Fontan Patients Research Articles

COVID-19 vaccination in adults with congenital heart disease: results of 1-year prospective study

Abstract Background Adults with congenital heart disease (ACHD) are a vulnerable population. Routine vaccination is the only strategy to prevent a life-threatening infection. However, concerns on the cardiac safety and efficacy of COVID-19 vaccines have been raised. Aim To assess safety and efficacy of available COVID-19 vaccines in ACHD patients. Methods Data on COVID-19 infection and vaccines including booster doses and any suspected or confirmed adverse events were prospectively collected for all ACHD patients attending our tertiary centre from the beginning of the vaccination campaign (March 2021). A group of 75 healthy volunteers, matched per age and sex, was included for comparison. Antispike IgG titre was routinely obtained at the ACHD clinic. Patients' attitude towards COVID-19 was explored with a questionnaire. Results As of February 2022, 498 ACHD patients (36.7±16 years, 54% male,69% with moderate-complex defects, 48% with advanced physiological stage) were enrolled. Four hundred and sixty-one (92%) were fully vaccinated: the type of vaccine was Pfizer-BioNTech for 399 (86%) patients, Moderna for 20 (4%) and AstraZeneca for 26 (6%), 9 received a mixed vaccine regimen (2%). Forty-two (9%) had a history of previous COVID-19 infection and therefore received only one dose. Two-hundred and sixty-nine (58%) patients received a booster dose. Adverse events were mainly mild and transient. One patient complaining of chest pain following administration of mRNA-based vaccination was diagnosed with acute pericarditis, which made full remission after appropriate therapy. Two patients reported a non-specific increment of inflammatory markers. No other severe adverse events were reported. Thirty-seven (7%) refused COVID-19 vaccination being scared of potential cardiac/extra-cardiac adverse events. Among those not-vaccinated, 9 (24%) had a history of previous mild COVID-19 infection. IgG titre was measured in 243 patients at 1915 [835–5934] BAU/ml, which was significantly higher compared to controls (1196 [827–2048] BAU/ml, p=0.002). Three ACHD patients contracted COVID-19 infection after the first dose, while 65 (14%) fully vaccinated patients tested positive for COVID-19, all with mild to moderate symptoms. COVID-19 symptoms duration was significantly longer in case of infection before vaccination (10 [2.7–15] vs 3 [1.2–7], p=0.03). One Fontan patient was tested positive for COVID-19 twice, before and after COVID-19 vaccination, requiring hospitalization in both cases. Four hundred and seven patients completed the questionnaire: 128 (31%) declared to be scared of potential cardiac effects of the vaccine and that the discussion with the ACHD cardiologist was crucial to decide to undergo COVID-19 vaccination. Conclusions Our data provide real-world evidence on COVID-19 vaccines safety and efficacy in ACHD patients. Patients' education from the ACHD team may play a key role in vaccine acceptance in this vulnerable population. Funding Acknowledgement Type of funding sources: None.

Lymphopenia and immunoglobulin deficiency in adult patients with a Fontan circulation

Abstract Background Patients with a functionally univentricular heart and a Fontan palliation are prone to a wide range of extra-cardiac complications. Lymphopenia and immunoglobulin deficiency are insufficiently characterized in this population. Purpose The aim of this study was to analyze prevalence and associations of lymphopenia and immunoglobulin deficiency in a cohort of adult Fontan patients. Methods Ninety-five consecutive patients with a Fontan circulation that were seen at our institution between 2011 and 2021 were screened. Laboratory results and clinical characteristics were extracted from the patient's charts. Results Fifty-five patients (47% male) underwent evaluation of lymphocyte and/or immunoglobulin subpopulations at a mean age of 28.9±9.7 years. Baseline characteristics are depicted in the Table. Seven patients (7/55, 12.7%) had immunoglobulin G (IgG) levels below the lower limit of normal (i.e. <7.0 g/l). Patients with IgG deficiency had a higher prevalence of protein-losing enteropathy (43% versus 4%, p=0.001). Fifteen patients (15/52, 28.8%) had lymphocyte counts below the lower limit of normal (i.e. <850/μl). Lymphocyte counts and lymphocyte subpopulations were comparable in groups with and without protein-losing enteropathy. There was a moderately positive correlation between absolute lymphocyte counts and IgG levels (r=0.301, p=0.032). In a subgroup of 24 patients that underwent liver biopsy, there was no difference in terms of absolute lymphocyte counts and immunoglobulin subpopulations in patients with a low (i.e. 1–2) and high (i.e. 3–4) congestive hepatic fibrosis score. Conclusion IgG deficiency is present in 13% of patients with a Fontan circulation and seems to be associated with the presence of protein-losing enteropathy. Lymphopenia is more common and occurs in a quarter of all patients with a Fontan circulation; however, its etiology is likely more complex and multifactorial. Funding Acknowledgement Type of funding sources: None.

