Low voltage zones detected by omnipolar Vmax map accurately identifies the potential atrial substrate and predicts the AF ablation outcome after PV isolation.

INTRODUCTION: The presence of bipolar low-voltage zone (LVZ) is a predictor of AF recurrence after PV isolation (PVI). However, changes of wavefront and bipole directions may cause different electrogram characteristics. We aimed to investigate whether using omnipolar maximum voltage (Vmax) map derived from high density (HD) Grid mapping catheter could assess LVZ and AF ablation outcome accurately. METHODS: Fifty paroxysmal AF patients (27 males, 57.8 ± 9.5 years old) who underwent 3D mapping guided PVI were enrolled. Left atrial voltage mapping during sinus rhythm before ablation was performed. The significant LVZ (<0.5 mV with area > 5 cm2) were defined as sites by omnipolar Vmax, bipolar HD wave map, conventional bipolar electrograms acquired from electrode pairs along to and across to the catheter shaft. The primary end point was the first documented recurrence of any AF during follow-ups. RESULTS: PVI was performed in all patients, and there were 2 patients (4%) who also received additional non-PV triggers ablation. After a follow-up of 11.4 ± 5.4 months, recurrence of AF occurred in 12 patients (24%). The presence of a significant LVZ was less detected by omnipolar Vmax map, compared to HD wave map (24.0% vs. 58.0%, p = 0.001). LVZ detected by omnipolar Vmax map independently predicted the AF recurrence (odds ratio 16.91; 95% CI, 3.17-90.10; p = 0.001). CONCLUSION: LVZ detected by omnipolar Vmax map accurately predicts the AF recurrence following ablation in paroxysmal AF, compared to conventional bipolar and HD wave maps, suggesting the omnipolar Vmax map can precisely define the atrial substrate property.

Incidence of Nonalcoholic Fatty Liver Disease in Children: 2009-2018.

BACKGROUND AND OBJECTIVES: In 2007, the American Academy of Pediatrics recommended that children with obesity should be screened for nonalcoholic fatty liver disease (NAFLD). Population epidemiology reveals that NAFLD is common in children; however, little is known about rates of clinical diagnosis. In this study, we aim to determine screening practices, annual incidence, and clinical characteristics of NAFLD in children within an integrated community health system. METHODS: Using electronic health records, we identified patients newly diagnosed (aged 5-18) with NAFLD on the basis of diagnostic codes from the 9th and 10th revisions of the International Classification of Diseases. We calculated screening rates and annual incidence rates of NAFLD from January 1, 2009, to December 31, 2018. RESULTS: In this study, we evaluated 7 884 844 patient-years. Screening was performed in 54.0% of children with obesity and 24.0% of children with overweight. The results revealed 36 658 children aged 9 to 18 with overweight or obesity and alanine aminotransferase >30 U/L. Of these children, 12.3% received further workup for NAFLD. The incidence of an NAFLD diagnosis significantly increased over time, with 36.0 per 100 000 in 2009 and 58.2 per 100 000 in 2018 (P < .0001). CONCLUSIONS: Our study of a large integrated health care system in southern California revealed that the incidence of NAFLD in children is increasing, although many children may remain undiagnosed.

Extent and spatial distribution of left atrial arrhythmogenic sites, late gadolinium enhancement at magnetic resonance imaging, and low-voltage areas in patients with persistent atrial fibrillation: comparison of imaging vs. electrical parameters of fibrosis and arrhythmogenesis.

