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Background Clinical studies have reported that epicardial adipose tissue (EpAT) accumulation associates with the progression of atrial fibrillation (AF) pathology and adversely affects AF management. The role of local cardiac EpAT deposition in disease progression is unclear, and the electrophysiological, cellular, and molecular mechanisms involved remain poorly defined. Objectives The purpose of this study was to identify the underlying mechanisms by which EpAT influences the atrial substrate for AF. Methods Patients without AF undergoing coronary artery bypass surgery were recruited. Computed tomography and high-density epicardial electrophysiological mapping of the anterior right atrium were utilized to quantify EpAT volumes and to assess association with the electrophysiological substrate in situ. Excised right atrial appendages were analyzed histologically to characterize EpAT infiltration, fibrosis, and gap junction localization. Co-culture experiments were used to evaluate the paracrine effects of EpAT on cardiomyocyte electrophysiology. Proteomic analyses were applied to identify molecular mediators of cellular electrophysiological disturbance. Results Higher local EpAT volume clinically correlated with slowed conduction, greater electrogram fractionation, increased fibrosis, and lateralization of cardiomyocyte connexin-40. In addition, atrial conduction heterogeneity was increased with more extensive myocardial EpAT infiltration. Cardiomyocyte culture studies using multielectrode arrays showed that cardiac adipose tissue-secreted factors slowed conduction velocity and contained proteins with capacity to disrupt intermyocyte electromechanical integrity. Conclusions These findings indicate that atrial pathophysiology is critically dependent on local EpAT accumulation and infiltration. In addition to myocardial architecture disruption, this effect can be attributed to an EpAT-cardiomyocyte paracrine axis. The focal adhesion group proteins are identified as new disease candidates potentially contributing to arrhythmogenic atrial substrate.

Background Female gender is associated with an increased recurrence of atrial fibrillation (AF) after catheter ablation (CA). Although AF is more common in men, women constitute a significant proportion with persistent atrial fibrillation (PsAF). Objective The purpose of this study was to determine whether multiple ablation procedures improves arrhythmia outcomes in females with PsAF compared to men. Methods We performed a multicenter observational study to determine long-term arrhythmia outcomes in patients undergoing >1 CA for PsAF. CA involved pulmonary vein (PV) isolation with additional ablation including linear, posterior wall isolation, electrogram-guided, or a combination of these. Results A total of 281 patients had >1 ablation procedure for PsAF and were included in this analysis (mean age 58.7 ± 9.3 years; 86 [30.6%] female; left atrial [LA] area 27.0 ± 5.3 cm2; PsAF duration 1.7 ± 1.7 years). At mean follow-up of 45.5 ± 31.8 months, freedom from recurrent AF was present in 148 patients(52.7%) after 2.2 ± 0.5 procedures. After multivariate analysis, female gender (hazard ratio [HR] 2.10; P Conclusion Female gender was independently and strongly associated with arrhythmia recurrence in patients undergoing multiple procedures for PsAF. PV reconnection was less likely, and fewer reconnected PVs occurred in women. Further studies are required to better understand the mechanisms responsible for AF in females to assist in closing the gender gap in the success of CA.

Background: Population studies have demonstrated a range of sex differences including a higher prevalence of atrial fibrillation (AF) in men and a higher risk of AF recurrence in women. However, the underlying reasons for this higher recurrence are unknown. This study evaluated whether sex-based electrophysiological substrate differences exist to account for worse AF ablation outcomes in women. Methods: High-density electroanatomic mapping of the left atrium was performed in 116 consecutive patients with AF. Regional analysis was performed across 6 left atrium segments. High-density maps were created using a multipolar catheter (Biosense Webster) during distal coronary sinus pacing at 600 and 300 ms. Mean voltage and conduction velocity was determined. Complex fractionated signals and double potentials were manually annotated. Results: Overall, 42 (36%) were female, mean age was 61±8 years and AF was persistent in 52%. Global mean voltage was significantly lower in females compared with males at 600 ms (1.46±0.17 versus 1.84±0.15 mV, P P =0.013) pacing. These differences were seen uniformly across the left atrium. Females demonstrated significant conduction velocity slowing (34.9±6.1 versus 44.1±6.9 cm/s, P =0.002) and greater proportion of complex fractionated signals (9.9±1.7% versus 6.0±1.7%, P =0.014). After a median follow-up of 22 months (Q1–Q3: 15–29), females had significantly lower single-procedure (22 [54%] versus 54 [75%], P =0.029) and multiprocedure (24 [59%] versus 60 [83%], P =0.005) arrhythmia-free survival. Female sex and persistent AF were independent predictors of single and multiprocedure arrhythmia recurrence. Conclusions: Female patients demonstrated more advanced atrial remodeling on high-density electroanatomic mapping and greater post-AF ablation arrhythmia recurrence compared with males. These changes may contribute to sex-based differences in the clinical course of females with AF and in part explain the higher risk of recurrence. Graphic Abstract: A graphic abstract is available for this article.

Observational studies report that obstructive sleep apnea (OSA) is associated with an increasingly remodeled atrial substrate in atrial fibrillation (AF). However, the impact of OSA management on the electrophysiologic substrate has not been evaluated.In this study, the authors sought to determine the impact of OSA management on the atrial substrate in AF.We recruited 24 consecutive patients referred for AF management with at least moderate OSA (apnea-hypopnea index [AHI] ≥15). Participants were randomized in a 1:1 ratio to commence continuous positive airway pressure (CPAP) or no therapy (n = 12 CPAP; n = 12 no CPAP). All participants underwent invasive electrophysiologic study (high-density right atrial mapping) at baseline and after a minimum of 6 months. Outcome variables were atrial voltage (mV), conduction velocity (m/s), atrial surface area 0.5 mV (%), proportion of complex points (%), and atrial effective refractory periods (ms). Change between groups over time was compared.Clinical characteristics and electrophysiologic parameters were similar between groups at baseline. Compliance with CPAP therapy was high (device usage: 79% ± 19%; mean usage/day: 268 ± 91 min) and resulted in significant AHI reduction (mean reduction: 31 ± 23 events/h). There were no differences in blood pressure or body mass index between groups over time. At follow-up, the CPAP group had faster conduction velocity (0.86 ± 0.16 m/s vs 0.69 ± 0.12 m/s; P (time × group) = 0.034), significantly higher voltages (2.30 ± 0.57 mV vs 1.94 ± 0.72 mV; P 0.05), and lower proportion of complex points (8.87% ± 3.61% vs 11.93% ± 4.94%; P = 0.011) compared with the control group. CPAP therapy also resulted in a trend toward lower proportion of atrial surface area 0.5 mV (1.04% ± 1.41% vs 4.80% ± 5.12%; P = 0.065).CPAP therapy results in reversal of atrial remodeling in AF and provides mechanistic evidence advocating for management of OSA in AF.

Objectives This study sought to determine the impact of rate and direction on left atrial (LA) substrate. Background The extent to which substrate mapped in sinus rhythm varies according to cycle length and direction of wave front propagation is unknown. Methods A total of 73 consecutive patients with atrial fibrillation (AF) underwent electroanatomic LA mapping before pulmonary vein isolation using multipolar catheter during distal coronary sinus (CS) pacing at 600 ms and 300 ms. Additional maps were created during left superior pulmonary vein pacing at 300 ms. Bipolar voltage, conduction velocity (CV), and complex signals were determined. Results Mean age was 61 ± 9 years, 67% were men, and 53% had persistent AF. Global mean voltage was lower with CS pacing at 300 ms compared with 600 ms (1.56 ± 0.47 mV vs. 1.74 ± 0.48 mV; p Conclusions In patients with AF, variation in cycle length and direction of wave front activation produce both generalized and regional changes in voltage, CV, and complex fractionation, resulting in significant changes in substrate maps. This study highlights the potential limitations of static low-voltage maps to identify the AF ablation target zone.

