Progress in Arrhythmia: Insights in Integrated Care, Anticoagulation Therapy and Precision Medicine

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: closed (15 March 2023) | Viewed by 24708

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Guest Editor
Department of Cardiology, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), CIBERCV, Hospital Clinico Universitario Virgen Arrixaca, University of Murcia, 30120 Murcia, Spain
Interests: atrial fibrillation; oral nticoagulants; stroke; bleeding; acute coronary syndrome; antiplatelets; nursing

Special Issue Information

Dear Colleagues, 

The management of AF has evolved during the last decades but continues to be complex. Classically, much of the interest has been focused on stroke prevention by using oral anticoagulation therapy and more evidence is needed regarding 1) the efficacy and safety of direct-acting oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs), particularly in certain subgroups of patients with AF or special situations, and 2) more precise methods to estimate the risk of thromboembolism/bleeding and therefore the net benefit of anticoagulation.

However, there is more than stroke in AF. The management of AF-related symptoms, the complex decision of rhythm or rate control therapies, and the management of comorbidities and cardiovascular risk factors have gained attention. Indeed, recent international clinical practice guidelines recommend personalized medicine through integrated care and more emphasis on patient-reported outcomes. On the other hand, new technologies open the possibility of precision medicine. Thus, artificial intelligence, biomarkers, the use of smartwatches, patches, and other electronic devices, may lead to a substantial change in the detection and management of AF.

This issue aims to shed light on some controversial and scarcely investigated topics in relation to novel approaches that should be considered for detection, stroke prevention, and risk-factor optimization in AF patients. Original researches, systematic reviews, review articles and mini-review articles will be welcomed, although other articles types will be also considered.

Dr. José Miguel Rivera-Caravaca
Guest Editor

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Keywords

  • atrial fibrillation
  • integrated care
  • oral anticoagulants
  • stroke prevention
  • artificial intelligence
  • biomarkers
  • precision medicine

Published Papers (11 papers)

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Editorial

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3 pages, 211 KiB  
Editorial
Progressions in Cardiac Arrhythmia: Specific Populations and the Need for Precision Medicine
by José Miguel Rivera-Caravaca and Jeroen M. Hendriks
J. Pers. Med. 2023, 13(7), 1122; https://doi.org/10.3390/jpm13071122 - 11 Jul 2023
Viewed by 759
Abstract
Atrial fibrillation (AF) is the most common cardiac arrhythmia in the general population [...] Full article

