Search Results (30)

Background: Patient reported outcomes (PROs) are important measures in acquired heart disease but have not been well defined in Adult Congenital Heart Disease (ACHD). Our aim was to explore the discriminatory capacity of PRO survey tools in Fontan circulatory failure (FCF). Methods: Consecutive adults were enrolled from our ambulatory clinics. Inclusion criteria were age ≥18 years, a Fontan circulation or a hemodynamically insignificant shunt lesion, and sufficient cognitive/language abilities to complete PROs. A comprehensive package of PRO measures, designed to assess perceived health-related quality of life (HRQOL) was administered (including the Kansas City Cardiomyopathy Questionnaire [KCCQ-12], EuroQol-5-dimension [EQ5D], Short Form Health Status Survey [SF-12], self-reported New York Heart Association [NYHA] Functional Class, and Specific Activity Scale [SAS]). Results: We compared 54 Fontan patients (35 ± 10 years) to 25 simple shunt lesion patients (34 ± 11 years). The KCCQ-12 score was lower in Fontan versus shunt lesion patients (87 [IQR 79, 95] versus 100 [IQR 97, 100], p-value < 0.001). The FCF subgroup was associated with lower KCCQ-12 scores as compared with the non-FCF subgroup (82 [IQR 56, 89] versus 93 [IQR 81, 98], p-value = 0.002). Although the KCCQ-12 had the best discriminatory capacity for determination of FCF of all PRO tools studied (c-statistic 0.75 [CI 0.62, 0.88]), superior FCF discrimination was achieved when the KCCQ-12 was combined with all PRO tools (c-statistic 0.82 [CI 0.71, 0.93]). Conclusions: The KCCQ-12 questionnaire demonstrated good discriminatory capacity for the identification of FCF, which was further improved through the addition of complementary PRO tools. Further research will establish the value of PRO tools to guide management strategies in ACHD. Full article

Over the last four decades, the Fontan operation has been the treatment of choice for children born with complex congenital heart diseases and a single-ventricle physiology. However, therapeutic options remain limited and despite ongoing improvements in initial surgical repair, patients still experience a multiplicity of cardiovascular complications. The causes for cardiovascular failure are multifactorial and include systemic ventricular dysfunction, pulmonary vascular resistance, atrioventricular valve regurgitation, arrhythmia, development of collaterals, protein-losing enteropathy, hepatic dysfunction, and plastic bronchitis, among others. The mechanisms leading to these late complications remain to be fully elucidated. Experimental animal models have been developed as preclinical steps that enable a better understanding of the underlying pathophysiology. They furthermore play a key role in the evaluation of the efficacy and safety of new medical devices prior to their use in human clinical studies. However, these experimental models have several limitations. In this review, we aim to provide an overview of the evolution and progress of the various types of experimental animal models used in the Fontan procedure published to date in the literature. A special focus is placed on experimental studies performed on animal models of the Fontan procedure with or without mechanical circulatory support as well as a description of their impact in the evolution of the Fontan design. We also highlight the contribution of animal models to our understanding of the pathophysiology and assess forthcoming developments that may improve the contribution of animal models for the testing of new therapeutic solutions. Full article

This study introduces an innovative approach leveraging physics-informed neural networks (PINNs) for the efficient computation of blood flows at the boundaries of a four-vessel junction formed by a Fontan procedure. The methodology incorporates a 3D mesh generation technique based on the parameterization of the junction’s geometry, coupled with an advanced physically regularized neural network architecture. Synthetic datasets are generated through stationary 3D Navier–Stokes simulations within immobile boundaries, offering a precise alternative to resource-intensive computations. A comparative analysis of standard grid sampling and Latin hypercube sampling data generation methods is conducted, resulting in datasets comprising $1.1\times {10}^4$ and $5\times {10}^3$ samples, respectively. The following two families of feed-forward neural networks (FFNNs) are then compared: the conventional “black-box” approach using mean squared error (MSE) and a physically informed FFNN employing a physically regularized loss function (PRLF), incorporating mass conservation law. The study demonstrates that combining PRLF with Latin hypercube sampling enables the rapid minimization of relative error (RE) when using a smaller dataset, achieving a relative error value of $6\%$ on the test set. This approach offers a viable alternative to resource-intensive simulations, showcasing potential applications in patient-specific 1D network models of hemodynamics. Full article

