Issues in multi-organ transplantation of the liver with kidney or heart in polycystic liver-kidney disease or congenital heart disease: Current practices and immunological aspects.

Solid organ transplantation has become an integral part of the management of patients with end-stage diseases of the kidney, liver, heart and lungs. Most procedures occur in isolation, but multi-organ transplantation of the liver with either the kidney or heart has become an option. As more patients with congenital heart disease and cardiac cirrhosis survive into adulthood, particularly after the Fontan procedure, liver transplant teams are expected to face questions regarding multi-organ (heart-liver) transplantation. Similarly, patients with polycystic kidneys and livers may be managed by multi-organ transplantation. Herein, we review the indications and outcomes of simultaneous liver-kidney transplantation for polycystic liver-kidney disease, and discuss the indications, timing and procedural aspects of combined heart-liver transplantation. We also summarise the evidence for, and potential mechanisms underlying, the immunoprotective impact of liver allografts on the simultaneously transplanted organs.

Diagnosis and management of the adult patient with a failing Fontan circulation.

Since the original description, the Fontan operation has been widely used for the palliation of children with single ventricle physiology. Although the Fontan operation revolutionized the survival rates of patients with single ventricle physiology, it carries an inevitable risk for long-term morbidity and mortality that impacts clinical outcomes and quality of life. This review will focus on the evaluation and treatment of the patient with the failing Fontan phenotype, with an emphasis on creating an individualized treatment plan.

Post-operative Assessment of the Arterial Switch Operation: A Comparison of Magnetic Resonance Imaging and Echocardiography.

After an arterial switch operation (ASO), serial imaging is necessary to monitor for maladaptive changes. We compared cardiac magnetic resonance imaging (CMR) to 2-D transthoracic echocardiography (TTE) in assessing post-operative ASO patients. We performed a retrospective review of patients at a single tertiary care center who underwent an ASO and subsequently had a CMR performed from 7/2010 to 7/2016. Those with single ventricle anatomy, congenitally corrected transposition of the great arteries, or previous atrial switch operation were excluded. TTE obtained within 6 months of the CMR was used for comparison. Parameters compared included ventricular size and systolic function, semilunar valve regurgitation, neo-aortic root dimension, and the presence of branch pulmonary artery (PA) stenosis (on CMR by the Nakata index or right/left flow differential; on TTE by peak velocity > 2 m/s or PA diameter Z score < - 2). Forty-seven patients with 90 CMR and 86 TTE studies met inclusion criteria. CMR and TTE assessment of right ventricular (RV) and left ventricular function did not statistically differ. RV dilation was overdetected by TTE (p = 0.046). Right pulmonary artery and left pulmonary artery (LPA) visualization by TTE was worse than CMR (p < 0.01). There was no statistically significant difference between CMR and TTE assessment of branch PA stenosis; however, there was poor agreement between the use of Z score and velocity when determining branch PA stenosis by TTE (κ < 0). Assessment of neo-pulmonary regurgitation (PR) and neo-aortic regurgitation (AR) was significantly different between CMR and TTE (p < 0.05). Assessment for delayed enhancement was performed in 18% of CMR studies (n = 16), with perfusion defects appreciated in three patients. Substantial differences between CMR and TTE exist when examining the post-operative ASO patient. CMR was superior for evaluation of the branch PAs, which commonly require re-intervention. TTE failed to recognize altered ventricular function in several cases. Differences between TTE and CMR could alter management is some cases. Incorporation of CMR into the routine surveillance of patients who received an ASO is warranted.

Better Late Than Never: Definitive Anatomic Repair of Dextro-Transposition of the Great Arteries.

We present a case of anatomic repair of dextro-transposition of the great arteries (d-TGA) with ventricular septal defect (VSD) in a 55-year-old man who presented with acute heart failure. This case highlights the importance of multimodal imaging and multidisciplinary involvement in developing a comprehensive surgical and medical plan for adults with congenital heart disease. We think this is the oldest reported patient undergoing anatomic surgical repair of d-TGA with VSD.

Continuous-Flow Ventricular Assist Device Support in Adult Congenital Heart Disease: A 15-Year, Multicenter Experience of Temporary and Durable Support.