Research

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16 pages, 2275 KiB  
Article
Preoperative Prediction of Catheter Ablation Outcome in Persistent Atrial Fibrillation Patients through Spectral Organization Analysis of the Surface Fibrillatory Waves
by Pilar Escribano, Juan Ródenas, Manuel García, Miguel A. Arias, Víctor M. Hidalgo, Sofía Calero, José J. Rieta and Raúl Alcaraz
J. Pers. Med. 2022, 12(10), 1721; https://doi.org/10.3390/jpm12101721 - 14 Oct 2022
Cited by 3 | Viewed by 1912
Abstract
Catheter ablation (CA) is a commonly used treatment for persistent atrial fibrillation (AF). Since its medium/long-term success rate remains limited, preoperative prediction of its outcome is gaining clinical interest to optimally select candidates for the procedure. Among predictors based on the surface electrocardiogram, [...] Read more.
Catheter ablation (CA) is a commonly used treatment for persistent atrial fibrillation (AF). Since its medium/long-term success rate remains limited, preoperative prediction of its outcome is gaining clinical interest to optimally select candidates for the procedure. Among predictors based on the surface electrocardiogram, the dominant frequency (DF) and harmonic exponential decay (γ) of the fibrillatory waves (f-waves) have reported promising but clinically insufficient results. Hence, the main goal of this work was to conduct a broader analysis of the f-wave harmonic spectral structure to improve CA outcome prediction through several entropy-based measures computed on different frequency bands. On a database of 151 persistent AF patients under radio-frequency CA and a follow-up of 9 months, the newly introduced parameters discriminated between patients who relapsed to AF and those who maintained SR at about 70%, which was statistically superior to the DF and approximately similar to γ. They also provided complementary information to γ through different combinations in multivariate models based on lineal discriminant analysis and report classification performance improvement of about 5%. These results suggest that the presence of larger harmonics and a proportionally smaller DF peak is associated with a decreased probability of AF recurrence after CA. Full article
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13 pages, 4170 KiB  
Article
Comparative Study of Methods for Cycle Length Estimation in Fractionated Electrograms of Atrial Fibrillation
by Diego Osorio, Aikaterini Vraka, José Moreno-Arribas, Vicente Bertomeu-González, Raúl Alcaraz and José J. Rieta
J. Pers. Med. 2022, 12(10), 1712; https://doi.org/10.3390/jpm12101712 - 13 Oct 2022
Cited by 1 | Viewed by 1246
Abstract
Atrial cycle length (CL) is an important feature for the analysis of electrogram (EGM) characteristics acquired during catheter ablation (CA) of atrial fibrillation (AF), the commonest cardiac arrhythmia. Nevertheless, a robust ACL estimator requires the precise detection of local activation waves (LAWs), which [...] Read more.
Atrial cycle length (CL) is an important feature for the analysis of electrogram (EGM) characteristics acquired during catheter ablation (CA) of atrial fibrillation (AF), the commonest cardiac arrhythmia. Nevertheless, a robust ACL estimator requires the precise detection of local activation waves (LAWs), which still remains a challenge. This work aims to compare the performance in (CL) estimation, especially under fractionated EGMs, of three different LAW detection methods relying on different operation strategies. The methods are based on the hyperbolic tangent (HT) function, an adaptive amplitude threshold (AAT) and a (CL) iteration (ACLI), respectively. For each method, LAW detection has been assessed with respect to manual annotations made by two experts and performance has been estimated by confusion matrix and mean and individual (CL) error calculation by EGM types of fractionation. The influence of EGM length on the individual (CL) error has been additionally considered. For the HT method, accuracy, sensitivity and precision were 92.77–100%, while for the AAT and ACLI methods they were 78.89–99.91% for all EGM types. The CL error on the HT method was lower than AAT and ACLI methods (up to 12 ms versus up to 20 ms), with the difference being more prominent in complex EGMs. The HT method also showed the lowest dependency on EGM length, presenting the lowest and least variable error values. Therefore, the HT method achieves higher performance in (CL) estimation in comparison with previous LAW detection techniques. The high robustness and precision demonstrated by this method suggest its implementation on CA mapping devices for a more successful location of ablation targets and improved results during CA procedures. Full article
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7 pages, 467 KiB  
Article
A Differential Profile of Biomarkers between Patients with Atrial Fibrillation and Healthy Controls
by Ana Merino-Merino, Ruth Saez-Maleta, Ricardo Salgado-Aranda, Daniel AlKassam-Martinez, Virginia Pascual-Tejerina, Javier Martin-Gonzalez, Javier Garcia-Fernandez and Jose-Angel Perez-Rivera
J. Pers. Med. 2022, 12(9), 1406; https://doi.org/10.3390/jpm12091406 - 30 Aug 2022
Cited by 4 | Viewed by 1461
Abstract