Social life in adult patients after Fontan procedure

BackgroundLittle is known about the social life in adult patients after Fontan palliation. The study aimed to assess the long-term social life of patients after Fontan surgery, including school achievement, employment, and marital status.ResultsWe conducted a cross-sectional study on patients aged 18 years or above who had a Fontan operation for a single ventricle pathology. Our outcomes were the academic performance and marital and employment status of adult Fontan patients. Patients or their families were interviewed directly or by phone, and a set of questions were asked to address their educational level, employment, and marital status. Ninety-nine patients were included in the study. Their median age was 21 years (min–max: 18–41), and 60% were females (n= 59). The most common diagnoses were double inlet left ventricle (n= 24, 24%), tricuspid atresia (n= 21, 21%), and the unbalanced atrioventricular canal (n= 21, 21%). Fourteen patients (14%) were married, and 6 of them had children (two were females). Eleven percent were college graduates (either diploma or bachelor’s degree), and 47% were high school graduates.ConclusionsFontan operation could negatively affect the social life of the patients. It may affect employment patterns, educational levels, and marital status.

The efficacy and safety of macitentan in Fontan-palliated patients: results of the 52-week randomised, placebo-controlled RUBATO trial

Abstract Background The clinical utility and long-term effects of endothelin receptor antagonists (ERAs) in Fontan-palliated patients remain unclear and there are currently no approved therapies. A decline in peak VO2 between consecutive cardiopulmonary exercise tests (CPETs) is highly prognostic for death or transplant in adult Fontan patients, hence its use as a primary endpoint in clinical trials of ERAs in patients with Fontan circulation. Purpose The RUBATO trial aimed to assess the efficacy and safety of macitentan, an endothelin receptor antagonist, in Fontan-palliated patients over 52 weeks. Methods In the multicentre, double-blind, randomised, placebo-controlled, phase 3 RUBATO trial, Fontan-palliated patients were randomised 1:1 to macitentan 10 mg once-daily or placebo for 52 weeks. Eligible patients were aged ≥12 years, in New York Heart Association functional class II or III, had no limitations for CPET (including no pacemakers), had undergone lateral tunnel or extracardiac conduit Fontan (total cavopulmonary connection) >1 year before screening and showed no signs of Fontan failure or clinical deterioration within 3 months before screening. Primary efficacy endpoint was change in peak VO2 from baseline to week 16. Secondary endpoints were change in peak VO2 from baseline over 52 weeks and change in mean count per minute of daily physical activity from baseline to week 16 as measured by an accelerometer. Adverse events were also assessed. Results 137 patients were randomised to macitentan (n=68) or placebo (n=69). 92.7% of patients completed 52 weeks of double-blind treatment: 7 and 3 patients prematurely discontinued study treatment in macitentan and placebo arms, respectively. Patient baseline characteristics are shown in Table 1. At week 16, the mean (SD) change from baseline in peak VO2 was –0.16 (2.86) with macitentan vs –0.67 (2.66) mL/kg/min with placebo (median unbiased estimate of the difference between macitentan and placebo: 0.62 mL/kg/min [99% repeated confidence interval –0.62; 1.85], p=0.1930). No treatment effect was observed in the two secondary endpoints (Table 2): mean (SD) count per minute of daily physical activity decreased from baseline to week 16 by 3.02 (92.44) with macitentan and by 14.34 (117.56) with placebo (p=0.4512). The most common AEs were headache (10.3% vs 8.7% on placebo), nasopharyngitis (5.9% vs 4.3%), and pyrexia (5.9% vs 4.3%). AEs leading to treatment discontinuation were reported in 3 (4.4%) and 1 (1.4%) of macitentan and placebo patients. Conclusion The 52-week RUBATO trial provides an important addition to data on the clinical utility of ERAs in Fontan-palliated patients. The primary efficacy endpoint was not met and no treatment effect was observed for the two secondary endpoints. Macitentan was well tolerated; safety findings were consistent with the known safety profile of macitentan 10 mg. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Actelion Pharmaceuticals Ltd., a Janssen pharmaceutical company of Johnson & Johnson.

