Impact of Appropriate Use Criteria for Cross-Sectional Imaging on Medical Decision-Making in Patients with Conotruncal Defects.

Associations between Appropriate Use Criteria (AUC) ratings and medical decision-making in congenital heart disease are not well-established. We applied the 2020 AUC for multimodality imaging in follow-up care of pediatric and young adult patients with conotruncal defects to evaluate appropriateness of cardiac magnetic resonance (CMR) and computed tomography (CCT) use in this population and impact on clinical decision-making. Records were reviewed and assigned AUC indications and corresponding ratings for CMR and CCT. We examined the relationship between AUC indications, their ratings, and change in management. Of the 200 studies (133 CMR, 67 CCT) performed on 187 patients, no studies were rated Rarely Appropriate (R), and most studies were obtained for routine follow-up (151/200 [75.5%]) and were not prompted by clinical concerns. There were 70/200 (35.0%) studies which led to management changes; these included transcatheter intervention (29/70 [41.4%]), surgical intervention (25/70 [35.7%]), other interventions (10/70 [14.3%]), and medical intervention (6/70 [8.6%]). Among all studies, studies prompted by clinical concerns and studies rated M more frequently resulted in change in management (46.9 vs 31.1%, p = 0.04 and 54.1 vs 30.7%, p = 0.003, respectively). In conclusion, we found that all studies were ordered for indications rated Appropriate (A) or May be Appropriate (M), indicating compliance in ordering practices as outlined by published AUC. Studies ordered for clinical change or rated M more frequently led to management change in patient care. Findings may help inform provider expectations of testing yield in this population and serve as a platform for development of future iterations of AUC.

End-stage heart failure in congenitally corrected transposition of the great arteries: a multicentre study.

BACKGROUND AND AIMS: For patients with congenitally corrected transposition of the great arteries (ccTGA), factors associated with progression to end-stage congestive heart failure (CHF) remain largely unclear. METHODS: This multicentre, retrospective cohort study included adults with ccTGA seen at a congenital heart disease centre. Clinical data from initial and most recent visits were obtained. The composite primary outcome was mechanical circulatory support, heart transplantation, or death. RESULTS: From 558 patients (48% female, age at first visit 36 ± 14.2 years, median follow-up 8.7 years), the event rate of the primary outcome was 15.4 per 1000 person-years (11 mechanical circulatory support implantations, 12 transplantations, and 52 deaths). Patients experiencing the primary outcome were older and more likely to have a history of atrial arrhythmia. The primary outcome was highest in those with both moderate/severe right ventricular (RV) dysfunction and tricuspid regurgitation (n = 110, 31 events) and uncommon in those with mild/less RV dysfunction and tricuspid regurgitation (n = 181, 13 events, P < .001). Outcomes were not different based on anatomic complexity and history of tricuspid valve surgery or of subpulmonic obstruction. New CHF admission or ventricular arrhythmia was associated with the primary outcome. Individuals who underwent childhood surgery had more adverse outcomes than age- and sex-matched controls. Multivariable Cox regression analysis identified older age, prior CHF admission, and severe RV dysfunction as independent predictors for the primary outcome. CONCLUSIONS: Patients with ccTGA have variable deterioration to end-stage heart failure or death over time, commonly between their fifth and sixth decades. Predictors include arrhythmic and CHF events and severe RV dysfunction but not anatomy or need for tricuspid valve surgery.

Design of a multi-institutional neurocognitive discovery study in adult congenital heart disease (MINDS-ACHD).