AIMS: Atrial fibrosis contributes to arrhythmogenesis in atrial fibrillation and can be detected by MRI or electrophysiological mapping. The current study compares the spatial correlation between delayed enhancement (DE) areas to low-voltage areas (LVAs) and to arrhythmogenic areas with spatio-temporal dispersion (ST-Disp) or continuous activity (CA) in atrial fibrillation (AF). METHODS AND RESULTS: Sixteen patients with persistent AF (nine long-standing) underwent DE-magnetic resonance imaging (1.25 mm × 1.25 mm × 2.5 mm) prior to pulmonary vein isolation. Left atrial (LA) voltage mapping was acquired in AF and the regional activation patterns of 7680 AF wavelets were analysed. Sites with ST-Disp or CA were characterized (voltage, duration) and their spatial relationship to DE areas and LVAs <0.5 mV was assessed. Delayed enhancement areas and LVAs covered 55% and 24% (P < 0.01) of total LA surface, respectively. Delayed enhancement area was present at 61% of LVAs, whereas low voltage was present at 28% of DE areas. Most DE areas (72%) overlapped with atrial high-voltage areas (>0.5 mV). Spatio-temporal dispersion and CA more frequently co-localized with LVAs than with DE areas (78% vs. 63%, P = 0.02). Regional bipolar voltage of ST-Disp vs. CA was 0.64 ± 0.47 mV vs. 0.58 ± 0.51 mV. All 28 ST-Disp and 56 CA areas contained electrograms with prolonged duration (115 ± 14 ms) displaying low voltage (0.34 ± 0.11 mV). CONCLUSION: A small portion of DE areas and LVAs harbour the arrhythmogenic areas displaying ST-Disp or CA. Most arrhythmogenic activities co-localized with LVAs, while there was less co-localization with DE areas. There is an important mismatch between DE areas and LVAs which needs to be considered when used as target for catheter ablation.

Voltage during atrial fibrillation is superior to voltage during sinus rhythm in localizing areas of delayed enhancement on magnetic resonance imaging: An assessment of the posterior left atrium in patients with persistent atrial fibrillation.

BACKGROUND: Bipolar electrogram voltage during sinus rhythm (VSR) has been used as a surrogate for atrial fibrosis in guiding catheter ablation of persistent atrial fibrillation (AF), but the fixed rate and wavefront characteristics present during sinus rhythm may not accurately reflect underlying functional vulnerabilities responsible for AF maintenance. OBJECTIVE: The purpose of this study was determine whether, given adequate temporal sampling, the spatial distribution of mean AF voltage (VmAF) better correlates with delayed-enhancement magnetic resonance imaging (MRI-DE)-detected atrial fibrosis than VSR. METHODS: AF was mapped (8 seconds) during index ablation for persistent AF (20 patients) using a 20-pole catheter (660 ± 28 points/map). After cardioversion, VSR was mapped (557 ± 326 points/map). Electroanatomic and MRI-DE maps were co-registered in 14 patients. RESULTS: The time course of VmAF was assessed from 1-40 AF cycles (∼8 seconds) at 1113 locations. VmAF stabilized with sampling >4 seconds (mean voltage error 0.05 mV). Paired point analysis of VmAF from segments acquired 30 seconds apart (3667 sites; 15 patients) showed strong correlation (r = 0.95; P <.001). Delayed enhancement (DE) was assessed across the posterior left atrial (LA) wall, occupying 33% ± 13%. VmAF distributions were (median [IQR]) 0.21 [0.14-0.35] mV in DE vs 0.52 [0.34-0.77] mV in non-DE regions. VSR distributions were 1.34 [0.65-2.48] mV in DE vs 2.37 [1.27-3.97] mV in non-DE. VmAF threshold of 0.35 mV yielded sensitivity of 75% and specificity of 79% in detecting MRI-DE compared with 63% and 67%, respectively, for VSR (1.8-mV threshold). CONCLUSION: The correlation between low-voltage and posterior LA MRI-DE is significantly improved when acquired during AF vs sinus rhythm. With adequate sampling, mean AF voltage is a reproducible marker reflecting the functional response to the underlying persistent AF substrate.

Transcatheter Myocardial Needle Chemoablation During Real-Time Magnetic Resonance Imaging: A New Approach to Ablation Therapy for Rhythm Disorders.

