Conduction Velocity and Anisotropic Properties of Fibrillation Waves During Acutely Induced and Long-Standing Persistent AF.

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.

Identification of Atrial Transmural Conduction Inhomogeneity Using Unipolar Electrogram Morphology.

(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.

Biatrial arrhythmogenic substrate in patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: Atrial fibrillation (AF) in patients with hypertrophic obstructive cardiomyopathy (HOCM) may be caused by a primary atrial myopathy. Whether HOCM-related atrial myopathy affects mainly electrophysiological properties of the left atrium (LA) or also the right atrium (RA) has never been investigated. OBJECTIVE: The purpose of this study was to characterize atrial conduction and explore differences in the prevalence of conduction disorders, potential fractionation, and low-voltage areas (LVAs) between the RA and LA during sinus rhythm (SR) as indicators of potential arrhythmogenic areas. METHODS: Intraoperative epicardial mapping of both atria during SR was performed in 15 HOCM patients (age 50 ± 12 years). Conduction delay (CD) and conductin block (CB), unipolar potential characteristics (voltages, fractionation), and LVA were quantified. RESULTS: Conduction disorders and LVA were found scattered throughout both atria in all patients and did not differ between the RA and LA (CD: 2.9% [1.9%-3.6%] vs 2.6% [2.1%-6.4%], P = .541; CB: 1.7% [0.9%-3.1%] vs 1.5% [0.5%-2.8%], P = .600; LVA: 4.7% [1.6%-7.7%] vs 2.9% [2.1%-7.1%], P = .793). Compared to the RA, unipolar voltages of single potentials (SPs) and fractionated potentials (FPs) were higher in the LA (SP: P75 7.3 mV vs 10.9 mV; FP: P75 2.0 mV vs 3.7 mV). FP contained low-voltage components in only 18% of all LA sites compared to 36% of all RA sites. CONCLUSION: In patients with HOCM, conduction disorders, LVA, and FP are equally present in both atria, supporting the hypothesis of a primary atrial myopathy. Conceptually, the presence of a biatrial substrate and high-voltage FP may contribute to failure of ablative therapy of atrial tachyarrhythmias in this population.

A novel diagnostic tool to identify atrial endo-epicardial asynchrony using signal fingerprinting.

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.

How sex affects the sinus rhythm heartbeat.

Background: There is increasing awareness of sex-specific differences in epidemiology and pathophysiology of atrial fibrillation (AF). It is, however, unknown whether males and females differ in atrial electrophysiological properties during sinus rhythm (SR). The aim of this study was therefore to investigate sex-based (regional) differences in electrophysiological properties during SR of the right (RA) and left (LA) atrium including Bachmanns Bundle (BB) and pulmonary vein region (PVA). Methods: Intra-operative, high resolution mapping during SR was performed in 53 matched females with males (without a history of AF), to measure lines of conduction block (CB), continuous conduction delay and block (cCDCB), conduction velocities (CV), total atrial activation times (TAT), unipolar potential voltages and percentage of low voltage areas (LVA). Results: Compared to males, females have significantly 1) lower unipolar potential voltages and slower CV at both RA and BB, 2) more LVAs, CB and cCDCB lines and longer CB and cCDCB lines at the RA only (all P < 0.05). Conclusions: Electrophysiological properties of the atria during SR differ between males and females. These sex-based differences are particularly present at the RA and to a lesser degree at BB. In females, both the RA and BB contained more areas of conduction disorders and low voltage potentials. Future studies are required to investigate whether these areas play a role in sex-based differences in vulnerability to arrhythmias such as atrial fibrillation.

Characterization of unipolar electrogram morphology: a novel tool for quantifying conduction inhomogeneity.

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, <1 mV) 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.

Insights Into the Effects of Low-Level Vagus Nerve Stimulation on Atrial Electrophysiology: Towards Patient-Tailored Cardiac Neuromodulation.

