Introduction: Atrial fibrillation (AF) is not effectively treated in clinics due to a lack of adequate tools for identifying AF drivers as targets in ablation treatment. Recent studies revealed that 30-50% of patients with persistent AF have drivers not only in the left atrium (LA) but also in the right atrium (RA). However, the precise substrate underlying RA AF drivers remains elusive. Hypothesis: High-resolution analysis of human atrial wall 3D structure can predict the occurrence of right atrial drivers. Methods: Coronary perfused explanted human atria (N=10, 46.2±14.7 y.o.;40% female) were optically mapped with high-resolution CMOS cameras. Sustained AF was induced by fast pacing and perfusion of adenosine and/or isoproterenol. Hearts were imaged at ~170μm 3 resolution by 9.4T gadolinium-enhanced MRI (Fig. A). A coupled PDE approach was utilized to estimate the atrial wall thickness (Fig. B). Fibrosis was identified above a signal intensity threshold validated by histology; and fibrosis density was constructed for each voxel by determining the percent of neighboring fibrotic voxels within a radius of 5 voxels. Results: Optical mapping identified 9 RA drivers in 6 hearts (H1-6) and 7 LA drivers in 5 hearts (H5, 6 and 8-10, Fig. C). All 9 RA AF drivers were anchored in myobundle structure in close proximity to the crista terminalis (CT). Wall thickness distribution in RA excluding the CT was similar to that in the LA (N=10, Fig. D). Structural analysis showed that RA with AF drivers (N=6) was thicker with greater wall variation and higher fibrosis density than RA without AF drivers (N=4, Fig. E). Furthermore, RA driver regions (N=9) were thicker and varied more than other RA regions (4.64±2.86 mm vs 4.56±2.57mm, p<0.05). Conclusions: For the first time, the 3D structural analysis demonstrates that structural features including atrial wall thickness and its variation near the CT can predict RA driver occurrences in human hearts and be used to improve targeted ablation.
The organization of a behavioral act as a systemic process is always the result of an interaction between the cerebral cortex and many subcortical formations. Experiments carried out in our laboratory [8, 10, 16, 19, 22, 24] have demonstrated an important role for the striato-nigro-thalamic system in the structural-functional organization of behavioral acts. In particular, experiments have shown that anodic polarization of the sensorimotor and orbital cortex and thalamus temporarily switches off the functions of these structures, leading to a disturbance in conditioned reflexes and alteration in neuronal activity in the neostriatum [10, 16]. This is accompanied by a slowing of the process of forming a program of conditioned reflex behavior and encoding it via efferent pathways. Analogous results have been obtained in experiments with pharmacological blockade of outputs to the neostriatum from the substantia nigra, the medial center of the thalamus, and the ventral field of the tegmentum. In dogs subjected to these conditions, there is a disturbance in the formation of motor feeding and operant-defensive conditioned reflexes, and there is failure to produce previously developed programs of behavior linked with the analysis of environmental signals [4, 5, 23].Studies were carried out on the correlates of neuronal rearrangements in the caudate nucleus and parafascicular nuclei of the thalamus during the development of operant-defensive reflexes [15][16][17]. The spatial organization of many subcortical projections of the striopallidum have been determined, these involving interactions of the striato-nigro-thalamic structures during the formation of food and defensive reflexes of different levels of complexity; this is the classical model for the study of behavior in experimental conditions [8].Intensive studies are under way in a number of Russian and foreign laboratories on these questions of the structural-functional organization of behavioral acts [2, 6, 18, 26, 27, 29]. Despite numerous investigations of the subcortical mechanisms of behavior, particularly those aimed at elucidating the role in these processes of the neostriatum and its associated thalamic nuclei and the substantia nigra, many aspects of the interactions of these structures during the formation and execution of behavioral acts remain unclear. Thus, there has been insufficient study of the role of the neurochemical mechanisms of the neostriatum in the organization of conditioned feeding reflexes during free behavior. Additionally, the topical organization of dopamine-containing connections in the midbrain with the neostriatal nuclei in cats has not received full study. In dogs, these afferents have not been studied at all. The nature of the relationship between the spike activity of the caudate nucleus and the ventral anterior and ventrolateral nuclei of the thalamus during operant-defensive behavior remains unclear.The aim of the present work was to study these questions, which are linked to an understanding of the function of striato-nigro-tha...
