Intrahepatic Transcriptomics Differentiate Advanced Fibrosis and Clinical Outcomes in Adults With Fontan Circulation.

BACKGROUND: The molecular mechanisms underlying Fontan-associated liver disease (FALD) remain largely unknown. OBJECTIVES: This study aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. METHODS: This retrospective cohort study included adults with the Fontan circulation. Baseline clinical, laboratory, imaging, and hemodynamic data as well as a composite clinical outcome (CCO) were extracted from medical records. Patients were classified into early or advanced fibrosis. RNA was isolated from formalin-fixed paraffin-embedded liver biopsy samples; RNA libraries were constructed with the use of an rRNA depletion method and sequenced on an Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were performed with the use of DESeq2 and Metascape. RESULTS: A total of 106 patients (48% male, median age 31 years [IQR: 11.3 years]) were included. Those with advanced fibrosis had higher B-type natriuretic peptide levels and Fontan, mean pulmonary artery, and capillary wedge pressures. The CCO was present in 23 patients (22%) and was not predicted by advanced liver fibrosis, right ventricular morphology, presence of aortopulmonary collaterals, or Fontan pressures on multivariable analysis. Samples with advanced fibrosis had 228 upregulated genes compared with early fibrosis. Samples with the CCO had 894 upregulated genes compared with those without the CCO. A total of 136 upregulated genes were identified in both comparisons and were enriched in cellular response to cytokine stimulus or oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-ß signaling pathway, and vasculature development. CONCLUSIONS: Patients with FALD and advanced fibrosis or the CCO exhibited upregulated genes related to inflammation, congestion, and angiogenesis.

Emphasizing Sexual Orientation and Gender Identity Data Capture for Improved Cardiovascular Care of the LGBTQ+ Population.

Importance: The rising self-identifying lesbian, gay, bisexual, transgender, and queer (LGBTQ+) population makes understanding the unique health care needs of sexual and gender minoritized patients an urgent one. The interaction between minority stress and cardiovascular disease has been well described among underrepresented minoritized populations. The underrepresentation of minoritized populations in clinical research is partly responsible for worse cardiovascular outcomes in these populations. The absence of sexual orientation and gender identity and expression (SOGIE) data makes it difficult to understand the cardiovascular health of LGBTQ+ adults, thereby widening health care disparities in this population. Advancing cardiovascular health equity for LGBTQ+ patients must begin with careful and accurate SOGIE data collection. Observations: Current SOGIE data capture remains inadequate despite federal mandates. Challenges in data collection include political and regulatory discrimination, patient/practitioner hesitancy, lack of supportive guidance on SOGIE data collection, improper terminology, regulatory inertia, and inadequate and often incorrect integration of SOGIE data into electronic health records (EHRs). Additional challenges include grouping participants as "others" for statistical significance. The inclusion of SOGIE data has demonstrated an impact in other fields like cancer survivorship and surgery. The same needs to be done for cardiology. Conclusions and Relevance: Potential solutions for improving much-needed SOGIE data collection include (1) implementing LGBTQ+ inclusive policies, (2) integrating SOGIE data into the EHR, (3) educating health care professionals on the relevance of SOGIE to patient-centered care, and (4) creating a diverse cardiovascular workforce. These steps can substantially enhance the ability to collect SOGIE data to address LGBTQ+ cardiovascular health care disparities.

Intrahepatic transcriptomics differentiate advanced fibrosis and clinical outcomes in adults with the Fontan circulation.

