Anand N. Ganesan

Long‐term Outcomes of Catheter Ablation of Atrial Fibrillation: A Systematic Review and Meta‐analysis

Background In the past decade, catheter ablation has become an established therapy for symptomatic atrial fibrillation (AF). Until very recently, few data have been available to guide the clinical community on the outcomes of AF ablation at ≥3 years of follow‐up. We aimed to systematically review the medical literature to evaluate the long‐term outcomes of AF ablation. Methods and Results A structured electronic database search (PubMed, Embase, Web of Science, Cochrane) of the scientific literature was performed for studies describing outcomes at ≥3 years after AF ablation, with a mean follow‐up of ≥24 months after the index procedure. The following data were extracted: (1) single‐procedure success, (2) multiple‐procedure success, and (3) requirement for repeat procedures. Data were extracted from 19 studies, including 6167 patients undergoing AF ablation. Single‐procedure freedom from atrial arrhythmia at long‐term follow‐up was 53.1% (95% CI 46.2% to 60.0%) overall, 54.1% (95% CI 44.4% to 63.4%) in paroxysmal AF, and 41.8% (95% CI 25.2% to 60.5%) in nonparoxysmal AF. Substantial heterogeneity (I2>50%) was noted for single‐procedure outcomes. With multiple procedures, the long‐term success rate was 79.8% (95% CI 75.0% to 83.8%) overall, with significant heterogeneity (I2>50%).The average number of procedures per patient was 1.51 (95% CI 1.36 to 1.67). Conclusions Catheter ablation is an effective and durable long‐term therapeutic strategy for some AF patients. Although significant heterogeneity is seen with single procedures, long‐term freedom from atrial arrhythmia can be achieved in some patients, but multiple procedures may be required.

Role of AV nodal ablation in cardiac resynchronization in patients with coexistent atrial fibrillation and heart failure a systematic review.

OBJECTIVES The aim of this study was to systematically review the medical literature to evaluate the impact of AV nodal ablation in patients with heart failure and coexistent atrial fibrillation (AF) receiving cardiac resynchronization therapy (CRT). BACKGROUND CRT has a substantial evidence base in patients in sinus rhythm with significant systolic dysfunction, symptomatic heart failure, and prolonged QRS duration. The role of CRT is less well established in AF patients with coexistent heart failure. AV nodal ablation has recently been suggested to improve outcomes in this group. METHODS Electronic databases and reference lists through September 15, 2010, were searched. Two reviewers independently evaluated citation titles, abstracts, and articles. Studies reporting the outcomes after AV nodal ablation in patients with AF undergoing CRT for symptomatic heart failure and left ventricular dyssynchrony were selected. Data were extracted from 6 studies, including 768 CRT-AF patients, composed of 339 patients who underwent AV nodal ablation and 429 treated with medical therapy aimed at rate control alone. RESULTS AV nodal ablation in CRT-AF patients was associated with significant reductions in all-cause mortality (risk ratio: 0.42 [95% confidence interval: 0.26 to 0.68]), cardiovascular mortality (risk ratio: 0.44 [95% confidence interval: 0.24 to 0.81]), and improvement in mean New York Heart Association functional class (risk ratio: -0.52 [95% confidence interval: -0.87 to -0.17]). CONCLUSIONS AV nodal ablation was associated with a substantial reduction in all-cause mortality and cardiovascular mortality and with improvements in New York Heart Association functional class compared with medical therapy in CRT-AF patients. Randomized controlled trials are warranted to confirm the efficacy and safety of AV nodal ablation in this patient population.

Clinical ResearchHeart Rhythm DisordersRole of AV Nodal Ablation in Cardiac Resynchronization in Patients With Coexistent Atrial Fibrillation and Heart Failure: A Systematic Review

