Disruption of Sarcoplasmic Reticulum-Mitochondrial Contacts Underlies Contractile Dysfunction in Experimental and Human Atrial Fibrillation: A Key Role of Mitofusin 2.

Background Atrial fibrillation (AF) is the most common and progressive tachyarrhythmia. Diabetes is a common risk factor for AF. Recent research findings revealed that microtubule network disruption underlies AF.

Atrial heat shock protein levels are associated with early postoperative and persistence of atrial fibrillation.

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.

Identification of Low-Voltage Areas: A Unipolar, Bipolar, and Omnipolar Perspective.

[Figure: see text].

Blood-based 8-hydroxy-2'-deoxyguanosine level: A potential diagnostic biomarker for atrial fibrillation.

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.

Evaluating Serum Heat Shock Protein Levels as Novel Biomarkers for Atrial Fibrillation.

Staging of atrial fibrillation (AF) is essential to understanding disease progression and the accompanied increase in therapy failure. Blood-based heat shock protein (HSP) levels may enable staging of AF and the identification of patients with higher risk for AF recurrence after treatment. This study evaluates the relationship between serum HSP levels, presence of AF, AF stage and AF recurrence following electrocardioversion (ECV) or pulmonary vein isolation (PVI).

Sinus Rhythm Conduction Properties across Bachmann's Bundle: Impact of Underlying Heart Disease and Atrial Fibrillation.

Valvular heart disease (VHD) is a common risk factor for atrial fibrillation (AF). Conduction abnormalities (CA) during sinus rhythm (SR) across Bachmann's bundle (BB) are associated with AF development. The study goal is to compare electrophysiological characteristics across BB during SR between patients with ischemic (IHD) and/or VHD either with or without ischemic heart disease ((I)VHD), with/without AF history using high-resolution intraoperative epicardial mapping.

Distribution of Conduction Disorders in Patients With Congenital Heart Disease and Right Atrial Volume Overload.

Objectives: This study sought to quantify characteristics of atrial conduction disorders in patients with right atrial (RA) volume overload.

Background: Patients with an interatrial shunt are prone to developing atrial fibrillation (AF), which may be related to conduction disorders occurring due to atrial stretch.

Methods: Thirty-one patients undergoing surgery for an interatrial shunt (49 ± 14 years of age) underwent epicardial sinus rhythm mapping of the RA, Bachmann's bundle (BB), and left atrium (LA).

Cell-Free Circulating Mitochondrial DNA: A Potential Blood-Based Marker for Atrial Fibrillation.

Atrial fibrillation (AF), the most common, progressive tachyarrhythmia is associated with serious complications, such as stroke and heart failure. Early recognition of AF, essential to prevent disease progression and therapy failure, is hampered by the lack of accurate diagnostic serum biomarkers to identify the AF stage. As we previously showed mitochondrial dysfunction to drive experimental and human AF, we evaluated whether cell-free circulating mitochondrial DNA (cfc-mtDNA) represents a potential serum marker.

Early markers of atrial fibrillation recurrence after pulmonary vein isolation.

Background: Postprocedural atrial extrasystole (AES) frequency predicts atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) in patients with paroxysmal AF. However, the predictive value of preprocedural AES frequency is unknown. We investigate whether preprocedural AES frequency is a feasible marker to predict (timing of) AF recurrence after PVI.

Atrial fibrillation: A never ending story?

Atrial fibrillation (AF) often recurs after ablative therapy. In our patient, intraoperative epicardial mapping during therapy- resistant AF revealed highly dissociated atrial conduction patterns and that long lines of conduction block throughout the entire atria. Given the extensiveness of the substrate, it is not surprising that ablations were not successful.

The Effects of Valvular Heart Disease on Atrial Conduction During Sinus Rhythm.

Different arrhythmogenic substrates for atrial fibrillation (AF) may underlie aortic valve (AV) and mitral valve (MV) disease. We located conduction disorders during sinus rhythm by high-resolution epicardial mapping in patients undergoing AV (n = 85) or MV (n = 54) surgery. Extent and distribution of conduction delay (CD) and block (CD) across the entire right and left atrial surface was determined from circa 1880 unipolar electrogram recordings per patient.

Ventricular Dysrhythmias During Long-Term Follow-Up in Patients With Inherited Cardiac Arrhythmia.

Reports on development of frequent ventricular premature complexes (fVPC), (non)sustained ventricular tachycardias ([n]sVT), or ventricular fibrillation (VF) and their interrelationship in patients with different inherited cardiac arrhythmia (ICA) have sofar not been reported. The aim of this study is therefore to examine incidences and recurrences rates of sVT and VF ("malignant ventricular tachyarrhythmias, VTA") in addition to the incidence of fVPC and nsVT ("ventricular dysrhythmias, VDR") in patients with various ICA during long-term follow up. Patients (N = 167, 88 male, age 45 ± 15 years) with ICA including definite/borderline arrhythmogenic right ventricular cardiomyopathy (ARVC, N = 47), Brugada syndrome (BrS, N = 71), catecholaminergic polymorphic ventricular tachycardia (CPVT, N = 7), long QT syndrome (LQTS, N = 41) or short QT syndrome (SQTS, N = 1) who had frequent 24-hour Holter monitoring during a follow-up period of 4.

The impact of obesity on early postoperative atrial fibrillation burden.

Background: Obesity has been linked to the development of postoperative atrial fibrillation. This study is aimed at investigating the role of body mass index in the evolution of de novo, early postoperative atrial fibrillation by assessing differences between obese and nonobese patients undergoing cardiac surgery.

