Increased rates of atrial fibrillation recurrence following pulmonary vein isolation in overweight and obese patients.

INTRODUCTION: Catheter ablation is common for patients with symptomatic, drug-refractory atrial fibrillation (AF). Obesity is a known risk factor for incident AF. The impact of obesity on AF ablation outcomes is incompletely understood. We sought to determine the impact of elevated body mass index (BMI) on pulmonary vein isolation (PVI) procedural outcomes and associated complications. METHODS AND RESULTS: We evaluated patients undergoing PVI from 2001 to 2015, dividing them into four groups: normal weight (BMI ≥ 18.5 to < 25), overweight (BMI ≥ 25 to < 30), obese (BMI > 30 to < 40), and morbidly obese (BMI ≥ 40). Demographic and procedural characteristics, complications, and ablation outcomes were compared among groups. A total of 701 patients (146 time-matched controls, 227 overweight, 244 obese, and 84 morbidly obese) with complete demographic, procedural, and follow-up data were included. Increasing BMI correlated positively with HTN, OSA, CHA2 DS2 -VASC score, and persistent AF (P ≤ 0.001 for all associations). Radiofrequency application time and intraprocedural heparin dose increased with BMI (P ≤ 0.001). Arrhythmia recurrence at 1 year was 39.9% in controls, while higher in all high-BMI groups (overweight, 51.3%; obese, 57%; morbidly obese, 58.1 %; P  =  0.007 for all versus controls). Impact of BMI on AF recurrence was not seen in persistent AF patients. Complication rates across groups were similar. CONCLUSIONS: AF recurrence after catheter ablation is higher in overweight, obese, and morbidly obese patients comparing to normal-weight controls, driven primarily by outcomes differences in paroxysmal AF patients. Complications were not associated with increased BMI.

Effect of intensive versus standard blood pressure control on major adverse cardiac events and serious adverse events: A bivariate analysis of randomized controlled trials.

BACKGROUND: Intensive blood pressure (BP) lowering may offer protective effects against major adverse cardiac event (MACE) but is also associated with a greater risk of a serious adverse event (SAE). The risk-benefit profile of intensive versus standard BP control has not been comprehensively assessed. METHODS: Four studies were identified from a systematic literature search for randomized controlled trials comparing intensive versus standard BP lowering that reported both MACE and SAE endpoints. A previously described statistical approach was applied to characterize the efficacy-safety tradeoff of BP control. The bivariate outcome was computed to quantitatively assess the net clinical benefit (NCB) of intensive BP lowering as compared to standard treatment, with positive values indicating increased risks and negative values indicating decreased risks. RESULTS: Data from the SPRINT trial demonstrated that intensive strategy was superior in MACE but inferior in SAE, thereby eroding the NCB (bivariate outcome: 0.33% [-0.50% to 1.21%]). Intensive strategy from the SPS3 trial fulfilled non-inferiority in both MACE and SAE but did not reach a favorable NCB (-1.31% [-2.25% to 0.01%]). The ACCORD trial suggested that intensive strategy was non-inferior in MACE but inferior in SAE (-0.19% [-0.79% to 1.37%]). Results from the VALISH trial were inconclusive for SAE but suggested non-inferiority in MACE (-1.19% [-3.24% to 0.68%]). CONCLUSIONS: Compared to the standard blood pressure target, pooled data from randomized controlled trials suggest that intensive strategy did not achieve a net clinical benefit when weighing the benefit of MACE reduction against the risk of SAE under the bivariate framework. ABBREVIATIONS: Blood pressure (BP), diastolic blood pressure (DBP), major adverse cardiac event (MACE), net clinical benefit (NCB), serious adverse event (SAE), systolic blood pressure (SBP).

Factors impacting complication rates for catheter ablation of atrial fibrillation from 2003 to 2015.

