Search Results (28)

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

Background/Objectives: Growth failure is a common complication in children with congenital heart disease (CHD), yet its underlying mechanisms and consequences remain incompletely understood. This review aims to provide a comprehensive overview of growth failure in children with CHD and outline a framework of factors contributing to this condition. Methods: To lay the foundation for this narrative review, several databases were searched using broad search terms related to CHD and growth failure. Results: Growth failure is most pronounced during the first year of life, but often improves after achieving hemodynamic stability through surgical or medical interventions. However, children with complex conditions, such as single-ventricle physiology or multiple heart defects, may experience persistent growth impairment due to chronic disease effects. Specific features of CHD—cyanosis, pulmonary hypertension, and low cardiac output—can further hinder growth by disrupting endocrine function and impairing musculoskeletal development. Long-term use of medications and exposure to repeated diagnostic procedures also contribute to growth failure. Beyond physical effects, growth failure profoundly influences neurodevelopment, psychosocial well-being, and survival outcomes. Based on our review, we have developed a knowledge map to better understand the complexities of growth failure in children with CHD. Conclusions: A thorough understanding of the multifaceted contributors to growth failure in CHD is essential for identifying high-risk children and devising strategies to support optimal growth. Integrating this knowledge into clinical practice can improve long-term outcomes for children with CHD. 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

17β-estradiol (E2) is the most active metabolite of estrogen with a wide range of physiological action on cardiac muscle. Previous studies have reported E2 effects predominantly for the ventricles, while the E2 impact on the atria has been less examined. In this study, we focused on the direct E2 effects on atrial and ventricular contractility at the cellular and molecular levels. Single atrial and ventricular cardiomyocytes (CM) from adult (24 weeks-old) female Wistar rats were incubated with 10 nM E2 for 15 min. Sarcomere length and cytosolic [Ca²⁺]_i transients were measured in mechanically non-loaded CM, and the tension–length relationship was studied in CM mechanically loaded by carbon fibers. The actin–myosin interaction and sarcomeric protein phosphorylation were analyzed using an in vitro motility assay and gel electrophoresis with Pro-Q Diamond phosphoprotein stain. E2 had chamber-specific effects on the contractile function of CM with a pronounced influence on ventricular CM. The characteristics of [Ca²⁺]_i transients did not change in both atrial and ventricular CM. However, in ventricular CM, E2 reduced the amplitude and maximum velocity of sarcomere shortening and decreased the slope of the passive tension–length relationship that was associated with increased TnI and cMyBP-C phosphorylation. E2 treatment accelerated the cross-bridge cycle of both atrial and ventricular myosin that was associated with increased phosphorylation of the myosin essential light chain. This study shows that E2 impairs the mechanical function of the ventricular myocardium while atrial contractility remains mostly preserved. Hormonal replacement therapy (HRT) with estrogen is by far the most effective therapy for treating climacteric symptoms experienced during menopause. Here we found a chamber specificity of myocardial contractile function to E2 that should be taken into account for the potential side effects of HRT. Full article

Patent ductus arteriosus (PDA) continues to be a significant finding among infants, as well as adults. What is widely considered to be a problem though, in a group of patients with congenital heart disease, it is the only lifeline. We will initially study the anatomical and biochemical mechanisms affecting the PDA. The main focus of this review is on ductal-dependent congenital heart disease and biochemical and pharmacological approaches to maintaining ductus arteriosus patency, as well as surgical and interventional options for maintaining circulation. The present review aims to highlight gaps in the knowledge regarding the multifunctional role of ductus arteriosus endothelium and possibly propose a new approach to pharmacological maintenance of ductus arteriosus patency. Full article

Background/Objectives: Better understanding of and addressing umbilical entanglement in the third trimester of pregnancy is necessary to estimate its impact on fetal circulation. An analysis of single physiological pregnancies wrapped with one or two coils of the umbilical cord around the neck makes it possible to understand the severity of the problem and distinguish it from perinatal umbilical strangulation. Methods: In an echocardiographic study performed at 32.1 weeks of pregnancy in fetuses with one and two coils of the umbilical cord around the neck, the pulsatility index (PI) and the Tei index for the left (Tei LV) and right ventricle (Tei RV) of the heart were measured to evaluate cardiac function. Results: The study showed significantly higher Tei RV and Tei LV for fetuses with one (93 cases) and two coils of the umbilical cord around the fetal neck (26 cases) with respect to the control group of fetuses (680 cases) with no umbilical cord around the fetal neck, whereas PI UMBA did not differ significantly. Conclusions: Wrapping of the umbilical cord around the fetal neck may affect the study of the fetal heart without any mechanically induced compression of the umbilical vessels in normal pregnancy. Full article

Over the past five decades, the Fontan procedure has been developed to improve the life expectancy of patients with congenital heart defects characterized by a functionally single ventricle. The Fontan circulation aims at redirecting systemic venous return to the pulmonary circulation in the absence of an impelling subpulmonary ventricle, which makes this physiology quite fragile and leads to several long-term complications. Despite the importance of hemodynamic assessment through cardiac catheterization in the management and follow-up of these patients, a thorough understanding of the ultimate functioning of this type of circulation is lacking, and the interpretation of the hemodynamic data is often complex. In recent years, new tools such as combined catheterization with cardiopulmonary exercise testing have been incorporated to improve the understanding of the hemodynamic profile of these patients. Furthermore, extensive percutaneous treatment options have been developed, addressing issues ranging from obstructive problems in Fontan pathway and acquired shunts through compensatory collaterals to the percutaneous treatment of lymphatic circulation disorders and transcatheter edge-to-edge repair of atrioventricular valves. The aim of this review is to detail the various tools used in cardiac catheterization for patients with Fontan circulation, analyze different percutaneous treatment strategies, and discuss the latest advancements in this field. Full article

