• CD133
• Klotho
• congenital heart defects
• exosomes
• kidney disease
• urine

• Humans
• Fontan Procedure/adverse effects
• Male
• Female
• Child
• Child, Preschool
• Extracellular Vesicles/chemistry
• Extracellular Vesicles/metabolism
• Biomarkers/urine
• Adolescent
• Infant
• Klotho Proteins
• Heart Defects, Congenital/surgery
• Heart Defects, Congenital/urine
• Heart Ventricles/abnormalities
• Heart Ventricles/surgery
• Nephritis/urine
• Nephritis/etiology
• Kidney/pathology
• Inflammation/urine

• ISEV

• Atrioventricular valve function
• Failing Fontan
• Systemic ventricular function
• Total cavopulmonary connection

• Humans
• Fontan Procedure/adverse effects
• Male
• Female
• Child, Preschool
• Infant
• Retrospective Studies
• Heart Defects, Congenital/surgery
• Heart Defects, Congenital/physiopathology
• Echocardiography
• Child
• Ventricular Function/physiology
• Heart Ventricles/physiopathology
• Heart Ventricles/diagnostic imaging
• Heart Failure/physiopathology
• Heart Failure/etiology
• Follow-Up Studies
• Treatment Failure

• Failing fontan
• heart transplantation
• total cavopulmonary connection
• ventricular assist device

• Humans
• Retrospective Studies
• Female
• Fontan Procedure/adverse effects
• Male
• Incidence
• Heart Defects, Congenital/surgery
• Heart Defects, Congenital/physiopathology
• Risk Factors
• Child
• Child, Preschool
• Protein-Losing Enteropathies/epidemiology
• Protein-Losing Enteropathies/etiology
• Adolescent
• Heart Transplantation
• Postoperative Complications/epidemiology
• Postoperative Complications/physiopathology
• Postoperative Complications/therapy
• Treatment Failure
• Heart Failure/epidemiology
• Heart Failure/etiology
• Germany/epidemiology
• Infant
• Young Adult
• Adult
• Bronchitis/epidemiology
• Bronchitis/etiology

• 1-D model
• Congenital heart disease
• Fontan circulation
• Parameter estimation

• Fontan
• biventricular
• heart failure
• ketogenic therapy
• ketones
• metabolism
• nutrition
• single ventricle

• KLI 1036-B FWF Austrian Science Fund

• dynamic contrast magnetic resonance lymphangiography
• fontanoperation
• hypoplastic left heart syndrome
• innominate vein turn-down procedures
• lymphatic insufficiency
• lymphatic interventional techniques
• plastic bronchitis
• protein-losingenteropathy

• Adult congenital heart disease
• Heart failure
• Mechanical circulatory support
• Orthotopic heart transplant

Despite 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.

Metabolic liver function measured by liver maximum function capacity test (LiMAx®) correlates with Fontan hemodynamics and Fontan failure.

From 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.

LiMAx® 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).

Maximum 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.

• Kinderherzen Fördergemeinschaft Deutsche Kinderherzzentren

• Adult
• Anticoagulants/therapeutic use
• Child
• Fontan Procedure/adverse effects
• Fontan Procedure/methods
• Heart Defects, Congenital/epidemiology
• Heart Defects, Congenital/surgery
• Humans
• Stroke/etiology
• Venous Thromboembolism/drug therapy
• Warfarin/therapeutic use

Objectives: Fontan-associated liver disease (FALD) is the most common end-organ dysfunction affecting up to 70–80% of the Fontan population. The clinical significance of FALD is incompletely understood and no unambiguous correlation between hepatic function and FALD severity has been established. In this study, we sought to evaluate maximal liver function capacity with liver maximum function capacity test (LiMAx®) in adult Fontan patients.

Methods: Thirty-nine adult Fontan patients (median age: 29.4 years [IQR 23.4; 37.4], median follow-up after Fontan operation: 23.9 years [IQR 17.8;26.4]) were analyzed in a cross-sectional observational study using LiMAx® test (Humedics GmbH, Berlin, Germany), laboratory testing, transient elastography (TE) and hepatic ultrasound. The LiMAx® test is based on the metabolism of ¹³C-methacetin, which is administered intravenously and cleaved by the hepatic cytochrome P4501A2 to paracetamol and ¹³CO₂, which is measured in exhaled air and correlates with maximal liver function capacity.

Results: Maximal liver function capacity assessed by LiMAx® test was normal in 28 patients (>315 μg/h^*kg) and mildly to moderately impaired in 11 patients (140–314 μg/h^*kg), while no patient displayed severe hepatic impairment (<139 μg/kg^*h). No correlation was found between maximal liver function capacity and hepatic stiffness by TE (r² = −0.151; p = 0.388) or the presence of sonographic abnormalities associated with FALD (r² = −0.204, p = 0.24). There was, however, an association between maximal liver function capacity and the laboratory parameters bilirubin (r² = −0.333, p = 0.009) and γ-glutamyl transferase (r² = −0.367; p = 0.021). No correlation was detected between maximal liver function capacity and the severity of FALD (r² = −0.235; p = 0.152).

Conclusion: To the best of our knowledge, this is the first study to evaluate maximal liver function capacity using LiMAx® test in Fontan patients, which is a useful complementary diagnostic instrument to assess chronic hepatic injury. Maximal liver function capacity was preserved in most of our adult Fontan patients despite morphologic evidence of FALD. Moreover, maximal liver function capacity does not correlate with the extent of FALD severity evaluated by sonography or laboratory analysis. Thus, the development and progression of FALD in Fontan patients is not a uniform process and diagnostics of chronic hepatic injury during follow-up should encompass various modalities.

