Alternative stable scroll waves and conversion of autowave turbulence

Wave propagation in the heart has a discrete nature, because it is mediated by discrete intercellular connections via gap junctions. Although effects of discreteness on wave propagation have been studied for planar traveling waves and vortexes (spiral waves) in two dimensions, its possible effects on vortexes (scroll waves) in three dimensions are not yet explored. In this article, we study the effect of discrete cell coupling on the filament dynamics in a generic model of an excitable medium. We find that reduced cell coupling decreases the line tension of scroll wave filaments and may induce negative filament tension instability in three-dimensional excitable lattices.

Despite extensive research, the fundamental biophysical mechanisms underlying severe heart rhythm disorders such as ventricular fibrillation remain poorly understood. Ventricular fibrillation is an acute and highly lethal medical condition, in which the heart's electrical system, which normally activates the contractions of the cardiac muscle, becomes highly disorganized and ineffective in orchestrating the orderly beating of the heart. Understanding the nature of the underlying abnormal electrical activity is thought to be key to the development of novel diagnostic and therapeutical strategies in treating cardiac arrhythmias. However, current imaging technology provides only very limited insight into the complex spatial-temporal electrical patterns underlying ventricular fibrillation within the heart muscle. In this work, a novel imaging approach is presented, which aims at imaging both electrical and elasto-mechanical activity of the cardiac muscle during cardiac tachyarrhythmias to better understand the correlation of electrical activity and resultant mechanical deformation and to explore the possibility to infer the electrical activity from the mechanical deformation. The work includes computational modeling and data analysis as well as ex vivo imaging experiments with isolated, intact hearts. Using mathematical concepts from nonlinear physics that describe universal pattern formation processes in excitable electrical systems such as the heart, the imaging experiments were guided and potential interpretations and methods for processing of data were validated. It was found that both electrical and elasto-mechanical activity of the cardiac muscle are highly correlated during ventricular tachycardia and fibrillation. For instance, rotating electrical activity, which was filmed on the surface of the fibrillating, contracting heart using fluorescence imaging, was found to induce similarly rotating rate of deformation patterns. Moreover, the rotating elasto-mechanical patterns could simultaneously be imaged within the heart wall using ultrasound. The data suggests that the rotational mechanical patterns are the finger-print of electrical spiral and scroll wave activity during cardiac fibrillation. In computer simulations, it was found that the core regions of spiral and scroll waves can similarly be described by electrical or elasto-mechanical lines of phase singularity, the electrical lines of phase singularity corresponding to electrical scroll vortex wave filaments and the mechanical lines of phase singularity corresponding to topological defect lines that arise in the dynamic elasto-mechanical deformation patterns resulting from the rapid fibrillatory activity of the cardiac muscle. Both the experimental and numerical findings suggest that a mechanical measurement can provide insight into the organizational structure of ventricular fibrillation throughout the volume of the heart muscle tissue. Next to these findings, the development of the methodological approach, including high-speed fluorescence imaging equipment and data processing techniques with which it is possible to perform imaging experiments with contracting cardiac tissue preparations, to perform simultaneous voltage, calcium and strain measurements as well as to perform imaging combined with intramural strain measurements using ultrasound, is the main result of this thesis. The findings presented in this thesis have important implications on potential future clinical applications.

