Fibrosing Mediastinitis Caused by Histoplasmosis in an Adolescent.

Fibrosing mediastinitis (FM) is a rare, potentially progressive disease resulting from an idiosyncratic immune response to a variety of stimuli that lead to fibrous infiltration of the mediastinum and possible narrowing of the bronchovascular structures. We report an unusual case of FM in a pediatric patient presenting as myopericarditis and progressing to pericardial thickening and encasement of the mediastinal vascular structures needing surgical intervention. Imaging, including transthoracic echocardiography, cardiac computed tomography, and cardiac magnetic resonance played a crucial role in the diagnosis, assessment, and follow-up. Contrast-enhanced computed tomography can be especially helpful to demonstrate potential findings associated with FM.

Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation.

BACKGROUND: The impact of Fontan-associated liver disease (FALD) on post-transplant mortality and indications for combined heart-liver transplant (CHLT) in adult Fontan patients remains unknown. OBJECTIVES: The purpose of this study was to assess the impact of FALD on post-transplant outcomes and compare HT vs CHLT in adult Fontan patients. METHODS: We performed a retrospective-cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers. Inclusion criteria were as follows: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at referral. Pretransplant FALD score was calculated using the following: 1) cirrhosis; 2) varices; 3) splenomegaly; or 4) ≥2 paracenteses. RESULTS: A total of 131 patients (91 HT and 40 CHLT) were included. CHLT recipients were more likely to be older (P = 0.016), have a lower hemoglobin (P = 0.025), require ≥2 diuretic agents pretransplant (P = 0.051), or be transplanted in more recent decades (P = 0.001). Postmatching, CHLT demonstrated a trend toward improved survival at 1 year (93% vs 74%; P = 0.097) and improved survival at 5 years (86% vs 52%; P = 0.041) compared with HT alone. In patients with a FALD score ≥2, CHLT was associated with improved survival (1 year: 85% vs 62%; P = 0.044; 5 years: 77% vs 42%; P = 0.019). In a model with transplant decade and FALD score, CHLT was associated with improved survival (HR: 0.33; P = 0.044) and increasing FALD score was associated with worse survival (FALD score: 2 [HR: 14.6; P = 0.015], 3 [HR: 22.2; P = 0.007], and 4 [HR: 27.8; P = 0.011]). CONCLUSIONS: Higher FALD scores were associated with post-transplant mortality. Although prospective confirmation of our findings is necessary, compared with HT alone, CHLT recipients were older with higher FALD scores, but had similar survival overall and superior survival in patients with a FALD score ≥2.

Morbidity and Mortality in Adult Fontan Patients After Heart or Combined Heart-Liver Transplantation.

BACKGROUND: An increasing number of adult Fontan patients require heart transplantation (HT) or combined heart-liver transplant (CHLT); however, data regarding outcomes and optimal referral time remain limited. OBJECTIVES: The purpose of this study was to define survivorship post-HT/CHLT and predictors of post-transplant mortality, including timing of referral, in the adult Fontan population. METHODS: A retrospective cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers in the United States and Canada was performed. Inclusion criteria included the following: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at the time of referral. Date of "failing" Fontan was defined as the earliest of the following: worsening fluid retention, new ascites, refractory arrhythmia, "failing Fontan" diagnosis by treating cardiologist, or admission for heart failure. RESULTS: A total of 131 patients underwent transplant, including 40 CHLT, from 1995 to 2021 with a median post-transplant follow-up time of 1.6 years (Q1 0.35 years, Q3 4.3 years). Survival was 79% at 1 year and 66% at 5 years. Survival differed by decade of transplantation and was 87% at 1 year and 76% at 5 years after 2010. Time from Fontan failure to evaluation (HR/year: 1.23 [95% CI: 1.11-1.36]; P < 0.001) and markers of failure, including NYHA functional class IV (HR: 2.29 [95% CI: 1.10-5.28]; P = 0.050), lower extremity varicosities (HR: 3.92 [95% CI: 1.68-9.14]; P = 0.002), and venovenous collaterals (HR: 2.70 [95% CI: 1.17-6.20]; P = 0.019), were associated with decreased post-transplant survival at 1 year in a bivariate model that included transplant decade. CONCLUSIONS: In our multicenter cohort, post-transplant survival improved over time. Late referral after Fontan failure and markers of failing Fontan physiology, including worse functional status, lower extremity varicosities, and venovenous collaterals, were associated with post-transplant mortality.

