SYMPHONY · Sudden Cardiac Death and Electrical Dyssynchrony Mediated by Purkinje-His Dysfunctional Activity

Cardiovascular disease is the first cause of mortality in the whole world (WHO 2008), responsible for 700000 deaths each year in Europe; a huge burden on healtcare. Half of this mortality is due to heart failure (HF), which can be caused or further aggravated by electrical dyssynchrony. The other half of cardiac mortality occurs suddenly, essentially due to ventricular tachyarrhythmias.The main objectives of SYMPHONY are (i) to advance our fundamental understanding in the mechanisms underlying SCD and electrical dyssynchrony in HF, with a strong focus on the specialized ventricular conduction network, and (ii) to improve current preventive, diagnostic and treatment methods for these life-threatening cardiac electrical disorders.SYMPHONY is a multidisciplinary project that will benefit from a wide array of state-of-the-art methodologies and expertise, both in fundamental and clinical sciences. A large mammalian species, the sheep, will be used for a detailed characterization of the properties of the conduction network in health and disease. Importantly, a limited number of explanted human hearts will be available on which all these techniques will equally be applicable. From our clinical work, SYMPHONY will benefit from cutting edge tools in epicardial and catheter mapping allowing simultaneous mapping of the Purkinje system and ventricular substrate. The gathered data will be fed into large-scale computer models that will allow personalized investigations into the mechanisms of SCD and electrical dyssynchrony.SYMPHONY has a significant potential for industrial valorisation and is likely to introduce new targets for interventions, and new methods for risk stratification and prevention. Therefore we can affirm that this unprecedented, comprehensive and translational project will lead to major advances in scientific knowledge, will have a significant impact on healthcare budgets and, most importantly, will dramatically improve quality of life and patient care.