Growing interest lies in the assessment of the metabolic status of patients with a univentricular circulation after Fontan operation, especially in changes of amino acid metabolism. Using targeted metabolomic examinations, we investigated amino acid metabolism in a homogeneous adult Fontanpatient group with a dominant left ventricle, seeking biomarker patterns that might permit better understanding of fontan pathophysiology and early detection of subtle ventricular or circulatory dysfunction. We compared serum amino acid levels (42 analytes; AbsoluteIDQ p180 kit, Biocrates Life Sciences, Innsbruck, Austria) in 20 adult Fontan patients with a dominant left ventricle and those in age-and sex-matched biventricular controls. Serum concentrations of asymmetric dimethylarginine, methionine sulfoxide, glutamic acid, and trans-4-hydroxyproline and the methionine sulfoxide/ methionine ratio (Met-SO/Met) were significantly higher and serum concentrations of asparagine, histidine, taurine, and threonine were significantly lower in patients than in controls. Met-SO/ Met values exhibited a significant negative correlation with oxygen uptake during exercise. The alterations in amino acid metabolome that we found in fontan patients suggest links between fontan pathophysiology, altered cell energy metabolism, oxidative stress, and endothelial dysfunction like those found in biventricular patients with congestive heart failure. Studies of extended amino acid metabolism may allow better understanding of fontan pathophysiology that will permit early detection of subtle ventricular or circulatory dysfunction in Fontan patients. Ventricular dysfunction and circulatory failure with progressing end-organ impairment like renal or liver dysfunction are an important cause of morbidity and mortality in adults with complex congenital heart disease (CHD), especially in patients with single-ventricle types of CHD and Fontan circulation 1,2. Besides limited cardiac output, alterations that mark Fontan hemodynamics are passive flow to the lungs, chronically elevated venous pressures, and congestion. Unfortunately, the clinical use of traditional markers such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels for non-invasive diagnostics and monitoring in such patients is limited 3,4. Thus, for early detection of cardiac and circulatory derangement and for evaluation and tailoring of treatment options, regular functional assessment of these patients is crucial, with complete clinical examination, electrocardiogram, imaging studies, determination of values for traditional laboratory markers, or exercise capacity testing.

Background: Patients with a Fontan circulation have altered cholesterol and lipoprotein values. We analysed small organic molecules in extended phopsholipid and acylcarnitine metabolic pathways (‘metabolomes’) in adult Fontan patients with a dominant left ventricle, seeking differences between profiles in baseline and Fontan circulations. Methods: In an observational matched cross-sectional study, we compared phosphatidylcholine (PC), sphingomyelin (SM), and acylcarnitine metabolomes (105 analytes; AbsoluteIDQ® p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) in 20 adult Fontan patients having a dominant left ventricle with those in 20 age- and sex-matched healthy controls. Results: Serum levels of total PC ( q-value 0.01), total SM ( q-value 0.0002) were significantly lower, and total acylcarnitines ( q-value 0.02) were significantly higher in patients than in controls. After normalisation of data, serum levels of 12 PC and 1 SM Fontan patients were significantly lower ( q-values <0.05), and concentrations of 3 acylcarnitines were significantly higher than those in controls ( q-values <0.05). Conclusion: Metabolomic profiling can use small specimens to identify biomarker patterns that track derangement in multiple metabolic pathways. The striking alterations in the phospholipid and acylcarnitine metabolome that we found in Fontan patients may reflect altered cell signalling and metabolism as found in heart failure in biventricular patients, chronic low-level inflammation, and alteration of functional or structural properties of lymphatic or blood vessels. Trial registration number: ClinicalTrials.gov Identifier NCT03886935

