Paediatric heart failure - understanding the pathophysiology and the current role of cardiac biomarkers in clinical practice.

INTRODUCTION: Paediatric heart failure is a common clinical syndrome that may be experienced by children with congenital heart disease (CHD) and/or cardiomyopathy. It is characterised by clinical signs/symptoms which reflect the underlying pathophysiology based on one of three main clinical states: Pulmonary over-circulation, pressure overload, and ventricular failure. Current diagnosis relies on clinical assessment and echocardiogram imaging as cardiac biomarkers has been predominantly scientific to date. This review provides a comprehensive overview of paediatric heart failure pathophysiology and considers the available evidence for cardiac biomarkers in this setting. METHODS: A literature review was completed using MEDLINE ALL, EMBASE, and PubMed on 10th November, 2022. Search terms included biomarkers, heart failure, heart defects, congenital heart disease, fontan circulation, single ventricle circulation, cardiomyopathy, and child. This allowed the identification of individual cardiac biomarkers which are the focus of this review. These included NT-proBNP, MR-proANP, MR-proADM, troponin, sST2, galectin 3, and growth differentiation factor-15. RESULTS: Paediatric studies have established reference ranges for NT-proBNP and troponin for children with structurally normal hearts. Of all the biomarkers reviewed, NT-proBNP appears to correlate most closely with symptoms of heart failure and ventricular dysfunction on echocardiogram. However, there remains limited longitudinal data for NT-proBNP, and no validated reference ranges for patients with CHD and/or cardiomyopathy. None of the other biomarkers reviewed were consistently superior to NT-proBNP. CONCLUSION: Further large paediatric studies of patients with heart failure are needed to validate NT-proBNP in CHD and to evaluate the role of novel biomarkers in specific types of CHD, e.g. single ventricle physiology.

How to interpret cardiac biomarkers in children?

Cardiac biomarkers are used as first-line diagnostic tools in suspected myocardial injury and heart failure in adult patients. Their use in paediatric patients has been limited by variability caused by age, gender and the presence of an underlying congenital cardiac condition. There are established reference ranges for both NT-proBNP and troponin in healthy children, but these cannot be applied to all paediatric patients because of limited large studies focusing on children with congenital heart disease and/or cardiomyopathy.This article will focus on the pathophysiology of myocardial injury and heart failure in children and the subsequent cardiac biomarker correlation. It will explain how to interpret the biomarker assay levels obtained for both troponin and NT-proBNP and highlights the importance of a clear clinical question prior to requesting a cardiac biomarker assay level.Clinical cases outline scenarios that may prompt consideration of biomarker analysis in children and aims to equip the reader with an understanding of how to interpret the results.

The CHIP-Family study to improve the psychosocial wellbeing of young children with congenital heart disease and their families: design of a randomized controlled trial.