Heart failure (HF) is common in adult congenital heart disease (ACHD) patients; however, use of continuous-flow ventricular assist devices (CF-VADs) remains rare. We reviewed outcomes of patients with congenital heart disease greater than or equal to 18 years of age at the time of CF-VAD implant at the affiliated pediatric and adult institutions between 2006 and 2020. In total, 18 ACHD patients (15 with great anatomical complexity) received 21 CF-VADs. Six patients (median age 34 years) received seven percutaneous CF-VADs with a median duration of support of 20 days (3-44 days) with all patients survived to hospital discharge and two patients were bridged to durable CF-VADs. Fourteen patients (median age 38 years) received durable CF-VADs. Thirteen patients (93%) survived to hospital discharge and the median duration of support was 25.8 months (6.4-52.1 months). Estimated survival on durable CF-VAD at 1, 3, and 5 years was 84%, 72%, and 36%, respectively. Three patients were successfully bridged to transplantation. Device-related complications include cerebrovascular accident (n = 5), driveline infection (n = 3), device infection requiring chronic antibiotic therapy (n = 4), gastrointestinal bleeding (n = 6), and presumed pump thrombosis (n = 5). These results show percutaneous and durable CF-VADs can support ACHD patients with advanced HF.

COVID-19-Related Thrombotic and Bleeding Events in Adults With Congenital Heart Disease.

Background: Altered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications. Objectives: The purpose of this study was to investigate the prevalence and risk factors for COVID-19 TE/bleeding complications in ACHD patients. Methods: COVID-19-positive ACHD patients were included between May 2020 and November 2021. TE events included ischemic cerebrovascular accident, systemic and pulmonary embolism, deep venous thrombosis, myocardial infarction, and intracardiac thrombosis. Major bleeding included cases with hemoglobin drop >2 g/dl, involvement of critical sites, or fatal bleeding. Severe infection was defined as need for intensive care unit, endotracheal intubation, renal replacement therapy, extracorporeal membrane oxygenation, or death. Patients with TE/bleeding were compared to those without events. Factors associated with TE/bleeding were determined using logistic regression. Results: Of 1,988 patients (age 32 [IQR: 25-42] years, 47% male, 59 ACHD centers), 30 (1.5%) had significant TE/bleeding: 12 TE events, 12 major bleeds, and 6 with both TE and bleeding. Patients with TE/bleeding had higher in-hospital mortality compared to the remainder cohort (33% vs 1.7%; P < 0.0001) and were in more advanced physiological stage (P = 0.032) and NYHA functional class (P = 0.01), had lower baseline oxygen saturation (P = 0.0001), and more frequently had a history of atrial arrhythmia (P < 0.0001), previous hospitalization for heart failure (P < 0.0007), and were more likely hospitalized for COVID-19 (P < 0.0001). By multivariable logistic regression, prior anticoagulation (OR: 4.92; 95% CI: 2-11.76; P = 0.0003), cardiac injury (OR: 5.34; 95% CI: 1.98-14.76; P = 0.0009), and severe COVID-19 (OR: 17.39; 95% CI: 6.67-45.32; P < 0.0001) were independently associated with increased risk of TE/bleeding complications. Conclusions: ACHD patients with TE/bleeding during COVID-19 infection have a higher in-hospital mortality from the illness. Risk of coagulation disorders is related to severe COVID-19, cardiac injury during infection, and use of anticoagulants.

Construction and Evaluation of a Bio-Engineered Pump to Enable Subpulmonary Support of the Fontan Circulation: A Proof-of-Concept Study.

Our objective was to create a bio-engineered pump (BEP) for subpulmonary Fontan circulation support capable of luminal endothelialization and producing a 2-6 mmHg pressure gradient across the device without flow obstruction. To accomplish this, porcine urinary bladder submucosa was decellularized to produce a urinary bladder matrix (UBM) which produced acellular sheets of UBM. The UBM was cultured with human umbilical vein endothelial cells producing a nearly confluent monolayer of cells with the maintenance of typical histologic features demonstrating UBM to be a suitable substrate for endothelial cells. A lamination process created bilayer UBM sheets which were formed into biologic reservoirs. BEPs were constructed by securing the biologic reservoir between inlet and outlet valves and compressed with a polyurethane balloon. BEP function was evaluated in a simple flow loop representative of a modified subpulmonary Fontan circulation. A BEP with a 92-mL biologic reservoir operating at 60 cycles per minute produced pulsatile downstream flows without flow obstruction and generated a favorable pressure gradient across the device, maintaining upstream pressure of 6 mm Hg and producing downstream pressure of 13 mm Hg. The BEP represents potential long-term assistance for the Fontan circulation to relieve venous hypertension, provide pulsatile pulmonary blood flow and maintain cardiac preload.

