Abstract Background The underlying mechanisms sustaining human persistent atrial fibrillation (PsAF) is poorly understood. Objectives This study sought to investigate the complexity and distribution ...of AF drivers in PsAF of varying durations. Methods Of 135 consecutive patients with PsAF, 105 patients referred for de novo ablation of PsAF were prospectively recruited. Patients were divided into 3 groups according to AF duration: PsAF presenting in sinus rhythm (AF induced), PsAF <12 months, and PsAF >12 months. Patients wore a 252-electrode vest for body surface mapping. Localized drivers (re-entrant or focal) were identified using phase-mapping algorithms. Results In this patient cohort, the most prominent re-entrant driver regions included the pulmonary vein (PV) regions and inferoposterior left atrial wall. Focal drivers were observed in 1 or both PV regions in 75% of patients. Comparing between the 3 groups, with longer AF duration AF complexity increased, reflected by increased number of re-entrant rotations (p < 0.05), number of re-entrant rotations and focal events (p < 0.05), and number of regions harboring re-entrant (p < 0.01) and focal (p < 0.05) drivers. With increased AF duration, a higher proportion of patients had multiple extra-PV driver regions, specifically in the inferoposterior left atrium (p < 0.01), superior right atrium (p < 0.05), and inferior right atrium (p < 0.05). Procedural AF termination was achieved in 70% of patients, but decreased with longer AF duration. Conclusions The complexity of AF drivers increases with prolonged AF duration. Re-entrant and focal drivers are predominantly located in the PV antral and adjacent regions. However, with longer AF duration, multiple drivers are distributed at extra-PV sites. AF termination rate declines as patients progress to longstanding PsAF, underscoring the importance of early intervention.
Specific noninvasive signal processing was applied to identify drivers in distinct categories of persistent atrial fibrillation (AF).
In 103 consecutive patients with persistent AF, accurate biatrial ...geometry relative to an array of 252 body surface electrodes was obtained from a noncontrast computed tomography scan. The reconstructed unipolar AF electrograms acquired at bedside from multiple windows (duration, 9±1 s) were signal processed to identify the drivers (focal or reentrant activity) and their cumulative density map. The driver domains were catheter ablated by using AF termination as the procedural end point in comparison with the stepwise-ablation control group. The maps showed incessantly changing beat-to-beat wave fronts and varying spatiotemporal behavior of driver activities. Reentries were not sustained (median, 2.6 rotations lasting 449±89 ms), meandered substantially but recurred repetitively in the same region. In total, 4720 drivers were identified in 103 patients: 3802 (80.5%) reentries and 918 (19.5%) focal breakthroughs; most of them colocalized. Of these, 69% reentries and 71% foci were in the left atrium. Driver ablation alone terminated 75% and 15% of persistent and long-lasting AF, respectively. The number of targeted driver regions increased with the duration of continuous AF: 2 in patients presenting in sinus rhythm, 3 in AF lasting 1 to 3 months, 4 in AF lasting 4 to 6 months, and 6 in AF lasting longer. The termination rate sharply declined after 6 months. The mean radiofrequency delivery to AF termination was 28±17 minutes versus 65±33 minutes in the control group (P<0.0001). At 12 months, 85% patients with AF termination were free from AF, similar to the control population (87%,); P=not significant.
Persistent AF in early months is maintained predominantly by drivers clustered in a few regions, most of them being unstable reentries.
Noninvasive Panoramic Mapping of Human Atrial Fibrillation Mechanisms
Introduction
Recent developments in body surface mapping and computer processing have allowed noninvasive mapping of atrial ...activation responsible for various cardiac arrhythmias with increasingly greater resolution. We developed specific algorithms to identify localized sources and atrial propagation occurring simultaneously during ongoing atrial fibrillation (AF).
