Development of an automaton model of rotational activity driving atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is difficult to treat effectively, owing to uncertainty in where to best ablate to eliminate arrhythmogenic substrate. A model providing insight into the electrical activation events would be useful to guide catheter ablation strategy. Method A two-dimensional, 576×576 node automaton was developed to simulate atrial electrical activity. The substrate field was altered by the presence of differing refractory period at varying locations. Fibrosis was added in the form of short, randomly positioned lines of conduction block. Larger areas of block were used to simulate ablation lesions. Anisotropy was imposed in a 2:1 ratio. A premature electrical impulse from one of four grid corners was utilized to initiate activation. RESULTS: Rotational activity was uninducible when refractory patch dimensions were less than 20×20mm. For larger refractory regions, a single premature stimulus was capable of inducing an average of 1.19±1.10 rotors, which often formed near the patch edges. A maximum of 5 rotors formed when refractory patch dimensions approached the size of the entire left atrial virtual field. Rotors formed along a refractory patch edge, after wavefront arrival was delayed at turning points or due to the presence of a fiber cluster of sufficient size. However, rotational activity could also occur around a large fiber cluster without the need of spatially variable refractoriness. When obstacles to conduction were lacking in size, nascent rotors drifted and either extinguished, or stabilized upon anchoring at a sufficiently large fiber cluster elsewhere in the field. Transient rotors terminated when traversing a region with differing refractory periods, if no obstacle to conduction was present to sufficiently delay wavefront arrival beyond the longest refractory period. Other rotors were annihilated when a nearby rotor with faster spin rate gradually interrupted the activation pathway. Elimination of anchors by removal, or by simulated ablation over a sufficient region, prevented rotor onset at a particular location where it would otherwise form. CONCLUSIONS: The presence of obstacles to conduction and spatial differences in refractory period are important parameters for initiating and maintaining rotational activity in this simulation of an atrial substrate.

Living with coeliac disease: survey results from the U.S.A.

BACKGROUND: The only treatment for coeliac disease is lifelong adherence to a rigorous gluten-free diet. The present study aimed to evaluate the influence of coeliac disease on the social aspects of daily life of individuals in the U.S.A. METHODS: The present study used a self-administered survey including the standard Quality of Life questionnaire (12-item short-form) with validated disease-specific questions. sas statistical software 2010 (SAS Institute, Cary, NC, U.S.A.) was used to calculate the mean (SD). RESULTS: Individuals with coeliac disease overall had a low positive health perception. Validated diet and disease-specific questions revealed a significant negative impact on quality of life in social settings. Specifically, the areas of travel, dining out and family life are most affected. The negative impact of diet significantly decreased over time, although it did not resolve for the domains of dining out of the home and travel. Those diagnosed in childhood and maintained on the diet had less of an impact on the quality of life as an adult. CONCLUSIONS: Individuals with coeliac disease in the U.S.A. have a diminished quality of life, especially in the social aspects of life.

High-density substrate mapping in Brugada syndrome: combined role of conduction and repolarization heterogeneities in arrhythmogenesis.

BACKGROUND: Two principal mechanisms are thought to be responsible for Brugada syndrome (BS): (1) right ventricular (RV) conduction delay and (2) RV subepicardial action potential shortening. This in vivo high-density mapping study evaluated the conduction and repolarization properties of the RV in BS subjects. METHODS AND RESULTS: A noncontact mapping array was positioned in the RV of 18 BS patients and 20 controls. Using a standard S(1)-S(2) protocol, restitution curves of local activation time and activation recovery interval were constructed to determine local maximal restitution slopes. Significant regional conduction delays in the anterolateral free wall of the RV outflow tract of BS patients were identified. The mean increase in delay was 3-fold greater in this region than in control (P=0<0.001). Local activation gradient was also maximally reduced in this area: 0.33+/-0.1 (mean+/-SD) mm/ms in BS patients versus 0.51+/-0.15 mm/ms in controls (P<0.0005). The uniformity of wavefront propagation as measured by the square of the correlation coefficient, r(2), was greater in BS patients versus controls (0.94+/-0.04 versus 0.89+/-0.09 [mean+/-SD]; P<0.05). The odds ratio of BS hearts having any RV segment with maximal restitution slope >1 was 3.86 versus controls. Five episodes of provoked ventricular tachycardia arose from wave breaks originating from RV outflow tract slow-conduction zones in 5 BS patients. CONCLUSIONS: Marked regional endocardial conduction delay and heterogeneities in repolarization exist in BS. Wave break in areas of maximal conduction delay appears to be critical in the initiation and maintenance of ventricular tachycardia. These data indicate that further studies of mapping BS to identify slow-conduction zones should be considered to determine their role in spontaneous ventricular arrhythmias.