BACKGROUND: Neurocognitive dysfunction (NCD) is a common comorbidity among children with congenital heart disease (CHD). However, it is unclear how underlying CHD and its sequelae combine with genetics and acquired cardiovascular and neurological disease to impact NCD and outcomes across the lifespan in adults with CHD. METHODS: The Multi-Institutional Neurocognitive Discovery Study in Adults with Congenital Heart Disease (MINDS-ACHD) is a partnership between the Pediatric Heart Network (PHN) and the Adult Alliance for Research in Congenital Cardiology (AARCC) that examines objective and subjective neurocognitive function and genetics in young ACHD. This multicenter cross-sectional pilot study is enrolling 500 young adults between 18 and 30 years with moderate or severe complexity CHD at 14 centers in North America. Enrollment includes 4 groups (125 participants each): (1) d-looped Transposition of the Great Arteries (d-TGA); (2) Tetralogy of Fallot (TOF); (3) single ventricle (SV) physiology; and (4) "other moderately or severely complex CHD." Participants complete the standardized tests from the NIH Toolbox Cognitive Battery, the NeuroQoL, the Hospital Anxiety and Depression Scale, and the PROMIS Global QoL measure. Clinical and demographic variables are collected by interview and medical record review, and an optional biospecimen is collected for genetic analysis. Due to the COVID-19 pandemic, participation may be done remotely. Tests are reviewed by a Neurocognitive Core Laboratory. CONCLUSIONS: MINDS-ACHD is the largest study to date characterizing NCD in young adults with moderate or severely complex CHD in North America. Its results will provide valuable data to inform screening and management strategies for NCD in ACHD and improve lifelong care.

Absent B cells, agammaglobulinemia, and hypertrophic cardiomyopathy in folliculin-interacting protein 1 deficiency.

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondrial numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1-/- animal model. Moreover, we identified either uniparental disomy or copy-number variants (CNVs) in 2 patients, expanding the variant spectrum of this novel inborn error of immunity. The results indicate that FNIP1 deficiency can be caused by complex genetic mechanisms and support the clinical utility of exome sequencing and CNV analysis in patients with broad phenotypes, including agammaglobulinemia and HCM. FNIP1 deficiency is a novel inborn error of immunity characterized by early and severe B-cell development defect, agammaglobulinemia, variable neutropenia, and HCM. Our findings elucidate a functional and relevant role of FNIP1 in B-cell development and metabolism and potentially neutrophil activity.

A Multisite Retrospective Review of Direct Oral Anticoagulants Compared to Warfarin in Adult Fontan Patients.

PURPOSE: Direct oral anticoagulants (DOACs) are not recommended in adult Fontan patients (Level of Evidence C). We hypothesized that DOACs are comparable to warfarin and do not increase thrombotic and embolic complications (TEs) or clinically significant bleeds. METHODS: We reviewed the medical records of adult Fontan patients on DOACs or warfarin at three major medical centers. We identified 130 patients: 48 on DOACs and 107 on warfarin. In total, they were treated for 810 months on DOACs and 5637 months on warfarin. RESULTS: The incidence of TEs in patients on DOACs compared to those on warfarin was not increased in a statistically significant way (hazard ratio [HR] 1.7 and p value 0.431). Similarly, the incidence of nonmajor and major bleeds in patients on DOACs compared to those on warfarin was also not increased in a statistically significant way (HR for nonmajor bleeds in DOAC patients was 2.8 with a p value of 0.167 and the HR for major bleeds was 2.0 with a p value 0.267). In multivariate analysis, congestive heart failure (CHF) was a risk factor for TEs across both groups (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.3-17.6) and bleed history was a risk factor for clinically significant bleeds (OR = 6.8, 95% CI = 2.7-17.2). CONCLUSION: In this small, retrospective multicenter study, the use of DOACs did not increase the risk of TEs or clinically significant bleeds compared to warfarin in a statistically significant way.

Health Care Transition Perceptions Among Parents of Adolescents with Congenital Heart Defects in Georgia and New York.

