The Enigma of the Fontan circulation

Kinderen die worden geboren met een complexe aangeboren hartafwijking, waarbij slechts één hartkamer goed ontwikkeld is en de andere hartkamer onderontwikkeld of afwezig is, hebben meestal al op jonge leeftijd een operatie nodig. De Fontan procedure is ontwikkeld om patiënten met een dergelijk functioneel univentriculair hart (één-kamer-hart) te behandelen. Deze procedure resulteert is een unieke, niet-fysiologische circulatie, waarin slechts één hartkamer zowel de pulmonale als de circulatoire circulatie ondersteunt. Achteruitgang van de Fontan circulatie, meest waarschijnlijk gerelateerd aan een on-fysiologische karakteristieken van de circulatie, is een opkomend probleem waarmee een groeiende groep patiënten geconfronteerd wordt. In dit proefschrift hebben wij aangetoond dat de uitkomst na de Fontan operatie verbeterd is in de afgelopen decennia. We hebben echter ook geïdentificeerd dat de Fontan circulatie nog steeds meerdere nadelige gevolgen heeft, zoals een beperkt inspanningsvermogen, verminderde hart- en longfunctie, en longvaatremodelering. Verder hebben wij met de hulp van een nieuw toegepaste magnetische resonantie (MRI) techniek gezien dat het ontwikkelen van leverziekte bij Fontan patiënten veel vaker voorkomt dan voorheen werd gedacht. Tenslotte hebben wij gedemonstreerd dat de behandeling van uiteindelijke falen van de Fontan circulatie is geassocieerd met een aanzienlijke mortaliteit, en dat de ene chirurgische ingreep geen voordelen toont boven de andere. Concluderend is de overleving na de Fontan operatie toegenomen in de afgelopen decennia, en zouden de inspanningstolerantie, een biomarker genaamd NT-proBNP en de ontwikkeling van leverziekte potentiële markers kunnen zijn voor een achteruitgang van de Fontan circulatie in de toekomst

COVID-related school absence in prmary school:considerations of parents and the role of preventive child health care

Inleiding: Na de heropening van de scholen per 11 mei 2020 bleef 3–5 % van alle leerlingen thuis vanwege COVID-19. Vraagstelling van dit onderzoek was wat de afwegingen zijn van ouders om hun kind thuis te houden, en welke rol de jeugdgezondheidszorg (JGZ) hierbij speelt. Methode: Kwalitatief onderzoek bestaande uit semigestructureerde interviews met vijf schoolmedewerkers (van drie reguliere basisscholen en twee speciaal (basis)onderwijsscholen) en ouders van vier gezinnen die hun kind(eren) thuis hebben gehouden, in Groningen. De interviews zijn thematisch geanalyseerd. Resultaten: De gepercipieerde risico’s voor de gezondheid van een van de gezinsleden was de meest voorkomende reden om een kind niet naar school te laten gaan. Andere redenen waren zorgen over de gezondheid van het kind zelf en een algemene angst voor het virus, zonder dat er gezinsleden waren die binnen de risicogroepen vielen. De JGZ is nauwelijks bij de afweging van ouders betrokken geweest. Conclusie: Dit onderzoek naar COVID-19-gerelateerd schoolverzuim op basisscholen laat zien dat ouders angstig zijn vanwege de gezondheidsrisico’s voor hun gezin, ook in een regio met een lage besmettingsgraad, zoals Groningen in de eerste COVID-19-golf. De rol die de JGZ voor scholen en ouders kan spelen was in deze fase van de epidemie onvoldoende bij hen bekend

N-terminal pro-brain natriuretic peptide serum levels reflect attrition of the Fontan circulation