BACKGROUND: Low-level vagus nerve stimulation through the tragus (tLLVNS) is increasingly acknowledged as a therapeutic strategy to prevent and treat atrial fibrillation. However, a lack in understanding of the exact antiarrhythmic properties of tLLVNS has hampered clinical implementation. OBJECTIVES: In this study, the authors aimed to study the effects of tLLVNS on atrial electrophysiology by performing intraoperative epicardial mapping during acute and chronic tLLVNS. METHODS: Epicardial mapping of the superior right atrium was performed before and after arterial graft harvesting in patients undergoing coronary artery bypass grafting without a history of atrial fibrillation. The time needed for arterial graft harvesting was used to perform chronic tLLVNS. Electrophysiological properties were compared before and during chronic tLLVNS. RESULTS: A total of 10 patients (median age 74 years [IQR: 69-78 years]) underwent tLLVNS for a duration of 56 minutes (IQR: 43-73 minutes). During acute and chronic tLLVNS, a shift of the sinoatrial node exit site toward a more cranial direction was observed in 5 (50%) patients. Unipolar potential voltage increased significantly during acute and chronic tLLVNS (3.9 mV [IQR: 3.1-4.8 mV] vs 4.7 mV [IQR: 4.0-5.3 mV] vs 5.2 mV [IQR: 4.8-7.0 mV]; P = 0.027, P = 0.02, respectively). Total activation time, slope of unipolar potentials, amount of fractionation, low-voltage areas and conduction velocity did not differ significantly between baseline measurements and tLLVNS. Two patients showed consistent "improvement" of all electrophysiological properties during tLLVNS, while 1 patient appeared to have no beneficial effect. CONCLUSIONS: We demonstrated that tLLVNS resulted in a significant increase in unipolar potential voltage. In addition, we observed the following in selective patients: 1) reduction in total activation time; 2) steeper slope of unipolar potentials; 3) decrease in the amount of fractionation; and 4) change in sinoatrial node exit sites.

Atrial extrasystoles enhance low-voltage fractionation electrograms in patients with atrial fibrillation.

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.

Mapping-guided atrial lead placement determines optimal conduction across Bachmann's bundle: a rationale for patient-tailored pacing therapy.

AIMS: Conventional right atrial appendage (RAA) pacing is associated with increased atrial activation time resulting in higher incidences of atrial tachyarrhythmia. Optimal pacing sites ideally shorten inter-atrial conduction delay, thereby decreasing atrial excitation time. We therefore examined the impact of programmed electrical stimulation (PES) from the right atrium (RA) and left atrium (LA) on the electrophysiological properties of Bachmann's bundle (BB). METHODS AND RESULTS: High-resolution epicardial mapping of BB was performed during sinus rhythm (SR) and PES in 34 patients undergoing cardiac surgery. Programmed electrical stimulation was performed from the RAA, junction of the RA with inferior caval vein (LRA), and left atrial appendage (LAA). Pacing from either the RAA or LAA resulted in, respectively, right- and left-sided conduction across BB. However, during LRA pacing in most patients (n = 15), activation started in the centre of BB. The total activation time (TAT) of BB during RAA pacing [63 (55-78) ms] was similar to that of SR [61 (52-68) ms, P = 0.464], while it decreased during LRA [45 (39-62) ms, P = 0.003] and increased during LAA pacing [67 (61-75) ms, P = 0.009]. Reduction of both conduction disorders and TAT was most often achieved during LRA pacing (N = 13), especially in patients who already had a higher amount of conduction disorders during SR [9.8 (7.3-12.3) vs. 4.5 (3.5-6.6)%, P < 0.001]. CONCLUSION: Pacing from the LRA results in a remarkable decrease of TAT compared with pacing from the LAA or RAA. As the most optimal pacing site varies between patients, individualized positioning of the atrial pacing lead guided by mapping of BB may be one of the new frontiers for atrial pacing.

The HF-AF ENERGY Trial: Nicotinamide Riboside for the Treatment of Atrial Fibrillation in Heart Failure Patients.

BACKGROUND: The presence of atrial fibrillation (AF) in heart failure (HF) patients with reduced ejection fraction is common and associated with an increased risk of stroke, hospitalization and mortality. Recent research findings indicate that a reduction in nicotinamide adenine dinucleotide (NAD+) levels results in mitochondrial dysfunction, DNA damage and consequently cardiomyocyte impairment in experimental and clinical HF and AF. The HF-AF ENERGY trial aims to investigate the cardioprotective effects of the NAD+ precursor nicotinamide riboside (NR) treatment in ischemic heart disease patients diagnosed with AF. STUDY DESIGN: The HF-AF ENERGY trial is a prospective intervention study. The study consists of a (retrospective) 4 months observation period and a 4 months intervention period. The cardioprotective effect of NR on AF burden is investigated by remote monitoring software of implantable cardiac defibrillators (ICDs), which enables continuous atrial rhythm monitoring detection. Cardiac dimension and function are examined by echocardiography. Laboratory blood analysis is performed to determine mitochondrial function markers and energy metabolism. All the study parameters are assessed at two fixed time points (pre- and post-treatment). Pre- and post-treatment outcomes are compared to determine the effects of NR treatment on AF burden, mitochondrial function markers and energy metabolism. CONCLUSION: The HF-AF ENERGY trial investigates the cardioprotective effects of NR on AF burden and whether NR normalizes blood-based mitochondrial function markers and energy metabolites of the NAD metabolome in ischemic heart disease patients diagnosed with AF. The study outcomes elucidate whether NAD+ metabolism can be used as a future therapy for HF patients with AF.