Regular electrical activation waves in cardiac tissue lead to the rhythmic contraction and expansion of the heart that ensures blood supply to the whole body. Irregularities in the propagation of these activation waves can result in cardiac arrhythmias, like ventricular tachycardia (VT) and ventricular fibrillation (VF), which are major causes of death in the industrialised world. Indeed there is growing consensus that spiral or scroll waves of electrical activation in cardiac tissue are associated with VT, whereas, when these waves break to yield spiral- or scroll-wave turbulence, VT develops into life-threatening VF: in the absence of medical intervention, this makes the heart incapable of pumping blood and a patient dies in roughly two-and-a-half minutes after the initiation of VF. Thus studies of spiral- and scroll-wave dynamics in cardiac tissue pose important challenges for in vivo and in vitro experimental studies and for in silico numerical studies of mathematical models for cardiac tissue. A major goal here is to develop low-amplitude defibrillation schemes for the elimination of VT and VF, especially in the presence of inhomogeneities that occur commonly in cardiac tissue. We present a detailed and systematic study of spiral- and scroll-wave turbulence and spatiotemporal chaos in four mathematical models for cardiac tissue, namely, the Panfilov, Luo-Rudy phase 1 (LRI), reduced Priebe-Beuckelmann (RPB) models, and the model of ten Tusscher, Noble, Noble, and Panfilov (TNNP). In particular, we use extensive numerical simulations to elucidate the interaction of spiral and scroll waves in these models with conduction and ionic inhomogeneities; we also examine the suppression of spiral- and scroll-wave turbulence by low-amplitude control pulses. Our central qualitative result is that, in all these models, the dynamics of such spiral waves depends very sensitively on such inhomogeneities. We also study two types of control schemes that have been suggested for the control of spiral turbulence, via low amplitude current pulses, in such mathematical models for cardiac tissue; our investigations here are designed to examine the efficacy of such control schemes in the presence of inhomogeneities. We find that a local pulsing scheme does not suppress spiral turbulence in the presence of inhomogeneities; but a scheme that uses control pulses on a spatially extended mesh is more successful in the elimination of spiral turbulence. We discuss the theoretical and experimental implications of our study that have a direct bearing on defibrillation, the control of life-threatening cardiac arrhythmias such as ventricular fibrillation.

Critical Care Medicine| October 01 2006 Outcome of Ventricular Fibrillation in Children AAP Grand Rounds (2006) 16 (4): 41–42. https://doi.org/10.1542/gr.16-4-41 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Outcome of Ventricular Fibrillation in Children. AAP Grand Rounds October 2006; 16 (4): 41–42. https://doi.org/10.1542/gr.16-4-41 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: tachycardia, ventricular, ventricular fibrillation, cardiopulmonary resuscitation, cardiac arrest Source: Samson RA, Nadkarni VM, Meaney PA, et al. Outcomes of in-hospital ventricular fibrillation in children. N Engl J Med. 2006;354:2328–2339; doi:10.1056/NEJMoa052917 Ventricular tachycardia and fibrillation are among the most common causes of cardiac arrest in adults and “shockable” rhythms have been associated with improved survival. However, children more typically suffer electrocardiographic asystole or pulseless electrical activity as the consequence of hypoxia from other organ system disease progression rather than a primary cardiac arrest. The authors evaluated patients (<18 years of age) with inhospital cardiac arrests captured in the National Registry of CPR, a large, multi-center database sponsored by the American Heart Association. They investigated whether children with initial ventricular tachycardia or fibrillation as the cause of cardiac arrest had improved survival when compared to children who developed ventricular dysrhythmias prior to the start of cardiopulmonary resuscitation (CPR). The study period was January 2000–June 2004 and included 1005 children who experienced a cardiac arrest. One hundred-fifty cases (15%) were excluded because the initial cardiac rhythm was unknown. Of the 855 cases reviewed, 104 children (10%) had initial ventricular tachycardia or fibrillation, and 35% survived to hospital discharge. Thirty-four of 36 survivors had a good neurologic outcome. Of the 149 children (15%) who developed ventricular tachycardia or fibrillation during resuscitation, only 11% survived to hospital discharge and 12 of 16 survivors had a good neurological outcome. Among children who never had documented ventricular tachycardia or fibrillation (n=733, 73%), 27% survived to hospital discharge and 144 of 164 survivors had a good neurological outcome. The authors conclude that children with initial ventricular tachycardia or fibrillation had improved survival compared to children who never had ventricular tachycardia or fibrillation and compared to children who developed ventricular dysrhythmias during CPR. Dr. Bratton has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of a commercial product/device. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. This report and another recent study1 using the same database reports improving survival of children after CPR. In-hospital arrest survival in this cohort was 27% for children overall which is much better than prior reports.2 Furthermore, 65% of those who survive do so with acceptable neurological outcomes.1 The current paper shows that approximately 10% of children had initial ventricular tachycardia or fibrillation, and that their survival is better than children with other initial pulseless rhythms. However, the prognosis for pediatric patients who develop ventricular fibrillation or tachycardia during CPR is worse. This finding conflicts with experimental reports demonstrating improved outcome with induction of ventricular fibrillation during CPR for asystole, followed by defibrillation.3 The authors speculate on the reasons for this finding and question whether excessive administration of epinephrine or underlying myocardial status play a role; however, they conclude that their data cannot answer that question. Pediatricians need to review the new CPR guidelines published by the American Heart Association,5 which have changed to focus more immediately on... You do not currently have access to this content.

