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A boy aged 1 year, recently diagnosed with dilated cardiomyopathy, has to be treated with enalapril according to the heart failure protocol. The physician wants to know which adverse events she can expect. What are the potential adverse events related to administration of an ACE inhibitor to children with heart failure? What is the prevalence and what are the possible risk factors? Secondary sources—nil Electronic databases (PubMed/Medline and Embase) and reference lists of relevant articles were searched with the following strategy: ‘angiotensin-converting enzyme inhibitors’ and ‘heart failure’ and ‘children’. The search yielded 415 individual articles, of which 14 were identified as relevant. Heart failure is an important cause of morbidity and mortality in children.1 It is commonly treated with ACE inhibitors (ACE-i) despite the lack of evidence on its efficacy.2 This treatment is based on the assumption that blocking of the renin-angiotensin-aldosterone system has a positive effect on morbidity and mortality, as it does in adults with heart failure.3–6 In adults, the most prevalent adverse events (AEs) related to the use of ACER-i are renal failure,7 8 hypotension,9 10 hyperkalemia,9 11 cough12 and angioedema.13 It is assumed that the safety profile of ACE-i differs for children and differs from that for adults, and for children of different ages, as growth and development contribute to variation in the disposition and effect of most drugs administered …

BackgroundACE-inhibitors are first choice treatment for adult and paediatric patients with heart failure. Since there are no systematic data on pharmacokinetics and safety in the young heart failure population, the EU funded a drug development program1 to fill those gaps for the ACE-inhibitor enalapril. An age appropriate paediatric formulation was also required.MethodsA paediatric patient cohort with heart failure was recruited to fulfil the paediatric investigation plan (PIP) requirements. The PIP required a total of 85 evaluable patients from birth to less than 12 years of age with a subset cohort of 25 patients with heart failure due to dilated cardiomyopathy and a subset of 60 heart failure patients of congenital heart disease. Out of these, 54% of patients must be aged below 12 months to provide a substantial amount of young patients.ResultsThe LENA consortium recruited 102 children from birth to 12 years. Out of those, 89 patients fulfilled relevant protocol criteria and could be regarded as evaluable. Of these, 26 demonstrated heart failure due to cardiomyopathy and 63 due to congenital heart disease. Sixty five patients (73%) were below 12 months of age. Moreover, 22 patients were below 3 months of age, 26 patients from 3 months to less than 6 months and 17 patients from 6 months up to 12 months of age.ConclusionsThe LENA consortium had recruited the PDCO required number of paediatric patients for the drug development program LENA. As more than 2/3 of patients belong to the most vulnerable patient population below the age of 12 months, relevant data can be generated to fill gaps for the safe and reliable treatment with ACE-inhibitors of children with heart failure.ReferencesThe research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement n°602295 (LENA)Disclosure(s)Nothing to disclose

IntroductionACE inhibitors (ACEi) have a prominent place in the treatment of heart failure in children. However, there is a significant interpatient variability in efficacy and safety in those children that is not completely understood. Metabolomics provides an interesting innovative approach to better understand underlying mechanisms for variation in disease and response to therapy. With this review, we aim to provide an overview of metabolomics in the field of heart failure therapy with or without ACEi in both adults and children and try to identify gaps in this field.MethodsThe PubMed database was systematically searched using several search strategies. Articles were labelled as relevant when they included information on either metabolomics of adult patients with heart failure and/or ACEi-therapy or in children. This yielded 42 relevant articlesResults24 articles were found describing metabolomics in adults with heart failure, either with or without ACEi-therapy. In addition, several metabolites were identified in adults correlating with either ACEi-efficacy or safety. No metabolomics articles were found in children with heart failure or in children on ACEi-therapy. Several papers (18) were found on metabolomics in children for other diseases and/or treatments.ConclusionMetabolomics in adult heart failure patients has helped to unravel part of observed disease and therapy variability, and appears helpful in identifying patients at risk for therapy failure as well as detecting novel targets for heart failure therapy. In children, a significant information gap exists. This provides exciting opportunities for personalized treatment of heart failure.Disclosure(s)This work was partially supported by LENA, a Collaborative Project funded by the European Union under the 7th Framework Programme under grant agreement n° 602295.

BackgroundLittle evidence is presently available to help clinicians guide decisions when tackling the pharmacological management of paediatric heart failure (HF). As a consequence, therapeutic strategies are largely supported by adults' data extrapolation and own expertise. The variability in drug treatment routines across Europe is expected to be high. Nevertheless, there are no epidemiological data that describe the current situation.AimTo develop a survey in the context of the LENA project to characterise the different therapeutic strategies for the management of paediatric HF that are currently practiced across Europe with special focus in the use of Angiotensin Converting Enzyme Inhibitors (ACE-I).MethodsItems to be included in the survey were selected through a thorough literature review and expert group discussions. European hospitals providing paediatric cardiology care were identified using websites of European and national paediatric cardiology associations as well as the ones of congresses and conferences related to the field. Standard recommendations for survey design were followed. The study protocol was approved by a data protection officer and an ethics committee. Web-survey tool EvaSys® was used. The survey was pre- and pilot-tested by a group of experts. A statistical analysis plan for the later processing and analysis of the data to be obtained was elaborated.ResultsA Europe-wide web-based survey was started in January 2015. 203 clinicians were invited via e-mail to participate. The questionnaire consisted of 23 questions addressing different aspects of drug therapy for HF in children. Use patterns of ACE-I (dosage by age group, effectiveness and toxicity assessment, use according to HF aetiology) and drug therapy for dilated cardiomyopathy where explored. Participants' demographic characteristics were also asked.ConclusionsThe procedure followed for the survey development should assure the quality of the tool. The results of this survey will provide an overview of the clinical treatment routine of paediatric heart failure across Europe.The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement n°602295 (LENA).The following authors will also be included in the later poster: Ingrid Klingmann (PHARMAPLEX BVBA, Germany), András Szatmári (GOTTSEGEN GYORGY ORSZAGOS KARDIOLOGIAI INTEZET, Hungary), László Ablonczy (GOTTSEGEN GYORGY ORSZAGOS KARDIOLOGIAI INTEZET, Hungary), Holger Schwender (HEINRICH-HEINE-UNIVERSITÄT DÜSSELDORF, GERMANY)

