Mechanistically based mapping of human cardiac fibrillation

Abstract

The mechanisms underpinning human cardiac fibrillation remain elusive. In his 1913 paper ‘On dynamic equilibrium in the heart’, Mines proposed that an activation wave front could propagate repeatedly in a circle, initiated by a stimulus in the vulnerable period. While the dynamics of activation and recovery are central to cardiac fibrillation, these physiological data are rarely used in clinical mapping. Fibrillation is a rapid irregular rhythm with spatiotemporal disorder resulting from two fundamental mechanisms – sources in preferred cardiac regions or spatially diffuse self‐sustaining activity, i.e. with no preferred source. On close inspection, however, this debate may also reflect mapping technique. Fibrillation is initiated from triggers by regional dispersion in repolarization, slow conduction and wavebreak, then sustained by non‐uniform interactions of these mechanisms. Notably, optical mapping of action potentials in atrial fibrillation (AF) show spiral wave sources (rotors) in nearly all studies including humans, while most traditional electrogram analyses of AF do not. Techniques may diverge in fibrillation because electrograms summate non‐coherent waves within an undefined field whereas optical maps define waves with a visually defined field. Also fibrillation operates at the limits of activation and recovery, which are well represented by action potentials while fibrillatory electrograms poorly represent repolarization. We conclude by suggesting areas for study that may be used, until such time as optical mapping is clinically feasible, to improve mechanistic understanding and therapy of human cardiac fibrillation.

Three‐dimensional Integrated Functional, Structural, and Computational Mapping to Define the Structural “Fingerprints” of Heart‐Specific Atrial Fibrillation Drivers in Human Heart Ex Vivo

“…However, most studies accept the importance of atrial structure, and all mechanisms would benefit from a method that can quantify the contribution of atrial structural substrates to AF maintenance 32, 33, 34, 35, 36, 37, 38, 39. Spach and colleagues were the first to report local conduction delay and morphological changes in electrical signals caused by abrupt changes in myofiber orientations and geometric tissue variations in the dog atria ex vivo 40.…”

Memory effects, transient growth, and wave breakup in a model of paced atrium

“…The spectrum of the evolution operator U (t, 0) was computed using the Arnoldi method implemented by the Matlab function eigs 41 with accuracy yielding eight significant digits. In both instances matrix-free evaluation of the the matrix-vector product U (t, 0) δu was accomplished via simultaneous numerical time-integration of (1) and (8). The matrix-free calculation of the product U (t, 0)…”

“…The weaker the asymptotic decay, the larger the amplification that can be achieved. Computation of max t σ 1 (t) is numerically rather expensive, since SVD requires alternate direction integration of the linear PDEs (8) and (14) on the time interval [0, t] and there is no simple relation that allows one to compute the singular values at time t + dt based on their values at time t. We therefore performed this calculation over many pacing periods on a coarse grid with ∆t = T /10.…”

“…Understanding of the transition from the normal cardiac rhythm, also known as the 1:1 response, to fibrillation is critical for the development of therapies for the prevention or termination of this dangerous arrhythmia. Abundant experimental evidence points to the role of alternans 3 , a beat-to-beat alternation in the action potential duration (APD) at high excitation rates, also known as the 2:2 response, as a precursor of fibrillation both in the ventricles 4,5 and in the atria [6][7][8] . Strong correlation between alternans and fibrillation was also found in the simulations employing high-fidelity models of twodimensional ventricular 9 and atrial 10 tissue.…”

Atrial fibrillation: Can electrograms be interpreted without repolarization information?

“…Accurate repolarization data may clarify the debate on complex fractionated atrial electrograms by identifying which signal components are far-field vs “pivot points.” 1 Repolarization data also may help resolve the dichotomy that optical mapping—the gold standard—mostly shows that rotors sustain AF (including in human atria 8 ), yet most classic electrogram analyses of AF do not 15 . Finally, repolarization data may enable tracking of response to therapy.…”