Atrial fibrillation (AF) management guidelines recommend screening for symptoms of sleep-disordered breathing (SDB). We aimed to assess the role of self-reported daytime sleepiness in detection of patients with SDB and AF.A total of 442 consecutive ambulatory patients with AF who were considered candidates for rhythm control and underwent polysomnography comprised the study population. The utility of daytime sleepiness (quantified by the Epworth Sleepiness Scale [ESS]) to predict any (apnea-hypopnea index [AHI] ≥ 5), moderate-to-severe (AHI ≥ 15), and severe (AHI ≥ 30) SDB on polysomnography was tested.Mean age was 60 ± 11 years and 69% patients were men. SDB was present in two-thirds of the population with 33% having moderate-to-severe SDB. Daytime sleepiness was low (median ESS = 8/24) and the ESS poorly predicted SDB, regardless of the degree of SDB tested (area under the curve: 0.48-0.56). Excessive daytime sleepiness (ESS ≥ 11) was present in 11.9% of the SDB population and had a negative predictive value of 43.1% and a positive predictive value of 67.5% to detect moderate-to-severe SDB. Male gender (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.4-3.8, P = 0.001), obesity (OR: 3.5, 95% CI: 2.3-5.5, P0.001), diabetes (OR: 2.3, 95% CI: 1.2-4.4, P = 0.08), and stroke (OR: 4.6, 95% CI: 1.7-12.3, P = 0.002) were independently associated with an increased likelihood of moderate-to-severe SDB.In an ambulatory AF population, SDB was common but most patients reported low daytime sleepiness levels. Clinical features, rather than daytime sleepiness, were predictive of patients with moderate-to-severe SDB. Lack of excessive daytime sleepiness should not preclude patients from being investigated for the potential presence of concomitant SDB.

Objectives: This study sought to determine the long-term right atrial (RA) electrical and structural changes in a subgroup from the CAMERA-MRI (Catheter Ablation Versus Medical Rate Control...

Objectives This study sought to determine night-to-night variability in the severity of sleep-disordered breathing (SDB) and the dynamic intraindividual relationship to daily risk of incident atrial fibrillation (AF) by using simultaneous long-term day-by-day SDB and AF monitoring. Background Night-to-night variability in SDB severity may result in a dynamic exposure to SDB related conditions impacting the timing and extent of cardiovascular responses. Methods This study was an observational cohort study. Daily data for AF burden and average respiratory disturbance index (RDI) were extracted from pacemakers capable of monitoring nightly SDB and daily AF burden in 72 patients. Nightly RDI values were grouped into quartiles of severity within each patient. AF burdens of >5 min, >1 h, and >12 h were the outcome variables. Results A total of 32% of patients had a mean RDI of ≥20/h, indicative of overall severe SDB. There was significant night-to-night variation in RDI reflected by an absolute SD of ±6.3 events/h (range 2 to 14 events/h) within any given patient. Within each patient, the nights with the highest RDI (in their highest quartile) conferred a 1.7-fold (1.2 to 2.2; p Conclusions There is considerable night-to-night variability in SDB severity which cannot be detected by 1 single overnight sleep study. SDB burden may be a better metric with which to assess the extent of dynamic SDB related cardiovascular responses such as daily AF risk than the categorical diagnosis of SDB. (Night-to-Night Variability in Severity of Sleep Apnea and Daily Dynamic Atrial Fibrillation Risk [VARIOSA-AF]; ACTRN 12618000757213)

Background Regular alcohol intake is an important modifiable risk factor associated with atrial fibrillation (AF) and left atrial (LA) dilation. Objective The purpose of this study was to determine the impact of different degrees of alcohol consumption on atrial remodeling using high-density electroanatomic mapping. Methods We enrolled 75 patients before AF ablation to undergo high-density LA mapping (CARTO, Biosense Webster) using a multipolar catheter. The Confidense algorithm was used to create maps during distal coronary sinus pacing at 600 ms. Bipolar voltage and complex atrial activity were assessed, and isochronal activation maps were created to determine global conduction velocity (CV). Patients were classified as lifelong nondrinkers, mild drinkers (2–7 drinks/week), or moderate drinkers (8–21 drinks/week). Results High-density electroanatomic mapping (mean 1016 ± 445 points per patient) was performed on 25 lifelong nondrinkers, 25 mild drinkers (4.4 ± 2.3 drinks/week), and 25 moderate drinkers (14.0 ± 4.2 drinks/week). Moderate drinkers had significantly lower mean global bipolar voltages (1.53 ± 0.62 mV vs 1.89 ± 0.45 mV; P = .02), slower CV (33.5 ± 14.4 cm/s vs 41.7 ± 12.1 cm/s; P = .04), and a higher proportion of complex atrial potentials (7.8% ± 4.7% vs 4.5% ± 2.7%; P = .004) compared to nondrinkers. Global voltage and CV did not differ significantly in mild drinkers, but there was a significant increase in global complex potentials (6.6% ± 4.6%; P = .04) and regional low-voltage zones ( Conclusion Regular moderate alcohol consumption, but not mild consumption, is an important modifiable risk factor for AF associated with lower atrial voltage and conduction slowing. These electrical and structural changes may explain the propensity to AF in regular drinkers.

Background Sleep-disordered breathing (SDB) is highly prevalent in patients with atrial fibrillation (AF) and its treatment can improve rhythm control. Polysomnography (PSG) is the gold standard for the diagnosis of SDB but its high cost and limited availability constrain its role as a standard SDB screening tool. We sought to assess the diagnostic utility of overnight oximetry in predicting SDB in AF patients. Methods We analyzed prospectively collected data on 439 patients with documented AF (62% paroxysmal AF) who underwent PSG. Overnight oximetry was used to determine the oxygen desaturation index (ODI, number of desaturation/h) by a novel automated computer algorithm. ODI was validated against PSG derived apnea-hypopnea index (AHI). Results The sample consisted of 69% men with a mean age of 59.9 ± 11.3 years and body mass index of 30 ± 5 kg/m2. The median AHI was 9.5 [3.6–21.0]/h and the prevalence of moderate (AHI 15–29/h) and severe SDB (AHI ≥ 30/h) was 17.3% and 16.6% respectively. The ODI was able to detect moderate-to-severe SDB (AHI ≥ 15/h; area under the receiver-operating-characteristic curve (AUC): 0.951, 95% CI: 0.929–0.972) and severe SDB (AHI ≥ 30/h; 0.932, 95% CI: 0.895–0.968) with high diagnostic accuracy. An ODI cut-off of 4.1/h resulted in a 91% sensitivity and 83% specificity in discriminating between patients with and without AHI ≥ 15/h. An ODI of 7.6/h yielded a sensitivity and specificity for AHI ≥ 30/h of 89% and 83%, respectively. Conclusions ODI derived from a simple and low-cost overnight oximetry can be used as an accessible and reliable screening tool, particularly to rule out SDB.

