Asymptomatic children with ventricular pre-excitation/WPW pattern.

Paediatric patients with ventricular pre-excitation/asymptomatic WPW syndrome have a higher risk of atrial fibrillation degenerating into ventricular fibrillation and sudden cardiac death (SCD). In more than half of these patients this can be the first symptom presenting. Hence, it is important to conduct a risk stratification for SCD in asymptomatic patients with pre-excitation/delta wave in the ECGs. In this review, invasive risk stratification by electrophysiologic testing and ablation is recommended when possible. Catheter ablation is reported to have a high rate of success and low risk of complications.

Lung Function in Fontan Patients Over a Ten-Year Period: Is the Fontan Circulation Impairing Lung Development?

Few studies have investigated how the Fontan circulation affects lung function, and no studies have investigated the development of lung function over longer time in these patients. We aimed to describe the development of lung function in Fontan patients over a 10-year period. Pulmonary function tests (PFT), including spirometry and diffusion capacity for Carbon Monoxide (DLCO) and Nitric Oxide (DLNO), were conducted in a Danish Fontan cohort in 2011 (PFT-I). In 2021, re-investigations were performed (PFT-II). We investigated changes in percent predicted (%pred) lung function from PFT-I to PFT-II. Patients were categorized into a pediatric group (age under 18 at PFT-I) and an adult group (age 18 or older at PFT-I). Out of the 81 patients completing PFT-I, 48 completed PFT-II. In the pediatric group (32 patients), there were significant declines in %pred forced expiratory volume in 1s (99.7 (92.4, 104.4)-89.3 (84.9, 97.2), p < 0,001), forced vital capacity (98.3 (87.8, 106.1)-96.7 (86.7, 100.6), p = 0.008), and alveolar volume (95.5 (89.5, 101.6)-89.5 (79.7, 93.2), p < 0.001). The corresponding measurements remained stable in the adult group. However, the median %pred DLNO significantly declined in the adult group (58.4 (53.3, 63.5)-53.7 (44.1, 57.3), p = 0.005). Over a 10-year period, several lung function parameters declined significantly in the younger Fontan patients, suggesting possible impairments in lung development during growth. The decline in %pred DLNO in the adult patient group indicates deterioration of the membrane component of diffusion capacity, implying that the Fontan circulation might negatively affect the alveolar membrane over time.

Quality of Life in the Danish Fontan Population is Unchanged Over the Past Decade-A Nationwide Longitudinal Study.

Knowledge about health-related quality of life (HRQoL) over time in Fontan patients is sparse. We aimed to describe HRQoL over a ten-year period in a population-based Fontan cohort. Further, we compared HRQoL in Fontan patients with the general population. In 2011, Danish Fontan patients were invited to participate in a nationwide study assessing HRQoL. Depending on age, 152 participants filled out either the Pediatric Quality of Life Inventory or the 36-Item Short Form Health Survey. After a decade, patients from the initial study were invited to participate in a follow-up study. All were given the same questionnaire as in the first study, plus the 12-Item Short Form Health Survey (SF-12) as part of the Danish National Health Survey. HRQoL over time was described, and SF-12 scores were compared with the general population. A total of 109 Fontan patients completed the questionnaires in both studies. The mean patient age was 14.9 ± 6.6 years and 25.6 ± 6.5 years respectively. Despite an increase in complications, HRQoL did not decrease during the study period. Physical HRQoL scores were lower than mental HRQoL scores at both time points. The SF-12 physical component score was significantly lower in Fontan patients than in the general population (median score 52 vs. 56, p < 0.001), while the SF-12 mental component score was comparable (median score 51 vs. 50, p = 0.019). HRQoL remained stable over a ten-year period in a contemporary Danish Fontan cohort. Still, the physical HRQoL remained significantly lower than that of the general population.

EASL-ERN position paper on liver involvement in patients with Fontan-type circulation.

