Anthony G. Brooks

Outcomes of long-standing persistent atrial fibrillation ablation: A systematic review

BACKGROUND Ablation of long-standing persistent atrial fibrillation (AF) is highly variable, with differing techniques and outcomes. OBJECTIVE The purpose of this study was to undertake a systematic review of the literature with regard to the impact of ablation technique on the outcomes of long-standing persistent AF ablation. METHODS A systematic search of the contemporary English scientific literature (from January 1, 1990 to June 1, 2009) in the PubMed database identified 32 studies on persistent/long-standing persistent or long-standing persistent AF ablation (including four randomized controlled trials). Data on single-procedure, drug-free success, multiple procedure success, and pharmaceutically assisted success at longest follow-up were collated. RESULTS Four studies performed pulmonary vein isolation alone (21%-22% success). Four studies performed pulmonary vein antrum ablation with isolation (PVAI; n = 2; 38%-40% success) or without confirmed isolation (PVA; n = 2; 37%-56% success). Ten studies performed linear ablation in addition to PVA (n = 5; 11%-74% success) or PVAI (n = 5; 38%-57% success). Three studies performed posterior wall box isolation (n = 3; 44%-50% success). Five studies performed complex fractionated atrial electrogram ablation (n = 5; 24%-63% success). Six studies performed complex fractionated atrial electrogram ablation as an adjunct to PVA (n = 2; 50%-51% success), PVAI (n = 3; 36%-61% success), or PVAI and linear (n = 1; 68% success) ablation. Five studies performed the stepwise ablation approach (38%-62% success). CONCLUSION The variation in success within and between techniques suggests that the optimal ablation technique for long-standing persistent AF is unclear. Nevertheless, long-standing persistent AF can be effectively treated with a composite of extensive index catheter ablation, repeat procedures, and/or pharmaceuticals.

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.

Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: a randomized clinical trial.

IMPORTANCE Obesity is a risk factor for atrial fibrillation. Whether weight reduction and cardiometabolic risk factor management can reduce the burden of atrial fibrillation is not known. OBJECTIVE To determine the effect of weight reduction and management of cardiometabolic risk factors on atrial fibrillation burden and cardiac structure. DESIGN, SETTING, AND PATIENTS Single-center, partially blinded, randomized controlled study conducted between June 2010 and December 2011 in Adelaide, Australia, among overweight and obese ambulatory patients (N = 150) with symptomatic atrial fibrillation. Patients underwent a median of 15 months of follow-up. INTERVENTIONS Patients were randomized to weight management (intervention) or general lifestyle advice (control). Both groups underwent intensive management of cardiometabolic risk factors. MAIN OUTCOMES AND MEASURES The primary outcomes were Atrial Fibrillation Severity Scale scores: symptom burden and symptom severity. Scores were measured every 3 months from baseline to 15 months. Secondary outcomes performed at baseline and 12 months were total atrial fibrillation episodes and cumulative duration measured by 7-day Holter, echocardiographic left atrial area, and interventricular septal thickness. RESULTS Of 248 patients screened, 150 were randomized (75 per group) and underwent follow-up. The intervention group showed a significantly greater reduction, compared with the control group, in weight (14.3 and 3.6 kg, respectively; P < .001) and in atrial fibrillation symptom burden scores (11.8 and 2.6 points, P < .001), symptom severity scores (8.4 and 1.7 points, P < .001), number of episodes (2.5 and no change, P = .01), and cumulative duration (692-minute decline and 419-minute increase, P = .002). Additionally, there was a reduction in interventricular septal thickness in the intervention and control groups (1.1 and 0.6 mm, P = .02) and left atrial area (3.5 and 1.9 cm2, P = .02). CONCLUSIONS AND RELEVANCE In this study, weight reduction with intensive risk factor management resulted in a reduction in atrial fibrillation symptom burden and severity and in beneficial cardiac remodeling. These findings support therapy directed at weight and risk factors in the management of atrial fibrillation. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12610000497000.

Pericardial fat is associated with atrial fibrillation severity and ablation outcome.

