Piezo1 and BKCa channels in human atrial fibroblasts: interplay and remodelling in atrial fibrillation

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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Piezo1 and BKCa channels in human atrial fibroblasts: interplay and remodelling in atrial fibrillation

10.1101/2021.01.21.427388 ◽

2021 ◽

Author(s):

Dorothee Jakob ◽

Alexander Klesen ◽

Benoit Allegrini ◽

Elisa Darkow ◽

Diana Aria ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ion Channels ◽

Sinus Rhythm ◽

Calcium Influx ◽

Primary Cultures ◽

Developed Countries ◽

Bkca Channels ◽

Calcium Dependent ◽

Selective Channel ◽

In Cells

AbstractAimsAtrial Fibrillation (AF) is an arrhythmia of increasing prevalence in the aging population of developed countries. One of the important indicators of 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 changing mechanical forces, are not fully elucidated. Here, we characterise stretch-activated ion channels (SAC) in human atrial fibroblasts and changes in SAC-presence and -activity associated with AF.Methods and ResultsUsing primary cultures of human atrial fibroblasts, isolated from patients in sinus rhythm or 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, its sensitivity to calcium, paxilline and iberiotoxin (blockers), and NS11021 (activator), indicated presence of calcium-dependent ‘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 BKCa current during stretch. No co-immunoprecipitation of Piezo1 and BKCa was detected.ConclusionsHuman atrial fibroblasts contain at least two types of ion channels that are activated during stretch: Piezo1 and BKCa. 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 support the presence and interplay of Piezo1 and BKCa in human atrial fibroblasts in the absence of physical interactions between the two channel proteins.

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Rotational activity presence and its impact in persistent atrial fibrillation follow-up

European Heart Journal ◽

10.1093/eurheartj/ehab724.0375 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

G R Rios-Munoz ◽

N Soto ◽

P Avila ◽

T Datino ◽

F Atienza ◽

...

Keyword(s):

Atrial Fibrillation ◽

Treatment Success ◽

Persistent Atrial Fibrillation ◽

Recurrence Rates ◽

National Budget ◽

Funding Sources ◽

Cycle Lengths ◽

Public Grant ◽

Af Recurrence

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

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Distinguishing sinus rhythm from atrial fibrillation on single-lead ECGs using a deep neural network

European Heart Journal ◽

10.1093/ehjci/ehaa946.3442 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Oudkerk Pool ◽

B.D De Vos ◽

J.M Wolterink ◽

S Blok ◽

M.J Schuuring ◽

...

Keyword(s):

Neural Network ◽

Atrial Fibrillation ◽

Sinus Rhythm ◽

Roc Curve ◽

Model Development ◽

Independent Set ◽

Funding Source ◽

National Budget ◽

Validation Set ◽

Public Grant

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

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Computational modeling for antiarrhythmic drugs for atrial fibrillation according to the genotypes

EP Europace ◽

10.1093/europace/euab116.171 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

I Hwang ◽

J Park ◽

O Kwon ◽

B Lim ◽

M Hong ◽

...

Keyword(s):

Atrial Fibrillation ◽

Computational Modeling ◽

Antiarrhythmic Drugs ◽

Science Research ◽

Dominant Frequency ◽

Dependent Manner ◽

Wild Type ◽

National Budget ◽

In The Wild ◽

Public Grant

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

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Spatial and quantitative assessment of the correlation between sinus rhythm and atrial fibrillation voltage mapping to identify low voltage substrate in persistent atrial fibrillation

EP Europace ◽

10.1093/europace/euab116.163 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

D Nairn ◽

C Nagel ◽

B Mueller-Edenborn ◽

H Lehrmann ◽

A Jadidi ◽

...

Keyword(s):

Atrial Fibrillation ◽

Sinus Rhythm ◽

Left Atrial ◽

Low Voltage ◽

Persistent Atrial Fibrillation ◽

Posterior Wall ◽

Shape Modelling ◽

National Budget ◽

Spatial Concordance ◽

Public Grant

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.