Atrial fibrillation (AF) is explained by anatomical and electrophysiological changes in the atria determined by high pressure, dilatation, infiltration and inflammation in the myocardium. There are some biomarkers implicated in these processes, namely, NT-proBNP, high sensitivity troponin (Hs-Tn), urate, galectin-3, ST2, C reactive [...] Read more.
Atrial fibrillation (AF) is explained by anatomical and electrophysiological changes in the atria determined by high pressure, dilatation, infiltration and inflammation in the myocardium. There are some biomarkers implicated in these processes, namely, NT-proBNP, high sensitivity troponin (Hs-Tn), urate, galectin-3, ST2, C reactive protein and fibrinogen. The aim of this study was to assess differences in these biomarkers between patients with AF and healthy controls. We designed a cross-sectional study consecutively including all patients undergoing electrical cardioversion in our hospital for persistent AF and matched healthy controls. We included 115 patients with persistent non-valvular AF and 33 healthy subjects. The biomarkers NT-proBNP, ST2 and Hs-Tn T were significantly related to the presence of AF (1054 ± 833.30 vs. 58.31 ± 59.40, p < 0.001; 35.43 ± 15.89 vs. 27.43 ± 10.95, p < 0.001 and 10.25 ± 6.11 vs. 8.42 ± 6.85, p < 0.001, respectively). NT-proBNP was the best biomarker differentiating AF patients (area under the curve 0.995). The best NT-proBNP cut-off point to differentiate AF was 102 pg/mL; for Hs-Tn T it was 11.5 ng/L and for ST2 it was 37.7 ng/mL. It is possible that these biomarkers intervene at the onset of AF and have no role in AF maintenance. Full article
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10 pages, 13183 KiB  
Article
Inversion of Left Atrial Appendage Will Cause Compressive Stresses in the Tissue: Simulation Study of Potential Therapy
by Salvatore Pasta, Julius M. Guccione and Ghassan S. Kassab
J. Pers. Med. 2022, 12(6), 883; https://doi.org/10.3390/jpm12060883 - 27 May 2022
Cited by 5 | Viewed by 2208
Abstract
In atrial fibrillation (AF), thromboembolic events can result from the particular conformation of the left atrial appendage (LAA) bearing increased clot formation and accumulation. Current therapies to reduce the risk of adverse events rely on surgical exclusion or percutaneous occlusion, each of which [...] Read more.
In atrial fibrillation (AF), thromboembolic events can result from the particular conformation of the left atrial appendage (LAA) bearing increased clot formation and accumulation. Current therapies to reduce the risk of adverse events rely on surgical exclusion or percutaneous occlusion, each of which has drawbacks limiting application and efficacy. We sought to quantify the hemodynamic and structural loads of a novel potential procedure to partially invert the “dead” LAA space to eliminate the auricle apex where clots develop. A realistic left atrial geometry was first achieved from the heart anatomy of the Living Heart Human Model (LHHM) and then the left atrial appendage inversion (LAAI) was simulated by finite-element analysis. The LAAI procedure was simulated by pulling the elements at the LAA tip and prescribing a displacement motion along a predefined path. The deformed configuration was then used to develop a computational flow analysis of LAAI. Results demonstrated that the inverted LAA wall undergoes a change in the stress distribution from tensile to compressive in the inverted appendage, and this can lead to resorption of the LAA tissue as per a reduced stress/resorption relationship. Computational flow analyses highlighted a slightly nested low-flow velocity pattern for the inverted LAA with minimal differences from that of a model without inversion of the LAA apex. Our study revealed important insights into the biomechanics of LAAI and demonstrated the inversion of the stress field (from tensile to compressive), which &can ultimately lead the long-term resorption of the LAA. Full article
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9 pages, 1030 KiB  
Article
Clinical Phenotypes of Atrial Fibrillation and Mortality Risk—A Cluster Analysis from the Nationwide Italian START Registry
by Daniele Pastori, Emilia Antonucci, Alberto Milanese, Danilo Menichelli, Gualtiero Palareti, Alessio Farcomeni, Pasquale Pignatelli and the START2 Register Investigators
J. Pers. Med. 2022, 12(5), 785; https://doi.org/10.3390/jpm12050785 - 12 May 2022
Cited by 4 | Viewed by 1746
Abstract
Patients with atrial fibrillation (AF) still experience a high mortality rate despite optimal antithrombotic treatment. We aimed to identify clinical phenotypes of patients to stratify mortality risk in AF. Cluster analysis was performed on 5171 AF patients from the nationwide START registry. The [...] Read more.
