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

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

A Novel Mapping Strategy of Repetitive Patterns in Consecutive Recordings to Localize Atrial Fibrillation Sources:an In-Silico Study

In some patients with persistent atrial fibrillation (AF), localized functional mechanisms may sustain AF and thus represent ablation targets. We propose a novel mapping strategy to locate AF sources by combining repetitive patterns from consecutive high-density mapping recordings. The algorithm moves the catheter iteratively upstream of the main repetitive conduction direction to identify an AF source either by direct classification of local activation patterns or by encircling it. We tested the performance and robustness of this approach in two groups of detailed AF simulations, without and with severe structural remodeling (N=20 per group, 20 starting positions per simulation), using a 4times 4 grid mapping catheter (3mm spacing). Structural remodeling led to more simultaneous sources (median [IQR], 2 [1; 3] vs 3 [2; 5], p &lt; 0.001) that meandered in larger areas (127.5 [82.0; 216.0] vs 188.0 [121.2; 305.5] mm2, p &lt; 0.05. The mapping approach localized a source in 6 [4; 9] vs. 5 [5; 8] steps for the groups without and with structural remodeling (p &lt; 0.001), with an accuracy of 11 [7; 16] vs 9 [6; 14] mm (p=0.046). Sources were localized by encircling in 62.6% vs. 41.4% of the detection in both groups, respectively. The proposed mapping strategy detected AF sources accurately within a few steps, even in complex AF substrates, with a substantial contribution of encircling to detect sources.</p

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

Circulating BMP10 Levels Associate With Late Postoperative Atrial Fibrillation and Left Atrial Endomysial Fibrosis

Background: Serum bone morphogenetic protein 10 (BMP10) blood levels are a marker for history of atrial fibrillation (AF) and for major adverse cardiovascular events in patients with AF, including stroke, AF recurrences after catheter ablations, and mortality. The predictive value of BMP10 in patients undergoing cardiac surgery and association with morphologic properties of atrial tissues are unknown. Objectives: This study sought to study the correlation between BMP10 levels and preoperative clinical traits, occurrence of early and late postoperative atrial fibrillation (POAF), and atrial fibrosis in patients undergoing cardiac surgery. Methods: Patients with and without preoperative AF history undergoing first cardiac surgery were included (RACE V, n = 147). Preoperative blood biomarkers were analyzed, left (n = 114) and right (n = 125) atrial appendage biopsy specimens were histologically investigated after WGA staining, and postoperative rhythm was monitored continuously with implantable loop recorders (n = 133, 2.5 years). Results: Adjusted multinomial logistic regression indicated that BMP10 accurately reflected a history of persistent AF (OR: 1.24, 95% CI: 1.10-1.40, P = 0.001), similar to NT-pro-BNP. BMP10 levels were associated with increased late POAF90 occurrence after adjustment for age, sex, AF history, and early POAF occurrence (HR: 1.07 [per 0.1 ng/mL increase], 95% CI: 1.00-1.14, P = 0.041). Left atrial endomysial fibrosis (standardized β = 0.22, P = 0.041) but not overall fibrosis (standardized Β = 0.12, P = 0.261) correlated with circulating BMP10 after adjustment for age, sex, AF history, reduced LVF, and valvular surgery indication. Conclusions: Increased BMP10 levels were associated with persistent AF history, increased late POAF incidence, and LAA endomysial fibrosis in a diverse sample of patients undergoing cardiac surgery.</p

The electrocardiogram as a predictor of successful pharmacological cardioversion and progression of atrial fibrillation

Aims Non-invasive characterization of atrial fibrillation (AF) substrate complexity based on the electrocardiogram (ECG) may improve outcome prediction in patients receiving rhythm control therapies for AF. Multiple parameters to assess AF complexity and predict treatment outcome have been suggested. A comparative study of the predictive performance of complexity parameters on response to therapy and progression of AF in a large patient population is needed to standardize non-invasive analysis of AF.Methods and results A large variety of ECG complexity parameters were systematically compared in patients with recent onset AF undergoing pharmacological cardioversion (PCV) with flecainide. Parameters were computed on 10-s 12-lead ECGs of 221 patients before drug administration. The ability of ECG parameters to predict successful PCV and progression to persistent AF (mean follow-up 49 months) was evaluated and compared with common clinical predictors. Optimal prediction performance of successful PCV using only one ECG parameter was low, using dominant atrial frequency [lead II, receiver operating area under curve (AUC) 0.66, 95% confidence interval [0.64-0.67]], but the optimal combination of several ECG parameters strongly improved predictive performance (AUC 0.78 [0.76-0.79]). While predictive value of the optimal combination of clinical predictors was low (AUC 0.68 [0.66-0.70], using right atrial volume and weight), adding ECG parameters strongly increased performance (AUC 0.81 [0.79-0.82], P &lt;0.001). Interestingly, higher dominant frequency and higher f-wave amplitude were associated with increased risk of progression to persistent AF during follow-up.Conclusion Assessment of AF complexity from 12-lead ECGs significantly improves prediction of successful PCV and progression to persistent AF compared with common clinical and echocardiographic predictors.</p

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