Atrial Ectopy Increases Asynchronous Activation of the Endo- and Epicardium at the Right Atrium.

The predisposition of atrial extrasystoles (AES) to trigger cardiac tachyarrhythmia may arise from intramural conduction disorders causing endo-epicardial asynchrony (EEA). This study aimed to determine whether spontaneous AES disturb endo-epicardial conduction. Simultaneous endo-epicardial mapping of the right atrium was performed in patients during cardiac surgery with two 128-electrode arrays. Sixty spontaneous AES were observed in 23 patients and were analyzed for incidence of conduction delay, conduction block and amount of EEA compared to the previous sinus rhythm beat. Both conduction delay and block occurred more often in AES compared to sinus rhythm. The difference in lines of conduction block between the epicardium and endocardium increased in AES causing a greater imbalance of conduction disorders between the layers. The incidence of EEA with differences ≥10 ms increased significantly in AES. AES caused delays between the epicardium and endocardium up to 130 ms and EEA to increase for up to half (47%) of the mapping area. Conduction disturbances between the epicardial and endocardial layer giving rise to EEA increase during AES. Asynchronous activation of the atrial layers increases during AES which may be a mechanism for triggering cardiac tachyarrhythmia under the right conditions but EEA cannot be recognized by current mapping tools.

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. CD and CB were most pronounced at the superior intercaval area (2.5% of surface, maximal degree 6.6%/cm2). MV patients had a higher maximal degree of CD at the lateral left atrium than AV patients (4.2 vs 2.3%/cm2, p = 0.001). A history of AF was most strongly correlated to CD/CB at Bachmann's bundle and age. Although MV patients have more conduction disorders at the lateral left atrium, disturbed conduction at Bachmann's bundle during sinus rhythm indicates the presence of atrial remodeling which is related to AF episodes.

Epicardial atrial mapping during minimally invasive cardiothoracic surgery.

Mapping of the unorganized activation patterns of atrial fibrillation requires a high-resolution mapping approach to diagnose substrate-mediated pathophysiological mechanisms. At present, epicardial mapping is the only approach that is able to acquire electrograms of >200 high-density sites simultaneously. This study introduces a technique to perform high-resolution mapping in minimally invasive surgery. In 3 patients with mitral valve disease, epicardial mapping of the right atrium, Bachmann's bundle and parts of the left atrium was safely performed via minimal right thoracotomy.

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. METHODS AND RESULTS: Patients (N=496, 75% male) undergoing cardiothoracic surgery for coronary and/or valvular heart disease were included. AF induction was attempted by atrial pacing, before extracorporeal circulation. All patients were on continuous rhythm monitoring until discharge to detect EPoAF. During a follow-up period of 2 years, LPoAF was detected by ECGs and Holter recordings. Sustained AF was inducible in 56% of patients. There was no difference in patients with or without AF before surgery (P=0.159), or between different types of surgery (P=0.687). In patients without a history of AF, incidence of EPoAF and LPoAF was 37% and 2%, respectively. EPoAF recurred in 58% patients with preoperative AF, 53% developed LPoAF. There were no correlations between intraoperative inducibility and EPoAF or LPoAF (P>0.05). EPoAF was not correlated with LPoAF in patients without a history of AF (P=0.116), in contrast to patients with AF before surgery (P<0.001). CONCLUSIONS: Intraoperative AF inducibility does not predict development of either EPoAF or LPoAF. In patients with AF before surgery, EPoAF is correlated with LPoAF recurrences. This correlation is absent in patients without AF before surgery.

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. 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.