With increasing survival trends for children and adolescents with congenital heart defects (CHD), there is a growing need to focus on transition from pediatric to adult specialty cardiac care. To better understand parental perspectives on the transition process, a survey was distributed to 451 parents of adolescents with CHD who had recent contact with the healthcare system in Georgia (GA) and New York (NY). Among respondents, 90.7% reported excellent, very good or good health-related quality of life (HRQoL) for their adolescent. While the majority of parents (77.8%) had been told by a provider about their adolescent's need to transition to adult specialty cardiac care, most reported concerns about transitioning to adult care. Parents were most commonly concerned with replacing the strong relationship with pediatric providers (60.7%), locating an appropriate adult provider (48.7%), and accessing adult health insurance coverage (43.6%). These findings may offer insights into transition planning for adolescents with CHD.

Predicting 30-day readmission after congenital heart surgery across the lifespan.

INTRODUCTION: Hospital readmission is an important driver of costs among patients with CHD. We assessed predictors of 30-day rehospitalisation following cardiac surgery in CHD patients across the lifespan. METHODS: This was a retrospective analysis of 981 patients with CHD who had cardiac surgery between January 2011 and December 2012. A multivariate logistic regression model was used to identify demographic, clinical, and surgical predictors of 30-day readmission. Receiver operating curves derived from multivariate logistic modelling were utilised to discriminate between patients who were readmitted and not-readmitted at 30 days. Model goodness of fit was assessed using the Hosmer-Lemeshow test statistic. RESULTS: Readmission in the 30 days following congenital heart surgery is common (14.0%). Among 981 patients risk factors associated with increased odds of 30-day readmission after congenital heart surgery through multivariate analysis included a history of previous cardiac surgery (p < 0.001), longer post-operative length of stay (p < 0.001), as well as nutritional (p < 0.001), haematologic (p < 0.02), and endocrine (p = 0.04) co-morbidities. Patients who underwent septal defect repair had reduced odds of readmission (p < 0.001), as did children (p = 0.04) and adult (p = 0.005) patients relative to neonates. CONCLUSION: Risk factors for readmission include a history of cardiac surgery, longer length of stay, and co-morbid conditions. This information may serve to guide efforts to prevent readmission and inform resource allocation in the transition of care to the outpatient setting. This study also demonstrated the feasibility of linking a national subspecialty registry to a clinical and administrative data repository to follow longitudinal outcomes of interest.

Superior Mesenteric Arterial Flow Pattern is Associated with Major Adverse Events in Adults with Fontan Circulation.

Factors contributing to the failure of Fontan circulation in adults are poorly understood. Reduced superior mesenteric arterial (SMA) flow has been identified in pediatric Fontan patients with protein-losing enteropathy. SMA flow has not been profiled in an adult Fontan population and its association with adverse events is unknown. We aimed to examine associations between SMA flow patterns and adverse events in adult Fontan patients. We performed a retrospective review of adult Fontan patients who underwent echocardiograms between 2008 and 2014. SMA Doppler data included peak systolic and end-diastolic velocity and velocity time integral (VTI). Systolic/diastolic (S/D) ratio and resistive index were calculated. The relationship between SMA flow parameters and major adverse events (death or transplantation) was examined using proportional hazard Cox regression analyses. Kaplan-Meyer analysis was conducted to construct survival curve of patients with and without adverse events. 91 post-Fontan adult patients (76 % systemic left ventricle, 20 % atriopulmonary Fontan, mean age 27.9 years) were analyzed. Adverse events occurred in nine patients (death = 4, transplant = 5). When compared with the non-event group, the event group had increased end-diastolic velocity [hazard ratio (HR) 1.5, 95 % confidence interval (CI) 1.1-1.8; p = 0.002], increased systolic VTI (HR 1.5, 95 % CI 1.1-2.2, p = 0.02), increased diastolic VTI (HR 1.7, 95 % CI 1.2-2.4, p = 0.004), decreased S/D velocity ratio (HR 0.32, 95 % CI 0.14-0.71, p = 0.006), decreased S/D VTI ratio (HR 0.76, 95 % CI 0.61-0.97, p = 0.02), and decreased resistive index (HR 0.29, 95 % CI 0.14-0.60, p = 0.0007). Increased end-diastolic velocity and VTI in mesenteric arterial flow, with lower systolic/diastolic ratio and resistive index, were associated with death and need for heart transplant in adult Fontan patients. The mesenteric hyperemic flow was also associated with clinical signs of portal venous outflow obstruction, suggesting the presence of vasodilatory state in end-stage adult Fontan circulation.