BACKGROUND: Children with congenital heart disease (CHD) are at increased risk for behavioral, emotional, and cognitive problems. They often have reduced exercise capacity and participate less in sports, which is associated with a lower quality of life. Starting school may present more challenges for children with CHD and their families than for families with healthy children. Moreover, parents of children with CHD are at risk for psychosocial problems. Therefore, a family-centered psychosocial intervention for children with CHD when starting school is needed. Until now, the 'Congenital Heart Disease Intervention Program (CHIP) - School' is the only evidence-based intervention in this field. However, CHIP-School targeted parents only and resulted in non-significant, though positive, effects as to child psychosocial wellbeing. Hence, we expanded CHIP by adding a specific child module and including siblings, creating the CHIP-Family intervention. The CHIP-Family study aims to (1) test the effects of CHIP-Family on parental mental health and psychosocial wellbeing of CHD-children and to (2) identify baseline psychosocial and medical predictors for the effectiveness of CHIP-Family. METHODS: We will conduct a single-blinded randomized controlled trial comparing the effects of CHIP-Family with care as usual (no psychosocial intervention). Children with CHD (4-7 years old) who are starting or attending kindergarten or primary school (first or second year) at the time of first assessment and their families are eligible. CHIP-Family consists of a separate one-day workshop for parents and children. The child workshop consists of psychological exercises based on the evidence-based cognitive behavioral therapy Fun FRIENDS protocol and sports exercises. The parent workshop focuses on problem prevention therapy, psychoeducation, general parenting skills, skills specific to parenting a child with CHD, and medical issues. Approximately 4 weeks after the workshop, parents receive an individual follow-up session. The baseline (T1) and follow-up assessment (T2 = 6 months after T1) consist of online questionnaires filled out by the child, parents, and teacher (T2 only). Primary outcome measures are the CBCL for children and the SCL-90-R for parents. DISCUSSION: This trial aims to test the effects of an early family-centered psychosocial intervention to meet the compelling need of young children with CHD and their families to prevent (further) problems. If CHIP-Family proves to be effective, it should be structurally implemented in standard care. TRIAL REGISTRATION: Dutch Trial Registry; NTR6063 on 23 August, 2016.

Survey of paediatricians' opinions on a regional paediatric telecardiology service.

AIM: The aim of this study is to evaluate consultant general paediatricians' opinions of a UK paediatric telecardiology service. METHODS: A structured questionnaire was developed and sent to all consultant paediatricians working in a district general hospital in Northern Ireland. RESULTS: Paediatricians (n = 35) regarded the regional paediatric telecardiology service as very useful and of good value for money. Paediatricans in hospitals without access to telecardiology expressed a desire to join the network (86%, 12/14). More frequent use of the paediatric telecardiology service was associated with increased confidence in performing echocardiography and using the telemedicine equipment and a special interest in neonatology. The vast majority of paediatricians (32/35, 91%) believed that there should be a shared clinical responsibility for the patient following a teleconsultation. A total of 33/35 (94%) stated that the telephone costs of the consultation should be paid by the paediatrician but that the professional time of the cardiologist should be paid by the tertiary centre (29/35, 83%). CONCLUSIONS: Paediatricians have consistently positive experiences of a regional paediatric telecardiology service. They believe that clinical responsibility is shared, and there should not be any professional fee for telemedicine activities.

A sibling-controlled, prospective study of outcomes at home and school in children with severe congenital heart disease.

OBJECTIVES: The objectives of this study were to compare behaviour problems and competencies, at home and school, in 7-year-old children with congenital heart disease with a sibling control group, to examine the prospective determinants of outcome from infancy, and to explore whether any gains were maintained in our sub-group of children who had participated in a previous trial of psychological interventions in infancy. METHODS: A total of 40 children who had undergone surgery to correct or palliate a significant congenital heart defect in infancy were compared (Child Behavior Checklist) with a nearest-age sibling control group (18 participants). Comparisons were made between sub-groups of children and families who had and had not participated in an early intervention trial. RESULTS: Problems with attention, thought and social problems, and limitations in activity and school competencies, were found in comparison with siblings. Teacher reports were consistent with parents, although problems were of a lower magnitude. Disease, surgical, and neurodevelopmental functioning in infancy were related to competence outcomes but not behaviour problems. The latter were mediated by family and maternal mental health profiles from infancy. Limited, but encouraging, gains were maintained in the sub-group that had participated in the early intervention programme. CONCLUSIONS: The present study is strengthened by its longitudinal design, use of teacher informants, and sibling control group. The patterns of problems and limitations discerned, and differential determinants thereof, have clear implications for interventions. We consider these in the light of our previously reported intervention trial with this sample and current outcomes at the 7-year follow-up.

A fetal telecardiology service: patient preference and socio-economic factors.

