Junaid A.B. Zaman

Mechanisms for the Termination of Atrial Fibrillation by Localized Ablation Computational and Clinical Studies

Background—Human atrial fibrillation (AF) can terminate after ablating localized regions, which supports the existence of localized rotors (spiral waves) or focal drivers. However, it is unclear why ablation near a spiral wave tip would terminate AF and not anchor reentry. We addressed this question by analyzing competing mechanisms for AF termination in numeric simulations, referenced to clinical observations. Methods and Results—Spiral wave reentry was simulated in monodomain 2-dimensional myocyte sheets using clinically realistic rate-dependent values for repolarization and conduction. Heterogeneous models were created by introduction of parameterized variations in tissue excitability. Ablation lesions were applied as nonconducting circular regions. Models confirmed that localized ablation may anchor spiral wave reentry, producing organized tachycardias. Several mechanisms referenced to clinical observations explained termination of AF to sinus rhythm. First, lesions may create an excitable gap vulnerable to invasion by fibrillatory waves. Second, ablation of rotors in regions of low-excitability (from remodeling) produced re-entry in more excitable tissue allowing collision of wavefront and back. Conversely, ablation of rotors in high-excitability regions migrated spiral waves to less excitable tissue, where they detached to collide with nonconducting boundaries. Third, ablation may connect rotors to nonconducting anatomic orifices. Fourth, reentry through slow-conducting channels may terminate if ablation closes these channels. Conclusions—Limited ablation can terminate AF by several mechanisms. These data shed light on how clinical AF may be sustained in patients’ atria, emphasizing heterogeneities in tissue excitability, slow-conducting channels, and obstacles that are increasingly detectable in patients and should be the focus of future translational studies.

Mechanistically based mapping of human cardiac fibrillation

The mechanisms underpinning human cardiac fibrillation remain elusive. In his 1913 paper ‘On dynamic equilibrium in the heart’, Mines proposed that an activation wave front could propagate repeatedly in a circle, initiated by a stimulus in the vulnerable period. While the dynamics of activation and recovery are central to cardiac fibrillation, these physiological data are rarely used in clinical mapping. Fibrillation is a rapid irregular rhythm with spatiotemporal disorder resulting from two fundamental mechanisms – sources in preferred cardiac regions or spatially diffuse self‐sustaining activity, i.e. with no preferred source. On close inspection, however, this debate may also reflect mapping technique. Fibrillation is initiated from triggers by regional dispersion in repolarization, slow conduction and wavebreak, then sustained by non‐uniform interactions of these mechanisms. Notably, optical mapping of action potentials in atrial fibrillation (AF) show spiral wave sources (rotors) in nearly all studies including humans, while most traditional electrogram analyses of AF do not. Techniques may diverge in fibrillation because electrograms summate non‐coherent waves within an undefined field whereas optical maps define waves with a visually defined field. Also fibrillation operates at the limits of activation and recovery, which are well represented by action potentials while fibrillatory electrograms poorly represent repolarization. We conclude by suggesting areas for study that may be used, until such time as optical mapping is clinically feasible, to improve mechanistic understanding and therapy of human cardiac fibrillation.

The Rotor Revolution Conduction at the Eye of the Storm in Atrial Fibrillation

The recent explosion of literature on rotors in human atrial fibrillation (AF) is no surprise to followers of the history of science in which return to an old paradigm paradoxically heralds incremental progress based on the emergence of new evidence. Although the rotor paradigm is neither confirmed nor universal, it does revitalize a more mechanistic approach to addressing persistence in human AF. Although determining the relevance of rotors is the current obsession, we must reach beyond this existential debate and focus on the underpinning mechanisms. Critical to this is understanding how the underlying tissue architecture governs conduction and is manifest in electrograms and their spatiotemporal distribution and how therefore the hierarchical rotor paradigm can be unified with the anarchical paradigm of diffuse, widely distributed complex microreentry. It is the challenge of unifying these apparently irreconcilable bodies of evidence that is the stimulus for reviewing the areas of mechanistic importance common to the relationship between myocardial architecture and conduction that lies at the heart of understanding persistence in human AF. The rotor revolution has focussed attention on conduction characteristics that promote drivers as the underlying mechanism of persistence and increasing refractoriness to treatment of AF. This has shifted thinking away from a purely anatomic ablation strategy to a mechanistic one based on propagation mapping. Regardless of the discussion surrounding how rotors are detected and whether therefore they exist at all, mechanisms are now in fashion again. Although rotors are the paradigm of the moment,1 the debate with proponents of multiple wavelet reentry rages with renewed vigor, but unlike previously at stake now are the procedural outcomes and the welfare of our patients. Whatever the macroscopic panoramic pattern of activation, no coherent explanation exists for how rotors may result from the causative myocardial remodeling at the cellular and tissue level. In …

Recurrent Post-Ablation Paroxysmal Atrial Fibrillation Shares Substrates With Persistent Atrial Fibrillation : An 11-Center Study

INTRODUCTION The role of atrial fibrillation (AF) substrates is unclear in patients with paroxysmal AF (PAF) that recurs after pulmonary vein isolation (PVI). We hypothesized that patients with recurrent post-ablation (redo) PAF despite PVI have electrical substrates marked by rotors and focal sources, and structural substrates that resemble persistent AF more than patients with (de novo) PAF at first ablation. METHODS In 175 patients at 11 centers, we compared AF substrates in both atria using 64 pole-basket catheters and phase mapping, and indices of anatomical remodeling between patients with de novo or redo PAF and first ablation for persistent AF. RESULTS Sources were seen in all patients. More patients with de novo PAF (78.0%) had sources near PVs than patients with redo PAF (47.4%, p=0.005) or persistent AF (46.9%, p=0.001). The total number of sources per patient (p=0.444), and number of non-PV sources (p=0.701) were similar between groups, indicating that redo PAF patients had residual non-PV sources after elimination of PV sources by prior PVI. Structurally, left atrial size did not separate de novo from redo PAF (49.5±9.5 vs. 49.0±7.1mm, p=0.956) but was larger in patients with persistent AF (55.2±8.4mm, p=0.001). CONCLUSIONS Patients with paroxysmal AF despite prior PVI show electrical substrates that resemble persistent AF more closely than patients with paroxysmal AF at first ablation. Notably, these subgroups of paroxysmal AF are indistinguishable by structural indices. These data motivate studies of trigger versus substrate mechanisms for patients with recurrent paroxysmal AF after PVI.

Organized Sources Are Spatially Conserved in Recurrent Compared to Pre-Ablation Atrial Fibrillation: Further Evidence for Non-Random Electrical Substrates.

Recurrent atrial fibrillation (AF) after ablation is associated with reconnection of initially isolated pulmonary vein (PV) trigger sites. Substrates are often targeted in addition to PVI, but it is unclear how substrates progress over time. We studied if substrates in recurrent AF are conserved or have developed de novo from pre‐ablation AF.

Rotor mapping and ablation to treat atrial fibrillation.

Purpose of review Rotors have long been postulated to drive atrial fibrillation, but evidence has been limited to animal models. This changed recently with the demonstration using focal impulse and rotor modulation (FIRM) mapping that rotors act as human atrial fibrillation sources. This mechanistic approach to diagnosing the causes of atrial fibrillation in individual patients has been supported by substantially improved outcomes from FIRM-guided ablation, resulting in increased attention to rotors as therapeutic targets. Recent findings In this review, we outline the pathophysiology of rotors in animal and in-silico studies of fibrillation, and how this motivated FIRM mapping in humans. We highlight the characteristics of rotors in human atrial fibrillation, now validated by several techniques, with discussion on similar and discrepant findings between techniques. The interventional approaches to eliminate atrial fibrillation rotors are explained and the ablation results in latest studies using FIRM are discussed. Summary We propose that mapping localized sources for human atrial fibrillation, specifically rotors, is moving the field towards a unifying hypothesis that explains several otherwise contradictory observations in atrial fibrillation management. We conclude by suggesting areas of potential research that may reveal more about these critical sites and how these may lead to better and novel treatments for atrial fibrillation.

