A Novel Visually Guided Radiofrequency Balloon Ablation Catheter for Pulmonary Vein Isolation: One-Year Outcomes of the Multicenter AF-FICIENT I Trial.

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Automated rhythm-based control of radiofrequency ablation close to the atrioventricular node: Preclinical, animal, and first-in-human testing.

BACKGROUND: The risk of heart block during radiofrequency ablation of atrioventricular (AV) nodal reentrant tachycardia and septal accessory pathways is minimized by rapidly ceasing ablation in response to markers of risk, such as atrioventricular dissociation, fast junctional rhythm, PR interval prolongation, or 2 consecutive atrial or ventricular depolarizations. Currently this is done manually. OBJECTIVES: The objectives of this study were to build and test a control system able to monitor cardiac rhythm and automatically terminate ablation energy when required. METHODS: The device was built from off-shelf componentry. Preclinical testing involved real-time input of electrogram/electrocardiogram data from 209 ablation procedures (20 patients) over slow (n = 19) and fast (n = 1) AV nodal pathways. The device response speed was compared with the human response speed. The device's ability to prevent heart block was tested in 5 sheep. First-in-human testing was then performed in 12 patients undergoing AV nodal reentrant tachycardia ablation. RESULTS: Risk conditions necessitating shutoff of ablation (200 total; 111 preclinical and 89 first-in-human) were detected by the device with 100% sensitivity and 94% specificity, automatically terminating ablation while still allowing successful ablation in all patients. Device shutoff of ablation was always faster than human response (median difference 1.24 seconds). In each of 5 sheep, 40 consecutive attempts to cause heart block by ablating over the His bundle were unsuccessful because of automatic shutoff in response to rhythm change. CONCLUSION: Automated shutoff of ablation close to the AV node in response to markers of the risk of heart block is feasible with high accuracy as well as faster response than human response. The system may improve the safety of ablation near the AV node by preventing heart block.

High-density contact and noninvasive mapping of focal atrial tachycardia: Evidence of dual endocardial exits from an epicardial focus.

We report a case of recurrent focal atrial tachycardia (AT) which mechanisms could be resolved by using noninvasive electrocardiographic imaging (ECGI) reconstructing epicardial potentials and rapid high-density endocardial contact mapping (Rhythmia™, Boston Scientific, Natick, MA, USA). ECGI demonstrated focal activity from the anterior of the left superior pulmonary vein antrum, although Rhythmia™ showed focal activity from the high anterior left atrium with the 2nd focus originating from the site where identical to the focus on the ECGI map with slightly delay (by 8 ms). Elimination of the AT by radiofrequency applications for both of the endocardial focuses indicated the dual endocardial exits from an epicardial focus.

Atrial tachycardias: Cause or effect with ablation of persistent atrial fibrillation?

INTRODUCTION: It is largely believed that atrial tachycardias (ATs) encountered during ablation of persistent atrial fibrillation (PsAF) are a byproduct of ablative lesions. We aimed to explore the alternative hypothesis that they may be a priori drivers of AF remaining masked until other AF sources are reduced or eliminated. METHODS AND RESULTS: Radiofrequency ablation of fibrillatory drivers mapped by electrocardiographic imaging (ECGI; ECVUE™, Cardioinsight Technologies, Cleveland, OH, USA) terminated PsAF in 198 (73%) out of 270 patients (61 ± 10 years, 9 ± 9 m). Two hundred and six ATs in 158 patients were subsequently mapped. Their anatomic relationship to the fibrillatory drivers prospectively identified by ECGI was then established. There were 26 (13%), 52 (25%), and 128 (62%) focal, localized, and macrore-entrant ATs, respectively. In focal/localized re-entrant ATs, 64 (82%) were terminated within an AF-driver region, in which 26 (81%) among 32 focal/localized ATs analyzed with 3-D-mapping system merged to driver map occurred from AF-driver regions in 1.0 ± 1.0 cm distance from the driver core. Importantly, there was no attempt at ablation of the associated AF-driver region in 25 of 64 (39%) of focal/localized re-entrant ATs. The sites of ATs origin generally had low-voltage, fractionated, and long-duration electrograms in AF. All but two focal/localized re-entrant ATs were successfully ablated. CONCLUSION: The majority of post-AF-ablation focal and localized re-entrant ATs originate from the region of prospectively established AF-driver regions. A third of these are localized to regions not subsequently submitted to ablation. These data suggest that many ATs exist, although not necessarily manifest independently, prior to ablation. They may have a role in the maintenance of PsAF in these individuals.