OBJECTIVE: The aims of this study were to evaluate patients' opinions on a fetal cardiology telemedicine service compared with usual outpatient care, the effect of the telemedicine consultation on maternal anxiety and its impact on travel times and time absent from work. METHODS: Prospective study over 20 months. Eligible patients attended for routine anomaly scan followed by fetal echocardiogram transmitted to the regional centre with live guidance by a fetal cardiologist, followed by parental counselling. All patients were offered a fetal cardiology appointment at the regional centre. Structured questionnaires assessing maternal satisfaction, travel times/days off and anxiety scores completed at time of both fetal echocardiograms. RESULTS: Sixty-seven patients were recruited and 66 completed the study. Participants expressed very high satisfaction rates with fetal telecardiology, equivalent to face-to-face consultation. The telecardiology appointments were associated with significantly reduced travel times and days off work (p < 0.01). Expectant mothers expressed a clear inclination for a fetal cardiology appointment at the local hospital facilitated by telemedicine (p < 0.01). CONCLUSIONS: Fetal telecardiology is highly acceptable to patients and is even preferred compared with travelling to a regional centre. There are additional socio-economic benefits that should encourage the development of remote fetal cardiology services.

Editorial Board Composition Among Pediatric Cardiology Journals: Time to Cast the Net Wider.

Background: No data currently exist on the diversity of editorial board members (EBMs) of pediatric cardiology journals. Objectives: The objective was to investigate the editorial boards of 5 pediatric cardiology journals to assess the composition of these boards in terms of the geographical, gender, and economic representation of their members. Methods: Information on EBMs was collected directly from 5 journal websites accessed in February 2022. The following data were collected: country of practice (including World Bank geographical and income classification), institution of practice, role on editorial board, and whether an individual held a role on 1 or more of the boards included. Results: A total of 455 EBMs were identified. A total of 369 (81%) were male. All editors-in-chief were male, and 4 were from the United States. EBMs practicing in North America accounted for 278 individuals (61%) of the editorial boards reviewed. The next majority of EBMs are practicing within Europe and Central Asia (23%, n = 103), East Asia and Pacific (7%, n = 31), Middle East and North Africa (4%, n = 18), and Latin America and Caribbean (4%, n = 16). Less than 2% (n = 9) practice in Sub-Saharan Africa and South Asia. Over 90% (n = 415) practice in high-income countries. There was no representation from low-income countries. Conclusions: Women and pediatric cardiologists practicing in countries outside of Europe and North America were underrepresented on the editorial boards of the journals studied. Diversifying composition of editorial boards may provide greater representation of underserved areas and encourage broader avenues of investigation and research.

Exercise prescription improves exercise tolerance in young children with CHD: a randomised clinical trial.

OBJECTIVE: The main objective of this study was to ascertain if a structured intervention programme can improve the biophysical health of young children with congenital heart disease (CHD). The primary end point was an increase in measureable physical activity levels following the intervention. METHODS: Patients aged 5-10 years with CHD were identified and invited to participate. Participants completed a baseline biophysical assessment, including a formal exercise stress test and daily activity monitoring using an accelerometer. Following randomisation, the intervention group attended a 1 day education session and received an individual written exercise plan to be continued over the 4-month intervention period. The control group continued with their usual level of care. After 4 months, all participants were reassessed in the same manner as at baseline. RESULTS: One hundred and sixty-three participants (mean age 8.4 years) were recruited, 100 of whom were male (61.3%). At baseline, the majority of the children were active with good exercise tolerance. The cyanotic palliated subgroup participants, however, were found to have lower levels of daily activity and significantly limited peak exercise performance compared with the other subgroups. One hundred and fifty-two participants (93.2%) attended for reassessment. Following the intervention, there was a significant improvement in peak exercise capacity in the intervention group. There was also a trend towards increased daily activity levels. CONCLUSION: Overall physical activity levels are well preserved in the majority of young children with CHD. A structured intervention programme significantly increased peak exercise capacity and improved attitudes towards positive lifestyle changes.