Detection of endo-epicardial atrial low-voltage areas using unipolar and omnipolar voltage mapping.

Background: Low-voltage areas (LVA) can be located exclusively at either the endocardium or epicardium. This has only been demonstrated for bipolar voltages, but the value of unipolar and omnipolar voltages recorded from either the endocardium and epicardium in predicting LVAs at the opposite layer remains unknown. The goal of this study was therefore to compare simultaneously recorded endo-epicardial unipolar and omnipolar potentials and to determine whether their voltage characteristics are predictive for opposite LVAs. Methods: Intra-operative simultaneous endo-epicardial mapping (256 electrodes, interelectrode distances 2 mm) was performed during sinus rhythm at the right atrium in 93 patients (67 ± 9 years, 73 male). Cliques of four electrodes (2 × 2 mm) were used to define maximal omnipolar (Vomni,max) and unipolar (Vuni,max) voltages. LVAs were defined as Vomni,max ≤0.5 mV or Vuni,max ≤1.0 mV. Results: The majority of both unipolar and omnipolar LVAs were located at only the endocardium (74.2% and 82.0% respectively) or epicardium (52.7% and 47.6% respectively). Of the endocardial unipolar LVAs, 25.8% were also located at the opposite layer and 47.3% vice-versa. In omnipolar LVAs, 18.0% of the endocardial LVAs were also located at the epicardium and 52.4% vice-versa. The combination of epicardial Vuni,max and Vomni,max was most accurate in identifying dual-layer LVAs (50.4%). Conclusion: Unipolar and omnipolar LVAs are frequently located exclusively at either the endocardium or epicardium. Endo-epicardial LVAs are most accurately identified using combined epicardial unipolar and omnipolar voltages. Therefore, a combined endo-epicardial unipolar and omnipolar mapping approach is favoured as it may be more indicative of possible arrhythmogenic substrates.

Low-voltage potentials contribute to postoperative atrial fibrillation development in obese patients.

BACKGROUND: Obesity predisposes to the development of atrial fibrillation (AF); however, the pathophysiology underlying this relation is only partly understood. OBJECTIVE: As low-voltage areas are considered indicators of the arrhythmogenic substrates promoting AF, our study aimed to compare the extensiveness of atrial low-voltage areas between obese and nonobese patients by using high-resolution epicardial mapping in order to identify predilection sites of low-voltage areas. METHODS: A total of 430 patients (131 (30%) obese and 299 (70%) nonobese) were matched resulting in 212 patients (body mass index [BMI] ≥30 kg/m2: n = 106; BMI <30 kg/m2: n = 106) undergoing cardiac surgery (mean age 63 ± 11 years; 161 male). All patients underwent epicardial mapping of the right atrium, Bachmann bundle (BB), and left atrium during sinus rhythm. Low-voltage potentials were defined as potentials with peak-to-peak amplitudes below the fifth percentile of all potential amplitudes obtained from nonobese patients. RESULTS: Compared with nonobese patients, obese patients have potentials with lower voltages (median of medians) (4.5 mV [0.4-16.2 mV] vs 5.5 mV [0.8-18.0 mV]; P < .001), especially at BB (4.1 mV [0.4-12.3 mV] vs 6.2 mV [1.0-14.3 mV]; P < .001) and left atrium (5.1 mV [0.5-10.1 mV] vs 6.2 mV [0.8-15.9 mV]; P = .003). The percentage of low-voltage potentials was higher in obese (median 3.6% [0.0%-77.1%]) than in nonobese (median 2.3% [0.0%-57.9%]) patients (P < .001), again at BB (obese: 2.9% [0.0%-77.1%] vs nonobese: 0.9% [0.0%-42.0%]; P < .001). Percentages of low-voltage potentials correlated with incidences of conduction block (P < .001), while BMI (P = .044) and low-voltage potentials (P = .001) were independent predictors for the incidence of early postoperative AF. CONCLUSION: Obesity may predispose to an overall decrease in atrial voltage and a higher percentage in low-voltage potentials. BB was a predilection area for low voltage within the atria of obese patients.