The Impact of and Barriers to Cardiac Rehabilitation Following Cardiac Surgery in the Adult With Congenital Heart Disease.

INTRODUCTION: There is a paucity of literature evaluating the impact of and barriers to participation in cardiac rehabilitation (CR) in the adult congenital heart disease population. The aims of this study were to evaluate the impact of CR on physical activity and health-related quality of life, as well as to evaluate the barriers to participation in CR in a post-operative adult congenital heart disease population. METHODS: Patients ≥18 yr of age seen in the Wisconsin Adult Congenital Heart Disease Program and post-open sternotomy surgery from 2010-2015 were eligible for inclusion. Subjects were mailed a novel physical activity survey and the validated EuroQOL-5D 3L health questionnaire. A retrospective medical record review was performed to extract demographic and clinical data. RESULTS: One hundred thirty-five patients underwent open sternotomy surgery from 2010-2015. Of these, 22 were excluded because of intellectual disability, three opted out, and three survey packets were returned to the sender. A total of 54 of the remaining 107 patients returned completed surveys. Of these, 47 (87%) were referred to CR. Thirty-five patients completed the entire CR program (74%). Those who completed CR were more likely to develop a home/independent exercise program (P = .027). Barriers to completing CR included insurance coverage, psychiatric disease, and a perception that CR would not be of benefit. CONCLUSION: Completing CR was associated with developing a home/independent exercise program in post-sternotomy adult patients with congenital heart disease. Barriers to participating in and completing CR in this population could lead to an improved completion rate if modified.

The association between cardiac magnetic resonance-derived aortic stiffness parameters and aortic dilation in young adults with bicuspid aortic valve: With and without coarctation of aorta.

Background: Bicuspid aortic valve (BAV) is associated with progressive aortic dilation. Studies in aortopathies have shown a correlation between increased aortic stiffness and aortic dilation. We aimed to evaluate aortic stiffness measures as predictors of progressive aortic dilation by cardiac magnetic resonance (CMR) in BAV patients. Methods: This is a retrospective study of 49 patients with BAV (median age 21.1 years at first CMR visit) with ≥2 CMR at the Wisconsin Adult Congenital Heart Disease Program (WAtCH). Circumferential aortic strain, distensibility, and ß-stiffness index were obtained from CMR-derived aortic root cine imaging, and aortic dimensions were measured at aortic root and ascending aorta. A linear mixed-model and logistic regression were used to identify important predictors of progressive aortic dilation. Results: Over a median of 3.8 years follow-up, the annual growth rates of aortic root and ascending aorta dimensions were 0.25 and 0.16 mm/year, respectively. Aortic strain and distensibility decreased while ß-stiffness index increased with age. Aortic root strain and distensibility were associated with progressive dilation of the ascending aorta. Baseline aortic root diameter was an independent predictor of >1 mm/year growth rate of the aortic root (adjusted OR 1.34, 95 % CI 1.03-1.74, p = 0.028). Most patients (61 %) had coexisting coarctation of aorta. Despite the higher prevalence of hypertension in patients with aortic coarctation, hypertension or coarctation had no effect on baseline aorta dimensions, stiffness, or progressive aortic dilation. Conclusion: Some CMR-derived aortic stiffness parameters correlated with progressive aortic dilation in BAV and should be further investigated in larger and older BAV cohorts.

Prevalence, Risk Factors, and Impact of Obstructive Sleep Apnea in Adults with Congenital Heart Disease.

The objective of our study was to determine the prevalence, risk factors, and the impact of obstructive sleep apnea (OSA) in the adult with congenital heart disease (ACHD). One hundred forty-nine consecutive patients seen in our ACHD program were screened for OSA using the Berlin Questionnaire. Demographic and clinical details on subjects were collected through a chart review. Clinical variables were analyzed to determine risk factors for positive OSA screen, as well as associated outcomes. Seventy-seven (52%) of our cohort were females. The median age of the cohort was 33 years (range = 18-74) and median weight was 79 kg (range = 50-145 kg). Overall, 47 (31%) of our cohort were found to have a positive OSA screen using the Berlin questionnaire. Median age of the patients whom tested positive was 34 years. Compared to patients with a negative screen, patients with a positive OSA screen were more likely to be heavier with a median weight of 99 kg vs 71 kg (p < 0.01) and a larger BMI (31 vs 25 kg/m2, p < 0.01). Overall, 55% of patients whom screened positive were obese (defined as a BMI > 30) compared to 15% in the negative group (p < 0.02). Patients with a positive screen were more likely to have other co-morbidities including diabetes (p < 0.04), hypertension (p < 0.05), depression (p < 0.002), and were more likely to have decreased exercise capacity (p < 0.01) and a defibrillator (p < 0.007). Our data demonstrates that OSA is common in the ACHD patient and is associated with increasing weight and BMI. Patients with a positive screen are at increased risk for multiple co morbidities including diabetes, hypertension, and depression. We believe our data supports the use of screening protocols for OSA in the ACHD population in effort to identify early, treat, and potentially prevent late complications.

