Search Results (52)

Patients with Fontan circulation are at lifelong risk for a range of complications involving multiple organ systems. As survival into adulthood increases, there is an urgent need to refine strategies for long-term follow-up and the early detection of Fontan-related sequelae. This narrative review aims to provide a comprehensive summary of the current evidence regarding the use of circulating blood biomarkers as non-invasive tools for assessing and monitoring Fontan physiology. We critically analyzed available studies investigating serum biomarkers related to key pathological mechanisms associated with Fontan failure, encompassing not only cardiac dysfunction but also systemic inflammation, endothelial dysfunction, hepatic and renal impairment, and altered bone metabolism. Several biomarkers have shown promise in reflecting global systemic impairments as well as end-organ involvement in Fontan patients. However, current data are insufficient to support evidence-based clinical recommendations for standardized specific biomarkers, mainly due to the small sample sizes, heterogeneous patient populations, and limited longitudinal data in the available studies. Only a large-scale, prospective, multi-center, and multidisciplinary research will permit us to identify a panel of specific biomarkers of clinical utility in this population. Artificial intelligence (AI) and machine learning (ML) approaches could be applied to integrate all these heterogeneous datasets. Furthermore, “omics”-based studies, including proteomics, metabolomics, lipidomics, and microRNA profiling, hold great potential for uncovering novel biomarkers and pathophysiological pathways, ultimately paving the way for precision medicine in the management of Fontan patients. Full article

Background: Fontan circulation is associated with impaired cardiac output, reduced exercise capacity, and systemic metabolic stress. However, the underlying lipidomic alterations remain poorly defined. Methods: Using targeted mass spectrometry, we analyzed 291 lipid species in fasting plasma samples from 20 adults with Fontan circulation and 20 age- and sex-matched healthy controls. Results: Forty-eight lipids were significantly altered between groups (p < 0.05), including reductions in total lysophosphatidylcholines (LPC) and total ether-linked LPC [LPC(O)] and elevations in total phosphatidylserines (PS). Notably, LPC(O-22:1) and LPC(O-20:0) were decreased, while PS 40:5 was elevated, with several of these species demonstrating strong correlations (|r| > 0.5, p < 0.001) with the stroke index, cardiac index, and VO₂max. These three lipid species also showed excellent capability in discriminating Fontan patients from healthy controls (AUC > 0.78). Correlation network and pathway enrichment analyses revealed tightly coordinated lipid clusters containing LPC/LPC(O), PE, and PS species as central features of dysregulated Fontan metabolism. Conclusions: These exploratory findings highlight coordinated lipid alterations associated with impaired cardiovascular reserve in Fontan patients. While based on unadjusted p-values and therefore being hypothesis-generating, they provide novel insight into the metabolic landscape of Fontan physiology and warrant validation in larger, independent cohorts. Full article

Background/Objectives: This study aimed to investigate the prevalence of liver damage and its associated non-invasive markers and echocardiographic risk factors in patients who underwent surgery for congenital heart disease. Methods: This retrospective observational study was conducted at a single tertiary-care university hospital in Niigata, Japan. Of 142 patients (ventricular septal defect [VSD] n = 47, tetralogy of Fallot [TOF] n = 67, Fontan n = 28), 52.8% were male [median age: 22.7 years; VSD (24.3 years), TOF (24.0 years), and Fontan (12.5 years)]. Pediatric patients with liver diseases unrelated to congestive liver disease, such as viral hepatitis and alcoholic liver disease, were excluded. We compared non-invasive liver fibrosis age-invariant biomarkers, such as the aspartate aminotransferase-to-platelet ratio index (APRI), and various serum markers and echocardiographic parameters to assess the prevalence and predictors of hepatic fibrosis. Results: The Fontan circulation group had the highest APRI, followed by the TOF group, while the VSD group had a low risk of APRI elevation. Postoperative TOF patients required monitoring for cirrhosis progression. Inferior vena cava mobility was associated with echocardiographic parameters and fibrosis severity, along with a loss of respiratory variability. The limitations of other cardiac assessments were highlighted by poor anatomical measurements. Gamma-glutamyl transpeptidase (γ-GTP) demonstrated strong discriminatory ability. The optimal cutoff value was 53.0 U/L, suggesting its use as a clinical marker. Conclusions: Assessing fibrosis is crucial in CHD patients, especially those with late post-TOF repair findings. Non-invasive markers (APRI, γ-GTP, and B-type natriuretic peptide), along with echocardiographic findings, may help detect fibrosis early, enabling timely intervention and improving long-term outcomes. Clinical trial registration: 2020-0199. Full article

