RT Journal Article
SR Electronic
T1 Renewal theory provides a universal quantitative framework to characterise the continuous regeneration of rotational events in cardiac fibrillation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 599142
DO 10.1101/599142
A1 Dhani Dharmaprani
A1 Madeline Schopp
A1 Pawel Kuklik
A1 Darius Chapman
A1 Anandaroop Lahiri
A1 Lukah Dykes
A1 Feng Xiong
A1 Martin Aguilar
A1 Benjamin Strauss
A1 Lewis Mitchell
A1 Kenneth Pope
A1 Christian Meyer
A1 Stephan Willems
A1 Fadi G. Akar
A1 Stanley Nattel
A1 Andrew D McGavigan
A1 Anand N. Ganesan
YR 2019
UL http://biorxiv.org/content/early/2019/04/04/599142.abstract
AB Background Cardiac fibrillation is thought to be maintained by rotational activity, with pivoting regions called phase singularities (PSs). Despite a century of research, no clear quantitative framework exists to model the fundamental processes responsible for the continuous formation and destruction of rotors in fibrillation.Objective We conducted a multi-modality, multi-species study of AF/VF under the hypothesis that PS formation/destruction in fibrillation can be modelled as self-regenerating renewal processes, producing exponential distributions of inter-event times governed by constant rate-parameters defined by the prevailing properties of the system.Methods PS formation/destruction was studied and cross-validated in 5 models, using basket recordings and optical mapping from: i) human persistent AF (n = 20), ii) tachypaced sheep AF (n = 5), iii) rat AF (n = 4), iv) rat VF (n = 11) and v) computer simulated AF (SIM). Hilbert phase maps were constructed. PS lifetime data were fitted by exponential probability distribution functions (PDFs) computed using maximum entropy theory, and the rate parameter (λ) determined. A systematic review was conducted to cross-validate with source data from literature.Results PS destruction/formation distributions showed good fits to an exponential in all systems (R2 ≥ 0.90). In humans, λ = 4.6%/ms (95%CI,4.3,4.9)), sheep 4.4%/ms (95%CI,4.1,4.7)), rat AF 38%/ms (95%CI,22,55), rat VF 46%/ms (95%CI,31.2,60.2) and SIM 5.4%/ms (95%CI,4.1,6.7). All PS distributions identified through systematic review were exponential with λ comparable to experimental data.Conclusion These results provide a universal quantitative framework to explain rotor formation and destruction in AF/VF, and a platform for therapeutic advances in cardiac fibrillation.AFAtrial fibrillationVFVentricular FibrillationPSPhase SingularitiesEGMElectrocardiogramMaxEntMaximum Entropy