Cardiovascular disease is the leading cause of death worldwide. Evidence points towards an unfavorable cardiovascular risk profile of former preterm infants in adolescence and adulthood. The aim of this study was to determine whether cardiovascular risk predictors are detectable in former very preterm infants at a preschool age. Five- to seven-year-old children born at <32 weeks’ gestational age were included in the study. Same-aged children born at term served as controls. Basic data of study participants were collected by means of follow-up databases and standardized questionnaires. At study visit, anthropometric data, blood pressure readings and aortic intima-media thickness were assessed. Blood samples were obtained after an overnight fast. In comparison to children born at term, former preterm infants had higher systolic and diastolic blood pressure readings (odds ratio [95% confidence interval] per 1-SD higher blood pressure level 3.2 [2.0–5.0], p<0.001 and 1.6 [1.1–1.2], p = 0.008), fasting glucose levels (OR [95% CI] 5.2 [2.7–10.1], p<0.001), homeostasis model assessment index (OR [95% CI] 1.6 [1.0–2.6], p = 0.036), and cholesterol levels (OR [95% CI] 2.1 [1.3–3.4], p = 0.002). Systolic prehypertension (23.7% vs. 2.2%; OR [95% CI] 13.8 [3.1–60.9], p = 0.001), elevated glucose levels (28.6% vs. 5.9%; OR [95% CI] 6.4 [1.4–28.8], p = 0.016), and hypercholesterolemia (77.4% vs. 52.9%; OR [95% CI] 3.0 [1.3–7.1], p = 0.010) were significantly more prevalent in the preterm group. As former very preterm infants display an unfavorable cardiovascular risk profile already at a preschool age, implementation of routine cardiovascular follow-up programs might be warranted.

Objective-Preterm birth predisposes children to the development of cardiovascular diseases in adulthood. The aim of this study was to characterize elastic properties of the aorta at preschool age and test the hypothesis that prematurity is associated with decreased aortic distensibility and increased stiffness, both of which are predictors of increased cardiovascular risk. Approach and Results-In an observational study of 76 five-to seven-year-old children born at a gestational age <32 weeks and 79 term-born controls, elastic parameters of the ascending and descending abdominal aorta were determined noninvasively by means of M mode echocardiographic tracings and calculated using computerized wall contour analysis. Compared with children born at term, the preterm group showed significantly reduced distensibility and increased stiffness of the descending abdominal aorta. These results remained significant under multivariable adjustment for birth weight z score, maternal smoking in pregnancy, maternal education, family history of cardiovascular disease, breastfeeding, childhood nutrition, and current body mass index z score (multivariable odds ratios and 95% confidence intervals 5.1, 1.7-15.9; P=0.005 and 2.8, 1.0-7.9; P=0.046, respectively). Further adjustment for intravenous lipid therapy attenuated the strength of association. Elastic properties of the ascending aorta did not differ between the 2 study groups. Conclusions-Children

Preterm birth is frequently associated with altered thyroid hormone levels in the newborn period. Recent data suggest a role of prematurity independent of birth size also in childhood thyroid dysfunction. Whether the high-risk population of former very preterm infants (VPI) is particularly susceptible to thyroid hormone alterations is currently unknown. The aim of the present study was to assess whether former VPI display changes in thyroid hormone status in comparison to term-born controls at a preschool age. Free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) concentrations were determined in former VPI and same-aged children born at term at five to seven years of age. 31 former term infants and 82 former VPI were included in the study. In comparison to children born at term, former VPI had lower fT4 (16.1 ± 1.8 versus 17.0 ± 2.1 pmol/l), higher fT3 (6.8 ± 0.7 versus 6.5 pmol/l), and higher TSH levels (3.0 ± 1.4 versus 2.3 ± 1.0 μU/l), independent of major neonatal morbidities. As subclinical changes in thyroid hormone status are potentially associated with adverse health profiles, close follow-up of these children is warranted.

Former VPI show altered plasma amino acid profiles indicative of a dualistic cardiovascular risk profile (e.g., potentially beneficial elevations in citrulline, arginine, glutamine, and tryptophan, but also raised alanine/lysine ratios, low ornithine and taurine levels) at a preschool age. Whether this is associated with an adverse cardiovascular outcome has to be addressed by future studies. Long-term cardiometabolic follow-up of VPI might be warranted.

