NLRP3 inflammasome is a key driver of obesity-induced atrial arrhythmias.

AIMS: Obesity, an established risk factor of atrial fibrillation (AF), is frequently associated with enhanced inflammatory response. However, whether inflammatory signaling is causally linked to AF pathogenesis in obesity remains elusive. We recently demonstrated that the constitutive activation of the 'NACHT, LRR, and PYD Domains-containing Protein 3' (NLRP3) inflammasome promotes AF susceptibility. In this study, we hypothesized that the NLRP3 inflammasome is a key driver of obesity-induced AF. METHODS AND RESULTS: Western blotting was performed to determine the level of NLRP3 inflammasome activation in atrial tissues of obese patients, sheep, and diet-induced obese (DIO) mice. The increased body weight in patients, sheep, and mice was associated with enhanced NLRP3-inflammasome activation. To determine whether NLRP3 contributes to the obesity-induced atrial arrhythmogenesis, wild-type (WT) and NLRP3 homozygous knockout (NLRP3-/-) mice were subjected to high-fat-diet (HFD) or normal chow (NC) for 10 weeks. Relative to NC-fed WT mice, HFD-fed WT mice were more susceptible to pacing-induced AF with longer AF duration. In contrast, HFD-fed NLRP3-/- mice were resistant to pacing-induced AF. Optical mapping in DIO mice revealed an arrhythmogenic substrate characterized by abbreviated refractoriness and action potential duration (APD), two key determinants of reentry-promoting electrical remodeling. Upregulation of ultra-rapid delayed-rectifier K+-channel (Kv1.5) contributed to the shortening of atrial refractoriness. Increased profibrotic signaling and fibrosis along with abnormal Ca2+ release from sarcoplasmic reticulum (SR) accompanied atrial arrhythmogenesis in DIO mice. Conversely, genetic ablation of Nlrp3 (NLRP3-/-) in HFD-fed mice prevented the increases in Kv1.5 and the evolution of electrical remodeling, the upregulation of profibrotic genes, and abnormal SR Ca2+ release in DIO mice. CONCLUSION: These results demonstrate that the atrial NLRP3 inflammasome is a key driver of obesity-induced atrial arrhythmogenesis and establishes a mechanistic link between obesity-induced AF and NLRP3-inflammasome activation.

Implication of ventricular pacing burden and atrial pacing therapies on the progression of atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Atrial fibrillation (AF) is common after pacemaker implantation. However, the impact of pacemaker algorithms in AF prevention is not well understood. OBJECTIVE: The purpose of this study was to evaluate the role of pacing algorithms in preventing AF progression. METHODS: A systematic search of articles using the PubMed and Embase databases resulted in a total of 754 references. After exclusions, 21 randomized controlled trials (8336 patients) were analyzed, comprising studies reporting ventricular pacing percentage (VP%) (AAI vs DDD, n = 1; reducing ventricular pacing [RedVP] algorithms, n = 2); and atrial pacing therapies (atrial preference pacing [APP], n = 14; atrial antitachycardia pacing [aATP]+APP, n = 3; RedVP+APP+aATP, n = 1). RESULTS: Low VP% (<10%) lead to a nonsignificant reduction in the progression of AF (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.57-1.13; P = .21; I2 = 67%) compared to high VP% (>10%). APP algorithm reduced premature atrial complexes (PAC) burden (mean difference [MD] -1117.74; 95% CI -1852.36 to -383.11; P = .003; I2 = 67%) but did not decrease AF burden (MD 8.20; 95% CI -5.39 to 21.80; P = .24; I2 = 17%) or AF episodes (MD 0.00; 95% CI -0.24 to 0.25; P = .98; I2 = 0%). Similarly, aATP+APP programming showed no significant difference in AF progression (odds ratio 0.65; 95% CI 0.36-1.14; P = .13; I2 = 61%). No serious adverse events related to algorithm were reported. CONCLUSION: This meta-analysis of randomized controlled trials demonstrated that algorithms to reduce VP% can be considered safe. Low burden VP% did not significantly suppress AF progression. The atrial pacing therapy algorithms could suppress PAC burden but did not prevent AF progression.