OBJECTIVES The aim of this study was to systematically review the medical literature to evaluate the impact of AV nodal ablation in patients with heart failure and coexistent atrial fibrillation (AF) receiving cardiac resynchronization therapy (CRT). BACKGROUND CRT has a substantial evidence base in patients in sinus rhythm with significant systolic dysfunction, symptomatic heart failure, and prolonged QRS duration. The role of CRT is less well established in AF patients with coexistent heart failure. AV nodal ablation has recently been suggested to improve outcomes in this group. METHODS Electronic databases and reference lists through September 15, 2010, were searched. Two reviewers independently evaluated citation titles, abstracts, and articles. Studies reporting the outcomes after AV nodal ablation in patients with AF undergoing CRT for symptomatic heart failure and left ventricular dyssynchrony were selected. Data were extracted from 6 studies, including 768 CRT-AF patients, composed of 339 patients who underwent AV nodal ablation and 429 treated with medical therapy aimed at rate control alone. RESULTS AV nodal ablation in CRT-AF patients was associated with significant reductions in all-cause mortality (risk ratio: 0.42 [95% confidence interval: 0.26 to 0.68]), cardiovascular mortality (risk ratio: 0.44 [95% confidence interval: 0.24 to 0.81]), and improvement in mean New York Heart Association functional class (risk ratio: -0.52 [95% confidence interval: -0.87 to -0.17]). CONCLUSIONS AV nodal ablation was associated with a substantial reduction in all-cause mortality and cardiovascular mortality and with improvements in New York Heart Association functional class compared with medical therapy in CRT-AF patients. Randomized controlled trials are warranted to confirm the efficacy and safety of AV nodal ablation in this patient population.

Complications of Catheter Ablation of Atrial Fibrillation: A Systematic Review

Background—Atrial fibrillation ablation is an established therapy; however, limited data are available on associated complications. This systematic review determines the incidence and potential predictors of acute complications. Methods and Results—Electronic searches were conducted in MEDLINE and EMBASE for English scientific literature up to the 18th June 2012. A total of 2065 references were retrieved and evaluated for relevance. Reference lists of retrieved studies and review articles were examined to ensure all relevant studies were included. Data were extracted from 192 studies, total of 83 236 patients. The incidence of periprocedural complications for catheter ablation of atrial fibrillation was 2.9% (95% confidence interval, 2.6–3.2). There was a significant decrease in the acute complication rate in 2007 to 2012 compared with 2000 to 2006 (2.6% versus 4.0%; P=0.003). The complication rates reported were higher in prospective studies compared with those that retrospectively described complications (3.5% versus 2.7%; P=0.03). There were no significant associations among procedure duration, ablation time or ablation strategy, and acute complication rate. Conclusions—Catheter ablation of atrial fibrillation has a low incidence of periprocedural complications. The acute complication rate has decreased significantly in recent years. This may reflect improved catheter technology and experience. The use of different strategies across centers worldwide seems to be safe with no established relationship between procedural variables and complication rate.

The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis.

AIMS Thromboembolic risk stratification schemes and clinical guidelines for atrial fibrillation (AF) regard risk as independent of classification into paroxysmal (PAF) and non-paroxysmal atrial fibrillation (NPAF). The aim of the current study was to conduct a systematic review evaluating the impact of AF type on thromboembolism, bleeding, and mortality. METHODS AND RESULTS PubMed was searched through 27 November 2014 for randomized controlled trials, cohort studies, and case series reporting prospectively collected clinical outcomes stratified by AF type. The incidence of thromboembolism, mortality, and bleeding was extracted. Atrial fibrillation clinical outcome data were extracted from 12 studies containing 99 996 patients. The unadjusted risk ratio (RR) for thromboembolism in NPAF vs. PAF was 1.355 (95% CI: 1.169-1.571, P < 0.001). In the study subset off oral anticoagulation, unadjusted RR was 1.689 (95% CI: 1.151-2.480, P = 0.007). The overall multivariable adjusted hazard ratio (HR) for thromboembolism was 1.384 (95% CI: 1.191-1.608, P < 0.001). The overall unadjusted RR for all-cause mortality was 1.462 (95% CI: 1.255-1.703, P < 0.001). Multivariable adjusted HR for all-cause mortality was 1.217 (95% CI: 1.085-1.365, P < 0.001). Rates of bleeding were similar, with unadjusted RR 1.00 (95% CI: 0.919-1.087, P = 0.994) and adjusted HR 1.025 (95% CI: 0.898-1.170, P = 0.715). CONCLUSION Non-paroxysmal atrial fibrillation is associated with a highly significant increase in thromboembolism and death. These data suggest the need for new therapies to prevent AF progression and further studies to explore the integration of AF type into models of thromboembolic risk.