Aims: Complications from catheter ablation for atrial fibrillation (AF) are well described. Changing aspects of AF ablation including patient populations referred, institutional experience, and emerging catheter and pharmacological options may impact complication rates. We assessed procedural complication trends in AF ablation patients from 2003­2015 to identify what factors affect adverse event rates. Methods and Results: We evaluated consecutively enrolled patients undergoing initial AF ablation from 2003 through 2015. Statistical analyses were performed to identify predictors of increased risk for major complications, which were defined as death, stroke, atrio-oesophageal fistula, phrenic nerve injury, cardiovascular events requiring blood transfusions or procedural interventions, or non-cardiovascular events requiring intervention. A total of 1475 patients (mean age 59.5 ± 10.5, 82% male) were evaluated. Major complications occurred in 3.9% (n = 58) of cases, including vascular access-site haematoma (1.3%), cardiac tamponade (1.1%), and cerebrovascular accident (CVA) (0.9%). Univariate analysis revealed increased risk of complications associated with hypertension (P = 0.048), CHA2DS2VASc score ≥1 (P = 0.015), and early institutional experience (P = 0.003). Populations with higher CHA2DS2VASc scores underwent AF ablation more frequently over time (P < 0.001). Novel catheters and anticoagulants did not appreciably affect complication rates. Multivariate analysis adjusting for hypertension, CHA2DS2VASc score, and institutional experience showed that higher CHA2DS2VASc score and early institutional experience were independent predictors of adverse events. Conclusion: Patient characteristics reflected in CHA2DS2VASc scoring and early institutional experience predict increased complication rates following AF ablation. Despite more patients with higher CHA2DS2VASc scores undergoing AF ablation, complication rates fell over time as institutional experience increased.

Intra-Atrial Dyssynchrony During Sinus Rhythm Predicts Recurrence After the First Catheter Ablation for Atrial Fibrillation.

OBJECTIVES: The purpose of this study was to evaluate the usefulness of intra-atrial dyssynchrony as a marker of underlying left atrial (LA) remodeling to predict recurrence after the first atrial fibrillation (AF) ablation. BACKGROUND: Catheter ablation for AF remains far from curative with relatively high recurrence rates. One of the causes of recurrence is poor patient selection out of a diverse patient population with different degrees of LA remodeling. METHODS: We included 208 patients with a history of AF (59.4 ± 10.0 years of age; 26.0% nonparoxysmal AF) referred for catheter ablation of AF who underwent pre-ablation cardiac magnetic resonance in sinus rhythm. Clinical follow-up was 20 ± 6 months. Using tissue tracking cardiac magnetic resonance, we measured the LA longitudinal strain in each of 12 equal-length segments in 2- and 4-chamber views. We defined intra-atrial dyssynchrony as the standard deviation of the time to the peak longitudinal strain corrected by the cycle length (SD-time to peak strain [TPS], %). RESULTS: Patients with AF recurrence after ablation (n = 101) had significantly higher SD-TPS than those without (n = 107; 3.9% vs. 2.2%; p < 0.001). Multivariable cox analysis showed that SD-TPS was associated with recurrence after adjusting for clinical risk factors, AF type, LA structure and function, and fibrosis (p < 0.001). Furthermore, receiver-operating characteristics analysis showed SD-TPS improved prediction of recurrence better than clinical risk factors, LA structure and function, and fibrosis. CONCLUSIONS: Intra-atrial dyssynchrony during sinus rhythm is an independent predictor of recurrence after the first catheter ablation of paroxysmal or persistent AF. Assessment of intra-atrial dyssynchrony may improve ablation outcomes by refining patient selection.

Intra-Atrial Dyssynchrony Using Cardiac Magnetic Resonance to Quantify Tissue Remodeling in Patients with Atrial Fibrillation.