Background and Clinical Significance: Left ventricular hypoplasia is often repaired surgically in sequence to a Fontan circulation, which is a physiologic state that presents unique challenges during pregnancy. Although women with Fontan physiology can achieve successful pregnancy outcomes, they remain at elevated risk for cardiac, thrombotic, and obstetric complications. Case Presentation: We describe a 38-year-old woman with Fontan physiology and acquired von Willebrand syndrome (AVWS) who was admitted at 23 weeks gestation for preterm premature rupture of membranes. The patient had history of prior classical cesarean delivery and two previous miscarriages. Her pregnancy was further complicated by abnormal placental vasculature and uterine arteriovenous malformation. Given her bleeding diathesis, hematology advised against anticoagulation or antiplatelet therapy, and she ultimately underwent a successful low transverse cesarean delivery under general anesthesia at 24 weeks. Postpartum hemorrhage was managed with clotting factor replacement and supportive care. Conclusions: This case illustrates how AVWS may mitigate thrombotic risk in Fontan physiology and how early activation of a cardio-obstetrics team can enable tailored planning. As more patients with complex congenital heart disease reach reproductive age, multidisciplinary coordination, shared infrastructure, and individualized birth plans will be essential to achieving optimal maternal–fetal outcomes. Full article

As the population of adults with congenital heart disease (ACHD) continues to grow, a significant and often underrecognized complication is the development of cardiorenal syndrome (CRS)—a complex, bidirectional interaction between cardiac and renal dysfunction. While CRS has been extensively studied in acquired heart failure, its manifestations and implications in ACHD remain insufficiently understood. Emerging data suggest that renal dysfunction is highly prevalent in ACHD, with significant associations to adverse outcomes regardless of cardiac lesion type or functional status. This review explores CRS within three key physiologic categories in ACHD: patients with a systemic right ventricle, those with a subpulmonary right ventricle, and those with Fontan circulation. Each subgroup presents unique hemodynamic challenges that affect renal perfusion, filtration pressure, and systemic congestion, contributing to both acute and chronic renal impairment. The utility of renal biomarkers such as albuminuria, cystatin C, and estimated glomerular filtration rate (eGFR) is emphasized, alongside the importance of early detection and multidisciplinary management. Heart failure therapy tailored to congenital anatomy, neurohormonal modulation, and careful volume control remain the cornerstones of treatment, while transplantation strategies must consider the potential for irreversible end-organ damage. Given the profound implications of CRS on quality of life and survival, a comprehensive understanding of its pathophysiology and management in ACHD is critical to optimizing long-term outcomes in this increasingly complex patient population. Full article

Background: The aim of this study was to describe our centre experience in the use of pulmonary vasodilator therapy in Fontan patients. Methods: We retrospectively enrolled patients that underwent Fontan operation between 2000 and 2024, reporting demographic and operative data and noting complications and the use of pulmonary vasodilators. Results: A total of 117 patients were followed for a median time of 150 months (90–207). In total, 36.7% were female, and the median age during the intervention was 50 months (37–64), and 53% had a single left ventricle physiology. In 20 of these 117 patients (17.1%), at least one pulmonary vasodilator drug was used during their life for the following reasons: 6 elevated pressures in the circuit, 3 low oxygen saturation, 2 plastic bronchitis, 2 pleural effusion, 1 chylothorax, 1 persistent pericardial effusion, 1 haemoptysis, 1 protein losing enteropathy, 1 poor exercise tolerance, 1 pulmonary arterial hypertension present since birth and 1 diastolic dysfunction. They had a significantly higher prevalence of single right ventricle physiology (65% vs. 37%, p = 0.03), pulmonary hypertension (60% vs. 0, p = 0.0001), plastic bronchitis (10% vs. 0, p = 0.03) and declivous oedema in the follow-up period (10% vs. 0, p = 0.03), with a higher assumption of warfarin (35% vs. 6.2%, p = 0.001). Conclusions: We found that in the absence of a standardise protocol, we usually use pulmonary vasodilator therapy in Fontan patients, as it is guided by clinical aspects and hemodynamic conditions, which lead us to start and stop this therapy. Full article

