Adrenergic Effects on VF. Introduction: We hypothesized that drugs which alter ventricular refractoriness or excitability produce quantifiable changes in ventricular fibrillation. Methods and Results: We used a 528‐channel mapping system to quantify the effects of the beta‐antagonist, propranolol, and the beta‐agonist, isoproterenol, on activation patterns in ventricular fibrillation. A plaque of 506 (22 × 23) electrodes spaced 1.12 mm apart and covering about 5% of the ventricular epicardium was sewn to the anterior right ventricle in 18 pigs (30 kg). Propranolol (0.25 to 0.4 mg/kg) increased the refractory period at a right ventricular epicardial site while isoproterenol (3 to 5 μg/min) shortened it. Ventricular fibrillation was induced by programmed stimulation, and unipolar electrograms were recorded from the 506 plaque electrodes for 2 seconds beginning 1, 15, and 30 seconds after the onset of fibrillation. Active epicardial recording sites were identified from the first derivative of the unipolar potentials (dV/dt) detected at each electrode. Then, neighboring active sites were grouped into activation fronts by computer analysis. In six pigs the effect of repeated inductions of ventricular fibrillation was assessed by comparing ventricular fibrillation after saline with a preceding control episode of fibrillation. Each activation front excited 40%± 46% of the mapped region before blocking. No changes were observed with saline and multiple inductions of fibrillation. In another six pigs, ventricular fibrillation after propranolol was compared with a preceding control episode of fibrillation. Ventricular fibrillation alter propranolol exhibited a decreased activation rate per epicardial recording site and fewer activation fronts per second. There was no change in the amount of tissue excited by each activation front or the number of reentry cycles per activation front compared with control. In addition, there was no change in the maximum negative dV/dt detected per activation at an epicardial site. In six pigs ventricular fibrillation during isoproterenol was compared with control episodes of ventricular fibrillation before and 45 minutes after washout of the drug. The control episodes of fibrillation were not different from each other. Compared with control, ventricular fibrillation during isoproterenol exhibited an increased activation rate per epicardial site, an increased amount of tissue excited by each activation front, and an increased maximum negative dV/dt for each activation. There was no change in the number of activation fronts per second or the number of reentry cycles per activation front compared with control. Conclusions: Quantitative analysis revealed that propranolol and isoproterenol do not have symmetrically opposite effects on ventricular fibrillation. Propranolol decreased the number of activation fronts while isoproterenol increased the amount of tissue excited by each activation front. Thus, drugs that alter ventricular refractoriness or excitability alter ventricular fibrillation.

Cardiac activation sequences are normally determined by (i) the detection and timing of local activations in cardiac electrograms, (ii) the grouping together of activations in different electrodes that are generated by the same activation fronts, and (iii) the construction by interpolation of isochronal maps showing the pathways of the activation fronts. This process is typically carried out by manual or semiautomated methods. These methods are usually adequate for stable, repeatable rhythms in normal hearts. However, in situations in which the electrograms are distorted, as in those recorded from abnormal myocardium, or the mapped rhythms are rapidly changing, as in ventricular fibrillation, they are tedious and time-consuming and yield results that are subjective and not repeatable from one investigator to another. Therefore, we developed a computer-based method for automating the identification and analysis of activation fronts recorded from a large array of electrodes. The electrodes are closely spaced (1 mm) so that interpolation is not required. Electrodes are identified as recording an activation when the temporal derivative of the potential is more negative than a user-specified value. Activations occurring less than a user-specified distance apart in time and space are identified as part of the same activation front. Characteristics of the activation fronts, such as their number, size, and the presence of reentry or collision, are then quantified. The differences between the results obtained by this automated method and those obtained by four human investigators was no greater than the differences in results among the four investigators themselves. Because the method is automated and algorithmic, it is both rapid and repeatable.

The identification of local activation events in bipolar cardiac electrograms, the first step of isochronal map construction, is a time-consuming and difficult process. Owing to the variability among bipolar activation complexes and the lack of practical knowledge concerning the relationship of the bipolar waveform to action potential characteristics, a set of empirical rules to guide the assignment of local activation times have been adopted. A computer program, called AP, has been designed, which implements these rules in the form of a syntactic analyser. Canine epicardial recordings were used to evaluate AP by comparing local activation times, assigned by AP, with times assigned independently by three investigators. The Hermes-Cox model for detector evaluation and a bootstrap statistical method were used in conjunction with ROC analysis to evaluate the ability of AP to detect events. Analysis of discrepancies among investigator-assigned times showed that the reliabilities of AP event detection and AP-assigned times were comparable to those of the investigators. The methods used in system design and evaluation are applicable to a broad range of problems in the detection and localisation of waveform components.

