retrospective longitudinal cohort study was performed using data from patients who underwent a Fontan operation between 1975 and 2016 from the ANZ Fontan Registry. The data obtained included Fontan operation, reinterventions and most recent follow-up status. We examined the type and timing of reinterventions and survival. RESULTS: Of the 1428 patients identified, 435 (30%) underwent at least one reintervention after the Fontan operation: 110 patients underwent early reintervention and 413 underwent late reinterventions. Excluding Fontan conversion and transplantation, 220 patients underwent at least one interventional procedure and 209 patients underwent at least one reoperation. Fenestration closure and pacemaker-related procedures were the most common catheter and surgical interventions, respectively. The cumulative incidence of reintervention following Fontan was 23%, 37% and 55% at 10, 20 and 30 years, respectively. Survival and freedom from failure were worse in patients requiring later reintervention after Fontan surgery (51% vs 83% and 42% vs 69%, respectively at 30 years, p<0.001). This difference persisted after excluding pacemaker-related procedures (p<0.001). Operative mortality for non-pacemaker late reoperations after Fontan was 6%. CONCLUSIONS: A substantial proportion of Fontan patients require further intervention to maintain effective single-ventricle circulation. Patients undergoing reoperation after Fontan have higher rates of mortality and failure, despite intervention.

Liver Strain Using Feature Tracking of Cine Cardiac Magnetic Resonance Imaging: Assessment of Liver Dysfunction in Patients with Fontan Circulation and Tetralogy of Fallot.

We propose a novel method to quantify pulsatile liver deformation using the feature tracking method of cardiac cine magnetic resonance imaging (MRI) and investigate its association with liver dysfunction in long-term postoperative patients after Fontan and intracardiac repair for the tetralogy of Fallot (TOF). Standard cine MRI which was previously performed for cardiac evaluation of 85 patients who underwent Fontan operation (mean age, 22.9 years), 43 patients with TOF (mean age, 34.6 years), and 32 healthy controls (mean age, 42.3 years) were retrospectively analyzed. Pulsatile liver deformation in the craniocaudal direction was calculated using the feature tracking method of cardiac cine imaging derived from cine-balanced turbo field-echo sequences performed on a 1.5 Tesla MR scanner, and was defined as liver strain. The liver strain was compared across the three patient groups using one-way analysis of variance. Liver dysfunction by a liver strain were compared using the Mann-Whitney U test. Liver strain for patients who underwent Fontan operation and TOF patients was significantly lower than controls (Fontan, 13.3 ± 6.5%; TOF, 15.0 ± 11.2%; controls, 23.1 ± 10.2%, p < 0.0001). In Fontan and TOF patients, MELD score was significantly greater for patients with a liver strain < 15% than those with values > 15% (5.9 ± 5.8 vs. 2.9 ± 2.9, p < 0.001). Lower liver strain values were found in adolescent and adult patients after Fontan operation and TOF, and correlates with the severity of liver injury, expressed as MELD score. Our method can evaluate hepatic function in adult congenital heart disease, together with the assessment of cardiac function.

Incidence and Nutritional Management of Chylothorax after Surgery for Congenital Heart Diseases in Children.

BACKGROUND: Chylothorax is caused by thoracic lymphatic system injury that leads to lymph extravasates in the thoracic cavity. Cardiac surgery was the most common cause. Reports comparing therapeutic effects between enteral nutrition (EN) with medium-chain triglycerides (MCT) and total parenteral nutrition (TPN) are few and inconsistent. Our study aimed to analyze the incidence of chylothorax in children in our hospital and optimum nutritional management modalities. METHODS: We retrospectively reviewed the medical records of children admitted to our hospital with a diagnosis of chylothorax from 2014 to 2018. We analyzed the incidence of chylothorax, therapeutic effectiveness, and cost effectiveness of EN with MCT or TPN. RESULTS: 136 patients with chylothorax after surgery for congenital heart disease (CHD) were identified from 172 patients with chylothorax (79.07%); chylothorax occurred in 5.62% of all 2420 congenital heart disease surgeries that were performed during that period. Tetralogy of Fallot (TOF), ventricular septal defect (VSD), and double-outlet right ventricle (DORV) were the most common primary diagnoses. Fontan surgery, TOF repair, and VSD repair were the most common primary procedures. We enrolled 45 patients with cured chylothorax. Nutrition support costs in the EN with MCT group (n = 28) were significantly lower than in the TPN group (n = 17) (P = .000). Time to resolution and time to removal of the drainage tube were shorter in EN with MCT versus TPN (P = .003), and the length of hospital stay was shorter (P = .032). There were no significant differences between the 2 groups in time from admission to surgery, postoperative days before diagnosing chylothorax, or length of PICU stay (P > .05). CONCLUSIONS: The therapeutic effects of EN with MCT were significantly better than those of TPN, with lower costs. Therefore, we suggest that EN with MCT be chosen first to treat chylothorax caused by surgery with mild chest drainage volume when gastrointestinal tract function is allowed.