Myocardial wall thinning predicts transmural substrate in patients with scar-related ventricular tachycardia.

BACKGROUND: Scar-related ventricular tachycardia (VT) arises from specific substrate according to etiology. OBJECTIVE: The purpose of this study was to evaluate the relationship between wall thinning (WT) on multidetector computed tomography (MDCT) and local abnormal ventricular activity (LAVA) in patients with ischemic cardiomyopathy (ICM), postmyocarditis (PMC), and dilated cardiomyopathy (DCM). METHODS: Forty-two patients (40 male, age 58 ± 13 years, 22 ICM, 11 PMC, 9 DCM) underwent MDCT before a combined endo-/epicardial VT ablation procedure. WT (<5 mm) and severe wall thinning (SWT) (<2 mm) area on MDCT were compared to the prevalence of endo-/epicardial LAVA during sinus rhythm. RESULTS: WT and SWT were found on MDCT in 36 (86%) and 20 (48%) with 42 ± 37 cm2 and 26 ± 24 cm2, respectively. SWT was frequently detected in ICM (ICM 77% vs PMC 27% vs DCM 0%, P <.001). LAVA were frequently observed on the endocardium in ICM and on the epicardium in PMC. Endo-/epicardial facing LAVA were frequently found within SWT areas (91% in <2 mm, 9% in 2-5 mm, and 0% in >5 mm, P < .001). In SWT areas, the presence of endocardial LAVA in ICM and epicardial LAVA in PMC predicted opposite facing LAVA with sensitivity and specificity of 78% and 48% and 79% and 98%, respectively. SWT predicted epicardial LAVA in ICM and endocardial LAVA in PMC with sensitivity and specificity of 89% and 100%, and 100% and 100%, respectively. CONCLUSION: SWT is frequently found in ICM and PMC but is not common in DCM. SWT predicts LAVA on the opposite side of the wall (epicardial in ICM and endocardial in PMC), indicating transmural VT substrate. MDCT is useful for identifying VT substrate and helpful for understanding the mechanisms of the location of VT substrate domain.

Characterization of repolarization in Brugada syndrome patients during exercise testing: Dynamic angle evaluation.

BACKGROUND: A new ECG criterion has been studied in Brugada syndrome (BrS) at rest to differentiate type 2 and incomplete right bundle branch block (IRBBB). METHODS: We assessed this criterion during exercise comparing BrS (46 patients) and IRBBB (17 patients). A beta angle was measured from lead V1 between the upslope of S-wave and the downslope of the r'-wave. RESULTS: Beta angle was significantly larger in BrS at rest (58±24° vs 25±15°, p<0.001), exercise (47±26° vs 15±11°, p<0.001), and recovery (46±24° vs 21±12°, p<0.001) with a reduction in angle at exercise compared to rest. There was a significant rebound in angle at recovery in the control group to (p<0.001); no such rebound was observed in the BrS group (p=NS). CONCLUSION: Beta angle study at rest and its evolution at exercise could help discriminate BrS patients from healthy subjects.

nMARQ Ablation for Atrial Fibrillation: Results from a Multicenter Study.