Electroanatomical Remodeling of the Atria in Obesity: Impact of Adjacent Epicardial Fat.

OBJECTIVES: The aims of the study were to characterize: 1) electrical and electroanatomical remodeling in patients with atrial fibrillation (AF) with obesity; and 2) the impact of epicardial fat depots on adjacent atrial tissue. BACKGROUND: Obesity is associated with an increased risk of AF. METHODS: A total of 115 patients with AF who underwent AF ablation were screened. After exclusion, 26 patients were divided into 2 groups (obese: body mass index [BMI] ≥27 kg/m2 and reference: BMI <27 kg/m2). They underwent cardiac magnetic resonance (CMR) imaging and electroanatomic mapping of the left atrium (LA) in sinus rhythm before AF ablation. Atrial and ventricular epicardial adipose tissue (EAT) were assessed by CMR. The following electrophysiological parameters were assessed: global and regional voltage, conduction velocity (CV), electrogram fractionation, and CV heterogeneity. In addition, the regional relationship between LA EAT depots and the electrophysiological substrate was evaluated. RESULTS: The BMIs of the obese and reference groups were 30.2 ± 2.6 and 25.2 ± 1.3 kg/m2, respectively (p < 0.001). There was no difference in the left ventricular ejection fraction and a nonsignificant increase in LA size with obesity. Obesity was associated with increase in all measures of EAT (p < 0.05), with a predominant distribution adjacent to the posterior LA and the atrioventricular groove. Obesity was associated with reduced global CV (0.86 ± 0.31 m/s vs. 1.26 ± 0.29 m/s; p < 0.001), with a nonsignificant increase in conduction heterogeneity (p = 0.10), increased fractionation (54 ± 17% vs. 25 ± 10%; p < 0.001), and regional alteration in voltage (p < 0.001). Although the global LA voltage was preserved, there was greater voltage heterogeneity (p = 0.001) and increased low-voltage areas (13.9% vs. 3.4%; p < 0.001) in the obese group compared with the reference group. The low voltage areas were predominantly seen in the posterior and/or inferior LA, which was similar to location of EAT on CMR imaging. Among various measures of obesity, LA EAT volume correlated best with posterior LA fractionation (r2 = 0.55 for LA EAT volume vs. r2 = 0.36 for BMI) and CV (r2 = 0.31 for LA EAT volume vs. r2 = 0.22 for BMI). CONCLUSIONS: Obesity is associated with electroanatomical remodeling of the atria, with areas of low voltage, conduction slowing, and greater fractionation of electrograms. These changes were more pronounced in regions adjacent to epicardial fat depots, which suggested a role for fat depots in the development of the AF substrate.

PREVEntion and regReSsive Effect of weight-loss and risk factor modification on Atrial Fibrillation: the REVERSE-AF study.

Aims: Atrial fibrillation (AF) is a progressive disease. Obesity is associated with progression of AF. This study evaluates the impact of weight and risk factor management (RFM) on progression of the AF. Methods and results: As described in the Long-Term Effect of Goal-Directed Weight Management in an Atrial Fibrillation Cohort: A Long-Term Follow-Up (LEGACY) Study, of 1415 consecutive AF patients, 825 had body mass index ≥ 27 kg/m2 and were offered weight and RFM. After exclusion, 355 were included for analysis. Weight loss was categorized as: Group 1 (<3%), Group 2 (3-9%), and Group 3 (≥10%). Change in AF type was determined by clinical review and 7-day Holter yearly. Atrial fibrillation type was categorized as per the Heart Rhythm Society consensus. There were no differences in baseline characteristic or follow-up duration between groups (P = NS). In Group 1, 41% progressed from paroxysmal to persistent and 26% from persistent to paroxysmal or no AF. In Group 2, 32% progressed from paroxysmal to persistent and 49% reversed from persistent to paroxysmal or no AF. In Group 3, 3% progressed to persistent and 88% reversed from persistent to paroxysmal or no AF (P < 0.001). Increased weight loss was significantly associated with greater AF freedom: 45 (39%) in Group 1, 69 (67%) in Group 2, and 116 (86%) in Group 3 (P ≤ 0.001). Conclusion: Obesity is associated with progression of the AF disease. This study demonstrates the dynamic relationship between weight/risk factors and AF. Weight-loss management and RFM reverses the type and natural progression of AF.

