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As more adults survive with congenital heart disease, the need to better understand the long‐term complications, and comorbid disease will become increasingly important. Improved care and survival into the early and late adult years for all patients equitably requires accurate, timely, and comprehensive data to support research and quality‐based initiatives. National data collection in adult congenital heart disease will require a sound foundation emphasizing core ethical principles that acknowledge patient and clinician perspectives and promote national collaboration. In this document we examine these foundational principles and offer suggestions for developing an ethically responsible and inclusive framework for national ACHD data collection.

Background American Heart Association and American College of Cardiology consensus guidelines introduce an adult congenital heart disease anatomic and physiological (AP) classification system. We assessed the association between AP classification and clinical outcomes. Methods and Results Data were collected for 1000 outpatients with ACHD prospectively enrolled between 2012 and 2019. AP classification was assigned based on consensus definitions. Primary outcomes were (1) all‐cause mortality and (2) a composite of all‐cause mortality or nonelective cardiovascular hospitalization. Cox regression models were developed for AP classification, each component variable, and additional clinical models. Discrimination was assessed using the Harrell C statistic. Over a median follow‐up of 2.5 years (1.4–3.9 years), the composite outcome occurred in 185 participants, including 49 deaths. Moderately or severely complex anatomic class (class II/III) and severe physiological stage (stage D) had increased risk of the composite outcome (AP class IID and IIID hazard ratio, 4.46 and 3.73, respectively, versus IIC). AP classification discriminated moderately between patients who did and did not suffer the composite outcome (C statistic, 0.69 [95% CI, 0.67–0.71]), similar to New York Heart Association functional class and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide); it was more strongly associated with mortality (C statistic, 0.81 [95% CI, 0.78–0.84]), as were NT‐proBNP and functional class. A model with AP class and NT‐proBNP provided the strongest discrimination for the composite outcome (C statistic, 0.73 [95% CI, 0.71–0.75]) and mortality (C statistic, 0.85 [95% CI, 0.82–0.88]). Conclusions The addition of physiological stage modestly improves the discriminative ability of a purely anatomic classification, but simpler approaches offer equivalent prognostic information. The AP system may be improved by addition of key variables, such as circulating biomarkers, and by avoiding categorization of continuous variables.

Background Hepatic steatosis, caused by nonalcoholic fatty liver disease, is a leading cause of chronic liver disease. The interplay between hepatic steatosis and the development of liver disease following the Fontan procedure is not well understood. This study examined the prevalence and associations of hepatic steatosis in patients with a Fontan circulation. Methods and Results This was a single‐center retrospective study of 95 patients with a Fontan circulation with liver magnetic resonance imaging performed between 2012 and 2019. The average age at magnetic resonance imaging was 21.5±8.5 years. The percent liver fat signal was determined using magnetic resonance chemical shift‐encoded proton density fat fraction imaging. Hepatic steatosis was defined as liver fat ≥5% and was present in 10.5% of the cohort. The presence of hepatic steatosis was associated with higher body mass index (29±4 versus 24±6 kg/m 2 , P =0.006), a higher frequency of obesity (50% versus 12%, P =0.015), lower high‐density lipoprotein cholesterol (35±9 versus 43±14 mg/dL, P =0.050), and greater subcutaneous fat thickness (2.6±0.7 versus 1.8±1.0 cm, P =0.043). There was no association between hepatic steatosis and cardiovascular imaging or hemodynamic variables from cardiac catheterization. Conclusions Risk factors for hepatic steatosis in patients with Fontan circulation include obesity and dyslipidemia, similar to what is seen in the general population. Fontan hemodynamics were not associated with hepatic steatosis.

Background Hypocholesterolemia is a marker of liver disease, and patients with a Fontan circulation may have hypocholesterolemia secondary to Fontan‐associated liver disease or inflammation. We investigated circulating lipids in adults with a Fontan circulation and assessed the associations with clinical characteristics and adverse events. Methods and Results We enrolled 164 outpatients with a Fontan circulation, aged ≥18 years, in the Boston Adult Congenital Heart Disease Biobank and compared them with 81 healthy controls. The outcome was a combined outcome of nonelective cardiovascular hospitalization or death. Participants with a Fontan (median age, 30.3 [interquartile range, 22.8–34.3 years], 42% women) had lower total cholesterol (149.0±30.1 mg/dL versus 190.8±41.4 mg/dL, P P P r =−0.30, P r =−0.27, P =0.0006), and alanine aminotransferase ( r =−0.18, P =0.02) but not with other liver disease markers. Lower high‐density lipoprotein cholesterol was independently associated with greater hazard for the combined outcome adjusting for age, sex, body mass index, and functional class (hazard ratio [HR] per decrease of 10 mg/dL, 1.37; 95% CI, 1.04–1.81 [ P =0.03]). This relationship was attenuated when log high‐sensitivity C‐reactive protein was added to the model (HR, 1.26; 95% CI, 0.95–1.67 [ P =0.10]). Total cholesterol, low‐density lipoprotein cholesterol, and triglycerides were not associated with the combined outcome. Conclusions The Fontan circulation is associated with decreased cholesterol levels, and lower high‐density lipoprotein cholesterol is associated with adverse outcomes. This association may be driven by inflammation. Further studies are needed to understand the relationship between the severity of Fontan‐associated liver disease and lipid metabolism.