BACKGROUND: nMARQ is a multipolar catheter designed to simultaneously ablate at multiple sites around the pulmonary vein (PV) circumference with a single radiofrequency application. We sought to define the safety and efficacy of atrial fibrillation (AF) ablation with the nMARQ catheter. METHODS: In a multicenter study, patients with drug-refractory AF were included. Procedural outcomes were documented at 1 year. RESULTS: 374 patients underwent PV isolation using nMARQ (age 60 ± 10 years, 264 male), of whom 263 patients had paroxysmal AF (PAF), while 111 patients had persistent AF. A total of 1,468 of 1,474 veins (99.6%) were isolated with the nMARQ catheter alone. Thirty-five (13%) PAF patients and 30 (27%) persistent AF patients underwent additional ablation at non-PV sites (2.4 ± 1.4 non-PV sites). Procedure time for PV isolation only was 1.9 ± 0.7 hours (fluoroscopy 24 ± 14 minutes). Procedure time for PV isolation and non-PV ablation was 2.4 ± 1.0 hours (fluoroscopy 30 ± 23 minutes). Major adverse events occurred in two patients (0.5%); one esophago-pericardial fistula and a second, mortality due to sepsis of unknown cause. One-year follow-up data were available in 65 (25%) PAF and 20 (18%) persistent AF patients. Forty-two (65%) PAF and 13 (65%) persistent AF patients were free of arrhythmia at 1 year. In patients undergoing repeat procedures (n = 17) the most frequent points of PV reconnection were: anterior RSPV, inferior RIPV, and superior LSPV. CONCLUSIONS: AF ablation with nMARQ is associated with short procedure times and high acute success rates. Further research is necessary to more clearly define long-term outcome.

New strategies for ventricular tachycardia and ventricular fibrillation ablation.

Patients with ventricular tachycardia (VT) and ventricular fibrillation (VF) and no reversible cause are difficult to treat. While implantable defibrillators prolong survival, many patients remain symptomatic due to device shocks and syncope. To address this, there have been recent advances in the catheter ablation of VT and VF. For example, non-invasive imaging has improved arrhythmia substrate characterisation, 3D catheter navigation tools have facilitated mapping of arrhythmia and substrate and ablation catheters have advanced in their ability to deliver effective lesions. However, the long-term success rates of ablation for VT and VF remain modest, with nearly half of treated patients developing recurrence within 2-3 years, and this drives the ongoing innovation in the field. This review focuses on the challenges particular to ablation of life-threatening ventricular arrhythmia, and the strategies that have been recently developed to improve procedural efficacy. Patient sub-groups that illustrate the use of new strategies are described.

History and clinical significance of early repolarization syndrome.

The early repolarization (ER) pattern has historically been regarded as a benign ECG variant. However, in recent years this view has been challenged based on multiple reports linking the ER pattern with an increased risk of sudden cardiac death. The mechanistic basis of ventricular arrhythmogenesis in ER syndrome is presently incompletely understood. Furthermore, strategies for risk stratification and therapy for ER syndrome remain suboptimal. The recent emergence of novel mapping techniques for cardiac arrhythmia has ushered a new era of research into the mechanistic basis of ER syndrome. This review provides an overview of current evidence relating to ER and risk of ventricular arrhythmias and discusses potential future areas of research to elucidate the mechanisms of ventricular arrhythmogenesis.

Three distinct directions of intramural activation reveal nonuniform side-to-side electrical coupling of ventricular myocytes.

BACKGROUND: The anisotropy of cardiac tissue is a key determinant of 3D electric propagation and the stability of activation wave fronts in the heart. The electric properties of ventricular myocardium are widely assumed to be axially anisotropic, with activation propagating most rapidly in the myofiber direction and at uniform velocity transverse to this. We present new experimental evidence that contradicts this view. METHODS AND RESULTS: For the first time, high-density intramural electric mapping (325 electrodes at approximately 4x4x1-mm spacing) from pig left ventricular tissue was used to reconstruct 3D paced activation surfaces projected directly onto 3D tissue structure imaged throughout the same left ventricular volume. These data from 5 hearts demonstrate that ventricular tissue is electrically orthotropic with 3 distinct propagation directions that coincide with local microstructural axes defined by the laminar arrangement of ventricular myocytes. The maximum conduction velocity of 0.67+/-0.019 ms(-1) was aligned with the myofiber axis. However, transverse to this, the maximum conduction velocity was 0.30+/-0.010 ms(-1), parallel to the myocyte layers and 0.17+/-0.004 ms(-1) normal to them. These orthotropic conduction velocities give rise to preferential activation pathways across the left ventricular free wall that are not captured by structurally detailed computer models, which incorporate axially anisotropic electric properties. CONCLUSIONS: Our findings suggest that current views on uniform side-to-side electric coupling in the heart need to be revised. In particular, nonuniform laminar myocardial architecture and associated electric orthotropy should be included in future models of initiation and maintenance of ventricular arrhythmia.

