scholarly journals Extent of atrium with 1:1 electrogram activation predicts response to ablation of atrial fibrillation

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
P Ganesan ◽  
N Bhatia ◽  
AJ Rogers ◽  
D Krummen ◽  
P Wang ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): US National Institutes of Health Background Mechanisms associated with successful termination of persistent atrial fibrillation (AF) are still under debate. We sought to study the association between spatial extent of atrium with organized conduction and AF ablation success. We hypothesized that patients with large areas of atrium having 1:1 electrogram activation akin to ‘atrial tachycardia’ may have a higher likelihood of AF termination by ablation. Methods In n = 40 AF patients, n = 20 had termination by ablation ("Term"), and the remaining did not have AF termination by ablation ("Non-term"). Basket catheters (64 poles) were used to record unipolar electrograms (EGMs) in one or both atrium. Ablation targeted localized rotational/focal regions, after which pulmonary vein isolation was performed. Unipolar EGMs of 4sec duration at each 2x2 electrode neighborhood within 8x8 catheter grid were processed using a statistical correlation technique to identify the duration of 1:1 activations. Any EGM activation cycle that had a correlation above 80% was considered to be 1:1. Duration of contiguous 1:1 cycles was determined as percentage of total duration (4 sec). Results Spatial area of atrium (percentage of mapping field) and the corresponding 1:1 durations were assessed for patients in Term and Non-term groups. Fig A shows spatial 1:1 maps of a Term and a Non-term patient. Fig B shows examples of 1:1 and non-1:1 EGMs. Patients in Term group had higher average 1:1 atrial area than non-term group for any 1:1 duration (Fig C, 15 ± 22% vs 2 ± 4% with ≥70% 1:1 duration, p = 0.03). Positive and negative predictive values of duration≥70% for AF termination were 64.7%, and 75%, with specificity 60% and sensitivity 78.6%, exceeding clinical risk scores. Conclusion Persistent AF atrium shows areas of organized 1:1 conduction. Larger 1:1 atrial areas were identified in patients in whom AF terminated by ablation. Future studies should investigate mechanistic bases of organized conduction in AF. Abstract Figure.

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
G R Rios-Munoz ◽  
N Soto ◽  
P Avila ◽  
T Datino ◽  
F Atienza ◽  
...  

Abstract Introduction Treatment of atrial fibrillation (AF) remains sub-optimal, with low success in pulmonary vein isolation (PVI) ablation procedures in long-standing-persistent AF patients. The maintenance mechanisms of AF are still under debate. Rotational activity (RA) events, also known as rotors, may play a role in perpetuating AF. The characterisation of these drivers during electroanatomical (EA) guided ablation procedures in relationship with follow-up and recurrence ratios in AF patients is necessary to design new ablation strategies to improve the AF treatment success. Purpose We report an AF patient cohort of endocardial mapping and PVI ablation procedures with additional RA events detected during the EA study. We aim to study the presence and distribution of RA in AF patients and its impact on AF recurrence when only PVI ablation is performed. Methods 75 persistent consecutive AF patients (age 60.7±9.8, 74.7% men) underwent EA mapping and RA detection with an automatic algorithm. The presence of RA was annotated on the EA map based on the unipolar electrograms (EGMs) registered with a 20-pole catheter. RA presence was analysed at different left atrial locations (37.2±14.8 sites per patient). AF recurrence was evaluated in follow-up after treatment. Results At follow-up (9±5 months), 50% of the patients presented AF recurrence. Patients with RA had more dilated atria in terms of volumes (p=0.002) and areas (p=0.001). Patients with RA exhibited higher mean voltage EGMs 0.6±0.3 mV vs 0.5±0.2 mV (p=0.036), with shorter cycle lengths 169.1±26.0 ms vs. 188.4±44.2 ms (p=0.044). Finally, patients with RA presented more AF recurrence rates than patients with no RA events (p=0.007). No significant differences were found in terms of comorbidities, e.g., heart failure, hypertension, COPD, stroke, SHD, or diabetes mellitus. Conclusions The results show that patients with more RA events and those with RA outside the PVI ablated regions presented higher AF recurrence episodes than those with no RA or events inside the areas affected by radio-frequency ablation. The study suggests that further ablation treatment of the areas harboring RA might be necessary to reduce the recurrence ratio in AF patients. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III; Sociedad Española de Cardiología