Subclinical device-detected atrial fibrillation and stroke risk: a systematic review and meta-analysis.

Aims: To determine stroke risk in subclinical atrial fibrillation (AF) and temporal association between subclinical AF and stroke. Methods and results: Pubmed/Embase was searched for studies reporting stroke in subclinical AF in patients with cardiac implantable electronic devices (CIEDs). After exclusions, 11 studies were analysed. Of these seven studies reported prevalence of subclinical AF, two studies reported association between subclinical and clinical AF, seven studies reported stroke risk in subclinical AF, and five studies reported temporal relationship between subclinical AF and stroke. Subclinical AF was noted after CIEDs implant in 35% [interquartile range (IQR) 34-42] of unselected patients with pacing indication over 1-2.5 years. The definition and cut-off duration (for stroke risk) of subclinical AF varied across studies. Subclinical AF was strongly associated with clinical AF (OR 5.7, 95% CI 4.0-8.0, P < 0.001, I2 = 0%). The annual stroke rate in patients with subclinical AF > defined cut-off duration was 1.89/100 person-year (95% CI 1.02-3.52) with 2.4-fold (95% CI 1.8-3.3, P < 0.001, I2 = 0%) increased risk of stroke as compared to patients with subclinical AF < cut-off duration (absolute risk was 0.93/100 person-year). Three studies provided mean CHADS2 score. In these studies, with mean CHADS2 score of 2.1 ± 0.1, subclinical AF was associated with annual stroke rate of 2.76/100 person-years (95% CI 1.46-5.23). After excluding patients without AF, only 17% strokes occurred in presence of ongoing AF. Subclinical AF was noted in 29% [IQR 8-57] within 30 days preceding stroke. Conclusion: Subclinical AF strongly predicts clinical AF and is associated with elevated absolute stroke risk albeit lower than risk described for clinical AF.

Outcomes of persistent and long-standing persistent atrial fibrillation ablation: a systematic review and meta-analysis.

Aims: Several techniques have been utilized for the ablation of persistent (P) and long-standing persistent (LsP) atrial fibrillation (AF); however, the best approach of substrate ablation remains poorly defined. This study aims to examine the impact of ablation approach on outcomes associated with P or LsP AF ablation by conducting a meta-analysis and regression on contemporary literature. Methods and results: A systematic literature review was conducted up to 29 July 2015 for scientific literature reporting on outcomes associated with P or LsP AF ablation. One hundred and thirteen studies reported outcomes in a total of 18 657 patients undergoing various ablation approaches for the treatment of P-LsP AF between 2001 and 2015. The point efficacy estimate of a single-AF ablation procedure without the use of anti-arrhythmic drugs was 43% (95% CI; 39-47%). Multiple procedures and/or the use of anti-arrhythmic drugs increase success to 69% (95% CI; 66-71%). Meta-regression revealed that ablation technique (P < 0.001) and left atrial size (P = 0.02) were predictive of single procedure, drug-free success. The addition of extra-pulmonary substrate approaches was associated with declining efficacy when compared to a pulmonary vein ablation alone. Conclusion: The efficacy of a single-AF ablation procedure for P or LsP AF is 43%; however, can be increased to 69% with the use of multiple procedures and/or anti-arrhythmic drugs. Current literature supports the finding that pulmonary vein antrum ablation/isolation is at least equivalently efficacious to other contemporary P-LsP ablation strategies.

Premature Trigger of ERI in Medtronic EnRhythm Devices.