Examination of the physical and psychosocial determinants of health behaviour in 4-5-year-old children with congenital cardiac disease.

OBJECTIVES: To assess the general health and activity levels of 4- and 5-year-old children after intervention for congenital cardiac disease. METHODS: Health behaviour outcomes were assessed in 91 children who had surgery or catheter intervention for congenital cardiac disease. The children were classified into four groups according to severity. The main parameters of classification were the presence of residual symptoms, frequency of visits to general practitioner or the Accident and Emergency Department, and ability to participate in physical activity according to a calculated "activity score". RESULTS: Children had very few residual symptoms after "corrective surgery". Those with complex congenital cardiac disease post-Fontan-type repair still had symptoms on average 18.2 days per month. Surprisingly, the complex group had fewer days "sick" from non-cardiac causes and had fewer visits to general practitioner or Accident and Emergency Departments. Regression analysis indicates that three variables had significant relevance to the general practitioner or Accident and Emergency visits: complex congenital cardiac disease, fewer visits; Townsend score - more deprivation - more visits; and maternal worry - higher maternal worry score - more visits. Regression analysis indicates that lower activity score is significantly related to complex cardiac disease and higher maternal worry score. CONCLUSIONS: The majority of this group of 4- and 5-year-old children had few residual symptoms and had good exercise tolerance. Maternal worry is a significant factor in influencing both activity levels and frequency of unscheduled health service demands - general practitioner or Accident and Emergency visits.

32 year follow up of patients following atrial redirection surgery for transposition of the great arteries.

OBJECTIVE: A significant body of patients who have undergone Mustard or Senning procedure require lifelong follow up. In this retrospective review, we examined the cohort of such patients currently attending our center. DESIGN: Patients who had undergone either Mustard or Senning procedure were identified. We retrospectively reviewed medical records, recorded demographic information and data regarding the clinical state, NHYA class, cardiopulmonary exercise testing, NT-proBNP measurement, and recent cardiac MRI findings. RESULTS: Forty-six patients were identified, the mean age was 32.2 years (± 6.1 years), 67.4% were male. Thirty-two patients (69.6%) had undergone a Senning procedure. The median length of the follow-up was 32 years. Thirty-two patients (69.6%) were NHYA class 1. The mean VO2max achieved was 24.2 ± 5.8 mL/min/kg. The mean NT-proBNP was 266.4 pg/mL (± 259.9 pg/mL). The mean right ventricular end-diastolic volume (RVEDV) was 212.4 mL ± 73.1 mL (indexed 114.2 mL/m2  ± 34.4 mL/m2 ). The mean right ventricular ejection fraction (RVEF) was 53.7% ± 7.9%. The mean left ventricular end-diastolic volume (LVEDV) was 161.5 mL ± 73.7 mL (indexed 87.8 mL/m2  ± 41.1 mL/m2 ). The mean left ventricular ejection fraction (LVEF) was 59.8% ± 5.7%. There was a significant correlation between right ventricular (RV) size on MRI and NT-proBNP level. CONCLUSIONS: We present a relatively well cohort of patients with overall favorable long-term outcome. The majority of patients are NHYA class 1 and the systemic right ventricular function appears to be well preserved as assessed by MRI. The exercise tolerance is reduced, with the majority of patients achieving around 60% of the estimated VO2max . Regular specialist follow-up and assessment with advanced imaging at regular intervals remain important for this group.

Diagnosis of congenital heart disease in neonates by videoconferencing: an eight-year experience.

Over an eight-year period, echocardiograms were transmitted by ISDN at 384 kbit/s for a total of 132 patients suspected of having congenital heart disease (CHD). Five transmitted scans were inadequate. Hands-on echocardiograms were performed subsequently on 116 of the remaining 127 cases (91%). Major CHD was diagnosed in 42 of the 116 infants (36%) and minor CHD in 49 (42%). The telemedicine diagnosis was accurate in 97% of the cases (kappa = 0.90). There were four diagnostic errors. Transfer to the regional unit was avoided in 95 patients (72%). The present study shows that high diagnostic accuracy is possible using a telemedicine link to transmit images obtained with the assistance of real-time guidance by a paediatric cardiologist. The results also demonstrate the importance of an expert interpreting the echocardiographic images, since the accuracy of diagnosis was considerably improved (the kappa coefficient increased from 0.14 to 0.90).