BACKGROUND: Recent studies suggest that left atrial (LA) late gadolinium enhancement (LGE) can quantify the underlying tissue remodeling that harbors atrial fibrillation (AF). However, quantification of LA-LGE requires labor-intensive magnetic resonance imaging acquisition and postprocessing at experienced centers. LA intra-atrial dyssynchrony assessment is an emerging imaging technique that predicts AF recurrence after catheter ablation. We hypothesized that 1) LA intra-atrial dyssynchrony is associated with LA-LGE in patients with AF and 2) LA intra-atrial dyssynchrony is greater in patients with persistent AF than in those with paroxysmal AF. METHOD: We conducted a cross-sectional study comparing LA intra-atrial dyssynchrony and LA-LGE in 146 patients with a history of AF (60.0 ± 10.0 years, 30.1% nonparoxysmal AF) who underwent pre-AF ablation cardiac magnetic resonance (CMR) in sinus rhythm. Using tissue-tracking CMR, we measured the LA longitudinal strain in two- and four-chamber views. We defined intra-atrial dyssynchrony as the standard deviation (SD) of the time to peak longitudinal strain (SD-TPS, in %) and the SD of the time to the peak pre-atrial contraction strain corrected by the cycle length (SD-TPSpreA, in %). We used the image intensity ratio (IIR) to quantify LA-LGE. RESULTS: Intra-atrial dyssynchrony analysis took 5 ± 9 minutes per case. Multivariable analysis showed that LA intra-atrial dyssynchrony was independently associated with LA-LGE. In addition, LA intra-atrial dyssynchrony was significantly greater in patients with persistent AF than those with paroxysmal AF. In contrast, there was no significant difference in LA-LGE between patients with persistent and paroxysmal AF. LA intra-atrial dyssynchrony showed excellent reproducibility and its analysis was less time-consuming (5 ± 9 minutes) than the LA-LGE (60 ± 20 minutes). CONCLUSION: LA Intra-atrial dyssynchrony is a quick and reproducible index that is independently associated with LA-LGE to reflect the underlying tissue remodeling.

Multimodal Examination of Atrial Fibrillation Substrate: Correlation of Left Atrial Bipolar Voltage Using Multi-Electrode Fast Automated Mapping, Point-by-Point Mapping, and Magnetic Resonance Image Intensity Ratio.

Background: Bipolar voltage mapping, as part of atrial fibrillation (AF) ablation, is traditionally performed in a point-by-point (PBP) approach using single-tip ablation catheters. Alternative techniques for fibrosis-delineation include fast-anatomical mapping (FAM) with multi-electrode circular catheters, and late gadolinium-enhanced magnetic-resonance imaging (LGE-MRI). The correlation between PBP, FAM, and LGE-MRI fibrosis assessment is unknown. Objective: In this study, we examined AF substrate using different modalities (PBP, FAM, and LGE-MRI mapping) in patients presenting for an AF ablation. Methods: LGE-MRI was performed pre-ablation in 26 patients (73% males, age 63±8years). Local image-intensity ratio (IIR) was used to normalize myocardial intensities. PBP- and FAM-voltage maps were acquired, in sinus rhythm, prior to ablation and co-registered to LGE-MRI. Results: Mean bipolar voltage for all 19,087 FAM voltage points was 0.88±1.27mV and average IIR was 1.08±0.18. In an adjusted mixed-effects model, each unit increase in local IIR was associated with 57% decrease in bipolar voltage (p<0.0001). IIR of >0.74 corresponded to bipolar voltage <0.5 mV. A total of 1554 PBP-mapping points were matched to the nearest FAM-point. In an adjusted mixed-effects model, log-FAM bipolar voltage was significantly associated with log-PBP bipolar voltage (ß=0.36, p<0.0001). At low-voltages, FAM-mapping distribution was shifted to the left compared to PBP-mapping; at intermediate voltages, FAM and PBP voltages were overlapping; and at high voltages, FAM exceeded PBP-voltages. Conclusion: LGE-MRI, FAM and PBP-mapping show good correlation in delineating electro-anatomical AF substrate. Each approach has fundamental technical characteristics, the awareness of which allows proper assessment of atrial fibrosis.

Acute Pulmonary Vein Reconnection after Ablation using Contact-force Sensing Catheters: Incidence, Timing, and Ablation Lesion Characteristics.