We study the asymptotic behavior of scroll wave turbulence in large three-dimensional excitable media modeled by FitzHugh-Nagumo equations. The focus is on the type of turbulence caused by negative tension of scroll wave filaments, which is considered to be one of the mechanisms of cardiac fibrillation. We discovered that the initial increase in turbulence complexity can be followed by intermittent self-organization, when complex filament tangles are replaced by a small number of relatively stable triple filament strands. The intermittency is the result of a competition between the destabilizing effect of negative tension and mutual attraction of filaments with similar orientation.

Surgical management of refractory ventricular arrhythmias in patients with prior inferior myocardial infarction: A preliminary report

Spiral waves are a well-known and intensively studied dynamic phenomenon in excitable media of various types. Most studies have considered an excitable medium with a single stable resting state. However, spiral waves can be maintained in an excitable medium with bistability. Our calculations, performed using the widely used Barkley model, clearly show that spiral waves in the bistability region exhibit unique properties. For example, a spiral wave can either rotate around a core that is in an unexcited state, or the tip of the spiral wave describes a circular trajectory located inside an excited region. The boundaries of the parameter regions with positive and ‘negative’ cores have been defined numerically and analytically evaluated. It is also shown that the creation of a positive or ‘negative’ core may depend on the initial conditions, which leads to hysteresis of spiral waves. In addition, the influence of gradient flow on the dynamics of the spiral wave, which is related to the tension of the scroll wave filaments in a three-dimensional medium, is studied.

The characteristics of premature ventricular beats predisposing to ventricular tachycardia or fibrillation were assessed by 24-h ambulatory monitoring and maximal treadmill exercise testing in 339 cardiac patients with premature ventricular beats. Premature ventricular beats were divided into early (Q-premature ventricular beat less than QT), late (within the last 20% of the cardiac cycle), and midcycle. Ventricular tachycardia was recorded in 45 patients and ventricular fibrillation, in three. The frequency of ventricular tachycardia or fibrillation was 32% in patients with late, 16% in patients with early, and 7% in patients with midcycle premature ventricular beats (P less than 0.05). Patients with frequent (less than 10/min) multiformed premature ventricular beats had a frequency of ventricular tachycardia or fibrillation of 44%, while only 13% of patients with frequent uniformed premature ventricular beats had ventricular tachycardia (P less than 0.05). Ambulatory patients with ventricular tachycardia or fibrillation have frequent multiformed premature ventricular beats, and the ventricular tachycardia or fibrillation is usually triggered by late premature ventricular beats.