Background Rapid access cardiology services have been proposed for assessment of acute cardiac conditions via an outpatient model-of-care that potentially could reduce hospitalisations. We describe a new Rapid Access Arrhythmia Clinic (RAAC) and compare major safety endpoints to usual care. Methods We matched 312 adult patients with suspected arrhythmia in RAAC to historical age and sex-matched controls discharged from hospital within Western Sydney Local Health District with suspected arrhythmia. The primary endpoint was a composite of time to first unplanned cardiovascular hospitalisation or cardiac death over 12 months. Results The average age of RAAC patients was 52.2±18.8 years and 51.6±18.8 years for controls, and 48.4% were female in both groups. Mean time from referral to first attended RAAC appointment was 10.5 days. Most were referred from emergency (177, 56.7%) and cardiologists at time of discharge (65, 20.8%). The most common reason for referral was palpitations (180, 57.7%). In total, 155 (49.7%) had a documented arrhythmia, with the most common being atrial fibrillation/flutter (88, 28.2%). The primary endpoint occurred in 35 (11.2%) patients in the RAAC pathway (97.1[95% CI 70–131.3] per 1,000 person-years), compared to 72 (23.1%) patients for usual care controls (229.5[95% CI 180.2–288.1] per 1,000 person-years). Using a propensity score analysis, RAAC pathway significantly reduced the primary endpoint by 59% compared to usual care (HR 0.41, 95% CI 0.27–0.62; p Conclusions RAACs for the early investigation and management of suspected arrhythmia is superior to usual care in terms of reduction in unplanned cardiovascular hospitalisation and death.

Background: Endocardial-epicardial dissociation and focal breakthroughs in humans with atrial fibrillation (AF) have been recently demonstrated using activation mapping of short 10-second AF segments. In the current study, we used simultaneous endo-epi phase mapping to characterize endo-epi activation patterns on long segments of human persistent AF. Methods: Simultaneous intraoperative mapping of endo- and epicardial lateral right atrium wall was performed in patients with persistent AF using 2 high-density grid catheters (16 electrodes, 3 mm spacing). Filtered unipolar and bipolar electrograms of continuous 2-minute AF recordings and electrodes locations were exported for phase analyses. We defined endocardial-epicardial dissociation as phase difference of ≥20 ms between paired endo-epi electrodes. Wavefronts were classified as rotations, single wavefronts, focal waves, or disorganized activity as per standard criteria. Endo-Epi wavefront patterns were simultaneously compared on dynamic phase maps. Complex fractionated electrograms were defined as bipolar electrograms with ≥5 directional changes occupying at least 70% of sample duration. Results: Fourteen patients with persistent AF undergoing cardiac surgery were included. Endocardial-epicardial dissociation was seen in 50.3% of phase maps with significant temporal heterogeneity. Disorganized activity (Endo: 41.3% versus Epi: 46.8%, P =0.0194) and single wavefronts (Endo: 31.3% versus Epi: 28.1%, P =0.129) were the dominant patterns. Transient rotations (Endo: 22% versus Epi: 19.2%, P =0.169; mean duration: 590±140 ms) and nonsustained focal waves (Endo: 1.2% versus Epi: 1.6%, P =0.669) were also observed. Apparent transmural migration of rotational activations (n=6) from the epi- to the endocardium was seen in 2 patients. Electrogram fractionation was significantly higher in the epicardium than endocardium (61.2% versus 51.6%, P Conclusions: Simultaneous endo-epi phase mapping of prolonged human persistent AF recordings shows significant Endocardial-epicardial dissociation marked temporal heterogeneity, discordant and transitioning wavefronts patterns and complex fractionations. No sustained focal activity was observed. Such complex 3-dimensional interactions provide insight into why endocardial mapping alone may not fully characterize the AF mechanism and why endocardial ablation may not be sufficient. Graphic Abstract: A graphic abstract is available for this article.

Aims Obstructive sleep apnoea (OSA) associates with atrial fibrillation (AF), but the relationship of OSA severity and AF phenotype with the atrial substrate remains poorly defined. We sought to define the atrial substrate across the spectrum of OSA severity utilizing high-density mapping. Methods and results Sixty-six consecutive patients (male 71%, age 61 ± 9) having AF ablation (paroxysmal AF 36, persistent AF 30) were recruited. All patents underwent formal overnight polysomnography and high-density left atrial (LA) mapping (mean 2351 ± 1244 points) in paced rhythm. Apnoea–hypopnoea index (AHI) (mean 21 ± 18) associated with lower voltage (−0.34, P = 0.005), increased complex points (r = 0.43, P Conclusion High-density mapping observed that OSA associates with marked atrial remodelling, predominantly among paroxysmal AF cohorts with severe OSA. This may facilitate the identification of AF patients that stand to derive the greatest benefit from OSA management.

Background The 3-dimensional (3D) nature of sinoatrial node (SAN) function has not been characterized in the intact human heart. Objective The purpose of this study was to characterize the 3D nature of SAN function in patients with structural heart disease (SHD) using simultaneous endocardial–epicardial (endo–epi) phase mapping. Methods Simultaneous intraoperative endo–epi SAN mapping was performed during sinus rhythm at baseline (SRbaseline) and postoverdrive suppression at 600 ms (SRpost-pace600) and 400 ms (SRpost-pace400) using 2 Abbott Advisor HD Grid Mapping Catheters. Unipolar and bipolar electrograms (EGMs) were exported for phase analysis to determine (1) activation exits; (2) wavefront propagation sequence; (3) endo–epi dissociation; and (4) fractionation. Comparison of these variables was made among the 3 rhythms from an endo–epi perspective. Results Sixteen patients with SHD were included. SRbaseline activations were unicentric and predominantly exited cranially (87.5%) with endo–epi synchrony. However, with overdrive suppression, a tendency for caudal exit shift and endo–epi asynchrony was observed: SRpost-pace600 vs SRbaseline: cranial endo 75% vs 87.5% (P = .046); cranial epi 68.8% vs 87.5% (P = 0.002); caudal endo 12.5% vs 6.2% (P = 0.215); caudal epi 25% vs 6.2% (P = .0003); and SRpost-pace400 vs SRbaseline: cranial endo 81.3% vs 87.5% (P = 0.335); cranial epi 68.7% vs 87.5% (P = 0.0034; caudal endo 12.5% vs 6.2% (P = .148); caudal epi 31.2% vs 6.2% (P = 0.0017), consistent with multicentricity. EGM fractionation was more prevalent with overdrive suppression. Conclusion During mapping of the intact human heart, SAN demonstrated redundancy of sinoatrial exits with postoverdrive shift in sites of earliest activation and epi–endo dissociation of sinoatrial exits.

This study sought to assess the atrial electrophysiological properties and post-ablation outcomes in patients with atrial fibrillation (AF) with and without the rs2200733 single nucleotide variant.The phenotype associated with chromosome 4q25 of the AF-susceptibility locus remains unknown.In this study, 102 consecutive patients (ages 61 ± 9 years, 64% male) with paroxysmal or persistent AF were prospectively recruited prior to ablation. Patients were genotyped for rs2200733 and high-density left atrial (LA) electroanatomic maps were created using a multipolar catheter during distal coronary sinus (CS) pacing at 600 ms. Voltage, conduction velocity (CV), CV heterogeneity, and fractionated signals of 6 LA segments were determined. Arrhythmia recurrence was assessed by continuous device (51%) and Holter monitoring.Overall, 41 patients (40%) were single nucleotide variant carriers (38 heterozygous, 3 homozygous). A mean of 2,239 ± 852 points per patient were collected. Carriers had relatively increased CV heterogeneity (45.7 ± 7.5% vs. 35.9 ± 2.3%; p 0.001), complex signals (9.4 ± 2.9% vs 6.0 ± 1.2%; p = 0.008), regional LA slowing, or conduction block (31.7 ± 8.2% vs. 17.9 ± 1.9%; p = 0.013) particularly in the posterior and lateral walls. There were no differences in CV, voltage, atrial refractoriness, or sinus node function. At follow-up (median: 27 months; range 19 to 31 months), carriers had lower arrhythmia-free survival (51% vs. 80%; p = 0.003). On multivariable analysis, carrier status was independently associated with CV heterogeneity (p = 0.001), complex signals (p = 0.002), and arrhythmia recurrence (p = 0.019).These data provide the first evidence that the rs2200733-tagged haplotype alters LA electrical remodeling and is a determinant of long-term outcome following AF ablation. The molecular mechanisms underpinning these changes warrant further investigation.

Excessive alcohol consumption is associated with incident atrial fibrillation and adverse atrial remodeling; however, the effect of abstinence from alcohol on secondary prevention of atrial fibrillation is unclear.We conducted a multicenter, prospective, open-label, randomized, controlled trial at six hospitals in Australia. Adults who consumed 10 or more standard drinks (with 1 standard drink containing approximately 12 g of pure alcohol) per week and who had paroxysmal or persistent atrial fibrillation in sinus rhythm at baseline were randomly assigned in a 1:1 ratio to either abstain from alcohol or continue their usual alcohol consumption. The two primary end points were freedom from recurrence of atrial fibrillation (after a 2-week "blanking period") and total atrial fibrillation burden (proportion of time in atrial fibrillation) during 6 months of follow-up.Of 140 patients who underwent randomization (85% men; mean [±SD] age, 62±9 years), 70 were assigned to the abstinence group and 70 to the control group. Patients in the abstinence group reduced their alcohol intake from 16.8±7.7 to 2.1±3.7 standard drinks per week (a reduction of 87.5%), and patients in the control group reduced their alcohol intake from 16.4±6.9 to 13.2±6.5 drinks per week (a reduction of 19.5%). After a 2-week blanking period, atrial fibrillation recurred in 37 of 70 patients (53%) in the abstinence group and in 51 of 70 patients (73%) in the control group. The abstinence group had a longer period before recurrence of atrial fibrillation than the control group (hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.84; P = 0.005). The atrial fibrillation burden over 6 months of follow-up was significantly lower in the abstinence group than in the control group (median percentage of time in atrial fibrillation, 0.5% [interquartile range, 0.0 to 3.0] vs. 1.2% [interquartile range, 0.0 to 10.3]; P = 0.01).Abstinence from alcohol reduced arrhythmia recurrences in regular drinkers with atrial fibrillation. (Funded by the Government of Victoria Operational Infrastructure Support Program and others; Australian New Zealand Clinical Trials Registry number, ACTRN12616000256471.).

Aims Obesity is associated with higher electrical cardioversion (ECV) failure in persistent atrial fibrillation (PeAF). For ease-of-use, many centers prefer patches over paddles. We assessed the optimum modality and shock vector, as well as the safety and efficacy of the Manual Pressure Augmentation (MPA) technique. Methods Patients with obesity (BMI ≥ 30) and PeAF undergoing ECV using a biphasic defibrillator were randomized into one of four arms by modality (adhesive patches or handheld paddles) and shock vector (anteroposterior [AP] or anteroapical [AA]). If the first two shocks (100 and 200 J) failed, then patients received a 200-J shock using the alternative modality (patch or paddle). Shock vector remained unchanged. In an observational substudy, 20 patients with BMI of 35 or more, and who failed ECV at 200 J using both patches/paddles underwent a trial of MPA. Results In total, 125 patients were randomized between July 2016 and March 2018. First or second shock success was 43 of 63 (68.2%) for patches and 56 of 62 (90.3%) for paddles (P = 0.002). There were 20 crossovers from patches to paddles (12 of 20 third shock success with paddles) and six crossovers from paddles to patches (three of six third shock success with patches). Paddles successfully cardioverted 68 of 82 patients compared with 46 of 69 using patches (82.9% vs 66.7%; P = 0.02). Shock vector did not influence first or second shock success rates (82.0% AP vs 76.6% AA; P = 0.46). MPA was successful in 16 of 20 (80%) who failed in both (patches/paddles), with 360 J required in six of seven cases. Conclusion Routine use of adhesive patches at 200 J is inadequate in obesity. Strategies that improve success include the use of paddles, MPA, and escalation to 360 J.

Objectives This study sought to determine the impact of regular alcohol consumption on left atrial (LA) mechanical and reservoir function. Background Earlier studies suggest that regular alcohol intake is associated with increased atrial fibrillation (AF) and LA dilatation. Methods This study prospectively enrolled 160 patients with paroxysmal or persistent AF to undergo 3-T cardiac magnetic resonance (CMR) imaging in sinus rhythm. Patients self-reported alcohol consumption in standard drinks (∼12 g alcohol) per week over the preceding 12 months and were categorized into 4 groups: 1) lifelong nondrinkers; 2) mild drinkers (3 to 10 standard drinks/week); 3) moderate drinkers (11 to 20 standard drinks/week); 4) heavy drinkers (>20 standard drinks/week). Permanent AF and cardiomyopathy were excluded. On CMR, maximum LA volume (LAmax) and minimum LA volume (LAmin), global LA emptying fraction (LAEF) as (LAmax − LAmin) / LAmax, and LA reservoir function as (LAmax − LAmin) / LAmin were calculated. Results Regular alcohol consumption (mean 15.8 ± 6.9 standard drinks/week, n = 120) was associated with larger LA size (LA volume index 50 ± 13 ml/m2 vs. 43 ± 12 ml/m2; p = 0.005), reduction in LAEF (40 ± 14% vs. 52 ± 15%; p Conclusions In patients with AF, habitual alcohol consumption is associated with significantly increased LA size and atrial mechanical dysfunction compared with nondrinkers.

Objectives This study sought to determine if diffuse ventricular fibrosis improves in patients with atrial fibrillation (AF)-mediated cardiomyopathy following the restoration of sinus rhythm. Background AF coexists in 30% of heart failure (HF) patients and may be an underrecognized reversible cause of left ventricular systolic dysfunction. Myocardial fibrosis is the hallmark of adverse cardiac remodeling in HF, yet its reversibility is unclear. Methods Patients with persistent AF and an idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%) were randomized to catheter ablation (CA) or ongoing medical rate control as a pre-specified substudy of the CAMERA-MRI (Catheter Ablation versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction—an MRI-Guided Multi-centre Randomised Controlled Trial) trial. All patients had cardiac magnetic resonance imaging scans (including myocardial T1 time), serum B-type natriuretic peptide, 6-min walk tests, and Short Form-36 questionnaires performed at baseline and 6 months. Sixteen patients with no history of AF or left ventricular systolic dysfunction were enrolled as normal controls for T1 time. Results Thirty-six patients (18 in each treatment arm) were included in this substudy. Demographics, comorbidities, and myocardial T1 times were well matched at baseline. At 6 months, patients in the CA group had a significant reduction in myocardial T1 time from baseline compared with the medical rate control group (−124 ms; 95% confidence interval [CI]: −23 to −225 ms; p = 0.0176), although it remained higher than that of normal controls at 6 months (p = 0.0017). Improvements in myocardial T1 time with CA were associated with significant improvements in absolute LVEF (+12.5%; 95% CI: 5.9% to 19.0%; p = 0.0004), left ventricular end-systolic volume (p = 0.0019), and serum B-type natriuretic peptide (−216 ng/l; 95% CI: −23 to −225 ng/l; p = 0.0125). Conclusions The improvement in LVEF and reverse ventricular remodeling following successful CA of AF-mediated cardiomyopathy is accompanied by a regression of diffuse fibrosis. This suggests timely treatment of arrhythmia-mediated cardiomyopathy may minimize irreversible ventricular remodeling.

To determine stroke risk in subclinical atrial fibrillation (AF) and temporal association between subclinical AF and stroke.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.Subclinical AF strongly predicts clinical AF and is associated with elevated absolute stroke risk albeit lower than risk described for clinical AF.

Objectives This study sought to characterize the biatrial substrate in heart failure (HF) and persistent atrial fibrillation (PeAF). Background Atrial fibrillation (AF) and HF frequently coexist; however, the contribution of HF to the biatrial substrate in PeAF is unclear. Methods Consecutive patients with PeAF and normal left ventricular (NLV) systolic function (left ventricular ejection fraction [LVEF] >55%) or idiopathic cardiomyopathy (LVEF ≤45%) undergoing AF ablation were enrolled. In AF, pulmonary vein (PV) cycle length (PVCL) was recorded via a multipolar catheter in each PV and in the left atrial appendage for 100 consecutive cycles. After electrical cardioversion, biatrial electroanatomic mapping was performed. Complex electrograms, voltage, scarring, and conduction velocity were assessed. Results Forty patients, 20 patients with HF (mean age: 62 ± 8.9 years; AF duration: 15 ± 11 months; LVEF: 33 ± 8.4%) and 20 with NLV (mean age: 59 ± 6.7 years; AF duration: 14 ± 9.1 months; p = 0.69; mean LVEF: 61 ± 3.6%; p Conclusions HF is associated with significantly reduced biatrial tissue voltage, fractionation, and prolongation of PVCL. Advanced biatrial remodeling may have implications for invasive and noninvasive rhythm control strategies in patients with AF and HF.

A correlation exists between the extent of pericardial adipose and atrial fibrillation (AF) risk, though the underlying mechanisms remain unclear. Selected adipose depots express high levels of aromatase, capable of converting androgens to estrogens - no studies have investigated aromatase occurrence/expression regulation in pericardial adipose. The Women's Health Initiative reported that estrogen-only therapy in women elevated AF incidence, indicating augmented estrogenic influence may exacerbate cardiac vulnerability. The aim of this study was to identify the occurrence of pericardial adipose aromatase, evaluate the age- and sex-dependency of local cardiac steroid synthesis capacity and seek preliminary experimental evidence of a link between pericardial adipose aromatase capacity and arrhythmogenic vulnerability. Both human atrial appendage and epicardial adipose exhibited immunoblot aromatase expression. In rodents, myocardium and pericardial adipose aromatase expression increased >20-fold relative to young controls. Comparing young, aged and aged-high fat diet animals, a significant positive correlation was determined between the total aromatase content of pericardial adipose and the occurrence/duration of triggered atrial arrhythmias. Incidence and duration of arrhythmias were increased in hearts perfused with 17β-estradiol. This study provides novel report of pericardial adipose aromatase expression. We show that aromatase expression is remarkably upregulated with aging, and aromatase estrogen conversion capacity significantly elevated with obesity-related cardiac adiposity. Our studies suggest an association between adiposity, aromatase estrogenic capacity and atrial arrhythmogenicity - additional investigation is required to establish causality. The potential impact of these findings may be considerable, and suggests that focus on local cardiac steroid conversion (rather than systemic levels) may yield translational outcomes.

Background Atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) frequently co-exist despite adequate rate control. Existing randomized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy. Objectives The goal of this study was to determine whether catheter ablation (CA) for AF could improve LVSD compared with medical rate control (MRC) where the etiology of the LVSD was unexplained, apart from the presence of AF. Methods This multicenter, randomized clinical trial enrolled patients with persistent AF and idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%). After optimization of rate control, patients underwent cardiac magnetic resonance (CMR) to assess LVEF and late gadolinium enhancement, indicative of ventricular fibrosis, before randomization to either CA or ongoing MRC. CA included pulmonary vein isolation and posterior wall isolation. AF burden post-CA was assessed by using an implanted loop recorder, and adequacy of MRC was assessed by using serial Holter monitoring. The primary endpoint was change in LVEF on repeat CMR at 6 months. Results A total of 301 patients were screened; 68 patients were enrolled between November 2013 and October 2016 and randomized with 33 in each arm (accounting for 2 dropouts). The average AF burden post-CA was 1.6 ± 5.0% at 6 months. In the intention-to-treat analysis, absolute LVEF improved by 18 ± 13% in the CA group compared with 4.4 ± 13% in the MRC group (p Conclusions AF is an underappreciated reversible cause of LVSD in this population despite adequate rate control. The restoration of sinus rhythm with CA results in significant improvements in ventricular function, particularly in the absence of ventricular fibrosis on CMR. This outcome challenges the current treatment paradigm that rate control is the appropriate strategy in patients with AF and LVSD. (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction [CAMERA-MRI]; ACTRN12613000880741)

Introduction The right atrium (RA) is readily accessible; however, it is unclear whether changes in the RA are representative of the LA. We performed detailed bi-atrial electroanatomic mapping to determine the electrophysiological relationship between the atria. Methods and results Consecutive patients with persistent AF underwent bi-atrial electroanatomical mapping with a contact force catheter acquiring points with a CF > 10 g prior to ablation. Points were analyzed for tissue voltage, complex electrograms, low voltage (

Background Studies investigating the relationship between sleep-disordered breathing (SDB) and atrial fibrillation (AF) have largely assessed SDB-severity by the apnea–hypopnea index (AHI). However, the AHI does not incorporate nocturnal hypoxemic burden, which may increase the risk of non-paroxysmal AF (nPAF) as the clinical manifestation of more progressed AF substrates. This investigation sought to systematically characterize and compare the composition of AHI and hypoxemic burden with the aim to defining a disease-orientated metric for SDB-severity best associated with prevalent nPAF. Methods Polysomnography including overnight oximetry data were obtained in 435 consecutive ambulatory AF patients to determine the composition of AHI (apneas vs. hypopneas), the number of acute episodic desaturations per hour (oxygen desaturation index, ODI) and the composition of total time spent below 90% oxygen saturation (T90Total) attributed to acute desaturations (T90Desaturation). Logistic regression analysis was used to characterize the association with prevalent nPAF. Results One hundred sixty-nine AF patients (38%) had nPAF and one third (n=149, 34%) had moderate-to-severe SDB (AHI>15). 82% of the median total AHI (9.4 [3.6–20.1]) could be attributed to hypopneas. Only 29% of events were associated with episodic desaturations, which contributed to 96% (T90Desaturation) of the variation in T90Total. The high variability in durations and nadirs of distinct desaturation events can expose patients to long T90Total, even if the AHI is low. Not AHI, but T90Total and ODI were associated with nPAF independent of gender and age. However, diabetes, hypertension and body mass index contributed more significantly to the overall risk of nPAF. Conclusions In AF patients, hypopneas constitute a majority of respiratory events during sleep. Patients with low AHI can still be exposed to high nocturnal hypoxemic burden, which is mainly a cumulative consequence of episodic desaturations. T90Total and ODI, but not AHI, were associated with nPAF independent of gender and age, but concomitant modifiable risk factors made a more significant contribution to the overall risk of nPAF versus PAF.

