Noninvasive Assessment of Spatio-Temporal Recurrence in Atrial Fibrillation

Propagation of Atrial Activity during atrial fibrillation (AF) is a complex phenomenon characterized by a certain degree of recurrence (periodic repetition). In this study, we investigated the possibility to detect recurrence noninvasively from body surface potential map recordings in patients affected by persistent AF, and localize this recurrence both in time and space. Results showed that clusters of recurrence can be identified from body surface recordings in these patients. Moreover, the number of clusters detected and their location on the top-right of the back of the torso were significantly associated with AF recurrence 4 to 6 weeks after electrical cardioversion. This suggests that noninvasive quantification of recurrence in persistent AF patients is possible, and may contribute to improve patient stratification

Time course and mechanisms of endo-epicardial electrical dissociation during atrial fibrillation in the goat

Aims This study aims to determine the degree and mechanisms of endo-epicardial dissociation of electrical activity during atrial fibrillation (AF) and endo-epicardial differences in atrial electrophysiology at different stages of atrial remodelling. Methods and results Simultaneous high-density endo-epicardial mapping of AF was performed on left atrial free walls of goats with acute AF, after 3 weeks, and after 6 months of AF (all n = 7). Endo-epicardial activation time differences and differences in the direction of conduction vectors were calculated, endocardial and epicardial effective refractory periods (ERP) were determined, and fractionation of electrograms was quantified. Histograms of endo-epicardial activation time differences and differences in the direction of conduction vectors revealed two distinct populations, i.e. dissociated and non-dissociated activity. Dyssynchronous activity (dissociated in time) increased from 17 ± 7% during acute AF to 39 ± 17% after 3 weeks, and 68 ± 13% after 6 months of AF. Dissociation was more pronounced in thicker parts of the atrial wall (thick: 49.3 ± 21.4%, thin: 42.2 ± 19.0%, P < 0.05). At baseline, endocardial ERPs were longer when compared with epicardial ERPs (ΔERP, 21.8 ± 18 ms; P < 0.001). This difference was absent after 6 months of AF. The percentage of fractionated electrograms during rapid pacing increased from 9.4 ± 1.9% (baseline) to 18.6 ± 0.6% (6 months). Conclusion During AF, pronounced dissociation of electrical activity occurs between the epicardial layer and the endocardial bundle network. The increase in dissociation is due to owing to progressive uncoupling between the epicardial layer and the endocardial bundles and correlates with increasing stability and complexity of the AF substrat

Acute Changes in P-Wave Morphology by Pulmonary Vein Isolation in Atrial Fibrillation Patients

International audiencePulmonary vein (PV) plays an important role in atrial fibrillation (AF) initiation, progression, and stability. Successful PV isolation (PVI), either by radiofrequency catheter or Cryoballoon ablation, may terminate AF and prevent its recurrence. Whereas, incomplete PV isolation or reconnection of isolated PVs underlies mechanisms of AF recurrence. Hence, defining parameters able to predict a successful PVI and detect reconnections can assist clinicians in treatment of AF patients. Here, we developed a highly detailed human atrial model to simulate PVI and its acute effect on the P-wave morphology. Afterwards, the simulation results were compared and validated by recorded ECGs from patients before and after PVI procedure. In both simulation data and clinical recordings, we observed morphological changes in P-wave after PVI. More importantly our simulation helped us to find electrode positions in which the differences in P-wave morphology before and after PVI were more pronounced

Incidence, prevalence, and trajectories of repetitive conduction patterns in human atrial fibrillation

AIMS: Repetitive conduction patterns in atrial fibrillation (AF) may reflect anatomical structures harbouring preferential conduction paths and indicate the presence of stationary sources for AF. Recently, we demonstrated a novel technique to detect repetitive patterns in high-density contact mapping of AF. As a first step towards repetitive pattern mapping to guide AF ablation, we determined the incidence, prevalence, and trajectories of repetitive conduction patterns in epicardial contact mapping of paroxysmal and persistent AF patients. METHODS AND RESULTS: A 256-channel mapping array was used to record epicardial left and right AF electrograms in persistent AF (persAF, n = 9) and paroxysmal AF (pAF, n = 11) patients. Intervals containing repetitive conduction patterns were detected using recurrence plots. Activation movies, preferential conduction direction, and average activation sequence were used to characterize and classify conduction patterns. Repetitive patterns were identified in 33/40 recordings. Repetitive patterns were more prevalent in pAF compared with persAF [pAF: median 59%, inter-quartile range (41-72) vs. persAF: 39% (0-51), P < 0.01], larger [pAF: = 1.54 (1.15-1.96) vs. persAF: 1.16 (0.74-1.56) cm2, P < 0.001), and more stable [normalized preferentiality (0-1) pAF: 0.38 (0.25-0.50) vs. persAF: 0.23 (0-0.33), P < 0.01]. Most repetitive patterns were peripheral waves (87%), often with conduction block (69%), while breakthroughs (9%) and re-entries (2%) occurred less frequently. CONCLUSION: High-density epicardial contact mapping in AF patients reveals frequent repetitive conduction patterns. In persistent AF patients, repetitive patterns were less frequent, smaller, and more variable than in paroxysmal AF patients. Future research should elucidate whether these patterns can help in finding AF ablation targets

Clinical and electrophysiological predictors of device-detected new-onset atrial fibrillation during 3 years after cardiac surgery

