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Background: Early detection and staging of atrial fibrillation (AF) is of importance for clinical management. Serum (bio)markers, such as heat shock proteins (HSP), may enable AF staging and identify patients at risk for AF recurrence and postoperative AF (PoAF)., Objective: This study evaluates the relation between serum and atrial tissue HSP levels, stages of AF, AF recurrence after treatment, and PoAF from patients undergoing cardiothoracic surgery., Methods: Patients without (control) and with paroxysmal, persistent (PerAF), or longstanding persistent (LSPerAF) AF were included. HSPB1, HSPA1, HSPB7, and HSPD1 levels were measured in serum obtained prior to and post intervention. HSPB1, HSPA1, HSPA5, HSPD1, HSPB5, and pHSF1 levels were measured in left and/or right atrial appendages (respectively, LAA and RAA)., Results: In RAA, HSPA5 levels were significantly lower in LSPerAF and HSPD1 levels significantly higher in PerAF patients compared to controls. In RAA of controls who developed PoAF, HSPA1 and HSPA5 levels were significantly higher compared to those without PoAF. Also, HSPB1 RAA levels were lower and HSPA5 LAA levels higher in patients undergoing arrhythmia surgery who developed AF recurrence within 1 week after surgery compared to patients who did not., Conclusion: HSPA5 RAA and HSPD1 RAA and LAA levels are altered in persistent stages of AF. RAA HSPA1 and HSPA5 levels associate with development of PoAF. Additionally, HSPB1 RAA and HSPA5 LAA levels can predict AF recurrence in patients who underwent arrhythmia surgery. Nevertheless, HSP levels in serum cannot discriminate AF stages from controls, nor predict PoAF or AF recurrence after treatment., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Recent research findings have revealed a key role of oxidative DNA damage in the pathogenesis of atrial fibrillation (AF). Therefore, the circulating oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) may represent a biomarker for staging AF and identifying patients at risk for AF recurrence and postoperative atrial fibrillation (POAF) after treatment., Objective: The purpose of this study was to investigate whether serum levels of 8-OHdG correlate with the stage of AF, recurrence after AF treatment, and onset of POAF after cardiac surgery., Methods: In this prospective observational study, 8-OHdG levels were detected by enzyme-linked immunosorbent assay in human serum samples. Blood samples were collected from control patients without AF history; patients with paroxysmal AF and persistent AF undergoing electrical cardioversion or pulmonary vein isolation (PVI); and patients with sinus rhythm (SR) undergoing cardiac surgery. AF recurrence was determined during 12-month follow-up. Univariate and multivariate analyses were used to identify changes in 8-OHdG levels between the groups., Results: Compared to the control group, 8-OHdG levels in the patient groups gradually and significantly increased during arrhythmia progression. 8-OHdG levels in AF patients showing AF recurrence after PVI treatment were significantly increased compared to patients without AF recurrence. Moreover, in SR patients undergoing cardiac surgery, 8-OHdG levels were significantly elevated in those showing POAF compared to patients without POAF., Conclusion: 8-OHdG level may represent a potential diagnostic biomarker for AF staging as well as for predicting AF recurrence and POAF after treatment., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Areas of conduction delay (CD) or conduction block (CB) are associated with higher recurrence rates after ablation therapy for atrial fibrillation (AF)., Objective: Thus far, there are no reports on the quantification of the extensiveness of CD and CB at the pulmonary vein area (PVA) and their clinical relevance., Methods: Intraoperative high-density epicardial mapping of the PVA (interelectrode distance 2 mm) was performed during sinus rhythm in 268 patients (mean ± SD [minimum-maximum] 67 ± 11 [21-84] years) with and without preoperative AF. For each patient, extensiveness of CD (conduction velocity 17-29 cm/s) and CB (conduction velocity <17 cm/s) was assessed and related to the presence and type of AF., Results: CD and CB occurred in, respectively, 242 (90%) and 183 (68%) patients. Patients with AF showed a higher incidence of continuous conduction delay and block (CDCB) lines (AF: n = 37 [76%]; no AF: n = 132 [60%]; P = .046), a 2-fold number of lines per patient (CD: 7 [0-30] vs 4 [0-22], P < .001; CB: 3 [0-11] vs 1 [0-12], P = .003; CDCB: 2 [0-6] vs 1 [0-8], P = .004), and a higher incidence of CD or CB lines ≥6 mm and CDCB lines ≥16 mm (P = .011, P = .025, and P = .027). The extensiveness of CD, CB, and CDCB could not distinguish between the different AF types., Conclusion: Patients with AF more often present with continuous lines of adjacent areas of CD and CB, whereas in patients without AF, lines of CD and CB are shorter and more often separated by areas with normal intra-atrial conduction. However, a considerable overlap in the amount of conduction abnormalities at the PVA was observed between patients with a history of paroxysmal and persistent AF., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Dysregulation of protein kinase-mediated signaling is an early event in many diseases, including the most common clinical cardiac arrhythmia, atrial