OBJECTIVES The aim of this study was to characterize the relationship between pericardial fat and atrial fibrillation (AF). BACKGROUND Obesity is an important risk factor for AF. Pericardial fat has been hypothesized to exert local pathogenic effects on nearby cardiac structures above and beyond that of systemic adiposity. METHODS One hundred ten patients undergoing first-time AF ablation and 20 reference patients without AF underwent cardiac magnetic resonance imaging for the quantification of periatrial, periventricular, and total pericardial fat volumes using a previously validated technique. Together with body mass index and body surface area, these were examined in relation to the presence of AF, the severity of AF, left atrial volume, and long-term AF recurrence after ablation. RESULTS Pericardial fat volumes were significantly associated with the presence of AF, AF chronicity, and AF symptom burden (all p values <0.05). Pericardial fat depots were also predictive of long-term AF recurrence after ablation (p = 0.035). Finally, pericardial fat depots were also associated with left atrial volume (total pericardial fat: r = 0.46, p < 0.001). Importantly, these associations persisted after multivariate adjustment and additional adjustment for body weight. In contrast, however, systemic measures of adiposity, such as body mass index and body surface area, were not associated with these outcomes in multivariate-adjusted models. CONCLUSIONS Pericardial fat is associated with the presence of AF, the severity of AF, left atrial volumes, and poorer outcomes after AF ablation. These associations are both independent of and stronger than more systemic measures of adiposity. These findings are consistent with the hypothesis of a local pathogenic effect of pericardial fat on the arrhythmogenic substrate supporting AF.

Atrial remodeling in obstructive sleep apnea: implications for atrial fibrillation.

BACKGROUND There is a known association between obstructive sleep apnea (OSA) and atrial fibrillation (AF); however, how OSA affects the atrial myocardium is not well described. OBJECTIVE To determine whether patients with OSA have an abnormal atrial substrate. METHODS Forty patients undergoing ablation of paroxysmal AF and in sinus rhythm (20 with OSA [apnea-hypopnea index ≥ 15] and 20 reference patients with no OSA [apnea-hypopnea index < 15] by polysomnography) were studied. Multipolar catheters were positioned at the lateral right atrium (RA), coronary sinus, crista terminalis, and RA septum to determine the effective refractory period at 5 sites, conduction time along linear catheters at the RA and the coronary sinus, conduction at the crista terminalis, and sinus node function (corrected sinus node recovery time). Biatrial electroanatomic maps were created to determine the voltage, conduction, and distribution of complex electrograms (duration ≥ 50 ms). RESULTS The groups had no differences in the prevalence of established risk factors for AF. Patients with OSA had the following compared with those without OSA: no difference in effective refractory period (P = .9), prolonged conduction times along the coronary sinus and RA (P = .02), greater number (P = .003) and duration (P = .03) of complex electrograms along the crista terminalis, longer P-wave duration (P = .01), longer corrected sinus node recovery time (P = .02), lower atrial voltage (RA, P <.001; left atrium, P <.001), slower atrial conduction velocity (RA, P = .001; left atrium, P = .02), and more widespread complex electrograms in both atria (RA, P = .02; left atrium, P = .01). CONCLUSION OSA is associated with significant atrial remodeling characterized by atrial enlargement, reduction in voltage, site-specific and widespread conduction abnormalities, and longer sinus node recovery. These features may in part explain the association between OSA and AF.

Obesity results in progressive atrial structural and electrical remodeling: implications for atrial fibrillation

BACKGROUND Obesity is associated with atrial fibrillation (AF); however, the mechanisms by which it induces AF are unknown. OBJECTIVE To examine the effect of progressive weight gain on the substrate for AF. METHODS Thirty sheep were studied at baseline, 4 months, and 8 months, following a high-calorie diet. Ten sheep were sampled at each time point for cardiac magnetic resonance imaging and hemodynamic studies. High-density multisite biatrial epicardial mapping was used to quantify effective refractory period, conduction velocity, and conduction heterogeneity index at 4 pacing cycle lengths and AF inducibility. Histology was performed for atrial fibrosis, inflammation, and intramyocardial lipidosis, and molecular analysis was performed for endothelin-A and -B receptors, endothelin-1 peptide, platelet-derived growth factor, transforming growth factor β1, and connective tissue growth factor. RESULTS Increasing weight was associated with increasing left atrial volume (P = .01), fibrosis (P = .02), inflammatory infiltrates (P = .01), and lipidosis (P = .02). While there was no change in the effective refractory period (P = .2), there was a decrease in conduction velocity (P<.001), increase in conduction heterogeneity index (P<.001), and increase in inducible (P = .001) and spontaneous (P = .001) AF. There was an increase in atrial cardiomyocyte endothelin-A and -B receptors (P = .001) and endothelin-1 (P = .03) with an increase in adiposity. In association, there was a significant increase in atrial interstitial and cytoplasmic transforming growth factor β1 (P = .02) and platelet-derived growth factor (P = .02) levels. CONCLUSIONS Obesity is associated with atrial electrostructural remodeling. With progressive obesity, there were changes in atrial size, conduction, histology, and expression of profibrotic mediators. These changes were associated with spontaneous and more persistent AF.

