Estimating the time scale and anatomical location of atrial fibrillation spontaneous termination in a biophysical model

Due to their transient nature, spontaneous terminations of atrial fibrillation (AF) are difficult to investigate. Apparently, confounding experimental findings about the time scale of this phenomenon have been reported, with values ranging from 1s to 1min. We propose a biophysical modeling approach to study the mechanisms of spontaneous termination in two models of AF with different levels of dynamical complexity. 8s preceding spontaneous terminations were studied and the evolution of cycle length and wavefront propagation were documented to assess the time scale and anatomical location of the phenomenon. Results suggest that termination mechanisms are dependent on the underlying complexity of AF. During simulated AF of low complexity, the total process of spontaneous termination lasted 3,200ms and was triggered in the left atrium 800ms earlier than in the right atrium. The last fibrillatory activity was observed more often in the right atrium. These asymmetric termination mechanisms in both time and space were not observed during spontaneous terminations of complex AF simulations, which showed less predictable termination patterns lasting only 1,600ms. This study contributes to the interpretation of previous clinical observations, and illustrates how computer modeling provides a complementary approach to study the mechanisms of cardiac arrhythmia

Maritime Networks, Port Efficiency, and Hinterland Connectivity in the Mediterranean

International audience; For millennia, the Mediterranean has been one of the most active trading areas, supported by a transport network connecting riparian cities and beyond to their hinterland. The Mediterranean has complex trade patterns and routes--but with key differences from the past. It is no longer an isolated world economy: it is both a trading area and a transit area linking Europe and North Africa with the rest of the world through the hub-and-spoke structure of maritime networks. Understanding how trade connectivity works in the Mediterranean, and elsewhere, is important to policy makers, especially those in developing countries in the Mediterranean, concerned with the economic benefits of large investment in infrastructure. Better connectivity is expected to increase trade with distant markets and stimulate activities in the hinterland. This book is a practical exploration of the three interdependent dimensions of trade connectivity: maritime networks, port efficiency, and hinterland connectivity. Because of the complexity and richness of maritime and trade patterns in the Mediterranean, the research book combines both a regional focus and globally scalable lessons. This book is intended for a wide readership of policy makers in maritime affairs, trade, or industry; professionals from the world of finance or development institutions; and academics. It combines empirical analysis of microeconomic shipping and port data with three case studies of choice of port (focusing on Spain, Egypt, and Morocco) and five case studies on hinterland development (Barcelona; Malta; Marseilles; Port Said East, Egypt; and Tanger Med, Morocco). Document type: Boo

Estimating the time scale and anatomical location of atrial fibrillation spontaneous termination in a biophysical model

Due to their transient nature, spontaneous terminations of atrial fibrillation (AF) are difficult to investigate. Apparently, confounding experimental findings about the time scale of this phenomenon have been reported, with values ranging from 1 s to 1 min. We propose a biophysical modeling approach to study the mechanisms of spontaneous termination in two models of AF with different levels of dynamical complexity. 8 s preceding spontaneous terminations were studied and the evolution of cycle length and wavefront propagation were documented to assess the time scale and anatomical location of the phenomenon. Results suggest that termination mechanisms are dependent on the underlying complexity of AF. During simulated AF of low complexity, the total process of spontaneous termination lasted 3,200 ms and was triggered in the left atrium 800 ms earlier than in the right atrium. The last fibrillatory activity was observed more often in the right atrium. These asymmetric termination mechanisms in both time and space were not observed during spontaneous terminations of complex AF simulations, which showed less predictable termination patterns lasting only 1,600 ms. This study contributes to the interpretation of previous clinical observations, and illustrates how computer modeling provides a complementary approach to study the mechanisms of cardiac arrhythmias

A single-beat algorithm to discriminate farfield from nearfield bipolar voltage electrograms from the pulmonary veins.

BACKGROUND Superimposition of farfield (FF) and nearfield (NF) bipolar voltage electrograms (BVE) complicates the confirmation of pulmonary vein (PV) isolation after catheter ablation of atrial fibrillation. Our aim was to develop an automatic algorithm based on a single-beat analysis to discriminate PV NF from atrial FF BVE from a circular mapping catheter during the cryoballoon PV isolation. METHODS During freezing cycles in cryoablation PVI, local NF and distant FF signals were recorded, identified and labelled. BVEs were classified using four different machine learning algorithms based on four frequency domain (high-frequency power (PHF), low-frequency power (PLF), relative high power band, PHF ratio of neighbouring electrodes) and two time domain features (amplitude (Vmax), slew rate). The algorithm-based classification was compared to the true identification gained during the PVI and to a classification by cardiac electrophysiologists. RESULTS We included 335 BVEs from 57 consecutive patients. Using a single feature, PHF with a cut-off at 150 Hz showed the best overall accuracy for classification (79.4%). By combining PHF with Vmax, overall accuracy was improved to 82.7% with a specificity of 89% and a sensitivity of 77%. The overall accuracy was highest for the right inferior PV (96.6%) and lowest for the left superior PV (76.9%). The algorithm showed comparable accuracy to the classification by the EP specialists. CONCLUSIONS An automated farfield-nearfield discrimination based on two simple features from a single-beat BVE is feasible with a high specificity and comparable accuracy to the assessment by experienced cardiac electrophysiologists

Association of Heart Rate Variability With Silent Brain Infarcts in Patients With Atrial Fibrillation