Postoperative atrial fibrillation (POAF) after cardiac surgery is an independent predictor of stroke and mortality late after discharge. We aimed to determine the burden and predictors of early (up to 5th postoperative day) and late (after 5th postoperative day) new-onset atrial fibrillation (AF) using implantable loop recorders (ILRs) in patients undergoing open chest cardiac surgery Seventy-nine patients without a history of AF undergoing cardiac surgery underwent peri-operative high-resolution mapping of electrically induced AF and were followed 36 months after surgery using an ILR (Reveal XTTM). Clinical and electrophysiological predictors of late POAF were assessed. POAF occurred in 46 patients (58%), with early POAF detected in 27 (34%) and late POAF in 37 patients (47%). Late POAF episodes were short-lasting (mostly between 2 min and 6 h) and showed a circadian rhythm pattern with a peak of episode initiation during daytime. In POAF patients, electrically induced AF showed more complex propagation patterns than in patients without POAF. Early POAF, right atrial (RA) volume, prolonged PR time, and advanced age were independent predictors of late POAF

Heart Failure, Female Sex, and Atrial Fibrillation Are the Main Drivers of Human Atrial Cardiomyopathy: Results From the CATCH ME Consortium

Background: Atrial cardiomyopathy (atCM) is an emerging prognostic factor in cardiovascular disease. Fibrotic remodeling, cardiomyocyte hypertrophy, and capillary density are hallmarks of atCM. The contribution of etiological factors and atrial fibrillation (AF) to the development of differential atCM phenotypes has not been quantified. This study aimed to evaluate the association between histological features of atCM and the clinical phenotype. Methods and results: We examined left atrial (LA, n=95) and right atrial (RA, n=76) appendages from a European cohort of patients undergoing cardiac surgery. Quantification of histological atCM features was performed following wheat germ agglutinin/CD31/vimentin staining. The contributions of AF, heart failure, sex, and age to histological characteristics were determined with multiple linear regression models. Persistent AF was associated with increased endomysial fibrosis (LA: +1.13±0.47 μm, P=0.038; RA: +0.94±0.38 μm, P=0.041), whereas total extracellular matrix content was not. Men had larger cardiomyocytes (LA: +1.92±0.72 μm, P<0.001), while women had more endomysial fibrosis (LA: +0.99±0.56 μm, P=0.003). Patients with heart failure showed more endomysial fibrosis (LA: +1.85±0.48 μm, P<0.001) and extracellular matrix content (LA: +3.07±1.29%, P=0.016), and a higher capillary density (LA: +0.13±0.06, P=0.007) and size (LA: +0.46±0.22 μm, P=0.044). Fuzzy k-means clustering of histological features identified 2 subtypes of atCM: 1 characterized by enhanced endomysial fibrosis (LA: +3.17 μm, P<0.001; RA: +2.86 μm, P<0.001), extracellular matrix content (LA: +3.53%, P<0.001; RA: +6.40%, P<0.001) and fibroblast density (LA: +4.38%, P<0.001), and 1 characterized by cardiomyocyte hypertrophy (LA: +1.16 μm, P=0.008; RA: +2.58 μm, P<0.001). Patients with fibrotic atCM were more frequently female (LA: odds ratio [OR], 1.33, P=0.002; RA: OR, 1.54, P=0.004), with persistent AF (LA: OR, 1.22, P=0.036) or heart failure (LA: OR, 1.62, P<0.001). Hypertrophic features were more common in men (LA: OR=1.33, P=0.002; RA: OR, 1.54, P=0.004). Conclusions: Fibrotic atCM is associated with female sex, persistent AF, and heart failure, while hypertrophic features are more common in men

Analysis of drug-induced and spontaneous cardioversions reveals similar patterns leading to termination of atrial fibrillation

Introduction: The mechanisms leading to the conversion of atrial fibrillation (AF) to sinus rhythm are poorly understood. This study describes the dynamic behavior of electrophysiological parameters and conduction patterns leading to spontaneous and pharmacological AF termination. Methods: Five independent groups of goats were investigated: (1) spontaneous termination of AF, and drug-induced terminations of AF by various potassium channel inhibitors: (2) AP14145, (3) PA-6, (4) XAF-1407, and (5) vernakalant. Bi-atrial contact mapping was performed during an open chest surgery and intervals with continuous and discrete atrial activity were determined. AF cycle length (AFCL), conduction velocity and path length were calculated for each interval, and the final conduction pattern preceding AF termination was evaluated. Results: AF termination was preceded by a sudden episode of discrete activity both in the presence and absence of an antiarrhythmic drug. This episode was accompanied by substantial increases in AFCL and conduction velocity, resulting in prolongation of path length. In 77% ± 4% of all terminations the conduction pattern preceding AF termination involved medial to lateral conduction along Bachmann’s bundle into both atria, followed by anterior to posterior conduction. This finding suggests conduction block in the interatrial septum and/or pulmonary vein area as final step of AF termination. Conclusion: AF termination is preceded by an increased organization of fibrillatory conduction. The termination itself is a sudden process with a critical role for the interplay between spatiotemporal organization and anatomical structure

An angiopoietin 2, FGF23, and BMP10 biomarker signature differentiates atrial fibrillation from other concomitant cardiovascular conditions

Abstract Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69 years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n = 933) and validated in the remaining patients (n = 552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation