scholarly journals Study on the Stability of CFAEs to Characterize the Atrial Substrate in Atrial Fibrillation

Author(s):  
Emanuela Finotti ◽  
Edward J Ciaccio ◽  
Hasan Garan ◽  
Fernando Hornero ◽  
Raul Alcaraz ◽  
...  
2020 ◽  
Vol 11 ◽  
Author(s):  
Wei Wang ◽  
Weijian Shen ◽  
Shanzhuo Zhang ◽  
Gongning Luo ◽  
Kuanquan Wang ◽  
...  

This simulation study aims to investigate how the Calcium/calmodulin-dependent protein kinase II (CaMKII) overexpression and oxidation would influence the cardiac electrophysiological behavior and its arrhythmogenic mechanism in atria. A new-built CaMKII oxidation module and a refitted CaMKII overexpression module were integrated into a mouse atrial cell model for analyzing cardiac electrophysiological variations in action potential (AP) characteristics and intracellular Ca2+ cycling under different conditions. Simulation results showed that CaMKII overexpression significantly increased the phosphorylation level of its downstream target proteins, resulting in prolonged AP and smaller calcium transient amplitude, and impaired the Ca2+ cycling stability. These effects were exacerbated by extra reactive oxygen species, which oxidized CaMKII and led to continuous high CaMKII activation in both systolic and diastolic phases. Intracellular Ca2+ depletion and sustained delayed afterdepolarizations (DADs) were observed under co-existing CaMKII overexpression and oxidation, which could be effectively reversed by clamping the phosphorylation level of ryanodine receptor (RyR). We also found that the stability of RyR release highly depended on a delicate balance between the level of RyR phosphorylation and sarcoplasmic reticulum Ca2+ concentration, which was closely related to the genesis of DADs. We concluded that the CaMKII overexpression and oxidation have a synergistic role in increasing the activity of CaMKII, and the unstable RyR may be the key downstream target in the CaMKII arrhythmogenic mechanism. Our simulation provides detailed mechanistic insights into the arrhythmogenic effect of CaMKII overexpression and oxidation, which suggests CaMKII as a promising target in the therapy of atrial fibrillation.


2005 ◽  
Vol 15 (3-4) ◽  
pp. 157-163 ◽  
Author(s):  
Hilary Wynne ◽  
Tayyaba Khan ◽  
Elizabeth Sconce ◽  
Farhad Kamali

Meta-analyses of randomized controlled trials have reported the efficacy of dose-adjusted warfarin therapy (target International Normalised Ratio (INR) 2–3) in reducing stroke risk in atrial fibrillation by 68%, with aspirin reducing relative risk by 22%. Absolute benefit for an individual patient depends on the presence of the risk factors for stroke; these include previous stroke, transient ischaemic attack, hypertension, diabetes, valvular heart disease, heart failure and advanced age. In spite of reported benefit, many people with atrial fibrillation and a high risk of stroke are not receiving anticoagulation: disappointingly, risk stratification is not being sufficiently used to guide treatment.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Markus Rottmann ◽  
Anna Pfenniger ◽  
Shin Yoo ◽  
David Johnson ◽  
Gail Elizabeth Geist ◽  
...  