Neonatal Assessment of Infants with Heterotaxy.

Heterotaxy is a generalized term for patients who have an abnormality of laterality that cannot be described as situs inversus. Infants with heterotaxy can have significant anatomic and medical complexity and require personalized, specialized care, including comprehensive anatomic assessment. Common and rare anatomic findings are reviewed by system to help guide a thorough phenotypic evaluation. General care guidelines and considerations unique to this patient population are included. Future directions for this unique patient population, particularly in light of improved neonatal survival, are discussed.

Novel KLHL26 variant associated with a familial case of Ebstein's anomaly and left ventricular noncompaction.

BACKGROUND: Ebstein's anomaly (EA) is a rare congenital heart disease of the tricuspid valve and right ventricle. Patients with EA often manifest with left ventricular noncompaction (LVNC), a cardiomyopathy. Despite implication of cardiac sarcomere genes in some cases, very little is understood regarding the genetic etiology of EA/LVNC. Our study describes a multigenerational family with at least 10 of 17 members affected by EA/LVNC. METHODS: We performed echocardiography on all family members and conducted exome sequencing of six individuals. After identifying candidate variants using two different bioinformatic strategies, we confirmed segregation with phenotype using Sanger sequencing. We investigated structural implications of candidate variants using protein prediction models. RESULTS: Exome sequencing analysis of four affected and two unaffected members identified a novel, rare, and damaging coding variant in the Kelch-like family member 26 (KLHL26) gene located on chromosome 19 at position 237 of the protein (GRCh37). This variant region was confirmed by Sanger sequencing in the remaining family members. KLHL26 (c.709C > T p.R237C) segregates only with EA/LVNC-affected individuals (FBAT p < .05). Investigating structural implications of the candidate variant using protein prediction models suggested that the KLHL26 variant disrupts electrostatic interactions when binding to part of the ubiquitin proteasome, specifically Cullin3 (CUL3), a component of E3 ubiquitin ligase. CONCLUSION: In this familial case of EA/LVNC, we have identified a candidate gene variant, KLHL26 (p.R237C), which may have an important role in ubiquitin-mediated protein degradation during cardiac development.

Three year experience of a clinical cardiovascular genetics program for infants with congenital heart disease.

OBJECTIVE: To describe the first 3 years of experience of having an inpatient "cardiogenetics" program which involves medical geneticist assessment of infants with major congenital heart disease (CHD) requiring surgical intervention in the first year of life. PATIENTS: Patients less than a year of age admitted to Children's Hospital of Wisconsin's Herma Heart Institute for surgical intervention for CHD seen by the cardiogenetics program. Patients with major trisomies (13, 18, and 21) were excluded. OUTCOME MEASURES: Utilization and yield of genetic testing, and diagnostic rate were assessed as outcome measures and compared to a baseline time period and a genetic testing protocol time period. RESULTS: There were 201 infants with CHD evaluated by the cardiogenetics program over 3 years. A total of patients 46 patients of the 196 who underwent genetic testing had multiple tests completed. This is a significant decrease from the baseline (247/329, P < .0001) and from the genetic testing protocol (29/81, P < .0387) time periods. The diagnostic rate was 33% which is significantly increased compared to the baseline rate of 15% (80/524, P < .0001) and trends toward a significant increase during the testing protocol rate (25/113, P = .0520). The number of dual diagnosis increased to 9 of 201 compared to the baseline (2/524) and the genetic testing protocol (1/113) time periods. The rate of incidental diagnoses altering care increased to 6 of 201 from the baseline (1/524) and the genetic testing protocol (1/113) time periods. CONCLUSION: An inpatient cardiogenetics program significantly increases the diagnostic rate, the detection of complex phenotypes with dual diagnoses, the identification of incidental genetic diagnoses associated with changes in care, and significantly decreases the likelihood of multiple tests being completed on an individual patient. Increased medical geneticist involvement in programs that care for infants with CHD should be encouraged to improve patient care and genetic testing utilization.