Long-term course of pulmonary arterial hypertension in adults with congenital heart disease under targeted therapy: a retrospective analysis of a single tertiary center.

Pulmonary arterial hypertension (PAH), a common complication in adults with congenital heart disease (CHD), leads to significant morbidity and mortality. Targeted PAH medication is available, but PAH-CHD patient data are limited. Several questions regarding indication, treatment escalation, and combination therapy remain unanswered. The aim of this study was therefore to evaluate PAH-specific treatment in adults with PAH-CHD to better understand PAH-specific therapy management. In this cross-sectional study we retrospectively examined clinical, demographic, and cardiac-catheterization data and medical management for PAH-CHD, and analyzed clinical course and midterm outcome. Over up to 14 years (median, 6.2 years), 103 PAH-CHD patients (66% female) receiving targeted PAH-therapy for pre-tricuspid-shunt (15.5%), post-tricuspid-shunt (32.0%), and complex CHD (52.4%) were followed. Based on modified clinical European Society of Cardiology (ESC) classification, patients were assigned to the following subgroups: Eisenmenger syndrome (ES) (45.6%), severe pulmonary vascular disease (PVD) in complex CHD (20.4%), post-repair patients (19.4%), prevalent systemic-to-pulmonary shunt (3.9%), coincidental/small defects (0%), and Fontan circulation (10.7%). Changes in targeted PAH therapy were observed 249 times, with up to 6 (median, 2) therapy changes over a median period of 1.3 years. Over the study course, the medical treatment strategy changed towards combination therapy (baseline, 13.6%; study-end, 41%), resulting mostly in stabilized functional class or even improvement in cases of prevalent systemic-to-pulmonary shunt, ES, and patients with repaired CHD. Functional class deterioration, however, was seen in patients with severe PVD due to complex CHD, and Fontan patients. Of the 103 patients in the study, 25 died (24.3%). Patients with repaired CHD and patients with systemic-to-pulmonary shunt or ES showed the best survival rates. Mortality was remarkably higher in patients with severe PVD in complex CHD and Fontan patients. Many patients with PAH-CHD benefited from targeted PAH therapy over a median period of 6.2 years. Treatment decisions after targeted PAH-medication initiation were based mainly on clinical assessment. To counteract disease progression, an escalation towards combination therapy was observed during the study course. We consider survival rates under targeted PAH medication to be favorable, particularly in the ES subgroup. Nevertheless, further research is needed to optimize the use of PAH medication, especially in patients with complex CHD.

Successful Preoperative Partial Splenic Artery and Aneurysm Embolization for Thrombocytopenia Associated with Failed Fontan Circulation.

Long-term complications after the Fontan procedure are important concerns for patients with pediatric and adult congenital heart disease. Although thrombocytopenia due to portal hypertension and hypersplenism is a well-known complication of the Fontan circulation, few studies have reported on its management. Herein we describe a young adult Fontan patient with thrombocytopenia and a splenic artery aneurysm caused by conduit stenosis. The patient required conduit replacement due to high venous pressure. We performed partial splenic artery embolization (PSE) and embolization of the aneurysm preoperatively to reduce the risk of bleeding, resulting in successful subsequent cardiac surgery. Preoperative evaluation of the splenic artery aneurysm was informative, and PSE was a safe and effective treatment option for thrombocytopenia to avoid bleeding during open-heart surgery in this patient.