Background Adults with a Fontan circulation tend to have myopenia and elevated adiposity when measured by dual energy x‐ray absorptiometry. Bioelectrical impedance analysis is an alternative validated approach to assess body composition. We used bioelectrical impedance analysis to compare body composition between pediatric patients with a Fontan circulation and control individuals without heart disease. Methods and Results A retrospective chart review identified all patients aged P =0.005), skeletal muscle mass (−13.6±1.4%; Z‐score, −0.5±1; P =0.004), skeletal muscle indexed to height (−10.3±13.3%; Z‐score, −0.5±1; P =0.005), and higher percent body fat (+13.8±18.6%; Z‐score, 0.4±1.2; P =0.03). Greater skeletal muscle mass was associated with higher peak oxygen consumption ( r 2 =0.52, P r 2 =0.68, P P =0.048) and higher body fat percentage ( P =0.003). Conclusions The Fontan circulation is associated with marked myopenia and increased adiposity. Higher muscle mass was associated with better exercise capacity. Fontan complications are associated with lower muscle mass and increased adiposity.

The Fontan procedure has provided patients with single ventricle physiology extended survival into adulthood and in many cases has improved their quality of life. Atrioventricular valve regurgitation ( AVVR ) is common in single ventricle patients and is associated with increased risk of mortality. AVVR is more common in patients with a systemic tricuspid or common atrioventricular valve but is generally progressive irrespective of underlying valve morphology. AVVR can be attributable to diverse structural and functional abnormalities at multiple levels of the valvar apparatus, as well as ventricular dysfunction and dilation. Multiple imaging modalities including recent advances in 3‐dimensional echocardiography and cross‐sectional imaging have been used to further understand AVVR . Surgery to address AVVR must be tailored to the underlying mechanism and the timing of surgical repair should be chosen carefully. In this review, we discuss the etiologies, treatment options, surgical timing, and outcomes of valve repair or replacement for AVVR in patients with single ventricle congenital heart disease, with a focus on those with a Fontan circulation as AVVR is associated with increased risk for Fontan failure and mortality. In‐depth understanding of the current literature will help guide clinicians in their approach and management of AVVR in this population.

Background In adults with acquired heart disease, depression is common and associated with adverse outcomes. Depression may also be important in adults with congenital heart disease ( CHD ). Methods and Results We conducted a cohort study of outpatients with CHD, aged ≥18 years, enrolled in a prospective biobank between 2012 and 2017. Clinical data were extracted from medical records. Survival analysis assessed the relationship between depression, defined by a history of clinical diagnosis of major depression, with all‐cause mortality and a composite outcome of death or nonelective cardiovascular hospitalization. A total of 1146 patients were enrolled (age, 38.5±13.8 years; 49.6% women). Depression had been diagnosed in 219 (prevalence=19.1%), and these patients were more likely to have severely complex CHD (41.3% versus 33.7%; P =0.028), cyanosis (12.1% versus 5.7%; P =0.003), and worse functional class (≥ II ; 33.3% versus 20.4%; P P P P CI , 1.4–6.4; P =0.005) and the composite outcome (multivariable hazard ratio, 1.6; 95% CI, 1.1–2.5; P =0.025), adjusting for age, sex, history of atrial arrhythmia, systolic ventricular function, CHD complexity, and corrected QT interval. Conclusions In adults with CHD, major depression is associated with impaired functional status, heart failure, systemic inflammation, and increased risk for adverse outcomes.