Fate of the liver in the survivors of adult heart transplant for a failing Fontan circulation.

The Fontan circulation has inherent long-term vulnerabilities such that adult Fontan patients now comprise the largest, most rapidly growing subgroup of adult congenital heart disease referred for transplant assessment. Almost all have Fontan Associated Liver Disease (FALD). There is an absence of mid to late hepatic outcome data after heart transplant alone. Therefore, we analyzed outcomes of survivors of heart only transplant in patients with failing Fontan circulation. Including all 10 of our adult Fontan patients surviving >1 year after isolated heart transplant, we report evolution of their clinical features, bloodwork, hemodynamic data, and liver ultrasound findings over a median of 4.7 years. Nonprogression of FALD, resolution of ascites and freedom from hepatocellular carcinoma in the mid-term highlight the outcomes in this selected group once normal cardiac output and venous pressures are established by heart transplant.

Heart Block in Unpalliated Complex Adult Congenital Heart Disease: Massive Collateral Burden Precludes Epicardial Pacemaker.

Complete heart block is a common complication for adults with congenital heart disease (CHD). Epicardial pacing is preferred in patients with septal shunting due to risk of thromboembolism. Anatomic changes in complex CHD may preclude surgical epicardial lead placement. Thromboembolism risk reduction in such patients requiring endocardial pacing remains questionable. (Level of Difficulty: Advanced.).

Disparities in insurance coverage among hospitalized adult congenital heart disease patients before and after the Affordable Care Act.

BACKGROUND: Data are lacking regarding the insurance status of adults with congenital heart disease (ACHD). We investigated whether the Affordable Care Act (ACA) impacted insurance status among hospitalized ACHD, identified associated sociodemographic factors, and compared coverage to adults with other chronic childhood conditions. METHODS: Serial cross-sectional analysis of National Inpatient Sample hospitalizations from 2007 to 2016 was performed for patients 18-64 years old. ACHD were identified using ICD-9/10-CM codes and compared to patients with sickle cell disease (SCD), cystic fibrosis (CF), and the general population. Age was dichotomized as 18-25 years (transition aged) or 26-64 years. Groups were compared by era (pre-ACA [January 2007-June 2010]; early-ACA [July 2010-December 2013], which eliminated pre-existing condition exclusions; and full-ACA [January 2014-December 2016]) using interrupted time series and multivariable Poisson regression analyses. RESULTS: Overall, uninsured hospitalizations decreased from pre-ACA (12.0%) to full-ACA (8.5%). After full ACA implementation, ACHD had lower uninsured rates than the general hospitalized population (6.0 vs. 8.6%, p < .01), but higher rates than those with other chronic childhood diseases (SCD [4.5%]; CF [1.6%]). Across ACA eras, transition aged ACHD had higher uninsured rates than older patients (8.9 vs. 7.6%, p < .01), and Hispanic patients remained less insured than other groups. CONCLUSIONS: Hospitalized ACHD were better insured than the general population but less insured than those with SCD or CF. Full ACA implementation was associated with improved insurance coverage for all groups, but disparities persisted for transition aged and Hispanic patients. Ongoing evaluation of the effects of insurance and health policy on ACHD remains critical to diminish health disparities.

COVID-19 in Adults With Congenital Heart Disease.

BACKGROUND: Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. OBJECTIVES: This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. METHODS: Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. RESULTS: From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. CONCLUSIONS: COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity.

Use of Intracardiac Echocardiography in the Evaluation and Management of Iatrogenic Aortopulmonary Communication After Percutaneous Intervention in Postoperative Patients With Congenital Heart Disease.

Iatrogenic aortopulmonary communications (IAPCs) are an uncommon but important complication after percutaneous intervention in postoperative patients. Iatrogenic aortopulmonary communications typically occur after balloon angioplasty or other interventions of the pulmonary outflow tract in certain anatomic configurations in which there is a denuded tissue plane between the pulmonary artery and aorta. They can present with signs and symptoms ranging from subtle clues which are difficult to recognize to near immediate hemodynamic instability. Once recognized, these lesions can become management dilemmas, and intraprocedural interventions can be complicated by complex anatomy and inadequate visualization by standard imaging techniques. We report cases where intracardiac echocardiography (ICE) was integral in the evaluation and management of IAPC as complications of prior transcatheter interventions. We found using ICE safely and effectively identified IAPCs and reduced the technical difficulty of intervention after IAPC discovery.