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.

Effect of Atrial Fibrillation on Atrial Thrombogenesis in Humans: Impact of Rate and Rhythm

OBJECTIVES We sought to assess the effect of atrial fibrillation (AF) on atrial thrombogenesis in humans by determining the impact of rate and rhythm. BACKGROUND Although AF is known to increase the risk of thromboembolic stroke from the left atrium (LA), the exact mechanisms remain poorly understood. METHODS We studied 55 patients with AF who underwent catheter ablation while in sinus rhythm; 20 patients were induced into AF, 20 patients were atrial paced at 150 beats/min, and 15 were control patients. Blood samples were taken from the LA, right atrium, and femoral vein at baseline and at 15 min in all 3 groups. Platelet activation (P-selectin) was measured by flow cytometry. Thrombin generation (thrombin-antithrombin [TAT] complex), endothelial dysfunction (asymmetric dimethylarginine [ADMA]), and platelet-derived inflammation (soluble CD40 ligand [sCD40L]) were measured using enzyme-linked immunosorbent assay. RESULTS Platelet activation increased significantly in both the AF (p < 0.001) and pacing (p < 0.05) groups, but decreased in control patients (p < 0.001). Thrombin generation increased specifically in the LA compared with the periphery in both the AF (p < 0.01) and pacing (p < 0.01) groups, but decreased in control patients (p < 0.001). With AF, ADMA (p < 0.01) and sCD40L (p < 0.001) levels increased significantly at all sites, but were unchanged with pacing (ADMA, p = 0.5; sCD40L, p = 0.8) or in control patients (ADMA, p = 0.6; sCD40L, p = 0.9). CONCLUSIONS Rapid atrial rates and AF in humans both result in increased platelet activation and thrombin generation. Prothrombotic activation occurs to a greater extent in the human LA compared with systemic circulation. AF additionally induces endothelial dysfunction and inflammation. These findings suggest that although rapid atrial rates increase the thrombogenic risk, AF may further potentiate this risk.

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.

Electrophysiological, Electroanatomical, and Structural Remodeling of the Atria as Consequences of Sustained Obesity

BACKGROUND Obesity and atrial fibrillation (AF) are public health issues with significant consequences. OBJECTIVES This study sought to delineate the development of global electrophysiological and structural substrate for AF in sustained obesity. METHODS Ten sheep fed ad libitum calorie-dense diet to induce obesity over 36 weeks were maintained in this state for another 36 weeks; 10 lean sheep with carefully controlled weight served as controls. All sheep underwent electrophysiological and electroanatomic mapping; hemodynamic and imaging assessment (echocardiography and dual-energy x-ray absorptiometry); and histology and molecular evaluation. Evaluation included atrial voltage, conduction velocity (CV), and refractoriness (7 sites, 2 cycle lengths), vulnerability for AF, fatty infiltration, atrial fibrosis, and atrial transforming growth factor (TGF)-β1 expression. RESULTS Compared with age-matched controls, chronically obese sheep demonstrated greater total body fat (p < 0.001); LA volume (p < 0.001); LA pressure (p < 0.001), and PA pressures (p < 0.001); reduced atrial CV (LA p < 0.001) with increased conduction heterogeneity (p < 0.001); increased fractionated electrograms (p < 0.001); decreased posterior LA voltage (p < 0.001) and increased voltage heterogeneity (p < 0.001); no change in the effective refractory period (ERP) (p > 0.8) or ERP heterogeneity (p > 0.3). Obesity was associated with more episodes (p = 0.02), prolongation (p = 0.01), and greater cumulative duration (p = 0.02) of AF. Epicardial fat infiltrated the posterior LA in the obese group (p < 0.001), consistent with reduced endocardial voltage in this region. Atrial fibrosis (p = 0.03) and TGF-β1 protein (p = 0.002) were increased in the obese group. CONCLUSIONS Sustained obesity results in global biatrial endocardial remodeling characterized by LA enlargement, conduction abnormalities, fractionated electrograms, increased profibrotic TGF-β1 expression, interstitial atrial fibrosis, and increased propensity for AF. Obesity was associated with reduced posterior LA endocardial voltage and infiltration of contiguous posterior LA muscle by epicardial fat, representing a unique substrate for AF.