Introduction: Oxidative Stress (OS) is thought to be a mediator of atrial fibrillation (AF). However, the precise role of OS in electrical remodeling in AF is unknown. We assessed the effect of a novel gene-based strategy by performing knockdown of NOX2 in a clinically relevant large animal on the maintenance of rotational drivers in AF. Hypothesis: We hypothesized that the gene-based strategy by performing knockdown of NOX2 reduces rotational activities in AF. Methods: 1 week after pacemaker implantation, open-chest sub-epicardial gene injection of NOX2 shRNA was performed in the LA (PLA, LAFW, LAA), to significantly knockdown NOX2 in 6 dogs and 10 controls were also used. Epicardial high-density mapping was performed (117 electrodes, inter-elec.-distance 2.5mm) at day1 (gene injection) and at terminal day (up to 12weeks RAP) in 6 atrial regions. Number and stability of rotational activities were detected based on activation maps and CL was analyzed. Results: AF developed in controls (>30 min) in 4-9 days, compared to >21 days in NOX2 shRNA animals (p<0.01). The stability of observed rotational drivers decreased (baseline gene delivery vs terminal day) in all left atrial regions: in the LAA (315.88±123.53ms, median 300.00ms vs 282.55±175.04ms, median 270ms), PLA (462.46±477.04ms, median 360ms vs 280.39±101.55ms, median 240ms), LAFW (416.67±162.50ms, median 405ms vs 241.67±92.63ms, median 195ms) (Figure A). Number of rotational activities reduced by 36.58% (P=0.14) after gene delivery. CL increased in the PLA from (93.74±30.11ms, median 85.00ms to 102.15±33.07ms, median 92.00ms after gene delivery (Figure C). Conclusions: Gene injection by NOX2 shRNA reduced the stability of rotational activities in AF. OS may be an important, dynamic mechanism underlying the formation and maintenance of the AF disease state. Targeted disruption of NOX2-dependent oxidative injury with a new gene therapy approach prevents onset as well as the perpetuation of AF.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Vijay Swarup ◽  
Tina Baykaner ◽  
Junaid Zaman ◽  
James Daubert ◽  
John Hummel ◽  
...  

Introduction: Several groups now report electrical rotors or focal sources sustaining human atrial fibrillation (AF) after it has been triggered. However, some groups report stable sources while others report transient rotational activity. Hypothesis: We hypothesized that AF rotors would be spatially stable in a large multi center experience, using phase mapping. Methods: We prospectively mapped AF in 277 patients (181 persistent, 61±12 years) at 6 centers in the FIRM-registry, using basket catheters with 64 contact electrodes per atrium. AF was mapped by RhythmView (Topera Inc) before ablation. FIRM uses phase analysis and dynamic physiological analysis of repolarization and conduction. AF propagation movies were interpreted by each operator to assess the stability and dynamics of AF sources in multiple maps over tens of minutes prior to ablation. Results: Sources were identified in 258 of 260 of patients in whom AF was mapped (99%), for 2.8±1.4 sources/patient. Patients showed 1.8±1.1 left atrial and 1.1±0.8 right atrial sources. On FIRM mapping, each source was stable for 4196±6360 cycles, with no difference between patients with paroxysmal vs persistent AF (4290±5847 vs 4150±6604, p=0.78), or right vs left atrial sources (p=0.26) (Figure). Rotors showed precession ('wobble') in ~2 cm2 areas, and spiral arms disorganized (‘fibrillatory conduction)’ beyond a spatial domain that varied around each rotor core for each patient, and between patients. Conclusions: Rotors and focal sources for human AF are stable for thousands of cycles during mapping using FIRM. These data show that AF rotors are distinct from macro-reentry. Notably, rotors precess within small atrial regions, and emanating spiral arms disorganize variably into the fibrillatory milieu in agreement with basic science studies. These results provide a rationale for FIRM-guided ablation at AF sources, and explain why rotors have been difficult to detect using traditional mapping approaches.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Zoppo ◽  
E Bacchiega ◽  
V Bottazzo ◽  
A Brazzolotto ◽  
C Carraro ◽  
...  

