Predictive value of unshielded magnetocardiographic mapping to differentiate atrial fibrillation patients from healthy subjects

Background: P‐wave duration, its dispersion and signal‐averaged ECG, are currently used markers of vulnerability to atrial fibrillation (AF). However, since tangential atrial currents are better detectable at the body surface as magnetic than electric signals, we investigated the accuracy of magnetocardiographic mapping (MCG), recorded in unshielded clinical environments, as predictor of AF occurrence. Methods: MCG recordings, in sinus rhythm (SR), of 71 AF patients and 75 controls were retrospectively analyzed. Beside electric and magnetic P‐wave and PR interval duration, two MCG P‐wave subintervals, defined P‐dep and P‐rep, were measured, basing on the point of inversion of atrial magnetic field (MF). Eight parameters were calculated from inverse solution with “Effective Magnetic Dipole (EMD) model” and 5 from “MF Extrema” analysis. Discriminant analysis (DA) was used to assess MCG predictive accuracy to differentiate AF patients from controls. Results: All but one (P‐rep) intervals were significantly longer in AF patients. At univariate analysis, three EMD parameters differed significantly: in AF patients, the dipole‐ angle‐elevation angular speed was lower during P‐dep (p < 0.05) and higher during P‐rep (p < 0.001) intervals. The space‐trajectory during P‐rep and the angledynamics during P‐dep were higher (p < 0.05), whereas ratio‐dynamics P‐dep was lower (p < 0.01), in AF. At DA, with a combination of MCG and clinical parameters, 81.5% accuracy in differentiating AF patients from controls was achieved. At Cox‐regression, the angle‐dynamics P‐dep was an independent predictor of AF recurrences (p = 0.037). Conclusions: Quantitative analysis of atrial MF dynamics in SR and the solution of the inverse problem provide new sensitive markers of vulnerability to AF

Multimodal Characterization of the Atrial Substrate - Risks and Rewards of Electrogram and Impedance Mapping

The treatment of atrial rhythm disorders such as atrial fibrillation has remained a major challenge predominantly for patients with severely remodeled substrate. Individualized ablation strategies beyond pulmonary vein isolation in combination with real-time assess- ment of ablation lesion formation have been striven for insistently. Current approaches for identifying arrhythmogenic regions predominantly rely on electrogram-based features such as activation time and voltage or electrogram fractionation as a surrogate for tissue pathology. Despite bending every effort, large-scale clinical trials have yielded ambiguous results on the efficacy of various substrate mapping approaches without significant improvement of patient outcomes. This work focuses on enhancing the understanding of electrogram features and local impedance measurements in the atria towards the extraction of clinically relevant and predic- tive substrate characteristics. Features were extracted from intra-atrial electrograms with particular reference to the un- derlying excitation patterns to address morphological alterations caused by structural and functional changes. The noise level of unipolar electrograms was estimated and reduced by tailored filtering to enhance unipolar signal quality. Electrogram features exhibited nar- row distributions for healthy substrate across patients while a wide range was observed for pathologically altered excitation. Additionally, local impedance was investigated as a novel parameter and mapping modality. Having been introduced to the medical device market recently for monitoring ablative lesion formation, initial clinical experiences with local impedance-enabled catheters lack comple- mentary systematic investigations. Confounding factors and the potential for application as a tool for substrate mapping need elucidation. This work pursued a trimodal approach combining in human, in vitro, and in silico experiments to quantitatively understand the effect of distinct ambient conditions on the measured local impedance. Forward simulations of the spread of the electrical field with a finite element approach as well as the application of inverse solution methods to reconstruct tissue conductivity were implemented in silico. Adequate preprocessing steps were developed for measurements in human to eliminate artefacts automatically. Two clinical studies on local impedance as an indicator for ablation lesion formation and on local impedance based substrate mapping were conducted. Local impedance recordings identified both previously ablated and native scar areas irrespective of local excitation. A highly detailed in silico environment for local impedance measurements was validated with in vitro recordings and provided quantitative insights into the influence of changes in clinically relevant scenarios. Inverse reconstruction of relative tissue conductivity yielded promising results in silico. This work demonstrates that local impedance mapping shows great potential to comple- ment electrogram-based substrate mapping. A validated in silico environment for local impedance measurements can facilitate and optimize the development of next generation local impedance-enabled catheters. Conduction velocity, electrogram features, and recon- structed tissue conductivity suggest to be promising candidates for enhancing future clinical mapping systems

Predicting Successful Pulmonary Vein Isolation In Patients With Atrial Fibrillation By Brain Natriuretic Peptide Plasma Levels