The effect of substituting alternative grains in the diet on the nutritional profile of the gluten-free diet.

BACKGROUND: The only treatment for coeliac disease is lifelong adherence to a gluten-free diet. Several studies have reported nutritional deficiencies in individuals on a gluten-free diet. The present study aimed to determine whether the nutritional profile of gluten-free diet could be improved through the use of alternative grains. METHODS: A retrospective review of diet history records by a celiac specialist dietitian were used to establish a 'standard' gluten-free dietary pattern. An 'alternative' gluten-free dietary pattern was developed that substituted naturally gluten-free grains or gluten-free products made from 'alternative' flours (oats, high fibre gluten-free bread and quinoa) in the standard pattern. A paired t-test was performed to identify statistical significance between the 'alternative' and standard gluten-free dietary pattern. RESULTS: Analysis of standard pattern indicated that 38% of meals and snacks contained no grain or starch choice. Of those meals that contained a grain or starch component, rice was the grain chosen 44% of the time. The inclusion of alternative grains or grain products provided a higher nutrient profile compared to the standard gluten-free dietary pattern (P = 0.002). Several nutrients; protein (20.6 g versus 11 g), iron (18.4 mg versus 1.4 mg), calcium (182 mg versus 0 mg) and fibre (12.7 g versus 5 g) were significantly increased by changing the grain or starch component in the dietary pattern. The B vitamin content (riboflavin, niacin and folate) was improved, although this was not statistically significant (P = 0.125). DISCUSSION: The inclusion of alternative grain-based products increased the nutrient profile of the gluten-free dietary pattern significantly.

Quantitative assessment of the degree of villous atrophy in patients with coeliac disease.

BACKGROUND: Endoscopy and biopsy are used to diagnose coeliac disease. There are, however, observer-dependent interpretations of the degree of villous atrophy in biopsies. A pilot study using quantitative image-processing procedures was performed to quantify the degree of villous atrophy in patients with coeliac disease. METHOD: The degree of villous atrophy in duodenal biopsy images was quantified by calculating the ratio of villous edge-to-piecewise arc length (E/P ratio), and this value was compared with the blinded assessment of Marsh score for degree of villous atrophy. RESULTS: Mean E/P ratios for n = 31 biopsy images, 2.76 (SD 0.44) (Marsh IIIa), 1.91 (0.50) (Marsh IIIb) and 1.18 (0.22) (Marsh IIIc), were significantly different (p = 0.006). Based on non-parametric testing, the E/P ratios were inversely correlated with Marsh scores (Spearman coefficient rho = -0.798, Kendall tau = -0.681; p<0.0001). CONCLUSIONS: Biopsy images quantified by image analysis correlated exceedingly well with the histopathological grade of villous atrophy. Since quantified measurements are real-numbered values and lack observer bias, measurement of villous atrophy based on image analysis lends itself to standardisation of histological grading.

Static relationship of cycle length to reentrant circuit geometry.