Construction and validation of a plunge electrode array for three-dimensional determination of conductivity in the heart.

The heart's response to electrical shock, electrical propagation in sinus rhythm, and the spatiotemporal dynamics of ventricular fibrillation all depend critically on the electrical anisotropy of cardiac tissue. Analysis of the microstructure of the heart predicts that three unique intracellular electrical conductances can be defined at any point in the ventricular wall; however, to date, there has been no experimental confirmation of this concept. We report the design, fabrication, and validation of a novel plunge electrode array capable of addressing this issue. A new technique involving nylon coating of 24G hypodermic needles is performed to achieve nonconductive electrodes that can be combined to give moderate-density multisite intramural measurement of extracellular potential in the heart. Each needle houses 13 silver wires within a total diameter of 0.7 mm, and the combined electrode array gives 137 sites of recording. The ability of the electrode array to accurately assess conductances is validated by mapping the potential field induced by a point current source within baths of saline of varying concentration. A bidomain model of current injection in the heart is then used to test an approximate relationship between the monodomain conductivities measured by the array, and the full set of bidomain conductivities that describe cardiac tissue.

Laminar arrangement of ventricular myocytes influences electrical behavior of the heart.

The response of the heart to electrical shock, electrical propagation in sinus rhythm, and the spatiotemporal dynamics of ventricular fibrillation all depend critically on the electrical anisotropy of cardiac tissue. A long-held view of cardiac electrical anisotropy is that electrical conductivity is greatest along the myocyte axis allowing most rapid propagation of electrical activation in this direction, and that conductivity is isotropic transverse to the myocyte axis supporting a slower uniform spread of activation in this plane. In this context, knowledge of conductivity in two directions, parallel and transverse to the myofiber axis, is sufficient to characterize the electrical action of the heart. Here we present new experimental data that challenge this view. We have used a novel combination of intramural electrical mapping, and experiment-specific computer modeling, to demonstrate that left ventricular myocardium has unique bulk conductivities associated with three microstructurally-defined axes. We show that voltage fields induced by intramural current injection are influenced by not only myofiber direction, but also the transmural arrangement of muscle layers or myolaminae. Computer models of these experiments, in which measured 3D tissue structure was reconstructed in-silico, best matched recorded voltages with conductivities in the myofiber direction, and parallel and normal to myolaminae, set in the ratio 4:2:1, respectively. These findings redefine cardiac tissue as an electrically orthotropic substrate and enhance our understanding of how external shocks may act to successfully reset the fibrillating heart into a uniform electrical state. More generally, the mechanisms governing the destabilization of coordinated electrical propagation into ventricular arrhythmia need to be evaluated in the light of this discovery.

Illumination and fluorescence collection volumes for fiber optic probes in tissue.

Optical fibers can deliver light to, and collect it from, regions deep in tissue. However, reported illumination and fluorescence collection volumes adjacent to the fiber tip have been inconsistent, and systematic data on this topic are not available. Illumination and fluorescence collection profiles were characterized with high spatial resolution for different optical fibers in tissue and various fluids using two-photon flash photolysis and excitation. We confirm that illumination and fluorescence collection volumes for optical fibers are near identical. Collection volume is determined by the core dimensions and numerical aperture (NA) of the fiber and the scattering properties of the medium. For a multimode optical fiber with 100 microm core diam and NA=0.22, 80% of the total fluorescence is collected from a depth of 170 microm in tissue and 465 microm in nonscattering fluid. A semiempirical mathematical description of photon flux adjacent to the fiber tip was also developed and validated. This was used to quantify the extent of temporal blurring associated with propagation of a wavefront of altered fluorescence emission across the region addressed by fiber optic probes. We provide information that will facilitate the design of optical probes for tissue imaging or therapeutic applications.

Myocardial segment-specific model generation for simulating the electrical action of the heart.