BACKGROUND: Acute pulmonary vein (PV) reconnection predicts atrial fibrillation (AF) recurrence after ablation. Contact-force (CF) sensing catheters improve lesion delivery. We assessed the incidence, timing, location, and lesion characteristics of acute reconnection after PV isolation with CF sensing catheters. METHODS: Patients undergoing radiofrequency ablation for AF from October 2016 to February 2017 were studied. Assessment for acute reconnection at 20 and 40 minute intervals was performed in each isolated PV. Additional lesions were applied as needed. Lesion location, contact force, power, duration, impedance, and force-time integral values were compared at sites with and without reconnection. RESULTS: Twenty-two patients (60.6 + 1.8 years; 36.4% female; 27.3% persistent AF; CHA2DS2VASC 1.9 + 0.3) were included. Eighty-eight veins were isolated. Eleven reconnections occurred in 10 patients; 9 occurred by 20 minutes and 2 between 20 - 40 minutes. Most reconnections (6/11) were in the left superior PV. Of 4993 ablation points analyzed, 72 were at acute reconnection sites, and no differences in average contact force (11.4 + 8.1 vs 11.3 + 7.1 gm, p=0.868), power (29.7 + 3.9 vs 29.9 + 4.6 watts, p=0.620), impedance (64.1 + 60 vs 72.5 + 60, p=0.236) and the force time integral (86.9 + 78.8 vs 99.7 + 100 gm/sec, p=0.282) were found. CONCLUSION: Acute PV reconnection rates using CF sensing catheters are roughly 12.5%, with the majority occurring within 20 minutes. We found no significant differences in characteristics of ablation points in areas of reconnection. Optimum wait periods after isolation to check for acute reconnection may be as brief as 20 minutes.

Dual antithrombotic plus adjunctive antiinflammatory therapy to improve cardiovascular outcome in atrial fibrillation patients with concurrent acute coronary syndrome: A triple-pathway strategy.

The concurrence of atrial fibrillation and acute coronary syndrome poses a conundrum in the antithrombotic management as intensification of anticoagulation or antiplatelet therapy inevitably comes at the price of an increased bleeding risk. Various antithrombotic combinations have been attempted to prevent the recurrent cardiovascular events, however, there has been limited success in effective risk reduction for this high risk population. Given the overarching effect of interleukin 1ß-driven inflammation on the arrhythmogenesis, thrombogenesis, and hypercoagulability, we hypothesize that the triple-pathway strategy (i.e., incorporating antiinflammatory therapy into anticoagulant and antiplatelet therapy) would grant incremental cardiovascular benefits for atrial fibrillation patients with coexisting acute coronary syndrome and stent placement.

Visualization of acute edema in the left atrial myocardium after radiofrequency ablation: Application of a novel high-resolution 3-dimensional magnetic resonance imaging sequence.

BACKGROUND: Ablation-induced left atrial (LA) edema may result in procedural failure due to reversible pulmonary vein isolation. Conventional T2-weighted magnetic resonance edema imaging is limited by low spatial resolution. OBJECTIVE: The purpose of this pilot study was to optimize and validate a 3-dimensional (3D) sampling perfection with application-optimized contrasts using different flip-angle evolution (SPACE) sequence for quantification of T2 signal in the LA, and to apply it in recently ablated patients, comparing myocardial edema on T2-SPACE to tissue damage on late gadolinium enhancement (LGE) imaging. METHODS: Phantom studies were performed to identify 3D-SPACE parameters for optimal contrast between normal and edematous myocardium. Fourteen AF patients were imaged with both 3D-SPACE and dark-blood turbo-spin echo (DB-TSE) to compare image quality and signal intensity between the 2 techniques. Eight patients underwent pre- and postablation 3D-SPACE and 3D-LGE imaging. Ablation points were co-registered with corresponding myocardial sectors, and ablation-induced changes in T2 and LGE signal intensities were measured. RESULTS: Signal-to-noise ratio and contrast-to-noise ratio were higher on SPACE vs DB-TSE (65.5 ± 33.9 vs 35.7 ± 17.9; P = .01; and 59.4 ± 33.0 vs 32.9 ± 17.7; P = .04, respectively). T2-signal correlated well on 3D-SPACE and DB-TSE, such that each unit increase in TSE intensity correlated with a 0.69-unit increase in SPACE intensity (95% confidence interval 0.56-0.82; P <.001). T2 and LGE signal intensities were acutely increased at ablation sites. The extent of postablation edema was higher compared to LGE, although the spatial distribution of hyperenhancement around pulmonary veins seemed similar in both modalities. CONCLUSION: T2-SPACE can be used to map the extent of acute postablation edema in the thin LA myocardium, with improved resolution and lower artifact compared to traditional DB-TSE.