Home support for children with complex congenital heart disease using videoconferencing via broadband: initial results.

We originally developed a home support service for babies with complex congenital heart disease, in which videoconferencing was delivered via three ISDN lines. We have now investigated the feasibility of using broadband (Internet protocol) transmission instead of ISDN lines. Five patients were enrolled (age range 14-58 days) and 78 videoconferences were conducted over a six-month period. In 70 videoconferences (90%), a successful connection was established at the first attempt. In the last 56 videoconferences a connection bandwidth of 256 kbit/s was consistently achieved. The clinician's opinions of the videoconferences were good. Parental opinions on the videoconferences were very high. There was also a significant reduction in parental anxiety following the video consultations: the median reduction in the STAI score was 6 points (P < 0.05) (n = 78). Home support for infants or children with complex congenital heart disease can be provided successfully by video consultations utilizing home broadband links.

A randomised trial of a remote home support programme for infants with major congenital heart disease.

OBJECTIVES: To assess the sustainability, clinical utility and acceptability to clinicians and parents of a tele-homecare programme for infants with major congenital heart disease (CHD), and to evaluate the impact on healthcare resource use. DESIGN: Randomised control trial. SETTING: UK tertiary congenital cardiac centre. PARTICIPANTS: 83 infants with major CHD. INTERVENTION: Participants were randomised to one of three groups: video-conferencing support (n=35), telephone support (n=24) and a control group (n=24). Patients in the two intervention groups received regular, standardised remote consultations. Video-conferences (VCs) were facilitated by Integrated Systems Digital Network lines and replaced by home broadband connections later in the study. MAIN OUTCOME MEASURES: Healthcare resource use, utilisation including hospitalisation, clinicians' opinions on utility and quality of interventions, parental opinions on quality of interventions. RESULTS: Clinicians were more confident making medical decisions following VCs compared with telephone consultations (p=0.01). Both VC and telephone support were very well received, but parents expressed significantly higher levels of satisfaction with VC support (p=0.001). Healthcare resource use was 37% lower in the video-conferencing group compared with both telephone support and control groups (p<0.001), as was the risk of hospitalisation (p=0.006). Direct health service costs were significantly lower in the video-conferencing group (p<0.05). CONCLUSIONS: A tele-medicine home support programme for families of infants with major CHD is feasible, sustainable and effective. Home support with video-conferencing is superior to telephone consultations. Parents are highly satisfied with tele-homecare. Tele-homecare significantly reduces health service utilisation and may reduce health service costs.

Fetal diagnosis of congenital heart disease by telemedicine.

OBJECTIVES: This study aimed to evaluate the feasibility, accuracy and user acceptability of performing remote fetal echocardiograms (FEs). SETTING: A regional fetal cardiology unit and a district general hospital (DGH). DESIGN: A prospective study over 20 months. An initial FE was performed by a radiographer in the DGH (D1) followed by a second FE transmitted to the regional centre, in real time, via a telemedicine link with live guidance by a fetal cardiologist (D2). A FE was performed later at the regional centre (D3, reference standard). Structured questionnaires were employed to evaluate the technical quality of each tele-link and the radiographers' confidence at performing FE. RESULTS: 69 remote FEs were performed and showed 58 normal hearts and 11 with congenital heart disease (CHD). D2 was accurate in 97% of cases compared with D3 (κ score=0.89) indicating excellent agreement. All tele-links connected at first attempt with a mean study time = 13.9 min. Overall tele-link quality was rated highly (median=4/5). In 94% of tele-links, at least 11/12 components of the FE were confidently assessed. The mean composite radiographer's questionnaire score increased significantly during the study period (p<0.05). CONCLUSIONS: To date this is the largest study of its kind. CHD can be confidently diagnosed and excluded by remote FE. Radiographers report increased confidence and proficiency following involvement in real-time telemedicine. This application of telemedicine could improve access to fetal cardiology and support radiographers screening for CHD.