Adult patients with congenital heart disease have now surpassed the pediatric population due to advances in surgery and improved survival. One such complex congenital heart disease seen in adult patients is the Fontan circulation. These patients have complex physiology and are at risk for several complications, including thrombosis of the Fontan pathway, pulmonary vascular disease, heart failure, atrial arrhythmias, atrioventricular valve regurgitation, and protein-losing enteropathy. This review discusses the commonly encountered phenotypes of Fontan circulatory failure and their contemporary management. Full article

Previous omics research in patients with complex congenital heart disease and single-ventricle circulation (irrespective of the stage of palliative repair) revealed alterations in cardiac and systemic metabolism, inter alia abnormalities in energy metabolism, and inflammation, oxidative stress or endothelial dysfunction. We employed an affinity-proteomics approach focused on cell surface markers, cytokines, and chemokines in the serum of 20 adult Fontan patients with a good functioning systemic left ventricle, and we 20 matched controls to reveal any specific processes on a cellular level. Analysis of 349 proteins revealed 4 altered protein levels related to chronic inflammation, with elevated levels of syndecan-1 and glycophorin-A, as well as decreased levels of leukemia inhibitory factor and nerve growth factor-ß in Fontan patients compared to controls. All in all, this means that Fontan circulation carries specific physiological and metabolic instabilities, including chronic inflammation, oxidative stress imbalance, and consequently, possible damage to cell structure and alterations in translational pathways. A combination of proteomics-based biomarkers and the traditional biomarkers (uric acid, γGT, and cholesterol) performed best in classification (patient vs. control). A metabolism- and signaling-based approach may be helpful for a better understanding of Fontan (patho-)physiology. Syndecan-1, glycophorin-A, leukemia inhibitory factor, and nerve growth factor-ß, especially in combination with uric acid, γGT, and cholesterol, might be interesting candidate parameters to complement traditional diagnostic imaging tools and the determination of traditional biomarkers, yielding a better understanding of the development of comorbidities in Fontan patients, and they may play a future role in the identification of targets to mitigate inflammation and comorbidities in Fontan patients. 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

A heart with a borderline ventricle refers to a situation where there is uncertainty about whether the left or right underdeveloped ventricle can effectively support the systemic or pulmonary circulation with appropriate filling pressures and sufficient physiological reserve. Pediatric cardiologists often deal with congenital heart diseases (CHDs) associated with various degrees of hypoplasia of the left or right ventricles. To date, no specific guidelines exist, and surgical management may be extremely variable in different centers and sometimes even in the same center at different times. Thus, the choice between the single-ventricle or biventricular approach is always controversial. The aim of this review is to better define when “small is too small and large is large enough” in order to help clinicians make the decision that could potentially affect the patient’s entire life. Full article

Most studies on single ventricle (SV) circulation take a physiological or anatomical approach. Although there is a tight coupling between cardiac contractility and metabolism, the metabolic perspective on this patient population is very recent. Early findings point to major metabolic disturbances, with both impaired glucose and fatty acid oxidation in the cardiomyocytes. Additionally, Fontan patients have systemic metabolic derangements such as abnormal glucose metabolism and hypocholesterolemia. Our literature review compares the metabolism of patients with a SV circulation after Fontan palliation with that of patients with a healthy biventricular (BV) heart, or different subtypes of a failing BV heart, by Pubmed review of the literature on cardiac metabolism, Fontan failure, heart failure (HF), ketosis, metabolism published in English from 1939 to 2023. Early evidence demonstrates that SV circulation is not only a hemodynamic burden requiring staged palliation, but also a metabolic issue with alterations similar to what is known for HF in a BV circulation. Alterations of fatty acid and glucose oxidation were found, resulting in metabolic instability and impaired energy production. As reported for patients with BV HF, stimulating ketone oxidation may be an effective treatment strategy for HF in these patients. Few but promising clinical trials have been conducted thus far to evaluate therapeutic ketosis with HF using a variety of instruments, including ketogenic diet, ketone esters, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. An initial trial on a small cohort demonstrated favorable outcomes for Fontan patients treated with SGLT2 inhibitors. Therapeutic ketosis is worth considering in the treatment of Fontan patients, as ketones positively affect not only the myocardial energy metabolism, but also the global Fontan physiopathology. Induced ketosis seems promising as a concerted therapeutic strategy. Full article

Background: A progressively increasing prevalence of congenital heart disease (CHD) in adulthood has been noticed in recent decades; CHD cases with a systemic right ventricle have a poorer outcome. Methods: Seventy-three patients with SRV evaluated in an outpatient clinic between 2014 and 2020 were enrolled in this study. Thirty-four patients had a transposition of the great arteries treated with an atrial switch operation; 39 patients had a congenitally corrected transposition of the great arteries (ccTGA). Results: Mean age at the first evaluation was 29.6 ± 14.2 years; 48% of the patients were female. The NYHA class at the visit was III or IV in 14% of the cases. Thirteen patients had at least one previous pregnancy. In 25% of the cases, complications occurred during pregnancy. Survival free from adverse events was 98.6% at one year and 90% at 6-year follow-up without any difference between the two groups. Two patients died and one received heart transplantation during follow-up. The most common adverse event during follow-up was the presence of arrhythmia requiring hospitalization (27.1%), followed by heart failure (12.3%). The presence of LGE together with lower exercise capacity, higher NYHA class and more dilated and/or hypokinetic RV predicted a poorer outcome. Quality of life was similar to the QoL of the Italian population. Conclusions: Long-term follow-up of patients with a systemic right ventricle is characterized by a high incidence of clinical events, prevalently arrhythmias and heart failure, which cause most of the unscheduled hospitalizations. Full article