An Analysis of Hospital Mortality After Cardiac Operations in Children With Down Syndrome.

Children with Down syndrome (DS) have lower mortality compared to nonsyndromic (NS) children after atrioventricular septal defect (AVSD) repair. Limited data exist regarding hospital mortality and utilization after other congenital heart disease (CHD) operations in DS. We compared hospital mortality and utilization after CHD operations in both populations and hypothesized that the survival benefit in children with DS is not consistent across CHD lesions. The Texas Inpatient Public Use Datafile was queried for all patients <18 years old undergoing operations for CHD between 1999 and 2016. Hospital mortality, length-of-stay and charges were compared between DS and NS groups, stratified by CHD operation using mixed-effects multivariable analyses and propensity score matching analyses adjusting for prematurity, low birth weight, age, and sex. Over the 18-year period, 2841 cases with DS underwent CHD operations compared to 25,063 NS cases. The most common types of interventions performed in DS were AVSD repair, isolated ventricular septal defect (VSD) repair and tetralogy of Fallot (TOF) repair. By multivariable analyses, DS was associated with lower mortality after isolated AVSD repair (RR 0.40 [IQR 0.20-0.79]), and higher hospital mortality after bidirectional Glenn anastomosis (BDG) (RR 5.17 [IQR 2.10-12.77]) and TOF/pulmonary atresia repair (RR 9.71 [IQR 2.16-43.68]) compared to NS children. Similar results were noted using propensity score matching. Children with DS had lower mortality after AVSD repair than NS children, but higher mortality after operations for BDG and TOF/pulmonary atresia. Further study is needed to determine if the presence of pulmonary hypertension in DS modifies the association between DS and mortality depending on cardiac lesion.

Improvement in Protein-Losing Enteropathy in a Patient With Fontan Circulation After Cardiac Rehabilitation and Prescriptive Exercise.

Fontan-associated protein-losing enteropathy is difficult to treat and associated with poor prognosis. Cardiac rehabilitation and exercise are thought to have beneficial effects for patients with Fontan circulation. We report the case of a young adult patient palliated to Fontan circulation, with a decade-long history of symptoms related to protein-losing enteropathy. At age 23 years, he appreciated an improvement in symptoms and laboratory values after cardiac rehabilitation and prescriptive exercise.

Opportunities for training to advance the care for adults with congenital heart disease with advanced circulatory failure.

Heart failure is an emerging issue with important implications in adult patients with congenital heart disease. Practitioners with expertise in both adult congenital heart disease and heart failure are needed to manage this growing and often complex population. In the United States, the optimal training pathway to enable practitioners to best care for these patients is ill-defined. This article explores possibilities and issues that interested trainees may encounter during their training experience.

Outcomes in adults with congenital heart disease and heterotaxy syndrome: A single-center experience.

BACKGROUND: Heterotaxy syndrome (HS) is a condition in which the thoracoabdominal organs demonstrate an abnormal lateral arrangement and is often associated with congenital heart disease (CHD). Little is known about the adult HS population with CHD. OBJECTIVE: To describe the outcomes and sociodemographics of the adult CHD population with HS. METHODS: Records of patients 18 years of age or older with diagnoses of both CHD and HS at Texas Children's Hospital from 1964 to 2018 were reviewed. RESULTS: Sixty-two patients met inclusion criteria. Median age was 22.7 [IQR 19.6-30.0] years; 26 (42%) were female; and 13 (21%) of patients had a gap in care of >3 years. Median follow-up time in adulthood was 2.9 [IQR 1.3-8.2] years. Forty-three (69%) of patients had single ventricle heart disease, 31 (71%) of whom completed Fontan circulation. A total of 36 interventions occurred in 24 patients which included 16 cardiac catherization interventions, 13 electrophysiology-related procedures, and 18 surgical procedures including 2 orthotopic heart transplants. The median age for death or heart transplant was 45.3 (95%CI 34.3-56.1) years. Heart failure-free survival was 80.8 ± 5.2%, 58.7 ± 11.0%, and 31.1 ± 15.7% at 20, 30, and 40 years old, respectively. Cerebrovascular accident-free survival was 84.3 ± 5.1%, 54.2 ± 11.3%, and 40.6 ± 14.5% at 20, 30, and 40 years old, respectively. Tachyarrhythmia-free survival was 54.0 ± 7.1%, 29.2 ± 8.3%, and 19.5 ± 9.7% at 20, 30, and 40 years old and bradyarrhythmia-free survival was 66.0 ± 6.3%, 41.7 ± 9.4%, and 33.4 ± 10.6% at ages 20, 30, and 40 years, respectively. CONCLUSIONS: At a tertiary referral center, adult patients with CHD and HS have high rates of comorbidities and early death or heart transplant. Longitudinal surveillance and further exploration into factors associated with improved survival in this population are warranted.