Remote diagnosis of congenital heart disease: the impact of telemedicine.

OBJECTIVES: To determine the accuracy of remote diagnosis of congenital heart disease (CHD) by real-time transmission of echocardiographic images via integrated services digital network (ISDN) lines, to assess the impact on patient management and examine cost implications. DESIGN: Prospective comparison of echocardiograms on infants with suspected significant CHD performed as follows: (1) hands-on evaluation and echocardiogram by a paediatrician at a district general hospital (DGH) followed by (2) transmission of the echocardiogram via ISDN 6 with guidance from a paediatric cardiologist and finally (3) hands-on evaluation and echocardiogram by a paediatric cardiologist. The economic analysis compares the cost of patient care associated with the telemedicine service with a hypothetical control group. SETTING: Neonatal units of three DGH and a UK regional paediatric cardiology unit. RESULTS: Echocardiograms were transmitted on 124 infants. In five cases scans were inadequate for diagnosis. Of the remaining 119 tele-echocardiograms, a follow-up echocardiogram was performed on 109/119 (92%). Major CHD was diagnosed in 39/109 infants (36%) and minor CHD in 45 (41%). The tele-echo diagnosis was accurate in 96% of cases (kappa=0.89). Unnecessary transfer to the regional unit was avoided in 93/124 patients (75%). Despite relatively high implementation costs, telemedicine care was substantially cheaper than standard care. Each DGH potentially saved money by utilising the telemedicine service (mean saving: pound728/patient). CONCLUSIONS: CHD is accurately diagnosed by realtime transmission of echocardiograms performed by paediatricians under live guidance and interpretation by a paediatric cardiologist. Remote diagnosis and exclusion of CHD affects patient management and may be cost saving.

A ten year review of atrioventricular septal defects.

OBJECTIVES: To review all cases of atrioventricular septal defects in Northern Ireland from January 1990 to February 1999, examining clinical and morphological features, management, and outcome. METHODS: A retrospective case note analysis of 106 subjects with comparisons between subgroups. RESULTS: An atrioventricular septal defect was part of a more complex abnormality in 50 of the patients (47%). Down's syndrome was present in 57 (54%). Cardiac surgery was performed in 81%. The defects were unrestrictive in 69 patients (65%), 45 of whom had Down's syndrome. Complex associated abnormalities existed in 36 patients, and 10 of these died without cardiac surgery. Operative mortality was 9.5% for those with co-existing Down's syndrome group, and 14.3% for the chromosomally normal patients. The ventricular components of the septal defect were restrictive in 23 patients (22%), with 9 having Down's syndrome. Spontaneous closure occurred in more than half of these patients. Mortality was zero. The septal defect was exclusively at atrial level in 14 patients ("primum" defects--13%), and 3 of these had Down's syndrome. Operative mortality was again zero. Median duration of postoperative follow-up was 3 and a half years. Overall, moderate to severe left atrioventricular valvar regurgitation was observed postoperatively in 23% at follow-up. CONCLUSIONS: Mortality was highest in the atrioventricular septal defects with an unrestrictive ventricular component. Uncomplicated cases had good outcomes. Patients without Down's syndrome tended to have more associated cardiac abnormalities, and to have more postoperative arrhythmias. Approximately half of the defects with restrictive ventricular components closed spontaneously. Moderate postoperative left atrioventricular valvar regurgitation was commonest in patients with the defect exclusively at atrial level.