BACKGROUND: Medical technology has made significant advances over the last few decades with smaller and more dynamic pacemakers. However, technical failures leading to premature replacement is a cause of concern. We present a series of Medtronic EnRhythm devices that reached premature elective replacement indicator (ERI). METHODS: The database of Centre of Heart Rhythm Disorders was searched for EnRhythm device implantation from 2006 to 2011. Battery depletion <8.5 years was considered premature considering the projected average longevity to be 8.5-10.5 years. An unexpected premature ERI was defined when it was reached within 3 months of last normal check. Device follow-up was conducted every 3 months after advisory. RESULTS: A total of 88 EnRhythm pacemakers were implanted. Over a median follow-up of 6.2 years (range: 0.3-9.2), 39 (44.3%) EnRhythm devices reached premature ERI. In 11 (28%), ERI was not recognized and patients were being investigated for other causes of unsteadiness or dyspnea prior to device check. Notably, three (7%) patients had premature ERI < 3.5 years. Ten (25.6%) had sudden and unexpected premature ERI. While asynchronous pacing was observed, there were no cases of absence of pacing. CONCLUSIONS: The rate of premature ERI for EnRhythm devices was 44.3%, significantly higher than reported by the manufacturer. Of concern, a sizeable proportion occurred unexpectedly, warranting more frequent reviews and empirical replacement in some patients. With the experience of the EnRhythm, appropriate monitoring strategies are recommended for future advisories.

Spatiotemporal characteristics of atrial fibrillation electrograms: A novel marker for arrhythmia stability and termination.

BACKGROUND: Sequentially mapped complex fractionated atrial electrograms (CFAE) and dominant frequency (DF) sites have been targeted during catheter ablation for atrial fibrillation (AF). However, these strategies have yielded variable success and have not been shown to correlate consistently with AF dynamics. Here, we evaluated whether the spatiotemporal stability of CFAE and DF may be a better marker of AF sustenance and termination. METHODS: Eighteen sheep with 12 weeks of "one-kidney, one-clip" hypertension underwent open-chest studies. A total of 42 self-terminating (28-100 s) and 6 sustained (>15 min) AF episodes were mapped using a custom epicardial plaque and analyzed in 4-s epochs for CFAE, using the NavX CFE-m algorithm, and DF, using a Fast Fourier Transform. The spatiotemporal stability index (STSI) was calculated using the intraclass correlation coefficient of consecutive AF epochs. RESULTS: A total of 67,733 AF epochs were analyzed. During AF initiation, mean CFE-m and the STSI of CFE-m/DF were similar between sustained and self-terminating episodes, although median DF was higher in sustained AF (p=0.001). During sustained AF, the STSI of CFE-m increased significantly (p=0.02), whereas mean CFE-m (p=0.5), median DF (p=0.07), and the STSI of DF remained unchanged (p=0.5). Prior to AF termination, the STSI of CFE-m was significantly lower (p<0.001), with a physiologically non-significant decrease in median DF (-0.3 Hz, p=0.006) and no significant changes in mean CFE-m (p=0.14) or the STSI of DF (p=0.06). CONCLUSIONS: Spatiotemporal stabilization of CFAE favors AF sustenance and its destabilization heralds AF termination. The STSI of CFE-m is more representative of AF dynamics than are the STSI of DF, sequential mean CFE-m, or median DF.

Cost-Effectiveness and Clinical Effectiveness of the Risk Factor Management Clinic in Atrial Fibrillation: The CENT Study.

BACKGROUND: Atrial fibrillation (AF) imposes a substantial cost burden on the healthcare system. Weight and risk factor management (RFM) reduces AF burden and improves the outcomes of AF ablation. OBJECTIVES: This study sought to evaluate the cost and clinical effectiveness of integrating RFM into the overall management of AF. METHODS: Of 1,415 consecutive patients with symptomatic AF, 825 patients had body mass index ≥27 kg/m2. After screening for exclusion criteria, the final cohort comprised 355 patients: 208 patients who opted for RFM and 147 control subjects and were followed by 3 to 6 monthly clinic review, 7-day Holter monitoring, and AF Symptom Score. A decision analytical model calculated the incremental cost-effectiveness ratios of cost per unit of global well-being gained and unit of AF burden reduced. RESULTS: There were no differences in baseline characteristics or follow-up duration (p = NS). Arrhythmia-free survival was better in the RFM compared with control subjects (Kaplan-Meier: 79% vs. 44%; p < 0.001). At follow-up, RFM group had less unplanned specialist visits (0.19 ± 0.40 vs. 1.94 ± 2.00; p < 0.001), hospitalizations (0.74 ± 1.3 vs. 1.05 ± 1.60; p = 0.03), cardioversions (0.89 ± 1.50 vs. 1.51 ± 2.30; p = 0.002), emergency presentations (0.18 ± 0.50 vs. 0.76 ± 1.20; p < 0.001), and ablation procedures (0.60 ± 0.69 vs. 0.72 ± 0.86; p = 0.03). Antihypertensive (0.53 ± 0.70 vs. 0.78 ± 0.60; p = 0.04) and antiarrhythmic (0.26 ± 0.50 vs. 0.91 ± 0.60; p = 0.003) use declined in RFM. The RFM group had an increase of 0.1930 quality-adjusted life years and a cost saving of $12,094 (incremental cost-effectiveness ratios of $62,653 saved per quality-adjusted life years gained). CONCLUSIONS: A structured physician-directed RFM program is clinically effective and cost saving.

