Abstract-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. (Circ Res. 2007;101:e103-e112.)

Confocal microscopy enables constitutive elements of cells and tissues to be viewed at high resolution and reconstructed in three dimensions, but is constrained by the limited extent of the volumes that can be imaged. We have developed an automated technique that enables serial confocal images to be acquired over large tissue areas and volumes. The computer-controlled system, which integrates a confocal microscope and an ultramill using a high-precision translation stage, inherently preserves specimen registration, and the user control interface enables flexible specification of imaging protocols over a wide range of scales and resolutions. With this system it is possible to reconstruct specified morphological features in three dimensions and locate them accurately throughout a tissue sample. We have successfully imaged various samples at 1-mum voxel resolution on volumes up to 4 mm3 and on areas up to 75 mm2. Used in conjunction with appropriate embedding media and immuno-histochemical probes, the techniques described in this paper make it possible to routinely map the distributions of key intracellular structures over much larger tissue domains than has been easily achievable in the past.

OBJECTIVES This study sought to assess the relationship between fibrosis and re-entrant activity in persistent atrial fibrillation (AF). BACKGROUND The mechanisms involved in sustaining re-entrant activity during AF are poorly understood. METHODS Forty-one patients with persistent AF (age 56 ± 12 years; 6 women) were evaluated. High-resolution electrocardiographic imaging (ECGI) was performed during AF by using a 252-chest electrode array, and phase mapping was applied to locate re-entrant activity. Sites of high re-entrant activity were defined as re-entrant regions. Late gadolinium-enhanced (LGE) cardiac magnetic resonance (CMR) was performed at 1.25 × 1.25 × 2.5 mm resolution to characterize atrial fibrosis and measure atrial volumes. The relationship between LGE burden and the number of re-entrant regions was analyzed. Local LGE density was computed and characterized at re-entrant sites. All patients underwent catheter ablation targeting re-entrant regions, the procedural endpoint being AF termination. Clinical, CMR, and ECGI predictors of acute procedural success were then analyzed. RESULTS Left atrial (LA) LGE burden was 22.1 ± 5.9% of the wall, and LA volume was 74 ± 21 ml/m2. The number of re-entrant regions was 4.3 ± 1.7 per patient. LA LGE imaging was significantly associated with the number of re-entrant regions (R = 0.52, p = 0.001), LA volume (R = 0.62, p < 0.0001), and AF duration (R = 0.54, p = 0.0007). Regional analysis demonstrated a clustering of re-entrant activity at LGE borders. Areas with high re-entrant activity showed higher local LGE density as compared with the remaining atrial areas (p < 0.0001). Failure to achieve AF termination during ablation was associated with higher LA LGE burden (p < 0.001), higher number of re-entrant regions (p < 0.001), and longer AF duration (p = 0.008). CONCLUSIONS The number of re-entrant regions during AF relates to the extent of LGE on CMR, with the location of these regions clustering to LGE areas. These characteristics affect procedural outcomes of ablation.

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 Ϸ4ϫ4ϫ1-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 0.67Ϯ0.019 ms Ϫ1 was aligned with the myofiber axis. However, transverse to this, the maximum conduction velocity was 0.30Ϯ0.010 ms Ϫ1, parallel to the myocyte layers and 0.17Ϯ0.004 ms Ϫ1 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. (Circ Arrhythmia Electrophysiol. 2009;2:433-440.)Key Words: anisotropy Ⅲ mapping Ⅲ structure Ⅲ computer modeling Ⅲ intramural pacing A ccurate information about the electric properties of cardiac tissue is central to understanding the biophysical basis of normal and aberrant heart rhythm. Electric anisotropy influences the spread of activation in the heart, plays a critical role both in the initiation and maintenance of reentrant arrhythmia, and is an important determinant of the effectiveness of cardioversion. Knowledge of the nature and extent of electric anisotropy is required for computer models of heart activation that provide a means of probing intramural electric behavior that cannot be accessed from clinical and experimental measurements made on the surfaces of the heart. Clinical Perspective on p 440Normal ventricular myocardium is generally thought to function as a syncytium in which side-to-side electric coupling between adjacent myocytes is uniform. 1,2 The electric properties of ventricular myocardium are assumed to be axially anisotropic with respect to the local myofiber axis, 1,2 with activation propagating most rapidly in the myofiber direction and at uniform velocity in planes transverse to this.This view is not consistent with the laminar model of ventricular myocardium t...

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.

Heart surface optical mapping of transmembrane potentials has been widely used in studies of normal and pathological heart rhythms and defibrillation. In these studies, three-dimensional spatio-temporal events can only be inferred from two-dimensional surface potential maps. We present a novel optical system that enables high fidelity transmural recording of transmembrane potentials. A probe constructed from optical fibers is used to deliver excitation light and collect fluorescence from seven positions, each 1 mm apart, through the left ventricle wall of the rabbit heart. Excitation is provided by the 488-nm line of a water-cooled argon-ion laser. The fluorescence of the voltage-sensitive dye di-4-ANEPPS from each tissue site is split at 600 nm and imaged onto separate photodiodes for later signal ratioing. The optics and electronics are easily expandable to accommodate multiple optical probes. The system is used to record the first simultaneous measurements of transmembrane potential at a number of sites through the intact heart wall.

Multipolar mapping catheters with small electrodes provide more accurate and higher density maps, with a higher sensitivity to near-field signals. Agreement between PR and NAV is low.

Background— During the past years, many innovations have been introduced to facilitate catheter ablation of post–myocardial infarction ventricular tachycardia. However, the predictors of outcome after ablation were not thoroughly studied. Methods and Results— From 2009 to 2013, consecutive patients referred for post–myocardial infarction ventricular tachycardia ablation were included. The end point of the procedure was complete elimination of local abnormal ventricular activities (LAVA) and ventricular tachycardia (VT) noninducibility. The predictors of outcome with primary end point of VT recurrence were assessed. A total of 125 patients were included (age: 64±11 years; 7 women) for 142 procedures. The left ventricle was accessed via transseptal, retrograde aortic, and epicardial approaches in 87%, 33%, and 37% of patients, respectively. Three-dimensional electroanatomical mapping system was used in 70%, multipolar catheter in 51%, and real-time image integration in 38% (from magnetic resonance imaging in 39% and multidetector computed tomography in 93%) of patients. Before ablation, VT was inducible in 75%, and endocardial/epicardial LAVA were present in 88%/75%. After ablation, complete LAVA elimination was achieved in 60%, and VT noninducibility in 83%. During a median follow-up of 850 days (interquartile range, 439–1707), VT recurrence was observed in 36%. Multivariable analysis identified 3 independent outcome predictors: the ability to achieve complete LAVA elimination ( R 2 =0.29; P <0.0001; risk ratio=0.52 [0.38–0.70]), the use of real-time image integration ( R 2 =0.21; P =0.0006; risk ratio=0.49 [0.33–0.74]), and the use of multipolar catheters ( R 2 =0.08; P =0.05; risk ratio=0.75 [0.56–1.00]). Conclusions— Achievement of complete LAVA elimination and use of scar integration from imaging and multipolar catheters to focus high-density mapping are independent predictors of VT-free survival after catheter ablation for post–myocardial infarction ventricular tachycardia.