Methods: Patients with early de novo postoperative atrial fibrillation were included.

QRS Vector Magnitude as Predictor of Ventricular Arrhythmia in Patients With Brugada Syndrome.

Risk stratification is the most challenging part in management of patients with Brugada syndrome (BrS). Conduction delay in the right ventricular outflow tract (RVOT) is the major mechanism underlying ventricular tachyarrhythmia (VTA) in BrS. However, QRS duration was not useful in stratifying high-risk patients in large registries.

DNA damage-induced PARP1 activation confers cardiomyocyte dysfunction through NAD depletion in experimental atrial fibrillation.

Atrial fibrillation (AF) is the most common clinical tachyarrhythmia with a strong tendency to progress in time. AF progression is driven by derailment of protein homeostasis, which ultimately causes contractile dysfunction of the atria. Here we report that tachypacing-induced functional loss of atrial cardiomyocytes is precipitated by excessive poly(ADP)-ribose polymerase 1 (PARP1) activation in response to oxidative DNA damage.

Impact of the arrhythmogenic potential of long lines of conduction slowing at the pulmonary vein area.

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.

Novel Insights in the Activation Patterns at the Pulmonary Vein Area.

Background: Extensiveness of conduction delay and block at the pulmonary vein area (PVA) was quantified in a previous study. We hypothesized that the combination of lines of conduction block with multiple concomitantly entering sinus rhythm wavefronts at the PVA may result in increased arrhythmogenicity and susceptibility to atrial fibrillation (AF).

Methods: Intraoperative high-density epicardial mapping of PVA (N≈450 sites, interelectrode distances: 2 mm) was performed during sinus rhythm in 327 patients (241 male [74%], 67±10 [21-84] years) with and without preoperative AF.

Application of kinomic array analysis to screen for altered kinases in atrial fibrillation remodeling.

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).

Prediction of ventricular tachyarrhythmia in Brugada syndrome by right ventricular outflow tract conduction delay signs.

Background: Brugada syndrome (BrS) is an autosomal dominant disease responsible for sudden cardiac death in young individuals without structural anomalies. The most critical part in the management of this channelopathy is identification of high-risk patients, especially asymptomatic subjects. Prior studies have shown that conduction delay in the right ventricular outflow tract (RVOT) is the main mechanism for developing ventricular tachyarrhythmia (VTA) in BrS patients.

Intraoperative Inducibility of Atrial Fibrillation Does Not Predict Early Postoperative Atrial Fibrillation.

Background: Early postoperative atrial fibrillation (EPoAF) is associated with thromboembolic events, prolonged hospitalization, and development of late PoAF (LPoAF). It is, however, unknown if EPoAF can be predicted by intraoperative AF inducibility. The aims of this study are therefore to explore (1) the value of intraoperative inducibility of AF for development of both EPoAF and LPoAF and (2) the predictive value of de novo EPoAF for recurrence of LPoAF.

Impact of Ischemic and Valvular Heart Disease on Atrial Excitation:A High-Resolution Epicardial Mapping Study.

Background: The influence of underlying heart disease or presence of atrial fibrillation (AF) on atrial excitation during sinus rhythm (SR) is unknown. We investigated atrial activation patterns and total activation times of the entire atrial epicardial surface during SR in patients with ischemic and/or valvular heart disease with or without AF.

Methods And Results: Intraoperative epicardial mapping (N=128/192 electrodes, interelectrode distances: 2 mm) of the right atrium, Bachmann's bundle (BB), left atrioventricular groove, and pulmonary vein area was performed during SR in 253 patients (186 male [74%], age 66±11 years) with ischemic heart disease (N=132, 52%) or ischemic valvular heart disease (N=121, 48%).

Unipolar atrial electrogram morphology from an epicardial and endocardial perspective.

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.

Quantification of the Arrhythmogenic Effects of Spontaneous Atrial Extrasystole Using High-Resolution Epicardial Mapping.

Background: Atrial extrasystoles (AES) can initiate atrial fibrillation. However, the impact of spontaneous AES on intra-atrial conduction is unknown. The aims of this study were to examine conduction disorders provoked by AES and to correlate these conduction differences with patient characteristics, mapping locations, and type of AES.

Impact of Supraventricular Tachyarrhythmia in Patients With Inherited Cardiac Arrhythmia.

Supraventricular tachyarrhythmia (SVT), especially atrial fibrillation (AF), has been observed in patients with inherited cardiac arrhythmia (ICA). Data on the time course of SVT and the occurrence of SVT other than AF is limited. In this study, we examined the prevalence, co-existence, and the time course of different types of SVT in patients with various ICAs.

Epicardial Breakthrough Waves During Sinus Rhythm: Depiction of the Arrhythmogenic Substrate?

Background: Epicardial breakthrough waves (EBW) during atrial fibrillation are important elements of the arrhythmogenic substrate and result from endo-epicardial asynchrony, which also occurs to some degree during sinus rhythm (SR). We examined the incidence and characteristics of EBW during SR and its possible value in the detection of the arrhythmogenic substrate associated with atrial fibrillation.

Methods And Results: Intraoperative epicardial mapping (interelectrode distances 2 mm) of the right atrium, Bachmann's bundle, the left atrioventricular groove, and the pulmonary vein area was performed during SR in 381 patients (289 male, 67±10 years) with ischemic or valvular heart disease.