Background: Areas of conduction disorders play an important role in both initiation and perpetuation of AF and can be recognized by specific changes in unipolar potential morphology. For example, EGM fractionation may be caused by asynchronous activation of adjacent cardiomyocytes because of structural barriers such as fibrotic strands. However, it is unknown whether there are sex differences in unipolar potential morphology. Therefore, atrial potential morphologies during sinus rhythm (SR) were compared between male and female patients. Methods: Based on propensity score matching, 62 male and female patients in whom high-resolution mapping of the right atrium (RA), left atrium (LA), and pulmonary vein area (PVA) including Bachmann's bundle (BB) was performed during coronary bypass grafting surgery and/or valvular heart surgery. Unipolar potentials were classified as single potentials (SPs), short double potentials (SDPs), long double potentials (LDP), fractionated potentials (FPs) and fraction duration (FD). The proportion of conduction block lines was also determined. Results: Female patients had a higher proportion of SDPs, LDPs and FPs at the RA, and SDPs at BB. At the PVA, there were less SPs and more SDPs and FPs. In females, FDs were longer at the RA and PVA, and potential voltages of only SPs were lower at the RA (all P < 0.05). Females also had more CB at the RA and at PVA (P < 0.05). Conclusion: In females, the proportion of single unipolar potentials indicative of smooth conduction, was lower compared to males, at the RA and PVA and to a lesser degree at BB. Females also had more CB at RA and PVA. Hence, these results may reflect sex-differences in the degree of electrical remodeling.

Background: Quantified features of local conduction heterogeneity due to pathological alterations of myocardial tissue could serve as a marker for the degree of electrical remodeling and hence be used to determine the stage of atrial fibrillation (AF). Objectives: In this study, the authors investigated whether local directional heterogeneity (LDH) and anisotropy ratio, derived from estimated local conduction velocities (CVs) during AF, are suitable electrical parameters to stage AF. Methods: Epicardial mapping (244-electrode array, interelectrode distance 2.25 mm) of the right atrium was performed during acute atrial fibrillation (AAF) (n = 25, 32 ± 11 years of age) and during long-standing persistent atrial fibrillation (LSPAF) (n = 23, 64 ± 9 years of age). Episodes of 9 ± 4 seconds of AF were analyzed. Local CV vectors were constructed to assess the degree of anisotropy. Directions and magnitudes of individual vectors were compared with surrounding vectors to identify LDH. Results: Compared with the entire AAF group, LSPAF was characterized by slower conduction (71.5 ± 6.8 cm/s vs 67.6 ± 5.6 cm/s; P = 0.037) with a larger dispersion (1.59 ± 0.21 vs 1.95 ± 0.17; P < 0.001) and temporal variability (32.0 ± 4.7 cm/s vs 38.5 ± 3.3 cm/s; P < 0.001). Also, LSPAF was characterized by more LDH (19.6% ± 4.4% vs 26.0% ± 3.4%; P < 0.001) and a higher degree of anisotropy (1.38 ± 0.07 vs 1.51 ± 0.14; P < 0.001). Compared with the most complex type of AAF (type III), LSPAF was still associated with a larger CV dispersion, higher temporal variability of CV, and larger amount of LDH. Conclusions: Increasing AF complexity was associated with increased spatiotemporal variability of local CV vectors, local conduction heterogeneity, and anisotropy ratio. By using these novel parameters, LSPAF could potentially be discriminated from the most complex type of AAF. These observations may indicate pathological alterations of myocardial tissue underlying progression of AF.