Methods and Results
We report the feasibility of noninvasive panoramic mapping of human AF mechanisms and its validation by successful ablation. We used a commercially available mapping system using an array of 252 body surface electrodes and noncontrast thoracic CT scan to obtain high‐resolution images of the biatrial geometry and the relative electrode positions. On the surface unipolar electrograms acquired during AF we developed specific signal‐analysis process combining filtering, wavelet transform, and phase mapping. At least 5 windows with spontaneous, long ventricular pauses were selected for mapping. The incidence, location and characteristics of localized sources (foci and rotors) were assessed on the cumulative duration of all recorded windows.
In a patient with paroxysmal AF, noninvasive maps showed multiple single or repetitive discharges from 3 pulmonary veins (PVs), a rotor meandering along the right venous ostia, and their mutual interplay. All areas outside the left posterior wall were passively activated. AF terminated during isolation of right PV.
In a patient with persistent AF for 7 months, a rotor was identified recurrently, drifting in the left atrial inferior and posterior wall and in the roof. It was not stationary for more than 2 rotations. The right atrial free wall was activated over the Bachman's bundle by a passive wavefront propagating in a counterclockwise pattern. Ablation at the rotor locations abruptly converted AF into atrial tachycardia after 10 minutes of radiofrequency application. Further mapping and ablation confirmed a counterclockwise cavotricuspid isthmus—dependent flutter.
Conclusions
This report demonstrates the feasibility of noninvasive panoramic mapping of AF in identifying active sources, which include unstable rotors and PV foci, and its validation by ablation results.
In susceptible individuals, inhalation of Aspergillus spores can affect the respiratory tract in many ways. These spores get trapped in the viscid sputum of asthmatic subjects which triggers a ...cascade of inflammatory reactions that can result in Aspergillus-induced asthma, allergic bronchopulmonary aspergillosis (ABPA), and allergic Aspergillus sinusitis (AAS). An immunologically mediated disease, ABPA, occurs predominantly in patients with asthma and cystic fibrosis (CF). A set of criteria, which is still evolving, is required for diagnosis. Imaging plays a compelling role in the diagnosis and monitoring of the disease. Demonstration of central bronchiectasis with normal tapering bronchi is still considered pathognomonic in patients without CF. Elevated serum IgE levels and Aspergillus-specific IgE and/or IgG are also vital for the diagnosis. Mucoid impaction occurring in the paranasal sinuses results in AAS, which also requires a set of diagnostic criteria. Demonstration of fungal elements in sinus material is the hallmark of AAS. In spite of similar histopathologic features, co-existence of ABPA and AAS is still uncommon. Oral corticosteroids continue to be the mainstay of management of allergic aspergillosis. Antifungal agents play an adjunctive role in ABPA as they help reduce the fungal load. Saprophytic colonization in cavitary ABPA may lead to aspergilloma formation, which could increase the severity of the disease. The presence of ABPA, AAS, and aspergilloma in the same patient has also been documented. All patients with Aspergillus-sensitized asthma must be screened for ABPA, and AAS should always be looked for.
The mechanisms responsible for perpetuation of human persistent atrial fibrillation (AF) are controversial and probably vary between individuals. A wide spectrum of mechanisms have been described in ...experimental studies, ranging from a single localized stable (focal/reentrant) source, to multiple sources, up to diffuse bi‐atrial wavelets. We characterized AF drivers in patients with persistent AF (lasting less than 1 year) using novel high resolution mapping, imaging and modelling approaches with the objective of evaluating their relationship to atrial structural heterogeneities. Using panoramic non‐invasive mapping in humans, focal or reentrant sources driving AF waves were identified, originating from multiple distinct regions and exhibiting short lifespans and periodic recurrences in the same locations. The reentrant driver regions harboured long, fractionated electrograms covering most of the fibrillatory cycle lengths with varying beat‐to‐beat sequences suggestive of unstable trajectories attached to slow conducting heterogeneous tissue. MRI atrial imaging demonstrated that such drivers preferentially clustered at the borders of fibrotic atrial regions. In patient‐specific computer simulations, sustained AF was shown to be driven by meandering transitory reentries attached to fibrosis borders expressing specific metrics in density and extent. Finally, random microstructural alterations devoid of cellular electrical changes were modelled, showing that a percolation mechanism could also explain atrial reentries and complex fractionated electrograms. These data from clinical, imaging and computational studies strongly suggest that intermittent and spatially unstable drivers anchoring to structural heterogeneities are a major pathophysiological mechanism in human persistent atrial fibrillation.