Objective: N-terminal pro-brain natriuretic peptide has an established role in the diagnosis and prognosis of heart failure. In Fontan patients, this peptide is often increased, but its diagnostic value in this particular non-physiologic, univentricular circulation is unclear. We investigated whether N-terminal pro-brain natriuretic peptide represents ventricular function or other key variables in Fontan patients.Methods and results: Ninety-five consecutive Fontan patients ≥10 years old who attended the outpatient clinic of the Center for Congenital Heart Diseases in 2012-2013 were included. Time since Fontan completion was 16 ± 9 years. Median N-terminal pro-brain natriuretic peptide was 114 (61-264) ng/l and was higher than gender-and age-dependent normal values in 54% of the patients. Peptide Z-scores were higher in patients in NYHA class III/IV compared to those in class I/II, but did not correlate with ventricular function assessed by MRI and echocardiography, nor with peak exercise capacity. Instead, peptide Z-scores significantly correlated with follow-up duration after Fontan completion (p < 0.001), right ventricular morphology (p = 0.004), indexed ventricular mass (p = 0.001), and inferior caval vein diameter (p < 0.001) (adjusted R= 0.615).Conclusions: N-terminal pro-brain natriuretic peptide levels in Fontan patients correlate with functional class, but do not necessarily indicate ventricular dysfunction. Increased peptide levels were associated with a longer existence of the Fontan circulation, morphologic ventricular characteristics, and signs of increased systemic venous congestion. Since the latter are known to be key determinants of the performance of the Fontan circulation, these findings suggest increase in N-terminal pro-brain natriuretic peptide levels to indicate attrition of the Fontan circulation, independent of ventricular function

Serial cardiovascular magnetic resonance feature tracking indicates early worsening of cardiac function in Fontan patients

Background: In Fontan patients, attrition of ventricular function is well recognized, but early detection of ventricular dysfunction is difficult. The aim of this study is to longitudinally assess ventricular strain in Fontan patients using a new method for cardiac magnetic resonance (CMR) feature tracking, and to investigate the relationship between ventricular strain and cardiac systolic function. Methods and results: In this prospective, standardized follow-up study in 51 Fontan patients, age ≥ 10 years, CMR and concomitant clinical assessment was done at the start of the study and after 2 years. CMR feature tracking was done combining the dominant and hypoplastic ventricles. Global longitudinal strain (GLS) (−17.3% versus −15.9%, P = 0.041) and global circumferential strain (GCS) (−17.7 versus −16.1, P = 0.047) decreased over 2 years' time. Ejection fraction (EF) (57%), cardiac index (CI) (2.7 l/min/m2) and NYHA functional class (97% in class I/II) were preserved. The strain values of the combined dominant and hypoplastic ventricles were significantly worse compared to those of the dominant ventricle only (GLS −16.8 (−19.5 to −14.0) versus −18.8 (−21.3 to −15.3) respectively, P = 0.001, GCS −18.3 (−22.1 to −14.8) versus −22.5 (−26.3 to −19.4) respectively, P < 0.001). Conclusions: This study showed a decrease in cardiac strain over 2 years in Fontan patients without clinical signs of Fontan failure, where EF, CI and clinical status were still preserved. Cardiac strain might be a sensitive early indicator of systolic ventricular decline. Furthermore, combined strain of the hypoplastic and dominant ventricles seems a more accurate representation of cardiac strain in functionally univentricular hearts

GDF-15 (Growth Differentiation Factor 15) Is Associated With Hospitalization and Mortality in Patients With a Fontan Circulation