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. METHODS AND RESULTS: High-resolution epicardial mapping (electrodes N=128 or N=192; interelectrode distance, 2 mm) of the entire atrial surface was performed in patients (N=164; 69.5% male; age 67.2±10.5 years) undergoing open-chest cardiac surgery. AES were classified as premature, aberrant, or prematurely aberrant. Conduction delay and conduction block were quantified during sinus rhythm and AES and subsequently compared. Median incidence of conduction delay and conduction block during sinus rhythm was 1.2% (interquartile, 0%-2.3%) and 0.4% (interquartile, 0%-2.1%). In comparison, the median incidence of conduction delay and conduction block during 339 AES was respectively 2.8% (interquartile, 1.3%-4.6%) and 2.2% (interquartile, 0.3%-5.1%) and differed between the types of AES (prematurely aberrant>aberrant>premature). The degree of prematurity was not associated with a higher incidence of conduction disorders (P>0.05). In contrast, a higher degree of aberrancy was associated with a higher incidence of conduction disorders; AES emerging as epicardial breakthrough provoked most conduction disorders (P≥0.002). AES caused most conduction disorders in patients with diabetes mellitus and left atrial dilatation (P<0.05). CONCLUSIONS: Intraoperative high-resolution epicardial mapping showed that conduction disorders are mainly provoked by prematurely aberrant AES, particularly in patients with left atrial dilation and diabetes mellitus or emerging as epicardial breakthrough.

Usefulness of the R-Wave Sign as a Predictor for Ventricular Tachyarrhythmia in Patients With Brugada Syndrome.

Brugada syndrome (BrS) is an autosomal dominant channelopathy which is responsible for a large number of sudden cardiac deaths in young subjects without structural abnormalities. The most challenging step in management of patients with BrS is identifying who is at risk for developing malignant ventricular tachyarrhythmia (VTA). In patients with BrS, conduction delay in the right ventricular outflow tract (RVOT) causes a prominent R wave in lead aVR. This electrocardiographic parameter can be useful to detect these high-risk patients. The goal of this study was to test the significance of R-wave elevation in lead aVR as a predictor for VTA in patients with BrS. In this retrospective study, we included 132 patients with BrS (47 ± 15 years, 65% men) who visited the outpatient clinic for cardiogenetic screening. Patients' medical records were examined for the presence of a positive R-wave sign in lead aVR and VTA. A positive R-wave sign in lead aVR was observed in 41 patients (31%). This sign was more frequently observed in patients who experienced VTA (n = 24) before the initial diagnosis, during electrophysiological studies, or during follow-up (p <0.001). The positive R-wave sign occurred more frequently in symptomatic patients with a history of an out of hospital cardiac arrest, VTA, or syncope than asymptomatic patients (60% vs 26%; p = 0.002). During the follow-up period, this sign was more frequently detected in patients who developed either de novo (50%) or recurrent VTA (80%) (p = 0.017). Multivariable regression analysis showed that R-wave sign is an independent predictor for VTA development (odds ratio 4.8, 95% confidence interval 1.79 to 13.27). The presence of a positive R-wave sign in lead aVR is associated with the development of VTA. In conclusion, positive R-wave sign in lead aVR can be used to identify patients with BrS at risk for malignant VTA.

Relevance of Conduction Disorders in Bachmann's Bundle During Sinus Rhythm in Humans.

BACKGROUND: Bachmann's bundle (BB) is considered to be the main route of interatrial conduction and to play a role in development of atrial fibrillation (AF). The goals of this study are to characterize the presence of conduction disorders in BB during sinus rhythm and to study their relation with AF. METHODS AND RESULTS: High-resolution epicardial mapping (192 unipolar electrodes, interelectrode distance: 2 mm) of sinus rhythm was performed in 185 patients during coronary artery bypass surgery of whom 13 had a history of paroxysmal AF. Continuous rhythm monitoring was used to detect postoperative AF during the first 5 postoperative days. In 67% of the patients, BB was activated from right to left; in the remaining patients from right and middle (21%), right, central, and left (8%), or central (4%) site. Mean effective conduction velocity was 89 cm/s. Conduction block was present in most patients (75%; median 1.1%, range 0-12.8) and was higher in patients with paroxysmal AF compared with patients without a history of AF (3.2% versus 0.9%; P=0.03). A high amount of conduction block (>4%) was associated with de novo postoperative AF (P=0.02). Longitudinal lines of conduction block >10 mm were also associated with postoperative AF (P=0.04). CONCLUSIONS: BB may be activated through multiple directions, but the predominant route of conduction is from right to left. Conduction velocity across BB is around 90 cm/s. Conduction is blocked in both longitudinal and transverse direction in the majority of patients. Conduction disorders, particularly long lines of longitudinal conduction block, are more pronounced in patients with AF episodes.