fibrillation (AF). Kinomic profiling represents a promising technique to identify candidate kinases., Objective: In this study we used kinomic profiling to identify kinases altered in AF remodeling using atrial tissue from a canine model of AF (atrial tachypacing)., Methods: Left atrial tissue obtained in a previous canine study was used for kinomic array (containing 1024 kinase pseudosubstrates) analysis. Three groups of dogs were included: nonpaced controls and atrial tachypaced dogs, which were contrasted with geranylgeranylacetone-treated dogs with AF, which are protected from AF promotion, to enhance specificity of detection of putative kinases., Results: While tachypacing changed activity of 50 kinases, 40 of these were prevented by geranylgeranylacetone and involved in differentiation and proliferation (SRC), contraction, metabolism, immunity, development, cell cycle (CDK4), and survival (Akt). Inhibitors of Akt (MK2206) and CDK4 (PD0332991) and overexpression of a dominant-negative CDK4 phosphorylation mutant protected against tachypacing-induced contractile dysfunction in HL-1 cardiomyocytes. Moreover, patients with AF show down- and upregulation of SRC and Akt phosphorylation, respectively, similar to findings of the kinome array., Conclusion: Contrasting kinomic array analyses of controls and treated subjects offer a versatile tool to identify kinases altered in atrial remodeling owing to tachypacing, which include Akt, CDK4, and SRC. Ultimately, pharmacological targeting of altered kinases may offer novel therapeutic possibilities to treat clinical AF., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Background: Endo-epicardial asynchrony (EEA) and the interplay between the endocardial and epicardial layers could be important in the pathophysiology of atrial arrhythmias. The morphologic differences between epicardial and endocardial atrial electrograms have not yet been described, and electrogram morphology may hold information about the presence of EEA., Objective: The purpose of this study was to directly compare epicardial to endocardial unipolar electrogram morphology during sinus rhythm (SR) and to evaluate whether EEA contributes to electrogram fractionation by correlating fractionation to spatial activation patterns., Methods: In 26 patients undergoing cardiac surgery, unipolar electrograms were simultaneously recorded from the epicardium and endocardium at the inferior, middle, and superior right atrial (RA) free wall during SR. Potentials were analyzed for epi-endocardial differences in local activation time, voltage, RS ratio, and fractionation. The surrounding and opposite electrograms of fractionated deflections were evaluated for corresponding local activation times in order to determine whether fractionation originated from EEA., Results: The superior RA was predisposed to delayed activation, EEA, and fractionation. Both epicardial and endocardial electrograms demonstrated an S-predominance. Fractionation was mostly similar between the 2 sides; however, incidentally deflections up to 4 mV on 1 side could be absent on the other side. Remote activation was responsible for most fractionated deflections (95%) in SR, of which 4% could be attributed to EEA., Conclusion: Local epi-endocardial differences in electrogram fractionation occur occasionally during SR but will likely increase during arrhythmias due to increasing EEA and (functional) conduction disorders. Electrogram fractionation can originate from EEA, and this study demonstrated that unipolar electrogram fractionation can potentially identify EEA., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Length of lines of conduction block (CB) during sinus rhythm (SR) at Bachmann's bundle (BB) is associated with atrial fibrillation (AF). However, it is unknown whether extensiveness of CB at BB represents CB elsewhere in the atria. We aim to investigate during SR 1) the spatial distribution and extensiveness of CB 2) whether there is a predilection site for CB and 3) the association between CB and incidence of post-operative AF., Methods: During SR, epicardial mapping of the right atrium (RA), BB and left atrium was performed in 209 patients with coronary artery disease. The amount of conduction delay (CD, Δlocal activation time ≥7ms) and CB (Δ≥12ms) was quantified as % of the mapping area. Atrial regions were compared to identify potential predilection sites for CD/CB. Correlations between CD/CB and clinical characteristics were tested., Results: Areas with CD or CB were present in all patients, overall prevalence was respectively 1.4(0.2-4.0) % and 1.3(0.1-4.3) %. Extensiveness and spatial distribution of CD/CB varied considerably, however occurred mainly at the superior intercaval RA. Of all clinicalcharacteristics, CD/CB only correlated weakly with age and diabetes (P<0.05). A 1% increase in CD or CB caused a 1.1-1.5ms prolongation of the activation time (P<0.001). There was no correlation between CD/CB and post-operative AF., Conclusion: CD/CB during SR in CABG patients with electrically non-remodeled atria show considerable intra-atrial, but also inter-individual variation. Despite these differences, a predilection site is present at the superior intercaval RA. Extensiveness of CB at the superior intercaval RA or BB does not reflect CB elsewhere in the atria and is not associated with post-operative AF., (Copyright © 2017 Elsevier B.V. All rights reserved.)