Mechanisms of Ventricular Arrhythmias in Heart Failure

Patients with heart failure (HF) are at risk of sudden death due to abnormally fast heart rhythms (ventricular arrhythmias), which are produced by imbalances in the electrical system of the heart. At present, the only effective treatment is to implant a defibrillator (ICD) which can terminate ventricular arrhythmias by delivering a shock. In order to develop treatments which prevent these life-threatening arrhythmias, we must understand the mechanisms by which these conditions cause electrical imbalances in the heart.

There is evidence from decades of research in isolated heart cells that ventricular arrhythmias in HF arise from abnormalities in the electrical events which take place in each cell. However, treatments targeted at these individual abnormalities have not been successful. This is likely to be because the situation in the intact heart is much more complex.

We believe it is crucial to understand how cellular events in disease are expressed in the heart as a whole. To do this, we take a novel approach, using a unique imaging systems which combine electrical measurements at the cell-level with those from the whole heart.

Our research uses optical mapping systems to study the mechanisms of ventricular arrhythmias in heart failure, an area in which studies in isolated ventricular myocytes have failed to provide therapeutic advances. Our approach involves examining paradigms which have been demonstrated to cause arrhythmias in isolated failing myocytes and ask the question how these phenomena might be expressed in the whole heart, where there is spatial heterogeneity, structural discontinuity and electrotonic coupling. Clinical relevance is an important motivation in our studies - we have a major interest in the role of the infarct scar and repolarisation alternans in causing re-entrant arrhythmias in heart failure. We have recently developed our mapping systems to allow dual-modality (voltage and calcium) and dual-resolution (cell and tissue level) imaging which will allow us to expand our studies to calcium mediated focal arrhythmias which occur in heart failure and other pathologies.


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