Immunologic Aging in Adults with Congenital Heart Disease: Does Infant Sternotomy Matter?

Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized that lymphopenia in patients with adult congenital heart disease (ACHD) would be reflective of premature T cell maturation and exhaustion. Adults with ACHD who had sternotomy to repair congenital heart disease as infants (<1 year) and age-matched ACHD patients without prior sternotomy were studied using polychromatic flow cytometry interrogating markers of lymphocyte maturation, exhaustion and senescence. Group differences were analyzed using Mann-Whitney U and Fisher's exact tests. Eighteen ACHD patients aged 21-40 years participated: 10 cases and 8 controls. Median age at sternotomy for cases was 52 days. Cases and controls were matched for age (28.9 vs. 29.1 years; p = 0.83), gender (p = 0.15) and race (p = 0.62) and had similar case complexity. Cases had a lower mean percentage of cytotoxic CD8 lymphocytes compared to controls (26.8 vs. 33.9 %; p = 0.016), with fewer naive, undifferentiated CD8 T cells (31.0 vs. 53.6 %; p = 0.027). CD8 cells expressing PD1, a marker of immune exhaustion, trended higher in cases versus controls (25.6 vs. 19.0 %; p = 0.083). Mean percentage of CD4 cells was higher in cases versus controls (65.6 vs. 59.6 %; p = 0.027), without differences in CD4 T cell maturation subtype. In summary, ACHD patients who undergo sternotomy as infants exhibit differences in T lymphocyte composition compared to ACHD controls, suggesting accelerated immunologic exhaustion. Investigation is warranted to assess the progressive nature and clinical impact of this immune phenotypic change.

The epidemiology of heart failure in adults with congenital heart disease.

The impact of lifelong exposure to myocardial dysfunction in populations with congenital heart disease (CHD) is becoming increasingly recognized. Most children born with CHD now reach adulthood and the long-term sequelae of treatment are contributing to substantial comorbidity. The combination of structural changes present at birth with changes resulting from cardiac surgery can result in heart failure. This article reports on the current state of knowledge on the epidemiology of heart failure in this patient population.

Racial and Ethnic Disparities in Health Care Usage and Death by Neighborhood Poverty Among Individuals With Congenital Heart Defects, 4 US Surveillance Sites, 2011 to 2013.

BACKGROUND: Socioeconomic factors may lead to a disproportionate impact on health care usage and death among individuals with congenital heart defects (CHD) by race, ethnicity, and socioeconomic factors. How neighborhood poverty affects racial and ethnic disparities in health care usage and death among individuals with CHD across the life span is not well described. METHODS AND RESULTS: Individuals aged 1 to 64 years, with at least 1 CHD-related International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code were identified from health care encounters between January 1, 2011, and December 31, 2013, from 4 US sites. Residence was classified into lower- or higher-poverty neighborhoods on the basis of zip code tabulation area from the 2014 American Community Survey 5-year estimates. Multivariable logistic regression models, adjusting for site, sex, CHD anatomic severity, and insurance-evaluated associations between race and ethnicity, and health care usage and death, stratified by neighborhood poverty. Of 31 542 individuals, 22.2% were non-Hispanic Black and 17.0% Hispanic. In high-poverty neighborhoods, non-Hispanic Black (44.4%) and Hispanic (47.7%) individuals, respectively, were more likely to be hospitalized (adjusted odds ratio [aOR], 1.2 [95% CI, 1.1-1.3]; and aOR, 1.3 [95% CI, 1.2-1.5]) and have emergency department visits (aOR, 1.3 [95% CI, 1.2-1.5] and aOR, 1.8 [95% CI, 1.5-2.0]) compared with non-Hispanic White individuals. In high poverty neighborhoods, non-Hispanic Black individuals with CHD had 1.7 times the odds of death compared with non-Hispanic White individuals in high-poverty neighborhoods (95% CI, 1.1-2.7). Racial and ethnic disparities in health care usage were similar in low-poverty neighborhoods, but disparities in death were attenuated (aOR for non-Hispanic Black, 1.2 [95% CI=0.9-1.7]). CONCLUSIONS: Racial and ethnic disparities in health care usage were found among individuals with CHD in low- and high-poverty neighborhoods, but mortality disparities were larger in high-poverty neighborhoods. Understanding individual- and community-level social determinants of health, including access to health care, may help address racial and ethnic inequities in health care usage and death among individuals with CHD.