Feasibility and safety of Reveal LINQ insertion in a sterile procedure room versus electrophysiology laboratory.

BACKGROUND: Insertable cardiac monitors (ICMs) are increasingly utilized for diagnosis of unexplained syncope and arrhythmia monitoring. The Reveal LINQ is a novel miniaturized ICM with improved algorithms. The feasibility and safety of insertion outside the traditional electrophysiology laboratory is unknown. Here we compare outcomes of Reveal LINQ insertion in different environments. METHODS: We report on a prospective, single-centre, non-randomized, observational experience of consecutive Reveal LINQ implantation in the electrophysiology laboratory or a procedure room between October 2013 and October 2015. RESULTS: Of 178 consecutive patients who underwent LINQ device insertion, 80 were implanted in the electrophysiology laboratory and 98 in a procedure room. There were no significant differences in baseline patient characteristics. All implants were performed in the recommended manufacturer method with the exception of 1 which required suture closure. Only a minority received peri-procedural antibiotics with a greater number in the electrophysiology laboratory group (11 [14%] versus 1 [1%], p=0.007). Overall, there were 3 (1.7%) complications with no significant difference between the electrophysiology laboratory and the procedure room groups (2 [3%] versus 1 [1%], p=0.45). There was 1 superficial infection in the procedure room group and 1 superficial infection with device extrusion and 1 traumatic extrusion in the electrophysiology laboratory group. Procedure room implantation subjectively improved laboratory efficiency and patient flow. CONCLUSION: Reveal LINQ insertion can be safely performed outside of the cardiac laboratory provided a sterile technique is followed by the operator using manufacturer recommendations for insertion. These findings have significant resource implications for hospitals undertaking such procedures.

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)-ß1 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-ß1 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-ß1 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.

Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in Obese Individuals With Atrial Fibrillation: The CARDIO-FIT Study.

BACKGROUND: Obesity begets atrial fibrillation (AF). Although cardiorespiratory fitness is protective against incident AF in obese individuals, its effect on AF recurrence or the benefit of cardiorespiratory fitness gain is unknown. OBJECTIVES: This study sought to evaluate the role of cardiorespiratory fitness and the incremental benefit of cardiorespiratory fitness improvement on rhythm control in obese individuals with AF. METHODS: Of 1,415 consecutive patients with AF, 825 had a body mass index ≥27 kg/m(2) and were offered risk factor management and participation in a tailored exercise program. After exclusions, 308 patients were included in the analysis. Patients underwent exercise stress testing to determine peak metabolic equivalents (METs). To determine a dose response, cardiorespiratory fitness was categorized as: low (<85%), adequate (86% to 100%), and high (>100%). Impact of cardiorespiratory fitness gain was ascertained by the objective gain in fitness at final follow-up (≥2 METs vs. <2 METs). AF rhythm control was determined using 7-day Holter monitoring and AF severity scale questionnaire. RESULTS: There were no differences in baseline characteristics or follow-up duration between the groups defined by cardiorespiratory fitness. Arrhythmia-free survival with and without rhythm control strategies was greatest in patients with high cardiorespiratory fitness compared to adequate or low cardiorespiratory fitness (p < 0.001 for both). AF burden and symptom severity decreased significantly in the group with cardiorespiratory fitness gain ≥2 METs as compared to <2 METs group (p < 0.001 for all). Arrhythmia-free survival with and without rhythm control strategies was greatest in those with METs gain ≥2 compared to those with METs gain <2 in cardiorespiratory fitness (p < 0.001 for both). CONCLUSIONS: Cardiorespiratory fitness predicts arrhythmia recurrence in obese individuals with symptomatic AF. Improvement in cardiorespiratory fitness augments the beneficial effects of weight loss. (Evaluating the Impact of a Weight Loss on the Burden of Atrial Fibrillation [AF] in Obese Patients; ACTRN12614001123639).

