Specific Electrogram Characteristics Identify the Extra-Pulmonary Vein Arrhythmogenic Sources of Persistent Atrial Fibrillation – Characterization of the Arrhythmogenic Electrogram Patterns During Atrial Fibrillation and Sinus Rhythm

Abstract

Identification of atrial sites that perpetuate atrial fibrillation (AF), and ablation thereof terminates AF, is challenging. We hypothesized that specific electrogram (EGM) characteristics identify AF-termination sites (AFTS). Twenty-one patients in whom low-voltage-guided ablation after pulmonary vein isolation terminated clinical persistent AF were included. Patients were included if short RF-delivery for <8sec at a given atrial site was associated with acute termination of clinical persistent AF. EGM-characteristics at 21 AFTS, 105 targeted sites without termination and 105 non-targeted control sites were analyzed. Alteration of EGM-characteristics by local fibrosis was evaluated in a three-dimensional high resolution (100 µm)-computational AF model. AFTS demonstrated lower EGM-voltage, higher EGM-cycle-length-coverage, shorter AF-cycle-length and higher pattern consistency than control sites (0.49 ± 0.39 mV vs. 0.83 ± 0.76 mV, p < 0.0001; 79 ± 16% vs. 59 ± 22%, p = 0.0022; 173 ± 49 ms vs. 198 ± 34 ms, p = 0.047; 80% vs. 30%, p < 0.01). Among targeted sites, AFTS had higher EGM-cycle-length coverage, shorter local AF-cycle-length and higher pattern consistency than targeted sites without AF-termination (79 ± 16% vs. 63 ± 23%, p = 0.02; 173 ± 49 ms vs. 210 ± 44 ms, p = 0.002; 80% vs. 40%, p = 0.01). Low voltage (0.52 ± 0.3 mV) fractionated EGMs (79 ± 24 ms) with delayed components in sinus rhythm (‘atrial late potentials’, respectively ‘ALP’) were observed at 71% of AFTS. EGMs recorded from fibrotic areas in computational models demonstrated comparable EGM-characteristics both in simulated AF and sinus rhythm. AFTS may therefore be identified by locally consistent, fractionated low-voltage EGMs with high cycle-length-coverage and rapid activity in AF, with low-voltage, fractionated EGMs with delayed components/ ‘atrial late potentials’ (ALP) persisting in sinus rhythm.

Comparison of Unipolar and Bipolar Voltage Mapping for Localization of Left Atrial Arrhythmogenic Substrate in Patients With Atrial Fibrillation

“…Previous studies have shown that AF driver sites with acute AF termination frequently occur within LVA in bipolar mapping (Jadidi et al, 2016(Jadidi et al, , 2020. Considering our findings, atrial sites displaying low voltage in the bipolar map will also display these regions in the unipolar map, thus indicating that an important criterion for AF source localization during high-density Lasso mapping is reduced electrogram voltage irrespective of the mapping modality (uni-/bipolar).…”

“…Presence and accurate localization of low voltage areas was confirmed by contact force-sensing catheters (>5 g). Bipolar low voltage zones were defined as <0.35 or <0.5 mV in AF, according to the findings in recent studies (Jadidi et al, 2016(Jadidi et al, , 2020Rodríguez-Mañero et al, 2018).…”

“…However, additional arrhythmogenic atrial substrate is present in 30-50% of persistent AF patients and may be responsible for the maintenance of the arrhythmia, resulting in increased AF recurrences after pulmonary vein isolation (PVI) in these patients (Verma et al, 2005(Verma et al, , 2015. Procedural identification of arrhythmogenic AF sources with rapid, continuous, or repeated rotational activity has revealed their localization within fibrotic regions displaying low bipolar voltage <0.5 mV during AF (Jadidi et al, 2016(Jadidi et al, , 2020Seitz et al, 2017). Ablation of these atrial AF sources, in addition to PVI, improves the success rate in persistent AF patients from 30 to 50% with PVI only to 70% with additional selective ablation of arrhythmogenic low voltage areas (LVA) (Rolf et al, 2014;Jadidi et al, 2016;Blandino et al, 2017;Seitz et al, 2017).…”

Phase Singularities in Cardiac Patch Model with Non-conductive Fibrotic Area during Atrial Fibrillation

“…Fibrosis represents a complex structure comprised of different factorssuch as collagen deposition, inflammatory cytokines, proteins, among othersthat alter the electrophysiology of the cardiac tissue. For instance, heterogeneities induced by the presence of fibrosis alter conduction patterns in the cardiac tissue, creating regions of slow and anisotropic conduction [4]. Such delayed activation might favor the occurrence of re-entrant activity, which in turn participates in the perpetuation of the arrhythmia [5].…”

“…Such delayed activation might favor the occurrence of re-entrant activity, which in turn participates in the perpetuation of the arrhythmia [5]. The relationship between rotors and fibrosisas well as rotor detection related to fibrosisremains controversial [4]. Additionally, methods for automated rotor detection during cardiac electrophysiologic studies rely mostly on unipolar measurements, whereas the majority of clinical centers perform AF ablation guided by attributes extracted from bipolar electrograms (EGMs) [2].…”