The Extent of Left Atrial Low-Voltage Areas Included in Pulmonary Vein Isolation Is Associated With Freedom from Recurrent Atrial Arrhythmia.

BACKGROUND: The extent of left atrial (LA) baseline low-voltage areas (LVA-B), which may be a surrogate for fibrosis, is associated with recurrent atrial fibrillation (AF) after ablation. This study aimed to assess the relationship between the extent of LVA-B isolated by ablation (LVA-I) and AF recurrence. METHODS: The study cohort included 159 consecutive patients with drug-refractory AF who underwent an initial AF ablation with LA voltage mapping during sinus rhythm. The extent of LVA-B was quantified while excluding the pulmonary veins, LA appendage, and mitral valve area. LVA-I was quantified as the percentage of LVA-B encircled by pulmonary vein isolation. Surveillance and symptom-prompted electrocardiograms, Holter monitors, and event monitors were used to document atrial arrhythmia recurrence for a median follow-up of 712 days (1.95 years). RESULTS: Of 159 patients, 72% were men and 27% had persistent AF. The mean number of sampled bipolar voltage points was 119 ± 56. The mean LA surface area was 102.3 ± 37.3 cm2, and the mean LVA-B was 1.9 ± 3.8 cm2. The mean LVA-I was 51.05% ± 36.8% of LVA-B. In the multivariable Cox proportional hazards model adjusted for LA volume, CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age [≥ 75 years], Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age [65-74 years], Sex [Female] score), LVA-B, and AF type, LVA-I was inversely associated with recurrent atrial arrhythmia after the blanking period (hazard ratio, 0.42/percent LVA isolated; P = 0.037). CONCLUSIONS: The extent of LVA-I is independently associated with freedom from atrial arrhythmias after AF ablation, supporting ongoing efforts to target low LA voltage areas and other fibrosis indicators to improve ablation outcomes.

Mechanical dyssynchrony of the left atrium during sinus rhythm is associated with history of stroke in patients with atrial fibrillation.

Aims: We sought to evaluate the relationship between left atrial (LA) mechanical dyssynchrony and history of stroke or transient ischaemic attack (TIA) in patients with atrial fibrillation (AF). We hypothesized that mechanical dyssynchrony of the LA is associated with history of stroke/TIA independent of LA function and Cardiac failure, Hypertension, Age, Diabetes, Stroke/transient ischaemic attack (TIA), VAscular disease, and Sex category (CHA2DS2-VASc) score in patients with AF. Methods and results: We conducted a cross-sectional study of 246 patients with a history of AF (59 ± 10 years, 29% female, 26% non-paroxysmal AF) referred for catheter ablation to treat drug-refractory AF who underwent preablation cardiac magnetic resonance (CMR) in sinus rhythm. Using tissue-tracking CMR, we measured the LA longitudinal strain and strain rate in each of 12 equal-length segments in two- and four-chamber views. We defined indices of LA mechanical dyssynchrony, including the standard deviation of the time to the peak longitudinal strain (SD-TPS). Patients with a prior history of stroke or TIA (n = 23) had significantly higher SD-TPS than those without (n = 223) (39.9 vs. 23.4 ms, P < 0.001). Multivariable analysis showed that SD-TPS was associated with stroke/TIA after adjusting for the CHA2DS2-VASc score, LA minimum index volume, and the peak LA longitudinal strain (P < 0.001). The receiver-operating characteristics curve showed that SD-TPS identified patients with stroke/TIA more accurately than CHA2DS2-VASc score alone (c-statistics: 0.82 vs. 0.75, P < 0.001). Conclusion: Higher mechanical dyssynchrony of the LA during sinus rhythm is associated with a history of stroke/TIA in patients with AF.

Trends in Transesophageal Echocardiography Use, Findings, and Clinical Outcomes in the Era of Minimally Interrupted Anticoagulation for Atrial Fibrillation Ablation.