Clinical Implications of Ablation of Drivers for Atrial Fibrillation: A Systematic Review and Meta-Analysis

Background: The outcomes from pulmonary vein isolation (PVI) for atrial fibrillation (AF) are suboptimal, but the benefits of additional lesion sets remain unproven. Recent studies propose ablation of AF drivers improves outcomes over PVI, yet with conflicting reports in the literature. We undertook a systematic literature review and meta-analysis to determine outcomes from ablation of AF drivers in addition to PVI or as a stand-alone procedure. Methods: Database search was done using the terms atrial fibrillation and ablation or catheter ablation and driver or rotor or focal impulse or FIRM (Focal Impulse and Rotor Modulation). We pooled data using random effects model and assessed heterogeneity with I2 statistic. Results: Seventeen studies met inclusion criteria, in a cohort size of 3294 patients. Adding AF driver ablation to PVI reported freedom from AF of 72.5% (confidence interval [CI], 62.1%–81.8%; P<0.01) and from all arrhythmias of 57.8% (CI, 47.5%–67.7%; P<0.01). AF driver ablation when added to PVI or as stand-alone procedure compared with controls produced an odds ratio of 3.1 (CI, 1.3–7.7; P=0.02) for freedom from AF and an odds ratio of 1.8 (CI, 1.2–2.7; P<0.01) for freedom from all arrhythmias in 4 controlled studies. AF termination rate was 40.5% (CI, 30.6%–50.9%) and predicted favorable outcome from ablation(P<0.05). Conclusions: In controlled studies, the addition of AF driver ablation to PVI supports the possible benefit of a combined approach of AF driver ablation and PVI in improving single-procedure freedom from all arrhythmias. However, most studies are uncontrolled and are limited by substantial heterogeneity in outcomes. Large multicenter randomized trials are needed to precisely define the benefits of adding driver ablation to PVI.

Identification and Characterization of Sites Where Persistent Atrial Fibrillation Is Terminated by Localized Ablation

Background: The mechanisms by which persistent atrial fibrillation (AF) terminates via localized ablation are not well understood. To address the hypothesis that sites where localized ablation terminates persistent AF have characteristics identifiable with activation mapping during AF, we systematically examined activation patterns acquired only in cases of unequivocal termination by ablation. Methods and Results: We recruited 57 patients with persistent AF undergoing ablation, in whom localized ablation terminated AF to sinus rhythm or organized tachycardia. For each site, we performed an offline analysis of unprocessed unipolar electrograms collected during AF from multipolar basket catheters using the maximum –dV/dt assignment to construct isochronal activation maps for multiple cycles. Additional computational modeling and phase analysis were used to study mechanisms of map variability. At all sites of AF termination, localized repetitive activation patterns were observed. Partial rotational circuits were observed in 26 of 57 (46%) cases, focal patterns in 19 of 57 (33%), and complete rotational activity in 12 of 57 (21%) cases. In computer simulations, incomplete segments of partial rotations coincided with areas of slow conduction characterized by complex, multicomponent electrograms, and variations in assigning activation times at such sites substantially altered mapped mechanisms. Conclusions Local activation mapping at sites of termination of persistent AF showed repetitive patterns of rotational or focal activity. In computer simulations, complete rotational activation sequence was observed but was sensitive to assignment of activation timing particularly in segments of slow conduction. The observed phenomena of repetitive localized activation and the mechanism by which local ablation terminates putative AF drivers require further investigation.

The Five-Minute Moment

In todays hospital and clinic environment, the obstacles to bedside teaching for both faculty and trainees are considerable. As electronic health record systems become increasingly prevalent, trainees are spending more time performing patient care tasks from computer workstations, limiting opportunities to learn at the bedside. Physical examination skills rarely are emphasized, and low confidence levels, especially in junior faculty, pose additional barriers to teaching the bedside examination.

The Value of Physical Examination: A New Conceptual Framework

Abstract The physical examination defines medical practice, yet its role is being questioned increasingly, with statistical comparisons of diagnostic accuracy often the sole metric used against newer technologies. We set out to highlight seven ways in which the physical examination has value beyond diagnostic accuracy to reaffirm its place in the core skills of a physician and guide future research, teaching, and curriculum design. We show that this more comprehensive approach to the physical examination of its “utility” beyond that of reaching a diagnosis can be beneficial to both doctor and patient.