Neurocognitive Impairment and Its Long-term Impact on Adults With Congenital Heart Disease.

It is well-recognized now that adult survivors with congenital heart disease (ACHD) are at risk for non-cardiac co-morbidities and complications that can impact symptoms and clinical outcomes. Cognitive dysfunction, in particular, is common in this population, but likely an under-recognized and undertreated cause for long-term morbidity. Abnormal cognitive function has a major impact on all aspects of quality of life, including employment opportunities, educational attainment, and the ability to maintain meaningful social relationships, such as marriage. The association and impact of cognitive dysfunction in ACHD is not fully understood and continues to be understudied. Nevertheless, cognitive dysfunction may be a potentially modifiable risk factor in this population that is amenable to intervention, which may in-turn translate to improved outcomes. This review summarizes our current understanding of the prevalence, impact, and management of cognitive dysfunction in ACHD.

Identifying self-reported neurocognitive deficits in the adult with congenital heart disease using a simple screening tool.

OBJECTIVE: Children with congenital heart disease (CHD) and adults with acquired heart disease are at an increased risk of neurocognitive impairment. The objective of this study was to determine the prevalence of self-reported neurocognitive impairment and its risk factors in the adult congenital heart disease (ACHD) population. DESIGN: The Wisconsin Adult Congenital Heart Disease Program recently began screening ACHD patients to identify those with significant self-perceived neurocognitive impairments. Screening consists of using a validated neuro-oncology screening instrument that has been modified for the ACHD population. Patients who answer this survey in a predetermined fashion consistent with significant self-perceived neurocognitive deficits are referred for a formal neurocognitive evaluation. Demographic and clinical information are obtained by chart review. RESULTS: Three hundred ten patients (49% males) completed the screening process. The average age was 30 years (range: 17-69 years). For the cohort, 57 (18%) patients had no prior cardiac surgeries, 85 (28%) one surgery, 77 (25%) two, and 91 (29%) at least three surgeries. Of those screened, 106 (34%) met criteria for a formal neurocognitive evaluation. Patients who were referred had undergone a greater number of prior cardiac surgeries (2.2 vs 1.7, P = .008) and were more likely to have severe complexity CHD (P = .006). Of those patients who were referred, the worst perceived functioning was in math and attention. CONCLUSION: There is a high prevalence of ACHD patients with significant self-perceived neurocognitive deficits. Simple screening questionnaires may help identify those patients at high risk and allow for timely and appropriate referral for formal neurocognitive evaluation, diagnosis, and therapy.

Genetic evaluation of patients with congenital heart disease.

PURPOSE OF REVIEW: The aim of this study is to review genetics of congenital heart disease (CHD) with a focus on clinical applications, genetic testing and clinical challenges. RECENT FINDINGS: With improved clinical care, there is a rapidly expanding population of adults, especially women, with CHD who have not undergone contemporary genetic assessment and do not understand their risk for having a child with CHD. Many patients have never undergone assessment or had genetic testing. A major barrier is medical geneticist availability, resulting in this burden of care shifting to providers outside of genetics. Even with current understanding, the cause for the majority of cases of CHD is still not known. There are significant gaps in knowledge in the realms of more complex causes such as noncoding variants, multigenic contribution and small structural chromosomal anomalies. SUMMARY: Standard assessment of patients with CHD, including adult survivors, is indicated. The best first-line genetic assessment for most patients with CHD is a chromosomal microarray, and this will soon evolve to be genomic sequencing with copy number variant analysis. Due to lack of medical geneticists, creative solutions to maximize the number of patients with CHD who undergo assessment with standard protocols and plans for support with result interpretation need to be explored.

Preoperative Evaluation of Adult Congenital Heart Disease Patients for Non-cardiac Surgery.