Underuse and overuse of anticoagulation for atrial fibrillation: A study in Indigenous and non-Indigenous Australians.

BACKGROUND: Atrial fibrillation (AF) is a leading cause of preventable stroke in Australia. Given that anticoagulation therapy can significantly reduce this stroke risk, we sought to characterise anticoagulation use in Indigenous and non-Indigenous Australians with AF. METHODS: Administrative, clinical and prescription data from patients with AF were linked. Anticoagulation use was characterised according to guideline-recommended risk scores and Indigenous status. RESULTS: 19,613 individuals with AF were studied. Despite a greater prevalence of other risk factors, Indigenous Australians were significantly younger than their non-Indigenous counterparts (p<0.001) and thus had lower CHADS2- (1.19±0.32 vs 1.99±0.47, p<0.001) and CHA2DS2VASc-scores (1.47 ± 0.03 vs 2.82 ± 0.08, p<0.001). Correspondingly, the percentage of Indigenous Australians with CHADS2 ≥ 2 (39.6% vs 44.1%, p<0.001) and CHA2DS2VASc-scores ≥ 2 (62.9% vs 78.8%, p<0.001) was also lower. Indigenous Australians, however, had greater rates of under- and over-anticoagulation. Overall, 72.1% and 68.9% of Indigenous and non-Indigenous Australians with CHADS2 scores ≥2, and 76.3% and 71.3% with CHA2DS2VASc scores ≥2, were under-anticoagulated. Similarly, 27.4% and 24.1% of Indigenous and non-Indigenous Australians with CHADS2 scores=0, and 24.0% and 16.7% with CHA2DS2VASc-scores=0, were over-anticoagulated. In multivariate analyses, Indigenous Australians were more likely to receive under- or over-anticoagulation according to CHADS2- or CHA2DS2VASc-score (p=0.045 and p<0.001 respectively). CONCLUSION: Anticoagulation for AF is frequently not prescribed in accordance with guideline recommendations. Under-anticoagulation in those at high stroke risk, and over-anticoagulation in those at low risk, is common and more likely in Indigenous patients with AF. Improving adherence to guideline recommendations for anticoagulation in AF may reduce both ischaemic and haemorrhagic strokes in Indigenous and non-Indigenous Australians.

Remote Monitoring of Implantable Cardioverter-Defibrillators: A Systematic Review and Meta-Analysis of Clinical Outcomes.

BACKGROUND: Remote monitoring (RM) of implantable cardioverter-defibrillators (ICD) is an established technology integrated into clinical practice. One recent randomized controlled trial (RCT) and several large device database studies have demonstrated a powerful survival advantage for ICD patients undergoing RM compared with those receiving conventional in-office (IO) follow-up. OBJECTIVES: This study sought to conduct a systematic published data review and meta-analysis of RCTs comparing RM with IO follow-up. METHODS: Electronic databases and reference lists were searched for RCTs reporting clinical outcomes in ICD patients who did or did not undergo RM. Data were extracted from 9 RCTs, including 6,469 patients, 3,496 of whom were randomized to RM and 2,973 to IO follow-up. RESULTS: In the RCT setting, RM demonstrated clinical outcomes comparable with office follow-up in terms of all-cause mortality (odds ratio [OR]: 0.83; p = 0.285), cardiovascular mortality (OR: 0.66; p = 0.103), and hospitalization (OR: 0.83; p = 0.196). However, a reduction in all-cause mortality was noted in the 3 trials using home monitoring (OR: 0.65; p = 0.021) with daily verification of transmission. Although the odds of receiving any ICD shock were similar in RM and IO patients (OR: 1.05; p = 0.86), the odds of inappropriate shock were reduced in RM patients (OR: 0.55; p = 0.002). CONCLUSIONS: Meta-analysis of RCTs demonstrates that RM and IO follow-up showed comparable overall outcomes related to patient safety and survival, with a potential survival benefit in RCTs using daily transmission verification. RM benefits include more rapid clinical event detection and a reduction in inappropriate shocks.