OBJECTIVES: This study assessed trends in transesophageal echocardiography (TEE) use, rate of left atrial appendage (LAA) thrombus detection, and incidence of periprocedural cerebrovascular accident (CVA) since transitioning to a strategy of uninterrupted warfarin or briefly interrupted novel oral anticoagulant therapy in 2010. BACKGROUND: TEE is routinely performed before ablation for atrial fibrillation (AF) to ensure absence of LAA thrombus. METHODS: Patients with AF ablation presenting between January 2010 and September 2015 at Johns Hopkins Hospital were enrolled in an AF ablation registry; TEE and ablation outcomes were retrospectively analyzed. Presence of LAA thrombus, dense spontaneous echo contrast (SEC), or patent foramen ovale (PFO) were recorded. CVA incidence from procedure onset to 30 days post-procedure was evaluated using electronic medical record review. RESULTS: Pre-procedure TEE was performed in 646 of 1,224 AF ablation cases (52.8%). There was a decline in pre-procedure TEE use from 86% in 2010 to 42% in 2015 (p < 0.001). CVA incidence was 4/1,224 (0.33%) cases, and did not change during the study period. TEE findings included LAA thrombus (n = 6; 0.93%), PFO (n = 23; 3.6%), and dense spontaneous echo contrast (n = 99; 15.3%). Both SEC and LAA thrombus were associated with persistent AF, higher CHA2DS2VASC score, increased LA size, reduced LAA flow velocity, and decreased left ventricular ejection fraction. PFO was not associated with prior AF ablation, and SEC was not associated with increased CVA incidence. CONCLUSIONS: CVA is a rare complication of AF ablation in patients with minimally interrupted anticoagulation. Pre-ablation TEE may be reasonably avoided in patients without high-risk features.

Impact of rotor temperospatial stability on acute and one-year atrial fibrillation ablation outcomes.

BACKGROUND: The utility of rotor ablation using commercially available systems as an adjunct to pulmonary vein isolation (PVI) is controversial. Variable results may stem from heterogeneous practice patterns. We investigated whether a prespecified protocol to determine temperospatial rotor stability improved acute and intermediate outcomes following rotor ablation. HYPOTHESIS: Protocolized rotor mapping and ablation, with prespecified metrics to determine temporal rotor stability prior to ablation, will improve short- and long-term PVI/rotor ablation outcomes. METHODS: Patients undergoing PVI plus rotor ablation at Johns Hopkins during 2015 were included. The first cohort underwent rotor mapping and ablation at the operator's discretion, whereas the second cohort underwent protocolized rotor mapping, with ablation limited to temperospatially stable rotors. Both cohorts underwent PVI. Acute results (rotor elimination, atrial fibrillation [AF] termination), procedural data, and 1-year outcomes were assessed. RESULTS: Twenty-seven patients underwent ablation (mean age, 64.4 ± 9 years, male 81.5%, persistent AF 85.2%, long-standing persistent AF 14.8%, mean AF duration 4.4 ± 4 years, repeat cases 51.8%, and mean LA size 4.6 ± 0.8 cm). In the protocolized cohort, rotors were reproducible in 83% (10/12) of cases in at least 1 chamber. Acute rhythm change was achieved in 8/27 (29.6%) patients. Sinus rhythm on presentation (62.5% vs 15.8%, P = 0.03) and higher total targeted rotors (3.8 ± 1.7 vs 2.5 ± 1.0, P = 0.02) predicted acute change. At 12 months, freedom from AF/atrial tachycardia was achieved in 5/15 (33.3%) patients in the first cohort and 5/11 patients in the protocolized cohort (45.5%; P = 0.53 for comparison). CONCLUSIONS: Acute and intermediate results did not change with protocolized mapping designed to identify temperospatially stable rotors. Outcomes at 12 months were similar in both groups.

Ablation as targeted perturbation to rewire communication network of persistent atrial fibrillation.

