Theoretical considerations for mapping activation in human cardiac fibrillation.
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ABSTRACT:
SUBMITTER: Rappel WJ
PROVIDER: S-EPMC3676373 | biostudies-other | 2013 Jun
REPOSITORIES: biostudies-other
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Project description:BACKGROUND:Phase analysis of cardiac arrhythmias, particularly atrial fibrillation, has gained interest because of the ability to detect organized stable drivers (rotors) and target them for therapy. However, the lack of methodology details in publications on the topic has resulted in ongoing debate over the phase mapping technique. By comparing phase maps and activation maps, we examined advantages and limitations of phase mapping. METHODS AND RESULTS:Seven subjects were enrolled. We generated phase maps and activation maps from electrocardiographic imaging-reconstructed epicardial unipolar electrograms. For ventricular signals, phase was computed with (1) pseudoempirical mode decomposition detrending and (2) a novel Moving Average (MVG) detrending approach. For atrial fibrillation signals, MVG was modified to incorporate dynamic cycle length (DCL) changes (MVG-DCL). Phase maps were visually analyzed to study phase singularity points and rotors. Results show that phase is sensitive to cycle length choice, a limitation that was addressed by the MVG-DCL algorithm. MVG-DCL was optimal for atrial fibrillation analysis. Phase maps helped to highlight high-curvature wavefronts and rotors. However, for some activation patterns, phase generated nonrotational singularity points and false rotors. CONCLUSIONS:Phase mapping computes singularity points and visually highlights rotors. As such, it can help to provide a clearer picture of the spatiotemporal activation characteristics during atrial fibrillation. However, it is advisable to incorporate electrogram characteristics and the time-domain activation sequence in the analysis, to prevent misinterpretation and false rotor detection. Therefore, for mapping complex arrhythmias, a combined time-domain activation and phase mapping with variable cycle length seems to be the most reliable method.
| S-EPMC5137810 | biostudies-literature
Project description:BackgroundElectrogram-based identification of the regions maintaining persistent Atrial Fibrillation (AF) is a subject of ongoing debate. Here, we explore the concept of local electrical dyssynchrony to identify AF drivers.Methods and resultsLocal electrical dyssynchrony was calculated using mean phase coherence. High-density epicardial mapping along with mathematical model were used to explore the link between local dyssynchrony and properties of wave conduction. High-density mapping showed a positive correlation between the dyssynchrony and number of fibrillatory waves (R2 = 0.68, p<0.001). In the mathematical model, virtual ablation at high dyssynchrony regions resulted in conduction regularization. The clinical study consisted of eighteen patients undergoing catheter ablation of persistent AF. High-density maps of left atrial (LA) were constructed using a circular mapping catheter. After pulmonary vein isolation, regions with the top 10% of the highest dyssynchrony in LA were targeted during ablation and followed with ablation of complex atrial electrograms. Catheter ablation resulted in termination during ablation at high dyssynchrony regions in 7 (41%) patients. In another 4 (24%) patients, transient organization was observed. In 6 (35%) there was no clear effect. Long-term follow-up showed 65% AF freedom at 1 year and 22% at 2 years.ConclusionsLocal electrical dyssynchrony provides a reasonable estimator of regional AF complexity defined as the number of fibrillatory waves. Additionally, it points to regions of dynamical instability related with action potential alternans. However, despite those characteristics, its utility in guiding catheter ablation of AF is limited suggesting other factors are responsible for AF persistence.
| S-EPMC5079563 | biostudies-literature
Project description:Experimental and clinical data demonstrate that atrial fibrillation (AF) maintenance in animals and groups of patients depends on localized reentrant sources localized primarily to the pulmonary veins and the left atrium posterior wall in paroxysmal AF but elsewhere, including the right atrium, in persistent AF. Moreover, AF can be eliminated by directly ablating AF-driving sources, or “rotors,” that exhibit high- frequency periodic activity.