Fontan-type surgery is the final step in the sequential palliative surgical treatment of infants born with a univentricular heart. The resulting long-term haemodynamic changes promote liver damage, leading to Fontan-associated liver disease (FALD), in virtually all patients with Fontan circulation. Owing to the lack of a uniform definition of FALD and the competitive risk of other complications developed by Fontan patients, the impact of FALD on the prognosis of these patients is currently debatable. However, based on the increasing number of adult Fontan patients and recent research interest, the European Association for The Study of the Liver and the European Reference Network on Rare Liver Diseases thought a position paper timely. The aims of the current paper are: (1) to provide a clear definition and description of FALD, including clinical, analytical, radiological, haemodynamic, and histological features; (2) to facilitate guidance for staging the liver disease; and (3) to provide evidence- and experience-based recommendations for the management of different clinical scenarios.

Outcomes of out-of-hospital cardiac arrest in adult congenital heart disease: a Danish nationwide study.

AIMS: The risk, characteristics, and outcome of out-of-hospital cardiac arrest (OHCA) in patients with congenital heart disease (CHD) remain scarcely investigated. METHODS AND RESULTS: An epidemiological registry-based study was conducted. Using time-dependent Cox regression models fitted with a nested case-control design, hazard ratios (HRs) with 95% confidence intervals of OHCA of presumed cardiac cause (2001-19) associated with simple, moderate, and severe CHD were calculated. Moreover, using multiple logistic regression, we investigated the association between pre-hospital OHCA characteristics and 30-day survival and compared 30-day survival in OHCA patients with and without CHD. Overall, 43 967 cases (105 with simple, 144 with moderate, and 53 with severe CHD) and 219 772 controls (median age 72 years, 68.2% male) were identified. Any type of CHD was found to be associated with higher rates of OHCA compared with the background population [simple CHD: HR 1.37 (1.08-1.70); moderate CHD: HR 1.64 (1.36-1.99); and severe CHD: HR 4.36 (3.01-6.30)]. Pre-hospital cardiopulmonary resuscitation and defibrillation were both associated with improved 30-day survival in patients with CHD, regardless of CHD severity. Among patients with OHCA, simple, moderate, and severe CHD had a similar likelihood of 30-day survival compared with no CHD [odds ratio 0.95 (0.53-1.69), 0.70 (0.43-1.14), and 0.68 (0.33-1.57), respectively]. CONCLUSION: A higher risk of OHCA was found throughout the spectrum of CHD. Patients with and without CHD showed the same 30-day survival, which relies on the pre-hospital chain of survival, namely cardiopulmonary resuscitation and defibrillation.

Exercise capacity in the Danish Fontan population remains stable after ten years of follow-up - is physical activity the key to success?

BACKGROUND: Most Fontan patients have impaired exercise capacity, and a further decline in exercise capacity over time seems inevitable. However, few longitudinal studies exist, and there is a lack of data from newer eras. We aimed to describe the natural evolution of exercise capacity over a 10-year period in a contemporary, population-based cohort of Danish Fontan patients. METHODS: The study was a nationwide, prospective study. A cardiopulmonary exercise test (CPET) was used to assess the exercise capacity. All Danish Fontan patients who participated in a national study in 2011 (CPET1), were invited to a follow-up visit in 2021 (CPET2). All patients who completed CPET1 and CPET2 with a respiratory exchange ratio over 1.0 were included. The main outcome was percent predicted VO2peak (%pred VO2peak). At the time of CPET2, patients filled out a questionnaire including questions regarding physical activity. RESULTS: Seventy-seven patients completed both CPET1 and CPET2, and seventy patients completed the questionnaire. The time interval between the two CPETs was 10.4 ± 0.9 years. The median age was 15 years at CPET1 and 26 years at CPET2. The exercise capacity remained stable with a mean %pred VO2peak of 53.8 ± 11.3 at CPET1 and 55.6 ± 10.9 in CPET2 (p = 0.314). Higher levels of vigorous physical activity were associated with higher %pred VO2peak in CPET2 in a multivariate regression model. CONCLUSION: The %pred VO2peak remained stable over a ten-year period in this population-based Fontan cohort. Higher levels of self-reported vigorous physical activity were associated with higher %pred VO2peak in the most recent CPET.

Cardiac arrest in previously asymptomatic child with Wolff-Parkinson-White syndrome.