Background: The molecular mechanisms underlying Fontan associated liver disease (FALD) remain largely unknown. We aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. Methods: This retrospective cohort study included adults with the Fontan circulation at the Ahmanson/UCLA Adult Congenital Heart Disease Center. Clinical, laboratory, imaging and hemodynamic data prior to the liver biopsy were extracted from medical records. Patients were classified into early (F1-F2) or advanced fibrosis (F3-F4). RNA was isolated from formalin-fixed paraffin embedded liver biopsy samples; RNA libraries were constructed using rRNA depletion method and sequencing was performed on Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were carried out using DESeq2 and Metascape. Medical records were comprehensively reviewed for a composite clinical outcome which included decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, protein-losing enteropathy, chronic kidney disease stage 4 or higher, or death. Results: Patients with advanced fibrosis had higher serum BNP levels and Fontan, mean pulmonary artery and capillary wedge pressures. The composite clinical outcome was present in 23 patients (22%) and was predicted by age at Fontan, right ventricular morphology and presence of aortopulmonary collaterals on multivariable analysis. Samples with advanced fibrosis had 228 up-regulated genes compared to early fibrosis. Samples with the composite clinical outcome had 894 up-regulated genes compared to those without it. A total of 136 up-regulated genes were identified in both comparisons and these genes were enriched in cellular response to cytokine stimulus, response to oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-beta signaling pathway, and vasculature development. Conclusions: Patients with FALD and advanced liver fibrosis or the composite clinical outcome exhibit up-regulated genes including pathways related to inflammation, congestion, and angiogenesis. This adds further insight into FALD pathophysiology.

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.

Recessive ciliopathy mutations in primary endocardial fibroelastosis: a rare neonatal cardiomyopathy in a case of Alstrom syndrome.

Among neonatal cardiomyopathies, primary endocardial fibroelastosis (pEFE) remains a mysterious disease of the endomyocardium that is poorly genetically characterized, affecting 1/5000 live births and accounting for 25% of the entire pediatric dilated cardiomyopathy (DCM) with a devastating course and grave prognosis. To investigate the potential genetic contribution to pEFE, we performed integrative genomic analysis, using whole exome sequencing (WES) and RNA-seq in a female infant with confirmed pathological diagnosis of pEFE. Within regions of homozygosity in the proband genome, WES analysis revealed novel parent-transmitted homozygous mutations affecting three genes with known roles in cilia assembly or function. Among them, a novel homozygous variant [c.1943delA] of uncertain significance in ALMS1 was prioritized for functional genomic and mechanistic analysis. Loss of function mutations of ALMS1 have been implicated in Alstrom syndrome (AS) [OMIM 203800], a rare recessive ciliopathy that has been associated with cardiomyopathy. The variant of interest results in a frameshift introducing a premature stop codon. RNA-seq of the proband's dermal fibroblasts confirmed the impact of the novel ALMS1 variant on RNA-seq reads and revealed dysregulated cellular signaling and function, including the induction of epithelial mesenchymal transition (EMT) and activation of TGFß signaling. ALMS1 loss enhanced cellular migration in patient fibroblasts as well as neonatal cardiac fibroblasts, while ALMS1-depleted cardiomyocytes exhibited enhanced proliferation activity. Herein, we present the unique pathological features of pEFE compared to DCM and utilize integrated genomic analysis to elucidate the molecular impact of a novel mutation in ALMS1 gene in an AS case. Our report provides insights into pEFE etiology and suggests, for the first time to our knowledge, ciliopathy as a potential underlying mechanism for this poorly understood and incurable form of neonatal cardiomyopathy. KEY MESSAGE: Primary endocardial fibroelastosis (pEFE) is a rare form of neonatal cardiomyopathy that occurs in 1/5000 live births with significant consequences but unknown etiology. Integrated genomics analysis (whole exome sequencing and RNA sequencing) elucidates novel genetic contribution to pEFE etiology. In this case, the cardiac manifestation in Alstrom syndrome is pEFE. To our knowledge, this report provides the first evidence linking ciliopathy to pEFE etiology. Infants with pEFE should be examined for syndromic features of Alstrom syndrome. Our findings lead to a better understanding of the molecular mechanisms of pEFE, paving the way to potential diagnostic and therapeutic applications.

Orthotopic Heart and Combined Heart Liver Transplantation: the Ultimate Treatment Option for Failing Fontan Physiology.