Previous studies have demonstrated that both ventricular tachycardia (VT) and ventricular fibrillation (VF) may begin as figure-eight reentry: VT with a longer cycle length from spared tissue adjacent to an infarct by programmed stimulation and VF with a shorter cycle length from noninfarcted tissue by a large premature S2 stimulus. These results suggest that the type of tissue or cycle length of the arrhythmia rather than the mode of induction determines whether the figure eight becomes sustained VT or degenerates into VF. Thus, a protocol similar to that by which a VF threshold is determined may induce VT rather than VF when performed in the spared tissue over an infarct. In 10 dogs, 4 days after occlusion-reperfusion of the left anterior descending coronary artery, 10 S1 stimuli were delivered from a total of 34 right and left ventricular sites outside the infarct. An epicardial S2 stimulus over the infarct was increased in 10-mA steps and introduced in diastole at decreasing cycle lengths of 5 msec until VT or VF was induced. Sustained monomorphic figure-eight VT was induced from 24 S1 sites and VF from nine (p = 0.03). The mean cycle lengths for the initial six arrhythmic cycles was 152 +/- 33 msec for VT and 115 +/- 13 msec for VF (p less than 0.001). Mean transmural infarct extent was 80% in five dogs with only VT, 63% in three dogs with both VT and VF, and 15% in two dogs with only VF. Different morphologies of VT were induced by changing the S1 site, the S2 strength, or the S1S2 coupling interval. In 25 of the 34 arrhythmias, the central part of the initial figure-eight pathway was oriented opposite the S1 activation sequence in that region. A large S2 stimulus over a nontransmural infarct induces VT if the spared myocardium is thin. This study introduces a useful technique for inducing sustained monomorphic VT in which the location and direction of the figure-eight pathway are known a priori and in which different morphologies of sustained VT can be produced by changing the S1 site.

The relative prognostic significance of ventricular tachycardia and ventricular fibrillation inducible at programmed stimulation within 1 month of acute myocardial infarction was compared in a prospective study of 403 clinically well survivors of transmural infarction who were 65 years old or younger. The prognostic significance of delayed potentials on the signal-averaged electrocardiogram was also examined in a subset of 306 patients without bundle branch block. Among the study patients, 20% had inducible ventricular tachycardia, 14% had inducible ventricular fibrillation, and 66% had no inducible arrhythmias. The 2 year probability of remaining free from cardiac death or nonfatal ventricular tachycardia or fibrillation was 0.73 for those with inducible ventricular tachycardia, 0.93 for those with inducible ventricular fibrillation, and 0.92 for those with no inducible arrhythmias. The cycle length of inducible ventricular tachycardia was 230 msec or more in 70% of the patients with inducible tachycardia who died. Of the patients studied by signal-averaged electrocardiography, 26% had delayed potentials. At 2 years, the probability of remaining free from cardiac death or nonfatal ventricular tachycardia or fibrillation was 0.73 for patients with delayed potentials and 0.95 for patients with no delayed potentials. There was a significant correlation (p less than .001) between the presence of delayed potentials and the ability to induce ventricular tachycardia. In conclusion, in survivors of recent infarction who have not had spontaneous ventricular tachycardia or fibrillation, inducible tachycardia (but not inducible fibrillation) at programmed stimulation predicts a significant risk of death or spontaneous tachycardia or fibrillation. A similar risk is found for patients with delayed potentials on the signal-averaged electrocardiogram.

The recommendations for electrical therapies described in this section are designed to improve survival from SCA and life-threatening arrhythmias. Whenever defibrillation is attempted, rescuers must coordinate high-quality CPR with defibrillation to minimize interruptions in chest compressions and to ensure immediate resumption of chest compressions after shock delivery. The high first-shock efficacy of newer biphasic defibrillators led to the recommendation of single shocks plus immediate CPR instead of 3-shock sequences that were recommended prior to 2005 to treat VF. Further data are needed to refine recommendations for energy levels for defibrillation and cardioversion using biphasic waveforms.