Background: Catheter ablation for atrial fibrillation is a clinically established treatment by now while success rate varies between 60% and 85%. Interventional treatment of atrial fibrillation is still a challenging technique associated with a long procedure time and risk of major complications in up to 6 % of treated patients. The aim of this study was to investigate the predictive value of plasma brain natriuretic peptide (BNP) in patients undergoing pulmonary vein isolation concerning stable sinus rhythm after ablation.Methods: In 68 consecutive patients with atrial fibrillation (AF) and normal left ventricular ejection fraction, BNP was measured at baseline before pulmonary vein isolation (PVI). All patients received a 7-days-holter monitoring 3 months after radiofrequency (RF) ablation in order to detect recurrent AF episodes. Results: 48 patients with paroxysmal and 20 patients with persistent AF were enrolled. Baseline BNP was significantly higher in patients with persistent AF compared to patients with paroxysmal AF (145,5 pg/ml vs. 84,4 pg/ml; p<0,05). 3 months after PVI 38 patients (79,1%) with paroxysmal AF had a stable sinus rhythm documented on 7-days-holter monitoring, where as in 10 patients (20,9%) AF episodes were detected. Patients with a successful PVI showed significantly lower BNP plasma levels at baseline compared to patients with AF recurrrence (68,7 pg/ml vs. 144,1 pg/ml; p<0,05). In patients with persistent AF 55% (11 cases) had no recurrence of AF at 3 months 7-days holter and in 9 patients (45%) AF recurred. BNP plasma levels at baseline were lower in patients with stable sinusrhythm after 3 months compared to the group of recurrent AF (105,8 pg/ml vs. 193,3 pg/ml; p=0,11). Conclusion: Patients with AF and low preprocedural BNP plasma levels showed a better outcome after PVI. Thus BNP may be helpful in patient selection for a successful treatment of AF by PVI

The contact electrogram and its architectural determinants in atrial fibrillation

The electrogram is the sine qua non of excitable tissues, yet classification in atrial fibrillation (AF) remains poorly related to substrate factors. The objective of this thesis was to establish the relationship between electrograms and two commonly implicated substrate factors, connexin 43 and fibrosis in AF. The substrates and methods chosen to achieve this ranged from human acutely induced AF using open chest surgical mapping (Chapter 6), ex vivo whole heart Langendorff (Chapter 7) with in vivo telemetry confirming spontaneous AF in a new species of rat, the Brown Norway and finally isolated atrial preparations from an older cohort of rats using orthogonal pacing and novel co-localisation methods at sub-millimetre resolution and in some atria, optical mapping (Chapter 8). In rodents, electrode size and spacing was varied (Chapters 5, 10) to study its effects on structure function correlations (Chapter 9). Novel indices of AF organisation and automated electrogram morphology were used to quantify function (Chapter 4). Key results include the discoveries that humans without any history of prior AF have sinus rhythm electrograms with high spectral frequency content, that wavefront propagation velocities correlated with fibrosis and connexin phosphorylation ratios, that AF heterogeneity of conduction correlates to fibrosis and that orthogonal pacing in heavily fibrosed atria causes anisotropy in electrogram-fibrosis correlations. Furthermore, fibrosis and connexin 43 have differing and distinct spatial resolutions in their relationship with AF organisational indices. In conclusion a new model of AF has been found, and structure function correlations shown on an unprecedented scale, but with caveats of electrode size and direction dependence. These findings impact structure function methods and prove the effect of substrate on AF organisation.Open Acces

3Dマッピングシステムを用いた両心房Stimulus-V mapによる順行性速伝導路入口部の解剖学的位置並び特徴の検討

Purpose Previous studies examined the right atrial (RA) input site of the antegrade fast pathway (AFp) (AFpI). However, the left atrial (LA) input to the atrioventricular (AV) node has not been extensively evaluated. In this study, we created three-dimensional (3-D) bi-atrial stimulus-ventricle (St-V) maps and analyzed the input site and characteristics of the AFp in both the RA and LA. Methods Forty-four patients diagnosed with atrial fibrillation or WPW syndrome were included in this study. Three-dimensional bi-atrial St-V mapping was performed using an electroanatomical mapping system. Sites exhibiting the minimal St-V interval (MinSt-V) were defined as AFpIs and were classified into seven segments, four in the RA (F, S, M, and I) and three in the LA (M1, M2, and M3). By combining the MinSt-V in the RA and LA, the AFpIs were classified into three types: RA, LA, and bi-atrial (BA) types. The clinical and electrophysiological characteristics were compared. Results AFpIs were most frequently observed at site S in the RA (34%) and M2 in the LA (50%), and the BA type was the most common (57%). AFpIs in the LA were recognized in 75% of the patients. There were no clinical or electrophysiological indicators for predicting AFpI sites. Conclusions Three-dimensional bi-atrial St-V maps could classify AFpIs in both the RA and LA. AFpIs in the LA were frequently recognized. There were no significant clinical or electrophysiological indicators for predicting AFpI sites, and 3-D bi-atrial St-V mapping was the only method to reveal the precise AFp input site