Purpose of the Review: This is a comprehensive update on failing Fontan physiology and the role of heart and combined heart and liver transplantation in the current era. Recent Findings: Single ventricle physiology encompasses a series of rare congenital cardiac abnormalities that are characterized by absence of or hypoplasia of one ventricle. This effectively results in a single ventricular pumping chamber. These abnormalities are rarely compatible with long-term survival if left without surgical palliation in the first few years of life. Surgical treatment of single ventricle physiology has evolved over the past 60 years and is characterized by numerous creative innovations. These include the development of arteriopulmonary shunts, the evolution of partial cavopulmonary connections, and the eventual development of the "Fontan" operation. Regardless of the type of Fontan modification, the long-term consequences of the Fontan operation are predominantly related to chronic central venous hypertension and the multi-organ consequences thereof. Atrial arrhythmias can further compromise this circulation.Patients with single ventricle physiology represent a special sub-segment of congenital cardiac transplants and are arguably the most challenging patients considered for transplantation. Summary: This review describes in detail the challenges and opportunities of heart and liver transplantation in Fontan patients, as viewed and managed by the experienced team at the Ahmanson/UCLA Adult Congenital Heart Center.

Knowledge of Life-Long Cardiac Care by Adolescents and Young Adults with Congenital Heart Disease.

National management guidelines recommend that patients with moderate and complex congenital heart disease (CHD) receive life-long cardiac care (LLCC), guided in adulthood by an adult congenital heart disease (ACHD) specialist. However, the percentage of adult CHD patients who receive such care is quite low. Inadequate knowledge regarding LLCC may contribute to care interruption. We, therefore, sought to determine the knowledge of adolescents and young adults regarding LLCC. In this multi-center study, we administered a survey to patients 13-20 years of age with surgically repaired congenital heart disease. We assessed the understanding of both their need for LLCC and awareness of the type of recommended care providers. A total of 290/302 (96%) patients approached in the outpatient clinic setting (10 centers) agreed to study participation; mean age was 16.3 ± 2.3 years; patients were 62% male. While the need for LLCC was recognized by 78% of subjects, only 37% understood that an ACHD specialist in adulthood should guide this care. Only 37% of respondents stated that their current cardiology team had spoken to them about LLCC, but 90% wished to learn more. A substantial number of adolescents and young adults with moderate and complex CHD lack adequate knowledge about LLCC, but most have a desire to learn more about the type of care they will require in adulthood. Transition education/assessment ensuring successful transfer to adult-oriented care for this population should emphasize the importance of LLCC.

Implantation techniques and outcomes after cardiac resynchronization therapy for congenitally corrected transposition of the great arteries.

BACKGROUND: Patients with congenitally corrected transposition of the great arteries (CCTGA) are at risk of congestive heart failure (CHF). There are limited data on cardiac resynchronization therapy (CRT) techniques and long-term outcomes in this population. OBJECTIVE: The purpose of this study was to determine implantation techniques and efficacy of CRT for CCTGA. METHODS: A 15-year retrospective review of patients with CCTGA undergoing CRT was performed. RESULTS: Twenty patients were identified (mean age 40.1 ± 15.3 years; baseline New York Heart Association class 2.0 [interquartile range 1.5-3.5]). Indication was pacing-induced ventricular dysfunction in 12 (60%), atrioventricular block with anticipation for >40% ventricular pacing in 5 (25%), and intact atrioventricular conduction with CHF and QRS prolongation in 3 (15%). A transvenous approach was successful in 18 of 19 patients (95%) in whom it was attempted, with cannulation of a posteroseptal ostium in 14 (78%), vein of Marshall in 2 (11%), and superior ectopic ostium in 2 (11%). Of patients with baseline CHF, 8 (67%) were acute responders, with loss of response in 2 patients (median 1.1 and 1.5 years, respectively). Of 4 patients referred for heart transplantation, 3 (75%) could be de-listed following CRT. Only lead location in the right ventricular outflow tract predicted poor CRT response (P = .026). Post-procedure, the QRS duration increased by 4.3 ms/y (P < .001) despite stable pacing characteristics. CRT revision was required in 4 patients for infection (n = 2) or phrenic nerve capture (n = 2) and was associated with loss of CRT response in 1 patient. CONCLUSION: A transvenous approach to CRT involving distinct coronary venous patterns is feasible for most patients with CCTGA anatomy. Long-term outcome is favorable, but is characterized by return of right ventricular dysfunction in some patients.