Bipolar Electrogram Shannon Entropy at Sites of Rotational Activation: Implications for Ablation of Atrial Fibrillation

Background—The pivot is critical to rotors postulated to maintain atrial fibrillation (AF). We reasoned that wavefronts circling the pivot should broaden the amplitude distribution of bipolar electrograms because of directional information encoded in these signals. We aimed to determine whether Shannon entropy (ShEn), a measure of signal amplitude distribution, could differentiate the pivot from surrounding peripheral regions and thereby assist clinical rotor mapping. Methods and Results—Bipolar electrogram recordings were studied in 4 systems: (1) computer simulations of rotors in a 2-dimensional atrial sheet; (2) isolated rat atria recorded with a multi-electrode array (n=12); (3) epicardial plaque recordings of induced AF in hypertensive sheep (n=11); and (4) persistent AF patients (n=10). In the model systems, rotation episodes were identified, and ShEn calculated as an index of amplitude distribution. In humans, ShEn distribution was analyzed at AF termination sites and with respect to complex fractionated electrogram mean. We analyzed rotation episodes in simulations (4 cycles) and animals (rats: 14 rotors, duration 80±81 cycles; sheep: 13 rotors, 4.2±1.5 cycles). The maximum ShEn bipole was consistently colocated with the pivot zone. ShEn was negatively associated with distance from the pivot zone in simulated spiral waves, rats, and sheep. ShEn was modestly inversely associated with complex fractionated electrogram; however, there was no relationship at the sites of highest ShEn. Conclusions—ShEn is a mechanistically based tool that may assist AF rotor mapping.Background— The pivot is critical to rotors postulated to maintain atrial fibrillation (AF). We reasoned that wavefronts circling the pivot should broaden the amplitude distribution of bipolar electrograms because of directional information encoded in these signals. We aimed to determine whether Shannon entropy (ShEn), a measure of signal amplitude distribution, could differentiate the pivot from surrounding peripheral regions and thereby assist clinical rotor mapping. Methods and Results— Bipolar electrogram recordings were studied in 4 systems: (1) computer simulations of rotors in a 2-dimensional atrial sheet; (2) isolated rat atria recorded with a multi-electrode array (n=12); (3) epicardial plaque recordings of induced AF in hypertensive sheep (n=11); and (4) persistent AF patients (n=10). In the model systems, rotation episodes were identified, and ShEn calculated as an index of amplitude distribution. In humans, ShEn distribution was analyzed at AF termination sites and with respect to complex fractionated electrogram mean. We analyzed rotation episodes in simulations (4 cycles) and animals (rats: 14 rotors, duration 80±81 cycles; sheep: 13 rotors, 4.2±1.5 cycles). The maximum ShEn bipole was consistently colocated with the pivot zone. ShEn was negatively associated with distance from the pivot zone in simulated spiral waves, rats, and sheep. ShEn was modestly inversely associated with complex fractionated electrogram; however, there was no relationship at the sites of highest ShEn. Conclusions— ShEn is a mechanistically based tool that may assist AF rotor mapping.

Importance of the underlying substrate in determining thrombus location in atrial fibrillation: implications for left atrial appendage closure

Context The left atrial appendage (LAA) has been suggested to be the dominant location of thrombus in atrial fibrillation (AF) and has led to the development of LAA occlusion as a therapeutic modality to reduce stroke risk. However, the patient populations that would benefit most from this therapy are not well defined. Objective A systematic review was performed to better define subgroups amenable to appendage closure. Data sources The English scientific literature was searched using Pubmed through to March 1, 2011. Reference lists of relevant and review articles were screened to retrieve additional articles. Study selection Studies were only included if they described the location of thrombus in left atrium. Case reports and case series describing less than 10 thrombi were excluded. Data extraction Two reviewers independently extracted data and assessed quality of each study. Results A total of 34 studies reporting on the location of atrial thrombus in patients with AF were included: 17 in valvular AF, 10 non-valvular AF and 8 in mixed valvular and non-valvular AF. Atrial thrombi were located outside the LAA in 56% (95% CI 53, 60) of valvular AF, 22% (95% CI 19, 25) in mixed cohorts and 11% (95% CI 6, 15) non-valvular AF. In non valvular AF, the studies with higher proportion of thrombi in the left atrial cavity had non-anticoagulated patients and a greater proportion of ventricular dysfunction and history of stroke. Conclusion The location of atrial thrombus in patients with AF is dependent on the underlying substrate. In valvular AF, more than half the thrombi are located in the left atrial cavity. In the non-valvular AF group, a smaller proportion of thrombi were located outside the appendage. However, in certain subgroups (ie. non anti-coagulated, left ventricular dysfunction or prior stroke) the chances of left atrial cavity thrombus are higher.