This study sought to determine the impact of rate and direction on left atrial (LA) substrate.The extent to which substrate mapped in sinus rhythm varies according to cycle length and direction of wave front propagation is unknown.A total of 73 consecutive patients with atrial fibrillation (AF) underwent electroanatomic LA mapping before pulmonary vein isolation using multipolar catheter during distal coronary sinus (CS) pacing at 600 ms and 300 ms. Additional maps were created during left superior pulmonary vein pacing at 300 ms. Bipolar voltage, conduction velocity (CV), and complex signals were determined.Mean age was 61 ± 9 years, 67% were men, and 53% had persistent AF. Global mean voltage was lower with CS pacing at 300 ms compared with 600 ms (1.56 ± 0.47 mV vs. 1.74 ± 0.48 mV; p 0.001). This was seen in all LA segments. Global CV was reduced (30.4 ± 13.0 cm/s vs. 38.6 ± 14.0 cm/s; p 0.001) with greater complex signals at 300 ms (8.9% vs. 5.3%; p 0.005). Compared with CS pacing, left superior pulmonary vein pacing demonstrated highly regional changes with decreased voltage (1.04 ± 0.43 mV vs. 1.47 ± 0.53 mV; p = 0.01) and CV (24.4 ± 13.0 cm/s vs. 39.9 ± 16.6 cm/s; p = 0.008), and greater complex signals posteriorly. Longer AF duration in paroxysmal AF (p = 0.02) and shorter duration in persistent AF (p = 0.015) and left ventricular ejection fraction (p = 0.016) were independent predictors of voltage change.In patients with AF, variation in cycle length and direction of wave front activation produce both generalized and regional changes in voltage, CV, and complex fractionation, resulting in significant changes in substrate maps. This study highlights the potential limitations of static low-voltage maps to identify the AF ablation target zone.

The goal of this study was to describe functional endocardial-epicardial dissociation (FEED), signal complexities, and three-dimensional activation dynamics of the human atrium with structural heart disease (SHD).SHD commonly predisposes to arrhythmias. Although progressive remodeling is implicated, direct demonstration of FEED in the human atrium has not been reported previously.Simultaneous intraoperative mapping of the endocardial and epicardial lateral right atrial wall was performed by using 2 high-density grid catheters during sinus rhythm, pacing drive (600 ms and 400 ms cycle length), and premature extrastimulation (PES). Unipolar electrograms (EGMs) were exported into custom-made software for activation and phase mapping. Difference of ≥20 ms between paired endocardial and epicardial electrodes defined dissociation. EGMs with ≥3 deflections were classified as fractionated.Sixteen patients (mean age 60.5 ± 4.1 years; 18.7% with a history of atrial fibrillation) with SHD (43% ischemia, 57% valvular disease) were included. A total of 9,218 EGMs were analyzed. Compared with sinus rhythm, phase and activation analyses showed significant FEED during pacing at 600 ms and 400 ms (phase mapping 22.4% vs. 10% [p 0.0001] and 25.8% vs. 10% [p 0.0001], respectively; activation mapping 25.4% vs. 7.8% [p 0.0001] and 27.7% vs. 7.8% [p 0.0001]) and PES (phase mapping 34% vs. 10% [p 0.0001]; activation mapping 29.5% vs. 7.8% [p 0.0001]). Fractionated EGMs occurred significantly more during PES compared with sinus rhythm (50.2% vs. 39.5%; p 0.0001). Activation patterns differed significantly during pacing drive and PES, with preferential epicardial exit during the latter (15.9% vs. 13.8%; p = 0.046).Simultaneous endocardial-epicardial mapping revealed significant FEED with signal fractionation and preferential epicardial breakthroughs with PES. Such complex three-dimensional interaction in electrical activation provides mechanistic insights into atrial arrhythmogenesis with SHD.

This study sought to determine the long-term right atrial (RA) electrical and structural changes in a subgroup from the CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction-Magnetic Resonance Imaging) study.Catheter ablation (CA) is successful in restoring ventricular function in patients with atrial fibrillation (AF) and otherwise unexplained cardiomyopathy, as demonstrated in the randomized study of CA versus rate control (CAMERA-MRI). It is unknown if this is associated with atrial remodeling.Detailed electroanatomical (EA) mapping of the RA using CARTO3 and a force sensing catheter was performed at initial CA and electively at least 12 months after CA in patients with90% reduction in AF burden following ablation. Bipolar voltage, fractionation, and conduction velocity were collected in 4 segments together with echo and cardiac magnetic resonance imaging.Fifteen patients (mean age 59.1 ± 6.8 years) underwent repeat RA EA mapping. At a mean follow-up of 23.4 ± 11.9 months, left ventricular (LV) ejection fraction improved from 33.6 ± 3.2% to 54.1 ± 3.2% (p = 0.001), RA area decreased from 28.4 ± 2.0 cmRecovery of atrial electrical and structural changes was observed following restoration of sinus rhythm and recovery of LV function in patients who underwent CA for persistent AF and LV systolic dysfunction. The randomized CAMERA MRI study demonstrated significant improvement in LV systolic function with AF ablation compared with rate control. The present study demonstrated reverse electrical and structural atrial recovery in concert with recovery of LV systolic function at 2 years post-AF ablation. This may partially explain the long-term success of CA in patients with AF and otherwise unexplained cardiomyopathy.

This study sought to determine night-to-night variability in the severity of sleep-disordered breathing (SDB) and the dynamic intraindividual relationship to daily risk of incident atrial fibrillation (AF) by using simultaneous long-term day-by-day SDB and AF monitoring.Night-to-night variability in SDB severity may result in a dynamic exposure to SDB related conditions impacting the timing and extent of cardiovascular responses.This study was an observational cohort study. Daily data for AF burden and average respiratory disturbance index (RDI) were extracted from pacemakers capable of monitoring nightly SDB and daily AF burden in 72 patients. Nightly RDI values were grouped into quartiles of severity within each patient. AF burdens of5 min,1 h, and12 h were the outcome variables.A total of 32% of patients had a mean RDI of ≥20/h, indicative of overall severe SDB. There was significant night-to-night variation in RDI reflected by an absolute SD of ±6.3 events/h (range 2 to 14 events/h) within any given patient. Within each patient, the nights with the highest RDI (in their highest quartile) conferred a 1.7-fold (1.2 to 2.2; p 0.001), 2.3-fold (1.6 to 3.5; p 0.001), and 10.2-fold (3.5 to 29.9; p 0.001) increase risk of having at least 5 min, 1 h, and 12 h, respectively, of AF during the same day compared with the best sleep nights (in their lowest quartiles).There is considerable night-to-night variability in SDB severity which cannot be detected by 1 single overnight sleep study. SDB burden may be a better metric with which to assess the extent of dynamic SDB related cardiovascular responses such as daily AF risk than the categorical diagnosis of SDB. (Night-to-Night Variability in Severity of Sleep Apnea and Daily Dynamic Atrial Fibrillation Risk [VARIOSA-AF]; ACTRN 12618000757213).

The DORMANT-AF Study: Electrophysiological and Hemodynamic Assessment. DORMANT-AF StudyIntroduction: Electrophysiological and Hemodynamic Assessment. DORMANT-AF Study The significance of adenosine induced dormant pulmonary vein (PV) conduction in atrial fibrillation (AF) ablation remains controversial. The optimal dose of adenosine to determine dormant PV conduction is yet to be systematically explored. Methods and Results: Electrophysiological and Hemodynamic Assessment. DORMANT-AF Study Consecutive patients undergoing index AF ablation received 3 adenosine doses (12, 18, and 24 mg) in a randomized blinded order, immediately after pulmonary vein isolation (PVI). Electrophysiological (PR prolongation, AV block (AVB) and PV reconnection) and hemodynamic (BP) parameters were measured. A total, 339 doses (113/dose) assessed 191 PVs in 50 patients (66% male, 72% PAF, 52% hypertensive). Dormant PV conduction occurred in 28% of patients (16.5% [32] of PVs). All cases were associated with AVB (AVB: PV reconnection vs. no PV reconnection 100% vs. 83%, P = 0.007). AVB occurred more frequently at 24 mg versus 12 mg (92% vs. 82%, P = 0.019) but not versus 18 mg (91%, P = 0.62). AVB duration progressed between 12 mg (12.0 ± 8.9 seconds), 18 mg (16.1 ± 9.1 seconds, P = 0.001), and 24 mg (19.0 ± 9.3 seconds, P 110 kg (65% vs. 91% in 70–110 kg group, P < 0.001) in response to adenosine was seen. Conclusion: Electrophysiological and Hemodynamic Assessment. DORMANT-AF Study An adenosine dose producing AVB is required to unmask dormant PV conduction. AVB is significantly reduced in patients >110 kg. Weight and dosing variability may in part explain the conflicting results of studies evaluating the clinical utility of adenosine in PVI.

