Feasibility of improving risk stratification in the inherited cardiac conditions

Abstract

Fatal ventricular arrhythmias can occur in patients with Hypertrophic Cardiomyopathy, Brugada Syndrome and rarely in patients with normal cardiac investigations. Despite very different pathogeneses, we hypothesised that a common electrophysiological substrate precipitates these arrhythmias and could be used as a marker for risk stratification. In Chapter 3 of this thesis, we found that fewer than half the cardiac arrest survivors with Brugada Syndrome would have been offered prophylactic defibrillators based on current risk scoring, highlighting the need for better risk stratification. Our group previously used a commercially available 252-electrode vest which constructs ventricular electrograms onto a CT image of the heart to show exercise related differences in high-risk patients. In Chapter 4, we applied this method to Brugada patients, but could not reproduce prior results. Further investigation revealed periodic changes in activation patterns after exercise that could explain this discrepancy. An alternative matrix approach was developed to overcome this problem. Exercise induced conduction heterogeneity differentiated Brugada patients from unaffected controls, but not those surviving cardiac arrest. However, if considered alongside spontaneous type 1 ECG and syncope, inducible conduction heterogeneity markedly improved identification of Brugada cardiac arrest survivors. In Chapter 5 the method was shown to differentiate idiopathic ventricular fibrillation patients from those fully recovered from acute ischaemic cardiac arrest, implying a permanent electrophysiological abnormality. In Chapter 8, we showed prolonged mean local activation times and activation-recovery intervals in hypertrophic cardiomyopathy cardiac arrest survivors compared to those without previous ventricular arrhythmia. These metrics were combined into both logistic regression and support vector machine models to strongly differentiate the groups. We concluded that electrophysiological changes could identify cardiac arrest survivors in various cardiac conditions, but a single factor common pathway was not established. Prospective studies are required to determine if using these parameters could enhance current risk stratification for sudden death.