Purpose: Univentricular heart is corrected with the Fontan procedure (FP). In the long term, so-called Fontan-associated liver diseases (FALDs) can develop. The aim of this study is to analyze the molecular profile of FALDs. Methods: FALDs between January 1990 and December 2022 were reviewed for histology and immunohistochemistry, laboratory data, and images. Targeted next generation sequencing (NGS), performed on the DNA and RNA of both neoplastic and non-lesional liver tissue, was applied. Results: A total of 31/208 nodules > 1 cm in diameter were identified on imaging, but a liver biopsy was available for five patient demonstrating the following: one hepatocellular adenoma (HA), two hepatocellular carcinomas (HCCs), one fibrolamellar carcinoma (FLC), and one intrahepatic cholangiocarcinoma (ICC). Molecular analysis showed a copy number alteration involving FGFR3 in three cases (two HCCs and one ICC) as well as one HCC with a hotspot mutation on the CTNNB1 and NRAS genes. Tumor mutational burden ranged from low to intermediate. A variant of uncertain significance in GNAS was present in two HCCs and in one ICC. The same molecular profile was observed in a non-lesional liver. A DNAJB1-PRKACA fusion was detected only in one FLC. Conclusions: Neoplastic FALDs show some unusual molecular profiles compared with non-Fontan ones. The presence of the same alterations in non-lesional cardiac cirrhosis could contribute to the development of FALD. Full article

Background: Phrenic nerve injury is a devastating complication that results in significant morbidity and mortality. We developed a novel technique to localize the phrenic nerve and evaluate its success. Methods: Two groups of children underwent repeat sternotomy for a variety of indications. Group I (69 patients, nerve stimulator) and Group II (78 patients, no nerve stimulator). Results: There was no significant difference in the mean age and weight between the two groups: (6.4 ± 6.5 years vs. 5.6 ± 6.4 years; p = 0.65) and (25.2 ± 24.1 vs. 22.6 ± 22.1; p = 0.69), respectively. The two groups were comparable in the following procedures: pulmonary conduit replacement, bidirectional cavopulmonary anastomosis, aortic arch repair, and Fontan, while Group I had more pulmonary arterial branch reconstruction (p = 0.009) and Group II had more heart transplant patients (p = 0.001). There was no phrenic nerve injury in Group I, while there were 13 patients who suffered phrenic nerve injury in Group II (p < 0.001). No early mortality in Group I, while five patients died prior to discharge in Group II. Eleven patients underwent diaphragm plication in Group II (p = 0.001). The mean number of hours on the ventilator was significantly higher in Group II (137.3 ± 324.9) compared to Group I (17 ± 66.9), p < 0.001. Group II had a significantly longer length of ICU and hospital stays compared to Group I (p = 0.007 and p = 0.006 respectively). Conclusion: Phrenic nerve injury in children continues to be associated with significant morbidities and increased length of stay. The use of intraoperative phrenic nerve stimulator can be an effective way to localize the phrenic nerve and avoid its injury. Full article

Background: Adults with congenital heart disease (ACHD) are a growing population needing ongoing care. The aim of this study was to investigate if a dedicated ACHD team impacted the timing and indication of invasive cardiology procedures in these patients at our hospital. Methods: Our retrospective single-center study enrolled adult patients with moderate or complex congenital heart disease and with at least one cardiac catheterization between January 2010 and December 2021. According to the period, procedures were labeled as group A (2010 to 2015) or group B (2016 to 2021) and further divided into diagnostic (DCC) and interventional cardiac catheterizations (ICC). Results: 594 patients were eligible for the study. Both DCC (p < 0.05) and ICC increased between groups A and B (p < 0.05). In group B: Fontan patients accounted for the majority of DCC (p < 0.001), while DCC decreased in arterial switch repair (p < 0.001). In Fontan patients, conduit stenting was prevalent (p < 0.001), while fenestration closures dropped (p < 0.01). In patients with tetralogy of Fallot and native outflow tract, percutaneous pulmonary valve implantations (PPVI) increased, with a concurrent reduction in pulmonary valve replacements (p < 0.001 vs. surgical series). In right ventricular conduits, ICC increased (p < 0.01), mainly due to PPVI. Among Mustard/Senning patients, baffle stenting increased from Group A to Group B (p < 0.001). In patients with pulmonary atresia and biventricular repair, ICC often increased for pulmonary artery stenting. Conclusions: A dedicated working group could improve ACHD patients’ indications for interventional procedures, leading to tailored treatment, better risk stratification and optimizing time until heart transplantation. Full article