Prevalence rates of atrial fibrillation (AF) and obstructive sleep apnea (OSA) are rising on a global scale. Epidemiological data have consistently demonstrated an independent association between the 2 conditions. Investigators pose that pathophysiologic features of OSA enable progression of the AF substrate; these features include abnormalities of gas exchange, autonomic remodeling, atrial stretch, and inflammation. Furthermore, many of the mechanistic perturbations that impact the AF substrate in OSA can be substantially attenuated by effective treatment with continuous positive airway pressure (CPAP). Clear associations of OSA treatment and improved AF control have been observed across multiple clinical contexts. However, the precision and generalizability of these findings are unclear in view of the data's observational nature. Although risk factor management has emerged as a critical component of AF treatment, effective control of many AF risk factors can be challenging in the longer term. In view of the efficacy and sustainability of CPAP therapy, OSA raises its profile as a prime candidate for intervention. However, translation of this strategy to the broader framework for AF management requires robust data from randomized controlled trials.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans, affecting more than 33 million people globally. Its association with complex, resource intensive medical conditions such as stroke, heart failure and dementia have had profound impacts across existing health care structures. The global prevalence of AF has enjoyed significant growth despite significant improvement in our armamentarium for arrhythmia treatment. Efforts aimed at curtailing the incidence, prevalence, or progression of AF have prompted re-evaluation of traditional frameworks for understanding and managing this debilitating disease. It is in this context that focus has shifted toward lifestyle-associated factors such as obesity, hypertension, sleep apnoea, exercise, alcohol and diet, as mechanistic drivers and putative targets for therapy. Compelling evidence exists for weight loss and management of associated risk factors to improve outcomes of AF treatment. This review will address the epidemiologic and mechanistic evidence that link lifestyle-associated factors with AF and in light of this analysis evaluate the clinical impacts of their upstream management. Traditional paradigms of AF are shifting in light of emerging evidence, such that risk factor modification has become positioned as the fourth pillar of AF management.

This study sought to determine if diffuse ventricular fibrosis improves in patients with atrial fibrillation (AF)-mediated cardiomyopathy following the restoration of sinus rhythm.AF coexists in 30% of heart failure (HF) patients and may be an underrecognized reversible cause of left ventricular systolic dysfunction. Myocardial fibrosis is the hallmark of adverse cardiac remodeling in HF, yet its reversibility is unclear.Patients with persistent AF and an idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%) were randomized to catheter ablation (CA) or ongoing medical rate control as a pre-specified substudy of the CAMERA-MRI (Catheter Ablation versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction-an MRI-Guided Multi-centre Randomised Controlled Trial) trial. All patients had cardiac magnetic resonance imaging scans (including myocardial T1 time), serum B-type natriuretic peptide, 6-min walk tests, and Short Form-36 questionnaires performed at baseline and 6 months. Sixteen patients with no history of AF or left ventricular systolic dysfunction were enrolled as normal controls for T1 time.Thirty-six patients (18 in each treatment arm) were included in this substudy. Demographics, comorbidities, and myocardial T1 times were well matched at baseline. At 6 months, patients in the CA group had a significant reduction in myocardial T1 time from baseline compared with the medical rate control group (-124 ms; 95% confidence interval [CI]: -23 to -225 ms; p = 0.0176), although it remained higher than that of normal controls at 6 months (p = 0.0017). Improvements in myocardial T1 time with CA were associated with significant improvements in absolute LVEF (+12.5%; 95% CI: 5.9% to 19.0%; p = 0.0004), left ventricular end-systolic volume (p = 0.0019), and serum B-type natriuretic peptide (-216 ng/l; 95% CI: -23 to -225 ng/l; p = 0.0125).The improvement in LVEF and reverse ventricular remodeling following successful CA of AF-mediated cardiomyopathy is accompanied by a regression of diffuse fibrosis. This suggests timely treatment of arrhythmia-mediated cardiomyopathy may minimize irreversible ventricular remodeling.

Background Pulmonary vein (PV) isolation (PVI) remains the cornerstone of catheter ablation (CA) in persistent atrial fibrillation (AF) (PeAF), although less successful than for paroxysmal AF. Whether rapid or fibrillatory (PV AF) PV firing may identify patients with PeAF more likely to benefit from a PV-based ablation approach is unclear. Objective The purpose of this study was to determine the relationship between the PV cycle length (PVCL) and the PV AF outcome after CA. Methods Before ablation, the multipolar catheter was placed in each PV and the left atrial appendage (LAA) for 100 consecutive cycles. The presence of PV AF, the average PVCL of all 4 veins (PV 4VAverage ), the fastest vein average (PV FVAverage ), the fastest cycle length (PV Fast ) both individually and relative to the average LAA cycle length were calculated. The ablation strategy included PVI and posterior wall isolation with a minimum of 12 months follow-up. Results A total of 123 patients underwent CA (age 62 ± 9.1 years; CHA 2 DS 2 -VASC score 1.6 ± 1.1; left ventricular ejection fraction 48% ± 13%; left atrial area 31 ± 8.7 cm 2 ; AF duration 16 ± 17 months). PVI was achieved in 100% of patients. Multiprocedure success (MPS; freedom from AF/atrial tachycardia episodes lasting >30 seconds) was achieved in 76% of patients at 24 ± 8.1 months of follow-up after 1.2 ± 0.4 procedures. PV activity was not associated with MPS either absolutely (PV 4VAverage [MPS no vs yes: 178 ± 27 ms vs 177 ± 24 ms; P = .92], PV FVAverage [ P = .69], or PV Fast [ P = .82]) or as a ratio relative to the LAA cycle length (PV 4VAverage /LAA 1.05 ± 0.11 vs 1.06 ± 0.21; P = .87). The presence of PV AF (31% vs 47%; P = .13) did not predict MPS. Conclusion The rapidity of PV firing or presence of fibrillation within the PV was not predictive of outcome of CA for PeAF. PV activity does not identify patients most likely to benefit from a PV-based ablation strategy.