Background We investigated serial serum levels of GDF-15 (growth differentiation factor 15) in Fontan patients and their relation to outcome. Methods and Results In this single-center prospective study of consecutive Fontan patients, serial serum GDF-15 measurement and clinical assessment was done at baseline (n=81) and after 2 years (n=51). The association between GDF-15 and the combined end point of all-cause mortality, heart transplant listing, and Fontan-related hospitalization was investigated. Median age at baseline was 21 years (interquartile range: 15-28 years). Median GDF-15 serum levels at baseline were 552 pg/mL (interquartile range: 453-729 pg/mL). GDF-15 serum levels correlated positively with age, age at Fontan initiation, New York Heart Association class, and serum levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and ɣGT (γ-glutamyltransferase) and negatively with exercise capacity. During a median follow-up of 4.8 years (interquartile range: 3.3-5.5 years), the combined end point occurred in 30 patients (37%). Multivariate Cox regression showed that patients with the highest baseline GDF-15 (n=20, defined as the upper quartile) had a higher risk of hospitalization or death than the lowest 3 quartiles (hazard ratio [HR], 2.76; 95% CI, 1.27-6.00; P=0.011). After 2 years of follow-up, patients in whom serum level of GDF-15 increased to >70 pg/mL (n=13) had a higher risk of hospitalization or death than the lowest 3 quartiles (HR, 2.69; 95% CI, 1.03-6.99; P=0.043). Conclusions In Fontan patients, elevated serum levels of GDF-15 are associated with worse functional status and predict Fontan-related events. Furthermore, serial measurements showed that an increase in GDF-15 serum level was associated with increased risk for adverse outcome

Diminished liver microperfusion in Fontan patients:A biexponential DWI study

It has been demonstrated that hepatic apparent diffusion coefficients (ADC) are decreasing in patients with a Fontan circulation. It remains however unclear whether this is a true decrease of molecular diffusion, or rather reflects decreased microperfusion due to decreased portal blood flow. The purpose of this study was therefore to differentiate diffusion and microperfusion using intravoxel incoherent motion (IVIM) modeled diffusion-weighted imaging (DWI) for different liver segments in patients with a Fontan circulation, compare to a control group, and relate with liver function, chronic hepatic congestion and hepatic disease. For that purpose, livers of 59 consecutively included patients with Fontan circulation (29 men; mean-age, 19.1 years) were examined (Oct 2012-Dec 2013) with 1.5T MRI and DWI (b = 0,50,100,250,500, 750,1500,1750 s/mm(2)). IVIM (D-slow,D-fast,f(fast)) and ADC were calculated for eight liver segments, compared to a control group (19 volunteers; 10 men; mean-age, 32.9 years), and correlated to follow-up duration, clinical variables, and laboratory measurements associated with liver function. The results demonstrated that microperfusion was reduced (p <0.001) in Fontan livers compared to controls with -38.1% for D-fast and -32.6% for f(fast). Molecular diffusion (D-slow) was similar between patients and controls, while ADC was significantly lower (-14.3%) in patients (p <0.001). ADC decreased significantly with follow-up duration after Fontan operation (r = -0.657). D-slow showed significant inverse correlations (r = -0.591) with follow-up duration whereas D-fast and f(fast) did not. From these results it was concluded that the decreasing ADC values in Fontan livers compared with controls reflect decreases in hepatic microperfusion rather than any change in molecular diffusion. However, with the time elapsed since the Fontan operation molecular diffusion and ADC decreased while microperfusion remained stable. This indicates that after Fontan operation initial blood flow effects on the liver are followed by intracellular changes preceding the formation of fibrosis and cirrhosis

CBD-olie bij kinderen

Useof cannabidiol oil in children The use of cannabidioloil (CBD oil), a cannabis-derived chemical, is increasing. CBD oil is freely available in the Netherlands, but its composition and quality are not monitored. However, the alternative, pharmacist-prepared oil, is more expensive and difficult to acquire. Common reasons for CBD oil use in children include impulsive behaviour, itch, epilepsy, stress, pain and sleeping problems. However, evidence of its effectiveness is scarce and focuses primarily on the effectiveness of the oil in reducing epileptic seizures. Known side-effects are vomiting, diarrhoea, fever, sleepiness, and abnormal liver function test results. We advise medical professionals who encounter young patients who may potentially be using CBD oil, to discuss its questionable quality and potential side effects and interactions. If a patient presents with poorly-understood fever, diarrhoea, vomiting or drowsiness, then the side effects of CBD oil should be considered. Finally, CBD should be differentiated from delta-THC, a cannabis-derived chemical with a psychoactive effect, the use of which should be discouraged in children