Abstract 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.
Abstract
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.
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.
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.
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.
Abstract 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/m2 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.
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.
This study sought to conduct a systematic published data review and meta-analysis of RCTs comparing RM with IO follow-up.
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.
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).
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.
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.
...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).
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.
Abstract
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.
Graphical Abstract
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.
Obesity is associated with an increased risk of AF.
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/m
and reference: BMI <27 kg/m
). 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.
The BMIs of the obese and reference groups were 30.2 ± 2.6 and 25.2 ± 1.3 kg/m
, 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 (r
= 0.55 for LA EAT volume vs. r
= 0.36 for BMI) and CV (r
= 0.31 for LA EAT volume vs. r
= 0.22 for BMI).
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.
Abstract 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.
Abstract 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.
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