Nutritional Management of Patients with Fontan Circulation: A Potential for Improved Outcomes from Birth to Adulthood.

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.

Quantification of systemic-to-pulmonary collateral flow in univentricular physiology with 4D flow MRI.

Systemic-to-pulmonary collateral flow is a well-recognised phenomenon in patients with single ventricle physiology, but remains difficult to quantify. The aim was to compare the reported formula's that have been used for calculation of systemic-to-pulmonary-collateral flow to assess their consistency and to quantify systemic-to-pulmonary collateral flow in patients with a Glenn and/or Fontan circulation using four-dimensional flow MRI (4D flow MR). Retrospective case-control study of Glenn and Fontan patients who had a 4D flow MR study. Flows were measured at the ascending aorta, left and right pulmonary arteries, left and right pulmonary veins, and both caval veins. Systemic-to-pulmonary collateral flow was calculated using two formulas: 1) pulmonary veins - pulmonary arteries and 2) ascending aorta - caval veins. Anatomical identification of collaterals was performed using the 4D MR image set. Fourteen patients (n = 11 Fontan, n = 3 Glenn) were included (age 26 [22-30] years). Systemic-to-pulmonary collateral flow was significantly higher in the patients than the controls (n = 10, age 31.2 [15.1-38.4] years) with both formulas: 0.28 [0.09-0.5] versus 0.04 [-0.66-0.21] l/min/m2 (p = 0.036, formula 1) and 0.67 [0.24-0.88] versus -0.07 [-0.16-0.08] l/min/m2 (p < 0.001, formula 2). In patients, systemic-to-pulmonary collateral flow differed significantly between formulas 1 and 2 (13% versus 26% of aortic flow, p = 0.038). In seven patients, veno-venous collaterals were detected and no aortopulmonary collaterals were visualised. 4D flow MR is able to detect increased systemic-to-pulmonary collateral flow and visualise collaterals vessels in Glenn and Fontan patients. However, the amount of systemic-to-pulmonary collateral flow varies with the formula employed. Therefore, further research is necessary before it could be applied in clinical care.

Fitter Fontans for future-Impact of physical exercise on cardiopulmonary function in Fontan patients.

BackgroundIn Fontans, exercise tolerance is poorer compared to their healthy peers. Higher represents a strong predictor for mortality and morbidity in these patients. Cardiac rehabilitation programs have been shown to improve cardiopulmonary function in Fontans. More habitual physical activity should therefore lead to a better exercise tolerance.MethodsWe performed cardiopulmonary exercise testing in 24 Fontan patients who had engaged in physical activity for a minimum of 3 h per week over their lifetime. As a control we performed cardiopulmonary exercise testing in 20 Fontan patients who had undertaken no physical activity or <3 h per week in the past.ResultsA total of 44 Fontan patients was included (mean age 18.1 years). The mean parameters measured at peak exercise differed significantly between the active and inactive group (peak oxygen uptake [] of 34.0 vs. 25.0 ml/min/kg, peak heart rate (HR) of 169.8/min vs. 139.8/min). Even though the O2pulse and the EF did not differ significantly between both groups, N-Terminal-Pro-B-Type Natriuretic Peptide (NT-pro BNP) was significantly higher in the inactive group. The two groups did not differ with respect to their cardiac function determined by magnetic resonance imaging (MRI). was positively correlated with hours of sports performed by Fontans.Conclusions and maximum HR were significantly higher in Fontans who had been physically active compared to those who had been inactive. The values reported in this study were higher than in other studies and reached normal values for for most Fontans in the physically active group. The positive correlation between and physical activity is an indicator of the importance of incorporating physical exercise programs into the treatment of Fontan patients.

Functional hepatic deterioration determined by 13C-methacetin breath test is associated with impaired hemodynamics and late Fontan failure in adults.