Background— Late recurrence of atrial fibrillation (AF) after radiofrequency ablation remains significant. Asymptomatic recurrence poses a difficult clinical problem as it is associated with an equally increased risk of stroke and death compared with symptomatic AF events. Meta-analyses reveal that no single preablation patient characteristic efficiently predicts these AF recurrences. This study aimed to evaluate the prognostic value of premature atrial complex (PAC) occurrence with regard to the risk of late AF recurrence after radiofrequency ablation. Methods and Results— The study cohort consisted of 124 patients with 7-day Holter recordings at 6 months post radiofrequency ablation for AF. No patients had AF recurrence before this time. Patients were followed-up every 6 months. Holter-detected PACs were defined as any supraventricular complexes occurring >30% earlier than expected. During a median follow-up of 4.2 years (first quartile to third quartile [Q1–Q3]=1.6–4.5), 32 patients (26%) had late recurrences of AF at a median of 462 days (Q1–Q3=319–1026) post radiofrequency ablation. The number of PACs per 24 hours was 248 (Q1–Q3=62–1026) in patients with and 77 (Q1–Q3=24–448) in patients without recurrence of AF ( P =0.02). Multivariate analysis of the risk of late AF recurrence found ≥142 PACs per 24 hours to have a hazard ratio 2.84 (confidence interval, 1.26–6.43), P =0.01. Conclusions— This study showed that occurrence of ≥142 PACs per day at 6 months after PVI was independently associated with a significantly increased risk of late AF recurrence. These results could have important clinical implications for the design of post-PVI follow-up. Clinical Trial Registration— URL: http://www.anzctr.org.au . Unique identifier: ACRTN12606000467538.

This review aims to examine the breadth of data associating atrial fibrillation (AF) with obesity at epidemiologic, mechanistic, and clinical levels. We then proceed to place surgical weight loss within that context. Epidemiologic studies have demonstrated a robust correlation between overweight and AF. Various mechanistic factors including concomitant risk factors, diastolic impairment, inflammation, and pericardial fat have been observed to contribute to the atrial substrate for AF. However, weight loss can institute a process of reverse atrial remodeling improving arrhythmias profile. Thus, weight loss has emerged as an indispensable aspect of effective AF management. Yet, effective weight management is often a challenging and frustrating journey for clinician and patient, raising surgical weight loss as a potential option. However, data on the role of surgical weight loss on AF are limited. Observations indicate that the dramatic and sustained weight loss availed by surgical intervention may be capable of attenuating rates of incident AF. The impact of surgical weight loss on AF populations remains unknown. However, it is likely that most of the antiarrhythmic benefits of non-surgical weight loss would be paralleled in surgical candidates, mediated by similar mechanisms. Surgical weight loss has been associated with reverse structural remodeling, improvement of diastolic function, and modulation of the autonomic profile. There exists a compelling case for the utilization of surgical weight loss to circumvent the obstacle of treatment failure. However, resort to an invasive procedure with antedant risks for AF management alone would be premature in the absence of robust data. However, it may find a more immediate role in the context of AF ablation, where exposure to procedural risk must be justified by optimizing procedural success. Further data surrounding surgical weight loss and its antiarrhythmic benefits are required to define its role in the battle against the dual and closely linked epidemics of AF and obesity. Surgical weight loss would be a powerful weapon in the clinician’s armamentarium that would further consolidate weight loss as the fourth pillar of AF management.

Objectives This study sought to validate a 3-dimensional (3D) phase mapping system and determine the distribution of dominant propagation patterns in persistent atrial fibrillation (AF). Background Currently available systems display phase as simplified 2-dimensional maps. We developed a novel 3D phase mapping system that uses the 3D location of basket catheter electrodes and the patient’s 3D left atrial surface geometry to interpolate phase and create a 3D representation of phase progression. Methods Six-minute AF recordings from the left atrium were obtained in 14 patients using the Constellation basket catheter and analyzed offline. Exported signals underwent both phase and traditional activation analysis and were then visualized using a novel 3D mapping system. Analysis involved: 1) validation of phase analysis by comparing beat-to-beat AF cycle length calculated using phase inversion with that determined from activation timing in the same 20-s segment; 2) validation of 3D phase by comparing propagation patterns observed using 3D phase with 3D activation in the same 1-min segment; and 3) determining the distribution of dominant propagation patterns in 6-min recordings using 3D phase. Results There was strong agreement of beat-to-beat AF cycle length between activation analysis and phase inversion ( R 2 = 0.91). There was no significant difference between 3D activation and 3D phase in mean percentage of propagation patterns classified as single wavefronts (p = 0.99), focal activations (p = 0.26), disorganized activity (p = 0.76), or multiple wavefronts (p = 0.70). During prolonged 3D phase, single wavefronts were the most common propagation pattern (50.2%). A total of 34 rotors were seen in 9 of 14 patients. All rotors were transient with mean duration of 1.0 ± 0.6 s. Rotors were only observed in areas of high electrode density where the interelectrode distance was significantly shorter than nonrotor sites (7.4 [interquartile range: 6.3 to 14.6] vs. 15.3 mm [interquartile range: 10.1 to 22.2]; p Conclusions During prolonged 3D phase mapping, transient rotors were observed in 64% of patients and reformed at the same anatomic location in 44% of patients. The electrode density of the basket catheter may limit the detection of rotors.

This study sought to characterize the biatrial substrate in heart failure (HF) and persistent atrial fibrillation (PeAF).Atrial fibrillation (AF) and HF frequently coexist; however, the contribution of HF to the biatrial substrate in PeAF is unclear.Consecutive patients with PeAF and normal left ventricular (NLV) systolic function (left ventricular ejection fraction [LVEF]55%) or idiopathic cardiomyopathy (LVEF ≤45%) undergoing AF ablation were enrolled. In AF, pulmonary vein (PV) cycle length (PVCL) was recorded via a multipolar catheter in each PV and in the left atrial appendage for 100 consecutive cycles. After electrical cardioversion, biatrial electroanatomic mapping was performed. Complex electrograms, voltage, scarring, and conduction velocity were assessed.Forty patients, 20 patients with HF (mean age: 62 ± 8.9 years; AF duration: 15 ± 11 months; LVEF: 33 ± 8.4%) and 20 with NLV (mean age: 59 ± 6.7 years; AF duration: 14 ± 9.1 months; p = 0.69; mean LVEF: 61 ± 3.6%; p 0.001), were enrolled. HF reduced biatrial tissue voltage (p 0.001) with greater voltage heterogeneity (p 0.001). HF was associated with significantly more biatrial fractionation (left atrium [LA]: 30% vs. 9%; p 0.001; right atrium [RA]: 28% vs. 11%; p 0.001), low voltage (0.5 mV) (LA: 23% vs. 6%; p = 0.002; RA: 20% vs 11%; p = 0.006), and scarring (0.05 mV) in the LA (p = 0.005). HF was associated with a slower average PVCL (185 vs. 164 ms; p = 0.016), which correlated significantly with PV antral bipolar voltage (R = -0.62; p 0.001) and fractionation (R = 0.46; p = 0.001).HF is associated with significantly reduced biatrial tissue voltage, fractionation, and prolongation of PVCL. Advanced biatrial remodeling may have implications for invasive and noninvasive rhythm control strategies in patients with AF and HF.

Prevalence rates of atrial fibrillation (AF) and obstructive sleep apnea (OSA) are rising on a global scale. Epidemiological data have consistently demonstrated an independent association between the 2 conditions. Investigators pose that pathophysiologic features of OSA enable progression of the AF substrate; these features include abnormalities of gas exchange, autonomic remodeling, atrial stretch, and inflammation. Furthermore, many of the mechanistic perturbations that impact the AF substrate in OSA can be substantially attenuated by effective treatment with continuous positive airway pressure (CPAP). Clear associations of OSA treatment and improved AF control have been observed across multiple clinical contexts. However, the precision and generalizability of these findings are unclear in view of the data's observational nature. Although risk factor management has emerged as a critical component of AF treatment, effective control of many AF risk factors can be challenging in the longer term. In view of the efficacy and sustainability of CPAP therapy, OSA raises its profile as a prime candidate for intervention. However, translation of this strategy to the broader framework for AF management requires robust data from randomized controlled trials.