BACKGROUND: Knowledge of the pathway common to both wave fronts in figure-8 reentrant circuits (ie, the isthmus) is of importance for catheter ablation to stop reentrant ventricular tachycardia. It was hypothesized that quantitative measures of reentry isthmus geometry were interrelated and could be correlated with tachycardia cycle length. METHODS AND RESULTS: A canine infarct model of reentrant ventricular tachycardia in the epicardial border zone with a figure-8 pattern of conduction was used for initial analysis (experiments in 20 canine hearts with monomorphic reentry). Sinus-rhythm and reentry activation maps were constructed, and quantitative (skeletonized) geometric parameters of the isthmus and border zone were measured from the maps. Regression equations were used to determine significant correlation relationships between skeletonized variables, which can be described as follows. Tachycardia cycle length, measured from the ECG R-R interval, increases with increasing isthmus length, width, narrowest width, angle with respect to muscle fibers, and circuit path length determined by use of sinus-rhythm measurements. After this procedure, in 5 test-set experiments, tachycardia cycle length measured from the R-R interval, in combination with regression coefficients calculated from initial experiments, correctly predicted isthmus geometry (mean estimated/actual isthmus overlap 70.5%). Also, the circuit path length determined with sinus-rhythm measurements correctly estimated the tachycardia cycle length (mean error 6.2+/-2.5 ms). CONCLUSIONS: Correlation relationships derived from measurements using reentry and sinus-rhythm activation maps are useful to assess isthmus geometry on the basis of tachycardia cycle length. Such estimates may improve catheter ablation site targeting during clinical electrophysiological study.

Relationship between sinus rhythm activation and the reentrant ventricular tachycardia isthmus.

BACKGROUND: In canine hearts with inducible reentry, the isthmus tends to form along an axis from the area of last to first activity during sinus rhythm. It was hypothesized that this phenomenon could be quantified to predict reentry and the isthmus location. METHODS AND RESULTS: An in situ canine model of reentrant ventricular tachycardia occurring in the epicardial border zone was used in 54 experiments (25 canine hearts in which primarily long monomorphic runs of figure-8 reentry were inducible, 11 with short monomorphic or polymorphic runs, and 18 lacking inducible reentry). From the sinus rhythm activation map for each experiment, the linear regression coefficient and slope were calculated for the activation times along each of 8 rays extending from the area of last activation. The slope of the regression line for the ray with greatest regression coefficient (called the primary axis) was used to predict whether or not reentry would be inducible (correct prediction in 48 of 54 experiments). For all 36 experiments with reentry, isthmus location and shape were then estimated on the basis of site-to-site differences in sinus rhythm electrogram duration. For long and short runs of reentry, estimated isthmus location and shape partially overlapped the actual isthmus (mean overlap of 71.3% and 43.6%, respectively). On average for all reentry experiments, a linear ablation lesion positioned across the estimated isthmus would have spanned 78.2% of the actual isthmus width. CONCLUSIONS: Parameters of sinus rhythm activation provide key information for prediction of reentry inducibility and isthmus location and shape.

Dynamic relationship of cycle length to reentrant circuit geometry and to the slow conduction zone during ventricular tachycardia.

BACKGROUND: Knowledge of cycle-to-cycle changes in isthmus geometry is of potential importance for radiofrequency catheter ablation to stop reentrant ventricular tachycardia. It was hypothesized that isthmus geometry often undergoes continuous evolution throughout reentry and that cycle-length variability measurements could be used to segment reentry into distinct phases and to predict changes in isthmus geometry. METHODS AND RESULTS: A canine infarct model of reentrant ventricular tachycardia in the epicardial border zone with a figure 8 pattern of conduction was used for analysis (25 monomorphic reentry episodes, 20 experiments). Tachycardias were segmented, on the basis of cycle-length variations, into 2 to 3 distinct phases corresponding to onset, maintenance, and spontaneous termination, when it occurred (6/25 episodes). Trends of linear cycle-length change occurred throughout the maintenance phase in all tachycardias. For each trend, quantitative geometric parameters of the isthmus were measured, and the following linear relationships were established. During a trend, the slow conduction zone activation interval and tachycardia cycle length increased, while isthmus length decreased. When isthmus length decreased, isthmus width decreased at its narrowed portion. Larger decreases in isthmus length corresponded to higher rates of linear cycle-length prolongation. Also, greater cycle-length variability tended to prolong tachycardia. CONCLUSIONS: Cycle-length alterations occur throughout reentry in this canine model and are predictive of isthmus geometry changes. Because similar reentry dynamics, which affect catheter ablation efficacy, have been observed clinically, estimation of changes in geometry during electrophysiological study may help target ablation sites.