Heart and heart-liver transplantation in adults with failing Fontan physiology.

BACKGROUND: As the population of patients with a Fontan palliation grows so does, the number of patients with cardiac failure necessitating orthotopic heart transplant (OHT) and combined heart-liver transplant (CHLT). There is recent evidence that current era cardiac transplant in Fontan patients has improved outcomes, but most studies have a preponderance of pediatrics patients in their cohorts. We examine our institutional experience with adult OHT and CHLT transplantation for failed Fontan physiology. METHODS AND RESULTS: Retrospective analysis of patients at the Ahmanson/UCLA Adult Congenital Heart Disease Center who underwent OHT or CHLT for failing Fontan physiology from January 1, 2002 to May 31, 2017. We identified 20 patients with single-ventricle physiology and Fontan palliation who underwent OHT or CHLT. The median age was 29.5 years (range 19-44). Five patients underwent CHLT because of biopsy proven hepatic cirrhosis. The median length of hospital stay was 23 days (range 8-76) post-OHT and 51 days (range 26-77) post-CHLT. During a median follow-up of 56 months (range 2-178), there was one mortality occurring at 34 months post-OHT due to coronary vasculopathy. Most frequent early postoperative complications included bleeding and infection (55% and 20%, respectively) and surgical reintervention for bleeding complications (n = 8, 40%). One CHLT patient experienced clinically significant hepatic rejection requiring admission and steroid treatment. CONCLUSIONS: Despite inherent risks and complexities of OHT or CHLT in patients with a failed Fontan, transplant is a reasonable therapy. Peri- and postoperative complications are common and may require surgical reintervention. Continued observation of practices and unifying themes may help improve patient selection, pre- and postoperative treatment and ultimately outcomes.

Prognostic utility of MELD-XI in adult congenital heart disease patients undergoing cardiac transplantation.

BACKGROUND: Model of End-Stage Liver Disease eXcluding INR (MELD-XI) at cardiac transplant has demonstrated prognostic survival utility, but has not been specifically validated in adult congenital heart disease (ACHD) in a registry study. METHODS: Adults undergoing first-time orthotopic heart transplant from 2005 to 2015 in the United Network for Organ Sharing (UNOS) registry were examined in parallel: ACHD (n = 543), ischemic-dilated cardiomyopathy (IDCM, n = 6954) and valvular heart disease (VHD, n = 355). Our primary endpoint was a composite of death, graft failure, and retransplantation assessed at 3 months (early), and those with freedom from early endpoint were reassessed at 5 years (late). Interactions between hepatorenal indices and waitlist time were examined. Secondary outcomes relating to long-term morbidity were assessed at late endpoint. Freedom from endpoint analysis in ACHD at clinically relevant endpoints was also conducted. RESULTS: Model of End-Stage Liver Disease eXcluding INR score at transplant associated with an increased risk of early endpoint in all cohorts. At late endpoint, bilirubin level associated with increased risk uniquely in ACHD. CONCLUSIONS: Model of End-Stage Liver Disease eXcluding INR holds prognostic application to ACHD in early time points and demonstrates unique waitlist interactions. Transplant bilirubin level may hold significance in long-term risk stratification of the ACHD population. Time on waitlist is an important consideration to contextualize these values.

A composite noninvasive index correlates with liver fibrosis scores in post-Fontan patients: Preliminary findings.