Anchoring of AF drivers from mapping, imaging and computational studies.
This study aimed to determine 5-year efficacy of catheter ablation for persistent atrial fibrillation (AF) using AF termination as a procedural end point.
One hundred fifty patients (57±10 years) ...underwent persistent AF ablation using a stepwise ablation approach (pulmonary vein isolation, electrogram-guided, and linear ablation) with the desired procedural end point being AF termination. Repeat ablation was performed for recurrent AF or atrial tachycardia. AF was terminated by ablation in 120 patients (80%). Arrhythmia-free survival rates after a single procedure were 35.3%±3.9%, 28.0%±3.7%, and 16.8%±3.2% at 1, 2, and 5 years, respectively. Arrhythmia-free survival rates after the last procedure (mean 2.1±1.0 procedures) were 89.7%±2.5%, 79.8%±3.4%, and 62.9%±4.5%, at 1, 2, and 5 years, respectively. During a median follow-up of 58 (interquartile range, 43-73) months after the last ablation procedure, 97 of 150 (64.7%) patients remained in sinus rhythm without antiarrhythmic drugs. Another 14 (9.3%) patients maintained sinus rhythm after reinitiation of antiarrhythmic drugs, and an additional 15 (10.0%) patients regressed to paroxysmal recurrences only. Failure to terminate AF during the index procedure (hazard ratio 3.831; 95% confidence interval, 2.070-7.143; P<0.001), left atrial diameter≥50 mm (hazard ratio 2.083; 95% confidence interval, 1.078-4.016; P=0.03), continuous AF duration≥18 months (hazard ratio 1.984; 95% confidence interval, 1.024-3.846; P<0.04), and structural heart disease (hazard ratio 1.874; 95% confidence interval, 1.037-3.388; P=0.04) predicted arrhythmia recurrence.
In patients with persistent AF, an ablation strategy aiming at AF termination is associated with freedom from arrhythmia recurrence in the majority of patients over a 5-year follow-up period. Procedural AF nontermination and specific baseline factors predict long-term outcome after ablation.
Electrical Burns Shah, Ashok C.
Indian Journal of Plastic Surgery/Indian journal of plastic surgery,
03/2024, Letnik:
17, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Summary The pathophysiology of electrical burns and the ways it differs from thermal turns are discussed. 134 cases of electrical burns during 5 years period are presented, out of which only 25 cases ...required different types of specialised surgical management.
Anaplastic thyroid cancer Ranganath, Rohit; Shah, Manish A; Shah, Ashok R
Current opinion in endocrinology, diabetes, and obesity,
10/2015, Letnik:
22, Številka:
5
Journal Article
Recenzirano
Anaplastic thyroid cancer (ATC) is a rare malignancy of the thyroid with a high mortality rate. Conventional therapy has not been effective. Several biological agents are being investigated. The ...purpose of the review is to highlight the current standards for treatment and review new targets for treating ATC.
Retrospective studies have led to formulation of guidelines for management, including those by the American Thyroid Association. An expansion in the understanding of the genetic mutations has led to several newer biological agents being tested to treat ATC. Aurora kinase inhibitors, PPAR γ agonists, and vascular targeting agents are some of the latest therapeutic agents that have shown promise and could become standard of therapy with further supporting research.
Further well coordinated preclinical and clinical research is needed to support the emerging treatments for ATC.
Left atrial appendage (LAA) is implicated in maintenance of atrial fibrillation (AF) and atrial tachycardia (AT) associated with persistent AF (PsAF) ablation, although little is known about the ...incidence and mechanism of LAA AT.
The purpose of this study was to characterize LAA ATs associated with PsAF ablation.