Normothermic ex-situ heart perfusion (ESHP) enables assessment of hearts donated after circulatory death (DCD) prior to transplantation. However, sensitive parameters of cardiac function of DCD hearts on ESHP are needed. This study proposes a novel approach using electrophysiological (EP) parameters derived from electrical mapping as biomarkers of post-ischemic cardiac performance. Porcine slaughterhouse hearts (PSH) were divided in two groups based on the type of warm ischemia (Group 1: 10 ± 1 min with animal depilation vs. Group 2: ≤5 min without depilation). Electrical mapping of the right (RV) and left ventricle (LV) was performed on ESHP. Potential voltages, slopes and conduction velocities were computed from unipolar electrograms and compared between groups. Voltages were lower in Group 1 compared to Group 2 (RV: 3.6 vs. 15.3 mV, p = 0.057; LV: 10.8 vs. 23.6 mV, p = 0.029). In addition, the percentage of low-voltage potentials was higher and potential slopes were flatter in Group 1. Voltages and slopes strongly correlated with the visual contractile performance of PSH, but showed weaker correlation with lactate profiles. In conclusion, unipolar potential voltages and potential slopes were decreased in hearts with severe warm ischemia. As such, EP parameters could aid transplantation teams in decision-making on transplantability of DCD hearts.

(1) Background: Structural remodeling plays an important role in the pathophysiology of atrial fibrillation (AF). It is likely that structural remodeling occurs transmurally, giving rise to electrical endo-epicardial asynchrony (EEA). Recent studies have suggested that areas of EEA may be suitable targets for ablation therapy of AF. We hypothesized that the degree of EEA is more pronounced in areas of transmural conduction block (T-CB) than single-sided CB (SS-CB). This study examined the degree to which SS-CB and T-CB enhance EEA and which specific unipolar potential morphology parameters are predictive for SS-CB or T-CB. (2) Methods: Simultaneous endo-epicardial mapping in the human right atrium was performed in 86 patients. Potential morphology parameters included unipolar potential voltages, low-voltage areas, potential complexity (long double and fractionated potentials: LDPs and FPs), and the duration of fractionation. (3) Results: EEA was mostly affected by the presence of T-CB areas. Lower potential voltages and more LDPs and FPs were observed in T-CB areas compared to SS-CB areas. (4) Conclusion: Areas of T-CB could be most accurately predicted by combining epicardial unipolar potential morphology parameters, including voltages, fractionation, and fractionation duration (AUC = 0.91). If transmural areas of CB indeed play a pivotal role in the pathophysiology of AF, they could theoretically be used as target sites for ablation.

The electrical arrhythmogenic substrate underlying the most common cardiac arrhythmia atrial fibrillation (AF) may consist of conduction disorders, low-voltage areas, or fractionated potentials. High-density and resolution epicardial mapping (HDREM) approaches have been introduced to quantify and visualize electrophysiological properties of the atria. These approaches are essential for obtaining innovative insights into arrhythmogenic substrates and identifying novel targets for therapy. The aim of this review is to summarize and discuss the (1) contribution of HDREM studies to the knowledge on atrial arrhythmogenesis and (2) future applications of HDREM of atria in daily clinical practice.

Background: Ablation strategies targeting fractionated or low-voltage potentials have been widely used in patients with persistent types of atrial fibrillation (AF). However, recent studies have questioned their role in effectively representing sites of conduction slowing, and thus arrhythmogenic substrates. Objectives: The authors studied the relationship between local conduction velocity (CV) and the occurrence of fractionated and/or low-voltage potentials in order to identify areas with critically slowing of conduction. Methods: Intraoperative epicardial mapping was performed during sinus rhythm. Unipolar potentials with an amplitude <1.0 mV were initially classified as low-voltage and potentials with ≥3 deflections as fractionation. A range of thresholds were also explored. Local CV was computed using discrete velocity vectors. Results: A total of 319 patients were included. Fractionated, low-voltage potentials were rare, accounting for only 0.36% (Q1-Q3: 0.15%-0.78%) of all atrial sites. Local CV at sites with fractionated, low-voltage potentials (46.0 cm/s [Q1-Q3: 22.6-72.7 cm/s]) was lowest compared with sites with either low-voltage, nonfractionated potentials (64.5 cm/s [Q1-Q3: 34.8-99.4 cm/s]) or fractionated, high-voltage potentials (65.9 cm/s [Q1-Q3: 41.7-92.8 cm/s]; P < 0.001). Slow conduction areas (CV <50 cm/s) could be most accurately identified by using a low voltage threshold (<1 mV) and a minimum of 3 deflections (positive predictive value: 54.2%-70.7%), although the overall sensitivity remained low (0.1%-1.9%). Conclusions: Sites with fractionated, low-voltage potentials have substantially slower local CV compared with sites with either low-voltage, nonfractionated potentials or fractionated, high-voltage potentials. However, the strong inverse relationship between the positive predictive value and sensitivity of a combined voltage and fractionation threshold for slowed conduction is likely to complicate the use of these signal-based ablation approaches in AF patients.