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Zfhx3 decreases expression of cardiac Nav1.5 channels and inhibits sodium current

European Heart Journal ◽

10.1093/eurheartj/ehab724.3209 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

R Caballero ◽

A Camara-Checa ◽

M Rubio-Alarcon ◽

T Crespo-Garcia ◽

M Dago ◽

...

Keyword(s):

Sodium Current ◽

Association Studies ◽

Luciferase Reporter ◽

National Budget ◽

Funding Sources ◽

Whole Cell Patch Clamp ◽

Reporter Assays ◽

Cardiac Excitability ◽

Public Grant ◽

In Cells

Abstract Background Zfhx3 (zinc finger homeobox 3) is a transcription factor (TF) encoded by the ZFHX3 gene. GWAS and gene-based association studies showed that ZFHX3 is one of the major atrial fibrillation (AF) susceptibility-conferring genes. The sodium current (INa), carried by Nav1.5 channels encoded by SCN5A, is responsible for atrial and ventricular action potential depolarization and determines cardiac excitability. Zfhx3 interacts with other TFs, such as Tbx5 and Pitx2c that increase and decrease INa, respectively. However, the effects of Zfhx3 on cardiac INa are currently unknown. Purpose We aimed to determine the effects of Zfhx3 on the INa on HL-1 cardiomyocytes. Methods cDNAs encoding human Zfhx3 together or not with Pitx2c or Tbx5 were transfected in HL-1 cells. Endogenous Zfhx3 expression in HL-1 cells was silenced by means of siRNAs. INa was recorded at room temperature using the whole-cell patch-clamp and luciferase reporter assays, qPCR and Western-blot (WB) analyses were also conducted. Results Expression analysis of RNA-seq data from human ventricular (n=432) samples (GTEx) demonstrated that Zfhx3 mRNA can be detected in the adult working myocardium. Transfection of Zfhx3 strongly reduced peak INa density (from −75.0±6.6 to −30.9±2.9 pA/pF; n≥26, P<0.001). In contrast, Zfhx3 silencing augmented INa density compared to cells transfected with scrambled siRNA (from −65.9±8.9 to −104.6±10.8 pA/pF; n≥8, P<0.05). Neither Zfhx3 expression nor silencing modified time and voltage dependence of activation and inactivation or the reactivation kinetics. Zfhx3 significantly reduced transcriptional activity of human SCN5A, PITX2 and TBX5 minimal promoters and, consequently, the mRNA and protein expression levels of Nav1.5, Pitx2c, and Tbx5 were diminished (n≥6, P<0.05). In cells transfected with Zfhx3 together with Pitx2c, but not with Tbx5, INa density was significantly smaller than in cells expressing WT Zfhx3 alone (n≥15, P<0.05). Further WB experiments demonstrated that Zfhx3 increased the expression of Nedd4–2 ubiquitin-protein ligase, which ubiquitinates Nav1.5 channels and favors their proteasomal degradation. Conclusions Zfhx3 inhibits INa as a result of a direct repressor effect on the SCN5A promoter, the modulation of Tbx5-increasing and Pitx2-decreasing effects on the INa, and the enhancement of Nav1.5 channel degradation. We propose a novel and complex mechanism that regulates the expression of sodium channels and the density of the INa, which are critical for the control of cardiac excitability. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministerio de Economía y CompetitividadComunidad Autόnoma de Madrid

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Relation of biomarkers of inflammation, oxidative stress and fibrosis in patient with atrial fibrillation

European Heart Journal ◽

10.1093/eurheartj/ehab724.0420 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

P Pauklin ◽

J Eha ◽

M Zilmer ◽

K Tootsi ◽

M Kals ◽

...