Staged palliation with the creation of a Fontan circulation is the standard surgical approach in patients with a single ventricle. The Fontan circulation is a complex circuit that is associated with various complications that may present early or later in life and can limit life quality and expectancy. In this context, a good understanding of the Fontan physiology is important to improve outcomes for single-ventricle patients. Cardiovascular magnetic resonance (CMR) is recommended for the long-term follow-up of Fontan patients, as it provides functional and haemodynamic information. Four-dimensional (4D) Flow MRI is a time-resolved, three-dimensional, velocity-encoded cardiovascular magnetic resonance technique that is increasingly used in Fontan patients because it not only enables measuring blood flow within a three-dimensional (3D) volume, but also allows for assessing more advanced haemodynamic parameters that may help in understanding the Fontan physiology and pathophysiology. Furthermore, 4D Flow is used for image-based simulations using computational fluid dynamics. In this review, we provide an overview of the use of cardiovascular magnetic resonance flow assessment, with a focus on four-dimensional flow (‘4D Flow’). Full article

Fontan circulation is a fragile system in which imperfections at any of multiple levels may compromise the quality of life, produce secondary pathophysiology, and shorten life span. Increased inferior vena caval pressure itself may play a role in “Fontan failure”. This study describes a mock flow loop model (MFL) designed to quantitatively estimate pulmonary flow entrainment induced by continuous and pulsed flow injections. A patient generic 3D-printed phantom model of the total cavopulmonary connection (TCPC) with average dimensions matching those of a 2–4-year-old patient was inserted in an MFL derived from a reduced lumped parameter model (LPM) representing cardiovascular circulation. The LPM comprises four 2-element Windkessel compartments (compliance and resistance), approximating the upper and lower systemic circulations and the right and left pulmonary circulations. The prescribed cardiac output is about 2.3 L/min for a body surface area of $0.675{ \mathrm{m}}^2$. The injections originate from an external pump through a 7–9 fr catheter, following a strict protocol suggested by the clinical team, featuring a variation in injection rate (flow rate), injection volume, and injection modality (continuous or pulsed). The key measurements in this study are the flow rates sampled at the distal pulmonary arteries, as well as at the upper and lower body boundaries. These measurements were then used to calculate effective entrainment as the difference between the measured and expected flow rates, as well as jet relaxation (rise and fall time of injection). The results show that for continuous or pulsed injections, varying the total volume injected has no significant influence on the entrainment rate across all injection rates. On the other hand, for both injection modalities, increasing the injection rate results in a reduction in entrainment that is consistent across all injected volumes. This study demonstrates the effectiveness of a high-speed injection jet entraining a slow co-flow while determining the potential for fluid buildup, which could ultimately cause an increase in caval pressure. To avoid the increase in caval pressure due to mass accumulation, we added a fenestration to our proposed injection jet shunt-assisted Fontan models. It was found that for a set of well-defined parameters, the jet not only can be beneficial to the local flow, but any adverse effect can be obviated by careful tuning. These results were also cross-validated with similar in silico findings. Full article

Advances in surgical and medical management of congenital heart disease have improved survival rates, leading to a growing population of adult congenital heart disease (ACHD) patients requiring specialized perioperative care. Studies indicate that ACHD patients undergoing non-cardiac surgery (NC surgery) have increased mortality and morbidity risks compared to the general population, with complication rates particularly high in those with complex defects, such as Fontan circulation, Eisenmenger syndrome, or cyanotic congenital heart disease. Key perioperative concerns include hemodynamic instability, arrhythmias, thromboembolic events, and bleeding risks. Additionally, comorbidities, such as frailty, chronic inflammation, or respiratory disease, further complicate perioperative management. Multidisciplinary collaboration is critical, involving cardiologists, anesthesiologists, and surgeons to optimize preoperative preparation and perioperative monitoring. Preoperative risk stratification is essential, integrating congenital heart lesion complexity, functional status, and procedural risk. This review underscores the importance of structured preoperative assessment, appropriate risk evaluation, and individualized perioperative strategies to improve surgical outcomes in ACHD patients undergoing NC surgery. Further research is needed to refine risk prediction models and optimize perioperative protocols tailored to this unique patient population. Full article