Localization of the slow conduction zone during reentrant ventricular tachycardia.

BACKGROUND: Reentrant ventricular tachycardia is sometimes difficult to treat effectively because localizing the slow conduction zone (SCZ) for catheter ablation may be problematic. It was hypothesized that a linear relationship exists between activating wave-front acceleration and deceleration in the SCZ and, respectively, contractions and expansions of the far-field extracellular signal, which could be used for SCZ localization. METHODS AND RESULTS: To test the hypothesis, a model was developed to approximate SCZ location on the basis of the time interval between activation at the recording site and shifts in electrogram far-field deflections. Electrograms were recorded during reentry from 196 to 312 epicardial sites (canine model, 8 episodes). Activation maps of reentry were constructed to determine wave-front velocity, and piecewise linear adaptive template matching (PLATM) measured time shifts in far-field electrogram deflections. Linear trends of cycle length change often occurred during tachycardia (mean trend, +15 ms/96.8 cardiac cycles; r(2)=0.92). Alteration in the time interval for activation through the SCZ approximated the change in tachycardia cycle length (mean correspondence, 75.7%). The beginning and end times of far-field extracellular waveform time shifts measured by PLATM predicted the time from recording site activation to activation at the SCZ proximal and distal edges, respectively (mean absolute error with respect to activation mapping, 20.3 ms). CONCLUSIONS: During reentry, PLATM estimates the time interval from activation at any recording site near the circuit to SCZ activation. PLATM time intervals are convertible to arc lengths along the circuit for potentially more rapid and accurate update of a hand-held probe toward the SCZ for catheter ablation.

Relationship of specific electrogram characteristics during sinus rhythm and ventricular pacing determined by adaptive template matching to the location of functional reentrant circuits that cause ventricular tachycardia in the infarcted canine heart.

INTRODUCTION: It would be advantageous, for ablation therapy, to localize reentrant circuits causing ventricular tachycardia by quantifying electrograms obtained during sinus rhythm (SR) or ventricular pacing (VP). In this study, adaptive template matching (ATM) was used to localize reentrant circuits by measuring dynamic electrogram shape using SR and VP data. METHODS AND RESULTS: Four days after coronary occlusion, reentrant ventricular tachycardia was induced in the epicardial border zone of canine hearts by programmed electrical stimulation. Activation maps of circuits were constructed using electrograms recorded from a multichannel array to ascertain block line location. Electrogram recordings obtained during SR/VP then were used for ATM analysis. A template electrogram was matched with electrograms on subsequent cycles by weighting amplitude, vertical shift, duration, and phase lag for optimal overlap. Sites of largest cycle-to-cycle variance in the optimal ATM weights were found to be adjacent to block lines bounding the central isthmus during reentry (mean 61.1% during SR; 63.9% during VP). The distance between the mean center of mass of the ten highest ATM variance peaks and the narrowest isthmus width was determined. For all VP data, the center of mass resided in the isthmus region occurring during reentry. CONCLUSION: ATM high variance measured from SR/VP data localizes functional block lines forming during reentry. The center of mass of the high variance peaks localizes the narrowest width of the isthmus. Therefore, ATM methodology may guide ablation catheter position without resorting to reentry induction.

Knee cartilage topography, thickness, and contact areas from MRI: in-vitro calibration and in-vivo measurements.