Persistent atrial fibrillation (AF) can be viewed as disintegrated patterns of information transmission by action potential across the communication network consisting of nodes linked by functional connectivity. To test the hypothesis that ablation of persistent AF is associated with improvement in both local and global connectivity within the communication networks, we analyzed multi-electrode basket catheter electrograms of 22 consecutive patients (63.5 ± 9.7 years, 78% male) during persistent AF before and after the focal impulse and rotor modulation-guided ablation. Eight patients (36%) developed recurrence within 6 months after ablation. We defined communication networks of AF by nodes (cardiac tissue adjacent to each electrode) and edges (mutual information between pairs of nodes). To evaluate patient-specific parameters of communication, thresholds of mutual information were applied to preserve 10% to 30% of the strongest edges. There was no significant difference in network parameters between both atria at baseline. Ablation effectively rewired the communication network of persistent AF to improve the overall connectivity. In addition, successful ablation improved local connectivity by increasing the average clustering coefficient, and also improved global connectivity by decreasing the characteristic path length. As a result, successful ablation improved the efficiency and robustness of the communication network by increasing the small-world index. These changes were not observed in patients with AF recurrence. Furthermore, a significant increase in the small-world index after ablation was associated with synchronization of the rhythm by acute AF termination. In conclusion, successful ablation rewires communication networks during persistent AF, making it more robust, efficient, and easier to synchronize. Quantitative analysis of communication networks provides not only a mechanistic insight that AF may be sustained by spatially localized sources and global connectivity, but also patient-specific metrics that could serve as a valid endpoint for therapeutic interventions.

Association of left atrial epicardial adipose tissue with electrogram bipolar voltage and fractionation: Electrophysiologic substrates for atrial fibrillation.

BACKGROUND: Epicardial adipose tissue (EAdT) is metabolically active and likely contributes to atrial fibrillation (AF) through the release of inflammatory cytokines into the myocardium or through its rich innervation with ganglionated plexi at the pulmonary vein ostia. The electrophysiologic mechanisms underlying the association between EAdT and AF remain unclear. OBJECTIVE: The purpose of this study was to investigate the association of EAdT with adjacent myocardial substrate. METHODS: Thirty consecutive patients who underwent cardiac computed tomography as well as electroanatomic mapping in sinus rhythm before an initial AF ablation procedure were studied. Semiautomatic segmentation of atrial EAdT was performed and registered anatomically to the voltage map. RESULTS: In multivariable regression analysis clustered by patient, age (-0.01 per year) and EAdT (-0.29) were associated with log bipolar voltage as well as low-voltage zones (<0.5 mV). Age (odds ratio [OR]: 1.02 per year), male gender (OR: 3.50), diabetes (OR: 2.91), hypertension (OR: 2.55), and EAdT (OR: 8.56) were associated with fractionated electrograms, and age (OR: 2.80), male gender (OR: 3.00), and EAdT (OR: 7.03) were associated with widened signals. Age (OR: 1.03 per year) and body mass index (OR: 1.06 per kg/m2) were associated with atrial fat. CONCLUSION: The presence of overlaying EAdT was associated with lower bipolar voltage and electrogram fractionation as electrophysiologic substrates for AF. EAdT was not a statistical mediator of the association between clinical variables and AF substrate. Body mass index was directly associated with the presence of EAdT in patients with AF.

Improved understanding of the pathophysiology of atrial fibrillation through the lens of discrete pathological pathways.

Atrial fibrillation (AF) is a common disorder with a complex and incompletely understood pathophysiology. Genetic approaches to understanding the pathophysiology of AF have led to the identification of several biological pathways important in the pathogenesis of the arrhythmia. These include pathways important for cardiac development, generation and propagation of atrial electrical impulses, and atrial remodeling and fibrosis. While common and rare genetic variants in these pathways are associated with increased susceptibility to AF, they differ substantially among patients with lone versus typical AF. Furthermore, how these pathways converge to a final common clinical phenotype of AF is unclear and might also vary among different patient populations. Here, we review the contemporary knowledge of AF pathogenesis and discuss how derangement in cardiac development, ion channel dysfunction, and promotion of atrial fibrosis may contribute to this common and important clinical disorder.