BackgroundDespite improved survival a substantial number of Fontan patients eventually develop late failure. Fontan-associated liver disease (FALD) is the most frequent end-organ dysfunction. Although impaired hemodynamics and Fontan failure correlate with FALD severity, no association between hepatic functional metabolic impairment and Fontan hemodynamics has been established.HypothesisMetabolic liver function measured by liver maximum function capacity test (LiMAx®) correlates with Fontan hemodynamics and Fontan failure.MethodsFrom 2020 to 2022, 58 adult Fontan patients [median age: 29.3 years, IQR (12.7), median follow-up time after Fontan operation: 23.2 years, IQR (8.7)] were analyzed in a cross-sectional study. Hemodynamic assessment included echocardiography, cardiopulmonary exercise testing and invasive hemodynamic evaluation. Fontan failure was defined based on commonly applied clinical criteria and our recently composed multimodal Fontan failure score.ResultsLiMAx® test revealed normal maximum liver function capacity in 40 patients (>315 μg/h*kg). In 18 patients a mild to moderate impairment was detected (140–314 μg/h*kg), no patient suffered from severe hepatic deterioration (≤ 139 μg/kg*h). Fontan failure was present in 15 patients. Metabolic liver function was significantly reduced in patients with increased pulmonary artery pressure (p = 0.041. r = −0.269) and ventricular end-diastolic pressure (p = 0.033, r = −0.325), respectively. In addition, maximum liver function capacity was significantly impaired in patients with late Fontan failure (289.0 ± 99.6 μg/kg*h vs. 384.5 ± 128.6 μg/kg*h, p = 0.007).ConclusionMaximum liver function capacity as determined by LiMAx® was significantly reduced in patients with late Fontan failure. In addition, elevated pulmonary artery pressure and end-diastolic ventricular pressure were associated with hepatic functional metabolic impairment.

Orthostatic stress response in pediatric Fontan patients and the effect of ACE inhibition.

Many cardiocirculatory mechanisms are involved in the adaptation to orthostatic stress. While these mechanisms may be impaired in Fontan patients. However, it is yet unclear how Fontan patients, who exhibit a critical fluid balance, respond to orthostatic stress. Angiotensin converting enzyme inhibitors are often prescribed to Fontan patients, but they may negatively influence orthostatic tolerance. Therefore, we evaluated the response to orthostatic stress in pediatric Fontan patients before and after treatment with enalapril. Thirty-five Fontan patients (aged 14 years) with moderate-good systolic ventricular function without pre-existent enalapril treatment were included. Before and after a three-month enalapril treatment period, the hemodynamic response to head-up tilt test was evaluated by various parameters including cardiac index, blood pressure, cerebral blood flow, aortic stiffness and cardiac autonomous nervous activity. Thirty-four healthy subjects (aged 13 years) served as controls. Fontan patients had a decreased cerebral blood flow and increased aortic stiffness in the supine position compared to controls, while all other factors did not differ. Patients and controls showed a comparable response to head-up tilt test for most parameters. Twenty-seven patients completed the enalapril study with a mean dosage of 0.3±0.1mg/kg/day. Most parameters were unaffected by enalapril, only the percent decrease in cardiac index to tilt was higher after treatment, but the cardiac index during tilt was not lower (3.0L/min/m2 pre-enalapril versus 2.8L/min/m2 after treatment; P = 0.15). Pediatric Fontan patients adequately respond to orthostasis with maintenance of blood pressure and cerebral blood flow and sufficient autonomic response. Enalapril treatment did not alter the response. Scientific title: ACE inhibition in Fontan patients: its effect on body fluid regulation (sAFE-study). The Netherlands National Trial Register: Trail NL6415. Registered 2017-07-20. Trial information: https://www.trialregister.nl/trial/6415.