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
D Nairn ◽  
C Nagel ◽  
B Mueller-Edenborn ◽  
H Lehrmann ◽  
A Jadidi ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG) through DO637/22-3 Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg through the Research Seed Capital (RiSC) program. Introduction Presence of left atrial (LA) fibrotic low voltage substrate (LVS) is associated with high risk for arrhythmia recurrences in patients undergoing pulmonary vein isolation (PVI) for atrial fibrillation (AF). PVI and additional ablation of LVS - as identified by mapping in sinus rhythm (SR) or AF - has been reported to improve SR maintenance rates, despite differences of the extent and distribution of LA-LVS in SR versus AF.  Aims To study the relationship between SR and AF voltage maps, we sought to identify the optimal AF voltage threshold providing the highest concordance in the extent and distribution of LVS when comparing voltage maps in SR vs. AF. Methods Using the statistical shape modelling software Scalismo, the voltage information from the SR and AF maps (acquired prior to PVI) from 28 patients (66 ± 7 years, 46% male, 82% persistent AF) was projected onto a representative LA-geometry. Sensitivity and specificity of LVS identification were calculated for varying thresholds during AF and the correlation between the SR (threshold 0.5mV) and AF maps was assessed and areas of agreeing LVS classification (SR & AF) were identified for each patient. The data of all 28 patients were combined to a spatial histogram of agreement between SR and AF low voltage maps. Results  The correlation between SR and AF maps was high across all patients, with agreement at 60-95% of all mapped sites (Figure A: each red triangle represents one patient and the respective agreement of LVS classification and substrate extent).  The optimal AF threshold - to identify LA-LVS <0.5 mV in SR - was 0.29 mV (Q1-3: 0.20-0.37 mV) and was independent of the underlying extent of LVS during SR (Figure A: each blue asterisk represents one patient and the corresponding AF threshold and substrate extent). Agreement between LVS in AF vs. SR was high across most (>90) patients on the anterior LA, lateral LA and the left atrial appendage. Lower agreement (60% of patients) was observed in the posterior wall (Figure B). Conclusions SR and AF voltage maps reveal high spatial concordance in low voltage substrate at the anterior LA, lateral LA and LA appendage, however significant discordances in LVS are found in 40% of patients at the posterior LA. Further studies on an extended patient cohort should assess if regional voltage-thresholds would result in an improved substrate concordance between AF and SR substrate maps. Abstract Figure.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Rogers ◽  
N Ravi ◽  
N.K Bhatia ◽  
R.L Shah ◽  
T Pong ◽  
...  

Abstract Background The surgical maze is suggested to be effective in persistent atrial fibrillation (AF) by reducing the area for fibrillatory wavelets. However, the mechanism for recurrence and next treatment steps are unclear. Purpose We set out to evaluate the impact of complete transmural epicardial maze lesion sets on the extent atrial organization using novel analyses of wide-area recordings of AF. Methods 19 patients (age 50.9±12.0, 78% male) underwent maze followed by endocardial mapping of AF with a 64-pole basket catheter. Block across roof, floor, and pulmonary vein lesions sets was assessed by high-density voltage mapping and organized zones of AF were assessed by panoramic recordings. Total organized area and mean area of the dominant site were evaluated using automated custom scripts. Results Patients had 3.2±0.9 organized regions in 1 minute of LA recordings. A 54 yo F showed residual conduction to the posterior wall from the roof (purple, Fig. 1A) and a figure-of-8 propagation pattern during AF (arrows, fig B) which terminated with localized ablation (yellow lesions, Fig. 1A, red X, Fig. 1B). Overall, patients with complete block on epicardial lesion set had smaller areas of organization (13.7±8% vs. 45.7±32% of mapped areas, p=0.029) vs. those with gaps. The average size of the dominant area was smaller with complete transmural lines than with gaps (5.7±3% vs. 15.9±10%, p=0.033) (Fig. 1C). Conclusion These results show that complete transmural lesion sets constrain the critical mass available for AF, with smaller resulting organized zones. Future studies that quantify how partitioning the atrial surface affects AF may help personalize lesion sets after maze. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NIH NRSA F32 United States


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Oudkerk Pool ◽  
B.D De Vos ◽  
J.M Wolterink ◽  
S Blok ◽  
M.J Schuuring ◽  
...  

