None listed
Conditions
Brief summary
Each year, over 1000 children with congenital heart disease (CHD) in Australia require heart surgery. The short and long-term outcomes of these children are primarily determined by pre-existing comorbidities and genetic factors, direct impact of the surgical intervention, the response to cardiopulmonary bypass (CPB), and the consequences thereof during their intensive care stay. Neurodevelopmental disabilities remain amongst the most common, and the most damaging, outcomes in children undergoing surgery for CHD. Large longitudinal population-based studies assessing long-term outcome are lacking. One out of four infants undergoing heart surgery develop a harmful response to CPB, which leads to low cardiac output syndrome (LCOS). LCOS results in prolonged (multi-) organ dysfunction related to hypotension, organ hypoperfusion, renal failure, and brain ischemia. LCOS translates into adverse short-term outcomes (LCOS, need for extracorporeal life support (ECLS), and death), and determines adverse long-term outcomes manifesting into school age and beyond. Currently, there are no reliable, sensitive, and rapid predictors for LCOS or adverse early and long-term outcomes. In addition, the concept of LCOS remains poorly understood, and clinical evidence indicated highly variable presentations, suggestive of variability of host response. Preventive strategies to reduce LCOS remain of limited effectiveness. Thanks to rapid sequencing technology, discriminative patterns of the individual response to CPB can now be tested in real-time. Transcriptomics therefore has huge potential to unravel the mechanisms underlying adverse outcomes after CPB surgery, to reveal biological phenotypes, and to identify novel interventional strategies.
Interventions
The clinical cohort will be derived from the existing randomised controlled and blinded study NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC; ACTRN12617000821392), where children with congenital heart disease less than two years of age requiring cardiopulmonary bypass (CPB) were recruited to standard care or delivery of nitric oxide (NO) into the CPB circuit during open heart surgery. In this follow-up study, we are observing thes
The clinical cohort will be derived from the existing randomised controlled and blinded study NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC; ACTRN12617000821392), where children with congenital heart disease less than two years of age requiring cardiopulmonary bypass (CPB) were recruited to standard care or delivery of nitric oxide (NO) into the CPB circuit during open heart surgery. In this follow-up study, we are observing these children up to their fifth birthday. Participants in this study will be required to perform online yearly questionnaire-based longitudinal assessments until age five years, when a full face-to-face gold standard neuropsychological assessment will be performed (school entry/readiness assessment for school entry). The following tools will be administered during the online yearly assessments: * Ages and Stages Questionnaire (ASQ-3) * Behavior Rating Inventory of Executive Function-Preschool version (BRIEF-P) * Strengths and Difficulties Questionnaire * PedsQL Inventory 4 Generic Core Scales * PedsQL Multidimensional Fatigue Scale – General Fatigue Subscale (6 items) * Kessler Psychological Distress Scale (K6) * Parenting Stress Index (PSI-4) Short Form The following tools will be administered during the face-to-face assessment at five years of age: * Wechsler Preschool & Primary Scale of Intelligence Scale (WPPSI-IV), including working memory and processing speed indices * Movement Assessment Battery for Children (MABC2) * Day/Night Stroop Test * Test of Everyday Attention for Children (TEA-Ch2) – Balloon Hunt, Balloons 5 subtests only * Clinical Evaluation of Language Fundamentals – Australian and New Zealand 5th Edition Screening Test (CELF-5 ANZ Screening Test) * Social Responsiveness Scale (Autism) * ADHD Rating Scale * Adaptive Behaviour Assessment System (ABAS) Social Scale, 3rd Edition * Connors Kiddie Continuous Performance Test, 2nd Edition (CONNERS K-CPT 2) * Wide Range Assessment of Memory and Learning, 3rd Edition (WRAML3) – Story Memory subtest only * Working Memory Test Battery for Children (WMTB-C) – Digit Recall subtest only * PedsQL Multidimensional Fatigue Scale – Full scale * Attachment Relationship Inventory-Caregiver Perspective (ARI-CP 2-5) The face-to-face assessment will take place at the hospital, or for participants who live rurally or remotely, the neuropsychologist may visit their home. Participants are not required to provide any samples for the genomic analysis component of this study, as these samples were collected during the NITRIC trial. During this follow-up study, these biobanked samples will be analysed using RNA sequencing. All Australian and New Zealand participants from the NITRIC trial will be invited to participate.
Sponsors
The University of Queensland
Eligibility
Sex/Gender
All
Age
0 to 5 Years
Healthy volunteers
No
Inclusion criteria
* Enrolled in the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC; ACTRN12617000821392) randomised controlled trial * Consent of parents/guardian for long-term follow-up
Exclusion criteria
Children are enrolled in the original NITRIC RCT are eligible for this study, therefore the same exclusion criteria as for the NITRIC RCT will apply: •Signs of persistently elevated pulmonary vascular resistance preoperatively requiring inhaled NO or preoperative intravenous use of drugs involved in the NO pathway such as glyceryl trinitrate, within 48 hours prior to CPB (oral sildenafil treatment alone is not an exclusion); •Patient is on ECLS immediately prior to surgery; •Chronic ventilator dependency; •Concurrent known confirmed bacterial sepsis/septic shock, diagnosed within <48hours prior to surgery and being actively treated with antibiotics at time of surgery (suspected sepsis treated with antibiotics is not an exclusion criteria unless inotropes are required for treatment of septic shock at time of surgery); •Preoperative acute respiratory distress syndrome requiring high frequency oscillatory ventilation <48 hours of surgery; •Patient requires high doses of vasoactive drugs prior to surgery with an inotrope score >=15 met within 24 hours prior to surgery: Inotrope requirement will be calculated by means of the Vasoactive-Inotrope Score (VIS) (2): VIS = dopamine dose (mcg/kg/min) + dobutamine dose (mcg/kg/min) + 100 x adrenaline dose (mcg/kg/min) + 100 x noradrenaline dose (mcg/kg/min) + 10 x milrinone dose (mcg/kg/min) + 10,000 x vasopressin dose (U/kg/min); •Cardiac arrest within one week (seven days) prior to surgery; •Emergency cardiac surgery which may preclude obtaining informed consent (defined as acutely required life-saving procedure in a patient unlikely to survive the next hours without the surgery); and •Pre-existing methaemoglobinemia (MetHb>3%).
Outcome results
None listed