Introduction: Persistent atrial fibrillation (perAF) may be maintained by localized extra-pulmonary vein (PV) drivers. Most clinical studies have focused on left atrial (LA) sources ablation, but right atrial (RA) arrhythmogenic substrate, due to certain comorbidities, may also maintain perAF. Hypothesis: Patient (Pt)-specific characteristics and comorbidities may predict occurrence of RA AF drivers. Methods: Consecutive Pts (n=105) underwent driver ablation in addition to PV isolation for perAF after panoramic multi-electrode mapping (MEM) at a single medical center. Logistic regression (LR) models were used to characterize the relationship between Pt characteristics and presence of AF drivers in each atrium. LR was used to predict 12-month AF-free survival. Results: Pts were 63.1±9.9 years old, 24.8% female, 21.9% in HF, 76.2% had HTN, 24.8% had DM, 22.9% had CAD and 59.0% had OSA. MEM identified a mean of 1.6±1.2 LA drivers and 1.4±1.2 RA drivers per Pt. Forty two Pts had drivers in both LA and RA, 19 in RA only, and 26 in LA only. Older age was a predictor of RA drivers presence (p=0.06), factors that predicted presence of LA drivers were female gender (p=0.19), HTN (p=0.03), and comorbidity score (p = 0.07). CHADS 2 -VASc score and LVEF predicted both LA and RA drivers. Following ablation, 75% of the Pts sustained sinus rhythm after 6 months, 70% after 12 months and 72% after 18 months. AF recurrence within 12 months of ablation was associated with DM (p=0.03), BMI (p=0.03) and RV systolic pressure (p=0.07). Presence of RA drivers was not associated with the 12 and 18-months freedom from AF. Conclusions: In this cohort of perAF patients, older age and higher CHADS 2 -VASc score predicted RA driver occurrence. These preliminary findings suggest that patient-specific clinical characteristics may uniquely impact LA vs RA myocardium by promoting development of chamber-specific arrhythmogenic structural and functional substrates of AF drivers.
Introduction: Conventional multielectrode mapping is not sufficient to reveal subsurface intramural activation. Thus, atrial fibrillation (AF) driver identification remains challenging. To overcome these limitations we utilized machine learning (ML) to identify AF drivers based on the combination of electrogram (EGM) and 3D structural magnetic resonance imaging (MRI) features. Hypothesis: Detailed electrogram features analysis, including minor deflections, combined with local structural features, can be used to define AF driver. Methods: Sustained AF was mapped in coronary perfused explanted human atria (n=7) with near-infrared optical mapping (NIOM) (0.3-0.9mm 2 resolution) and 64-electrode mapping catheter (3mm 2 resolution). Unipolar EGMs were analyzed for multiple features of the steepest negative deflection and the 2nd-4th steepest deflections in multicomponent EGMs. Atria underwent 9.4T MRI (154-180μm 3 resolution) with gadolinium enhancement and histology validation of fibrosis. Both 3D structural and EGM data from NIOM defined driver and non-driver regions were processed by ML algorithms (LR; PLSDA; GBM; CRF; PSVM; RSVM) using double cross-validation. Results: AF drivers’ reentrant tracks were defined by NIOM activation mapping, the gold-standard, and confirmed by targeted ablation. The best performing ML algorithm (PLSDA) correctly classified mapped driver region with 76.1% accuracy on the testing data. The most important features included sub-endocardial fibrosis, sub-epicardial fiber orientation, local wall thickness, beat-to-beat variability of multicomponent EGM deflections. Conclusions: The ML models pre-trained on combined EGM and structural features allow efficient classification of AF driver vs non-driver regions defined by the NIOM gold-standard. The results suggest that AF driver substrates formed by the combination of 3D fibrotic structural features, which correlate with local EGM characteristics.
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