Abstract Background The growing availability of mobile phones increases the popularity of portable telemonitoring devices. An atrial fibrillation diagnosis can be reached with a recording of 30s on such telemonitoring devices. However, current commercially available automatic algorithms still require approval by experts. Purpose In this research we aimed to build an artificial intelligence (AI) algorithm to improve automatic distinction of atrial fibrillation (AF) from sinus rhythm (SR), to ultimately save time, costs, and to facilitate telemonitoring programs. Methods We developed a deep convolutional neural network (CNN), based on a residual neural network (ResNet), tailored to single-lead ECG analysis. The CNN was trained using publicly available single-lead ECGs from the 2017 PhysioNet/ Computing in Cardiology Challenge. This dataset consists of 60% SR, 9% AF, 30% alternative rhythm, and 1% noise ECGs. The 8528 available ECGs were divided into a training (90%) and validation set (10%) for model development and hyperparameter optimization. Results The trained CNN was applied to an independent set containing single-lead ECGs of 600 patients equally divided into two groups: SR and AF. Both groups comprised of 300 unique ECGs (SR; 60% male, 63±11 years, AF; 38% male, 56±14 years). In distinguishing between AF and SR, the method achieved an accuracy of 0.92, an F1-score of 0.91, and area under the ROC-curve of 0.98. Conclusion The results demonstrate that distinguishing SR and AF by a fully automatic AI algorithm is feasible. This approach has the potential to reduce cost by minimizing expert supervision, especially when extending the algorithm to other heart rhythms, like premature atrial/ventricular contractions and atrial flutter. Figure 1. ROC curve Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Dekkerbeurs - Hartstichting