Background/Objectives: Management of complex congenital heart defects with functionally single ventricle remains one of the greatest challenges of pediatric cardiology. The multistage surgical treatment completed with Fontan procedure is related to multiple complications. Due to non-pulsatile continuous pulmonary flow and chronic hypoxia, Fontan circulation may induce pulmonary endothelial dysfunction. However, the impact of Fontan physiology on respiratory system function is not well studied. The aim of the research was to assess respiratory function in Fontan pediatric patients with hypoplastic left heart syndrome (HLHS) and other morphologies of functionally single ventricle. The article presents the preliminary results drawn from the pilot study, focusing on Fontan patients, without a healthy children control group. Methods: A cross-sectional study involved Fontan patients hospitalized in the Pediatric Cardiology Clinic of the Medical University of Silesia in Katowice between August 2023 and November 2024. The exclusion criteria were lack of parental and/or patient’s consent, age < 6 years old, decompensated heart failure, asthma, atopy, respiratory infection within two weeks before the hospitalization, or significant psychomotor disability. Respiratory function assessment involved spirometry and fractional exhaled nitric oxide (FeNO) measurement. Results: A total of 32 patients who met inclusion criteria performed respiratory measurements. The mean age was 12.9 years old; there were 12 females. A total of 12 patients had HLHS and 20 patients had other morphologies of univentricular heart. FeNO values were relatively high with a mean of 30 ppb. Spirometry showed restrictive or mixed restrictive and obstructive ventilatory pattern. The mean forced vital capacity (FVC) levels were 79.2 ± 12.3% of predicted value (%pv) and forced expiratory volume in the first second (FEV1) 77.3 ± 13.8%pv. Children with HLHS presented statistically significantly lower percentages of predicted value of FEV1. There were statistically significant negative correlations between NT-proBNP concentrations and FEV1, FEV1%pv, MEF25-75 and MEF25-75%pv. Conclusions: Fontan pediatric patients present a restrictive or mixed restrictive and obstructive ventilatory pattern and relatively high FeNO levels. Patients with HLHS have worse pulmonary function than patients with other univentricular heart morphologies. This may be related to worse ventricular function in patients with HLHS. Full article

Background: The Fontan procedure has provided pediatric patients suffering from severe congenital heart disease the opportunity to reach adulthood. Increasingly, we encounter the liver repercussions of Fontan circulation, alongside a decline in heart function and exercise performance. This study aims to identify the univentricular heart malformations that are most susceptible to liver dysfunction; assess which markers of liver injury are essential for multidisciplinary clinical follow-up of Fontan patients; determine the optimal approach for evaluating liver function in Fontan patients; and explore how a congenital cardiology team can interpret the data and respond effectively to signs of organ failure. Methods: Cross-sectional clinical study including patients who underwent a Fontan procedure at the University Hospital of Padua between 1982 and 2017. Patients were admitted for elective hospitalization between June 2021 and June 2022 and underwent clinical assessment, laboratory tests, and instrumental examinations. Results: Seventy patients were included in the study. On admission, 48 patients (72%) were in New York Heart Association (NYHA) functional class I, and the cardiopulmonary exercise test was normal for age and gender. At laboratory tests, 56% of patients showed changes in NTproBNP values, most of whom had right-sided ventricular morphology. Liver function tests showed abnormal Gamma-Glutamyl Transferase (GGT) blood levels in 68%. On cardiac imaging, at least moderate atrioventricular valve insufficiency was found in 9% of cases. Fibroscan showed altered hepatic stiffness values in 25% of cases. Statistical analysis showed that systemic atrioventricular valve (SAVV) dysfunction was significantly associated with a reduction of maximum oxygen consumption (VO₂ max) and hepatic stiffness. Conclusions: SAVV dysfunction is significantly responsible for worse functional outcomes and the development of hepatic fibrosis due to an increase in venous congestion. Setting up a careful multidisciplinary follow-up in these patients is mandatory for early detection of complications, prompt treatment, and better outcomes. Full article

Patients with a univentricular heart live with chronic hypoxia (75–85%) in their first years of life, which could affect adaptation to altitude or other hypoxic insults later in life. To test this hypothesis, we exposed 18 patients with Fontan circulation (age: 24.5 [16.3–38.8] years; f/m 9/9) to simulated altitude using normobaric hypoxia (15.2% oxygen, equivalent to 2500 masl) for 24 h. In blood samples obtained in normoxia (T1, 21% oxygen) and after 24 h hypoxia after a submaximal stress test, we measured hypoxia-regulated molecules involved in angiogenesis and tissue homeostasis. A significant increase was displayed for IL-10 (p = 0.001), CCL2 (p = 0.006), ANG-1 (p = 0.001), ANG-2 (p = 0.029), FGF-1 (p = 0.001) and FGF-2 (p = 0.024). E-Selectin (p < 0.001) and NRG-1 were significantly different at p = 0.026 at T2 compared to baseline. However, OPN and OSF-1 did not exhibit significant changes (p = 0.348; p = 0.065). Fontan patients show hypoxia-related protein patterns similar to healthy individuals despite intermittent hypoxemia, but their response to standardised hypoxia was described here for the first time, requiring further study. Full article

