New insights into the mechanisms of atrial arrhythmias using novel three dimensional mapping techniques

© 2017 Dr. Manaswi Bhupesh PathikAdvances in our understanding of the pathophysiology of atrial fibrillation (AF) and atrial macro-reentry through improvements in technology has led to the development of treatment approaches involving catheter ablation. However, outcomes have been suboptimal possibly due to an incomplete understanding of the underlying mechanisms of these arrhythmias. Using novel three-dimensional (3D) mapping techniques, this thesis aims to answer unresolved questions in our understanding of the mechanisms of human persistent AF and atrial macro-reentry. Recent work using phase mapping has suggested that rotors may act as drivers for persistent AF with studies from different centers reporting promising findings of acute termination and long term freedom from AF with ablation at the rotor center. However, these encouraging results have not been observed consistently possibly due to the two-dimensional (2D) representation of the left atrium (LA) in this mapping technique. In Chapter 2, we used a novel 3D phase mapping technology that takes into account patient-specific left atrial geometry to display phase to determine the dominant propagation patterns in patients with persistent AF. We observed transient rotors in the majority of patients, however, they were present for only a small fraction of the total recording time with the dominant propagation pattern overall being single broad wavefronts. An additional assumption of the abovementioned 2D phase mapping system is that the 64 electrodes of the Constellation basket catheter are arranged in a uniform 8x8 grid in a fixed position within the 2D representation of the LA. These spatial assumptions may lead to errors in phase animation as the actual 3D locations of the basket catheter are not taken into consideration. In Chapter 3, we therefore determined whether rotational activity detected in 2D phase maps were observed in corresponding 3D phase maps. We found that none of the rotors observed in 2D phase maps were seen in the same time segments and anatomical locations in 3D phase maps. The 2D phase detected rotors either corresponded in 3D phase maps to wavefronts (single or multiple), disorganized activity or an absence of basket coverage at the corresponding 3D anatomical site. With the increasing clinical use of the Constellation basket catheter in currently available mapping systems, Chapter 4 evaluated the efficacy of this catheter. We found that there were significant limitations of the basket catheter in terms of electrode contact and coverage of the LA. In addition, there was regional variation of coverage with preferential coverage of the lateral wall and absence of contact with the septum. These findings suggest that there is a need for the development of high density basket catheters which provide uniform LA coverage. Prior to the current focus on AF, atrial macro-reentry was the subject of extensive research. The recent development of high-density high-resolution 3D mapping provides an opportunity to study atrial macro-reentry to a level of detail not previously attainable. In Chapter 5, we sought to determine the location of the posterior line of block and characterize the relationship between substrate and conduction in patients with right atrial macro-reentry. We found that in the majority of patients with cavotricuspid-isthmus (CTI) dependent atrial macro-reentry, the posterior line of block was located at the posteromedial right atrium (RA). In addition, we observed the presence of highly variable and localized zones of slow conduction which were associated with abnormal atrial substrate resulting in individual variation of propagation patterns. In Chapter 6, using high-density high-resolution 3D mapping, we evaluated the concept of epicardial-endocardial breakthrough (EEB) that has been postulated as a mechanism for persistent AF. We hypothesized that if EEB is present during AF, and dependent on anatomically located muscle bundles, then evidence for this may be present during stable atrial macro-reentry. We observed that EEB sites were predominantly located at the posterior RA. Activation maps during tachycardia and stable CS pacing demonstrated EEB at the same anatomical location. Systematic entrainment confirmed that these EEB sites were part of the active circuit. The ongoing utility of entrainment has been questioned in the current era of high-density high-resolution 3D mapping. Entrainment has many pitfalls such as an unexpectedly long post-pacing interval (PPI) despite proximity to the active circuit. However, the limitations of visual representation of high-density 3D maps are unclear. In Chapter 7, using both 3D mapping and systematic entrainment in atrial macro-reentry, we observed that entrainment was critical in distinguishing between active and passive circuits. High-density 3D mapping alone may create the appearance of a complete circuit which is actually passive. On other hand, high-density 3D mapping provided new insights by identifying highly localized zones of slow conduction that when located proximal to an entrainment pacing site resulted in long PPI despite proximity to the active circuit. These findings suggest that high-density 3D mapping and entrainment are complementary techniques in atrial macro-reentry

Isolation of the posterior left atrium for patients with persistent atrial fibrillation: routine adenosine challenge for dormant posterior left atrial conduction improves long-term outcome

Aims: Catheter ablation to achieve posterior left atrial wall (PW) isolation may be performed as an adjunct to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF). We aimed to determine whether routine adenosine challenge for dormant posterior wall conduction improved long-term outcome. Methods and results: A total of 161 patients with persistent AF (mean age 59 +/- 9 years, AF duration 6 +/- 5 years) underwent catheter ablation involving circumferential PVI followed by PW isolation. Posterior left atrial wall isolation was performed with a roof and inferior wall line with the endpoint of bidirectional block. In 54 patients, adenosine 15 mg was sequentially administered to assess reconnection of the pulmonary veins and PW. Sites of transient reconnection were ablated and adenosine was repeated until no further reconnection was present. Holter monitoring was performed at 6 and 12 months to assess for arrhythmia recurrence. Posterior left atrial wall isolation was successfully achieved in 91% of 161 patients (procedure duration 191 +/- 49 min, mean RF time 40 +/- 19 min). Adenosine-induced reconnection of the PW was demonstrated in 17%. The single procedure freedom from recurrent atrial arrhythmia was superior in the adenosine challenge group (65%) vs. no adenosine challenge (40%, P < 0.01) at a mean follow-up of 19 +/- 8 months. After multiple procedures, there was significantly improved freedom from AF between patients with vs. without adenosine PW challenge (85 vs. 65%, P = 0.01).Conclusion Posterior left atrial wall isolation in addition to PVI is a readily achievable ablation strategy in patients with persistent AF. Routine adenosine challenge for dormant posterior wall conduction was associated with an improvement in the success of catheter ablation for persistent AF