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
I Hwang ◽  
J Park ◽  
O Kwon ◽  
B Lim ◽  
M Hong ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant [HI19C0114] from the Ministry of Health and Welfare. Additionally, the work was funded by grants [NRF-2019R1C1C100907512], and [NRF-2020R1A2B01001695] from the Basic Science Research Program run by the National Research Foundation of Korea (NRF) under the Ministry of Science, ICT & Future Planning (MSIP). Background The efficacy of antiarrhythmic drugs (AAD) can vary in patients with atrial fibrillation (AF) and the PITX2 gene affects the responsiveness of AADs. We explored the virtual AAD (V-AAD) responses between wild-type and PITX2+/- deficient AF conditions by realistic in-silico AF modeling. Methods We tested the V-AADs in AF modeling integrated with patients’ 3D-computed tomography and 3D-electroanatomical mapping, acquired in 25 patients (68% male, 59.8 ± 9.8 years old, 32.0% paroxysmal type). The ion currents for the PITX2+/- deficiency and each AAD (amiodarone, sotalol, dronedarone, flecainide, and propafenone) were defined based on previous publications. Results We compared the wild-type and PITX2+/- deficiency in terms of the action potential duration (APD90), conduction velocity (CV), maximal slope of restitution (Smax), and wave-dynamic parameters, such as the dominant frequency (DF), phase singularities (PS), and AF termination rates according to the V-AADs. The PITX2+/- deficient model exhibited a shorter APD90 (p < 0.001), a lower Smax (p < 0.001), mean DF (p = 0.012), PS number (p < 0.001), and a longer AF cycle length (AFCL, p = 0.011). Five V-AADs changed the electrophysiology in a dose dependent manner. AAD-induced AFCL lengthening (p < 0.001) and reductions in the CV (p = 0.033), peak DF (p < 0.001) and PS number (p < 0.001) were more significant in PITX2+/- deficient than wild-type AF. PITX2+/- deficient AF was easier to terminate with class IC AADs than the wild-type AF (p = 0.018). Conclusions The computational modeling-guided AAD test was feasible for evaluating the efficacy of multiple AADs in patients with AF. AF wave-dynamics and electrophysiological characteristics are different among the PITX2 deficient and the wild-type genotype models. BaselineChanges after AADClass ICClass IIIWild-typePITX2+/-p-valueWild-typePITX2+/-p-valueWild-typePITX2+/-p-valueWild-typePITX2+/-p-valueAPD90, (ms)243.7 ± 33.8184.4 ± 15.5<0.00138.2 ± 37.343.4 ± 56.20.223275.9 ± 43.5219.0 ± 39.2<0.001284.9 ± 32.8233.8 ± 71.4<0.001CV, (m/s)0.78 ± 0.320.70 ± 0.210.347-0.15 ± 0.18-0.20 ± 0.260.0330.63 ± 0.320.53 ± 0.300.0270.60 ± 0.360.43 ± 0.33<0.001Mean Smax0.787 ± 0.280.531 ± 0.18<0.0010.005 ± 0.260.115 ± 0.24<0.0010.828 ± 0.310.694 ± 0.320.0030.768 ± 0.320.608 ± 0.27<0.001Mean AFCL, (ms)146.96 ± 24.61164.78 ± 22.730.01122.62 ± 24.5537.92 ± 32.72<0.001165.44 ± 36.96190.85 ± 35.61<0.001169.05 ± 25.26203.35 ± 34.78<0.001Peak DF, (Hz)10.68 ± 2.9711.82 ± 3.340.211-2.98 ± 4.94-5.46 ± 4.66<0.00110.01 ± 4.397.23 ± 4.20<0.0016.30 ± 4.325.80 ± 4.070.301Mean DF, (Hz)6.80 ± 0.886.22 ± 0.710.012-1.95 ± 2.44-2.20 ± 1.990.2065.75 ± 1.784.53 ± 2.00<0.0014.14 ± 2.393.69 ± 2.000.077PS Number, (N)101086 ± 9608814150 ± 24778<0.001-59322 ± 99288-7409 ± 27856<0.00150579 ± 6523611568 ± 21868<0.00132951 ± 558643524 ± 8302<0.001PS Life Span, (ms)109.36 ± 113.90102.24 ± 226.640.889-24.87 ± 72.06-41.38 ± 126.350.073103.36 ± 180.6868.05 ± 162.790.14871.91 ± 141.8655.99 ± 217.970.454Table. Effects of AADs in the Wild-type and PITX2+/- Deficiency groupAbstract Figure. Wild-type vs. PITX2+/- baseline model


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
G Rios-Munoz ◽  
C Perez-Hernandez ◽  
F Fernandez-Aviles ◽  
A Arenal

Abstract Introduction There exist many imaging techniques and systems to reproduce atrial chambers in 3D. These technologies include electroanatomical (EA) mapping systems, noninvasive electrocardiographic imaging (ECGI), magnetic resonance imaging (MRI), or computed tomography (CT) scans. In the case of atrial fibrillation (AF), the most employed non-pharmacological treatment is catheter ablation to electrically isolate the pulmonary veins from the rest of the left atrium. Driver mechanisms such as focal or rotational activity have been proposed as possible initiating and maintaining mechanisms of AF. However, correspondence and validation of these sites when several systems are employed in the same patient remains a challenge, as they are mostly manually aligned based on visual inspection. Purpose To develop an automatic 3D alignment algorithm for cardiac 3D meshes to colocalize points between atrial maps generated with multiple EA mapping systems, ECGI, MRI, or CT scans. Methods A total of 25 left atrial meshes from persistent AF patients were exported from an EA mapping system. The total number of vertices for all the meshes was 2545444 points (101817.8±13593.3 points per map). A reference mesh was employed with minor modifications [1]. All meshes were manually segmented into 12 different left atrial regions, see Table for the region names. The method implements a non-rigid variant of the iterative closest point algorithm to transform the atrial mesh onto the reference one, see Figure. The geographical distance between the mean position of the 12 different segmented reference areas and the 12 transformed points was employed as the performance metric. Results The global error for all the fiducial points in all left atrial meshes was 11.57±2.55 mm. The average local errors for the 12 atrial areas are summarized in the Table. The best three aligned areas were the RSPV, atrial septum, and lateral wall. The areas with less alignment accuracy were the LAA, LSPV, and atrial roof. Conclusions The algorithm provides a promising solution to evaluate and validate site-related results from different systems, e.g., rotational activity presence between EA mapping and ECGI systems. The method works automatically for any given chamber anatomy or any number of points. No prior segmentation is needed since the transformation and co-localization are applied to the raw chamber mesh. Further analysis with a larger mesh database is needed. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III and Ministerio de Ciencia, Innovaciόn y Universidades