BACKGROUND: Radiofrequency ablation for ventricular arrhythmias is limited by inability to visualize tissue destruction, by reversible conduction block resulting from edema surrounding lesions, and by insufficient lesion depth. We hypothesized that transcatheter needle injection of caustic agents doped with gadolinium contrast under real-time magnetic resonance imaging (MRI) could achieve deep, targeted, and irreversible myocardial ablation, which would be immediately visible. METHODS AND RESULTS: Under real-time MRI guidance, ethanol or acetic acid was injected into the myocardium of 8 swine using MRI-conspicuous needle catheters. Chemoablation lesions had identical geometry by in vivo and ex vivo MRI and histopathology, both immediately and after 12 (7-17) days. Ethanol caused stellate lesions with patchy areas of normal myocardium, whereas acetic acid caused homogeneous circumscribed lesions of irreversible necrosis. Ischemic cardiomyopathy was created in 10 additional swine by subselective transcoronary ethanol administration into noncontiguous territories. After 12 (8-15) days, real-time MRI-guided chemoablation-with 2 to 5 injections to create a linear lesion-successfully eliminated the isthmus and local abnormal voltage activities. CONCLUSIONS: Real-time MRI-guided chemoablation with acetic acid enabled the intended arrhythmic substrate, whether deep or superficial, to be visualized immediately and ablated irreversibly. In an animal model of ischemic cardiomyopathy, obliteration of a conductive isthmus both anatomically and functionally and abolition of local abnormal voltage activities in areas of heterogeneous scar were feasible. This represents the first report of MRI-guided myocardial chemoablation, an approach that could improve the efficacy of arrhythmic substrate ablation in the thick ventricular myocardium.

Inverse relationship between fractionated electrograms and atrial fibrosis in persistent atrial fibrillation: combined magnetic resonance imaging and high-density mapping.

OBJECTIVES: This study sought to evaluate the relationship between fibrosis imaged by delayed-enhancement (DE) magnetic resonance imaging (MRI) and atrial electrograms (Egms) in persistent atrial fibrillation (AF). BACKGROUND: Atrial fractionated Egms are strongly related to slow anisotropic conduction. Their relationship to atrial fibrosis has not yet been investigated. METHODS: Atrial high-resolution MRI of 18 patients with persistent AF (11 long-lasting persistent AF) was registered with mapping geometry (NavX electro-anatomical system (version 8.0, St. Jude Medical, St. Paul, Minnesota)). DE areas were categorized as dense or patchy, depending on their DE content. Left atrial Egms during AF were acquired using a high-density, 20-pole catheter (514 ± 77 sites/map). Fractionation, organization/regularity, local mean cycle length (CL), and voltage were analyzed with regard to DE. RESULTS: Patients with long-lasting persistent versus persistent AF had larger left atrial (LA) surface area (134 ± 38 cm(2) vs. 98 ± 9 cm(2), p = 0.02), a higher amount of atrial DE (70 ± 16 cm(2) vs. 49 ± 10 cm(2), p = 0.01), more complex fractionated atrial Egm (CFAE) extent (54 ± 16 cm(2) vs. 28 ± 15 cm(2), p = 0.02), and a shorter baseline AF CL (147 ± 10 ms vs. 182 ± 14 ms, p = 0.01). Continuous CFAE (CFEmean [NavX algorithm that quantifies Egm fractionation] <80 ms) occupied 38 ± 19% of total LA surface area. Dense DE was detected at the left posterior left atrium. In contrast, the right posterior left atrium contained predominantly patchy DE. Most CFAE (48 ± 14%) occurred at non-DE LA sites, followed by 41 ± 12% CFAE at patchy DE and 11 ± 6% at dense DE regions (p = 0.005 and p = 0.008, respectively); 19 ± 6% CFAE sites occurred at border zones of dense DE. Egms were less fractionated, with longer CL and lower voltage at dense DE versus non-DE regions: CFEmean: 97 ms versus 76 ms, p < 0.0001; local CL: 153 ms versus 143 ms, p < 0.0001; mean voltage: 0.63 mV versus 0.86 mV, p < 0.0001. CONCLUSIONS: Atrial fibrosis as defined by DE MRI is associated with slower and more organized electrical activity but with lower voltage than healthy atrial areas. Ninety percent of continuous CFAE sites occur at non-DE and patchy DE LA sites. These findings are important when choosing the ablation strategy in persistent AF.

Functional nature of electrogram fractionation demonstrated by left atrial high-density mapping.