In this case report, a previously asymptomatic 11-year-old boy presented with sudden palpitations and syncope. He eventually went into cardiac arrest and was successfully resuscitated. The ECG showed pre-excited atrial fibrillation degenerating into pulseless ventricular tachycardia. The patient was found to have Wolff-Parkinson-White syndrome (WPW) with an accessory pathway between right atrium and ventricle which was successfully ablated. Sudden cardiac death (SCD) is rare in WPW, however, early diagnosis is essential for eliminating the risk of SCD.

Lifetime risk of comorbidity in patients with simple congenital heart disease: a Danish nationwide study.

AIMS: In a continuously ageing population of patients with congenital heart disease (CHD), understanding the long-term risk of morbidity is crucial. The aim of this study was to compare the lifetime risks of developing comorbidities in patients with simple CHD and matched controls. METHODS AND RESULTS: Using the Danish nationwide registers spanning from 1977 to 2018, simple CHD cases were defined as isolated atrial septal defect (ASD), ventricular septal defect (VSD), pulmonary stenosis, or patent ductus arteriosus in patients surviving until at least 5 years of age. There were 10 controls identified per case. Reported were absolute lifetime risks and lifetime risk differences (between patients with simple CHD and controls) of incident comorbidities stratified by groups and specific cardiovascular comorbidities. Of the included 17 157 individuals with simple CHD, the largest subgroups were ASD (37.7%) and VSD (33.9%), and 52% were females. The median follow-up time for patients with CHD was 21.2 years (interquartile range: 9.4-39.0) and for controls, 19.8 years (9.0-37.0). The lifetime risks for the investigated comorbidities were higher and appeared overall at younger ages for simple CHD compared with controls, except for neoplasms and chronic kidney disease. The lifetime risk difference among the comorbidity groups was highest for neurological disease (male: 15.2%, female: 11.3%), pulmonary disease (male: 9.1%, female: 11.7%), and among the specific comorbidities for stroke (male: 18.9%, female: 11.4%). The overall risk of stroke in patients with simple CHD was mainly driven by ASD (male: 28.9%, female: 17.5%), while the risks of myocardial infarction and heart failure were driven by VSD. The associated lifetime risks of stroke, myocardial infarction, and heart failure in both sexes were smaller in invasively treated patients compared with untreated patients with simple CHD. CONCLUSION: Patients with simple CHD had increased lifetime risks of all comorbidities compared with matched controls, except for neoplasms and chronic kidney disease. These findings highlight the need for increased attention towards early management of comorbidity risk factors.

[Acute neonatal myocarditis with cardiogenic shock caused by enterovirus infection].

In this case report, a 16-days-old boy presented with reduced feeding, vomiting, respiratory distress and pallor. He developed cardiogenic shock with cardiac arrest and was resuscitated. Echocardiography showed reduced left ventricular systolic function and he was diagnosed with enterovirus myocarditis since enterovirus RNA was found in the blood by polymerase chain reaction. After one month of hospitalization, the patient was discharged without any apparent sequelae. The condition is rare but associated with a high mortality. Early diagnosis and initiation of treatment is essential for survival.

Time Trends in Simple Congenital Heart Disease Over 39 Years: A Danish Nationwide Study.

Background We describe calendar time trends of patients with simple congenital heart disease. Methods and Results Using the nationwide Danish registries, we identified individuals diagnosed with isolated ventricular septal defect, atrial septal defect, patent ductus arteriosus, or pulmonary stenosis during 1977 to 2015, who were alive at 5 years of age. We reported incidence per 1 000 000 person-years with 95% CIs, 1-year invasive cardiac procedure probability and age at time of diagnosis stratified by diagnosis age (children ≤18 years, adults >18 years), and 1-year all-cause mortality stratified by diagnosis age groups (5-30, 30-60, 60+ years). We identified 15 900 individuals with simple congenital heart disease (ventricular septal defect, 35.2%; atrial septal defect, 35.0%; patent ductus arteriosus, 25.2%; pulmonary stenosis, 4.6%), of which 75.7% were children. From 1977 to 1986 and 2007 to 2015, the incidence rates increased for atrial septal defect in adults (8.8 [95% CI, 7.1-10.5] to 31.8 [95% CI, 29.2-34.5]) and in children (26.6 [95% CI, 20.9-32.3] to 150.8 [95% CI, 126.5-175.0]). An increase was only observed in children for ventricular septal defect (72.1 [95% CI, 60.3-83.9] to 115.4 [95% CI, 109.1-121.6]), patent ductus arteriosus (49.2 [95% CI, 39.8-58.5] to 102.2 [95% CI, 86.7-117.6]) and pulmonary stenosis (5.7 [95% CI, 3.0-8.3] to 21.5 [95% CI, 17.2-25.7]) while the incidence rates remained unchanged for adults. From 1977-1986 to 2007-2015, 1-year mortality decreased for all age groups (>60 years, 30.1%-9.6%; 30-60 years, 9.5%-1.0%; 5-30 years, 1.9%-0.0%), and 1-year procedure probability decreased for children (13.8%-6.6%) but increased for adults (13.3%-29.6%) were observed. Conclusions Increasing incidence and treatment and decreasing mortality among individuals with simple congenital heart disease point toward an aging and growing population. Broader screening methods for asymptomatic congenital heart disease are needed to initiate timely treatment and follow-up.

