Search

Longstanding left-to-right shunting associated with congenital heart disease (CHD) can ultimately lead to pulmonary vascular remodeling, pulmonary arterial hypertension, and shunt reversal, the hallmark feature of Eisenmenger Syndrome (ES). ES is a multisystem disease, with hematologic, cardiovascular, renal, neurologic, immune, and other manifestations, each of which inform its management. Many of the most distinct and clinically important consequences relate to chronic hypoxemia. The incidence of ES in in countries with access to pediatric cardiology and cardiac surgery services has declined in recent decades, due to earlier diagnosis and intervention for CHD. Moreover, in the era of disease targeting therapies (DTT), ES appears to be associated with better quality of life and less limiting symptoms. In addition, observational studies suggest that these therapies, alone and in combination, may be associated with improved survival. Despite these developments, ES mortality remains high, with heart failure being the most common cause of death. In this review, we discuss the pathophysiology of ES, the evolving understanding of risk stratification, as well as recent progress in pharmacologic and surgical management. Ultimately, despite strides in understanding and management of this complex disease, significant knowledge gaps remain.

Background: Gaps in subspecialty cardiology care could potentially delay identification and care for multi-organ complications common in patients with Fontan circulation. This study analyzed the frequency of gaps in care for individuals with Fontan circulation during the COVID-19 pandemic and associated demographic and clinical factors. Methods: This retrospective study evaluated individuals with Fontan circulation followed at our center since 2010. A gap in care was defined as an absence of any formal cardiology provider-patient contact (clinic visit or telehealth) for >15 months. Results: Over a third of 308 patients with Fontan circulation experienced at least one gap in care between 2010 and 2022, and 77 experienced a gap in care during the COVID-19 pandemic. Of this latter group, 27 (35%) had never experienced a prior gap in cardiology care until the pandemic. Those who experienced gaps in care during the pandemic were on average older (18.0 [IQR 9.6–25.6] vs. 14.2 [7.2–21.2] years, p = 0.01), more likely to be of Black/African American race (23.4% vs 7.4%, p = 0.001), and less likely to have a diagnosis of protein-losing enteropathy or plastic bronchitis (0% vs. 8.6%, p = 0.005). Those without a gap in care during the pandemic were more likely to have utilized telehealth visits (13% vs 3%, p = 0.02). Conclusion: Gaps in care are common and appear to have been exacerbated by the COVID-19 pandemic in those with a Fontan circulation. Such gaps are particularly common among African American and adult patients, and may potentially be mitigated by expanding telehealth access.

Introduction: The number of heart transplants in adults with congenital heart disease (CHD) is increasing, though outcomes remain unfavorable compared to those without CHD. The etiology of this mortality difference remains uncertain. Panel reactive antibody (PRA) is a predictor of survival post-transplantation, and adult CHD patients have been observed to have higher PRA levels. Here we assessed the relationship between PRA and outcomes in adult patients with CHD who underwent heart transplantation. Methods: This is a retrospective cohort study using the 2004–2015 ISHLT Thoracic Organ Transplant Registry to investigate the role of sensitization in the observed excess mortality. The composite outcome of mortality or graft failure within 1-year of transplantation was compared among CHD vs. non-CHD recipients, according to sensitization as measured by pre-transplant panel reactive antibodies (PRA). Results: Adults with CHD (n = 1188) had higher PRA level compared to non-CHD (n = 38,201) recipients (27% vs. 18% PRA>10%, respectively, p 10% (OR 1.1 [0.6–2.0], p = 0.852). Conclusions: Adults with CHD are more likely to have higher sensitization and worse outcomes than non-CHD recipients. Higher sensitization rates alone do not fully explain their excess risk of adverse outcomes after heart transplantation.