OBJECTIVE: This study assessed the three-dimensional accuracy of magnetic resonance imaging (MRI) for measuring articular surface topographies and cartilage thicknesses of human cadaveric knee joints, by comparison with the calibrated stereophotogrammetric (SPG) method. METHODS: Six fresh frozen cadaveric knees and the knees of four volunteers were imaged with a three-dimensional spoiled gradient-recalled acquisition with fat suppression using a linear extremity coil in a 1.5 T superconducting magnet. The imaging voxel size was 0.47 x 0.47 x 1.0 mm. Both a manual and a semi-automated segmentation method were employed to extract topographic measurements from MRI. Following MRI, each of the six cadaveric knees was dissected and its articular surfaces quantified using stereophotogrammetry. The MRI surface measurements were compared numerically with the SPG measurements. RESULTS: For six cadaveric knees, the average accuracies of cartilage and subchondral bone surface measurements were found to be 0.22 mm and 0.14 mm respectively and the thickness measurements demonstrated an average accuracy of 0.31 mm. It was found that while most of the error may be attributed to random measurement error, the accuracy was somewhat affected by systematic errors. For each bone of the knee, accuracies were most favorable in the patella, followed by the femur and then the tibia. The more efficient semi-automated method provided equally good and sometimes better accuracies than manual segmentation. CONCLUSIONS: This study demonstrates that clinical MRI can provide accurate measurements of cartilage topography, thickness, contact areas and surface curvatures of the knee.

Dynamic changes in electrogram morphology at functional lines of block in reentrant circuits during ventricular tachycardia in the infarcted canine heart: a new method to localize reentrant circuits from electrogram features using adaptive template matching.

INTRODUCTION: Fractionated, low-amplitude or long-duration electrograms have limited specificity for locating reentrant circuits causing ventricular tachycardia (VT). In this study a new method is described, adaptive template matching (ATM), based on the quantification of beat-to-beat changes in electrograms, for locating functional reentrant circuits that are relatively stable and cause monomorphic VT. METHODS AND RESULTS: Monomorphic VTs were induced in 4-day-old infarcted canine hearts by programmed stimulation and reentrant circuits mapped in the epicardial border zone with a 196 or 312 bipolar electrode array. For ATM analysis, a template electrogram from each electrode, during an early cycle, was matched with all subsequent (input) electrograms at the same site by weighting the inputs of amplitude, duration, average baseline, and phase lag. The mean square error (MSE) between template and input was the criterion used to adapt the weights, and was also a measure of changes in electrogram shape that occur from cycle to cycle. The variance of each of the weighting parameters at all electrode sites were plotted on a representation of the electrode array, and the location of the functional lines of block bounding the central common pathway of reentrant circuits with figure-of-eight characteristics, overlaid on the ATM map. Peaks of high variance were found to be coincident with functional lines of block during all tachycardia episodes. CONCLUSION: Specific beat-to-beat changes in electrograms occur at functional lines of block in reentrant circuits that can be quantified by ATM analysis, suggesting that these regions might be located without activation mapping. The method might be useful to guide ablation catheter position.

Mechanisms causing sustained ventricular tachycardia with multiple QRS morphologies: results of mapping studies in the infarcted canine heart.

BACKGROUND: Sustained reentrant ventricular tachycardias (VTs) with different QRS morphologies have been observed to occur spontaneously and during programmed stimulation in human hearts. We determined mechanisms that can cause tachycardias with multiple morphologies in a canine model of myocardial infarction by mapping reentrant circuits. METHODS AND RESULTS: Reentrant VT with multiple QRS morphologies was induced in 11 canine hearts with 4-day-old infarcts. Comparison of activation maps of the reentrant circuits in the epicardial border zone associated with each morphology indicated two basic mechanisms. Less frequently, VTs of different morphologies in the same heart were caused by reentrant circuits in different regions of the infarct. Most commonly, the reentrant circuits associated with different morphologies were in the same region. Three different factors caused different exit routes from circuits in the same region, leading to the multiple morphologies. (1) The reentrant wave front for each morphology rotated around the same line of block but in different directions. (2) Reentrant circuits associated with each morphology were similar, but there were small changes in the extent of the central line of block. (3) Reentrant circuits with completely different sizes and shapes caused different morphologies. CONCLUSIONS: In this canine model, tachycardias with multiple morphologies most commonly arise from reentrant circuits in the same region of the infarct, suggesting that most often only one area has electrophysiological properties necessary to sustain reentry.

Prediction of the location and time of spontaneous termination of reentrant ventricular tachycardia for radiofrequency catheter ablation therapy.