Cardiovascular complications in patients with total cavopulmonary connection: A nationwide cohort study.

BACKGROUND: Long-term outcomes are not well established at the population level after completion of the total cavopulmonary connection (TCPC) among patients with functional univentricular hearts. PURPOSE: To evaluate the incidence of cardiovascular events after TCPC completion. METHODS: From a validated population-based cohort, we identified 178 patients with TCPC circulation completed after January 1, 1995. We established a comparison cohort by frequency-matching patients 1:200 on sex, and month and year of birth to the general Danish population (n = 35,600 population controls). We started follow-up at date of TCPC completion for cases and, for controls, at the index date of their matched case. The risks of cardiovascular events were assessed using cumulative incidence rates and Poisson regression models adjusted for age, sex, and calendar year. RESULTS: The median age at TCPC completion was 3.3 years (interquartile range 2.6 to 5.3 years). Over a median follow-up of 12.5 years, 10 (5.6%) TCPC patients died and 7 (4.5%) had a heart transplantation compared with a 0.2% mortality in the matched population. In TCPC patients, 15.7% had an arrhythmia (11.8% supraventricular tachycardia), 3.4% had a stroke (all ischemic), and 21.4% of TCPC patients initiated a combination of a diuretic and a renin-angiotensin system (RAS)-inhibitor. These rates were >50-fold higher than in the comparison cohort: 0.2% arrhythmia, 0.06% stroke, and 0.04% starting a diuretic and a RAS-inhibitor. CONCLUSIONS: Patients with TCPC circulation face a high risk of cardiovascular events during intermediate term follow-up.

Impact of congenital heart surgery on quality of life in children and adolescents with surgically corrected Ventricular Septal Defect, Tetralogy of Fallot, and Transposition of the Great Arteries.

OBJECTIVE: To describe the impact of CHD surgery in early childhood on quality of life in children aged 10-16 years with surgically corrected Ventricular Septal Defect, Transposition of the Great Arteries, and Tetralogy of Fallot. METHOD: A cross-sectional survey study of quality of life survey on 161 children and adolescents aged 10-16 years with surgically corrected Ventricular Septal Defect, Transposition of the Great Arteries, and Tetralogy of Fallot. The international Paediatric Quality of Life 4.0 quality of life questionnaires were applied and collected for assessment from patients and parents. The endpoints were total, physical, emotional, social, and school quality of life scores. RESULTS: The quality of life total and school scores was significantly lower in children with CHD than their healthy peers. There was no significant difference in quality of life between the three CHD groups. All three CHD groups had a significantly lower total (7.7-13.2%, p<0.001) and school scores (21.1-31.6%, p<0.001) than the control group. The tetralogy of Fallot group was the only group that had significantly lower scores in the physical subscale (p<0.001) than the controls. CONCLUSION: Children and adolescents with surgically corrected CHD show losses in quality of life in total and school scores compared to healthy controls. The tetralogy of Fallot group was the only CHD group that had significantly lower physical score than the controls.

Subclinical hypothyroidism: A common finding in adult patients with cyanotic congenital heart disease.