Cost-Effectiveness of Percutaneous Lymphatic Embolization for Management of Plastic Bronchitis.

BACKGROUND: Plastic bronchitis is a dreaded complication of single ventricle physiology occurring following palliation via Fontan procedure. Medical management of plastic bronchitis often fails, requiring heart transplantation. Percutaneous lymphatic embolization is an emerging treatment for plastic bronchitis. METHODS: To determine the cost-effectiveness of competing management strategies, a modified Markov model was constructed with patients transiting through treatments-medical management, lymphatic embolization, or heart transplantation from a hospital system perspective. Health state transitions were modeled using an institutional review board-approved retrospective review of the Children's Hospital of Pennsylvania's plastic bronchitis cohort. Medication pricing data were obtained from the National Inpatient Sample. Differences in costs and quality-adjusted life years (QALYs) over a five-year horizon for each group were determined. The incremental cost-effectiveness ratio was then calculated. RESULTS: The mean cost of lymphatic embolization from procedure performance was US$340,941, US$385,841 for heart transplantation, and US$594,520 for medical management. The mean quality-adjusted survival of lymphatic embolization yielded an additional 0.66 QALYs (P < .03) relative to heart transplantation and 1.3 (P < .0001) relative to medical management. Orthotopic heart transplantation yielded an additional 0.66 QALYs (P = .06) when comparing heart transplantation to medical management. Compared to medical management, lymphatic embolization generated an incremental cost-effectiveness ratio of US$192,105. Similarly, compared to heart transplantation, lymphatic embolization yielded an incremental cost-effectiveness ratio of US$68,030. CONCLUSIONS: Of the available plastic bronchitis treatments, with a willingness to pay of US$150,000, lymphatic embolization produces an incremental cost-effectiveness ratio within the bounds considered to be cost-effective, potentially causing financial benefits to the health system.

Saline Contrast Transesophageal Echocardiography in Fontan Patients: Assessment of the Presence, Type, and Size of Right to Left Shunts.

Right to left (R-L) shunts resulting in cyanosis or systemic embolization occur after the Fontan procedure. The primary modality of diagnosing these is angiography. Successful delineation of these shunts in Fontan patients using selective saline contrast transesophageal echocardiography (SCTEE) may allow for reduced radiation and contrast exposure. We hypothesized that SCTEE could accurately determine the presence, type, and semiquantitative shunt size of R-L shunts in Fontan patients. SCTEE was performed in Fontan patients undergoing angiography for clinical indications. Injections were performed in six sites: mid-Fontan, right and left pulmonary arteries, superior and inferior vena cavae, and innominate vein. R-L shunt size was subjectively graded as 0 = absent, 1 = small, and 2 = medium or large based on echo contrast density in the left atrium. SCTEE was compared to angiography. 33 patients with Fontan were studied with median age 15 years, median weight 50.1 kg, and median O2 saturation of 90% in the R-L shunt group and 95% in the no R-L shunt group. R-L shunt types included intracardiac shunts (ICS), veno-venous collaterals (VVCs), arteriovenous malformations (AVMs), and their combinations. SCTEE versus angiography results were the same for the presence, type, and size of R-L shunts in 79% (26/33). SCTEE identified shunts in 88% (29/33). Angiography identified shunts in 85% (28/33). Neither method missed any medium or large R-L shunts. SCTEE and angiography had similar accuracy. SCTEE accurately detected the presence, type, and size of R-L shunts in most Fontan patients in this study. This can be used to guide targeted angiography, reducing radiation exposure and contrast load.

Noninvasive assessment of liver status in adult patients after the Fontan procedure.