Cardiac transplantation in children with Down syndrome, Turner syndrome, and other chromosomal anomalies: A multi-institutional outcomes analysis.

BACKGROUND: The purpose of this study was to describe the prevalence, characteristics, and outcomes in pediatric patients with chromosomal anomalies (CA) undergoing orthotopic heart transplantation (OHT). METHODS: A query of the database of the Pediatric Health Information System, a large administrative and billing database of 43 tertiary children's hospitals, was performed for the Years 2004 to 2016. Pediatric patients who received OHT were analyzed based on presence and type of CA. CA analyzed included: Down syndrome (DS); Turner syndrome (TS)/gonadal dysgenesis; conditions due to anomaly of unspecified chromosome; autosomal deletion; microdeletion; and autosomal anomaly. Healthcare-associated charge analysis during hospitalization for OHT and survival after OHT were assessed. RESULTS: A total of 3,080 hospitalizations were identified in which OHTs were performed. Of these OHTs, 64 (2.1%) were performed in patients with a concomitant diagnosis of CA. The presence of CA did not confer a higher risk of in-hospital mortality after OHT (odds ratio 1.2 [0.5 to 3.2], p = 0.651). Differences in in-hospital mortality between different types of CA, including DS and TS, did not reach statistical significance. Survival at 1-year post-OHT was similar in patients with CA compared to those without CA (p = 0.248). Length of stay after OHT was longer in patients with CA: 76 (interquartile range [IQR] 76 to 142 days vs 49 [IQR 21 to 98] days) (p < 0.001), respectively. Overall adjusted hospital charges were significantly higher in the CA group: $1.2 million (IQR $740,000 to $2.2 million) vs $792,000 (IQR $425,000 to $1.5 million] (p < 0.001), respectively. CONCLUSIONS: CA is present in ~2% of pediatric patients undergoing OHT. The presence of CA was not associated with increased mortality in pediatric patients undergoing OHT. Limitations of this study include the small number of patients available for analysis and a likely highly selective cohort of patients with CA.

Renal dysfunction is associated with higher central venous pressures in patients with Fontan circulation.

PURPOSE: Elevated central venous pressure (CVP) has deleterious effects on several organ systems in patients with Fontan circulation. However, the relationship between CVP and estimated glomerular filtration rate (eGFR) has not been assessed in patients with Fontan circulation. METHODS: Patients with Fontan circulation whose hemodynamics were assessed by catheterization between 1987 and 2015 and had a serum creatinine measured within 72 hours prior to the procedure were included for analysis. Patients with primary kidney disease were excluded. Renal function was calculated by "bedside Schwartz" equation in children (< 18 years) and Modification of Diet in Renal Disease equation in adults. Renal dysfunction (RD) was defined by eGFR < 90mL/min/1.73m2 . Fontan patients with and without RD were compared based on demographics, co-morbidities, medication use, echocardiographic findings, hemodynamics assessed at time of catheterization, and laboratory testing values. RESULTS: Sixty-seven patients with Fontan circulation met inclusion criteria and 15 patients (22%) had RD; eGFR (mL/min/1.73m2 ) was 60-89in 13 (87%), 45-59in 1 (7%), and 30-45in 1 (7%). Compared to patients with eGFR equal to or greater than 90, patients with RD had higher CVP (18.0 [15.0-21.0] mm Hg vs 13.5 [12.3-16.0] mm Hg (P = 0.001), lower pulmonary blood flow 2.2 [1.9-2.6] L/min/m2 vs 2.8 [2.3-3.7] L/min/m2 , higher ventricular end-diastolic pressure 10.5 [7.0-17.3] mm Hg vs 8.0 [6.0-10.0] mm Hg (P = 0.050), were more likely to have worse atrioventricular valve regurgitation (P = 0.02) and were more likely to be African American (P = 0.009). CONCLUSIONS: In this study population, renal dysfunction in patients with Fontan circulation is associated with increased CVP and factors that affect CVP. African Americans with Fontan circulation may be at particular risk for renal dysfunction. Continued investigation of the effects of venous congestion on kidneys and other factors associated with renal dysfunction in patients with Fontan circulation is warranted.