Background: Biomarkers are increasingly part of assessing and managing heart failure (HF) in adults with congenital heart disease (CHD). Objectives: To understand the response of cardiac biomarkers with therapy for acute decompensated heart failure (ADHF) and the relationship to prognosis after discharge in adults with CHD. Design: A prospective, observational cohort study with serial blood biomarker measurements. Settings: Single-center study in the inpatient setting with outpatient follow-up. Participants: Adults (≥18 years old) with CHD admitted with ADHF between August 1, 2019, and March 1, 2020. Exposure: We measured body mass, Kansas City Cardiomyopathy Questionnaire (KCCQ-12) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) at enrollment, discharge, and 1st clinic follow-up visit; soluble suppression of tumorigenicity 2 (sST2) was measured at the first two time points. Measures: Univariate regression assessed the association between changes in weight, biomarkers, and changes in KCCQ-12 scores, between enrollment and discharge (ΔHospitalization) and between discharge and 1st clinical follow-up visit (ΔPost−discharge). Wilcoxon rank-sum tests assessed the association between change in biomarkers, KCCQ-12 scores, and the composite outcome of cardiovascular death or rehospitalization for ADHF. Results: A total of 26 patients were enrolled. The median age was 51.9 years [IQR: 38.8, 61.2], 13 (54.2%) were women, and median hospital stay was 6.5 days [IQR: 4.0, 15.0] with an associated weight loss of 2.8 ​kg [IQR -5.1, −1.7]. All three cardiac biomarkers decreased during hospitalization with diuresis while KCCQ-12 scores improved; a greater decrease in sST2 was associated with an improved KCCQ-12 symptom frequency (SF) subdomain score (p ​= ​0.012), but otherwise, there was no significant relationship between biomarkers and KCCQ-12 change. Change in hsCRP and NT-proBNP after discharge was not associated with the composite outcome (n ​= ​8, vs. n ​= ​16 who did not experience the outcome; Δ Post-discharge hsCRP +5.1 vs. −1.0 ​mg/l, p ​= ​0.061; NT-proBNP +785.0 vs. +130.0 ​pg/ml, p ​= ​0.220). Conclusions: Serial biomarker measurements respond to acute diuresis in adults with CHD hospitalized for ADHF. These results should motivate further research into the use of biomarkers to inform HF therapy in adults with CHD.

The Fontan or Fontan Kreutzer procedure is the culmination of staged, surgical palliation of functional single ventricle congenital heart disease, offering the potential for survival and good quality of life well into adulthood. As more patients with Fontan circulation age, a variety of complications involving almost every organ system may occur. Protein-losing enteropathy is a major cause of morbidity and mortality after the Fontan operation, occurring more often in patients with adverse hemodynamics and presenting weeks to years after Fontan surgery. The causes are not well understood, but likely include a combination of lymphatic insufficiency, high central venous pressure, loss of heparan sulfate from intestinal epithelial cells, abnormal mesenteric circulation, and intestinal inflammation. A comprehensive evaluation including multimodality imaging and cardiac catheterization is necessary to diagnose and treat any reversible causes. In advanced cases, early referral for heart transplantation evaluation or lymphatic decompression procedures (if the single ventricle function remains adequate) is indicated. Despite the improvement in detection and management options, the mortality remains high. Standardization of protein-losing enteropathy definition and management strategies will help facilitate interpretation of research and clinical experience, potentially fostering the identification of new therapies. Based on the published data, this review suggests a standardized approach to diagnosis and treatment.

Background: The Fontan circulation is associated with low skeletal muscle mass, which affects the accuracy of creatinine-based glomerular filtration rate estimates (eGFR/GFR). Cystatin C, another filtration marker, is less impacted by muscle mass. We examined associations between characteristics of individuals with a Fontan circulation and both creatinine-based and cystatin C-based eGFR. Methods and results: This single-center retrospective study included 107 individuals with a Fontan circulation who had clinical measurements of serum cystatin C and creatinine. GFR was estimated using different equations for adults (≥19 years of age, Chronic Kidney Disease-Epidemiology Collaboration equations for both creatinine and cystatin C) and children (

Background: The Model for End-stage Liver Disease excluding INR (MELD-XI) is commonly used to identify patients with a Fontan circulation at increased risk of adverse events, However, this approach has not been evaluated in unselected ambulatory adults. Methods: We enrolled a cohort of 163 outpatients with a Fontan circulation aged ≥18-years in the Boston Adult Congenital Heart Disease Biobank from 2012 to 2018. Survival analysis was performed to assess the relationship between MELD-XI with both all-cause mortality and a composite outcome of mortality or non-elective cardiovascular hospitalization. Results: Mean age was 30.2±9.7 years, and 41.1% were women. Most had a lateral tunnel Fontan (62.6%). MELD-XI score averaged 10.6±2.1 (median = 13). Both creatinine and total bilirubin were ≤1.0 mg/dL in 94/163 (57.7%), translating to the lowest possible score. MELD-XI18. During follow-up of 3.2±2.2 years, the composite outcome occurred in 58 patients (35.6%), with 16 deaths (9.8%). Most deaths (n = 11, 68.8%) and composite outcomes (n = 39, 67.2%) occurred among patients with MELD-XI less than the median. MELD-XI score did not differ between those who did and did not have events (death: 10.8±2.2 vs. 10.6±2.1; p = 0.92; composite outcome: 10.6±2.2 vs. 10.7±2.1, p = 0.45). Likewise, survival analysis did not suggest an association between MELD-XI and either outcome. Conclusions: MELD-XI score does not appear to be associated with risk for adverse outcomes in an unselected cohort of outpatients with a Fontan circulation. Prior findings may reflect conditioning on a clinical referral for laboratory testing.