BACKGROUND: Computer models of the electrical and mechanical actions of the heart, solved on geometrically realistic domains, are becoming an increasingly useful scientific tool. Construction of these models requires detailed measurement of the microstructural features which impact on the function of the heart. Currently a few generic cardiac models are in use for a wide range of simulation problems, and contributions to publicly accessible databases of cardiac structures, on which models can be solved, remain rare. This paper presents to-date the largest database of porcine left ventricular segment microstructural architecture, for use in both electrical and mechanical simulation. METHODS: Cryosectioning techniques were used to reconstruct the myofibre and myosheet orientations in tissue blocks of size ~15 x 15 x 15 mm, taken from the mid-anterior left ventricular freewall, of seven hearts. Tissue sections were gathered on orthogonal planes, and the angles of intersection of myofibres and myosheets with these planes determined automatically with a gradient intensity based algorithm. These angles were then combined to provide a description of myofibre and myosheet variation throughout the tissue, in a form able to be input to biophysically based computational models of the heart. RESULTS: Several microstructural features were common across all hearts. Myofibres rotated through 141 +/- 18 degrees (mean +/- SD) from epicardium to endocardium, in near linear fashion. In the outer two-thirds of the wall sheet angles were predominantly negative, however, in the inner one-third an abrupt change in sheet angle, with reversal in sign, was seen in six of the seven hearts. Two distinct populations of sheets with orthogonal orientations often co-existed, usually with one population dominating. The utility of the tissue structures was demonstrated by simulating the passive and active electrical responses of two of the tissue blocks to current injection. Distinct patterns of electrical response were obtained in the two tissue blocks, illustrating the importance of testing model based predictions on a variety of tissue architectures. CONCLUSION: This study significantly expands the set of geometries on which models of cardiac function can be solved.

Modeling cardiac electrical activity at the cell and tissue levels.

Significant tissue structures exist in cardiac ventricular tissue, which are of supracellular dimension. It is hypothesized that these tissue structures contribute to the discontinuous spread of electrical activation, may contribute to arrhythmogenesis, and also provide a substrate for effective cardioversion. However, the influences of these mesoscale tissue structures in intact ventricular tissue are difficult to understand solely on the basis of experimental measurement. Current measurement technology is able to record at both the macroscale tissue level and the microscale cellular or subcellular level, but to date it has not been possible to obtain large volume, direct measurements at the mesoscales. To bridge this scale gap in experimental measurements, we use tissue-specific structure and mathematical modeling. Our models, which can incorporate ion channel models at the cell level into the reaction-diffusion equations at the tissue level, have enabled us to consider key hypotheses regarding discontinuous activation.

Do intramural virtual electrodes facilitate successful defibrillation? Model-based analysis of experimental evidence.

INTRODUCTION: Recent computer model and experimental studies have suggested that microscopic intramural collagenous planes may facilitate successful defibrillation through the generation of shock-induced virtual electrodes deep within the ventricular wall. Evidence supporting the existence of intramural virtual electrodes has been drawn from several recent studies, which map shock-induced membrane potential (Vm) over the cut transmural surface of dissected segments of porcine left ventricle (LV). The artificially created transmural boundary in these experiments is impermeable to intracellular current. It is not known how this constraint limits the interpretation of these experiments in terms of the shock response of the intact ventricle. METHODS AND RESULTS: This study uses a realistic 3D computer model of LV myocardium to aid experimental interpretation. The model incorporates a microstructural description of intramural cleavage plane discontinuities measured by confocal microscopy of rat LV. Electrical shocks are applied across the model tissue, with and without introduced transmural boundaries. Shocks of varying strength (4-40 V/cm) are also applied to the model and the response analyzed. Results show that shock-induced Vm changes (deltaVm) on a transmural tissue boundary are significantly different to deltaVm of the intact ventricle, and the extent of difference depends on boundary orientation. However, the presence and qualitative behavior of intramural virtual electrodes is preserved irrespective of boundary placement. The model also confirms experimental observations that most rapid transmural activation occurs for shocks of strength 5-10 V/cm. Two distinct mechanisms suppress virtual electrode propagation, and hence slow tissue activation, outside of this optimal shock strength range. CONCLUSIONS: This study supports the hypothesis that distributed microscopic intramural virtual electrodes contribute to rapid activation of the ventricular wall during defibrillation.