Fontan patients undergo multiple cardiothoracic surgeries in childhood. Following these procedures, ventricular function is temporarily decreased, and recovers over months. This is presumably related to cardiopulmonary bypass, but this is incompletely understood. Throughout the Fontan palliation, cardiac function is also affected by volume unloading. We aimed to gain insight into the biological processes related to impaired ventricular function and recovery following Fontan palliations using a panel of biomarkers. Furthermore, we described changes in ventricular function across the Fontan palliation due to volume unloading. We performed a prospective multicenter observational study in patients undergoing partial (PCPC) or total cavo-pulmonary connection (TCPC). Patients underwent assessment—including echocardiography and blood sampling—before surgery (T1), at first follow-up (T2), and 1 year after their procedures (T3). Blood samples were analyzed using a biomarker panel (OLINK CVD-III). Ninety-two biomarkers were expressed as principal components (PC) to limit multiple statistical testing. We included 32 PCPC patients aged 7.2 [5.3–10.3] months, and 28 TCPC patients aged 2.7 [2.2–3.8] years. The single ventricular longitudinal strain (SV GLS) temporarily decreased for PCPC patients at T2 (−15.1 ± 5.6 (T1) to −13.5 ± 5.2 (T2) to −17.3 ± 4.5 (T3), p < 0.047 for all differences), but not following TCPC. The serum biomarkers were expressed as 4 PCs. PC1, including biomarkers of cell–cell adhesion, was not related to any patient characteristic. PC2, including biomarkers of superoxide anion regulation, increased at T2. PC3, including biomarkers of cardiovascular development, related to the stage of Fontan palliation. PC4 was of uncertain biological or clinical significance. No PC was found that related to ventricular performance. The SV GLS was temporarily diminished following PCPC, but not following TCPC. Several biomarkers were related to post-operative stress and adaptation to the PCPC or TCPC circulation, but none were related to the outcome. Full article

Background: Morbidity and mortality following Fontan (FO) surgery are primarily thromboembolic in nature. However, follow-up data regarding thromboembolic complications (TECs) in adult patients after FO procedure are inconsistent. In this multicenter study, we investigated the incidence of TECs in FO patients. Methods: We studied 91 patients who underwent FO procedure. Clinical data, laboratory, and imaging investigations were collected prospectively during the scheduled medical appointments in 3 Adult Congenital Heart Disease Departments in Poland. TECs were recorded during a median follow-up of 31 months. Results: Four patients (4.4%) were lost to follow-up. The mean age of patients was 25.3 (±6.0) years at enrollment, and the mean time between FO operation and investigation was 22.1 (±5.1) years. A total of 21 out of 91 patients (23.1%) had a history of 24 TECs since an FO procedure, mainly pulmonary embolism (PE; n = 12, 13.2%), including 4 (33.3%) silent PE. The mean time since FO operation to the first TEC was 17.8 (±5.1) years. During follow-up, we documented 9 TECs in 7 (8.0%) patients, mainly PE (n = 5, 5.5%). Most patients with TEC had a left type of systemic ventricle (57.1%). Three patients (42.9%) were treated with aspirin, 3 (3.4%) with Vitamin K antagonists or novel oral anticoagulants, and 1 patient had no antithrombotic treatment at the time of TEC occurrence. Supraventricular tachyarrhythmias were present in 3 patients (42.9%). Conclusions: This prospective study shows that TECs are common in FO patients, and a significant number of these events occur during adolescence and young adulthood. We also indicated how much TECs are underestimated in the growing adult FO population. The complexity of the problem requires more studies, especially to standardize the prevention of TECs in the whole FO population. Full article

