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.

Mechanical Circulatory Support for the Failing Sub-Aortic Right Ventricle in Adults.

Patients with ccTGA or d-TGA managed via atrial switch (Mustard or Senning operations) have biventricular circulations with a sub-aortic right ventricle (2V-RV). Other than in a tiny percentage of ccTGA patients, premature heart failure (HF) is common, driven by chronic RV dilatation and dysfunction and/or tricuspid regurgitation. These patients are different from the general HF population in that they are younger, more heterogeneous, are predisposed to pulmonary hypertension and present unique and complex surgical challenges. Despite their young age, they experience disproportionately poor access to advanced therapies and are often disqualified for transplant by pulmonary hypertension, HLA sensitization, program risk-tolerance and psychosocial issues. Mechanical support of the subaortic RV with ventricular assist device (subaortic RVAD, also known as SVAD), although technically challenging, can be an effective alternative to palliative care and offers high likelihood of bridging patients to heart transplant candidacy. In addition, temporary trans-catheter SVAD Impella support has been advantageous for stabilization of decompensated 2V-RV patients or as bridge to durable SVAD support. Improved awareness of and access to specialist ACHD-HF teams offering mechanical support (and transplantation) for 2V-RV patients is increasingly urgent for this aging population, and will improve options and outcomes for these patients as HF emerges.

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.

Hemodynamic Effect of a Fontan Assist Device on a Numerical Fontan Circulatory Model under Various Medication Scenarios.

Patients with single-ventricle heart disease and failing Fontan circulation represent the largest and most rapidly growing subgroup of adults with congenital heart disease referred for transplant assessment. Few clinical therapies are available for improving Fontan hemodynamics. Mechanical circulatory support devices have been used successfully in the clinical setting to assist the single ventricle, but no device is currently available to support the subpulmonary circulation. A subpulmonary pump could be used to support patients with failing Fontan circulation by mitigating chronic venous hypertension and restoring normal physiology. Our group designed a Fontan assist device (FAD) to augment right-heart (subpulmonary) flow and decrease venous pressures. To ensure that our FAD could achieve target hemodynamic parameters, we developed a numerical Fontan circulatory model to evaluate the interaction between the cardiovascular system and the FAD. To ensure that the circulatory model can mimic real-world clinical conditions, we investigated the effects of various medications in the FAD loop. Results showed that the FAD can significantly increase cardiac output in Fontan patients and can create a pressure difference between the pulmonary arteries and venae cavae. Further, the systemic venous pressure can be significantly reduced by using the FAD plus diuretic treatment. The downstream pulmonary artery pressure can be increased by augmenting the FAD with vasodilator treatment, diuretic treatment, or both.Clinical Relevance- This work supports FAD development by providing a method for studying human cardiovascular effects under various hemodynamic scenarios.

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.

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.

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.

Engineered cartilage covered ear implants for auricular cartilage reconstruction.

Cartilage tissues are often required for auricular tissue reconstruction. Currently, alloplastic ear-shaped medical implants composed of silicon and polyethylene are being used clinically. However, the use of these implants is often associated with complications, including inflammation, infection, erosion, and dislodgement. To overcome these limitations, we propose a system in which tissue-engineered cartilage serves as a shell that entirely covers the alloplastic implants. This study investigated whether cartilage tissue, engineered with chondrocytes and a fibrin hydrogel, would provide adequate coverage of a commercially used medical implant. To demonstrate the in vivo stability of cell-fibrin constructs, we tested variations of fibrinogen and thrombin concentration as well as cell density. After implantation, the retrieved engineered cartilage tissue was evaluated by histo- and immunohistochemical, biochemical, and mechanical analyses. Histomorphological evaluations consistently showed cartilage formation over the medical implants with the maintenance of dimensional stability. An initial cell density was determined that is critical for the production of matrix components such as glycosaminoglycans (GAG), elastin, type II collagen, and for mechanical strength. This study shows that engineered cartilage tissues are able to serve as a shell that entirely covers the medical implant, which may minimize the morbidity associated with implant dislodgement.

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.

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.

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.

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.