The Fontan operation has become the primary palliative treatment for patients with a functionally univentricular heart. The population of patients with Fontan circulation is constantly growing and aging. As the number of Fontan patients surviving into adulthood increases, there is a clear need for research on how best to follow these patients and manage their complications. Monitoring blood biomarkers is a promising method for the non-invasive assessment of the Fontan circulation. In this article, we provide a comprehensive review of the available evidence on this topic. The following biomarkers were included: natriuretic peptides, red blood cell distribution width (RDW), cystatin C, high-sensitivity C-reactive protein, vitamin D, parathyroid hormone, von Willebrand factor, carbohydrate antigen 125, lipoproteins, hepatocyte growth factor, troponins, ST2 protein, galectin-3, adrenomedullin, endothelin-1, components of the renin–angiotensin–aldosterone system, norepinephrine, interleukin 6, tumor necrosis factor α, and uric acid. We did not find strong enough data to propose evidence-based recommendations. Nevertheless, significantly elevated levels of brain natriuretic peptide (BNP)/N-terminal prohormone of BNP (NT-proBNP) are most likely associated with the failure of the Fontan circulation. The use of the RDW is also promising. Several biomarkers appear to be useful in certain clinical presentations. Certainly, robust longitudinal, preferably multicenter, prospective studies are needed to determine the sensitivity, specificity, evidence-based cut-off values and overall predictive value of different biomarkers in monitoring Fontan physiology. Full article

Background: Systemic-to-pulmonary collaterals (SPCs) are common in congenital heart disease (CHD). Particularly in single ventricle anatomy and Fontan circulation, SPC can both complicate the postoperative course and lead to clinical deterioration in the long term. The treatment of SPC is controversial. The aim of our study was (1) to retrospectively analyse patients who underwent SPC embolization using Concerto™ Helix nylon-fibred microcoils (CHMs) and (2) to describe the interventional technique. Methods: In this single-centre retrospective observational cohort study, we analysed clinical and imaging data of all patients who underwent transcatheter embolization of SPCs using CHMs from January 2016 to December 2023. Results: In 38 consecutive patients (65.8% male, median age 41 months, range 2–490), a total number of 141 CHMs had been implanted into 64 SPCs in 49 procedures. The majority were arterial SPCs (n = 59/64) originating from the thoracic aorta or its branches; 5/64 were veno-venous SPCs. Primary closure succeeded in all procedures. The CHM diameters ranged from 3 to 8 mm, with 5 mm being the most commonly used diameter. The mean coil/SPC ratio was 2.6 (range 1.3–5.3). CHM implantation was performed via four French sheaths. Both detachment and stable positioning were simple and safe. Neither non-target embolization nor coil migration occurred. One complication was a vascular injury with resulting extravasation of contrast medium. In 18/49 procedures (36.7%), coils other than CHMs or vascular plugs were additionally inserted into separate SPCs. Conclusions: CHMs are appropriate for SPC embolization in all age groups, including infants, with a low complication rate. The coils are particularly suitable for the closure of collaterals with a small diameter or tortuous course. They can be used in combination with other embolization devices to achieve comprehensive collateral closure. Full article

Background: Fontan circulation maintains an elevated venous pressure; this promotes venous and lymphatic congestion and may lead to late circuit failure. Our objective was to determine the association between thoracic lymphatic perfusion patterns assessed by magnetic resonance imaging and late Fontan failure. Methodology: A retrospective study was performed. We included patients who underwent the Fontan procedure between January 2005 and December 2019 and who were evaluated with lymphatic mapping using magnetic resonance imaging. Lymphatic abnormalities were classified into four types. The prevalence of late failure was determined, and logistic regression analysis was performed to establish the association between the variables of interest and the outcome. Results: Fifty-four patients were included with a mean age at surgery of 8.8 years ± 3.5 years; 42.6% (n = 23) were men. The most frequent diagnosis was tricuspid atresia (50%, n = 27), and the Fontan procedures were mainly performed using an extracardiac conduit (96.3%, n = 52). The prevalence of late Fontan failure was 35.2%. The lymphatic perfusion patterns observed were Type 1 in 25.9% (n = 14), Type 2 in 46.3% (n = 25), Type 3 in 25.9% (n = 14), and Type 4 in 1.8% (n = 1), with no differences in relation to late failure. (p = 0.42). The age at surgery was found to be a factor associated with the late Fontan failure (OR: 1.23; 95% CI: 1.02–1.48; p = 0.02). Conclusions: One-third of patients with Fontan circulation may experience late failure, not significantly associated with lymphatic changes, but when the total cavopulmonary connection is completed at an older age. Full article