A 528 channel data acquisition and display system has been developed which allows the authors to study electrical therapies of the heart. The acquisition system records defibrillation shock potentials and electrograms from the heart. The display system presents animated sequences of potentials or their derivative on a two dimensional projection of the recording array. Using the system, the authors measured the distribution of potentials on the heart during transvenous defibrillation shocks in pigs. For failed defibrillation shocks near threshold, the authors studied the post-shock activation sequences that led to reinitiation of fibrillation. The earliest epicardial activation following failed shocks was in the region of the heart opposite and inferior to the right ventricular electrode. The first few beats were organized and rapid. The rapid activation led to unidirectional block and reentry after 3 or 4 beats. This mapping system provides a comprehensive tool for studying electrical therapies of the heart

A novel, language-based interface to the specification of multivariate volume classification and shading algorithms has been implemented. The system facilitates experimentation by providing access to data relevant to volume classification and shading (scalars, gradients, and gradient magnitudes) in a C-like language environment. The user writes code to calculate opacity and colour on a per voxel basis. The code is interpreted and compiled in a transparent fashion and then executed on a volume data-set. The output is a volume primitive suitable for input to standard volume rendering algorithms.

Cardiac activation sequences are normally determined by the detection and timing of local activations in cardiac electrograms, but assigning of a unique activation time, especially during ventricular fibrillation (VF), is often difficult. Even if distinct activations can be derived, it is difficult to group activations into wavefronts. A method was developed for automating the identification and analysis of distinct wavefronts of electrical activity that eliminates the inconsistencies of manual analysis and the ambiguities of isochronal mapping. After individual wavefronts have been identified, analysis of their characteristics became a simple task that was also automated. This automated method shows promise as an accurate and powerful tool for quantitative analysis of VF

Biomedical investigators are currently able to acquire and analyze physiological and anatomical data from three-dimensional structures in the body. Often, multiple kinds of data can be recorded simultaneously. The usefulness of this information, either for exploratory viewing or for presentation to others, is limited by the lack of techniques to display it in intuitive, accessible formats. Unfortunately, the complexity of scientific visualization techniques and the inflexibility of commercial packages deter investigators from using sophisticated visualization methods that could provide them added insight into the mechanisms of the phenomena under study. Also, the sheer volume of such data is a problem. High-performance computing resources are often required for storage and processing, in addition to visualization. This chapter describes a novel, language-based interface that allows scientists with basic programming skills to classify and render multivariate volumetric data with a modest investment in software training. The interface facilitates data exploration by enabling experimentation with various algorithms to compute opacity and color from volumetric data. The value of the system is demonstrated using data from cardiac mapping studies, in which multiple electrodes are placed in an on the heart to measure the cardiac electrical activity intrinsic to the heart and its response to external stimulation.

The authors have developed a visualization method that aids in visualizing cardiac activation sequences before and after a defibrillation shock and in visualizing the associated extrinsic potentials and potential gradients generated by the shock. The examples are taken from studies designed to explore these types of phenomena. This method is used to visualize the results of mapping studies and operates by superimposing values of electrical variables on realistic three-dimensional renderings of cardiac anatomy. The system consists of a user interface that allows an investigator with basic programming skills to specify transformations of multivariate volume data to color and opacity values for volume rendering. The environment allows and encourages exploration of complex data by providing a convenient method for the application of different transformation algorithms.< >

A three-dimensional cellular automata model of activation wavefront propagation in ventricular cardiac tissue was created. The model geometry was obtained from magnetic resonance (MR) images of a canine heart which was used in a ventricular fibrillation (VF) study. Propagation within the simulated and real hearts was compared. Activation times in the simulated heart had a moderately high correlation when compared to the activation times recorded in the actual heart study. The model was run with and without fiber orientation included. Inclusion of fiber orientation did not greatly increase the correlation.