Use of approximate entropy measurements to classify ventricular tachycardia and fibrillation

Defibrillation/cardioversion thresholds were measured in 33 patients undergoing defibrillator implants. Each patient had a 12 cm2 patch placed near the left ventricular apex via a thoracotomy and a 10 cm2 spring lead placed pervenously at the right atrial-superior vena caval junction. Ventricular tachycardia of stable morphology, polymorphic ventricular tachycardia, or ventricular fibrillation was induced four times in each patient and 1, 5, 10, and 25 J truncated exponential shocks with 60% tilt were given in a random sequence. The conversion rate was constant (77%, 86%, 87%, 85%) with increasing energy for ventricular tachycardia but progressively increased for polymorphic ventricular tachycardia and ventricular fibrillation (8%, 33%, 58%, 92%). The ventricular tachycardia acceleration rates for 1, 5, 10, and 25 J were 23%, 14%, 10%, and 15%. Patients not reliably converted with 25 J may require repositioning of leads or two patches. We conclude that for the spring-patch electrodes, increasing energy from 1 to 25 J improves the conversion rate for polymorphic ventricular tachycardia and ventricular fibrillation; the ventricular tachycardia conversion rate is constant. Acceleration of ventricular tachycardia occurs at all energies. Defibrillator implantation requires extensive intraoperative electrophysiologic testing to ensure safe and reliable termination of ventricular tachycardia and fibrillation.

Background: There are many studies to investigate mechanisms of induction and maintenance of ventricular fibrillation (VF); however, the mechanisms have not been clarified yet. It is known that the thickness of ventricular wall varies with time during VF; i.e., thickness of left ventricular wall is increased whereas that of right ventricular wall is decreased. We hypothesized that such deformation of ventricular walls during VF alters the stability of VF. To clarify this issue, we conducted computer simulation of VF in the ventricular wall slab models deformed with time. Methods: We constructed slab models with 10-mm thickness for left ventricular wall and with 5-mm thickness for right ventricular wall. Electrical heterogeneity and rotational anisotropy through the ventricular wall were included. After the onset of VF, thicknesses of the slabs were varied dynamically. The scroll wave filament (3-dimensional reentrant center) was expressed as a continuum of phase singularities. Results: In the deforming right ventricular wall, filament trajectory on the epicardial surface was gradually decreased, confirming stability of the scroll wave reentry. In the deforming left ventricular wall, filament was separated into several parts and filament trajectories traced complicated patterns. In contrast, the scroll waves without deformation were terminated by the annihilation of all filaments. Conclusion: Deforming ventricular walls during VF play important roles to maintain VF.

Electrical waves in the heart form rotating spiral or scroll waves during life-threatening arrhythmias, such as atrial or ventricular fibrillation. The wave dynamics are typically modeled using coupled partial differential equations, which describe reaction-diffusion dynamics in excitable media. More recently, data-driven generative modeling has emerged as an alternative to generate spatio-temporal patterns in physical and biological systems. Here, we explore denoising diffusion probabilistic models for the generative modeling of electrical wave patterns in cardiac tissue. We trained diffusion models with simulated electrical wave patterns to be able to generate such wave patterns in unconditional and conditional generation tasks. For instance, we explored the diffusion-based (i) parameter-specific generation, (ii) evolution, and (iii) inpainting of spiral wave dynamics, including reconstructing three-dimensional scroll wave dynamics from superficial two-dimensional measurements. Furthermore, we generated arbitrarily shaped bi-ventricular geometries and simultaneously initiated scroll wave patterns inside these geometries using diffusion. We characterized and compared the diffusion-generated solutions to solutions obtained with corresponding biophysical models and found that diffusion models learn to replicate spiral and scroll wave dynamics so well that they could be used for data-driven modeling of excitation waves in cardiac tissue. For instance, an ensemble of diffusion-generated spiral wave dynamics exhibits similar self-termination statistics as the corresponding ensemble simulated with a biophysical model. However, we also found that diffusion models produce artifacts if training data are lacking, e.g., during self-termination, and "hallucinate" wave patterns when insufficiently constrained.