Benjamin Bussmann

BA BMBCh

BHF clinical research fellow

• I am a cardiology trainee and I am on a three-year BHF Clinical Research and Training Fellowship, providing me with an opportunity to undertake full time research, working towards a DPhil. Sympathetic activation is a hallmark of cardiac disease. While initially sympathetic activation is a physiological response to preserve cardiac function in response to acute cardiac insult, overtime this becomes maladaptive and actively contributes to the progression of cardiac disease. In particular, sympathetic stimulation is highly pro-arrhythmic, decreasing fibrillatory threshold and triggering life threatening ventricular arrhythmias. Current methods for predicting arrhythmic risk and preventing ventricular arrhythmias are imperfect. Most patients deemed high enough risk to require implantable cardioverter defibrillator (ICD) implant never actually go on to require ICD therapy. Conversely, despite optimised contemporary medial therapy, many patients experience recurrent ventricular arrhythmias resulting in repetitive ICD shocks. Cardiac sympathetic denervation through surgical removal of the stellate ganglia (where sympathetic innervation to the heart originates) is highly effective at preventing ventricular arrhythmias but carries a high risk of complications. We propose a novel non-invasive method of achieving cardiac sympathetic denervation (CSD) through radiotherapy to the stellate ganglia. We hypothesise this will lead to fewer complications compared to the surgical procedure while still maintaining efficacy. To test this, we are running the RADIO-STAR phase 1 clinical study to assess the feasibility and safety of image guided radiotherapy to the stellate ganglia in patients with recurrent ventricular arrhythmias. Furthermore, to better understand the mechanisms underlying sympathetic activation in cardiac disease we use techniques such as single cell RNA sequencing of human stellate ganglion tissue from patients with recurrent arrythmias. By identifying differentially expressed genes in cell populations such as sympathetic neurons, glial cells and immune cells, we hope to identify novel biomarkers which could ultimately lead to improved prediction of arrhythmic risk in clinical practice.