| S-EPMC5547885 | biostudies-other
Project description:Background:Global simultaneous recording of atrial activation during atrial fibrillation (AF) can elucidate underlying mechanisms contributing to AF maintenance. A better understanding of these mechanisms may allow for an individualized ablation strategy to treat persistent AF. The study aims to characterize left atrial endocardial activation patterns during AF using noncontact charge-density mapping. Methods:Twenty-five patients with persistent AF were studied. Activation patterns were characterized into three subtypes: (i) focal with centrifugal activation (FCA); (ii) localized rotational activation (LRA); and (iii) localized irregular activation (LIA). Continuous activation patterns were analyzed and distributed in 18 defined regions in the left atrium. Results:A total of 144 AF segments with 1068 activation patterns were analyzed. The most common pattern during AF was LIA (63%) which consists of four disparate features of activation: slow conduction (45%), pivoting (30%), collision (16%), and acceleration (7%). LRA was the second-most common pattern (20%). FCA accounted for 17% of all activations, arising frequently from the pulmonary veins (PVs)/ostia. A majority of patients (24/25; 96%) showed continuous and highly dynamic patterns of activation comprising multiple combinations of FCA, LRA, and LIA, transitioning from one to the other without a discernible order. Preferential conduction areas were typically seen in the mid-anterior (48%) and lower-posterior (40%) walls. Conclusion:Atrial fibrillation is characterized by heterogeneous activation patterns identified in PV-ostia and non-PV regions throughout the LA at varying locations between individuals. Clinical implications of individualized ablation strategies guided by charge-density mapping need to be determined.
| S-EPMC7411208 | biostudies-literature
Project description:BackgroundModels for complex biological systems may involve a large number of parameters. It may well be that some of these parameters cannot be derived from observed data via regression techniques. Such parameters are said to be unidentifiable, the remaining parameters being identifiable. Closely related to this idea is that of redundancy, that a set of parameters can be expressed in terms of some smaller set. Before data is analysed it is critical to determine which model parameters are identifiable or redundant to avoid ill-defined and poorly convergent regression.Methodology/principal findingsIn this paper we outline general considerations on parameter identifiability, and introduce the notion of weak local identifiability and gradient weak local identifiability. These are based on local properties of the likelihood, in particular the rank of the Hessian matrix. We relate these to the notions of parameter identifiability and redundancy previously introduced by Rothenberg (Econometrica 39 (1971) 577-591) and Catchpole and Morgan (Biometrika 84 (1997) 187-196). Within the widely used exponential family, parameter irredundancy, local identifiability, gradient weak local identifiability and weak local identifiability are shown to be largely equivalent. We consider applications to a recently developed class of cancer models of Little and Wright (Math Biosciences 183 (2003) 111-134) and Little et al. (J Theoret Biol 254 (2008) 229-238) that generalize a large number of other recently used quasi-biological cancer models.Conclusions/significanceWe have shown that the previously developed concepts of parameter local identifiability and redundancy are closely related to the apparently weaker properties of weak local identifiability and gradient weak local identifiability--within the widely used exponential family these concepts largely coincide.
| S-EPMC2811744 | biostudies-literature
Project description:Experimental and clinical data demonstrate that atrial fibrillation (AF) maintenance in animals and groups of patients depends on localized reentrant sources localized primarily to the pulmonary veins (PVs) and the left atrium(LA) posterior wall in paroxysmal AF but elsewhere, including the right atrium (RA), in persistent AF. Moreover, AF can be eliminated by directly ablating AF-driving sources or "rotors," that exhibit high-frequency, periodic activity. The RADAR-AF randomized trial demonstrated that an ablation procedure based on a more target-specific strategy aimed at eliminating high frequency sites responsible for AF maintenance is as efficacious as and safer than empirically isolating all the PVs. In contrast to the standard ECG, global atrial noninvasive frequency analysis allows non-invasive identification of high-frequency sources before the arrival at the electrophysiology laboratory for ablation. Body surface potential map (BSPM) replicates the endocardial distribution of DFs with localization of the highest DF (HDF) and can identify small areas containing the high-frequency sources. Overall, BSPM had a sensitivity of 75% and specificity of 100% for capturing intracardiac EGMs as having LARA DF gradient. However, raw BSPM data analysis of AF patterns of activity showed incomplete and instable reentrant patterns of activation. Thus, we developed an analysis approach whereby a narrow band-pass filtering allowed selecting the electrical activity projected on the torso at the HDF, which stabilized the projection of rotors that potentially drive AF on the surface. Consequently, driving reentrant patterns ("rotors") with spatiotemporal stability during >70% of the AF time could be observed noninvasibly after HDF-filtering. Moreover, computer simulations found that the combination of BSPM phase mapping with DF analysis enabled the discrimination of true rotational patterns even during the most complex AF. Altogether, these studies show that the combination of DF analysis with phase maps of HDF-filtered surface ECG recordings allows noninvasive localization of atrial reentries during AF and further a physiologically-based rationale for personalized diagnosis and treatment of patients with AF.