INTRODUCTION A hemodynamic derangement in Fontan circulation causes liver pathology known as Fontan­­associated liver disease. Although liver biopsy is a standard for diagnosis of liver fibrosis, noninvasive methods are being developed, including shear wave elastography (SWE). OBJECTIVES We aimed to evaluate the degree of liver stiffness (LS) using SWE in patients with Fontan circulation in a long­­term follow­­up and to investigate a relationship between patient characteristics and LS. PATIENTS AND METHODS The study included 59 patients after the Fontan procedure. Clinical examinations and laboratory tests were performed. According to the stage of LS, patients were divided into 2 subgroups: group 1 (METAVIR stages F1 and F2) and group 2 (METAVIR stages F3 and F4). The ratio of aspartate transaminase to alanine transaminase, aspartate transaminase­­to­­platelet ratio index (APRI), fibrosis­­4 (FIB­­4) score, and Forns index were assessed. RESULTS The median LS was 9.1 kPa (interquartile range, 3.9-18.5 kPa). Five patients (9%) demonstrated LS in stage F1; 14 (26%), F2; 28 (52%), F3; and 7 (13%), F4. Group 2 had significantly higher aspartate transaminase and γ­­glutamyltranspeptidase levels, APRI, FIB­­4, and Forns index, and lower platelet count than group 1. A canonical correlation analysis indicated that LS and thrombocytopenia were related to time from the Fontan procedure, age at procedure, and single ventricular ejection fraction. CONCLUSIONS We showed that adult patients after the Fontan procedure develop liver dysfunction. Time from surgery, age at procedure, and single ventricular ejection fraction are related to the degree of LS assessed by SWE. Finally, SWE, APRI, Forns index, and FIB­4 score may help assess the degree of liver fibrosis.

Assessment of Late Thromboembolic Complications Post-Fontan Procedure in Relation to Different Antithrombotic Regimens: 30-Years' Follow-up Experience.

Background: The current CHEST guidelines recommend the use of antithrombotic therapy, either aspirin or warfarin, as a primary thromboembolic complications (TECs) prophylaxis in patients who undergo Fontan procedure, without specification on drug selection or duration of therapy. Objective: To investigate the incidence rate of late TECs, occurring after 1-year post-Fontan procedure and to assess the difference in rate of late TECs between warfarin and aspirin. Methods: A retrospective cohort study included patients who had Fontan procedures between 1985-2010 at our institution. Patients were stratified according to the antithrombotic regimen-warfarin, aspirin, or no therapy-at the time of TECs. Results: We screened 499 patients who underwent Fontan procedures; 431 procedures met the inclusion criteria. Over a median follow-up of 13.6 years (IQR= 8.7), freedom from late TECs at 5, 10, 15, and 20 years was 97.54%, 96.90%, 90.78%, and 88.07%, respectively. There was no difference in late TEC incidence rates per 1000 patient-years between warfarin and aspirin: 7.82 and 5.83 events, respectively; rate ratio= 1.34 (95% CI= 0.68-2.60). Warfarin was associated with a higher major bleeding incidence rate per 1000 patient-years: 3.70 versus 2.91 events with aspirin; rate ratio= 1.27 (95% CI= 0.49 to 3.29). Conclusion and Relevance: The incidence rate of late clinical TECs post-Fontan procedure in our population is low. Warfarin was not superior to aspirin for prevention of late TECs. Yet warfarin was associated with a higher rate of bleeding. This finding suggests a simpler antithrombotic regimen for prevention of TEC after 1-year post-Fontan procedure.

Assessment of global and regional strain left ventricular in patients with preserved ejection fraction after Fontan operation using a tissue tracking technique.