Epicardial high-resolution mapping of advanced interatrial block: Relating ECG, conduction abnormalities and excitation patterns.

Background: Impairment of conduction across Bachmann's Bundle (BB) may cause advanced interatrial block (a-IAB), which in turn is associated with development of atrial fibrillation. However, the exact relation between a complete transverse line of conduction block (CB) across BB and the presence of a-IAB has not been studied. Objective: The aims of this study are to determine whether (1) a complete transversal line of CB across BB established by high resolution mapping correlates with a-IAB on the surface ECG, (2) conduction abnormalities at the right and left atria correlate with a-IAB, and (3) excitation patterns are associated with ECG characteristics of a-IAB. Methods: We included 40 patients in whom epicardial mapping revealed a complete transverse line of CB across BB. Pre-operative ECGs and post-operative telemetry were assessed for the presence of (a) typical a-IAB and de novo early post-operative AF (EPOAF), respectively. Total atrial excitation time (TAET) and RA-LA delay were calculated. Entry site and trajectory of the main sinus rhythm wavefront at the pulmonary vein area (PVA) were assessed. Results: Thirteen patients were classified as a-IAB (32.5%). In the entire atria and BB there were no differences in conduction disorders, though, patients with a-IAB had an increased TAET and longer RA-LA delay compared to patients without a-IAB (90.0 ± 21.9 ms vs. 74.9 ± 13.0 ms, p = 0.017; 160.0 ± 27.0 ms vs. 136.0 ± 24.1 ms, p = 0.012, respectively). Patients with typical a-IAB solely had caudocranial activation of the PVA, without additional cranial entry sites. Prevalence of de novo EPOAF was 69.2% and was similar between patients with and without a-IAB. Conclusion: A transverse line of CB across BB partly explains the ECG characteristics of a-IAB. We found atrial excitation patterns underlying the ECG characteristics of both atypical and typical a-IAB. Regardless of the presence of a-IAB, the clinical impact of a complete transverse line of CB across BB was reflected by a high incidence of de novo EPOAF.

Detection of Endo-epicardial Asynchrony in the Atrial Wall Using One-Sided Unipolar and Bipolar Electrograms.

Endo-epicardial asynchrony (EEA) is a new mechanism possibly maintaining atrial fibrillation. We aimed to determine the sensitivity and best recording modus to detect EEA on electrograms recorded from one atrial side using electrogram fractionation. Simultaneously obtained right atrial endo- and epicardial electrograms from 22 patients demonstrating EEA were selected. Unipolar and (converted) bipolar electrograms were analyzed for presence and characteristics of fractionation corresponding to EEA. Sensitivity of presence of EEA corresponding fractionation was high in patients (86-96%) and moderately high (65-78%) for the asynchronous surface area for unipolar and bipolar electrograms equally. In bipolar electrograms, signal-to-noise ratio of EEA corresponding fractionation decreased and additional fractionation increased for electrograms recorded at the endocardium. Sensitivity of fractionation corresponding to EEA is high for both unipolar and bipolar electrograms. Unipolar electrograms are more suited for detection of EEA due to a larger signal-to-noise ratio and less disturbance of additional fractionation. Unipolar electrograms are more suited than bipolar electrograms to detect endo-epicardial asynchrony on one side of the atrial wall using electrogram fractionation.

Simultaneous Endo-Epicardial Mapping of the Human Right Atrium: Unraveling Atrial Excitation.