PURPOSE OF REVIEW: Highlight the extracardiac comorbidities that adult congenital heart disease patients and summarize the current recommendations for non-cardiac surgery. RECENT FINDINGS: Adult congenital heart disease patients are living longer, becoming more complex and developing adult comorbidities as they age. These patients have multiorgan involvement including higher prevalence of kidney disease and decreased lung function. Non-cardiac comorbidities can complicate surgery in this patient population. Most patients have non-cardiac surgery in community settings. These settings may increase adverse events during and in the post-operative period. Survival is improved when moderate and complex patients are seen in regional referral centers. Improved awareness of long-term complications of congenital heart disease and extracardiac comorbidities for adult congenital heart disease patients is needed. Appropriate care settings with both congenital heart disease expertise and adult subspecialty care reduces morbidity and mortality in these complex patients.

When the Heart Is Not to Blame: Managing Lung Disease in Adult Congenital Heart Disease.

It is well-recognized now that adult survivors with congenital heart disease (CHD) are at risk for non-cardiac co-morbidities and complications that can impact symptoms and clinical outcomes. Lung disease, in particular, is common in this population, but likely an under-recognized and undertreated cause for long-term morbidity. Abnormal lung function contributes to exercise intolerance and is associated with a higher risk for mortality in this population. The exact mechanisms that contribute to abnormal measurements of lung function are not entirely known, and are likely multifactorial and variable depending on the underlying CHD. Nevertheless, lung disease is a potentially modifiable risk factor in this patient population, the management of which may result in improved clinical outcomes. This review summarizes our current understanding of the prevalence, impact and management of lung disease in adults with CHD.

Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association.

Life expectancy and quality of life for those born with congenital heart disease (CHD) have greatly improved over the past 3 decades. While representing a great advance for these patients, who have been able to move from childhood to successful adult lives in increasing numbers, this development has resulted in an epidemiological shift and a generation of patients who are at risk of developing chronic multisystem disease in adulthood. Noncardiac complications significantly contribute to the morbidity and mortality of adults with CHD. Reduced survival has been documented in patients with CHD with renal dysfunction, restrictive lung disease, anemia, and cirrhosis. Furthermore, as this population ages, atherosclerotic cardiovascular disease and its risk factors are becoming increasingly prevalent. Disorders of psychosocial and cognitive development are key factors affecting the quality of life of these individuals. It is incumbent on physicians who care for patients with CHD to be mindful of the effects that disease of organs other than the heart may have on the well-being of adults with CHD. Further research is needed to understand how these noncardiac complications may affect the long-term outcome in these patients and what modifiable factors can be targeted for preventive intervention.

Forced vital capacity predicts morbidity and mortality in adults with repaired tetralogy of Fallot.

OBJECTIVE: Abnormal lung function characterized by a reduced forced vital capacity (FVC) is common in adults with repaired tetralogy of Fallot (TOF) and is associated with previous thoracotomies and sternotomies. The impact of abnormal lung function on clinical outcomes in adult patients with repaired TOF is unclear. The aim of this study was to determine the impact of abnormal lung function on the outcome of hospitalization and death in adults with repaired TOF when analyzed with other traditional cardiac risk factors. DESIGN: Retrospective study of adults with repaired TOF, who underwent spirometry between 2000 and 2014. FVC < 60% of predicted was categorized as moderate-to-severely reduced lung function. Primary outcome measure was the combined clinical endpoint of death, cardiac transplantation, or nonelective hospitalization for primary cardiac or respiratory indication. RESULTS: A total of 122 patients were included. Average age at spirometry testing was 31 ± 10.1 years. FVC was < 60% predicted in 23 (19%) patients. During a mean follow-up period of 3.97 ± 2.65 years, 23 (19%) patients reached the combined clinical outcome of nonelective hospitalization and/or death. FVC < 60% predicted was independently associated with the risk for the combined clinical outcome (RR 6.68 (95% CI 2.49-17.94), P < .001). CONCLUSIONS: Abnormal pulmonary function characterized by reduced FVC is common in adults with repaired TOF. Patients with FVC < 60% predicted had a 6 times higher rate of hospitalization and/or death compared to those with FVC ≥ 60%.

Liver health in adults with Fontan circulation: A multicenter cross-sectional study.