Patients with atrial fibrillation (AF) still experience a high mortality rate despite optimal antithrombotic treatment. We aimed to identify clinical phenotypes of patients to stratify mortality risk in AF. Cluster analysis was performed on 5171 AF patients from the nationwide START registry. The risk of all-cause mortality in each cluster was analyzed. We identified four clusters. Cluster 1 was composed of the youngest patients, with low comorbidities; Cluster 2 of patients with low cardiovascular risk factors and high prevalence of cancer; Cluster 3 of men with diabetes and coronary disease and peripheral artery disease; Cluster 4 included the oldest patients, mainly women, with previous cerebrovascular events. During 9857 person-years of observation, 386 deaths (3.92%/year) occurred. Mortality rates increased across clusters: 0.42%/year (cluster 1, reference group), 2.12%/year (cluster 2, adjusted hazard ratio (aHR) 3.306, 95% confidence interval (CI) 1.204–9.077, p = 0.020), 4.41%/year (cluster 3, aHR 6.702, 95%CI 2.433–18.461, p < 0.001), and 8.71%/year (cluster 4, aHR 8.927, 95%CI 3.238–24.605, p < 0.001). We identified four clusters of AF patients with progressive mortality risk. The use of clinical phenotypes may help identify patients at a higher risk of mortality. Full article
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10 pages, 1185 KiB  
Article
Relation of the ‘Atrial Fibrillation Better Care (ABC) Pathway’ to the Quality of Anticoagulation in Atrial Fibrillation Patients Taking Vitamin K Antagonists
by Vanessa Roldán, Lorena Martínez-Montesinos, Raquel López-Gálvez, Lucía García-Tomás, Gregory Y. H. Lip, José Miguel Rivera-Caravaca and Francisco Marín
J. Pers. Med. 2022, 12(3), 487; https://doi.org/10.3390/jpm12030487 - 17 Mar 2022
Cited by 4 | Viewed by 2006
Abstract
The Atrial Fibrillation Better Care (ABC) pathway was proposed for a more integrated atrial fibrillation (AF) care. We investigated if adherence to the ABC pathway was associated to the quality of anticoagulation control in a cohort of AF outpatients starting vitamin K antagonists [...] Read more.
The Atrial Fibrillation Better Care (ABC) pathway was proposed for a more integrated atrial fibrillation (AF) care. We investigated if adherence to the ABC pathway was associated to the quality of anticoagulation control in a cohort of AF outpatients starting vitamin K antagonists (VKAs) between July 2016 and June 2018. Patients were considered adherent to the ABC pathway if they met all of its components. The time in therapeutic range (TTR) was estimated at one year. In total, 1045 patients (51.6% female; median age 77 years; 63% ABC pathway adherent) were included. At one year, 474 (51.6%) of 919 patients with international normalized ratio (INR) data for TTR estimation had a TTR < 65%. Among ABC pathway non-adherent patients, a greater proportion had TRT < 65% (56.4% vs. 43.6%, p = 0.025), and TTR < 70% (64.9% vs. 35.1%, p = 0.033), with lower mean TTR in non-adherent patients (59.4 ± 22.3% vs. 63.9 ± 21.1%; p = 0.004). Logistic regression models demonstrated that the ABC pathway adherence in its continuous (aOR: 0.75, 95% CI 0.59–0.96) and categorical (aOR: 0.75, 95% CI 0.57–0.98) forms was independently associated with TTR ≥ 65%. In this ‘real-world’ cohort of AF patients starting VKAs, the ABC pathway adherent patients had better TTR, and more ABC criteria fulfilled increased the probability of achieving good TTR. Full article
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18 pages, 2749 KiB  
Article
The Dissimilar Impact in Atrial Substrate Modificationof Left and Right Pulmonary Veins Isolation after Catheter Ablation of Paroxysmal Atrial Fibrillation
by Aikaterini Vraka, Vicente Bertomeu-González, Lorenzo Fácila, José Moreno-Arribas, Raúl Alcaraz and José J. Rieta
J. Pers. Med. 2022, 12(3), 462; https://doi.org/10.3390/jpm12030462 - 14 Mar 2022
Cited by 2 | Viewed by 1974
Abstract
Since the discovery of pulmonary veins (PVs) as foci of atrial fibrillation (AF), the commonest cardiac arrhythmia, investigation revolves around PVs catheter ablation (CA) results. Notwithstanding, CA process itself is rather neglected. We aim to decompose crucial CA steps: coronary sinus (CS) catheterization [...] Read more.
Since the discovery of pulmonary veins (PVs) as foci of atrial fibrillation (AF), the commonest cardiac arrhythmia, investigation revolves around PVs catheter ablation (CA) results. Notwithstanding, CA process itself is rather neglected. We aim to decompose crucial CA steps: coronary sinus (CS) catheterization and the impact of left and right PVs isolation (LPVI, RPVI), separately. We recruited 40 paroxysmal AF patients undergoing first-time CA and obtained five-minute lead II and bipolar CS recordings during sinus rhythm (SR) before CA (B), after LPVI (L) and after RPVI (R). Among others, duration, amplitude and atrial-rate variability (ARV) were calculated for P-waves and CS local activation waves (LAWs). LAWs features were compared among CS channels for reliability analysis. P-waves and LAWs features were compared after each ablation step (B, L, R). CS channels: amplitude and area were different between distal/medial (p0.0014) and distal/mid-proximal channels (p0.0025). Medial and distal showed the most and least coherent values, respectively. Correlation was higher in proximal (≥93%) than distal (≤91%) areas. P-waves: duration was significantly shortened after LPVI (after L: p=0.0012, 13.30%). LAWs: insignificant variations. ARV modification was more prominent in LAWs (L: >+73.12%, p0.0480, R: <−33.94%, p0.0642). Medial/mid-proximal channels are recommended during SR. CS LAWs are not significantly affected by CA but they describe more precisely CA-induced ARV modifications. LPVI provokes the highest impact in paroxysmal AF CA, significantly modifying P-wave duration. Full article
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Review