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
IA Zaigraev ◽  
IS Yavelov ◽  
OM Drapkina ◽  
EV Bazaeva

Abstract Funding Acknowledgements Type of funding sources: None. Background. Left atrial thrombus (LAT) is the main source of cardiac emboly in patients with non-valvular atrial fibrillation (NAF). Several risk scores – mostly modified CHADS2 and CHA2DS2-VASc – were offered to predict LAT in patients with NAF. However, their relative predictive value requires further evaluation. Purpose. Compare the ability of different risk scores to predict LAT before catheter ablation or cardioversion in patients with NAF. Methods. In a retrospective single-center study, medical records of 1994 patients with NAF who underwent transesophageal echocardiography before catheter ablation or cardioversion were analyzed. LAT was identified in 33 (1.6%) of them. For the control group 167 patients without LAT were randomly selected from this database. Logistic regression analysis and C-statistic were used for evaluation and comparison of predictive values of CHADS2, R2CHADS2, CHA2DS2-VASc, R-CHA2DS2-VASc, R2CHA2DS2-VASc, CHA2DS2-VASc-RAF, mCHA2DS2-VASc and CHA2DS2-VASc-AFR scores. Results. The mean age of studied patients was 60.3 ± 10.9 years, 110 (55%) of them were males. The mean CHA2DS2-VASc score was 2.54 ± 1.79. Results of univariate analysis and C-statistic for above mentioned risk scores are presented in the table. Each of them was associated with LAT. In comparison with a CHA2DS2-VASc score C-statistic was significantly higher for CHA2DS2-VASc-RAF and CHA2DS2-VASc-AFR scores (p values 0.03 and 0.001 respectively). In multivariate analysis only CHA2DS2-VASc-RAF score was associated with LAT (OR 1.37; 95% CI 1.21-1.55, p < 0.0001). OR for LАT in patients with CHA2DS2-VASc-RAF >3 was 12.8 (95% CI 3.75-43.9; p < 0.0001) with sensitivity, specificity, positive and negative predictive values 90.6%, 57.1%, 33.3% and 58.9% respectively. Conclusion. In a group of patients with NAF and relatively low incidence of LAT all studied scores were associated with LAT and CHA2DS2-VASc-RAF score has appeared the most informative. Predictors of LAT in patients with NAF Risk stratification models OR (95% CI) p-value C-statistic (95% CI) CHADS2 2.12 (1.55-2.91) <0.0001 0.77 (0.68-0.85) R2CHADS2 2.00 (1.53-2.62) <0.0001 0.78 (0.69-0.87) CHA2DS2-VASc 1.65 (1.36-2.05) <0.0001 0.74 (0.65-0.84) R-CHA2DS2-VASc 1.64 (1.34-2.03) <0.0001 0.76 (0.66-0.85) R2CHA2DS2-VASc 1.59 (1.32-1.92) <0.0001 0.76 (0.66-0.85) CHA2DS2-VASc- RAF 1.35 (1.27-1.52) <0.0001 0.84 (0.76-0.91) mCHA2DS2-VASc 1.83 (1.42-2.35) <0.0001 0.75 (0.65-0.85) CHA2DS2-VASc-AFR 1.75 (1.41-2.17) <0.0001 0.80 (0.71-0.88)


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Fauchier ◽  
A Bisson ◽  
A Bodin ◽  
N Clementy ◽  
B Pierre ◽  
...  