Association of symptoms with myocardial fibrosis in adults with Fontan circulation

The extent and significance of cardiac remodeling in Fontan patients are unclear. The aim of this study was to measure myocardial fibrosis in single ventricle (SV) and to determine its relationship with Fontan failure. A prospective cross-sectional study was performed in 25 patients (mean age 32 ± 9 years, 48% male) with SV. Echocardiography, cardiopulmonary exercise test, BNP measurement and cardiac magnetic resonance imaging (CMR) were performed within the same day. Assessment of late gadolinium enhancement in combination with T1 mapping to quantify diffuse myocardial fibrosis with assessment of myocardial extracellular volume (ECV) were performed. Associations between parameters of SV remodeling, BNP and exercise performances were evaluated. Ten patients (40%) showed clinical signs of Fontan failure. SV volumes and mass were significantly increased in these patients compared to asymptomatic patients ( P < 0.01), while there was no difference in SV ejection fraction. Compared to asymptomatic Fontan patients, those with failing Fontan had significantly higher native T1 (1030 ± 29 ms vs. 982 ± 25 ms, P < 0.001) and ECV (32% (interquartile range (IQR) 30–36) vs. 27% IQR [25–30], P = 0.002). Amongst CMR parameters, only native T1 was significantly correlated with the peak VO2 [r = −0.49, P = 0.017] and BNP (r = 0.41, P = 0.046). No association was observed with echocardiographic parameters of SV systolic and diastolic function. Diffuse myocardial fibrosis is a determinant of Fontan circulation failure independently of systolic ventricular function.

Transvenous retrograde thoracic duct embolization for effective treatment of recurrent plastic bronchitis after Fontan palliation

Plastic bronchitis (PB) is a rare but potentially detrimental complication of the Fontan circulation. Retrograde transvenous thoracic duct embolization (TDE) has been proposed as a treatment strategy for lymphatic dysfunction. A 5.5-year-old patient (16 kg/105 cm) was referred to our institution for severe PB refractory to conservative treatment 3 months after completion of Fontan palliation. CT-scan showed multiple bilateral areas of patchy consolidation and ground-glass opacity with obstruction of the right main and right lower bronchi. Bi-inguinal transnodal fluoroscopy-guided lymphangiogram confirmed the diffuse and abnormal lymphatic leak originating from the thoracic duct into the chest, predominantly right-sided, and showed the TD ostium near the left venous angle. There was no opacification of any target central lymphatic vessel for direct transabdominal puncture. Retrograde approach from the femoral vein was adopted to catheterize the thoracic duct and selectively embolize its distal portion using intercalation of microcoils and liquid embolic adhesive. Recurrence of symptoms after 2 months indicated a redo catheterization that revealed the persistence of dilated peribronchial lymphatic network with a minimal residual leak across the previously embolized caudal section of the TD. Complete occlusion of the TD over its entire length was performed using the same technique. The procedure was technically successful and the patient was uneventfully discharged after 2 days. There was no cast recurrence or procedure-related complications and sustained clinical improvement at 18-month of postoperative follow-up. Fluoroscopy-guided lymphangiography was essential to understand the anatomy and flow pattern of the lymphatic system and to plan the lymphatic intervention. End-to-end TDE is an effective minimally invasive treatment in Fontan patients with PB and can be necessary in case of relapse after selectively embolizing the TD distal section.

Pharmacology Management in Improving Exercise Capacity of Patients with Fontan Circulation: A Systematic Review and Meta-analysis.

The Fontan procedure is currently the mainstay therapy for single functional ventricles. However, with prolonged follow-up duration, various complications have been observed that seriously influence the quality of life of patients. The aim of this meta-analysis is to compare the effectiveness of pharmacologic agents in improving exercise capacity in patients with Fontan circulation. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and has been registered in the International Prospective Register for Systematic Reviews database with registration no. 282352. Quality assessments of the included studies were assessed using the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) statement. Twelve studies met the predetermined inclusion criteria and were included in this metaanalysis. This meta-analysis found that treatment with bosentan significantly improved New York Heart Association Functional Class (NYHA FC) in Fontan patients (standard mean difference - 0.59, 95% CI -0.94 - -0.25; P=0.0008; I2 = 1%). However, the use of bosentan (P=0.66) and sildenafil (P=0.13) did not show a significant improvement in the maximum rate of oxygen consumption (VO2 max). This meta-analysis shows that people with Fontan circulation may benefit from using bosentan as it decreases postexercise heart rate and improves NYHA FC and 6-minute walking test results. Therefore, indirectly improving exercise capacity. Nonetheless, considerable work is required to strengthen our knowledge in improving the exercise capacity of Fontan patients.