Intra-Atrial Dyssynchrony Using Cardiac Magnetic Resonance to Quantify Tissue Remodeling in Patients with Atrial Fibrillation / Dessincronia Intra-atrial à Ressonância Magnética Cardíaca para Quantificação da Remodelação Tecidual em Pacientes com Fibrilação Atrial

Abstract Background: Recent studies suggest that left atrial (LA) late gadolinium enhancement (LGE) can quantify the underlying tissue remodeling that harbors atrial fibrillation (AF). However, quantification of LA-LGE requires labor-intensive magnetic resonance imaging acquisition and postprocessing at experienced centers. LA intra-atrial dyssynchrony assessment is an emerging imaging technique that predicts AF recurrence after catheter ablation. We hypothesized that 1) LA intra-atrial dyssynchrony is associated with LA-LGE in patients with AF and 2) LA intra-atrial dyssynchrony is greater in patients with persistent AF than in those with paroxysmal AF. Method: We conducted a cross-sectional study comparing LA intra-atrial dyssynchrony and LA-LGE in 146 patients with a history of AF (60.0 ± 10.0 years, 30.1% nonparoxysmal AF) who underwent pre-AF ablation cardiac magnetic resonance (CMR) in sinus rhythm. Using tissue-tracking CMR, we measured the LA longitudinal strain in two- and four-chamber views. We defined intra-atrial dyssynchrony as the standard deviation (SD) of the time to peak longitudinal strain (SD-TPS, in %) and the SD of the time to the peak pre-atrial contraction strain corrected by the cycle length (SD-TPSpreA, in %). We used the image intensity ratio (IIR) to quantify LA-LGE. Results: Intra-atrial dyssynchrony analysis took 5 ± 9 minutes per case. Multivariable analysis showed that LA intra-atrial dyssynchrony was independently associated with LA-LGE. In addition, LA intra-atrial dyssynchrony was significantly greater in patients with persistent AF than those with paroxysmal AF. In contrast, there was no significant difference in LA-LGE between patients with persistent and paroxysmal AF. LA intra-atrial dyssynchrony showed excellent reproducibility and its analysis was less time-consuming (5 ± 9 minutes) than the LA-LGE (60 ± 20 minutes). Conclusion: LA Intra-atrial dyssynchrony is a quick and reproducible index that is independently associated with LA-LGE to reflect the underlying tissue remodeling.

Resumo Fundamento: Estudos recentes sugerem que o realce tardio com gadolínio (RTG) no átrio esquerdo (AE) pode quantificar a remodelação tecidual subjacente que abriga a fibrilação atrial (FA). No entanto, a quantificação do RTG-AE requer um trabalho intenso de aquisição por ressonância magnética e pós-processamento em centros experientes. A avaliação da dessincronia intra-atrial no AE é uma técnica de imagem emergente que prediz a recorrência da FA após ablação por cateter. Nós levantamos as hipóteses de que 1) a dessincronia intra-atrial está associada ao RTG-AE em pacientes com FA e 2) a dessincronia intra-atrial é maior em pacientes com FA persistente do que naqueles com FA paroxística. Método: Realizamos um estudo transversal comparando a dessincronia intra-atrial no AE e o RTG-AE em 146 pacientes com história de FA (60,0 ± 10,0 anos, 30,1% com FA não paroxística) submetidos à ressonância magnética cardíaca (RMC) durante ritmo sinusal antes da ablação da FA. Com utilização de RMC com tissue tracking, medimos o strain longitudinal do AE em cortes de duas e quatro câmaras. Definimos a dessincronia intra-atrial como o desvio padrão (DP) do tempo até o pico do strain longitudinal (DP-TPS, em %) e o DP do tempo até o pico do strain antes da contração atrial corrigido pela duração do ciclo (DP-TPSpreA, em %). Utilizamos a razão da intensidade da imagem (RIM) para quantificar o RTG-AE. Resultados: A análise da dessincronia intra-atrial levou 9 ± 5 minutos por caso. A análise multivariada mostrou que a dessincronia intra-atrial no AE esteve independentemente associada ao RTG-AE. Além disso, a dessincronia intra-atrial no AE foi significativamente maior em pacientes com FA persistente do que naqueles com FA paroxística. Por outro lado, não houve diferença significativa no RTG-AE entre pacientes com FA persistente e paroxística. A dessincronia intra-atrial no AE mostrou excelente reprodutibilidade e sua análise foi menos demorada (5 ± 9 minutos) do que o RTG-AE (60 ± 20 minutos). Conclusão: A dessincronia intra-atrial no AE é um índice rápido, reprodutível e independentemente associado ao RTG-AE para indicar remodelação tecidual subjacente. (Arq Bras Cardiol. 2019; 112(4):441-450)