• David PATERSON, University of Oxford (UK)
  • Kalyanam SHIVKUMAR, University of California, Los Angeles (USA)
  • Olivier BERNUS, University of Bordeaux (Université de Bordeaux, u-bordeaux) (France)
  • Igor EFIMOV, Northwestern University (USA)
  • Michel HAÏSSAGUERRE, University of Bordeaux (Université de Bordeaux, u-bordeaux) (France)
  • John ROGERS, Northwestern University (USA)
  • Natalia TRAYANOVA, Johns Hopkins University – Krieger School of Arts & Sciences (USA)
  • Vigmond EDWARD, University of Bordeaux (Université de Bordeaux, u-bordeaux) (France)

The autonomic nervous system (ANS) powerfully modulates cardiac physiology and plays a crucial role in pathophysiology. During the pathogenesis of heart disease, alterations in ANS leads to increased sympathetic and reduced parasympathetic tone, contributing to arrhythmias and sudden cardiac death (SCD). The fundamental hypothesis underlying this proposal is that heart failure progression and arrhythmias occur due to spatiotemporal heterogeneities in cardiac electromechanical and metabolic substrates resulting from adverse ANS remodeling and neuromodulation mitigates these derangements providing both therapeutic and cardioprotective benefits. We propose the development of organ-conformal bioelectronic technologies for highresolution, real-time measurements of cardiac autonomic, metabolic, and simultaneous electrophysiological & mechanical parameters. This data will be leveraged using machine learning enabled methods to guide ANS modulating therapy via real-time ‘closed-loop’ feedback control. Advanced analytics for data derived from intramyocardial biomolecule, physical, chemical, and other sensors, coupled with the deployment of organ-conformal high-resolution biointerfaces on the heart, will define metabolic, electrical, and mechanical heterogeneities across diseased areas of the heart. ANS assessment will include real-time in vivo measurement of regional cardiac neurotransmitter release, leveraging electrochemical cyclic voltammetry (catecholamine) and capacitive immunoprobes (neuropeptides). Combining real-time readouts of intramyocardial neurotransmitters, with advances in electrophysiological mapping of the heart, provides our team the unparalleled ability to (i) identify subjects at high risk for SCD, (ii) define the specific contribution of abnormal electrophysiological substrate amplified by heterogeneities in autonomic neurotransmitters, and (iii) tailor closed-loop neuromodulation therapeutic interventions to prevent the progression of heart disease.