Single ventricle dysfunction is the main trigger for late Fontan failure in adult patients

A substantial number of patients experiences late Fontan circulation failure. Previous concepts of Fontan failure implicate increasing pulmonary vascular resistance (PVR) as a key contributor to late circulatory failure. However, data to support this assumption are sparse. We sought to characterize hemodynamic findings in adult failing Fontan patients. We performed a bicentric retrospective cohort study in adult Fontan patients, identifying patients with Fontan failure. Patients were divided into systolic dysfunction (rEF) when ejection fraction (EF) < 40%, diastolic dysfunction (pEF) when EF ≥ 40% with systemic ventricular end-diastolic pressure ≥ 12 mmHg or elevated BNP level (> 200 pg/mL) and pulmonary hypertension (PH) when indexed pulmonary vascular resistance were elevated (≥ 2 WU*m 2 ). Hemodynamic, echocardiographic, and clinical data were recorded. Between 2000 and 2021, 55 adult patients were diagnosed with failing Fontan. Median age at diagnosis was 27 years (interquartile range (IQR), 22–30.7) i.e., 18.0 years [12.0–23.0] after Fontan surgery. The main hemodynamic cause of failing Fontan was the dysfunction of the systemic ventricle in 25 patients (45%), including 15 rEF and 10 pEF without additional hemodynamic lesions. PH was diagnosed in 6 (11%) patients and was isolated in 4 of them. Nine patients (16%) exhibited significant valvular dysfunction and 6 (11%) conduit stenosis. During a median FU of 5 years [1.25–12], Fontan failure-associated morbidity (33/55; 60%) and mortality (6/55, 11%) were substantial regardless of underlying hemodynamic lesions. Dysfunction of the systemic ventricle, systolic and/or diastolic, is frequent feature in late Fontan failure in adults, while increases in PVR were rarely observed. The intricate interplay between hemodynamic compromises in Fontan failure deserves further research to optimize treatment strategies and outcome.

Ventricular Flow Profile in Young Patients With Single Left Ventricle Fontan Using Echocardiographic Contrast Particle Imaging Velocimetry

The modern Fontan palliation directs systemic venous blood from the superior and inferior vena cava to the pulmonary arteries, bypassing the heart. Its success depends on low pulmonary vascular resistance and optimal systolic and diastolic ventricular function.1,2 Diastolic dysfunction in Fontan circulation is a well-known phenomenon, but its clinical impact remains underappreciated. Assessment of diastolic dysfunction in Fontan patients is challenging but might be enhanced by novel, advanced imaging techniques.

Long-term management of Fontan patients: The importance of a multidisciplinary approach.

The Fontan operation is a palliative procedure that leads to increased survival of patients with a functional single ventricle (SV). Starting from 1967 when the first operation was performed by Francis Fontan, more and more patients have reached adulthood. Furthermore, it is expected that in the next 20 years, the population with Fontan circulation will reach 150,000 subjects. The absence of right ventricular propulsion and the inability to improve cardiac output because of the low cardiac reserve are the main issues with the Fontan circulation; however, potential complications may also involve multiple organ systems, such as the liver, lungs, brain, bones, and the lymphatic system. As these patients were initially managed mainly by pediatric cardiologists, it was important to assure the appropriate transition to adult care with the involvement of a multidisciplinary team, including adult congenital cardiologists and multiple subspecialists, many of whom are neither yet familiar with the pathophysiology nor the end-organ consequences of the Fontan circulation. Therefore, the aim of our work was to collect all the best available evidence on Fontan's complications management to provide “simple and immediate” information sources for practitioners looking for state of the art evidence to guide their decision-making and work practices. Moreover, we suggest a model of follow-up of patients with Fontan based on a patient-centered multidisciplinary approach.

Incidence and impact of malnutrition in patients with Fontan physiology.