Supervised Text Classification System Detects Fontan Patients in Electronic Records With Higher Accuracy Than ICD Codes.

Background The Fontan operation is associated with significant morbidity and premature mortality. Fontan cases cannot always be identified by International Classification of Diseases (ICD) codes, making it challenging to create large Fontan patient cohorts. We sought to develop natural language processing-based machine learning models to automatically detect Fontan cases from free texts in electronic health records, and compare their performances with ICD code-based classification. Methods and Results We included free-text notes of 10 935 manually validated patients, 778 (7.1%) Fontan and 10 157 (92.9%) non-Fontan, from 2 health care systems. Using 80% of the patient data, we trained and optimized multiple machine learning models, support vector machines and 2 versions of RoBERTa (a robustly optimized transformer-based model for language understanding), for automatically identifying Fontan cases based on notes. For RoBERTa, we implemented a novel sliding window strategy to overcome its length limit. We evaluated the machine learning models and ICD code-based classification on 20% of the held-out patient data using the F1 score metric. The ICD classification model, support vector machine, and RoBERTa achieved F1 scores of 0.81 (95% CI, 0.79-0.83), 0.95 (95% CI, 0.92-0.97), and 0.89 (95% CI, 0.88-0.85) for the positive (Fontan) class, respectively. Support vector machines obtained the best performance (P<0.05), and both natural language processing models outperformed ICD code-based classification (P<0.05). The sliding window strategy improved performance over the base model (P<0.05) but did not outperform support vector machines. ICD code-based classification produced more false positives. Conclusions Natural language processing models can automatically detect Fontan patients based on clinical notes with higher accuracy than ICD codes, and the former demonstrated the possibility of further improvement.

A machine learning model for predicting congenital heart defects from administrative data.

INTRODUCTION: International Classification of Diseases (ICD) codes recorded in administrative data are often used to identify congenital heart defects (CHD). However, these codes may inaccurately identify true positive (TP) CHD individuals. CHD surveillance could be strengthened by accurate CHD identification in administrative records using machine learning (ML) algorithms. METHODS: To identify features relevant to accurate CHD identification, traditional ML models were applied to a validated dataset of 779 patients; encounter level data, including ICD-9-CM and CPT codes, from 2011 to 2013 at four US sites were utilized. Five-fold cross-validation determined overlapping important features that best predicted TP CHD individuals. Median values and 95% confidence intervals (CIs) of area under the receiver operating curve, positive predictive value (PPV), negative predictive value, sensitivity, specificity, and F1-score were compared across four ML models: Logistic Regression, Gaussian Naive Bayes, Random Forest, and eXtreme Gradient Boosting (XGBoost). RESULTS: Baseline PPV was 76.5% from expert clinician validation of ICD-9-CM CHD-related codes. Feature selection for ML decreased 7138 features to 10 that best predicted TP CHD cases. During training and testing, XGBoost performed the best in median accuracy (F1-score) and PPV, 0.84 (95% CI: 0.76, 0.91) and 0.94 (95% CI: 0.91, 0.96), respectively. When applied to the entire dataset, XGBoost revealed a median PPV of 0.94 (95% CI: 0.94, 0.95). CONCLUSIONS: Applying ML algorithms improved the accuracy of identifying TP CHD cases in comparison to ICD codes alone. Use of this technique to identify CHD cases would improve generalizability of results obtained from large datasets to the CHD patient population, enhancing public health surveillance efforts.