Methods ECG electrodes and a PO sensor were attached as soon as possible after birth in healthy pre (term) infants. PO data with Signal Identification and Quality <0.30 were excluded. HR ECG and HR PO were compared every 30 s from 1-10 min.Results 755 data pairs of 53 patients were analysed. Median (range) gestational age was 36 (27-41) weeks. Data from ECG and PO were acquired from 82 (26) and 99 (33)s after birth. Median HR PO was <100 bpm the first 2 min after which it rapidly increased. HR ECG remained stable at 150-160 bpm (table). Conclusion HR measured by PO is significantly lower compared to ECG, which has important implications for clinical care in the first minutes after birth. Background and aims Cardiovascular disease is the leading cause of death worldwide. A growing body of evidence suggests that preterm infants develop an unfavourable cardiovascular risk profile in adult life. The aim of this study was to investigate whether early laboratory and ultrasonographic markers of an increased cardiovascular risk are present in former preterm infants at a preschool age. Methods Former preterm infants born in Tyrol between 2006 and 2008 with a gestational age <32 weeks were followed up at a corrected age of five to seven years. Healthy preschoolers born at term served as controls. Glucose and cholesterol levels were determined after a minimum overnight fasting period of twelve hours. Aortic intima-media thickness (aIMT) was assessed by means of high resolution ultrasound and a software quantification tool. Results 137 children (preterm: 64, term: 73) were examined. Blood samples were obtained from 80 participants (preterm: 57, term: 23). In comparison to children born at term, former preterm infants had significantly higher HDL cholesterol, but also fasting glucose levels. Total and LDL cholesterol levels tended to be higher in the preterm group, but these findings did not reach statistical significance. aIMT measurements did not differ between groups. All parameters were independent of current BMI percentile and gender. Conclusions In comparison to children born at term, former preterm infants have higher fasting glucose levels and show dualistic cholesterol alterations at a preschool age. The relevance of these findings with regard to future cardiovascular health will be addressed by additional studies. PS-104

Background Using an age-appropriate new dobutamine formulation, the aims of the study were: to validate superior vena cava flow (SVCF) as a marker of cardiac output (CO), and to study drug-related changes in haemodynamics and oxygen metabolism in response to escalating doses of dobutamine in hypoxic neonatal piglets. Methods 2-days-old-piglets were exposed to hypoxia (10-15% oxygen) for 2 h followed by reoxigenation with 21-30% oxygen for 6 h. After 60-min of reoxigenation, 18 piglets were randomised to: Control group, hypoxic animals without treatment, and 10-15 mg/kg/min or 15-20 mg/kg/min dose groups, each animal received two doses of dobutamine (Proveca Ltd.) during 30-min with 60-min washout period between doses. All animals were monitored for arterial blood pressure (MABP), heart-rate (HR), CO, stroke-volume-index (SVI), systemic-vascular-resistance-index (SVRI), oxygen-delivery (OD), systemic consumption (VO 2 ) and fractional-tissue-oxygen extraction (FTOE). In three animals an ultrasonic perivascular flow probe was placed around superior vena cava to continuously measure SVCF. Statistics: Mean ± SD, ANOVA, p < 0.05. Result A good positive correlation was observed between SVCF and CO. Hypoxia resulted in a significant decreased on CO, SVI, SVRI and MABP. All dobutamine doses improved significantly HR, CO and SVRI without changes in SVI and MABP. All doses increased OD but only 10-15 mg/kg/min increased VO 2 without changes in FTOE. Conclusion The new dobutamine formulation targeted to support neonatal cardiovascular function reveals a significant improvement of haemodynamic status, but dose-specific differences in metabolic response in hypoxic neonatal piglets. Further studies are needed to evaluate those drug effects in other vital organs. FP7-HEALTH-F5-2011 (nº282533). PS-099TRANSITIONAL CHANGES IN CEREBRAL BLOOD VOLUME AT BIRTH Background and aims Near-infrared spectroscopy (NIRS) is a non-invasive method to measure changes in the concentration of oxygenated (ÁO2Hb) and deoxygenated haemoglobin (ÁHHb). Changes in total haemoglobin (ÁcHb = ÁO2Hb+ÁHHb) give information on changes in cerebral blood volume (CBV). Moreover cerebral tissue oxygenation index (cTOI = ÁO2Hb/Á cHb*100%) is detected.The aim was to evaluate changes of CBV during postnatal transition in term newborns. Methods This observational study was conducted at the Medical University Graz. Included were term infants without need for respiratory support after caesarean section. NIRS measurements were carried out with 'NIRO-200-NX' (Hamamatsu; Japan) over 15 min.