Keyword(s):

Oxidative Stress ◽

Atrial Fibrillation ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

High Sensitivity ◽

National Budget ◽

Funding Sources ◽

Markers Of Inflammation ◽

Public Grant

Abstract Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice. The patogenesis of AF is linked to an inflammatory reaction and oxidative stress that leads to fibrosis of the atria and progression of the disease. However, the role of different biomarkers in patients with AF is poorly defined. The purpose of this study is to define the role of several biomarkers of inflammation, oxidative stress and fibrosis (myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), galectin-3 (Gal-3), oxidized low-density lipoprotein (oxLDL)) in patients with AF. Methods We included 75 patients with paroxysmal/persistent AF, who were admitted for electrical cardioversion or pulmonary vein isolation. MPO, hsCRP, Gal-3 and oxLDL were measured before the procedures. We compared the results with 75 healthy age-, sex- and blood pressure-matched individuals. Results Patients with AF had higher MPO (77.1 vs 41.7 ng/ml, p<0.001) compared the healthy subjects. There was also significantly higher hsCRP (3.7 vs 1.6 mg/L, p<0.001) and Gal-3 (12.3 vs 10.4 mg/L, p=0.003). No difference in oxLDL levels (78.8 vs 75.3 U/L, p=0.414) were seen (Table 1). MPO (β=0.012, p=0.014), hsCRP (β=0.213, p=0.046), and weight (β=0.037, p=0.006), were independently associated with AF in a logistic regression analysis (Table 2). Conclusions Patients with AF have increased markers of inflammation and fibrosis, whereas no increase in oxidative stress markers was detected. MPO, hsCRP and age weight were independently predictive of AF. These findings support the role of inflammatory and fibrotic mechanisms as important factors in the electrical and structural remodelling progress in the atria of patients with AF. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Estonian Research Council

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Low incidence of major complications after the first six hours post-atrial fibrillation ablation – same-day discharge safe and feasible in most patients

European Heart Journal ◽

10.1093/eurheartj/ehab724.0514 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

A Paul Nordin ◽

N Drca ◽

P Insulander ◽

H Bastani ◽

T Bourke ◽

...

Keyword(s):

Atrial Fibrillation ◽

Catheter Ablation ◽

National Budget ◽

Funding Sources ◽

Tertiary Centre ◽

Major Complications ◽

Complication Risk ◽

Same Day Discharge ◽

Low Incidence ◽

Public Grant

Abstract Background/Introduction Catheter ablation of atrial fibrillation (AF) is associated with a complication risk. It is common practice to monitor patients overnight post-procedurally which is resource craving. Purpose To evaluate the incidence of procedural complications related to catheter ablation of AF to assess the potential feasibility and safety of same day discharge in a large cohort. Methods We performed an analysis of prospectively collected data of complications of all patients staying overnight after undergoing AF ablation between 2001 and 2020 at a tertiary centre. By studying medical records, we analysed complications occurring intraprocedurally until six hours post-ablation, and between six hours post-ablation until discharge the day after ablation procedure (up to 24 hours post-procedure). Results In 5414 AF ablations we identified a total of 108 (2.0%) major complications occurring intraprocedural or until discharge the day after procedure. Most major complications occurred early and were detected intraprocedurally or within six hours after completed procedure (n=96, 1.8%). Twelve (0.2%) major complications occurred between six hours post-ablation and until discharge the day after procedure. The most common of these were congestive heart failure (n=6) and transient ischemic attack (TIA, n=4). In addition, there were 61 (1.1%) minor complications which occurred in this time span. Factors independently associated with major complications intraprocedurally or within 24 hours were age (p=0.046), body mass index (BMI) ≥30 kg/m2 (p=0.009), significant valvular disease (p=0.001), cardiomyopathy (p<0.001), prior stroke or TIA (p=0.014), first time procedure vs. repeat procedure (p=0.013), cryoablation vs. radiofrequency (p<0.001) and procedure duration (p<0.001). Conclusion Very few complications occurred between six hours and until discharge after ablation of atrial fibrillation. Therefore, same-day discharge may be a safe option for a large proportion of patients. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Region Stockholm funding

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Anatomical localization and classification of bundle branch blocks using novel CineECG

EP Europace ◽

10.1093/europace/euab116.039 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

MJ Boonstra ◽

BN Hilderink ◽

ET Locati ◽

FW Asselbergs ◽

P Loh ◽

...