OBJECTIVE: We hypothesized that clinic-based, hepatic-ultrasound, elastography measurements, either alone or in combination with other noninvasive variables, might correlate with liver-biopsy fibrosis scores in patients post-Fontan. METHODS: Between March 2012 and February 2017, we identified patients post-Fontan that underwent elective cardiac catheterization and simultaneous transvenous hepatic biopsy. From this group, we selected patients that met inclusion criteria for liver-ultrasound, shear-wave elastography. Utilizing the results of elastography, laboratory testing, and time post-Fontan, we constructed a composite Fontan hepatic index as a sum of elastography measurements in kilopascals, model for end-stage liver disease excluding INR scores, and the square root of the number of years post-Fontan. Further, we analyzed correlations between Fontan hepatic index values and fibrosis scores from hepatic biopsy. RESULTS: We identified a total of 79 post-Fontan patients that underwent cardiac catheterization and liver biopsy. Of the 79 patients, 53 met inclusion criteria, and 32 consented to undergo hepatic-ultrasound elastography. Of the 32 that underwent elastography, data from 30 patients was used for analysis. We found no statistically significant differences in demographics, laboratory values, or cardiac catheterization data between the 30 included patients and the 21 that did not participate. Utilizing data from the 30 included patients, we found a strong, highly statistically significant correlation between the Fontan hepatic index values and total fibrosis scores (R = 0.8, P < .00001). However, the cohort size prevented reliable discriminating cut-off values for the range of total fibrosis scores. CONCLUSIONS: In a small cohort of patients post-Fontan, preliminary findings suggest that the composite Fontan hepatic index might be a clinically useful, noninvasive method of serially monitoring for hepatic fibrosis. Further studies, with large patient cohorts, are necessary to validate our findings and develop clinically useful discriminatory cutoff values.

Mortality Risk Stratification in Fontan Patients Who Underwent Heart Transplantation.

The number of patients who require orthotopic heart transplantation (OHT) for failing Fontan physiology continues to grow; however, the methods and tools to evaluate risk of OHT are limited. This study aimed to identify a set of preoperative variables and characteristics that were associated with a greater risk of postoperative mortality in patients who received OHT for failing Fontan physiology. Thirty-six Fontan patients were identified as having undergone OHT at University of California-Los Angeles Medical Center from 1991 to 2014. Data were collected retrospectively and analyzed. The primary end point was designated as postoperative mortality. After an average follow-up time of 3.5 years, 17 (44%) patients suffered postoperative mortality. Patient characteristics including (1) age <18 years at the time of OHT, (2) Fontan-OHT interval of <10 years, (3) systemic ventricular ejection fraction <20%, (4) moderate-to-severe atrioventricular valve insufficiency, (5) an elevated Model of End-stage Liver Disease, eXcluding INR score, or (6) need for advanced mechanical support before surgery were associated with an increased incidence of postoperative mortality. Using these risk factors, we present a theoretical framework to stratify risk of postoperative death in failing Fontan patients after OHT. In conclusion, a method such as this may aid in the transplantation evaluation and listing process of patients with failing Fontan physiology.

An Observation from Liver Biopsies Two Decades Post-Fontan.

This brief report describes an observation from liver biopsy results in nonfailing Fontan patients, currently in their second postoperative decade. In three patients, with either atriopulmonary or atrioventricular connections and functional left ventricles, we found no portal fibrosis. In contrast, we found portal fibrosis in three clinically similar, nonfailing Fontan patients with lateral tunnel connections and functional left ventricles. We recognize the results may be secondary to chance; nevertheless, we speculate about possible relevancy.

Takotsubo Cardiomyopathy in a 22-Year-Old Single-Ventricle Patient.

We report a highly unusual case of a 22-year-old woman with single-ventricle anatomy and a history of Fontan palliation who developed takotsubo cardiomyopathy. To our knowledge, takotsubo cardiomyopathy has not previously been described in a patient with single-ventricle anatomy, or more generally in any patient with congenital heart disease. The patient presented at our clinic for urgent examination after a 2-day history of chest pain that had begun upon the death of her dog. Invasive evaluation was refused by the patient; instead, she underwent electrocardiogram-gated coronary computed tomographic angiography, to rule out obstructive coronary disease. A physician who suspects takotsubo cardiomyopathy in a patient should look for new-onset chest pain and dyspnea coupled with these features: immediate onset of segmental akinesia in the midventricular or apical aspects of the heart, elevation of brain natriuretic peptide level 12 to 24 hours after onset of akinesia, elevation of troponin level 24 to 48 hours after onset, and disappearance of the segmental akinesia a few days after onset.