Objective: Patients with persistent atrial fibrillation (AF) have more electrical endo-epicardial asynchrony (EEA) during sinus rhythm (SR) than patients without AF. Prior mapping studies indicated that particularly unipolar, endo- and/or epicardial electrogram (EGM) morphology may be indicators of EEA. This study aim to develop a novel method for estimating the degree of EEA by using unipolar EGM characteristics recorded from either the endo- and/or epicardium. Methods: Simultaneous endo-epicardial mapping during sinus rhythm was performed in 86 patients. EGM characteristics, including unipolar voltages, low-voltage areas (LVAs), potential types (single, short/long double and fractionated potentials: SP, SDP, LDP and FP) and fractionation duration (FD) of double potentials (DP) and FP were compared between EEA and non-EEA areas. Asynchrony Fingerprinting Scores (AFS) containing quantified EGM characteristics were constructed to estimate the degree of EEA. Results: Endo- and epicardial sites of EEA areas are characterized by lower unipolar voltages, a higher number of LDPs and FPs and longer DP and FP durations. Patients with AF have lower potential voltages in EEA areas, along with alterations in the potential types. The EE-AFS, containing the proportion of endocardial LVAs and FD of epicardial DPs, had the highest predictive value for determining the degree of EEA (AUC: 0.913). Endo- and epi-AFS separately also showed good predictive values (AUC: 0.901 and 0.830 respectively). Conclusions: EGM characteristics can be used to identify EEA areas. AFS can be utilized as a novel diagnostic tool for accurately estimating the degree of EEA. These characteristics potentially indicate AF related arrhythmogenic substrates.

Aims: Areas of conduction inhomogeneity (CI) during sinus rhythm may facilitate the initiation and perpetuation of atrial fibrillation (AF). Currently, no tool is available to quantify the severity of CI. Our aim is to develop and validate a novel tool using unipolar electrograms (EGMs) only to quantify the severity of CI in the atria. Methods and results: Epicardial mapping of the right atrium (RA) and left atrium, including Bachmann's bundle, was performed in 235 patients undergoing coronary artery bypass grafting surgery. Conduction inhomogeneity was defined as the amount of conduction block. Electrograms were classified as single, short, long double (LDP), and fractionated potentials (FPs), and the fractionation duration of non-single potentials was measured. The proportion of low-voltage areas (LVAs, <1mV) was calculated. Increased CI was associated with decreased potential voltages and increased LVAs, LDPs, and FPs. The Electrical Fingerprint Score consisting of RA EGM features, including LVAs and LDPs, was most accurate in predicting CI severity. The RA Electrical Fingerprint Score demonstrated the highest correlation with the amount of CI in both atria (r = 0.70, P < 0.001). Conclusion: The Electrical Fingerprint Score is a novel tool to quantify the severity of CI using only unipolar EGM characteristics recorded. This tool can be used to stage the degree of conduction abnormalities without constructing spatial activation patterns, potentially enabling early identification of patients at high risk of post-operative AF or selection of the appropriate ablation approach in addition to pulmonary vein isolation at the electrophysiology laboratory.