Abstract Background Charlson comorbidity index (CCI) is a tool to measure comorbid disease status and a strong estimator of mortality. The quantifiable frailty phenotype has also been validated as predictive of mortality and disability. Claims data can be used to classify individuals as frail and non-frail using the Claims-based Frailty Index (CFI). We evaluated whether these tools may help to predict the risk of bleeding in patients with atrial fibrillation (AF). Methods All patients with AF seen in an academic institution were identified and followed up for mortality, stroke and bleeding events. HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores, CCI and CFI were calculated for each patient. Hazard ratios were calculated and predictive abilities of the scores were compared using the c-statistic in the whole population and then separately in elderly patients (>75 yo). Results Among 8962 patients with AF, 274 major bleeding events were recorded during a follow-up of 874±1054 days. Bleeding occurred more commonly in patients with higher bleeding risk scores, CCI and CFI. The 4 bleeding risk scores significantly had lower c-statistics than CCI and CFI for predicting major bleeding (table). Results were similar whether patients were treated with OAC or no OAC. In elderly patients, the c-statistics were all lower and were not significantly different for the 4 scores, CCI and CFI scores (0.594, 0,572, 0.595, 0.594, 0.616 and 0.591 for HAS-BLED, HEMORR2HAGES, ATRIA, ORBIT, CCI and CFI, respectively). Predictive values for major bleeding ROC Area 95% Conf. Interval P value vs CCI/CFI HASBLED 0.588 0.555–0.621 0.002/0.003 HEMORR2HAGES 0.564 0.531–0.598 <0.0001/<0.0001 ATRIA 0.559 0.522–0.595 <0.0001/<0.0001 ORBIT 0.577 0.542–0.612 0.0002/0.0003 Charlson, CCI 0.652 0.619–0.684 –/0.58 Frailty index, CFI 0.648 0.615–0.681 0.58/– Conclusion Comorbidities and frailty, respectively assessed with CCI and CFI, demonstrated statistically better performances in predicting major bleeding than the 4 established bleeding risk scores in AF, although all c-indexes were broadly similar. The 4 bleeding risk scores, CCI and CFI showed lower performance in predicting bleeding within elderly patients in whom they all performed equally to predict bleeding events. Given their simplicity and similar performances, the user-friendly bleeding risk scores remain attractive tools for the estimation of bleeding risk in elderly patients with AF.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
D Jakob ◽  
A Klesen ◽  
B Allegrini ◽  
E Darkow ◽  
D Aria ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Science, Research and Arts Baden-Württemberg (MWK-BW Sonderlinie Medizin) Atrial Fibrillation (AF) is an arrhythmia of increasing prevalence. One of the important indicators for AF is sustained atrial dilatation, highlighting the importance of mechanical overload in the pathophysiology of AF. The mechanisms by which atrial cells, including fibroblasts, sense and react to such changing mechanical forces, are not fully elucidated. Here, we characterise stretch-activated ion channels (SAC) in human atrial fibroblasts and changes in their expression and activity associated with AF. Using primary cultures of human atrial fibroblasts, isolated from patients in sinus rhythm or with sustained AF, we combine electrophysiological, molecular and pharmacological tools to identify SAC. Two electrophysiological SAC-signatures were detected, indicative of cation-nonselective and potassium-selective channels. Using siRNA-mediated knockdown, we identified the nonselective SAC as Piezo1. Biophysical properties of the potassium-selective channel and its pharmacology indicated presence of ‘big potassium channels’, BKCa. In cells from AF patients, Piezo1 activity and mRNA expression levels were higher than in cells from sinus rhythm patients, while BKCa activity (but not expression) was downregulated. Both Piezo1-knockdown and removal of extracellular calcium from the patch pipette resulted in a significant reduction of stretch-induced BKCa current. No co-immunoprecipitation of Piezo1 and BKCa was detected. Human atrial fibroblasts express functional Piezo1 and BKCa channels. While Piezo1 is directly stretch-activated, the increase in BKCa activity during mechanical stimulation appears to be mainly secondary to calcium influx via SAC such as Piezo1. During sustained AF, Piezo1 is increased, while BKCa activity is reduced, highlighting differential regulation of both channels. Our data show the presence and activity of Piezo1 and BKCa in human atrial fibroblasts and suggest an interplay between the two in the absence of direct physical interactions.


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