QUest for the Arrhythmogenic Substrate of Atrial fibRillation in Patients Undergoing Cardiac Surgery (QUASAR Study): Rationale and Design.

The heterogeneous presentation and progression of atrial fibrillation (AF) implicate the existence of different pathophysiological processes. Individualized diagnosis and therapy of the arrhythmogenic substrate underlying AF may be required to improve treatment outcomes. Therefore, this single-center study aims to identify the arrhythmogenic areas underlying AF by intra-operative, high-resolution, multi-site epicardial mapping in 600 patients with different heart diseases. Participants are divided into 12 groups according to the underlying heart diseases and presence of prior AF episodes. Mapping is performed with a 192-electrode array for 5-10 s during sinus rhythm and (induced) AF of the entire atrial surface. Local activation times are converted into activation and wave maps from which various electrophysiological parameters are derived. Postoperative cardiac rhythm registrations and a 5-year follow-up will show the incidence of postoperative and persistent AF. This project provides the first step in the development of a tool for individual AF diagnosis and treatment.

Dynamics of Endo- and Epicardial Focal Fibrillation Waves at the Right Atrium in a Patient With Advanced Atrial Remodelling.

Focal waves appear frequently at the epicardium during persistent atrial fibrillation (AF), however, the origin of these waves is under debate. We performed simultaneous endo-epicardial mapping of the right atrial wall during longstanding persistent AF in a patient undergoing cardiac surgery. During 10 seconds 53 and 59 focal waves appeared at random at respectively the endocardium and epicardium. Repetitive focal activity did not last longer than 3 cycles. Transmural asynchrony and conduction might be the origin of focal waves. Asynchronous propagation of fibrillation waves in 3 dimensions would stabilize the arrhythmia and could explain the limited success of persistent AF ablation.

A novel intra-operative, high-resolution atrial mapping approach.

PURPOSE: A new technique is demonstrated for extensive high-resolution intra-operative atrial mapping that will facilitate the localization of atrial fibrillation (AF) sources and identification of the substrate perpetuating AF. METHODS: Prior to the start of extra-corporal circulation, a 8 × 24-electrode array (2-mm inter-electrode distance) is placed subsequently on all the right and left epicardial atrial sites, including Bachmann's bundle, for recording of unipolar electrograms during sinus rhythm and (induced) AF. AF is induced by high-frequency pacing at the right atrial free wall. A pacemaker wire stitched to the right atrium serves as a reference signal. The indifferent pole is connected to a steal wire fixed to subcutaneous tissue. Electrograms are recorded by a computerized mapping system and, after amplification (gain 1000), filtering (bandwidth 0.5-400 Hz), sampling (1 kHz) and analogue to digital conversion (16 bits), automatically stored on hard disk. During the mapping procedure, real-time visualization secures electrogram quality. Analysis will be performed offline. RESULTS: This technique was performed in 168 patients of 18 years and older, with coronary and/or structural heart disease, with or without AF, electively scheduled for cardiac surgery and a ventricular ejection fraction above 40 %. The mean duration of the entire mapping procedure including preparation time was 9 ± 2 min. Complications related to the mapping procedure during or after cardiac surgery were not observed. CONCLUSIONS: We introduce the first epicardial atrial mapping approach with a high resolution of ≥1728 recording sites which can be performed in a procedure time of only 9±2 mins. This mapping technique can potentially identify areas responsible for initiation and persistence of AF and hopefully can individualize both diagnosis and therapy of AF.