Post-Operative Myocardial Performance and Pulmonary Hypertension in Infants with Down Syndrome: The Role of Inflammation

Introduction: Down syndrome (DS) is the commonest chromosomal abnormality of live born infants globally with an incidence of 1:546 live births in Ireland which is the highest in Europe (Ni She & Filan, 2014). Approximately 50% of children with DS have congenital heart disease (CHD). Pulmonary hypertension (PH) is well described as having an increased incidence in all children with DS both with and without CHD. When it occurs in the presence of CHD it adds an additional layer of complexity to the management of children both in the pre-operative and post-operative periods. DS is also associated with abnormal immune function and immune defects; children with DS exhibit distinct abnormalities in cells of the innate immune system favouring a pro-inflammatory state. The impact of this inflammatory state on myocardial performance, PH and short term outcomes in infants with DS in the peri-operative period is not clearly understood and needs further study.

Objectives: We aim to use novel functional echocardiography assessment in addition to a comprehensive assessment of inflammatory cytokines to better characterise peri-operative myocardial function and the inflammatory response of infants with Down syndrome and systemic to pulmonary shunts secondary to CHD. We aim to compare this group of patients to a population with a systemic to pulmonary shunt (STPS) secondary to CHD without DS and also with a control population of healthy infants, to assess short term post-surgical outcomes including in hospital mortality, length of intensive care and total inpatient stay and persistent PH.

Methods: Three cohorts of infants were recruited, the first with a confirmed diagnosis of DS who were admitted for surgical repair of CHD, the second with CHD undergoing cardiac surgery without DS and third group of healthy infants who had neither DS nor CHD. We collected vital signs data, performed echocardiographic assessments and measured inflammatory cytokines at three time points: pre-operatively, post-operatively within the first 24 hours and pre-discharge from the hospital. We compared the results of the DS/CHD cohort with those of infants with CHD without DS and to the group of healthy infants.

Results: We assessed and characterised the myocardial function and inflammatory response in infants with DS/CHD peri-operatively and compare them to the CHD only and control groups. We demonstrated significant differences in the haemodynamic and immune status between groups pre-operatively, post-operatively and prior to discharge from the hospital.

Conclusion: Clear differences were demonstrated between the three groups. The infants with DS/CHD exhibited both increased morbidity and post-operative complications. The phenotypic features of the immune response and myocardial function may reflect autonomic dysfunction with increased prevalence of pulmonary hypertension in children with DS/CHD. This may have important clinical implications, especially where infants with DS/CHD are undergoing surgery and also in the evaluation and treatment of cardiac function post-operatively. Long term follows up of these children is required to assess their myocardial performance and to correlate these findings with neurodevelopment.