BackgroundACE inhibitors (ACE-I) are a cornerstone in the treatment of children with heart failure. Little is known on the pharmacokinetics (PK) and pharmacodynamics (PD) of enalapril in children. LENA trials will investigate a novel child-appropriate solid drug formulation of enalapril and obtain PK, PD and safety data. For this study clear safety cut-offs need to determined.AimTo review the literature on safety of ACE-I in paediatric heart failure.MethodsWe searched electronic databases and reference lists of relevant studies. Inclusion criteria were 1. Randomized Controlled Trials (RCT), Controlled trials (CT), case reports or retrospective cohorts. 2. Patients under 18 years with congestive heart failure. 3. Any kind of ACE-I 4. Outcome measures: Mortality, hypotension, renal failure, hyperkalaemia, liver enzyme rise, cough, neutropenia.ResultsWe assessed 12 of 593 articles as relevant: 2 RCTs, 5 CTs, 3 retrospective cohort studies and 2 case reports on a total of 734 children with heart failure. Systematic analyses was hampered by the heterogeneity of the study designs. In summary, we identified renal failure, hypotension and hyperkalemia as the most important side effects. Renal failure was found in 80 patients (11%), hypotension in 33 (4,5%) and hyperkalemia in 5 (0,7%). Five studies (n= 315 children) suggest that young age and low weight increases the risk of renal failure.ConclusionsRenal failure, hypotension and hyperkalemia are the most reported adverse events in children on an ACE-I for heart failure. We defined strict adjusting- and stopping rules for enalapril based on an Acute Kidney Injury scale, b. on values of systolic blood pressure and on c. serum levels potassium.The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement n°602295 (LENA).

Background and aims For children and young adults with end-stage heart failure or other severe heart diseases paediatric heart transplantation (HTx) means a good therapeutic option. Parents have to decide for or with their children whether they want them to be transplanted. Congenital heart disease per se has a major influence on the child’s and the family’s life. Relatively little is known about the psychosocial impact of HTx. Therefore we aimed to better understand how parents perceive the health related quality of life (HRQoL) of their child. Methods Between 2000 and January 2014 28 children have received a successful heart transplantation at our institution. All parents (n = 56) were asked to complete the Child Health Questionnaire-Parent Form 50 (CHQ-PF50). Results 42 parents (n = 22 female, n = 20 male) of 22 patients (median age mothers: 46 years, median age fathers: 51 years) answered the CHQ-PF50 questionnaire. Two parents were divorced. All children lived with at least one parent. On most of the CHQ-PF50 subscales parents gave significantly lower ratings on their child’s HRQoL compared to parents of healthy children. Only on the subscales general behaviour and family cohesion scores were comparable to normative data. On most scales mothers gave significantly lower, thus more unfavourable ratings, than the fathers. Conclusion Paediatric HTx has a major impact on the HRQoL of the affected families. In order to improve HRQoL further follow-up and more psychological support not only for the patient but also for the whole family’s needs to be offered as routine care.

Background and aims In children with end-stage heart disease heart transplantation (HTx) offers a good therapeutic option with favourable outcomes. Patients are expected to improve in general health, but unfortunately little is known about the health-related quality of life (HRQoL) after HTx, which is also influenced by factors such as the psychosocial adaptation of children and parents. We aimed to better understand children’s HRQoL after HTx with the aim to give them adequate support. Methods Between 2000 and January 2014 28 children underwent successful heart transplantation at our institution. All patients older than 8 years (n = 21) were asked to complete a validated and reliable questionnaire, the Child Health Questionnaire-Child Form 87 (CHQ-CF87) questionnaire themselves. Results 76% of the patients participated; median age was 15.2 years (range: 13.6–19.6), median time after HTx was 31 months (range 7–134). All children attended school. Even though they scored comparable to normative data on most of the subscales, their general health perception (GHP) (50.0 vs. 74.6, p Conclusion In children after HTx, overall HRQoL, especially on the psychosocial scales, seems to be good. Only the subscales general health perception and physical functioning were significant lower. This might be explained by their chronic need for treatment, follow-up and concomitant diseases frequently seen in HTx patients. Nevertheless, in order to learn dealing with their situation all children should be supported by a specialised multidisciplinary team, including psychologists and child life specialists.