Background The significance of endo-epicardial asynchrony (EEA) and atrial conduction block (CB), which play an important role in the pathophysiology of atrial fibrillation (AF) during sinus rhythm is poorly understood. The aim of our study was therefore to examine 3-dimensional activation of the human right atrium (RA). Methods and Results Eighty patients (79% men, 39% history of AF) underwent simultaneous endo-epicardial sinus rhythm mapping of the inferior, middle and superior RA. Areas of CB were defined as conduction delays of ≥12 ms, EEA as activation time differences of opposite electrodes of ≥15 ms and transmural CB as CB at similar endo-epicardial sites. CB was more pronounced at the endocardium (all locations P<0.025). Amount, extensiveness and severity of CB was higher at the superior RA. Transmural CB at the inferior RA was associated with a higher incidence of post-operative AF (P=0.03). EEA occurred up to 84 ms and was more pronounced at the superior RA (superior: 27 ms [interquartile range, 18.3-39.3], versus mid-RA: 20.3 ms [interquartile range, 0-29.9], and inferior RA: 0 ms [interquartile range, 0-21], P<0.001). Hypertension (P=0.009), diabetes mellitus (P=0.018), and hypercholesterolemia (P=0.015) were associated with a higher degree of EEA. CB (P=0.007) and EEA (P=0.037) were more pronounced in patients with a history of persistent AF compared with patients without AF history. Conclusions This study provides important insights into complex atrial endo-epicardial excitation. Significant differences in conduction disorders between the endo- and epicardium and a significant degree of EEA are already present during sinus rhythm and are more pronounced in patients with cardiovascular risk factors or a history of persistent AF.

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. In total, 304 patients (IHD: n = 193, (I)VHD: n = 111) were mapped; 40 patients (13%) had a history of AF. In 116 patients (38%) there was a mid-entry site with a trend towards more mid-entry sites in patients with (I)VHD vs. IHD (p = 0.061), whereas patients with AF had significant more mid-entry sites than without AF (p = 0.007). CA were present in 251 (95%) patients without AF compared to 39 (98%) with AF. The amount of CA was comparable in patients with IHD and (I)VHD (p > 0.05); AF history was positively associated with the amount of CA (p < 0.05). Receiver operating characteristic (ROC) curve showed 85.0% sensitivity and 86.4% specificity for cut-off values of CA lines of respectively ≤ 6 mm and ≥ 26 mm. Patients without a mid-entry site or long CA lines (≥ 12 mm) were unlikely to have AF (sensitivity 90%, p = 0.002). There are no significant differences in entry-sites of wavefronts and long lines of CA between patients with IHD compared to (I)VHD. However, patients with AF have more wavefronts entering in the middle of BB and a higher incidence of long CA lines compared to patients without a history of AF. Moreover, in case of absence of a mid-entry site or long line of CA, patients most likely have no history of AF.

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). Conduction delay (CD) was defined as interelectrode conduction time (CT) of 7 to 11 ms and conduction block (CB) as CT ≥12 ms. Prevalence of CD or CB (percentage of mapped region), length of lines, and severity of CB (75th percentile of CTs ≥12 ms) were analyzed. RESULTS: All patients had some degree of CD and CB. Prevalence of CD and CB was higher in the RA and BB than in the LA (p < 0.0083 after Bonferroni correction). The longest CB line within each patient was found in the RA in most patients (52%). Interindividual variation in prevalence and lengths of lines was considerable. CB was more severe in the RA than in the LA (p < 0.0083). Within the RA, conduction disorders were more prevalent and more severe in the intercaval region than in the RA free wall (p < 0.05). CONCLUSIONS: In patients with an interatrial shunt, conduction disorders during sinus rhythm are most pronounced in the RA-particularly the intercaval region-and BB. Knowledge of the conduction during sinus rhythm is essential to determine the relevance of conduction disorders for initiation and perpetuation of AF.

The Impact of Filter Settings on Morphology of Unipolar Fibrillation Potentials.

Using unipolar atrial electrogram morphology as guidance for ablative therapy is regaining interest. Although standardly used in clinical practice during ablative therapy, the impact of filter settings on morphology of unipolar AF potentials is unknown. Thirty different filters were applied to 2,557,045 high-resolution epicardial AF potentials recorded from ten patients. Deflections with slope ≤ - 0.05 mV/ms and amplitude ≥ 0.3 mV were marked. High-pass filtering decreased the number of detected potentials, deflection amplitude, and percentage of fractionated potentials (≥ 2 deflections) as well as fractionation delay time (FDT) and increased percentage of single potentials. Low-pass filtering decreased the number of potentials, percentage of fractionated potentials, whereas deflection amplitude, percentage of single potentials, and FDT increased. Notch filtering (50 Hz) decreased the number of potentials and deflection amplitude, whereas the percentage of complex fractionated potentials (≥ 3 deflections) increased. Filtering significantly impacted morphology of unipolar fibrillation potentials, becoming a potential source of error in identification of ablative targets. Graphical Abstract Impact of filtering on morphology of unipolar AF potentials. High-pass, low-pass and notch filters were applied to 2,557,045 high-resolution epicardial AF potentials recorded from ten patients. Filtering significantly impacted AF potential morphology, i.e., number of detected potentials, peak-to-peak amplitude, number of deflections, and fractionation delay time. CFP, complex fractionated potential (≥ 3 deflections); DP, double potential (two deflections); FDT, fractionation delay time; SP, single potential (one deflection).

