Pro-inflammatory cytokine profiling in children with LCOS following surgery for CHD requiring CPB

Summary

Is there a new therapeutic option for treating children who suffer with poor cardiac function following cardiac surgery for congenital heart disease (CHD)? We believe that there is - Tocilizumab, an anti-inflammatory drug used in the treatment of COVID-19 patients which could also be useful in the post cardiac surgery setting when significant inflammation occurs leading to poor cardiac function and worse outcomes for children. We have a ready-made platform to answer this question by profiling this inflammatory process and investigating its association with poor cardiac function. We anticipate that this will help us create preliminary data to support the investigation of Tocilizumab as a drug treatment to improve the post-operative recovery of these children.

Around 4,000 babies (~1% births) are diagnosed with CHD each year in the UK and ~1,000 (25%) of these children require heart surgery within the first year of life during which the heart may need to be stopped and oxygenated blood pumped around the body using a cardiopulmonary bypass (CPB) machine. Patients have a whole-body inflammatory reaction to this which can result in poor heart function, manifesting as a condition called low cardiac output syndrome (LCOS) which leads to complications or death postoperatively.

Cytokines are proteins which are important in the body's immune response and have been shown to be elevated in children post heart surgery as part of this inflammatory reaction to CPB. One of these cytokines, interleukin-6 (IL-6) is thought to play a role in the development of LCOS. The drug Tocilizumab is an IL-6 inhibitor and is effective in treating rheumatology and COVID-19 patients, although it is not currently licensed under 2 years of age and has significant side effects.$ In the same way that the inflammatory process in COVID-19 is mitigated by Tocilizumab and leads to improved outcomes, we believe that there is potential to reduce the deleterious effects of the inflammatory response to CPB in children who undergo heart surgery. We believe Tocilizumab will reduce levels of IL-6 post CPB and that this could lead to a reduction in the occurrence and severity of LCOS.

We plan to first undertake a project to review the correlation between inflammation (specifically raised cytokine levels) and evidence of poor cardiac function in children who have required CPB for CHD. We already have stored blood samples from children in this group that we can analyse.* After identifying patients with LCOS post CPB we will match them to controls and compare these 2 groups. If we demonstrate a correlation we can justify a future trial assessing Tocilizumab as a treatment for LCOS. It may even be superior to standard care, for example replacing the use of steroids. We believe this work will translate into significantly improved outcomes for children undergoing cardiac surgery for CHD in the UK.