Reconstruction of instantaneous phase of unipolar atrial contact electrogram using a concept of sinusoidal recomposition and Hilbert transform

The Hilbert transform has been used to characterize wave propagation and detect phase singularities during cardiac fibrillation. Two mapping modalities have been used: optical mapping (used to map atria and ventricles) and contact electrode mapping (used only to map ventricles). Due to specific morphology of atrial electrograms, phase reconstruction of contact electrograms in the atria is challenging and has not been investigated in detail. Here, we explore the properties of Hilbert transform applied to unipolar epicardial electrograms and devise a method for robust phase reconstruction using the Hilbert transform. We applied the Hilbert transform to idealized unipolar signals obtained from analytical approach and to electrograms recorded in humans. We investigated effects of deflection morphology on instantaneous phase. Application of the Hilbert transform to unipolar electrograms demonstrated sensitivity of reconstructed phase to the type of deflection morphology (uni- or biphasic), the ratio of R and S waves and presence of the noise. In order to perform a robust phase reconstruction, we propose a signal transformation based on the recomposition of the electrogram from sinusoidal wavelets with amplitudes proportional to the negative slope of the electrogram. Application of the sinusoidal recomposition transformation prior to application of the Hilbert transform alleviates the effect of confounding features on reconstructed phase.

Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future directions.

Obesity is increasingly recognized as a major modifiable determinant of atrial fibrillation (AF). Although body mass index and other clinical measures are useful indications of general adiposity, much recent interest has focused on epicardial fat, a distinct adipose tissue depot that can be readily assessed using non-invasive imaging techniques. A growing body of data from epidemiological and clinical studies has demonstrated that epicardial fat is consistently associated with the presence, severity, and recurrence of AF across a range of clinical settings. Evidence from basic science and translational studies has also suggested that arrhythmogenic mechanisms may involve adipocyte infiltration, pro-fibrotic, and pro-inflammatory paracrine effects, oxidative stress, and other pathways. Despite these advances, however, significant uncertainty exists and many questions remain unanswered. In this article, we review our present understanding of epicardial fat, including its classification and quantification, existing evidence implicating its role in AF, potential mechanisms, implications for clinicians, and future directions for research.

High-density mapping of ventricular scar: a comparison of ventricular tachycardia (VT) supporting channels with channels that do not support VT.

Background—Surviving myocytes within scar may form channels that support ventricular tachycardia (VT) circuits. There are little data on the properties of channels that comprise VT circuits and those that are non-VT supporting channels. Methods and Results—In 22 patients with ischemic cardiomyopathy and VT, high-density mapping was performed with the PentaRay catheter and Ensite NavX system during sinus rhythm. A channel was defined as a series of matching pace-maps with a stimulus (S) to QRS time of ≥40 ms. Sites were determined to be part of a VT channel if there were matching pace-maps to the VT morphology. This was confirmed with entrainment mapping when possible. Of the 238 channels identified, 57 channels corresponded to an inducible VT. Channels that were part of a VT circuit were more commonly located within dense scar than non-VT channels (97% versus 82%; P=0.036). VT supporting channels were of greater length (mean±SEM, 53±5 versus 33±4 mm), had higher longest S-QRS (130±12 versus 82±12 ms), longer conduction time (103±14 versus 43±13 ms), and slower conduction velocity (0.87±0.23 versus 1.39±0.21 m/s) than non-VT channels (P<0.001). Of all the fractionated, late, and very late potentials located in scar, only 21%, 26%, and 29%, respectively, were recorded within VT channels. Conclusions—High-density mapping shows substantial differences among channels in ventricular scar. Channels supporting VT are more commonly located in dense scar, longer than non-VT channels, and have slower conduction velocity. Only a minority of scar-related potentials participate in the VT supporting channels.