• Fontan failure
• Fontan-associated liver disease
• enzymatic liver function
• hepatic assessment
• second-organ dysfunction

• Fontan
• Fontan failure
• heart failure
• medications
• single ventricle
• ventricular assist device

• Pediatrics
• complications
• congenital
• fontan
• heart defects
• treatment

• Bronchitis/etiology
• Bronchitis/therapy
• Fontan Procedure/adverse effects
• Fontan Procedure/methods
• Heart Defects, Congenital/surgery
• Humans
• Protein-Losing Enteropathies/complications
• Protein-Losing Enteropathies/therapy
• Vascular Resistance

• Fontan
• Fontan circuit
• complications
• failure Fontan
• multidisciplinary

• Cardiac transplantation
• Congenital heart disease
• Single ventricle physiology

• Cardiac transplantation
• FALD severity
• Fontan failure
• Fontan-associated liver disease

• Adult congenital heart disease
• CHD
• Congenital heart disease
• Noncardiac surgery
• Single ventricle

• Complications
• Failure
• Fontan
• Operation

Mechanical circulatory support (MCS) for failing single ventricle (SV) physiology is a complex and challenging problem, which has not yet been satisfactorily addressed. Advancements in surgical strategies and techniques along with intensive care management have substantially improved the outcomes of neonatal palliation for SV physiology, particularly for hypoplastic left heart syndrome (HLHS). This is associated with a steady increase in the number of SV patients who are susceptible to develop heart failure (HF) and would potentially require MCS at a certain stage in their palliation. We have reviewed the literature regarding the reported modalities of MCS use in the management of SV patients. This includes analysis of various devices and strategies used for failing circulation at distinct stages of the SV pathway: after neonatal palliation, after the superior cavo-pulmonary connection (SCPC), and after total cavo-pulmonary connection (TCPC).

• VA ECMO
• fontan physiology
• mechanical circulatory support
• single ventricle
• ventricular assist devices

• circulatory assist device
• failing fontan
• fontan circulation
• subpulmonary assist
• total cavopulmonary connection

• Fontan circulation
• bosentan
• drug therapy
• enalapril
• sildenafil

• Fontan failure
• Lumped parameter models
• Ventricular assist devices

• left superior vena cava

Current treatment strategies for single ventricle patients include non-intervention strategy, surgical palliation or primary transplantation. Surgical palliation includes a staged operative course culminating in the Fontan operation. With progress in surgical techniques, the survival has been improving. However, almost all of these Fontan patients will demonstrate pathophysiologic changes that ultimately constitute “Fontan failure physiology”. This article reviews the pathophysiologic changes, current approach to management of these patients and proposes a novel way of reversing some of the pathophysiologic changes by utilization of negative pressure ventilation.

• Fontan
• Single ventricle physiology
• Negative pressure ventilation
• Cardiorespiratory interactions
• Congenital heart disease

• fontan procedure
• heart defects
• congenital
• pediatrics
• functional health status

• Congenital Heart Disease
• Endocarditis
• Health Behavior
• Risk Factors
• “Binge Drinking”

Parallel advancements in surgical technique, preoperative and postoperative care, as well as a better understanding of physiology in patients with duct-dependent pulmonary or systemic circulation and a functional single ventricle, have led to superb results in staged palliation of most complex congenital heart disease (CHD) [1]. The Fontan procedure and its technical modifications have resulted in markedly improved outcomes of patients with single ventricle anatomy [2,3,4]. The improved early survival has led to an exponential increase of the proportion of Fontan patients surviving long into adolescence and young adulthood [5]. Improved early and late survival has not yet abolished late mortality secondary to myocardial failure, therefore increasing the referrals for cardiac transplantation [6]. Interstage attrition [7] is moreover expected in staged palliation towards completion of a Fontan-type circulation, while Fontan failure represents a growing indication for heart transplantation [8]. Heart transplantation has therefore become the potential “fourth stage” [9] or a possible alternative to a high-risk Fontan operation [10] in a strategy of staged palliation for single ventricle physiology. Heart transplant barely accounts for 16% of pediatric solid organ transplants [11]. The thirteenth official pediatric heart transplantation report- 2010 [11] indicates that pediatric recipients received only 12.5% of the total reported heart transplants worldwide. Congenital heart disease is not only the most common recipient diagnosis, but also the most powerful predictor of 1-year mortality after OHT. Results of orthotopic heart transplantations (OHT) for failing single ventricle physiology are mixed. Some authors advocate excellent early and mid-term survival after OHT for failing Fontan [9], while others suggest that rescue-OHT after failing Fontan seems unwarranted [10]. Moreover, OHT outcome appears to be different according to the surgical staging towards the Fontan operation and surgical technique of Fontan completion [12].

The focus of this report is a complete review of the recent literature on OHT for failing single ventricles, outlining the clinical issues affecting Fontan failure, OHT listing and OHT outcome. These data are endorsed reporting our experience with OHT for failing single ventricle physiology in recent years.

• Pediatric heart transplantation
• fontan failure
• univertricular physiology.

A 2-year-old patient with hypoplastic left heart syndrome presented 6 months following Fontan completion with protein-losing enteropathy (PLE). He had undergone stent implantation in the left pulmonary artery after the Norwood procedure, followed by redilation of the stent prior to Fontan completion. Combined bronchoscopic and catheterization studies during spontaneous breathing confirmed left bronchial stenosis behind the stent, and diastolic systemic ventricular pressure during expiration of 25 mm Hg. We postulate that the stent acts as a valve, against which the patient generates high expiratory pressures, which are reflected in the ventricular diastolic pressure. This may be the cause of PLE.

• Bronchial compression
• protein losing enteropathy
• stents