Background: Dominant frequencies (DFs) or complex fractionated atrial electrograms (CFAEs), indicative of focal sources or rotational activation, are used to identify target sites for atrial fibrillation (AF) ablation in clinical studies, although the relationship among DF, CFAE, and activation patterns remains unclear. Objectives: This study sought to investigate the relationship between patterns of activation underlying DF and CFAE sites during AF. Methods: Epicardial high-resolution mapping of the right and left atrium including Bachmann's bundle was performed in 71 participants. We identified the highest dominant frequency (DF _max) and highest degree of CFAE (CFAE _max) with the use of existing clinical criteria and classified patterns of activation as focal or rotational activation and smooth propagation, conduction block (CB), collision and remnant activity, and fibrillation potentials as single, double, or fractionated potentials containing, respectively, 1, 2, or 3 or more negative deflections. Relationships among activation patterns, DF _max, and potential types were investigated. Results: DF _max were primarily located at the left atrioventricular groove and did not harbor focal activation (proportion focal waves: 0% [IQR: 0%-2%]). Compared with non-DF _max sites, DF _max were characterized by more frequent smooth propagation (22% [IQR: 7%-48%] vs 17% [IQR: 11%-24%]; P = 0.001), less frequent conduction block (69% [IQR: 51%-81%] vs 74% [IQR: 69%-78%]; P = 0.006), a higher proportion of single potentials (72% [IQR: 55%-84%] vs 6%1 [IQR: 55%-65%]; P = 0.003), and a lower proportion of fractionated potentials (4% [IQR: 1%-11%] vs 12% [IQR: 9%-15%]; P = 0.004). CFAE _max were mainly found at the pulmonary veins area, and only 1% [IQR: 0%-2%] of all CFAE _max contained focal activation. Compared with non-CFAE _max sites, CFAE _max sites were characterized by less frequent smooth propagation (1% [IQR: 0%-1%] vs 17% [IQR: 12%-24%]; P < 0.001) and more frequent remnant activity (20% [IQR: 12%-29%] vs 8% [IQR: 5%-10%]; P < 0.001), and harbored predominantly fractionated potentials (52% [IQR: 43%-66%] vs 12% [IQR: 9%-14%]; P < 0.001). Conclusions: Focal or rotational patterns of activation were not consistently detected at DF _max domains and CFAE _max sites. These findings do not support the concept of targeting DF _max or CFAE _max according to existing criteria for AF ablation.

BACKGROUND AND AIMS: Atrial extrasystoles (AES) provoke conduction disorders and may trigger episodes of atrial fibrillation (AF). However, the direction- and rate-dependency of electrophysiological tissue properties on epicardial unipolar electrogram (EGM) morphology is unknown. Therefore, this study examined the impact of spontaneous AES on potential amplitude, -fractionation, -duration, and low-voltage areas (LVAs), and correlated these differences with various degrees of prematurity and aberrancy. METHODS AND RESULTS: Intra-operative high-resolution epicardial mapping of the right and left atrium, Bachmann's Bundle, and pulmonary vein area was performed during sinus rhythm (SR) in 287 patients (60 with AF). AES were categorized according to their prematurity index (>25% shortening) and degree of aberrancy (none, mild/opposite, moderate and severe). In total, 837 unique AES (457 premature; 58 mild/opposite, 355 moderate, and 154 severe aberrant) were included. The average prematurity index was 28% [12-45]. Comparing SR and AES, average voltage decreased (-1.1 [-1.2, -0.9] mV, P < 0.001) at all atrial regions, whereas the amount of LVAs and fractionation increased (respectively, +3.4 [2.7, 4.1] % and +3.2 [2.6, 3.7] %, P < 0.001). Only weak or moderate correlations were found between EGM morphology parameters and prematurity indices (R2 < 0.299, P < 0.001). All parameters were, however, most severely affected by either mild/opposite or severely aberrant AES, in which the effect was more pronounced in AF patients. Also, there were considerable regional differences in effects provoked by AES. CONCLUSION: Unipolar EGM characteristics during spontaneous AES are mainly directional-dependent and not rate-dependent. AF patients have more direction-dependent conduction disorders, indicating enhanced non-uniform anisotropy that is uncovered by spontaneous AES.