Single-ventricle patients require a series of surgeries, with the final stage being the Fontan. This form of circulation results in several long-term complications, but the impact and consequences of nutrition status remain unclear. We sought to evaluate the incidence of malnutrition in Fontan patients and the impact on outcomes. This study was a retrospective cohort study of children who underwent Fontan surgery between 1997 and 2018. Clinical, demographic, and nutrition data were collected, including weight, height, body mass index (BMI), and their respective z scores (z score for weight-for-age [WAZ], z score for height-for-age [HAZ], and z score for BMI-for-age [BMIZ]) pre-Fontan, at discharge, 6 months, and 1, 5, and 10 years post-Fontan. Malnutrition status was categorized using the American Society for Parenteral and Enteral Nutrition guidelines and the Michigan MTool. Fontan failure was defined as listing for heart transplant or death. Of the 69 patients, moderate-severe malnutrition occurred at any time point in 11% (n = 8) by WAZ, 16% (n = 11) by HAZ, and 6% (n = 4) by BMIZ. Moderate-severe malnutrition persisted in 6.5%-12.9% at 10 years post-Fontan. Compared with the pre-Fontan period, there was no change in these parameters over time. There was no statistically significant difference in Fontan failure between degrees of pre-Fontan malnutrition. There is a 6%-16% incidence of moderate-severe malnutrition in Fontan patients. Malnutrition is a condition that remains present in follow-up. There was no association with anthropometric parameters and transplant-free survival. A prospective multi-institutional study is needed to understand the impact of malnutrition on long-term outcomes.

Adequate exercise response at artificial altitude in Fontan patients

PurposeFor Fontan-palliated patients, altitude exposure is still a part of discussion since the extent of hypoxic pulmonary vasoconstriction potentially resulting in decreasing cardiac output (Qc), especially during physical exercise, is still unclear. We investigated the effects of normobaric hypoxia (15.2% O2) simulating 2,500 m above sea level on cardiopulmonary and metabolic parameters and the benefit of daily physical activity (PA) on hypoxic exercise capacity.MethodsA total of 21 Fontan patients (14–31 years) and 20 healthy controls performed cardiopulmonary exercise tests on a bicycle ergometer in normoxia and hypoxia until subjective exhaustion, measuring capillary lactate (cLa) every 2 min. In between, participants underwent an activity tracking over 5 days with a triaxial accelerometer.ResultsHypoxic exercise was well tolerated by Fontan patients, and no adverse clinical events were observed. Fontan patients showed reduced physical capacity under both conditions compared to controls (63% normoxia, 62% hypoxia), but the relative impairment due to hypoxia was similar for both (≈10%). Up to workloads of 2 W/kg oxygen uptake (O2) and heart rate (HR) developed similarly in patients and controls. cLa increased faster in relation to workload in Fontan patients, but remained significantly lower at peak workload (normoxia 3.88 ± 1.19 mmol/l vs. 7.05 ± 2.1 mmol/l; hypoxia 4.01 ± 1.12 mmol/l vs. 7.56 ± 1.82 mmol/l). Qc was diminished but could be increased similar to controls. Fontan patients with higher PA levels showed a higher O2peak in hypoxia.ConclusionExercise during short-time artificial altitude exposure seems to be safe for young Fontan patients. Further studies are needed to validate longer exposure under real conditions. O2, HR, and Qc might not be a limiting factor for exercise until workloads of 2 W/kg. Higher daily PA levels might improve physical capacity under altitude conditions.

Perioperative Management of an Adolescent Fontan Patient with Narrowing of the Aortopulmonary Space for Posterior Scoliosis Surgery

Congenital cardiac patients who received neonatal reconstructive aortic arch surgery are at risk of aortopulmonary space narrowing with compression of the left pulmonary artery and left main bronchus (LMB) later in life. We discuss a challenging adolescent single ventricle patient who presented for surgical treatment of a non-idiopathic thoracic scoliosis (posterior spinal fusion) with severe stenosis of the LMB and left pulmonary artery due to a narrow aortopulmonary space. Careful preoperative imaging, evaluation, and decision making resulted in successful surgical treatment and uneventful perioperative course.