OBJECTIVE: Cyanotic congenital heart disease is a systemic disease, with effects on multiple organ systems. A high prevalence of subclinical hypothyroidism (SCH) has been reported in a small cohort of cyanotic congenital heart disease patients. Subclinical hypothyroidism has been associated with various adverse cardiovascular effects, as well as an increased risk of progression to overt hypothyroidism. The aim of this study was to examine the prevalence of SCH in cyanotic congenital heart disease patients, consider possible etiologies, and evaluate thyroid function over time. METHODS: First, 90 clinically stable cyanotic congenital heart disease patients were examined with blood samples (thyroid-stimulating hormone, C-reactive protein, hemoglobin, hematocrit, and N-terminal pro-brain-natriuretic peptide) in a cross-sectional descriptive study. Second, a longitudinal follow-up study of 43 patients originating from the first study part, was carried out. These patients had thyroid function parameters (thyroid-stimulating hormone, thyroid hormones, and thyroid peroxidase antibodies) evaluated biannually. RESULTS: Elevated thyroid-stimulating hormone was present in 24% of the 90 screened patients. During follow-up (6.5 ± 1.0 years), SCH (defined as ≥2 consecutive elevated thyroid-stimulating hormone values) was present in 26%. Three patients progressed to overt hypothyroidism. Patients with SCH were younger (34 ± 12 vs 42 ± 16 years; P = .01) and had a lower oxygen saturation (80 ± 5 vs 84 ± 6%; P = .03). CONCLUSION: Subclinical hypothyroidism is a very common finding in cyanotic congenital heart disease. This is not associated with increased levels of C-reactive protein, heart failure, or autoimmunity but appears to be associated with cyanosis and age. Since the clinical impact of SCH is uncertain, further studies are needed to determine this. Regular thyroid evaluation is recommended in cyanotic congenital heart disease patients since SCH can develop to overt hypothyroidism.

Bosentan improves exercise capacity in adolescents and adults after Fontan operation: the TEMPO (Treatment With Endothelin Receptor Antagonist in Fontan Patients, a Randomized, Placebo-Controlled, Double-Blind Study Measuring Peak Oxygen Consumption) study.

BACKGROUND: The Fontan procedure has improved survival in children with functionally univentricular hearts. With time, however, complications such as reduced exercise capacity are seen more frequently. Exercise intolerance is multifactorial, but pulmonary vascular resistance probably plays a crucial role. Elevated pulmonary vascular resistance has been associated with raised levels of endothelin-1, which are common both before and after Fontan operations. Treatment with endothelin-1 receptor antagonists could theoretically improve cardiopulmonary hemodynamics and exercise capacity. The aim of this study was therefore to examine the efficacy and safety of bosentan in Fontan patients. METHODS AND RESULTS: Seventy-five adolescents and adults were randomized 1:1 to 14 weeks of treatment with bosentan or placebo. Cardiopulmonary exercise test, functional class, blood samples, and quality-of-life questionnaires were evaluated at baseline and at the end of treatment. Sixty-nine patients (92%) completed the study. Peak oxygen consumption increased 2.0 mL·kg(-1)·min(-1) (from 28.7 to 30.7 mL·kg(-1)·min(-1)) in the bosentan group compared with 0.6 mL·kg(-1)·min(-1) (from 28.4 to 29.0 mL·kg(-1)·min(-1)) in the placebo group (P=0.02). Cardiopulmonary exercise test time increased by 0.48 minute (from 6.79 to 7.27 minutes) versus 0.08 minute (from 6.94 to 7.02 minutes; P=0.04). Nine bosentan-treated patients improved 1 functional class, whereas none improved in the placebo group (P=0.0085). Side effects were mild and occurred equally in both groups. No serious adverse effects were seen, and no patients had liver enzyme levels above the 3-fold upper limit. CONCLUSIONS: Bosentan improves exercise capacity, exercise time, and functional class in Fontan patients without serious adverse events or hepatotoxicity. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01292551.

Hemodynamic causes of exercise intolerance in Fontan patients.