Ventricular tachycardia caused by reentrant excitation can lead to cardiac arrest and sudden death. Drug treatment and surgical procedures have been used with limited effectiveness. Catheter ablation methods are more promising because they are less invasive than surgery. Although ablation has come to be highly effective in the treatment of supraventricular tachycardias, the overall success rate remains low for ventricular tachycardias, which may be due in part to an inaccurate localization of the reentrant pathway. The authors hypothesize that a site in the myocardium exists that is critical for the maintenance or reentry and that when ablated, will result in permanent cessation of the tachycardia. The authors also hypothesize that this is the same site where the reentrant impulse blocks during spontaneous termination of tachycardia. A series of experiments has been designed to determine if there are specific properties of extracellular electrograms recorded from reentrant circuits that would enable the circuits to be identified without activation maps and, more specifically, allow the site of block causing spontaneous termination to be localized. For quantitative analysis of electrograms, a paradigm is developed to characterize electrogram morphology using a canine infarct model. Changes in morphology (shape, size, and location of signal deflections) can be considered (1) motions of a coordinate system and/or (2) conformational changes of shape. To a first approximation, stationarity over short time segments is assumed so that the motions and conformations can be parameterized. These parameters were extracted for 50 cardiac cycles during an episode of nonsustained ventricular tachycardia, in which 196-bipolar electrode pairs were positioned in an array format across the epicardial surface of the heart. The results of these studies of changes in electrogram morphology suggest that during cycles 5 to 49 of ventricular tachycardia, in many electrograms near the circuit, the cycle length increases linearly, the amplitude increases, and the duration of activation decreases. During cycles 50 to 54, the cycle length increases much more markedly, the amplitude decreases, and the duration of activation increases. These observations suggest that cycle lengthening may be an important property of some spontaneous terminations, and moreover that other morphologic characteristics are affected differently at different stages of cycle lengthening. Further, all motion parameters tended to oscillate from cycle to cycle in either an alternans pattern or longer oscillation. The variations in morphology were typically only a few percent from cycle to cycle. Such variability would not be evident using only ruler-and-caliper measurements made by hand because of the lack of precision and the sheer volume of data. It is expected that this approach for characterization of electrogram morphology will be extremely useful clinically to (1) increase speed and accuracy of ablation site selection and (2) reduce multichannel electrogram recording complexity during ablation site selection.

Localized spatial discrimination of epicardial conduction paths after linear transformation of variant information.

We present a method for the localized statistical discrimination of class populations based on the Karhunen-Loève and Fukunaga-Koontz transforms. These transforms provide features that model the variance of a sample distribution. The spatial series of a 196 channel epicardial electrogram recording from an arrythmogenic postinfarct canine were analyzed. For each type of rhythm studied, Karhunen-Loève and Fukunaga-Koontz expansions were computed from five training sets of spatial data, corresponding to five locations across the surface of the heart. Nonparametric statistical tests were then used for discriminant analysis to compare properties representative of the distribution from each proposed class. In a comparison of properties from sinus rhythm to those of two ventricular tachycardias, several spatial regions exhibited statistically significantly different propagation characteristics. These areas were observed by visual inspection of electrogram activation maps to be characterized by conductive gradients, which differed in magnitude and direction from one rhythm to another. The regions in which the propagation characteristics are of greatest difference in each tachycardia were centered upon sites of conduction block, manifested by reentrant circuit rhythms. Therefore, the importance of the technique for the localization of specific electrophysiologic events is demonstrated. This study extends previous work of our group on biosignal pattern recognition to encompass localized spatial data.

Pattern recognition and interpretation of electromyogram data from cat jaw muscle.

This study investigates the effect of emotional behavior on the masseteric muscle EMG response patterns. Two experimental protocols are utilized: (1) does not elicit emotional behavior (stick chewing) and (2) elicits emotional behavior (hypothalamic stimulation). The Karhunen-Loève transform is used to compute features which exactly represent the correlated patterns of mean-zero observations, with data compression and noise immunity. Using nonparametric tests, it is found that the populations of biting and hissing features are significantly different (p < 0.05), with increased statistical significance as the size of the training set is increased. No statistically significant difference is seen in a test of the two biting populations.