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14 pages, 951 KiB  
Review
Atrial Fibrillation Specific Exercise Rehabilitation: Are We There Yet?
by Benjamin J. R. Buckley, Signe S. Risom, Maxime Boidin, Gregory Y. H. Lip and Dick H. J. Thijssen
J. Pers. Med. 2022, 12(4), 610; https://doi.org/10.3390/jpm12040610 - 10 Apr 2022
Cited by 6 | Viewed by 5065
Abstract
Regular physical activity and exercise training are integral for the secondary prevention of cardiovascular disease. Despite recent advances in more holistic care pathways for people with atrial fibrillation (AF), exercise rehabilitation is not provided as part of routine care. The most recent European [...] Read more.
Regular physical activity and exercise training are integral for the secondary prevention of cardiovascular disease. Despite recent advances in more holistic care pathways for people with atrial fibrillation (AF), exercise rehabilitation is not provided as part of routine care. The most recent European Society of Cardiology report for AF management states that patients should be encouraged to undertake moderate-intensity exercise and remain physically active to prevent AF incidence or recurrence. The aim of this review was to collate data from primary trials identified in three systematic reviews and recent real-world cohort studies to propose an AF-specific exercise rehabilitation guideline. Collating data from 21 studies, we propose that 360–720 metabolic equivalent (MET)-minutes/week, corresponding to ~60–120 min of exercise per week at moderate-to-vigorous intensity, could be an evidence-based recommendation for patients with AF to improve AF-specific outcomes, quality of life, and possibly prevent long-term major adverse cardiovascular events. Furthermore, non-traditional, low-moderate intensity exercise, such as Yoga, seems to have promising benefits on patient quality of life and possibly physical capacity and should, therefore, be considered in a personalised rehabilitation programme. Finally, we discuss the interesting concepts of short-term exercise-induced cardioprotection and ‘none-response’ to exercise training with reference to AF rehabilitation. Full article
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21 pages, 376 KiB  
Review
Current Therapeutic Approach to Atrial Fibrillation in Patients with Congenital Hemophilia
by Minerva Codruta Badescu, Oana Viola Badulescu, Lacramioara Ionela Butnariu, Mariana Floria, Manuela Ciocoiu, Irina-Iuliana Costache, Diana Popescu, Ioana Bratoiu, Oana Nicoleta Buliga-Finis and Ciprian Rezus
J. Pers. Med. 2022, 12(4), 519; https://doi.org/10.3390/jpm12040519 - 23 Mar 2022
Cited by 5 | Viewed by 2770
Abstract
Cardiovascular disease in hemophiliacs has an increasing prevalence due to the aging of this population. Hemophiliacs are perceived as having a high bleeding risk due to the coagulation factor VIII/IX deficiency, but it is currently acknowledged that they also have an important ischemic [...] Read more.
Cardiovascular disease in hemophiliacs has an increasing prevalence due to the aging of this population. Hemophiliacs are perceived as having a high bleeding risk due to the coagulation factor VIII/IX deficiency, but it is currently acknowledged that they also have an important ischemic risk. The treatment of atrial fibrillation (AF) is particularly challenging since it usually requires anticoagulant treatment. The CHA2DS2-VASc score is used to estimate the risk of stroke and peripheral embolism, and along with the severity of hemophilia, guide the therapeutic strategy. Our work provides the most complete, structured, and updated analysis of the current therapeutic approach of AF in hemophiliacs, emphasizing that there is a growing interest in therapeutic strategies that allow for short-term anticoagulant therapy. Catheter ablation and left atrial appendage occlusion have proven to be efficient and safe procedures in hemophiliacs, if appropriate replacement therapy can be provided. Full article