Abstract Introduction The remote control (RC) of CIED has become necessary, though the human resources and technical facilities needed are limited. In most of Centers, the ratio of RC CIED /CIED with in-office follow up, is continuously increasing and is expected to reach the 100% of CIED remotely controlled. We sought assess an organizational model based on available facilities and a long-term projection of RC data burden. Pacemakers, ICD and implantable loop recorders were considered. Methods The total population served by the Hospital area has been obtained (271.260 citizens), timed at December 31st 2014. By checking our Hospital data files, the total number of followed up CIED patients timed at January 1st 2011 (3995; 1.47% of all population), was compared with the same data timed at January 1st 2015 (3902; 1.43% of all population), in order to the check for the “stability” of that data over time. At the analyzed time 1582/3902 (40,5%) of CIED were followed by RC. We have then considered an yearly average of 465 CIEDs implanted/replaced (yearly implants 2012 to 2015) and excluded a roughly 10% of them because not provided of RC facilities (unwilling patients or CIED not RC “ready”); all the other patients were provided with RC. On these basis, we can assume a ratio of RC CIEDs /non-RC CIED, deemed to increase by 10 to 11% per year, to reach the break-even of 100% of RC CIEDs, in 2021 (projection). The number of RC transmissions (Tx) have been gathered in 5 types of events (Fig. left upper). The timing of RC patient managing from opening the CIED web site to complete patient file assessment (RC file analysis) performed by expert nurses, was arbitrarily calculated over a sample of 10 Tx per day in 3 different days. Results Of 3902 CIED patient, 1582 (40.5%) were RC followed up (3261 pacemakers, 594 ICDs and 47 implantable loop recorder); the CIED brands were represented as follows: Medtronic 685 (43.3%); St. Jude 180 (11.4%), Boston Sc. 330 (20.8%), Biotronik 318 (20.1%) and Livanova (previously SorinGroup) 69 (4.4%). During the year 2015 we received a total number of 10396 Tx: 128 (1.2%) red alert; 1944 (18.6%) yellow alert, 141 (1.3%) atrial fibrillation; 403 (3.9%) lost Tx (disconnected transmitters or un-compliant patients for remote interrogation) and 7780 (75%) Tx “OK” with NO events. (Fig. right upper). The projection model at 2021 with 100% RC patients (break-even) shows a total 25990 Tx: 320 red alert; 1944 yellow alert, 352 atrial fibrillation; 1007 lost Tx and 19459 Tx “OK”. The 2021 monthly Tx would be 2320 (26 red alert; 405 yellow alert, 29 atrial fibrillation; 91 lost Tx and 1769 (75%) Tx “OK”) (Fig. both lower panels) The RC file analysis was roughly calculated around 3 minutes (116 hours/month); 5.8 hours/business day (Monday–Friday). Conclusion The rate of RC followed up CIEDs will inexorably increase by time. The projection management model presented could help to build a sustainable organization.


2021 ◽  
Vol 20 (3) ◽  
pp. 203-212
Author(s):  
A. M. Chaulin ◽  
D. V. Duplyakov

The aim of the study was to analyze medical literature on the role of microRNA in the pathophysiology of atrial fibrillation and the possibilities of using microRNAs as biomarkers.The analysis of modern medical literature was carried out using the PubMed – NCBI database.Atrial fibrillation (AF) is a common and serious cardiovascular disease. The pathophysiological mechanisms underlying the development of atrial fibrillation are not entirely clear. In addition, there are no optimal biomarkers for early detection and assessment of the prognosis for patients with atrial fibrillation. Recently, the attention of researchers has been directed to the molecules of microRNA. There is a lot of evidence that they are involved in the pathogenesis of neurological, oncological, and cardiovascular diseases. This review examines the role of microRNAs in the pathophysiology of atrial fibrillation. The possibility of using microRNA as a biomarker for the diagnosis and prediction of atrial fibrillation is also discussed.MicroRNAs play a crucial role in the pathophysiology of atrial fibrillation, regulating the mechanisms of atrial remodeling, such as electrical remodeling, structural remodeling, remodeling of the autonomic nervous system, and impaired regulation of calcium levels. The stability of microRNAs and the possibility to study them in various biological fluids and tissues, including blood, make these molecules a promising diagnostic biomarker for various cardiovascular diseases. The presented data clearly indicate that AF is associated with changes in the expression level of various microRNAs, which can be quantified using a polymerase chain reaction. Further research is required to assess the role of microRNAs as biomarkers for atrial fibrillation, in particular to establish precise reference limits.


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