Understanding the mechanisms of ventricular fibrillation and defibrillation requires analysis of epicardial and endocardial potentials throughout the heart. Plunge electrodes permit recording of cardiac potentials at epicardial and endocardial sites, and allow determination of electrical gradients. They also enable us to determine the arrhythmia recurrence sites following failed defibrillation; these sites may be epicardial or endocardial. Therefore, it is necessary to relate the position of the plunge electrodes to the cardiac geometry. We have developed an interactive, computer graphics based system that allows us to locate plunge electrodes on digitized MRI slices of a heart. The system, which can work with any type of image, allows us to identify the epicardial and endocardial points of each plunge electrode on the different MRI slices. Up to 128 different plunge electrodes may be identified to the system. Normalized 3-D coordinates for each epicardial and endocardial electrode point are computed and stored in data files on the computer. Geometry information obtained from this system permits a more thorough understanding of the electrical signals recorded by the plunge electrodes. This information can be used in the study of cardiac excitation and arrhythmias and could help in the development of a more effective lead system for ventricular defibrillation.

A graphical display system for animating mapped cardiac potentials is described. The system displays recorded voltages from 121 epicardial electrodes simultaneously on a computer monitor using color to indicate the magnitude of the voltage. Numerous options accessible through the mouse-driven user interface provide the user with a high degree of interaction with the data. The user can observe the changes in the recorded voltages over time by defining a portion of the data over which to animate the voltages. Animation speeds of up to 2 1/4 frames per second can be achieved, depending on the workstation used. Use of the graphical display system provides a new tool for studying the electrical conduction properties of the heart. Through its use, a more complete understanding (and potentially a more effective treatment) of arrhythmias might be achieved.<>

Discrete smooth interpolation (DSI) has been applied to the visualization of data gathered during canine epicardial and transmural mapping studies. It is found that this method facilitates the mapping of reentrant pathways and the three-dimensional mapping of electrical potentials and potential gradients measuring transmurally during defibrillation shocks. It easily customizes the interpolation criteria to an application. A variation of J.L. Mallet's (1989) interpolation criteria which is suitable for transmural mapping is proposed. These criteria can be used for the first three dimensions and a new set of criteria would be used for the fourth dimension, allowing interpolation to be performed with one set of simultaneous equations. Discontinuities are easily incorporated into the DSI model.< >

A set of programs developed to display the potentials and the magnitudes of the estimated potential gradients generated by defibrillation shocks are discussed. There are three types of displays. The first type displays three-dimensional surfaces constructed from electrode locations. Potentials or gradient magnitudes are interpolated over each surface and are displayed as spatial changes in intensity or hue. The second type of display is a three-dimensional surface reconstruction of the heart and electrodes. This display is used to verify the three-dimensional electrode coordinates that are obtained from digitized images of the heart. The third type of display is a volume reconstruction of the myocardium. In this display, spatial changes in potentials or gradient magnitudes in the myocardial volume are represented by spatially varying the hues of the volume elements. The electrical values of most volume elements are interpolated by means of a three-dimensional method based on discrete smooth interpolating.< >

A program (AP) for automatically picking (detecting and timing) local activations in bipolar cardiac electrograms has been developed. The program is used in mapping the activation sequence of the heart during normal rhythms and ventricular arrhythmias, particularly ventricular tachycardia and ventricular fibrillation, in experimental and clinical environments. The difficult conditions under which the program can be applied, the lack of technical background of many of the system's users, and the nature of the programs which are used in conjunction with the detector required careful design of the software. The design constraints observed during the development of AP and how the system has been integrated with the rest of the hardware and software of the mapping system used in the authors' laboratory are described.<>

The use of cardiac activation mapping to study ventricular fibrillation (VF) is discussed. The locations of isochrones in maps are based on decisions on whether and when segments of the electrogram have local electrical activation. The authors compare two quantitative criteria for making decisions about local activity in electrograms. The criteria are based on the comparison of electrograms recorded in those excitable zones with electrograms recorded in normal myocardium. One uses the first derivative of the electrogram (only one electrogram affects the decision); the second uses the first derivative of the primarily local component of the waveform

It is shown how to use the bootstrap to construct a nonparametric confidence interval for a receiver operating characteristic (ROC) curve. The method is used to perform a statistical comparison of a detectors curve with a particular point in ROC space or to compare curves derived from two similar detectors. The method is illustrated with a specific example in which a computer algorithm (AP) that was designed to detect cardiac activations in recordings taken from extracellular bipolar electrodes is evaluated. Twelve recordings of ventricular fibrillation were made on the epicardial surface of the heart in anesthetized mongrel dogs. Each recording contained between 115 and 237 activations. A cardiologist examined each recording, identified all activation events, and assigned a time of local activation (latC) to each event. Next, each recording was analyzed by the computer program, AP, which produced its own list of local activation times (lat AP). The total numbers of true detections (NTD ), false detections (NFD), and false negatives (NFN) were calculated for each recording. A true detection was defined as a latAP that fell within ±6 ms of a latC