BACKGROUND: Exercise intolerance is frequent among Fontan patients and an important determinant for quality of life. This study investigated the hemodynamic causes of impaired exercise capacity in Fontan patients with particular focus on the influence of stroke volume index (SVI) and heart rate (HR). METHODS AND RESULTS: In 38 Fontan patients, peak oxygen consumption (VO2), SVI and HR were recorded during incremental load exercise test and compared with 19 age and gender matched controls. SVI (ml/m(2)) was lower in patients than controls during warm-up (28[26-31] vs. 35[30-39], p=0.0093), at submaximal (40[37-43] vs. 55[51-59], p<0.0001) and at maximal exercise (38[35-40] vs. 54[51-58], p<0.0001). Similarly, HR (% of expected maximum) was lower in patients at warm-up (45[43-48]% vs. 64[57-64]%, p<0.0001), submaximal (71[68-75]% vs 85[82-88]%, p<0.0001) and maximal exercise (84[80-88]% vs. 97[95-99]%, p<0.0001). Furthermore, SVI dropped 14% (from 44[41-48] to 38[35-40] ml/m(2)) in Fontan patients from the peak plateau to maximal exercise vs. 5% (from 57[53-61] to 54[51-58] ml/m(2)) in controls, p<0.0001. The low SVI and HR explained 67% and 20% of the difference in peak VO2 between Fontan patients and controls respectively. CONCLUSION: SVI decreased significantly in Fontan patients near the end of maximal effort exercise. The low SVI at maximal exercise was the most important hemodynamic factor limiting exercise capacity in Fontan patients, whereas chronotropic impairment had a smaller impact. The low SVI and HR at maximal exercise accounted for the difference in peak VO2 between Fontan patients and controls in this study. CLINICAL TRIAL REGISTRATION: http://www.cvk.sum.dk/CVK/Home/English.aspx (protocol nr: H-3-2010-045).

New insights into the aspects of pulmonary diffusing capacity in Fontan patients.

BACKGROUND: Patients with a functionally univentricular heart, palliated a.m. Fontan, consequently have non-pulsatile pulmonary blood flow and are known to have a reduced pulmonary diffusing capacity. However, the cause of this reduction remains unclear. We aimed to assess the possible determinants in the aetiology of a reduced diffusing capacity and also to assess whether it could be increased. Furthermore, we aimed to search for predictors of a reduced diffusing capacity. MATERIAL AND METHODS: A total of 87 Fontan patients (mean age 16.3 ± 7.6 years) performed advanced pulmonary function tests and maximal cycle ergometer tests. A total of 10 Fontan patients and nine matched controls performed a supine pulmonary function test after a supine rest. RESULTS: In the sitting pulmonary function test, the mean z-scores were: diffusing capacity, 2.38 ± 1.20; pulmonary capillary blood volume, 2.04 ± 0.80; and alveolar capillary membrane diffusing capacity, 0.14 ± 0.84. In the supine compared with the sitting pulmonary function test, the diffusing capacity increased by 51.7 ± 11.9% in the Fontan group and by 23.3 ± 17.7% in the control group (p < 0.001); moreover, the pulmonary capillary blood volume increased by 48.3 ± 17.4% in the Fontan group and by 20.2 ± 13.9% in the control group (p = 0.001). In a multiple linear regression analysis including the explanatory variables of surgical data and exercise data at rest and peak exercise, the resting cardiac index was an independent predictor of the diffusing capacity (regression coefficient: 0.18, p < 0.001). CONCLUSIONS: The pulmonary diffusing capacity was reduced in Fontan patients because of a reduced pulmonary capillary blood volume, whereas the alveolar capillary membrane diffusing capacity was preserved. The diffusing capacity was highly increasable in Fontan patients compared with controls, and the resting cardiac index was an independent predictor of the diffusing capacity.

The effect of bosentan on exercise capacity in Fontan patients; rationale and design for the TEMPO study.