Keyword(s):

Time Interval ◽

Heart Model ◽

National Budget ◽

Funding Sources ◽

Conduction Disorders ◽

Bundle Branch Blocks ◽

Anatomical Localization ◽

The Mean ◽

Diagnostic Work ◽

Public Grant

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Dutch Heart Foundation Background Ventricular conduction disorders can induce arrhythmias and impair cardiac function. Bundle branch blocks are diagnosed by 12-lead ECG, but discrimination between complete bundle branch blocks, incomplete bundle branch blocks and normal tracings can be challenging. CineECG computes the mean temporo-spatial isochrone (mTSI) trajectory of activation waveforms in a 3D-heart model from 12-lead ECGs. This trajectory represents the mean trajectory of the ventricular electrical activation at any time interval directly related to ventricular anatomy. In Brugada patients, CineECG has localized the terminal components of ventricular depolarization to right ventricle outflow tract (RVOT). Also, for the localization of bundle branch blocks, the region of latest activation contains the most information. Using CineECG, subject specific anatomically related information about the location of bundle branch blocks is obtained. Purpose This study aimed at exploring whether CineECG can improve the discrimination between complete left/right bundle branch blocks (LBBB/RBBB), and incomplete RBBB (iRBBB). Methods We utilized 400 12-lead ECGs from the online Physionet-XL-PTB-Diagnostic ECG Database with a certified ECG diagnosis. The mTSI trajectory was calculated and projected into the anatomical 3D-heart model. Five CineECG classes were established: "Normal", "iRBBB", "RBBB", "LBBB" and "Undetermined", to which each tracing was allocated. We determined the accuracy of CineECG classification with the gold standard diagnosis. Results A total of 391 ECGs were analyzed (9 ECGs were excluded for noise) and 240/266 were correctly classified as "normal", 14/17 as "iRBBB", 55/55 as "RBBB", 51/51 as "LBBB" and 31 as "undetermined". Average mTSI trajectories were calculated according to ECG diagnosis (Figure). The terminal mTSI contained most information about the BBB localization, as that part directs to the site of latest activation (Figure, red arrow). Conclusion CineECG provided the anatomical localization of different BBBs and accurately differentiated between normal, LBBB and RBBB, and iRBBB. CineECG may aid clinical diagnostic work-up, potentially also contributing to the difficult discrimination between normal, iRBBB and Brugada patients. Abstract Figure. Average CineECG trajectories

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CT-based cardiovascular risk stratification benefits in asymptomatic patients

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeab111.021 ◽

2021 ◽

Vol 22 (Supplement_3) ◽

Author(s):

AN Rozhkov ◽

DY Shchekochikhin ◽

PYU Kopylov

Keyword(s):

Computed Tomography ◽

Roc Analysis ◽

Basic Research ◽

Cardiovascular Risks ◽

Diagnostic Significance ◽

National Budget ◽

Funding Sources ◽

Asymptomatic Patients ◽

Outpatient Practice ◽

Public Grant

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Russian Foundation for Basic Research Background Cardiovascular risks (CVR) stratification and assessment of atherosclerotic plaques vulnerability in asymptomatic patients are serious challenges in outpatient practice. The use of modern CT techniques can help to personalize stratification. Methods The study included ambulatory patients with suspected coronary heart disease, who underwent computed tomography coronary angiography (CTA) in 2019-2020. CVR was estimated via Score, ACC/AHA, Framingham, MESA scales, CTA was performed on 640-slice computed tomography station. The patients were divided into two groups: patent arteries and atherosclerotic lesions (30-99%). We analyzed of the estimated CVR distribution, using coronary arteries visualization as the cut-off. Then ROC analysis of the scales, and Agatson Index was performed. Results The study included 60 patients, mean age is 61,5 years (65% female). 36,7% had no atherosclerosis; 56,7% had 30-99% coronary artery stenosis. Our results showed risks overestimation using the SCORE and Framingham scales (+33.33% and +52.38%) and underestimation using ACC/AHA and MESA (-33.33% and -9.52%) in patients without coronary atherosclerosis. The ROC analysis showed that the "standard" scales have no diagnostic significance for zero atherosclerosis (p > 0.05) or for >30% plaques (p > 0.05). Conclusion Our data shows a significant predictive superiority of CTA. Asymptomatic patients with zero or low coronary calcium with low estimated CVR may have a REAL high risk based on morphological plaque criteria.

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