Background People with a Fontan circulation experience a range of physical, psychosocial and neurodevelopmental challenges alongside, or caused by, their cardiac condition, with significant consequences for health‐related quality of life ( HRQOL ). We meta‐analyzed HRQOL outcomes reported by people with a Fontan circulation or their proxies and evaluated predictors of poorer HRQOL . Methods and Results Six electronic databases were searched for peer‐reviewed, English‐language articles published before March 2019. Standardized mean differences (SMD) were calculated using fixed and random‐effects models. Fifty articles reporting on 29 unique studies capturing HRQOL outcomes for 2793 people with a Fontan circulation and 1437 parent‐proxies were analyzed. HRQOL was lower in individuals with a Fontan circulation compared with healthy referents or normative samples (SMD, −0.92; 95% CI , −1.36 to −0.48; P HRQOL domains, with the largest differences found for physical (SMD, −0.90; 95% CI , −1.13 to −0.67; P CI , −0.90 to −0.52; P P =0.004), and diagnosis of hypoplastic left heart was associated with poorer social functioning (β=−0.007; P =0.048). Sensitivity analyses showed use of the PedsQL Core Module was associated with lower HRQOL scores compared with the Short‐Form Health Survey‐36. Conclusions HRQOL outcomes for people with a Fontan circulation are lower than the general population. Optimal care acknowledges the lifelong impact of the Fontan circulation on HRQOL and offers targeted strategies to improve outcomes for this growing population.

Background This study assessed trends in heart failure ( HF) hospitalizations and health resource use in patients with adult congenital heart disease ( ACHD ). Methods and Results The Nationwide Inpatient Sample was used to compare ACHD with non‐ ACHD HF hospitalization and health resource trends. Health resource use was assessed using total hospital charges, hospital length of stay, and procedural burden. A total of 87 175±2676 ACHD ‐related HF hospitalizations occurred between 1998 and 2011. During this time, ACHD HF hospitalizations increased 91% (4620±438–8809±740, P ACHD HF hospitalizations ( P =0.003). ACHD HF hospitalization was associated with longer length of stay ( ACHD HF versus non‐ ACHD HF, 7.2±0.09 versus 6.8±0.02 days; P P ACHD HF hospitalization charges increased 258% during the study period ($26 533±$1816 in 1998 versus $94 887±$8310 in 2011; P =0.0002), more than double that for non‐ ACHD HF ( P =0.04). Patients with ACHD HF hospitalized in high‐volume ACHD centers versus others were more likely to undergo invasive hemodynamic testing (30.2±0.6% versus 20.7±0.5%; P P P Conclusions ACHD ‐related HF hospitalizations have increased dramatically in recent years and are associated with disproportionately higher costs, procedural burden, and health resource use.

Background Adults with repaired coarctation of the aorta (CoA) have reduced long‐term survival compared with the general population. This study aimed to determine whether CoA is independently associated with premature ischemic and hemorrhagic stroke in the contemporary era. Methods and Results This was a cross‐sectional study utilizing the National Inpatient Sample database from 2005 to 2014. We hypothesized that patients with CoA are hospitalized with ischemic and hemorrhagic stroke at a younger age compared with the general population. To test this hypothesis, we compared the age at stroke in patients with and without a diagnosis of CoA using simple and multivariable weighted linear regression. Among 4 894 582 stroke discharges, 207 had a diagnosis of CoA. Patients with CoA had strokes at significantly younger age compared with patients without CoA: 18.9 years younger for all‐cause stroke ( P P P P =0.50). However, CoA patients had a higher proportion of subarachnoid hemorrhage (11.8% versus 4.8%, P =0.039) than those without CoA. Among patients who had a hemorrhagic stroke, the prevalence of unruptured intracranial aneurysms was higher in patients with CoA compared with those without CoA (23.3% versus 2.5%, P =0.002). Conclusions Patients with CoA have both ischemic and hemorrhagic strokes at significantly younger ages compared with the general population.

Mandalenakis and colleagues present a population‐based analysis of the risk of stroke in over 25 000 patients with congenital heart disease (CHD).[1][1] The investigators identified patients from a Swedish registry, which included almost all cardiothoracic procedures and hospitalizations between

Background Galectin‐3 may play a role in cardiac and noncardiac fibrosis, and elevated circulating levels of this protein predict adverse outcomes in patients with heart failure who do not have congenital heart disease. We investigated galectin‐3 in adults with single‐ventricle Fontan circulation, patients who are prone to premature clinical deterioration in the context of extensive multiorgan fibrosis. Methods and Results We measured plasma galectin‐3 concentrations in 70 ambulatory adult Fontan patients and 21 age‐ and sex‐matched control participants. Galectin‐3 level was significantly higher in the Fontan group (11.85 ng/mL, interquartile range 9.9 to 15.0 ng/mL) versus the control group (9.4 ng/mL, interquartile range 8.2 to 10.8 ng/mL; P 2 SD above the control group mean value) had a higher risk of nonelective hospitalization or death (hazard ratio 6.0, 95% CI 2.1 to 16.8, P CI 2.4 to 35.2, P =0.001). Conclusions Galectin‐3 concentrations are elevated among adults with a Fontan circulation, and elevated galectin‐3 is associated with an increased risk of nonelective cardiovascular hospitalization or death.