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).

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.

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.

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.

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.