BACKGROUND: Palliative treatment with the Fontan procedure has greatly improved survival for children with functionally univentricular heart. Since Fontan performed the first successful operation, the procedure has evolved and is now performed as Total Cavo-Pulmonary Connection (TCPC).An increasing prevalence and longer life expectancy of TCPC patients have raised new challenges. The survivors are often suffering complications such as arrhythmias, myocardial dysfunction, thromboembolic events, neuropsychological deficit, protein-losing enteropathy and reduced exercise capacity. Several causes for the reduced exercise capacity may be present e.g. impaired function of the single ventricle, valve dysfunction and chronotropic impairment, and perhaps also increased pulmonary vascular resistance. Thus, plasma endothelin-1 has been shown to correlate with increased pulmonary vascular resistance and the risk of failing Fontan circulation. This has raised the question of the role for pulmonary vasodilation therapy, especially endothelin receptor antagonist in the management of TCPC patients. METHODS/DESIGN: The TEMPO trial aims to investigate whether Bosentan, an endothelin receptor antagonist, can be administered safely and improve exercise capacity in TCPC patients. The trial design is randomized, double-blind and placebo-controlled. Bosentan/placebo is administered for 14 weeks with control visits every four weeks. The primary endpoint is change in maximal oxygen consumption as assessed on bicycle ergometer test. Secondary endpoints include changes in pulmonary blood flow during exercise test, pro brain natriuretic peptide and quality of life. DISCUSSION: We hypothesize that treatment with Bosentan, an endothelin receptor antagonist, can be administered safely and improve exercise capacity in TCPC patients.

Quality of life and cognitive function in Fontan patients, a population-based study.

BACKGROUND: After the Fontan procedure patients are at risk for reduced quality of life (QoL) and cognitive function. We aimed to assess these important factors in Danish Fontan patients and to compare the results with a group of healthy controls. METHODS: All Fontan patients living in Denmark were identified and invited to participate. QoL was evaluated using the Pediatric Quality of Life Inventory (PedsQL) version 4.0 generic core module in patients <16 years and the Short Form 36 questionnaire (SF-36) in patients ≥16 years. Cognitive function was evaluated in all patients ≥6 years using the Quick Test of Cognitive Speed. To evaluate if QoL correlated with exercise capacity, patients performed a symptom-limited bicycle test. RESULTS: 158 of 179 eligible patients (88%) consented to participate. Median age was 13.9 years (IQR: 10.2-19.3). PedsQL scores increased with age but were significantly lower among patients than among controls. SF-36 physical scores were significantly lower in patients compared to controls while psychosocial scores were similar. Cognitive speed was significantly reduced in patients at all ages compared to controls. No significant difference in PedsQL-/SF-36 scores or cognitive speed was found between hypoplastic left heart syndrome (HLHS) and non-HLHS Fontan patient. PedsQL-/SF-36 scores in patients ≥10 years correlated significantly to cognitive speed but not to peak exercise capacity. CONCLUSION: QoL is reduced in Fontan children compared to their healthy counterparts whereas in patients ≥16 years only physical, but not psychosocial QoL is reduced. Cognitive speed was significantly lower in patients at all ages compared to controls.

Major stroke in a 19-year-old patient with a univentricular heart.

Patients with univentricular heart malformations are at increased risk of suffering from thromboembolic events. We present a case of a 19-year-old woman born with a univentricular heart who suffered a major stroke while being treated with only salicylic acid. At least 20% of patients with univentricular hearts have been reported to experience thromboembolic events, of which 25% are fatal. Despite the high incidence of thromboembolic events, no consensus has been reached regarding the role of long-term anti-thrombotic treatment in this group of patients. This lack of consensus warrants future studies that compare the different therapeutic strategies.

Somatic growth in 94 single ventricle children -- comparing systemic right and left ventricle patients.

AIM: We sought to compare and assess growth in single ventricle children with a systemic right or left ventricle in five time periods: at birth, before neonatal surgery, before the Glenn anastomosis and finally before and after the Fontan operation to 11 years of age. METHODS: We reviewed medical records on 116 single ventricle patients operated at Rigshospitalet, Denmark from 1987 to 2007. Surgical procedures, feeding route, hemodynamic variables and anthropometric measurements such as weight and height were registered and converted to z-scores. RESULTS: Ninety four single ventricle patients were included for analysis. Gestational age and birth weight was not significantly different between the left and right ventricle group. Before neonatal surgery and before the Glenn anastomosis, both groups showed equal growth retardation. However, a significant difference in catch-up growth was found before the Fontan operation. Thus, patients in the right ventricle group had a smaller median weight-for-age z-score compared with the left ventricle group in the pre-Fontan period (-1.9 and -1.6; p = 0.049) and in the post-Fontan period (-1.1 and -0.7; p = 0.034). CONCLUSION: After the Glenn anastomosis single ventricle children with a systemic left ventricle have better weight gain compared with children with a systemic right ventricle.