In 74 consecutive patients undergoing stepwise PsAF ablation, 142 ATs were encountered during index and repeat procedures. Out of 78 focal-source ATs diagnosed by activation and entrainment mapping, 15 (19%) arose from the base of LAA. Using a 20-pole catheter, high-density maps were constructed (n = 10; age 57 ± 6 years) to characterize the mechanism of LAA-AT. The LAA orifice was divided into the posterior ridge and anterior-superior and inferior segments to characterize the location of AT.
Fifteen patients with LAA AT had symptomatic PsAF for 17 ± 15 months before ablation. LAA AT (cycle length CL 283 ± 30 ms) occurred during the index procedure in four and after 9 ± 7 months in 11 patients. We could map 89% ± 8% AT CLs locally with favorable entrainment from within the LAA, which is suggestive of localized reentry with centrifugal atrial activation. ATs were localized to inferior segment (n = 4), anterior-superior segment (n = 5), and posterior ridge (n = 6) with 1:1 conduction to the atria. Ablation targeting long fractionated or mid-diastolic electrogram within the LAA resulted in tachycardia termination. Postablation, selective contrast radiography demonstrated atrial synchronous LAA contraction in all but one patient. At 18 ± 7 months, 13/15 (87%) patients remained in sinus rhythm without antiarrhythmic drugs.
LAA is an important source of localized reentrant AT in patients with PsAF at index and repeat ablation procedures. Ablation targeting the site with long fractionated or mid-diastolic LAA electrogram is highly effective in acute and medium-term elimination of the arrhythmia.
This study sought to evaluate the relationship between fibrosis imaged by delayed-enhancement (DE) magnetic resonance imaging (MRI) and atrial electrograms (Egms) in persistent atrial fibrillation ...(AF).
Atrial fractionated Egms are strongly related to slow anisotropic conduction. Their relationship to atrial fibrosis has not yet been investigated.
Atrial high-resolution MRI of 18 patients with persistent AF (11 long-lasting persistent AF) was registered with mapping geometry (NavX electro-anatomical system (version 8.0, St. Jude Medical, St. Paul, Minnesota)). DE areas were categorized as dense or patchy, depending on their DE content. Left atrial Egms during AF were acquired using a high-density, 20-pole catheter (514 ± 77 sites/map). Fractionation, organization/regularity, local mean cycle length (CL), and voltage were analyzed with regard to DE.
Patients with long-lasting persistent versus persistent AF had larger left atrial (LA) surface area (134 ± 38 cm(2) vs. 98 ± 9 cm(2), p = 0.02), a higher amount of atrial DE (70 ± 16 cm(2) vs. 49 ± 10 cm(2), p = 0.01), more complex fractionated atrial Egm (CFAE) extent (54 ± 16 cm(2) vs. 28 ± 15 cm(2), p = 0.02), and a shorter baseline AF CL (147 ± 10 ms vs. 182 ± 14 ms, p = 0.01). Continuous CFAE (CFEmean NavX algorithm that quantifies Egm fractionation <80 ms) occupied 38 ± 19% of total LA surface area. Dense DE was detected at the left posterior left atrium. In contrast, the right posterior left atrium contained predominantly patchy DE. Most CFAE (48 ± 14%) occurred at non-DE LA sites, followed by 41 ± 12% CFAE at patchy DE and 11 ± 6% at dense DE regions (p = 0.005 and p = 0.008, respectively); 19 ± 6% CFAE sites occurred at border zones of dense DE. Egms were less fractionated, with longer CL and lower voltage at dense DE versus non-DE regions: CFEmean: 97 ms versus 76 ms, p < 0.0001; local CL: 153 ms versus 143 ms, p < 0.0001; mean voltage: 0.63 mV versus 0.86 mV, p < 0.0001.
Atrial fibrosis as defined by DE MRI is associated with slower and more organized electrical activity but with lower voltage than healthy atrial areas. Ninety percent of continuous CFAE sites occur at non-DE and patchy DE LA sites. These findings are important when choosing the ablation strategy in persistent AF.
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