OBJECTIVES: Liver disease is an important contributor to morbidity and mortality in patients after Fontan surgery. There has been no large-scale survey of liver health in this population. We sought to explore the prevalence and predictors of liver disease in a multicenter cohort of adults with Fontan physiology. METHODS: Subjects were recruited from 6 adult congenital heart centers. Demographics; clinical history; and laboratory, imaging, and histopathology data were obtained. RESULTS: Of 241 subjects (median age 25.8 years [11.8-59.4], median time since Fontan 20.3 years [5.4-34.5]), more than 94% of those who underwent testing (208 of 221) had at least 1 abnormal liver-related finding. All hepatic imaging (n = 54) and liver histology (n = 68) was abnormal. Subjects with abnormal laboratory values had higher sinusoidal fibrosis stage (2 vs 1, P = .007) and higher portal fibrosis stage (3 vs 1, P = .003) compared with those with all normal values. Low albumin correlated with lower sinusoidal fibrosis stage (1 vs 2; P = .02) and portal fibrosis stage (0 vs 3, P = .002); no other liver studies correlated with fibrosis. Regenerative nodules were seen on 33% of histology specimens. CONCLUSIONS: Regardless of modality, findings of liver disease are common among adults with Fontan circulation, even those appearing clinically well. Cirrhosis is present in up to one-third of subjects. Correlations between hepatic fibrosis stage and clinical history or findings on noninvasive testing are few. Further research is needed to identify patients at risk for more severe liver disease and to determine the best methods for assessing liver health in this population.

The prevalence of sexual dysfunction and its association with quality of life in adults with congenital heart disease.

BACKGROUND: The prevalence of sexual dysfunction (SD) and its impact on quality of life (QOL) in adults with congenital heart disease (CHD) is not well known. The aims of this study were to: determine the prevalence of SD, evaluate the risk factors associated with SD, and determine the association between SD and QOL in adults with CHD. METHODS: This was a cross-sectional study of adults (≥18years) with CHD presenting for routine follow-up at our institution. Subjects completed the CDC HRQOL-14 "Health Days Measure" to assess mental and physical health, and either the Sexual Health Inventory for Men or the Female Sexual Function Index to assess sexual function. Baseline characteristics were obtained via chart review. RESULTS: 105 subjects were enrolled. The mean age was 31.9±11.7years, 53 (51%) were men, 81% were NYHA Functional Class 1, and 76% had moderate or complex CHD. The rates of SD were 28% overall in the cohort, 30% in men and 25% in women. Men with SD were more likely to be taking spironolactone (p<0.001) and digoxin (p=0.002). Men with SD reported a greater number of days of poor mental health (p=0.004), feeling anxious, worried or tense (p=0.003), needing assistance (p=0.042), and inhibited activity of daily living (p=0.009). Women with SD were more likely to have atrial arrhythmias (p=0.002) and to report fewer days feeling healthy and energetic (p=0.031). CONCLUSIONS: SD is highly prevalent and associated with several indicators of worse health-related QOL in this young and well-functioning population.

Predictive value of biomarkers of hepatic fibrosis in adult Fontan patients.

BACKGROUND: Hepatic fibrosis is highly prevalent in individuals with Fontan circulation. FibroSure (LabCorp, Burlington, NC) and hyaluronic acid (HA) have been validated for assessment of hepatic fibrosis in several forms of liver disease. We sought to determine whether these tests could identify Fontan patients with advanced hepatic fibrosis or cirrhosis. METHODS: Subjects who had liver biopsy and FibroSure or HA testing within 6 months of biopsy were identified from the Alliance for Adult Research in Congenital Cardiology Fontan Liver Health study. Biopsy specimens were scored for degree of sinusoidal and portal fibrosis on a 3- and 5-point scale, respectively. Histologic findings were correlated with FibroSure and HA results. RESULTS: The study included 27 subjects. Median age was 26.8 years (range, 17.4-59.8 years), and the median time since the Fontan surgery was 20.4 years (range, 12.0-31.3 years). FibroSure scores were elevated (>0.21) in 21 of 23 subjects (91%), and the scores for 3 (13%) suggested cirrhosis (>0.74). HA suggested cirrhosis (>46 ng/mL) in 3 of 17 subjects (18%). One subject died during the collection period. Eleven of 26 subjects (42%) had 4/5 or 5/5 portal fibrosis, consistent with cirrhosis; 17 (63%) had 3/3 sinusoidal fibrosis involving >66% of sinusoids. The FibroSure score and HA levels did not correlate with the degree of hepatic fibrosis and did not predict cirrhosis. CONCLUSIONS: Abnormal biomarkers of hepatic fibrosis and specimen-proven hepatic fibrosis are common in adults with Fontan circulation. However, FibroSure and HA do not accurately predict the degree of histologic hepatic fibrosis. Further studies are needed to guide strategies for surveillance of liver disease in this population.