Heterogeneity in Conduction Underlies Obesity-Related Atrial Fibrillation Vulnerability.

BACKGROUND: Obese patients are more vulnerable to development of atrial fibrillation but pathophysiology underlying this relation is only partly understood. The aim of this study is to compare the severity and extensiveness of conduction disorders between obese patients and nonobese patients measured at a high-resolution scale. METHODS: Patients (N=212) undergoing cardiac surgery (male:161, 63±11 years) underwent epicardial mapping of the right atrium, Bachmann bundle, and left atrium during sinus rhythm. Conduction delay (CD) was defined as interelectrode conduction time of 7 to 11 ms and conduction block (CB) as conduction time ≥12 ms. Prevalence of CD/CB, continuous CDCB (cCDCB), length of CD/CB/cCDCB lines, and severity of CB were analyzed. RESULTS: In obese patients, the overall incidence of CD (3.1% versus 2.6%; P=0.002), CB (1.8% versus 1.2%; P<0.001), and cCDCB (2.6% versus 1.9%; P<0.001) was higher and CD (P=0.012) and cCDCB (P<0.001) lines are longer. There were more conduction disorders at Bachmann bundle and this area has a higher incidence of CD (4.4% versus 3.3%, P=0.002), CB (3.1% versus 1.6%, P<0.001), cCDCB (4.6% versus 2.7%, P<0.001) and longer CD (P<0.001) or cCDCB (P=0.017) lines. The severity of CB is also higher, particularly in the Bachmann bundle (P=0.008) and pulmonary vein (P=0.020) areas. In addition, obese patients have a higher incidence of early de-novo postoperative atrial fibrillation (P=0.003). Body mass index (P=0.037) and the overall amount of CB (P=0.012) were independent predictors for incidence of early postoperative atrial fibrillation. CONCLUSIONS: Compared with nonobese patients, obese patients have higher incidences of conduction disorders, which are also more extensive and more severe. These differences in heterogeneity in conduction are already present during sinus rhythm and may explain the higher vulnerability to atrial fibrillation of obese patients.

Atrial fibrillation fingerprinting; spotting bio-electrical markers to early recognize atrial fibrillation by the use of a bottom-up approach (AFFIP): Rationale and design.

BACKGROUND: The exact pathophysiology of atrial fibrillation (AF) remains incompletely understood and treatment of AF is associated with high recurrence rates. Persistence of AF is rooted in the presence of electropathology, defined as complex electrical conduction disorders caused by structural damage of atrial tissue. The atrial fibrillation fingerprinting (AFFIP) study aims to characterize electropathology, enabling development of a novel diagnostic instrument to predict AF onset and early progression. HYPOTHESES: History of AF, development of post-operative AF, age, gender, underlying heart disease, and other clinical characteristics impact the degree of electropathology. METHODS: This study is a prospective observational study with a planned duration of 48 months. Three study groups are defined: (1) patients with (longstanding) persistent AF, (2) patients with paroxysmal AF, and (3) patients without a history of AF, all undergoing open-chest cardiac surgery. Intra-operative high-resolution epicardial mapping is performed to identify the patient-specific electrical profile, whereas the patient-specific biological profile is assessed by evaluating proteostasis markers in blood samples and atrial appendage tissue samples. Post-operative continuous rhythm monitoring is performed for detection of early post-operative AF. Late post-operative AF (during 5-year follow-up) is documented by either electrocardiogram or 24-hour Holter registration. RESULTS: The required sample size for this study is estimated at 447 patients. Up till now, 105 patients were included, of whom 36 have a history of AF. CONCLUSION: The AFFIP study will elucidate whether electrophysiological and structural characteristics represent a novel diagnostic tool, the AF fingerprint, to predict onset and early progression of AF in cardiac surgery patients.