Other

12 pages, 3042 KiB  
Protocol
Supermarket/Hypermarket Opportunistic Screening for Atrial Fibrillation (SHOPS-AF): A Mixed Methods Feasibility Study Protocol
by Ian D. Jones, Deirdre A. Lane, Robyn R. Lotto, David Oxborough, Lis Neubeck, Peter E. Penson, Gabriela Czanner, Andy Shaw, Emma Johnston Smith, Aimeris Santos, Emily E. McGinn, Aderonke Ajiboye, Nicola Town and Gregory Y. H. Lip
J. Pers. Med. 2022, 12(4), 578; https://doi.org/10.3390/jpm12040578 - 04 Apr 2022
Cited by 3 | Viewed by 2582
Abstract
Aims: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a key risk factor for ischaemic stroke. Following AF detection, treatment with oral anticoagulation can significantly lower mortality and morbidity rates associated with this risk. The availability of several hand-held devices [...] Read more.
Aims: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a key risk factor for ischaemic stroke. Following AF detection, treatment with oral anticoagulation can significantly lower mortality and morbidity rates associated with this risk. The availability of several hand-held devices which can detect AF may enable trained health professionals to adopt AF screening approaches which do not interfere with people’s daily routines. This study aims to investigate the effectiveness of a hand-held device (the MyDiagnostick single-lead Electrocardiogram (ECG) sensor) in screening for AF when embedded into the handles of supermarket trolleys. Methods: A mixed methods two-phase approach will be taken. The quantitative first phase will involve the recruitment of 2000 participants from a convenience sample at four large supermarkets with pharmacies. Prospective participants will be asked to conduct their shopping using a trolley embedded with a MyDiagnostick sensor. If the device identifies a participant with AF, the in-store pharmacist will be dispatched to take a manual pulse measurement and a static control sensor reading and offer a cardiologist consultation referral. When the sensor does not detect AF, a researcher will confirm the reading with a manual pulse measurement. ECGs will be compiled, and the sensitivity, specificity and positive and negative predictive values will be determined. A qualitative second phase will consist of semi-structured interviews carried out with those pharmacists and store managers in-store during the running of the trial period. These will explore the perceptions of staff regarding the merits of embedding sensors in the handles of supermarket trolleys to detect AF. Conclusion: This feasibility study will inform a larger future definitive trial. Full article
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