Patients with hypoplastic left heart syndrome who have been palliated with the Fontan procedure are at risk for adverse neurodevelopmental outcomes, lower quality of life, and reduced employability. We describe the methods (including quality assurance and quality control protocols) and challenges of a multi-center observational ancillary study, SVRIII (Single Ventricle Reconstruction Trial) Brain Connectome. Our original goal was to obtain advanced neuroimaging (Diffusion Tensor Imaging and Resting-BOLD) in 140 SVR III participants and 100 healthy controls for brain connectome analyses. Linear regression and mediation statistical methods will be used to analyze associations of brain connectome measures with neurocognitive measures and clinical risk factors. Initial recruitment challenges occurred that were related to difficulties with: (1) coordinating brain MRI for participants already undergoing extensive testing in the parent study, and (2) recruiting healthy control subjects. The COVID-19 pandemic negatively affected enrollment late in the study. Enrollment challenges were addressed by: (1) adding additional study sites, (2) increasing the frequency of meetings with site coordinators, and (3) developing additional healthy control recruitment strategies, including using research registries and advertising the study to community-based groups. Technical challenges that emerged early in the study were related to the acquisition, harmonization, and transfer of neuroimages. These hurdles were successfully overcome with protocol modifications and frequent site visits that involved human and synthetic phantoms. Full article

Background: Children with congenital heart disease (CHD) have impaired pulmonary function both before and after surgery; therefore, pulmonary function assessments are important and should be performed both before and after open-heart surgery. This study aimed to compare pulmonary function between variant pediatric CHD types after open-heart surgery via spirometry. Methods: In this retrospective study, the data for forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the ratio between FEV1 and FVC (FEV1/FVC) were collected from patients with CHD who underwent conventional spirometry between 2015 and 2017. Results: A total of 86 patients (55 males and 31 females, with a mean age of 13.24 ± 3.32 years) were enrolled in our study. The diagnosis of CHD included 27.9% with atrial septal defects, 19.8% with ventricular septal defects, 26.7% with tetralogy of Fallot, 7.0% with transposition of the great arteries, and 46.5% with other diagnoses. Abnormal lung function was identified by spirometry assessments after surgery. Spirometry was abnormal in 54.70% of patients: obstructive type in 29.06% of patients, restrictive type in 19.76% of patients, and mixed type in 5.81% of patients. More abnormal findings were found in patients who received the Fontan procedure (80.00% vs. 35.80%, p = 0.048). Conclusions: Developing novel therapies to optimize pulmonary function will be critical for improving clinical outcomes. Full article

Background: Sarcopenia is an increasingly recognized marker of frailty in cardiac patients. Patients with a history of congenital heart disease and Fontan procedure have a higher risk of developing progressive muscle wasting. Our objective was to determine if we could use routine cardiac MRI (CMR) for the surveillance of muscle wasting. Methods: A retrospective study of all Fontan patients (n = 75) was conducted at our institution, with CMR performed from 2010 to 2022 and exercise stress testing performed within 12 months (4.3 ± 4.2 months). The skeletal muscle area (SMA) for the posterior paraspinal and anterior thoracic muscles were traced and indexed for body surface area (BSA). Patients were stratified by percentile into the upper and lower quartiles, and the two groups were compared. Multivariable regression was performed to control for sex and age. Results: There was a significant positive association of both anterior (r = 0.34, p = 0.039) and paraspinal (r = 0.43, p = 0.007) SMA to peak VO₂. Similarly, paraspinal but not anterior SMA was negatively associated with the V_E/V_CO2 (r = –0.45, p = 0.006). The upper quartile group had significantly more males (18/19 vs. 8/20; p = 0.0003) and demonstrated a significantly higher peak VO₂ (32.2 ± 8.5 vs. 23.8 ± 4.7, p = 0.009), a higher peak RER (1.2 ± 0.1 vs. 1.1 ± 0.04, p = 0.007), and a significantly lower V_E/V_CO2 (32.9 ± 3.6 vs. 40.2 ± 6.2, p = 0.006) compared to the lowest quartile. The association of SMA to VO₂ peak and V_E/V_CO2 was redemonstrated after controlling for sex and age. Conclusion: Thoracic skeletal muscle area may be an effective surrogate of muscle mass and is correlated to several measures of cardiorespiratory fitness post-Fontan. CMR would be an effective tool for the surveillance of sarcopenia in post-Fontan patients given its accessibility and routine use in these patients. Full article