| S-EPMC4341909 | biostudies-literature
Project description:Atrial fibrillation is the most common rhythm disorder of the heart associated with a rapid and irregular beating of the upper chambers. Activation mapping remains the gold standard to diagnose and interpret atrial fibrillation. However, fibrillatory activation maps are highly sensitive to far-field effects, and often disagree with other optical mapping modalities. Here we show that computational modeling can identify spurious non-local components of atrial fibrillation electrograms and improve activation mapping. We motivate our approach with a cohort of patients with potential drivers of persistent atrial fibrillation. In a computational study using a monodomain Maleckar model, we demonstrate that in organized rhythms, electrograms successfully track local activation, whereas in atrial fibrillation, electrograms are sensitive to spiral wave distance and number, spiral tip trajectories, and effects of fibrosis. In a clinical study, we analyzed n = 15 patients with persistent atrial fibrillation that was terminated by limited ablation. In five cases, traditional activation maps revealed a spiral wave at sites of termination; in ten cases, electrogram timings were ambiguous and activation maps showed incomplete reentry. By adjusting electrogram timing through computational modeling, we found rotational activation, which was undetectable with conventional methods. Our results demonstrate that computational modeling can identify non-local deflections to improve activation mapping and explain how and where ablation can terminate persistent atrial fibrillation. Our hybrid computational/physiological approach has the potential to optimize map-guided ablation and improve ablation therapy in atrial fibrillation.
| S-EPMC5880222 | biostudies-literature
Project description:UnlabelledIt is widely accepted that cyanobacteria-dependent oxygen that was released into Earth's atmosphere ca. 2.5 billion years ago sparked the evolution of the aerobic metabolism and the antioxidant system. In modern aerobes, enzymes such as superoxide dismutases (SODs), peroxiredoxins (PXs), and catalases (CATs) constitute the core of the enzymatic antioxidant system (EAS) directed against reactive oxygen species (ROS). In many anaerobic prokaryotes, the superoxide reductases (SORs) have been identified as the main force in counteracting ROS toxicity. We found that 93% of the analyzed strict anaerobes possess at least one antioxidant enzyme, and 50% have a functional EAS, that is, consisting of at least two antioxidant enzymes: one for superoxide anion radical detoxification and another for hydrogen peroxide decomposition. The results presented here suggest that the last universal common ancestor (LUCA) was not a strict anaerobe. O2 could have been available for the first microorganisms before oxygenic photosynthesis evolved, however, from the intrinsic activity of EAS, not solely from abiotic sources.Key wordsArchaea-Atmospheric gases-Evolution-H2O2 resistance-Oxygenic photosynthesis. Astrobiology 16, 348-358.
| S-EPMC4876498 | biostudies-literature
Project description:The concept of Receptor Mosaic (RM) is discussed; hence the integrative functions of the assemblage of G-protein coupled receptors physically interacting in the plane of the plasma membrane. The main focus is on a hetero-trimer of G-protein coupled receptors, namely the A2A-D2-CB1 receptor trimer. A bioinformatics analysis was carried out on the amino acid sequence of these receptors to indicate domains possibly involved in the receptor-receptor interactions. Such a bioinformatic analysis was also carried out on the RM formed by mGLU R5, D2 and A2A. The importance of topology, i.e., of the reciprocal localisation of the three interacting receptors in the plan of the membrane for the RM integrative functions is underlined. However, it is also pointed out that this fundamental aspect still waits techniques capable of an appropriate investigation. Finally, it is discussed how RM topology can give hints for a structural definition of the concept of hub receptor. Thus, just as in any network, the receptor operating as a hub is the one that in the molecular network formed by the receptors has the highest number of inputs.
| S-EPMC2949285 | biostudies-literature
Project description:We describe the first mapping of biological current in a live heart using ultrasound current source density imaging (UCSDI). Ablation procedures that treat severe heart arrhythmias require detailed maps of the cardiac activation wave. The conventional procedure is time-consuming and limited by its poor spatial resolution (5-10 mm). UCSDI can potentially improve on existing mapping procedures. It is based on a pressure-induced change in resistivity known as the acousto-electric (AE) effect, which is spatially confined to the ultrasound focus. Data from 2 experiments are presented. A 540 kHz ultrasonic transducer (f/# = 1, focal length = 90 mm, pulse repetition frequency = 1600 Hz) was scanned over an isolated rabbit heart perfused with an excitation-contraction decoupler to reduce motion significantly while retaining electric function. Tungsten electrodes inserted in the left ventricle recorded simultaneously the AE signal and the low-frequency electrocardiogram (ECG). UCSDI displayed spatial and temporal patterns consistent with the spreading activation wave. The propagation velocity estimated from UCSDI was 0.25 +/- 0.05 mm/ms, comparable to the values obtained with the ECG signals. The maximum AE signal-to-noise ratio after filtering was 18 dB, with an equivalent detection threshold of 0.1 mA/ cm(2). This study demonstrates that UCSDI is a potentially powerful technique for mapping current flow and biopotentials in the heart.
| S-EPMC2823813 | biostudies-literature