To evaluate the use of the tissue tracking (TT) technique to measure myocardial strain left ventricular in post-Fontan children with preserved ejection fraction (pEF). Nineteen (male/female, 10/9) patients with univentricular hearts after completion of the Fontan circulation (post-Fontan group) and 19 age- and gender-matched healthy children (control group) were retrospectively enrolled. Cardiovascular magnetic resonance (CMR) imaging was conducted on a 1.5-T MRI scanner. Global and regional strains of the left ventricle in post-Fontan patients (EF > 55%) and controls were obtained using CMR-TT software. The Mann-Whitney U test was used to compare parameters between the two groups. Correlation between EF and strain was investigated using Pearson correlation coefficients. The Bland-Altman method was used to identify the inter- and intra-observer agreement in measurement of global strain. Global longitudinal strain was lower in post-Fontan patients than in healthy controls (- 18.87 ± 4.61 vs. -19.72 ± 1.58; P = 0.54), though the difference was not statistically significant. Global circumferential strain and global radial strain were significantly lower in post-Fontan patients than in healthy controls (- 14.55 ± 3.79 vs. -19.91 ± 1.97; P < 0.001; and 29.62 ± 8.41 vs. 36.85 ± 5.95; P = 0.01; respectively). The regional circumferential strain (RCS) decrease was marked in regional segments compare with post-Fontan patients and controls (basal, - 11.81 ± 2.98 vs. - 16.21 ± 2.72, P < 0.001; mid, - 15.05 ± 3.31 vs. - 20.17 ± 2.28, P = 0.005; apical, - 16.86 ± 3.09 vs. - 23.37 ± 2.62, P < 0.001). All circumferential and longitudinal parameters had an inter-observer ICC of ≥ 0.85, but this coefficient was lower for radial parameters. CMR-TT appears to be a feasible technique for identification of early myocardial dysfunction in post-Fontan with pEF.

Imaging Assessment of Hepatic Changes after Fontan Surgery.

The aim of this study was to evaluate hepatic dysfunction over 10 years following Fontan surgery. We assessed the clinical usefulness of diagnostic tools for the detection and follow-up of hepatic dysfunction in patients with Fontan circulation.A total of 26 post-Fontan patients (median age 13 years, range 10-35 years; median duration from Fontan procedure 10.5 years, range 4-17 years) were enrolled in this study. Hepatic assessment was performed by ultrasonography, computed tomography (CT), and transient elastography (TE) with biochemical tests, echocardiography, and cardiac catheterization. Related parameters were compared on the basis of different findings in liver sonography, CT, and TE.Liver CT and TE showed abnormal findings in all patients. Liver ultrasonography revealed abnormal results in 24 patients (92.3%). However, liver function test was normal and did not correlate with imaging studies. C-reactive protein was significantly correlated with severity of CT findings. White blood cell, platelet count, and N-terminal pro-brain natriuretic peptide were correlated with severity on TE. Post-Fontan high pulmonary vascular resistance (P = 0.046) and high mean pulmonary artery pressure (P = 0.046) correlated with hepatic changes on liver CT.Changes in the liver post-Fontan surgery are common and occur even after 10 years the procedure. Liver imaging is more sensitive, and CT seems to be more useful for differentiation of severe hepatic changes.

Assessment of central venous physiology of Fontan circulation using peripheral venous pressure.

OBJECTIVE: Elevated central venous pressure is a major cause of morbidity and mortality after the Fontan operation. The difference between mean circulatory filling pressure and central venous pressure, a driving force of venous return, is important in determining dynamic changes in central venous pressure in response to changes in ventricular properties or loading conditions. Thus, noninvasive central venous pressure and mean circulatory filling pressure estimation may contribute to optimal management in patients undergoing the Fontan operation. We tested the hypothesis that central venous pressure and mean circulatory filling pressure in those undergoing the Fontan operation can be simply estimated using peripheral venous pressure and arm equilibrium pressure, respectively. METHODS: This study included 30 patients after the Fontan operation who underwent cardiac catheterization (median 8.6, 3.4-42 years). Peripheral venous pressure was measured at the peripheral vein in the upper extremities. Mean circulatory filling pressure was calculated by the changes of arterial pressure and central venous pressure during the Valsalva maneuver. Arm equilibrium pressure was measured as equilibrated venous pressure by rapidly inflating a blood pressure cuff to 200 mm Hg. RESULTS: Central venous pressure and peripheral venous pressure were highly correlated (central venous pressure = 1.6 + 0.68 × peripheral venous pressure, R = 0.86, P < .0001). Stepwise multivariable regression analysis showed that only peripheral venous pressure was a significant determinant of central venous pressure. Central venous pressure was accurately estimated using regression after volume loading by contrast injection (R = 0.82, P < .0001). In addition, arm equilibrium pressure measurements were highly reproducible and robustly reflected invasively measured mean circulatory filling pressure (mean circulatory filling pressure = 9.1 + 0.63 × arm equilibrium pressure, R = 0.88, P < .0001). CONCLUSIONS: Central venous pressure and mean circulatory filling pressure can be noninvasively estimated by peripheral venous pressure and arm equilibrium pressure, respectively. This should help clarify unidentified Fontan pathophysiology and the mechanisms of Fontan failure progression, thereby helping construct effective tailor-made approaches to prevent Fontan failure.