Low-Energy Anti-Fibrillation Pacing - A Dynamical Systems Perspective on Cardiac Arrhythmias

Spatially extended non-equilibrium systems display spatial-temporal dynamics that can range from ordered to turbulent. Controlling such systems is one of the central problems in nonlinear science and has far-reaching technological consequences. Few examples of successful control with applications in physics and chemistry have been demonstrated [1]. In biological excitable media, however, the systems’ complexity makes successful control challenging [2]. This difficulty applies in particular to electrical turbulence in cardiac tissue, known as fibrillation. During fibrillation, synchronous contraction of the muscle is disrupted by fast, vortex-like, rotating waves of electrical activity. The loss of synchronous contraction of the ventricles, i.e. the main chambers of the heart, results in a loss of pumping function and is immediately life threatening. In the European Union, an estimated 700,000 cardiac deaths per year are associated with ventricular fibrillation (VF). Controlling the complex spatial-temporal dynamics underlying life-threatening cardiac arrhythmias such as VF is extremely difficult, because of the nonlinear interaction of excitation waves with the heterogeneous multicellular substrate. In the absence of a better strategy, strong, globally resetting electrical shocks remain the only reliable treatment for VF. However, high-energy shocks (typically 1kV, 30 A, 12 ms) may have significant side effects including tissue damage and intolerable pain, indicating a substantial medical need. 

Translational research at the Biomedical Physics Group focuses on molecular, genetic, and dynamic mechanisms underlying the onset, perpetuation and control of cardiac arrhythmias. We are driven by the vision that the systematic integration and evaluation of dynamics on all levels from sub- cellular, cellular, tissue, and organ to the in vivo organism is key to the understanding of complex biological systems and will open – on a long-term perspective – new paths for translating fundamental scientific discoveries into practical applications that may improve human health. Combining high-resolution multimodal fluorescence imaging of intact Langendorff-perfused hearts with optogenetic tools and detailed in silico modeling, we have shown, that simultaneous and direct access to multiple vortex cores results in rapid synchronization of cardiac tissue and therefore, efficient termination of fibrillation. Exploring the biophysical mechanisms of the interaction of weak electric pulses with heterogeneities in electrical conductance [3], we demonstrate that Low-Energy Anti-Fibrillation Pacing (LEAP) terminates fibrillation in vivo with 80-90% less energy compared to conventional defibrillation shocks [4, 5]. 

Our results give new insights into the mechanisms and dynamics underlying the control of spatial-temporal chaos in heterogeneous excitable media and provide new research perspectives towards painless and non-damaging defibrillation. 

[1] T. Sakurai, E. Mihaliuk, F. Chirila, K. Showalter, K. Science 296, 2009 (2002). 

[2] A. Karma, Annu. Rev. Condens. Matter Phys. 4, 313 (2013) 

[3] P. Bittihn, M. Hörning, S. Luther Phys. Rev. Lett. 109, 118106 (2012) 

[4] S. Luther*, F. H. Fenton* et al. Nature 475, 235 (2011) 

[5] F.H. Fenton*, S. Luther* et al. Circulation 120, 467 (2009) * Authors have contributed equally. 

This work has received support through the Max Planck Society, the DZHK e.V., the BMBF (Gründungsoffensive Biotechnologie, FKZ 031A147), the DFG (SFB 1002 Modulatory Units in Heart Failure), and European Community’s Seventh Framework Programme FP7/2007–2013 agreement HEALTH-F2-2009-241526 (EUTrigTreat)