Purpose: Silent brain infarcts (SBI) are frequently detected in patients with atrial fibrillation (AF), but it is unknown whether SBI are linked to autonomic dysfunction. We aimed to explore the association of autonomic dysfunction with SBI in AF patients. Methods: 1,358 AF patients without prior stroke or TIA underwent brain MRI and 5-min resting ECG. We divided our cohort into AF patients who presented in sinus rhythm (SR-group, n = 816) or AF (AF-group, n = 542). HRV triangular index (HRVI), standard deviation of normal-to-normal intervals, mean heart rate, root mean square root of successive differences of normal-to-normal intervals, 5-min total power and power in the low frequency, high frequency and very low frequency range were calculated. Primary outcome was presence of SBI in the SR group, defined as large non-cortical or cortical infarcts. Secondary outcomes were SBI volumes and topography. Results: Mean age was 72 ± 9 years, 27% were female. SBI were detected in 10.5% of the SR group and in 19.9% of the AF group (p < 0.001). HRVI <15 was the only HRV parameter associated with the presence of SBI after adjustment for clinical covariates in the SR group [odds ratio (OR) 1.67; 95% confidence interval (CI): 1.03–2.70; p = 0.037]. HRVI <15 was associated with larger brain infarct volumes [β (95% CI) −0.47 (−0.84; −0.09), p = 0.016] in the SR group and was more frequently observed in patients with right- than left-hemispheric SBI (p = 0.017). Conclusion: Impaired HRVI is associated with SBI in AF patients. AF patients with autonomic dysfunction might undergo systematic brain MRI screening to initiate intensified medical treatment

Influence of atrial substrate on local capture induced by rapid pacing of atrial fibrillation

Preliminary studies showed that the septum area was the only location allowing local capture of both the atria during rapid pacing of atrial fibrillation (AF) from a single site. The present model-based study investigated the influence of atrial substrate on the ability to capture AF when pacing the septum. Three biophysical models of AF with an identical anatomy from human atria but with different AF substrates were used: (i) AF based on multiple wavelets, (ii) AF based on heterogeneities in vagal activation, (iii) AF based on heterogeneities in repolarization. A fourth anatomical model without Bachmann's bundle (BB) was also implemented. Rapid pacing was applied from the septum at pacing cycle lengths in the range of 50-100% of AF cycle length. Local capture was automatically assessed with 24 pairs of electrodes evenly distributed on the atrial surface. The results were averaged over 16 AF simulations. In the homogeneous substrate, AF capture could reach 80% of the atrial surface. Heterogeneities degraded the ability to capture during AF. In the vagal substrate, the capture tended to be more regular and the degradation of the capture was not directly related to the spatial extent of the heterogeneities. In the third substrate, heterogeneities induced wave anchorings and wavebreaks even in areas close to the pacing site, with a more dramatic effect on AF capture. Finally, BB did not significantly affect the ability to capture. Atrial fibrillation substrate had a significant effect on rapid pacing outcomes. The response to therapeutic pacing may therefore be specific to each patient

Influence of Right and Left Atrial Tissue Heterogeneity on Atrial Fibrillation Perpetuation

We propose a biophysical modelling approach to separately investigate the impact of right and left atrial (RA/LA) electrical heterogeneity on atrial fibrillation (AF) perpetuation. The baseline AF substrate was based on a 4:1 anisotropy ratio and uniform membrane properties. AF was initiated by a ramp-pacing protocol applied in the pulmonary veins region. Once AF was observed, random patchy heterogeneities in action potential duration (shorter duration inside the patches) were introduced in the cellular model for the subsequent simulation of AF. The effect of tissue heterogeneity on AF perpetuation was quantified by the duration of AF episodes (an AF episode lasting more than 50 s was considered as sustained). For high percentages of heterogeneities, the mean AF episode duration and the number of non-terminated AF episodes were significantly higher for the RA compared to the LA. This could be indicative of a very probable involvement of the RA substrate into the persistent AF process in this model. A direct link between the spatial localization of tissue heterogeneity and AF duration was also observed

Study of the impact of electrical heterogeneities in the right and left atrium on atrial fibrillation perpetuation

Introduction: Electrical heterogeneity in the atria has been consistently linked with the initiation and perpetuation of atrial fibrillation (AF). The present model-based study investigated the contribution of action potential duration (APD) heterogeneities in the left atrium (LA) and right atrium (RA) on the perpetuation of the reentrant activity during AF. Methods: A computer model with a geometry based on computed tomography of AF patients and a Courtemanche atrial cellular model was implemented. Self-terminated AF episodes were initiated via ramp pacing in a model with modified channel conductance, homogeneous tissue and 4:1 anisotropy ratio. Once AF was observed, random patchy heterogeneities with shorter APD were separately introduced in the LA and the RA. Percentage of heterogeneities was progressively increased from 20% to 80% of each atrium size (characteristic length scale of patches was 7.5mm). For each simulation, the following values were assessed: average AF duration, the number of sustained AF episodes (lasting more than 50s), number of wave-fronts (#WF) and AF cycle length (AFCL). The results were averaged across the atria surface over 130 simulations (26 AF initial conditions and 5 random localizations of heterogeneities). Results: For the model with no heterogeneities, #WF was 6.82±3.67, AFCL 278±52ms and the average AF duration 15.42±9s. For low percentage of heterogeneities there were no significant differences between RA, LA and the model with no heterogeneities. For high percentage of heterogeneities the results showed that a significant right-to-left atrial APD gradient was associated with more sustained AF episodes, longer duration, higher #WF and shorter AFCL compared to the left-to-right APD gradient (sustained AF episodes: 95% vs. 52%, p<10-4; duration: 48±9s vs. 32.8±21s, p<0.05; #WF: 11.72±3.3 vs. 9.7±3.1, p<10-4; AFCL: 209±69ms vs. 223±64ms, p<0.05). Conclusion: High inter-atria differences in APD significantly affect the dynamics and the duration of the reentrant activity. Our findings are in line with previous studies reporting the right atrium as the dominant driver in some persistent AF cases