Long-Term Effect of Goal-Directed Weight Management in an Atrial Fibrillation Cohort: A Long-Term Follow-Up Study (LEGACY).

BACKGROUND: Obesity and atrial fibrillation (AF) frequently coexist. Weight loss reduces the burden of AF, but whether this is sustained, has a dose effect, or is influenced by weight fluctuation is unknown. OBJECTIVES: This study sought to evaluate the long-term impact of weight loss and weight fluctuation on rhythm control in obese individuals with AF. METHODS: Of 1,415 consecutive patients with AF, 825 had a body mass index ≥ 27 kg/m(2) and were offered weight management. After screening for exclusion criteria, 355 were included in this analysis. Weight loss was categorized as group 1 (≥ 10%), group 2 (3% to 9%), and group 3 (<3%). Weight trend and/or fluctuation was determined by yearly follow-up. We determined the impact on the AF severity scale and 7-day ambulatory monitoring. RESULTS: There were no differences in baseline characteristics or follow-up among the groups. AF burden and symptom severity decreased more in group 1 compared with groups 2 and 3 (p < 0.001 for all). Arrhythmia-free survival with and without rhythm control strategies was greatest in group 1 compared with groups 2 and 3 (p < 0.001 for both). In multivariate analyses, weight loss and weight fluctuation were independent predictors of outcomes (p < 0.001 for both). Weight loss ≥ 10% resulted in a 6-fold (95% confidence interval: 3.4 to 10.3; p < 0.001) greater probability of arrhythmia-free survival compared with the other 2 groups. Weight fluctuation >5% partially offset this benefit, with a 2-fold (95% confidence interval: 1.0 to 4.3; p = 0.02) increased risk of arrhythmia recurrence. CONCLUSIONS: Long-term sustained weight loss is associated with significant reduction of AF burden and maintenance of sinus rhythm. (Long-Term Effect of Goal directed weight management on Atrial Fibrillation Cohort: A 5 Year follow-up study [LEGACY Study]; ACTRN12614001123639).

Obesity and the Risk of Incident, Post-Operative, and Post-Ablation Atrial Fibrillation: A Meta-Analysis of 626,603 Individuals in 51 Studies.

OBJECTIVES: The purpose of this study was to quantify the magnitude of association between incremental increases in body mass index (BMI) and the development of incident, post-operative, and post-ablation atrial fibrillation (AF). BACKGROUND: Obesity has been estimated to account for one-fifth of all AF and approximately 60% of recent increases in population AF incidence. From a public health perspective, obesity, therefore, is a modifiable risk factor that could be profitably targeted. METHODS: A systematic review and meta-analysis was conducted. Medline and EMBASE databases were searched for observational studies reporting data on the association between obesity and incident, post-operative, and post-ablation AF. Studies were included if they reported or provided data allowing calculation of risk estimates. RESULTS: Data from 51 studies including 626,603 individuals contributed to this analysis. There were 29% (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.23 to 1.36) and 19% (OR: 1.19, 95% CI: 1.13 to 1.26) greater excess risks of incident AF for every 5-U BMI increase in cohort and case-control studies, respectively. Similarly, there were 10% (OR: 1.10, 95% CI: 1.04 to 1.17) and 13% (OR: 1.13, 95% CI: 1.06 to 1.22) greater excess risks of post-operative and post-ablation AF for every 5-U increase in BMI, respectively. CONCLUSIONS: Incremental increases in BMI are associated with a significant excess risk of AF in different clinical settings. For every 5-U increase in BMI, there were 10% to 29% greater excess risks of incident, post-operative, and post-ablation AF. By providing a comprehensive and reliable quantification of the relationship between incremental increases in obesity and AF across different clinical settings, our findings highlight the potential for even moderate reductions in population body mass indexes to have a significant effect in mitigating the rising burden of AF.