Positive Predictive Value of International Classification of Diseases, Ninth Revision, Clinical Modification, and International Classification of Diseases, Tenth Revision, Clinical Modification, Codes for Identification of Congenital Heart Defects.

Background Administrative data permit analysis of large cohorts but rely on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes that may not reflect true congenital heart defects (CHDs). Methods and Results CHDs in 1497 cases with at least 1 encounter between January 1, 2010 and December 31, 2019 in 2 health care systems, identified by at least 1 of 87 ICD-9-CM/ICD-10-CM CHD codes were validated through medical record review for the presence of CHD and CHD native anatomy. Interobserver and intraobserver reliability averaged >95%. Positive predictive value (PPV) of ICD-9-CM/ICD-10-CM codes for CHD was 68.1% (1020/1497) overall, 94.6% (123/130) for cases identified in both health care systems, 95.8% (249/260) for severe codes, 52.6% (370/703) for shunt codes, 75.9% (243/320) for valve codes, 73.5% (119/162) for shunt and valve codes, and 75.0% (39/52) for "other CHD" (7 ICD-9-CM/ICD-10-CM codes). PPV for cases with >1 unique CHD code was 85.4% (503/589) versus 56.3% (498/884) for 1 CHD code. Of cases with secundum atrial septal defect ICD-9-CM/ICD-10-CM codes 745.5/Q21.1 in isolation, PPV was 30.9% (123/398). Patent foramen ovale was present in 66.2% (316/477) of false positives. True positives had younger mean age at first encounter with a CHD code than false positives (22.4 versus 26.3 years; P=0.0017). Conclusions CHD ICD-9-CM/ICD-10-CM codes have modest PPV and may not represent true CHD cases. PPV was improved by selecting certain features, but most true cases did not have these characteristics. The development of algorithms to improve accuracy may improve accuracy of electronic health records for CHD surveillance.

Successful Medical-Surgical Management of Intracardiac Thrombosis and Pulmonary Pseudoaneurysms in an Adolescent With Hughes-Stovin Syndrome.

We present an adolescent male with a single intracardiac mass and pulmonary emboli, complicated by peripheral venous thrombosis and subsequent development of pulmonary pseudoaneurysms, leading to diagnosis of Hughes-Stovin syndrome. Remission was achieved with cyclophosphamide, corticosteroids, and pseudoaneurysm resection and maintained with infliximab and methotrexate.

Perioperative predictors for complications in patients with Xanthogranulomatous Pyelonephritis treated with nephrectomy.

INTRODUCTION: Xanthogranulomatous pyelonephritis is an inflammatory disease characterized by chronic obstruction and infection. This pathology is a life-threatening condition when surgical treatment is carried out. We decided to retrospectively evaluate whether there were perioperative factors that predict complications in patients who undergo nephrectomy. METHODS: We reviewed all nephrectomies done in the period of 2013-2018, in a tertiary referral Hospital with the histopathological diagnosis of Xanthogranulomatous Pyelonephritis. RESULTS: The presence of renal abscess at admission was observed as a risk factor associated with perioperative complications (p = 0.002), presence of abscess was observed in 47.4% of subjects without complications compared to 89.3% of the perioperative complication group. Higher rates of blood transfusion requirement were observed in the perioperative complication group, 89.3% compared to 68.4% (p = 0.029), furthermore, perioperative bleeding was slightly greater in the complication group compared to its counterpart, 700 mL, and 600 mL, respectively (p = 0.01). CONCLUSIONS: Anemia and the presence of abscess were important perioperative factors that predict perioperative complications.

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.