BACKGROUND: Complex fractionated atrial electrograms (CFAE) are targets of atrial fibrillation (AF) ablation. Serial high-density maps were evaluated to understand the impact of activation direction and rate on electrogram (EGM) fractionation. METHODS AND RESULTS: Eighteen patients (9 persistent) underwent high-density, 3-dimensional, left-atrial mapping (>400 points/map) during AF, sinus (SR), and CS-paced (CSp) rhythms. In SR and CSp, fractionation was defined as an EGM with ≥4 deflections, although, in AF, CFE-mean <80 ms was considered as continuous CFAE. The anatomic distribution of CFAE sites was assessed, quantified, and correlated between rhythms. Mechanisms underlying fractionation were investigated by analysis of voltage, activation, and propagation maps. A minority of continuous CFAE sites displayed EGM fractionation in SR (15+/-4%) and CSp (12+/-8%). EGM fractionation did not match between SR and CSp at 70+/-10% sites. Activation maps in SR and CSp showed that wave collision (71%) and regional slow conduction (24%) caused EGM fractionation. EGM voltage during AF (0.59+/-0.58 mV) was lower than during SR and CSp (>1.0 mV) at all sites. During AF, the EGM voltage was higher at continuous CFAE sites than at non-CFAE sites (0.53 mV (Q1, Q3: 0.33 to 0.83) versus 0.30 mV (Q1, Q3: 0.18 to 0.515), P<0.00001). Global LA voltage in AF was lower in patients with persistent AF versus patients with paroxysmal AF (0.6+/-0.59 mV versus 1.12+/-1.32 mV, P<0.01). CONCLUSIONS: The distribution of fractionated EGMs is highly variable, depending on direction and rate of activation (SR versus CSp versus AF). Fractionation in SR and CSp rhythms mostly resulted from wave collision. All sites with continuous fractionation in AF displayed normal voltage in SR, suggesting absence of structural scar. Thus, many fractionated EGMs are functional in nature, and their sites dynamic.

Is there a relationship between complex fractionated atrial electrograms recorded during atrial fibrillation and sinus rhythm fractionation?

BACKGROUND: Ablation of persistent atrial fibrillation (AF) may require adjunctive methods of substrate modification. Both ablation-targeting complex fractionated atrial electrograms (CFAEs) recorded during AF and fractionated electrograms recorded during sinus rhythm (sinus rhythm fractionation [SRF]) have been described. However, the relationship of CFAEs with SRF is unclear. METHODS: Twenty patients (age 62 ± 9 years, 13 males) with persistent AF and 9 control subjects without organic heart disease or AF (age 36 ± 6 years, 4 males) underwent detailed CFAE and SRF left atrial electroanatomic maps. The overlap in left atrial regions with CFAEs and SRF was compared in the AF population, and the distribution of SRF was compared among patients with AF and normal controls. Propagation maps were analyzed to identify the activation patterns associated with SR fractionation. RESULTS: SRF (338 ± 150 points) and CFAE (418 ± 135 points) regions comprised 29% ± 14% and 25% ± 15% of the left atrial surface area, respectively. There was no significant correlation between SRF and CFAE maps (r = .2; P = NS). On comparing patients with AF and controls, no significant difference was found in the distribution of SRF between groups (P = .74). Regions of SRF overlapped areas of wave-front collision 75% ± 13% of the time. CONCLUSIONS: (1) There is little overlap between regions of CFAEs during AF and regions of SRF measured in the time domain or the frequency domain, (2) the majority of SRF appears to occur in regions with wave-front collision, (3) the distribution of SRF is similar in patients with AF and normal controls, suggesting that this may not have an important role in AF maintenance and may not be a suitable ablation target.

Dynamically shaped magnetic fields: initial animal validation of a new remote electrophysiology catheter guidance and control system.