Introduction: The overshoot of the respiratory exchange ratio (RER) after exercise is reduced in patients with heart failure. Aim: The present study aimed to investigate the presence of this phenomenon in young patients with congenital heart disease (CHD), who generally present reduced cardiorespiratory fitness. Methods: In this retrospective study, patients with CHD underwent a maximal cardiopulmonary exercise testing (CPET) assessing the RER recovery parameters: the RER at peak exercise, the maximum RER value reached during recovery, the magnitude of the RER overshoot and the linear slope of the RER increase after the end of the exercise. Results: In total, 117 patients were included in this study. Of these, there were 24 healthy age-matched control subjects and 93 young patients with CHD (transposition of great arteries, Fontan procedure, aortic coarctation and tetralogy of Fallot). All patients presented a RER overshoot during recovery. Patients with CHD showed reduced aerobic capacity and cardiorespiratory efficiency during exercise, as well as a lower RER overshoot when compared to controls. RER magnitude was higher in the controls and patients with aortic coarctation when compared to those with transposition of great arteries, previous Fontan procedure, and tetralogy of Fallot. The RER magnitude was found to be correlated with the most relevant cardiorespiratory fitness and efficiency indices. Conclusions: The present study proposes new recovery indices for functional evaluation in patients with CHD. Thus, the RER recovery overshoots analysis should be part of routine CPET evaluation to further improve prognostic risk stratifications in patients with CHD. Full article

Women with single ventricle physiology after the Fontan procedure, despite numerous possible complications, can reach adulthood and give birth. Pregnancy poses a hemodynamic burden for distorted physiology of Fontan circulation, but according to the literature, it is usually well tolerated unless the patient is a “failing” Fontan. Our study aimed to assess maternal and fetal outcomes in patients after the Fontan procedure followed up in two tertiary Polish medical centers. We retrospectively evaluated all pregnancies in women after the Fontan procedure who were followed up between 1995–2022. During the study period, 15 women after the Fontan procedure had 26 pregnancies. Among 26 pregnancies, eleven ended with miscarriages, and 15 pregnancies resulted in 16 live births. Fetal complications were observed in 9 (56.3%) live births, with prematurity being the most common complication (n = 7, 43.8%). We recorded 3 (18.8%) neonatal deaths. Obstetrical complications were present in 6 (40%) out of 15 completed pregnancies—two (13.3%) cases of abruptio placentae, two (13.3%) pregnancies with premature rupture of membranes, and two (13.3%) patients with antepartum hemorrhage. There was neither maternal death nor heart failure decompensation during pregnancy. In two (13.3%) women, atrial arrhythmia developed. One (6.7%) patient in the second trimester developed ventricular arrhythmia. None of the patients suffered from systemic thromboembolism during pregnancy. Pregnancy in women after the Fontan procedure is well tolerated. However, it is burdened by a high risk of miscarriage and multiple obstetrical complications. These women require specialized care provided by both experienced cardiologists and obstetricians. Full article

Since its first description in 1971, the Fontan procedure and its modifications have led to a substantial improvement in the survival rates of patients with a variety of types of complex Congenital Heart Disease (CHD) characterised by the presence of a single, dominant ventricle. However, despite the significant improvement of the prognosis over the years, Fontan patients are still exposed to several cardiovascular and systemic complications. It is, therefore, important to fully understand the pitfalls hidden behind a Fontan anatomy and the potential predictors of ventricular failure. Cardiovascular imaging plays a key role in this context, allowing for the early identification of complications with important prognostic implications. Echocardiography remains the first-line imaging modality for serial evaluation of Fontan patients. However, there is a growing role of cardiovascular magnetic resonance and cardiac computed tomography from pre-operative assessment to longitudinal follow-up. The aim of this paper will be to provide a comprehensive overview of the role, strengths, and weaknesses of each imaging modality in the assessment of congenital cardiac conditions palliated with the Fontan procedure. Full article

Fontan circulation (FC) is a surgically achieved palliation state offered to patients affected by a wide variety of congenital heart defects (CHDs) that are grouped under the name of univentricular heart. The procedure includes three different surgical stages. Malnutrition is a matter of concern in any phase of life for these children, often leading to longer hospital stays, higher mortality rates, and a higher risk of adverse neurodevelopmental and growth outcomes. Notwithstanding the relevance of proper nutrition for this subset of patients, specific guidelines on the matter are lacking. In this review, we aim to analyze the role of an adequate form of nutritional support in patients with FC throughout the different stages of their lives, in order to provide a practical approach to appropriate nutritional management. Firstly, the burden of faltering growth in patients with univentricular heart is analyzed, focusing on the pathogenesis of malnutrition, its detection and evaluation. Secondly, we summarize the nutritional issues of each life phase of a Fontan patient from birth to adulthood. Finally, we highlight the challenges of nutritional management in patients with failing Fontan. Full article