Fontan Outcomes and Pulmonary Blood Flow at Birth.

We previously noted, in a small group of post-Fontan patients, a possible association between hepatic fibrosis scores and the status of pulmonary blood flow at birth. To further explore this observation, we examined data from all Fontan patients seen in our center from July 2010 to March 2015. We identified 200 patients for analysis. Of the 200 patients, 56 underwent transvenous-hepatic biopsy. Of the 200 patients, 13 (6.5%) had protein-losing enteropathy. We divided both the 56 biopsy patients and the entire cohort of 200 patients into 4 groups: (1) unobstructed pulmonary blood flow at birth with functional left ventricles, (2) unobstructed pulmonary blood flow at birth with functional right ventricles, (3) obstructed pulmonary blood flow at birth with functional left ventricles, and (4) obstructed pulmonary blood flow at birth with functional right ventricles. Analysis of the 56 liver-biopsy patient groups showed median hepatic total-fibrosis scores for the 4 groups of 2 (0-6), 2 (0-8), 3 (2-6), and 4 (1-8), respectively, with statistical significance between groups 4 and 1 (p = 0.031). For the entire cohort of 200 patients, we analyzed the incidence of protein-losing enteropathy for each of the four groups and found protein-losing enteropathy percent occurrences of 0, 2.9, 8.8, and 16.1, respectively, with statistical significance between groups 4 and 2 (p = 0.031) and between groups 4 and 1 (p = 0.025). A history of obstructed pulmonary blood flow at birth, coupled with a functional right ventricle, may predict a poorer long-term Fontan outcome.

Superior vena cava stenting guided by alternative imaging modalities in a patient with severe contrast allergy: a case report and brief literature review.

Major adverse reactions to iodinated radiocontrast media are an uncommon but serious complication of cardiac catheterizations. We present a case of a 52-year-old woman with a sinus venosus atrial septal defect and partial anomalous pulmonary venous connection status post repair who presented with superior vena cava graft obstruction. Two overlapping stents were placed within the superior vena cava using gadolinium, CO2 angiography and transesophageal echocardiography for visualization of the graft stenoses. No iodinated media were used.

Usefulness of serum brain natriuretic peptide to predict adverse events in patients with the Eisenmenger syndrome.

The aim of this study was to evaluate the prognostic value of brain natriuretic peptide (BNP) in outpatients with the Eisenmenger syndrome (ES). BNP is often elevated in patients with cyanotic congenital heart disease. The clinical utility of BNP in patients with cyanotic congenital heart disease and the ES has not been clearly delineated. Records of adults with ES who had undergone serum BNP measurement were reviewed. The primary end point was death or heart failure admission. Fifty-three patients were included, with 15 patients (28%) meeting the primary end point (death in 7, heart failure hospitalization in 8). Mean and median baseline BNP in patients meeting the primary end point were 322 ± 346 and 179 pg/ml, compared to 100 ± 157 and 41 pg/ml in those not meeting the primary end point (p = 0.0029). A Cox proportional-hazards model using baseline BNP between the 2 groups yielded a hazard ratio of 1.84 (95% confidence interval [CI] 1.19 to 2.85, p = 0.006). The relative risk for baseline BNP level >140 pg/ml was 4.62 (95% CI 1.80 to 11.3, p = 0.008). Patients who met the primary end point increased their BNP levels by 42.5 pg/ml per year (95% CI 12.09 to 72.95, p = 0.006) compared to 7.2 pg/ml per year (95% CI 2.01 to 12.47, p = 0.007) in patients who did not meet the primary end point. In conclusion, elevated BNP levels are predictive of death or heart failure admission in patients with the ES. A serum BNP level >140 pg/ml is a useful tool in identifying high-risk patients.