BACKGROUND: To address some of the shortcomings of existing remote catheter navigation systems (RNS), a new magnetic RNS has been developed that provides real-time navigation of catheters within the beating heart. The initial experience using this novel RNS in animals is described. METHODS AND RESULTS: A real-time, high-speed, closed-loop, magnetic RNS system (Catheter Guidance Control and Imaging) comprises 8 electromagnets that create unique dynamically shaped ("lobed") magnetic fields around the subject's torso. The real-time reshaping of these magnetic fields produces the appropriate 3D motion or change in direction of a magnetized electrophysiology ablation catheter within the beating heart. The RNS is fully integrated with the Ensite-NavX 3D electroanatomic mapping system (St Jude Medical) and allows for both joystick and automated navigation. Conventional and remote navigational mapping of the left atrium were performed using a 4-mm-tip ablation catheter in 10 pigs. A multielectrode transseptal sheath allowed for additional motion compensation. Linear and circumferential radiofrequency lesion sets were performed; in a subset of cases, selective pulmonary vein isolation was also performed. Recording and fluoroscopic equipments were unaffected by the magnetic fields generated by Catheter Guidance Control and Imaging. Automated mode navigation was highly reproducible (96±8.4% of attempts), accurate (1.9±0.4 mm from target site), and rapid (11.6±3.5 seconds to reach targets). At postmortem examination, radiofrequency lesion depth was 78.5±12.1% of atrial wall thickness. CONCLUSIONS: A new magnetic RNS using a dynamically shaped magnetic field concept can reproducibly and effectively reach target radiofrequency ablation points within the pig left atrium. Validation of the system in clinical settings is under way.

Mechanism of complex fractionated electrograms recorded during atrial fibrillation in a canine model.

BACKGROUND: Complex fractionated atrial electrograms (CFEs) have been described as a target during atrial fibrillation (AF) ablation; however, the mechanism leading to CFEs is poorly understood. We used noncontact mapping in a canine model of AF to determine the activation patterns in areas of CFEs. METHODS: Sustained AF was induced in 10 canines with 10-12 weeks of atrial tachy-pacing at 440 ppm. A roving mapping catheter and noncontact multielectrode array (MEA) were deployed in the left atrium (LA). NavX software was used to construct a contact bipolar CFE LA map. The MEA was then used to reconstruct wavefront propagation in proximity to CFE regions. Wavefront propagation was assessed during three separate recording segments for each site. RESULTS: There were 34 CFE regions identified (3.4/dog) and 102 noncontact CFE regional activation sequences studied. The CFE regions were stereotypically located at the junctions of (1) the left pulmonary vein (PV)/posterior LA, (2) right inferior PV/posterior LA, (3) right superior PV/anterior LA, and (4) the LA roof. The majority (47%) of CFE recordings were characterized by wavefront collision, usually between circulating LA wavefronts and entry/exit from the PVs. Thirty-eight (38%) CFE recordings were noted to be the central functional barrier of a reentrant wavefront. Ablation through CFE regions due to reentry led to AF termination and noninducibility in 3/5 animals. CONCLUSIONS: In this pacing-induced AF model, common causes of CFEs include: (1) wavefront collision, (2) conduction through channels of functional block, (3) reentry. The vast majority of these CFE regions were caused by wavefront collision rather than true "drivers" of AF.

Impact of pharmacological autonomic blockade on complex fractionated atrial electrograms.

INTRODUCTION: The influence of the autonomic nervous system on the pathogenesis of complex fractionated atrial electrograms (CFAE) during atrial fibrillation (AF) is incompletely understood. This study evaluated the impact of pharmacological autonomic blockade on CFAE characteristics. METHODS AND RESULTS: Autonomic blockade was achieved with propanolol and atropine in 29 patients during AF. Three-dimensional maps of the fractionation degree were made before and after autonomic blockade using the Ensite Navx system. In 2 patients, AF terminated following autonomic blockade. In the remaining 27 patients, 20,113 electrogram samples of 5 seconds duration were collected randomly throughout the left atrium (10,054 at baseline and 10,059 after autonomic blockade). The impact of autonomic blockade on fractionation was assessed by blinded investigators and related to the type of AF and AF cycle length. Globally, CFAE as a proportion of all atrial electrogram samples were reduced after autonomic blockade: 61.6 +/- 20.3% versus 57.9 +/- 23.7%, P = 0.027. This was true/significant for paroxysmal AF (47 +/- 23% vs 40 +/- 22%, P = 0.003), but not for persistent AF (65 +/- 22% vs 62 +/- 25%, respectively, P = 0.166). Left atrial AF cycle length prolonged with autonomic blockade from 170 +/- 33 ms to 180 +/- 40 ms (P = 0.001). Fractionation decreases only in the 14 of 27 patients with a significant (>6 ms) prolongation of the AF cycle length (64 +/- 20% vs 59 +/- 24%, P = 0.027), whereas fractionation did not reduce when autonomic blockade did not affect the AF cycle length (58 +/- 21% vs 56 +/- 25%, P = 0.419). CONCLUSIONS: Pharmacological autonomic blockade reduces CFAE in paroxysmal AF, but not persistent AF. This effect appears to be mediated by prolongation of the AF cycle length.