Catheter ablation of atrial fibrillation in patients with concomitant left ventricular impairment: a systematic review of efficacy and effect on ejection fraction.

INTRODUCTION: Catheter ablation of atrial fibrillation (AF) is an established rhythm control strategy; however, the impact of co-existing LV systolic dysfunction (LVSD) on ablation success is less well understood. This systematic review compiles the outcomes of catheter ablation of atrial fibrillation in patients with LVSD. METHODS: An electronic database (Pubmed, Scopus, Embase) search using the keywords 'atrial fibrillation AND ablation AND (ventricular dysfunction OR heart failure OR cardiomyopathy)' was performed for English scientific literature up to 01/01/2014. 2484 references were retrieved and evaluated for relevance by three reviewers. Reviews and reference lists of retrieved articles were also examined to ensure all relevant studies were included. Data was extracted from 19 studies, including a total of 914 patients. RESULTS: Single-procedure success in LVSD patients for AF ablation was 56.5% (95% CI: 48%-64%). Overall multiple-procedure (including the use of anti-arrhythmic drugs) in LVSD patients for AF ablation was 81.8% (95% CI: 75%-87%). The mean increase in LVEF following AF ablation was 13.3% (95% CI: 10.8%-15.9%). Seven studies reported improvements in exercise capacity and quality of life information using standardised criteria. The pooled rate of serious adverse events was 5.5% (95% CI: 3.7%-8.1%). CONCLUSIONS: Catheter ablation may be an effective therapy in AF patients with left ventricular systolic impairment, and can be associated with improvements in left ventricular function, quality of life, exercise capacity, and modest rates of serious adverse events.

Atrial macroreentry in congenital heart disease.

Macroreentrant atrial tachycardia is a common complication following surgery for congenital heart disease (CHD), and is often highly symptomatic with potentially significant hamodynamic consequences. Medical management is often unsuccessful, requiring the use of invasive procedures. Cavotricuspid isthmus dependent flutter is the most common circuit but atypical circuits also exist, involving sites of surgical intervention or areas of scar related to abnormal hemodynamics. Ablation can be technically challenging, due to complex anatomy, and difficulty with catheter stability. A thorough assessment of the patients status and pre-catheter ablation planning is critical to successfully managing these patients.

Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF cohort study.

BACKGROUND: The long-term outcome of atrial fibrillation (AF) ablation demonstrates attrition. This outcome may be due to failure to attenuate the progressive substrate promoted by cardiovascular risk factors. OBJECTIVES: The goal of this study was to evaluate the impact of risk factor and weight management on AF ablation outcomes. METHODS: Of 281 consecutive patients undergoing AF ablation, 149 with a body mass index ≥27 kg/m(2) and ≥1 cardiac risk factor were offered risk factor management (RFM) according to American Heart Association/American College of Cardiology guidelines. After AF ablation, all 61 patients who opted for RFM and 88 control subjects were assessed every 3 to 6 months by clinic review and 7-day Holter monitoring. Changes in the Atrial Fibrillation Severity Scale scores were determined. RESULTS: There were no differences in baseline characteristics, number of procedures, or follow-up duration between the groups (p = NS). RFM resulted in greater reductions in weight (p = 0.002) and blood pressure (p = 0.006), and better glycemic control (p = 0.001) and lipid profiles (p = 0.01). At follow-up, AF frequency, duration, symptoms, and symptom severity decreased more in the RFM group compared with the control group (all p < 0.001). Single-procedure drug-unassisted arrhythmia-free survival was greater in RFM patients compared with control subjects (p < 0.001). Multiple-procedure arrhythmia-free survival was markedly better in RFM patients compared with control subjects (p < 0.001), with 16% and 42.4%, respectively, using antiarrhythmic drugs (p = 0.004). On multivariate analysis, type of AF (p < 0.001) and RFM (hazard ratio 4.8 [95% confidence interval: 2.04 to 11.4]; p < 0.001) were independent predictors of arrhythmia-free survival. CONCLUSIONS: Aggressive RFM improved the long-term success of AF ablation. This study underscores the importance of therapy directed at the primary promoters of the AF substrate to facilitate rhythm control strategies.