Balloon catheter ablation to treat paroxysmal atrial fibrillation: what is the level of pulmonary venous isolation?

BACKGROUND: Unlike the initial balloon ablation catheters that were designed to deliver ablation lesions within the pulmonary veins (PVs), the current balloon prototypes are fashioned to deliver lesions at the PV ostia. OBJECTIVE: Using electroanatomical mapping, this study evaluates the actual location of ablation lesions generated by cryo-based, laser-based, or ultrasound-based balloon catheters. METHODS: In a total of 14 patients with paroxysmal atrial fibrillation, PV isolation was performed using either a cryoballoon catheter (8 patients), laser catheter (4 patients) or ultrasound balloon catheter (2 patients). Patients underwent preprocedural computed tomographic/magnetic resonance imaging. An intracardiac ultrasound catheter was used to aid in positioning the balloon catheter at the PV ostium/antrum. In all patients, sinus rhythm bipolar voltage amplitude maps (using either CARTO with computed tomographic/magnetic resonance image integration or NavX mapping) were generated at baseline and after electrical PV isolation as confirmed by use of a circular mapping catheter. RESULTS: Electrical isolation was achieved in 100% of the PVs. Electroanatomical mapping revealed that after ablation with any of the 3 balloon catheters, the extent of isolation included the tubular portions of each PV to the level of the PV ostia. However, the PV antral portions were left largely unablated with all 3 balloon technologies. CONCLUSION: Using the current generation of balloon ablation catheters, electrical isolation occurs at the level of the PV ostia, but the antral regions are largely unablated.

Atrial tachycardia after ablation of persistent atrial fibrillation: identification of the critical isthmus with a combination of multielectrode activation mapping and targeted entrainment mapping.

BACKGROUND: Atrial tachycardia (AT) that develops after ablation of atrial fibrillation often poses a more difficult clinical situation than the index arrhythmia. This study details the use of an impedance-based electroanatomic mapping system (Ensite NavX) in concert with a specialized multielectrode mapping catheter for rapid, high-density atrial mapping. In this study, this activation mapping was combined with entrainment mapping to eliminate ATs developing late after atrial fibrillation ablation. METHODS AND RESULTS: All study patients developed AT after ablation for atrial fibrillation. The approach to AT ablation consisted of 4 steps: use of a 20-pole penta-array catheter to map the chamber rapidly during the rhythm of interest, analysis of the patterns of atrial activation to identify wave fronts of electric propagation, targeted entrainment at putative channels, and catheter ablation at these "isthmuses." All ablations were performed with irrigated radiofrequency ablation catheters. Forty-one ATs were identified in 17 patients (2.4+/-1.6 ATs per patient). Using the multielectrode catheter in conjunction with the Ensite NavX system, we created activation maps of 33 of 41 ATs (81%) (mean cycle length, 284+/-71 seconds) with a mean of 365+/-108 points per map and an average mapping time of 8+/-3 minutes. Of the 33 mapped ATs, 7 terminated either spontaneously or during entrainment maneuvers. Radiofrequency energy was used to attempt ablation of 26 ATs; 25 of 26 of the ATs (96%) were terminated successfully by ablation or catheter pressure. CONCLUSIONS: This study demonstrates a strategy for rapidly defining and eliminating the scar-related ATs typically encountered after ablation of atrial fibrillation.